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Criptococosis meníngea asociada al SIDAFecha: 5/5/2018

 

 

Criptococosis meníngea asociada al SIDA.
Análisis de pacientes varones HIV (+) con criptococosis meníngea internados.

                                                         D Cangelosi, L De Carolis, L Trombetta, C Wainstein

                         Hospital de Enfermedades Infecciosas Francisco J Muñiz. Ciudad Autónoma de Buenos Aires. Argentina

                                       Revista de la Asociación Médica Argentina, Vol. 120, Número 3 de 2007.
                                                                               ACTUALIZACIÓN

 

Resumen

La criptococosis es una micosis sistémica oportunista con distribución universal causada por una levadura capsulada, El Cryptococcus neoformans (C. neoformans). C. neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. Crece preferentemente en ambientes ricos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. La diseminación hematógena del agente causal provoca múltiples localizaciones, las cuales se hacen clínicamente evidentes en pacientes con deterioro de la inmunidad mediada por células. A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa predisponente más importante de esta micosis. La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos y síntomas de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución. La anfotericina B es el pilar terapéutico del tratamiento. En nuestro estudio analizamos las características demográficas, epidemiológicas, clínicas, el líquido cefalorraquídeo, el diagnóstico micológico y el tratamiento empleado en los pacientes hospitalizados en Sala 11 con diagnóstico de criptococosis meníngea. En la criptococosis meníngea asociada al SIDA, el diagnóstico puede realizarse por el análisis de distintos tipos de especímenes biológicos, siendo los principales el examen microscópico directo del LCR con tinción de tinta china y cultivo.

Introducción

La criptococosis es una micosis sistémica cosmopolita de carácter oportunista cuyo agente causal es una levadura capsulada termomonomorfa, el Cryptococcus neoformans.1-3 El C neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. La diseminación sanguínea del agente causal origina múltiples localizaciones, las cuales se hacen clínicamente evidentes ante defectos de la inmunidad mediada por células asociándose con frecuencia a linfomas, leucemia, enfermedades del sistema retículo endotelial, sarcoidosis, artritis reumatoidea, hepatitis, cirrosis y diabetes.2-3 A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa favorecedora más importante.3-4

Etiología

C neoformans es una levadura capsulada que desarrolla colonias cremosas o mucoides en agar glucosado de Sabouraud o similares, tras 48-72 horas de incubación a 28ºC - 37ºC. Mientras la incubación en una atmósfera hipercádmica favorece la producción de cápsula, la presencia de cicloheximida en los medios inhibe su desarrollo. Micromorfológicamente esta levadura corresponde a células redondas u ovales, de 4 a 15 µm de diámetro, con brotes únicos o múltiples, rodeada por una cápsula polisacárida de tamaño variable. Las tinciones de Mucicarmín de Mayer y Alcian blue, aplicadas a cortes histopatológicos, permiten la coloración de la cápsula y así su diferenciación de otras levaduras. La especie C neoformans posee dos variedades: C neoformans variedad neoformans, que incluye las cepas de los serotipos A, D y AD; y C neoformans variedad gattii, constituida por cepas de los serotipos B y C.5 Con la actualización de la clasificación taxonómica se ha propuesto que las cepas del serotipo A se clasifiquen en una variedad diferente, C neoformans variedad grubii, mientras que el serotipo D debe continuar en la variedad neoformans.5

Epidemiología

El C neoformans posee una distribución universal, desarrollándose preferentemente en ambientes enriquecidos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. Las levaduras pueden mantenerse viables en los excrementos de las palomas durante dos o más años, siempre que se encuentren a resguardo de los rayos solares, ya que éstos son esterilizantes. En la naturaleza las levaduras poseen cápsulas de tamaño reducido, lo cual favorece su inhalación y su actividad de propágulos.1
El criptococo es incapaz de infectar a las palomas probablemente porque la temperatura corporal relativamente alta de las aves es adversa al criptococo.2-5-6 A diferencia de las otras variedades, C neoformans variedad gattii no se ha cultivado de excrementos de aves. Ellis y Pfeiffer  cultivaron a C neoformans variedad gattii a partir de muestras tomadas de especies de Eucaliptos: E camaldulensis (eucalipto rojo) y E tereticornis en Australia. Debido a que estos árboles fueron exportados a otras partes del mundo, los autores interpretaron que estas especies de árboles podían ser un vector infeccioso. Sin embargo, otros autores hallaron que esta variedad de Cryptococcus está asociada a muchas especies de eucaliptus de distintas partes del mundo.5

Patogenia

La amplia distribución de C neoformans en la naturaleza y la relativa baja frecuencia de casos clínicos de criptococosis implica que algunas personas se exponen al hongo sin desarrollar síntomas. Las levaduras escasamente capsuladas serían los elementos infecciosos, aunque también ese papel ha sido adjudicado a los basidiosporos de la fase sexuada de este Basidiomycete: Filobasidiella neoformans. Sólo estas formas, por su pequeño tamaño, podrían acceder al alveolo pulmonar. En los espacios alveolares se enfrentan inicialmente con los macrófagos locales. El desarrollo de la enfermedad depende directamente del estado inmunológico del huésped, del tamaño del inóculo y de la virulencia de la cepa infecciosa. El polisacárido capsular, la manoproteína y tal vez otros componentes fúngicos actúan como inmunomoduladores de la respuesta inmune del huésped.6 La producción de cápsula es un fenómeno de adaptación al estado parasitario que se observa cuando el hongo se encuentra en los tejidos o fluidos biológicos con el propósito de evitar la fagocitosis. La presencia de polisacárido capsular en los tejidos y fluidos biológicos agregaría sus efectos inmunosupresores potenciando a los defectos inmunológicos ya existentes en el individuo enfermo.6 Si bien la diseminación sanguínea produciría múltiples localizaciones, en el SNC se producen las manifestaciones clínicas más relevantes de la enfermedad. Entre las probables causas de esta predilección se destacan la ausencia de factores solubles séricos anti-criptococos en el LCR, la falta de respuesta inflamatoria anti-Cryptococcus en el cerebro debido a la deficiencia de factores quimiotácticos y opsóninas, y de la actividad de complemento en el LCR. La progresión de las lesiones en el cerebro encuentra vía libre a diferencia de otros tejidos donde da lugar a una respuesta inflamatoria que destruiría o controlaría la infección
Si bien la base del neurotropismo no está clara, puede relacionarse a la evasión selectiva de las defensas del huésped o la afinidad del criptococo por tejidos ricos en catecolaminas, particularmente la dopamina, que son sustratos de la fenoloxidasa para la síntesis de melanina y son abundantes en el sistema nervioso central y en las adrenales, característica que podría favorecer su desarrollo.3-6 La fenoloxidasa convierte a los sustratos hidroxibenzoicos en pigmentos negros o marrones que oscurecen las colonias en los medios de cultivo y colaboraría con la virulencia del criptococo mediante su participación en la melanogénesis, que podría relacionarse con el neurotropismo del hongo.6

Criptococosis clásica

El hongo penetra en el organismo por inhalación y raramente por inoculación. La localización primaria ocurre en el pulmón, donde solo una pequeña cantidad de casos presentan sintomatología respiratoria. En estos últimos llama la atención la escasez de síntomas respiratorios subjetivos a pesar de la existencia de extensas lesiones radiológicas. Mucho antes del SIDA, Pedro-Pons describió dos cuadros clínicos fundamentales: las formas pulmonares y las del sistema nervioso central. También describió otras localizaciones y señaló que en el 20% de los enfermos existen adenomegalias y esplenomegalia (recordando a la enfermedad de Hodgkin), en el 8% lesiones osteolíticas y en el 5% lesiones en la piel, de tipo papulosos con vesiculación incompleta. En el SNC destacó que la criptococsis motiva signos de hipertensión intracraneal o meningitis.7 Describió el cuadro clínico con cefaleas frontales cada vez más intensas, generalizadas y persistentes, acompañadas de vómitos, vértigo y rigidez de nuca. Con frecuencia se acompañaba de nistagmus, diplopía, ptosis palpebral y alteraciones del estado psíquico, con irritabilidad, inquietud y confusión. La ataxia y la hemiplejía eran considerados fenómenos asiduos, y la enfermedad, lentamente progresiva, sin fiebre y con manifestaciones de hipertensión intracraneal conducía a la muerte en un plazo de dos a seis meses, situación que mejoró luego de la introducción de la anfotericina B para el tratamiento antifúngico.7 Con anterioridad al SIDA, Negroni describió las siguientes formas clínicas: asintomática o subclínica, respiratoria aguda, respiratoria crónica y la forma miliar diseminada (con frecuentes metástasis en el SNC). En esta última, la meningitis es la más común y de evolución subaguda o crónica, menos frecuentemente aguda. La localización cerebral puede asociarse a la formación de granulomas, abscesos o quistes gelatinosos que contienen gran cantidad de criptococos. La meningitis criptocócica comienza en forma solapada, con cefalea frontal intermitente que se hace continua y difusa, y es observada en el 70% de los casos. La fiebre se observa en el 60% de los enfermos, las alteraciones visuales en el 40%, y en diferente porcentaje síndrome meníngeo y signos neurológicos focales, hipertensión endocraneana e hidrocefalia, síntomas psíquicos como apatía, confusión, inversión del sueño, cambios de personalidad seudopsiquiátricos y en casos más graves coma.1-2
El síndrome meníngeo es completo, con rigidez de nuca, signos de Kerning y Brudzinski, diplopía y nistagmus, ptosis palpebral, anisocoria, edema de papila, pérdida de control de esfínteres y LCR hipertenso.2
El LCR es semejante al observado en la meningitis tuberculosa: su aspecto es del cristal de roca, opalescente o xantocrómico y forma una red de fibrina después de algunas horas. La presión de apertura está elevada, con hiperproteinorraquia variable de 40 a 500 mg/dl o más, disminución de los cloruros y de la glucosa y pleocitosis a predominio linfocitario con 200 y 800 células/ml. La microscopía del concentrado del LCR centrifugado, utilizando como contraste tinta china, revela la presencia de levaduras capsuladas en el 50% de los casos. La prueba de aglutinación de partículas de látex para detectar la presencia del antígeno polisacárido capsular del C neoformans es positiva durante la enfermedad activa.2 También pueden emplearse las tinciones de PAS, Gomori - Grocott y menos frecuentemente el Mucicarmín de Mayer, que pone en evidencia la cápsula.1 En el 10% de las criptococosis diseminadas se observan manifestaciones cutáneas y en el 3% aparecen lesiones en la mucosa orofaríngea, mientras que el compromiso óseo se comprueba en el 10% de los casos. En 1987 Lucentini y col comunicaron 5 casos de criptococosis meníngea no asociados a SIDA, tratados entre 1983 y 1985 en la IV Cátedra de Medicina del Hospital de Clínicas José de San Martín. El diagnóstico se realizó por el hallazgo del C neoformans en el LCR mediante el examen microscópico directo previo agregado de preparación con tinta china, el cultivo, la inoculación intracerebral al ratón y la determinación del antígeno capsular. Cuatro de los pacientes con esta patología no habitual, según la opinión de los autores, poseían grados variables de inmunodepresión, tres de ellos debidos al padecimiento de lupus eritematoso sistémico y uno de pénfigo vulgar generalizado, mientras que el quinto era un alcohólico crónico severo. Los casos se presentaron clínicamente con un síndrome meníngeo acompañado de fiebre; dos pacientes tuvieron manifestaciones psíquicas (cambios de carácter y deterioro del sensorio) y vegetativas, y se comprobó en dos oportunidades la existencia de adenopatías, axilares y cervicales en un caso (adenitis reactiva) y supraclavicular en el restante (con presencia de C neoformans). El examen del LCR evidenció un líquido claro, con pleocitosis a predominio linfocitario, hiperproteinorraquia y aglucorraquia o hipoclorurorraquia.8

Criptococosis meníngea en los pacientes con SIDA

Entre las enfermedades oportunistas que se asocian al SIDA, la criptococosis meníngea es la micosis más común entre las que ponen en peligro la vida. Si bien no existen pruebas concluyentes, la enfermedad se ocasionaría como consecuencia de una infección primaria adquirida recientemente, más que por la reactivación de una infección pasada.
Hacia 1993 Powderly señalaba que la criptococosis meníngea era la tercera infección más frecuente del SNC en los pacientes con SIDA, luego de la encefalopatía provocada por el HIV y las encefalitis por Toxoplasma gondii.9
Aproximadamente del 6 al 10% de los pacientes con SIDA desarrollarán meningitis criptocócica y en cerca del 40% de los casos será el primer evento definitorio de SIDA.
La micosis se asocia a una marcada inmunodeficiencia, con un recuento de linfocitos T CD4+ menor a 100 cél/µL.
En nuestro medio en 1995 Bava relataba que la criptococosis era la micosis sistémica más frecuente, lo que contrastaba con la rareza de su observación antes de los años 80.10 Esta micosis fue reconocida como "enfermedad signo", ya que su sola presencia orientaba a los médicos a la búsqueda de enfermedades subyacentes concomitantes.
La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución.5 El síndrome neurológico se presenta en más del 90% de los casos, caracterizándose por la presencia de cefalea persistente, vómitos, fotofobia y síndrome meníngeo incompleto.4-5-11 Las alteraciones de replica breitling bentley watches la conciencia y las convulsiones son signos de mal pronóstico. Las manifestaciones de foco, entre ellas la parálisis del recto externo, la afasia, el síndrome cerebeloso y la paresia de los miembros, aparecen con poca frecuencia.4 La sola presencia de cefalea y fiebre durante más de una semana en un individuo HIV+ indica la necesidad de realizar la punción lumbar y el examen del LCR.
Por lo general la TAC de encéfalo no exhibe masas ocupantes y las alteraciones observadas suelen ser determinadas por el HIV: atrofia cerebral, aumento del espacio sub-aracnoideo y del tamaño de los ventrículos, y en menor medida, con signos de vasculitis. En algunos casos la RMN muestra la presencia de lesiones nodulares pequeñas y situadas en la base del encéfalo.4 El examen de fondo de ojo puede revelar edema de papila, borramiento de sus bordes o signos de coriorretinitis y en los casos más graves se observa atrofia del nervio óptico.
La meningoencefalitis por C neoformans en los pacientes con serología positiva para el HIV se presenta con una elevada carga fúngica y un alto contenido de antígeno polisacárido capsular que determina una elevada carga osmótica en el espacio subaracnoideo y que es responsable de los graves cuadros de hipertensión endocraneana, en los que puede producirse la pérdida brusca de la agudeza visual.4-12
El tratamiento antirretrovial de gran actividad (TARGA) ha originado un nuevo síndrome de reconstitución inmune en las infecciones criptocócicas. Después del comienzo del TARGA algunos pacientes desarrollan síntomas agudos de meningitis criptocócica o dolor e inflamación de los ganglios periféricos, hiliares o mediastínicos. Este síndrome también puede ocurrir durante el tratamiento de la meningitis criptocócica en los primeros meses después de iniciado el TARGA y parece correlacionarse con un descenso significativo de la carga de HIV, pero con sólo un modesto incremento del número de linfocitos T CD4+.
Se ha sugerido que conforme la inmunidad mejora con el tratamiento antirretrovial, las infecciones criptocócicas latentes o silentes se manifiestan desde el punto de vista clínico.
El síndrome de reconstitución inmunitaria estaría marcado por cefaleas intensas, nuevos signos neurológicos, aparición de más células inflamatorias en el LCR y una posible hipertensión intracraneal. La distinción entre la reconstitución inmunitaria y la infección progresiva puede ser difícil, pero los cultivos del LCR y del aspirado de los ganglios linfáticos son negativos en el primer caso.6
En pacientes con SIDA y criptococosis meníngea, el LCR fluye a goteo rápido o a chorro y debe tomarse sistemáticamente la presión de apertura. Su aspecto es cristal de roca y las alteraciones físico-químicas son muy escasas, la respuesta inflamatoria es menor que en la criptococosis clásica (<20 células/mm3) y el examen con tinta china del LCR es positivo en más del 90% de los enfermos.4-10
Habitualmente las proteínas están ligeramente elevadas y la glucorraquia por lo general es normal. Así también, en los pacientes con SIDA los niveles de antígeno polisacárido capsular en LCR y sangre son muchos más elevados que en los pacientes con criptococosis asociada a otras causas favorecedoras.10 Sin embargo, el hallazgo de un LCR normal desde el punto de vista físico, químico y citológico no descarta el diagnóstico de meningoencefalitis por C neoformans en pacientes con SIDA. Al respecto, Metta y col han comprobado que en algunos de estos casos la microscopía con tinta china del sedimento deL LCR presentaba el campo cubierto de levaduras capsuladas.12
Los cultivos de LCR son positivos en el 90% de los casos y los hemocultivos por el método de centrifugación lisis permiten el aislamiento del agente causal en el 17% AL 70% de los casos, según diferentes autores.12 En la serie examinada por Metta y col los síntomas neurológicos predominantes fueron la cefalea y la fiebre y estuvieron presentes en la totalidad de los pacientes. El diagnóstico se estableció a través de la microscopía con tinta china que, de acuerdo a la serie de 51 pacientes en su estudio, alcanzó el 80% de positividad.12 En el mismo estudio el cultivo del LCR alcanzó el 94% de resultados positivos, al igual que el 65% de los hemocultivos realizados con la técnica de lisis-centrifugación con saponina.12 Similares resultados son señalados por Rodríguez Pedezert y col2 para la confirmación diagnóstica de la localización de la criptococosis en el SNC, con 90% de positividad en cultivos del LCR y hemocultivos positivos en el 67%.11
La detección de antígeno capsular polisacárido del C neoformans en sangre o LCR es un procedimiento con una sensibilidad y especificidad de 90%.8-15 Por este motivo, esta prueba puede ser usada como prueba de detección en pacientes HIV positivos con fiebre, sin claro foco de origen. Un porcentaje bajo puede dar falsos positivos en la sangre por la presencia de factor reumatoideo.11

Tratamiento de la criptococosis meníngea asociada al SIDA

La meningitis criptocócica es mortal de manera uniforme sin tratamiento antifúngico.5 La anfotericina B es el pilar terapéutico contra la meningitis criptocócica. En la actualidad se ha establecido la dosis habitual de inducción para la anfotericina B desoxicolato en 0,7 mg/kg/día. La anfotericina B liposómica a dosis de 4 mg/kg/día ha tenido un éxito terapéutico similar al desoxicolato, con menos toxicidad y puede recomendarse como un tratamiento alternativo.
La flucitosina se utiliza en tratamiento combinado con anfotericina B y la dosis en pacientes con función renal normal suele ser de 100 mg/kg/día. Se deben monitorizar las concentraciones del fármaco para mantener sus niveles a las 2 horas de la dosis por debajo de 100 mg/ml y así reducir la aparición de mielosupresión en los pacientes con riesgo de sufrir esta toxicidad, como aquellos con insuficiencia renal o los que reciben dosis elevadas de polienos.
Los azoles se han utilizado con eficacia en el tratamiento de la meningitis criptocócica.
El fluconazol se ha empleado de manera extensa en esta infección debido a su excelente farmacocinética en LCR y su seguridad oral a largo plazo. Tiende a ser fungistático y quizás sea mejor utilizarlo en la fase de la infección en la que haya una carga baja de levaduras en LCR.
El itraconazol tiene baja penetración en el LCR y biodisponibilidad oral irregular, por lo cual es inferior a fluconazol en el tratamiento de la meningitis criptocócica.
Un triazol nuevo, el voriconazol, se ha estudiado en un número limitado de casos refractarios de criptococosis con un éxito moderado.
Los inhibidores de la β-glucano sintasa, como la caspofungina, micafungina y anidulafungina, no poseen actividad anticriptocócica y no se utilizan para el tratamiento de esta enfermedad. Un algoritmo habitual para el tratamiento de la meningitis criptocócica en pacientes con SIDA es un régimen de 3 etapas. El tratamiento se inicia con anfotericina B (0,7 mg/kg/día) más flucitosina (100 mg/kg/día) durante al menos 2 semanas. Los pacientes que presenten una respuesta clínica adecuada pueden cambiar a fluconazol (400 - 800 mg/día) durante 8 - 10 semanas. Por último, comienza una fase supresora crónica con fluconazol (200 mg) una vez al día. La administración de TARGA, con su capacidad de producir reconstitución inmune al elevar el recuento de CD4 y disminuir la carga viral, permite interrumpir el tratamiento antifúngico después de 1 - 2 años en pacientes que poseen un recuento de CD4 superior a 200/µL durante al menos 6 meses, una carga viral indetectable y un antígeno criptocócico sérico negativo.
La identificación de una recidiva puede ser difícil en los pacientes con infecciones criptocócicas. Los dos signos más claros de recidiva que sugieren un cambio terapéutico son el desarrollo de nuevos signos y síntomas clínicos, y cultivos positivos repetidos.
La persistencia de un examen de tinta china positivo o títulos cambiantes del antígeno polisacárido capsular no son indicaciones precisas de recidivas. Un aspecto fundamental en el tratamiento de la meningitis criptocócica es el manejo de la hipertensión endocraneana.
Los síntomas son confusión, somnolencia, intensas cefaleas, vómitos, parálisis de los nervios craneales y pérdida de la visión. Puede que se precise el control de la hipertensión intracraneal durante la fase temprana del tratamiento mediante drenajes externos, como punciones lumbares repetidas. La hipertensión persistente y sintomática puede justificar la colocación de una derivación ventricular permanente del LCR. Por desgracia, a pesar de la intervención, puede aparecer ceguera, demencia permanente o el fallecimiento.5

Bibliografía

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10. Bava AJ. Estado actual de la criptococosis en la Argentina. Revista Argentina de Infectología 1995;Vol VIII, Nº 1:3-8. 
11. Rodríguez Pedezert M, Vacarezza M, Savio E. Meningitis por Cryptococcus neoformans -Experiencia clínica y consideraciones terapéuticas- Rev Panam Infectol 2004;6(3):34-40. 
12. Metta H, Corti M, Negroni R, y col. Criptococosis diseminada en pacientes con SIDA. Análisis clínico, microbiológico e inmunológico de 51 pacientes. Revista Argentina de microbiología 2002;34:117-123.

 

 

Cesárea de término programada: la suplemetación materna de oxígeno modifica los gases sanguíneos del feto?Fecha: 1/4/2018

 

 

Cesárea de término programada: ¿la suplementación materna con oxígeno modifica los gases sanguíneos del feto

 

                                                                                          Simon VB, Fong A, Nageotte MP.

                                                                                          Am J Perinatol. 2018 Jan; 35(1):84-89

 

INTRODUCCIÓN

En caso de trazados cardíacos fetales anormales, habitualmente se suplementa a la madre con oxígeno con el objetivo de mejorar la oxigenación fetal. Se cuenta con alguna evidencia que sugiere que la suplementación con oxígeno durante el parto brinda beneficio al feto en algunas situaciones. Sin embargo, no está establecida la relación entre la suplementación materna con oxígeno y el impacto en el pH de la arteria umbilical (como medida de acidosis metabólica fetal). Dos ensayos aleatorizados que evaluaron la suplementación materna con oxígeno durante el trabajo de parto observaron una tendencia hacia un pH menor a 7,2 en la arteria umbilical en los grupos que recibían la intervención.
El objetivo de éste trabajo fue determinar el efecto de la suplementación materna con oxígeno sobre los gases sanguíneos umbilicales del feto, al ser comparado con el aire ambiente en una cesárea programada a término.


DISEÑO

Estudio aleatorizado y controlado.


CONTEXTO

El estudio se llevó adelante en un hospital materno infantil en California, Estados Unidos, con reclutamiento entre junio y octubre del año 2015.


PACIENTES

Se incluyeron pacientes a partir de los18 años, que tuvieran programada una cesárea para un embarazo de feto único a partir de la semana 37,0.
Fueron criterios de exclusión la enfermedad crónica materna como (hipertensión y patología pulmonar), preeclampsia, retraso del crecimiento intrauterino, sospecha de malformaciones fetales, embarazos múltiples y presentación pelviana.


INTERVENCIÓN

Las pacientes eran aleatorizadas en bloques de 10 a recibir oxígeno suplementario con un flujo de 10 L/min a través de una máscara facial simple (grupo Intervención) o aire ambiente (grupo Control).
El lapso mínimo entre el inicio de la suplementación con oxígeno y la incisión quirúrgica era de 10 minutos.
Al momento del nacimiento, se recolectaban gases del cordón umbilical, que eran procesados dentro de los 30 minutos.


MEDIDAS DE EVOLUCIÓN

Las principales medidas de evolución fueron los valores de gases sanguíneos arteriales y venosos en los vasos umbilicales fetales.
La medida de evolución secundaria fue un compuesto de la evolución clínica materna y neonatal.


PRINCIPALES RESULTADOS

-Los investigadores enrolaron un total de 70 pacientes, analizando los datos de 65. Las características demográficas de ambos grupos se encontraban bien balanceadas. 
-No hubo diferencias en el tiempo entre el inicio de la anestesia y el nacimiento ni entre el comienzo de la incisión y el nacimiento, entre los grupos. 
-Ninguna paciente presentó hipotensión que requiriera intervención médica, ni hipoxia por oximetría de pulso.
-No encontraron diferencias entre el pH de la arteria umbilical (7,29; rango inter-cuartilo [RIC] 7,26-7,30 para el grupo Intervención y 7,28; RIC 7,25-7,30 para el grupo Control).
-La intervención aumentó de manera significativa la presión parcial de oxígeno (pO2) de la arteria umbilical (18 mm Hg; RIC 13,5-20,5 contra 16 mmHg; RIC 12-18 para el grupo Control; p=0,04).
-La pO2 de la vena umbilical fue significativamente mayor en el grupo con Intervención (32 mmHg; RIC 26,5-36,0 contra 28,5 mmHg; RIC 22-34,3; p=0,04).
-No encontraron diferencias entre ambos para la medida compuesta de complicaciones maternas y fetales.


CONCLUSIÓN

Los autores concluyen que mujeres con embarazo de feto único que recibieron oxígeno a un flujo de 10 L/min durante una cesárea programada no mostraron cambios significativos en los valores de pH del cordón umbilical, al compararse con aquellas que respiraban aire ambiente. Hubo un aumento significativo del contenido arterial y venoso de oxígeno en los vasos umbilicales en aquellas que recibieron la intervención.


COMENTARIOS

Los autores comentan que su estudio es vulnerable a un error tipo II. Encontraron una diferencia en el pH arterial de 0,01 entre cada grupo, cuando esperaban encontrar una diferencia de 0,05 entre los grupos. Si esa diferencia fuera real, necesitarían una muestra mayor, así como si su estudio fuera realmente un estudio de no-inferioridad.
Las pacientes y los médicos tratantes no pudieron ser cegados al tratamiento. Al considerar el uso de máscaras faciales para el aire ambiente, sin flujo de oxígeno suplementario, concluyeron que podía producir hiperventilación inducida por ansiedad (lo cual podría eventualmente afectar los gases umbilicales), además de que no reflejaría la práctica habitual. Los autores también entendían que el conocimiento del tratamiento por el médico tratante no podía afectar los valores de los gases umbilicales, ya que el tiempo a la incisión y al nacimiento, así como el procesamiento de los gases fue similar en ambos grupos.
Resaltan que la suplementación con oxígeno en el momento del nacimiento por cesárea no puede ser extrapolada a la mujer cursando un trabajo de parto. El control de los potenciales confundidores dentro de un trabajo de parto podrían ser muy difíciles sino imposibles.

 

 

 

 

I feel how you feelFecha: 2/3/2018

 

 

I feel how you feel": reflections about empathy in the relationship between ICU physicians and relatives

 

                                                                                                             Michael Quintel

                                                                                   Intesive Care Medicine (2017);43:1723-24

 

Do you remember when it happened to you for the first time? You were talking to the family, the spouse, the mother, the father, sister, brother or friend of a patient lying in a life-threatening state in the ICU trying to explain the actual status of the patient and you realized that your counterpart tried to follow your words but remained immersed in a sea of fear, pain, doubt, uncertainty-a world of conflicting emotions. You stopped because all of a sudden you realized that some of these emotions had become your own-at least in part you felt what she, he, they felt.

I do. It was during the early phase of my career as an ICU physician when I tried to explain replica watches full-blown ARDS in a 16-year-old girl to the family. I felt helpless and failing. While sharing the emotions of the family, I also felt bound to my role as physician and realized that not only was I unable to offer a cure but I did not even see a way to usefully improve her condition. I did the only thing I felt able to do-I remained silent and tried to endure the situation and to share the emotions. Some days later I realized that my relationship with the family had deeply changed. The situation the days before had set up a sense of "he is able to feel what we feel" in the family. From that day on we were able to find the balance between presenting dry medical information and effective explanation of therapeutic steps in such a way as to remain sensitive to emotional response. We simply found the balance between empathy and factual needs. From his own experience, Thomas Bein reported impressively in this journal how important the need is for striking this balance between "unemotional" factual action and empathy for the critically ill patient and relatives.

There is clear evidence that the ICU stay of a family member has a large impact on the health status of the affected relatives. Spouses having lost their partners on the ICU die earlier and develop more diseases. We know that family members of ICU patients experience depression and anxiety, post-traumatic stress disorders (PTSD) and even mental disorders seemingly unrelated to the episode. We also know that very simple steps might help to reduce the risk of developing such disorders and help the relatives to endure without becoming seriously sick themselves. If "relatives are walking wounded on the ICU" is true, then we have to be aware and respond compassionately-but not act in the role of a therapist. It would be naïve to believe that empathy and feeling what they feel will relieve their burden or solve their problems.

But they view the ICU environment as something alien, governed apparently by logic and technical rules where emotions seem to be excluded because they might even endanger "effective" and lifesaving therapy. Some of them might even not be able to say to us: "but it's my wife, husband, father, mother, brother, sister, son, daughter or friend..." because they feel guilt in disturbing this technical wonderland that keeps their loved one alive and tries to ensure survival. That is why so many relatives describe the ICU as technical, sterile and inhuman and that is the point why 'feeling what they feel' becomes so important. With our empathetic awareness, our alien world gets a human face and soul. It is not a cure but does help them to get their feet back on the ground, while allowing them to become a respected and valued part of the process.

Having stated that, what can or should we do to make physicians empathic? Can we simply rely on the 'mirror neurons' of our conscience and instinct, trusting that they will more or less automatically do their job in creating the empathy needed? Independent from the actual role of these neurons, which is a matter of an ongoing scientific debate, there is no doubt that they are governed by individual experience and regulated by our brain. Experience is to a large part a matter of age. If you have not experienced the loss of a loved one it is difficult to feel what those engulfed by critical illness feel, and most of our younger caregivers lack this experience. That is why "grey-haired" ICU physicians play such an important role in the ICU team as life-experienced mentors and contact partners for patients, relatives and team members. We have to take care to make the ICU a liveable place for them so as to keep access to their treasure of experience for the sake of everyone. Our brain regulates according to rules that can be trained and taught. In all the discussions about medical education and reformation of training for physicians, we should never forget that medicine remains an empiric science that requires thoughtful training of physiology and pathophysiology but also education in communication and interpersonal relationships.
Training and teaching are one important part. But I take the liberty to state that good mentors and bright archetypes play a more important role than any type of modern teaching and training will ever do. Our medical environment must encourage individual archetypes to develop. Unfortunately, current economic pressures, seeming objectivity and so-called evidence might represent obstacles against the development of such personalities.
Finally, feeling what they feel teaches humility. Skills, profound knowledge and the ability to use these aptitudes for therapeutic intervention make a competent physician but, empathy, respect and humility finally distinguish between Mephisto and Faust. In my view the truly good physician lives in balance between thoughtful unemotional actions and honest empathy; both require readiness for life-long learning. That is why feeling what they feel is so importan

 

 

 

 

 

Los elevados niveles de aclaramiento renal mejoran la evolución de los pacientes con sepsis severa?Fecha: 2/2/2018

 

Los elevados niveles de aclaramiento renal mejoran la evolución de los pacientes con sepsis severa que reciben antibioterapia con betalactámicos?

Artículo original:
Association between augmented renal clearance and clinical outcomes in patients receiving beta-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial.

            Udy AA, Dulhunty JM, Roberts JA y col.(investigadores a cargo del estudio BLING II) .

                                                                           Int J Antimicrob Agents. 2017; 49: 624-30.


INTRODUCCIÓN

Los pacientes críticos sufren a menudo infecciones bacterianas, contra las que se suele recurrir a la administración empírica de antibióticos betalactámicos, ya que estos casos requieren antibioterapia inmediata. Pero sucede que entre los sujetos en estado crítico la farmacocinética de los betalactámicos es diferente, y requiere mantener siempre elevados niveles de concentración inhibitoria. Una estrategia posible es administrar el antibiótico en infusión continua, lo cual puede coadyuvar a mantener niveles adecuados de concentración de las drogas suministradas. Sin embargo, no hay datos sobre la efectiva utilidad de ese enfoque terapéutico. El presente trabajo, estudio subsidiario del ensayo BLING II, está dedicado a determinar si los niveles elevados de aclaramiento renal, ligados al tipo de infusión utilizada, se ven reflejados en la aparición de diferencias estadísticamente significativas en la evolución clínica de los pacientes tratados.


DISEÑO

Estudio de cohorte anidado elaborado a partir del estudio BLING II, Beta-Lactam InfusioN Group.* El BLING II fue un ensayo aleatorizado, por distribución oculta, no ciego y controlado, con seguimiento máximo a 90 días.**

* En los estudios anidados (variante de los tradicionales estudios de casos y controles) se utiliza un cierto número de pacientes del estudio principal, de quienes ya hay información suficiente, para cotejarlos con un número adecuado de controles provenientes de la misma muestra. Es una manera de anticipar o completar conclusiones [nota de redacción].
** Bajo la orientación de la ANZICS ("Australia and New Zealand Intensive Care Society"), investigadores de varios países han producido también los estudios BLING I y BLING III.


CONTEXTO

Integraban el BLING II 65 investigadores de Australia, 31 de Nueva Zelanda y 2 de la Región Administrativa Especial de Hong Kong, China. Los 14 autores de este estudio anidado cumplían servicios en centros de Sydney, Melbourne, Brisbane, Darwin, Newcastle y Perth (Australia), y de Hong Kong (China). Los pacientes cuyos datos fueron seleccionados habían sido atendidos en las unidades de cuidados intensivos de 25 diferentes centros, bajo la coordinación general del Royal Brisbane and Women´s Hospital de Brisbane, estado de Queensland, Australia.


PACIENTES

A partir de una población total de 432 individuos con sepsis severa que debían recibir antibioterapia con betalactámicos, 212 en un grupo de tratamiento continuo y 220 en otro de infusión intermitente, fueron incluidos los datos de 254 sujetos que integrarían la cohorte retrospectiva de este estudio anidado. La edad de los pacientes variaba entre los 52 y los 73 años; las infecciones más frecuentes eran pulmonares, seguidas por las intraabdominales, las del tracto urinario y las del torrente sanguíneo. La terapia antibiótica era llevada a cabo con piperacilina / tazobactam, con meropenem o con ticarcilina / ácido clavulánico. En esta sinopsis se identificará como de «aclaramiento renal intensificado» (sintéticamente, ARI) a los participantes con altos niveles de aclaramiento de creatinina.


INTERVENCIÓN

Se había establecido que los pacientes que en el día 1 evidenciaran aclaramiento de creatinina a las 8 horas de 130 mililitros por minuto o más serían considerados integrantes de la porción de población ARI. La cohorte seleccionada estuvo integrada por 45 individuos con aclaramiento intensificado (el 17,7%) y por 209 que no se hallaban en tal condición. Quedarían excluidos aquellos pacientes que en cualquier momento del estudio recibieran una cualquiera de las formas de terapia renal sustitutiva (hemodiálisis, diálisis peritoneal, hemofiltración, hemodiafiltración, trasplante renal).


MEDIDAS DE EVOLUCIÓN

La medida esencial sería el número de días transcurridos sin necesidad de permanecer en la unidad de cuidados intensivos al día 28 de seguimiento. En segundo término se evaluaría la cantidad de casos con curación clínica a los 14 días de concluida la antibioterapia, y la  mortalidad a 90 días.


PRINCIPALES RESULTADOS

Entre los 45 participantes con ARI, la mediana de aclaramiento de creatinina era de 165 mL/minuto, con diferencia intercuartil entre 144 y 198 mL/minuto. Como características de ese subgrupo se observa edad menos avanzada (diferencia estadísticamente significativa, p < 0,001), preponderancia del sexo masculino (p = 0,04) y menor incidencia de disfunción orgánica (p < 0,001). A continuación se indican los principales hallazgos.

-- A los 28 días, los pacientes del grupo ARI mostraban una mediana de 21 días sin permanencia en la unidad de cuidados intensivos (entre 12 y 24 días), En el otro grupo la mediana era también de 21 días (entre 11 y 25). La diferencia resulta estadísticamente no significativa: p = 0,89. 
-- Entre 252 individuos, experimentaban curación clínica 14 días después de cesar la terapia antibiótica 33 pacientes del grupo ARI y 115 del grupo sin intensificación (respectivamente, el 73,3 y el 55,0%; p = 0,024). Se observa de todos modos que, después de ajustar por análisis multivariante, la diferencia entre grupos decrece. El área bajo la curva es de 0,63, con intervalo de confianza (IC) del 95% entre 0,56 y 0,70. 
-- La mortalidad a 90 días, medida en 253 individuos, fue de 6 decesos en el grupo ARI y de 41 en el grupo sin aclaramiento intensificado, respectivamente el 13,3 y el 19,6%. La diferencia resulta estadísticamente no significativa: p = 0,33. 
-- Entre el grupo ARI y el de aclaramiento no intensificado tampoco se observan diferencias en la evolución clínica que puedan ser relacionadas con la dosificación o con la modalidad de suministro de los antibióticos.


CONCLUSIÓN

Esta cohorte anidada se formó con una parte de los datos reunidos en el BLING II, estudio desarrollado bajo el patrocinio de una organización de investigaciones en medicina intensiva de Australia y Nueva Zelanda. En ella se exploran los efectos clínicos concretos de la intensificación del aclaramiento de creatinina en pacientes con sepsis severa que recibían antibioterapia de betalactámicos en infusión continua o intermitente. La información así reunida permite afirmar que el aclaramiento renal intensificado no ejerce efectos significativos sobre la mortalidad a 90 días, los índices de curación clínica o la cantidad de días pasados en unidades de cuidados intensivos.


FUENTES DE FINANCIAMIENTO

(Parcial) National Health and Medical Research Council, Australia; Health Research Council, Nueva Zelanda; Baxter Healthcare Pty Limited, Old Toongabbie, Nueva Gales del Sur, Australia. Distintas compañías farmacéuticas han pagado contribuciones personales y honorarios a los investigadores.

 

 

 

 

Individual Physician Penalities From Violation of Emergency Medical TreatmentFecha: 2/1/2018

 

 

Individual Physician Penalties Resulting From Violation of Emergency Medical Treatment and Labor Act: A Review of Office of the Inspector General Patient Dumping Settlements, 2002-2015

Sophie Terp, MD, MPH, Brandon Wang, BS, Brian Raffetto, MD, MPH, Seth A. Seabury, PhD, and Michael Menchine, MD, MPH

ABSTRACT Objective: The objective was to describe characteristics of civil monetary penalty settlements levied by the Office of the Inspector General (OIG) against individual physicians related to violation of the Emergency Medical Treatment and Labor Act (EMTALA). Methods: Descriptions of all civil monetary penalty settlements between 2002 and 2015 were obtained from the OIG. Characteristics of settlements against individual physicians related to EMTALA violations were described including settlement date, location, amount, whether there was an associated hospital settlement, the medical specialty of the physician involved, and the nature of the allegation. Results: Of 196 OIG civil monetary penalty settlements related to EMTALA, eight (4%) were levied against individual physicians, and 188 (96%) against facilities. Seven of the eight penalties against individual physicians were imposed upon on-call specialists, including six who failed to respond to evaluate and treat a patient in the emergency department (ED), and one who failed to accept appropriate transfer of a patient requiring higher level of care. The only penalty imposed on an emergency physician involved a case where a provider repeatedly failed to provide a medical screening examination to a pregnant teen based on the erroneous belief that a minor could not be evaluated or treated absent parental consent. Four of eight penalties against individual physicians were levied within the first 3 years of the 14-year study period. Half of all physician settlements were associated with a separate hospital civil monetary penalty settlement. Conclusions: For emergency physicians, a civil monetary penalty is a feared consequence of EMTALA enforcement, as a physician can be held individually liable for fine of up to $50,000 not covered by malpractice insurance. Although EMTALA is an actively enforced law, and violation of the EMTALA statute often results in hospital citations and fines, and occasionally facility closure, we found that individual physicians are rarely penalized

_____________________________________________________________________________


The Emergency Medical Treatment and Labor Act (EMTALA) is often feared by emergency physicians.1 Enforcement of EMTALA is delegated primarily to the regional offices of the Centers for Medicare & Medicaid Services (CMS), which authorize investigations, determine whether a violation occurred, and enforce corrective actions when violations are identified. Information regarding EMTALA violations is reviewed by the Office of the Inspector General (OIG) of the Department of Health and Human Services, which assigns civil monetary penalties to facilities and/ or individual physicians found to be in violation of EMTALA.2 For emergency physicians, a civil monetary penalty is a feared consequence of EMTALA enforcement, as individuals can be held liable for a fine of up to $50,000 not covered by malpractice insurance. Recent studies have reported that only a small proportion of EMTALA violations result in civil monetary penalties against hospitals and that penalties against individual physicians are rare.3,4 However, little is known about characteristics of civil monetary penalties levied against individual physicians related to violations of EMTALA. The goal of this investigation is to describe characteristics of civil monetary penalty settlements levied by the OIG against individual physicians related to EMTALA violations between 2002 and 2015. METHODS Descriptions of all civil monetary penalty settl

METHODS
Descriptions of all civil monetary penalty settlements between 2002 and 2015 were obtained from the OIG website.5 All civil monetary penalty settlements related to EMTALA violations specifically were identified by inclusion of the terms "EMTALA" or "patient dumping" in the title or text of the settlement description for inclusion in this analysis. OIG civil monetary penalty settlements unrelated to EMTALA (e.g., kickback allegations, fraudulent Medicare claims) were excluded from analysis. Available synopses describing particulars of the OIG civil monetary penalty settlement agreement and circumstances of the related EMTALA violation include varying levels of detail. Entries often contained the name of the physician, associated hospital, medical specialty/on-call status of the provider, and information about the involved patient's medical condition. Specific identifiers were not consistently provided. For a complete list of all individual physician civil monetary penalty settlement entries published by OIG between 2002 and 2015, refer to Data Supplement S1 (available as supporting information in the online version of this paper). Characteristics of settlements against individual physicians related to EMTALA violations were described including settlement date, location, amount, whether there was an associated hospital settlement, the specialty of the physician involved, and the nature of the allegation. For instances in which the specialty of the fined physician was not specifically stated, specialty was obtained by cross-referencing the physician's name with the state medical board or inferred by the nature of the emergency medical condition, or additional details regarding the case were obtained from the CMS Technical Lead (M. E. Palowitch, EMTALA Technical Lead, CMS, personal communication, 2016). This study utilized publically available data from OIG settlements, without individual patient-level identifiers, and therefore, does not qualify as human subjects research.

RESULT
Between 2002 and 2015, a total of 196 civil monetary penalty settlements related to EMTALA were identified. Of these, 188 (96%) were levied against facilities, and eight (4%) against individual physicians. Characteristics of OIG settlements against individual physicians related to EMTALA violations are included in Table 1. The average settlement amount for an individual physician was $25,625, with total fines against physicians amounting to $205,000. Half of settlements against physicians were associated with a separate hospital settlement. A quarter of settlements against physicians involved cases in which a patient was specifically noted to have died. Both cases involving patient death resulted in settlements with both individual physicians and hospitals. Half of penalties against physicians occurred cheap rolex explorer replica watches within the first 3 years of the 14-year study period. Only one penalty was levied against an emergency physician. This settlement resulted after a pregnant 17-year-old presented to a Louisiana emergency department (ED) complaining of vaginal bleeding, abdominal pain, and perineal numbness. According to documentation provided by CMS, the patient presented to the ED on two separate occasions where the on-duty physician failed to provide a medical screening examination based upon the erroneous belief that the patient, who was a minor, could not be evaluated or treated absent parental consent. The remaining seven settlements against individual physicians involved on-call specialists. In one case, a neurosurgeon was fined for refusing to accept an appropriate transfer of an individual with an unstable emergency medical condition requiring specialized capabilities available at his institution. Three-quarters of settlements against individual physicians resulted from an on-call physician failing to respond to request to evaluate and treat an ED patient with an emergency medical condition requiring specialty care including two obstetricians, two general surgeons, an ophthalmologist, and an orthopedist.

DISCUSSION
Recent studies have demonstrated that EMTALA is an actively enforced law, with more than a quarter of U.S. hospitals cited for EMTALA violations over the past decade3 and approximately 7.9% of these violations resulting in OIG fines.4 For emergency physicians, civil monetary penalties are an often-feared consequence of an EMTALA citation, as fines up to $50,000 imposed by OIG are not covered by malpractice insurance. However, our findings suggest that individual physicians are rarely targeted by OIG penalties. During the study period, there were eight settlements against individual physicians, of which only one was imposed upon an emergency physician. Comparatively, on an annual basis, 7.6% of emergency physicians face a malpractice claim, and 1.4% have a claim resulting in payment to a plaintiff.6
Furthermore, more than twice as many hospitals were closed or downgraded emergency services as a result of EMTALA violations than individual physicians were fined over the past decade. Between 2005 and 2014, twelve hospitals had CMS provider agreements terminated as a result of EMTALA citations, with resulting hospital closure or downgrading of emergency services at nine of these facilities.3 Over the same period, we found only four instances of individual physician penalties related to EMTALA violations (four cases described in this report occurred prior to 2005). Although continued active enforcement of the law would suggest that physicians are not always adherent to the EMTALA statute, our findings indicate that hospitals rather than individual physicians are typically held responsible for EMTALA violations. The sole case in which an emergency physician was subject to an individual settlement involved a clear violation of the EMTALA law. Physicians still need to be diligent to ensure appropriate patient care and that facilities are compliant with the EMTALA statute, but fears of individual penalties by emergency physicians appear to be largely unwarranted. Though rare, when settlements against physicians were levied, they were primarily against on-call specialists who refused to evaluate and treat ED patients with emergency medical conditions. Surveys of ED medical directors suggest that since passage of EMTALA, erosion of on-call panels and the ability to transfer patients for higher level of care have worsened.7,8 Erosion of call panels has likely reduced EMTALA liability for hospitals over time and may be contributory to the temporal decline in EMTALA citations and OIG fines against facilities noted in prior studies3,4 and relative rarity of OIG fines against individual physicians in the past decade of this study. Although fewer on-call physicians may limit obligations of both facilities and individual physicians to EMTALA, this is also likely to be associated with reduced access to specialty care for vulnerable populations. EMTALA was intended to ensure access to emergency care. Whether the relative rarity of individual settlements against physicians in the last decade of the study period reflects improved access to emergency care or whether it reflects strategic reduction of call panels resulting in a paradoxical effect on access to emergency services is an important policy question that remains to be answered

Table 1 Characteristics of OIG Settlements Involving Individual Physicians

Apr 15, 2014 Iowa On-call Surgery $35,000 Hospital Settlement Amount: No. Refusal to examine and treat patient with an EMC.
Dec 20, 2011 Tennessee On-call Neurosurgery* $35,000. Hospital Settlement  Amount:  Yes. $45,000 Refusal to accept appropriate transfer of a patient with an EMC who required the specialized capabilities available at the physician's hospital. The patient died.
Feb 25, 2009 Illinois On-call Orthopedics† $35,000. Hospital Settlement  Amount: No. Failure to respond to a request to evaluate and treat an ED patient with an open leg fracture.
Feb 17, 2006 Texas On-call Obstetrics $15,000. Hospital Settlement  Amount: No.  Failure to respond to a request to evaluate and treat a pregnant patient in the ED with symptoms of preeclampsia and pulmonary edema.
Jun 23, 2004 Louisiana On duty Emergency medicine‡ $10,000. Hospital Settlement Amount: Yes, $15,000. Failure to provide MSE and stabilizing treatment to a pregnant 17-year-old in the ED with perineal numbness and vaginal bleeding. Refusal to treat reportedly based on erroneous belief that could not evaluate or treat a minor absent parental consent.
Apr 7, 2003 Virginia On-call Obstetrics $15,000. Hospital Settlement  Amount: Yes, $35,000. Failure to provide appropriate MSE, stabilizing treatment, and transfer for a pregnant woman in labor.
Mar 3, 2003 California On-call Surgery $50,000. Hospital Settlement  Amount: Yes, $7,500. Failure to respond to a request to evaluate and treat an ED patient. The patient died.
May 9, 2002 Missouri On-call Ophthalmology $10,000. Hospital Settlement  Amount: No. Failure to respond to a request to evaluate and treat an ED patient.

EMC = emergency medical condition; EMTALA = Emergency Medical Treatment and Labor Act; MSE = medical screening examination; OIG = Office of the Inspector General.

 

LIMITATIONS
Although this study is the most comprehensive assessment of penalties to individual physicians resulting from EMTALA citations to date, there are several potential limitations. First, findings depended on administrative data provided by the OIG and CMS and may be limited by variability in reporting of cases across regions or over time. However, we doubt systematic error in recording or reporting of data by the OIG or CMS. Furthermore, we believe that this represents the best available data source to study penalties against individual physicians. Second, available data only included cases resulting in settlement agreements to resolve civil monetary penalties. Information on cases for which penalties may have been recommended, but for which a settlement agreement was not reached was not available. Third, although OIG can impose exclusion of providers with repeated or egregious violations from future participation in CMS, information on exclusion was not included in available data. Finally, our evaluation is limited to the years for which OIG settlement data was available online. To better understand trends in OIG enforcement during the first decade and a half of EMTALA enforcement, hard copies of historic settlement agreements will need to be obtained and abstracted.

CONCLUSION
 Emergency Medical Treatment and Labor Act is an actively enforced law, and violations of the Emergency Medical Treatment and Labor Act statute often result in fines and citations to hospitals and may even result in facility closure. Physicians should be diligent to ensure appropriate patient care and that facilities are compliant with the Emergency Medical Treatment and Labor Act statute, but should be aware that settlements against individual physicians are a rare consequence of Emergency Medical Treatment and Labor Act enforcement.

References
1. Linzer JF. EMTALA: a clearer road in the future? Clin Pediatr Emerg Med 2003;4:249-55.
2. The Emergency Medical Treatment and Labor Act: The Enforcement Process. OEI-09-98-00221. Washington, DC: Office of the Inspector General, U.S. Department of Health and Human Services, 2001.
3. Terp S, Seabury SA, Arora S, Eads A, Lam CN, Menchine M. Enforcement of the Emergency Medical Treatment and Active Labor Act, 2005 to 2014. Ann Emerg Med 2017;69 (2):155-162. 4. Zuabi N, Weiss LD, Langdorf MI. Emergency Medical Treatment and Labor Act (EMTALA) 2002-15: review of Office of Inspector General patient dumping settlements. West J Emerg Med 2016; 17:245-51.
5. Office of Inspector General, U.S. Department of Health and Human Services. Civil Monetary Penalties and Affirmative Exclusions. Office_of_the_Inspector_General_Patient_Dumping_Websites: http://oig.hhs.gov/fraud/enforce ment/cmp/patient_dumping.asp (Accessed 9 December 2015), http://oig.hhs.gov/reports-andpublications/archives/enforcement/patient_dumping_archive.asp (Accessed 7 March 2016), http://oig.hhs.gov/fraud/enforcement/cmp/. (Accessed Jun 15, 2016)
6. Jena AB, Seabury S, Lakdawalla D, Chandra A. Malpractice risk according to physician specialty. N Engl J Med 2011; 365:629-36.
7. Menchine MD, Baraff LJ. On-call specialists and higher level of care transfers in California emergency departments. Acad Emerg Med 2008; 15:329-36.
8. On-call specialist coverage in U.S. emergency departments: ACEP survey of emergency department directors. American College of Emergency Physicians, Irvine, TX: September 2004.

http://www.fakewatches.co.uk

 

 

Focus on infection and sepsis 2017Fecha: 2/12/2017

 

 

Focus on infection and sepsis 2017

                                                Ignacio Martin‑Loeches, Jose Garnacho‑Montero and Saad Nsei

                                                                                   Intensive Care Med (2017) 43:867-869

 

Introduction

Management of severe infections and sepsis in intensive care units (ICU) represents one of the most common and complex problems in daily clinical practice. Year by year, new studies are helping to improve physicians'

management and this manuscript aims to summarize the most relevant works published during 2015-2016 on these difficult areas of knowledge (Table 1).

 

Table 1 Selected recent findings on infection and sepsis in the critically ill patient

2017 Surviving Sepsis Campaign


Controversies

  • Critically ill patients frequently not receiving the recommended quantity of fluids during the first 24 h of sepsis or septic shock, mortality increased in patients with severe sepsis receiving <5 L of fluids
  • Lower hemoglobin levels not associated with higher mortality or worse quality of life at 1 year after randomization

"Area of need" population studies in sepsis

  • Refractory septic shock in pediatric population
  • Sepsis in resource‑limited settings

qSOFA‑65?

  • qSOFA accurate in patients with community‑acquired pneumonia
  • Older patients with influenza prone to higher rates of bacterial co‑infection, and higher mortality rates

ICU‑acquired infections

  • Duration of mechanical ventilation, but not antibiotics, associated with changes in lung microbiome
  • Highly heterogeneous patterns of intestinal microbiota in both septic and non‑septic ICU patients
  • Treatment with probiotics effective and safe to prevent VAP
  • De‑escalation in ICU patients feasible and associated with better outcomes

 

2017 Surviving Sepsis Campaign controversies

Probably, one of the most important landmarks in 2016 was the publication of the new edition of theSurviving Sepsis Campaign guidelines [1]. Not all is done andnew data will be incorporated in further editions. Forinstance, in this edition, it is recommended to give a minimum of 30 mL/kg of crystalloid solutions within the first 3  h. Interestingly, a recent study found [2] that less fluids were administered to patients with severe sepsis and septic shock in the USA during the first ICU day than recommended by the Surviving Sepsis Campaign guidelines, and this was associated with an increased mortality of 2.3% per liter of fluid administered above 5 L.Hjortrup [3] randomized 151 adult patients with septic shock in Scandinavia and found that in patients assigned to fluid restriction (fluid boluses only if severe hypoperfusion was detected), fluid volumes at day  5 and during ICU stay were lower than in the standard care group by more than 1 L with no differences in outcome. The trial was a feasibility trial that actually suggested benefit with fluid restriction but was not powered to address patient centered outcomes. Following the same idea of "less is more", Rygard [4] reported that a lower hemoglobin threshold for transfusion was associated with neither higher long-term mortality (1  year after randomization) rates in patients with sepsis nor a worse health-related quality of life (HRQoL).

"Area of need" population studies in sepsis


Intensive Care Medicine
published several special papers in 2016 focused on sepsis management in two types of populations that are commonly not addressed widely: resource-limited settings and the pediatric population.

Pediatric populations will benefit from the recently published consensus documents for refractory septic shock in children that included a clinical case-based Delphi survey involving 114 pediatric intensivists [5]. Regarding resource-limited settings, recommendations were published by a multidisciplinary group of experts from different geographic areas who agreed that there is scarce evidence for the management of pediatric and adult sepsis in resource-limited settings [6]. Further efforts should be made from scientific societies to adequately provide resources for this population. A worldwide study demonstrated that gross national income (GNI) was a major determinant of time to death in hospital in ICU patients[7]. Not only GNI but also age (older patients), type of population (surgical), and infection increased the duration of hospital stay prior to death in critically ill patients.

Quick sequential organ failure assessment (qSOFA)‑65?


Studies of sepsis have shown an exponential increase in the population-based incidence of sepsis with age, followed closely by an increased mortality [8]. New sepsis definitions (Sepsis  3.0) were launched in 2016 [9] and have generated some controversy [10]. As Community Acquired Pneumonia (CAP) is the most common cause of sepsis, Kolditz [11] performed a multicenter validation of the qSOFA score (also known as quickSOFA) in patients with CAP. qSOFA uses three criteria, assigning one point for low blood pressure (SBP ≤ 100  mmHg), high respiratory rate (≥22  breaths per min), or altered mentation (Glasgow coma scale  <15). The authors compared its accuracy to predict disease course to the CRB-65 (confusion, respiratory rate ≥ 30/min, systolic blood pressure  < 90  mmHg or diastolic blood pressure ≤ 60mmHg, age ≥65 years) score. qSOFA and CRB(-65) score do share the same items except age, and the authors found that qSOFA was similar to CRB(-65), with a slightly higher sensitivity and lower specificity.
On the basis of their findings, age (>65  years) might be applied as an additional criterion in both scores for optimal low-risk prediction. In a recent observational multicenter study with almost 3000 patients with severe CAP, older patients more often had co-infection when infected by influenza, and co-infection was independently associated with higher mortality [12]. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making, and improved prediction models should be incorporated in aging populations [13].

ICU‑acquired infections

Nosocomial infections play a major role in the development of sepsis, and ventilator-associated pneumonia (VAP) remains the most common infection in ICU [14]. controlled trial involving 235 critically ill adult patients, therapy with the probiotic bacteria Bacillus  subtilis and Enterococcus faecalis were found to be effective and safe for preventing VAP and the acquisition ofmultidrugresistant pathogen (MDR) colonization [17].
Antibiotic stewardship programs have been found to be effective in ICU settings to face the ongoing problem of bacterial resistance and acquisition of MDR [18].
Recently, the World Health Organization, US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, European Medicines Agency, Institute of Medicine, World Economic Forum, and the US Presidential Advisory Council on Science and Technology asked for action to take in this mater [19]. A recent pooled individual data analysis of prospective studies of de-escalation in critically ill patients with sepsis found that while SOFA score and aging were both factors independently associated with mortality, de-escalation was independently associated with a better outcome in the adjusted multivariate analysis [20]. Formal antibiotic stewardship programs are essential to help in reducing either unnecessary or inappropriate antibiotic prescription and subsequently to avoid a rise in antimicrobial resistance.

Concluding remarks

Mortality and morbidity associated with sepsis remain unacceptably high. Detection of patients in their early stages of the infection is crucial to diminish the high mortality rate associated with sepsis. Further studies are warranted to determine the optimal targets for resuscitation and the best antimicrobial management especially when MDR pathogens are involved.
A recent manuscript by Zakharkina et  al. found that duration of mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome [15]. Recent studies reported that despite previous evidence [16], highly heterogeneous patterns of intestinal microbiota existed in both septic and non-septic critically ill patients. This might shed light on our understanding of the conflicting results with the effect of probiotics on the incidence of VAP in critically ill patients. In an open-label, multicenter randomized.

 

References

1. Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving Sepsis Campaign:international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43:304-377. doi:10.1007/s00134‑017‑4683‑6

2. Marik PE, Linde‑Zwirble WT, Bittner EA et al (2017) Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. doi:10.1007/ s00134‑016‑4675‑y

3. Hjortrup PB, Haase N, Bundgaard H et al (2016) Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel‑group, multicentre feasibility trial. Intensive Care Med 42:1695-1705. doi:10.1007/s00134‑016‑4500‑7

4. Rygard SL, Holst LB, Wetterslev J et al (2016) Long‑term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial. Intensive Care Med 42:1685-1694. doi:10.1007/s00134‑016‑4437‑x

5. Morin L, Ray S, Wilson C et al (2016) Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition. Intensive Care Med 42:1948-1957. doi:10.1007/s00134‑016‑4574‑2

6. Thwaites CL, Lundeg G, Dondorp AM (2016) Infection management in patients with sepsis and septic shock in resource‑limited settings. Intensive Care Med 42:2117-2118. doi:10.1007/s00134‑016‑4547‑5

7. Martin‑Loeches I, Wunderink RG, Nanchal R et al (2016) Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med 42:1454-1460. doi:10.1007/s00134‑016‑4479‑0

8. Yebenes JC, Ruiz‑Rodriguez JC, Ferrer R et al (2017) Epidemiology of sepsis in Catalonia: analysis of incidence and outcomes in a European setting. Ann Intensive Care 7:19. doi:10.1186/s13613‑017‑0241‑1
9. Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (Sepsis‑3). JAMA 315:801-810. doi:10.1001/jama.2016.0287

 

 

 

 

 

 

 

 

 

 

Cortisol may link gut micobes and brainFecha: 4/11/2017

 

 

Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig.

                                                         Mudd A.T;Berding K:Donovan S.M;Dilger R.N.
                                                                                 University of Illinois

                                                                       Journal Gut Microbes - July 2017

 

Abstract

A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.

Introduction

The term microbiota-gut-brain axis is used to describe the bi-directional communication between the gut microbiota and the brain. Early in life the microbial community of the gut is rapidly evolving in parallel with brain development, providing a window during which highly dynamic changes in the brain could be susceptible to microbial alterations. Throughout this period, myelination, growth and expansion of neurons, and changes in neuro-metabolites are occurring, and the trajectory of these processes may be influenced by microbial dysbiosis.1,2  In fact, other findings from animal studies have suggested an influence of the microbiota on brain metabolites, 3 Although the underlying mechanisms for these interactions are widely unknown, it has been suggested that bacterial metabolites could mediate the communication between the gut and the brain.6
Early-life changes in the structure and function of the brain commonly result in neurodevelopmental disorders, and there is increasing evidence linking the microbiome to psychiatric and neurodevelopmental disorders, including autism spectrum disorder (ASD). While the microbiome is suggested to play a role in the etiopathogenesis of neurodevelopmental disorders, it is unclear which gut bacteria might be most influential in the observed comorbid brain differences. Current literature is limited in the characterization of specific microbiota, which might modulate particular aspects of brain development. Accordingly, studies using a multimodal, interdisciplinary approach are necessary to understand the complex communication between the gut, the brain, and mediating factors. Use of magnetic resonance imaging (MRI) offers a novel, non-invasive approach to answering fundamental questions relating to the gut-brain-axis. To our knowledge, only 2 studies have used this technique, these studies showed that dietary probiotics alter brain function in adult women7 By elucidating the effects of specific members of microbiota on measures of brain health using MRI, researchers can better understand the underlying mechanisms through which gut microbiota modulate brain development.
When studying the underlying mechanisms of host-microbe interactions in humans, researchers must account for genetic and environmental variation, including diet and supplement use (i.e., probiotics and prebiotics). The use of gnotobiotic and germ-free rodent models has significantly advanced mechanistic microbiome-gut-brain axis research; however, rodent models are limited by physiologic and metabolic differences when compared with humans. Pigs and humans exhibit strikingly similar physiology, immune system function, dietary patterns, and disease progression, thereby elevating the pig as optimal translational model for assessing the interactions between diet, micriobiota and host physiology.8 Moreover, the piglet is a well-established translational model for gastrointestinal9 and its use allows for tightly controlled dietary, genetic, and environmental influences. The objective of this exploratory study was to apply an interdisciplinary approach using the piglet model to: 1) identify predictive relationships between microbiota and magnetic resonance spectroscopy-derived neurometabolites, 2) identify predictive relationships between microbiota and intermediary biomarkers, and 3) characterize how the identified biomarkers mediate the relationship between microbiota and brain metabolites. To our knowledge, this is the first time this multimodal approach has been applied to elucidate possible mechanisms between the microbiome-gut-brain axis.

Methods and materials

All animal care and experimental procedures were in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals and approved by the University of Illinois at Urbana-Champaign Institutional Animal Care and Use Committee.

Animals and housing

Twenty-four vaginally-derived intact male Yorkshire piglets from the University of Illinois Imported Swine Research Laboratory were obtained 48 h after birth, to allow for adequate colostrum consumption, and were subsequently artificially reared over a 30 d trial period. Piglets were provided one of 2 experimental diets, over the course of the 30 d trial, a detailed description of dietary treatment was described previously,11,12 and diet was not significant in any of the outcomes assessed herein. A detailed description of animal husbandry was described previously,11,12 and details of the non-invasive neuroimaging procedures performed at 30 d of age are described below. At 31 d of age, piglets were anesthetized by intramuscular injection at 0.03 mL/kg bodyweight using a telzol:ketamine:xylazine solution [50.0 mg tiletamine plus 50.0 mg zolazepam reconstituted with 2.50 mL ketatmine (100 g/L) and 2.50 mL xylazine (100 g/L); Fort Dodge Animal Health]. Upon verifying anesthetic induction, piglets were euthanized via intracardiac administration of sodium pentobarbital (86.0 mg/kg bodyweight; Fatal Plus, Vortech Pharmaceuticals, Dearborn, MI, USA). Immediately following intracardiac injection, piglet heads were removed and trunk blood was collected. Whole blood was centrifuged and serum was collected and stored at -80°C for future analysis. Ascending colon (AC) (the proximal one third of the colon) contents and feces were snap-frozen in liquid nitrogen and stored at -80°C for volatile fatty acids and microbiota analyses.

Magnetic resonance imaging

Piglets were subjected to MRI procedures at 30 d-of-age, as described previously.11 All scans were acquired using a Siemens MAGNETOM Trio 3T Imager using a Siemens 32-channel head coil. Magnetic resonance spectroscopy (MRS) was used to non-invasively quantify metabolites both in the hippocampi and intervening tissue, as described previously.13,14 In short, an MRS spin-echo chemical shift sequence was used to assess a voxel which centered over the left and right dorsal hippocampi with a size of 12 mm × 25 mm × 12 mm. Sequence parameters used for MRS data acquisition are as follows: TR = 3000 ms; TE = 30 ms; signal averages = 128 (water-suppressed scan) and 8 (non-water supressed scan); vector size = 1024 point. Water-suppressed and non-water-suppressed data were acquired in institutional units, and all MRS data were analyzed using LC Model (version 6.3), using methods described previously.13,14 Only neurometabolites for which a single data point was obtained for all piglets on the study were analyzed. Thus, neurometabolites in this analysis include: creatine + phosphocreatine (Cr+Pcr), glycerophosphocholine + phosphocholine (GPC+PCh), myo-inositol (mI), n-acetylaspartate (NAA), n-acetylaspartate + n-acetylaspartylglutamate (NAA+NAAG).

Volatile fatty acid quantification

Concentrations of volatile fatty acids (VFA) in AC contents were determined as described previously.15 The VFA concentrations were quantified using a Hewlett-Packard 5890A Series gas chromatograph and a glass column (180 cm 3 4 mm i.d.) packed with 10% SP-1200/1% H3PO4 on 80/100 mesh Chromosorb WAW (Superlco). Volatile fatty acid production was calculated as VFA concentrations of substrate-containing tubes minus the VFA content of blank tubes divided by substrate weight expressed on a dry matter basis.

Pyrosequencing of bacterial 16S RRNA genes

DNA extraction, 16S rRNA gene sequencing and sequence analysis were performed as described previously.12. DNA concentration was determined with a NanoDrop 1000 spectrophotometer (NanoDrop Technologies). The V3 to V5 regions of the bacterial 16S rRNA genes were amplified for bacterial pyrosequencing with primers 341F and 907R (Klindworth et al 2013). Pyrosequencing was performed at Research Testing Laboratory (RTL; Lubbock, TX) using 454 Life Sciences Genome Sequencer FLX with Titanium series reagents and protocol (Roche Applied Science, Indianapolis, IN) (Dowd et al 2008, Handl et al 2011). Sequences processing and analysis were performed using a bioinformatic pipeline developed at RTL as described previously.12 Candidate bacteria used in subsequent regression analysis were limited to only bacterial genera for which data was present for each individual piglet, thus resulting in 18 candidate genera for analysis.

Metabolomics

Serum samples were prepared as described previously16 Briefly, sample extracts were divided into 5 fractions: 1) acidic positive ion conditions, chromatographically optimized for more hydrophilic compounds; 2) acidic positive ion conditions, chromatographically optimized for more hydrophobic compounds; 3) basic negative ion optimized conditions using a separate dedicated C18 column; 4) negative ionizations following elution from HILIC column; and 5) reserved for backup. Next, non-targeted mass spectrometry analyses were performed, where extracts were subjected to UPLC-MS/MS using methods optimized for each sample fraction; detailed methods described previously.16 Using a proprietary data analysis pipeline (Metabolon, Inc.), metabolites were characterized by ion features and compared with a reference library of chemical standards.17,18 Ion peaks were quantified using area-under-the-curve counts. Raw area counts were normalized to account for variation from instrument inter-day tuning differences by the median value for each run-day. As such the median value for each run day was set to 1.0, thus allowing for metabolites of different raw peak curves to be similarly compared.

Statistical analysis

Stepwise regression for genera and diet predicting brain neurometabolites

Statistical analysis was performed using SPSS Statistical Packages version 24 (SPSS, Inc., Chicago, IL, USA). First, a linear regression equation was created using the stepwise regression procedure in which candidate independent variables (i.e., relative abundances of AC bacterial genera and diet or fecal bacterial genera and diet) predicted the concentration of individual brain metabolites (i.e., derived from MRS); Table 1. Multicollinearity between independent variables was assessed using the variance inflation factor (VIF). Within each model, none of the independent variables exceeded VIF factors of 2, thus all candidate variables remained available for use in the final models. Upon construction of models, a Cook's D test was applied to each model to determine the influence of individual observations on the dependent variable; 3 models that met the criterion of a Cook's D value less than 0.5 and are reported herein. The Mallows' Cp value was also calculated and reported for each regression to assess goodness of fit. In the stepwise selection method, entry and stay α levels were set at 0.05 and 0.10, respectively, for independent variables to be included and remain in the final model. Only linear relationships were tested and unstandardized regression coefficients (β) ± SE are presented. This initial regression approach was used to characterize fecal microbiota which may serve as predictive fecal biomarkers for brain neurometabolites.

Stepwise regression for individual genus and diet predicting serum serotonin, serum cortisol, and ascending colon volatile fatty acids

From the initial stepwise regressions, the following candidate fecal genera were identified as significant predictors of one or more neurometabolites and were used in subsequent regression analyses to identify possible mediating variables: Bacteroides, Clostridium XIVb, Ruminococcus, and Butyricimonas. A linear regression equation was created using the stepwise regression procedure in which candidate independent variables (i.e., individual ascending color or fecal bacterial genus and diet) predicted one of the dependent variables (i.e., serum serotonin, serum cortisol, or ascending colon volatile fatty acids). It is known that volatile fatty acids and microbiota are related, thus all volatile fatty acids (i.e., acetate, butyrate, proprionate, valterate, isobutyrate, and isovalerate) were assessed as possible mediators in this analysis. Previous research indicates serum serotonin and serum cortisol relate to microbiota, thus in an effort to limit the metabolites analyzed in as possible mediators, only serotonin and cortisol were analyzed herein.1,2 All selection criteria described above were applied to the regression described herein, and only models that met all specified criteria are presented.

Mediation analysis

A mediation analysis was performed using the Process macro designed for SPSS.19 The mediation model was used to characterize the relationship between relative abundances of fecal Ruminococcus, serum cortisol, and a MRS-derived brain metabolite (NAA) using a 3-step process. In the context of the following mediation, we tested whether the relationship between the fecal Ruminococcus and the MRS-derived brain NAA was mediated by serum cortisol. For a mediation to occur, there must have been a significant indirect effect,20 meaning the effect of the independent variable (fecal Ruminococcus) through the mediator (serum cortisol) on the dependent variable (spectroscopy-derived NAA) must be significant.

The following 3-step framework was used to determine the mediation:

1.

Path A: A regression model was used to describe the relationship between the independent variable (Ruminococcus) and the dependent variable (NAA).

2.

Path B: A regression model was used to describe the relationship between the independent variable (Ruminococcus) and the mediator (cortisol).

3.

In the third step, the Process macro was used and a bootstrapping method applied to estimate the mediation effects. The bootstrapping used 5000 samples with replacement from the data set to estimate the distribution for the direct and the indirect effects. The direct effect indicates the relationship between the indepdendent variable (Ruminococcus) and the dependent variable (NAA) (Path A'). The indirect effect describes the relationship from the independent variable (Ruminococcus) through the mediator (cortisol) to the dependent variable (NAA) (Path B × C).

A significant mediation occurred when the indirect effect did not include zero within the 95% bias-corrected confidence interval, and if the direct mediation effect did include zero within the 95% bias-corrected confidence interval.20 Unstandardized regression coefficients (β) ± SE and P-values for each regression relationship are presented herein.

Results

Piglet characteristics

One piglet was determined to be an outlier (i.e., >3 SD from the mean) in all analyses and was therefore excluded from the data set, thus 23 subjects were used to generate the results presented herein. Piglet growth assessment was described previously.12

Ascending colon eubacterium predicts brain NAA

Diet and 18 ascending colon genera (candidate independent variables) were entered into a stepwise regression procedure to generate individual linear models for 5 neurometabolites (dependent variables). Using a stepwise regression approach to identify candidate independent variables that predict brain NAA concentrations, Eubacterium (β1 = -0.412 ± 0.119; R2model = 0.364; Pmodel = 0.002) entered the model first; diet and all other candidate genera did not meet criteria to enter the model. Predictive models for brain mI, GPC+PCh, NAA+NAAG, and Cr+PCr did not meet criteria set forth above and were therefore excluded.

Specific fecal bacterial genera predict brain myo-Inositol (mI), N-acetylaspartate (NAA), and creatine+phosphocreatine (Cr+PCr)

Diet and 18 fecal genera (candidate independent variables) were entered into a stepwise regression procedure to generate individual linear models for 5 neurometabolites (dependent variables) Using a stepwise regression approach to identify candidate independent variables that predict brain mI concentration (Table 2), Bacteroides1 = 0.039 ± 0.011; Pβ1 = 0.001; Pmodel = 0.002) entered the model first and ClostridiumXIVb (β2 = 0.127 ± 0.054; Pβ2 = 0.031; Pmodel = 0.001) entered the model second; diet and all other candidate genera did not meet criteria to enter the model. When identifying candidate variables that predict brain NAA (Table 2), Ruminococcus (β1 = -0.160 ± 0.045; Pβ1 = 0.002; Pmodel = 0.002) entered the model first and Butyricimonas (β2 = 0.155 ± 0.060; Pβ2 = 0.017; Pmodel = 0.001) entered the model second; diet and all other candidate genera did not meet criteria to enter the model. Lastly, a linear model for brain Cr+PCr (Table 2) indicated that Bacteroides (β1 = 0.010 ± 0.004; Pβ1 = 0.013; Pmodel = 0.013) entered the model, and diet and all other candidate genera did not meet criteria to enter the model. Predictive models for brain GPC+PCh and NAA+NAAG did not meet criteria set forth above and were therefore excluded.

Identification of candidate mediating variables for individual genus and MRS metabolite relationships

From the initial stepwise regressions, the following candidate genera were identified as predictors of one or more brain metabolites: ascending colon Eubacterium, fecal Bacteroides, fecal Clostridium XIVb, fecal Ruminococcus, and fecal Butyricimonas. Candidate mediating variables in this analysis included: serum serotonin, serum cortisol, and ascending colon volatile fatty acids. Individual stepwise regressions indicated fecal Bacteroides was predictive of: serum serotonin (β1 = 0.016 ± 0.007; Pmodel = 0.038; Table 3), ascending colon valerate (β1 = -0.174 ± 0.048; Pmodel = 0.002; Table 4), and total branched-chain fatty acids (β1 = -0.317 ± 0.103; Pmodel = 0.006; Table 4); diet did not meet criteria to enter any of the described models. Similarly, stepwise linear models indicated fecal Ruminococcus was predictive of serotonin (β1 = -0.169 ± 0.057; Pmodel = 0.008; Table 3) and cortisol (β1 = -0.109 ± 0.032; Pmodel = 0.002; Table 3); diet did not meet criteria to enter any of the described models. Individual regressions with ascending colon Eubacterium or fecal Clostridium XIVb and Butryricimonas did not meet selection criteria for inclusion into stepwise predictive models of serum serotonin, serum cortisol, or volatile fatty acids, and were therefore excluded. Previous research indicates serum cortisol and serum serotonin influence the expression of one another, however there was no observed correlation (P = 0.148) between cortisol and serotonin in this study.

Serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain NAA

A formal mediation analysis was performed to assess the relationship between Ruminococcus and NAA through cortisol. The following regression framework was used to elucidate the characteristics of this relationship.

Higher Ruminococcus predicted decreased cortisol (Table 3), therefore cortisol was considered as a candidate mediating variable for the previously identified relationship between Ruminococcus and NAA (Table 2). Using the 3-step framework for a formal mediation analysis, higher Ruminococcus predicted decreased NAA concentrations (β = -0.160 ± 0.045; R2model = 0.367; Pmodel = 0.002, Fig. 1 path A). Next, higher Ruminococcuspredicted decreased cortisol concentrations (β = -0.109 ± 0.032; R2model = 0.360; Pmodel = 0.002, Fig. 1 path B). Lastly, the formal mediation model, assessing the effects of serum cortisol concentrations on the relationship between Ruminococcus and NAA, was significant (R2model = 0.450, Pmodel = 0.003). The indirect pathway of the mediation was significant ([95%CI: -0.150 - -0.009; Fig. 1 path B × C] [β = 0.573 ± 0.330; Pβ = 0.098; Fig. 1path C]), and the direct pathway of the mediation was not significant (95%CI: -0.238 - 0.012; β = -0.113 ± 0.060; Pβ = 0.075; Fig. 1 path A'). Thus, cortisol concentrations fully mediated the relationship between fecal Ruminococcus and brain NAA concentrations.

Figure 1. Serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain N-acetylaspartate. First, fecal Ruminococcus negatively predicted MRS-derived brain NAA concentrations (path A). Second, fecal Ruminococcus negatively predicted serum cortisol concentrations (path B). Third, mediation effects were assessed for serum cortisol concentrations. The indirect effect (i.e., the effect of fecal Ruminococcusthrough serum cortisol on MRS-derived brain NAA; path B × C) was significant, and the direct effect (path A') was not significant. Thus, serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain NAA. Abbreviation: N-acetylaspartate (NAA).

 

                         

 

Discussion

This study uses multimodal methodology to provide a novel insight into the complex interactions between the microbiome-gut-brain axis in early development. Due to their strikingly similar physiology, immune system function, dietary patterns, and disease progression, pigs have been identified as an optimal translational model for assessing the interactions between diet, micriobiota and host physiology.8 The piglet is considered the best model for human gastrointestinal9 with proven clinical translatability. Recent studies have used gnotobiotic piglet models,21,22 thereby establishing the piglet as a useful model for assessing the influence of specific microbiota throughout development. Using the biomedical piglet model, these findings provide a previously unidentified link between relative abundances of specific bacterial genera, neurometabolites and serum metabolites. In doing so, these results may identify a novel mechanism through which the microbiome may influence neurodevelopment. However, it should be noted that the proposed mechanism described herein should be further substantiated through empirical studies, thus this finding is reported as an exploratory analysis and should be considered as hypothesis generating evidence for future work. In the following paragraphs, we will discuss:
i) predictive models between fecal microbiota and brain metabolites,
ii) predictive models between fecal microbiota and serum/colonic biomarkers, and
iii) a mediation model through which serum biomarkers mediate the relationship between fecal microbiota and brain metabolites.

Fecal microbiota predict neurometabolites

The first objective of this analysis was to identify novel relationships between fecal microbiota and neurometabolites. Our results indicated brain mI, a marker for glial cells and pre-myelinating events in the developing brain,23 was positively predicted by both Bacteroides and  Clostridium  XIVb. Additionally, brain Cr+PCr, an indicator of energy metabolism,24. Lastly, these analyses indicated brain NAA, a marker of neuronal health,24 was negatively predicted by Ruminococcusbut positively predicted by Butyricimonas. Concentrations of these brain metabolites change over the course of development23 and our research suggests gut colonization of microbiota may play a pivotal role in this phenomenon. Dysbiosis in the gut microbiota is known to alter behavior in both humans and animal models,,4,25,26 and changes in neurometabolites may underlie these behavioral phenotypes. Interestingly, altered brain Cr+PCr,27-29  have been reported in subjects diagnosed with ASD, yet no studies have identified specific links between gut microbes and these metabolites. Mice supplemented with a daily dose of Lactobacillus rhamnosus for 2 weeks showed an increase in brain NAA quantified by MRS, thus providing evidence that brain metabolite concentrations can be modulated by microbial shifts in the gut.3 in this study, we assessed the interaction of Lactobacillus and brain NAA and the correlation was not significant, data not shown.

Fecal microbiota predict serum/colonic biomarkers

The next step of the analysis framework was to identify possible mediatory biomarkers that relate to the previously identified fecal bacterial genera. This analysis showed that Bacteroides positively predicted serum serotonin, whereas Ruminococcus negatively predicted both serum serotonin and cortisol. These findings have not previously been reported in the literature. However, correlations between operational taxonomic units that belong to Ruminococcus and daily cortisol levels in depressed patients have been reported.32 Previous research indicates both serotonin and cortisol release can be influenced by bacterial strains.25 In a probiotic study, supplementation of Lactobacillus helveticus R0052 and  Bifidobacterium longum R0175 decreased urinary cortisol levels in healthy human volunteers, further indicating bacterial strains can influence cortisol levels.33 Although Lactobacillus was not identified as a predictive bacteria for neurometabolites in this study, we assessed the interaction of Lactobacillus and serum cortisol and the correlation was not significant, data not shown. Interestingly, alterations in serum serotonin and cortisol, as well as fecal Bacteroides and Ruminococcus levels, have been described in patients with ASD.6

Serum cortisol as a mediator between fecal ruminococcus and brain NAA

Given the relationships reported in our predictive models, we used a mediation model to characterize the mediatory effects of serum biomarkers on the relationship between fecal microbiota and neurometabolites. Our results provided clear evidence that serum cortisol mediated the relationship between fecal Ruminococcus and brain NAA. Interestingly, Ruminococcus, cortisol, and NAA have all independently been implicated in ASD; however, this is the first time a relationship between the 3 has been reported.
First, higher Ruminococcus predicted lower NAA. Previous research indicates elevated fecal Ruminococcus in subjects with ASD,34,35 and fecal Ruminococcus positively correlated with autistic-like behaviors in a mouse model of ASD.36 In addition, MRS indicates NAA was decreased in the cerebellum,37 hippocampus and amygdala,38 temporal lobe,39 gray matter and white matter,28 and whole brains27. To our knowledge, no other study has reported a link between Ruminococcusand NAA.

Second, higher Ruminococcus predicted lower cortisol concentrations. This finding is supported by previous research in which decreased serum cortisol was observed in individuals with ASD.40 It should be noted that the implications of cortisol in ASD vary widely, with some research suggesting elevated cortisol in ASD patients.41 Although these inconsistent results could be attributed to differences in methodological approach (i.e., salivary vs. serum cortisol) as well as the heterogeneity of symptoms among individuals with ASD, it is important to note that diverse microbial populations may differentially influence serum cortisol concentrations. As stated previously, supplementation of specific bacterial strains resulted in reduced cortisol in healthy human volunteers.33 These findings further suggest that specific bacterial strains may differentially impact serum cortisol concentrations, rather than attributing the cortisol changes to a particular disease state.
Third, the indirect pathway of the mediation indicated cortisol has a mediatory effect on the relationship between Ruminococcus and NAA. Previous research shows salivary cortisol positively relates to hippocampal NAA, although it should be noted this observation was made in patients exhibiting posttraumatic stress disorder.42 Thus, it follows that lower levels of cortisol would relate to lower levels of NAA, thereby supporting our finding. Given the independent reports on Ruminococcus, cortisol, and NAA in individuals with ASD (Fig. 2), this mediation analysis could provide a possible mechanism underlying the complex relationship between the microbiota and neurodevelopment in the context of ASD. Interestingly, provision of fructo-oligosaccharides and galacto-oligosaccharides in mice resulted in a reduction in cecal  Ruminoccocus among other bacterial genera, indicating a possible dietary approach to reducing Ruminococcus concentrations.43

Figure 2. Cited literature for mediation results. Previous studies which support the findings of our mediation analysis are presented in the figure with appropriate literature citations. Abbreviations: autism spectrum disorder (ASD), N-acetylaspartate (NAA)

 

 

Conclusion

This study used an interdisciplinary approach through the use of fecal microbiota measures, serum biomarkers, and MRS. To our knowledge, this approach has not been undertaken in previously published studies. The relationships identified herein provide several novel perspectives on the possible mechanisms of microbiome-gut-brain-axis. First, due to the high diversity of the gut microbiota, unravelling specific relationships between bacterial genera and particular brain metabolites is difficult; however, these predictive models identify the most influential genera on individual brain metabolites. Second, identification of these relationships permits a focused approach for selection of mediatory biomarkers. Third, identification of predictive microbes on brain metabolites enables sensitive targeting of the gut microbiota to alter neurometabolites, thereby influencing neurodevelopment. This study reported a predictive relationship between levels of fecal Ruminococcus, serum cortisol, and brain NAA, 3 observations that have independently been reported in patients with ASD. While the initial aim of this study was not to focus on ASD etiology, these results provide preliminary data for future research aiming to investigate the microbiota-brain communication in ASD and to develop targeted treatment options for a subgroup of affected individuals.

Our study was limited to assessing fecal microbiota at the genera taxonomic level; thus, future work assessing the impact of specific microbial species may reveal a more detailed microbial signature as it relates to specific aspects of neurodevelopment. Provided the continued maturation of the brain and the gastrointestinal tract into childhood, longitudinal assessment in the pig model may provide key evidence of critical developmental windows during which microbiota are most influential. Lastly, this novel approach can be implemented in the assessment of other neurodevelopmental disorders that may be influenced by microbiota. While these findings do not specifically identify mechanisms of action between the observed relationships, this exploratory study used a statistical approach that aids in identifying potential mechanisms, which can set the framework for future interventional studies.

From our results we: i) provide a novel perspective into the interaction between fecal microbiota and brain metabolites, ii) provide novel links between fecal microbiota and serum biomarkers implicated in ASD, and iii) bring together 3 independently reported observations in ASD patients to provide a potential mechanism for the communication between one bacterial genera and a specific brain metabolite. The relationships identified in this study may serve as hypothesis-generating findings from which future empirical studies can aim to further investigate the underlying mechanisms proposed in this paper. Additionally, these novel findings may serve as preclinical evidence through which future dietary intervention can be implemented to alter microbial populations and influence neurodevelopment.

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Cateteres venosos - InfeccionesFecha: 2/10/2017

 

 

 

Los paquetes de medidas para la inserción y el mantenimiento de catéteres venosos contribuyen a reducir las infecciones del torrente sanguíneo, en pacientes asistidos en unidades de cuidados intensivos?

INFECCIONES DEL TORRENTE SANGUÍNEO RELACIONADAS CON LA PRESENCIA DE CATÉTERES VENOSOS CENTRALES. LA EFICACIA PREVENTIVA DE LOS PAQUETES DE MEDIDAS QUE REGULAN SU INSERCIÓN Y MANTENIMIENTO EN PACIENTES CRÍTICOS DE CUALQUIER EDAD. REVISIÓN SISTEMÁTICA Y METAANÁLISIS.                   

                                              Ista E, van der Hoven B, Kornelisse RF y colaboradores.

                                                                              Lancet Infect Dis. 2016; 16: 724-34.


INTRODUCCIÓN

En inglés se conoce como "prevention bundle" a un conjunto de prácticas pensadas y formuladas para llevar a cabo correctamente una determinada acción médica preventiva. Habitualmente, esta expresión se traduce como «paquetes de medidas». El requisito esencial es que TODAS las disposiciones que integran un determinado paquete de medidas sean llevadas a cabo juntas y de la manera adecuada. Desde 2006 se sabe que, en unidades de cuidados intensivos de adultos, la inserción de catéteres venosos centrales siguiendo los criterios de un paquete de medidas específico contribuye a reducir la incidencia de infecciones del torrente sanguíneo. La presente revisión sistemática ha sido desarrollada para definir si el uso combinado de paquetes de medidas preventivas y de mantenimiento resulta efectivo para controlar las infecciones relacionadas con la presencia de catéteres.


FUENTES DE INFORMACIÓN

Se identificaron estudios mediante búsqueda directa entre 1990 y 2015 en las bases de datos MEDLINE, EMBASE y "Web of Science" y en la Biblioteca Cochrane, y en otras fuentes a través de PubMed y Google Scholar. También eran revisadas las listas de referencias bibliográficas de los estudios ya identificados.


SELECCIÓN DE ESTUDIOS

Serían incluidos estudios que comunicaran la implementación de paquetes de medidas preventivas y de mantenimiento de los catéteres en unidades de cuidados intensivos de adultos, y en unidades pediátricas en general y de recién nacidos.


EXTRACCIÓN DE DATOS

Se extrajeron los datos demográficos y clínicos pertinentes. La principal medida de evolución sería el número de infecciones del torrente sanguíneo registradas por cada 1000 días-catéter cumplidos.


PRINCIPALES RESULTADOS

Sobre más de cuatro mil registros identificados, reunían los criterios de elegibilidad algo menos de cien estudios. Finalmente, fueron incorporados 79 trabajos. Se utilizó el modelo de efectos al azar DerSimonian-Laird para determinar el número de infecciones y calcular el riesgo relativo de incidencia. A continuación se indican los principales hallazgos. 

-- En unidades de cuidados intensivos de adultos se registra una medianade infecciones del torrente sanguíneo de 5,7 por cada 1000 días-catéter (entre 1,2 y 46,3, con espectro intercuartil de 3,1 a 9,5). 
-- En unidades pediátricas generales, la mediana es de 5,9 por 1000 (entre 2,6 y 31,1; espectro intercuartil, 4,8 a 9,4). En unidades neonatales, la mediana es de 8,4 por 1000 (entre 2,6 y 24,1; espectro intercuartil, 3,7-16,0). 
-- Antes de la implementación de paquetes de medidas, la incidencia de infecciones en todos los tipos de unidades variaba entre 0 y 19,5 por cada mil días / catéterer. La mediana era de 2,6, con espectro intercuartil entre 1,2 y 4,4. 
-- En el metaanálisis se observa que la incidencia de infecciones decrecía significativamente tras la implementación de los paquetes de medidas: de 6,4 por cada 1000 días / catéter (espectro intercuartil, 3,8-10,9) hasta 2,5 por 1000 (1,4-4,8). Esto implica un riesgo relativo de incidencia de 0,44, con intervalo de confianza (IC) del 95% entre 0,39 y 0,50 (p < 0,0001). Con todo, la heterogeneidad entre estudios ha sido alta: I al cuadrado [I2] de 89%.


CONCLUSIÓN

Los datos reunidos permiten afirmar que la implementación de paquetes de medidas concretas para la instalación y el mantenimiento de catéteres venosos centrales en pacientes críticos internados en unidades de cuidados intensivos logra reducir significativamente el desarrollo de infecciones del torrente sanguíneo relacionadas con la presencia de esos catéteres. Dicho efecto se observa tanto en unidades de adultos como en las pediátricas generales y de neonatología.

 

 

 

Manifestaciones cutáneas de la resistencia a la insulinaFecha: 1/9/2017

 

 

Manifestaciones cutáneas de la resistencia a la insulina

                                                                                                                                                       González-Saldivar G, Rodríguez-Gutiérrez R, Ocampo Candiani                                                       

                                                              J. Dermatol. Ther (Heibel) (2017) 7: 37-51                              

                                                 Resumen y comentario objetivo: Dr. Ricardo Ferreira

 

Resumen

  • Unos 382 millones de personas viven con diabetes y el 40-50% de la población mundial es considerada de ''alto riesgo'' (prediabetes). Estas dos entidades no solo causan aumento de la morbimortalidad, sino que también impactan por su costo, la carga de enfermedad y la disminución de la calidad de vida relacionada con la salud.  
  • El 70-80% de los pacientes con obesidad y prácticamente todos los pacientes  con diabetes tipo 2 tienen resistencia a la insulina. Esta aparece años antes del diagnóstico de la enfermedad.  
  • El método de referencia para el diagnóstico de la resistencia a la insulina es el pinzamiento euglucémico, pero este es costoso, complejo e invasivo. Las pruebas de laboratorio y los índices derivados de ellas (HOMA-IR-)] son pruebas indirectas y poco exactas. En cambio, las manifestaciones cutáneas de la resistencia a la insulina (acrocordones, acantosis pigmentaria, alopecia androgénica, acné, hirsutismo) son una manera fiable y directa de detectar la resistencia a la insulina. El diagnóstico de estas manifestaciones cutáneas puede impactar positivamente sobre la salud del paciente al generar su evaluación metabólica y su tratamiento oportuno.

INTRODUCCIÓN

Durante las últimas décadas la epidemia de obesidad y diabetes tipo 2 (DT2) aumentó tanto que se ha convertido en una de los desafíos para la salud más importantes en todo el mundo debido a la morbimortalidad y la disminución de la calidad de vida relacionada con esta epidemia. A pesar de todos los esfuerzos preventivos la frecuencia de estas dos entidades continúa creciendo exponencialmente. Un estudio proyectó que para 2050 hasta un tercio de la población de los EE. UU y probablemente también de la población mundial padecerá DT2 [1]

La respuesta biológica subnormal de los tejidos a concentraciones normales de insulina se denomina resistencia a la insulina (es decir, el cuerpo produce insulina, habitualmente en concentraciones mayores que en sujetos normales, pero no la emplea eficazmente) [2].

Este es uno de los factores fisiopatológicos clave de la DT2 y suele aparecer años antes del diagnóstico clínico de diabetes. Se sugirió que la resistencia a la insulina se produce por el exceso de tejido adiposo (obesidad), que tiene efectos bioquímicos debidos a la secreción de múltiples citocinas [MCP-1, TNF-a, IL-6, IL-18, leptina, resistina, e inhibidor del activador de plasminógeno (PAI)-1, entre otros], que se traducen clínicamente como síndrome metabólico [3].  

El pinzamiento euglucémico es una técnica compleja que se considera el método de referencia para el diagnóstico de resistencia a la insulina [4].

Dada la complejidad inherente de esta prueba, su costo y la falta de implementación en la práctica médica habitual, hay varias pruebas indirectas para evaluar la resistencia a la insulina, entre ellas: el aumento de la glucemia en ayunas, la relación triglicéridos/ lipoproteínas de alta densidad y la concentración de insulina en ayunas. A fin de evaluar la resistencia a la insulina, estas mediciones se emplearon para crear índices como el modelo homeostático de evaluación de la resistencia a la insulina (HOMA-IR, por las siglas del inglés) y el índice de verificación cuantitativa de sensibilidad a la insulina (QUICKI) [4].

No obstante, ninguna de estas pruebas es suficientemente fiable y por lo tanto no se recomiendan. La observación de las manifestaciones cutáneas de resistencia a la insulina, en cambio, es fiable y coincide con los resultados de la prueba de pinzamiento euglucémico [5, 6].

Además, tiene ciertas ventajas importantes: se observan durante el examen físico, no son invasivas, no llevan tiempo, no son molestas ni significan aumento de los costos. Este artículo intenta ayudar a los médicos generalistas, los médicos de familia y los dermatólogos a reconocer las manifestaciones cutáneas de la resistencia a la insulina. Esto puede poner de manifiesto qué pacientes están en riesgo de sufrir DT2, generando la evaluación adecuada y, de ser necesario el tratamiento oportuno. Se podría así contribuir a evitar la carga de diabetes/síndrome metabólico y aumentar la calidad de la atención para estos pacientes

► La resistencia a la insulina y su asociación con manifestaciones cutáneas

La resistencia a la insulina se define como la disminución de la respuesta de una célula o un órgano a la concentración de insulina a la que está expuesto

La insulina es una hormona peptídica sintetizada y segregada por las células beta del páncreas. La glucosa es el principal regulador de la secreción de insulina; a medida que la concentración de glucosa aumenta, estimula la secreción de insulina. Algunos de los efectos glucorreguladores de la insulina son la inhibición de la glucogenólisis y la gluconeogénesis, el aumento de transporte de la glucosa al tejido adiposo y al músculo, la estimulación de la síntesis de glucógeno, así como su importancia central en el metabolismo de lípidos y proteínas [2, 7].

Como ya se mencionó, la resistencia a la insulina se define como la disminución de la respuesta de una célula o un órgano a la concentración de insulina a la que está expuesto: en la práctica, se refiere al estado en el que la secreción de insulina se asocia con una respuesta anormal de la glucosa (por ejemplo, intolerancia a la glucosa o diabetes) [8].

Existen cuatro tipos de la resistencia a la insulina: tipos A, B, C y causas secundarias.

  1. Tipo A: se asocia con disfunción o disminución de la cantidad de receptores de insulina.  
  2. Tipo B: se refiere a anticuerpos contra los receptores de insulina (por ejemplo, leprechaunismo con mutaciones del receptor de insulina).  
  3. Tipo C: se caracteriza por defectos en los posrreceptores (lipodistrofias).  
  4. Tipo secundario: la gran mayoría de los pacientes, sin embargo, tienen resistencia a la insulina secundaria (por ej, intolerancia a la glucosa, diabetes, obesidad, estrés, infección, uremia, acromegalia, exceso de glucocorticoides y embarazo) [9].

Alrededor del 50% de los pacientes con resistencia a la insulina, a pesar de la hiperinsulinemia compensatoria, tienen cierto grado de hiperglucemia ([100 mg/dl). Sin embargo, no todos los pacientes con hiperinsulinemia y resistencia a la insulina tendrán intolerancia a la glucosa o diabetes. Es importante reconocer que prácticamente todo paciente con DT2 tendrá resistencia a la insulina años -o por lo menos meses- antes del diagnóstico de diabetes. La resistencia a la insulina se puede presentar con un amplio espectro de manifestaciones, tales como:

  • acantosis pigmentaria
  • papilomas cutáneos
  • hirsutismo, (hiperandrogenismo ovárico)
  • alopecia androgénica [10].

Esta asociación se produce porque la hiperinsulinemia activa directa e indirectamente los receptores del factor 1 de crecimiento insulínico (IGF-1) ubicado en los fibroblastos y los queratinocitos, estimulando su proliferación [11, 12].

La hiperinsulinemia también puede influir sobre la producción de esteroides sexuales. Asimismo, la insulina y el IGF-1 aumentan los andrógenos ováricos. Es importante mencionar que enfermedades de la piel como:

  • psoriasis
  • hidradenitis supurativa
  • vitiligo

Se han asociado fuertemente con resistencia a la insulina y síndrome metabólico [4].

► Importancia de la obesidad y la DT2

La prevalencia de obesidad y la DT2 continúa en aumento a pesar de numerosos esfuerzos y ambas parecen imparables. En 2014, más de 1900 millones de adultos tenían sobrepeso y más de 600 millones eran obesos. Al mismo tiempo, más de 380 millones de personas en el mundo padecen diabetes y el 35-50% de la población mundial (>3000 millones) tiene gran riesgo de padecerla-la llamada prediabetes, que en todos los casos se acompaña de resistencia a la insulina.

El impacto de estas dos entidades no es solo por la carga de enfermedad, sino más por el aumento del riesgo cardiovascular, los trastornos musculoesqueléticos, el costo, la mortalidad, la carga del tratamiento y la disminución de la calidad de vida asociados. Ambas entidades sufren la influencia de factores genéticos, epigenéticos y ambientales. Entre estos últimos están el sedentarismo, las comidas poco saludables y el bajo nivel socioeconómico, entre otros [10].

La obesidad se considera la enfermedad concomitante y el factor de riesgo más frecuente para la diabetes, ya que el 80% de los pacientes con diabetes tienen sobrepeso o son obesos. El 70-80% de los pacientes con obesidad tendrán resistencia a la insulina. La obesidad y la DT2 se asocian con una cantidad considerable de dermatosis, entre ellas acantosis pigmentaria, acrocordones, hirsutismo y queratosis pilaris [10].

Alrededor de un tercio de los pacientes con diabetes tendrán algún tipo de manifestación cutánea durante el curso de su enfermedad [13]. Un estudio reciente publicó que el 91% de los pacientes con diabetes tienen por lo menos una manifestación dermatológica [13]. De ahí que todos estos trastornos cutáneos deben alertar a los médicos para estudiar las características metabólicas de estas personas, lo que puede generar un rápido diagnóstico.

► Manifestaciones cutáneas de resistencia a la insulina

♦ Acrocordones

Los acrocordones, también llamados pólipos fibroepiteliales, papilomas cutáneos o fibromas blandos, son uno de los tumores cutáneos más frecuentes [14]. Son benignos, raros antes de los 30 años, pero muy comunes después, especialmente en la ancianidad. Son más frecuentes entre las mujeres y en los pacientes con sobrepeso u obesidad, aunque también tienen una relación familiar/genética. Recientemente, varios estudios asociaron los acrocordones con la intolerancia a la glucosa y la diabetes [15-18].

En 1976, Margolis et al, efectuaron uno de los primeros estudios y publicaron que el 9,4% de 500 pacientes hospitalizados tenían acrocordones y de ellos, el 72% padecían DT2 y sugirió que los acrocordones podrían ser un factor de riesgo para la diabetes [19]. A fines de la década de 1980, Norris et a, informaron una relación entre los papilomas cutáneos y la resistencia a la insulina (el 61% de la población que estudiaron tenía hiperinsulinemia). Sin embargo, sólo el 15% tenía también aumento de la glucemia en ayunas. El estudio de Kahana et al, revelaron que el 34% de los pacientes con acrocordones padecía DT2 [20].

La insulina es una hormona promotora del crecimiento. La hiperinsulinemia se ha vinculado directamente con el IFG-1 y la disminución de la proteína 3 de unión al factor de crecimiento tipo insulina (IGFBP-3). El IGF-1 se une a los receptores de los queratocitos, desencadenando la hiperplasia epidérmica, y la reducción de la IGFBP-3 puede disminuir la transcripción de los genes antiproliferativos activados normalmente. Estas perturbaciones endócrinas alteran la proliferación celular y a la larga se hacen evidentes como papilomas cutáneos [12].

Estas lesiones son tumores pequeños, blandos, levemente hiperpigmentados de tamaño variable y característicamente pediculados (véase Fig. 1). Los acrocordones con frecuencia son múltiples, pero pueden parecer una lesión única. Aparecen con más frecuencia en las zonas intertriginosas, como cuello, axilas e ingles, aunque también se las puede hallar en párpados y pliegues inframamarios [16, 18, 21]. Estas lesiones cutáneas son totalmente asintomáticas, pero pueden ser dolorosas cuando se irritan [22]. El diagnóstico diferencial es con los nevus melanocíticos, los neurofibromas y la queratosis seborreica pediculada.

                                   

Las enfermedades con las que se asocian son el síndrome de Gardner, el síndrome de Birt-Hogg-Dube y la esclerosis tuberosa, entre otras [18, 23]. El diagnóstico es clínico; si bien puede haber casos atípicos en los que la extirpación quirúrgica y la histopatología confirmarán el diagnóstico. El tratamiento es más una preocupación estética que médica. Los métodos más empleados son la electrocirugía y la crioterapia, aunque el problema con esta última es la dificultad para limitar la zona a congelar exclusivamente a la lesión [25]. Lo más sencillo es extirpar el papiloma con una tijera afilada de buena calidad.

♦ Acantosis pigmentaria (o nigricans).

La acantosis pigmentaria (AP) se caracteriza por placas simétricas, aterciopeladas, hiperpigmentadas, especialmente en las zonas intertriginosas: cuello, axilas y codos, (véase Fig. 2, [5, 9, 26, 33, 36] aunque también pueden estar en otros sitios.

                                  

Habitualmente se relaciona con trastornos asociados con resistencia a la insulina (por ej DT2 y obesidad). En casos raros puede aparecer como signo de un tumor maligno (por ej, adenocarcinomas agresivos del tubo digestivo) [26-28]. La AP se clasifica según su etiología en ocho tipos: benigno, asociado con la obesidad, sindrómico, maligno, distal, unilateral, inducido por fármacos y mixto [26].

El ácido nicotínico es el medicamento que causa AP con mayor frecuencia, aunque no el único

La AP asociada con la obesidad, también llamada ''pseudo-AP'', es la causa más frecuente de AP y es una expresión de resistencia a la insulina. La AP sindrómica comprende los síndromes de resistencia a la insulina tipo A y B (por ej síndrome de Berardinelli-Seip, síndrome de Lawrence), síndrome de Crouzon y otros numerosos trastornos sindrómicos raros. La AP maligna se asocia con adenocarcinomas del tubo digestivo; es grave, abrupta, exuberante y afecta las membranas mucosas.

El ácido nicotínico es el medicamento que causa AP con mayor frecuencia, aunque no el único. En estos casos la AP desaparece espontáneamente en 4-11 meses después de suspender la medicación [26]. Los datos sobre la verdadera frecuencia de la AP son contradictorios, ya que varía mucho según la edad, la etnia, el fototipo cutáneo y las características antropométricas [32-34]. Un estudio con 675 adolescentes halló una prevalencia de AP del 18,9%.

La prevalencia de AP fue mayor en estudiantes obesos que en aquellos con IMC normal (49,2% vs. 7,7%) [6]. Un estudio con 703 estudiantes latinos halló una prevalencia de AP del 47,8% [32]. Además, se encontró AP en alrededor del 50% de los pacientes con síndrome de Down, que también son proclives a la obesidad, el síndrome metabólico y la diabetes [35]. La patogenia es similar a la de los acrocordones y se produce por estimulación del factor de crecimiento de los queratinocitos y los fibroblastos en la dermis.

La familia del receptor de tirosina cinasa comprende la insulina, el IGF, el factor de crecimiento epidérmico y los receptores del factor de crecimiento de los fibroblastos, entre otros. El aumento de la concentración de insulina se traduce en la proliferación de queratinocitos y fibroblastos debido a la estimulación de los receptores del IGF-1 [9, 11, 26].

Además de los lugares anteriormente mencionados un estudio de los autores de este artículo reveló que la ubicación más frecuente de AP, incluso en sujetos con IMC normal fue en los nudillos [32]. Los cambios histopatológicos son sutiles y consisten en hiperqueratosis, acantosis y papilomatosis leve. El color amarronado de esta dermatosis se debe al engrosamiento del estrato córneo. El primer paso en la evaluación de la AP es determinar su etiología.

La información importante comprende:

  • la edad
  • el momento de inicio
  • la evolución
  • las mediciones antropométricas
  • los antecedentes familiares del síndrome metabólico
  • las medicaciones y los datos relacionados con el síndrome diabético (por ej , poliuria, polidipsia, polifagia, adelgazamiento)
  • síntomas sugestivos de tumor maligno

En todos los pacientes con sobrepeso u obesidad se recomienda la pesquisa de hiperglucemia en ayunas y pruebas de función hepática.

Para la mayoría de los casos (AP inducida por obesidad), se debe recomendar descenso de peso y ejercicio como tratamiento de primera línea [26, 39]. Otros autores comunicaron el empleo de retinoides orales o tópicos (que probablemente regulen la proliferación y la diferenciación de los queratinocitos) como tratamientos eficaces [26, 40, 41]. También se emplean tratamientos locales con acitretina, lactato de amonio, ácido láctico, exfoliación con ácido tricloroacético, con respuesta variable [39, 43].

♦ Alopecia androgénica

La alopecia androgénica (AAG) es el subtipo más frecuente de alopecia no cicatrizal. La AAG es un rasgo físico hereditario andrógenodependiente, producido por la conversión de los pelos terminales del cuero cabelludo en vellos diminutos con un patrón característico [44]. Afecta a hombres y mujeres en las mismas proporciones y habitualmente aparece al término de la adolescencia [45-47]. Al llegar a los 30 años casi un tercio de los hombres tendrán AAG. Esta proporción aumenta con la edad (alrededor del 50% a los 50 años) [48].

El riesgo de tener AAG depende de varios factores, entre ellos los antecedentes familiares y factores genéticos. Otros factores relacionados son el tabaquismo, la hiperplasia prostática benigna y el cáncer de próstata. Paradójicamente, uno de los factores más frecuentes fue mencionado recién hace poco tiempo-el síndrome metabólico (es decir, la resistencia a la insulina) [45, 48]. Recientemente, Nabaie et al, comunicaron una relación no significativa entre la alopecia androgénica y la resistencia a la insulina en un estudio de casos y controles; sin embargo otros argumentaron que la alopecia androgénica temprana es un marcador de resistencia a la insulina [49, 50].

La dihidrotestosterona (DHT) es el andrógeno implicado en la patogénesis de la AAG. La testosterona se metaboliza en muchos tejidos de la piel; penetra en la membrana celular y es convertida por la 5-alfa reductasa del citoplasma en su forma más potente: la DHT. La 5-alfa reductasa tiene dos isotipos [44, 52]. El tipo II domina en la vaina externa de los folículos pilosos del cuero cabelludo, la barba y el tórax [44]. La DHT se une a los receptores del andrógeno y es transferida al núcleo, donde estimula la  transcripción de genes. Esta activación es clave, ya que es la responsable de la transformación gradual de los folículos terminales en pelos vellosos más pequeños [51, 53].

En un estudio de casos y controles en hombres jóvenes con AAG y sin ella, González-González et al, evaluaron diferentes mediciones de resistencia a la insulina en esta población. El índice HOMA-IR y la testosterona libres fueron significativamente más altos en los casos que en los controles [45]. Bakry et al, estudiaron a 100 varones con AAG y sugirieron que a los pacientes en etapa III o mayor se los debería evaluar para síndrome metabólico y resistencia a la insulina [54]. Una revisión sistemática más reciente, que incluyó 31 estudios y 50956 personas (29254 con AAG), reveló que estos pacientes tenían aumento del riesgo de enfermedad coronaria, hipertensión, resistencia a la insulina y dislipidemia [55]. La calvicie en los hombres con AAG suele comenzar con retroceso bitemporal del nacimiento del pelo, así como adelgazamiento difuso del pelo en la coronilla (véase Fig. 3).

                                                       

 

Más tarde, la pérdida total del pelo centralmente en la coronilla produce un parche de calvicie que se expande gradualmente, uniéndose al retroceso del nacimiento del pelo. La pérdida del pelo habitualmente comienza después de la pubertad [56]. Este tipo de alopecia suele ser progresivo, simétrico y asintomático. En las mujeres la AAG típicamente comienza con la disminución difusa de la densidad capilar sobre las zonas frontal y central, aunque las zonas parietal y occipital también pueden estar afectadas [46] (véase Fig. 3).

La anamnesis debe incluir la edad, el sexo, la existencia de tabaquismo, la evolución de la pérdida de pelo, los antecedentes familiares, los síntomas asociados, los tratamientos previos y el empleo de medicamentos (por ejemplo esteroides anabólicos). En las mujeres se debe efectuar una anamnesis ginecológica detallada que incluya menarca, ciclo menstrual, amenorrea, menopausia, empleo de tratamiento hormonal, trastornos de la fecundidad y signos de hiperandrogenismo.

El examen dermatológico debe incluir, además del cuero cabelludo, la distribución capilar en el cuerpo, piel y uñas [46]. El cuero cabelludo suele ser normal, pero es común hallar dermatitis seborreica. En pacientes con AAG el examen físico total es especialmente importante, ya que está muy asociado con otras enfermedades, como la enfermedad coronaria y el síndrome metabólico [45, 47, 48, 54, 55, 57].

La prueba de pilotracción se debe efectuar siempre en las zonas parietal derecha e izquierda, frontal y occipital, así como en la zonas afectadas. Esta prueba solo es positiva en sujetos en la fase activa de la AAG. Según el contexto, se puede considerar la medición de la tirotropina, el hierro y los andrógenos, a fin de descartar otras causas de [47]. La dermatoscopia es útil para el diagnóstico de AAG. El signo dermatoscópico clásico es la diferencia mayor del 20% del diámetro del pelo (anisotricosis) con los pelos vellosos

Un halo marronáceo, hundido, en las aberturas foliculares también es frecuente (signo peripilar). Cuando el diagnóstico no es evidente, se deben tomar dos biopsias en sacabocados no menores de 4 mm de diámetro, siempre siguiendo la dirección de la vaina del pelo y profundas dentro de la grasa subcutánea, donde normalmente están los bulbos pilosos en fase anágena.

El lugar preferido para la biopsia es el cuero cabelludo central. La biopsia nunca se debe tomar de la zona bitemporal, ya que pueden existir pelos en miniatura independientemente de la AAG [46, 47]. La histopatología muestra el reemplazo de los pelos terminales por vellos secundarios, así como el aumento de la proporción de pelos telógenos sobre los anágenos.

Las recomendaciones generales para el tratamiento de la AAG son la alimentación adecuada, evitar los productos para el cuidado del pelo que podrían empeorar el proceso, suspender los medicamentos que podrían afectar negativamente el crecimiento del pelo (por ej.  retinoides, citotóxicos, anticoagulantes) y tratar toda enfermedad de base local o sistémica (por ej. hipotiroidismo, anemia, dermatitis seborreica, psoriasis) [47, 51, 56].

El tratamiento médico es con finasteride o dutasteride por vía oral y minoxidil tópico al 2% y al 5%, que se debe emplear por lo menos durante un año antes de descartar su eficacia. Las operaciones de recuperación del pelo son el trasplante capilar, la cirugía de reducción del cuero cabelludo o una combinación de ambas [47, 59]. La AAG produce estrés psicológico moderado en la mayoría de los hombres y para algunos significa disminución de su calidad de vida [60].

► Hirsutismo, acné e irregularidades menstruales

El síndrome de ovario poliquístico (SOPQ) es una entidad metabólica y reproductiva que aumenta el riesgo de sufrir DT2 y esterilidad [61]. Además de obesidad, las mujeres con SOPQ tienen resistencia a la insulina. La frecuencia de la obesidad es del 25%-70% y contribuye a la resistencia a la insulina [63]. El hiperandrogenismo es una de las características diagnósticas principales del SOPQ y se manifiesta clínicamente como hirsutismo, acné y AAG [65].

El hirsutismo en las mujeres es el exceso de pelo corporal terminal con distribución masculina, en el abdomen inferior , la línea alba, la zona periareolar, el mentón y el labio superior. Afecta al 5% - 10% de las mujeres premenopáusicas y la mayoría de los casos son secundarios al SOPQ [66]. La actividad de la enzima 5-alfa reductasa está aumentada en los folículos pilosos y es estimulada por los andrógenos, el IGF y la insulina para  convertir la testosterona a dihidrotestosterona, estimulando el crecimiento capilar [65].

Los diagnósticos  diferenciales incluyen, entre otros, la hipertricosis, medicamentos como los glucocorticoides o la ciclosporina, la hiperplasia suprarrenal congénita, el síndrome de Cushing, los tumores secretores de andrógenos y la disfunción tiroidea [68]. El tratamiento comprende modificaciones de los hábitos de vida (hábitos alimentarios, ejercicio y descenso de peso) y tratamientos mecánicos y médicos [69]. El empleo de blanqueadores, la afeitada, la depilación con cera y la depilación con láser son útiles, pero pueden ser dolorosos y caros.

El tratamiento médico comprende los anticonceptivos orales, los agonistas de la hormona liberadora de gonadotropina, los fármacos que sensibilizan a la insulina, como la metformina o los que tienen efectos antiandrogénicos, como el acetato de ciproterona, la eflornitina y la espironolactona [69, 70].

El acné es otra característica de la resistencia a la insulina-hiperandrogenemia en el SPQO y coexiste en el 15-25% de las mujeres con SPQO [71]. Las pacientes con acné con frecuencia tienen aumento de la glucemia y de la insulina, así como resistencia a la insulina [72].

En pacientes con acné vulgar, la desnutrina, también llamada lipasa adiposa de  triglicéridos, está baja y se relaciona con los valores de insulina y HOMA-IR [73].

El aspecto del acné es el de lesiones inflamatorias en la zona mandibular, el cuello, el pecho y la parte superior de la espalda. El tratamiento consiste en cambios de los hábitos de vida, como la nutrición y el ejercicio. Se demostró que un pequeño descenso de peso (2-5%) es beneficioso [75, 76].

El tratamiento tópico es con retinoides y benzoil peróxido. Otros tratamientos son sistémicos, con anticonceptivos orales (acetato de ciproterona o drospirenona), espironolactona y antibióticos (minociclina, doxiciclina, azitromicina) y en determinados casos resistentes, isotretinoína [76].


CONCLUSIÓN

La resistencia a la insulina es una característica bioquímica patognomónica de la obesidad y la diabetes. Es uno de los mecanismos de base fisiopatológicos de la diabetes y aparece años antes de su diagnóstico. El diagnóstico preciso de la resistencia a la insulina es complejo e invasivo. Las mediciones y los índices de laboratorio son imprecisos y poco fiables.

Las manifestaciones cutáneas de la resistencia a la insulina, en cambio, ofrecen una manera fiable y fácil de detectarla. Los médicos siempre deben recordar que los trastornos cutáneos de la resistencia a la insulina podrían reflejar un desequilibrio metabólico subyacente que pone al paciente en riesgo de sufrir diabetes si es que ya no la padece. Al mismo tiempo, los profesionales no sólo los deben reconocer, sino evaluar el estado metabólico del paciente y, de ser necesario, aconsejarle con respecto a cambios en sus hábitos de vida, como alimentación saludable, ejercicio, evitar el tabaquismo y descenso de peso.

 

NOTA: Ud muede consultar en trabajo original completo y bibliografía en la mencionada revista

 

 

Do parasitic worms help keep arteries young?Fecha: 5/8/2017

 

Do parasitic worms help keep arteries young?

 

                                                                   Dr. M.Gurven; H. Kaplan;R.C Thompson et al.
                                                                                University of California, Santa Barbara

Researchers from the University of New Mexico; the Institute for Advanced Study in Toulouse, France; and the Horus Project are coauthors of the work

                                                                                       Lancet (2017); 389:1730-39 (summary)

 

Among an indigenous group of people in the Amazon region of Bolivia, atherosclerosis is practically nonexistent, whereas it's a common fact of life for most Americans over 60. It's a complicated comparison,.The Tsimane have the lowest reported prevalence of atherosclerosis than any population recorded to date.
Atherosclerosis is a disease in which plaque-composed of fat, cholesterol, calcium, and other substances-builds up inside the arteries. Over time, the plaque hardens and can impede blood flow. When the buildup occurs, plaque can rupture and blood clots form in a coronary artery, leading to a heart attack-or worse.
Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden.
Researchers measured the participants' risk of heart disease using non-invasive chest CT scans of 705 adults over age 40. They measured the extent of coronary atherosclerosis by computing the coronary artery calcification (CAC) score, which has been shown to be a reliable predictor of heart attacks and other cardiovascular events. Based on the CAC scores, 85 percent had no risk of heart disease, 13 percent had low risk, and only 3 percent had moderate or high risk. Consistent with this low overall risk of coronary atherosclerosis, heart rate, blood pressure, cholesterol, and blood glucose also were low. And these findings extend into old age. Sixty-five percent of 80-year-old Tsimane had almost no risk and only 8 percent had moderate risk.
By comparison, the United States-based Multi-Ethnic Study of Atherosclerosis, which included 6,814 people ages 45 to 84, found that only 14 percent of Americans had no risk of heart disease and a whopping 50 percent had a moderate or high risk-a five-fold higher prevalence than in the Tsimane population.
Tsimane men and women also showed similar risk, while CAC scores in the US and elsewhere are two to four times higher in men than women. Based on the comparison with the US study, an 80-year-old Tsimane has the same arterial age as an American in his or her mid-50s. 

Two reasons why

The Tsimane have minimal smoking, and they have no trans fat, and little saturated fat in their diets. They eat a lot of carbs, but they aren't processed or refined. They're mostly fiber-rich crops from their fields. They're also active physically-not vigorously running marathons, but they are rarely sedentary. In combination, these factors put the Tsimane at lower levels of heart disease risk. Tis just proof that if Americans lived a more Paleo-friendly lifestyle atherosclerosis would be the exception for us as well?
Two aspects of Tsimane health are difficult to reconcile with their minimal atherosclerosis,Their 'good cholesterol'-or HDL-is really low. Low enough to be classified as high-risk for most Tsimane. The second point has to do with inflammation, which, has been implicated in all stages of atherosclerosis, Tsimane have elevated levels of inflammation, no matter which biomarker of inflammation we examine. Chronically elevated levels of low-grade inflammation have been consistently associated with atherosclerosis and its clinical manifestations in most studies.The fact that the same people have been sampled multiple times throughout their longitudinal Tsimane Health and Life History study demonstrates that the inflammation experienced by Tsimane is a chronic condition. Tsimane do suffer from acute infections, but inflammation is still relatively high even among those without active infections, and levels are consistent over time,.

Worms and inflammation

So why might elevated inflammation not place the Tsimane at higher risk for coronary artery disease? That leads to the role of intestinal helminths (worms) in heart disease,assessed in a review paper in the journal Evolution, Medicine and Public Health, this study show that among the Tsimane, people with worms have lower cholesterol and higher energy expenditures. Worms may also help modulate and regulate immune function. And that is where opportunities for building new understanding can arise.
There is some novelty here. In the poly-infected Tsimane world, most have helminthes, distinct gut microbiota and other infections. The initiation and progression of atherosclerosis, from lesion and atheroma development to plaque rupture, all involve inflammatory immune responses."

Parasites are part of the story

The interesting possibility is that worms-perhaps in combination with other types of infections-might promote anti-inflammatory activity that protects against inflammation. Or they might help regulate immune function in ways that make inflammation less destructive to Tsimane arteries than it is for us.
Among Tsimane, the source of elevated inflammation is different than the chronic low-grade inflammation that affects Americans. Our inflammation isn't coming from infection, for the most part,  It's 'sterile'-that is, it comes from smoking and obesity. But that's not what we're seeing with the Tsimane."
Parasites are part of the story of Tsimane lives, and so should be considered in combination with more conventional risk factors like diet, smoking, and activity, .

Figuring out the relative contributions of the risk factors in isolation, and in combination, is the complicated part. It's hard to know whether there are threshold levels. Some experts believe, for example, that if your LDL cholesterol is so low [e.g. <70 mg/dL], there's nothing to oxidize and build up in the arteries, and so it might not matter how sedentary you are. But without taking statins, there is probably no way a sedentary American eating a typical diet will ever get their LDL that low. Recommendations concerning "healthy" cholesterol levels and the point at which statins become an appropriate course of action have changed, Even the levels typically recommended as being desirable [<100 mg/dL] are still a lot higher than those observed among Tsimane and other subsistence populations.
At the beginning of our longitudinal study, the average Tsimane LDL was 72 mg/dL,but now it's higher-91 mg/dL-as Tsimane lifestyles have begun to change. Disentangling how the mix of risk factors and exposures now shifting over the life course will impact heart disease risk in the coming years is a critical next step."

 

 

 

 

 

 

Síndrome HellpFecha: 1/7/2017

 

 

Síndrome HELLP

Artículo de REVISIÖN

 

Dr.Paulino Vigil-De Gracia (Departamento de Ginecología y Obstetricia. Complejo Hospitalario-Panama)
Dr. Arnulfo Arias Madrid    (Caja de Seguro Social-Panmá)

                                                                                               Ginecol Obstet Mex 2015;83:48-57.

 

RESUMEN

El trastorno hipertensivo del embarazo es una de las complicaciones más frecuentes de éste y una de las expresiones más serias de esta enfermedad es el síndrome HELLP. Éste se distingue por el trastorno hipertensivo más las triada: hemólisis microangiopática, elevación de enzimas hepáticas y disminución del conteo de plaquetas.
Las pacientes con síndrome HELLP tienen mayor riesgo de complicaciones maternas, como: hemorragia cerebral, desprendimiento de retina, hematomarotura hepática, insuficiencia renal aguda, coagulación intravascular diseminada, desprendimiento de placenta y, en algunas ocasiones, muerte materna. Se recomienda la identificación de hallazgos de síndrome HELLP en pacientes con trastorno hipertensivo del embarazo. La principal confusión clínica del síndrome HELLP es el hígado graso agudo del embarazo; sin embargo, existen parámetros que ayudan a su correcta identificación.
 El síndrome HELLP implica la interrupción del embarazo a corto plazo; la administración de corticoides no produce efectos favorables en la morbilidad y mortalidad materna, pero puede elevar la concentración de plaquetas, disminuir la necesidad de transfusión y acortar la estancia hospitalaria. Gran parte de la disminución de la morbilidad y mortalidad materna asociada con los trastornos hipertensivos del embarazo consiste en establecer el diagnóstico adecuado y el correcto tratamiento del síndrome HELLP

INTRODUCCION

Los trastornos o alteraciones hipertensivas del embarazo son un grupo de complicaciones asociadas con la gestación y se dividen en cuatro subgrupos, según sus características particulares.(1,2)
 La preeclampsia y eclampsia se observan con una frecuencia de entre 2 a 10% de todos los embarazos.(1-4) Además, es una de las tres principales causas de muerte materna en todo el mundo, y la segunda en Latinoamérica.(4). Se estima que en todo el mundo cada año fallecen 50,000 mujeres por causas relacionadas con la hipertensión; desafortunadamente, entre 95 y 97% de esas muertes ocurren en países de bajo ingreso per cápita.(5) La preeclampsia y eclampsia afectan a la madre y a su hijo, de hecho la preeclampsia es una de las principales causas de prematuridad y mortalidad neonatal. Estas son las principales razones por las que esta complicación es objeto de múltiples estudios y de educación médica continuada.
El síndrome HELLP es una complicación de los trastornos hipertensivos del embarazo, principalmente observado en pacientes con preeclampsia severa y eclampsia; sin embargo, puede diagnosticarse en pacientes con preeclampsia agregada y en mujeres con hipertensión gestacional (preeclampsia sin proteinuria).
Esta revisión describe los principales conceptos asociados con la patogénesis, diagnóstico y tratamiento del síndrome HELLP.

Definición
 
Para establecer el diagnóstico se requiere, primero: identificar algún trastorno hipertensivo del embarazo y, después, la triada necesaria para establecer el síndrome HELLP: hemólisis, elevación de las enzimas hepáticas y trombocitopenia.
       a) Hemólisis: es lo más característico en estas pacientes y se demuestra por la alteración de la morfología del glóbulo rojo documentado en un frotis de sangre periférica (esquisto citos, células en plato, células diana, etc.), elevación de la deshidrogenasa láctica sérica ≥ 600 U/L, bilirrubinas totales ≥ 1.2 mg/dL, descenso de la hemoglobina y hematócrito, y de la hepatoglobina sérica.
      b) Elevación de enzimas hepáticas: aspartato transaminasa ≥ 70 U/L, alanina transferasa ≥ 50 U/L y deshidrogenasa láctica sérica ≥ 600 U/L. No existe un consenso relacionado con las concentraciones mencionadas(6-10), por lo que se recomienda utilizar como valores normales los que se establecen en el laboratorio de cada hospital. Si los valores de las pacientes están por encima de los aceptados en la entidad y coexisten los otros dos criterios, deberá documentarse este síndrome.
      c) Disminución del conteo de plaquetas: definido como(7,10):
            #  HELLP clase-tipo 1 cuando el conteo plaquetario es ≤ 50,000/UL
            #  HELLP clase-tipo 2, con concentraciones de plaquetas entre 50,000 y 100,000/UL
            #  HELLP clase-tipo 3, cuando las plaquetas se encuentran entre 100,000 y 150,000/ UL. Otros autores sugieren que el síndrome HELLP requiere una concentración inferior a 100,000 plaquetas/UL.7(9-12).
La propuesta de Sibai y colaboradores (9,12) (aún no aceptada ampliamente) plantea que si una paciente no cumple con los tres criterios, deberá definirse como HELLP parcial (12) o síndrome ELLP (12) (sin hemólisis).
Nosotros somos partidarios de utilizar la clasificación de Mississippi (8) porque se ajusta más a los conceptos fisiológicos conocidos por los médicos. Por ejemplo, si una paciente tiene elevación de las enzimas hepáticas, hemólisis y plaquetas en 110,000 U/L, no podemos considerar que se trata de HELLP parcial; para la clasificación de Martin y sus colaboradores (8) y aceptada por nosotros, esta paciente tiene HELLP clase-tipo 3.

Fisiopatología

 El mecanismo exacto de la alteración biológica o fisiológica en pacientes con síndrome HELLP no ha sido claramente definido.
La inadecuada tolerancia inmunitaria resulta en alteración a la invasión trofoblástica fetal, y ocurre en el primer trimestre del embarazo. Esto conduce a la aberrante función placentaria con isquemia y producción de sustancias aún no identificadas. Finalmente, se produce vasoconstricción generalizada, formación de microtrombos en los vasos pequeños, se reduce el volumen plasmático y, por lo tanto, se altera el flujo plasmático en órganos y tejidos. Las alteraciones fisiopatológicas del síndrome HELLP implican la triada: invasión anormal del trofoblasto, mala adaptación-función placentaria y alteración vascular materna generalizada. Este fenómeno se observa en las pacientes con preeclampsia y, principalmente, en mujeres con síndrome HELLP.(13)
La placenta es un factor predisponente para padecer preeclampsia-síndrome HELLP, y se ha observado mayor expresión genética placentaria en pacientes con síndrome HELLP. Buimer y colaboradoes (14) sugieren que los hallazgos de genes hacen pensar que el síndrome HELLP es una alteración diferente, pero se requieren más estudios para confirmar o descartar esta aseveración. Además, hace poco se observó que la frecuencia alélica y portadora del polimorfismo BclI de los receptores genéticos de glucocorticoides fue significantemente mayor en pacientes con síndrome HELLP, en comparación con pacientes sanas o con preeclampsia severa.(15) Los signos del síndrome HELLP (hipertensión, proteinuria, elevación de enzimas hepáticas y hemólisis) pueden explicarse por la actividad inflamatoria sistémica que afecta la disfunción de las células endoteliales maternas. La hipertensión con vasoespasmos y alteración endotelial provoca la formación de microtrombos en los pequeños vasos, agregación placentaria y necrosis periportal o focal del parénquima de los hepatocitos.(7,8,10) Otra característica importante del síndrome HELLP es lo heterogéneo del flujo sanguíneo en los pequeños vasos. El flujo heterogéneo afecta mucho más la oxigenación del tejido, que aquel flujo reducido pero homogéneo. Cornette y sus colaboradores (16) estudiaron la perfusión en la microcirculación de pacientes embarazadas sanas, con preeclampsia severa y con síndrome HELLP, y demostraron con técnicas modernas que la microcirculación sublingual no se encuentra alterada en pacientes con embarazos normales o con preeclampsia severa; sin embargo, en quienes tienen síndrome HELLP se altera la perfusión capilar. Hallazgos clínicos Las pacientes con síndrome HELLP pueden tener los mismos signos y síntomas que las que padecen preeclampsia-eclampsia; sin embargo, también pueden encontrarse diferentes hallazgos clínicos a los que casi siempre se manifiestan en esta enfermedad. Los síntomas más frecuentes son: cefalea, dolor en el cuadrante superior derecho o epigastralgia, y náusea o vómito en 30 a 90% de los casos. (6,8,10,12,17) El síntoma más frecuente y orientador en pacientes con síndrome HELLP es la epigastralgia, razón por la que se aconseja al clínico que ante el hallazgo de preeclampsia-eclampsia con epigastralgia se descarte este síndrome. La epigastralgia se ha explicado por la distensión de la cápsula hepática, nosotros descartamos totalmente esta explicación (11,18) pues no todas las pacientes con epigastralgia tienen hematoma hepático o edema que distienda la cápsula del hígado; de hecho, en hallazgos de resonancia y tomografía no se demuestra la lesión en esta zona (11,17) Quizá el dolor se asocie directamente con la hemólisis e isquemia en los sinusoides hepáticos. (9 )Los trastornos visuales y auditivos, la hematuria y los sangrados por sitios de punción o encías aparecen, incluso, en 30% de los casos. (9,10) En nuestra opinión, la hematuria es un signo característico en pacientes con síndrome HELLP clase 1 (severo).(10) En casos excepcionales se ha observado hematuria en pacientes con preeclampsia-eclampsia, pero no es síndrome HELLP. Obviamente, primero se descartan los traumatismos en la vejiga por la colocación de sondas vesicales, o lesiones durante el parto y la cesárea. En cuanto al grado de hipertensión, aunque cerca de 90% de los casos la padecen, ésta puede ser leve en 15 a 50%, (6,7,10) y estar ausente en 10% (10,12,13) de las pacientes con el síndrome

Cuadro 1. Características patológicas, de laboratorio, síntomas y complicaciones en pacientes con síndrome HELLP

Hallazgos patológicos

a) Trofoblasto 1. Invasión anormal del trofoblasto.
                          2. Mala adaptación-función placentaria.
                          3. Alteración vascular materna generalizada.
 b) Vascular     1. Vasoconstricción generalizada con vasoespasmos.
                          2. Formación de microtrombos en los vasos pequeños (lesión endotelial          depósitos de fibrina y agregación de plaquetas).
                          3. Disminución del volumen plasmático.

Hallazgos de laboratorio, , síntomas y signos

a)      Lesión vascular: hemólisis microangiopática (elevación de la deshidrogenasa láctica sérica, aumento de bilirrubinas, alteración de la morfología del glóbulo rojo).
b) Lesión hepática: elevación de enzimas hepáticas (aspartato transaminasa, alanina transferasa, deshidrogenasa láctica sérica).
c) Alteración hematológica: disminución de las plaquetas.
d) Síntomas y signos:, cefalea, alteraciones visuales y auditivas, epigastralgia, hematuria, náuseas, vómito, hemorragias.

Complicaciones

Hematomas y hemorragia cerebral, desprendimiento de retina, hematoma hepático, insuficiencia renal, coagulación intravascular diseminada, desprendimiento de placenta, muerte perinatal o materna, o ambas.

Diagnóstico diferencial

Las pacientes con preeclampsia-eclampsia manifiestan síntomas y signos particulares. Estos hallazgos clínicos pueden aparecer en mujeres con síndrome HELLP; sin embargo, existen otras complicaciones obstétricas que pueden provocar síntomas y signos similares. Además, cerca de 10% de las pacientes con síndrome HELLP pueden no sufrir hipertensión o manifestar hipertensión muy leve, además de tener complicaciones respiratorias, hematológicas o gastrointestinales, lo que erróneamente puede llevar al clínico a sospechar alguna alteración distinta a la preeclampsia-eclampsia. Entre las alteraciones distintas a la pre-eclampsia deberá descartarse el hígado graso agudo del embarazo (19), púrpura trombocitopénica idiopática, síndrome urémico hemolítico, lupus eritematoso sistémico, síndrome antifosfolipídico, colelitiasis, pancreatitis aguda, entre otras.(9) El trastorno que genera más confusión es el hígado graso agudo del embarazo; sin embargo, en el síndrome HELLP es poco probable la hipoglucemia, hipocolesterolemia e hipotrigliceridemia (19,20) Además, las náuseas, el vómito e ictericia son frecuentes en pacientes con hígado graso agudo del embarazo.(20)

Resultados maternos y perinatales

La preeclampsia-eclampsia se distinguen por el alto riesgo de morbilidad, mortalidad materna y perinatal, en pacientes con síndrome HELLP aumenta la posibilidad de estas complicaciones.
La mortalidad materna se reporta en 1% (11,12,17) y las complicaciones médicas son más comunes en este síndrome; por ejemplo, la insuficiencia renal puede aparecer en 10% de las pacientes  (10,13), edema agudo de pulmón9 y coagulación intravascular diseminada entre 5 y 15% (10,12,17), desprendimiento de placenta en 10% (9,10), septicemia, hematomas de la herida quirúrgica, choque hipovolémico, desprendimiento de retina (21) y rotura hepática (18) Además, es común la transfusión de sangre y sus derivados en pacientes con síndrome HELLP (9,10,12,17). Estas complicaciones varían según la población estudiada y los criterios para definir el síndrome HELLP y la complicación asociada.
La mortalidad perinatal varía según la población analizada; sin embargo, puede alcanzar 20% (10,17).  Por ahora no se ha documentado que la mortalidad perinatal aumente debido al síndrome HELLP, pues depende de la edad gestacional, al igual que ocurre en la preeclampsia y eclampsia (17,22), obviamente, a mayor prematuridad es más alto el riesgo de complicaciones y los trastornos hipertensivos del embarazo son causa frecuente de prematuridad. La mortalidad perinatal más alta se observa en pacientes con embarazo menor de 28 semanas, en quienes además sufren restricción del crecimiento intrauterino o desprendimiento de placenta (22).

 Tratamiento

Las pacientes con sospecha de síndrome HELLP deben hospitalizarse inmediatamente para una evaluación minuciosa por parte de médicos experimentados en este diagnóstico. La salud de estas pacientes puede deteriorarse rápidamente, con gran afectación materna y fetal. Las pacientes con preeclampsia severa y sospecha de síndrome HELLP deben tratarse con protocolo de preeclampsia severa, confirmar o descartar el síndrome y evaluar todos los diagnósticos diferenciales. El tratamiento de la paciente embarazada con síndrome HELLP difiere poco del protocolo de la paciente con preeclampsia severa sin el síndrome (17). Estas pacientes requieren tratamiento antihipertensivo para la hipertensión severa, además de sulfato de magnesio para evitar y tratar las convulsiones, al igual que la paciente con preeclampsia severa. La curación definitiva de la enfermedad es la interrupción del embarazo. Entre las variaciones del tratamiento se encuentran:

Sulfato de magnesio: con la sospecha y el diagnóstico, estas pacientes deben recibir 4 a 6 g de sulfato de magnesio por vía intravenosa, diluido según la concentración de preparación del medicamento. Cuando la concentración es de 10%, la dilución de los 4 g puede ser en 50 a 100 cc de lactato ringer o dextrosa en agua al 5%, transfundido en un lapso de 10 a 20 minutos. Después, se mantiene una dosis continua de 1 a 2 g cada hora, hasta por 24 horas posterior al nacimiento (2)

 Antihipertensivos: los medicamentos para las crisis hipertensivas (hipertensión severa) son hidralazina, labetalol o nifedipino (2 )Se decide iniciar el tratamiento cuando la tensión sistólica es ≥ 160 mmHg o la diastólica ≥ 110 mmHg. El objetivo es mantener la tensión diastólica entre 90 y 100 mmHg, pues las tensiones más bajas representan riesgo materno y fetal.

Hhidralazina: se prescribe a dosis de 5 mg por vía intravenosa cada 15 a 20 minutos y se repite si es necesario por tres a cinco veces; cuando no se obtiene efecto satisfactorio con hidralazina se recomienda labetalola dosis de 20 mg por vía intravenosa y si no hay disminución adecuada de la tensión arterial se duplica la dosis después de 10 a 20 minutos y, de ser necesario, esta última dosis se puede repetir tres veces cada 10 a 20 minutos. Cuando no hay hidralazina ni labetalol se recurre al nifedipino por vía sublingual u oral a dosis de 10 mg cada 15 minutos durante cinco dosis (1,2)

Corticoides: para maduración fetal: está bien establecido que los corticoides prenatales reducen la morbilidad y mortalidad neonatal en pacientes con preeclampsia severa antes de las 34 semanas (23). Con embarazo entre 24 y 34 semanas es importante iniciar los corticoides para maduración fetal. Las dosis de corticoides para maduración fetal son: betametasona 12 mg cada 24 horas (dos dosis) o dexametasona 6 mg cada 12 horas (cuatro dosis).

Probablemente, ante la sospecha o confirmación del síndrome HELLP, la terminación del embarazo pueda ocurrir entre 24 a 48 horas, según la concentración de plaquetas. Tratamiento conservador o expectante: el curso clínico de las pacientes con este síndrome es impredecible y suele evolucionar rápidamente hacia daño materno y fetal. Por esta razón, diferentes autores consideran la interrupción del embarazo al confirmar el diagnóstico (6,24) Algunas series de casos han descrito el tratamiento expectante en pacientes con síndrome HELLP (25-27) y sugieren resultados transitorios en los estudios de laboratorio de las pacientes, lo que permite la prolongación del embarazo por algunos días. Sin embargo, los resultados perinatales no son mejores que los de igual edad gestacional, en quienes no recibieron tratamiento conservador o expectante; además, no hay investigaciones aleatorizadas que comprueben tal ventaja. En nuestra opinión, toda paciente con sospecha o diagnóstico de síndrome HELLP y edad gestacional entre 24 y 34 semanas, debe recibir corticoesteroides para lograr las ventajas fetales satisfactorias y terminar el embarazo. En pacientes con síndrome HELLP clase-tipo 1 y 2, la interrupción deberá realizarse lo antes posible; sin embargo, en los casos de HELLP leve (clase-tipo 3) puede ser un poco más conservador o expectante hasta alcanzar el máximo beneficio de los corticoides. Hasta que las nuevas evidencias lo demuestren, principalmente investigaciones clínicas aleatorizadas, no se justifica prescribir tratamiento conservador o expectante a pacientes con diagnóstico de síndrome HELLP.

Corticoides para el tratamiento de síndrome HELLP: los corticoides, específicamente la dexametasona y betametasona, se han sugerido para el alivio de pacientes con síndrome HELLP (28-34). Desafortunadamente existe diferencia en la metodología, tiempo de administración, gravedad del síndrome HELLP y fármaco prescrito en estos estudios. Los resultados de investigaciones clínicas aleatorizadas (31-34) muestran resultados satisfactorios en las pruebas de laboratorio y diuresis, pero no se observan diferencias en las morbilidades maternas más severas. Un estudio realizado en Cali, Colombia, publicado en 2005 (35) muestra resultados contradictorios en las investigaciones anteriores y sugiere no prescribir corticoides en esta enfermedad, aunque un análisis más detallado parece justificar su prescripción en pacientes con síndrome HELLP clase-tipo 1 o severo. Los resultados de esta investigación (35) los han cuestionado otros investigadores (36-38).
 Los resultados del grupo Cochrane (39) demuestran que no se disminuye la morbilidad y mortalidad materna ni perinatal con corticoides en dosis altas para pacientes con síndrome HELLP; sin embargo, sugieren recuperación más rápida de las plaquetas, menos tiempo de hospitalización y plantean la necesidad de más investigaciones en mujeres con síndrome HELLP tipo 1. Similar a los hallazgos de Cochrane, otras revisiones (40,41) concluyen que es necesaria la prescripción de corticoides en esta enfermedad, sobre todo por la disminución en la estancia hospitalaria y menos transfusiones de sangre y sus derivados. Nuestros resultados (29,32) coinciden con estas revisiones y, por lo tanto, consideramos que deben prescribirse corticoides a dosis altas en pacientes con síndrome HELLP clase-tipo 1 y 2. No existen reportes de efectos secundarios con estas dosis (28-35), pero se han reportado menos transfusiones sanguíneas y disminución de la estancia hospitalaria.
Un hallazgo importante (29) es la prescripción simultánea de plaquetas y corticoides en pacientes con síndrome HELLP severo (clase 1). Nuestros hallazgos (29) muestran que la transfusión de plaquetas y corticoides no es superior al protocolo único de corticoides; por lo tanto, es posible prescribir corticoides a dosis altas y no transfundir concentrados de plaquetas, sólo con base en el conteo de plaquetas.
Evidentemente estos hallazgos necesitan su comprobación a través de investigaciones aleatorizadas y controladas. La dosis de dexametasona recomendada es de 10 mg por vía intravenosa o intramuscular cada 12 horas (tres dosis). Se refiere a "dosis alta", en vista de que la dosis para maduración fetal es de 6 mg.  A pesar de las investigaciones existentes se necesitan pruebas clínicas aleatorizadas, con una muestra adecuada para responder algunas interrogantes y aclarar otras.

Interrupción del embarazo: las pacientes con síndrome HELLP y edad gestacional superior a 34 semanas o menos de 24 deberán interrumpir el embarazo lo antes posible cuando se confirme el diagnóstico.
En las pacientes con 24 a 34 semanas de embarazo deberá considerarse la prescripción de corticoides para maduración fetal y, de ser posible, la interrupción después de recibir el fármaco. En las pacientes con edad gestacional superior a 34 semanas no deberá esperarse más tiempo; por el contrario, las complicaciones maternas y fetales pueden ser peores. En casos de menos de 24 semanas no hay evidencia que sugiera que la no interrupción mejore el resultado perinatal y contrariamente el riesgo materno es mayor, de hecho la mortalidad perinatal en este grupo de edad gestacional llega a ser de 90%.9
El diagnóstico de síndrome HELLP no es sinónimo de cesárea ni de interrupción inmediata del embarazo (9,17) La interrupción inmediatamente después de establecer el diagnóstico y efectuar la cesárea puede ser peor para la madre y el feto.
Definitivamente deben individualizarse los casos, pero la decisión de cesárea se asocia con la edad gestacional, condiciones fetales, labor de parto y condiciones cervicales o índice de Bishop. Sibai (9) recomienda la cesárea electiva en pacientes con síndrome HELLP con edad gestacional menor de 30 semanas, que no se encuentren en labor de parto y con índice de Bishop desfavorable. Nosotros compartimos y aplicamos esta recomendación y, a la vez, sugerimos dicha conducta. Además del síndrome y oligoamnios, restricción del crecimiento fetal, o ambos, sin labor de parto o cambios cervicales favorables sugerimos la cesárea.
En otras condiciones, la cesárea debe realizarse sólo por indicaciones obstétricas, por ejemplo: en caso de afectación fetal, presentación pélvica, cesárea anterior, entre otras.
 En las pacientes con síndrome HELLP y embarazo menor de 24 semanas debe interrumpirse el embarazo. La decisión de parto o cesárea está determinada por el bienestar materno. Si la condición materna y la labor de parto, o los cambios cervicales permiten la evolución rápida del parto, éste deberá ser la vía de terminación del embarazo. Prescripción de analgésicos y anestesia: pueden prescribirse dosis bajas de opioides sistémicos durante la labor de parto para aliviar el dolor (9) Podrán indicarse anestésicos locales en caso de hacer episiotomía o haber laceraciones vaginales que ameritan sutura. Los bloqueos pudendos están contraindicados en pacientes con preeclampsia-eclampsia.
En caso de cesárea se sugiere anestesia general, sobre todo en pacientes con síndrome HELLP 1 y en casos donde está contraindicada la anestesia regional (por ejemplo, en pacientes con coagulación intravascular diseminada). No hay consenso ni investigaciones que demuestren que el bloqueo regional (anestesia raquídea o epidural) esté contraindicado en estas pacientes; sin embargo, por el riesgo teórico no se administra en pacientes con síndrome HELLP severo. En Panamá (42) una investigación demostró que las pacientes con síndrome HELLP severo recibieron bloqueo regional y no tuvieron complicaciones. Otros investigadores (43) no encontraron complicaciones con este tipo de anestesia, que es inocua en pacientes obstétricas y en quienes sufren síndrome HELLP. Es posible que las investigaciones clínicas aleatoriazadas ayuden a resolver este dilema; sin embargo, es difícil realizar estos estudios. Un estudio anterior (44) comprueba que la peor complicación de los trastornos hipertensivos del embarazo es el síndrome HELLP. Este síndrome representa mayor posibilidad de complicaciones y muerte materna, incluso superior a la eclampsia, por lo que se sugiere cambiar el paradigma de eclampsia e insistir en la importancia del diagnóstico y tratamiento del síndrome HELLP (44,45)
Recientemente hicimos un estudio en 14 maternidades en Latino América (en publicación) donde analizamos durante un año a las pacientes con eclampsia. En ese periodo hubo 115,000 nacimientos y 196 casos de eclampsia. De estas últimas 54 tuvieron síndrome HELLP (27.5%). Del total de pacientes con eclampsia, 8 (4%) fallecieron. En esos 8 fallecimientos se encontró síndrome HELLP y un análisis multivariable demuestró que los dos factores directamente asociados con la mortalidad son la baja concentración de plaquetas (debido al síndrome HELLP) y las crisis hipertensivas.

CONCLUSIONES

El síndrome HELLP es una complicación que aparece en 15% de los trastornos hipertensivos del embarazo. Se distingue por la triada de hemólisis microangiopática, elevación de enzimas hepáticas y trombocitopenia. Aún se desconoce el mecanismo fisiopatológico que explique por qué las pacientes con preeclampsia-eclampsia evolucionan a síndrome HELLP. El síndrome pone en riesgo a la madre, debido a las altas posibilidades de complicaciones, como: hemorragia cerebral, insuficiencia renal, ruptura hepática y mayor posibilidad de muerte asociada con eclampsia, principalmente cuando coexiste hipertensión severa. La prescripción de corticoides para disminuir la morbilidad y mortalidad materna o neonatal no ha demostrado su eficacia e inocuidad. Su protocolo consiste en la interrupción del embarazo y tratamiento de las complicaciones asociadas

REFERENCIAS

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2. Federación Latinoamericana de Sociedades de Obstetricia y Ginecollogía. Módulo de Capacitación en Pre-eclampsia/ eclampsia. Guía clínica. 2012: Noviembre. [en línea]. Dirección URL: . [Consulta: junio, 2014].
3. Witlin AG, Sibai BM. Hypertension. Clin Obstet Gynecol 1998;41:533-544.
4. Say L, Chou D, Gemmill A, Tunçalp Ö, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014;2:e323-332.
5. Villar J, Say L, Shennan A, Lindheimer M, et al. Methodological and technical issues related to the diagnosis, screening, prevention, and treatment of preeclampsia and eclampsia. Int J Gynaecol Obstet 2004;85:S28-41.
6. Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982;142:159-167.
7. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol 1990;162:311-316.
8. Martin JN, Blake PG, Perry KG, McCaul JF, et al. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Obstet Gynecol 1991;164:1500-1513.
9. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;103:981-991.
10. Vigil-De Gracia P. Pregnancy complicated by preeclampsiaeclampsia with HELLP syndrome. Int J Obstet Gynecol 2001;72:17-23.
11. Vigil-De Gracia P, Tenorio-Marañón RF, Cejudo-Caranza E, Helguera-Martinez A, García-Cáceres E. Diferencias entre preeclampsia, síndrome de HELLP y eclampsia: Evaluación materna. Ginecol Obstet Mex 1996;64:337-382.
12. Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996;175:460-464.
13. Abildgaard U, Heimdal K. Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review. Eur J Obst Gynecol Rep Biol 2013;166:117-123.
14. Buimer M, Keijser R, Jebbink JM, Wehkamp D, van Kampen, et al. Seven placental transcripts characterize HELLPsyndrome. Placenta 2008;29:444-453.
15. Bertalan R, Patocs A, Nagy B, Derzsy Z, et al. Overrepresentation of BclI polymorphism of the glucocorticoid receptor gene in pregnant women with HELLP syndrome. Clin Chim Acta 2009;405:148-152.
16. Cornette J, Herzog E, Buijs EAB, Duvekot JJ, et al. Microcirculation in women with severe preeclampsia and HELLP syndrome: a case-control study. BJOG 2014;121(3):363-370.
17. Martin JN, Rinehart B, May WL, Magann EF, et al. The spectrum of severe preeclampsia: comparative analysis by HELLP syndrome classification. Am J Obstet Gynecol 1999;180:1373-1384.
18. Vigil-De Gracia P, Ortega Paz L. Preeclampsia/eclampsia and hepatic rupture. Int J Gynecol Obstet 2012:118:186-189.
19. Vigil-De Gracia P. Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders. Int J Gynecol Obstet 2001;73:215-220.
20. Vigil-De Gracia P, Montufar-Rueda C. Acute fatty liver of pregnancy: diagnosis, treatment, and outcome based on 35 consecutive cases. J Matern Fetal Neonatal Med 2011;24:1143-46.
21. Vigil-De Gracia, Ortega-Paz L. Retinal detachment in association with preeclampsia, eclampsia, and HELLP synrome. Int J Gynecol Obstet 2011:114(3):223-225.
22. Abramovici D, Friedman SA, Mercer BM, Audibert F, et al. Neonatal outcome in severe preeclampsia at 24 to 36 weeks' gestation: does HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter? Am J Obstet Gynecol 1999;180:221-225.
23. Amorium MMR, Santas LC, Faundes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am J Obstet Gynecol 1999;180:1283-1288.
24. Rath W, Loos W, Kuhn W, Graeff H. The importance of early laboratory screening methods for maternal and fetal outcome in cases of HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 1990;36:43-51.
25. Van Pampus MG, Wolf H, Ilsen A, Treffers PE. Maternal outcome following temporizing management of the HELLP syndrome. Hypertens Pregnancy 2000;19:211-220.
26. Visser W, Wallenburg HCS. Temporising management of severe preeclampsia with and without the HELLP syndrome. Br J Obstet Gynecol 1995;102:111-117.
27. MacKenna J, Dover NL, Brame RG. Preeclampsia associated with hemolysis, elevated liver enzymes, and low platelets: an Obstet emergency? Obstet Gynecol 1983;62:751-754.
28. Martin JN, Thigsen BD, Rose CH, Cushman J, et al. Maternal benefit of high-dose intravenous corticosteroids therapy for HELLP. Am J Obstet Gynecol 2003;189:830-834.
29. Vigil-De Gracia P. Addition of platelet transfusions to corticosteroids does not increase the recovery of severe HELLP syndrome. Eur J Obstet Gynecol Rep Biol 2006;128:194-198.
30. Magann EF, Bass D, Cahuhan SP, Sullivan, Martin JN. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). AM J Obstet Gynecol 1994;171:1148-1153.
31. Magann EF, Perry KG, Meydrech EF, Harris RL, et al. Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;17:1154-1158.
32. Vigil-De Gracia P, García-Cáceres E. Dexamethasone in the postpartum treatment of HELLP syndrome. Int J Gynaecol Obstet 1997;59:217-221.
33. Yalcin OT, SEner T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int J Gynaecol Obstet 1998;61:141-148.
34. Isler CM, Barrilleaux PS, Magann EF, Bass D, Martin JN. A prospective, randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP syndrome. Am J Obstet Gynecol 2001;184:1332-1339.
35. Fonseca JE, Mendez F, Catano C, Arias F. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a double blind, placebo controlled, randomized clinical trial. Am J Obstet Gynecol 2005;1591- 1598.
36. -Tita A, Patrick R. Corticosteroids and HELLP. Am J Obstet Gyneco 2006;195:e7.
37. Vigil-De Gracia P. Dexamethasone treatment and HELLP syndrome. Am J Obstet Gynecol 2006;195:e10.
38. O´Brien J. Dexamethasone, HELLP syndrome, and study design. Am J Obstet Gynecol 2006;195:e13.
39. Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy. Cochrane Database Syst Rev 2010;8:CD008148.
40. Clenney TL, Viera AJ. Corticosteroids for HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome. BMJ 2004;329:270-272.
41. Martin JN, Rose CH, Briery CM. Understanding and managing HELLP syndrome: the integral role of aggressive glucocorticoids for mother and child. Am J Obstet Gynecol 2006;195:914-34.
42. Vigil-De Gracia, Silva S, Montufar C, Carrol I, De Los Rios S. Anesthesia in pregnan women with HELLP syndrome. Int J Gynecol Obstet 2001;74:23-27.
43. Guzmán J, Echevarría G, Kuzmanic G, Storaker M, et al. Síndrome de HELLP: Implicaciones anestésicas. Rev Chilena anestesia 2005;34.
44. Vigil-De Gracia P. Maternal deaths due to eclampsia and HELLP syndrome. Int J Obstet Gynecol 2009;104:90-94.
45. Martin JN, Owens MY, Keiser SD, Parrish MR, et al. Standardized Mississippi protocol treatment of 190 patients with HELLP syndrome: Slowing disease progression and preventing new major maternal morbidity. Hyperten Pregnancy 2012:31:79-90.

 

 

Quality Control and Operator Training at Point at Point of Care TestingFecha: 4/6/2017

 

 

Quality Control and Operator Training at Point-of-Care Testing

A College of American Pathologists Q-Probes Study of 106 Institutions

 

Kathryn S. Dyhdalo, MD; Peter J. Howanitz, MD; David S. Wilkinson, MD, PhD; Rhona J. Souers, MS; Bruce A. Jones, MD


Context.-Operator training, quality control, and proper follow-up for out-of-range quality control (QC) events are crucial steps that must be adequately performed and documented to ensure excellent patient care and regulatory compliance.

Objective.-To examine point-of-care testing (POCT) personnel training and QC documentation/compliance.  Design.-Participants in a POCT documentation study of the College of American Pathologists Q-Probes program collected data retrospectively for glucose and urine dipstick testing regarding test operators, operator competency assessment, and QC documentation. Documentation was assessed for participant adherence to 4 quality indicators: (1) whether test operator training was up to date, (2) whether the test operator names were noted in the test records, (3) whether QC was performed, and (4) whether out-of-range QC events were followed up. Data were analyzed for associations with institutional demographic and practice variables.

Results.-The institutional median number of POCT personnel was 648 for blood glucose and 76 for urine dipstick testing, with a median number of 105 948 glucose tests and 9113 urine tests performed. Ninety-four percent (3830 of 4074) of the test operators completed training or competency assessment within the prior 12 months, 96.8% (21 603 of 22 317) of the test records documented the operator, and 95.7% (19 632 of 20 514) of the expected QC events (per institutional regulations) were documented.  Approximately 3% (659 of 20 514) of the QC events were outside the designated range (an average of 6 out-ofrange QC events were identified per institution [n¼ 106]).  Of the out-of-range QC events, 92.6% (610 of 659) had documentation of appropriate follow-up. Most laboratories (176 of 179; 98.3%) violated specimen requirements by storing POCT urine specimens for less than 24 hours.  Conclusions.-There was greater than 90% compliance for POCT documentation and nearly 96% of expected QC events were properly documented.

(Arch Pathol Lab Med. 2014;138:1444-1448; doi: 10.5858/arpa.2013-0552-CP)

 

 

Point-of-care testing (POCT) is defined as testing that occurs at or near the site of patient care, with the goal of providing rapid information and improving patient outcomes.1,2 Point-of-care testing is growing several times faster than is central laboratory testing in the United States2,3 and has become ubiquitous in both hospitals and outpatient care settings. Because POCT is typically performed by nonlaboratory personnel, many health care workers are now performing a wide variety of tests. Quality patient care is dependent on accurate laboratory results, necessitating assurance that POCT is well documented, equipment is well maintained, and testing operators are qualified to perform the tests. It is also important to ensure that quality control (QC) procedures are run consistently and that documentation of QC performance and follow-up of out-of-range QC results are recorded to ensure accurate results and high-quality patient care. Additionally, POCT is subject to regulatory requirements that, if ignored, can lead to loss of accreditation.4 The College of American Pathologists (CAP) POCT accreditation checklist requires that (1) POCT instruments have defined QC ranges, (2) QC results are evaluated daily, (3) corrective action is taken when results exceed defined tolerance limits, and (4) QC results are verified before patient results are reported.5 A complete POCT program includes organization, supervision, written procedures, operator training and competency, instrument evaluation, quality control, proficiency testing, and appropriate recording of result and notification, all with the necessary documentation. However, achieving compliance with regulatory guidelines and ensuring the quality of POCT has proved challenging in many institutions.

 In the authors' experience, performance of traditional QC is a misunderstood and undervalued concept for many nonlaboratory personnel because they are largely unfamiliar with laboratory operations, standards, and limitations.

Although proficiency testing provides a periodic audit of testing accuracy, periodic audits of testing documentation can provide valuable information regarding the operational performance of the POCT program. The CAP Q-Probes program administers voluntary quality improvement studies that provide valuable information regarding current practice patterns and opportunities for improvement in anatomic and clinical pathology. We report the results of a Q-Probes study that examined POCT personnel training, proficiency testing, and QC documentation compliance.

MATERIALS AND METHODS

Participants voluntarily enrolled in the CAP Q-Probes program for documentation of POC testing; data collection instructions were distributed in 2008. Participants collected data in 2 parts: (1) a retrospective review of records (test logs, patient charts, or other documentation that showed testing had been performed) for glucose testing and urine reagent strip (dipstick) testing; and (2) a retrospective review of QC documentation for glucose testing and urine dipstick testing. Point-of-care testing from outpatient, inpatient, and emergency department settings was included.  Excluded events included POCT performed by physicians and testing performed on POCT instruments in the laboratory.  In the first part of the study, participants retrospectively reviewed consecutive testing documentation for glucose and urine reagent strip (dipstick) tests from up to 3 locations until 25 different operators were identified. If fewer than 25 operators were identified after a maximum of 500 consecutive records were reviewed, the participant recorded the number of unique operators identified.  From those documents, participants recorded the total number of consecutive records reviewed and the number of records with no documentation about the testing personnel. Participants also determined the total number of unique operators for each test, the number of test operators per testing location (emergency department, outpatient clinic, or inpatient ward), and the total number of operators who had training or competency assessment in the prior 12 months. In each testing location, the number of operators with documented training or competency assessment for each test was also recorded.

The second part of the study involved a retrospective review of QC documentation from glucose and urine dipstick testing from 2 testing sites for 1 month. If only one site was available for each test, 2 months of information was reviewed. If there was only one site but 2 instruments were used for a test, then documentation for both instruments was recorded for 1 month. For each site, participants recorded the total number of QC events that should have occurred (according to institutional policy), the number of times QC was not recorded when it should have been (according to institutional policy), the number of times QC was outside the acceptable range, and, when the QC was outside the acceptable range, the number of times an appropriate response or action was documented (according to institutional policy).  Four quality indicators were determined: (1) percentage of test operators with documentation of current training and/or competency assessment, (2) percentage of test records with documentation of test operator name, (3) percentage of documented QC events, and (4) percentage of out-of-range QC events with documentation on the follow-up action taken.  The overall quality indicators and the test-specific quality indicators were analyzed for associations with institutional demographics and practice characteristics. Initially, the indicator distributions were tested for normality, and results from all 4 indicators had severely skewed distributions. Those nonnormal distributions required rank-based analyses for the preliminary tests and log transformations for the multivariate regression analyses.  Individual associations between the indicators and the demographic and practice variables were investigated using Kruskal-Wallis tests for discrete-valued, independent variables and regression analysis for continuous, independent variables. Variables with significant associations (P , .10) were then introduced into a forward-selection, multivariate, regression model. A P value less than .05 was considered statistically significant.  In addition, the Wilcoxon signed rank test was used to analyze the pairwise differences between the glucose testing and urine testing documentation rates. The significance level of P , .05 was also used for this testing. All analyses were performed with SAS 9.1 statistical software (SAS Institute, Cary, North Carolina).

RESULTS

Participants from 106 institutions submitted data for analysis. Most of the 106 institutions (96.2%; n ¼ 102) were located in the United States, with the remaining located in Saudi Arabia (1.9%; n ¼ 2), Bermuda (0.9%; n ¼ 1), and Spain (0.9%; n ¼ 1). Of the participating institutions, 34.2% (26 of 76) were teaching hospitals, and 21.0% (17 of 81) had a pathology residency program. Within the prior 2 years, the CAP inspected 85.2% (69 of 81) of these laboratories.  Laboratory inspections were conducted by the Joint Commission at approximately 33.3% (27 of 81) of these institutions within the prior 2 years. Participant demographic information is summarized in Table 1.

Table 2 summarizes the volumes of point-of-care tests for blood glucose and urine reagent strip, the number of testing personnel, the number of personnel responsible for POCT oversight, and the percentage of personnel types (nursing or laboratory personnel) responsible for testing.

The distributions of the quality indicators for this study are summarized in Table 3. Participants from 106 institutions reviewed 22 317 POC test records from inpatient, outpatient, and emergency department settings. A total of 94.0% (3830 of 4074) of the test operators had completed training or competency assessment within the previous 12 months, and 96.8% (21 603 of 22 317) of the glucose and urine reagent strip test records had documentation of the name of the individual who performed the test. The average number of test records reviewed per institution was 219. For all institutions combined, the overall number of test operators monitored was 4074 with an average of 40 test operators monitored per institution.

Participants identified a total of 20 514 QC events that should have occurred (per institutional regulations) for glucose and urine reagent strip testing, with an average of 195 QC events per institution. Documentation of those QC events was identified for 95.7% (19 632 of 20 514) of those expected QC events. Of the 20 514 events, approximately 3% (n ¼ 659) were outside the designated range, with an average of 6 out-of-range QC events identified per institution. Of the out-of-range QC results, 92.6% (610 of 659, with 75 institutions reporting) had documentation of appropriate follow-up action per institutional policy. A statistically significant association (P ¼ .01) was found between higher percentages of out-of-range QC events that had documentation of follow-up action and institutions with a higher percentage of laboratory personnel responsible for POC testing, as summarized in Table 4.

Data were analyzed to determine whether the documentation rates differed significantly between the urine tests and the glucose tests (Table 5). There was significantly lower compliance in documentation of the test operator and documentation of QC events for point-of-care urinalysis (P , .001) as compared with glucose testing. The widespread use of computerized data-management systems for pointof-care glucose testing may account for those differences (Table 6). Institutions with CAP inspections (n ¼ 42; 40%)

during the prior 2 years had significantly higher test
operator documentation rates for urine testing (Kruskal-

Wallis; P ¼ .01). The 42 CAP-inspected institutions had documentation rates ranging from 50% to 100%; the 10 institutions without a recent CAP inspection had documentation rates ranging from 28% to 100%.

COMMENTS

The institution performance patterns are similar. Approximately one quarter of participants (19 of 75) were less than 90% compliant for documentation of follow-up for out-ofrange QC events and 9% of these laboratories (7 of 75) had less than 50% compliance. Approximately 10% of laboratories (14 of 106) were less than 90% compliant for documentation of test operator and documentation of QC events (11 of 105 institutions) (Table 3).

The median participating institution performed almost 12 times the number of POCT glucose tests (n ¼ 105 948) as urine reagent strip tests (n ¼ 9113), with almost 9 times the number of individuals performing the tests (glucose, 648; urine, 76). Most participating institutions (75 of 105; 71.4%) had one or more full-time equivalent employees dedicated to the oversight of POCT. Most of the individuals performing POCT were nursing department personnel (Table 2). Although overall compliance for follow-up action taken for out-of-range QC events was good (92.6% [610 of 659] of all such events), institutions reporting that more than 10% of individuals performing POCT were laboratory personnel exhibited a small, but statistically significant advantage in compliance (mean of 98.6% versus 95.4%) (Table 4).

Although overall compliance in documentation of followup for out-of-range QC events was greater than 90%, it is concerning that 10% of laboratories reported less than 50% compliance (Table 3).

The underlying etiologies are likely institution specific, and any proposed solutions would depend on root cause analysis and are perhaps best left to each individual institution. Investigations should address the adequacy of POCT oversight; provide education regarding the importance of QC for both regulatory compliance and patient care; establish institutional policy and training of both POCT personnel and supervisors; ensure competency in POCT instrumentation, software, and design regarding QC; and monitor QC performance and compliance, as well as any other variables that may affect the POCT program at an institution. Some authors2,6 have suggested solutions such as increased oversight by a dedicated POCT supervisor, improved or reeducation of POCT personnel, and enhanced QC design features, such as instrument locks in the event of a QC failure.

Some differences were noted between documentation for blood glucose testing and urinalysis. In particular, point-ofcare urinalysis testing has significantly lower compliance in the rate of documentation of the test operator and the percentage of documented QC events. It is likely that data management system technology for POCT blood glucose testing, interfaced with the laboratory information system, facilitates compliance for those aspects of documentation.  Most respondents use a computerized data management system for their point-of-care blood glucose testing, and most of these are interfaced with a laboratory information system (Table 6).

Nearly 96% (19 632 of 20 514) of expected QC events (per institutional guidelines) were properly documented. This is an improvement from previous Q-Probes studies,7,8 which showed a 90% documentation rate. The increased focus on POCT by various regulatory agencies likely has a role in those improved compliance rates.9 Close attention and adherence to POCT glucose QC procedures is important because a positive relationship exists between the performance of QC testing and the accuracy of point-of-care glucose values.8 Although accurate POCT glucose values are important for patient care, patient outcomes related to the quality of POCT results are difficult to quantitate.10 According to the Centers for Medicare and Medicaid Services, competency assessment of POCT personnel requires 6 procedures, which include monitoring the recording and reporting of test results (1 of 6) and review of the test results and QC records (2 of 6).11 The CAP Laboratory Accreditation Program general checklist12 requires that urine specimens be retained for 24 hours, without specifying the location of testing. However, the current practice for most participating institutions (143 of 179; 79.9%) is to discard point-of-care urine specimens immediately after initial testing (Table 7). This is likely due to the lack of a written policy addressing that issue in most institutions (written policy in 33 of 178 [18.5%] respondents; (Table 7). Most laboratories appear to apply a different standard of care for their point-of-care urine testing versus urine testing performed in the rolex cellini date fake watches central laboratory. Each institution should reassess its current practice, standardize its practice, and develop a uniform written policy that is compliant with current regulatory guidelines.

The continuing growth of POCT, coupled with its presence in a variety of clinical settings, ensures that it will continue to be both an area of regulatory focus and a focal point in the struggle to comply with strict regulatory guidelines. The involvement of a variety of nonlaboratory personnel introduces both an additional challenge and an opportunity for education about good laboratory testing practices. Although many institutions are appropriately documenting POCT-associated events most of the time, improvements should still be actively pursued to continue to ensure both patient safety and high-quality patient care.

   

 

References

 

1.  Howanitz PJ, Jones BA; College of American Pathologists. Comparative analytical costs of central laboratory glucose and bedside glucose testing: a College of American Pathologists Q-probes study. Arch Pathol Lab Med. 2004;128(7):739-745.

2.  Kost GJ. Preventing medical errors in point-of-care testing: security, validation, safeguards, and connectivity. Arch Pathol Lab Med. 2001;125(10):1307-1315.

3.  Bowman C, Hamill T. Assuring quality in point-of-care testing. Arch Pathol Lab Med. 2012;136(5):472-473.

4.  Centers for Medicare & Medicaid Services, Department of Health and Human Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Regist. 1992;57(40):7139-7186. Codified at 42 CFR §49342 CFR Part 493. h t t p : / /www.gpo.gov/fdsys/pkg/CFR-2003- t itle42-vol3/xml/ CFR-2003-title42-vol3-part493.xml. Accessed July 25, 2013.

5.  College of American Pathologists. Point-of-Care-Testing Checklist. Northfield, IL: College of American Pathologists; 2013.

6.  Lewandrowski K, Gregory K, Macmillan D. Assuring quality in point-ofcare testing: evolution of technologies, informatics, and program management.  Arch Pathol Lab Med. 2011;135(11):1405-1414.

7.  Jones BA, Howanitz PJ. Bedside glucose monitoring quality control practices: a College of American Pathologists Q-Probes study of program quality control documentation, program characteristics, and accuracy performance in 544 institutions. Arch Pathol Lab Med. 1996;120(4):339-345.

8.  Novis DA, Jones BA. Interinstitutional comparison of bedside blood glucose monitoring program characteristics, accuracy performance, and quality control documentation: a College of American Pathologists Q-probes study of bedside blood glucose monitoring performed in 226 small hospitals. Arch Pathol Lab Med. 1998;122(6):495-502.

9.  Belanger AC. Alternate site testing: the regulatory perspective. Arch Pathol Lab Med. 1995;119(10):902-906.

10.       Howanitz PJ, Jones BA. Bedside glucose monitoring: comparison of performance as studied by the College of American Pathologists Q-Probes program. Arch Pathol Lab Med. 1996;120:333-338.

11.       Centers for Medicare & Medicaid Services. What do I need to do to assess personnel competency? http://www.cms.gov/Regulations-and-Guidance/ Legislation/CLIA/Downloads/CLIA_CompBrochure_508.pdf. Published November 2012. Accessed August 21, 2013.

12.       College of American Pathologists. GEN.20377: record/specimen retention. In: Laboratory General Checklist. Northfield, IL: College of American Pathologists; 2013; v072913

 

 

Angioplastia-Troponina: busqueda de trabajos 2015-2016Fecha: 1/5/2017

 


1. Circulation. 2016 Jun 7;133(23):2235-42. doi: 10.1161/CIRCULATIONAHA.116.021700. Epub 2016 May 5.
Electrophysiological Effects of Selective Atrial Coronary Artery Occlusion inHumans.
Álvarez-García J(1), Vives-Borrás M(2), Gomis P(2), Ordoñez-Llanos J(2),Ferrero-Gregori A(2), Serra-Peñaranda A(2), Cinca J(2).
Author information: (1)From Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB-SantPau,Universidad Autónoma de Barcelona, Spain (J.A.-G., M.V.-B., A.F.-G., A.S.-P.,J.C.); Department ESAII, EUETIB, Universidad Politécnica de Cataluña, Barcelona, Spain (P.G.); and Biochemistry and Molecular Biology Department, Hospital de laSanta Creu i Sant Pau, IIB-SantPau, Universidad Autónoma de Barcelona, Spain(J.O.-L.). jalvarezg@santpau.cat. (2)From Cardiology Department, Hospital de laSanta Creu i Sant Pau, IIB-SantPau, Universidad Autónoma de Barcelona, Spain(J.A.-G., M.V.-B., A.F.-G., A.S.-P., J.C.); Department ESAII, EUETIB, UniversidadPolitécnica de Cataluña, Barcelona, Spain (P.G.); and Biochemistry and Molecular Biology Department, Hospital de la Santa Creu i Sant Pau, IIB-SantPau,Universidad Autónoma de Barcelona, Spain (J.O.-L.).
BACKGROUND: The arrhythmogenesis of ventricular myocardial ischemia has beenextensively studied, but models of atrial ischemia in humans are lacking. Thisstudy aimed at describing the electrophysiological alterations induced by acuteatrial ischemia secondary to atrial coronary branch occlusion during electivecoronary angioplasty.METHODS AND RESULTS: Clinical data, 12-lead ECG, 12-hour Holter recordings,coronary angiography, and serial plasma levels of high-sensitivity troponin T andmidregional proatrial natriuretic peptide were prospectively analyzed in 109patients undergoing elective angioplasty of right or circumflex coronaryarteries. Atrial coronary branches were identified and after the procedurepatients were allocated into two groups: atrial branch occlusion (ABO, n=17) and atrial branch patency (non-ABO, n=92). In comparison with the non-ABO, patientswith ABO showed: (1) higher incidence of periprocedural myocardial infarction(20% versus 53%, P=0.01); (2) more frequent intra-atrial conduction delay (19%versus 46%, P=0.03); (3) more marked PR segment deviation in the Holterrecordings; and (4) higher incidence of atrial tachycardia (15% versus 41%,P=0.02) and atrial fibrillation (0% versus 12%, P=0.03). After adjustment by apropensity score, ABO was an independent predictor of periprocedural infarction(odds ratio, 3.4; 95% confidence interval, 1.01-11.6, P<0.05) and atrialarrhythmias (odds ratio, 5.1; 95% confidence interval, 1.2-20.5, P=0.02).CONCLUSIONS: Selective atrial coronary artery occlusion during electivepercutaneous transluminal coronary angioplasty is associated with myocardialischemic damage, atrial arrhythmias, and intra-atrial conduction delay. Our data suggest that atrial ischemic episodes might be considered as a potential cause ofatrial fibrillation in patients with chronic coronary artery disease.
© 2016 American Heart Association, Inc.
DOI: 10.1161/CIRCULATIONAHA.116.021700 PMID: 27151531  [PubMed - indexed for MEDLINE]

2. Arq Bras Cardiol. 2016 Apr;106(4):304-10. doi: 10.5935/abc.20160029. Epub 2016Mar 8.
Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test.
[Article in English, Portuguese]
Vaz HA(1), Vanz AP(1), Castro I(1).
Author information: (1)Fundação Universitária de Cardiologia, Instituto de Cardiologia, Porto Alegre,RS, Brazil.
BACKGROUND: The kinetics of high-sensitivity troponin T (hscTnT) release shouldbe studied in different situations, including functional tests with transientischemic abnormalities.OBJECTIVE: To evaluate the release of hscTnT by serial measurements afterexercise testing (ET), and to correlate hscTnT elevations with abnormalitiessuggestive of ischemia.METHODS: Patients with acute ST-segment elevation myocardial infarction (STEMI)undergoing primary angioplasty were referred for ET 3 months after infarction.Blood samples were collected to measure basal hscTnT immediately before (TnT0h), 2 (TnT2h), 5 (TnT5h), and 8 hours (TnT8h) after ET. The outcomes were peakhscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC) for hscTnT levels. Log-transformation was performed on hscTnT values, andcomparisons were assessed with the geometric mean ratio, along with their 95%confidence intervals. Statistical significance was assessed by analysis ofcovariance with no adjustment, and then, adjusted for TnT0h, age and sex,followed by additional variables (metabolic equivalents, maximum heart rateachieved, anterior wall STEMI, and creatinine clearance).RESULTS: This study included 95 patients. The highest geometric means wereobserved at 5 hours (TnT5h). After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002), 59% (p = 0.003) and 45% (p = 0.003) higher, respectively,in patients with an abnormal ET as compared to those with normal tests.CONCLUSION: Higher elevations of hscTnT may occur after an abnormal ET ascompared to a normal ET in patients with STEMI.
DOI: 10.5935/abc.20160029 PMCID: PMC4845703PMID: 26959404  [PubMed - in process]

3. Microvasc Res. 2016 May;105:34-9. doi: 10.1016/j.mvr.2015.12.010. Epub 2015 Dec22.
Endothelial dysfunction evaluated by peripheral arterial tonometry is relatedwith peak TnI values in patients with ST elevation myocardial infarction treated with primary angioplasty.
Baptista SB(1), Faustino M(2), Simões J(3), Nédio M(3), Monteiro C(3), LourençoE(3), Leal P(3), Farto eAbreu P(3), Gil V(3).
Author information: (1)Cardiology Department, Hospital Fernando Fonseca, Amadora, Portugal.Electronic address: sergio.b.baptista@gmail.com. (2)Cardiology Department,Hospital Fernando Fonseca, Amadora, Portugal. Electronic address:marianafaustino85@gmail.com. (3)Cardiology Department, Hospital Fernando Fonseca,Amadora, Portugal.
PURPOSE: The role of endothelial-dependent function in patients with acute STelevation myocardial infarction (STEMI) is not clear. Endothelial dysfunction maycontribute to the pathophysiological processes occurring after STEMI andinfluence the extension of myocardial necrosis. Endothelial-dependent dysfunctionevaluated by peripheral arterial tonometry (PAT) has already showed to becorrelated with microvascular coronary endothelial dysfunction. Our purpose wasto evaluate the impact of endothelial dysfunction on peak Troponin I (TnI)values, as a surrogate for the extension of myocardial infarction, in patientswith STEMI treated with primary angioplasty (P-PCI).METHODS: 58 patients with STEMI treated with P-PCI (mean age 59.0 ± 14.0 years,46 males) were included. Endothelial function was assessed by reactive hyperaemiaindex (RHI) determined by PAT. Patients were divided in two groups according tothe previously reported RHI threshold for high risk (1.67). The extension ofmyocardial necrosis was evaluated by peak TnI levels.RESULTS: RHI median value was 1.78 (IQR0.74);25 patients had endothelialdysfunction (RHI b 1.67). The two groups had no significant differences in age,gender, main risk factors and pain-to-balloon time. Patients with an RHI b 1.67had significant larger infarcts: TnI 73.5 ng/mL (IQR 114.42 ng/mL) versus TnI33.2 ng/mL (IQR 65.2 ng/mL); p = 0.028. On multivariate analysis, the presence ofan RHI b 1.67 kept significant impact on TnI peak values (p=0.02).CONCLUSIONS: The presence of endothelial-dependent dysfunction, assessed by PAT, is related with higher peak TnI values in STEMI patients treated with P-PCI.These results strength the possibility that endothelial-dependent dysfunction maybe a marker of poor prognosis and eventually a therapeutic target in patientswith STEMI.
DOI: 10.1016/j.mvr.2015.12.010 PMID: 26721522  [PubMed - indexed for MEDLINE]

4. J Cardiovasc Magn Reson. 2015 Dec 1;17:106. doi: 10.1186/s12968-015-0197-y.
Distal coronary embolization following acute myocardial infarction increasesearly infarct size and late left ventricular wall thinning in a porcine model.
Thomas RM(1,)(2), Lim SY(3,)(4,)(5), Qiang B(6,)(7), Osherov AB(8,)(9), GhugreNR(10,)(11), Noyan H(12,)(13), Qi X(14), Wolff R(15,)(16), Ladouceur-WodzakM(17), Berk TA(18), Butany J(19,)(20), Husain M(21,)(22), WrightGA(23,)(24,)(25), Strauss BH(26,)(27).
Author information: (1)Schulich Heart Centre, Sunnybrook Health Sciences Center, 2075 Bayview Avenue,Room D-406, Toronto, ON, M4N 3M5, Canada. reuben.thomas@mail.utoronto.ca.(2)University of Toronto, Toronto, Canada. reuben.thomas@mail.utoronto.ca.(3)Schulich Heart Centre, Sunnybrook Health Sciences Center, 2075 Bayview Avenue,Room D-406, Toronto, ON, M4N 3M5, Canada. vnlover@hanmail.net. (4)University ofToronto, Toronto, Canada. vnlover@hanmail.net. (5)Korea University AnsanHospital, Ansan, Korea. vnlover@hanmail.net. (6)Schulich Heart Centre, SunnybrookHealth Sciences Center, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5,Canada. beipingqiang@yahoo.com. (7)University of Toronto, Toronto, Canada.beipingqiang@yahoo.com. (8)Schulich Heart Centre, Sunnybrook Health SciencesCenter, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada.uziosherov@yahoo.com. (9)Barzilai Medical Centre, Ashkelon, Israel.uziosherov@yahoo.com. (10)Physical Sciences Platform, Sunnybrook ResearchInstitute, Sunnybrook Health Sciences Centre, Toronto, Canada. nghugre@gmail.com.(11)University of Toronto, Toronto, Canada. nghugre@gmail.com. (12)TorontoGeneral Research Institute, Toronto, Canada. h.noyanashraf@utoronto.ca.(13)University of Toronto, Toronto, Canada. h.noyanashraf@utoronto.ca.(14)Physical Sciences Platform, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada. xiuling.qi@sri.utoronto.ca. (15)Schulich Heart Centre, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Room D-406,Toronto, ON, M4N 3M5, Canada. wolffdr@hotmail.com. (16)University of Toronto,Toronto, Canada. wolffdr@hotmail.com. (17)Schulich Heart Centre, SunnybrookHealth Sciences Center, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5,Canada. michelle.rose21@gmail.com. (18)Schulich Heart Centre, Sunnybrook HealthSciences Center, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada.toviberk@gmail.com. (19)Department of Pathology, University Health Network,Toronto, Canada. Jagdish.Butany@uhn.ca. (20)University of Toronto, Toronto,Canada. Jagdish.Butany@uhn.ca. (21)Toronto General Research Institute, Toronto,Canada. Mansoor.Husain@uhn.ca. (22)University of Toronto, Toronto, Canada.Mansoor.Husain@uhn.ca. (23)Schulich Heart Centre, Sunnybrook Health SciencesCenter, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada.gawright@sri.utoronto.ca. (24)Physical Sciences Platform, Sunnybrook ResearchInstitute, Sunnybrook Health Sciences Centre, Toronto, Canada.gawright@sri.utoronto.ca. (25)University of Toronto, Toronto, Canada.gawright@sri.utoronto.ca. (26)Schulich Heart Centre, Sunnybrook Health SciencesCenter, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada.bradley.strauss@sunnybrook.ca. (27)University of Toronto, Toronto, Canada.bradley.strauss@sunnybrook.ca.
BACKGROUND: Distal coronary embolization (DCE) of thrombotic material occursfrequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size andmyocardial function remains unsettled. The aims of this study were to evaluatethe effects of DCE sufficient to cause no-reflow on infarct size, cardiacfunction and ventricular remodeling in a porcine acute myocardial infarctionmodel.METHODS AND RESULTS: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion andinjection of either microthrombi (prepared from autologous porcine blood)sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificedat 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascularmagnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) andsurvival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size(CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences ininfarct size, ventricular volume or ejection fraction between the two groups,although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning(percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03)were significantly increased in the DCE group.CONCLUSIONS: DCE increased early infarct size, but without affecting laterinfarct size, cardiac function or ventricular volumes. The significance of thelater remodelling changes (ventricular thinning and transmurality) following DCE,possibly due to changes in MMP-2 activity and Akt activation, merits furtherstudy.
DOI: 10.1186/s12968-015-0197-y PMCID: PMC4666124PMID: 26620277  [PubMed - indexed for MEDLINE]

5. Am J Cardiol. 2015 Nov 1;116(9):1334-9. doi: 10.1016/j.amjcard.2015.07.061. Epub 2015 Aug 14.
Comparison of Changes in Global Longitudinal Peak Systolic Strain AfterST-Segment Elevation Myocardial Infarction in Patients With Versus WithoutDiabetes Mellitus.
Hoogslag GE(1), Abou R(1), Joyce E(1), Boden H(1), Kamperidis V(1), Regeer MV(1),van Rosendael PJ(1), Schalij MJ(1), Bax JJ(1), Marsan NA(1), Delgado V(2).
Author information: (1)Department of Cardiology, Leiden University Medical Center, Leiden, TheNetherlands. (2)Department of Cardiology, Leiden University Medical Center,Leiden, The Netherlands. Electronic address: v.delgado@lumc.nl.
Global longitudinal strain (GLS) measured by 2-dimensional longitudinalspeckle-tracking echocardiography may be a more sensitive measure of leftventricular (LV) mechanics than conventional LV ejection fraction (EF) tocharacterize adverse post-ST-segment elevation myocardial infarction (STEMI)remodeling. The aim of the present evaluation was to compare changes in LV GLS inpatients with versus without diabetes after the first STEMI. Patients with first STEMI and diabetes (n = 143; age 64 ± 12 years; 68% men; 50% left anteriordescending artery as culprit vessel) and 290 patients with first STEMI andwithout diabetes matched on age, gender, and infarct location were included. LVvolumes and function and 2-dimensional LV GLS were measured after primarypercutaneous coronary intervention (baseline) and at 6-month follow-up. Atbaseline, patients with and without diabetes had similar LVEF (46.8 ± 0.7% vs48.0 ± 0.5%, p = 0.19) and infarct size (peak cardiac troponin T: 3.1 [1.2 to6.5] vs 3.7 [1.3 to 7.3] μg/l, p = 0.10; peak creatine phosphokinase:1,120 [537to 2,371] vs 1,291 [586 to 2,613] U/l, p = 0.17), whereas LV GLS wassignificantly more impaired in diabetic patients (-13.7 ± 0.3% vs -15.3 ± 0.2%, p<0.001). Although diabetic patients showed an improvement in LVEF over timesimilar to nondiabetic patients (52.0 ± 0.8% vs 53.1 ± 0.6%, p = 0.25), GLSremained more impaired at 6-month follow-up compared with nondiabetic patients(-15.8 ± 0.3% vs -17.3 ± 0.2%, p <0.001). After adjusting for clinical andechocardiographic characteristics, diabetes was independently associated withchanges in GLS from baseline to 6-month follow-up (β 1.41, 95% confidenceinterval 0.85 to 1.96, p <0.001). In conclusion, after STEMI, diabetic patientsshow more impaired LV GLS at both baseline and follow-up compared with a matched group of patients without diabetes, despite having similar infarct size and LVEF at baseline and follow-up.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.amjcard.2015.07.061 PMID: 26341185  [PubMed - indexed for MEDLINE]

6. JAMA Intern Med. 2015 May;175(5):821-6. doi: 10.1001/jamainternmed.2014.8307.
Familial spontaneous coronary artery dissection: evidence for geneticsusceptibility.
Goel K(1), Tweet M(1), Olson TM(2), Maleszewski JJ(3), Gulati R(1), Hayes SN(1).
Author information: (1)Division of Cardiovascular Diseases, Department of Internal Medicine, MayoClinic College of Medicine, Rochester, Minnesota. (2)Division of CardiovascularDiseases, Department of Internal Medicine, Mayo Clinic College of Medicine,Rochester, Minnesota2Division of Pediatric Cardiology, Department of Pediatricand Adolescent Medicine, Mayo Clinic, Rochester, Minnesota. (3)Division ofAnatomic Pathology, Mayo Clinic, Rochester, Minnesota.
Comment in    JAMA Intern Med. 2015 Oct;175(10):1721-2.    JAMA Intern Med. 2015 Oct;175(10):1721.
IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is a major cause ofacute coronary syndrome in young women, especially among those withouttraditional cardiovascular risk factors. Prior efforts to study SCAD have beenhampered by underrecognition and lack of registry-based studies. Risk factors andpathogenesis remain largely undefined, and inheritability has not been reported.OBSERVATIONS: Using novel research methods, patient champions, and social media, the Mayo Clinic SCAD Registry has been able to better characterize thiscondition, which was previously considered rare. Of 412 patient enrollees, weidentified 5 familial cases of SCAD comprising affected mother-daughter,identical twin sister, sister, aunt-niece, and first-cousin pairs, implicatingboth recessive and dominant modes of inheritance. The mother-daughter pair alsoreported fatal myocardial infarction in 3 maternal relatives. None of theparticipants had other potential risk factors for SCAD, including connectivetissue disorders or peripartum status.CONCLUSIONS AND RELEVANCE: To our knowledge, this series is the first to identifya familial association in SCAD suggesting a genetic predisposition. Recognitionof SCAD as a heritable disorder has implications for at-risk family members andfurthers our understanding of the pathogenesis of this complex disease.Whole-exome sequencing provides a unique opportunity to identify the molecularunderpinnings of SCAD susceptibility.
DOI: 10.1001/jamainternmed.2014.8307 PMID: 25798899  [PubMed - indexed for MEDLINE]

7. Gut Liver. 2014 Nov;8(6):674-9. doi: 10.5009/gnl13301. Epub 2014 Nov 15.
Endoscopic retrograde cholangiopancreatography in patients with previous acutecoronary syndrome.
Koh HR(1), Park CH(1), Chung MW(1), Park SY(1), Hong YJ(1), Jeong MH(1), KimHS(1), Choi SK(1), Rew JS(1).
Author information: (1)Department of Internal Medicine, Chonnam National University Medical School,Gwangju, Korea.
BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) isconsidered a high-risk procedure in patients with previous acute coronarysyndrome (ACS); however, clinical studies are rare in the literature. The aim of this study was to investigate the safety and efficacy of ERCP in patients withprevious ACS.METHODS: We retrospectively reviewed the medical records of patients withprevious ACS who underwent ERCP between January 2007 and August 2012. Theclinical characteristics, ERCP diagnoses, treatment results, and complicationswere analyzed.RESULTS: Fifty patients underwent ERCP an average of 41.6 months after ACS. Themost common indication for ERCP was calculous cholangitis. After deep biliarycannulation, endoscopic sphincterotomy, biliary stone removal and endoscopicbiliary drainage were successfully performed. Immediate postsphincterotomybleeding occurred in seven patients, which was successfully controlled usingendoscopic therapy. Elevation of cardiac troponin I levels were observed in threepatients (6%) before ERCP, and all of these patients were diagnosed withpancreatobiliary disease combined with recurrent ACS, which was treated withcoronary artery stent insertion (n=2) and balloon angioplasty (n=1).CONCLUSIONS: Therapeutic ERCP is effective and safe in patients with previousACS. Cardiac troponin I elevation should be considered a warning sign forrecurrent ACS in patients who undergo ERCP.
DOI: 10.5009/gnl13301 PMCID: PMC4215456PMID: 25368756  [PubMed - indexed for MEDLINE]

8. Heart Vessels. 2016 Jan;31(1):88-95. doi: 10.1007/s00380-014-0589-1. Epub 2014Oct 16.
Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevationmyocardial infarction.
Ekeløf SV(1), Halladin NL(2), Jensen SE(3), Zaremba T(3), Aarøe J(3), KjærgaardB(4), Simonsen CW(5), Rosenberg J(2), Gögenur I(2).
Author information: (1)Department of Surgery, Herlev Hospital, Centre for Perioperative Optimization,University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.sarahekeloef@gmail.com. (2)Department of Surgery, Herlev Hospital, Centre forPerioperative Optimization, University of Copenhagen, Herlev Ringvej 75, 2730,Herlev, Denmark. (3)Department of Cardiology, Aalborg University Hospital,Hobrovej 18, 9000, Aalborg, Denmark. (4)Department of Cardiothoracic Surgery,Aalborg University Hospital, Hobrovej 18, 9000, Aalborg, Denmark. (5)Departmentof Diagnostic Imaging, Aalborg University Hospital, Hobrovej 18, 9000, Aalborg,Denmark.
Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment anunavoidable consequence of the procedure. Oxidative stress is central in thedevelopment of ischemia-reperfusion injury. Melatonin, an endogenous hormone,acts through antioxidant mechanisms and could potentially minimize the myocardialinjury. The aim of the experimental study was to examine the cardioprotectiveeffects of melatonin in a porcine closed-chest reperfused infarction model. Atotal of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL)melatonin or placebo (saline). The intervention was administered intracoronaryand intravenous. Infarct size, area at risk and microvascular obstruction weredetermined ex vivo by cardiovascular magnetic resonance imaging. Myocardialsalvage index was calculated. The plasma levels of high-sensitive troponin T wereassessed repeatedly. The experimenters were blinded with regard to treatmentregimen. Melatonin did not significantly increase myocardial salvage indexcompared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9;27.0), p = 1.00]. The extent of microvascular obstruction was similar between thegroups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. Thearea under the curve for high-sensitive troponin T release was insignificantlyreduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4)ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combinedintracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.
DOI: 10.1007/s00380-014-0589-1 PMID: 25319673  [PubMed - indexed for MEDLINE]

9. G Ital Cardiol (Rome). 2014 Jul-Aug;15(7-8):405-7. doi: 10.1714/1596.17414.
[Use of noninvasive cardiac imaging for the evaluation of patients with chestpain: its use improves diagnostic accuracy].
[Article in Italian]
Trambaiolo P.
DOI: 10.1714/1596.17414 PMID: 25174593  [PubMed - indexed for MEDLINE]

10. Atherosclerosis. 2014 Oct;236(2):456-60. doi:10.1016/j.atherosclerosis.2014.07.037. Epub 2014 Aug 15.
Early inflammatory cytokine response: a direct comparison between spontaneouscoronary plaque destabilization vs angioplasty induced.
Brunetti ND(1), Correale M(2), Pellegrino PL(2), Munno I(3), Cuculo A(2), DeGennaro L(2), Gaglione A(2), Di Biase M(2).
Author information: (1)Cardiology Department, University of Foggia, Viale Pinto 1, 71100 Foggia,Italy. Electronic address: natale.brunetti@unifg.it. (2)Cardiology Department,University of Foggia, Viale Pinto 1, 71100 Foggia, Italy. (3)ImmunologyDepartment, University of Bari, Piazza Giulio Cesare, 1, 70121 Bari, Italy.
AIM: To compare inflammatory response accompanying acute coronary syndrome (ACS) with that following coronary plaque rupture caused by coronary angioplasty (PCI).METHODS: Twenty-seven consecutive subjects with either ACS or treated with PCI inthe subacute phase of ACS underwent serial evaluation of circulating interleukin (IL)-2, IL-8, IL-10, interferon (IFN)-γ and tumor-necrosis-factor (TNF)-α levels.Blood samples were drawn immediately before angioplasty (T0) in the PCI group or at admission in the ACS group, 12 h (T1) and 24 h later (T2).RESULTS: Differences between cytokine levels were substantially not statisticallysignificant when comparing PCI, non-ST-elevation-ACS, and ST-elevation-ACSgroups, especially 24 h after plaque rupture (T2, Type-II error 85-94%).CONCLUSIONS: Inflammatory activation during the first 24 h of ACS or after PCI iscomparable, regardless of myocardial damage in terms of troponin levels. Coronaryplaque rupture may be presumed as being the main responsible for increasedcirculating cytokine levels in this early phase.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.atherosclerosis.2014.07.037 PMID: 25173071  [PubMed - indexed for MEDLINE]

11. Med J Aust. 2014 Aug 4;201(3):158-61.
Impact of high-sensitivity cardiac troponin I assays on patients presenting to anemergency department with suspected acute coronary syndrome.
Yip TP(1), Pascoe HM(2), Lane SE(3).
Author information: (1)Geelong Cardiology Practice, Barwon Health, Geelong, VIC, Australia.thomasy@barwonhealth.org.au. (2)Geelong Cardiology Practice, Barwon Health,Geelong, VIC, Australia. (3)Biostatistics Unit, Barwon Health, Geelong, VIC,Australia.
Comment in    Med J Aust. 2014 Aug 4;201(3):125-6.
OBJECTIVE: To determine whether introduction of high-sensitivity cardiac troponinI (hscTn-I) assays affected management of patients presenting with suspectedacute coronary syndrome (ACS) to the emergency department (ED) of a tertiaryreferral hospital.DESIGN, PATIENTS AND SETTING: A retrospective analysis of all patients presentingto the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013-2 years before and 1 year after the changeover to hscTn-I assays on 23 April2012.MAIN OUTCOME MEASURES: Hospital admission rates, time spent in the ED, rates ofcoronary angiography, rates of percutaneous coronary intervention (PCI) andcoronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosisof ACS, and rates of inhospital mortality.RESULTS: 12 360 consecutive patients presented with suspected ACS during thestudy period; 1897 were admitted to Geelong Hospital in the 2 years before and944 in the 1 year after the changeover to hscTn-I assays. Comparing the twopatient groups, there was no statistically significant difference in all-hospitaladmission rates (95% CI for the difference, - 3.1% to 0.3%; P = 0.10) orproportion of patients subsequently discharged with a diagnosis of ACS (95% CIfor the difference, - 2.3% to 5.4%; P = 0.43). After the changeover, the mediantime patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for thedifference, 4.3 to 12.0 percentage points; P < 0.001), but there was nostatistically significant rise in the proportion of patients who had invasivetreatment (PCI and/or CABGS) (95% CI for the difference, - 0.4% to 6.3%; P =0.08). Inhospital mortality rates from ACS did not change significantly (95% CIfor the difference, - 1.5% to 0.8%; P = 0.43).CONCLUSION: The introduction of hscTn-I assays appeared to be associated withmore rapid diagnosis, resulting in less time spent in the ED, without a change inhospital admission rates. A higher proportion of patients had coronaryangiographies after the changeover, but there was no significant change in rates of invasive treatment or inhospital mortality.

PMID: 25128951  [PubMed - indexed for MEDLINE]

12. Curr Cardiol Rep. 2014;16(6):492. doi: 10.1007/s11886-014-0492-5.
Universal MI definition update for cardiovascular disease.
White H(1), Thygesen K, Alpert JS, Jaffe A.
Author information: (1)Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, Victoria St West, Auckland, 1142, New Zealand, HarveyW@adhb.govt.nz.
The new third universal definition of myocardial infarction (MI) is based ontroponin elevation together with ischemic symptoms, ischemic ECG changes, andimaging evidence. MIs are classified into five types as to whether they arespontaneous, secondary to imbalance between coronary artery blood supply anddemand, related to sudden death, or related to revascularization procedures. The definition is based on a rise and/or fall in troponin levels occurring in aclinical setting. There have been modifications over previous definitions withadding intracoronary thrombus as a criterion, adding a new type of MI type 4c,and raising the cutpoint for the diagnosis of MI related to percutaneous coronaryintervention to five times the 99(th) percentile upper reference limit andrequiring evidence of ischemia or angiographic complications. In clinicalpractice, trials, and registries, different definitions are used. There is a needfor consistency with regard to the definition of MI and the universal definition should be implemented.
DOI: 10.1007/s11886-014-0492-5 PMID: 24803385  [PubMed - indexed for MEDLINE]

13. Am J Cardiol. 2014 Jun 15;113(12):2013-7. doi: 10.1016/j.amjcard.2014.03.043.Epub 2014 Apr 1.
Effect of one-cycle remote ischemic preconditioning to reduce myocardial injuryduring percutaneous coronary intervention.
Zografos TA(1), Katritsis GD(2), Tsiafoutis I(3), Bourboulis N(3), Katsivas A(3),Katritsis DG(4).
Author information: (1)First Department of Cardiology, Athens Red Cross Hospital, Athens, Greece;Department of Cardiology, Athens Euroclinic, Athens, Greece. (2)Faculty ofMedicine, University of Bristol, Bristol, United Kingdom. (3)First Department of Cardiology, Athens Red Cross Hospital, Athens, Greece. (4)Department ofCardiology, Athens Euroclinic, Athens, Greece. Electronic address:dkatritsis@euroclinic.gr.
Up to 1/3 of percutaneous coronary interventions (PCIs) are complicated bytroponin release. Remote ischemic preconditioning (IPC) confers effectivecardioprotection; however, a 30-minute remote IPC protocol may be difficult toimplement during ad hoc PCI. This study was performed to assess the ability of a brief remote IPC protocol to attenuate cardiac troponin I (cTnI) release after adhoc PCI. Ninety-four patients undergoing ad hoc PCI for stable coronary arterydisease, with undetectable preprocedural cTnI, were recruited and randomized toreceive remote IPC (induced by one 5-minute inflation of a blood pressure cuff to200 mm Hg around the upper arm) or control after the decision for PCI was made.The primary outcome was the difference between cTnI levels 24 hours after PCI andcTnI levels before coronary angiography (ΔcTnI). ΔcTnI in the remote IPC groupwas significantly lower compared with the control group (0.04 ng/ml[interquartile range 0.01 to 0.14] vs 0.19 ng/ml [interquartile range 0.18 to0.59], p <0.001). The incidence of PCI-related myocardial infarction (MI) wasgreater in the control group (42.6% vs 19.1%, p = 0.014). In multivariateanalysis, remote IPC was independently associated with ΔcTnI and PCI-related MI. In conclusion, our results suggest that even 1 cycle of remote IPC immediatelybefore ad hoc PCI attenuates periprocedural cTnI release and reduces theincidence of type 4a MI.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.amjcard.2014.03.043 PMID: 24793669  [PubMed - indexed for MEDLINE]

14. Eur Heart J Acute Cardiovasc Care. 2014 Jun;3(2):118-25. doi:10.1177/2048872614527006. Epub 2014 Feb 27.
High-sensitivity troponin level pre-catheterization predicts adversecardiovascular outcomes after primary angioplasty for ST-elevation myocardialinfarction.
Wang TK(1), Snow TA, Chen Y, Rostom H, White JM, Stewart JT, Webster MW, Ruygrok PN, Watson T, White HD.
Author information: (1)Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand.
BACKGROUND: Cardiac troponins are the preferred biomarkers for diagnosingmyocardial infarction (MI). High-sensitivity troponin T (hs-TnT) assays haveincreased sensitivity and enable more rapid diagnosis of infarction. We assessed the prognostic utility of admission hs-TnT to detect outcomes after primaryangioplasty for ST-elevation/new left bundle branch block myocardial infarction(STEMI).METHODS: Patients admitted to Auckland City Hospital for acute coronarycatheterization with a diagnosis of STEMI between October 2010 and September 2011were identified, and included if hs-TnT levels were measured at admission.Clinical characteristics and major adverse cardiovascular events (MACE: death,myocardial infarction and revascularization) at 30 days and 1 year were collectedfrom national statistics and electronic medical records.RESULTS: Median admission hs-TnT level in the 173 STEMI patients studied was 59ng/L (interquartile range (IQR) 19-310). Incidences of MACE at 30 days and 1 yearwere 10% (n=17) and 18% (n=31), respectively. C-statistics and 95% confidenceinterval (CI) (95% CI) for hs-TnT on admission at detecting MACE at 30 days and 1year were 0.800 (0.696-0.904) and 0.750 (0.655-0.845) respectively, with theoptimal cut-point of 225 ng/L giving sensitivities/specificities of 76.5%/75.6%and 64.5%/78.2% respectively. Admission log(hs-TnT) independently predicted both MACE at 30 days with hazards ratio 5.16, 95% CI (2.25-11.9) and 1 year withhazards ratio 2.88, 95% CI (1.79-4.63), as did age and cardiogenic shock. Age,Maori or Pacific ethnicity and chronic respiratory disease were independentpredictors of hs-TnT>225 ng/L.CONCLUSION: Admission hs-TnT measured in primary angioplasty is stronglyprognostic of MACE at 30 days and 1 year, even following adjustment for potentialconfounding variables.
DOI: 10.1177/2048872614527006 PMID: 24576774  [PubMed - indexed for MEDLINE]

15. Am J Cardiol. 2014 Mar 1;113(5):757-64. doi: 10.1016/j.amjcard.2013.11.034. Epub 2013 Dec 12.
Influence of the extent of coronary atherosclerotic disease on ST-segment changesinduced by ST elevation myocardial infarction.
Noriega FJ(1), Vives-Borrás M(2), Solé-González E(2), García-Picart J(2),Arzamendi D(2), Cinca J(2).
Author information: (1)Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Institute ofBiomedical Research (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona,Spain. Electronic address: fnoriega@santpau.cat. (2)Department of Cardiology,Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain.
The accuracy of the admission electrocardiogram (ECG) in predicting the site ofacute coronary artery occlusion in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease is not well known. This study aimed toassess whether the presence of multivessel coronary artery disease (CAD) modifiesthe artery-related ST-segment changes in patients with acute coronary arteryocclusion. We reviewed the admission ECG, clinical records, and coronaryangiography of 289 patients with STEMI caused by acute occlusion of left anteriordescending (LAD; n = 140), right (n = 118), or left circumflex (LCx; n = 31)coronary arteries. All patients underwent primary percutaneous coronaryreperfusion during the first 12 hours. The magnitude and distribution ofartery-related ST-segment patterns were comparable in patients with single (n =149) and multivessel (n = 140) CAD. Occlusion of proximal (n = 55) or mid-distal (n = 85) LAD artery induced ST-segment elevation in leads V1 to V5, but only the proximal occlusion induced reciprocal ST-segment depression in leads II, III, andaVF (p <0.001). Proximal and mid-distal occlusion of right (n = 45 and 73,respectively) or LCx (n = 15 and 16) coronary artery always induced ST-segmentelevation in leads II, III, and aVF and reciprocal ST-segment depression in leadsV2 and V3. ST-segment elevation in lead V6 >0.1 mV predicted LCx arteryocclusion. In conclusion, patients with STEMI with single or multivessel CAD haveconcordant artery-related ST-segment patterns on the admission ECG; in bothgroups, reciprocal ST-segment depression in LAD artery occlusion predicts a largeinfarct. Subendocardial ischemia at a distance is not a requisite for the genesisof reciprocal ST-segment changes.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.amjcard.2013.11.034 PMID: 24406107  [PubMed - indexed for MEDLINE]

IAM - Troponina: búsqueda de trabajos 2015-2016Fecha: 8/4/2017

 


1. S Afr Med J. 2016 Mar;106(3):239-45.
Approach to chest pain and acute myocardial infarction.
Pandie S, Hellenberg D, Hellig F, Ntsekhe M.
Patient history, physical examination, 12-lead electrocardiogram (ECG) andcardiac biomarkers are key components of an effective chest pain assessment. The first priority is excluding serious chest pain syndromes, namely acute coronarysyndromes (ACSs), aortic dissection, pulmonary embolism, cardiac tamponade andtension pneumothorax. On history, the mnemonic SOCRATES (Site Onset CharacterRadiation Association Time Exacerbating/relieving factor and Severity) helpsdifferentiate cardiac from non-cardiac pain. On examination, evaluation of vital signs, evidence of murmurs, rubs, heart failure, tension pneumothoraces and chestinfections are important. A 12-lead ECG should be interpreted within 10 minutesof first medical contact, specifically to identify ST elevation myocardialinfarction (STEMI). High-sensitivity troponins improve the rapid rule-out ofmyocardial infarction (MI) and confirmation of non-ST elevation MI (NSTEMI). ACS (STEMI and NSTEMI/unstable anginapectoris (UAP)) result from acutedestabilisation of coronary atheroma with resultant complete (STEMI) or subtotal (NSTEMI/UAP) thrombotic coronary occlusion. The management of STEMI patientsincludes providing urgent reperfusion: primary percutaneous coronaryintervention(PPCI) if available, deliverable within 60 - 120 minutes, andfibrinolysis if PPCI is not available. Essential adjunctive therapies includeantiplatelet therapy (aspirin, P2Y12 inhibitors), anticoagulation (heparin orlow-molecular-weight heparin) and cardiac monitoring.

PMID: 27303759  [PubMed - indexed for MEDLINE]

2. Lancet. 2016 Jun 4;387(10035):2289. doi: 10.1016/S0140-6736(16)30686-9.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Fujita T(1).
Author information: (1)Department of Surgery, Jikei University School of Medicine, Tokyo, Japan.Electronic address: tetsu@jg8.so-net.ne.jp.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30686-9 PMID: 27302265  [PubMed - indexed for MEDLINE]

3. Lancet. 2016 Jun 4;387(10035):2289. doi: 10.1016/S0140-6736(16)30687-0.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Ford C(1), Whitehead SJ(1), Gama R(2), Willmer KA(3).
Author information: (1)Department of Clinical Chemistry, Royal Wolverhampton NHS Trust,Wolverhampton, UK. (2)Department of Clinical Chemistry, Royal Wolverhampton NHSTrust, Wolverhampton, UK. Electronic address: rousseau.gama@nhs.net.(3)Department of Acute Medicine, Royal Wolverhampton NHS Trust, Wolverhampton,UK.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30687-0 PMID: 27302264  [PubMed - indexed for MEDLINE]

4. Lancet. 2016 Jun 4;387(10035):2289-91. doi: 10.1016/S0140-6736(16)30517-7.
Measurement of cardiac troponin for exclusion of myocardial infarction - Authors'reply.
Shah AS(1), Anand A(2), Chapman AR(2), Newby DE(2), Mills NL(2); High-STEACSInvestigators.
Author information: (1)BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.Electronic address: Anoop.Shah@ed.ac.uk. (2)BHF Centre for CardiovascularScience, University of Edinburgh, Edinburgh, UK.
Comment on    Lancet. 2016 Jun 4;387(10035):2289.    Lancet. 2016 Jun 4;387(10035):2288.    Lancet. 2016 Jun 4;387(10035):2289.    Lancet. 2016 Jun 4;387(10035):2288-9.    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30517-7 PMID: 27302263  [PubMed - indexed for MEDLINE]

5. Lancet. 2016 Jun 4;387(10035):2288. doi: 10.1016/S0140-6736(16)30684-5.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Boeddinghaus J(1), Twerenbold R(1), Nestelberger T(1), Wildi K(1), Mueller C(2).
Author information: (1)Cardiovascular Research Institute Basel and Department of Cardiology,University Hospital Basel, Basel, Switzerland. (2)Cardiovascular ResearchInstitute Basel and Department of Cardiology, University Hospital Basel, Basel,Switzerland. Electronic address: christian.mueller@usb.ch.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30684-5 PMID: 27302262  [PubMed - indexed for MEDLINE]

6. Lancet. 2016 Jun 4;387(10035):2288-9. doi: 10.1016/S0140-6736(16)30685-7.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Mullen L(1), Chew PG(2), Frost F(2), Obafemi T(2), Khand A(3).
Author information: (1)University Hospital Aintree, Liverpool, UK. Electronic address:liammullen@nhs.net. (2)University Hospital Aintree, Liverpool, UK. (3)University Hospital Aintree, Liverpool, UK; Liverpool Heart and Chest Hospital, Liverpool,UK.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30685-7 PMID: 27302261  [PubMed - indexed for MEDLINE]

7. Mymensingh Med J. 2016 Apr;25(2):226-31.
Correlation between Troponin-I and B-Type Natriuretic Peptide Level in AcuteMyocardial Infarction Patients with Heart Failure.
Islam MN(1), Alam MF, Debnath RC, Aditya GP, Ali MH, Hossain MA, Siddique SR.
Author information: (1)Dr Mirza Md Nazrul Islam, Associate Professor, Department of Cardiology,Mymensingh Medical College (MMC), Mymensingh, Bangladesh.
Troponins are regarded as markers of choice for the diagnosis of acute myocardialinfarction (AMI). But B-type natriuretic peptide (BNP) level is also elevated in AMI and is a quantitative biochemical marker related to the extent of infarction and the left ventricle systolic dysfunction. Thus, BNP has prognostic value. Inthis study, we investigate the correlation of Troponin-I with BNP levels inpatients presenting with AMI with or without Acute Heart Failure. Rationale ofthis study is to see, whether quantitative Troponin alone can serve for bothdiagnosis and prognosis of AMI Patients with heart failure or not. Thiscross-sectional analytical study was conducted in the Department of Cardiology inMymensingh Medical College Hospital from January 2014 to December 2014. Total 100patients were studied and divided into two groups - 50 patients in each group.Group I: Patients with first attack of acute myocardial infarction (without heartfailure) & Group II: Patients with first attack of acute myocardial infarctionwith acute heart failure. Mean Troponin-I of Group I and Group II were 3.10±2.68 and 62.93±32.75ng/ml respectively & mean BNP value of Group I and Group II were20.96±14.18 and 615.65±249.27pg/ml respectively. In this study, it was shown thatthe levels of BNP had positive correlation with Troponin-I levels, with mediumstrength of association (r=0.734, p<0.05). Echocardiography shows that patientswith high BNP level has low ejection fraction (LVEF) and patients with low BNPlevel has preserved ejection fraction (LVEF). Thus, the present study shows that the higher the Troponin-I levels, the higher the BNP levels in first attack ofAMI patients and the more severe the heart failure (more severe left ventricledysfunction). There is positive correlation between Troponin-I and BNP levels in first attack of AMI patients with acute heart failure.

PMID: 27277352  [PubMed - indexed for MEDLINE]

8. Med Intensiva. 2016 Apr;40(3):200. doi: 10.1016/j.medin.2016.01.010. Epub 2016Mar 22.
[Methods can influence the value of copeptin to rule-out acute myocardialinfarction without ST segment elevation].
[Article in Spanish]
García de Guadiana-Romualdo L(1), Consuegra-Sánchez L(2), Esteban-Torrella P(3), Martínez-Díaz JJ(2), Albaladejo-Otón MD(3).
Author information: (1)Servicio de Análisis Clínicos, Hospital Universitario Santa Lucía, Cartagena, Murcia, España. Electronic address: guadianarom@yahoo.es. (2)Servicio deCardiología y Hemodinámica, Hospital Universitario Santa Lucía, Cartagena,Murcia, España. (3)Servicio de Análisis Clínicos, Hospital Universitario SantaLucía, Cartagena, Murcia, España.
Comment on    Med Intensiva. 2016 Apr;40(3):199.    Med Intensiva. 2015 Nov;39(8):477-82.
DOI: 10.1016/j.medin.2016.01.010 PMID: 27015787  [PubMed - indexed for MEDLINE]

9. J Am Heart Assoc. 2016 Mar 9;5(3):e002708. doi: 10.1161/JAHA.115.002708.
Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index,Infarct Size, or Biochemical Markers as Endpoint.
Engblom H(1), Heiberg E(2), Erlinge D(3), Jensen SE(4), Nordrehaug JE(5),Dubois-Randé JL(6), Halvorsen S(7), Hoffmann P(8), Koul S(3), Carlsson M(1), AtarD(7), Arheden H(9).
Author information: (1)Department of Clinical Sciences Lund, Clinical Physiology, Skane UniversityHospital, Lund University, Lund, Sweden. (2)Department of Clinical Sciences Lund,Clinical Physiology, Skane University Hospital, Lund University, Lund, SwedenDepartment of Biomedical Engineering, Faculty of Engineering, Lund University,Lund, Sweden. (3)Department of Cardiology, Skåne University Hospital and LundUniversity, Lund, Sweden. (4)Department of Cardiology, Aalborg UniversityHospital, Aalborg, Denmark. (5)Department of Clinical Science, University ofBergen, Norway. (6)Department of Cardiology, Henri Mondor Hospital, Creteil,France. (7)Department of Cardiology B, Oslo University Hospital Ullevål,University of Oslo, Norway Faculty of Medicine, University of Oslo, Norway.(8)Section for Interventional Cardiology, Department of Cardiology, OsloUniversity Hospital, Ullevål, Norway. (9)Department of Clinical Sciences Lund,Clinical Physiology, Skane University Hospital, Lund University, Lund, Swedenhakan.arheden@med.lu.se.
BACKGROUND: Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI)size and myocardium at risk (MaR), enabling assessment of myocardial salvageindex (MSI). We assessed how MSI impacts the number of patients needed to reachstatistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size.METHODS AND RESULTS: Controls (n=90) from the recent CHILL-MI and MITOCARE trialswere included. MI size, MaR, and MSI were assessed from CMR. High-sensitivitytroponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessedin CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000clinical trials were simulated for calculation of sample size required to reachsufficient power. For a treatment effect of 25% decrease in outcome variables, 50patients were required in each arm using MSI compared to 93, 98, 120, 141, and143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUCand peak) in order to reach a power of 90%. If average CMR scan day betweentreatment and control arms differed by 1 day, sample size needs to be increasedby 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%.CONCLUSION: Sample size in cardioprotection trials can be reduced 46% to 65%without compromising statistical power when using MSI by CMR as an outcomevariable instead of MI size alone or biochemical markers. It is essential toensure lack of bias in scan day between treatment and control arms to avoidcompromising statistical power.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
DOI: 10.1161/JAHA.115.002708 PMCID: PMC4943247PMID: 26961520  [PubMed - indexed for MEDLINE]

10. Clin Chim Acta. 2016 May 1;456:42-8. doi: 10.1016/j.cca.2016.02.017. Epub 2016Feb 26.
Pilot study on harmonization of cardiac troponin I immunoassays using patientsand quality control plasma samples. On behalf of the Italian Section of theEuropean Ligand Assay Society (ELAS) and of the Study Group on CardiovascularBiomarkers of the Società Italiana di Biochimica Clinica (SIBioC).
Clerico A(1), Ripoli A(2), Masotti S(3), Prontera C(2), Storti S(2), FortunatoA(4), Buzzi P(5), Casagranda I(5), Franzini M(6), Ndreu R(7), Zucchelli GC(7),Zaninotto M(8), Plebani M(8).
Author information: (1)Fondazione CNR Regione Toscana G. Monasterio, Pisa, Italy; Scuola SuperioreSant'Anna, Pisa, Italy. (2)Fondazione CNR Regione Toscana G. Monasterio, Pisa,Italy. (3)Scuola Superiore Sant'Anna, Pisa, Italy. (4)Department of LaboratoryMedicine, San Bortolo Hospital, Vicenza, Italy. (5)Dipartimento di Emergenza,Ospedale Civile Santi Antonio e Biagio e Cesare Arrigo di Alessandria,Alessandria, Italy. (6)Dipartimento di Ricerca Traslazionale e delle NuoveTecnologie in Medicina e Chirurgia, Università di Pisa, Pisa, Italy.(7)QualiMedLab, Istituto di Fisiologia Clinica del CNR, Pisa, Italy.(8)Department of Laboratory Medicine, University of Padova, Italy.
BACKGROUND: The aim of this study is to evaluate whether it is possible to reducethe between-methods variability of troponin I (cTnI) immunoassays usingmathematical algorithms calculated from the results of both patients' samples andquality control materials distributed in an external quality assessment (EQA)scheme.METHODS: We collected 122 heparinized plasma samples of patients admitted to the emergency department with thoracic pain or supraventricular tachyarrhythmia.Moreover, we also analyzed 20 control samples distributed in an EQA and 26 plasmapools prepared from healthy subjects and patients with myocardial infarction. We evaluated 4 different methods for cTnI assay: STAT Architect High Sensitive TnI(Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens HealthcareDiagnostics), ST AIA-Pack cTnI Third Generation (Tosoh Bioscience), and AccessAccuTnI+3 (Beckman Coulter Diagnostics).RESULTS: Systematic differences between cTnI methods were observed. However,correlation coefficients (R from 0.976 to 0.990) between the log-transformed cTnIvalues measured in all 168 samples were significantly better (p=0.0037) thanthose obtained considering only the 122 patients' samples. cTnI values measuredin EQA and pool samples were included within the 95% prediction intervals oflinear regressions calculated with those of patients' samples. After therecalibration of cTnI values based on the robust principal component analysisapproach the between-methods variability decreased significantly (about 40%around the cut off values).CONCLUSIONS: Our pilot study suggests that EQA schemes for cTnI immunoassaymethods, based on both quality control samples with tested commutability androbust statistical analyses, are able to evaluate between-methods variability as well as allow a reliable recalibration and harmonization of results.
Copyright © 2016 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.cca.2016.02.017 PMID: 26923393  [PubMed - indexed for MEDLINE]

11. Nat Commun. 2016 Feb 24;7:10794. doi: 10.1038/ncomms10794.
Rationally engineered Troponin C modulates in vivo cardiac function andperformance in health and disease.
Shettigar V(1), Zhang B(1), Little SC(2), Salhi HE(1), Hansen BJ(1), Li N(1),Zhang J(1), Roof SR(3), Ho HT(1), Brunello L(1), Lerch JK(4), Weisleder N(1),Fedorov VV(1), Accornero F(1), Rafael-Fortney JA(1), Gyorke S(1), Janssen PM(1), Biesiadecki BJ(1), Ziolo MT(1), Davis JP(1).
Author information: (1)Davis Heart and Lung Research Institute and Department of Physiology and Cell Biology, Columbus, Ohio 43210, USA. (2)Bristol-Myers Squibb, Department ofDiscovery Biology, Wallingford, Connecticut 06492, USA. (3)Q-Test Labs, Columbus,Ohio 43235, USA. (4)Center for Brain and Spinal Cord Repair, Department ofNeuroscience, The Ohio State University College of Medicine, Columbus, Ohio43210, USA.
Treatment for heart disease, the leading cause of death in the world, hasprogressed little for several decades. Here we develop a protein engineeringapproach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca(2+) signal. Promisingly, our smartly formulatedCa(2+)-sensitizing TnC (L48Q) enhances heart function without any adverse effectsthat are commonly observed with positive inotropes. In a myocardial infarction(MI) model of heart failure, expression of TnC L48Q before the MI preservescardiac function and performance. Moreover, expression of TnC L48Q after the MItherapeutically enhances cardiac function and performance, without compromisingsurvival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as atherapeutic strategy for heart disease.
DOI: 10.1038/ncomms10794 PMCID: PMC4770086PMID: 26908229  [PubMed - indexed for MEDLINE]

12. Eur J Vasc Endovasc Surg. 2016 Apr;51(4):481. doi: 10.1016/j.ejvs.2015.12.041.Epub 2016 Feb 16.
Commentary on 'The Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy'.
De Rango P(1).
Author information: (1)Vascular Surgery Unit, Hospital S. Maria Misericordia, Perugia, Italy.Electronic address: plderango@gmail.com.
Comment on    Eur J Vasc Endovasc Surg. 2016 Apr;51(4):473-80.
DOI: 10.1016/j.ejvs.2015.12.041 PMID: 26895945  [PubMed - indexed for MEDLINE]

13. Int J Cardiol. 2016 Apr 15;209:26-33. doi: 10.1016/j.ijcard.2016.01.213. Epub2016 Feb 3.
Diagnostic and prognostic implications using age- and gender-specific cut-offsfor high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study.
Mueller-Hennessen M(1), Lindahl B(2), Giannitsis E(3), Biener M(1), Vafaie M(1), deFilippi CR(4), Christ M(5), Santalo-Bel M(6), Panteghini M(7), Plebani M(8),Verschuren F(9), Jernberg T(10), French JK(11), Christenson RH(12), Body R(13),McCord J(14), Dilba P(15), Katus HA(1), Mueller C(16); TRAPID-AMI Investigators.
Author information: (1)Department of Internal Medicine III, Cardiology, Angiology & Pulmonology,Heidelberg University Hospital, Heidelberg, Germany. (2)Department of MedicalSciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. (3)Department of Internal Medicine III,Cardiology, Angiology & Pulmonology, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: evangelos_giannitsis@med.uni-heidelberg.de.(4)Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States. (5)Department of Emergency and Critical Care Medicine,Community Hospital, Paracelsus Medical University, Nuremberg, Germany.(6)Semicritical Unit, Hospital de Sant Pau &, Institut d'InvestigacionsBiomèdiques Sant Pau, Barcelona, Spain. (7)Department of Biomedical and Clinical Sciences 'Luigi Sacco', University of Milan Medical School, Milano, Italy.(8)Department of Laboratory Medicine, University Hospital of Padova, Padua,Italy. (9)Department of Acute Medicine, Cliniques Universitaires St-Luc,Université Catholique de Louvain, Brussels, Belgium. (10)Department of Medicine, KarolinskaInstitutet, Huddinge, Sweden. (11)Liverpool Hospital, University of NewSouth Wales, Sydney, Australia. (12)Department of Pathology, University ofMaryland School of Medicine, Baltimore, MD, United States. (13)Central ManchesterUniversity Hospitals NHS Foundation Trust, United Kingdom. (14)Henry Ford Heartand Vascular Institute, Henry Ford Health System, Detroit, MI, United States.(15)Roche Diagnostics Germany, Penzberg, Germany. (16)Cardiology & CardiovascularResearch Institute Basel, University Hospital Basel, Switzerland.
OBJECTIVES: To evaluate the impact of age- and gender-specific cut-offs forhigh-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99thpercentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardialinfarction (AMI).METHODS: 1282 unselected patients presenting to the emergency department withsuspected AMI were enrolled as part of the TRAPID-AMI study. In the presentsub-analysis, reclassification of AMI diagnosis was performed by comparing thegeneral hs-cTnT cut-off of 14ng/L to previously proposed age- andgender-dependent hs-cTnT 99th percentile cut-offs (28ng/L for ≥65years, 9ng/L forfemale and 15.5ng/L for male patients). Patients were further clinicallyadjudicated into acute coronary syndrome (ACS) and non-ACS.RESULTS: For patients ≥65years, application of age-specified cut-offs resulted ina decrease of AMI from 29.8% to 18.3% in the entire cohort (n=557) and 54.7% to40.9% in the ACS subcohort (n=225). Using gender-specific cut-offs, AMI-rateincreased from 16.6% to 22.6% (entire cohort, n=477) and 62.6% to 71.7% (ACSsubcohort, n=99) in women, whereas in men, rates decreased from 23.1% to 21.1%(entire cohort, n=805) and 48.8% to 45.9% (ACS, n=281), respectively.Age-specified cut-offs significantly reclassified patients for outcomes of1-month and 3-month mortality in the entire and ACS cohort (14.2% netreclassification improvement, p<0.001, respectively). Contrary, no significantdifferences in outcomes could be found using gender-specific cut-offs.CONCLUSIONS: While influence of gender-specific hs-cTnT cut-offs on diagnosticand prognostic reclassification was only modest in patients with suspected AMI,age-specific cut-offs showed a significant impact and may be considered forfurther validation.
Copyright © 2016. Published by Elsevier Ireland Ltd.
DOI: 10.1016/j.ijcard.2016.01.213 PMID: 26878470  [PubMed - indexed for MEDLINE]

14. Clin Chim Acta. 2016 May 1;456:36-41. doi: 10.1016/j.cca.2016.01.022. Epub 2016Feb 11.
Diagnosis of acute myocardial infarction in hemodialysis patients may be feasibleby comparing variation of cardiac troponins during acute presentation to baselinevariation.
van Berkel M(1), Dekker MJ(1), Bogers H(1), Geerse DA(1), Konings CJ(1),Scharnhorst V(2).
Author information: (1)Clinical Laboratory and Department of Internal Medicine, Catharina Hospital,Eindhoven, The Netherlands. (2)Department of Biomedical Engineering, TechnicalUniversity of Eindhoven, The Netherlands.
Acute myocardial infarction (AMI) is defined as a dynamic change in cardiactroponin (cTn) with at least one cTn value exceeding the 99 th percentile of areference population in combination with typical clinical symptoms. Inhemodialysis (HD) patients, a broad range of cTn concentrations is found,partially due to patient-specific comorbidities. Therefore, the 99 th percentile cannot be used in HD patients and decision algorithms to diagnose AMI should bebased on temporal variations of troponin. In this study, relative and absolutevariations of cTn in a large population of asymptomatic hemodialysis patientswere established during a period of 15 months. Patients were stratified accordingto their history of coronary artery disease (CAD). An intra-individual long term variation of 23% for cTroponin I (cTnI) and 12% for cTroponin T (cTnT) was found for patients without a history of CAD. The corresponding reference change values (RCVs) were 69% and 39% respectively. For patients with a history of CAD thisvariation was 29% for cTnI and 10% for cTnT, with RCVs of 86% and 35%respectively. During follow up, 27 HD patients developed an acute myocardialinfarction (AMI). During these events, irrespective of CAD history, cTnIincreased>172% and cTnT increased>97% above baseline cTn as measured duringclinically stable periods three months separate to the event. Therefore, if a HD patient has symptoms of an acute event and a cTn increase that exceeds the RCVsdescribed here, AMI may be suspected. If the troponin increase exceeds 172% forcTnI or 97% for cTnT, AMI is likely.
Copyright © 2016. Published by Elsevier B.V.
DOI: 10.1016/j.cca.2016.01.022 PMID: 26874043  [PubMed - indexed for MEDLINE]

15. Med Intensiva. 2016 Apr;40(3):199. doi: 10.1016/j.medin.2015.11.007. Epub 2016Feb 8.
[Methods can influence the value of copeptin to rule-out acute myocardialinfarction without ST segment elevation].
[Article in Spanish]
Alquézar-Arbé A(1), Rizzi M(2), Álvarez-Albarrán M(2), Lozano-Polo L(2).
Author information: (1)Servicio de Urgencias, Hospital de la Santa Creu i Sant Pau, Barcelona,España. Electronic address: aalquezar@santpau.cat. (2)Servicio de Urgencias,Hospital de la Santa Creu i Sant Pau, Barcelona, España.
Comment in    Med Intensiva. 2016 Apr;40(3):200.
Comment on    Med Intensiva. 2015 Nov;39(8):477-82.
DOI: 10.1016/j.medin.2015.11.007 PMID: 26868934  [PubMed - indexed for MEDLINE]

16. Sci Rep. 2016 Feb 11;6:20812. doi: 10.1038/srep20812.
Analyzing the Release of Copeptin from the Heart in Acute Myocardial InfarctionUsing a Transcoronary Gradient Model.
Boeckel JN(1,)(2,)(3), Oppermann J(1), Anadol R(1), Fichtlscherer S(1), ZeiherAM(1,)(3), Keller T(1,)(3).
Author information: (1)Department of Cardiology, Internal Medicine III, Goethe-University Hospital,Theodor Stern Kai 7 60590 Frankfurt; Germany. (2)Institute for CardiovascularRegeneration, Center of Molecular Medicine, Theodor Stern Kai 7, 60590 Frankfurt;Germany. (3)German Center of Cardiovascular Research (DZHK), RheinMain, 60590Frankfurt, Germany.
Copeptin is the C-terminal end of pre-provasopressin released equimolar tovasopressin into circulation and recently discussed as promising cardiovascularbiomarker amendatory to established markers such as troponins. Vasopressin is acytokine synthesized in the hypothalamus. A direct release of copeptin from theheart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of apotential release of copeptin from the human heart in acute myocardial infarction(AMI) has been done.
DOI: 10.1038/srep20812 PMCID: PMC4749978PMID: 26864512  [PubMed - indexed for MEDLINE]

17. Eur J Vasc Endovasc Surg. 2016 Apr;51(4):607. doi: 10.1016/j.ejvs.2015.12.007.Epub 2016 Feb 6.
Response to 'Re: Clinical Relevance of Cardiac Troponin Assessment in PatientsUndergoing Carotid Endarterectomy'.
Grobben RB(1), Nathoe HM(2), van Klei WA(3), de Borst GJ(4).
Author information: (1)Department of Cardiology, University Medical Center Utrecht, The Netherlands. Electronic address: r.b.grobben@umcutrecht.nl. (2)Department of Cardiology,University Medical Center Utrecht, The Netherlands. (3)Department ofAnesthesiology, University Medical Center Utrecht, The Netherlands. (4)Departmentof Vascular Surgery, University Medical Center Utrecht, The Netherlands.
Comment on    Eur J Vasc Endovasc Surg. 2016 Apr;51(4):473-80.    Eur J Vasc Endovasc Surg. 2016 Apr;51(4):606-7.
DOI: 10.1016/j.ejvs.2015.12.007 PMID: 26860253  [PubMed - indexed for MEDLINE]

18. Acta Cardiol. 2016 Feb;71(1):47-54. doi: 10.2143/AC.71.1.3132097.
ST-segment elevation in lead aVR in the setting of acute coronary syndrome.
Nabati M, Emadi M, Mollaalipour M, Bagheri B, Nouraei M.
OBJECTIVES: The purpose of our study was to assess the value of aVR ST-segmentelevation (STE) during acute non ST-segment elevation myocardial infarction(NSTEMI) or unstable angina.BACKGROUND: STE in lead aVR has been associated with severe coronary lesions inpatients with acute coronary syndromes. However, there are conflicting dataregarding the prognostic significance of this finding.METHODS: We evaluated the initial electrocardiogram (ECG) in 129 patientsadmitted to our hospital with acute NSTEMI or unstable angina without STE inleads other than aVR or V1. STE in aVR lead was measured and echocardiography andcoronary angiography were performed within 48-72 hours after hospitalization.RESULTS: Overall, 40.3% (52 patients) had more than 0.05 mv STE in lead aVR.These patients had an increased prevalence of ST ≥ 1 mm in lead V1, a morefrequent and extensive ST-segment depression (STD) in other leads, a higherprevalence of anterior and lateral STD and a lower frequency of isolated negativeT waves. It was also strongly associated with cardiac enzyme rising and a trendtoward higher 3-month mortality. Furthermore, patients with STE in lead aVR were more likely to have three-vessel or multivessel disease, higher Gensini score of the coronary arteries, lower left ventricular ejection fraction (LVEF) and higherincidence of mitral regurgitation (MR).CONCLUSIONS: Our study showed that among ECG markers, the sole criterion STE inlead aVR was independently associated with atherosclerosis severity and decreasedLVEF. Also, it was significantly associated with the presence of MR.
DOI: 10.2143/AC.71.1.3132097 PMID: 26853253  [PubMed - indexed for MEDLINE]

19. Circulation. 2016 Feb 2;133(5):e375. doi: 10.1161/CIRCULATIONAHA.115.017572.
Letter by Yang and Xu Regarding Article, "Optimal Cutoff Levels of More SensitiveCardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction inPatients With Renal Dysfunction".
Yang P(1), Xu G(2).
Author information: (1)Medical Center of the Graduate School, Nanchang University, Nanchang, Jiangxi,China. (2)Department of Nephrology, Second Affiliated Hospital, NanchangUniversity, Nanchang, Jiangxi, China.
Comment on    Circulation. 2015 Jun 9;131(23):2041-50.
DOI: 10.1161/CIRCULATIONAHA.115.017572 PMID: 26831440  [PubMed - indexed for MEDLINE]

20. Circulation. 2016 Feb 2;133(5):e374. doi: 10.1161/CIRCULATIONAHA.115.018157.
Letter by Lippi and Cervellin Regarding Article, "Optimal Cutoff Levels of MoreSensitive Cardiac Troponin Assays for the Early Diagnosis of MyocardialInfarction in Patients With Renal Dysfunction".
Lippi G(1), Cervellin G(2).
Author information: (1)Section of Clinical Biochemistry, University of Verona, Verona, Italy.(2)Emergency Department, Academic Hospital of Parma, Parma, Italy.
Comment on    Circulation. 2015 Jun 9;131(23):2041-50.
DOI: 10.1161/CIRCULATIONAHA.115.018157 PMID: 26831439  [PubMed - indexed for MEDLINE]

21. Clin Chim Acta. 2016 Apr 1;455:189-94. doi: 10.1016/j.cca.2016.01.029. Epub 2016 Jan 29.
Unrecognized myocardial infarctions detected by cardiac magnetic resonanceimaging are associated with cardiac troponin I levels.
Nordenskjöld AM(1), Hammar P(2), Ahlström H(3), Bjerner T(3), Duvernoy O(3),Eggers KM(4), Fröbert O(5), Hadziosmanovic N(6), Lindahl B(4).
Author information: (1)Department of Cardiology, Faculty of Health, Örebro University, Örebro,Sweden. Electronic address: anna.nordenskjold@regionorebrolan.se. (2)Departmentof Radiology, Västerås Hospital, Västerås, Sweden; Department of Radiology,Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.(3)Department of Radiology, Oncology and Radiation Science, Uppsala University,Uppsala, Sweden. (4)Department of Medical Sciences, Cardiology, UppsalaUniversity, Uppsala, Sweden; Uppsala Clinical Research Centre, Uppsala, Sweden.(5)Department of Cardiology, Faculty of Health, Örebro University, Örebro,Sweden. (6)Uppsala Clinical Research Centre, Uppsala, Sweden.
BACKGROUND: Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels ofcardiac biomarkers, UMI and extent of CAD in patients with stable CAD.METHODS: A total of 235 patients (median age: 65years; 34% women) with stable CADwithout previously known myocardial infarction were examined with late gadoliniumenhancement cardiovascular magnetic resonance imaging and coronary angiography.Blood samples were drawn at enrolment and high sensitivity cardiac troponin I(cTnI), NT-proBNP and Galectin-3 were analyzed.RESULTS: UMI was detected in 58 patients (25%). The median levels of cTnI,NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renalfunction, cTnI remained independently associated with the presence of UMI(p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, wasindependently associated with UMI or extent of CAD.CONCLUSIONS: The independent association between levels of cTnI and UMI indicatesa common pathophysiological pathway for the cTnI elevation and development ofUMI.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01257282).
Copyright © 2016 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.cca.2016.01.029 PMID: 26828531  [PubMed - indexed for MEDLINE]

22. Int J Cardiol. 2016 Mar 15;207:238-45. doi: 10.1016/j.ijcard.2016.01.112. Epub2016 Jan 11.
Characterization of the observe zone of the ESC 2015 high-sensitivity cardiactroponin 0h/1h-algorithm for the early diagnosis of acute myocardial infarction.
Nestelberger T(1), Wildi K(1), Boeddinghaus J(1), Twerenbold R(1), Reichlin T(1),Giménez MR(1), Puelacher C(1), Jaeger C(1), Grimm K(1), Sabti Z(2), HillingerP(2), Kozhuharov N(2), du Fay de Lavallaz J(1), Pinck F(2), Lopez B(3), SalgadoE(3), Miró Ò(3), Bingisser R(4), Lohrmann J(5), Osswald S(2), Mueller C(6).
Author information: (1)Department of Cardiology, University Hospital Basel, Switzerland;Cardiovascular Research Institute Basel (CRIB), University Hospital Basel,Switzerland; GREAT network. (2)Department of Cardiology, University HospitalBasel, Switzerland; Cardiovascular Research Institute Basel (CRIB), UniversityHospital Basel, Switzerland. (3)GREAT network; Emergency department, HospitalClinic, Barcelona, Catalonia, Spain. (4)Department of Emergency Medicine,University Hospital Basel, Switzerland. (5)Department of Cardiology, UniversityHospital Basel, Switzerland; Cardiovascular Research Institute Basel (CRIB),University Hospital Basel, Switzerland; Department of Emergency Medicine,University Hospital Basel, Switzerland. (6)Department of Cardiology, UniversityHospital Basel, Switzerland; Cardiovascular Research Institute Basel (CRIB),University Hospital Basel, Switzerland; GREAT network. Electronic address:christian.mueller@usb.ch.
OBJECTIVE: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithmsubstantially improves the early triage of patient's assigned "rule-out" or"rule-in" of acute myocardial infarction (AMI), while diagnostic uncertaintyremains in that 25-30% of patients assigned to "observe". We aimed to bettercharacterize these patients.METHODS: In a prospective multicenter diagnostic study, we applied the hs-cTnT0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestiveof AMI to the emergency department. The final diagnosis was adjudicated by twoindependent cardiologists using all available information. Survival at 720-dayswas the prognostic endpoint. Findings were validated using a hs-cTnI0h/1h-algorithm.RESULTS: Twenty-four percent (n=523) of patients were assigned to "observe" bythe hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiplecharacteristics from "rule-out" and "rule-in" patients: they were older, in 75%male, and very often (57%) had pre-existing coronary artery disease (CAD).Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% ofpatients were suitable for coronary computed tomography angiography (CCTA). Themost common final adjudicated diagnoses were non-cardiac disease (38%),non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%).Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI(AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantlylower as compared to "rule-out" (p<0.001) and comparable to "rule-in" (p=ns).Findings were similar for the hs-cTnI "observe" zone.CONCLUSION: "Observe" patients are typically elderly men with pre-existing CADand high long-term mortality. Absolute hs-cTn-changes within 3h, functionalstress imaging and coronary angiography are the key diagnostic modalities.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.ijcard.2016.01.112 PMID: 26808985  [PubMed - indexed for MEDLINE]

23. Clin Chem. 2016 Mar;62(3):494-504. doi: 10.1373/clinchem.2015.249508. Epub 2016Jan 21.
Two-Hour Algorithm for Triage toward Rule-Out and Rule-In of Acute MyocardialInfarction by Use of High-Sensitivity Cardiac Troponin I.
Boeddinghaus J(1), Reichlin T(2), Cullen L(3), Greenslade JH(3), Parsonage WA(4),Hammett C(5), Pickering JW(6), Hawkins T(3), Aldous S(7), Twerenbold R(2), Wildi K(8), Nestelberger T(1), Grimm K(1), Rubini-Gimenez M(2), Puelacher C(8), KernV(8), Rentsch K(9), Than M(7), Mueller C(10).
Author information: (1)Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, and Department of Internal Medicine, University Hospital Basel, Basel, Switzerland;(2)Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, and.(3)Department of Emergency Medicine, Royal Brisbane and Women's Hospital,Brisbane, Australia; School of Public Health, The Queensland University ofTechnology, Brisbane, Australia; (4)School of Public Health, The QueenslandUniversity of Technology, Brisbane, Australia; School of Medicine, The Universityof Queensland, Brisbane, Australia; (5)School of Medicine, The University ofQueensland, Brisbane, Australia; (6)Department of Medicine, University of Otago, Christchurch, New Zealand; Emergency Department, Christchurch Hospital,Christchurch, New Zealand; (7)Emergency Department, Christchurch Hospital,Christchurch, New Zealand; (8)Cardiovascular Research Institute Basel (CRIB).(9)Laboratory Medicine, University Hospital Basel, Basel, Switzerland.(10)Cardiovascular Research Institute Basel (CRIB), Department of Cardiology, andchristian.mueller@usb.ch.
BACKGROUND: The early triage of patients toward rule-out and rule-in of acutemyocardial infarction (AMI) is challenging. Therefore, we aimed to develop a 2-h algorithm that uses high-sensitivity cardiac troponin I (hs-cTnI).METHODS: We prospectively enrolled 1435 (derivation cohort) and 1194 (externalvalidation cohort) patients presenting with suspected AMI to the emergencydepartment. The final diagnosis was adjudicated by 2 independent cardiologists.hs-cTnI was measured at presentation and after 2 h in a blinded fashion. Wederived and validated a diagnostic algorithm incorporating hs-cTnI values atpresentation and absolute changes within the first 2 h.RESULTS: AMI was the final diagnosis in 17% of patients in the derivation and 13%in the validation cohort. The 2-h algorithm developed in the derivation cohortclassified 56% of patients as rule-out, 17% as rule-in, and 27% as observation.Resulting diagnostic sensitivity and negative predictive value (NPV) were 99.2%and 99.8% for rule-out; specificity and positive predictive value (PPV) were95.2% and 75.8% for rule-in. Applying the 2-h algorithm in the externalvalidation cohort, 60% of patients were classified as rule-out, 13% as rule-in,and 27% as observation. Diagnostic sensitivity and NPV were 98.7% and 99.7% forrule-out; specificity and PPV were 97.4% and 82.2% for rule-in. Thirty-daysurvival was 100% for rule-out patients in both cohorts.CONCLUSIONS: A simple algorithm incorporating hs-cTnI baseline values andabsolute 2-h changes allowed a triage toward safe rule-out or accurate rule-in ofAMI in the majority of patients.
© 2015 American Association for Clinical Chemistry.
DOI: 10.1373/clinchem.2015.249508 PMID: 26797687  [PubMed - indexed for MEDLINE]

24. Heart. 2016 Apr;102(8):610-6. doi: 10.1136/heartjnl-2015-308917. Epub 2016 Jan21.
Direct comparison of clinical decision limits for cardiac troponin T and I.
Kimenai DM(1), Henry RM(2), van der Kallen CJ(2), Dagnelie PC(3), Schram MT(2),Stehouwer CD(4), van Suijlen JD(5), Niens M(5), Bekers O(1), Sep SJ(2), SchaperNC(4), van Dieijen-Visser MP(1), Meex SJ(1).
Author information: (1)Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC),Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM),Maastricht University, Maastricht, The Netherlands. (2)Cardiovascular ResearchInstitute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands. (3)CardiovascularResearch Institute Maastricht (CARIM), Maastricht University, Maastricht, TheNetherlands Department of Epidemiology, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht,The Netherlands. (4)Cardiovascular Research Institute Maastricht (CARIM),Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI),Maastricht University, Maastricht, The Netherlands. (5)Department of ClinicalChemistry, Gelre Hospital, Apeldoorn, The Netherlands.
OBJECTIVE: The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosingacute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche)and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds forhs-cTnT and hs-cTnI were derived from different reference cohorts it is unclearwhether they are biologically equivalent. We directly assessed sex-specific andage-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in asingle reference cohort, to investigate whether current divergent thresholds ofhs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohortvariation.METHODS: A healthy reference population was derived from a population-basedcohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals withdiabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG,N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerularfiltration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits.RESULTS: 1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits ofhs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limitswere higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age.CONCLUSIONS: Direct comparison reveals numerically similar thresholds for hs-cTnTand hs-cTnI assays. This finding is in line with recently reported underdiagnosisof AMI with the current decision limit of 26 ng/L for hs-cTnI, especially amongwomen. Downwards adjustment of the hs-cTnI threshold, differentiated for sex,would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI.
Published by the BMJ Publishing Group Limited. For permission to use (where notalready granted under a licence) please go tohttp://www.bmj.com/company/products-services/rights-and-licensing/
DOI: 10.1136/heartjnl-2015-308917 PMID: 26794233  [PubMed - indexed for MEDLINE]

25. Genet Mol Res. 2015 Dec 22;14(4):17959-65. doi: 10.4238/2015.December.22.21.
Clinical application of high-sensitivity cardiac troponin T test in acutemyocardial infarction diagnosis.
Wang JA(1), Qin Y(1), Lv J(1), Tian YF(1), Dong YJ(1).
Author information: (1)Department of Laboratory Medicine, Shandong Rizhao People's Hospital, Rizhao, China.
The aim of this study was to investigate the clinical application of ahigh-sensitivity cardiac troponin T (hs-cTnT) test in the diagnosis of acutemyocardial infarction (AMI). Serum levels of hs-cTnT and cardiac troponin I(cTnI) were detected in 240 AMI patients and 200 healthy donors and used to plot receiver operating characteristic (ROC) curves. A clinically applicablediagnostic cut-off value of hs-cTnT was determined from the ROC curve and thediagnostic accuracy of hs-cTnT and cTnI levels in AMI were compared.The serumhs-cTnT levels in the AMI group were higher than 0.014 ng/mL (the 99th percentileof the healthy population), among which hs-cTnT levels in patients withST-segment elevation myocardial infarction (STEMI) were higher than in patientswith non-STEMI (NSTEMI). The area under the ROC curve (AUC) for hs-cTnT wassignificantly higher than for cTnI, and the detection combining hs-cTnT andcreatine kinase isoenzyme (CK-MB) further increased the AUC. When 0.014 ng/mL wasset as the cut-off value for hs-cTnT, the diagnostic sensitivity for AMI reached 100% but the specificity was only 45.5%. The diagnostic ability of hs-cTnT forAMI peaked at a cut-off value of 0.035 ng/mL, resulting in the highest Youdenindex (0.654) and sensitivity and specificity values of 91.8 and 74.9%,respectively. The diagnostic utility of the hs-cTnT test for AMI is superior tothe traditional cTnI method. However, since hs-cTnT levels of non-AMI patientscan be over the diagnostic cut-off value, further studies are necessary to defineclinically applicable cut-off values of hs-cTnT.
DOI: 10.4238/2015.December.22.21 PMID: 26782442  [PubMed - indexed for MEDLINE]

26. Am J Med. 2016 Feb;129(2):e45. doi: 10.1016/j.amjmed.2015.10.005.
The Reply.
Mickley H(1).
Author information: (1)Odense University Hospital, Denmark.
Comment on    Am J Med. 2016 Feb;129(2):e43.    Am J Med. 2015 Aug;128(8):852-60.
DOI: 10.1016/j.amjmed.2015.10.005 PMID: 26777619  [PubMed - indexed for MEDLINE]

27. Am J Med. 2016 Feb;129(2):e43. doi: 10.1016/j.amjmed.2015.08.042.
Troponinemia: An Area That Still Needs to Be Explored.
Arunachalam K(1).
Author information: (1)Alpert Medical School of Brown University, Providence, RI.
Comment in    Am J Med. 2016 Feb;129(2):e45.
Comment on    Am J Med. 2015 Aug;128(8):852-60.
DOI: 10.1016/j.amjmed.2015.08.042 PMID: 26777618  [PubMed - indexed for MEDLINE]

28. Eur J Vasc Endovasc Surg. 2016 Apr;51(4):606-7. doi: 10.1016/j.ejvs.2015.11.018. Epub 2016 Jan 8.
Re: 'Clinical Relevance of Cardiac Troponin Assessment in Patients UndergoingCarotid Endarterectomy'.
Filis K(1), Vavuranakis M(2), Galyfos G(3).
Author information: (1)First Department of Propaedeutic Surgery, University of Athens Medical School,Hippocration Hospital, Athens, Greece. (2)First Department of Cardiology,University of Athens Medical School, Hippocration Hospital, Athens, Greece.(3)First Department of Propaedeutic Surgery, University of Athens Medical School,Hippocration Hospital, Athens, Greece. Electronic address:georgegalyfos@hotmail.com.
Comment in    Eur J Vasc Endovasc Surg. 2016 Apr;51(4):607.
Comment on    Eur J Vasc Endovasc Surg. 2016 Apr;51(4):473-80.
DOI: 10.1016/j.ejvs.2015.11.018 PMID: 26776707  [PubMed - indexed for MEDLINE]

29. Biosens Bioelectron. 2016 May 15;79:495-9. doi: 10.1016/j.bios.2015.12.083. Epub 2015 Dec 25.
Graphene quantum dots FRET based sensor for early detection of heart attack inhuman.
Bhatnagar D(1), Kumar V(2), Kumar A(3), Kaur I(4).
Author information: (1)CSIR-Central Scientific Instruments Organization, Sector 30-C, Chandigarh160030, India; CSIR-Institute of Genomics and Integrative Biology, Mall Road,Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), NewDelhi, India. (2)CSIR-Central Scientific Instruments Organization, Sector 30-C,Chandigarh 160030, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. (3)CSIR-Institute of Genomics and Integrative Biology, MallRoad, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR),New Delhi, India. Electronic address: ashokigib@rediffmail.com. (4)CSIR-CentralScientific Instruments Organization, Sector 30-C, Chandigarh 160030, India;Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.Electronic address: inderpreety@yahoo.co.in.
Cardiac immunosensor for early detection of heart attack (myocardial infarction) was developed using amine functionalized graphene quantum dots (afGQDs)conjugated with antibody anti-cardiac Troponin I (anti-cTnI) to detect cardiacmarker antigen Troponin I (cTnI) in blood based on fluorescence resonance energy transfer (FRET) between conjugate and graphene (quencher) only in 10 min. Theanti-cTnI was covalently conjugated to afGQDs through carbodiimide couplingreaction. The conjugate was characterized by zeta potential UV-vis spectroscopyand field emission scanning electron microscopy (FESEM). The sensing performance of the sensor was studied with respect to changes in the photon count andphotoluminescence of GQDs based on interaction of target cTnI with its specificanti-cTnI antibody. The sensor is highly specific and shows negligible responseto non-specific antigens. The sensor displayed a linear response to cTnI from0.001 to 1000 ng mL(-1) with a limit of detection of 0.192 pg mL(-1).
Copyright © 2015 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bios.2015.12.083 PMID: 26748366  [PubMed - indexed for MEDLINE]

30. Microvasc Res. 2016 May;105:34-9. doi: 10.1016/j.mvr.2015.12.010. Epub 2015 Dec22.
Endothelial dysfunction evaluated by peripheral arterial tonometry is relatedwith peak TnI values in patients with ST elevation myocardial infarction treated with primary angioplasty.
Baptista SB(1), Faustino M(2), Simões J(3), Nédio M(3), Monteiro C(3), LourençoE(3), Leal P(3), Farto eAbreu P(3), Gil V(3).
Author information: (1)Cardiology Department, Hospital Fernando Fonseca, Amadora, Portugal.Electronic address: sergio.b.baptista@gmail.com. (2)Cardiology Department,Hospital Fernando Fonseca, Amadora, Portugal. Electronic address:marianafaustino85@gmail.com. (3)Cardiology Department, Hospital Fernando Fonseca,Amadora, Portugal.
PURPOSE: The role of endothelial-dependent function in patients with acute STelevation myocardial infarction (STEMI) is not clear. Endothelial dysfunction maycontribute to the pathophysiological processes occurring after STEMI andinfluence the extension of myocardial necrosis. Endothelial-dependent dysfunctionevaluated by peripheral arterial tonometry (PAT) has already showed to becorrelated with microvascular coronary endothelial dysfunction. Our purpose wasto evaluate the impact of endothelial dysfunction on peak Troponin I (TnI)values, as a surrogate for the extension of myocardial infarction, in patientswith STEMI treated with primary angioplasty (P-PCI).METHODS: 58 patients with STEMI treated with P-PCI (mean age 59.0 ± 14.0 years,46 males) were included. Endothelial function was assessed by reactive hyperaemiaindex (RHI) determined by PAT. Patients were divided in two groups according tothe previously reported RHI threshold for high risk (1.67). The extension ofmyocardial necrosis was evaluated by peak TnI levels.RESULTS: RHI median value was 1.78 (IQR0.74);25 patients had endothelialdysfunction (RHI b 1.67). The two groups had no significant differences in age,gender, main risk factors and pain-to-balloon time. Patients with an RHI b 1.67had significant larger infarcts: TnI 73.5 ng/mL (IQR 114.42 ng/mL) versus TnI33.2 ng/mL (IQR 65.2 ng/mL); p = 0.028. On multivariate analysis, the presence ofan RHI b 1.67 kept significant impact on TnI peak values (p=0.02).CONCLUSIONS: The presence of endothelial-dependent dysfunction, assessed by PAT, is related with higher peak TnI values in STEMI patients treated with P-PCI.These results strength the possibility that endothelial-dependent dysfunction maybe a marker of poor prognosis and eventually a therapeutic target in patientswith STEMI.
DOI: 10.1016/j.mvr.2015.12.010 PMID: 26721522  [PubMed - indexed for MEDLINE]

31. Arch Pathol Lab Med. 2016 Jan;140(1):75-80. doi: 10.5858/arpa.2014-0580-OA.
Diagnosis of Acute Myocardial Infarction in Hemodialysis Patients WithHigh-Sensitivity Cardiac Troponin T Assay.
Huang HL(1), Zhu S, Wang WQ, Nie X, Shi YY, He Y, Song HL, Miao Q, Fu P, Wang LL,Li GX.
Author information: (1)From the Departments of Laboratory Medicine (Drs Li and Wang L-L; Mss Huang,Wang W-Q, Nie, He, and Song; and Messrs Zhu and Miao) and Nephrology (Drs Shi andFu), West China Hospital, Sichuan University, Chengdu, China.
CONTEXT: Cardiac troponins have become the gold standard for diagnosing acutemyocardial infarction (AMI) in the general population; however, their diagnostic accuracy for hemodialysis (HD) patients presenting with chest pain or dyspnea is uncertain.OBJECTIVE: To examine the diagnostic accuracy of high-sensitivity cardiactroponin T (hs-cTnT) assay for AMI in HD patients.DESIGN: In this prospective study, we enrolled 670 consecutive stable HD patientspresenting with chest pain or dyspnea on routine predialysis therapy in thenephrology department. Receiver operating characteristic (ROC) curves were usedto examine the diagnostic accuracy of hs-cTnT levels at enrollment in HD patientspresenting with chest pain or dyspnea, and the dynamic change in these levelsafter 3 hours.RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 12%of HD patients. Among patients with a final diagnosis other than AMI, 97% had aplasma hs-cTnT concentration above the 99th percentile. At the time ofenrollment, the area under the ROC curve of hs-cTnT levels for diagnosis of AMIwas 0.68 (95% confidence interval [CI], 0.62-0.74; P < .001) with a cutoff value of 107.7 ng/L; the relative change after 3 hours was 0.90 (95% CI, 0.82-0.96, P <.001) with a cutoff value of 24%, and the absolute change was 0.88 (95% CI,0.82-0.94, P < .001) with a cutoff value of 32.6 ng/L. The prognostic value for40-day mortality varied with the magnitude of elevation in hs-cTnT levels.CONCLUSIONS: Tracking the dynamic change in hs-cTnT levels during the short term significantly increased this measure's diagnostic accuracy for AMI in HDpatients.
DOI: 10.5858/arpa.2014-0580-OA PMID: 26717058  [PubMed - indexed for MEDLINE]

32. Am Heart J. 2016 Jan;171(1):92-102.e1-5. doi: 10.1016/j.ahj.2015.07.022. Epub2015 Jul 26.
One-hour rule-in and rule-out of acute myocardial infarction usinghigh-sensitivity cardiac troponin I.
Jaeger C(1), Wildi K(1), Twerenbold R(1), Reichlin T(1), Rubini Gimenez M(2),Neuhaus JD(1), Grimm K(1), Boeddinghaus J(1), Hillinger P(1), Nestelberger T(1), Singeisen H(1), Gugala M(1), Pretre G(1), Puelacher C(1), Wagener M(1), Honegger U(3), Schumacher C(3), Moreno Weidmann Z(1), Kreutzinger P(1), Krivoshei L(1),Freese M(1), Stelzig C(1), Dietsche S(3), Ernst S(4), Rentsch K(5), Osswald S(6),Mueller C(7).
Author information: (1)Department of Cardiology, University Hospital, Basel, Switzerland;Cardiovascular Research Institute Basel (CRIB), University Hospital, Basel,Switzerland. (2)Department of Cardiology, University Hospital, Basel,Switzerland; Cardiovascular Research Institute Basel (CRIB), University Hospital,Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III,Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain.(3)Cardiovascular Research Institute Basel (CRIB), University Hospital, Basel,Switzerland. (4)Department of Internal Medicine, Kantonsspital, Olten,Switzerland. (5)Laboratory Medicine, University Hospital, Basel, Switzerland.(6)Department of Cardiology, University Hospital, Basel, Switzerland.(7)Department of Cardiology, University Hospital, Basel, Switzerland;Cardiovascular Research Institute Basel (CRIB), University Hospital, Basel,Switzerland. Electronic address: Christian.Mueller@usb.ch.
We aimed to prospectively derive and validate a novel 0-/1-hour algorithm usinghigh-sensitivity cardiac troponin I (hs-cTnI) for the early "rule-out" and"rule-in" of acute myocardial infarction (AMI).METHODS: In a prospectivemulticenter diagnostic study, we enrolled 1,500 patients presenting withsuspected AMI to the emergency department. The final diagnosis was centrallyadjudicated by 2 independent cardiologists blinded to hs-cTnI concentrations. Thehs-cTnI (Siemens Vista) 0-/1-hour algorithm incorporated measurements performedat baseline and absolute changes within 1 hour, was derived in the first 750patients (derivation cohort), and then validated in the second 750 (validationcohort).RESULTS: Overall, AMI was the final diagnosis in 16% of patients. Applying thehs-cTnI 0-/1-hour algorithm developed in the derivation cohort to the validation cohort, 57% of patients could be classified as "rule-out"; 10%, as "rule-in"; and33%, as "observe." In the validation cohort, the sensitivity and the negativepredictive value for AMI in the "rule-out" zone were 100% (95% CI 96%-100%) and100% (95% CI 99%-100%), respectively. The specificity and the positive predictivevalue (PPV) for AMI in the "rule-in" zone were 96% (95% CI 94%-97%) and 70% (95% CI 60%-79%), respectively. Negative predictive value and positive predictivevalue of the 0-/1-hour algorithm were higher compared to the standard of carecombining hs-cTnI with the electrocardiogram (both P < .001).CONCLUSION: The hs-cTnI 0-/1-hour algorithm performs very well for early rule-outas well as rule-in of AMI. The clinical implications are that used in conjunctionwith all other clinical information, the 0-/1-hour algorithm will be a safe andeffective approach to substantially reduce time to diagnosis.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ahj.2015.07.022 PMID: 26699605  [PubMed - indexed for MEDLINE]

33. Talanta. 2016 Jan 1;146:823-30. doi: 10.1016/j.talanta.2015.06.006. Epub 2015 Jun7.
SPR detection of cardiac troponin T for acute myocardial infarction.
Pawula M(1), Altintas Z(1), Tothill IE(2).
Author information: (1)Cranfield University, Cranfield, Bedfordshire, MK43 0AL England, UK.(2)Cranfield University, Cranfield, Bedfordshire, MK43 0AL England, UK.Electronic address: i.tothill@cranfield.ac.uk.
A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive andspecific detection of cardiac troponin T (cTnT) in serum samples is reported inthis work. An extensive optimisation of assay parameters was conducted to achieveoptimal detection strategy. Both direct and sandwich immunoassay formats wereinvestigated and optimised. The response obtained was enhanced further by the useof gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. Aregeneration method was developed to enable the reuse of the SPR sensor formultiple sample application. The SPR immunosensor showed good reproducibility forcTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ngmL(-1) for the direct and sandwich assays in buffer, respectively. The linearregression analysis was performed and R(2) value was found as 0.99 for bothassays. In order to optimise the sensor for serum analysis, nonspecific bindingof serum proteins was reduced through the use of additives in the dilutionbuffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serumwas assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ngmL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) Musing Langmuir binding model which indicates high affinity between cTnT and itsantibody. The proposed SPR immunosensor has a promising potential to be developedfor point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers incentral nervous system diseases.
Copyright © 2015 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.talanta.2015.06.006 PMID: 26695335  [PubMed - indexed for MEDLINE]

34. J Med Assoc Thai. 2015 Oct;98(10):935-41.
CK-MB Activity, Any Additional Benefit to Negative Troponin in EvaluatingPatients with Suspected Acute Myocardial Infarction in the Emergency Department.
Jaruvongvanich V, Rattanadech W, Damkerngsuntorn W, Jaruvongvanich S,Vorasettakarnkij Y.
BACKGROUND: Coronary heart disease is now the leading cause of death. Diagnosing myocardial infraction (MI) needs cardiac marker in case of equivocal clinicalpresentations and EKG interpretations. Troponin yields high sensitivity andspecificity and could be used as a single screening assay. However, in actualpractice, clinicians send CK-MB activity (CKMBa) as a combined marker with anexpectation of providing additional diagnostic value due to large historicaldata. Discordant results from both markers lead to unclear management. Our study was to determine whether CKMBa has potential benefit for initial screening of MI in addition to cardiac troponin T (cTpT) in the Emergency Department (ED), andcan this marker be safely removed from the routine laboratory panel in theemergency setting in Thailand.MATERIAL AND METHOD: We conducted a retrospective cohort single-center study toexamine the usefulness of CKMBa in the ED from 907 patients who presented withclinically suspected acute M, and investigated with both biomarkers (CKMBa andcTpT). In these patients, 97 patients were included in the final analysis as theyhad negative cTpT associated with positive CKMBa or CKMBa turned to be positivewithin 24 hours after serial biomarkers measurements. The outcome was assessed bythe final diagnosis, the cause of death if patients died during admission, andthe 180-day mortality from medical chart review. In patients highly suspectedfor MI, further investigations were done including echocardiogram, exercise stresstest, and coronay angiogram by experienced cardiologists.RESULTS: During the studyperiod, cTpTwere sent 1,772 times and most (95.2%) ofthesamples were associated with CKMBa results. The outcome showed that no one withnegative cTpT was diagnosed as MI on a discharge diagnosis. Fourteen patientsdied during admission. The definitive cause was not defined as MI. The 180-daymortality was zero. During the follow-up, there was no MI suspected issues thatneeded further cardiac evaluations. The positive predictive value of CKMBa withnegative cTpT was 0% (95% CI, 0-0.047).CONCLUSION: CKMBa added no benefit to cTpT in diagnosing acute MI in ED. RemovingCKMBa from emergency panel could be considered.

PMID: 26638584  [PubMed - indexed for MEDLINE]

35. Can J Anaesth. 2016 Feb;63(2):227-32. doi: 10.1007/s12630-015-0539-0. Epub 2015Dec 3.
Chasing myocardial outcomes: perioperative myocardial infarction and cardiactroponin.
Royo MB(1), Fleisher LA(2,)(3).
Author information: (1)Department of Anesthesiology and Critical Care, Perelman School of Medicine,University of Pennsylvania, 310 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-4865, USA. Marc.Royo@uphs.upenn.edu. (2)Department of Anesthesiologyand Critical Care, Perelman School of Medicine, University of Pennsylvania, 310Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-4865, USA. (3)SeniorScholar Leonard Davis Institute, University of Pennsylvania, Philadelphia, PA,USA.
Perioperative myocardial infarction represents the most common cardiovascularcomplication following non-cardiac surgery, but frequently presents without theusual clinical signs and symptoms c

hs-Troponina: busqueda de trabajos 2015-2016Fecha: 1/3/2017

 


1. Bratisl Lek Listy. 2016;117(8):442-7.
Parathyroid hormone is associated with heart failure with preserved ejectionfraction.
Bezgin T, Elveran A, Karagoz A, Canga Y, Dogan C.
BACKGROUND: Parathyroid hormone (PTH) is a novel promising biomarker that canpredict hospitalization, functional status and mortality in patients who sufferedheart failure with preserved ejection fraction (HFpEF).OBJECTIVE: We aimed to investigate the association of serum PTH levels andmeasures of disease severity (NYHA functional class, NT-proBNP, CRP, EF, TroponinI) in patients with HFpEF.METHODS: A total of consecutive 58 outpatients with HFpEF and 30 controls wereprospectively studied. All patients underwent laboratory tests, includingNT-proBNP and PTH analyses.RESULTS: PTH, NT-proBNP, troponin I, and CRP levels were significantly higher in patients with HFpEF when compared with control group (54.61 ± 31.02 vs 40.40 ±14.22 pg/ml, p < 0.05; 126.05 ± 162.94 vs 44.57 ± 14.95 pg/ml, p < 0.01; 0.011 ± 0.013 vs 0.004 ± 0.001 ug/L, p < 0.01; 4.65 ± 4.24 vs 1.63 ± 0.97 mg/L, p < 0.01,respectively). Left atrium was found to be more enlarged in HFpEF patients (LAVI = 36 ± 18 vs 28 ± 11 ml/m², p < 0.01). Most indices of left ventricular diastolicfunction were more severely impaired compared to controls (p < 0.05). There wasno correlation between PTH and CRP, troponin I, LVMI, LV volumes, LV diameters,E/E', age, and BMI in both groups (p = NS). There was strong positive correlationbetween PTH and NT-proBNP levels in all study participants (r = 0.359; p < 0.01).CONCLUSION: PTH together with other markers of heart failure may provide valuableinformation both in the diagnosis and staging of heart failure syndromes (Tab. 4,Fig. 1, Ref. 40).

PMID: 27546695  [PubMed - indexed for MEDLINE]

2. Rev Fac Cien Med Univ Nac Cordoba. 2016;73(1):8-14.
[High sensitivity T troponin and CA-125 as prognostic biomarkers in patients withend stage renal disease in hemodialysis].
[Article in Spanish]
Moreno JS(1), Lépori AJ(1), Novoa P(2), De Elia R(3), Guglielmone R(3), BonoJP(1).
Author information: (1)Servicio de Cardiología, Sanatorio Allende Nueva Córdoba, Córdoba, Argentina. (2)Servicio de Nefrología, Sanatorio Allende Nueva Córdoba, Córdoba, Argentina.(3)Laboratorio central, Sanatorio Allende Nueva Córdoba, Córdoba, Argentina.
INTRODUCTION: The end stage renal disease confers a high morbidity and mortality risk, mainly due to cardiovascular disease. The cardiac T troponin andcarbohydrate antigen-125 (CA-125) are useful biomarkers to determinecardiovascular prognosis in order to start preventive treatment in the high risk patients.METHODS: We included patients with end stage renal disease in hemodialysistreatment. Plasma high sensitivity cardiac T troponin (hs-TNT) and CA-125 weremeasured at the beginning of follow up. The patients with clinical evidence of anacute myocardial infarction were excluded. Twelve month after the measurement of the biomarkers the patients were called to assess the occurrence of major adversecardiovascular events (MACE) and hospitalizations for any reason.RESULTS: Eighty seven patients were included. The mean age was 5815 years, and76% were male. The hs-TNT was elevated in 95.4% of the patients and the medianvalue was 49 ng/l (15.3 - 214.1). CA-125 median value was 13.7 U/ml (6.1 - 52.7).The patients that presented a MACE had higher CA-125 (p< 0.03) and hs-TNT (p<0.001); and all of them had a troponin value ≥ 69.37 ng/l.CONCLUSIONS: The prevalence of high hs-TNT was 95.4% and of CA-125 10%. MACE weresignificantly higher in patients with elevated biomarkers, conferring themprognostic utility in this group of patients.

PMID: 27419890  [PubMed - indexed for MEDLINE]

3. Biochem Med (Zagreb). 2016;26(2):233-9. doi: 10.11613/BM.2016.025.
Recovery of spiked troponin I in four routine assays.
Loh TP(1), Lim XC(1), Kieu K(1), Sajiir H(1), Neo SF(1), Cheng WL(1), SethiSK(1).
Author information: (1)Department of Laboratory Medicine, National University Hospital, Singapore,Singapore.
INTRODUCTION: This study aimed to examine the recovery of spiked human cardiactroponin I (cTnI) results measured by four routine assays, and investigatepossible interference from microclots.MATERIALS AND METHODS: 457 consecutive samples with cTnI concentration belowlimit of quantitation (12 ng/L), declared by the Vitros TnI ES assay (referenceassay), were measured on Beckman Coulter Accu TnI+3, Siemens TnI-Ultra and Roche TnI STAT assays. These samples were enriched with native full-length cTnI to aconcentration of 100 ng/L and retested. A post-spiking result that exceeded thecritical difference at a predefined probability of 0.0005 of the targetconcentration (the median post-spiking result for each individual assay) wasconsidered as outlier. To determine whether microclots were a significant causeof critically discrepant outlier results, a separate 50 samples were centrifuged twice between two post-spiking measurements using the Vitros TnI ES assay.RESULTS: The median recovery of the enriched cTnI was highest with the Rocheassay (271 ng/L) and lowest with the Vitros assay (29 ng/L). The Vitros assay hadthe highest percentage of results that exceeded the critical difference (49%),followed by the Siemens (38%), Roche (18%) and Beckman Coulter (7%) assays. None of the 50 additional samples produced a critically lower cTnI result afterre-centrifugation.CONCLUSIONS: Our findings underscored the variability of cTnI assays in measuringnative cTnI. The lack of cTnI results that became significantly lower afterre-centrifugation suggested that microclots are unlikely to be a major cause ofthe outlier results.
DOI: 10.11613/BM.2016.025 PMCID: PMC4910266PMID: 27346968  [PubMed - indexed for MEDLINE]

4. S Afr Med J. 2016 Mar;106(3):239-45.
Approach to chest pain and acute myocardial infarction.
Pandie S, Hellenberg D, Hellig F, Ntsekhe M.
Patient history, physical examination, 12-lead electrocardiogram (ECG) andcardiac biomarkers are key components of an effective chest pain assessment. The first priority is excluding serious chest pain syndromes, namely acute coronarysyndromes (ACSs), aortic dissection, pulmonary embolism, cardiac tamponade andtension pneumothorax. On history, the mnemonic SOCRATES (Site Onset CharacterRadiation Association Time Exacerbating/relieving factor and Severity) helpsdifferentiate cardiac from non-cardiac pain. On examination, evaluation of vital signs, evidence of murmurs, rubs, heart failure, tension pneumothoraces and chestinfections are important. A 12-lead ECG should be interpreted within 10 minutesof first medical contact, specifically to identify ST elevation myocardialinfarction (STEMI). High-sensitivity troponins improve the rapid rule-out ofmyocardial infarction (MI) and confirmation of non-ST elevation MI (NSTEMI). ACS (STEMI and NSTEMI/unstable anginapectoris (UAP)) result from acutedestabilisation of coronary atheroma with resultant complete (STEMI) or subtotal (NSTEMI/UAP) thrombotic coronary occlusion. The management of STEMI patientsincludes providing urgent reperfusion: primary percutaneous coronaryintervention(PPCI) if available, deliverable within 60 - 120 minutes, andfibrinolysis if PPCI is not available. Essential adjunctive therapies includeantiplatelet therapy (aspirin, P2Y12 inhibitors), anticoagulation (heparin orlow-molecular-weight heparin) and cardiac monitoring.

PMID: 27303759  [PubMed - indexed for MEDLINE]

5. Lancet. 2016 Jun 4;387(10035):2289. doi: 10.1016/S0140-6736(16)30686-9.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Fujita T(1).
Author information: (1)Department of Surgery, Jikei University School of Medicine, Tokyo, Japan.Electronic address: tetsu@jg8.so-net.ne.jp.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30686-9 PMID: 27302265  [PubMed - indexed for MEDLINE]

6. Lancet. 2016 Jun 4;387(10035):2289. doi: 10.1016/S0140-6736(16)30687-0.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Ford C(1), Whitehead SJ(1), Gama R(2), Willmer KA(3).
Author information: (1)Department of Clinical Chemistry, Royal Wolverhampton NHS Trust,Wolverhampton, UK. (2)Department of Clinical Chemistry, Royal Wolverhampton NHSTrust, Wolverhampton, UK. Electronic address: rousseau.gama@nhs.net.(3)Department of Acute Medicine, Royal Wolverhampton NHS Trust, Wolverhampton,UK.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30687-0 PMID: 27302264  [PubMed - indexed for MEDLINE]

7. Lancet. 2016 Jun 4;387(10035):2289-91. doi: 10.1016/S0140-6736(16)30517-7.
Measurement of cardiac troponin for exclusion of myocardial infarction - Authors'reply.
Shah AS(1), Anand A(2), Chapman AR(2), Newby DE(2), Mills NL(2); High-STEACSInvestigators.
Author information: (1)BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.Electronic address: Anoop.Shah@ed.ac.uk. (2)BHF Centre for CardiovascularScience, University of Edinburgh, Edinburgh, UK.
Comment on    Lancet. 2016 Jun 4;387(10035):2289.    Lancet. 2016 Jun 4;387(10035):2288.    Lancet. 2016 Jun 4;387(10035):2289.    Lancet. 2016 Jun 4;387(10035):2288-9.    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30517-7 PMID: 27302263  [PubMed - indexed for MEDLINE]

8. Lancet. 2016 Jun 4;387(10035):2288. doi: 10.1016/S0140-6736(16)30684-5.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Boeddinghaus J(1), Twerenbold R(1), Nestelberger T(1), Wildi K(1), Mueller C(2).
Author information: (1)Cardiovascular Research Institute Basel and Department of Cardiology,University Hospital Basel, Basel, Switzerland. (2)Cardiovascular ResearchInstitute Basel and Department of Cardiology, University Hospital Basel, Basel,Switzerland. Electronic address: christian.mueller@usb.ch.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30684-5 PMID: 27302262  [PubMed - indexed for MEDLINE]

9. Lancet. 2016 Jun 4;387(10035):2288-9. doi: 10.1016/S0140-6736(16)30685-7.
Measurement of cardiac troponin for exclusion of myocardial infarction.
Mullen L(1), Chew PG(2), Frost F(2), Obafemi T(2), Khand A(3).
Author information: (1)University Hospital Aintree, Liverpool, UK. Electronic address:liammullen@nhs.net. (2)University Hospital Aintree, Liverpool, UK. (3)University Hospital Aintree, Liverpool, UK; Liverpool Heart and Chest Hospital, Liverpool,UK.
Comment in    Lancet. 2016 Jun 4;387(10035):2289-91.
Comment on    Lancet. 2015 Dec 19;386(10012):2481-8.
DOI: 10.1016/S0140-6736(16)30685-7 PMID: 27302261  [PubMed - indexed for MEDLINE]

10. Mymensingh Med J. 2016 Apr;25(2):226-31.
Correlation between Troponin-I and B-Type Natriuretic Peptide Level in AcuteMyocardial Infarction Patients with Heart Failure.
Islam MN(1), Alam MF, Debnath RC, Aditya GP, Ali MH, Hossain MA, Siddique SR.
Author information: (1)Dr Mirza Md Nazrul Islam, Associate Professor, Department of Cardiology,Mymensingh Medical College (MMC), Mymensingh, Bangladesh.
Troponins are regarded as markers of choice for the diagnosis of acute myocardialinfarction (AMI). But B-type natriuretic peptide (BNP) level is also elevated in AMI and is a quantitative biochemical marker related to the extent of infarction and the left ventricle systolic dysfunction. Thus, BNP has prognostic value. Inthis study, we investigate the correlation of Troponin-I with BNP levels inpatients presenting with AMI with or without Acute Heart Failure. Rationale ofthis study is to see, whether quantitative Troponin alone can serve for bothdiagnosis and prognosis of AMI Patients with heart failure or not. Thiscross-sectional analytical study was conducted in the Department of Cardiology inMymensingh Medical College Hospital from January 2014 to December 2014. Total 100patients were studied and divided into two groups - 50 patients in each group.Group I: Patients with first attack of acute myocardial infarction (without heartfailure) & Group II: Patients with first attack of acute myocardial infarctionwith acute heart failure. Mean Troponin-I of Group I and Group II were 3.10±2.68 and 62.93±32.75ng/ml respectively & mean BNP value of Group I and Group II were20.96±14.18 and 615.65±249.27pg/ml respectively. In this study, it was shown thatthe levels of BNP had positive correlation with Troponin-I levels, with mediumstrength of association (r=0.734, p<0.05). Echocardiography shows that patientswith high BNP level has low ejection fraction (LVEF) and patients with low BNPlevel has preserved ejection fraction (LVEF). Thus, the present study shows that the higher the Troponin-I levels, the higher the BNP levels in first attack ofAMI patients and the more severe the heart failure (more severe left ventricledysfunction). There is positive correlation between Troponin-I and BNP levels in first attack of AMI patients with acute heart failure.

PMID: 27277352  [PubMed - indexed for MEDLINE]

11. Clin Lab. 2016;62(4):743-8.
High-Sensitivity Cardiac Troponin T: a Preanalytical Evaluation.
Michel M, Mestari F, Alkouri R, Atlan Grégory, Dever S, Devilliers C,Imbert-Bismut F, Bonnefont-Rousselot D, Monneret D.
BACKGROUND: Little is known about the effects of preanalytical conditions onhigh-sensitivity cardiac troponin T (hs-cTnT) concentrations.METHODS: Variations of hs-cTnT concentrations were evaluated under the following preanalytical conditions: 1) serum vs. lithium-heparin (Li-Hep) plasma, with orwithout separator gel; 2) centrifugation time (15-minutes vs. 10-minutes) andspeed (1467 to 3756 g); 3) stability in Li-Hep plasma at room temperature and +4 degrees C for 4 days and at -80 degrees C for up to 12 months, for threeconcentrations; 4) four freeze-thaw cycles at -20 degrees C and -80 degrees C,for three concentrations.RESULTS: No significant changes were found regarding the type of blood collectiontube, the centrifugation, and storage conditions. Minor decreases were observedafter four freeze-thaw cycles at -20 degrees C (< 6.5%) and -80 degrees C (<3.4%).CONCLUSIONS: High-sensitivity cardiac troponin T may be considered as notimpacted by usual preanalytical conditions, thus strengthening its reliability inlaboratory practice and clinical research.

PMID: 27215098  [PubMed - indexed for MEDLINE]

12. Clin Lab. 2016;62(4):739-42.
Performance Evaluation of the FREND Cardiac Triple Cartridge on the FREND System.
Lee K, Han M, Song SH, Park KU, Song WH, Song J.
BACKGROUND: We evaluated the performance of the FREND Cardiac Triple cartridge onthe FREND system in the detection of cardiac markers-myoglobin, cardiac troponin I (cTnI), and creatine kinase-MB (CK-MB).METHODS: Quantitative immunoassays were performed using the FREND system(NanoEnTek, Seoul, Korea) and its cartridge. The precision, detection limits,linearity, and correlation with the Siemens Dimension Vista 500 (SiemensHealthcare Diagnostics, Deerfield, IL, USA) were evaluated. The cutoff value for each marker was calculated in healthy individuals (men and women, n = 138 each).RESULTS: The coefficients of variation for imprecision were less than 19.0% atlow and high serum concentrations. The lower limits of quantification formyoglobin, cTnI, and CK-MB were 3.11, 0.073, and 0.70 ng/mL, respectively.Acceptable linearity was achieved for each marker (R2 < 0.99). The results fromthe FREND system were in good agreement with those from the Siemens DimensionVista (correlation coefficients > 0.9). The cutoff values in male and femaleindividuals (n = 138 each) were 104.3 and 98.9 ng/mL, respectively, formyoglobin, and 4.35 and 5.37 ng/mL, respectively, for CK-MB. The cutoff value forcTnI was 0.073 ng/mL.CONCLUSIONS: The FREND Cardiac Triple cartridge exhibited good precision,clinically acceptable linearity, and reliable correlation with the DimensionVista.

PMID: 27215097  [PubMed - indexed for MEDLINE]

13. Clin Lab. 2016;62(4):705-9.
The Influence of Blood Collection Tubes on Measurement of Cardiac Biomarkers.
Lan H, Du W, Mo Z, Huang H.
BACKGROUND: The tube used to collect a blood specimen may have an effect on some test results. This study evaluated three different types of blood collectiontubes manufactured in China for use in testing three cardiac biomarkers.METHODS: Blood samples were drawn from 42 patients in the Intensive Care Unit andwere sampled into three different types of blood collection tubes at the sametime. All samples were subjected to analysis of myoglobin (MYO), creatine kinase MB (CK-MB), and high-sensitive cardiac troponin T (hs-cTnT) using the Roche Cobase411 chemistry analyzer.RESULTS: There was no statistically significant difference in the test resultsfor MYO and CK-MB among the three different types of blood collection tubes.However, there was a statistically significant difference in the measured levelof hs-cTnT. The hs-cTnT values in tubes with clot activator were significantlylower than the values from tubes with no additive (p = 0.000) or lithium heparin (p = 0.002).CONCLUSIONS: Three types of blood collection tubes are safe for myoglobin andCK-MB determination without altering the results. However, the hs-cTnT value was lower in clot activator tubes than in tubes with no additive or with heparinlithium. Thus, we conclude that using clot activator tubes can affect thedetermination of hs-cTnT concentration which should be noted in clinicalpractice.

PMID: 27215091  [PubMed - indexed for MEDLINE]

14. BMC Cardiovasc Disord. 2016 May 4;16:79. doi: 10.1186/s12872-016-0255-x.
Troponin I levels in permanent atrial fibrillation-impact of rate control andexercise testing.
Horjen AW(1,)(2), Ulimoen SR(3), Enger S(3), Norseth J(4), Seljeflot I(5,)(6),Arnesen H(5,)(6), Tveit A(3).
Author information: (1)Department of Medical Research, Baerum Hospital, Vestre Viken Hospital Trust, N-3004, Drammen, Norway. awhorjen@gmail.com. (2)Faculty of Medicine, Universityof Oslo, Oslo, Norway. awhorjen@gmail.com. (3)Department of Medical Research,Baerum Hospital, Vestre Viken Hospital Trust, N-3004, Drammen, Norway. (4)Clinic for Medical Diagnostics, Vestre Viken Hospital Trust, Drammen, Norway. (5)Facultyof Medicine, University of Oslo, Oslo, Norway. (6)Center for Clinical HeartResearch, Department of Cardiology, Oslo University Hospital Ullevål, Oslo,Norway.
BACKGROUND: High-sensitivity troponin I (hs-TnI) and troponin T (hs-TnT) aremoderately correlated and independently related to outcome in atrial fibrillation(AF). Rate controlling therapy has been shown to reduce hs-TnT, however thepotential impact on hs-TnI levels, and whether this differs from the effects onhs-TnT, has not been investigated previously.METHODS: Sixty patients with stable, permanent AF without heart failure or known ischemic heart disease were included in a randomised crossover study (mean age 71± 9 years, 18 women). Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for three weeks, in a randomisedsequence. At baseline and on the last day of each treatment period, hs-TnI wasmeasured at rest and after a maximal exercise test and compared to hs-TnT.RESULTS: Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p <0.001). All drugs reduced both the resting and the peak exercise levels of hs-TnIcompared with baseline (p < 0.001 for all). The decline in resting hs-TnI andhs-TnT values relative to baseline levels was similar for all drugs except forverapamil, which reduced hs-TnI more than hs-TnT (p = 0.017). Levels of hs-TnIincreased significantly in response to exercise testing at baseline and at alltreatment regimens (p < 0.001 for all). The relative exercise-induced increase inhs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001), ondiltiazem (p < 0.001) and on verapamil (p = 0.001).CONCLUSIONS: In our population of stable, permanent AF patients, all four ratecontrol drug regimens reduced hs-TnI significantly, both at rest and duringexercise. The decline in hs-TnI and hs-TnT levels associated with beta-blockerand calcium channel blocker treatment was similar, except for a larger relativedecrease in hs-TnI levels following verapamil treatment.TRIAL REGISTRATION: www.clinicaltrials.gov ( NCT00313157 ).
DOI: 10.1186/s12872-016-0255-x PMCID: PMC4855853PMID: 27142292  [PubMed - indexed for MEDLINE]

15. PLoS One. 2016 Apr 20;11(4):e0153300. doi: 10.1371/journal.pone.0153300.eCollection 2016.
High-Sensitivity Cardiac Troponin Concentrations in Patients with ChestDiscomfort: Is It the Heart or the Kidneys As Well?
Cardinaels EP(1), Altintas S(2), Versteylen MO(2), Joosen IA(2), Jellema LJ(3),Wildberger JE(4), Das M(4), Crijns HJ(2), Bekers O(1), van Dieijen-Visser MP(1), Kietselaer BL(2,)(4), Mingels AM(1).
Author information: (1)Central Diagnostic Laboratory, Department of Clinical Chemistry,Cardiovascular Research Institute Maastricht (CARIM), Maastricht UniversityMedical Center (MUMC+), Maastricht, the Netherlands. (2)Department of Cardiology,CARIM, MUMC+, Maastricht, the Netherlands. (3)Department of Clinical Chemistryand Hematology, Gelre Hospitals, Apeldoorn, the Netherlands. (4)Department ofRadiology, CARIM, MUMC+, Maastricht, the Netherlands.
BACKGROUND: High-sensitivity cardiac troponins (hs-cTn) are the preferredbiomarkers to detect myocardial injury, making them promising risk-stratifyingtools for patients with symptoms of chest pain. However, circulating hs-cTn arealso elevated in other conditions like renal dysfunction, complicatingappropriate interpretation of low-level hs-cTn concentrations.METHODS: A cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwentcardiac computed tomographic angiography (CCTA). Serum samples were analyzedusing hs-cTnT and hs-cTnI assays. Renal function was measured by the estimatedglomerular filtration rate (eGFR), established from serum creatinine and cystatinC. On follow-up, the incidence of adverse events was assessed.RESULTS: Median hs-cTnT and hs-cTnI concentrations were 7.2(5.8-9.2) ng/L and2.6(1.8-4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR(hs-cTnT:stβ:-0.290;hs-cTnI:stβ:-0.222) than with cardiac imaging parameters,such as coronary calcium score, CCTA plaque severity score and left ventricularmass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT[HR(95%CI), 1.02(1.00-1.03) compared to 1.07(1.05-1.09)] and hs-cTnI[1.01(1.00-1.01) compared to 1.02(1.01-1.02)] (all p<0.001).CONCLUSION: In patients with chest discomfort, we identified an independentinfluence of renal function on hs-cTn concentrations besides CAD, that affectedthe association of hs-cTn concentrations with adverse events. Estimating renalfunction is therefore warranted when interpreting baseline hs-cTn concentrations.
DOI: 10.1371/journal.pone.0153300 PMCID: PMC4838230PMID: 27096420  [PubMed - indexed for MEDLINE]

16. PLoS One. 2016 Apr 14;11(4):e0153492. doi: 10.1371/journal.pone.0153492.eCollection 2016.
Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients inan Emergency Department: A Retrospective Cohort Study.
Yang Z(1,)(2), Qdaisat A(1), Hu Z(1,)(3), Wagar EA(4), Reyes-Gibby C(1), MengQH(4), Yeung SC(1,)(5).
Author information: (1)Department of Emergency Medicine, The University of Texas MD Anderson CancerCenter, 1515 Holcombe Blvd., Houston, Texas 77030, United States of America.(2)Department of Intensive Care, Guangzhou First People's Hospital, GuangzhouMedical University, 1 Panfu Road, Guangdong, People's Republic of China.(3)Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651Dongfeng East Rd., West F16, Guangzhou, Guangdong 510060, People's Republic ofChina. (4)Laboratory Medicine, The University of Texas MD Anderson Cancer Center,1515 Holcombe Blvd., Houston, Texas 77030, United States of America.(5)Department of Endocrine Neoplasia and Hormonal Disorders, The University ofTexas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030,United States of America.
BACKGROUND: Septic shock may be associated with myocardial damage; however, theprognostic value of cardiac enzymes in cancer patients with septic shock isunknown. In this study, we evaluated the prognostic significance of cardiacenzymes in combination with established prognostic factors in predicting the7-day mortality rate of patients with septic shock, and we constructed a newscoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates.METHODS AND FINDINGS: We performed a retrospective cohort study of 375 adultcancer patients with septic shock who visited the emergency department of acomprehensive cancer center between 01/01/2004 and 12/31/2013. The 7-day and28-day mortality rates were 19.7% and 37.6%, respectively. The creatine kinasemyocardial band fraction and troponin-I were significantly higher in patients whodied in ≤7 days and ≤28 days than in those who did not. In Cox regression models,troponin-I >0.05 ng/mL plus Predisposition, Infection, Response, and OrganFailure (PIRO2011) or Mortality in Emergency Department Sepsis (MEDS) score was asignificant predictor of survival for ≤7 days. With our new SOPED scoring system,the receiver operating characteristic area under the curve was 0.836, higher thanthose for PIRO2011 and MEDS.CONCLUSIONS: Troponin-I >0.05 ng/mL was an important predictor of short-termmortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, wasmore prognostically accurate than were other scores for 7-day mortality. Largemulticenter studies are needed to verify our results and prospectively validatethe prognostic performance of the SOPED score.
DOI: 10.1371/journal.pone.0153492 PMCID: PMC4831781PMID: 27077648  [PubMed - indexed for MEDLINE]

17. Evid Based Med. 2016 Jun;21(3):100. doi: 10.1136/ebmed-2016-110405. Epub 2016 Apr13.
High-sensitivity troponin predicts coronary disease outcomes in type 2 diabetesbut yields no benefit in selecting patients for revascularisation.
Junttila J(1).
Author information: (1)Medical Research Center Oulu, University of Oulu and Oulu University Hospital,Oulu, Finland.
Comment on    N Engl J Med. 2015 Aug 13;373(7):610-20.
DOI: 10.1136/ebmed-2016-110405 PMID: 27075268  [PubMed - indexed for MEDLINE]

18. JACC Cardiovasc Interv. 2016 Apr 11;9(7):754. doi: 10.1016/j.jcin.2016.02.003.
Reply: Immediate Invasive Strategy for Patients With Both New IschemicElectrocardiographic Changes and Troponin Elevation.
Milosevic A, Vasiljevic-Pokrajcic Z, Milasinovic D, Vukcevic V, Asanin M,Stankovic G.
Comment on    JACC Cardiovasc Interv. 2016 Mar 28;9(6):541-9.    JACC Cardiovasc Interv. 2016 Apr 11;9(7):753.
DOI: 10.1016/j.jcin.2016.02.003 PMID: 27056318  [PubMed - indexed for MEDLINE]

19. JACC Cardiovasc Interv. 2016 Apr 11;9(7):753. doi: 10.1016/j.jcin.2016.01.019.
Immediate Invasive Strategy for Patients With Both New IschemicElectrocardiographic Changes and Troponin Elevation.
Sanchis J, Núñez J.
Comment in    JACC Cardiovasc Interv. 2016 Apr 11;9(7):754.
Comment on    JACC Cardiovasc Interv. 2016 Mar 28;9(6):541-9.
DOI: 10.1016/j.jcin.2016.01.019 PMID: 27056317  [PubMed - indexed for MEDLINE]

20. Ann Card Anaesth. 2016 Apr-Jun;19(2):321-7. doi: 10.4103/0971-9784.179638.
Troponin elevations in patients with chronic cardiovascular disease: An analysis of current evidence and significance.
Martin AK, Malhotra AK, Sullivan BL, Ramakrishna H(1).
Author information: (1)Division of Cardiovascular and Thoracic Anesthesiology, Mayo Clinic Arizona,AZ, USA.
Serum troponin elevation above the 99th percentile of the upper reference limitin healthy subjects (<0.01 ng/ml measured using currently availablehigh-sensitivity cardiac troponin laboratory assays) is required to establish thediagnosis the diagnosis of myocardial necrosis in acute cardiovascular syndromes,as well as guide prognosis and therapy. In the perioperative period, for patientswith cardiac disease undergoing noncardiac surgery, it is a particularly criticalbiomarker universally used to assess the myocardial damage. The value of troponintesting and elevation (as well as its significance) in patients with chroniccardiac valvular, vascular, and renal disease is relatively less well understood.This evidence-based review seeks to examine the currently available dataassessing the significance of troponin elevation in certain chronic valvular and other disease states.
DOI: 10.4103/0971-9784.179638 PMCID: PMC4900336PMID: 27052076  [PubMed - indexed for MEDLINE]

21. Tex Heart Inst J. 2016 Feb 1;43(1):38-42. doi: 10.14503/THIJ-14-4712. eCollection2016.
Predictors of Elevated Cardiac Enzyme Levels in Hospitalized Patients with AtrialFibrillation and No Known Coronary Artery Disease.
Vinales KL, Najib MQ, Marella PC, Katayama M, Chaliki HP.
We retrospectively studied the predictive capabilities of elevated cardiac enzymelevels in terms of the prognosis of patients who were hospitalized with atrialfibrillation and who had no known coronary artery disease. Among 321 patientswith atrial fibrillation, 60 without known coronary artery disease had theircardiac enzyme concentrations measured during hospitalization and underwentstress testing or cardiac catheterization within 12 months before or afterhospitalization. We then compared the clinical and electrocardiographiccharacteristics of the 20 patients who had elevated cardiac enzyme levels and the40 patients who had normal levels. Age, sex, and comorbidities did not differbetween the groups. In the patients with elevated cardiac enzyme levels, the meanconcentrations of troponin T and creatine kinase-MB isoenzymes were 0.08 ± 0.08ng/mL and 6.49 ± 4.94 ng/mL, respectively. In univariate analyses, only peakheart rate during atrial tachyarrhythmia was predictive of elevated enzyme levels(P <0.0001). Mean heart rate was higher in the elevated-level patients (146 ± 22 vs 117 ± 29 beats/min; P=0.0007). Upon multivariate analysis, heart rate was the only independent predictor of elevated levels. Coronary artery disease was found in only 2 patients who had elevated levels and in one patient who had normallevels (P=0.26). Increased myocardial demand is probably why the presenting heartrate was predictive of elevated cardiac enzyme levels. Most patients withelevated enzyme levels did not have coronary artery disease, and none died ofcardiac causes during the 6-month follow-up period. To validate our findings,larger studies are warranted.
DOI: 10.14503/THIJ-14-4712 PMCID: PMC4810582PMID: 27047283  [PubMed - indexed for MEDLINE]

22. Med Intensiva. 2016 Apr;40(3):200. doi: 10.1016/j.medin.2016.01.010. Epub 2016Mar 22.
[Methods can influence the value of copeptin to rule-out acute myocardialinfarction without ST segment elevation].
[Article in Spanish]
García de Guadiana-Romualdo L(1), Consuegra-Sánchez L(2), Esteban-Torrella P(3), Martínez-Díaz JJ(2), Albaladejo-Otón MD(3).
Author information: (1)Servicio de Análisis Clínicos, Hospital Universitario Santa Lucía, Cartagena, Murcia, España. Electronic address: guadianarom@yahoo.es. (2)Servicio deCardiología y Hemodinámica, Hospital Universitario Santa Lucía, Cartagena,Murcia, España. (3)Servicio de Análisis Clínicos, Hospital Universitario SantaLucía, Cartagena, Murcia, España.
Comment on    Med Intensiva. 2016 Apr;40(3):199.    Med Intensiva. 2015 Nov;39(8):477-82.
DOI: 10.1016/j.medin.2016.01.010 PMID: 27015787  [PubMed - indexed for MEDLINE]

23. Swiss Med Wkly. 2016 Mar 21;146:w14285. doi: 10.4414/smw.2016.14285. eCollection 2016.
Elevated high-sensitivity troponin T levels are associated with adverse cardiacremodelling and myocardial fibrosis in hypertrophic cardiomyopathy.
Hasler S(1), Manka R(1), Greutmann M(1), Gämperli O(1), Schmied C, Tanner FC(1), Biaggi P(2), Lüscher TF(1), Keller DI(3), Gruner C(1).
Author information: (1)University Heart Centre, Department of Cardiology, University Hospital Zurich,Switzerland. (2)Heart Clinic, Hirslanden, Zurich, Switzerland. (3)EmergencyDepartment, University Hospital Zurich, Switzerland.
INTRODUCTION: Clinical manifestations of hypertrophic cardiomyopathy (HCM) range from asymptomatic disease to early-onset heart failure and sudden cardiac death(SCD). Risk stratification for SCD remains imperfect and novel risk markers areneeded. The aim of our study was to evaluate the association of elevatedhigh-sensitivity cardiac troponin T levels (hs-cTnT) with the severity of diseaseexpression and adverse events in patients with HCM.METHODS: All patients followed-up at a dedicated HCM clinic at a tertiary carecentre between April 2012 and March 2014 were analysed. The clinical care trackfor these patients includes 12-lead ECG, blood work-up, echocardiography, Holter ECG, exercise stress testing and cardiovascular magnetic resonance imaging (CMR).Clinical data were obtained from medical records.RESULTS: Of 91 HCM patients (77% males, mean age at follow up 51 ± 16 years), 46 (51%) had elevated hs-cTnT levels (>0.014 ng/ml). Patients with elevated hs-cTnT levels had greater maximum wall thickness (23 ± 7 mm vs 19 ± 3 mm, p = 0.001),more often had myocardial fibrosis (96% vs 54%, p <0.001), and lower exercisecapacity (90% predicted vs 76% predicted, p = 0.002). There was a trend towardslower event-free survival estimates (Kaplan-Meier method, 15% vs 7%, p = 0.16).CONCLUSIONS: Elevated hs-cTnT levels in HCM patients are associated with disease severity and, potentially, with more adverse cardiac events. Future studiesshould test whether integration of hs-cTnT in clinical decision algorithms willimprove risk stratification.
DOI: 10.4414/smw.2016.14285 PMID: 26999566  [PubMed - indexed for MEDLINE]

24. Am Heart J. 2016 Apr;174:43-50. doi: 10.1016/j.ahj.2015.12.015. Epub 2015 Dec 31.
High-sensitive troponin T is associated with all-cause and cardiovascularmortality in stable outpatients with type 2 diabetes (ZODIAC-37).
Hendriks SH(1), van Dijk PR(2), van Hateren KJ(2), van Pelt JL(3), GroenierKH(4), Bilo HJ(5), Bakker SJ(6), Landman GW(7), Kleefstra N(8).
Author information: (1)Diabetes Centre, Isala, Zwolle, the Netherlands. Electronic address:s.hendriks@isala.nl. (2)Diabetes Centre, Isala, Zwolle, the Netherlands.(3)Department of Clinical Chemistry, University Medical Center Groningen andUniversity of Groningen, Groningen, The Netherlands. (4)Diabetes Centre, Isala,Zwolle, the Netherlands; Department of General Practice, University MedicalCenter Groningen and University of Groningen, Groningen, the Netherlands.(5)Diabetes Centre, Isala, Zwolle, the Netherlands; Department of InternalMedicine, University Medical Center Groningen and University of Groningen,Groningen, the Netherlands; Department of Internal Medicine, Isala, Zwolle, theNetherlands. (6)Department of Internal Medicine, University Medical CenterGroningen and University of Groningen, Groningen, the Netherlands. (7)DiabetesCentre, Isala, Zwolle, the Netherlands; Department of Internal Medicine, Gelrehospital, Apeldoorn, the Netherlands. (8)Diabetes Centre, Isala, Zwolle, theNetherlands; Department of Internal Medicine, University Medical Center Groningenand University of Groningen, Groningen, the Netherlands; Langerhans MedicalResearch Group, Zwolle, the Netherlands.
BACKGROUND: We aimed to investigate whether high-sensitive cardiac troponin T(hs-cTnT) is associated with all-cause and cardiovascular mortality in stabletype 2 diabetes (T2D) outpatients treated in primary care.METHODS: Cardiac troponin T was measured with a high-sensitive assay at baseline in patients with T2D participating in the observational ZODIAC study. Coxproportional hazards models were used to investigate the relationship betweenhs-cTnT and mortality with adjustment for selected confounders. Risk predictioncapabilities of hs-cTnT were assessed with Harrell C statistics.RESULTS: Complete baseline data were available for 1,133 patients. During median follow-up of 11 (7-14) years, 513 (45%) patients died, of which 218 (42%) died ofcardiovascular causes. Of the patients with undetectable hs-cTnT levels (<3ng/L), only 23% died, compared with 58% with low detectable levels (3-14 ng/L)and 84% with raised levels (≥14 ng/L). Natural log hs-cTnT was significantlyassociated with all-cause mortality (hazard ratio 1.30, 95% CI 1.19-1.42) andcardiovascular mortality (hazard ratio 1.33, 95% CI 1.15-1.53), independent ofpotential confounders. The Harrell C statistic for the crude model of hs-cTnT was0.72 (95% CI 0.70-0.75) for all-cause mortality and 0.74 (95% CI 0.71-0.77) forcardiovascular mortality.CONCLUSIONS: Higher levels of hs-cTnT are associated with mortality in stableoutpatients with T2D. The high crude Harrell C values and the excellent prognosisof patients with undetectable levels illustrate the strength of hs-cTnT as apotential marker for mortality.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ahj.2015.12.015 PMID: 26995369  [PubMed - indexed for MEDLINE]

25. Eur J Med Res. 2016 Mar 17;21:11. doi: 10.1186/s40001-016-0206-0.
How rapid is rapid? Exemplary results of real-life rapid rule-out troponin timingin troponin-positive acute coronary syndromes without persistent ST-segmentelevation in two contrasting German chest pain unit facilities.
Fischer D(1), Remberg F(2), Böse D(2), Lichtenberg M(3), Kümpers P(4), LebiedzP(5), Pavenstädt HJ(4), Waltenberger J(5), Breuckmann F(2).
Author information: (1)Department of Cardiology and Angiology, University Hospital Münster,Albert-Schweitzer-Campus 1, A1, 48149, Münster, Germany.dieter.fischer@ukmuenster.de. (2)Department of Cardiology, Arnsberg MedicalCenter, Arnsberg, Germany. (3)Department of Angiology, Arnsberg Medical Center,Arnsberg, Germany. (4)Department of General Internal Medicine, Nephrology andRheumatology, University Hospital Münster, Münster, Germany. (5)Department ofCardiology and Angiology, University Hospital Münster, Albert-Schweitzer-Campus1, A1, 48149, Münster, Germany.
AIM: To analyse the timing of cardiac troponin (cTn) measurements in high-riskand cTn-positive acute coronary syndromes without persistent ST-segment elevation(NSTE-ACS) in two structurally different German chest pain units (CPUs),contrasting an urban university maximum care and a rural regional primary carefacility.METHODS: All patients encoded as NSTEMI during the year 2013 were retrospectivelyenrolled in two centres: site (I)--centre of maximum care in an urban university setting and site (II)--centre of primary care in a rural regional care setting.Data acquisition included time intervals from admission to baseline cTn and firstand second cTn control as well as type and timing of invasive management.RESULTS: The median times (site I vs. site II) from admission to cTn resultannouncement were 26.5 vs. 33.0 min (p = 0.02) for baseline, 4 vs. 4 h (p = 0.43)for the first and 11.0 vs. 16.5 h (p = 0.03) for the second control. Timelyannouncement, as recommended by guidelines, was available in 86.9% at baseline,59.4% for the first or 41.1% for the second cTn control. Rates and timing ofinvasive management were independent from the time point of positive cTnannouncement (p = 0.51 and p = 0.68, respectively).CONCLUSIONS: German CPUs provide timely identification of cTn-positive patientsin a narrow and guideline-adherent time frame using a rapid rule-out protocol.Especially, baseline and early cTn timing was comparable between the urbanuniversity maximum care and the rural regional primary care facility withoutrelevant impact on guideline-conforming invasive management, underlining the highstandard of care in those highly professional institutions.
DOI: 10.1186/s40001-016-0206-0 PMCID: PMC4794842PMID: 26984277  [PubMed - indexed for MEDLINE]

26. Am J Cardiol. 2016 May 1;117(9):1397-404. doi: 10.1016/j.amjcard.2016.02.002.Epub 2016 Feb 17.
Usefulness of High-Sensitivity Cardiac Troponin T for the Identification ofOutlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors.
Magnoni M(1), Masson S(2), Andreini D(3), Moccetti T(4), Modena MG(5), CanestrariM(6), Berti S(7), Casolo G(8), Gabrielli D(9), Marraccini P(10), Pontone G(3),Latini R(2), Maggioni AP(11), Maseri A(12); CAPIRE Study Group.
Collaborators: Maseri A, Andreini D, Berti S, Canestrari M, Casolo G, GabrielliD, Latini R, Magnoni M, Marraccini P, Masson S, Moccetti T, Modena MG, AndreiniD, Pontone G, Masson S, Gaspari F, Ferrari S, Cannata A, Stucchi N, Fois M,Bernasconi R, Balconi G, Vago T, Letizia T, Bottazzi B, Leone R, Suliman I,Sommaruga M, Gremigni P, Olivieri R, Pennacchietti L, Magnacca M, Rossi MG,Pasotti E, Moccetti T, Susini C, Andreini D, Pontone G, Mushtaq S, Spadafora G,Rossi R, Faggioni L, Ciardetti M, Piccoli G.
Author information: (1)Heart Care Foundation Onlus, Florence, Italy. Electronic address:magnoni.marco@tiscali.it. (2)Department of Cardiovascular Research, Istituto diRicovero e Cura a Carattere Scientifico, Istituto di Ricerche FarmacologicheMario Negri, Milan, Italy. (3)Centro Cardiologico Monzino, Milan, Italy.(4)Servizio di Ricerca Cardiovascolare, Cardiocentro Ticino, Lugano, Switzerland.(5)Department of Cardiology, Ospedale Policlinico, Modena, Italy. (6)Departmentof Cardiology, Santa Croce Hospital, Fano, Italy. (7)Fondazione Toscana Gabriele Monasterio, Stabilimento di Massa, Unità Operativa Adult Cardiology, Massa,Italy. (8)Department of Cardiology, Nuovo Ospedale Versilia, Lido di Camaiore,Italy. (9)Department of Cardiology, Ospedale Civile A. Murri, Fermo, Italy.(10)Istituto di Fisiologia Clinica-Consiglio Nazionale delle Ricerche, FondazioneToscana G. Monasterio, S.A. Emodinamica, Pisa, Italy. (11)Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy. (12)Heart CareFoundation Onlus, Florence, Italy.
Novel high-sensitivity assay can detect very low levels of circulating cardiactroponin (hs-cTnT) in apparently healthy subjects. Within normal range, higherlevels are associated with coronary artery disease (CAD) and cardiacabnormalities commonly associated to traditional risk factors (RFs) for CAD.Therefore, we investigated the relation between circulating hs-cTnT and CAD inpatients with a spectrum of RF burden aiming to assess the added value of hs-cTnTto identify "outlier" patients with CAD despite a low RF burden. Hs-cTnT wasmeasured in 525 stable patients without previous diagnosis of ischemic heartdisease with 0 to 1 RF, excluded diabetes, (low-RF group, n = 263) or ≥2 RFs(multiple-RF group, n = 262) and without CAD (segment involvement score = 0) ordiffuse CAD (segment involvement score >5) at coronary computed tomographyangiography. Outlier patients with diffuse CAD despite low-RF burden had similar extent, severity, and plaque composition than patients with multiple RFs.Overall, hs-cTnT was measurable in 81% of patients with median value of 6.0 ng/L.In both groups, hs-cTnT concentration was higher in patients with CAD than inpatients with normal coronary arteries (p <0.0001). Hs-cTnT was more accurate to detect patients with CAD in the low-RF group than in the multiple-RF group (p =0.04). In multivariate analysis, higher level of hs-cTnT (>6 ng/L) wasindependently associated with CAD in low-RF group only. Despite very lowcirculating concentrations, hs-cTnT may identify with a good accuracy the outlierpatients with diffuse CAD despite low-RF burden.
Copyright © 2016 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.amjcard.2016.02.002 PMID: 26976791  [PubMed - indexed for MEDLINE]

27. Clin Biochem. 2016 Apr;49(6):419-20. doi: 10.1016/j.clinbiochem.2016.03.001. Epub2016 Mar 10.
Use of high sensitivity cardiac troponin assays as an adjunct to cardiac stresstesting.
Jarolim P(1), Morrow DA(2).
Author information: (1)Department of Pathology, Brigham and Women's Hospital, Harvard Medical School,Boston, MA, USA. Electronic address: pjarolim@partners.org. (2)Department ofMedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
DOI: 10.1016/j.clinbiochem.2016.03.001 PMID: 26969798  [PubMed - indexed for MEDLINE]

28. J Am Heart Assoc. 2016 Mar 9;5(3):e002708. doi: 10.1161/JAHA.115.002708.
Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index,Infarct Size, or Biochemical Markers as Endpoint.
Engblom H(1), Heiberg E(2), Erlinge D(3), Jensen SE(4), Nordrehaug JE(5),Dubois-Randé JL(6), Halvorsen S(7), Hoffmann P(8), Koul S(3), Carlsson M(1), AtarD(7), Arheden H(9).
Author information: (1)Department of Clinical Sciences Lund, Clinical Physiology, Skane UniversityHospital, Lund University, Lund, Sweden. (2)Department of Clinical Sciences Lund,Clinical Physiology, Skane University Hospital, Lund University, Lund, SwedenDepartment of Biomedical Engineering, Faculty of Engineering, Lund University,Lund, Sweden. (3)Department of Cardiology, Skåne University Hospital and LundUniversity, Lund, Sweden. (4)Department of Cardiology, Aalborg UniversityHospital, Aalborg, Denmark. (5)Department of Clinical Science, University ofBergen, Norway. (6)Department of Cardiology, Henri Mondor Hospital, Creteil,France. (7)Department of Cardiology B, Oslo University Hospital Ullevål,University of Oslo, Norway Faculty of Medicine, University of Oslo, Norway.(8)Section for Interventional Cardiology, Department of Cardiology, OsloUniversity Hospital, Ullevål, Norway. (9)Department of Clinical Sciences Lund,Clinical Physiology, Skane University Hospital, Lund University, Lund, Swedenhakan.arheden@med.lu.se.
BACKGROUND: Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI)size and myocardium at risk (MaR), enabling assessment of myocardial salvageindex (MSI). We assessed how MSI impacts the number of patients needed to reachstatistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size.METHODS AND RESULTS: Controls (n=90) from the recent CHILL-MI and MITOCARE trialswere included. MI size, MaR, and MSI were assessed from CMR. High-sensitivitytroponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessedin CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000clinical trials were simulated for calculation of sample size required to reachsufficient power. For a treatment effect of 25% decrease in outcome variables, 50patients were required in each arm using MSI compared to 93, 98, 120, 141, and143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUCand peak) in order to reach a power of 90%. If average CMR scan day betweentreatment and control arms differed by 1 day, sample size needs to be increasedby 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%.CONCLUSION: Sample size in cardioprotection trials can be reduced 46% to 65%without compromising statistical power when using MSI by CMR as an outcomevariable instead of MI size alone or biochemical markers. It is essential toensure lack of bias in scan day between treatment and control arms to avoidcompromising statistical power.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
DOI: 10.1161/JAHA.115.002708 PMCID: PMC4943247PMID: 26961520  [PubMed - indexed for MEDLINE]

29. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):3257-62. doi:10.1073/pnas.1519541113. Epub 2016 Mar 8.
Atomic resolution probe for allostery in the regulatory thin filament.
Williams MR(1), Lehman SJ(2), Tardiff JC(3), Schwartz SD(4).
Author information: (1)Department of Chemistry and Biochemistry, The University of Arizona, Tucson,AZ 85721; (2)Physiological Sciences, The University of Arizona, Tucson, AZ 85724;(3)Department of Medicine, The University of Arizona, Tucson, AZ 85724;Department of Cellular and Molecular Medicine, The University of Arizona, Tucson,AZ 85724. (4)Department of Chemistry and Biochemistry, The University of Arizona,Tucson, AZ 85721; sschwartz@email.arizona.edu.
Calcium binding and dissociation within the cardiac thin filament (CTF) is afundamental regulator of normal contraction and relaxation. Although thedisruption of this complex, allosterically mediated process has long beenimplicated in human disease, the precise atomic-level mechanisms remain opaque,greatly hampering the development of novel targeted therapies. To address thisquestion, we used a fully atomistic CTF model to test both Ca(2+) bindingstrength and the energy required to remove Ca(2+) from the N-lobe binding site inWT and mutant troponin complexes that have been linked to geneticcardiomyopathies. This computational approach is combined with measurements of invitro Ca(2+) dissociation rates in fully reconstituted WT and cardiac troponin T R92L and R92W thin filaments. These human disease mutations represent knownsubstitutions at the same residue, reside at a significant distance from thecalcium binding site in cardiac troponin C, and do not affect either the binding pocket affinity or EF-hand structure of the binding domain. Both have been shown to have significantly different effects on cardiac function in vivo. We now show that these mutations independently alter the interaction between the Ca(2+) ionand cardiac troponin I subunit. This interaction is a previously unidentifiedmechanism, in which mutations in one protein of a complex indirectly affect athird via structural and dynamic changes in a second to yield a pathogenic changein thin filament function that results in mutation-specific disease states. Wecan now provide atom-level insight that is potentially highly actionable in drug design.
DOI: 10.1073/pnas.1519541113 PMCID: PMC4812746PMID: 26957598  [PubMed - indexed for MEDLINE]

30. Clin Chem. 2016 Apr;62(4):623-30. doi: 10.1373/clinchem.2015.250811. Epub 2016Mar 2.
High-Sensitivity Cardiac Troponin I Is a Strong Predictor of CardiovascularEvents and Mortality in the AGES-Reykjavik Community-Based Cohort of OlderIndividuals.
Thorsteinsdottir I(1), Aspelund T(2), Gudmundsson E(3), Eiriksdottir G(3), HarrisTB(4), Launer LJ(4), Gudnason V(2), Venge P(5).
Author information: (1)Icelandic Heart Association Research Institute, Kopavogur, Iceland; Departmentof Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland;(2)Icelandic Heart Association Research Institute, Kopavogur, Iceland; Faculty ofMedicine, University of Iceland, Reykjavik, Iceland; (3)Icelandic HeartAssociation Research Institute, Kopavogur, Iceland; (4)Laboratory ofEpidemiology, Demography and Biometry, Intramural Research Program, NationalInstitute on Aging Bethesda, MD; (5)Department of Medical Sciences, UppsalaUniversity, Uppsala, Sweden. per.venge@medsci.uu.se.
BACKGROUND: The objective of this study was to investigate the predictive powerof a high-sensitivity cardiac troponin I (hs-cTnI) assay for cardiovascularevents and mortality in a large population of older community dwellers.METHODS: Blood was collected from 5764 individuals (age 66-98 years) during theperiod of 2002-2006 and the outcome as to all-cause death and incidence ofcardiovascular disease (CVD) and coronary heart disease (CHD) followed up to 10years. hs-cTnI (Abbott) was measured in serum to assess the association of thismarker with CVD, CHD and death, and finally, to compare the results withconventional risk factors by multivariable statistical analysis.RESULTS: The median (interquartile range) concentrations of hs-cTnI were 8.4 ng/L(5.6-14.2 ng/L) and 5.3 ng/L (3.8-8.1 ng/L) in men (2416) and women (3275),respectively, and the concentrations increased linearly with age. Outcomes as to all-cause death and incidence of CVD and CHD were significantly associated withincreasing concentrations of hs-cTnI beginning well below the 99th percentileconcentrations. The associations with outcome remained after adjustments forconventional risk factors and were similar in men and women.CONCLUSIONS: Our findings suggest that hs-cTnI reflects the status of themyocardium even in seemingly healthy individuals and that the measurements ofhs-cTnI may be useful for primary prediction of heart disease; this should formthe basis for future prospective clinical trials for determining whethermeasuring hs-cTnI can be used in the prevention of CVD/CHD.
© 2016 American Association for Clinical Chemistry.
DOI: 10.1373/clinchem.2015.250811 PMID: 26936931  [PubMed - indexed for MEDLINE]

31. Circulation. 2016 Mar 29;133(13):1228-9. doi: 10.1161/CIRCULATIONAHA.116.021795. Epub 2016 Mar 1.
Relative Lack of Culprit and Obstructive Coronary Lesions in Patients With Acute Ischemic Stroke and Elevated Cardiac Troponin.
Hofmann Bowman MA(1), Liao JK(2).
Author information: (1)From Section of Cardiology, Department of Medicine, University of Chicago, IL.(2)From Section of Cardiology, Department of Medicine, University of Chicago, IL.jliao@medicine.bsd.uchicago.edu.
Comment on    Circulation. 2016 Mar 29;133(13):1264-71.
DOI: 10.1161/CIRCULATIONAHA.116.021795 PMCID: PMC4891305PMID: 26933084  [PubMed - indexed for MEDLINE]

32. Circulation. 2016 Mar 29;133(13):1264-71. doi: 10.1161/CIRCULATIONAHA.115.018547.Epub 2016 Mar 1.
Coronary Angiographic Findings in Acute Ischemic Stroke Patients With ElevatedCardiac Troponin: The Troponin Elevation in Acute Ischemic Stroke (TRELAS) Study.
Mochmann HC(1), Scheitz JF(1), Petzold GC(1), Haeusler KG(1), Audebert HJ(1),Laufs U(1), Schneider C(1), Landmesser U(1), Werner N(1), Endres M(1),Witzenbichler B(1), Nolte CH(2); TRELAS Study Group.
Author information: (1)From Klinik für Kardiologie (H.-C.M., U.L.) and Klinik für Neurologie (J.F.S.,K.G.H., H.J.A., M.E., C.H.N.), Charité-Universitätsmedizin Berlin, CampusBenjamin Franklin, Germany; Center for Stroke Research Berlin (J.F.S., K.G.H.,H.J.A., M.E., C.H.N.) and ExcellenceCluster NeuroCure (M.E.),Charité-Universitätsmedizin Berlin, Germany; German Center for Neurodegenerative Diseases and Department of Neurology(G.C.P., C.S.) and Department of InternalMedicine II (N.W.), University of Bonn, Germany; Klinik für Innere Medizin III,Kardiologie, Angiologie undInternistische Intensivmedizin, Universitätsklinikumdes Saarlandes, Homburg, Germany (U.L.); German Center for NeurodegenerativeDiseases, Berlin,Germany (M.E.); Berlin Institute of Health, Germany (M.E.); and Klinik für Kardiologie und Pneumologie, Helios Amper-Klinikum Dachau, Germany(B.W.). (2)From Klinik für Kardiologie (H.-C.M., U.L.) and Klinik für Neurologie (J.F.S., K.G.H., H.J.A., M.E., C.H.N.), Charité-Universitätsmedizin Berlin,Campus Benjamin Franklin, Germany; Center for Stroke Research Berlin (J.F.S.,K.G.H., H.J.A., M.E., C.H.N.) and ExcellenceCluster NeuroCure (M.E.),Charité-Universitätsmedizin Berlin, Germany; German Center for Neurodegenerative Diseases and Department of Neurology(G.C.P., C.S.) and Department of InternalMedicine II (N.W.), University of Bonn, Germany; Klinik für Innere Medizin III,Kardiologie, Angiologie undInternistische Intensivmedizin, Universitätsklinikumdes Saarlandes, Homburg, Germany (U.L.); German Center for NeurodegenerativeDiseases, Berlin,Germany (M.E.); Berlin Institute of Health, Germany (M.E.); and Klinik für Kardiologie und Pneumologie, Helios Amper-Klinikum Dachau, Germany(B.W.). christian.nolte@charite.de.
Comment in    Circulation. 2016 Mar 29;133(13):1228-9.
BACKGROUND: A relevant proportion of patients with acute ischemic stroke (AIS)have elevated levels of cardiac troponins (cTn). However, the frequency ofcoronary ischemia as the cause of elevated cTn is unknown. The aim of our studywas to analyze coronary vessel status in AIS patients with elevated cTn compared with patients presenting with non-ST-segment-elevation acute coronary syndrome(NSTE-ACS).METHODS AND RESULTS: Among 2123 consecutive patients with AIS prospectivelyscreened at 2 tertiary hospitals, 13.7% had cTn elevation (>50 ng/L). Accordingto a prespecified sample size estimation, 29 patients with AIS (median age, 76years [first-third quartiles, 70-82 years]; 52% male) underwent conventionalcoronary angiography and were compared with age- and sex-matched patients withNSTE-ACS. The primary end point was presence of coronary culprit lesions oncoronary angiograms as analyzed by independent interventional cardiologistsblinded for clinical data. Median cTn on presentation did not differ betweenpatients with AIS or NSTE-ACS (95 versus 94 ng/L; P=0.70). Compared with patientswith NSTE-ACS, patients with AIS were less likely to have coronary culpritlesions (7 of 29 versus 23 of 29; P<0.001) or any obstructive coronary arterydisease (15 of 29 versus 25 of 29; P=0.02; median number of vessels with >50%stenosis, 1 [first-third quartiles, 0-2] versus 2 [first-third quartiles, 1-3];P<0.01).CONCLUSIONS: Coronary culprit lesions are significantly less frequent in AISpatients compared with age- and sex-matched patients with NSTE-ACS despitesimilar baseline cTn levels. Half of all AIS patients had no angiographicevidence of coronary artery disease. Further studies are needed to clinicallyidentify the minority of patients with AIS and angiographic evidence of a culpritlesion.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Uniqueidentifier: NCT01263964.
© 2016 American Heart Association, Inc.
DOI: 10.1161/CIRCULATIONAHA.115.018547 PMID: 26933082  [PubMed - indexed for MEDLINE]

33. Rev Port Cardiol. 2016 Mar;35(3):195. doi: 10.1016/j.repc.2015.09.005. Epub 2016 Feb 28.
We need more data to determine the significance of NT-proBNP and troponin Ilevels in high-risk patients.
Eyuboglu M(1).
Author information: (1)Department of Cardiology, Dinar State Hospital Dinar, Afyonkarahisar, Turkey. Electronic address: mhmtybgl@gmail.com.
Comment on    Rev Port Cardiol. 2015 Apr;34(4):255-61.
DOI: 10.1016/j.repc.2015.09.005 PMID: 26928015  [PubMed - indexed for MEDLINE]

34. Clin Chim Acta. 2016 May 1;456:42-8. doi: 10.1016/j.cca.2016.02.017. Epub 2016Feb 26.
Pilot study on harmonization of cardiac troponin I immunoassays using patientsand quality control plasma samples. On behalf of the Italian Section of theEuropean Ligand Assay Society (ELAS) and of the Study Group on CardiovascularBiomarkers of the Società Italiana di Biochimica Clinica (SIBioC).
Clerico A(1), Ripoli A(2), Masotti S(3), Prontera C(2), Storti S(2), FortunatoA(4), Buzzi P(5), Casagranda I(5), Franzini M(6), Ndreu R(7), Zucchelli GC(7),Zaninotto M(8), Plebani M(8).
Author information: (1)Fondazione CNR Regione Toscana G. Monasterio, Pisa, Italy; Scuola SuperioreSant'Anna, Pisa, Italy. (2)Fondazione CNR Regione Toscana G. Monasterio, Pisa,Italy. (3)Scuola Superiore Sant'Anna, Pisa, Italy. (4)Department of LaboratoryMedicine, San Bortolo Hospital, Vicenza, Italy. (5)Dipartimento di Emergenza,Ospedale Civile Santi Antonio e Biagio e Cesare Arrigo di Alessandria,Alessandria, Italy. (6)Dipartimento di Ricerca Traslazionale e delle NuoveTecnologie in Medicina e Chirurgia, Università di Pisa, Pisa, Italy.(7)QualiMedLab, Istituto di Fisiologia Clinica del CNR, Pisa, Italy.(8)Department of Laboratory Medicine, University of Padova, Italy.
BACKGROUND: The aim of this study is to evaluate whether it is possible to reducethe between-methods variability of troponin I (cTnI) immunoassays usingmathematical algorithms calculated from the results of both patients' samples andquality control materials distributed in an external quality assessment (EQA)scheme.METHODS: We collected 122 heparinized plasma samples of patients admitted to the emergency department with thoracic pain or supraventricular tachyarrhythmia.Moreover, we also analyzed 20 control samples distributed in an EQA and 26 plasmapools prepared from healthy subjects and patients with myocardial infarction. We evaluated 4 different methods for cTnI assay: STAT Architect High Sensitive TnI(Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens HealthcareDiagnostics), ST AIA-Pack cTnI Third Generation (Tosoh Bioscience), and AccessAccuTnI+3 (Beckman Coulter Diagnostics).RESULTS: Systematic differences between cTnI methods were observed. However,correlation coefficients (R from 0.976 to 0.990) between the log-transformed cTnIvalues measured in all 168 samples were significantly better (p=0.0037) thanthose obtained considering only the 122 patients' samples. cTnI values measuredin EQA and pool samples were included within the 95% prediction intervals oflinear regressions calculated with those of patients' samples. After therecalibration of cTnI values based on the robust principal component analysisapproach the between-methods variability decreased significantly (about 40%around the cut off values).CONCLUSIONS: Our pilot study suggests that EQA schemes for cTnI immunoassaymethods, based on both quality control samples with tested commutability androbust statistical analyses, are able to evaluate between-methods variability as well as allow a reliable recalibration and harmonization of results.
Copyright © 2016 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.cca.2016.02.017 PMID: 26923393  [PubMed - indexed for MEDLINE]

35. Clin Chim Acta. 2016 May 1;456:19-23. doi: 10.1016/j.cca.2016.02.014. Epub 2016Feb 24.
Reference values of galectin-3 and cardiac troponins derived from a single cohortof healthy blood donors.
Mueller T(1), Egger M(2), Leitner I(2), Gabriel C(3), Haltmayer M(2), Dieplinger B(2).
Author information: (1)Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz,Linz, Austria. Electronic address: thomas.mueller@bs-lab.at. (2)Department ofLaboratory Medicine, Konventhospital Barmherzige Brueder Linz, Linz, Austria.(3)Red Cross Transfusion Service of Upper Austria, Linz, Austria.
BACKGROUND: Here we describe the determination of upper reference limits (URL)for galectin-3, high-sensitivity cardiac troponin I (hs-cTnI) andhigh-sensitivity cardiac troponin T (hs-cTnT) in a single cohort of healthy blooddonors using routine assays.METHODS: For this reference value study, we used a cohort of 402 consecutiveblood donors (64% were male and 36% were female). The median individuals' age was35.0 years (range, 18.0-64.4). Individuals of this reference population were free

Oximetro de pulso y Resulatdos en SaludFecha: 2/2/2017

 

 

Oxímetro de pulso y resultados en salud

 

                                                                     Abigail J Enoch, Mike English, Sasha Shepperd 

                                                                           Arch Dis Child 2016:101: 694-700 - METANALISIS

                                                                    Resumen y comentario objetivo: Dra. María José Chiolo

 

INTRODUCCIÓN

En recién nacidos, niños y adolescentes la hipoxemia se asocia con un mayor riesgo de muerte, y es una complicación común de la bronquiolitis, neumonía, asma y otras enfermedades graves (por ejemplo sepsis) 1-4 La oximetría de pulso es una intervención de bajo costo que podría reducir la mortalidad infantil, de acuerdo con los Objetivos de Desarrollo del Milenio 4, al permitir la detección temprana de la hipoxemia y mejorar el diagnóstico preciso, lo que aumenta la probabilidad de implementar rápidamente tratamiento efectivo.

A pesar del potencial de mejorar los resultados de salud, los oxímetros de pulso menudo no están disponibles, especialmente en entornos de bajos ingresos. Por ejemplo, sólo 38% de los hospitales terciarios de Nigeria y 3 de 22 hospitales de Kenia que proporcionan entrenamiento de prácticas médicas de tuvieron oxímetros de pulso en 2011 y 2012, respectivamente 5,6

Para promover el acceso, se han diseñado oxímetros de pulso para entornos de bajos ingresos, como el Lifebox, un oxímetro de bajo costo, portátil y resistente, que funciona con baterías.7 Otros diseños entregan resultados de oxímetros de pulso para teléfonos inteligentes, usando su propagación a las iniciativas de apoyo a las áreas de captación remotas. 8 Las iniciativas de apoyo a la captación de oxímetro de pulso incluyen el Proyecto Global de la OMS de oximetría de pulso, las donaciones de LifeBox, y la apelación de navidad de. 7 9 10

La evidencia sugiere que los oxímetros de pulso identifican 20-30% adicional de los niños con hipoxia en comparación con el uso de los signos clínicos solamente, por ejemplo, quejidos y depresión de la conciencia, que puede ser impreciso.1 11 Sin embargo, la evidencia de una asociación entre la hipoxemia y la mortalidad no es necesariamente evidencia de que la aplicación de la oximetría de pulso mejora los resultados, sobre todo teniendo una perspectiva amplia del sistema de salud, cuando las acciones del personal de salud, las características de los niños y las instalaciones de salud y los recursos adicionales, todos interactúan afectando los resultados.

En el complejo mundo de los sistemas de salud, la oximetría de pulso podría conducir a mejores resultados de salud y la eficiencia del sistema, y ​​el uso reducido de recursos, ayudando a los trabajadores de la salud a diagnosticar oportunamente a los niños e iniciar el tratamiento, y a mejorar la precisión diagnóstica, evitando de este modo las admisiones y tratamientos innecesarios. Como alternativa, la oximetría de pulso podría dar lugar a ingresos innecesarios, tratamiento, derivaciones y / o retrasos en el alta, si los umbrales de admisión, derivación o intervención no son apropiadas.

A medida que aumenta la disponibilidad de la oximetría de pulso en los niveles de atención primaria y comunitaria en los países de bajos ingresos, la comprensión de las implicaciones del sistema de salud es cada vez más importante, particularmente, cómo impacta en los recursos  el uso de la oximetría de pulso. En los países de altos ingresos, la guía para la detección de rutina con oximetría de pulso es inconsistente, y algunos sugirieron que no es util.12-17  El debate también se mantiene sobre las definiciones óptimas de hipoxemia, especialmente en la altura.2, 18-22

Por lo tanto, se revisó la evidencia sobre cómo impactaron los resultados con la introducción de la oximetría de pulso en la salud y uso de de servicios.

MÉTODOS

Pregunta principal: Los recién nacidos, niños y adolescentes hasta 19 años tienen tasas más bajas de mortalidad, menor morbilidad y menor duración de la internación cuando se utilizan los oxímetros de pulso para informar el diagnóstico y el tratamiento (con exclusión de la atención quirúrgica operatoria) en comparación con el lugar donde los oxímetros de pulso no se utilizan?"
Pregunta secundaria: Qué proporción de recién nacidos, niños y adolescentes se administra oxigenoterapia, donde se utilizan los oxímetros de pulso en comparación con las que no utilizan los oxímetros de pulso."

Se incluyeron los estudios que reclutaron a recién nacidos, niños y / o adolescentes de hasta 19 años, que se presentaron por primera vez a un hospital, departamento de emergencias (DE), o centro de atención primaria, independientemente del escenario. Se excluyeron los estudios que evaluaron los oxímetros de pulso en el cribado de los recién nacidos sanos antes del alta, o monitoreo, por ejemplo, durante la cirugía.
Se incluyeron estudios con al menos un grupo de intervención en la que se tomó una lectura de oxímetro de pulso y al menos un grupo de control en el que no se utilizó oximetría de pulso. Se incluyeron estudios que informaron la mortalidad, morbilidad (gravedad de la enfermedad, es decir, las puntuaciones de gravedad de la neumonía, la discapacidad al alta) y la duración de la internación. Se excluyeron los estudios descriptivos.
Se realizaron búsquedas sistemáticas en la base de datos de Resúmenes de Revisiones de Efectos, Cochrane, Medion, PubMed, Web of Science, Embase, Salud Global, CINAHL y Biblioteca de la OMS de Salud Global, sin restricciones de idioma. Se verificaron referencias de los estudios. Los sitios web de organizaciones no gubernamentales, organizaciones de salud y organizaciones de desarrollo, se realizaron búsquedas de informes no publicados que utilizaron los términos 'oxímetro de pulso" y "oximetría de pulso'.
Se contactaron expertos en el tema para obtener materiales adicionales. Se excluyeron los estudios que no fueron relevantes en función de título / resumen. Se leyeron los textos completos de los estudios restantes y se excluyeron aquellos que no cumplieron los criterios de inclusión. Los textos completos fueron leídos por una segunda persona, y si la inclusión era incierta, fueron leídos por una tercera. Se extrajeron los datos utilizando un formulario de Cochrane de recolección de datos a medida y evaluaron el riesgo de sesgo mediante la herramienta ACROBAT de Cochrane.23, 24
Se intentó  calcular los coeficientes de riesgo, las diferencias de medias y el IC, y si fuera posible agrupar los datos dentro de los subgrupos y llevar a cabo un meta-análisis. Debido al número de centros de estudios y la variabilidad del diseño de diseño / resultado, no era posible. En su lugar se describió de forma narrativa la evidencia usando un enfoque estructurado mientras que cuando fue posible se realizó un bosquejo de ideas, una estrategia habitual en este tipo de situaciones

RESULTADOS

 Resultados de la búsqueda

Se encontraron 7992 informes después de la eliminación de duplicados y se seleccionaron todos los títulos y resúmenes y los textos completos de 17 estudios potencialmente relevantes. Fueron incluidos cinco estudios25-29, no controlados de tipo antes y después (sin grupos de comparación independientes).

 Efectos de la intervención

Sólo se incluyeron cinco estudios elegibles, todos los estudios no controlados de tipo antes y después con alto riesgo de sesgo; Por lo tanto, la confianza en las estimaciones del efecto se limita con un alto nivel de incertidumbre.

 Tasas de mortalidad

Duke y colaboradores, 27 informaron que las tasas de mortalidad de los niños con neumonía en cinco hospitales de Papúa Nueva Guinea disminuyó en un 35% después de que los servicios se reorganizaron y se introdujeron oxímetros de pulso, concentradores de oxígeno y entrenamiento. No es posible determinar cuanta de la mejoría de la mortalidad se debía a la oximetría de pulso frente a la prestación de la formación, los sistemas de oxígeno y otros cambios.

 Morbilidad

Tres estudios evaluaron si los oxímetros de pulso influenciaron la toma de decisiones clínicas. Los médicos pediatras evaluaron a los niños que acudieron a un DE y decidieron su tratamiento antes y después de la obtención de los resultados de la oximetría de pulso.25 28 29 Los estudios definieron la hipoxemia de manera diferente y sus médicos utilizaron diferente los umbrales de saturación de oxígeno (SaO2) para indicar la necesidad de tratamiento. No se incluyeron controles independientes, que aumentan el riesgo de sesgo, así como el valor del diseño de estudio de la 'acentuación de la oximetría de pulso' en el proceso mediante la presentación de los resultados de la oximetría a los médicos después de sus evaluaciones iniciales.
Ningún estudio midió directamente la morbilidad; sin embargo, dos analizaron si los oxímetros de pulso facilitaron la medición de la morbilidad (puntuaciones de gravedad de la enfermedad y el diagnóstico). Anderson y colaboradores realizaron preguntas a los médicos 25 para registrar las evaluaciones de gravedad de la enfermedad, en una escala de 5 puntos, para los niños enfermos que se presentaban en la sala de pediatría, con exclusión de aquellos con lesiones ortopédicas/quirúrgicas menores, antes y después de obtener los resultados de los oxímetros de pulso. Los médicos cambiaron en el 53% de las puntuaciones de los  niños y se redujeron dos tercios de estas puntuaciones.

 Duración de la internación e influencia en las tasas de ingreso

En Choi and Claudius, 26 el tiempo medio de permanencia en un triage del DE pediátrico cuando se utilizaron los oxímetros de pulso fue 17% menos que en el mismo DE un año antes, cuando los oxímetros de pulso no se utilizaban.

Maneker y colaboradores 28, informaron que 46/69 niños (67%) que tenían baja SaO2(SaO<92%) para los cuales no es esperaba clínicamente que tuvieran SaObaja, mientras que 23 (33%) se esperaba que tuvieran baja SaO2.

Manwer y colaboradores, 29 encontraron que después de recibir los resultados del oxímetro de pulso, los médicos admitieron 5 niños adicionales de los 305 que tenían la SaO2 <95% (2%) y 5 niños adicionales de 1822 que tenían SaO2 ≥ 95% (0,3%). 29

Pregunta de investigación secundaria

Los planes de manejo cambiaron para el 19% de los niños en Anderson et al; 25 la mayoría de estos planes se hizo menos intenso. En Maneker y colaboradores, 28 los planes de manejo cambiaron para el 91%de los niños que tenían una SaOinesperadamente baja (SaO2 <92%); 90% de ellos se inició el tratamiento con oxígeno. Los planes de manejo también cambiaron en el 43% de los niños que como era de esperar tenían SaObaja; en 90% de ellos se inició oxigenoterapia. En Manwer y colaboradores 29 después de recibir los resultados del oxímetro de pulso, los médicos indicaron nuevas pruebas diagnósticas para el 20% de los niños con SaO2 <95% y el 0,5% de los niños con SaO2 ≥95%; indicaron nuevos tratamientos para el 11% de los niños con SaO2 <95% y el 1% de los niños con SaO2 ≥95%.

DISCUSIÓN

Los oxímetros de pulso se utilizan rutinariamente en los países de ingresos altos pero se implementan sin pautas consistentes de cuándo / cómo usarlos y hay poca investigación sobre cómo impactan sus resultados o su uso en los recursos de salud de rutina. Los nuevos programas que fomentan el uso del oxímetro de pulso en los países de bajos ingresos deberían abordar estas deficiencias en la base a pruebas y promover la toma de decisiones basadas en la evidencia.

Sólo se identificaron cinco estudios, todos de tipo antes y después con alto riesgo de sesgo. Las diferencias potenciales en las características del paciente / ubicación existían entre los períodos de tiempo en los dos estudios; 26 27 no hubo controles independientes en tres, 25 28 29 y en estos, los médicos tal vez se inclinaban más a responder a la oximetría de pulso, porque los resultados fueron dados después, no durante, las evaluaciones iniciales (a diferencia de la configuración  fuera del estudio).

En el estudio que proporcionó datos de mortalidad, concentradores de oxígeno, entrenamiento y otras mejoras se introdujeron oxímetros de pulso; 27 si bien este estudio apunta a importantes mejoras en los efectos de los sistemas de terapia de oxígeno, desde la identificación del manejo, que proporciona información indirecta sobre los posibles efectos de la adopción de la oximetría de pulso a gran escala, por ejemplo, centros de atención primaria para la remisión de guía.

Otros desafíos en la generalización de las conclusiones son que los estudios se llevaron a cabo en los EE.UU. y Papúa Nueva Guinea y ninguno se llevó a cabo en los centros de atención primaria. A pesar de que los datos provienen de estudios en Estados Unidos y aquellos llevados a cabo hace más de 15 años, los resultados disponibles tienen algún valor, ya que sugieren la forma en que la toma de decisiones de los médicos impacta en la introducción del oxímetro de pulso, el mecanismo clave por el cual las influencias de la oximetría de pulso practican limitaciones de diseño del estudio a reducir la confianza en las estimaciones del efecto de los estudios incluidos".

Sin embargo, existe cierta evidencia que indica que la oximetría de pulso puede conducir a mejores resultados de salud, con tasas de mortalidad más bajas (cuando se combina con la mejoría de la administración de oxígeno adecuada) y el tiempo de triage reducido; la oximetría de pulso puede cambiar las decisiones de los médicos con respecto a la gravedad de la enfermedad, e incrementar los ingresos hospitalarios relacionados con la hipoxemia no reconocida previamente (nota: las definiciones hipoxemia variaron de <92% a 95%).

La oximetría de pulso de rutina también puede influir en las pruebas de diagnóstico y tratamientos administrados. Mower y colaboradores29  argumentaron que los médicos juzgaron generalmente con precisión  cuando la SaO2 está muy alta o baja, pero no hicieron más cambios de manejo cuando es moderadamente baja. No está claro a partir de la literatura cómo impacta la utilización del recurso de la oximetría de pulso, a pesar de que las campañas de oximetría de pulso se centran en los entornos de bajos ingresos, donde la relación costo-eficacia es crucial. En Maneker y colaboradores 28, y Mower  y colaboradores, 29 la oximetría de pulso aumentó el uso de los recursos a través del aumento de las internaciones y administración de  oxigenoterapia para niños con hipoxemia que no hubiera sido detectada.  

La oximetría de pulso condujo a la utilización de recursos reducida en dos estudios: en Anderson y colaboradores 25 dos tercios de los niños cuyas puntuaciones de severidad de enfermedad había  cambiado luego fueron considerados menos gravemente enfermos, y dos tercios de los niños cuyos planes de manejo cambiaron, entonces fueron tratados de forma menos agresiva; en Choi y Claudius, 26 la oximetría de pulso dio lugar a un menor tiempo de triage.

La oximetría de pulso podría facilitar el diagnóstico rápido, por lo que un tratamiento efectivo se inicia antes y aumenta la probabilidad de recuperación, reduciendo el futuro uso de los recursos. La oximetría puede reducir el desperdicio de recursos mediante la indicación de cuándo terminar el tratamiento, y por disminuir los falsos positivos. Sin embargo, Schroeder y colaboradores, 30 señalaron que el tiempo de internación fue en promedio de 1,6 días más largo debido a la oximetría de pulso, ya que el 26% de los niños cumplían con los criterios de alta, excepto por necesitar oxígeno de acuerdo con los oxímetros de pulso.

Si el tratamiento adicional no fuera necesario (por ejemplo, si se utilizan umbrales inapropiados), en consecuencia, se desperdician recursos (como asumen los autores). Sin embargo, si la oximetría de pulso activa la detección de los niños con hipoxia, que de otro modo no recibirían tratamiento, entonces se justificaban los recursos adicionales. Aunque no se discute aquí, la oximetría de pulso también tiene importantes consecuencias para los recursos en centros de atención ambulatoria, donde la prevalencia de hipoxemia en los niños, a pesar que es más baja que en los hospitales, es aún considerable (por ejemplo, 4-12%), 2 y donde la oximetría de pulso podría facilitar el reconocimiento oportuno de cuidados necesarios o derivación al hospital.

Asignar aleatoriamente a los establecimientos de salud la introducción de oximetría de pulso (con entrenamiento) o no asignar oximetría de pulso podría proporcionar datos fiables sobre el uso de recursos (admisiones, herramientas de diagnóstico, tratamientos, derivaciones, duración de la estadía), los resultados de salud (mortalidad, morbilidad, re-internaciones), y cuyos umbrales, en su caso, sería más eficaz para el inicio del tratamiento, si los estudios fueran lo suficientemente grandes. Tales estudios pragmáticos podrían hacerse junto con los programas de aplicación y podrían dilucidar el impacto de la oximetría de pulso en el uso de recursos y los resultados de salud dentro del análisis de costo-efectividad.

Si la evidencia sugiere que la oximetría de pulso incrementa la utilización de recursos a continuación, los trabajadores de la salud, administradores de instalaciones y los profesionales de la salud pública tendrían que sopesar las comparaciones costo-beneficio y las compensaciones entre el uso de los escasos recursos en la oximetría de pulso o en otras intervenciones.

Los análisis de costo-efectividad formales específicos del contexto se podrían realizar para ayudar a resolver estos problemas, pero rara vez se realizan cuando las tecnologías se introducen en los sistemas de salud de los países de bajos ingresos. Esta investigación debe someterse a  evaluaciones independientes y transparentes que desemboquen en resultados más amplios, procesos inclusivos para la toma de decisiones sobre la asignación de recursos dentro de los sistemas de salud basados en la evidencia.

Es necesaria más investigación acerca de las mejores maneras de utilizar los oxímetros de pulso, especialmente en relación con los umbrales de SaO2.

En entornos de ingresos altos, las directrices de manejo de enfermedades raramente recomiendan  los umbrales de SaO2 para diagnosticar, evaluar o monitorizar niños.12 13Cuando se recomiendan los umbrales de SaO2 específicos, difieren entre organizaciones, a pesar de que las   Recomendaciones de la OMS de 2012 para el manejo de las condiciones comunes de los niños proporcionan una orientación clara de administrar oxígeno si la SaO2 <90% (para los niños en ≤2500 m) 14 15

Por el contrario, la Sociedad Canadiense de Pediatría advierte que "es importante reconocer que la fijación de umbrales arbitrarios para la terapia de oxígeno influirá en las tasas de admisión."16 Los umbrales de ajuste son complicados ya que los resultados del oxímetro de pulso no pueden considerarse aisladamente de los hallazgos clínicos, la SaO2puede fluctuar de forma natural más de un día, y los estudios muestran que en niños "sanos" la SaO2 difiere según la edad y la altitud.20-22 32

Pocos estudios han investigado si los resultados son comparables cuando se utilizan umbrales más altos que <90% como recomienda la OMS: Cunningham y colaboradores 33, encontraron que la resolución de la tos en niños con bronquiolitis fue equivalente a cuando el umbral era <94% o cuando <90 % se utilizó para la terapia de oxígeno, mientras que Lazzerini y colaboradores 34 encontraron que la hipoxemia predijo elevado riesgo de mortalidad en niños con infección respiratoria aguda baja cuando <92% o <90 % se utilizó como umbral hipoxemia. Por lo tanto, es quizás inesperado que ningún estudio ha examinado las consecuencias del sistema de salud de la aplicación de la guía de la OMS al utilizar umbrales SaO2 <90%.

En ausencia de guías claras, la opinión difiere de cuales umbrales deben indicar la hipoxemia y el ingreso hospitalario, la remisión, la terapia de oxígeno u otros tratamientos. Cuando se encuestaron a los médicos de emergencia, hubo una considerable variabilidad en la SaO2 más baja para el alta a 2 años de edad con neumonía y 10 meses de edad con bronquiolitis.18

Maneker y colaboradores 28 y Mower y colaboradores 29 definen SaObaja como ≤92% y <95%, respectivamente, reduciendo de este modo los resultados de la comparación. La elección del umbral puede afectar sustancialmente los resultados del sistema de salud; así, en el ensayo clínico aleatorizado de lactantes de Schuh y colaboradores 35 (excluido de esta revisión porque todos los niños recibieron lecturas del oxímetro de pulso), las tasas de ingreso fueron sensibles a pequeñas diferencias de saturación: 41% de los niños del grupo de control fueron admitidos dentro de las 72 hs en comparación con 25% de los niños cuyas SaO2s mostradas se aumentaron artificialmente por 3%.

CONCLUSIONES

Los oxímetros de pulso se utilizan rutinariamente en los países de altos ingresos y las organizaciones internacionales están invirtiendo en programas de promoción de la oximetría de pulso en los países de bajos ingresos, pero hay poca evidencia de cualquier región o entorno, sobre el impacto o la utilización óptima de los oxímetros de pulso cuando los niños se presentan a un centro de salud.

Se necesita más investigación sobre la forma en que los resultados de la oximetría de pulso impacta en los servicios de salud, y cómo el conocimiento de la SaO2 debe integrarse con otros hallazgos clínicos, si la definición de umbrales de "talla única" es posible o incluso útil, por hipoxemia y en el diagnóstico / monitoreo específico de enfermedades, y como la oximetría de pulso afecta a la utilización de recursos. Este tipo de investigación pragmática podría acompañar los esfuerzos de implementación del oxímetro de pulso y proporcionaría mucha evidencia necesaria.

Comentario:

El uso de los oxímetros de pulso se ha generalizado bastante en los últimos tiempos, sin embargo su impacto en los resultados de la salud es aún desconocido.

Este estudio, basado en una revisión sistemática de la literatura intenta abarcar todos los aspectos relacionados al uso de la oximetría de pulso y muestra como las organizaciones internacionales tienden a invertir en programas para aumentar el uso del oxímetro de pulso especialmente en países de menores recursos, dado que son una intervención de bajo costo que podría ayudar a reducir la mortalidad permitiendo un inicio más precoz del tratamiento y evitando,  en algunas oportunidades, derivaciones o internaciones innecesarias.

A pesar de no haber guías claras de manejo y no existir un consenso claro en los umbrales de saturación lo más importante sería considerar a la oximetría de pulso como una herramienta complementaria de valor aun indefinido que puede apoyar en la mayoría de los casos a la evaluación clínica.

Deberían aumentarse los esfuerzos por normatizar el uso sistemático de este elemento sumado al criterio clínico y la evaluación médica.

REFERENCIAS

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Magnesio Iónico: Búsqueda de Trabajos Fecha: 4/11/2016





1. Gynecol Obstet Invest. 2015;79(1):19-24. doi: 10.1159/000365813. Epub 2014 Nov
19.
Alterations of ionized and total magnesium levels in pregnant women with gestational diabetes mellitus.
Goker Tasdemir U(1), Tasdemir N, Kilic S, Abali R, Celik C, Gulerman HC.
Author information:
(1)Dr. Zekai Tahir Burak Women's Health and Research Hospital, Ankara, Turkey.
BACKGROUND/AIMS: The aim of this prospective study was to determine ionized and
total magnesium (Mg) levels in pregnant subjects with and without gestational
diabetes mellitus (GDM).
METHODS: Eighty-five women, 26-28 weeks pregnant, were recruited for routine oral
glucose tolerance tests (OGTT); 45 had normal OGTT results and 40 were diagnosed
with GDM. Electrolyte levels, including ionized and total Mg, were analyzed.
RESULTS: Gestational age and BMI were similar between the two groups (p = 0.800,
p = 0.025). Multivitamin use was higher in the control group (p = 0.036). Fasting
blood glucose was higher in the GDM group (p < 0.001). The median total Mg levels
were 1.9 mg/dl (range 1.6-2.2) in the control group and 1.8 mg/dl (range 1.2-2.1)
in the GDM group (p < 0.001). The median ionized Mg levels were 0.5 mmol/l (range
0.4-0.6) in the control group and 0.4 mmol/l (range 0.4-0.5) in the GDM group (p
< 0.001). ASME BPVC IX Download
CONCLUSION: Our study revealed a relationship between low total and ionized Mg
levels and GDM, as in type 2 diabetes mellitus (DM). The literature regarding
type 2 DM and our findings suggest that Mg is the key ion in the pathophysiology
of GDM. Low-dose Mg supplementation was not related to GDM; however,
pharmacological doses in the various stages of pregnancy could be beneficial and
should be investigated.
© 2014 S. Karger AG, Basel.
DOI: 10.1159/000365813
PMID: 25413174  [PubMed - indexed for MEDLINE]

2. Metabolism. 2014 Apr;63(4):502-9. doi: 10.1016/j.metabol.2013.12.003. Epub 2013
Dec 16.
Serum ionized magnesium in diabetic older persons.
Barbagallo M(1), Di Bella G(2), Brucato V(2), D'Angelo D(2), Damiani P(2),
Monteverde A(2), Belvedere M(2), Dominguez LJ(2).
Author information:
(1)Geriatric Unit, Dept. of Internal Medicine and Specialties, University of
Palermo, Italy. Electronic address: mario.barbagallo@unipa.it. (2)Geriatric Unit,
Dept. of Internal Medicine and Specialties, University of Palermo, Italy.
OBJECTIVE: Several alterations of magnesium metabolism have been associated with
type 2 diabetes pathophysiology, a condition particularly frequent in older
persons. We aimed to evaluate serum total (Mg-tot) and serum ionized magnesium
(Mg-ion) in older persons with type 2 diabetes in order to explore clinically
applicable methods for the detection of magnesium deficit.
MATERIAL/METHODS: Mg-tot and Mg-ion were measured in 105 fasting subjects with
type 2 diabetes (mean age: 71.1±0.8 years; M/F: 45/60) and in 100 age-matched
non-diabetic control persons (mean age: 72.2±0.8 years; M/F: 42/58).
RESULTS: Mg-ion concentrations were significantly lower in diabetic persons
compared with controls (0.49±0.05 mmol/L vs. 0.55±0.05 mmol/L; p<0.001). Mg-tot
was also slightly but significantly lower in diabetic patients (0.82±0.007 mmol/L
vs. 0.84±0.006 mmol/L; p<0.05). There was an almost complete overlap in the
values of Mg-tot in older diabetic patients and controls; conversely, 44.8% of
diabetic patients had Mg-ion values below 0.47 mmol/L, while none of the controls
did. After adjustment for age, sex, BMI, and triglycerides, Mg-tot was
significantly associated with FBG in all the participants (p<0.05) and Mg-ion was
significantly associated with FBG in all the participants (p<0.01) and with HbA1c
in diabetic participants (p<0.001).
CONCLUSIONS: Alterations of magnesium serum concentrations are common in type 2
diabetic older adults; Mg-ion evaluation may help to identify subclinical
magnesium depletion (i.e. in patients with normal Mg-tot); the close independent
associations of Mg-tot and Mg-ion with FBG and with HbA1c reinforce the possible
link between magnesium homeostasis and altered glucose metabolism.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.metabol.2013.12.003
PMID: 24462317  [PubMed - indexed for MEDLINE]

3. J Thorac Cardiovasc Surg. 2012 Aug;144(2):474-9. doi:
10.1016/j.jtcvs.2011.12.023. Epub 2012 Jan 13.
The relationship between plasma concentrations of ionized calcium and magnesium
with cardiac energetics and systemic oxygen transport in neonates after the
Norwood procedure.
Dhillon S(1), Yu X, Zhang G, Cai S, Li J.
Author information:
(1)Division of Pediatric Cardiology, Stollery Children's Hospital, Department of
Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
OBJECTIVE: We sought to determine the relationship between plasma calcium and
magnesium concentrations with postoperative systemic hemodynamics and oxygen
transport in neonates after the Norwood procedure.
METHODS: Postoperative systemic oxygen consumption was continuously measured
using respiratory mass spectrometry for 72 hours in 17 neonates. Arterial,
superior vena caval and pulmonary venous blood gases and pressures, plasma
calcium, and lactate levels were measured at 2- to 4-hour intervals to calculate
cardiac output, rate pressure product, cardiac power output, systemic oxygen
delivery, and oxygen extraction ratio. Plasma magnesium levels were measured at
2- to 8-hour intervals.
RESULTS: Plasma calcium levels decreased in the first 8 hours from 1.08±0.13
mmol/L to 0.98±0.08 mmol/L, followed by an increase to 1.10±0.26 mmol/L at 72
hours (P<.0001). Mg2þ change was significantly related to time after logarithmic
transformation, rapidly decreasing from 1.62±0.25 mg/L to 0.90±0.15 mg/L in the
first 40 hours and further decreasing slowly thereafter to 0.64±0.13 mg/L at 72
hours (P<.0001). Plasma magnesium levels had a significant positive correlation
with cardiac output (P=.008) and cardiac power output (P=.01), and a negative
correlation with heart rate (P=.05). Plasma magnesium levels correlated
positively with systemic oxygen delivery and negatively with systemic oxygen
consumption (P=.08 for both), resulting in significant negative correlations with
oxygen extraction ratio (P=.04) and lactate levels (P=.05). For a given cardiac
power output, plasma magnesium showed a significantly negative correlation with
rate pressure product (P=.01). Plasma calcium levels showed the opposite trend,
which was statistically insignificant except for lactate (P=.007).
CONCLUSIONS: Plasma magnesium may exert favorable effects on myocardial
energetics and systemic oxygen transport in neonates after the Norwood procedure,
whereas plasma calcium may be harmful. Maintaining a relatively high level of
plasma magnesium and a low level of plasma calcium may improve myocardial work
efficiency and the balance of systemic and myocardial oxygen transport.
Copyright © 2012 The American Association for Thoracic Surgery. Published by
Mosby, Inc. All rights reserved.
DOI: 10.1016/j.jtcvs.2011.12.023
PMID: 22244502  [PubMed - indexed for MEDLINE]

4. Magnes Res. 2011 Sep;24(3):S115-21. doi: 10.1684/mrh.2011.0287.
Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease.
Barbagallo M(1), Belvedere M, Di Bella G, Dominguez LJ.
Author information:
(1)Chair of Geriatrics, Department of Internal Medicine and Medical Specialties
(DIMIS), University of Palermo, Italy. mario.barbagallo@unipa.it
Magnesium deficiency is present in several chronic, age-related diseases,
including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer's
disease (AD) is the most common cause of dementia. The aim of the present study
was to study magnesium homeostasis in patients with mild to moderate AD. One
hundred and one elderly (≥65 years) patients were consecutively recruited (mean
age: 73.4±0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric
assessment was performed including cognitive and functional status. Admission
criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA
criteria) included: mild to moderate cognitive impairment (MMSE score: 11-24/30,
corrected for age and education). Blood samples were analyzed for serum total
magnesium (Mg-tot) and serum ionized magnesium (Mg-ion). AD patients had
significantly lower MMSE scores (20.5±0.7 vs 27.9±0.2; p<0.001), and for the
physical function tests. Mg-ion was significantly lower in the AD group as
compared to age-matched control adults without AD (0.50±0.01 mmol/L vs 0.53±0.01
mmol/L; p<0.01). No significant differences were found in Mg-tot between the two
groups (1.91±0.03 mEq/L vs 1.95±0.03 mEq/L; p=NS). For all subjects, Mg-ion
levels were significantly and directly related only to cognitive function
(Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this
group of patients between magnesium and ADL or IADL. Our results show the
presence of subclinical alterations in Mg-ion in patients with mild to moderate
AD.
DOI: 10.1684/mrh.2011.0287
PMID: 21951617  [PubMed - indexed for MEDLINE]

5. Am J Ther. 2011 Nov;18(6):463-5. doi: 10.1097/MJT.0b013e3181ea30ff.
Effect of bicarbonate on neonatal serum ionized magnesium in vivo.
Glatstein M(1), Mimouni FB, Dollberg S, Mandel D.
Author information:
(1)Department of Neonatology, Lis Maternity Hospital, Tel Aviv Sourasky Medical
Center, Israel.
Sodium bicarbonate is used to treat metabolic acidosis or to induce metabolic
alkalosis in sick neonates. The aim of this study was to quantify the decrease in
serum concentration of ionized magnesium ([Mg(2+)]) when sodium bicarbonate is
administered in vivo. We administered 1 mEq/kg body weight sodium bicarbonate
4.2% for correction of metabolic acidosis (n = 11) for management of persistent
pulmonary hypertension (n = 3). After sodium bicarbonate treatment, serum pH
increased by an average of 0.046 (P < 0.001), serum [Mg(2+)] decreased by an
average of 0.07 mmol/L (P < 0.01), and serum [Ca(2+)] decreased by an average of
0.06 mmol/L (P = 0.04). There was a significant correlation between baseline
[Mg(2+)] and baseline [Ca(2+)] (R(2) = 0.328, P = 0.032). Sodium bicarbonate
therapy in infants causes a significant decrease in [Mg(2+)] and serum [Ca(2+)].
We suggest that infusion of sodium bicarbonate be effected while monitoring serum
[Mg(2+)] and serum [Ca(2+)].
DOI: 10.1097/MJT.0b013e3181ea30ff
PMID: 20724914  [PubMed - indexed for MEDLINE]

6. Am J Perinatol. 2010 Aug;27(7):525-8. doi: 10.1055/s-0030-1248938. Epub 2010 Feb
22.
Effect of magnesium sulfate concentration on serum ionized magnesium in vitro.
Salamon M(1), Mimouni FB, Dollberg S, Mandel D.
Author information:
(1)Department of Neonatology, Lis Maternity Hospital, Tel Aviv Sourasky Medical
Center, Tel Aviv, Israel.
We undertook this in vitro study to quantify the effect that addition of
magnesium (Mg) sulfate to neonatal serum, as compared with adult serum, might
have on ionized Mg (Mg (2+)) concentration. We used one cord blood sample and one
adult blood sample that we made hypermagnesemic by adding various amounts of
magnesium sulfate to study five levels of serum Mg. Each sample was then studied
at one of three levels of pH, from extreme alkalosis to extreme acidosis. We
measured the changes in serum Mg (2+) and serum ionized calcium (Ca (2+)) in
reaction to these changes in pH and Mg. At each pH level, there was an
exponential increase in the serum Mg (2+) (and no significant change in serum Ca
(2+)) with increasing serum Mg. Multiple regression analysis using Mg (2+) as the
dependent variable and baseline Ca (2+), phosphorous, albumin, and blood type
(adult versus cord blood) as well as blood pH and serum Mg as independent
variables indicated that serum Mg and pH were the only variables significantly
influencing serum Mg (2+). Within the range of serum Mg considered, the addition
of magnesium sulfate in vitro causes an exponential increase in Mg (2+) and no
significant change in serum Ca (2+).
Copyright Thieme Medical Publishers.
DOI: 10.1055/s-0030-1248938
PMID: 20178068  [PubMed - indexed for MEDLINE]

7. Fertil Steril. 2010 Jun;94(1):276-82. doi: 10.1016/j.fertnstert.2009.02.024. Epub
2009 Mar 26.
Cerebral spinal fluid and serum ionized magnesium and calcium levels in
preeclamptic women during administration of magnesium sulfate.
Apostol A(1), Apostol R, Ali E, Choi A, Ehsuni N, Hu B, Li L, Altura BT, Altura
BM.
Author information:
(1)Department of Anesthesiology, State University of New York, Downstate Medical
Center, Brooklyn, New York 11203, USA.
OBJECTIVE: To study the distribution of ionized and total magnesium (Mg) in serum
and cerebral spinal fluid (CSF) in preeclamptic women receiving MgSO(4) and how
this treatment affects the ionized calcium (Ca(2+)) and ionized Ca:Mg ratios
compared with healthy nonpregnant women and pregnant control women (HP).
DESIGN: Controlled clinical study.
SETTING: An academic medical center.
PATIENT(S): African-American women older than 20 and less than 35 years. The
pregnant preeclamptic study and pregnant control groups each consisted of 16
women; the nonpregnant group consisted of 10 subjects.
INTERVENTION(S): The preeclamptic women received a 6-g bolus of MgSO(4) IV
started at least 4.5 hours before delivery during 15-20 minutes, then 2 g/h
baseline.
MAIN OUTCOME MEASURE(S): The CSF and serum levels of Ca(2+) and Mg(2+) and total
Mg were measured in all three groups of women. The Ca(2+):Mg(2+) ratios were
determined. Physiologic monitoring was done and recorded every 4 hours where
appropriate. Bloods were drawn every 6 hours for complete blood count, metabolic
panel, lactate dehydrogenase, uric acid, and electrolytes. Serum pH, total Mg,
Apgar scores, and general health of the infants born to preeclamptic mothers
given MgSO(4) were followed.
RESULT(S): The HP showed a reduction in mean serum ionized and total Mg, increase
in ionized Ca, and a large increase in Ca(2+):Mg(2+) ratios compared with healthy
nonpregnant women. Although the CSF ionized and total Mg and Ca(2+):Mg(2+) ratios
were not altered with MgSO(4) treatment in the preeclamptic women receiving
MgSO(4), the mean serum Mg values increased 3-fold. All infants were full-term,
regardless of MgSO(4) treatment, and normal with respect to birth weight, Apgar
scores, blood pH, total Mg, and neurologic scores.
CONCLUSION(S): The data indicate that there is a direct relationship between the
serum and CSF Ca(2+):Mg(2+) ratios in HP and this ratio may be crucial in
preventing vascular and neurologic complications in preeclampsia-eclampsia.
Copyright (c) 2010 American Society for Reproductive Medicine. Published by
Elsevier Inc. All rights reserved.
DOI: 10.1016/j.fertnstert.2009.02.024
PMID: 19324346  [PubMed - indexed for MEDLINE]

8. Asia Pac J Clin Nutr. 2008;17(3):525-9.
Intraoperative infusion of acetated Ringer solution containing glucose and
ionized magnesium reduces ketogenesis and maintains serum magnesium.
Yokoyama T(1), Suwa K, Yamasaki F, Yokoyama R, Yamashita K, Sellden E.
Author information:
(1)Department of Anesthesiology and Critical Care Medicine, Kochi Medical School,
Kohasu, Nankoku, Japan. yokoyamt@kochi-u.ac.jp
The effect of glucose infusion during surgery on glucose metabolism has not been
investigated sufficiently. We, therefore, examined the effect after the infusion
of 1% glucose acetated Ringer solution containing Mg2+ during surgery on
ketogenesis and serum Mg2+ concentrations. Patients, classified as ASA I-II, age
51-80 years, were randomly assigned to receive infusion of acetated Ringer
solution. The G/Mg group received infusion with 1% glucose, Na+ 140mEq/L, Mg2+ 2
mEq/L, and the C group received infusion with glucose free solution containing
Na+ 130 mEq/L without Mg2+. Both solutions were infused at a rate of 25 mL/kg for
the first hour, and main-tained at 4 mL/kg/hr thereafter. Blood samples were
collected three times: before infusion and at 1 hour and 4 hours after the start
of infusion. Electrolytes and glucose metabolism were evaluated at each sampling.
After rapid infusion, blood glucose level significantly increased to
170+/-19mg/dL in the G/Mg group, but it returned to close to baseline after 4
hours and serum ketone bodies did not increase during infusion. In the C group,
however, blood glucose never increased beyond 110 mg/dL, but both acetoacetic and
hydroxybutyric acids increased significantly at the third measurement.

PMID: 18818174  [PubMed - indexed for MEDLINE]

9. J Obstet Gynaecol Res. 2008 Feb;34(1):126, author reply 128. doi:
10.1111/j.1447-0756.2007.00717.x.
Ionized and total magnesium concentration in patients with severe
pre-eclampsia-eclampsia undergoing magnesium sulfate therapy.
Mahajan NN.
Comment on
    J Obstet Gynaecol Res. 2007 Apr;33(2):138-43.
DOI: 10.1111/j.1447-0756.2007.00717.x
PMID: 18226146  [PubMed - indexed for MEDLINE]

10. Indian J Pediatr. 2007 Nov;74(11):1025-8.
Ionized magnesium and gestational age.
Mehta R(1), Petrova A.
Author information:
(1)Department of Pediatrics, Division of Neonatal Medicine, Robert Wood Johnson
Medical School-UMDNJ, New Brunswick, New Jersey, USA. mehtara@umdnj.edu
OBJECTIVE: Investigation of magnesium (Mg) homeostasis has re-emerged as an area
of interest in preterm born neonates who are at risk for brain pathology.
However, data regarding the association between the biologically active ionized
form of Mg and gestational age (GA) at an early stage of life in newborn infants
are controversial.
METHODS: We evaluated the total and ionized Mg electrolyte (TMg and IMg) as well
as the calcium (TCa and ICa) and pH in the cord blood and on day 2 of life in 22
neonates born at different gestational ages (< 32, 32-34 and > or =35 week)
without magnesium tocolysis and absence of serious complications during pregnancy
and delivery.
RESULTS: The IMg fraction that accounted for 68.1+/-5.1% of the TMg in the cord
blood and 67.9+/-4.5% of the TMg on day 2 of life, was significantly higher in
very preterm infants (GA< 32 week) as compared to neonates with GA > 35 week.
Higher IMg levels were correlated with the lower pH that was recorded in the cord
blood of the very preterm infants (correlation coefficient, r=-0.80, p< 0.0001)
and ICa (r = -0.52, P< 0.01). Lower pH also was correlated with the GA (P<
0.0001). However, standard multiple regression analysis showed significant
association between IMg levels and decreased pH but not the gestational age or
ICa (beta=-1.10+/-0.21, p< 0.00009).
CONCLUSION: Extremely preterm infants even without additional exposure to
tocolytic magnesium are at risk for the lower pH associated elevation of ionized
Mg, which should be considered during the management of these infants in order to
prevent hypermagnesemia-related pathology.

PMID: 18057684  [PubMed - indexed for MEDLINE]

11. Clin Chem Lab Med. 2008;46(1):21-6.
IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma.
Ben Rayana MC(1), Burnett RW, Covington AK, D'Orazio P, Fogh-Andersen N, Jacobs
E, Külpmann WR, Kuwa K, Larsson L, Lewenstam A, Maas AH, Mager G, Naskalski JW,
Okorodudu AO, Ritter C, St John A; International Federation of Clinical Chemistry
and Laboratory Medicine (IFCC); IFCC Scientific Division Committee on Point of
Care Testing.
Author information:
(1)Department of Chemistry, University of Newcastle upon Tyne, UK.
Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should
yield comparable and unbiased results for iMg. This IFCC guideline on sampling,
measuring and reporting iMg in plasma provides a prerequisite to achieve this
goal [in this document, "plasma" refers to circulating plasma and the forms in
which it is sampled, namely the plasma phase of anticoagulated whole blood (or
"blood"), plasma separated from blood cells, or serum]. The guideline recommends
measuring and reporting ionized magnesium as a substance concentration relative
to the substance concentration of magnesium in primary aqueous calibrants with
magnesium, sodium, and calcium chloride of physiological ionic strength. The
recommended name is "the concentration of ionized magnesium in plasma". Based on
this guideline, results will be approximately 3% higher than the true substance
concentration and 4% lower than the true molality in plasma. Calcium ions
interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus
it is necessary to determine both ions simultaneously in each sample and correct
the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent.
Therefore, pH should be measured simultaneously with iMg to allow adjustment of
the result to pH 7.4. The concentration of iMg in plasma may be physiologically
and clinically more relevant than the concentration of total magnesium.
Furthermore, blood-gas analyzers or instruments for point-of-care testing are
able to measure plasma iMg using whole blood (with intact blood cells) as the
sample, minimizing turn-around time compared to serum and plasma, which require
removal of blood cells.
DOI: 10.1515/CCLM.2008.001
PMID: 17663628  [PubMed - indexed for MEDLINE]

12. Scand J Clin Lab Invest. 2007;67(3):317-26.
Serum ionized magnesium and calcium levels in adult patients with seizures.
Sinert R(1), Zehtabchi S, Desai S, Peacock P, Altura BT, Altura BM.
Author information:
(1)Department of Emergency Medicine, State University of New Yourk, Downstate
Medical Center, Brooklyn, NY 11203, USA. neprhon1@bellatlantic.net
OBJECTIVE: Prior studies have been equivocal about whether or not serum levels of
the divalent ions calcium and magnesium are altered during different types of
seizures. Magnesium is a potential modulator of seizure activity because of its
ability to antagonize the excitatory calcium influx through the
N-methyl-D-aspartate (NMDA) receptor. We hypothesize that serum ionized levels of
calcium (Ca(2+)) and magnesium (Mg(2+)) would be altered significantly during
certain types of seizures.
MATERIAL AND METHODS: A convenience sample of seizure patients presenting to an
emergency department (ED) were enrolled in this prospective study. Novel
ion-selective electrodes were used to measure Ca(2+) and Mg(2+). Data were
reported as mean values+/-standard deviations. Group comparisons were analyzed by
ANOVA with post-hoc testing using the Bonferroni, or the Fisher exact test, where
appropriate, alpha = 0.05 (two-tailed).
RESULTS: Forty-nine patients with seizure and 32 healthy racially matched
controls were included in the study. Seizure patients had a significantly
(p<0.001) lower mean Mg(2+), but not total serum Mg and a significantly (p<0.001)
higher Ca(2+)/Mg(2+) ratio than that in controls.
CONCLUSIONS: We were able to show significantly lower Mg(2+) and higher ionized
Ca(2+)/Mg(2+) ratios in seizure patients compared with a racially matched control
group.
DOI: 10.1080/00365510601051441
PMID: 17454846  [PubMed - indexed for MEDLINE]

13. Biol Trace Elem Res. 2007 Jan;115(1):13-21.
Weak relationship between ionized and total magnesium in serum of patients
requiring magnesium status.
Johansson M(1), Whiss PA.
Author information:
(1)Department of Natural Sciences, School of Health Sciences, Jönköping
University, Jönköping, Sweden.
Measurement and monitoring of magnesium (Mg) are important to prevent the
development of serious and potentially fatal complications in critically ill
patients. Although ion-selective electrodes are available and earlier reports
suggest that free ionized magnesium (iMg2+) is the most useful test to estimate
Mg status, most clinical laboratories still only measure total Mg. To compare the
relationship among iMg2+, total Mg, and albumin in serum, samples were collected
from 48 consecutive patients admitted to an intensive care unit or a primary
health center. The mean serum level of iMg2+ in 44 patients was 0.53 mmol/L, the
total Mg was 0.96 mmol/L, and the albumin was 34.93 g/L. The correlation between
iMg2+ and total Mg in serum was r=0.585; the correlation between iMg2+ and
albumin in serum was r=378; and the correlation between total Mg and albumin in
serum was r=0.340. The mean percent iMg2+ in relation to total Mg in serum was
calculated to be 55% in the patient samples. The important level of biologically
active iMg2+ was not reflected upon analysis of total Mg in 25% of consecutive
patients. This report shows that the correlation of iMg2+ and total Mg is weak,
not only in critically ill patients but also in patients in whom Mg status is
inquired as a whole.
DOI: 10.1385/BTER:115:1:13
PMID: 17406070  [PubMed - indexed for MEDLINE]

14. Eur J Obstet Gynecol Reprod Biol. 2007 Apr;131(2):246; author reply 246-7. Epub
2006 Dec 1.
Comment on "Serum ionized magnesium during magnesium sulfate administration for
preterm labor and preeclampsia" [Eur. J. Obstet. Gynecol. Reprod. Biol. 128
(2006) 125-128].
Ross MG, Adeniji A.
Comment on
    Eur J Obstet Gynecol Reprod Biol. 2006 Sep-Oct;128(1-2):125-8.
DOI: 10.1016/j.ejogrb.2006.10.012
PMID: 17141399  [PubMed - indexed for MEDLINE]

15. J Am Coll Nutr. 2006 Jun;25(3):210-5.
Serum ionized magnesium levels in relation to metabolic syndrome in type 2
diabetic patients.
Corica F(1), Corsonello A, Ientile R, Cucinotta D, Di Benedetto A, Perticone F,
Dominguez LJ, Barbagallo M.
Author information:
(1)Department of Internal Medicine, University of Messina, Messina, Italy.
OBJECTIVE: To evaluate circulating serum ionized magnesium (i-Mg) concentrations
in patients with type 2 diabetes mellitus, and to investigate its relationship
with the components of the metabolic syndrome.
DESIGN: cross-sectional study.
SETTING: Outpatients' service for diabetic patients at the University Hospital of
Messina, Italy.
SUBJECTS: 290 patients with type 2 diabetes mellitus.
MEASURES OF OUTCOME: Serum i-Mg was measured by ion selective electrode. Age,
gender, body mass index (BMI), waist circumference, blood pressure, fasting
glucose, HbA1c, HDL cholesterol, triglycerides, and urinary albumin excretion
rate (UAER) were considered in the analyses. Patients with hypomagnesemia,
defined as serum i-Mg <0.46 mmol/l, were compared with those having normal serum
i-Mg levels, and variables proven to be associated with low i-Mg levels in the
univariate analysis were entered in a multivariable logistic regression model to
obtain a deconfounded estimate of the association between metabolic parameters
and hypomagnesemia.
RESULTS: In univariate analysis, serum i-Mg levels were significantly reduced in
patients with low HDL cholesterol, high triglycerides values, high waist
circumference, high blood pressure, microalbuminuria and clinical proteinuria.
Hypomagnesemia was highly prevalent in our study population (N = 143, 49.3%).
After adjusting for potential confounders, plasma triglycerides (OR = 4.71; 95%
CI = 2.56-8.67), waist circumference (OR = 2.21; 95% CI = 1.21-4.04),
microalbuminuria (OR = 2.43; 95% CI = 1.16-5.08) and clinical proteinuria (OR =
2.04; 95% CI = 1.02-5.68) were independently associated with hypomagnesemia.
CONCLUSIONS: Hypomagnesemia is highly prevalent in diabetic outpatients. High
plasma triglycerides, waist circumference and albuminuria are independent
correlates of hypomagnesemia.

PMID: 16766779  [PubMed - indexed for MEDLINE]

16. Magnes Res. 2005 Dec;18(4):241-4.
Assessment of serum ionized magnesium levels in healthy volunteers, in patients
with coronary artery disease and/or hypertension and in hypertension alone.
Kozielec P(1), Kotkowiak L, Późniak J, Salacka A, Hornowska I, Brodowski J,
Michón P.
Author information:
(1)Pomeranian Medical University, Department of Family Medicine, Szczecin,
Poland. fammed@sci.pam.szczecin.pl
We examined ionized magnesium concentration by blood analysis in patients with
hypertonia arterialis, ischemic heart diseases, both of them and in a control
group. Slighty lower mean serum ionized magnesium concentration was found in the
study group hypertonia arterialis when compared to the control group. In patients
both group "B" with coronary artery diseases and group "C" with hypertonia
arterialis + ischemic heart diseases, mean serum ionized magnesium concentrations
were higher then in the control group, the differences were statistically
significant.

PMID: 16548138  [PubMed - indexed for MEDLINE]

17. Ginekol Pol. 2005 Aug;76(8):625-31.
[Total and ionized magnesium concentration in the blood plasma and erythrocytic
magnesium concentration of women in the third trimester of pregnancy with
imminent preterm labor].
[Article in Polish]
Gryboś M(1), Krzemieniewska J, Stacherzak-Pawlik J, Wilczyński A, Woźniak M,
Majsnerowicz M, Gryboś-Jagielska A.
Author information:
(1)I Katedra i Klinika Ginekologii i Połoznictwa AM we Wrocławiu.
OBJECTIVES: There are some data concerning magnesium concentration influence on
the risk of preterm labor. The estimation of magnesium concentration changes may
be useful in prevention of preterm labor.
DESIGN: Therefore the aim of our study was to find out the correlation between
magnesium concentration and the risk of preterm labor.
MATERIALS AND METHODS: Total magnesium concentration and ionized magnesium
concentration in blood plasma and erythrocytic magnesium concentration ware
examined in the three groups of: 23 women in the third trimester of pregnancy
with imminent preterm labor under tocolytic therapy; 20 women in the third
trimester of physiologic pregnancy and 19 non-pregnant healthy women in the
reproductive age.
RESULTS: We discovered statistically confirmed differences (p < 0,05 ) in ionized
magnesium concentration as well between the group of women in physiologic
pregnancy and non-pregnant women and between the group of pregnant women with
imminent preterm labor and non-pregnant women.
CONCLUSIONS: Although there were no statistically confirmed differences in total
magnesium concentration and erythrocytic magnesium concentration between the
three groups of examined women, there were statistically confirmed differences in
ionized magnesium concentration between the pregnant and non-pregnant women. Our
results suggest that ionized magnesium concentration is better indicator of
magnesium balance in human's body than total magnesium concentration.

PMID: 16363368  [PubMed - indexed for MEDLINE]

18. Eur J Obstet Gynecol Reprod Biol. 2006 Sep-Oct;128(1-2):125-8. Epub 2005 Dec 5.
Serum ionized magnesium during magnesium sulfate administration for preterm labor
and preeclampsia.
Yoshida M(1), Matsuda Y, Akizawa Y, Ono E, Ohta H.
Author information:
(1)Department of Obstetrics and Gynecology, Tokyo Women's Medical University,
Tokyo, Japan.
Comment in
    Eur J Obstet Gynecol Reprod Biol. 2007 Apr;131(2):246; author reply 246-7.
OBJECTIVE: The purpose of this study is to estimate the relations between ionized
and total Mg levels during MgSO4 administration in patients with preterm labor
and preeclampsia.
METHODS: Forty-three pregnant patients who were candidates for MgSO4 were studied
(preterm labor, 27; preeclampsia, 16). The administration method was intravenous
injection of MgSO4 4 g over 30 min followed by 1-2 g/h. Ionized Mg was measured
by the selective ion electrode method at bedside, and compared it with total Mg
levels.
RESULTS: Significant correlation was existed between levels of ionized and total
Mg throughout therapy for both preterm labor (ionized Mg=0.19 x total Mg+0.19;
r=0.61, p<0.001) and preeclampsia (ionized Mg=0.20 x total Mg+0.14; r=0.60,
p<0.001).
CONCLUSION: There are correlations between ionized and total Mg levels during
administration of MgSO4 for both preterm labor and preeclampsia.
DOI: 10.1016/j.ejogrb.2005.10.036
PMID: 16337073  [PubMed - indexed for MEDLINE]

19. Scand J Clin Lab Invest. 2005;65(8):659-70.
Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma
patients before and after treatment with magnesium.
Sinert R(1), Spektor M, Gorlin A, Doty C, Rubin A, Altura BT, Altura BM.
Author information:
(1)Department of Emergency Medicine, State University of New York, Downstate
Medical Center, Brooklyn, NY 11203, USA. nephron1@bellatlantic.net
OBJECTIVE: Prior studies have been equivocal about the efficacy of magnesium
therapy in acute asthma exacerbations. We hypothesize that pretreatment ionized
magnesium (Mg(2+)) levels and/or the ratio of ionized calcium to ionized
magnesium (Ca(2+)/Mg(2+)) may have been confounding variables in these previous
studies. Here, we report on the incidence of abnormal divalent ion levels in our
asthma population.
MATERIAL AND METHODS: The study was designed as a randomized, double-blind,
placebo-controlled trial of intravenous magnesium. Inclusion criteria were: age
>18 years, percentage predicted forced expiratory volume (FEV(1)) <75 % after an
initial beta-agonist. African-American patients (AA) at an urban university
hospital were randomized to 2 g IV Mg or placebo. Mg(2+) and Ca(2+)/Mg(2+) levels
were measured pre- and post-infusion. Data were reported as means+/-SD. Student's
t-test and Fisher's exact test were used where appropriate (alpha = 0.05, two
tailed).
RESULTS: Fifty-five AA patients (mean age of 42.7 years+/-15.6 years, range 18-75
years) were studied. A significantly (p<0.05) lower level of Mg(2+) was found in
asthma (AS) patients compared with that in the AA group, by 0.03 mmol/L (95 % CI,
0.007-0.053 mmol/L). The AS group had a mean increase in Ca(2+)/Mg(2+) ratios
over the AA group, of 0.27 (95 % CI, 0.16-0.38); 100 % of patients with abnormal
divalent ion levels were corrected with IV magnesium.
CONCLUSIONS: We identified a subgroup of asthmatic patients with significant
abnormalities in their divalent ion concentrations, which was corrected with IV
magnesium.
DOI: 10.1080/00365510500333825
PMID: 16319040  [PubMed - indexed for MEDLINE]

20. Scand J Clin Lab Invest. 2005;65(2):107-10.
Influence of air exposure and storage condition on serum ionized magnesium level.
Baek EJ(1), Park IK.
Author information:
(1)Department of Laboratory Medicine, Hanyang University College of Medicine,
Seoul, Korea.
The aim of this study was to evaluate whether reporting serum level of ionized
magnesium (iMg) is appropriate when affected by various conditions such as
exposure to air and delayed measurement. Serum levels of pH, iMg and normalized
magnesium (nMg, normalized or adjusted concentration of iMg to pH 7.40) from 28
inpatients were measured at intervals of 3 min after exposing the samples to air
at room temperature. Serum from 30 inpatients was stored in closed tubes at 4
degrees C and -20 degrees C and iMg and nMg levels were measured after 2 days. It
was found that serum iMg and nMg concentrations exposed to air were decreased by
0.0023 mmol/l and 0.0001 mmol/l per minute, respectively. nMg did not display any
significant changes compared with iMg at 0 min, whereas iMg showed significant
changes, which exceeded between-day precision. For the stored serum, only iMg of
serum at -20 degrees C showed no statistically significant changes (p = 0.169).
It is concluded that to report the result as iMg, the sample should be kept
anaerobically, and if exposed to air, the result should be reported as nMg. For
storage, iMg of serum kept anaerobically at -20 degrees C is reliable.

PMID: 16025833  [PubMed - indexed for MEDLINE]

21. Clin Chem Lab Med. 2005;43(5):564-9.
Guidelines for sampling, measuring and reporting ionized magnesium in undiluted
serum, plasma or blood: International Federation of Clinical Chemistry and
Laboratory Medicine (IFCC): IFCC Scientific Division, Committee on Point of Care
Testing.
Rayana MC(1), Burnett RW, Covington AK, D'Orazio P, Fogh-Andersen N, Jacobs E,
Külpmann WR, Kuwa K, Larsson L, Lewenstam A, Maas AH, Mager G, Naskalski JH,
Okorodudu AO, Ritter C, St John A.
Author information:
(1)Laboratory of Clinical Chemistry, National Institute of Nutrition, Bab
Saadoun, Tunis, Tunisia.
All analyzers with ion-selective electrodes for ionized magnesium (iMg) should
yield comparable and unbiased results. The prerequisite to achieve this goal is
to reach consensus on sampling, measurement and reporting. The recommended
guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers
to circulating plasma and the forms in which it is sampled: the plasma phase of
anticoagulated whole blood, plasma separated from blood cells, or serum) or
blood, referring to the substance concentration of iMg in the calibrants, will
provide results for iMg that are approximately 3% greater than its true
concentration, and 4% less than its true molality. Binding of magnesium to
proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be
simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The
substance concentration of iMg may be physiologically and consequently clinically
more relevant than the substance concentration of total magnesium.
DOI: 10.1515/CCLM.2005.098
PMID: 15899681  [PubMed - indexed for MEDLINE]

22. Heart Vessels. 2004 Nov;19(6):267-70.
Factors affecting the blood concentration of ionized magnesium in patients in the
acute phase of myocardial infarction.
Ueshima K(1), Tachibana H, Suzuki T, Hiramori K.
Author information:
(1)Memorial Heart Center, Second Division of Internal Medicine, Iwate Medical
University, 1-2-1 Chuo-dori, Morioka, Iwate 020-8505, Japan.
k_ueshima@imu.ncvc.go.jp
Magnesium is physiologically active in its free state (Mg2+). In the present
study, we attempted to clarify factors affecting blood concentrations of Mg2+ in
the acute phase of myocardial infarction (AMI). Subjects were 84 consecutive
patients with AMI. Blood samples were collected at the time of admission, 24h
after admission, and 1 week after admission, to measure blood concentration of
Mg2+ and noradrenaline (NA). Furthermore, to assess daily Mg intake the hardness
of local drinking water was determined, and a survey was conducted regarding
dietary preferences and habits. Based on the results of this survey, the patients
were defined as having a low Mg intake (L Group) or not. In addition, based on
chronological shifts in blood Mg2+ concentrations, subjects were divided into the
following four groups: Normal group, blood concentration of Mg2+ within normal
range at all measurement points; Early recovery group, low at time of admission,
but normalized on the next day; Delayed recovery group, low at time of admission,
but normalized 1 week after admission; and Unrecovered group, below normal range
at all measurement points. The mean blood Mg2+ concentration on admission was
0.52 +/- 0.06 mmol/l, significantly lower than the normal range (P < 0.05). A
negative correlation between blood Mg2+ and NA concentrations on admission was
observed (r = 0.49, P < 0.005). As a result, blood Mg2+ concentrations were
normalized in 94% of subjects by 1 week after admission. Mean blood Mg2+
concentration on admission in the L Group was 0.47 +/- 0.05 mmol/l, significantly
lower than that found in other subjects (0.52 +/- 0.05 mmol/l, P < 0.01). Eighty
percent of the patients classified into the Unrecovered group belonged to the L
Group. These findings suggest that lower blood concentrations of Mg2+ and higher
plasma NA levels may be a result of serious AMI. However, chronic Mg intake
deficiency may play a partial role in patients whose blood concentrations of Mg2+
remain low for long periods of time.

PMID: 15799172  [PubMed - indexed for MEDLINE]

23. Intensive Care Med. 2005 Jan;31(1):151-6. Epub 2004 Dec 17.
Total and ionized serum magnesium in critically ill patients.
Escuela MP(1), Guerra M, Añón JM, Martínez-Vizcaíno V, Zapatero MD, García-Jalón
A, Celaya S.
Author information:
(1)Intensive Care Unit, Hospital Clínico Universitario, Zaragoza, Spain.
OBJECTIVE: To assess the alterations in total serum magnesium (tsMg) and ionized
serum magnesium (Mg(2+)) and their association with prognosis in critically ill
patients.
DESIGN AND SETTING: Prospective, cohort study in the intensive care unit (ICU) of
a university teaching hospital.
PATIENTS: Adult patients admitted to the ICU without previous factors influencing
magnesium homeostasis were included during a 6-month period.
MEASUREMENTS AND RESULTS: One hundred forty four patients were included. Mean age
was 60.6+/-15.4 years; mean APACHE II score was 12.6+/-6.9. Blood samples were
collected in the first 24 h after ICU admission and again on the second, third,
and last days of stay in the ICU. At ICU admission 52.5% had total hypomagnesemia
and 13.5% total hypermagnesemia; with respect to the Mg(2+) 9.7% showed ionized
hypomagnesemia and 23.6% ionized hypermagnesemia. Patients who developed ionized
hypermagnesemia had higher mortality than patients without ionized
hypermagnesemia development (P=0.04). A moderate correlation between tsMg and
Mg(2+) concentrations was found; however, a number of patients with total
hypomagnesemia (69-85% during the study) had ionized normomagnesemia. The measure
of agreement between tsMg and Mg(2+) levels was poor.
CONCLUSIONS: Magnesium alterations are frequently found in critically ill
patients. The usually determined tsMg levels are not a reflection of Mg(2+)
levels. Development of ionized hypermagnesemia is associated with prognosis.
DOI: 10.1007/s00134-004-2508-x
PMID: 15605229  [PubMed - indexed for MEDLINE]

24. Pediatr Res. 2005 Mar;57(3):347-52. Epub 2004 Dec 7.
Total and ionized plasma magnesium concentrations in children after traumatic
brain injury.
Mendez DR(1), Corbett R, Macias C, Laptook A.
Author information:
(1)Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
drmendez@texaschildrenshospital.org
This study examined 1) whether plasma total Mg (TMg) and ionized Mg (IMg)
concentrations in children are reduced by traumatic brain injury (TBI) and 2)
whether the extent of reduction correlates with severity of trauma assessed by
the Glasgow Coma Scale (GSC) score. This was a prospective cohort study of 98
pediatric patients who had TBI and were admitted through the emergency
department. A GCS score was assigned and blood was obtained upon presentation and
24 h later. Plasma was analyzed for TMg and IMg. Patients were grouped into three
categories-GCS scores 13-15, 8-12, and <8-to designate mild (n=21), moderate
(n=37), and severe (n=40) TBI, respectively. Blood was obtained from 50 healthy
children before elective surgery as controls. Control subjects had a TMg and an
IMg of 0.94 +/- 0.08 and 0.550 +/- 0.06 mM. TBI patients had an initial TMg and
IMg of 0.83 +/- 0.09 and 0.520 +/- 0.05 mM, respectively. Initial TMg for mild,
moderate, and severe TBI subgroups (0.87 +/- 0.16, 0.81 +/- 0.15, and 0.83 +/-
0.14 mM, respectively) was reduced from control subjects (p <0.01). IMg was
reduced only in the severe TBI subgroup (0.516 +/- 0.07 mM; p=0.016). Twenty-four
hours later, TMg remained lower than in control subjects for all subgroups of
TBI; however, IMg normalized. TBI in children is associated with a reduction in
TMg, whereas IMg decreased only with severe TBI. IMg returned to control values
by 24 h despite a continued lower TMg, suggesting mechanisms to maintain IMg.
Changes in plasma IMg may serve as a marker for TBI but only over a limited time
interval.
DOI: 10.1203/01.PDR.0000150803.36315.FF
PMID: 15585675  [PubMed - indexed for MEDLINE]

25. Am J Hematol. 2004 Nov;77(3):215-22.
Serum ionized magnesium levels and ionized calcium-to-magnesium ratios in adult
patients with sickle cell anemia.
Zehtabchi S(1), Sinert R, Rinnert S, Chang B, Heinis C, Altura RA, Altura BT,
Altura BM.
Author information:
(1)Department of Emergency Medicine, State University of New York, Downstate
Medical Center, Brooklyn, New York 11203, USA. zehtab@yahoo.com
Low levels of total magnesium in sickle cell erythrocytes have been linked to
increased sickling due to cell dehydration. We tested the null hypothesis that
adult sickle cell anemia (SCA) patients have the same serum level of ionized Mg
(Mg(2+)) and Ca(2+)/Mg(2+) ratio as healthy African Americans (AA) and healthy
Caucasians (CAUC). We measured serum Mg(2+) and ionized calcium (Ca(2+)) with
ion-selective electrodes and calculated the serum Ca(2+)/Mg(2+) ratios in
patients with SCA and control groups (AA and CAUC). Seventy-four SCA patients and
61 controls were compared. SCA patients had significantly (P < 0.001) lower
levels of serum Mg(2+) (0.52 +/- 0.05) compared to healthy AA (0.57 +/- 0.04) and
CAUC (0.62 +/- 0.03). Eighty-six percent of the adult SCA patients had serum
Mg(2+) levels below the mean for the AA group, and 96% of SCA patients were above
the AA group's mean serum Ca(2+)/Mg(2+). Of the SCA patients studied, 25.6% (95%
CI, 16.2-37.2%) had serum Mg(2+) levels below the racially adjusted lower limit
of normal and 50% (95% CI, 38.1-61.9%) were above the upper limit of serum
Ca(2+)/Mg(2+) for AA controls. By measuring serum Mg(2+) and Ca(2+), we were able
to define a subset of SCA patients with hypomagnesemia and elevated Ca(2+)/Mg(2+)
ratios, who may benefit from magnesium supplementation.
DOI: 10.1002/ajh.20187
PMID: 15495259  [PubMed - indexed for MEDLINE]

26. Clin Chim Acta. 2004 Nov;349(1-2):67-73.
Ionized magnesium in erythrocytes--the best magnesium parameter to observe hypo-
or hypermagnesemia.
Malon A(1), Brockmann C, Fijalkowska-Morawska J, Rob P, Maj-Zurawska M.
Author information:
(1)Faculty of Chemistry, Warsaw University, Pasteura 1, 02093 Warsaw, Poland.
BACKGROUND: Almost 99% of the body magnesium is inside cells. The concentration
of intracellular ionized magnesium (iMg) is physiologically relevant. iMg in
erythrocytes is a new parameter that can help to establish reliable information
on the functional magnesium status.
METHODS: iMg concentration in erythrocytes and serum was measured by
ion-selective electrode, in clinical analyzer Microlyte (KONE). Total magnesium
(tMg) concentration was measured by atomic absorption spectrometry (AAS). Albumin
and total protein concentration were measured colorimetrically.
RESULTS: In critically ill postoperative patients, the mean of albumin, protein
and hematocrit concentration was significantly lower compared to healthy
individuals. Hypomagnesemia was found in 15.9% patients as tMgs, at 22.2% as iMgs
and 36.5% as iMge. Significant correlations are between iMgs and tMgs or iMge and
iMgs/tMgs. In dialyzed patients, the mean of hematocrit was significantly lower,
iMge was significantly higher compared with healthy individuals. Significant
negative correlations are between iMgs and tMge or iMge/tMge and tMge.
CONCLUSIONS: iMge is the best magnesium parameter to observe hypo- or
hypermagnesemia for both groups of patients. The function of magnesium is mainly
intracellular and intracellular magnesium concentrations can be the method to
evaluate the magnesium status.
DOI: 10.1016/j.cccn.2004.06.006
PMID: 15469857  [PubMed - indexed for MEDLINE]

27. Diabetes Care. 2004 Oct;27(10):2503-5.
Differences in serum ionized and total magnesium values during chronic renal
failure between nondiabetic and diabetic patients: a cross-sectional study.
Dewitte K(1), Dhondt A, Giri M, Stöckl D, Rottiers R, Lameire N, Thienpont LM.
Author information:
(1)Faculty of Pharmaceutical Sciences, Laboratory for Analytical Chemistry, Ghent
University, Harelbekestraat 72, Ghent 9000, Belgium.

PMID: 15451927  [PubMed - indexed for MEDLINE]

28. Magnes Res. 2004 Jun;17(2):90-3.
Effect of bicarbonate on neonatal serum ionized magnesium in vitro.
Zaidenberg G(1), Mimouni FB, Dollberg S.
Author information:
(1)The Department of Neonatology, Lis Maternity Hospital, Tel Aviv Sourasky
Medical Center, Tel Aviv, Israel.
Sodium bicarbonate is used to treat metabolic acidosis, or to induce metabolic
alkalosis in sick neonates. The aim of this study was to quantify the decrease in
serum concentration of ionized magnesium ([Mg2+]) when sodium bicarbonate is
added to neonatal serum in vitro. Sodium bicarbonate was added to 30 cord serum
samples of term infants to reach incremental concentrations of 0 to 2.0 mEq/L and
[Mg2+] was measured. Serum [Mg2+] decreased significantly with the addition of
sodium bicarbonate. At incremental sodium bicarbonate concentrations of 1.0 to
2.0 mEq/L, which is within the range of the desired aim in the treatment of
metabolic acidosis, the magnitude of the decrease in serum [Mg2+] was
approximately 0.084 to 0.158 mmol/L (18% to 34%) from the average baseline value.
The addition of sodium bicarbonate causes a significant decrease in [Mg2+]. From
this in vitro study we speculate that fast infusion of sodium bicarbonate in
human neonates may potentially cause a clinically significant decrease in serum
[Mg2+].

PMID: 15319140  [PubMed - indexed for MEDLINE]

29. J Anesth. 2004;18(3):216-9.
Changes in plasma total and ionized magnesium concentrations and factors
affecting magnesium concentrations during cardiac surgery.
Inoue S(1), Akazawa S, Nakaigawa Y, Shimizu R, Seo N.
Author information:
(1)Department of Anesthesiology and Critical Care Medicine, Jichi Medical School,
3311-1 Yakushiji, Minamikawachi, Kawachi-gun, 329-0498 Tochigi, Japan.
The purpose of this study was to measure blood total and ionized magnesium
concentrations ([TMg] and [Mg(2+)], respectively) and to investigate factors that
might be affecting their changes during cardiac surgery using hypothermic
cardiopulmonary bypass. Eight patients were examined. All the patients received
diuretics and predeposited autologous blood during surgery. No drugs containing
Mg(2+) were administered. Nine blood samples and eight urine samples were
collected from the pre-induction period to the end of surgery. Hematocrit, [TMg],
[Mg(2+)], plasma concentrations of calcium ([Ca(2+)]), creatinine, parathyroid
hormone (PTH), urinary concentrations of TMg, and creatinine were measured, and
the fractional excretion of Mg (FEMg) was calculated. Both [TMg] and [Mg(2+)]
decreased significantly in the prebypass period and remained significantly
depressed thereafter. The ionized fraction of magnesium ([Mg(2+)]/[TMg]) was
decreased during the postbypass period. Hematocrit decreased significantly from
the prebypass period, and FEMg increased significantly after aortic
cross-clamping. In conclusion, hemodilution and renal loss were main causes of
hypomagnesemia, and citrate in predeposited autologous blood may contribute to
the decrease in [Mg(2+)]/[TMg] in the postbypass period. These results suggest
that magnesium supplementation under close monitoring of [Mg(2+)] should be
required during cardiac surgery.
DOI: 10.1007/s00540-004-0235-7
PMID: 15290422  [PubMed - indexed for MEDLINE]

30. Biol Neonate. 2004;86(2):110-5. Epub 2004 May 19.
Plasma ionized magnesium levels in neonatal respiratory distress syndrome.
Sarici SU(1), Serdar MA, Erdem G, Alpay F, Tekinalp G, Yurdakök M, Yigit S,
Gökcay E.
Author information:
(1)Division of Neonatology, Department of Pediatrics, Hacettepe University
Faculty of Medicine, Ihsan, Turkey. thinker21001@yahoo.com
Measurement of ionized magnesium (IMg) provides an accurate assessment of the
free form of Mg, which is the physiologically active form and is most reflective
of the biologically active and not easily measurable intracellular Mg fraction.
Plasma levels of IMg were measured by ion-selective electrode method in premature
newborns with respiratory distress syndrome (RDS), and relationships and
correlations between IMg levels and various demographic, prognostic and
laboratory characteristics were investigated by comparing the premature newborns
with (study group; n = 19) and without RDS (control group; n = 20) in the present
study. The values of the postnatal arterial pH and base excess and plasma IMg
levels were significantly different between the study and control groups, and the
number of newborns with any morbidity was significantly higher in the study
group. Within the study group there were significant negative correlations
between the plasma IMg levels and the values of the umbilical cord arterial pH (r
= -0.621, p = 0.005) and base excess (r = -0.746, p = 0.001), and the value of
the postnatal arterial base excess (r = -0.585, p = 0.008). The newborns who died
later had higher plasma IMg levels than those who survived (0.89 +/- 0.45 vs.
0.63 +/- 0.24 mmol/l, p = 0.026). These findings suggest that increase of plasma
IMg may be due to extracellular movement of Mg, which is a principally
intracellular ion, as a result of acidosis, hypoxia and probable cellular injury
during the early course of RDS. The exact pathophysiological mechanism
responsible for IMg increase, and whether determination of plasma IMg level,
including umbilical cord blood IMg measurement, can be used as an early or
predictive indicator of RDS in the diagnosis remain to be determined in further
large-scale studies.
Copyright 2004 S. Karger AG, Basel
DOI: 10.1159/000078678
PMID: 15153707  [PubMed - indexed for MEDLINE]

31. Diabetes Care. 2004 May;27(5):1216-7.
Ionized magnesium in Danish children with type 1 diabetes.
Matthiesen G(1), Olofsson K, Rudnicki M.
Author information:
(1)Department of Pediatrics, Glostrup University Hospital, Glostrup, Denmark.

PMID: 15111552  [PubMed - indexed for MEDLINE]

32. Magnes Res. 2004 Mar;17(1):35-8.
Ionized magnesium in gestational diabetes.
Ertbeg P(1), Nørgaard P, Bang L, Nyholm H, Rudnicki M.
Author information:
(1)Department of Obstetrics and Gynecology, Glostrup University Hospital and
Roskilde University Hospital, Denmark.
A longitudinal prospective study was performed in order to describe variations in
ionized magnesium in patients with gestational diabetes. Twenty-two gestational
diabetic women and 24 healthy pregnant women were included consecutively. Blood
samples were obtained in the second and third trimester and 2 days postpartum in
both groups. The blood samples were analysed for serum ionized magnesium, serum
ionized calcium and pH. None of the groups demonstrated any time-related changes
in ionized magnesium. However, in the third trimester the level of ionized
magnesium was statistically significantly elevated in patients with gestational
diabetes compared to controls (0.57 +/- 0.05 mmol/l vs. 0.51 +/- 0.06 mmol/l; p <
0.01). The level of ionized calcium remained stable throughout the study period
in both groups. In conclusion our findings suggest that gestational diabetes is
associated with elevated levels of ionized magnesium.

PMID: 15083567  [PubMed - indexed for MEDLINE]

33. Pediatr Res. 2004 Feb;55(2):243-7. Epub 2003 Nov 19.
Evaluation of plasma ionized magnesium levels in neonatal hyperbilirubinemia.
Sarici SU(1), Serdar MA, Erdem G, Alpay F.
Author information:
(1)Department of Pediatrics, Hacettepe University Faculty of Medicine Ihsan
Dogramact Children's Hospital, Ankara, Turkey. yresearcher@yahoo.com
Plasma levels of ionized magnesium (IMg) measured by ion-selective electrode were
investigated in neonatal hyperbilirubinemia by comparing the newborns with (> or
=205 microM) and without (<205 microM) significant hyperbilirubinemia (groups of
severe and moderate hyperbilirubinemia, respectively). Serum bilirubin, plasma
IMg, and ionized calcium (ICa) levels were determined in 165 healthy term
newborns with nonhemolytic indirect hyperbilirubinemia during the first 10 d of
life. Mean serum bilirubin, plasma IMg, and ICa levels were 200.1 +/- 126.5
microM, 0.54 +/- 0.12 mM, and 1.15 +/- 0.12 mM, respectively, in 165 newborns
whose mean postnatal age was 156.1 +/- 46.5 h, and there was a significant
positive correlation between the mean serum bilirubin and plasma IMg levels (r =
0.535, p < 0.001). Serum bilirubin levels (304.4 +/- 83.8 microM versus 94.1 +/-
54.7 microM) and plasma IMg levels (0.6 +/- 0.12 mM versus 0.49 +/- 0.1 mM) were
significantly higher and plasma ICa levels (1.13 +/- 0.12 mM versus 1.18 +/- 0.12
mM) were significantly lower in the group of severe hyperbilirubinemia (n = 83)
when compared with the group with moderate hyperbilirubinemia (n = 82). Seventeen
of the 83 cases of severe hyperbilirubinemia had IMg levels above the normal
range (> or =0.69 mM), whereas none of the 82 cases of moderate
hyperbilirubinemia had elevated IMg levels. Fifteen of the 17 with high IMg
levels had bilirubin levels >290 microM. Results of the present study suggest
that increase in plasma IMg may be due to extracellular movement of Mg, a
principally intracellular ion, resulting from generalized cellular injury
including neurons and erythrocytes. Considering neuroprotective functions and
beneficial effects of Mg ion in improving neurologic outcome, we also may
speculate the possibility of a neuroprotective role or a compensatory mechanism
in IMg increase against emerging toxicity risk of increasing serum bilirubin
levels.
DOI: 10.1203/01.PDR.0000103874.01584.F3
PMID: 14630992  [PubMed - indexed for MEDLINE]

34. Ann Acad Med Stetin. 2002;48:85-97.
[Level of total and ionized magnesium fraction based on biochemical analysis of
blood and hair and effect of supplemented magnesium (Slow Mag B6) on selected
parameters in hypertension of patients treated with various groups of drugs].
[Article in Polish]
Michoń P(1).
Author information:
(1)Katedry i Zakładu Medycyny Rodzinnej Pomorskiej Akademii Medycznej w
Szczecinie, ul. Podgórna 22/23, 70-204 Szczecin.
The aim of this work was to determine the concentration of total and ionized
magnesium in hair and blood of patients with primary hypertension and the
influence of oral magnesium supplementation (Slow-Mag B6) on clinical parameters
and blood pressure values. 92 patients were recruited from the Family Care Unit,
Pomeranian Academy of Medicine in Szczecin. Each patient was treated during at
least 6 months preceding the study with a single antihypertensive agent from one
of the following groups: ACE inhibitors, beta-receptor inhibitors, Ca channel
blockers, diuretics. The control group included patients with hypertension not
treated pharmacologically. Changes in ionized magnesium concentration before and
after oral magnesium supplementation were studied in relation to total
cholesterol, triglycerides, and other parameters fake uhren deutschland of importance in hypertension.
Significantly lower total magnesium concentrations were demonstrated in hair of
patients receiving ACE inhibitors and diuretics in comparison to controls.
Ionized magnesium concentrations in serum of hypertensive patients were
significantly reduced as compared with controls. A highly significant increase in
these levels was noted after magnesium supplementation. Blood pressure values
after magnesium supplementation were reduced in the study group by an average of
15-20 mmHg for systolic and 5-9 mmHg for diastolic blood pressure. Correlations
between ionized magnesium and triglyceride concentrations in patients treated
with Ca channel blockers before oral Mg supplementation were found. Patients
treated with diuretics demonstrated correlations between total magnesium and
total cholesterol concentrations. Following oral magnesium supplementation with
Slow-Mag B6 at 320 mg/day, the frequency of complaints reported by patients,
including irregular heart beat, pricking heart pain, nervousness, sleep
disorders, irritability/tearfulness was reduced. There was no effect on other
complaints, such as mental and physical fatigue, constipation/diarrhea, and
anxiety.

PMID: 14601471  [PubMed - indexed for MEDLINE]

35. Magnes Res. 2003 Jun;16(2):127-30.
Lower whole blood ionized magnesium concentrations in hypocalcemic infants of
gestational diabetic mothers.
Banerjee S(1), Mimouni FB, Mehta R, Llanos A, Bainbridge R, Varada K, Sheffer G.
Author information:
(1)Department of Pediatrics, Maimonides Childrens Center, 977, 48th Street,
Brooklyn, NY 11219, USA.
Infants of insulin

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1. Conn Med. 2016 Jan;80(1):5-10.
Effectiveness and Safety of a Clinical Decision Rule to Reduce Repeat Ionized
Calcium Testing: A Pre/Post Test Intervention.
Salman M, Pike DC, Wu R, Oncken C.
The American Recovery and Reinvestment Act authorizes the Centers for Medicare
and Medicaid Services to reimburse hospitals that demonstrate meaningful use of
certified electronic health record technology. We sought to demonstrate
meaningful use by developing and implementing one clinical decision support rule
in the computerized physician order entry system that targets clinician-ordered
repeat ionized calcium measurement at the University of Connecticut Health
Center. The rule consists of a pop-up computer reminder that is triggered by
ordering a second ionized calcium test within 72 hours after an initial normal
test, with no clear indication for repeat testing. We implemented the rule on
December 14, 2010, and have reviewed all data collected through December 2014. We
found that the number of repeat tests decreased from 46% to 14% with no
significant increase in the number of serious adverse events. We conclude that
computerized reminders can decrease unnecessary repeat testing in the inpatient
setting.

PMID: 26882784  [PubMed - indexed for MEDLINE]

2. Chest. 2016 Mar;149(3):846-55. doi: 10.1016/j.chest.2015.12.001. Epub 2015 Dec
15.
Ionized Calcium in the ICU: Should It Be Measured and Corrected?
Aberegg SK(1).
Author information:
(1)Jordan Valley Medical Center, West Jordan, UT. Electronic address:
scottaberegg@gmail.com.
Serum ionized calcium (iCa) is often measured in patients admitted to ICUs, and
at least half of these patients will have values outside the reference range
during their ICU stay. The vast majority of these patients do not have an
underlying disease of calcium homeostasis. This Contemporary Review discusses the
rationale for measurement of iCa and whether available data support its
measurement and correction. It is determined that while measurement of serum iCa
is commonplace and attempted correction is popular, available evidence and
logical analysis do not wholly support these practices. Abnormal values of iCa
are likely a marker of disease severity in critical illness and most often
normalize spontaneously with resolution of the primary disease process.
Alternatively, low iCa levels in critical Buy NFPA Codes illness may be protective and attempted
correction of low levels may be harmful. Dramatic curtailment of iCa measurement
and calcium administration in several studies was not associated with worsening
outcomes. The absence of high-quality data to guide practice allows for a
spectrum of approaches to the measurement and treatment of iCa, but these
approaches should be guided by basic principles of rational clinical
decision-making. Widespread, protocolized measurement and administration with the
simple goal of normalizing values in the name of "euboxia" should be discouraged.
Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc.
All rights reserved.
DOI: 10.1016/j.chest.2015.12.001
PMID: 26836894  [PubMed - indexed for MEDLINE]

3. Crit Care. 2015 Dec 9;19:427. doi: 10.1186/s13054-015-1143-y.
Ionized calcium measurements during regional citrate anticoagulation in CRRT: we
need better blood gas analyzers.
Kindgen-Milles D(1), Ostermann M(2), Slowinski T(3).
Author information:
(1)Department of Anesthesiology, University Hospital Düsseldorf,
Heinrich-Heine-University, Moorenstr. 5, D-40225, Düsseldorf, Germany.
kindgen-milles@med.uni-duesseldorf.de. (2)Department of Critical Care, King's
College London, Guy's and St. Thomas' Foundation Hospital, Westminster Bridge
Road, London, SE1 7EH, UK. marlies.ostermann@gstt.nhs.uk. (3)Department of
Nephrology, Charité Universitätsmedizin Berlin, Campus Mitte (CCM), Charitéplatz
1, D-10117, Berlin, Germany. torsten.slowinski@charite.de.
Comment on
    Crit Care. 2015;19:321.
DOI: 10.1186/s13054-015-1143-y
PMCID: PMC4673790
PMID: 26645989  [PubMed - indexed for MEDLINE]

4. Crit Care. 2015 Dec 4;19:429. doi: 10.1186/s13054-015-1148-6.
Citrate anticoagulation for CRRT: don't always trust the postfilter iCa results!
Oudemans-van Straaten HM(1), Ostermann M(2).
Author information:
(1)Department of Adult Intensive Care, VU University Medical Centre, De Boelelaan
1118, 1081 HZ, Amsterdam, The Netherlands. hmoudemans@gmail.com. (2)Department of
Critical Care and Nephrology, King's College London, Guy's and St Thomas'
Hospital, London, SE1 7EH, UK. hmoudemans@gmail.com.
Comment on
    Crit Care. 2015;19:321.
Citrate has been recommended as the first-line Download ASTM Codes anticoagulant for continuous renal
replacement therapy (CRRT) in critically ill patients. Compared with heparin,
citrate anticoagulation is safer and more efficacious. Citrate inhibits the
coagulation cascade by lowering the ionized calcium (iCa) concentration in the
filter. Monitoring of systemic iCa concentrations is inherent to the protocol,
and monitoring of postfilter iCa is recommended to adjust citrate flow and
optimize anticoagulation. While systemic iCa targets are in the physiological
range, postfilter iCa concentrations are targeted between 0.20 and 0.35 mmol/l.
In a previous issue of Critical Care, Schwarzer et al. compared systemic and
postfilter iCa measurements of patients receiving citrate-based CRRT between six
devices. They highlight the unreliability of iCa concentrations in the postfilter
range, because the instruments cannot be validated in the low iCa range. The
maximum mean difference between two instruments was as high as 0.33 mmol/l (range
0.21-0.50 mmol/l). The authors call for dialysis companies to revise their
protocols. However, the first implication of their study is that the accuracy of
blood gas analyzers to measure iCa in the low range needs to improve; and,
secondly, clinicians using citrate anticoagulation need to be aware that the
postfilter iCa result may be falsely high or low. This is particularly relevant
when frequent premature filter clotting is observed despite postfilter iCa
results in the seemingly target range. In these situations, citrate flow can be
safely increased up to 4 mmol/l blood flow under monitoring of signs of citrate
accumulation.
DOI: 10.1186/s13054-015-1148-6
PMCID: PMC4669637
PMID: 26635277  [PubMed - indexed for MEDLINE]

5. Acta Med Iran. 2015;53(9):579-81.
Comparative Evaluation of Corrected QT and Ionized Calcium in Children.
Keihani Douste Z(1), Haghi Ashtiani MT(2), Shariat M(3), Tehrani F(4).
Author information:
(1)Department of Pediatric Neurology, Imam Khomeini Medical Complex, Tehran
University of Medical Sciences, Tehran, Iran. (2)Department of Pathology,
Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
(3)Family Health Institute, Maternal Fetal Neonatal Research Center, Tehran
University of Medical Sciences, Tehran, Iran. (4)Family Health Institute, School
of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Convulsion is one of the most common problems in children and hypocalcemia is one
the most frequent etiological items in children's convulsion. Corrected QT (QTc)
in EKG is prolonged in hypocalcemia, so it can be a useful tool for evaluation of
serum ionized calcium. In three groups (first seizure, multiple seizures, without
seizure or control ) every 25 cases, QTc, serum ionized ca, total ca, ABG, and
serum albumin level have been checked in the Latest AWS Codes PDF Department of Pediatrics of Imam
Khomeini Hospital and outpatient department of Ahari children's medical center in
2008. Prolonged QTc was observed in 72% of convulsive children (36 cases) but
only 19% of non-convulsive children (5 cases) showed this pattern. Ionized
calcium was significantly higher in non-convulsive than convulsive groups. There
was no correlation between prolonged QTc and total serum calcium; however, this
correlation with low ionized calcium was significant. QTc is an easy and rapid
method for serum ionized calcium evaluation.

PMID: 26553087  [PubMed - indexed for MEDLINE]

6. Crit Care. 2015 Nov 6;19:386. doi: 10.1186/s13054-015-1103-6.
Optimizing citrate dose for regional anticoagulation in continuous renal
replacement therapy: measuring citrate concentrations instead of ionized calcium?
Honore PM(1), Jacobs R(2), Hendrickx I(2), De Waele E(2), Van Gorp V(2), Spapen
HD(2).
Author information:
(1)ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel,
101, Laarbeeklaan, 1090, Jette, Brussels, Belgium. patrick.honore@az.vub.ac.be.
(2)ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel,
101, Laarbeeklaan, 1090, Jette, Brussels, Belgium.
Comment on
    Crit Care. 2015;19:321.
DOI: 10.1186/s13054-015-1103-6
PMCID: PMC4635622
PMID: 26542792  [PubMed - indexed for MEDLINE]

7. Crit Care. 2015 Sep 8;19:321. doi: 10.1186/s13054-015-1027-1.
Discrepant post filter ionized calcium concentrations by common blood gas
analyzers in CRRT using regional citrate anticoagulation.
Schwarzer P(1), Kuhn SO(2), Stracke S(3), Gründling M(4), Knigge S(5), Selleng
S(6), Helm M(7), Friesecke S(8), Abel P(9), Kallner A(10), Nauck M(11),
Petersmann A(12).
Author information:
(1)Institute of Clinical Chemistry and Laboratory Medicine, University Medicine
Greifswald, Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany.
patrik.schwarzer@outlook.de. (2)Department of Anaesthesiology and Intensive Care
Medicine, University Medicine Greifswald, Greifswald, Germany.
kuhn@uni-greifswald.de. (3)Department of Internal Medicine A, University Medicine
Greifswald, Greifswald, Germany. sylvia.stracke@uni-greifswald.de. (4)Department
of Anaesthesiology and Intensive Care Medicine, University Medicine Greifswald,
Greifswald, Germany. gruendli@uni-greifswald.de. (5)Department of Anaesthesiology
and Intensive Care Medicine, University Medicine Greifswald, Greifswald, Germany.
stephan.knigge@uni-greifswald.de. (6)Department of Anaesthesiology and Intensive
Care Medicine, University Medicine Greifswald, Greifswald, Germany.
sixten.selleng@uni-greifswald.de. (7)Institute of Clinical Chemistry and
Laboratory Medicine, University Medicine Greifswald,
Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany.
mhelm1994@googlemail.com. (8)Department of Internal Medicine B, University
Medicine Greifswald, Greifswald, Germany. frieseck@uni-greifswald.de.
(9)Department of Internal Medicine B, University Medicine Greifswald, Greifswald,
Germany. abel@uni-greifswald.de. (10)Karolinska University Hospital, Stockholm,
Sweden. Anders.Kallner@ki.se. (11)Institute of Clinical Chemistry and Laboratory
Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475,
Greifswald, Germany. matthias.nauck@uni-greifswald.de. (12)Institute of Clinical
Chemistry and Laboratory Medicine, University Medicine Greifswald,
Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany.
astrid.petersmann@uni-greifswald.de.
Comment in
    Crit Care. 2015;19:429.
    Crit Care. 2015;19:386.
    Crit Care. 2015;19:427.
INTRODUCTION: Ionized calcium (iCa) concentration is often used in critical care
and measured using blood gas analyzers at the point of care. Controlling and
adjusting regional citrate anticoagulation (RCA) for continuous renal replacement
therapy (CRRT) involves measuring the iCa concentration in two samples: systemic
with physiological iCa concentrations and post filter samples with very low iCa
concentrations. However, modern blood gas analyzers are optimized for
physiological iCa concentrations which might make them less suitable for
measuring low iCa in blood with a high concentration of citrate. We present
results of iCa measurements from six different blood gas analyzers and the impact
on clinical decisions based on the recommendations of the dialysis' device
manufacturer.
METHOD: The iCa concentrations of systemic and post filter samples were measured
using six distinct, frequently used blood gas analyzers. We obtained iCa results
of 74 systemic and 84 post filter samples from patients undergoing RCA for CRRT
at the University Medicine of Greifswald.
RESULTS: The systemic samples showed concordant results on all analyzers with
median iCa concentrations ranging from 1.07 to 1.16 mmol/L. The medians of iCa
concentrations for post filter samples ranged from 0.21 to 0.50 mmol/L. Results
of >70% of the post filter samples would lead to major differences in decisions
regarding citrate flow depending on the instrument used.
CONCLUSION: Measurements of iCa in post filter samples may give misleading
information in monitoring the RCA. Recommendations of the dialysis manufacturer
need to be revised. Meanwhile, little weight should be given to post filter iCa.
Reference methods for low iCa in whole blood containing citrate should be
established.
DOI: 10.1186/s13054-015-1027-1
PMCID: PMC4563947
PMID: 26353802  [PubMed - indexed for MEDLINE]

8. Bull Exp Biol Med. 2015 Jul;159(3):305-8. doi: 10.1007/s10517-015-2948-z. Epub
2015 Jul 25.
Estimation of Functional Activity of Ionized Calcium for Complement System
Reactivity Assessment.
Shoibonov BB(1), Grigor'eva DV, Shabalina AA, Kostyreva MV, Baronets VY,
Zamolodchikova TS.
Author information:
(1)P. K. Anokhin Research Institute of Normal Physiology, Russian Academy of
Medical Sciences, Moscow, Russia, shoibonov@mail.ru.
We proposed a new indicator for evaluation of functional activity of Ca(2+) in
human blood serum based on lysis of sheep erythrocytes with 10% human blood serum
in the presence of 0.55 mM ethylene glycol tetraacetic acid at 37°C for 10 min.
After incubation, the degree of sheep erythrocytes lysis inhibition is estimated:
inhibition of complement hemolytic activity <30% is considered as high functional
Са(2+) activity, inhibition by 31-70% corresponds to normal activity, and >71%
indicates low activity. The comparative studies of complement activating function
of heterophilic antibodies, complement system reactivity in the presence of 0.29
M NaCl, and functional activity of ionized Ca(2+) make possible estimation of the
individual's immune status.
DOI: 10.1007/s10517-015-2948-z
PMID: 26205720  [PubMed - indexed for MEDLINE]

9. Arch Endocrinol Metab. 2015 Oct;59(5):428-33. doi: 10.1590/2359-3997000000074.
Epub 2015 Jul 21.
Postoperative calcium levels as a diagnostic measure for hypoparathyroidism after
total thyroidectomy.
Rosa KM(1), Matos LL(2), Cernea CR(2), Brandão LG(2), Araújo Filho VJ(2).
Author information:
(1)Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
(2)Departamento de Cirurgia, Universidade de São Paulo, São Paulo, SP, Brazil.
OBJECTIVE: The aim of the present study was to identify a fast, efficient and
low-cost method to diagnose hypoparathyroidism after total thyroidectomy.
MATERIALS AND METHODS: One hundred and forty medical records, which contained
patients' clinical and laboratory data, were retrospectively analyzed. Patient
parathyroid hormone values, which were obtained immediately following operation,
were compared with their ionized calcium levels the morning after surgery. This
comparison was used to examine the correlation between the two variables in
predicting hypoparathyroidism because measuring calcium levels is low-cost and
more available in the hospitals compared to measuring parathormone (PTH) levels.
RESULTS: There was a positive and statistically significant correlation between
PTH and ionized calcium values (Pearson correlation coefficient, r = 0.456; p <
0.0001). The values of first postoperative day ionized calcium levels (stratified
by the 1.10 mmol/l cut-off value) were tested as a diagnostic measure for
hypoparathyroidism, and a PTH < 15 pg/mL obtained immediately following operation
served as a reference. This analysis showed that ionized calcium levels measured
on the first postoperative day had a sensitivity of 45.6% (95% CI 30.9-61.0%), a
specificity of 88.9% (95% CI 80.5-94.5%) and an accuracy of 76.7% (95% CI
68.7-83.5%) as a diagnostic measure for hypoparathyroidism.
CONCLUSION: In conclusion, we demonstrated that patients who had high ionized
calcium levels on the first postoperative day also had high PTH levels
immediately following operation and, therefore, they had lower rates of
hypoparathyroidism.
DOI: 10.1590/2359-3997000000074
PMID: 26201010  [PubMed - indexed for MEDLINE]

10. Eur J Endocrinol. 2015 Oct;173(4):441-6. doi: 10.1530/EJE-15-0341. Epub 2015 Jul
20.
Estimated glomerular filtration rate by serum cystatin C correlates with
cardiometabolic parameters in patients with primary hyperparathyroidism.
Ermetici F(1), Filopanti M(1), Verga U(1), Passeri E(1), Dito G(1), Malavazos
AE(1), Mapelli C(1), Raggi ME(1), Spada A(1), Corbetta S(2).
Author information:
(1)Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato
Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda
Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS
Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology
LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology
UnitDepartment of Clinical Sciences and Community Health, University of Milan,
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan,
ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University
of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato
Milanese, Milan, Italy. (2)Diabetology and Metabolic Disease UnitIRCCS
Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and
Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan,
Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese,
Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco,
ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community
Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore
Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical
Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via
Morandi 30, 20097 San Donato Milanese, Milan, Italy sabrina.corbetta@unimi.it.
OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) are at risk of
chronic kidney disease (CKD). Cystatin C (Cys-C) is considered a more reliable
tool to assess glomerular filtration rate (GFR) than creatinine. The study aimed
to assess circulating Cys-C and its relationships with biochemical PHPT and
cardiometabolic parameters.
DESIGN AND METHODS: The present cross-sectional study was performed in academic
endocrine units on PHPT patients (n=190) and non-hypertensive, non-diabetic, age-
and sex-matched healthy controls (n=135) with no established CKD. The main
outcomes were creatinine by alkaline picrate method, Cys-C by immunonephelometry
and calculation of estimated GFR based on creatinine and Cys-C (eGFRcr-cys) using
the CKD-EPI equation.
RESULTS: In PHPT patients, circulating Cys-C ranged 0.45-3.13  mg/l and
correlated with creatinine, age and BMI. Mean Cys-C level was higher in PHPT
patients than in controls (0.93±0.02 vs 0.78±0.14  mg/l; P=0.03). Cys-C levels in
PHPT patients were predicted by age, BMI, ionized calcium, hypertension and
HDL-cholesterol, the most significant determinant being ionized calcium. Cys-C
positively correlated with cardiovascular disease (CVD) occurrence. Overall,
18.4% of PHPT patients with eGFRcr >60  ml/min per 1.73  m(2) (n=169) had Cys-C
levels higher than the 95th percentile in controls (1.03  mg/l), consistent with
a preclinical CKD, which was associated with hypertension and insulin resistance.
Considering eGFRcr-cys, CKD (stages G3a, G3b, 4) was diagnosed in 13.7% of PHPT
patients. Estimated GFRcr-cys, but not eGFR based on creatinine, was predicted by
insulin resistance and hypertension and positively correlated with CVD.
CONCLUSIONS: Elevated Cys-C levels were associated with ionized calcium,
cardiometabolic risk factors and CVD, and identified preclinical CKD in PHPT
patients.
© 2015 European Society of Endocrinology.
DOI: 10.1530/EJE-15-0341
PMID: 26194503  [PubMed - indexed for MEDLINE]

11. Early Hum Dev. 2015 Sep;91(9):535-40. doi: 10.1016/j.earlhumdev.2015.06.008. Epub
2015 Jul 12.
Serum calcium concentrations and incidence of hypocalcemia in infants with
moderate or severe hypoxic-ischemic encephalopathy: Effect of therapeutic
hypothermia.
Prempunpong C(1), Efanov I(2), Sant'Anna G(3).
Author information:
(1)Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. (2)McGill
University Health Center, Montreal Children's Hospital, Montreal, Canada.
(3)McGill University Health Center, Montreal Children's Hospital, Montreal,
Canada. Electronic address: guilherme.santanna@mcgill.ca.
BACKGROUND: Hypocalcemia is a common morbidity in asphyxiated infants.
Therapeutic hypothermia (TH), the standard of care for infants with moderate and
severe hypoxic-ischemic encephalopathy (HIE), promotes neuroprotection by several
mechanisms including a decrease in intracellular calcium (Ca(2+)) influx which
may improve serum Ca(2+) levels and homeostasis.
AIMS: To evaluate the impact of TH on Ca(2+) homeostasis.
STUDY DESIGN: Historical, retrospective cohort analysis.
SUBJECTS: Infants with moderate or severe HIE admitted to the hospital
with≤24hours of age, gestational age≥36weeks, and birth weight ≥1800g, before
(pre-TH) and after (post-TH) TH was implemented.
OUTCOME MEASURES: Minimum and maximum serum levels of ionized Ca(2+) (iCa(2+))
and magnesium (Mg), Ca(2+) and Mg intakes, and incidence of hypo/hypercalcemia
during the first week of life.
RESULTS: A total of 67 infants were included: 29 pre-TH and 38 post-TH. Minimum
iCa(2+)levels were significantly lower in the pre-TH group; some infants required
Ca(2+) boluses infusions. In the post-TH group, a significantly lower intake of
Ca(2+) was necessary to maintain normal Ca(2+) levels and no infant required
boluses. The incidence of hypocalcemia was higher in the pre-TH group with a
statistically significant difference on day 2 of life (18 vs 0%; p=0.01).
CONCLUSIONS: After the implementation of TH, iCa(2+) levels were within normal
ranges despite lower Ca(2+) intakes. A lower incidence of hypocalcemia was
observed during cooling. Our findings support the hypothesis that TH improves
Ca(2+) homeostasis in HIE infants.
Copyright © 2015. Published by Elsevier Ireland Ltd.
DOI: 10.1016/j.earlhumdev.2015.06.008
PMID: 26172341  [PubMed - indexed for MEDLINE]

12. Surgery. 2015 Dec;158(6):1492-9. doi: 10.1016/j.surg.2015.04.041. Epub 2015 Jul 2.
Transient and permanent hypocalcemia after total thyroidectomy: Early predictive
factors and long-term follow-up results.
Seo ST(1), Chang JW(1), Jin J(2), Lim YC(3), Rha KS(1), Koo BS(4).
Author information:
(1)Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute,
Research Institute for Medical Sciences, Chungnam National University College of
Medicine, Daejeon, Korea. (2)Department of Otolaryngology-Head and Neck Surgery,
Yanbian University Hospital, Jilin Yanji, China. (3)Department of
Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science,
Konkuk University School of Medicine, Seoul, the Republic of Korea. (4)Department
of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Research
Institute for Medical Sciences, Chungnam National University College of Medicine,
Daejeon, Korea. Electronic address: bskoo515@cnuh.co.kr.
BACKGROUND: Post-thyroidectomy hypocalcemia is among the most common
complications of total thyroidectomy. The purpose of this study was to evaluate
early predictive factors and long-term changes in intact parathyroid hormone
(iPTH) levels in patients with transient and permanent hypocalcemia after total
thyroidectomy.
PATIENTS AND METHODS: A total of 349 consecutive patients who underwent total
thyroidectomy with or without neck dissection between 2009 and 2011 were
reviewed. PTH, total calcium (Ca), and ionized Ca (iCa) levels were evaluated at
1 hour, and 1, 3, 5, and 7 days, and 1, 3, 6, and 12 months postoperatively.
Biochemical profiles at 1 hour after total thyroidectomy in patients with
transient and permanent hypocalcemia were compared. Patients with postoperative
hypocalcemia were followed for 12 months.
RESULTS: Lesser preoperative serum levels of Ca and more extensive surgery were
significantly associated with postoperative hypocalcemia (P < .05). The absolute
level and relative decline (%) in iPTH at 1 hour were the most reliable
predictors of postoperative hypocalcemia according to the receiver operating
characteristics curve, with a threshold of 10.42 pg/mL and 70%. Sensitivity and
specificity of the predictors were 83.4% (95% CI, 76.4-89.1), 100% (95% CI,
84.6-100.0), 84.1 (95% CI, 77.2-89.7), and 95.5% (95% CI, 77.2-99.9),
respectively. Parathyroid function recovered in the first month after total
thyroidectomy in 78 of 99 patients (79%) with transient hypocalcemia. However, 46
of 61 patients (74%) with a subnormal iPTH level at 3 months after surgery had
permanent hypocalcemia.
CONCLUSION: Mean postoperative PTH level and the mean relative decline in PTH
measured 1 hour postoperatively were the most reliable predictors of
postoperative or permanent hypocalcemia.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.surg.2015.04.041
PMID: 26144879  [PubMed - indexed for MEDLINE]

13. PLoS One. 2015 May 13;10(5):e0123302. doi: 10.1371/journal.pone.0123302.
eCollection 2015.
The effects of a calcium-rich pre-exercise meal on biomarkers of calcium
homeostasis in competitive female cyclists: a randomised crossover trial.
Haakonssen EC(1), Ross ML(2), Knight EJ(3), Cato LE(4), Nana A(4), Wluka AE(5),
Cicuttini FM(5), Wang BH(5), Jenkins DG(6), Burke LM(7).
Author information:
(1)Sports Nutrition, Australian Institute of Sport, Belconnen, 2616, Australia;
Physiology, Australian Institute of Sport, Belconnen, 2616, Australia; Human
Movement Studies, University of Queensland, St Lucia, 4072, Australia. (2)Sports
Nutrition, Australian Institute of Sport, Belconnen, 2616, Australia; Physiology,
Australian Institute of Sport, Belconnen, 2616, Australia. (3)Performance
Research, Australian Institute of Sport, Belconnen, 2616, Australia. (4)Sports
Nutrition, Australian Institute of Sport, Belconnen, 2616, Australia.
(5)Department of Epidemiology & Preventive Medicine, School of Public Health &
Preventive Medicine, Monash University, Melbourne, 3004, Australia. (6)Human
Movement Studies, University of Queensland, St Lucia, 4072, Australia. (7)Sports
Nutrition, Australian Institute of Sport, Belconnen, 2616, Australia; School of
Exercise Science, Australian Catholic University, Melbourne, 3065, Australia.
PURPOSE: To examine whether a calcium-rich pre-exercise meal attenuates
exercise-induced perturbations of bone calcium homeostasis caused by maintenance
of sweat calcium losses.
METHODS: Using a randomized, counterbalanced crossover design, 32 well-trained
female cyclists completed two 90 min cycling trials separated by 1 day. Exercise
trials were preceded 2 hours by either a calcium-rich (1352 ± 53 mg calcium)
dairy based meal (CAL) or a control meal (CON; 46 ± 7 mg calcium). Blood was
sampled pre-trial; pre-exercise; and immediately, 40 min, 100 min and 190 min
post-exercise. Blood was analysed for ionized calcium and biomarkers of bone
resorption (Cross Linked C-Telopeptide of Type I Collagen (CTX-I), Cross Linked
C-Telopeptide of Type II Collagen (CTX-II), Parathyroid Hormone (PTH), and bone
formation (Procollagen I N-Terminal Propeptide (PINP)) using the established
enzyme-linked immunosorbent assay technique.
RESULTS: PTH and CTX-I increased from pre-exercise to post-exercise in both
conditions but was attenuated in CAL (p < 0.001). PTH was 1.55 [1.20, 2.01] times
lower in CAL immediately post-exercise and 1.45 [1.12, 1.88] times lower at 40
min post-exercise. CTX-I was 1.40 [1.15, 1.70] times lower in CAL at immediately
post-exercise, 1.30 [1.07, 1.57] times lower at 40 min post-exercise and 1.22
[1.00, 1.48] times lower at 190 min post-exercise (p < 0.05). There was no
significant interaction between pre-exercise meal condition and time point for
CTX-II (p = 0.732) or PINP (p = 0.819).
CONCLUSION: This study showed that a calcium-rich pre-exercise breakfast meal
containing ~1350 mg of calcium consumed ~90 min before a prolonged and high
intensity bout of stationary cycling attenuates the exercise induced rise in
markers of bone resorption--PTH and CTX-I.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12614000675628.
DOI: 10.1371/journal.pone.0123302
PMCID: PMC4430171
PMID: 25970439  [PubMed - indexed for MEDLINE]

14. Nutr Metab Cardiovasc Dis. 2015 Jun;25(6):562-8. doi:
10.1016/j.numecd.2015.02.013. Epub 2015 Mar 4.
Association between direct measurement of active serum calcium and risk of type 2
diabetes mellitus: A prospective study.
Zaccardi F(1), Webb DR(2), Carter P(2), Pitocco D(3), Khunti K(2), Davies MJ(2),
Kurl S(4), Laukkanen JA(5).
Author information:
(1)Diabetes Research Centre, University of Leicester, Leicester, UK. Electronic
address: frazac@fastwebnet.it. (2)Diabetes Research Centre, University of
Leicester, Leicester, UK. (3)Diabetes Research Unit, Catholic University School
of Medicine, Rome, Italy. (4)Institute of Public Health and Clinical Nutrition,
University of Eastern Finland, Kuopio, Finland. (5)Institute of Public Health and
Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Lapland
Central Hospital, Department of Internal Medicine, Rovaniemi, Finland.
BACKGROUND AND AIMS: Previous prospective studies showing a positive association
between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have
relied on total calcium or an indirect estimate of active, ionized calcium (iCa).
We aimed to assess this relationship using a direct measurement of iCa.
METHODS AND RESULTS: iCa and cardiometabolic risk factors were measured in a
population-based sample of 2350 men without a known history of T2DM at baseline.
Associations between iCa levels and incident cases of T2DM (self-reported,
ascertained with a glucose tolerance test, or determined by record linkage to
national registers) were estimated using Cox regression analyses adjusted for
potential confounders. At baseline, mean (standard deviation) age was 53 (5)
years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years,
140 new cases of T2DM were recorded. In a multivariable analysis adjusted for
age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family
history of T2DM, there was no association comparing second (hazard ratio 0.84;
95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98;
0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for
C-reactive protein, physical activity level, and triglycerides did not change the
estimates (p for trend 0.389).
CONCLUSION: In this study, we did not find evidence of an association between
direct measurement of active calcium and risk of T2DM. Further studies are needed
to confirm our findings and define the relationship between factors influencing
indirect calcium estimation and incident T2DM.
Copyright © 2015 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.numecd.2015.02.013
PMID: 25933474  [PubMed - indexed for MEDLINE]

15. J Clin Endocrinol Metab. 2015 May;100(5):2131-4. doi: 10.1210/jc.2014-4370. Epub
2015 Mar 9.
Brief report: Does PTH increase with age, independent of 25-hydroxyvitamin D,
phosphate, renal function, and ionized calcium?
Carrivick SJ(1), Walsh JP, Brown SJ, Wardrop R, Hadlow NC.
Author information:
(1)Department of Clinical Biochemistry (S.J.C., R.W., N.C.H.), PathWest
Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western
Australia 6009, Australia; Department of Endocrinology and Diabetes (S.J.C.,
J.P.W., S.J.B.), Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009,
Australia; and School of Medicine and Pharmacology (J.P.W.) and School of
Pathology and Laboratory Medicine (N.C.H.), The University of Western Australia,
Crawley, Western Australia 6009, Australia.
CONTEXT: Circulating PTH concentrations increase with age. It is uncertain
whether an age-related PTH increase occurs independent of changes in circulating
25-hydroxyvitamin D, phosphate, renal function, and ionized calcium.
OBJECTIVE: The purpose of this article was to analyze the relationship between
PTH and age, controlling for 25-hydroxyvitamin D, phosphate, renal function, and
ionized calcium.
METHODS: This was a retrospective, cross-sectional study analyzing the
relationship between PTH and age in 2 independent datasets (laboratory 1, n = 17
275 and laboratory 2, n = 4878). We further analyzed subgroups after excluding
participants with estimated glomerular filtration rate of <60 mL/min/1.73 m(2) or
25-hydroxyvitamin D of <50 nmol/L (for subgroups, n = 12 051 for laboratory 1 and
3473 for laboratory 2).
RESULTS: After adjustment for sex, ionized calcium, 25-hydroxyvitamin D,
phosphate, and estimated glomerular filtration rate, each 10-year increase in age
was associated with a 5.0% increase in PTH (95% confidence interval [CI],
4.4%-5.6%; P < .001) in laboratory 1 and a 4.2% increase in laboratory 2 (95% CI,
3.0%-5.4%; P < .001). In the subgroups, each 10-year increase in age was
associated with a 6.1% increase in PTH (95% CI, 5.5%-6.8%; P < .001) in
laboratory 1 and a 4.9% increase (95% CI 3.5%-6.2%; P < .001) in laboratory 2.
CONCLUSION: PTH concentrations increase with age, independent of
25-hydroxyvitamin D, ionized calcium, phosphate, and renal function. Further
research is required to explore the underlying mechanisms and clinical relevance
and to determine whether the use of age-related PTH reference ranges improves
diagnostic accuracy, particularly in elderly individuals.
DOI: 10.1210/jc.2014-4370
PMID: 25751107  [PubMed - indexed for MEDLINE]

16. Transpl Int. 2015 Jul;28(7):874-5. doi: 10.1111/tri.12548. Epub 2015 Mar 16.
Falsely decreased ionized calcium levels in kidney transplant recipients with
polyomavirus-associated nephropathy treated with leflunomide.
Verhoeven Y(1), Kemperman H(2), Abrahams AC(3).
Author information:
(1)Department of Nephrology and Hypertension, University Medical Center, Utrecht,
The Netherlands. Y.Verhoeven-3@umcutrecht.nl. (2)Department of Clinical Chemistry
and Haematology, University Medical Center, Utrecht, The Netherlands.
(3)Department of Nephrology and Hypertension, University Medical Center, Utrecht,
The Netherlands.
DOI: 10.1111/tri.12548
PMID: 25711674  [PubMed - indexed for MEDLINE]

17. Perm J. 2015 Winter;19(1):49-51. doi: 10.7812/TPP/14-108.
Intervention to reduce inappropriate ionized calcium ordering practices: a
quality-improvement project.
Newman DB(1), Siontis KC(2), Chandrasekaran K(3), Jaffe AS(4), Kashiwagi DT(5).
Author information:
(1)Cardiologist in the Division of Cardiovascular Diseases at the Mayo Clinic in
Rochester, MN. newman.darrell@mayo.edu. (2)Internist at the Mayo Clinic in
Rochester, MN. siontis.konstantinos@mayo.edu. (3)Cardiologist in the Division of
Cardiovascular Diseases at the Mayo Clinic in Rochester, MN. kchandra@mayo.edu.
(4)Cardiologist in the Division of Cardiovascular Diseases at the Mayo Clinic in
Rochester, MN. jaffe.allan@mayo.edu. (5)Internist in the Division of Internal
Medicine at the Mayo Clinic in Rochester, MN. kashiwagi.deanne@mayo.edu.
CONTEXT: The importance of an abnormal ionized calcium (iCa) measurement in
noncritically ill patients is unclear. Furthermore, iCa monitoring is more
expensive than measurement of total calcium and consumes more laboratory
resources. We hypothesize that most iCa tests are ordered for routine monitoring
in asymptomatic patients, and results do not influence clinical management.
OBJECTIVE: To characterize and to intervene on iCa test-ordering practices among
our institution's hospital-based internal medicine clinicians.
DESIGN: A quality-improvement project, with retrospective review of clinical
records. We retrospectively identified the first 100 consecutive patients
admitted to our hospital internal medicine (HIM) services during January 2012
with an iCa test ordered during their hospitalization. We reviewed clinical
records to determine the appropriateness of iCa test ordering and of the ordering
department. An educational intervention regarding the appropriateness of iCa
testing was undertaken targeting HIM clinicians.
MAIN OUTCOME MEASURES: The effect of the intervention was assessed by identifying
a sample of the first 100 consecutive patients admitted to HIM services during
November 2012 and by comparing the proportion of iCa tests ordered by HIM
clinicians before and after the intervention.
RESULTS: HIM services were responsible for 38% of iCa measurements before the
educational intervention, with the remainder originating primarily from the
Emergency Department (29%) and intensive care units (28%). After the
intervention, the internal medicine services were responsible for 13% of iCa
measurements, which represented a 66% reduction (p = 0.0007).
CONCLUSION: A simple intervention based on clinician education can reduce the
frequency of routine iCa monitoring in stable hospitalized patients.
DOI: 10.7812/TPP/14-108
PMCID: PMC4315377
PMID: 25663205  [PubMed - indexed for MEDLINE]

18. Medicina (B Aires). 2014;74(6):457-61.
[Normocalcemic primary hyperparathyroidism].
[Article in Spanish]
Spivacow FR(1), Sapag Durán A, Zanchetta MB.
Author information:
(1)Instituto de Investigaciones Metabólicas (IDIM), Cátedra de Osteología y
Metabolismo Mineral, Universidad del Salvador (USAL), Buenos Aires, Argentina.
E-mail: spiva@idim.com.ar.
This report shows our conclusions on the clinical, biochemical and densitometry
characteristics of 35 normocalcemic primary hyperparathyroidism (PHPT) patients.
This condition is defined by a high level of intact parathyroid hormone (iPTHI)
with persistently normal serum and ionized calcium in the absence of secondary
hyperparathyroidism. Our selection consisted of 30 women (90%) and 5 men (10%).
The control group of 55 hypercalcemic patients with primary hyperparathyroidism
included 51 women (93%) and 4 men (7%). The average age at diagnosis of
normocalcemic PHPT was 61.4 ± 11.7 years and 56.4 ± 11.3 years in hypercalcemic
PHPT. Besides the expected differences in serum calcium, ionized calcium,
phosphorus and 24 h urinary calcium, we found no significant changes in other
biochemical variables, and no differences in densitometry evaluations such as the
presence of osteopenia or osteoporosis and the number of fractures in the two
types of PHPT. But there was a significant difference in the presence of renal
lithiasis between normocalcemic PHPT (11.4%) and clasic PHPT (49.1%) p < 0.0005,
to some extent associated to the presence of hypercalciuria in classic PHPT. Two
of the 35 patients with normocalcemic PHPT became classic hypercalcemic PHPT over
a 4 year follow-up period. Our findings support the hypothesis that the
normocalcemic PHPT could be an early stage of the classic PHPT, both having
similar clinical effects to metabolic renal and bone levels.

PMID: 25555006  [PubMed - indexed for MEDLINE]

19. J Clin Endocrinol Metab. 2014 Dec;99(12):4704-11. doi: 10.1210/jc.2014-1869.
Low-dose calcium versus pentagastrin for stimulation of calcitonin in chronic
hemodialysis patients: a pilot study.
Thiem U(1), Marculescu R, Cejka D, Gessl A, Borchhardt K.
Author information:
(1)Department of Medicine III, Division of Nephrology and Dialysis (U.T., D.C.,
K.B.), Department of Laboratory Medicine (R.M.), Department of Medicine III,
Division of Endocrinology and Metabolism (A.G.), Medical University of Vienna,
1090 Vienna, Austria; and Dialysis Institute Klagenfurt (K.B.), 9020 Klagenfurt,
Austria.
CONTEXT: Elevated calcitonin levels occur in up to 46% of patients with chronic
hemodialysis (CHD) and frequently reflect benign C-cell hyperplasia rather than
medullary thyroid carcinoma. For the differential diagnosis of
hypercalcitoninemia, the pentagastrin-stimulated calcitonin test was used until
its availability became restricted.
OBJECTIVE: This study sought to compare calcium and pentagastrin in terms of
their ability to stimulate calcitonin secretion and their side effects in
patients with CHD.
SETTING AND DESIGN: This prospective pilot study was conducted at the chronic
hemodialysis unit of the Medical University of Vienna between December 2012 and
September 2013.
PATIENTS: We studied six male patients with CHD with elevated basal calcitonin
levels.
INTERVENTION: The stimulation test was performed first with 0.5 μg/kg
pentagastrin and then with 1 mg/kg calcium after a median washout period of 7
(6-9) months.
MAIN OUTCOME MEASURES: We measured calcitonin, serum ionized calcium, intact PTH
(iPTH), and C-terminal fibroblast growth factor 23 levels before and 2, 5, and 10
minutes after iv infusion of the stimulant and assessed the tolerability of the
two substances by a questionnaire.
RESULTS: Both pentagastrin and calcium significantly stimulated calcitonin
secretion at 2 and 5 minutes. Partial correlation analysis revealed a strong
association between calcium- and pentagastrin-stimulated calcitonin levels
(r=0.875, P < .0001). Only after calcium infusion serum ionized calcium levels
increased from 1.09 (0.91-1.16) mmol/l to 1.4 (1.14-1.65) mmol/l at 2 minutes (P
< .01) but returned to baseline levels at 5 minutes. Moreover, calcium infusion
led to a significant decrease in iPTH levels from 315 (203-723) pg/ml to 182
(121-415) pg/ml at 5 minutes (P < .05) and 171 (91-346) pg/ml at 10 minutes (P <
.001). In general, calcium caused fewer and less severe side effects than
pentagastrin.
CONCLUSIONS: In patients with CHD, the response of calcitonin to calcium and
pentagastrin was comparable, making calcium a potential substitute for
pentagastrin in these patients.
DOI: 10.1210/jc.2014-1869
PMID: 25215555  [PubMed - indexed for MEDLINE]

20. Calcif Tissue Int. 2014 Oct;95(4):374-81. doi: 10.1007/s00223-014-9898-8. Epub
2014 Aug 3.
Effects on calcium homeostasis of changing PTH replacement therapy of postoperative hypoparathyroidism from intact PTH to teriparatide: a case series.
Bislev LS(1), Sikjaer T, Rejnmark L.
Author information:
(1)Department of Internal Medicine and Endocrinology, MEA, Aarhus University
Hospital, Tage-Hansensgade 2, 8000, Aarhus, Denmark, lisesofieandersen@gmail.com.
The objective of this study was to assess the effect on calcium homeostasis of
changing PTH replacement therapy (PTH-RT) from intact PTH (PTH(1-84)) to
teriparatide (PTH(1-34)). This study is a consecutive case series. All patients
with postoperative hypoparathyroidism who changed medication from PTH(1-84) (100
µg) to PTH(1-34) (20 µg) were included. Plasma ionized calcium, daily dose of
1α-hydroxylated-vitamin D metabolites alfacalcidol, calcium, TSH and PTH was
collected. Eight patients (women = 88%) with a mean age of 54 ± 12 years and a
duration of hypoPT of 13 ± 6 years were included. Before initiation of PTH(1-84),
the mean daily dose of alfacalcidol was 1.9 ± 1.1 µg/d and calcium supplements
were 1,550 ± 705 mg. Alfacalcidol dose was reduced with 88 ± 29% (p < 0.01) after
6 months of PTH(1-84) treatment and terminated in six patients. Calcium levels
were reduced with 78 ± 36% (p = 0.02) to 273 ± 353 mg/d and stopped in five
patients. Six patients received 100 µg PTH(1-84) daily, the seventh 2 out of 3
days and the last every second day. When changing from PTH(1-84) to PTH(1-34),
plasma ionized calcium initially dropped and the demand for supplements
increased. Alfacalcidol was resumed in five patients; mean daily dose increased
to 1.50 ± 1.56 µg/d, (p = 0.02) and calcium increased to 329 ± 368 mg/d, (p =
0.72). Five patients received 20 µg PTH(1-34) a day, two patients twice-a-day and
one 20/40 µg/d alternately. Compared with PTH(1-34), PTH(1-84) has a longer
plasma half-life and a higher calcemic response. We have shown a need for higher
doses of alfacalcidol and calcium supplements to maintain normal serum calcium
when treated with PTH(1-34) compared to PTH(1-84) and in some a need for more
than one daily PTH(1-34) dose.
DOI: 10.1007/s00223-014-9898-8
PMID: 25086672  [PubMed - indexed for MEDLINE]

21. J Clin Endocrinol Metab. 2014 Oct;99(10):E1951-6. doi: 10.1210/jc.2014-2125. Epub
2014 Jul 25.
Lack of FGF23 response to acute changes in serum calcium and PTH in humans.
Wesseling-Perry K(1), Wang H, Elashoff R, Gales B, Jüppner H, Salusky IB.
Author information:
(1)Department of Pediatrics (K.W.-P., H.W., R.E., B.G., I.B.S.), David Geffen
School of Medicine at the University of California Los Angeles, Los Angeles,
California 90095; and Endocrine Unit and Division of Pediatric Nephrology (H.J.),
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
02114.
CONTEXT: 1,25-Dihydroxyvitamin D (1,25D) administration and long-term increases
in phosphate, PTH, and calcium concentrations are associated with increases in
circulating fibroblast growth factor 23 (FGF23); however, whether or not acute
changes in serum calcium modulate short-term FGF23 release is unknown.
OBJECTIVE/DESIGN: To assess the direct effect of acute changes in calcium and PTH
on circulating FGF23 levels.
SETTING: A university clinical and translational research center.
PATIENTS/PARTICIPANTS: Twelve healthy volunteers and 10 dialysis patients.
INTERVENTIONS: Calcium gluconate and sodium citrate were infused for 120 minutes
on 2 consecutive days.
MAIN OUTCOME MEASURES: Serum levels of ionized calcium, phosphorus, PTH, 1,25D,
and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120
minutes during the infusions.
RESULTS: During the calcium infusion, serum calcium concentrations increased from
1.33 ± 0.01 to 1.57 ± 0.04 mmol/L (P < .05 from baseline) and from 1.20 ± 0.05 to
1.50 ± 0.03 mmol/L (P < .05 from baseline) in healthy subjects and in dialysis
patients, respectively, whereas serum calcium values decreased from 1.33 ± 0.01
to 1.03 ± 0.02 mmol/L (P < .05 from baseline) and from 1.26 ± 0.04 to 1.07 ± 0.03
mmol/L (P < .05 from baseline) in the two groups, respectively during the sodium
citrate infusion. PTH levels decreased from 35 (29, 57) to 8 (2,10) pg/mL
(healthy subjects) (P < .05 from baseline) and from 292 (109, 423) to 44 (28, 86)
pg/mL (dialysis patients) (P < .05 from baseline) during the calcium infusion and
rose from 31 (25, 56) to 122 (95, 157) pg/mL and from 281 (117, 607) to 468 (169,
928) pg/mL (P < .05 from baseline) during sodium citrate infusion. Serum 1,25D
levels and plasma FGF23 values remained unchanged during both infusions in both
groups.
CONCLUSIONS: Short-term changes in calcium and PTH levels do not affect FGF23
concentrations in either healthy volunteers or dialysis patients.
DOI: 10.1210/jc.2014-2125
PMID: 25062462  [PubMed - indexed for MEDLINE]

22. PLoS One. 2014 Jul 25;9(7):e103602. doi: 10.1371/journal.pone.0103602. eCollection 2014.
Sulfate but not thiosulfate reduces calculated and measured urinary ionized calcium and supersaturation: implications for the treatment of calcium renal stones.
Rodgers A(1), Gauvin D(2), Edeh S(2), Allie-Hamdulay S(1), Jackson G(1), Lieske
JC(3).
Author information:
(1)Department of Chemistry, University of Cape Town, Cape Town, South Africa.
(2)Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota,
United States of America. (3)Division of Nephrology and Hypertension, Mayo
Clinic, Rochester, Minnesota, United States of America; Department of Laboratory
Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of
America.
BACKGROUND: Urinary sulfate (SO4(2-)) and thiosulfate (S2O3(2-)) can potentially
bind with calcium and decrease kidney stone risk. We modeled the effects of these
species on the concentration of ionized calcium (iCa) and on supersaturation (SS)
of calcium oxalate (CaOx) and calcium phosphate (CaP), and measured their in
vitro effects on iCa and the upper limit of stability (ULM) of these salts.
METHODS: Urine data from 4 different types of stone patients were obtained from
the Mayo Nephrology Clinic (Model 1). A second data set was obtained from healthy
controls and hypercalciuric stone formers in the literature who had been treated
with sodium thiosulfate (STS) (Model 2). The Joint Expert Speciation System
(JESS) was used to calculate iCa and SS. In Model 1, these parameters were
calculated as a function of sulfate and thiosulfate concentrations. In Model 2,
data from pre- and post STS urines were analyzed. ULM and iCa were determined in
human urine as a function of sulfate and thiosulfate concentrations.
RESULTS: Calculated iCa and SS values for all calcium salts decreased with
increasing sulfate concentration. Thiosulfate had no effect on these parameters.
In Model 2, calculated iCa and CaOx SS increased after STS treatment, but CaP SS
decreased, perhaps due to a decrease in pH after STS treatment. In confirmatory
in vitro experiments supplemental sulfate, but not thiosulfate, significantly
increased the calcium needed to achieve the ULM of CaP and tended to increase the
oxalate needed to reach the ULM of CaOx. Sulfate also significantly decreased iCa
in human urine, while thiosulfate had no effect.
CONCLUSION: Increasing urinary sulfate could theoretically reduce CaOx and CaP
stone risk. Although STS may reduce CaP stone risk by decreasing urinary pH, it
might also paradoxically increase iCa and CaOx SS. As such, STS may not be a
viable treatment option for stone disease.
DOI: 10.1371/journal.pone.0103602
PMCID: PMC4111609
PMID: 25061988  [PubMed - indexed for MEDLINE]

23. Sao Paulo Med J. 2014;132(4):243-8.
Rational use of blood calcium determinations.
Ferreira-Junior M(1), Lichtenstein A(1), Sales MM(1), Taniguchi LU(1), Aguiar
FJ(1), Fonseca LA(1), Sumita NM(1), Duarte AJ(2).
Author information:
(1)Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São
Paulo, Brazil. (2)Department of Pathology, Faculdade de Medicina, Universidade de
São Paulo, São Paulo, Brazil.
CONTEXT AND OBJECTIVE: This study was motivated by the recent excessive increase
in requests for blood calcium determinations and laboratory tests in general, in
the Hospital das Clínicas complex of Faculdade de Medicina, Universidade de São
Paulo (HCFMUSP). Its aim was to suggest rules for the determination of total and
ionized calcium in our intensive care units, emergency department, wards and
outpatient services, thus contributing towards improving the quality of medical
care and achieving more appropriate use of human and financial resources.
DESIGN AND SETTING: Critical analysis on clinical and laboratory data and the
pertinent scientific literature, conducted by the study group for rational
clinical laboratory use, which is part of the Central Laboratory Division,
HCFMUSP.
METHODS: The study group reviewed scientific publications, statistics and
clinical and laboratory data concerning requests for total and ionized calcium
determinations in the settings of intensive care units, emergency department,
wards and outpatient services.
RESULTS: From this critical analysis, clinical decision flow diagrams aimed at
providing guidance for ordering these tests were constructed.
CONCLUSIONS: Use of the proposed flow diagrams may help to limit the numbers of
inappropriate requests for ionized and total calcium determinations, with
consequent reductions in the number of tests, risks to patients and unnecessary
costs.

PMID: 25055071  [PubMed - indexed for MEDLINE]

24. Rinsho Byori. 2014 Feb;62(2):133-8.
[Evaluation of Payne's formula for the correction of calcium: comparison with
improved calcium and albumin measurement methods].
[Article in Japanese]
Ohbal T, Shiraishi T, Kabaya T, Watanabe S.
The ionized or free fraction of serum calcium is physiologically important for
cellular function, but we most often measure total serum calcium. There are a
number of correction formulas that can be used to estimate whether low total
serum calcium can be attributed simply to low albumin or serum protein. In Japan,
Payne's formula has been widely used to correct calcium concentration. However,
there are some problems in the measurement methods of total calcium and serum
albumin which were used to establish Payne's formula with respect to specificity,
calibration curve and stability. Recently, improved measurement methods of
calcium and albumin have been adopted at clinical laboratories. Here we evaluated
Payne's formula by comparing it with improved measurement methods of total
calcium and serum albumin. For the total calcium measurement, o-CPC
(o-cresolphthaleincomplexone), CPZ(chlorophosphonazo) III, and enzymatic methods
were used. For the serum albumin measurement, BCG (bromocresol green) and
improved BCP(bromocresol purple) methods were used. The results of this
comparison study suggest that the calcium correction equation is not affected by
changes in total calcium concentration, but the assay used for albumin may affect
the calcium correction equation. Using multiple linear regression, the following
equations were derived: BCG between CPZ III [corrected Ca(mg/dL) = total
Ca-0.76ALB + 3.2], and improved BCP between CPZ III [corrected Ca = total
Ca-0.7ALB + 2.6]. These formulas are simplified respectively as [corrected Ca =
total Ca + 0.8(4-ALB], and [corrected Ca = total Ca + 0.7 (4-ALB)]. We conclude
that Payne's formula is valid with the BCG method, but with the improved BCP
method, our formula is more suitable for correcting calcium.

PMID: 24800488  [PubMed - indexed for MEDLINE]

25. Scand J Clin Lab Invest. 2014 Sep;74(6):515-23. doi:
10.3109/00365513.2014.913186. Epub 2014 May 5.
Ionized calcium measurements are influenced by albumin--should ionized calcium be corrected?
Larsen TR(1), Galthen-Sørensen M, Antonsen S.
Author information:
(1)Department of Clinical Biochemistry, Odense University Hospital, Svendborg
Hospital , Svendborg , Denmark.
Measurement of ionized calcium (CaI) has been reported to be dependent on albumin
concentration. We examined the correlation between albumin and CaI measured on
different ion selective electrode analyzers and in different groups of patients
in a large dataset, extracted from the laboratory information system. In 17,281
outpatients and 16,194 inpatients, significantly positive correlations were found
between CaI and albumin, with changes in CaI per 10 g/L change in albumin ranging
from 0.007-0.043 mmol/L and 0.017-0.028 mmol/L, respectively. Correlations were
found to be significantly different when using different analyzers. In order to
examine whether the difference in correlations between the analyzers were really
due to different patient populations investigated on the different analyzers,
data analyzed on the same type of analyzer from inpatients from four different
wards (intensive care unit, medical ward, surgical ward and orthopedic ward) were
examined. There was no significant difference in correlations between patients
from the four wards. Although, these results points towards technical causes
behind the observed differences it cannot be entirely ruled out that clinical
diseases or treatment might influence albumin interaction with CaI measurements.
Combining all data from both out- and inpatients, a correction formula using a
change in CaI of 0.03 mmol/L per 10 g/L change in albumin, was constructed.
However, the albumin influence on CaI is only a minor part of the total CaI
variation and, in most situations, the relatively small effect of changes in
albumin on CaI-results is most likely of no clinical importance.
DOI: 10.3109/00365513.2014.913186
PMID: 24792368  [PubMed - indexed for MEDLINE]

26. PLoS One. 2014 Apr 15;9(4):e95204. doi: 10.1371/journal.pone.0095204. eCollection
2014.
Predictive value of ionized calcium in critically ill patients: an analysis of a large clinical database MIMIC II.
Zhang Z(1), Xu X(1), Ni H(1), Deng H(1).
Author information:
(1)Department of Critical Care Medicine, Jinhua Municipal Central Hospital,
Jinhua Hospital of Zhejiang University, Zhejiang, P.R. China.
BACKGROUND AND OBJECTIVE: Ionized calcium (iCa) has been investigated for its
association with mortality in intensive care unit (ICU) patients in many studies.
However, these studies are small in sample size and the results are conflicting.
The present study aimed to establish the association of iCa with mortality by
using a large clinical database.
METHODS: Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II)
database was used for analysis. Patients older than 15 years were eligible, and
patients without iCa measured during their ICU stay were excluded. Demographic
data and clinical characteristics were extracted and compared between survivors
and non-survivors. iCa measure on ICU admission was defined as Ca0; Camax was the
maximum iCa during ICU stay; Camin was the minimum value of iCa during the ICU
stay; Camean was the arithmetic mean iCa during ICU stay.
MAIN RESULTS: A total of 15409 ICU admissions satisfied our inclusion criteria
and were included in our analysis. The prevalence of hypocalcemia on ICU entry
was 62.06%. Ca0 was significantly lower in non-survivors than in survivors (1.11
± 0.14 vs 1.13 ± 0.10 mmol/l, p<0.001). In multivariate analysis, moderate
hypocalcemia in Ca0 was significantly associated with increased risk of death
(OR: 1.943; 95% CI: 1.340-2.817), and mild hypercalcemia was associated with
lower mortality (OR: 0.553, 95% CI: 0.400-0.767). While moderate and mild
hypocalcemia in Camean is associated with increased risk of death (OR: 1.153, 95%
CI: 1.006-1.322 and OR: 2.520, 95% CI: 1.485-4.278), hypercalcemia in Camean is
not significantly associated with ICU mortality.
CONCLUSION: The relationship between Ca0 and clinical outcome follows an "U"
shaped curve with the nadir at the normal range, extending slightly to
hypercalcemia. Mild hypercalcemia in Ca0 is protective, whereas moderate and mild
hypocalcemia in Camean is associated with increased risk of death.
DOI: 10.1371/journal.pone.0095204
PMCID: PMC3988144
PMID: 24736693  [PubMed - indexed for MEDLINE]

27. G Chir. 2014 Jan-Feb;35(1-2):27-35.
Is ionized calcium a reliable predictor of hypocalcemia after total thyroidectomy? A before and after study.
Tartaglia F, Giuliani A, Sgueglia M, Patrizi G, Di Rocco G, Blasi S, Russo G,
Tortorelli G, Giannotti D, Redler A.
Wanting to find a way of identifying patients suitable for early discharge after
thyroidectomy, we set out to establish whether ionized calcium concentration is a
better predictor of post-surgical hypocalcemia than total serum calcium. Data
were analyzed to establish whether serum ionized calcium concentrations are
correlated with total serum calcium levels and symptomatic hypocalcemia after
thyroidectomy. Sixty-two patients undergoing total thyroidectomy at the
Department of Surgical Sciences of the "Sapienza" University of Rome, Italy, in
2010. Ionized calcium was measured before (day 0) and after surgery (days 1, 2
and 60) in all the patients. These measurements were compared with preoperative
(day 0) and postoperative total serum calcium levels (days 1, 2 and 60). The
preoperative ionized calcium levels differed from the ionized calcium levels
recorded on days 1 and 2; this pattern was not observed for the total calcium
concentrations. Conversely, total calcium on days I and II correlated
significantly with the various ionized calcium measurements. The presence of
parathyroid gland

Anión Restante: Búsqueda de trabajos 2013 - 2016Fecha: 3/9/2016






1. Anesteziol Reanimatol. 2015 Nov-Dec;60(6):12-6.
[CHARACTERISTICS OF SURFACE ELECTROMYOGRAPHY AND ACID-BASE BALANCE IN PATIENTS
WITH INTENSIVE CARE UNIT-ACQUIRED WEAKNESS].
[Article in Russian]
Mejgal AY, Tret'jakova OG, Spasova AP.
OBJECTIVE: The study was aimed to search for correlation between parameters of
surface electromyography and acid-base balance (ABB) in patients with intensive
care unit-acquired weakness (ICUAW, n = 29, duration 7-180 days).
METHODS: The linear and nonlinear parameters of sEMG (mean frequency of spectrum,
fractal and correlation dimension, correlation entropy) and ABB and their
correlation coefficient with bed rest (BR) Download ASTM Codes and duration of mechanical ventilation
(MT) were computed.
RESULTS: Here we report that in first 40 days sEMG parameters were indicative of
the neurogenic process in the skeletal muscle, while within 41-100 days signs of
the myogenic pathology were documented. The ABB parameters statistically
signIficantly correlated with BR and MV duration.
CONCLUSION: ICUAW exerts effect on the skeletal muscle. Within first 40 days this
effect is actuated in a form of neuropathy, while further it has signs of
myopathy. We argue that MV duration appear to be a pathogenic factor in these
modifications.

PMID: 27025126  [PubMed - indexed for MEDLINE]

2. JEMS. 2016 Feb;41(2):38-42.
BALANCING FOR LIFE. Correcting common acid-base imbalances using bicarbonate &
CO2 exchange.
Tanis J, DiCorpo JE, Friedman D, Merlin M.

PMID: 27008729  [PubMed - indexed for MEDLINE]

3. Eur J Gastroenterol Hepatol. 2016 Mar;28(3):363. doi:
10.1097/MEG.0000000000000550.
Acid-base disturbance in liver cirrhosis.
Bruno CM(1).
Author information:
(1)Dipartimento di Medicina  Clinica e Sperimentale, Universita degli Studi di
Catania, Catania, Italy.
Comment on
    Eur J Gastroenterol Hepatol. 2015 Aug;27(8):920-7.
DOI: 10.1097/MEG.0000000000000550
PMID: 26825147  [PubMed - indexed for MEDLINE]

4. Zhonghua Yu Fang Yi Xue Za Zhi. 2015 Oct;49(10):930-2.
[A survey on the mineral contents and potential renal acid loads in primary and
secondary school-supplied drinking water in Chongqing].
[Article in Chinese]
Huang Y(1), Lan L, Yan Q, Tang W, Tan Y, Wang L, Shu W(2).
Author information:
(1)Department of Environmental Hygiene, College of Preventive Medicine, Third
Military Medical University, Chongqing 400038, China. (2)Email: xm0630@sina.com.

PMID: 26813729  [PubMed - indexed for MEDLINE]

5. J Pediatr. 2016 Jan;168:98. doi: 10.1016/j.jpeds.2015.07.061.
50 Years Ago in The Journal of Pediatrics: Arterial Blood Gas Tensions and
Acid-Base Balance in the Management of Respiratory Distress Syndrome.
Saugstad OD(1).
Author information:
(1)Department of Pediatric Research, University of Oslo, Oslo University
Hospital, Oslo, Norway.
DOI: 10.1016/j.jpeds.2015.07.061
PMID: 26719179  [PubMed - indexed for MEDLINE]

6. Ther Umsch. 2015 Dec;72(11-12):737-41. doi: 10.1024/0040-5930/a000745.
[5-0xoproline (pyroglutamic acid) Free ASTM Codes Download acidosis and acetaminophen- a differential
diagnosis in high anion gap metabolic acidosis].
[Article in German]
Weiler S(1), Bellmann R(2), Kullak-Ublick GA(1).
Author information:
(1)1 Klinik für Klinische Pharmakologie und Toxikologie und Regionales
Pharmacovigilance Zentrum, Universitätsspital Zürich und Universität Zürich. (2)2
Arbeitsgruppe für Klinische Pharmakokinetik, Gemeinsame Einrichtung für
Internistische Notfall- und Intensivmedizin, Universitätsklinik für Innere
Medizin I, Medizinische Universität Innsbruck.
Rare cases of high anion gap metabolic acidosis during long-term paracetamol
administration in therapeutic doses with causative 5-oxoproline (pyroglutamic
acid} accumulation have been reported. Other concomitant risk factors such as
malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with
flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The
etiology seems to be a drug-induced reversible inhibition of glutathione
synthetase or 5-oxoprolinase leading to elevated serum and urine levels of
5-oxoproline. Other more frequent differential diagnoses, such as intoxications,
ketoacidosis or lactic acidosis should be excluded. Causative substances should
be stopped. 5-oxoproline concentrations in urine can be quantified to establish
the diagnosis. Adverse drug reactions, which are not listed or insufficiently
described in the respective Swiss product information, should be reported to the
regional pharmacovigilance centres for early signal detection. 5-0 xoproline
acidosis will be integrated as a potential adverse drug reaction in the Swiss
product information for paracetamol.
DOI: 10.1024/0040-5930/a000745
PMID: 26654818  [PubMed - indexed for MEDLINE]

7. Nihon Naika Gakkai Zasshi. 2015 May 10;104(5):938-47.
[Kidney diseases and metabolic disorders--Basics and applications required for
general physicians. Topics: V. Acid-base disorders and kidney disease].
[Article in Japanese]
Kaname S.

PMID: 26591343  [PubMed - indexed for MEDLINE]

8. Clin Chem. 2015 Nov;61(11):1422. doi: 10.1373/clinchem.2015.242313.
Extreme Hypernatremia with Markedly Increased Anion Gap.
Miller PM(1), Dufour DR(2).
Author information:
(1)Department of Pathology, George Washington University, Washington, DC;
petermiller@jhu.edu. (2)Department of Pathology, George Washington University,
Washington, DC; Pathology and Hepatology, Veterans Affairs Medical Center,
Washington, DC.
DOI: 10.1373/clinchem.2015.242313
PMID: 26511354  [PubMed - indexed for MEDLINE]

9. Crit Care Clin. 2015 Oct;31(4):849-60. doi: 10.1016/j.ccc.2015.06.016. Epub 2015
Aug 13.
Understanding Acid Base Disorders.
Gomez H(1), Kellum JA(2).
Author information:
(1)Department of Critical Care Medicine, Center for Critical Care Nephrology, The
CRISMA Center, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA
15261, USA. (2)Department of Critical Care Medicine, Center for Critical Care
Nephrology, The CRISMA Center, University of Pittsburgh, 3550 Terrace Street,
Pittsburgh, PA 15261, USA. Electronic address: kellumja@ccm.upmc.edu.
The concentration of hydrogen ions is regulated in biologic solutions. There are
currently 3 recognized approaches to assess changes in acid base status. First is
the traditional Henderson-Hasselbalch approach, also called the physiologic
approach, which uses the relationship between HCO3(-) and Pco2; the second is the
standard base excess approach based on the Van Slyke equation. The third approach
is the quantitative or Stewart approach, which uses the strong ion difference and
the total weak acids. This article explores the origins of the current concepts
framing the existing methods to analyze acid base balance.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ccc.2015.06.016
PMID: 26410149  [PubMed - indexed for MEDLINE]

10. Am J Kidney Dis. 2016 Jan;67(1):143-50. doi: 10.1053/j.ajkd.2015.07.024. Epub
2015 Sep 10.
Approach to the Patient With a Negative Anion Gap.
Emmett M(1).
Author information:
(1)Nephrology Division, Department of Internal Medicine, Baylor University
Medical Center, Dallas, TX. Electronic address: m.emmett@baylorhealth.edu.
When anion gap calculation generates a very small or negative number, an
explanation must be sought. Sporadic (nonreproducible) measurement errors and
systematic (reproducible) laboratory errors must be considered. If an error is
ruled out, 2 general possibilities exist. A true anion gap reduction can be
generated by either reduced concentrations of unmeasured anions such as albumin
or increased concentrations of unmeasured cations such as magnesium, calcium, or
lithium. This teaching case describes a patient with aspirin (salicylate)
poisoning whose anion gap was markedly reduced (-47 mEq/L). The discussion
systematically reviews the possibilities and provides the explanation for this
unusual laboratory result.
Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All
rights reserved.
DOI: 10.1053/j.ajkd.2015.07.024
PMID: 26363848  [PubMed - indexed for MEDLINE]

11. Crit Care Resusc. 2015 Sep;17(3):211-3.
Acid-base physiology: comments on 10 contentious assertions.
Morgan TJ(1), Venkatesh B(2), Bellomo R(3).
Author information:
(1)Mater Research Institute, University of Queensland, Brisbane, QLD, Australia.
t.morgan@uq.edu.au. (2)Princess Alexandra and Wesley Hospitals, University of
Queensland, Brisbane, QLD, Australia. (3)Australian and New Zealand Intensive
Care Research Centre, Melbourne, VIC, Australia.

PMID: 26282261  [PubMed - indexed for MEDLINE]

12. Intern Med. 2015;54(15):1901-4. doi: 10.2169/internalmedicine.54.4272. Epub 2015
Aug 1.
High Anion Gap Metabolic Acidosis after a Suicide Attempt with Cyanide: The
Rebirth of Cyanide Poisoning.
Hsiao PJ(1), Chang CF, Chiu CC, Chan JS, Chiang WF, Wu CC, Lin SH, Chen JS.
Author information:
(1)Division of Nephrology, Department of Internal Medicine, Tri-Service General
Hospital, National Defense Medical Center, Taiwan.
A 33-year-old woman was admitted to our emergency department in a state of
unconsciousness after attempting suicide with unknown substances. Severe
metabolic acidosis (pH: 6.81), with a high anion gap (36.2) and high lactate
level (20.2 mmol/L), was observed. After four hours of intensive medical
treatment, the patient regained consciousness, with a return of the arterial pH
to 7.42. Finally, cyanide intoxication was diagnosed based on the detection of a
serum cyanide level of 3.5 mg/L. The presence of a high anion gap associated with
severe lactic acidosis is a clue for making a rapid differential diagnosis of
acute cyanide intoxication. Providing intensive and immediate supportive
management is also crucial, even in cases without obtainable specific antidotes.
DOI: 10.2169/internalmedicine.54.4272
PMID: 26234233  [PubMed - indexed for MEDLINE]

13. Trials. 2015 Aug 1;16:326. doi: 10.1186/s13063-015-0843-6.
Does oral sodium bicarbonate therapy improve function and quality of life in
older patients with chronic kidney disease and low-grade acidosis (the BiCARB
trial)? Study protocol for a randomized controlled trial.
Witham MD(1), Band MM(2), Littleford RC(3), Avenell A(4), Soiza RL(5), McMurdo
ME(6), Sumukadas D(7), Ogston SA(8), Lamb EJ(9), Hampson G(10), McNamee P(11);
BiCARB Study Group.
Author information:
(1)Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee,
DD1 9SY, UK. m.witham@dundee.ac.uk. (2)Tayside Clinical Trials Unit, University
of Dundee / NHS Tayside, Dundee, UK. m.band@dundee.ac.uk. (3)Tayside Clinical
Trials Unit, University of Dundee / NHS Tayside, Dundee, UK.
r.littleford@dundee.ac.uk. (4)Health Services Research Unit, University of
Aberdeen, Aberdeen, UK. a.avenell@abdn.ac.uk. (5)Health Services Research Unit,
University of Aberdeen, Aberdeen, UK. r.l.soiza@abdn.ac.uk. (6)Medical Research
Institute, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK.
m.e.t.mcmurdo@dundee.ac.uk. (7)Medical Research Institute, University of Dundee,
Ninewells Hospital, Dundee, DD1 9SY, UK. d.sumukadas@dundee.ac.uk.
(8)Epidemiology and Biostatistics Unit, University of Dundee, Dundee, UK.
s.a.ogston@dundee.ac.uk. (9)Department of Clinical Biochemistry, East Kent NHS
Trust, Canterbury, UK. elamb@nhs.net. (10)Department of Chemical Pathology, Guy's
and St Thomas' Hospitals, London, UK. geeta.hampson@kcl.ac.uk. (11)Health
Economics Research Unit, University of Aberdeen, Aberdeen, UK.
p.mcnamee@abdn.ac.uk.
BACKGROUND: Metabolic acidosis is more common with advancing chronic kidney
disease, and has been associated with impaired physical function, impaired bone
health, accelerated decline in kidney function and increased vascular risk.
Although oral sodium bicarbonate is widely used to correct metabolic acidosis,
there exist potential risks of therapy including worsening hypertension and fluid
overload. Little trial evidence exists to decide whether oral bicarbonate therapy
is of net benefit in advanced chronic kidney disease, particularly in older
people who are most commonly affected, and in whom physical function, quality of
life and vascular health are at least as important outcomes as decline in renal
function.
METHODS/DESIGN: BiCARB is a multi-centre, double-blind, placebo controlled,
randomised trial evaluating the clinical and cost-effectiveness of oral sodium
bicarbonate in the management of older people with chronic kidney disease and
severely reduced glomerular filtration rate (GFR) who have a mild degree of
metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for
the Elderly, and primary care services across centres in the United Kingdom. Male
and female patients aged 60 years and older with an estimated glomerular
filtration rate of <30 mL/min/1.73 m(2), not on dialysis, and with serum
bicarbonate concentrations <22 mmol/L will be eligible for participation. The
primary clinical outcome for the trial is the between-group difference in the
Short Physical Performance Battery score at 12 months. Secondary outcomes include
muscle strength, quality of life measured using the EQ-5D score and KDQoL tools,
cost effectiveness, renal function, presence of albuminuria and blood pressure.
Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D,
tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase)
and vascular health (B-type natriuretic peptide) will be measured. Participants
will receive a total of 24 months of either bicarbonate or placebo. The results
will provide the first robust test of the overall clinical and cost-effectiveness
of this commonly used therapy in older patients with severely reduced kidney
function.
TRIAL REGISTRATION: www.isrctn.com; ISRCTN09486651, registered 17 February 2012.
DOI: 10.1186/s13063-015-0843-6
PMCID: PMC4522127
PMID: 26231610  [PubMed - indexed for MEDLINE]

14. Int J Vitam Nutr Res. 2014;84(3-4):206-17. doi: 10.1024/0300-9831/a000207.
Higher Dietary Acidity is Associated with Lower Bone Mineral Density in
Postmenopausal Iranian Women, Independent of Dietary Calcium Intake.
Shariati-Bafghi SE(1), Nosrat-Mirshekarlou E, Karamati M, Rashidkhani B.
Author information:
(1)1 Department of Nutrition Sciences, Varastegan Institute for Medical Sciences,
Mashhad, Iran.
Findings of studies on the link between dietary acid-base balance and bone mass
are relatively mixed. We examined the association between dietary acid-base
balance and bone mineral density (BMD) in a sample of Iranian women,
hypothesizing that a higher dietary acidity would be inversely associated with
BMD, even when dietary calcium intake is adequate. In this cross-sectional study,
lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50-85 years
were measured using dual-energy x-ray absorptiometry. Dietary intakes were
assessed using a validated food frequency questionnaire. Renal net acid excretion
(RNAE), an estimate of acid-base balance, was then calculated indirectly from the
diet using the formulae of Remer (based on dietary intakes of protein,
phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary
intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the
residual method. After adjusting for potential confounders, multivariable
adjusted means of the lumbar spine BMD of women in the highest tertiles of
RNAERemer and RNAEFrassetto were significantly lower than those in the lowest
tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for
RNAEFrassetto: mean difference -0.088 g/cm2; P=0.004). Similar results were
observed in a subgroup analysis of subjects with dietary calcium intake of >800
mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is
associated with greater intake of acid-generating foods and lower intake of
alkali-generating foods, may be involved in deteriorating the bone health of
postmenopausal Iranian women, even in the context of adequate dietary calcium
intake.
DOI: 10.1024/0300-9831/a000207
PMID: 26098484  [PubMed - indexed for MEDLINE]

15. J Pediatr (Rio J). 2015 Sep-Oct;91(5):499-505. doi: 10.1016/j.jped.2014.12.003.
Epub 2015 Jun 10.
The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population.
Almeida HI(1), Mascarenhas MI(2), Loureiro HC(2), Abadesso CS(2), Nunes PS(2),
Moniz MS(2), Machado MC(3).
Author information:
(1)Pediatric Intensive Care Unit, Pediatric Department, Hospital Prof. Doutor
Fernando Fonseca EPE, Amadora, Portugal. Electronic address:
lenaizabel@gmail.com. (2)Pediatric Intensive Care Unit, Pediatric Department,
Hospital Prof. Doutor Fernando Fonseca EPE, Amadora, Portugal. (3)Faculty of
Medicine, Universidade de Lisboa, Lisbon, Portugal.
OBJECTIVES: To study the effect of two intravenous maintenance fluids on plasma
sodium (Na), and acid-base balance in pediatric intensive care patients during
the first 24h of hospitalization.
METHODS: A prospective randomized controlled study was performed, which allocated
233 patients to groups: (A) NaCl 0.9% or (B) NaCl 0.45%. Patients were aged 1 day
to 18 years, had normal electrolyte concentrations, and suffered an acute insult
(medical/surgical).
MAIN OUTCOME MEASURED: change in plasma sodium. Parametric tests: t-tests, ANOVA,
X(2) statistical significance level was set at α=0.05.
RESULTS: Group A (n=130): serum Na increased by 2.91 (±3.9)mmol/L at 24h
(p<0.01); 2% patients had Na higher than 150 mmol/L. Mean urinary Na: 106.6
(±56.8)mmol/L. No change in pH at 0 and 24h. Group B (n=103): serum Na did not
display statistically significant changes. Fifteen percent of the patients had
Na<135 mmol/L at 24h. The two fluids had different effects on respiratory and
post-operative situations.
CONCLUSIONS: The use of saline 0.9% was associated with a lower incidence of
electrolyte disturbances.
Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora
Ltda. All rights reserved.
DOI: 10.1016/j.jped.2014.12.003
PMID: 26070865  [PubMed - indexed for MEDLINE]

16. High Alt Med Biol. 2015 Sep;16(3):267. doi: 10.1089/ham.2015.0051. Epub 2015 Jun 9.
Does Cerebral Water and Ion Imbalance After Intense Exercise of Short Duration
Under Hypoxic Conditions Contribute to Occurrence of Acute Mountain Sickness?
Chawla A(1), Sikri G(1).
Author information:
(1)Department of Physiology, Armed Forces Medical College, Maharashtra, India .
Comment on
    High Alt Med Biol. 2015 Mar;16(1):18-25.
DOI: 10.1089/ham.2015.0051
PMID: 26057721  [PubMed - indexed for MEDLINE]

17. Adv Physiol Educ. 2015 Jun;39(2):120-1. doi: 10.1152/advan.00167.2014.
Collaborative teaching strategies lead to retention of skills in acid-base physiology: a 2-yr follow-up study.
Hartmann JP(1), Toksvang LN(2), Berg RM(3).
Author information:
(1)Renal and Vascular Research Section, Department of Biomedical Sciences,
Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
(2)Department of Pediatrics and Adolescent Medicine, University Hospital
Rigshospitalet, Copenhagen, Denmark; and. (3)Renal and Vascular Research Section,
Department of Biomedical Sciences, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Nuclear
Medicine & PET, University Hospital Rigshospitalet, Copenhagen, Denmark
ronan@dadlnet.dk.
DOI: 10.1152/advan.00167.2014
PMID: 26031729  [PubMed - indexed for MEDLINE]

18. Am J Emerg Med. 2015 Sep;33(9):1134-9. doi: 10.1016/j.ajem.2015.04.085. Epub 2015
May 7.
Comparing biomarkers of traumatic shock: the utility of anion gap, base excess,and serum lactate in the ED.
Caputo ND(1), Kanter M(1), Fraser R(1), Simon R(2).
Author information:
(1)Department of Emergency Medicine, Lincoln Medical and Mental Health Center,
Bronx, NY. (2)Department of Surgery, Division of Trauma, Lincoln Medical and
Mental Health Center, Bronx, NY.
BACKGROUND: Biomarkers such as serum lactate, anion gap (AG), and base excess
(BE) have been shown to be of use in determining shock in patients with seemingly
normal vital signs. We seek to determine if these biomarkers can be used
interchangeably in patients with trauma in the emergency setting based on their
test characteristics and correlation to each other.
METHODS: A prospective observational cohort study was undertaken at an urban
level 1 trauma center. Baseline vital signs, point-of-care BE, AG, and serum
lactate were recorded in all patients who presented for trauma. Correlation was
determined by linear regression model. Overall test characteristics and relative
risk were calculated.
RESULTS: One hundred patients were enrolled. The median age was 30 years
(interquartile range, 24-42 years), and 89% were male. Fifty-three percent of
injuries were blunt trauma. Pearson correlation of serum lactate to BE was -0.81
(r(2) = 0.66; 95% confidence interval [CI], 0.53-0.75; P < .001), that of BE to
AG was -0.71 (r(2) = 0.5; 95% CI, -0.80 to -0.57; P < .01), and that for serum
lactate to AG was 0.71 (r(2) = 0.5; 95% CI, 0.57-0.80; P < .01).
CONCLUSIONS: This study demonstrates that the biomarkers have similar test
characteristics which may make them interchangeable as indicators for the
presence of occult shock in patients with trauma. Lactate and BE correlate well
with each other; however, AG was not as strongly correlated with either.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ajem.2015.04.085
PMID: 26027886  [PubMed - indexed for MEDLINE]

19. J Perioper Pract. 2015 Mar;25(3):46-52.
Four steps to interpreting arterial blood gases.
Rogers KM, McCutcheon K.
This article examines acid-base balance and the interpretation of arterial blood
gases (ABG). The article begins with a brief revision of related physiology,
followed by a description of the primary disorders associated with acid-base
imbalance. The normal ranges and the significance of abnormal ABG results are
explored. The article concludes by providing an easy to follow four-step guide to
ABG interpretation with practice examples presented in the CPD task section.

PMID: 26016282  [PubMed - indexed for MEDLINE]

20. Acta Med Croatica. 2014 Apr;68(2):85-90.
[Acid-base status in patients treated with peritoneal dialysis].
[Article in Croatian]
Katalinić L, Blaslov K, Pasini E, Kes P, Bašić-Jukić N.
When compared to hemodialysis, peritoneal dialysis is very simple yet low cost
method of renal replacement therapy. Series of studies have shown its superiority
in preserving residual renal function, postponing uremic complications,
maintaining the acid-base balance and achieving better post-transplant outcome in
patients treated with this method. Despite obvious advantages, its role in the
treatment of chronic kidney disease is still not as important as it should be.
Metabolic acidosis is an inevitable complication associated with progressive loss
of kidney function. Its impact on mineral and muscle metabolism, residual renal
function, allograft function and anemia is very complex but can be successfully
managed. The aim of our study was to evaluate the efficiency in preserving the
acid-base balance in patients undergoing peritoneal dialysis at Zagreb University
Hospital Center. Twenty-eight patients were enrolled in the study. The mean time
spent on the treatment was 32.39 ± 43.43 months. Only lactate-buffered peritoneal
dialysis fluids were used in the treatment. Acid-base balance was completely
maintained in 73.07% of patients; 11.54% of patients were found in the state of
mild metabolic acidosis, and the same percentage of patients were in the state of
mild metabolic alkalosis. In one patient, mixed alkalosis with respiratory and
metabolic component was present. The results of this study showed that acid-base
balance could be maintained successfully in patients undergoing peritoneal
dialysis, even only with lactate-buffered solutions included in the treatment,
although they were continuously proclaimed as inferior in comparison with
bicarbonate-buffered ones. In well educated and informed patients who carefully
use this method, accompanied by the attentive and thorough care of their
physicians, this method can provide quality continuous replacement of lost renal
function as well as better quality of life.

PMID: 26012143  [PubMed - indexed for MEDLINE]

21. Eur J Gastroenterol Hepatol. 2015 Aug;27(8):920-7. doi:
10.1097/MEG.0000000000000382.
Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction.
Henriksen JH(1), Bendtsen F, Møller S.
Author information:
(1)aDepartment of Clinical Physiology and Nuclear Medicine bGastro Unit, Medical
Division, Hvidovre Hospital, Faculty of Medical and Health Sciences, University
of Copenhagen, Copenhagen, Denmark.
Comment in
    Eur J Gastroenterol Hepatol. 2016 Mar;28(3):363.
PURPOSE: Acid-base disturbances were investigated in patients with cirrhosis in
relation to hemodynamic derangement to analyze the hyperventilatory effects and
the metabolic compensation.
METHODS: A total of 66 patients with cirrhosis and 44 controls were investigated
during a hemodynamic study.
RESULTS: Hyperventilatory hypocapnia was present in all patients with cirrhosis
and progressed from Child class A to C (P<0.01). Arterial pH increased
significantly from class A to C (P<0.001) and was correlated inversely to the
mean arterial blood pressure (r=-0.30, P<0.02), systemic vascular resistance
(r=-0.25, P<0.05), indocyanine green clearance (r=-0.37, P<0.005), and serum
sodium (r=-0.38, P<0.002). Metabolic compensation was shown by a reduced standard
base excess in all patients (P<0.001). Standard base excess contained elements
related to changes in serum albumin, water dilution, and effects of unidentified
ions (all P<0.001). A significant hepatic component in the acid-base disturbances
could not be identified.
CONCLUSION: Hypocapnic alkalosis is related to disease severity and hyperdynamic
systemic circulation in patients with cirrhosis. The metabolic compensation
includes alterations in serum albumin and water retention that may result in a
delicate acid-base balance in these patients.
DOI: 10.1097/MEG.0000000000000382
PMID: 26011230  [PubMed - indexed for MEDLINE]

22. West J Emerg Med. 2015 May;16(3):364-6. doi: 10.5811/westjem.2015.2.23906. Epub
2015 Apr 2.
Is serum lactate necessary in patients with normal anion gap and serum bicarbonate?
Aronovich D(1), Trotter M(2), Rivera C(2), Dalley M(1), Farcy D(1), Betancourt
M(3), Howard L(3), Licciardi S(3), Cubeddu L(4), Goldszer R(2).
Author information:
(1)Mount Sinai Medical Center, Department of Emergency Medicine, Miami Beach,
Florida. (2)Mount Sinai Medical Center, Department of Internal Medicine, Miami
Beach, Florida. (3)Mount Sinai Medical Center, Department of Pathology, Miami
Beach, Florida. (4)Nova Southeastern University, Health Professions Division,
Fort Lauderdale, Florida.
INTRODUCTION: There has been an increase in patients having serum lactate drawn
in emergency situations. The objective of this study was to determine whether or
not it was necessary to obtain a lactate level in patients with a normal serum
bicarbonate level and anion gap.
METHODS: This is a retrospective chart review evaluation of 304 patients who had
serum lactate and electrolytes measured in an emergency setting in one academic
medical center.
RESULTS: In 66 patients who had elevated serum lactate (>2.2mmol/L), 45 (68%)
patients had normal serum bicarbonate (SB) (greater than 21 mmol/L). Normal anion
gap (AG) (normal range <16 mEq/l) was found in 51 of the 66 patients (77%).
CONCLUSION: We found that among patients with elevated serum lactate, 77% had a
normal anion gap and 68% had normal serum bicarbonate. We conclude serum lactate
should be drawn based on clinical suspicion of anaerobic tissue metabolism
independent of serum bicarbonate or anion gap values.
DOI: 10.5811/westjem.2015.2.23906
PMCID: PMC4427204
PMID: 25987907  [PubMed - indexed for MEDLINE]

23. N Engl J Med. 2015 May 14;372(20):1969. doi: 10.1056/NEJMc1502745#SA3.
Acid-base problems in diabetic ketoacidosis.
Frontino G, Rigamonti A, Bonfanti R.
Comment in
    N Engl J Med. 2015 May 14;372(20):1969-70.
Comment on
    N Engl J Med. 2015 Feb 5;372(6):546-54.
DOI: 10.1056/NEJMc1502745#SA3
PMID: 25970066  [PubMed - indexed for MEDLINE]

24. N Engl J Med. 2015 May 14;372(20):1968-9. doi: 10.1056/NEJMc1502745#SA2.
Acid-base problems in diabetic ketoacidosis.
Maury E, Bureau C, Offenstadt G.
Comment in
    N Engl J Med. 2015 May 14;372(20):1969-70.
Comment on
    N Engl J Med. 2015 Feb 5;372(6):546-54.
DOI: 10.1056/NEJMc1502745#SA2
PMID: 25970065  [PubMed - indexed for MEDLINE]

25. N Engl J Med. 2015 May 14;372(20):1968. doi: 10.1056/NEJMc1502745#SA1.
Acid-base problems in diabetic ketoacidosis.
Joy M.
Comment in
    N Engl J Med. 2015 May 14;372(20):1969-70.
Comment on
    N Engl J Med. 2015 Feb 5;372(6):546-54.
DOI: 10.1056/NEJMc1502745#SA1
PMID: 25970064  [PubMed - indexed for MEDLINE]

26. N Engl J Med. 2015 May 14;372(20):1969-70. doi: 10.1056/NEJMc1502745.
Acid-base problems in diabetic ketoacidosis.
Kamel KS, Halperin ML.
Comment on
    N Engl J Med. 2015 Feb 5;372(6):546-54.
    N Engl J Med. 2015 May 14;372(20):1969.
    N Engl J Med. 2015 May 14;372(20):1968-9.
    N Engl J Med. 2015 May 14;372(20):1968.
DOI: 10.1056/NEJMc1502745
PMID: 25970063  [PubMed - indexed for MEDLINE]

27. Clin Exp Nephrol. 2015 Aug;19(4):556-61. doi: 10.1007/s10157-015-1119-x. Epub
2015 May 9.
Comprehensive clinical approach to renal tubular acidosis.
Sharma S(1), Gupta A, Saxena S.
Author information:
(1)PSRI Hospital, Sheikh Sarai, Saket, New Delhi, India, sonyasharma01@gmail.com.
Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and
hyperchloremic metabolic acidosis. It is important to understand that despite
knowing the disease for 60-70 years, complexities in the laboratory tests and
their interpretation still make clinicians cautious to diagnose and label types
of tubular disorder. Hence, we are writing this mini-review to emphasize on the
step wise approach to RTA with some understanding on its basic etiopathogenesis.
This will definitely help to have an accurate interpretation of urine and blood
reports in correlation with the clinical condition. RTA can be a primary or
secondary defect and results either due to abnormality in bicarbonate ion
absorption or hydrogen ion secretion. Primary defects are common in children due
to gene mutation or idiopathic nature while secondary forms are more common in
adults. We are focusing and explaining here in this review all the clinical and
laboratory parameters which are essential for making the diagnosis of RTA and
excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic
acidosis.
DOI: 10.1007/s10157-015-1119-x
PMID: 25951806  [PubMed - indexed for MEDLINE]

28. Crit Care. 2015 Apr 17;19:177. doi: 10.1186/s13054-015-0746-7.
Relationship between reduced albumin and inflammation in the critically ill.
Marano M(1).
Author information:
(1)Hemodialysis Unit, Maria Rosaria Clinic, via Colle San Bartolomeo, 50,
Pompeii, 80045, Italy. marano965@gmail.com.
Comment on
    Crit Care. 2014;18(4):R154.
DOI: 10.1186/s13054-015-0746-7
PMCID: PMC4403944
PMID: 25928874  [PubMed - indexed for MEDLINE]

29. Am J Emerg Med. 2015 Nov;33(11):1714.e3-4. doi: 10.1016/j.ajem.2015.03.042. Epub
2015 Mar 18.
Normal anion gap salicylate poisoning.
Wright D(1), Sop J(2).
Author information:
(1)Emergency Medicine Residency Program, Department of Emergency Medicine,
Charleston Area Medical Center, 501 Morris St, Charleston, WV 25301. Electronic
address: dallas.wright@camc.org. (2)Emergency Medicine Residency Program,
Department of Emergency Medicine, Charleston Area Medical Center, 501 Morris St,
Charleston, WV 25301. Electronic address: Jessica.sop@camc.org.
DOI: 10.1016/j.ajem.2015.03.042
PMID: 25825032  [PubMed - indexed for MEDLINE]

30. J Vet Intern Med. 2015 Mar-Apr;29(2):678-87. doi: 10.1111/jvim.12556.
Quantitative physicochemical analysis of acid-base balance and clinical utility
of anion gap and strong ion gap in 806 neonatal calves with diarrhea.
Trefz FM(1), Constable PD, Lorenz I.
Author information:
(1)Clinic for Ruminants with Ambulatory and Herd Health Services at the Centre
for Clinical Veterinary Medicine, LMU Munich, Oberschleißheim, Germany.
Erratum in
    J Vet Intern Med. 2015 May-Jun;29(3):993.
BACKGROUND: Acid-base abnormalities in neonatal diarrheic calves can be assessed
by using the Henderson-Hasselbalch equation or the simplified strong ion approach
which use the anion gap (AG) or the strong ion gap (SIG) to quantify the
concentration of unmeasured strong anions such as D-lactate.
HYPOTHESIS/OBJECTIVES: To determine and compare the clinical utility of AG and
SIG in quantifying the unmeasured strong anion charge in neonatal diarrheic
calves, and to examine the associations between biochemical findings and
acid-base variables by using the simplified strong ion approach. We hypothesized
that the SIG provides a more accurate prediction of unmeasured strong anions than
the AG.
ANIMALS: Eight hundred and six neonatal diarrheic calves admitted to a veterinary
teaching hospital.
METHODS: Retrospective study utilizing clinicopathologic findings extracted from
medical records.
RESULTS: Hyperphosphatemia was an important predictor of venous blood pH. Serum
inorganic phosphorus and plasma D-lactate concentrations accounted for 58% of the
variation in venous blood pH and 77% of the variation in AG and SIG. Plasma D-
and total lactate concentrations were slightly better correlated with SIG (rs =
-0.69; -0.78) than to AG (rs = 0.63; 0.74).
CONCLUSIONS AND CLINICAL IMPORTANCE: Strong ion gap is slightly better at
quantifying the unmeasured strong anion concentration in neonatal diarrheic
calves than AG. Phosphorus concentrations should be included as part of the
calculation of Atot when applying the simplified strong ion approach to acid-base
balance to critically ill animals with hyperphosphatemia.
Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published
by Wiley Periodicals, Inc. on behalf of the American College of Veterinary
Internal Medicine.
DOI: 10.1111/jvim.12556
PMCID: PMC4895505
PMID: 25818222  [PubMed - indexed for MEDLINE]

31. Fetal Diagn Ther. 2015;38(2):103-12. doi: 10.1159/000371706. Epub 2015 Mar 14.
Neonatal Acid-Base Status in Fetuses with Abnormal Vertebro- and Cerebro-Placental Ratios.
Morales-Roselló J(1), Khalil A, Ferri-Folch B, Perales-Marín A.
Author information:
(1)Servicio de Obstetricia, Hospital Universitario y Politécnico La Fe, Valencia,
Spain.
OBJECTIVE: A low cerebro-placental ratio (CPR) at term suggests the existence of
failure to reach growth potential (FRGP) with a higher risk of poor neonatal
acid-base status. This study aimed to evaluate whether similar findings were also
seen in the vertebral artery (vertebro-placental ratio, VPR), supplying 30% of
the cerebral flow.
METHODS: We studied term fetuses classified into groups according to birth weight
(BW), CPR and VPR. BW was expressed in centiles and ratios in multiples of the
median (MoM). Subsequently, associations with neonatal pH values were evaluated
by means of regression curves and Mann-Whitney tests.
RESULTS: VPR MoM correlated with BW centiles (p < 0.0001, R2 = 0.042) and its
distribution resembled that of CPR MoM (p < 0.001). When both arteries were
compared, adequate-for-gestational-age (AGA) fetuses with either low CPR or low
VPR had lower neonatal venous pH values (p < 0.05, p < 0.01, respectively).
However, in case of small-for-gestational-age (SGA) fetuses, only those with low
VPR had significantly lower neonatal arterial and venous pH values (p < 0.05).
CONCLUSIONS: Blood flow in the vertebral artery mimics that in the middle
cerebral artery supporting the FRGP model. Both CPR and VPR identify AGA fetuses
with lower neonatal pH values, but only VPR identifies SGA with lower pH values.
Hypoxemia might be reflected as a generalized cerebral vasodilation demonstrated
as low CPR and VPR.
DOI: 10.1159/000371706
PMID: 25790772  [PubMed - indexed for MEDLINE]

32. High Alt Med Biol. 2015 Mar;16(1):18-25. doi: 10.1089/ham.2014.1075. Epub 2015
Mar 11.
Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise.
Avnstorp MB(1), Rasmussen P, Brassard P, Seifert T, Overgaard M, Krustrup P,
Secher NH, Nordsborg NB.
Author information:
(1)1 Department of Anesthesia, The Copenhagen Muscle Research Center,
Rigshospitalet, University of Copenhagen , Copenhagen, Denmark .
Comment in
    High Alt Med Biol. 2015 Sep;16(3):267.
BACKGROUND: Intense physical activity increases the prevalence of acute mountain
sickness (AMS) that can occur within 10 h after ascent to altitudes above 1500 m
and is likely related to development of cerebral edema. This study evaluated
whether disturbed cerebral water and ion homeostasis can be detected when intense
exercise is carried out in hypoxia and monitored the influence of muscle
metabolism for changes in arterial variables.
METHODS: On two separate days, in random order, 30 min cycling exercise was
performed in either hypoxia (10% O2) or normoxia at an intensity that was
exhaustive in the hypoxic trial (∼120 W; n=9).
RESULTS: Exercise in hypoxia affected muscle metabolism, as evidenced by higher
(p<0.05) leg lactate release at 7.5 min and a continuous decline in arterial pH
(p<0.001) that was not observed in normoxia. Middle cerebral artery flow velocity
increased (p<0.01) with exercise under both circumstances. No cerebral net
exchange of Na(+) or K(+) was evident. Likewise, no significant net-exchange of
water over the brain was demonstrated and the arterial and jugular venous
hemoglobin concentrations were similar.
CONCLUSION: Challenging exercise in hypoxia for 30 min affected muscle metabolism
and increased an index of cerebral blood flow, but cerebral net water and ion
homeostasis remained stable. Thus, although AMS develops within hours and may be
related to exercise-induced disturbance of cerebral ion and water balance, such
changes are not detectable when subjects are exposed to acute 30 min maximal
exercise in hypoxia.
DOI: 10.1089/ham.2014.1075
PMID: 25761236  [PubMed - indexed for MEDLINE]

33. Vestn Oftalmol. 2014 Sep-Oct;130(5):5-10.
[Ocular surface acidity and buffering system (by studying the conjunctival sac)].
[Article in Russian]
Avetisov SÉ, Safonova TN, Novikov IA, Pateiuk LS, Griboedova IG.
As any mucous membrane the conjunctiva is characterized by a definite pH value
which guarantees-physiological functioning of the ocular surface. The most
commonly used method of assessment is potentiometric pH measurement with
ion-specific glass microelectrodes. The results, however, can be affected by such
factors, as conjunctival sac zoning, tissue acidity, epithelial trauma, and
reflex tear secretion. Few data and hypotheses are available on mechanisms of
maintaining the acid-base balance of the conjunctival sac (bicarbonate buffering
system in particular).OBJECTIVE: to study spatial variability of conjunctival
tear fluid pH and possible mechanisms of its maintenance using original methods
of acidity measurement and mineral content assessment.
MATERIAL AND METHODS: Tear pH was determined in 42 healthy participants (84 eyes)
by means of litmus test strips and computer- aided colorimetry. Electron probe
microanalysis in combination with energy dispersive spectrometry was performed in
8 healthy participants (8 eyes, 8 samples).
RESULTS: In the group of 42 healthy participants (84 eyes) the pH value of
conjunctival tear fluid varied from 6.30 to 7.23 with the average of 6.76 and pH
mode 6.74. The pH value of conjunctival mucous discharge was measured in 25
healthy participants (28 eyes) and varied from 7.00 to 8.00 with the average of
7.26 and pH mode 7.30. The main mineral components of tear fluid are chlorine,
sodium, potassium, and boron. Borate buffer is regarded as a mechanism of
maintaining the acid-base balance of the ocular surface.
CONCLUSIONS: The developed method of pH measurement ensuresreliable determination
of conjunctival sac acidity in accordance with zoning and heterogeneity of its
media as well as the complex structure of the tear film. In a healthy population,
the acidity of tear significantly differs from that of conjunctival mucous
discharge. Soluble chlorine, sodium, potassium, and boron compounds are the
prevailing mineral components of tear fluid. Borate buffer appears to be the most
stable of all mechanisms of maintaining the acid-base status of tear fluid.

PMID: 25711055  [PubMed - indexed for MEDLINE]

34. Lancet. 2015 Feb 21;385(9969):744. doi: 10.1016/S0140-6736(15)60030-7. Epub 2015
Feb 20.
Encephalopathy and high anion gap metabolic acidosis: an unusual herald of buried bumper syndrome.
Lopez EM(1), Ghetmiri E(1), Gettle LM(2), Reed MF(3), McAllister BP(4).
Author information:
(1)Department of Medicine, Penn State Milton S Hershey Medical Center, Penn State
College of Medicine, Hershey, PA, USA. (2)Department of Radiology, Penn State
Milton S Hershey Medical Center, Penn State College of Medicine, Hershey, PA,
USA. (3)Department of Surgery, Penn State Milton S Hershey Medical Center, Penn
State College of Medicine, Hershey, PA, USA. (4)Department of Medicine, Penn
State Milton S Hershey Medical Center, Penn State College of Medicine, Hershey,
PA, USA. Electronic address: bmcallister@hmc.psu.edu.
DOI: 10.1016/S0140-6736(15)60030-7
PMID: 25706220  [PubMed - indexed for MEDLINE]

35. Nutrition. 2015 Mar;31(3):466-74. doi: 10.1016/j.nut.2014.09.012. Epub 2014 Oct
16.
Single pyruvate intake induces blood alkalization and modification of resting
metabolism in humans.
Olek RA(1), Luszczyk M(2), Kujach S(2), Ziemann E(2), Pieszko M(3), Pischel I(4),
Laskowski R(2).
Author information:
(1)Department of Biochemistry, University of Physical Education and Sport,
Gdansk, Poland. Electronic address: Robol@awf.gda.pl. (2)Department of
Physiology, University of Physical Education and Sport, Gdansk, Poland.
(3)Department of Clinical Nutrition, Medical University of Gdansk, Gdansk,
Poland. (4)Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy,
University of London, London, United Kingdom; Phytolab GmbH & Co. KG,
Vestenbergsgreuth, Germany.
OBJECTIVES: Three separate studies were performed with the aim to 1) determine
the effect of a single sodium pyruvate intake on the blood acid-base status in
males and females; 2) compare the effect of sodium and calcium pyruvate salts and
establish their role in the lipolysis rate; and 3) quantify the effect of single
pyruvate intake on the resting energy metabolism.
METHODS: In all, 48 individuals completed three separate studies. In all the
studies, participants consumed a single dose of pyruvate 0.1 g/kg 60 min before
commencing the measurements. The whole blood pH, bicarbonate concentration, base
excess or plasma glycerol, free fatty acids, glucose concentrations, or resting
energy expenditure and calculated respiratory exchange ratio were determined. The
analysis of variance for repeated measurements was performed to examine the
interaction between treatment and time.
RESULTS: The single dose of sodium pyruvate induced blood alkalization, which was
more marked in the male than in the female participants. Following the ingestion
of sodium or calcium pyruvate, the blood acid-base parameters were higher than in
the placebo trial. Furthermore, 3-h postingestion glycerol was lower in both
pyruvate trials than in placebo. Resting energy expenditure did not differ
between the trials; however, carbohydrate oxidation was increased after sodium
pyruvate ingestion.
CONCLUSION: Pyruvate intake induced mild alkalization in a sex-dependent fashion.
Moreover, it accelerated carbohydrate metabolism and delayed the rate of glycerol
appearance in the blood, but had no effect on the resting energy expenditure.
Furthermore, sodium salt seems to have had a greater effect on the blood
buffering level than calcium salt.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nut.2014.09.012
PMID: 25701336  [PubMed - indexed for MEDLINE]

36. Crit Care. 2014 Dec 4;18(6):664. doi: 10.1186/s13054-014-0664-0.
Acid-base status is an important factor for inflammation, but don't forget CO2!
Payen D, Haloui H.
Comment on
    Crit Care. 2014;18(4):R154.
Zampieri and colleagues used sophisticated statistical methods to create a
picture of acid-base pattern and inflammation relationship in a clinical context.
The observed independent relationship between acidosis and albumin concentration
and inflammatory pattern opens up a new area for research. It has become clear
that, in addition to the characterization of mediators, receptors, and cellular
phenotypes, the inflammatory response has to be interpreted in light of acid-base
status, albumin concentration, and probably also carbon dioxide level.
DOI: 10.1186/s13054-014-0664-0
PMCID: PMC4330932
PMID: 25673361  [PubMed - indexed for MEDLINE]

37. Ginekol Pol. 2014 Dec;85(12):939-43.
[Heliox augmented mechanical ventilation in the treatment of premature infants with respiratory distress syndrome].
[Article in Polish]
Szczapa T, Gadzinowski J, Moczko J.
OBJECTIVE: The aim of the study was to assess the influence of mechanical
ventilation with helium-oxygen mixture (heliox) on basic vital signs,
oxygenation, acid-base balance and respiratory mechanics in newborns with
respiratory distress syndrome (RDS), previously treated with surfactant.
MATERIAL AND METHODS: The study was carried out in preterm newborns with
respiratory failure requiring mechanical ventilation due to RDS, requiring
Fi02>0.4 after a single dose of surfactant. Patients were ventilated using
PC-SIMV Parameters of mechanical ventilation, respiratory function, oxygenation,
acid-base balance and vital signs were recorded at baseline, one hour during and
one hour after heliox ventilation.
RESULTS: Ten newborns with RDS were enrolled in the study Mechanical ventilation
with heliox did not affect vital signs and patient general condition remained
stable during and after ventilation with heliox. Mechanical ventilation with
heliox was associated with a statistically significant increase in tidal volume
(mean 5.48 vs. 6.55 ml/kg). There were no significant changes in minute
ventilation and peak expiratory flow rate. Mechanical ventilation with heliox
allowed the use of significantly lower fractions of inspired oxygen (mean 0.55
vs. 0.35), with a significant decrease in the oxygenation index (mean 8.77 vs.
5.02) and alveolar-arterial oxygen tension difference (mean 263.81 vs. 113.28 mm
Hg). After ventilation with this gas mixture was stopped, the patients required
higher Fi02, 01 and AaD02 levels increased.
CONCLUSIONS: Mechanical ventilation with heliox was safe, improved oxygenation
and caused an increase in tidai, volume in newborns with RDS previously treated
with surfactant.

PMID: 25669064  [PubMed - indexed for MEDLINE]

38. Annu Rev Physiol. 2015;77:363-78. doi: 10.1146/annurev-physiol-021014-071854.
The role of pendrin in renal physiology.
Wall SM(1), Lazo-Fernandez Y.
Author information:
(1)Department of Medicine and.
Pendrin is a Na(+)-independent Cl(-)/HCO3(-) exchanger that localizes to type B
and non-A, non-B intercalated cells, which are expressed within the
aldosterone-sensitive region of the nephron, i.e., the distal convoluted tubule,
the connecting tubule, and the cortical collecting duct. Type B cells mediate
Cl(-) absorption and HCO3(-) secretion primarily through pendrin-mediated
Cl(-)/HCO3(-) exchange. At least in some treatment models, pendrin acts in tandem
with the Na(+)-dependent Cl(-)/HCO3(-) exchanger (NDCBE) encoded by Slc4a8 to
mediate NaCl absorption. The pendrin-mediated Cl(-)/HCO3(-) exchange process is
greatly upregulated in models of metabolic alkalosis, such as following
aldosterone administration or dietary NaHCO3 loading. It is also upregulated by
angiotensin II. In the absence of pendrin [Slc26a4 (-/-) or pendrin null mice],
aldosterone-stimulated NaCl absorption is reduced, which lowers the blood
pressure response to aldosterone and enhances the alkalosis that follows the
administration of this steroid hormone. Pendrin modulates aldosterone-induced
Na(+) absorption by changing ENaC abundance and function through a
kidney-specific mechanism that does not involve changes in the concentration of a
circulating hormone. Instead, pendrin changes ENaC abundance and function at
least in part by altering luminal HCO3(-) and ATP concentrations. Thus,
aldosterone and angiotensin II also stimulate pendrin expression and function,
which likely contributes to the pressor response of these hormones. This review
summarizes the contribution of the Cl(-)/HCO3(-) exchanger pendrin in distal
nephron function.
DOI: 10.1146/annurev-physiol-021014-071854
PMID: 25668022  [PubMed - indexed for MEDLINE]

39. Fetal Diagn Ther. 2015;38(1):55-60. doi: 10.1159/000368829. Epub 2015 Feb 3.
Neonatal Acid-Base Status in Term Fetuses: Mathematical Models Investigating
Cerebroplacental Ratio and Birth Weight.
Morales-Roselló J(1), Khalil A, Alberola-Rubio J, Hervas-Marín D, Morlando M,
Bhide A, Papageorghiou A, Perales-Marín A, Thilaganathan B.
Author information:
(1)Fetal Medicine Unit, St George Hospital, London, UK.
OBJECTIVE: Cerebroplacental ratio (CPR) is emerging as a marker of fetal hypoxia
at term. The aim of this study was to demonstrate graphically the
interrelationships among CPR, birthweight (BW), and neonatal pH, and construct 2D
and 3D representations of the areas with potential low pH.
METHODS: This was a retrospective study of 2,927 term fetuses evaluated according
to BW and CPR. The outcome was the acid-base status at birth. Multivariate
relationships among CPR, BW, and arterial and venous pH were depicted in 3D
scattergrams. Subsequently, trend surfaces were calculated and represented in 2D
contour graphs. Finally, 3D representations were constructed by smothering pH
data using moving average filters.
RESULTS: The trend surfaces and the 2D and 3D contour graphs showed the complex
association among the three variables. Although pH changed with CPR and BW, the
influence of the BW was smaller than the influence of the CPR, with this effect
being more evident in the venous than in the arterial pH.
CONCLUSIONS: Two scenarios threaten fetal well-being at term: a very low birth
weight and a very low fetal CPR. Our findings suggest that the importance of
fetal hemodynamics in determining the acid-base status at birth surpasses that of
fetal weight.
© 2015 S. Karger AG, Basel.
DOI: 10.1159/000368829
PMID: 25660123  [PubMed - indexed for MEDLINE]

40. N Engl J Med. 2015 Feb 5;372(6):546-54. doi: 10.1056/NEJMra1207788.
Acid-base problems in diabetic ketoacidosis.
Kamel KS, Halperin ML.
Comment in
    N Engl J Med. 2015 May 14;372(20):1969-70.
    N Engl J Med. 2015 May 14;372(20):1968.
    N Engl J Med. 2015 May 14;372(20):1968-9.
    N Engl J Med. 2015 May 14;372(20):1969.
DOI: 10.1056/NEJMra1207788
PMID: 25651248  [PubMed - indexed for MEDLINE]

41. Biomed Res Int. 2015;2015:901590. doi: 10.1155/2015/901590. Epub 2015 Jan 8.
The effect of bicarbonate administration via continuous venovenous hemofiltration
on acid-base parameters in ventilated patients.
Allegretti AS(1), Flythe JE(2), Benda V(3), Robinson ES(3), Charytan DM(3).
Author information:
(1)Division of Nephrology, Department of Medicine, Massachusetts General
Hospital, 7 Whittier Place, Suite 106, Boston, MA 02114, USA. (2)Division of
Nephrology and Hypertension, Department of Medicine and Genetics, UNC School of
Medicine, UNC Kidney Center, 7024 Burnett-Womack, CB No. 7155, Chapel Hill, NC
27599-7155, USA. (3)Renal Division, Department of Medicine, Brigham and Women's
Hospital, 75 Francis Street, MRB4, Boston, MA 02115, USA.
BACKGROUND: Acute kidney injury (AKI) and metabolic acidosis are common in the
intensive care unit. The effect of bicarbonate administration on acid-base
parameters is unclear in those receiving continuous venovenous hemofiltration
(CVVH) and mechanical ventilatory support.
METHODS: Metabolic and ventilatory parameters were prospectively examined in 19
ventilated subjects for up to 96 hours following CVVH initiation for AKI at an
academic tertiary care center. Mixed linear regression modeling was performed to
measure changes in pH, partial pressure of carbon dioxide (pCO2), serum
bicarbonate, and base excess over time.
RESULTS: During the 96-hour study period, pCO2 levels remained stable overall
(initial pCO2 42.0±14.6 versus end-study pCO2 43.8±16.1 mmHg; P=0.13 for
interaction with time), for those with initial pCO2≤40 mmHg (31.3±5.7 versus
35.0±4.8; P=0.06) and for those with initial pCO2>40 mmHg (52.7±12.8 versus
53.4±19.2; P=0.57). pCO2 decreased during the immediate hours following CVVH
initiation (42.0±14.6 versus 37.3±12.6 mmHg), though this change was
nonsignificant (P=0.052).
CONCLUSIONS: We did not detect a significant increase in pCO2 in response to the
administration of bicarbonate via CVVH in a ventilated population. Additional
studies of larger populations are needed to confirm this finding.
DOI: 10.1155/2015/901590
PMCID: PMC4306401
PMID: 25648653  [PubMed - indexed for MEDLINE]

42. Clin J Am Soc Nephrol. 2015 Feb 6;10(2):305-24. doi: 10.2215/CJN.08880914. Epub
2015 Jan 28.
Collecting duct intercalated cell function and regulation.
Roy A(1), Al-bataineh MM(1), Pastor-Soler NM(2).
Author information:
(1)Renal-Electrolyte Division, Department of Medicine; and. (2)Renal-Electrolyte
Division, Department of Medicine; and Department of Cell Biology, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania A.R. and M.M.A.
contributed equally to this work. pastorn@pitt.edu.
Intercalated cells are kidney tubule epithelial cells with important roles in the
regulation of acid-base homeostasis. However, in recent years the understanding
of the function of the intercalated cell has become greatly enhanced and has
shaped a new model for how the distal segments of the kidney tubule integrate
salt and water reabsorption, potassium homeostasis, and acid-base status. These
cells appear in the late distal convoluted tubule or in the connecting segment,
depending on the species. They are most abundant in the collecting duct, where
they can be detected all the way from the cortex to the initial part of the inner
medulla. Intercalated cells are interspersed among the more numerous
segment-specific principal cells. There are three types of intercalated cells,
each having distinct structures and expressing different ensembles of transport
proteins that translate into very different functions in the processing of the
urine. This review includes recent findings on how intercalated cells regulate
their intracellular milieu and contribute to acid-base regulation and sodium,
chloride, and potassium homeostasis, thus highlighting their potential role as
targets for the treatment of hypertension. Their novel regulation by paracrine
signals in the collecting duct is also discussed. Finally, this article addresses
their role as part of the innate immune system of the kidney tubule.
Copyright © 2015 by the American Society of Nephrology.
DOI: 10.2215/CJN.08880914
PMCID: PMC4317747
PMID: 25632105  [PubMed - indexed for MEDLINE]

43. N Engl J Med. 2015 Jan 22;372(4):391. doi: 10.1056/NEJMc1414731#SA5.
Integration of acid-base and electrolyte disorders.
Bellomo R, Kellum JA.
Comment in
    N Engl J Med. 2015 Jan 22;372(4):391-2.
Comment on
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
DOI: 10.1056/NEJMc1414731#SA5
PMID: 25607445  [PubMed - indexed for MEDLINE]

44. N Engl J Med. 2015 Jan 22;372(4):390. doi: 10.1056/NEJMc1414731#SA4.
Integration of acid-base and electrolyte disorders.
Figge JJ.
Comment in
    N Engl J Med. 2015 Jan 22;372(4):391-2.
Comment on
    N Engl J Med. 2014 Oct 9;371(15):1434-45.
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
DOI: 10.1056/NEJMc1414731#SA4
PMID: 25607444  [PubMed - indexed for MEDLINE]

45. N Engl J Med. 2015 Jan 22;372(4):390. doi: 10.1056/NEJMc1414731#SA3.
Integration of acid-base and electrolyte disorders.
Van Regenmortel N, Malbrain M, Jorens P.
Comment in
    N Engl J Med. 2015 Jan 22;372(4):391-2.
Comment on
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
DOI: 10.1056/NEJMc1414731#SA3
PMID: 25607443  [PubMed - indexed for MEDLINE]

46. N Engl J Med. 2015 Jan 22;372(4):389. doi: 10.1056/NEJMc1414731#SA2.
Integration of acid-base and electrolyte disorders.
Adrogué HJ, Gennari FJ.
Comment in
    N Engl J Med. 2015 Jan 22;372(4):391-2.
Comment on
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
DOI: 10.1056/NEJMc1414731#SA2
PMID: 25607442  [PubMed - indexed for MEDLINE]

47. N Engl J Med. 2015 Jan 22;372(4):389. doi: 10.1056/NEJMc1414731#SA1.
Integration of acid-base and electrolyte disorders.
Vaughan-Jones RD, Boron WF.
Comment in
    N Engl J Med. 2015 Jan 22;372(4):391-2.
Comment on
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
DOI: 10.1056/NEJMc1414731#SA1
PMCID: PMC4678889
PMID: 25607441  [PubMed - indexed for MEDLINE]

48. N Engl J Med. 2015 Jan 22;372(4):391-2. doi: 10.1056/NEJMc1414731.
Integration of acid-base and electrolyte disorders.
Seifter JL.
Comment on
    N Engl J Med. 2014 Nov 6;371(19):1821-31.
    N Engl J Med. 2015 Jan 22;372(4):389.
    N Engl J Med. 2015 Jan 22;372(4):391.
    N Engl J Med. 2015 Jan 22;372(4):390.
    N Engl J Med. 2015 Jan 22;372(4):390.
    N Engl J Med. 2015 Jan 22;372(4):389.
DOI: 10.1056/NEJMc1414731
PMID: 25607440  [PubMed - indexed for MEDLINE]

49. Chest. 2015 Jan;147(1):e18-21. doi: 10.1378/chest.14-0935.
A 44-year-old woman with metabolic acidosis, high anion gap, and delayed neurologic deterioration.
Vakil A, Upadhyay H, Sherani K, Cervellione K, Trepeta S, Patel MC.
A 44-year-old woman was brought to the ED from John F. Kennedy International
Airport. The patient was returning with her son from a 3-month visit to
Bangladesh. Her journey started with a 4-h flight from Dhaka, Bangladesh to
Dubai, United Arab Emirates. She consumed 240 mL of whiskey during the flight.
This was followed by a 14-h flight from Dubai to New York. According to the
patient's son, she did not consume any alcohol during the second flight. The
patient was in her usual state of health with normal mentation throughout her
journey. Upon landing, she started complaining of shortness of breath. After
disembarking, she was witnessed to have seizure-like activity with involuntary
passage of urine, following which she collapsed. The patient was intubated by
emergency medical services in the field.
DOI: 10.1378/chest.14-0935
PMID: 25560868  [PubMed - indexed for MEDLINE]

50. Nutr Clin Pract. 2015 Feb;30(1):14-20. doi: 10.1177/08845336145628

Saturación venosa central: Búsqueda de trabajos 2013 - 2016Fecha: 1/8/2016

 


1. Medicine (Baltimore). 2016 Jan;95(2):e2483. doi: 10.1097/MD.0000000000002483.

Effects of Hypothermic Cardiopulmonary Bypass on Internal Jugular Bulb Venous
Oxygen Saturation, Cerebral Oxygen Saturation, and sale replica iwc jubilee uk Bispectral Index in Pediatric
Patients Undergoing Cardiac Surgery: A Prospective Study.

Hu Z(1), Xu L, Zhu Z, Seal R, McQuillan PM.

Author information:
(1)From the Department of Anesthesiology, School of Medicine, The Children's
Hospital, Zhejiang University (ZH, ZZ); Department of Anesthesiology, The Second
Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China (LX);
Department of Anesthesia and Pain Medicine, Stollery Children's Hospital,
University of Alberta, Edmonton, Canada (RS); and Department of Anesthesiology,
Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, PA
(PMM).

The objective of this study was to evaluate the effect of hypothermic
cardiopulmonary bypass (CPB) on cerebral oxygen saturation (rSO2), internal
jugular bulb venous oxygen saturation (SjvO2), mixed venous oxygen saturation
(SvO2), and bispectral index (BIS) used to monitor cerebral oxygen balance in
pediatric patients.Sixty American Society of Anesthesiologists Class II-III
patients aged 1 to 4 years old with congenital heart disease scheduled for
elective cardiac surgery were included in this study. Temperature, BIS, rSO2,
mean arterial pressure, central venous pressure, cerebral perfusion pressure
(CPP), and hematocrit were recorded. Internal jugular bulb venous oxygen
saturation and SvO2 were obtained from blood gas analysis at the time points:
after induction of anesthesia (T0), beginning of CPB (T1), ascending aortic
occlusion (T2), 20 minutes after initiating CPB (T3), coronary reperfusion (T4),
separation from CPB (T5), and at the end of operation (T6). The effect of
hypothermia or changes in CPP on rSO2, SjvO2, SvO2, and BIS were
analyzed.Compared with postinduction baseline values, rSO2 significantly
decreased at all-time points: onset of extracorporeal circulation, ascending
aortic occlusion, 20 minutes after CPB initiation, coronary reperfusion, and
separation from CPB (P < 0.05). Compared with measurements made following
induction of anesthesia, SjvO2 significantly increased with initiation of CPB,
ascending aortic occlusion, 20 minutes after initiating CPB, coronary
reperfusion, and separation from CPB (P < 0.05). Compared with induction of
anesthesia, BIS significantly decreased with the onset of CPB, aortic cross
clamping, 20 minutes after initiating CPB, and coronary reperfusion (P < 0.05).
Bispectral index increased following separation from CPB. There was no
significant change in SvO2 during cardiopulmonary bypass (P > 0.05). Correlation
analysis demonstrated that rSO2 was positively related to CPP (r = 0.687,
P = 0.000), with a low linear correlation to temperature (r = 0.453, P = 0.000).
Internal jugular bulb venous oxygen saturation was negatively related to
temperature (r = -0.689, P = 0.000). Bispectral index was positively related to
both temperature (r = 0.824, P = 0.000) and CPP (r = 0.782, P = 0.000). Cerebral
oxygen saturation had a positive linear correlation with CPP and a low linear
correlation to temperature. Internal jugular bulb venous oxygen saturation had a
negative linear correlation to temperature.Pre-and and early postbypass periods
are vulnerable times for adequate cerebral oxygenation. Anesthetic management
must aim to optimize the supply and demand relationship.

DOI: 10.1097/MD.0000000000002483  Newest ANSI Codes In PDF
PMCID: PMC4718280
PMID: 26765454  [PubMed - indexed for MEDLINE]


2. Anaesth Intensive Care. 2016 Jan;44(1):14-9.

Pitfalls in haemodynamic monitoring in the postoperative and critical care
setting.

Ho KM(1).

Author information:
(1)Department of Intensive Care Medicine, Royal Perth Hospital, Perth, Western
Australia.

Haemodynamic monitoring is a vital part of daily practice in anaesthesia and
intensive care. Although there is evidence to suggest that goal-directed therapy
may improve outcomes in the perioperative period, which haemodynamic targets we
should aim at to optimise patient outcomes remain elusive and controversial. This
review highlights the pitfalls in commonly used haemodynamic targets, including
arterial blood pressure, central venous pressure, cardiac output, central venous
oxygen saturation and dynamic haemodynamic indices. Evidence suggests that
autoregulation in regional organ circulation may change either due to chronic
hypertension or different disease processes such as traumatic brain injury,
cerebrovascular ischaemia or haemorrhage; this will influence the preferred blood
pressure target. Central venous pressure can be influenced by multiple
pathophysiological factors and, unless central venous pressure is very low, it is
rarely useful as a predictor for fluid responsiveness. Central venous oxygen
saturation can be easily increased by a high arterial oxygen tension, making it
useless as a surrogate marker of good cardiac output or systemic oxygen delivery
in the presence of hyperoxaemia. Many dynamic haemodynamic indices have been
reported to predict fluid responsiveness, but they all have their own
limitations. There is also insufficient evidence to support that giving fluid
until the patient is no longer fluid responsive can improve patient-centred
outcomes. With the exception in the context of preventing contrast-induced
nephropathy, large randomised controlled studies suggest that excessive fluid
treatment may prolong duration of mechanical ventilation without preventing acute
kidney injury in the critically ill.


PMID: 26673584  [PubMed - indexed for MEDLINE]


3. Crit Care. 2015 Oct 21;19:359. doi: 10.1186/s13054-015-1079-2.

Alleviating central venous oxygen saturation (ScvO2): a new approach of kidney
protection after cardiac surgery?

Honore PM(1), Jacobs R(2), Hendrickx I(3), De Waele E(4), Nguyen DN(5), Spapen
HD(6).

Author information:
(1)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. Patrick.Honore@az.vub.ac.be.
(2)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. Rita.Jacobs@uzbrussel.be.
(3)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. Inne.Hendrickx@uzbrussel.be.
(4)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. Elisabeth.Dewaele@uzbrussel.be.
(5)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. DucNam.Nguyen@uzbrussel.be.
(6)ICU Department, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel,
101 Laarbeeklaan, 1090, Jette, Brussels, Belgium. Herbert.Spapen@uzbrussel.be.

Comment in
    Crit Care. 2015;19:359.

Comment on
    Crit Care. 2015;19:168.

DOI: 10.1186/s13054-015-1079-2
PMCID: PMC4618129
PMID: 26486127  [PubMed - indexed for MEDLINE]


4. Pak J Pharm Sci. 2015 Jul;28(4 Suppl):1461-4.

Comparison of clinical effect of dopamine and norepinephrine in the treatment of
septic shock.

Du Y(1), Wang L(1), Shi H(1), Gao M(1).

Author information:
(1)ICU, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan,
China.

This study aims to compare the clinical effect of dopamine and nor epinephrine in
the treatment of septic shock. Fifty cases with septic shock were randomly
divided into two groups. Patients in both two groups revived after taking
effective liquid. Then dopamine was pumped into central veins of patients in the
research group (group DA) in 2 μ/(kg•min) upon the conventional treatment, while
nor epinephrine was pumped into patients in the control group (group NE) in 0.1
μ/(kg•min), besides conventional treatment. The improvement of haemodynamics and
microcirculation perfusion indexes were compared between two groups before and
after treatment, as well as the improvement of tissue oxygen metabolism. The
results demonstrated that, central venous pressure (CVP), mean arterial pressure
(MAP), urine volume and central venous oxygen saturation (Scv O2) in both groups
before treatment was not statistically significant (P>0.05); 6 h after treatment,
CVP, MAP, urine volume and Scv O2 of group NE were higher than group DA; 12h and
24h after treatment, blood lactic acid clearance of group NE was superior than
group DA (P<0.05). All the above findings suggested that, both dopamine and nor
epinephrine are beneficial to improve microcirculation and tissue oxygen
metabolism in the treatment of septic shock, and the clinical effect of nor
epinephrine was distinctly better than dopamine.


PMID: 26431658  [PubMed - indexed for MEDLINE]


5. Int J Med Sci. 2015 Aug 5;12(9):680-8. doi: 10.7150/ijms.11720. eCollection 2015.

Earliest Bedside Assessment of Hemodynamic Parameters and Cardiac Biomarkers:
Their Role as Predictors of Adverse Outcome in Patients with Septic Shock.

Sasko B(1), Butz T(1), Prull MW(1), Liebeton J(1), Christ M(1), Trappe HJ(1).

Author information:
(1)Department of Cardiology, Ruhr University Bochum, Marien Hospital Herne,
Herne, Germany.

BACKGROUND: Early assessment and aggressive hemodynamic treatment have been shown
to increase the survival of patients in septic shock. Current and past sepsis
guidelines recommend a resuscitation protocol including central venous pressure
(CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen
saturation (ScvO2) for resuscitation within the first six hours. Currently, the
established severity score systems like APACHE II score, SOFA score or SAPS II
score predict the outcome of critically ill patients on the bases of variables
obtained only after the first 24 hours. The present study aims to evaluate the
risk of short-term mortality for patients with septic shock by the earliest
possible assessment of hemodynamic parameters and cardiac biomarkers as well as
their role for the prediction of the adverse outcome.
METHODS: 52 consecutive patients treated for septic shock in the intensive care
unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were
prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO2,
left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin
I) at the ICU admission were evaluated in regard to their influence on mortality.
The primary endpoint was all-cause mortality within 28 days after the admission.
RESULTS: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5
years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28
patients reached the primary endpoint (mortality 54%). Patients presenting with
hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of
28-day mortality as compared with the group of patients without hypotension
(28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the
hypotension present group had significantly higher lactate concentration
(p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after
the first 24 hours higher APACHE II scores (p=0.04). A MAP <65 mmHg was the only
hemodynamic parameter significantly predicting the primary endpoint (OR: 4.1, CI:
1.1 - 14.8, p=0.008), whereas the remaining hemodynamic variables CVP, ScvO2,
Hematocrit, Troponin I and left ventricular ejection fraction (LVEF) seemed to
have no influence on survival. Besides, non-survivors had a significantly higher
age (74.1±9.0 vs. 68.4±6.9, p=0.01). If hypotension coincided with an age ≥72
years, the 28-day mortality rate escalated to 88%.
CONCLUSIONS: In our study, we identified a risk group with an exceedingly high
mortality rate: the patients with an age ≥72 years and presenting with
hypotension (MAP <65 mmHg). These data can be easily obtained at the time of the
very first patient contact. As a result, an aggressive and a more effective
treatment can be initiated within the first minutes of the primary care, possibly
reducing organ failure and short-term mortality in this risk group.

DOI: 10.7150/ijms.11720
PMCID: PMC4571544
PMID: 26392804  [PubMed - indexed for MEDLINE]


6. Crit Care. 2015 Sep 14;19:330. doi: 10.1186/s13054-015-1057-8.

Clinical classification of tissue perfusion based on the central venous oxygen
saturation and the peripheral perfusion index.

He H(1), Long Y(2), Liu D(3), Wang X(4), Zhou X(5).

Author information:
(1)Department of Critical Care Medicine, Peking Union Medical College Hospital,
Peking Union Medical College, Chinese Academy of Medical Science, 1 shuaifuyuan,
Dongcheng District, 100730, Beijing, China. tjmuhhw@126.com. (2)Department of
Critical Care Medicine, Peking Union Medical College Hospital, Peking Union
Medical College, Chinese Academy of Medical Science, 1 shuaifuyuan, Dongcheng
District, 100730, Beijing, China. iculong_yun@163.com. (3)Department of Critical
Care Medicine, Peking Union Medical College Hospital, Peking Union Medical
College, Chinese Academy of Medical Science, 1 shuaifuyuan, Dongcheng District,
100730, Beijing, China. tjmuhhw@163.com. (4)Department of Critical Care Medicine,
Peking Union Medical College Hospital, Peking Union Medical College, Chinese
Academy of Medical Science, 1 shuaifuyuan, Dongcheng District, 100730, Beijing,
China. icuwang_xiao_ting@163.com. (5)Department of Critical Care Medicine, Peking
Union Medical College Hospital, Peking Union Medical College, Chinese Academy of
Medical Science, 1 shuaifuyuan, Dongcheng District, 100730, Beijing, China.
xiangzhou_icu@163.com.

INTRODUCTION: We investigated whether combining the peripheral perfusion index
(PI) and central venous oxygen saturation(ScvO2) would identify subsets of
patients for assessing the tissue perfusion and predicting outcome during the
resuscitation in critically ill patients.
METHODS: A total of 202 patients with central venous catheters for resuscitation
were enrolled in this prospective observational study. The arterial, central
venous blood gas and the PI were measured simultaneously at the enrollment (T0)
and 8 h (T8) after early resuscitation. Based on the distribution of the PI in
healthy population, a cutoff of PI ≥ 1.4 was defined as a normal PI. Moreover,
the critical value of PI was defined as the best cutoff value related to the
mortality in the study population. The PI impairment stratification is defined as
follows: a normal PI(≥ 1.4), mild PI impairment (critical value < PI < 1.4) and
critical PI impairment (PI ≤ critical value).
RESULTS: The PI at T8 was with the greatest AUC for prediction the 30-day
mortality and PI is an independent risk factor for 30-day mortality. Moreover, a
cutoff of PI < 0.6 is related to poor outcomes following resuscitation. So, based
on cutoffs of ScvO2 (70%) and critical PI (0.6) at T8, we assigned the patients
to four categories: group 1 (PI ≤ 0.6 on ScvO2 < 70%), group 2 (PI ≤ 0.6 on
ScvO2 ≥ 70%), group 3 (PI > 0.6 on ScvO2 < 70%), and group 4 (PI > 0.6 on ScvO2 ≥
70%). The combination of low ScvO2(<70%) and PI(≤ 0.6) was associated with the
lowest survival rates at 30 days [log rank (Mantel-Cox) = 87.518, p < 0.0001].
The sub-group patients who had high ScvO2(>80%) at T8 were with low mortality and
high PI. Moreover, the normal PI (≥ 1.4) did not show a better outcome than mild
impaired PI (0.6-1.4) patients who had a normalized ScvO2(>70%) after
resuscitation. The PI was correlated with the lactate, P(v-a)CO2, and ScvO2 in
all the measurements (n = 404). These relationships are strengthened with
abnormal PI (PI < 1.4) but not with normal PI (PI ≥ 1.4).
CONCLUSION: Complementing ScvO2 assessment with PI can better identify endpoints
of resuscitation and adverse outcomes. Pursuing a normalized PI (≥ 1.4) may not
result in better outcomes for a mild impaired PI after ScvO2 is normalized.

DOI: 10.1186/s13054-015-1057-8
PMCID: PMC4568576
PMID: 26369784  [PubMed - indexed for MEDLINE]


7. Crit Care. 2015 Aug 31;19:304. doi: 10.1186/s13054-015-1014-6.

Association of left ventricular longitudinal strain with central venous oxygen
saturation and serum lactate in patients with early severe sepsis and septic
shock.

Lanspa MJ(1,)(2), Pittman JE(3), Hirshberg EL(4,)(5,)(6), Wilson EL(7), Olsen
T(8), Brown SM(9,)(10), Grissom CK(11,)(12).

Author information:
(1)Critical Care Echocardiography Service, Intermountain Medical Center, Salt
Lake City, UT, USA. michael.lanspa@imail.org. (2)Division of Pulmonary and
Critical Care Medicine, University of Utah, Salt Lake City, UT, USA.
michael.lanspa@imail.org. (3)Critical Care Echocardiography Service,
Intermountain Medical Center, Salt Lake City, UT, USA. joel.pittman@imail.org.
(4)Critical Care Echocardiography Service, Intermountain Medical Center, Salt
Lake City, UT, USA. ellie.hirshberg@imail.org. (5)Division of Pulmonary and
Critical Care Medicine, University of Utah, Salt Lake City, UT, USA.
ellie.hirshberg@imail.org. (6)Department of Pediatrics, University of Utah, Salt
Lake City, UT, USA. ellie.hirshberg@imail.org. (7)Critical Care Echocardiography
Service, Intermountain Medical Center, Salt Lake City, UT, USA.
emily.wilson@imail.org. (8)Critical Care Echocardiography Service, Intermountain
Medical Center, Salt Lake City, UT, USA. troy.olsen2@imail.org. (9)Critical Care
Echocardiography Service, Intermountain Medical Center, Salt Lake City, UT, USA.
samuel.brown@imail.org. (10)Division of Pulmonary and Critical Care Medicine,
University of Utah, Salt Lake City, UT, USA. samuel.brown@imail.org. (11)Critical
Care Echocardiography Service, Intermountain Medical Center, Salt Lake City, UT,
USA. colin.grissom@imail.org. (12)Division of Pulmonary and Critical Care
Medicine, University of Utah, Salt Lake City, UT, USA. colin.grissom@imail.org.

INTRODUCTION: In septic shock, assessment of cardiac function often relies on
invasive central venous oxygen saturation (ScvO2). Ventricular strain is a
non-invasive method of assessing ventricular wall deformation and may be a
sensitive marker of heart function. We hypothesized that it may have a
relationship with ScvO2 and lactate.
METHODS: We prospectively performed transthoracic echocardiography in patients
with severe sepsis or septic shock and measured (1) left ventricular longitudinal
strain from a four-chamber view and (2) ScvO2. We excluded patients for whom
image quality was inadequate or for whom ScvO2 values were unobtainable. We
determined the association between strain and ScvO2 with logistic and linear
regression, using covariates of mean arterial pressure, central venous pressure,
and vasopressor dose. We determined the association between strain and lactate.
We considered strain greater than -17% as abnormal and strain greater than -10%
as severely abnormal.
RESULTS: We studied 89 patients, 68 of whom had interpretable images. Of these
patients, 42 had measurable ScvO2. Sixty percent of patients had abnormal strain,
and 16% had severely abnormal strain. Strain is associated with low ScvO2 (linear
coefficient -1.05, p =0.006; odds ratio 1.23 for ScvO2 <60%, p =0.016). Patients
with severely abnormal strain had significantly lower ScvO2 (56.1% vs. 67.5%, p
<0.01) and higher lactate (2.7 vs. 1.9 mmol/dl, p =0.04) than those who did not.
Strain was significantly different between patients, based on a threshold ScvO2
of 60% (-13.7% vs. -17.2%, p =0.01) but not at 70% (-15.0% vs. -18.2%, p =0.08).
CONCLUSIONS: Left ventricular strain is associated with low ScvO2 and
hyperlactatemia. It may be a non-invasive surrogate for adequacy of oxygen
delivery during early severe sepsis or septic shock.

DOI: 10.1186/s13054-015-1014-6
PMCID: PMC4553920 Engineer Standards Download
PMID: 26321626  [PubMed - indexed for MEDLINE]


8. Crit Care. 2015 Aug 28;19:286. doi: 10.1186/s13054-015-1011-9.

Early goal-directed resuscitation of patients with septic shock: current evidence
and future directions.

Gupta RG(1), Hartigan SM(2), Kashiouris MG(3), Sessler CN(3), Bearman GM(4).

Author information:
(1)Division of Pulmonary Disease and Critical Care Medicine, Department of
Internal Medicine, Virginia Commonwealth University School of Medicine, P.O. Box
980050, Richmond, VA, 23298, USA. guptar4@vcu.edu. (2)Division of General
Internal Medicine, Department of Internal Medicine, Virginia Commonwealth
University School of Medicine, P.O. Box 980070, Richmond, VA, 23298, USA.
(3)Division of Pulmonary Disease and Critical Care Medicine, Department of
Internal Medicine, Virginia Commonwealth University School of Medicine, P.O. Box
980050, Richmond, VA, 23298, USA. (4)Division of Infectious Diseases, Department
of Internal Medicine, Virginia Commonwealth University School of Medicine, P.O.
Box 980019, Richmond, VA, 23298, USA.

Severe sepsis and septic shock are among the leading causes of mortality in the
intensive care unit. Over a decade ago, early goal-directed therapy (EGDT)
emerged as a novel approach for reducing sepsis mortality and was incorporated
into guidelines published by the international Surviving Sepsis Campaign. In
addition to requiring early detection of sepsis and prompt initiation of
antibiotics, the EGDT protocol requires invasive patient monitoring to guide
resuscitation with intravenous fluids, vasopressors technical codes download , red cell transfusions, and
inotropes. The effect of these measures on patient outcomes, however, remains
controversial. Recently, three large randomized trials were undertaken to
re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in
the United States, the ARISE trial in Australia and New Zealand, and the ProMISe
trial in England. These trials showed that EGDT did not significantly decrease
mortality in patients with septic shock compared with usual care. In particular,
whereas early administration of antibiotics appeared to increase survival,
tailoring resuscitation to static measurements of central venous pressure and
central venous oxygen saturation did not confer survival benefit to most
patients. In the following review, we examine these findings as well as other
evidence from recent randomized trials of goal-directed resuscitation. We also
discuss future areas of research and emerging paradigms in sepsis trials.

DOI: 10.1186/s13054-015-1011-9
PMCID: PMC4552276
PMID: 26316210  [PubMed - indexed for MEDLINE]


9. Einstein (Sao Paulo). 2015 Jul-Sep;13(3):462-8. doi:
10.1590/S1679-45082015RW3273. Epub 2015 Aug 21.

Fluid therapy for septic shock resuscitation: which fluid should be used?

[Article in English, Portuguese]

Corrêa TD(1), Rocha LL(1), Pessoa CM(1), Silva E(1), de Assuncao MS(1).

Author information:
(1)Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.

Early resuscitation of septic shock patients reduces the sepsis-related morbidity
and mortality. The main goals of septic shock resuscitation include volemic
expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided
by central venous pressure, mean arterial api standards in pdf pressure, mixed or central venous
oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation,
possibly in association with vasopressors, inotropes and red blood cell
concentrate transfusion may be necessary to achieve those hemodynamic goals.
Nonetheless, even though fluid administration is one of the most common
interventions offered to critically ill patients, the most appropriate type of
fluid to be used remains controversial. According to recently published clinical
trials, crystalloid solutions seem to be the most appropriate type of fluids for
initial resuscitation of septic shock patients. Balanced crystalloids have
theoretical advantages over the classic solutions, but there is not enough
evidence to indicate it as first-line treatment. Additionally, when large amounts
of fluids are necessary to restore the hemodynamic stability, albumin solutions
may be a safe and effective alternative. Hydroxyethyl starches solutions must be
avoided in septic patients due to the increased risk of acute renal failure,
increased need for renal replacement therapy and increased mortality. Our
objective was to present a narrative review of the literature regarding the major
types of fluids and their main drawbacks in the initial resuscitation of the
septic shock patients.

DOI: 10.1590/S1679-45082015RW3273
PMID: 26313437  [PubMed - indexed for MEDLINE]


10. Anaesth Intensive Care. 2015 Sep;43(5):628-34.

Central venous-to-arterial carbon dioxide gradient as a marker of occult tissue
hypoperfusion after major surgery.

Silbert BI(1), Litton E(2), Ho KM(3).

Author information:
(1)ICU Registrar, Department of Intensive Care Medicine, Royal Perth Hospital,
Perth, Western Australia. (2)Staff Specialist, Department of Intensive Care
Medicine, Royal Perth Hospital; Clinical Senior Lecturer, School of Medicine and
Pharmacology, University of Western Australia, Perth, Western Australia. (3)Staff
Specialist, Department of Intensive Care Medicine, Royal Perth Hospital; Clinical
Associate Professor, School of Population Health, University of Western
Australia, Perth, Western Australia.

The central venous-arterial carbon dioxide tension gradient ('CO₂gap') has been
shown to correlate with cardiac output and tissue perfusion in septic shock.
Compared to central venous oxygen saturation (SCVO2), the CO₂gap is less
susceptible to the effect of hyperoxia and may be particularly useful as an
adjunctive haemodynamic target in the perioperative period. This study
investigated whether a high CO₂gap was associated with an increased systemic
oxygen extraction (O2ER >0.3) or occult tissue hypoperfusion in 201 patients in
the immediate postoperative period. The median CO₂gap of all patients was 8 mmHg
(IQR 6 to 9), and a large CO₂gap was very common (> 6mmHg in 139 patients [69%],
95% CI 63 to 75; >5 mmHg in 170 patients [85%], 95% CI 79 to 89). A CO₂ gap >5
mmHg had a higher sensitivity (93%) and negative predictive value (74%) than a
CO₂gap >6 mmHg in excluding occult tissue hypoperfusion. Of the four variables
that were predictive of an increased O₂ER in the multivariate analysis-CO₂gap,
arterial pH, haemoglobin and arterial lactate concentrations-the CO₂gap (odds
ratio 4.41 per mmHg increment, 95% CI 1.7 to 11.2, P=0.002) was most important
and explained about 34% of the variability in the risk of occult tissue
hypoperfusion. In conclusion, a normal CO₂ gap (<5 mmHg) had a high sensitivity
and negative predictive value in excluding inadequate systemic oxygen delivery
and may be useful as an adjunct to other haemodynamic targets in avoiding occult
tissue hypoperfusion in the perioperative setting when high inspired oxygen
concentrations are used.


PMID: 26310414  [PubMed - indexed for MEDLINE]


11. Niger J Clin Pract. 2015 Nov-Dec;18(6):810-3. doi: 10.4103/1119-3077.163281.

Is there a relationship between the diameter of the inferior vena cava and
hemodynamic parameters in critically ill patients?

Aydin SA(1), Ozdemir F, Taskin G, Ocakoglu G, Yıldırım H, Koksal O.

Author information:
(1)Department of Emergency, Faculty of Medicine, Uludag University, Bursa,
Turkey.

INTRODUCTION: The early detection of critically ill patients together with the
rapid initiation of effective treatment in emergency departments(ED) increase the
survival rates.
AIM: This study investigated whether a correlation exists between haemodynamic
parameters of critically ill patients and the diameter of the inferior vena cava
(IVC).
MATERIALS AND METHODS: A cross-sectional study was performed included patients
aged ≥18 years with an unstable haemodynamic and/or respiratory status who were
referred to the ED for non-traumatic issues. IVC diameters were measured by
ultrasound (US) and then central venous pressures (CVP) were measured.
Anteroposterior (AP) and mediolateral (ML) diameters of the IVC, both in the
inspirium (IAP, IML) and expirium (EAP, EML), were measured by US.
RESULTS: 102 patients were evaluated with a median age of 59. The relationship
between the diameters of IVC and CVP was evaluated and significant correlation
was found in IAP, EAP according to CVP values (p<0.001). ROC analyses were
performed and significant relationship was found between the EAP diameter with
haemoglobin (Hmg), haemotocrit (Hct), and central venous oxygen saturation
(ScvO2) and also significant correlation was detected between the IAP diameter
and white blood cell (WBC).
DISCUSSION: We detected significant correlation between the CVP and the IVC
diameter in our study compatible with recent studies besides, significant
correlation was found between the diameter of the IVC and CVP values as well as
between the EAP diameter and Hmg, Hct, ScvO2 levels.
CONCLUSION: Measurement of IVC diameters, especially EAP may be useful at the
monitoring of critically ill patients in ED.

DOI: 10.4103/1119-3077.163281
PMID: 26289523  [PubMed - indexed for MEDLINE]


12. Am J Cardiol. 2015 Sep 15;116(6):965-8. doi: 10.1016/j.amjcard.2015.06.020. Epub
2015 Jun 25.

Usefulness of the Red Blood Cell Distribution Width to Predict Heart Failure in
Patients With a Fontan Circulation.

Kojima T(1), Yasuhara J(1), Kumamoto T(1), Shimizu H(1), Yoshiba S(1), Kobayashi
T(1), Sumitomo N(2).

Author information:
(1)Department of Pediatric Cardiology, Saitama Medical University International
Medical Center, Saitama, Japan. (2)Department of Pediatric Cardiology, Saitama
Medical University International Medical Center, Saitama, Japan. Electronic
address: sumitomo@saitama-med.ac.jp.

The red blood cell distribution width (RDW) is a quantitative measure of the
variability in the size of circulating erythrocytes. We aimed to study whether
higher levels of the RDW were associated with heart failure in a Fontan
circulation and to analyze its clinical value compared to brain natriuretic
peptide. This retrospective study included 38 consecutive pediatric patients with
a Fontan circulation who underwent routine cardiac catheterization at the
International Medical Center, Saitama Medical University from October 2010 to
July 2014. We assessed the relation between the RDW and catheterization data such
as the central venous pressure (CVP), mixed venous oxygen saturation (SvO2), and
cardiac index (CI). The RDW was positively correlated with the CVP (p = 0.0002).
The elevated RDW group had a significantly greater CVP than the normal RDW group
(p = 0.0003). Also, the RDW was negatively correlated with the SvO2 (p = 0.0004).
The elevated RDW group had a significantly less SvO2 than the normal RDW group (p
<0.0001). The CI in the elevated RDW group was lower than that in the normal RDW
group (p = 0.0421). In the multivariate regression analysis, the RDW was a
significant independent predictor of the CVP and SvO2. The BNP level did not have
any significant relation with the CVP, SvO2, or CI. The RDW is a convenient and
powerful marker for detecting heart failure in a Fontan circulation.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.amjcard.2015.06.020
PMID: 26239579  [PubMed - indexed for MEDLINE]


13. Crit Care Med. 2015 Oct;43(10):2164-70. doi: 10.1097/CCM.0000000000001191.

Prevalence and Risk Factors of Stress Cardiomyopathy After Convulsive Status
Epilepticus in ICU Patients.

Belcour D(1), Jabot J, Grard B, Roussiaux A, Ferdynus C, Vandroux D, Vignon P.

Author information:
(1)1Medical-Surgical ICU, Félix Guyon Hospital, Teaching Hospital of La Réunion,
Saint Denis, France. 2Department of Biostatistics, Félix Guyon Hospital, Teaching
Hospital of La Réunion, Saint Denis, France. 3Medical-Surgical ICU, Teaching
Hospital of Limoges, Limoges, France. 4INSERM CIC1435, Limoges, France.
5University of Limoges, Limoges, France.

OBJECTIVE: Although stress cardiomyopathy has been described in association with
epilepsy, its frequency in patients with convulsive status epilepticus remains
unknown. Accordingly, we sought to determine the prevalence and risk factors of
stress cardiomyopathy in patients admitted to the ICU for convulsive status
epilepticus.
DESIGN: Prospective, descriptive, single-center study.
SETTING: Medical-surgical ICU of a teaching hospital.
PATIENTS: Thirty-two consecutive ventilated patients (21 men; age, 50 ± 18 yr;
Simplified Acute Physiology Score II, 53 ± 15; Sequential Organ Failure
Assessment, 6 ± 2) hospitalized in the ICU for convulsive status epilepticus.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, transthoracic
echocardiography, biological data, and electrocardiogram were obtained serially
on ICU admission (H0), and after 6, 12, 24, and 48 hours of hospitalization (H6,
H12, H24, and H48). Stress cardiomyopathy was defined as a 20% decrease in left
ventricular ejection fraction between H0 or H6 and H48. Stress cardiomyopathy was
diagnosed in 18 patients (56%; 95% CI, 38-74%). Mean left ventricular ejection
fraction, left ventricular stroke index and cardiac index were initially (at H0
or H6 according to lowest individual values) significantly reduced in stress
cardiomyopathy patients (45 ± 14% vs 61 ± 6%, p < 0.001; 24 ± 8 vs 28 ± 8
mL/m(2), p < 0.05; 2.3 ± 0.7 vs 3.0 ± 0.8 L/min/m(2), p < 0.05, respectively) and
increased secondarily to reach similar mean values than those observed in
patients without transient left ventricular dysfunction at H24. Dobutamine was
more frequently used in patients with stress cardiomyopathy. Mean lactate level
was increased and significantly higher in stress cardiomyopathy patients at H0
and H6, whereas mean central venous oxygen saturation was preserved but
significantly lower in this group. Only three patients with stress cardiomyopathy
had left ventricular regional wall motion abnormalities but normal coronary
angiography. Risk factors of stress cardiomyopathy were age and Simplified Acute
Physiology Score II.
CONCLUSIONS: These results suggest that stress cardiomyopathy is common in
patients admitted to the ICU for convulsive status epilepticus. Accordingly,
these patients should be screened for stress cardiomyopathy and monitored if they
present with hemodynamic compromise.

DOI: 10.1097/CCM.0000000000001191
PMID: 26237133  [PubMed - indexed for MEDLINE]


14. Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1340-9. doi: 10.2215/CJN.02780314. Epub
2015 Jul 24.

Low Systemic Oxygen Delivery and BP and Risk of Progression of Early AKI.

Raimundo M(1), Crichton S(2), Syed Y(3), Martin JR(3), Beale R(3), Treacher D(3),
Ostermann M(4).

Author information:
(1)Department of Critical Care, King's College London, Guy's and St. Thomas'
Foundation Hospital, London, United Kingdom; Santa Maria Hospital, North Lisbon
Hospital Center, Lisbon, Portugal; and. (2)Division of Health and Social Care
Research, King's College London, London, United Kingdom. (3)Department of
Critical Care, King's College London, Guy's and St. Thomas' Foundation Hospital,
London, United Kingdom; (4)Department of Critical Care, King's College London,
Guy's and St. Thomas' Foundation Hospital, London, United Kingdom;
marlies.ostermann@gstt.nhs.uk.

Comment in
    Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1311-3.

BACKGROUND AND OBJECTIVES: The optimal hemodynamic management of patients with
early AKI is unknown. This study aimed to investigate the association between
hemodynamic parameters in early AKI and progression to severe AKI and hospital
mortality.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively
analyzed the data of all patients admitted to the adult intensive care unit in a
tertiary care center between July 2007 and June 2009 and identified those with
stage 1 AKI (AKI I) per the AKI Network classification. In patients in whom
hemodynamic monitoring was performed within 12 hours of AKI I, hemodynamic
parameters in the first 12 hours of AKI I and on the day of AKI III (if AKI III
developed) or 72 hours after AKI I (if AKI III did not develop) were recorded.
Risk factors for AKI III and mortality were identified using univariate and
multivariate logistic regression analyses.
RESULTS: Among 790 patients with AKI I, 210 (median age 70 years; 138 men) had
hemodynamic monitoring within 12 hours of AKI I; 85 patients (41.5%) progressed
to AKI III and 91 (43%) died in the hospital. AKI progressors had a significantly
higher Sequential Organ Failure Assessment score (8.0 versus 9.6; P<0.001), lower
indexed systemic oxygen delivery (DO2I) (median 325 versus 405 ml/min per m(2);
P<0.001), higher central venous pressure (16 versus 13; P=0.02), and lower mean
arterial blood pressure (MAP) (median 71 versus 74 mmHg; P=0.01) in the first 12
hours of AKI I compared with nonprogressors. Multivariate analysis confirmed that
raised lactate, central venous pressure, and Sequential Organ Failure Assessment
score as well as mechanical ventilation were independently associated with
progression to AKI III; higher DO2I and MAP were independently associated with a
lower risk of AKI III but not survival. The associations were independent of
sepsis, heart disease, recent cardiac surgery, or chronic hypertension.
CONCLUSIONS: Higher DO2I and MAP in early AKI were independently associated with
a lower risk of progression.

Copyright © 2015 by the American Society of Nephrology.

DOI: 10.2215/CJN.02780314
PMCID: PMC4527018 [Available on 2016-08-07]
PMID: 26209157  [PubMed - indexed for MEDLINE]


15. Crit Care. 2015 Jun 19;19:260. doi: 10.1186/s13054-015-0968-8.

Management of septic shock: a protocol-less approach.

Cabrera JL(1), Pinsky MR(2).

Author information:
(1)Department of Critical Care Medicine, University of Pittsburgh, 642A Scaife
Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA. cabrerajl@upmc.edu.
(2)Department of Critical Care Medicine, University of Pittsburgh, 606 Scaife
Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA. pinskymr@upmc.edu.

BACKGROUND: In a single-center study published more than a decade ago involving
patients presenting to the emergency department with severe sepsis and septic
shock, mortality was markedly lower among those who were treated according to a
6-h protocol of early goal-directed therapy (EGDT), in which intravenous fluids,
vasopressors, inotropes, and blood transfusions were adjusted to reach central
hemodynamic targets including central venous pressure, central venous oxygen
saturation, and indirect estimates of cardiac output, than among those receiving
usual care.
METHODS:
OBJECTIVE: The objective was to determine whether these EGDT findings were
generalizable and whether all aspects of the EGDT protocol were necessary to
achieve those outcomes.
DESIGN: A multicenter randomized three-arm controlled trial.
SETTING: Thirty-one academic emergency departments in the United States.
SUBJECTS: Patients older than 18 years of age presenting to the emergency
department with septic shock.
INTERVENTION: Patients were assigned to one of three groups for 6 h of
resuscitation: protocol-based EGDT as defined by River and colleagues;
protocol-based standard therapy that did not require the placement of a central
venous catheter, administration of inotropes, or blood transfusions; and usual
care which mandated no specific monitoring or management approaches.
OUTCOMES: The primary end point was 60-day in-hospital mortality. Also tested
sequentially was whether protocol-based care (EGDT and standard therapy groups
combined) was superior to usual care and whether protocol-based EGDT was superior
to protocol-based standard therapy. Secondary outcomes included longer-term
mortality and the need for organ support.
RESULTS: A total of 1,351 patients were enrolled, of whom 1,341 were evaluable
due to patient/family request: 439 were randomly assigned to protocol-based EGDT,
446 to protocol-based standard therapy, and 456 to usual care. Resuscitation
strategies differed significantly with respect to the monitoring of central
venous pressure and central venous oxygen and the use of intravenous fluids,
vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths
in the protocol-based EGDT group (21.0 %), 81 in the protocol-based standard
therapy group (18.2 %), and 86 in the usual care group (18.9 %) (relative risk
with protocol-based therapy versus usual care, 1.04; 95 % confidence interval,
0.82 to 1.31; P = 0.83; relative risk with protocol-based EGDT versus
protocol-based standard therapy, 1.15; 95 % CI, 0.88 to 1.51; P = 0.31). There
were no significant differences in 90-day mortality, 1-year mortality, or the
need for organ support.
CONCLUSIONS: In a multicenter trial conducted in the tertiary care setting,
protocol-based resuscitation of patients in whom septic shock was diagnosed in
the emergency department did not improve outcomes.

DOI: 10.1186/s13054-015-0968-8
PMCID: PMC4474443
PMID: 26088759  [PubMed - indexed for MEDLINE]


16. BMC Anesthesiol. 2015 Jun 12;15:91. doi: 10.1186/s12871-015-0072-2.

Using clinical parameters to guide fluid therapy in high-risk thoracic surgery. A
retrospective, observational study.

Bjerregaard LS(1), Møller-Sørensen H(2), Hansen KL(3), Ravn J(4), Nilsson JC(5).

Author information:
(1)Section for Surgical Pathophysiology & Department of Cardiothoracic
Anaesthesiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9,
DK-2100, Copenhagen, Denmark. lars.stryhn.bjerregaard@regionh.dk. (2)Department
of Cardiothoracic Anaesthesiology, Rigshospitalet, University of Copenhagen,
Blegdamsvej 9, DK-2100, Copenhagen, Denmark. hassedk@gmail.com. (3)Department of
Radiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100,
Copenhagen, Denmark. lindskov@gmail.com. (4)Department of Cardiothoracic Surgery,
Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen,
Denmark. jesper.ravn@regionh.dk. (5)Department of Cardiothoracic Anaesthesiology,
Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen,
Denmark. jens.christian.nilsson@regionh.dk.

BACKGROUND: Despite extensive research, the debate continues as to the optimal
way of guiding intraoperative and postoperative fluid therapy. In 2009 we changed
our institutional guideline for perioperative fluid therapy in patients
undergoing extrapleural pneumonectomy (EPP) and implemented the use of central
venous oxygen saturation and intended low urine output to guide therapy in the
early postoperative period. Here we evaluate the consequences of our changes.
METHODS: Retrospective, observational study of 30 consecutive patients undergoing
EPP; 18 who had surgery before and 12 who had surgery after the changes. Data
were collected from patient files and from institutional databases. Outcome
measures included: Volumes of administered fluids, fluid balances, length of
stays and postoperative complications. Dichotomous variables were compared with
Fisher's exact test, whereas continuous variables were compared with Student's
unpaired t-test or the Wilcoxon Two-Sample Test depending on the distribution of
data.
RESULTS: The applied changes significantly reduced the volumes of administered
fluids, both in the intraoperative (p = 0.01) and the postoperative period
(p = 0.04), without increasing the incidence of postoperative complications. Mean
length of stay in the intensive care unit (LOSI) was reduced from three to one
day (p = 0.04) after the changes.
CONCLUSION: The use of clinical parameters to balance fluid restriction and a
sufficient circulation in patients undergoing EPP was associated with a reduction
in mean LOSI without increasing the incidence of postoperative complications. Due
to methodological limitations these results are only hypothesis generating.

DOI: 10.1186/s12871-015-0072-2
PMCID: PMC4464224
PMID: 26063457  [PubMed - indexed for MEDLINE]


17. BMC Anesthesiol. 2015 Jun 4;15:82. doi: 10.1186/s12871-015-0064-2.

Continuous central venous oxygen saturation assisted intraoperative hemodynamic
management during major abdominal surgery: a randomized, controlled trial.

Mikor A(1), Trásy D(2), Németh MF(2), Osztroluczki A(2), Kocsi S(3), Kovács I(2),
Demeter G(2), Molnár Z(2).

Author information:
(1)Department of Anaesthesiology and Intensive Therapy, University of Szeged, 6.
Semmelweis str., 6725, Szeged, Hungary. andrasmikor@gmail.com. (2)Department of
Anaesthesiology and Intensive Therapy, University of Szeged, 6. Semmelweis str.,
6725, Szeged, Hungary. (3)Hungarian Defence Forces Medical Center, Budapest,
Hungary.

BACKGROUND: Major abdominal surgery is associated with significant risk of
morbidity and mortality in the perioperative period. Optimising intraoperative
fluid administration may result in improved outcomes. Our aim was to compare the
effects of central venous pressure (CVP), and central venous oxygen saturation
(ScvO2)-assisted fluid therapy on postoperative complications in patients
undergoing high risk surgery.
METHODS: Patients undergoing elective major abdominal surgery were randomised
into control and ScvO2 groups. The target level of mean arterial pressure (MAP)
was ≥ 60 mmHg in both groups. In cases of MAP < 60 mmHg patients received either
a fluid or vasopressor bolus according to the CVP < 8 mmHg in the control group.
In the ScvO2 group, in addition to the MAP, an ScvO2 of <75% or a >3% decrease
indicated need for intervention, regardless of the actual MAP. Data are presented
as mean ± standard deviation or median (interquartile range).
RESULTS: We observed a lower number of patients with complications in the ScvO2
group compared to the control group, however it did not reach statistical
significance (ScvO2 group: 10 vs.
CONTROL GROUP: 19; p = 0.07). Patients in the ScvO2 group (n = 38) received more
colloids compared to the control group (n = 41) [279(161) vs. 107(250) ml/h;
p < 0.001]. Both groups received similar amounts of crystalloid (1126 ± 471 vs.
1049 ± 431 ml/h; p = 0.46) and norepinephrine [37(107) vs. 18(73) mcg/h;
p = 0.84]. Despite similar blood loss in both groups, the ScvO2 group received
more blood transfusions (63% vs. 37%; p = 0.018). More patients in the control
group had a postoperative PaO2/FiO2 < 200 mmHg (23 vs. 10, p < 0.01). Twenty
eight day survival was significantly higher in the ScvO2 group (37/38 vs. 33/41
p = 0.018).
CONCLUSION: ScvO2-assisted intraoperative haemodynamic support provided some
benefits, including significantly better postoperative oxygenation and 28 day
survival rate, compared to CVP-assisted therapy without a significant effect on
postoperative complications during major abdominal surgery.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02337010.

DOI: 10.1186/s12871-015-0064-2
PMCID: PMC4453106
PMID: 26041437  [PubMed - indexed for MEDLINE]


18. Tidsskr Nor Laegeforen. 2015 Jun 2;135(10):954-8. doi: 10.4045/tidsskr.14.0850.
eCollection 2015.

Woman with high central venous oxygen saturation.

[Article in English, Norwegian]

Hegna TM(1), Qvigstad E(2), Kløw NE(3), Opdahl H(4).

Author information:
(1)Akuttklinikken Oslo universitetssykehus, Rikshospitalet. (2)Hjertemedisinsk
avdeling Enhet for thorax-, kar- og intervensjonsradiologi. (3)Enhet for thorax-,
kar- og intervensjonsradiologi. (4)Akuttmedisinsk avdeling Oslo
universitetssykehus, Ullevål.

DOI: 10.4045/tidsskr.14.0850
PMID: 26037758  [PubMed - indexed for MEDLINE]


19. J Emerg Med. 2015 Sep;49(3):261-7. doi: 10.1016/j.jemermed.2015.02.038. Epub 2015
May 30.

Initial Low Oxygen Extraction Ratio Is Related to Severe Organ Dysfunction and
High In-Hospital Mortality in Severe Sepsis and Septic Shock Patients.

Park JS(1), Kim SJ(1), Lee SW(1), Lee EJ(1), Han KS(1), Moon SW(1), Hong YS(1).

Author information:
(1)Department of Emergency Medicine, College of Medicine, Korea University,
Seoul, Republic of Korea.

BACKGROUND: In severe sepsis and septic shock, global tissue hypoxia is a key
development preceding multi-organ failure and death.
OBJECTIVE: Our aim was to find whether the initial low oxygen extraction ratio
(OER) is related to the severity of organ dysfunction and to predict the
in-hospital mortality in severe sepsis or septic shock patients.
METHODS: This was a secondary analysis of 169 patients with severe sepsis or
septic shock in an emergency department. We calculated OER with 1- central venous
oxygen saturation (ScvO2)/arterial oxygen saturation and compared the data
according to the level of OER (high > 0.3, 0.2 ≤ normal ≤ 0.3, lower < 0.2).
RESULTS: A total 133 patients were selected for analysis. OER was inversely
proportional to ScvO2 (r(2) = 0.878; p < 0.001). The sepsis-related organ failure
assessment score and in-hospital mortality of each group were 6.2 ± 3.7 and 37.0%
for high OER, 5.7 ± 3.0 and 11.8% for normal OER, and 7.7 ± 3.9 and 41.7% for low
OER, respectively (p = 0.034; p = 0.003). In patients with initial ScvO2 of >70%,
in-hospital mortality of patients with low OER was significantly higher than
patients with normal OER.
CONCLUSIONS: Initial low OER was associated with severe organ dysfunction that
resulted in high mortality with severe sepsis and septic shock. When patients had
initial ScvO2 of > 70% but abnormally low OER, their in-hospital mortality was
higher than in normal OER patients. Therefore, the OER should be considered when
attempting to predict the outcome of septic patients using ScvO2 at an early
stage of management for sepsis.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jemermed.2015.02.038
PMID: 26037480  [PubMed - indexed for MEDLINE]


20. Transplant Proc. 2015 May;47(4):1194-8. doi: 10.1016/j.transproceed.2014.10.071.

Optimal central venous pressure during the neohepatic phase to decrease peak
portal vein flow velocity for the prevention of portal hyperperfusion in patients
undergoing living donor liver transplantation.

Ryu TH(1), Jung JY(1), Choi DL(2), Han YS(3), Kim JD(2), Kim JH(4).

Author information:
(1)Department of Anesthesiology and Pain Medicine, School of Medicine, Catholic
University of Daegu, Daegu, Republic of Korea. (2)Division of Hepatobiliary
Pancreas Surgery and Abdominal Organ Transplantation, Department of Surgery,
School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
(3)Department of Surgery, School of Medicine, Kyungpook National University,
Daegu, Republic of Korea. (4)Department of Anesthesiology and Pain Medicine,
School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
Electronic address: usmed@cu.ac.kr.

BACKGROUND: The association between intraoperative systemic hemodynamic status
and preventing portal hyperperfusion, which induces shear stress on the
sinusoidal endothelial cells of liver grafts, resulting in poor graft function in
live-donor recipients, has not been identified. This study evaluates the effects
of systemic hemodynamic parameters (SHPs) during the neohepatic phase on changes
in hepatic hemodynamic parameters (HHPs) between the neohepatic phase and the 1st
postoperative day.
METHODS: Thirty-eight patients undergoing living donor liver transplantation
(LDLT) were enrolled in this study. HHPs (flow velocities of portal vein and
hepatic artery) were measured immediately after hepatic artery and bile duct
reconstruction and on the first postoperative day. SHPs (mean arterial pressure,
central venous pressure [CVP], cardiac index, stroke volume variation, stroke
volume index, systemic vascular resistance index, and central venous oxygen
saturation) were recorded and averaged for 5 minutes after the measurement of
HHPs. The relationships between the SHPs and HHPs were assessed using linear or
quadratic regression analysis.
RESULTS: Peak portal vein flow velocity (PVV) decreased on the 1st postoperative
day in 24 patients (63%). There was an inverted-U relationship between CVP and
the percentage change in PVV (R(2) = 0.241, P = .008). According to the quadratic
regression model, the PVV maximally decreased at a CVP of 7.8 mm Hg. No
significant correlations were found between the other SHPs and HHPs.
CONCLUSIONS: Maintaining CVP (approximately 8 mm Hg) during the neohepatic phase
was clinically beneficial in decreasing PVV to prevent portal hyperperfusion in
the early postoperative period of LDLT.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.transproceed.2014.10.071
PMID: 26036552  [PubMed - indexed for MEDLINE]


21. Crit Care. 2015 May 13;19:227. doi: 10.1186/s13054-015-0917-6.

Central venous-to-arterial carbon dioxide difference as a prognostic tool in
high-risk surgical patients.

Robin E(1), Futier E(2), Pires O(3), Fleyfel M(4), Tavernier B(5), Lebuffe G(6),
Vallet B(7).

Author information:
(1)Department of Anaesthesiology and Intensive Care Medicine, University Hospital
of Lille, Lille, France. emmanuel.robin@chru-lille.fr. (2)Department of
Anaesthesiology and Intensive Care Medicine, Hospital Estaing, University
Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
efutier@chu-clermontferrand.fr. (3)Department of Anaesthesiology and Intensive
Care Medicine, University Hospital of Lille, Lille, France.
oscarpires@hotmail.fr. (4)Department of Anaesthesiology and Intensive Care
Medicine, University Hospital of Lille, Lille, France.
maher.fleyfel@chru-lille.fr. (5)Department of Anaesthesiology and Intensive Care
Medicine, University Hospital of Lille, Lille, France.
benoit.tavernier@chru-lille.fr. (6)Department of Anaesthesiology and Intensive
Care Medicine, University Hospital of Lille, Lille, France.
gilles.lebuffe@chru-lille.fr. (7)Department of Anaesthesiology and Intensive Care
Medicine, University Hospital of Lille, Lille, France.
benoit.vallet@sante.gouv.fr.

Comment in
    Anasthesiol Intensivmed Notfallmed Schmerzther. 2016 Jan;51(1):4-6.

INTRODUCTION: The purpose of this study was to evaluate the clinical relevance of
high values of central venous-to-arterial carbon dioxide difference (PCO2 gap) in
high-risk surgical patients admitted to a postoperative ICU. We hypothesized that
PCO2 gap could serve as a useful tool to identify patients still requiring
hemodynamic optimization at ICU admission.
METHODS: One hundred and fifteen patients were included in this prospective
single-center observational study during a 1-year period. High-risk surgical
inclusion criteria were adapted from Schoemaker and colleagues. Demographic and
biological data, PCO2 gap, central venous oxygen saturation, lactate level and
postoperative complications were recorded for all patients at ICU admission, and
6 hours and 12 hours after admission.
RESULTS: A total of 78 (68%) patients developed postoperative complications, of
whom 54 (47%) developed organ failure. From admission to 12 hours after
admission, there was a significant difference in mean PCO2 gap (8.7 ± 2.8 mmHg
versus 5.1 ± 2.6 mmHg; P = 0.001) and median lactate values (1.54 (1.1-3.2)
mmol/l versus 1.06 (0.8-1.8) mmol/l; P = 0.003) between patients who developed
postoperative complications and those who did not. These differences were maximal
at admission to the ICU. At ICU admission, the area under the receiver operating
characteristic curve for occurrence of postoperative complications was 0.86 for
the PCO2 gap compared to Sequential Organ Failure Assessment score (0.82),
Simplified Acute Physiology Score II score (0.67), and lactate level (0.67). The
threshold value for PCO2 gap was 5.8 mmHg. Multivariate analysis showed that only
a high PCO2 gap and a high Sequential Organ Failure Assessment score were
independently associated with the occurrence of postoperative complications. A
high PCO2 gap (≥6 mmHg) was associated with more organ failure, an increase in
duration of mechanical ventilation and length of hospital stay.
CONCLUSION: A high PCO2 gap at admission in the postoperative ICU was
significantly associated with increased postoperative complications in high-risk
surgical patients. If the increase in PCO2 gap is secondary to tissue
hypoperfusion then the PCO2 gap might be a useful tool complementary to central
venous oxygen saturation as a therapeutic target.

DOI: 10.1186/s13054-015-0917-6
PMCID: PMC4486687
PMID: 25967737  [PubMed - indexed for MEDLINE]


22. Chin Med J (Engl). 2015 May 20;128(10):1306-13. doi: 10.4103/0366-6999.156770.

The Use of the Ratio between the Veno-arterial Carbon Dioxide Difference and the
Arterial-venous Oxygen Difference to Guide Resuscitation in Cardiac Surgery
Patients with Hyperlactatemia and Normal Central Venous Oxygen Saturation.

Du W, Long Y, Wang XT, Liu DW(1).

Author information:
(1)Department of Critical Care Medicine, Peking Union Medical College Hospital,
Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing
100730, China.

BACKGROUND: After cardiac surgery, central venous oxygen saturation (ScvO 2 ) and
serum lactate concentration are often used to guide resuscitation; however,
neither are completely reliable indicators of global tissue hypoxia. This
observational study aimed to establish whether the ratio between the
veno-arterial carbon dioxide and the arterial-venous oxygen differences (P(v-a)CO
2 /C(a-v)O 2 ) could predict whether patients would respond to resuscitation by
increasing oxygen delivery (DO 2 ).
METHODS: We selected 72 patients from a cohort of 290 who had undergone cardiac
surgery in our institution between January 2012 and August 2014. The selected
patients were managed postoperatively on the Intensive Care Unit, had a normal
ScvO 2 , elevated serum lactate concentration, and responded to resuscitation by
increasing DO 2 by >10%. As a consequence, 48 patients responded with an increase
in oxygen consumption (VO 2 ) while VO 2 was static or fell in 24.
RESULTS: At baseline and before resuscitative intervention in postoperative
cardiac surgery patients, a P(v-a)CO 2 /C(a-v)O 2 ratio ≥1.6 mmHg/ml predicted a
positive VO 2 response to an increase in DO 2 of >10% with a sensitivity of 68.8%
and a specificity of 87.5%.
CONCLUSIONS: P(v-a)CO 2 /C(a-v)O 2 ratio appears to be a reliable marker of
global anaerobic metabolism and predicts response to DO 2 challenge. Thus,
patients likely to benefit from resuscitation can be identified promptly, the
P(v-a)CO 2 /C(a-v)O 2 ratio may, therefore, be a useful resuscitation target.

DOI: 10.4103/0366-6999.156770
PMCID: PMC4830308
PMID: 25963349  [PubMed - indexed for MEDLINE]


23. J Cardiothorac Vasc Anesth. 2015 Aug;29(4):977-83. doi:
10.1053/j.jvca.2014.12.020. Epub 2014 Dec 18.

Extravascular Lung Water and Tissue Perfusion Biomarkers After Lung Resection
Surgery Under a Normovolemic Fluid Protocol.

Assaad S(1), Kyriakides T(2), Tellides G(3), Kim AW(3), Perkal M(4), Perrino
A(2).

Author information:
(1)Cardiothoracic Anesthesia Service. Electronic address: sherif.assaad@yale.edu.
(2)Cardiothoracic Anesthesia Service. (3)Cardiac Surgery Service. (4)Department
of Surgery and Intensive Care, VA Connecticut Healthcare System and Yale
University Sch

hs Troponina - Búsqueda de trabajos 2015 Fecha: 28/4/2016


1. World J Cardiol. 2016 Mar 26;8(3):293-301. doi: 10.4330/wjc.v8.i3.293.
Typical rise and fall of troponin in (peri-procedural) myocardial infarction: Asystematic review.
van Beek D(1), van Zaane B(1), Looije M(1), Peelen L(1), van Klei W(1).
Author information: (1)Dianne van Beek, Bas van Zaane, Linda Peelen, Wilton van Klei, Department ofAnesthesiology, University Medical Center Utrecht, 3508 GA Utrecht, TheNetherlands.
AIM: To identify the typical shape of the rise and fall curve of troponin (Tn)following the different types of myocardial infarction (MI).METHODS: We conducted a systematic search in PubMed and Embase including allstudies which focused on the kinetics of Tn in MI type 1, type 4 and type 5. Tnlevels were standardized using the 99(th) percentile, a pooled mean with 95%CIwas calculated from the weighted means for each time point until 72 h.RESULTS: A total of 34 of the 2528 studies identified in the systematic searchwere included. The maximum peak level of the Tn was seen after 6 h aftersuccessful reperfusion of an acute MI, after 12 h for type 1 MI and after 72 hfor type 5 MI. In type 1 MI there were additional smaller peaks at 1 h and at 24 h. After successful reperfusion of an acute MI there was a second peak at 24 h.There was not enough data available to analyze the Tn release after MI associatedwith percutaneous coronary intervention (type 4).CONCLUSION: The typical rise and fall of Tn is different for type 1 MI,successful reperfusion of an acute MI and type 5 MI, with different timing of thepeak levels and different slopes of the fall phase.
PMID: 27022461  [PubMed]

2. Mol Cell Proteomics. 2016 Mar 28. pii: mcp.M115.057380. [Epub ahead of print]
Delineation of molecular pathways involved in cardiomyopathies caused by troponinT mutations.
Gilda JE(1), Lai X(2), Witzmann FA(2), Gomes AV(3).
Author information: (1)University of California, Davis, United States; (2)Indiana University Schoolof Medicine, United States. (3)University of California, Davis, United States;avgomes@ucdavis.edu.
Familial hypertrophic cardiomyopathy (FHC) is associated with mild to severecardiac problems and is the leading cause of sudden death in young people andathletes. Although the genetic basis for FHC is well-established, the molecularmechanisms that ultimately lead to cardiac dysfunction are not well understood.To obtain important insights into the molecular mechanism(s) involved in FHC,hearts from two FHC troponin T (TnT) models (I79N and R278C) were investigatedusing label-free proteomics and metabolomics. Mutations in TnT are the third mostcommon cause of FHC, and the I79N mutation is associated with a high risk ofsudden cardiac death. Most FHC-causing mutations, including I79N, increase theCa2+ sensitivity of the myofilament; however the R278C mutation does not alterCa2+ sensitivity and is associated with a better prognosis than most FHCmutations. Out of more than 1200 identified proteins, 53 and 76 proteins weredifferentially expressed in I79N and R278C hearts, respectively, when compared towild-type hearts. Interestingly, more than 400 proteins were differentiallyexpressed when the I79N and R278C hearts were directly compared. The three major pathways affected in I79N hearts relative to R278C and WT hearts were theubiquitin-proteasome system, antioxidant systems, and energy production pathways.Further investigation of the proteasome system using western blotting andactivity assays showed that proteasome dysfunction occurs in I79N hearts.Metabolomic results corroborate the proteomic data and suggest the glycolytic,citric acid, and electron transport chain pathways are important pathways thatare altered in I79N hearts relative to R278C or WT hearts. Our findings suggestthat impaired energy production and protein degradation dysfunction are importantmechanisms in FHCs associated with poor prognosis and that cardiac hypertrophy isnot likely needed for a switch from fatty acid to glucose metabolism.
Copyright © 2016, The American Society for Biochemistry and Molecular Biology.
PMID: 27022107  [PubMed - as supplied by publisher]

3. Arch Gerontol Geriatr. 2016 Mar 17;65:111-115. doi:10.1016/j.archger.2016.03.010. [Epub ahead of print]
High-sensitivity cardiac troponin T in geriatric inpatients.
Zhang SJ(1), Wang Q(2), Cui YJ(1), Wu W(1), Zhao QH(1), Xu Y(1), Wang JP(1).
Author information: (1)Department of Geriatrics, Fuxing Hospital Affiliated to Capital MedicalUniversity, Beijing, China. (2)Department of Geriatrics, Fuxing HospitalAffiliated to Capital Medical University, Beijing, China. Electronic address:wq1122@medmail.com.cn.
BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is detectable inelderly patients without clinical diagnosed cardiovascular disease. Elevatedhs-cTnT levels predict increased cardiovascular risks and poor prognosis. The aimof this study was to determine the distribution and associated factors of hs-cTnTin geriatric inpatients without acute coronary syndrome (ACS).METHODS: Hs-cTnT was measured with a highly sensitive assay in 679 geriatricinpatients without ACS. Patients were further divided into 3 groups according to the tertile of hs-cTnT levels and single and multiple variable analyses wereperformed to assess the association of hs-cTnT to cardiovascular risk factors,biochemical measurements and echocardiographic abnormalities.RESULTS: Hs-cTnT was detectable (≥3ng/L) in 98.4% of the subjects and 52.0% ofthe subjects had hs-cTnT levels ≥14ng/L, which is at the 99th percentile UpperReference Limit (URL). The levels of hs-cTnT were independently associated withN-terminal pro-brain natriuretic peptide (NT-proBNP), male gender, older age,estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), diabetes mellitus (DM) and left ventricular ejection fraction (LVEF). There were no significant differences in hs-cTnT levels between geriatrics patients withstable coronary artery disease (SCAD) and those without SCAD.CONCLUSION: Hs-cTnT elevation caused by non-ischemic acute conditions was verycommon in geriatric hospitalized patients. Due to increases in baseline hs-cTnTin the elderly, detection of a rise and/or fall in hs-cTnT levels is essentialfor determining a diagnosis of ACS or AMI in geriatric patients. Further studies are needed to establish age-specific 99th percentile values of hs-cTnT forelderly individuals.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
PMID: 27017416  [PubMed - as supplied by publisher]

4. N Am J Med Sci. 2016 Jan;8(1):17-24. doi: 10.4103/1947-2714.175188.
Troponin T in Patients with Traumatic Chest Injuries with and without CardiacInvolvement: Insights from an Observational Study.
Mahmood I(1), El-Menyar A(2), Dabdoob W(3), Abdulrahman Y(1), Siddiqui T(1),Atique S(1), Arumugam SK(1), Latifi R(4), Al-Thani H(1).
Author information: (1)Department of Surgery, Section of Trauma Surgery, Hamad General Hospital,Doha, Qatar. (2)Department of Surgery, Section of Trauma Surgery, Hamad GeneralHospital, Doha, Qatar; Department of Clinical Medicine, Weill Cornell MedicalCollege, Doha, Qatar; Department of Internal Medicine, Cardiology Unit, AhmedMaher Teaching Hospital, Cairo, Egypt. (3)Department of Clinical Medicine, Weill Cornell Medical College, Doha, Qatar; Department of Cardiology, Hamad GeneralHospital, Doha, Qatar. (4)Department of Surgery, Section of Trauma Surgery, HamadGeneral Hospital, Doha, Qatar; Department of Surgery, University of Arizona,Tucson, Arizona, USA.
BACKGROUND: Serum troponin T (TnT) is a common marker of myocardial injury.However, its implication in the absence of clinical evidence of cardiac reason isnot well established.AIMS: The aim of this study was to identify the implications of positive TnT intraumatic chest injury (TCI) patients regardless of the cardiac involvement.MATERIALS AND METHODS: We conducted a retrospective analysis of all TCI patients admitted to level 1 trauma center between 2008 and 2011. Patients who underwentTnT testing were divided into two groups: Group 1 (positive TnT) and Group 2(negative TnT). The two groups were analyzed and compared, and multivariateregression analyses were performed to identify predictors of TnT positivity andmortality.RESULTS: Out of 993 blunt TCI patients, 19.3% had positive TnT (Group 1). Oncomparison to Group 2, patients in Group 1 were 5 years younger and more likelyto have head, cardiac, hepatic, splenic, and pelvic injuries, in addition to lungcontusion. Positive TnT was associated with higher Injury Severity Score (ISS) (P= 0.001), higher chest Abbreviated Injury Score (AIS) (P = 0.001), and longerhospital stay (P = 0.03). In addition, Group 1 patients were more likely toundergo chest tube insertion, exploratory laparotomy, mechanical ventilation, andtracheostomy. Twenty patients had cardiac involvement, and of them 14 hadpositive TnT. Among 973 patients who showed no evidence of cardiac involvement,178 had positive TnT (18.3%). There were 104 deaths (60% in Group 1). Onmultivariate regression analysis, the predictors of hospital mortality werepositive TnT, head injury, and high ISS, whereas, the predictors of TnTpositivity were cardiac, hepatic, and pelvic injuries; higher ISS; and age.CONCLUSIONS: Positive TnT in blunt TCI patients is a common challenge,particularly in polytrauma cases. Patients with positive TnT tend to have theworst outcome even in the absence of clinical evidence of acute cardiacinvolvement. Positive TnT is also a reflection of the severity of chest orextrathoracic injuries; however, further prospective studies are warranted.
PMCID: PMC4784179PMID: 27011943  [PubMed]

5. Ann Pediatr Cardiol. 2016 Jan-Apr;9(1):79-81. doi: 10.4103/0974-2069.171400.
Chest pain, troponin rise, and ST-elevation in an adolescent boy following theuse of the synthetic cannabis product K2.
Zaleta S(1), Kumar P(1), Miller S(1).
Author information: (1)Department of Pediatrics, Timaru Hospital, Timaru 7910, New Zealand.
"Legal highs" such as K2, which typically contain synthetic cannabinoids, areincreasingly popular with adolescents around the world. We have limited knowledgeconcerning their toxicity or adverse effects and their mechanism of action ispoorly understood. While synthetic cannabinoids have been linked to adversecardiovascular effects, cases of ST-elevation myocardial infarction (STEMI)associated with K2 use are exceedingly rare. We report a case of a 14-year-oldboy who suffered an STEMI after smoking K2. To our knowledge, this is not onlythe youngest case of an STEMI associated with K2 use, but also the first case to be reported outside of the United States of America. Pediatricians worldwide mustbe aware of the clinical significance and potential harm associated with the use of synthetic cannabinoids, to better educate patients and their familiesregarding the dangers of using such "legal" substances.
PMCID: PMC4782476PMID: 27011700  [PubMed]

6. Gerontology. 2016 Mar 24. [Epub ahead of print]
Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older PatientsCompared to Those with Normal Cardiac Troponin I and Patients with Acute CoronarySyndrome: A Cohort Study.
Mannu GS(1), Honney K, Spooner R, Clark AB, Bettencourt-Silva JH, Zaman MJ, Loke YK, Myint PK.
Author information: (1)Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
BACKGROUND: Incidentally elevated cardiac troponin I (cTnI) levels are common in acutely unwell older patients. However, little is known about how this impacts onthe prognosis of these patients.OBJECTIVE: We aimed to investigate whether incidentally elevated cTnI levels(group 1) are associated with poorer outcome when compared to age- andsex-matched patients without an elevated cTnI level (group 2), and to patientsdiagnosed with acute coronary syndrome (group 3).PATIENTS AND METHODS: This prospective, matched cohort study placed patients ≥75 years old who were admitted to a University teaching hospital into groups 1-3,based on the cTnI levels and underlying diagnosis. Outcomes were compared betweenthe groups using mixed-effects regression models and adjusted for renal function and C-reactive protein. All-cause mortality at discharge, at 1 month and 3months, alongside the length of hospital stay (LOS), were recorded.RESULTS: In total, 315 patients were included, with 105 patients in each of the 3groups. The mean age was 84.8 ± 5.5 years, with 41.9% males. All patients werefollowed up for 3 months. The percent all-cause mortality at discharge and theLOS for groups 1, 2 and 3 were 12.4, 3.8 and 8.6% and 11.2, 8.5 and 7.7 days,respectively. Group 1 had significantly increased mortality at 3 months [oddsratio (OR) 2.80, 95% confidence interval (CI) 1.12-6.96; p = 0.040] and LOS (OR1.39, 95% CI 1.08-1.79; p = 0.008) compared to group 2 and did not differsignificantly when compared to 3-month mortality (OR 2.39, 95% CI 0.91-6.29; p = 0.079) or LOS (OR 1.26, 95% CI 0.96-1.66; p = 0.097) in group 3.CONCLUSION: There is a significant association between an incidental rise in cTnIlevel with mortality and LOS in older patients. Further research is required toevaluate whether a more systematic management of these patients would improve theprognosis.
© 2016 S. Karger AG, Basel.
PMID: 27007948  [PubMed - as supplied by publisher]

7. J Am Heart Assoc. 2016 Mar 21;5(3). pii: e002777. doi: 10.1161/JAHA.115.002777.
Interplay Between the Effects of Dilated Cardiomyopathy Mutation (R206L) and the Protein Kinase C Phosphomimic (T204E) of Rat Cardiac Troponin T Are DifferentlyModulated by α- and β-Myosin Heavy Chain Isoforms.
Michael JJ(1), Chandra M(2).
Author information: (1)Department of Integrative Physiology and Neuroscience Washington StateUniversity, Pullman, WA. (2)Department of Integrative Physiology and NeuroscienceWashington State University, Pullman, WA murali@vetmed.wsu.edu.
BACKGROUND: We hypothesized that the functional effects of R206L-a rat analog of the dilated cardiomyopathy (DCM) mutation R205L in human cardiac troponin T(TnT)-were differently modulated by myosin heavy chain (MHC) isoforms and T204E, a protein kinase C (PKC) phosphomimic of TnT. Our hypothesis was based on twoobservations: (1) α- and β-MHC differentially influence the functional effects ofTnT; and (2) PKC isoforms capable of phosphorylating TnT are upregulated infailing human hearts.METHODS AND RESULTS: We generated 4 recombinant TnT variants: wild type; R206L;T204E; and R206L+T204E. Functional effects of the TnT variants were tested incardiac muscle fibers (minimum 14 per group) from normal (α-MHC) andpropylthiouracil-treated rats (β-MHC) using steady-state and dynamic contractile measurements. Notably, in α-MHC fibers, Ca(2+)-activated maximal tension wasattenuated by R206L (≈32%), T204E (≈63%), and R206L+T204E (≈64%). In β-MHCfibers, maximal tension was unaffected by R206L, but was attenuated by T204E(≈33%) and R206L+T204E (≈40%). Thus, β-MHC differentially counteracted theattenuating effects of the TnT variants on tension. However, in β-MHC fibers,R206L+T204E attenuated tension to a greater extent when compared to T204E alone. In β-MHC fibers, R206L+T204E attenuated the magnitude of the length-mediatedrecruitment of new cross-bridges (≈28%), suggesting that the Frank-Starlingmechanism was impaired.CONCLUSIONS: Our findings are the first (to our knowledge) to demonstrate thatthe functional effects of a DCM-linked TnT mutation are not only modulated by MHCisoforms, but also by the pathology-associated post-translational modificationsof TnT.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
PMID: 27001966  [PubMed - in process]

8. Swiss Med Wkly. 2016 Mar 21;146:w14285. doi: 10.4414/smw.2016.14285. eCollection 2016.
Elevated high-sensitivity troponin T levels are associated with adverse cardiacremodelling and myocardial fibrosis in hypertrophic cardiomyopathy.
Hasler S(1), Manka R(1), Greutmann M(1), Gämperli O(1), Schmied C, Tanner FC(1), Biaggi P(2), Lüscher TF(1), Keller DI(3), Gruner C(1).
Author information: (1)University Heart Centre, Department of Cardiology, University Hospital Zurich,Switzerland. (2)Heart Clinic, Hirslanden, Zurich, Switzerland. (3)EmergencyDepartment, University Hospital Zurich, Switzerland.
INTRODUCTION: Clinical manifestations of hypertrophic cardiomyopathy (HCM) range from asymptomatic disease to early-onset heart failure and sudden cardiac death(SCD). Risk stratification for SCD remains imperfect and novel risk markers areneeded. The aim of our study was to evaluate the association of elevatedhigh-sensitivity cardiac troponin T levels (hs-cTnT) with the severity of diseaseexpression and adverse events in patients with HCM.METHODS: All patients followed-up at a dedicated HCM clinic at a tertiary carecentre between April 2012 and March 2014 were analysed. The clinical care trackfor these patients includes 12-lead ECG, blood work-up, echocardiography, Holter ECG, exercise stress testing and cardiovascular magnetic resonance imaging (CMR).Clinical data were obtained from medical records.RESULTS: Of 91 HCM patients (77% males, mean age at follow up 51 ± 16 years), 46 (51%) had elevated hs-cTnT levels (>0.014 ng/ml). Patients with elevated hs-cTnT levels had greater maximum wall thickness (23 ± 7 mm vs 19 ± 3 mm, p = 0.001),more often had myocardial fibrosis (96% vs 54%, p <0.001), and lower exercisecapacity (90% predicted vs 76% predicted, p = 0.002). There was a trend towardslower event-free survival estimates (Kaplan-Meier method, 15% vs 7%, p = 0.16).CONCLUSIONS: Elevated hs-cTnT levels in HCM patients are associated with disease severity and, potentially, with more adverse cardiac events. Future studiesshould test whether integration of hs-cTnT in clinical decision algorithms willimprove risk stratification.
PMID: 26999566  [PubMed - in process]

9. Am Heart J. 2016 Apr;174:43-50. doi: 10.1016/j.ahj.2015.12.015. Epub 2015 Dec 31.
High-sensitive troponin T is associated with all-cause and cardiovascularmortality in stable outpatients with type 2 diabetes (ZODIAC-37).
Hendriks SH(1), van Dijk PR(2), van Hateren KJ(2), van Pelt JL(3), GroenierKH(4), Bilo HJ(5), Bakker SJ(6), Landman GW(7), Kleefstra N(8).
Author information: (1)Diabetes Centre, Isala, Zwolle, the Netherlands. Electronic address:s.hendriks@isala.nl. (2)Diabetes Centre, Isala, Zwolle, the Netherlands.(3)Department of Clinical Chemistry, University Medical Center Groningen andUniversity of Groningen, Groningen, The Netherlands. (4)Diabetes Centre, Isala,Zwolle, the Netherlands; Department of General Practice, University MedicalCenter Groningen and University of Groningen, Groningen, the Netherlands.(5)Diabetes Centre, Isala, Zwolle, the Netherlands; Department of InternalMedicine, University Medical Center Groningen and University of Groningen,Groningen, the Netherlands; Department of Internal Medicine, Isala, Zwolle, theNetherlands. (6)Department of Internal Medicine, University Medical CenterGroningen and University of Groningen, Groningen, the Netherlands. (7)DiabetesCentre, Isala, Zwolle, the Netherlands; Department of Internal Medicine, Gelrehospital, Apeldoorn, the Netherlands. (8)Diabetes Centre, Isala, Zwolle, theNetherlands; Department of Internal Medicine, University Medical Center Groningenand University of Groningen, Groningen, the Netherlands; Langerhans MedicalResearch Group, Zwolle, the Netherlands.
BACKGROUND: We aimed to investigate whether high-sensitive cardiac troponin T(hs-cTnT) is associated with all-cause and cardiovascular mortality in stabletype 2 diabetes (T2D) outpatients treated in primary care.METHODS: Cardiac troponin T was measured with a high-sensitive assay at baseline in patients with T2D participating in the observational ZODIAC study. Coxproportional hazards models were used to investigate the relationship betweenhs-cTnT and mortality with adjustment for selected confounders. Risk predictioncapabilities of hs-cTnT were assessed with Harrell C statistics.RESULTS: Complete baseline data were available for 1,133 patients. During median follow-up of 11 (7-14) years, 513 (45%) patients died, of which 218 (42%) died ofcardiovascular causes. Of the patients with undetectable hs-cTnT levels (<3ng/L), only 23% died, compared with 58% with low detectable levels (3-14 ng/L)and 84% with raised levels (≥14 ng/L). Natural log hs-cTnT was significantlyassociated with all-cause mortality (hazard ratio 1.30, 95% CI 1.19-1.42) andcardiovascular mortality (hazard ratio 1.33, 95% CI 1.15-1.53), independent ofpotential confounders. The Harrell C statistic for the crude model of hs-cTnT was0.72 (95% CI 0.70-0.75) for all-cause mortality and 0.74 (95% CI 0.71-0.77) forcardiovascular mortality.CONCLUSIONS: Higher levels of hs-cTnT are associated with mortality in stableoutpatients with T2D. The high crude Harrell C values and the excellent prognosisof patients with undetectable levels illustrate the strength of hs-cTnT as apotential marker for mortality.
Copyright © 2015 Elsevier Inc. All rights reserved.
PMID: 26995369  [PubMed - in process]

10. Emerg Med Australas. 2016 Mar 16. doi: 10.1111/1742-6723.12566. [Epub ahead ofprint]
Clinical impact of a high-sensitivity troponin assay introduction on patientspresenting to the emergency department.
Peck D(1), Knott J(1), Lefkovits J(1).
Author information: (1)Emergency Department, The Royal Melbourne Hospital, Melbourne, Victoria,Australia.
OBJECTIVE: Biomarkers are a critical component in the investigation of patientswith potential ischaemic heart disease. The proposed benefits of ahigh-sensitivity troponin (hs-Tn) assay include earlier diagnosis of myocardialinfarction. However, the decreased specificity may adversely affect clinicalpractice. The present study aims to investigate the impact that the introduction of a hs-Tn assay had on patients presenting to the ED.METHODS: A pre- and post-interventional analysis was performed on all patientspresenting to the Royal Melbourne Hospital ED, and had a troponin, in the12 months before and after the introduction of the hs-Tn assay. The main outcome measures were ED length of stay, admission rates, proportion of patientsundergoing interventional cardiac procedures and proportion diagnosed withmyocardial infarction.RESULTS: There were 6557 patients who had a conventional assay and 7335 patients who had a hs-Tn assay. The introduction of a hs-Tn assay was associated with anincreased abnormal troponin rate (23.4% vs 28.1%, P < 0.001). The median lengthof ED stay decreased by 9.1% (P < 0.001). The proportion admitted to hospitalincreased (60.9% vs 65.9%, P < 0.001); however, there was no difference in theproportion undergoing revascularisation or the proportion diagnosed withmyocardial infarction.CONCLUSIONS: Although the introduction of a hs-Tn assay led to an increase inhospital admissions, the unchanged rate of cardiac procedures or final diagnoses of acute myocardial infarction and ischaemic heart disease suggests that thehs-Tn did not improve the detection of these conditions. It remains unclearwhether there was a benefit admitting the additional cohort of patients.
© 2016 Australasian College for Emergency Medicine and Australasian Society forEmergency Medicine.
PMID: 26989877  [PubMed - as supplied by publisher]

11. Interact Cardiovasc Thorac Surg. 2016 Mar 16. pii: ivw060. [Epub ahead of print]
Predictive value of high-sensitivity troponin T in addition to EuroSCORE II incardiac surgery.
Petäjä L(1), Røsjø H(2), Mildh L(3), Suojaranta-Ylinen R(4), Kaukonen KM(3),Jokinen JJ(5), Salmenperä M(4), Hagve TA(6), Omland T(2), Pettilä V(3).
Author information: (1)Division of Anaesthesiology, Department of Anaesthesiology, Intensive Care andPain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki,Finland liisa.petaja@hus.fi. (2)Division of Medicine, Akershus UniversityHospital, Lørenskog, Norway Institute of Clinical Medicine, K.G. Jebsen CardiacResearch Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway. (3)Division of Intensive Care Medicine, Department of Anaesthesiology,Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. (4)Division of Anaesthesiology, Department ofAnaesthesiology, Intensive Care and Pain Medicine, University of Helsinki andHelsinki University Hospital, Helsinki, Finland. (5)Department of Thoracic andVascular Surgery, Päijät-Häme Central Hospital, Lahti, Finland. (6)Division ofDiagnostics and Technology, Akershus University Hospital, Lørenskog, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
OBJECTIVES: Plasma troponins, measured by fourth-generation assays, areassociated with increased mortality and morbidity after cardiac surgery. Theyalso offer predictive information in addition to EuroSCORE, a widely used riskmodel after cardiac surgery. However, preoperatively measured troponin hasprovided no additional information to postoperative values. Whether these factshold true also for the high-sensitivity fifth-generation troponin assay and thebetter calibrated risk model, EuroSCORE II, is unknown. We hypothesized thatpreoperative and/or postoperative high-sensitivity troponin T (hs-TnT) wouldincrease the predictive value of EuroSCORE II.METHODS: Consecutive coronary artery bypass grafting (CABG) and other cardiacsurgical patients were prospectively enrolled in a university hospital. Plasmasamples and EuroSCORE II variables were collected. The primary and secondaryend-points were 180-day mortality and any major adverse event within 30 days, and961-day mortality. The data were analysed by Kaplan-Meier survival curves,regression analyses, receiver operator characteristic curves and decision curveanalysis.RESULTS: Mortality rates in 180 days were 3.5% (15/428) in CABG and 6.4% (14/220)in other cardiac surgical patients. Survival curves differed only in patientswith not only high postoperative hs-TnT value (>500 ng/l), but also highpreoperative hs-TnT value (>14 ng/l), compared with patients with both hs-TnTvalues low. Adding hs-TnT to EuroSCORE II improved the prediction of 180-daymortality in other cardiac surgical patients (maximum net benefit of 1.5%), butnot in CABG patients. Regarding major adverse events, adding hs-TnT to EuroSCORE II improved the prediction in both CABG patients and other cardiac surgicalpatients (maximum net benefits of 3 and 7%).CONCLUSIONS: Elevated postoperative hs-TnT was predictive of mortality only when combined with elevated preoperative hs-TnT. Hs-TnT measurements added informationto the EuroSCORE II regarding major adverse events in all cardiac surgicalpatients and regarding 180-day mortality in non-CABG patients.
© The Author 2016. Published by Oxford University Press on behalf of the EuropeanAssociation for Cardio-Thoracic Surgery. All rights reserved.
PMID: 26984965  [PubMed - as supplied by publisher]

12. Data Brief. 2016 Mar 3;7:397-405. doi: 10.1016/j.dib.2016.02.051. eCollection2016.
Validation, optimisation, and application data in support of the development of atargeted selected ion monitoring assay for degraded cardiac troponin T.
Streng AS(1), de Boer D(1), Bouwman FG(2), Mariman EC(2), Scholten A(3), vanDieijen-Visser MP(1), Wodzig WK(1).
Author information: (1)Central Diagnostic Laboratory, Maastricht University Medical Centre,Maastricht, the Netherlands. (2)Department of Human Biology, MaastrichtUniversity, Maastricht, the Netherlands. (3)Biomolecular Mass Spectrometry andProteomics, Bijvoet Centre for Biomolecular Research and Utrecht Institute forPharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands;Netherlands Proteomics Centre, Utrecht University, Utrecht, the Netherlands;Current working address: Janssen, Pharmaceutical Companies of Johnson&Johnson,Infectious Diseases and Vaccines, Leiden, the Netherlands.
Cardiac troponin T (cTnT) fragmentation in human serum was investigated using anewly developed targeted selected ion monitoring assay, as described in theaccompanying article: "Development of a targeted selected ion monitoring assayfor the elucidation of protease induced structural changes in cardiac troponin T"[1]. This article presents data describing aspects of the validation andoptimisation of this assay. The data consists of several figures, an excel filecontaining the results of a sequence identity search, and a description of theraw mass spectrometry (MS) data files, deposited in the ProteomeXchangerepository with id PRIDE: PXD003187.
PMCID: PMC4782000PMID: 26977445  [PubMed]

13. Am J Cardiol. 2016 Feb 17. pii: S0002-9149(16)30215-6. doi:10.1016/j.amjcard.2016.02.002. [Epub ahead of print]
Usefulness of High-Sensitivity Cardiac Troponin T for the Identification ofOutlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors.
Magnoni M(1), Masson S(2), Andreini D(3), Moccetti T(4), Modena MG(5), CanestrariM(6), Berti S(7), Casolo G(8), Gabrielli D(9), Marraccini P(10), Pontone G(3),Latini R(2), Maggioni AP(11), Maseri A(12); CAPIRE Study Group.
Author information: (1)Heart Care Foundation Onlus, Florence, Italy. Electronic address:magnoni.marco@tiscali.it. (2)Department of Cardiovascular Research, Istituto diRicovero e Cura a Carattere Scientifico, Istituto di Ricerche FarmacologicheMario Negri, Milan, Italy. (3)Centro Cardiologico Monzino, Milan, Italy.(4)Servizio di Ricerca Cardiovascolare, Cardiocentro Ticino, Lugano, Switzerland.(5)Department of Cardiology, Ospedale Policlinico, Modena, Italy. (6)Departmentof Cardiology, Santa Croce Hospital, Fano, Italy. (7)Fondazione Toscana Gabriele Monasterio, Stabilimento di Massa, Unità Operativa Adult Cardiology, Massa,Italy. (8)Department of Cardiology, Nuovo Ospedale Versilia, Lido di Camaiore,Italy. (9)Department of Cardiology, Ospedale Civile A. Murri, Fermo, Italy.(10)Istituto di Fisiologia Clinica-Consiglio Nazionale delle Ricerche, FondazioneToscana G. Monasterio, S.A. Emodinamica, Pisa, Italy. (11)Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy. (12)Heart CareFoundation Onlus, Florence, Italy.
Novel high-sensitivity assay can detect very low levels of circulating cardiactroponin (hs-cTnT) in apparently healthy subjects. Within normal range, higherlevels are associated with coronary artery disease (CAD) and cardiacabnormalities commonly associated to traditional risk factors (RFs) for CAD.Therefore, we investigated the relation between circulating hs-cTnT and CAD inpatients with a spectrum of RF burden aiming to assess the added value of hs-cTnTto identify "outlier" patients with CAD despite a low RF burden. Hs-cTnT wasmeasured in 525 stable patients without previous diagnosis of ischemic heartdisease with 0 to 1 RF, excluded diabetes, (low-RF group, n = 263) or ≥2 RFs(multiple-RF group, n = 262) and without CAD (segment involvement score = 0) ordiffuse CAD (segment involvement score >5) at coronary computed tomographyangiography. Outlier patients with diffuse CAD despite low-RF burden had similar extent, severity, and plaque composition than patients with multiple RFs.Overall, hs-cTnT was measurable in 81% of patients with median value of 6.0 ng/L.In both groups, hs-cTnT concentration was higher in patients with CAD than inpatients with normal coronary arteries (p <0.0001). Hs-cTnT was more accurate to detect patients with CAD in the low-RF group than in the multiple-RF group (p =0.04). In multivariate analysis, higher level of hs-cTnT (>6 ng/L) wasindependently associated with CAD in low-RF group only. Despite very lowcirculating concentrations, hs-cTnT may identify with a good accuracy the outlierpatients with diffuse CAD despite low-RF burden.
Copyright © 2016 Elsevier Inc. All rights reserved.
PMID: 26976791  [PubMed - as supplied by publisher]

14. Clin Biochem. 2016 Mar 11. pii: S0009-9120(16)00084-9. doi:10.1016/j.clinbiochem.2016.01.024. [Epub ahead of print]
Determinants of minimal elevation in high-sensitivity cardiac troponin T in thegeneral population.
Rubin J(1), Matsushita K(2), Lazo M(2), Ballantyne CM(3), Nambi V(3), HoogeveenR(3), Sharrett AR(2), Blumenthal RS(4), Coresh J(2), Selvin E(5).
Author information: (1)Department of Medicine, Columbia University Medical Center, New York, NY, USA;Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA. (2)Departmentof Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. (3)Department of Medicine, Section of Atherosclerosis and Vascular Medicine,Baylor College of Medicine, Houston, TX, USA. (4)Johns Hopkins CiccaronePreventive Cardiology Center, Baltimore, MD, USA. (5)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronicaddress: eselvin@jhu.edu.
OBJECTIVES: To study the relationship between cardiovascular risk factors anddetectable cardiac troponin-T using a highly sensitive assay (hs-cTnT) amongpersons without a history of cardiovascular disease.DESIGN AND METHODS: We examined the cross-sectional associations betweencardiovascular risk factors and hs-cTnT in 9593 participants (mean age 65.6 (SD, 5.6), 41% female, 22% black) free of cardiovascular disease in a community-based cohort, through the Atherosclerosis Risk in Communities (ARIC) Study. We usedmultivariable logistic regression to characterize the association betweencardiovascular risk factors and detectable (≥3.0 to 13.9ng/L) and elevated(≥14.0ng/L) hs-cTnT.RESULTS: hs-cTnT was detectable in 59% and elevated in 7% of the studypopulation. Among persons with ideal cardiovascular health, hs-cTnT wasdetectable in 44%. In models adjusting for significant determinants of hs-cTnTconcentration, detectable hs-cTnT was more frequent among males, blacks andpersons with diabetes and hypertension and less frequent among statin users,current smokers and drinkers. Other risk factors associated with detectablehs-cTnT were older age, lower kidney function and higher body mass index. Theserisk factors were associated with elevated hs-cTnT in a similar pattern.CONCLUSION: In a community-based sample without cardiovascular disease hs-cTnT isdetectable in most adults, even among those with ideal cardiovascular health.Although most traditional cardiovascular risk factors were significantdeterminants of detectable and elevated hs-cTnT, the associations wereparticularly robust for sex, age, race, hypertension and diabetes.
Copyright © 2016. Published by Elsevier Inc.
PMID: 26975902  [PubMed - as supplied by publisher]

15. Atherosclerosis. 2016 Feb 18. pii: S0021-9150(16)30056-9. doi:10.1016/j.atherosclerosis.2016.02.013. [Epub ahead of print]
Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study.
Andersson C(1), Enserro D(2), Sullivan L(2), Wang TJ(3), Januzzi JL Jr(4),Benjamin EJ(5), Vita JA(6), Hamburg NM(6), Larson MG(7), Mitchell GF(8), VasanRS(5).
Author information: (1)The Boston University's and National Heart, Lung, Blood Institute's FraminghamHeart Study, Framingham, MA, USA. Electronic address: ca@heart.dk. (2)Department of Biostatistics, Boston University, MA, USA. (3)The Boston University's andNational Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA,USA; Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN,USA. (4)Cardiology Division, Massachusetts General Hospital, Harvard MedicalSchool, Boston, MA, USA. (5)The Boston University's and National Heart, Lung,Blood Institute's Framingham Heart Study, Framingham, MA, USA; Sections ofPreventive Medicine and Cardiology, Boston University School of Medicine, Boston,MA, USA; Department of Epidemiology, Boston University School of Public Health,Boston, MA, USA. (6)Evans Department of Medicine and Whitaker CardiovascularInstitute, Boston University School of Medicine, Boston, MA, USA. (7)The BostonUniversity's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA. (8)Cardiovascular Engineering, Inc., Norwood, MA, USA.
BACKGROUND AND AIMS: Growth differentiation factor-15 (GDF-15), soluble (s)ST2,and high-sensitivity troponin-I (hs-TnI) are associated with incidentcardiovascular disease (CVD) including heart failure, yet the underlyingmechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which mayexplain the relations of these biomarkers with CVD.METHODS: We evaluated 1823 Framingham Study participants (mean age 61 ± 10 years,54% women) who underwent routine assessment of vascular function. We relatedcirculating GDF-15, sST2, and hs-TnI concentrations to measures of arterialstiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; andforward pressure wave amplitude, FW), endothelial-dependent vasodilation(flow-mediated dilation, FMD), and baseline and hyperemic brachial flowvelocities using linear regression adjusting for standard risk factors.RESULTS: After multivariable adjustment, GDF-15 levels were positively associatedwith CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD]change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD(-0.051 [-0.101-0.0003] SD change per SD increase in loge[GDF-15], p = 0.048).sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated withhyperemic flow velocity (-0.041 [-0.082-0.0004] SD change per SD increase inloge[hs-TnI], p = 0.048).CONCLUSION: In our community-based investigation, individual cardiac stressbiomarkers were differentially related to select aspects of vascular function.These findings may contribute to the associations of circulating GDF-15, sST2,and hs-TnI with incident CVD and heart failure.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
PMID: 26972631  [PubMed - as supplied by publisher]

16. Arch Biochem Biophys. 2016 Mar 10. pii: S0003-9861(16)30062-5. doi:10.1016/j.abb.2016.03.010. [Epub ahead of print]
Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction.
Meyer NL(1), Chase PB(2).
Author information: (1)Department of Biochemistry and Molecular Biology, Oregon Health and ScienceUniversity, Portland, OR, USA. (2)Department of Biological Science and Program inMolecular Biophysics, Florida State University, Tallahassee, FL, USA. Electronic address: chase@bio.fsu.edu.
Inhibition of striated muscle contraction at resting Ca(2+) depends on theC-terminal half of troponin I (TnI) in thin filaments. Much focus has been on ashort inhibitory peptide (Ip) sequence within TnI, but structural studies andidentification of disease-associated mutations broadened emphasis to include alarger mobile domain (Md) sequence at the C-terminus of TnI. For Md to functioneffectively in muscle relaxation, tight mechanical coupling to troponin'score-and thus tropomyosin-is presumably needed. We generated recombinant, humancardiac troponins containing one of two TnI constructs: either an 8-amino acidlinker between Md and the rest of troponin (cTnILink8), or an Md deletion(cTnI1-163). Motility assays revealed that Ca(2+)-sensitivity of reconstitutedthin filament sliding was markedly increased with cTnILink8 (∼0.9 pCa unitleftward shift of speed-pCa relation compared to WT), and increased further when Md was missing entirely (∼1.4 pCa unit shift). Cardiac Tn's ability to turn offfilament sliding at diastolic Ca(2+) was mostly (61%), but not completelyeliminated with cTnI1-163. TnI's Md is required for full inhibition of unloadedfilament sliding, although other portions of troponin-presumably including Ip-arealso necessary. We also confirm that TnI's Md is not responsible forsuperactivation of actomyosin cycling by troponin.
Copyright © 2016 Elsevier Inc. All rights reserved.
PMID: 26971468  [PubMed - as supplied by publisher]

17. Postepy Kardiol Interwencyjnej. 2016;12(1):41-8. doi: 10.5114/pwki.2016.56948.Epub 2016 Feb 11.
Rise of serum troponin levels following uncomplicated elective percutaneouscoronary interventions in patients without clinical and procedural signssuggestive of myocardial necrosis.
Buturak A(1), Degirmencioglu A(1), Surgit O(2), Demir AR(2), Karakurt H(2),Erturk M(2), Yazıcı S(3), Serteser M(4), Norgaz T(1), Gorgulu S(1).
Author information: (1)Department of Cardiology, School of Medicine, Acıbadem University, Istanbul,Turkey. (2)Cardiology Department, Mehmet Akif Ersoy Education and ResearchHospital, Istanbul, Turkey. (3)Cardiology Department, Siyami Ersek Education and Research Hospital, Istanbul, Turkey. (4)Medical Biochemistry Department, Faculty of Medicine, Acibadem University, Istanbul, Turkey.
INTRODUCTION: The new definition of periprocedural myocardial infarction (type 4aMI) excludes patients without angina and electrocardiographic orechocardiographic changes suggestive of myocardial ischemia even thoughsignificant serum troponin elevations occur following percutaneous coronaryintervention (PCI).AIM: To evaluate the incidence and predictors of serum troponin rise followingelective PCI in patients without clinical and procedural signs suggestive ofmyocardial necrosis by using a high-sensitivite troponin assay (hsTnT).MATERIAL AND METHODS: Three hundred and four patients (mean age: 60.8 ±8.8 years,204 male) undergoing elective PCI were enrolled. Patients with periproceduralangina, electrocardiographic or echocardiographic signs indicating myocardialischemia or a visible procedural complication such as dissection or side branchocclusion were excluded. Mild-moderate periprocedural myocardial injury (PMI) andsevere PMI were defined as post-PCI (12 h later) elevation of serum hsTnTconcentrations to the range of 14-70 ng/l and > 70 ng/l, respectively.RESULTS: The median pre-procedural hsTnT level was 9.7 ng/l (interquartile range:7.1-12.2 ng/l). Serum hsTnT concentration elevated (p < 0.001) to 19.4 ng/l (IQR:12.0-38.8 ng/l) 12 h after PCI. Mild-moderate PMI and severe PMI were detected in49.3% and 12.2% of patients, respectively. Post-procedural hsTnT levels weresignificantly higher in multivessel PCI, overlapping stenting, predilatation and postdilatation subgroups. In addition, post-procedural hsTnT levels werecorrelated (r = 0.340; p < 0.001) with the stent lengths.CONCLUSIONS: High-sensitivite troponin measurements indicate a high incidence of PMI even though no clinical or procedural signs suggestive of myocardial ischemiaexist. Multivessel PCI, overlapping stenting, predilatation, postdilatation andlonger stent length are associated with PMI following elective PCI.
PMCID: PMC4777705PMID: 26966448  [PubMed]

18. Clin Chem. 2016 Apr;62(4):623-30. doi: 10.1373/clinchem.2015.250811. Epub 2016Mar 2.
High-Sensitivity Cardiac Troponin I Is a Strong Predictor of CardiovascularEvents and Mortality in the AGES-Reykjavik Community-Based Cohort of OlderIndividuals.
Thorsteinsdottir I(1), Aspelund T(2), Gudmundsson E(3), Eiriksdottir G(3), HarrisTB(4), Launer LJ(4), Gudnason V(2), Venge P(5).
Author information: (1)Icelandic Heart Association Research Institute, Kopavogur, Iceland; Departmentof Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland;(2)Icelandic Heart Association Research Institute, Kopavogur, Iceland; Faculty ofMedicine, University of Iceland, Reykjavik, Iceland; (3)Icelandic HeartAssociation Research Institute, Kopavogur, Iceland; (4)Laboratory ofEpidemiology, Demography and Biometry, Intramural Research Program, NationalInstitute on Aging Bethesda, MD; (5)Department of Medical Sciences, UppsalaUniversity, Uppsala, Sweden. per.venge@medsci.uu.se.
BACKGROUND: The objective of this study was to investigate the predictive powerof a high-sensitivity cardiac troponin I (hs-cTnI) assay for cardiovascularevents and mortality in a large population of older community dwellers.METHODS: Blood was collected from 5764 individuals (age 66-98 years) during theperiod of 2002-2006 and the outcome as to all-cause death and incidence ofcardiovascular disease (CVD) and coronary heart disease (CHD) followed up to 10years. hs-cTnI (Abbott) was measured in serum to assess the association of thismarker with CVD, CHD and death, and finally, to compare the results withconventional risk factors by multivariable statistical analysis.RESULTS: The median (interquartile range) concentrations of hs-cTnI were 8.4 ng/L(5.6-14.2 ng/L) and 5.3 ng/L (3.8-8.1 ng/L) in men (2416) and women (3275),respectively, and the concentrations increased linearly with age. Outcomes as to all-cause death and incidence of CVD and CHD were significantly associated withincreasing concentrations of hs-cTnI beginning well below the 99th percentileconcentrations. The associations with outcome remained after adjustments forconventional risk factors and were similar in men and women.CONCLUSIONS: Our findings suggest that hs-cTnI reflects the status of themyocardium even in seemingly healthy individuals and that the measurements ofhs-cTnI may be useful for primary prediction of heart disease; this should formthe basis for future prospective clinical trials for determining whethermeasuring hs-cTnI can be used in the prevention of CVD/CHD.
© 2016 American Association for Clinical Chemistry.
PMID: 26936931  [PubMed - in process]

19. Lung India. 2016 Jan-Feb;33(1):53-7. doi: 10.4103/0970-2113.173052.
Prognostic value of cardiac troponin I during acute exacerbation of chronicobstructive pulmonary disease: A prospective study.
Noorain S(1).
Author information: (1)Department of General Medicine, Kempegowda Institute of Medical Sciences,Bengaluru, Karnataka, India.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause ofmortality and morbidity. It is the fourth leading cause of death worldwide. Acuteexacerbations of COPD are common and are associated with worsening lung function and mortality.OBJECTIVES: To evaluate the prevalence of elevation of cTnI in patients admitted with acute exacerbation of COPD and to study its association with the need forventilator support, duration of hospital stay, and in-hospital mortality.METHODS: In a prospective design, 50 patients admitted to our hospital with acuteexacerbation of COPD were included. cTnI was assayed in a blood sample obtainedat admission and 24 h later. Levels above 0.017 µg/L were taken as positive. The following data were also recorded-demographic data, pattern of tobacco use,clinical symptoms and signs, comorbidities, Glasgow Coma Scale, arterial bloodgas, electrocardiogram/two-dimensional echocardiography, chest X-ray, and peakexpiratory flow rate.RESULTS: Among the 50 patients, 4 were females, and 46 were males. cTnI waspositive in 32% of patients with a mean value of 0.272. Patients with cTnIpositive were taken as Group I and those with negative were included in Group II.Prevalence of comorbidities was higher in cTnI positive group, so was theduration of COPD. cTnI elevation correlated significantly with the need for ICUadmission and ventilator support. No significant difference was found in theduration of ventilator support, hospital stay, and in-hospital mortality.CONCLUSION: cTnI is elevated in a significant subset of patients with acuteexacerbation of COPD. Duration of their illness was longer, higher incidence ofischemic heart disease was also found in these patients. Patients with cTnIelevation are more likely to require ICU care and ventilator support. However, itdid not predict in-hospital mortality. Thus, it can be used as a marker toidentify high-risk patients during acute exacerbation of COPD.
PMCID: PMC4748666PMID: 26933308  [PubMed]

20. Arch Biochem Biophys. 2016 Feb 23. pii: S0003-9861(16)30042-X. doi:10.1016/j.abb.2016.02.023. [Epub ahead of print]
The functional significance of the last 5 residues of the C-terminus of cardiactroponin I.
Gilda JE(1), Xu Q(1), Martinez ME(2), Nguyen ST(1), Chase PB(2), Gomes AV(3).
Author information: (1)Department of Neurobiology, Physiology, and Behavior, University ofCalifornia, Davis, 95616, USA. (2)Department of Biological Science, Florida StateUniversity, Tallahassee, FL, 32306, USA. (3)Department of Neurobiology,Physiology, and Behavior, University of California, Davis, 95616, USA. Electronicaddress: avgomes@ucdavis.edu.
The C-terminal region of cardiac troponin I (cTnI) is known to be important incardiac function, as removal of the last 17 C-terminal residues of human cTnI hasbeen associated with myocardial stunning. To investigate the C-terminal region ofcTnI, three C-terminal deletion mutations in human cTnI were generated: Δ1(deletion of residue 210), Δ3 (deletion of residues 208-210), and Δ5 (deletion ofresidues 206-210). Mammalian two-hybrid studies showed that the interactionsbetween cTnI mutants and cardiac troponin C (cTnC) or cardiac troponin T (cTnT)were impaired in Δ3 and Δ5 mutants when compared to wild-type cTnI. Troponincomplexes containing 2-[4'-(iodoacetamido) anilino] naphthalene-6-sulfonic acid(IAANS) labeled cTnC showed that the troponin complex containing cTnI Δ5 had asmall increase in Ca(2+) affinity (P < 0.05); while the cTnI Δ1- and Δ3 troponin complexes showed no difference in Ca(2+) affinity when compared to wild-typetroponin. In vitro motility assays showed that all truncation mutants hadincreased Ca(2+) dependent motility relative to wild-type cTnI. These resultssuggest that the last 5 C-terminal residues of cTnI influence the binding of cTnIwith cTnC and cTnT and affect the Ca(2+) dependence of filament sliding, anddemonstrate the importance of this region of cTnI.
Copyright © 2016 Elsevier Inc. All rights reserved.
PMID: 26919894  [PubMed - as supplied by publisher]

21. Atherosclerosis. 2016 Apr;247:135-41. doi: 10.1016/j.atherosclerosis.2016.02.012.Epub 2016 Feb 15.
High-sensitivity Troponin T in relation to coronary plaque characteristics inpatients with stable coronary artery disease; results of the ATHEROREMO-IVUSstudy.
Oemrawsingh RM(1), Cheng JM(2), García-García HM(3), Kardys I(2), van SchaikRH(4), Regar E(2), van Geuns RJ(2), Serruys PW(2), Boersma E(5), Akkerhuis KM(2).
Author information: (1)Thoraxcenter, Department of Cardiology, ErasmusMC and Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands; Netherlands HeartInstitute/Interuniversity Cardiology Institute of the Netherlands, Utrecht, TheNetherlands. (2)Thoraxcenter, Department of Cardiology, ErasmusMC andCardiovascular Research Institute COEUR, Rotterdam, The Netherlands.(3)Cardialysis BV, Rotterdam, The Netherlands; Washington Hospital Center,Department of Cardiology, Washington DC, United States. (4)Department of ClinicalChemistry, ErasmusMC, Rotterdam, The Netherlands. (5)Thoraxcenter, Department of Cardiology, ErasmusMC and Cardiovascular Research Institute COEUR, Rotterdam, TheNetherlands. Electronic address: h.boersma@erasmusmc.nl.
BACKGROUND AND AIMS: To assess the relationship between the extent and phenotype of coronary atherosclerosis, as assessed by in-vivo grayscale and radiofrequency intravascular ultrasound (IVUS), and circulating Troponin levels in patients withestablished stable coronary artery disease (CAD).METHODS: In this single-center, cross-sectional analysis, high-sensitivityTroponin T (hsTnT) was measured and IVUS was performed in a predefinednon-stenotic segment of a non-culprit coronary artery in 231 patients with stableCAD undergoing elective angiography.RESULTS: HsTnT was detectable (>3 pg/mL) in 212 patients (92%) and aconcentration above 14 pg/mL was observed in 19.5%. Normalised segmental plaquevolumes were positively associated with hsTnT levels (25.0 mm(3) increase insegmental plaque volume per SD increase in ln-transformed hsTnT, 95% CI:6.0-44.0, p = 0.010). Higher hsTnT levels were measured in patients with avirtual histology derived thin-cap fibroatheroma (VH-TCFA, adj. odds ratio forpresence of VH-TCFA = 1.52 per SD increase in ln-transformed hsTnT, 95% CI:1.10-2.11, p = 0.011). Patients with a VH-TCFA had a 2-fold increased prevalence of hsTnT concentration ≥14 pg/mL (adj. OR 2.35, 95% CI: 1.12-4.91, p = 0.024). Inaddition, a 3-fold increased prevalence of hsTnT concentration ≥14 pg/mL wasobserved in patients with a VH-TCFA with a lesional plaque volume higher than themedian (adj. OR 3.36, 95% CI: 1.44-7.84, p = 0.005).CONCLUSIONS: Segmental plaque volume and presence of VH-TCFA lesions areassociated with higher circulating hsTnT concentrations in stable CAD patients.Subclinical plaque rupture or erosion and distal embolisation may be hypothesizedas a potential pathophysiological mechanism with respect to Troponin elevationand its relation with adverse outcome in this patient population.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
PMID: 26917225  [PubMed - in process]

22. Eur Heart J. 2016 Feb 24. pii: ehw029. [Epub ahead of print]
Consequences of implementing a cardiac troponin assay with improved sensitivityat Swedish coronary care units: an analysis from the SWEDEHEART registry.
Eggers KM(1), Lindahl B(2), Melki D(3), Jernberg T(3).
Author information: (1)Department of Medical Sciences, Uppsala University, S-751 85 Uppsala, Swedenkai.eggers@ucr.uu.se. (2)Uppsala Clinical Research Center, Uppsala University,Uppsala, Sweden. (3)Department of Medicine, Section of Cardiology, KarolinskaInstitutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
AIMS: Cardiac troponin (cTn) assays with improved sensitivity are increasinglyutilized for the assessment of patients admitted because of suspected acutecoronary syndrome (ACS). However, data on the clinical consequences of theimplementation of such assays are limited.METHODS AND RESULTS: In a retrospective register-based study (37 710 coronarycare unit admissions; SWEDEHEART registry), we compared the case mix, the use of diagnostic procedures, treatments, and 1-year all-cause mortality 1 year beforethe implementation of a cTn assay with improved sensitivity (study period 1) and 1 year thereafter (study period 2). During study period 2, more at-risk patients were admitted and more patients had cTn levels above the myocardial infarctioncut-off (ACS patients +13.1%; non-ACS patients +160.1%). cTn levels above thiscut-off exhibited stronger associations with mortality risk in study period 2(adjusted HR 4.45 [95% confidence interval, CI, 3.36-5.89]) compared with period 1 (adjusted HR 2.43 [95% CI 2.11-2.80]), similar as for the cTn ratio relative tothe respective 99th percentile. While there was no multivariable-adjustedincrease in the use of diagnostic procedures, significant trends towards moredifferentiated treatment depending on the cause of cTn elevation, i.e. ACS ornon-ACS, were noted.CONCLUSIONS: The implementation of a cTn assay with improved sensitivity wasassociated with an increase in the number of patients who due to their cTn-statuswere identified as suitable for beneficial therapies. There was no inappropriate increase in hospital resource utilization. As such, cTn assays with improvedsensitivity provide an opportunity to improve the clinical management of patientswith suspected ACS.
Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2016. For permissions please email: journals.permissions@oup.com.
PMID: 26916797  [PubMed - as supplied by publisher]

23. Thromb Res. 2016 Mar;139:56-64. doi: 10.1016/j.thromres.2016.01.009. Epub 2016Jan 12.
NETosis promotes cancer-associated arterial microthrombosis presenting asischemic stroke with troponin elevation.
Thålin C(1), Demers M(2), Blomgren B(3), Wong SL(2), von Arbin M(1), von HeijneA(4), Laska AC(1), Wallén H(5), Wagner DD(6), Aspberg S(5).
Author information: (1)Department of Clinical Sciences, Danderyd Hospital, Division of InternalMedicine, Karolinska Institutet, Stockholm, Sweden. (2)Program in Cellular andMolecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department ofPediatrics, Harvard Medical School, Boston, MA, USA. (3)Department of ClinicalSciences, Danderyd Hospital, Department of Oncology-Pathology, KarolinskaInstitutet, Stockholm, Sweden. (4)Department of Clinical Sciences, DanderydHospital, Department of Radiology, Karolinska Institutet, Stockholm, Sweden.(5)Department of Clinical Sciences, Danderyd Hospital, Division of CardiovascularMedicine, Karolinska Institutet, Stockholm, Sweden. (6)Program in Cellular andMolecular Medicine, Boston Children's Hospital orologi replica italia, Boston, MA, USA; Department ofPediatrics, Harvard Medical School, Boston, MA, USA; Division ofHematology/Oncology, Boston Children's Hospital, Boston, MA, USA. Electronicaddress: denisa.wagner@childrens.harvard.edu.

INTRODUCTION: Large elevations of high sensitive Troponin T (hsTnT) in ischemicstroke patients is associated with a poor outcome. In a pilot study we found ahigh prevalence of malignancies among these patients. Since neutrophilextracellular traps (NETs) have been linked to cancer-associated thrombosis, wehypothesized that the concomitant cerebral and myocardial ischemia could be theresult of a NET-induced hypercoagulable state.MATERIALS AND METHODS: Clinical assessments, plasma analyses and autopsies withhistopathology (in cases of in-hospital mortality) were performed on ischemicstroke patients with high elevations of hsTnT (N=12) and normal hsTnT (N=19).RESULTS: Patients with hsTnT elevation had an unexpectedly higher prevalence ofcancer (p=0.002), half of which were diagnosed post-mortem. Autopsies of thesepatients revealed widespread myocardial, cerebral and pulmonary microthrombosiswith H3Cit in thrombi. A pro-coagulant state and an increase of the NET specific marker citrullinated histone H3 (H3Cit) was found in plasma of patients withelevated hsTnT compared to patients with normal levels (p<0.001). Plasma analysesin cancer patients showed even higher H3Cit levels (p<0.001), and an increase in granulocyte colony-stimulating factor, known to prime neutrophils towardsNETosis. H3Cit correlated positively with thrombin-antithrombin complex (p=0.004)and soluble P-selectin (p<0.001), further linking NETosis to the pro-thromboticstate.CONCLUSIONS: The high prevalence of known or occult cancer in our study suggests that cancer-associated arterial microthrombosis may be underestimated. By linkingthe thrombosis to NETs, we suggest markers of NETosis that could aid in revealingcancer in arterial microthrombosis as well as arterial microthrombosis in cancer.
Published by Elsevier Ltd.
PMCID: PMC4769435 [Available on 2017-03-01]PMID: 26916297  [PubMed - in process]

24. Transplantation. 2016 Jan 20. [Epub ahead of print]
B-Type Natriuretic Peptide and Cardiac Troponin I Are Associated With AdverseOutcomes in Stable Kidney Transplant Recipients.
Jarolim P(1), Claggett BL, Conrad MJ, Carpenter MA, Ivanova A, Bostom AG, KusekJW, Hunsicker LG, Jacques PF, Gravens-Mueller L, Finn P, Solomon SD, Weiner DE,Levey AS, Pfeffer MA.
Author information: (1)1 Department of Pathology, Brigham and Women's Hospital, Harvard MedicalSchool, Boston, MA. 2 Department of Medicine, Brigham and Women's Hospital,Harvard Medical School, Boston, MA. 3 Department of Biostatistics, University of North Carolina, Chapel Hill, NC. 4 Division of Nephrology, Rhode Island Hospital,Providence, RI. 5 National Institute of Diabetes and Digestive and KidneyDiseases, Bethesda, MD. 6 University of Iowa, Iowa City, IA. 7 US Department ofAgriculture, Jean Mayer Human Nutrition Research Center on Aging, Boston, MA. 8Tufts Medical Center, Boston, MA.
BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverseoutcomes. Biomarkers predicting these outcomes are needed. Using specimenscollected during the Folic Acid for Vascular Outcome Reduction in Transplantationtrial, we determined whether plasma levels of B-type natriuretic peptide (BNP)and cardiac troponin I are associated with adverse outcomes in stable kidneytransplant recipients.METHODS: Five hundred ten subjects were selected randomly from the 4110 FolicAcid for Vascular Outcome Reduction in Transplantation participants. This cohort was then enriched for all additional subjects with adverse outcomes (death,dialysis-dependent kidney failure (DDKF), and cardiovascular outcomes) for atotal of 1131 participants studied. Quartiles of BNP and high-sensitivity cardiactroponin I (hs-cTnI) were included in adjusted models. Combinations of normal andelevated hs-cTnI (>26.2 ng/L) and BNP (>100 pg/mL) were also studied.RESULTS: Median concentrations (interquartile ranges) were 5.6 (3.3-10.5) ng/Lfor hs-cTnI and 39 (15, 94) pg/mL for BNP. Hazard ratios for each adverse outcomewere higher with higher quartiles of BNP after adjustment and remainedstatistically significant after adding hs-cTnI to the model. The highest quartilehazard ratio for DDKF was 2.47 (95% confidence interval [95% CI], 1.21-5.05).Simultaneous elevations of BNP and hs-cTnI over clinical cutoffs were stronglyassociated with adverse outcomes with hazard ratios 8.8 (95% CI, 3.4-23.1) forDDKF and 6.3 (95% CI, 2.7-15.0) for cardiovascular outcomes.CONCLUSIONS: Higher BNP is associated with mortality and cardiovascular andkidney outcomes in stable kidney transplant recipients. Elevated BNP and hs-cTnI identify candidates for targeted risk reduction.
PMID: 26910333  [PubMed - as supplied by publisher]

25. J Trauma Acute Care Surg. 2016 Mar;80(3):477-83. doi:10.1097/TA.0000000000000916.
The role of cardiac troponin I in prognostication of patients with isolatedsevere traumatic brain injury.
Cai SS(1), Bonds BW, Hu PF, Stein DM.
Author information: (1)From the R Adams Cowley Shock Trauma Center (B.W.B., P.F.H., D.M.S.),Baltimore, Maryland; and University of Maryland School of Medicine (S.S.C.,P.F.H., D.M.S.), Baltimore, Maryland.
BACKGROUND: Cardiac dysfunction is frequently observed after severe traumaticbrain injury (sTBI); however, its significance is poorly understood. Our
ASME BPVC IX Download studysought to elucidate the association of cardiac troponin I (cTnI) elevation withall-cause in-hospital mortality following isolated sTBI (brain Abbreviated InjuryScale score ≥3 and admission Glasgow Coma Scale score ≤8, no Abbreviated InjuryScale score ≥3 to any other bodily regions).METHODS: We retrospectively reviewed all adult patients (aged ≥18 years) withisolated sTBI admitted to a Level I trauma center between June 2007 and SAE Codes In PDF January2014. Patients must have cTnI values within 24 hours of admission. Mortalityrisks were examined by Cox proportional hazard model.RESULTS: Of 580 patients identified, 30.9% had detectable cTnI in 24 hours ofadmission. The median survival time was 4.19 days (interquartile range,1.27-11.69). When adjusted for potential confounders, patients in the highestcTnI category (≥0.21 ng/mL) had a significantly higher risk of in-hospitalmortality (hazard ratio, 1.39; 95% confidence interval, 1.04-1.88) compared with patients with u

Circulatory Shock - REVIEWFecha: 2/4/2016

 

Circulatory Shock

REVIEW ARTICLE

 

                                     Jean-Louis Vincent, M.D., Ph.D., and Daniel De Backer, M.D., Ph.D.

                                                    N Engl J Med 2013; 369:1726-1734

 

 

Shock is the clinical expression of circulatory failure that results in inadequate cellular oxygen utilization. Shock is a common condition in critical care, affecting about one third of patients in the intensive care unit (ICU).1 A diagnosis of shock is based on clinical, hemodynamic, and biochemical signs, which can broadly be summarized into three components. First, systemic arterial hypotension is usually present, but the magnitude of the hypotension may be only moderate, especially in patients with chronic hypertension. Typically, in adults, the systolic arterial pressure is less than 90 mm Hg or the mean arterial pressure is less than 70 mm Hg, with associated tachycardia. Second, there are clinical signs of tissue hypoperfusion, which are apparent through the three "windows" of the body2: cutaneous (skin that is cold and clammy, with vasoconstriction and cyanosis, findings that are most evident in low-flow states), renal (urine output of <0.5 ml per kilogram of body weight per hour), and neurologic (altered mental state, which typically includes obtundation, disorientation, and confusion). Third, hyperlactatemia is typically present, indicating abnormal cellular oxygen metabolism. The normal blood lactate level is approximately 1 mmol per liter, but the level is increased (>1.5 mmol per liter) in acute circulatory failure.

 

PATHOPHYSIOLOGICAL MECHANISMS

Shock results from four potential, and not necessarily exclusive, pathophysiological mechanisms3: hypovolemia (from internal or external fluid loss), cardiogenic factors (e.g., acute myocardial infarction, end-stage cardiomyopathy, advanced valvular heart disease, myocarditis, or cardiac arrhythmias), obstruction (e.g., pulmonary embolism, cardiac tamponade, or tension pneumothorax), or distributive factors (e.g., severe sepsis or anaphylaxis from the release of inflammatory mediators) The first three mechanisms are characterized by low cardiac output and, hence, inadequate oxygen transport. In distributive shock, the main deficit lies in the periphery, with decreased systemic vascular resistance and altered oxygen extraction. Typically, in such cases cardiac output is high, although it may be low as a result of associated myocardial depression. Patients with acute circulatory failure often have a combination of these mechanisms. For example, a patient with distributive shock from severe pancreatitis, anaphylaxis, or sepsis may also have hypovolemia and cardiogenic shock from myocardial depression.

 

DIFFERENTIAL DIAGNOSIS

Septic shock, a form of distributive shock, is the most common form of shock among patients in the ICU, followed by cardiogenic and hypovolemic shock; obstructive shock is relatively rare. In a trial involving more than 1600 ANSI Codes Download patients with shock who were randomly assigned to receive either dopamine or norepinephrine, septic shock occurred in 62% of the patients, cardiogenic shock in 16%, hypovolemic shock in 16%, other types of distributive shock in 4%, and obstructive shock in 2%.4

The type and cause of shock may be obvious from the medical history, physical examination, or clinical investigations. For example, shock after traumatic injury is likely to be hypovolemic (due to blood loss), but cardiogenic shock or distributive shock may also occur, alone or in combination, caused by such conditions as cardiac tamponade or spinal cord injury. A full clinical examination should include assessment of skin color and temperature, jugular venous distention, and peripheral edema. The diagnosis can be refined with point-of-care echocardiographic evaluation, which includes assessment for pericardial effusion, measurement of left and right ventricular size and function, assessment for respiratory variations in vena cava dimensions, and calculation of the aortic velocity-time integral, a measure of stroke volume. Whenever possible, focused echocardiography should be performed as soon as possible in any patient presenting with shock.5,6

 

INITIAL APPROACH TO THE PATIENT IN SHOCK

Early, adequate hemodynamic support of patients in shock is crucial to prevent worsening organ dysfunction and failure. Resuscitation should be started even while investigation of the cause is ongoing. Once identified, the cause must be corrected rapidly (e.g., control of bleeding, percutaneous coronary intervention for coronary syndromes, thrombolysis or embolectomy for massive pulmonary embolism, and administration of antibiotics and source control for septic shock).

Unless the condition is rapidly reversed, an arterial catheter should be inserted for monitoring of arterial blood pressure and blood sampling, plus a central venous catheter for the infusion of fluids and vasoactive agents and to guide fluid therapy. The initial management of shock is problem-oriented, and the goals are therefore the same, regardless of the cause, although the exact treatments that are used to reach those goals may differ. A useful mnemonic to describe the important components of resuscitation is the VIP rule7: ventilate (oxygen administration), infuse (fluid resuscitation), and pump (administration of vasoactive agents).

Ventilatory Support

The administration of oxygen should be started immediately to increase oxygen delivery and prevent pulmonary hypertension. Pulse oximetry is often unreliable as a result of peripheral vasoconstriction, and precise determination of oxygen requirements will often require blood gas monitoring.

Mechanical ventilation by means of a mask rather than endotracheal intubation has a limited place in the treatment of shock because technical failure can rapidly result in respiratory and cardiac arrest. Hence, endotracheal intubation should be performed to provide invasive mechanical ventilation in nearly all patients with severe dyspnea, hypoxemia, or persistent or worsening acidemia (pH, <7.30). Invasive mechanical ventilation has the additional benefits of reducing the oxygen demand of respiratory muscles and decreasing left ventricular afterload by increasing intrathoracic pressure. An abrupt decrease in arterial pressure after the initiation of invasive mechanical ventilation strongly suggests hypovolemia and a decrease in venous return. The use of sedative agents should be kept to a minimum to avoid further decreases in arterial pressure and cardiac output.

Fluid Resuscitation

Fluid therapy to improve microvascular blood flow and increase cardiac output is an essential part of the treatment of any form of shock. Even patients with cardiogenic shock may benefit from fluids, since acute edema can result in a decrease in the effective intravascular volume. However, fluid administration should be closely monitored, since too much fluid carries the risk of edema with its unwanted consequences.

Pragmatic end points for fluid resuscitation are difficult to define. In general, the objective is for cardiac output to become preload-independent (i.e., on the plateau portion of the Frank-Starling curve), but this is difficult to assess clinically. In patients receiving mechanical ventilation, signs of fluid responsiveness may be identified either directly from beat-by-beat stroke-volume measurements with the use of cardiac-output monitors or indirectly from observed variations in pulse pressure on the arterial-pressure tracing during the ventilator cycle. However, such bedside inferences have some limitations8 - notably, that the patient must receive ventilation with relatively large tidal volumes, have no spontaneous breathing effort (which usually requires the administration of sedatives or even muscle relaxants), and be free of major arrhythmia and right ventricular dysfunction. A passive leg-raising test is an alternative method9 but requires a rapid-response device, since the effect is transient. Regardless of the test used, there remains a gray zone in which it is difficult to predict a patient's response to intravenous fluids.

A fluid-challenge technique should be used to determine a patient's actual response to fluids, while limiting the risks of adverse effects. A fluid challenge incorporates four elements that should be defined in advance.10 First, the type of fluid must be selected. Crystalloid solutions are the first choice, because they are well tolerated and cheap. The use of albumin to Buy NFPA Codes correct severe hypoalbuminemia may be reasonable in some patients.11 (A detailed examination of the choice of resuscitation fluids was provided in a previous article in this series12 and thus is not included in this review.) Second, the rate of fluid administration must be defined. Fluids should be infused rapidly to induce a quick response but not so fast that an artificial stress response develops; typically, an infusion of 300 to 500 ml of fluid is administered during a period of 20 to 30 minutes.13Third, the objective of the fluid challenge must be defined. In shock, the objective is usually an increase in systemic arterial pressure, although it could also be a decrease in heart rate or an increase in urine output. Finally, the safety limits must be defined. Pulmonary edema is the most serious complication of fluid infusion. Although it is not a perfect guideline, a limit in central venous pressure of a few millimeters of mercury above the baseline value is usually set to prevent fluid overload.13

Stimulation of the patient and any other change in therapy should be avoided during the test. Fluid challenges can be repeated as required but must be stopped rapidly in case of nonresponse in order to avoid fluid overload.

Vasoactive Agents

Vasopressors

If hypotension is severe or if it persists despite fluid administration, the use of vasopressors is indicated. It is acceptable practice to administer a vasopressor temporarily while fluid resuscitation is ongoing, with the aim of discontinuing it, if possible, after hypovolemia has been corrected.

Adrenergic agonists are the first-line vasopressors because of their rapid onset of action, high potency, and short half-life, which allows easy dose adjustment. Stimulation of each type of adrenergic receptor has potentially beneficial and harmful effects. For example, β-adrenergic stimulation can increase blood flow but also increases the risk of myocardial ischemia as a result of increased heart rate and contractility. Hence, the use of isoproterenol, a pure β-adrenergic agent, is limited to the treatment of patients with severe bradycardia. At the other extreme, α-adrenergic stimulation will increase vascular tone and blood pressure but can also decrease cardiac output and impair tissue blood flow, especially in the hepatosplanchnic region. For this reason, phenylephrine, an almost pure α-adrenergic agent, is rarely indicated.

We consider norepinephrine to be the vasopressor of first choice; it has predominantly α-adrenergic properties, but its modest β-adrenergic effects help to maintain cardiac output. Administration generally results in a clinically significant increase in mean arterial pressure, with little change in heart rate or cardiac output. The usual dose is 0.1 to 2.0 μg per kilogram of body weight per minute.

Dopamine has predominantly β-adrenergic effects at lower doses and α-adrenergic effects at higher doses, but its effects are relatively weak. Dopaminergic effects at very low doses (<3 μg per kilogram per minute, given intravenously) may selectively dilate the hepatosplanchnic and renal circulations, but controlled trials have not shown a protective effect on renal function,14 and its routine use for this purpose is no longer recommended. Dopaminergic stimulation may also have undesired endocrine effects on the hypothalamic-pituitary system, resulting in immunosuppression, primarily through a reduction in the release of prolactin.

In a recent randomized, controlled, double-blind trial, dopamine had no advantage over norepinephrine as the first-line vasopressor agent; moreover, it induced more arrhythmias and was associated with an increased 28-day rate of death among patients with cardiogenic shock.4Administration of dopamine, as compared with norepinephrine, may also be associated with higher rates of death among patients with septic shock.15 Hence, we no longer recommend dopamine for the treatment of patients with shock.

Epinephrine, which is a stronger agent, has predominantly β-adrenergic effects at low doses, with α-adrenergic effects becoming more clinically significant at higher doses. However, epinephrine administration can be associated with an increased rate of arrhythmia16,17 and a decrease in splanchnic blood flow16 and can increase blood lactate levels, probably by increasing cellular metabolism.16,18 Prospective, randomized studies have not shown any beneficial effects of epinephrine over norepinephrine in septic shock.17,18 We reserve epinephrine as a second-line agent for severe cases.13

The use of other strong vasopressor agents as continuous infusions (e.g., angiotensin or metaraminol) has largely been abandoned. Nonselective inhibition of nitric oxide has not been shown to be beneficial in patients with cardiogenic shock19 and is detrimental in patients with septic shock.20

Vasopressin deficiency can develop in patients with very hyperkinetic forms of distributive shock, and the administration of low-dose vasopressin may result in substantial increases in arterial pressure. In the Vasopressin and Septic Shock Trial (VASST), investigators found that the addition of low-dose vasopressin to norepinephrine in the treatment of patients with septic shock was safe21and may have been associated with a survival benefit for patients with forms of shock that were not severe and for those who also received glucocorticoids.22 Vasopressin should not be used at doses higher than 0.04 U per minute and should be administered only in patients with a high level of cardiac output.

Terlipressin, an analogue of vasopressin, has a duration of action of several hours, as compared with minutes for vasopressin. For this reason, we do not believe it offers an advantage over vasopressin in the ICU. Vasopressin derivatives with more selective V1-receptor activity are currently being studied.

Inotropic Agents

We consider dobutamine to be the inotropic agent of choice for increasing cardiac output, regardless of whether norepinephrine is also being given. With predominantly β-adrenergic properties, dobutamine is less likely to induce tachycardia than isoproterenol. An initial dose of just a few micrograms per kilogram per minute may substantially increase cardiac output. Intravenous doses in excess of 20 μg per kilogram per minute usually provide little additional benefit. Dobutamine has limited effects on arterial pressure, although pressure may increase slightly in patients with myocardial dysfunction as the primary abnormality or may decrease slightly in patients with underlying hypovolemia. Instead of routine administration of a fixed dose of dobutamine to increase oxygen delivery to supranormal, predetermined levels, the dose should be adjusted on an individual basis to achieve adequate tissue perfusion. Dobutamine may improve capillary perfusion in patients with septic shock, independent of its systemic effects.23

Phosphodiesterase type III inhibitors, such as milrinone and enoximone, combine inotropic and vasodilating properties. By decreasing the metabolism of cyclic AMP, these agents may reinforce the effects of dobutamine. They may also be useful when β-adrenergic receptors are down-regulated or in patients recently treated with beta-blockers. However, phosphodiesterase type III inhibitors may have unacceptable adverse effects in patients with hypotension, and the long half-lives of these agents (4 to 6 hours) prevent minute-to-minute adjustment. Hence, intermittent, short-term infusions of small doses of phosphodiesterase III inhibitors may be preferable to a continuous infusion in shock states.

Levosimendan, a more expensive agent, acts primarily by binding to cardiac troponin C and increasing the calcium sensitivity of myocytes, but it also acts as a vasodilator by opening ATP-sensitive potassium channels in vascular smooth muscle. However, this agent has a half-life of several days, which limits the practicality of its use in acute shock states.

Vasodilators

By reducing ventricular afterload, vasodilating agents may increase cardiac output without increasing myocardial demand for oxygen. The major limitation of these drugs is the risk of decreasing arterial pressure to a level that compromises tissue perfusion. Nevertheless, in some patients, prudent use of nitrates and possibly other vasodilators may improve microvascular perfusion and cellular function.24

 

MECHANICAL SUPPORT

Mechanical support with intraaortic balloon counterpulsation (IABC) can reduce left ventricular afterload and increase coronary blood flow. However, a recent randomized, controlled trial showed no beneficial effect of IABC in patients with cardiogenic shock,25 and its routine use in cardiogenic shock is not currently recommended. Venoarterial extracorporeal membrane oxygenation (ECMO) may be used as a temporary lifesaving measure in patients with reversible cardiogenic shock or as a bridge to heart transplantation.26

 

GOALS OF HEMODYNAMIC SUPPORT

Arterial Pressure

The primary goal of resuscitation should be not only to restore blood pressure but also to provide adequate cellular metabolism, for which the correction of arterial hypotension is a prerequisite. Restoring a mean systemic arterial pressure of 65 to 70 mm Hg is a good initial goal, but the level should be adjusted to restore tissue perfusion, assessed on the basis of mental status, skin appearance, and urine output, as described above. In patients with oliguria, in particular, the effects of a further increase in arterial pressure on urine output should be assessed regularly, unless acute renal failure is already established. Conversely, a mean arterial pressure lower than 65 to 70 mm Hg may be acceptable in a patient with acute bleeding who has no major neurologic problems, with the aim of limiting blood loss and associated coagulopathy, until the bleeding is controlled.

Cardiac Output and Oxygen Delivery

Since circulatory shock represents an imbalance between oxygen supply and oxygen requirements, maintaining adequate oxygen delivery to the tissues is essential, but all the strategies to achieve this goal have limitations. After correction of hypoxemia and severe anemia, cardiac output is the principal determinant of oxygen delivery, but the optimal cardiac output is difficult to define. Cardiac output can be measured by means of various techniques, each of which has its own benefits and drawbacks.6 Absolute measures of cardiac output are less important than monitoring trends in response to interventions such as a fluid challenge. The targeting of a predefined cardiac output is not advisable, since the cardiac output that is needed will vary among patients and in the same patient over time.

Measurements of mixed venous oxygen saturation (SvO2) may be helpful in assessing the adequacy of the balance between oxygen demand and supply; SvO2 measurements are also very useful in the interpretation of cardiac output.27 SvO2 is typically decreased in patients with low-flow states or anemia but is normal or high in those with distributive shock. Its surrogate, central venous oxygen saturation (ScvO2), which is measured in the superior vena cava by means of a central venous catheter, reflects the oxygen saturation of the venous blood from the upper half of the body only. Under normal circumstances, ScvO2 is slightly less than SvO2, but in critically ill patients it is often greater. Rivers et al.28 found that in patients presenting to the emergency department with septic shock, a treatment algorithm targeting an ScvO2 of at least 70% during the first 6 hours was associated with decreased rates of death. The robustness of this finding is currently being evaluated in three multicenter trials. (ClinicalTrials.gov numbers, NCT00975793 and NCT00510835; and Current Controlled Trials number, ISRCTN36307479).

Blood Lactate Level

An increase in the blood lactate level reflects abnormal cellular function. In low-flow states, the primary mechanism of hyperlactatemia is tissue hypoxia with development of anaerobic metabolism, but in distributive shock, the pathophysiology is more complex and may also involve increased glycolysis and inhibition of pyruvate dehydrogenase. In all cases, alterations in clearance can be due to impaired liver function.

The value of serial lactate measurements in the management of shock has been recognized for 30 years.29 Although changes in lactate take place more slowly than changes in systemic arterial pressure or cardiac output, the blood lactate level should decrease over a period of hours with effective therapy. In patients with shock and a blood lactate level of more than 3 mmol per liter, Jansen et al.24 found that targeting a decrease of at least 20% in the blood lactate level over a 2-hour period seemed to be associated with reduced in-hospital mortality.

Microcirculatory Variables

The development of handheld devices for orthogonal polarization spectral (OPS) imaging and its successor, sidestream dark-field (SDF) imaging, is providing new means of directly visualizing the microcirculation and evaluating the effects of interventions on microcirculatory flow in easily accessible surfaces, such as the sublingual area.30 Microcirculatory changes, including decreased capillary density, a reduced proportion of perfused capillaries, and increased heterogeneity of blood flow, have been identified in various types of circulatory shock and the persistence of these alterations is associated with worse outcomes.

Near-infrared spectroscopy is a technique that uses near-infrared light to determine tissue oxygen saturation from the fractions of oxyhemoglobin and deoxyhemoglobin. Analysis of the changes in tissue oxygen saturation during a brief episode of forearm ischemia can be used to quantify microvascular dysfunction32; such alterations are associated with worse outcomes.33 Various therapeutic interventions have been shown to have an effect on these microcirculatory variables, but whether therapy that is guided by monitoring or targeting the microcirculation can improve outcomes requires further study and cannot be recommended at this time.

THERAPEUTIC PRIORITIES AND GOALS

There are essentially four phases in the treatment of shock, and therapeutic goals and monitoring need to be adapted to each phase. In the first (salvage) phase, the goal of therapy is to achieve a minimum blood pressure and cardiac output compatible with immediate survival. Minimal monitoring is needed; in most cases, invasive monitoring can be restricted to arterial and central venous catheters. Lifesaving procedures (e.g., surgery for trauma, pericardial drainage, revascularization for acute myocardial infarction, and antibiotics for sepsis) are needed to treat the underlying cause. In the second (optimization) phase, the goal is to increase cellular oxygen availability, and there is a narrow window of opportunity for interventions targeting hemodynamic status.28 Adequate hemodynamic resuscitation reduces inflammation, mitochondrial dysfunction, and caspase activation.34,35 Measurements of SvO2 and lactate levels may help guide therapy, and monitoring of cardiac output should be considered. In the third (stabilization) phase, the goal is to prevent organ dysfunction, even after hemodynamic stability has been achieved. Oxygen supply to the tissues is no longer the key problem, and organ support becomes more relevant. Finally, in the fourth (de-escalation) phase, the goal is to wean the patient from vasoactive agents and promote spontaneous polyuria or provoke fluid elimination through the use of diuretics or ultrafiltration to achieve a negative fluid balance.

CONCLUSIONS

Circulatory shock is associated with high morbidity and mortality. Prompt identification is essential so that aggressive management can be started. Appropriate treatment is based on a good understanding of the underlying pathophysiological mechanisms. Treatment should include correction of the cause of shock and hemodynamic stabilization, primarily through fluid infusion and administration of vasoactive agents. The patient's response can be monitored by means of careful clinical evaluation and blood lactate measurements; microvascular evaluation may be feasible in the future.

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Peripheral Mechanisms in Irritable Bowel Syndrome - REVIEWFecha: 1/3/2016

 

 

Peripheral Mechanisms in Irritable Bowel Syndrome

REVIEW ARTICLE

 

                                                                                 Michael Camilleri, M.D.

                                                                   N Engl J Med 2012; 367:1626-1635

 

The irritable bowel syndrome (IBS) affects 10 to 20% of the population in developed countries. Specific peripheral mechanisms result in symptoms of IBS, including abnormal colonic transit and rectal evacuation; intraluminal intestinal irritants, such as maldigested carbohydrates (producing short-chain fatty acids) or fats, an excess of bile acids, and gluten intolerance; alterations in the microbiome; entero-endocrine-cell products; and genetic susceptibility to inflammation or altered bile acid synthesis. These luminal and mucosal irritants alter mucosal permeability and cause immune activation or inflammation, which in turn activates local reflexes that alter intestinal motility or secretion. The irritants also stimulate sensory mechanisms, leading to visceral hypersensitivity and pain. A greater understanding of these mechanisms may foster individualized, specific treatments for patients with IBS.

DIAGNOSIS AND CONVENTIONAL MECHANISMS

The diagnosis of IBS is traditionally based on symptoms of recurrent abdominal pain or discomfort at least 3 days per month in the previous 3 months, in association with two or more of the following: improvement with defecation, an onset associated with a change in the frequency of bowel movements, or an onset associated with a change in the form (appearance) of stool. In the past, it was generally considered that the predominant pathophysiological mechanisms in IBS were abnormalities intrinsic to the smooth muscle of the gut, visceral hypersensitivity, and central nervous system hypervigilance.1-3 Brain dysfunction and abnormal interaction of the peripheral and central nervous system are potential mechanisms causing hypersensitivity in IBS3; however, hypersensitivity4,5 and central nervous system dysfunction6,7 are not ubiquitous in patients with IBS. Thus, although persistent nociceptive mechanisms are activated in some patients,7 IBS is not "all in the head" in all patients. There is a renaissance in the understanding of IBS: symptoms are not specific to a single etiologic mechanism but are manifestations of several peripheral mechanisms that perturb motor and sensory functions.

ABNORMAL COLONIC TRANSIT AND DISORDERS OF EVACUATION

Symptoms of constipation-predominant IBS reflect those of chronic constipation,8 and many patients with constipation-predominant IBS can be treated first for constipation. About 25% of patients with constipation-predominant IBS (range among studies, 5 to 46) have slow colonic transit. 5,9,10 Treatment with intestinal secretagogues (i.e., lubiprostone and linaclotide) or prokinetic agents (e.g., tegaserod) is effective in relieving constipation and associated IBS symptoms such as pain and bloating. 11

Disorders of rectal evacuation (spasm of the puborectalis muscle, anismus, and the descending perineum syndrome) cause symptoms of constipation-predominant IBS12 - that is, constipation, straining, a sense of incomplete rectal evacuation, bloating, and left-sided abdominal pain, which are relieved with bowel movement. Treatment of the evacuation disorder relieves the symptoms of constipation-predominant IBS.13 An evacuation disorder should be suspected when patients with constipation do not have a response to first-line therapies such as fiber14 and simple (e.g., osmotic) laxatives.

Diarrhea-predominant IBS is associated with acceleration of colonic transit in 15 to 45% of patients.5,10 Several disorders mimic diarrhea-predominant IBS or cause accelerated transit and should be ruled out, such as food allergy or intolerance, disaccharidase deficiencies, celiac disease, gluten intolerance without celiac disease, microscopic colitis, and idiopathic bile acid malabsorption.15

MECHANISMS INVOLVED IN BOWEL IRRITATION

Luminal and mucosal factors activate immune, motor, and sensory mechanisms in the small intestine or colon. Such "irritation" leads to the symptoms and pathophysiological features of IBS

Luminal Factors

Responses to Food Ingestion

Pain is temporally related to eating in patients with IBS,16 especially in those with diarrhea-predominant IBS who have repeated, high-amplitude, propagated colonic contractions17 (i.e., contractions that traverse ≥10 cm of colon and propel colonic content). Patients with diarrhea-predominant IBS, as compared with healthy controls, also have increased ileocolonic transit,18 typically induced by meals containing fat and providing at least 500 kcal.18 In addition, one study involving patients with IBS showed that scores for urge, discomfort, and pain in response to rectal distention were significantly increased after a 368-kcal meal relative to fasting, though the magnitude of these differences in sensation was small.19 The fat content of the meal, rather than the carbohydrate content, appears to have a key role in sensations of discomfort and pain. 20

Malabsorbed or Maldigested Nutrients

Malabsorption of sugars, such as lactose, fructose, and sorbitol, may mimic the features of IBS, but its prevalence across ethnic groups and races is unclear.21,22 A Norwegian case-control study suggested that IBS and lactose malabsorption were separate entities.21 Fructose and sorbitol malabsorption were observed in patients with IBS from Denmark,22 but not in patients from the Netherlands.23

Maldigestion of complex carbohydrates may be more prevalent than malabsorption in patients with IBS. Fecal short-chain fatty acids, which contain fewer than 6 carbon atoms, are increased in stool from patients with diarrhea-predominant IBS.24 Short-chain fatty acids or medium-chain fatty acids (which contain 6 to 12 carbon atoms) reach the right colon in patients with borderline absorptive capacity or rapid transit in the small bowel. In a study involving healthy volunteers, 2 to 20% of dietary starch escaped absorption in the small bowel,25 providing substrate for the generation of short-chain fatty acids by colonic bacteria. The short-chain fatty acid receptor 2 (called free fatty acid receptor 2 [FFA2] or G-protein-coupled receptor 43) is expressed by enteroendocrine cells and mucosal mast cells in rat intestine.26 Short-chain fatty acids stimulate colonic transit and motility through intraluminal release of 5-hydroxytryptamine (5-HT)27 from enteroendocrine cells28 in rats. Short-chain fatty acids also initiate high-amplitude propagated contractions in the colon, propelling colonic content rapidly in dogs.29 An in vitro study in guinea-pig colon showed that the short-chain fatty acid propionate induced transepithelial ion and fluid transport in mucosal preparations from the distal colon and increased the expression of FFA2, which colocalizes with chromogranin A-enteroendocrine cells.30

Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) are poorly absorbed in the small intestine and may induce symptoms of IBS31 through the production of short-chain fatty acids and their effects on colonic motility and secretion. Conversely, dietary manipulation of FODMAP content may reduce IBS symptoms.32 The role of the colonic microbiota in these nutrient-induced symptoms requires further elucidation.

Gluten Intolerance

The prevalence of celiac disease among patients with IBS33 is similar to that among controls.Celiac disease-free patients with IBS who carry HLA-DQ2 or HLA-DQ8 genotypes (which confer a predisposition to celiac disease) were five times as likely to have a response to gluten withdrawal as were patients without these genotypes.34 A randomized, placebo-controlled trial involving patients who previously reported intolerance to gluten and a response to its withdrawal confirmed that gluten was associated with symptoms of IBS.35 In mice sensitized to wheat glycoprotein, gliadin treatment increased responses to contractile and secretory stimuli (carbachol and electrical-field stimulation).36 In a recent randomized, controlled trial of a gluten-containing diet versus a gluten-free diet in patients with diarrhea-predominant IBS, those receiving gluten had increased stool frequency and bowel permeability and reduced messenger RNA expression of tight-junction proteins in bowel mucosa.37

Increased Levels of Intracolonic Bile Acids

Although the ileum is excessively sensitive to the secretory effects of perfused bile acids in patients with IBS,38 the effects of bile acids are mainly manifested as cholerheic enteropathy with diarrhea. A systematic review of the literature suggested that bile acid malabsorption accounts for approximately 30% of cases of diarrhea-predominant IBS. 39 In other studies, about 25% of patients with diarrhea-predominant IBS had an elevated rate of either bile acid synthesis (as measured by the fasting concentration of serum 7α-hydroxy-4-cholesten-3-one [C4, a bile acid precursor]) or 48-hour total fecal bile acid excretion.40,41

Excess intracolonic bile acid in diarrhea-predominant IBS results from alterations in the enterohepatic circulation of bile acids. Synthesis of bile acid is regulated homeostatically by feedback inhibition of hepatocytes provided by fibroblast growth factor 19 (FGF19), which is produced by ileal enterocytes. FGF19 is secreted into the portal circulation and binds to fibroblast growth factor receptor 4 (FGFR4) and the klotho-β (KLB) receptor on the hepatocyte cell membrane, triggering intracellular signals that suppress bile acid synthesis. Given that a defect in bile acid absorption has been demonstrated in diarrhea-predominant IBS,39 it appears that excessive synthesis of bile acids overcomes ileal absorption capacity, leading to bile acid diarrhea.42

Various mechanisms have been suggested to cause the elevated levels of intracolonic bile acid reported in diarrhea-predominant IBS or functional diarrhea. One potential mechanism is a deficiency in ileal secretion of FGF19. Walters et al.43 found that ileal production of FGF19 (reflected in plasma levels of this hormone) was reduced in patients with chronic diarrhea associated with bile acid malabsorption. There was an inverse relationship between fasting serum FGF19 levels and serum C4 levels (a finding that is consistent with increased bile acid synthesis); this inverse correlation was confirmed in patients with diarrhea-predominant IBS.44,45 Another potential mechanism is mutation of the ileal bile acid transporter (also termed apical sodium-dependent bile acid transporter or solute carrier family 10, member 2), resulting in malabsorption of bile acid. This condition is extremely rare, even among familial cases of bile acid malabsorption.46,47 A third Breitling Replica Watches potential mechanism is genetic variation in bile acid synthesis or G-protein-coupled bile acid receptor 1 (GPBAR1), also known as TGR5 (discussed below).

Microbiota and Organic Acids

The precise role of the fecal or mucosal microbiome in IBS is unclear. An abundance of firmicutes bacteria in the fecal microbiome has been observed in patients with IBS, either as the sole finding48,49 or in combination with a decrease in bacteroidetes bacteria.50,51 An increase in the ratio of firmicutes to bacteroidetes has been reported to be associated with longer colonic transit time and increased levels of mental depression in IBS.52 Studies of mucosa-associated microbiota in patients with diarrhea-predominant IBS have shown increases in bacteroides and clostridia and a reduction in bifidobacteria.53

A role of the microbiome in the causation of IBS symptoms is supported by randomized, controlled trials of the minimally absorbed antibiotic rifaximin54 and a meta-analysis showing the efficacy of probiotics,55 particularly for abdominal pain and bloating. In addition, a probiotic mixture has been shown to retard colonic transit in patients with diarrhea-predominant IBS. 56

The fecal microbiome causes changes in colonic functions that induce IBS symptoms through microbial interactions with intraluminal factors. IBS is characterized by alterations in the profiles of organic acids (e.g., short-chain fatty acids) and the proportion of secondary bile acids (deoxycholic and lithocholic acids) as compared with primary bile acids (cholic and chenodeoxycholic acids). For example, the proportion of primary bile acid in stool is higher in patients with diarrhea-predominant IBS than in healthy controls, possibly reflecting the reduced time for bacterial dehydroxylation in the colon due to rapid transit.49,57 Colonic bacteria deconjugate and dehydroxylate bile acids to different extents, yet the primary or secondary bile acids with at least two α-hydroxyl groups (chenodeoxycholic, cholic, and deoxycholic acids) all induce secretion in mammalian intestine or colonic epithelial-cell monolayers.58,59 Moreover, chenodeoxycholic acid induces high-amplitude propagated contractions in healthy persons60 and acceleration of colonic transit in patients with constipation-predominant IBS,45 and deoxycholic acid induces colonic inflammation and hypersensitivity in rats.61 The bacterial dehydroxylation of chenodeoxycholic acid to lithocholic acid would theoretically reduce colonic secretion, but lithocholic acid constitutes only about 20% of total fecal bile acid.57 Therefore, the total proportion of secretory bile acids is only modestly altered by bacterial hydroxylation in the colon.

Overall, microbial differences appear to be unlikely to alter colonic function through changes in bile acid metabolism. Conversely, bile acids may modify the microbial content of the colon. For example, in rats, administration of cholic acid results in cecal microbiota that reflect the ratio of firmicutes to bacteroidetes observed in patients with IBS.62

Enteroendocrine Signals Arising in the Mucosa

The release of several peptides and amines, such as serotonin, from enteroendocrine cells is triggered by luminal factors, such as exogenous dietary amines or tastants or their metabolites (e.g., short-chain fatty acids), and by endogenous chemicals involved in the digestive process, such as bile acids.63,64 The potential role of serotonin in IBS is supported by the increased circulating levels of 5-HT in patients with diarrhea-predominant IBS and decreased 5-HT levels in patients with constipation-predominant IBS; the generally stimulatory effects of 5-HT on motor, secretory, and sensory functions65,66; and the effect of selective serotonergic agonists and antagonists in the treatment of different IBS phenotypes.11

Enteroendocrine cells also release granins. Chromogranins and secretogranins are present in secretory vesicles of nervous, endocrine, and immune cells. Activation of nicotinic cholinergic receptors (e.g., by acetylcholine released from submucosal nerves) induces granin release from these cells. Chromogranin A can induce the formation of mobile secretory granules and promote the sorting and release of other peptide hormones from enteroendocrine cells.67 Chromogranin-derived peptides secreted by such cells have antimicrobial properties against bacteria, fungi, and yeasts.68

As compared with healthy controls, patients with IBS, particularly those with rapid colonic transit, have higher levels of fecal chromogranin A, secretogranin II, and secretogranin III but lower levels of chromogranin B.69 These findings are nonspecific, since increased fecal granins or chromogranin cell density in colonic mucosa is observed in other diarrheal diseases, such as lymphocytic colitis70 and celiac disease.71,72 Chromogranin A cells also express FFA2 receptors that respond to short-chain fatty acids.40 Overall, the data are mostly consistent with the hypothesis that granins (through their role in the sorting and packaging of neuropeptides73) are indirect biomarkers, rather than direct stimulators, of colonic secretion or motility.74

CONSEQUENCES OF IRRITATION OF THE COLON

Immune Activation with Minimal Inflammation

Öhman and Simrén75 have summarized the evidence of inflammation or immune activation in the blood in at least some subsets of patients with IBS. The evidence of mast-cell and other immune (e.g., cytokine) activation in intestinal or colonic mucosa is less consistent.75 Inflammation, manifested as increased levels of T lymphocytes in the rectal mucosa in patients with IBS, has been associated with increased intestinal permeability.76 These data, in addition to the epidemiologic and clinical observations of postinfectious IBS77,78 and colonic mucosal gene-expression profiles showing functional alterations of several components of the host mucosal immune response to microbial pathogens,79 support a role of immune activation and altered bowel barrier function in a subgroup of patients with IBS. Genetic susceptibility may confer a predisposition to immune activation in a subset of patients with IBS (discussed below).

Increased Mucosal Permeability

Several studies in adults have documented increased small-bowel or colonic mucosal permeability in vivo, in mucosal biopsy specimens in vitro, or in Caco-2 monolayers in response to fecal supernatants from patients with IBS (summarized by Rao et al.80). Children with IBS also have evidence of increased proximal-gut and colonic permeability and low-grade inflammation.81 Factors associated with increased mucosal permeability and IBS include cow's milk allergy, previous nonspecific infection, atopic disease (e.g., rhinoconjunctivitis, rhinitis, and eczema),82-84 stress, and dietary fat.

Two lines of investigation support the role of stress in increased bowel permeability in humans. First, when the stress hormone corticotropin-releasing hormone was applied to the serosal side of colonic mucosal biopsy specimens from healthy persons, there was increased transcellular uptake of horseradish peroxidase, an effect that was mediated by mast cells.85 Second, stress induced by having study participants place their hands in cold water increased jejunal permeability in healthy women but not in healthy men.86

A high-fat diet results in gut-derived endotoxemia87 and may contribute to the immune activation observed in some patients with IBS. Studies in animals have shown that emulsified fats increase intestinal permeability, causing endotoxemia and inflammation.88

The link between increased mucosal permeability and IBS is supported by the observation that increased permeability enhances mucosal inflammation and activates local reflex mechanisms, stimulating secretion and sensory pathways that lead to increased visceral sensation.4

GENETIC FACTORS

The published literature on potential genetic factors conferring a predisposition to IBS is summarized elsewhere.89,90 The reported genetic factors of greatest interest confer a predisposition to inflammation, bile acid synthesis, expression of bioactive neuropeptides, and intestinal secretion through a mutation in the guanylate cyclase C secretory pathway.

Susceptibility to Inflammation and IBS Symptoms

Among 30 susceptibility loci for Crohn's disease that are associated with epithelial transport, barrier function, bacterial recognition, autophagy, prostaglandin production, and differentiation of interleukin-17-producing helper T cells, Zucchelli et al. identified a significant association between the gene encoding tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) and IBS phenotype in separate populations of Swedish and U.S. patients90; the strongest association was with constipation-predominant IBS (odds ratio for development of the disease, 1.79; 95% confidence interval, 1.41 to 2.26; P<0.001). In a cohort from the United Kingdom, genetic variations in TNFSF15 were protective against diarrhea-predominant IBS.91 Villani et al. reported that four genes were associated with postinfectious IBS in patients in Walkerton, Ontario, Canada, and these susceptibility loci included toll-like receptor 9 (TLR9).92 In a univariate analysis, colonic transit in patients with IBS was found to be associated with four inflammation-susceptibility genes that included TLR9 and the genes encoding cadherin 1 (CDH1) and interleukin 6 (IL6).93

Genetic Variation in Bile Acid Synthesis

Genetic variation in KLB, to which FGF19 binds,42 is associated with diarrhea-predominant IBS and accelerated colonic transit.94 A functional genetic variation in KLB (Arg728Gln), resulting in impaired KLB synthesis, prevents FGF19 from binding to the combined KLB-FGFR4 receptor on the hepatocyte. This reduces the FGF19 feedback inhibition of hepatocyte synthesis of bile acids, resulting in more bile acid reaching the bowel and, potentially, causing accelerated transit and diarrhea.

A second potential mechanism is genetic variation in GPBAR1. The receptor is located on myenteric, cholinergic, and nitrergic neurons in the colon and proximal small intestine. Genetic variation in GPBAR1 may be associated with small-bowel and colonic transit in healthy persons and in patients with IBS.95

Genetic Variation in Expression of Neurotransmitters and Cytokines

Neuropeptide S (NPS) receptor 1 (NPSR1) is expressed by gastrointestinal enteroendocrine cells and induces the production of several neuropeptides. The NPS-NPSR1 ligand-receptor complex is involved in inflammation, anxiety, and nociception. Three single-nucleotide polymorphisms (SNPs) of NPSR1 are significantly associated with colonic transit in IBS.96

The endocannabinoid anandamide is inactivated by fatty acid amide hydrolase (FAAH). A SNP in human FAAH (C385A or rs324420) reduces FAAH expression. FAAH heterozygosity or homozygosity for the minor allele A at this SNP, as compared with the CC genotype (homozygosity for the major allele C), increases the odds of diarrhea-predominant IBS or IBS with alternating bowel function and is significantly associated with accelerated colonic transit in diarrhea-predominant IBS.97

The gene controlling the serotonin transporter (SLC6A4) protein, 5-HTTLPR, is associated with IBS phenotype in some ethnic groups, but the findings are inconsistent. The short allele is associated with reduced SLC6A4 function. As compared with the long allele, the short allele is associated with higher ratings of rectal pain98 and increased activation of regional cerebral blood flow during painful colorectal distentions.99

Genetic Mutation in the Guanylate Cycle C Secretory Pathway

Fiskerstrand et al.100 described a Norwegian family with a rare form of familial diarrhea, characterized by the onset of symptoms in infancy and chronic, relatively mild diarrhea diagnosed as diarrhea-predominant IBS. This dominantly inherited, fully penetrant disease is due to a mutation in the gene encoding the guanylate cyclase C receptor (GUCY2C), which induces enterocyte secretion. The mutation was a heterozygous base substitution, c.2519G→T, in exon 22 of chromosome 12.

CLINICAL AND THERAPEUTIC IMPLICATIONS

IBS is no longer regarded as an idiopathic bowel dysfunction that originates exclusively from psychological stress or brain dysfunction. Fecal tests (e.g., measurements of fecal calprotectin and lactoferrin levels) or colonic imaging (e.g., colonoscopy) may be indicated clinically to rule out inflammatory bowel disease and neoplastic diseases. Patients who do not have a response to lifestyle and dietary modifications and symptomatic remedies should undergo tests to identify causative factors. These include tests of colonic transit and rectal evacuation in patients with constipation-predominant IBS and tests for carbohydrate or fat maldigestion (leading to the formation of short-chain fatty acids), increased bile acid synthesis or increased fecal bile acid excretion, and, possibly, dietary intolerance (e.g., gluten) in patients with diarrhea-predominant IBS.

It is anticipated that the relationship of diet, microbiome, endogenous irritants, barrier function, immune activation, and genetic factors to the motor, sensory, secretory, and psychological dysfunctions in IBS will be further elucidated. Future research will address the overall hypothesis that, like inflammatory bowel disease,101 IBS results from interactions between the host and genetic factors. These advances will lead to the development of more specific, individualized treatment that is based on the underlying peripheral pathophysiological mechanisms, including dietary recommendations (e.g., gluten or FODMAP exclusion32), biofeedback-based treatment of defecation disorders,13 bile acid sequestrants and 5-HT3 antagonists for diarrhea and urgency, prokinetics or secretagogues for patients with constipation-predominant IBS,11 and possibly probiotics, nonabsorbable antibiotics,54 antiinflammatory agents,10 or tight-junction modulators (e.g., larazotide) for patients with evidence of immune activation or increased mucosal permeability.

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Rao AS, Wong BS, Camilleri M, et al. C

The incidence of diagnostic error in medicineFecha: 2/2/2016

 

 

The incidence of diagnostic error in medicine

                                                                                              Mark L Graber

                                                                          BMJ Quality and Safety (Feb-2014). Vol 25

 

ABSTRACT

A wide variety of research studies suggest that breakdowns in the diagnostic process result in a staggering toll of harm and patient deaths. These include autopsy studies, case reviews, surveys of patient and physicians, voluntary reporting systems, using standardised patients, second reviews, diagnostic testing audits replica uhren and closed claims reviews. Although these different approaches provide important information and unique insights regarding diagnostic errors, each has limitations and none is well suited to establishing the incidence of diagnostic error in actual practice, or the aggregate rate of error and harm. We argue that being able to measure the incidence of diagnostic error is essential to enable research studies on diagnostic error, and to initiate quality improvement projects aimed at reducing the risk of error and harm. Three approaches appear most promising in this regard:

(1) using 'trigger tools' to identify from electronic health records cases at high risk for diagnostic error;

(2) using standardised patients (secret shoppers) to study the rate of error in practice

(3) encouraging both patients and physicians to voluntarily report errors they encounter, and facilitating this process.

The patient safety movement in the USA has entered its second decade. A wide range of important safety concerns have been studied, and to this point, including medication errors, hospital-acquired infections, wrong-site surgery and a host of other issues. Strangely lacking, however, is a concerted effort to find, understand and address diagnostic errors.2-4 One factor that may contribute to its relative neglect is that the true incidence of diagnostic error is not widely appreciated. Measuring the rate of error and, in particular, error-related harm,5 would provide the necessary motivation to begin addressing this large and silent problem. How likely is a diagnosis to be wrong, missed, or egregiously delayed?
How often do diagnostic errors cause harm? In this report, we briefly summarise the methods that have been used to estimate the rate of diagnostic error, and comment on their relative merits and limitations. A more comprehensive presentation of studies using each of these methodologies has been presented elsewhere.6

THE INCIDENCE OF DIAGNOSTIC ERROR

Arthur Elstein, a cognitive psychologist interested in 'how doctors think', studied clinical decision making for his entire career and concluded the diagnosis is wrong 10-15% of the time.7 A diverse range of  research approaches that have focused on this issue over the past several decades suggest that this estimate is very much on target.6

The incidence of diagnostic error has been estimated using eight different research approaches (table 1).

 

 

Autopsy studies identify major diagnostic discrepancies in 10-20% of cases.Most cases in autopsy series derive from inpatient settings, but they also include deaths from the emergency department which, for many reasons, is considered to be the natural laboratory for studying diagnostic error. Although autopsies have virtually disappeared in the USA, autopsies are still common in many other countries, and despite the availability of modern imaging, continue to show diagnoses being missed that might have been lifesaving, particularly infections and cardiovascular conditions.

Although autopsy data is considered the 'gold standard' in terms of providing the most definitive data on the accuracy of diagnosis, only a subset of cases ever reach autopsy, and in many cases, the relationship between clinical diagnoses and autopsy findings remains unclear.
Autopsies also discover a large number of incidental findings that were not suspected during life, but that were clinically irrelevant.
Surveys have found that diagnostic errors are a major concern of both patients and physicians.
A survey of over 2000 patients found that 55% listed a diagnostic error as their chief concern when seeing a physician in an outpatient setting.21 Similarly, physician surveys have consistently found that approximately half the respondents encounter diagnostic errors at least monthly.11 22 23 Moreover, compared with the many different safety concerns encountered in practice, physicians perceive diagnostic errors to be more likely to cause serious harm or death compared with other safety concerns.24
Standardised patients studies using 'secret shoppers' have also been used to estimate the accuracy of diagnosis. In these studies, real or simulated patients with classical presentations of common diseases, like rheumatoid arthritis, asthma, or chronic obstructive pulmonary disease (COPD) are sent anonymously into real practice settings.
The diagnostic error rates reported (13-15%) are very much in line with estimates from the other types of research approaches, and have substantial 'face' validity in that the studies are being carried out prospectively in real-world settings. In addition to providing an estimate of diagnostic error rates, this approach offers the unique ability to probe the various factors that promote or detract from optimal diagnosis.25 26

The chief limitation of these studies in regard to estimating error rates is that they are performed under research-directed conditions, presenting a much smaller subset of conditions than would be seen in usual practice. Moreover, in studies seeking to also study the factors relevant to accurate diagnosis, these patients may present with comorbid conditions or contextual complexities that are not representative of typical patients, and case complexity is a major factor in determining diagnostic accuracy.27

Second reviews refers to research protocols in the visual subspecialties (eg, radiology, pathology, dermatology) where a second radiologist examines the same films after a first radiologist, or a second pathologist reviews the same biopsy or cytology specimen as another pathologist. These second review studies may be performed under controlled conditions, involving the review of many or mostly abnormal cases. This approach has advantages from a research perspective, but substantially increases the possibility for diagnostic error, which can range from 10% to 50%.28-31

Interestingly, the studies also show that a diagnostician will also disagree with his or her own prior interpretation in a small fraction of cases. In 'real world' situations, the majority of examinations are normal. Under these conditions, a critical abnormality is detected by a second expert reviewer in the range of 2-5%.

Diagnostic testing audits are used to estimate the incidence of error in the clinical laboratory. Thanks to impressive advances in quality control procedures, diagnostic errors in the modern age are rarely the result of an error in the analytical test itself. Most laboratory-related errors now originate from the preanalytical and postanalytical phases, namely issues related to the physician ordering and interpreting the test result. Overall, it is estimated that laboratory results are misleadingly wrong in 2-4% of cases, and roughly the same error rates are found in diagnostic radiology. The major limitation of diagnostic testing audits is that, although they excel at finding errors in test performance per se, they underestimate the true clinical impact because of the related preanalytical and postanalytical errors occurring outside the walls of the laboratory or radiology department which, typically, escape detection. Lapses in the reliable communication of abnormal test results, for example, is a universal problem, even in systems with advanced electronic medical records.32 33
Malpractice claim databases are easily studied and have provided interesting data on diagnostic errors.

Typical data (eg, from the Physicians Insurers Institute of America, shown below) reveals that problems related to diagnostic error are the leading cause of paid claims. Essentially identical data has been reported from the Department of Veterans Affairs, Kaiser-Permanente Healthcare System, and CRICORMF (CRICO Risk Management Foundation), the self-insurance entity covering the Harvard teaching hospitals, and from studies in the UK.34 A recent analysis of malpractice cases extracted from the National Practitioner Data Bank over a 25-year period identified 100 249 cases of diagnostic error.35 Diagnostic error was the most common reason for a claim (29%) and the most costly, averaging $386 849 per claim.

Studying closed claims provides a convenient approach to analysing large numbers of cases, already preclassified as representing diagnostic errors. Limitations of this approach include the fact that only a small subset of errors results in claims, and these, typically, span just a narrow range of clinical conditions, predominated by cases involving cancer or cardiovascular disease in young or middle-aged patients.

Moreover, these cases provide only limited opportunities to study the aetiology of diagnostic errors, as the proceedings by their nature are focused more on consequences than causes.

Case Reviews. Many specific symptoms and disease states have been studied using retrospective case reviews, and in each of these the incidence of diagnostic error is unacceptably high. For example, a systematic review of more than 8000 ER patients found a delayed diagnosis of stroke in 9%.36 Kostopoulou and colleagues reported a systematic review of this literature and identified 21 studies meeting their quality criteria.37 In one such study, children with asthma experienced a median delay in making the correct diagnosis of more than 3 years, spanning 7 clinic/ER visits. Delayed or wrong diagnosis rates of 10-50% have been identified in studies of coronary artery disease, HIV-associated complications, tuberculosis and a wide range of malignancies. Very similar data has been reported by Gandhi and colleagues, who studied 181 cases of diagnostic error in ambulatory settings (figure 1).16 Delayed diagnosis of cancer and coronary artery disease were the most commonly identified problems in the study by Gandhi et al, and a growing number of studies have confirmed the frequency of missed opportunities for earlier cancer diagnosis.31 38 39 The point to be made is that whereas diagnostic errors may sometimes reflect encounters with extremely rare diseases or very unusual presentations of common diseases, in many cases, it is a relatively common disease that is mislabeled or missed entirely. A convenience sampling of studies that measured diagnostic error rates in 40 different symptom complexes or diseases is presented in online supplementary appendix table 1.

The chief limitation of case reviews is that they typically rely just on data contained in the medical record, and many diagnostic errors are missed as a result. As an example, Schwartz and colleagues used standardised patients to estimate costs resulting from diagnostic errors in ambulatory practices. Only their knowledge of the actual diagnosis allowed accurate estimates of these costs; virtually none could have been surmised from record reviews alone.26 An additional limitation is that the medical record, typically, is lacking documentation on what the clinician was thinking at the time the diagnosis was being considered.
Finally, random chart reviews are not well suited to replicas de relojes rolex españa measuring incidence rates of diagnostic error because the rate of error is low, thus requiring a large number of reviews.

     

 

Voluntary reports. Voluntary error-reporting systems are now in place in most healthcare organisations in the USA, and were expected to provide a reliable way of identifying both minor and major adverse events. When they are used, and especially if follow-up interviews with providers can be obtained, voluntary reporting offers the unique potential to explore both the systemrelated and cognitive aetiologies of diagnostic error.40 41

Unfortunately, these programmes capture only a small fraction of diagnostic errors. Factors that detract from reporting include the time required to submit cases, a natural reluctance to call attention to one's own mistakes, and the ever-present fear of provoking a malpractice suit despite the reassurance that reports can be submitted anonymously. Another barrier to voluntary reporting of diagnostic errors is the lack of a 'common format' for reporting. The Agency for Healthcare

Research and Quality has taken the lead in developing 'common formats' which healthcare organisations can use to report other types of patient safety incidents, but at the present time there is no specific common format tool to report diagnostic errors.

METHODS CURRENTLY USED TO IDENTIFY DIAGNOSTIC ERRORS IN PRACTICE

Diagnostic error rates are being measured in very few, if any, healthcare organisation in the USA. With regard to ambulatory settings, Tsang and colleagues recently reviewed the methods available for measuring adverse events and found that none were helpful in identifying diagnostic errors.42 The situation is no better for capturing diagnostic errors involving inpatients:

A recent Inspector General study of 785 hospitalised Medicare beneficiaries using five different approaches identified a 13% incidence of serious adverse events, but not a single episode categorised as diagnostic error.43

SUGGESTIONS ON IMPROVING MEASUREMENT

Given the limitations of the error-detection approaches currently in use, how can healthcare organisations begin to identify diagnostic errors? We suggest three novel approaches:

* Consider using trigger tools

Various types of trigger tools are now being used in quality programmes,44 the most widely known of which is the 'Global Trigger Tool' developed by the Institute for Healthcare Improvement.45 A growing fraction of US healthcare organisations are using this instrument, but it was designed specifically to identify treatment errors, specifically errors of commission, and is poorly suited to detecting diagnostic errors, many of which are errors of omission.46 A more promising approach was recently reported by Singh and colleagues, who designed an electronic trigger to identify patients with an unscheduled hospitalization within 2 weeks of a primary care visit. The frequency of diagnostic errors in patients meeting this criterion was about 20%, compared with just 2% for unselected patients.47-49 A similar process identifying hospitalizations after an ER 'treat and release' visit has recently been described by Newman-Toker et al.50

Electronic surveillance is also effective in identifying diagnostic errors through discrepancies between laboratory and pharmacy records,51 and discovering diagnostic errors through data mining is probably just around the corner. Although the use of trigger tools will not capture all diagnostic errors, their use will substantially enrich the yield compared with random chart reviews and, thus, bring more errors to attention.52

* Encourage and facilitate voluntary or prompted reports from patients

There is substantial preliminary evidence that patients are acutely aware of the diagnostic error problem.10 53 Several authors have called for patients to take a more active role in ensuring the reliability of the diagnostic process54-56 and enlisting their help to identify breakdowns is a logical, practical and simple approach to explore. Weingart and colleagues, for example, surveyed 228 inpatients who reported 20 adverse events, of which 11 were verified in the medical record but none were captured in the hospitals SE-detection programmes.57 Reports from Canada,58 Japan59 and Sweden60 have similarly found that patients are both willing and capable of participating effectively in identifying errors in their care.

The chief limitation of soliciting error reports from patients is that they will require verification by healthcare providers. As evident from the Weingart study and others,61 not all their safety concerns accurately reflect true lapses in care.

* Encourage and facilitate error reporting from physicians

At least two different approaches have successfully improved on the power of voluntary error reporting systems to capture diagnostic errors. Phillips and colleagues encouraged physicians, their staff and patients to report all safety concerns over just a constrained 10-week period, and to focus on specific 'intensive reporting' days. The approach yielded 935 reports from 10 practices, including 12 instances of suspected diagnostic error.62 Trowbridge was also successful in obtaining diagnostic error reports by acting as a clinical champion to encourage participation from colleagues. 63 In pilot work with this process at Maine Medical Center, 36 diagnostic errors were reported over 6 months that otherwise would have escaped detection. The severity of errors uncovered was high; 73% involving moderate or serious harm to the patient. By comparison, the facility identified only six diagnostic errors from their standard, existing systems for identifying medical errors during the same time period.

DISCUSSION

We have proposed that measuring the incidence of diagnostic error in everyday practice is an essential requirement of a comprehensive quality management programme.2 Of eight methods used to study diagnostic errors, some are more suitable than others in terms of their potential for providing meaningful data on diagnostic error rates (table 1). Analysing closed malpractice claims can provide only relative data on error rates; estimating absolute rates is not possible because so few true errors actually result in claims, and not all claims reflect true errors. Diagnostic testing audits are meaningful only to the extent that audits examine true clinical impact, because many diagnostic testing errors are ultimately detected and corrected, or discarded as meaningless. Of the remaining methods, each has its own advantages and limitations.

Moreover, it is probably safe to assume that each of these approaches will underestimate the actual rate of error, and may identify entirely separate cohorts of errors. This problem is compounded by the different definitions and classification systems of diagnostic error that have been applied in these various studies.

The goal of knowing the diagnostic error rate in practice may, therefore, require further research to standardize definitions and other methodologic issues, and combining results from several different approaches.

Similarly, the eight different approaches offer differing capabilities in their ability to provide insight regarding the aetiology of diagnostic error. Autopsies and second reviews reveal that an error was made, but not why. Using standardised patients is a particularly powerful way to study these factors, because at least some of the variables (case presentation and complexity, for example) can be controlled. Voluntary reports from physicians also provide unique opportunities to gather insights on the cognitive and system-related factors that might have contributed to the error. With the exception of using standardised patients, none of the approaches are well suited to study the human factor issues, such as distractions, fatigue and workload stress, thought to play dominant roles influencing clinical decision making.

Knowing the incidence of diagnostic error may be less important than being able to measure the likelihood of harm that results.5 Extrapolating from the Class 1 errors (a major discrepancy that likely leads to the patient's death) identified at autopsy, Leape, Berwick and Bates estimated that 80 000 deaths per year might be caused by diagnostic error, including both ambulatory and inpatient errors.64 A recent systematic review of autopsy data concluded that 36 000 deaths a year were due to diagnostic errors in just ICUs alone.65 These estimates, of course, do not include the many instances of non-fatal injury related to misdiagnosis, events that will be far more numerous, and the many instances where the harm is psychological or financial more than physical.

Preventability, however, is a difficult parameter to judge, and these estimates may exaggerate the impact of diagnostic error to the extent that it is overestimated. 66 Both case review studies and closed claims studies67 35 find that diagnostic errors are more likely to cause harm than other patient safety problems.

In summary, a wide range of different research approaches have been used to estimate diagnostic error rates, all suggesting that the incidence is unacceptably high. Although true incidence data are lacking, a wide variety of research studies suggest breakdowns in the diagnostic process result in a staggering toll of harm and patient deaths. A recent, authoritative review by the AMA of ambulatory patient safety concerns reached the same conclusion.68

What's missing from these estimates are true incidence data, as typically the denominators are not available or provided. Also missing are the aggregate rates of injury and harm. There is a clear need for additional research to identify better ways to bring diagnostic errors to light. Promising approaches in this regard include the use of trigger tools focusing on diagnostic error, the use of standardised patients, and encouraging both patients and physicians to voluntarily report errors they encounter.

The most fundamental principle of performance improvement is that 'You can't fix what you don't measure'. Efforts to begin addressing diagnostic error must begin with measurement. In no area of patient safety is this need more acute than in trying to identify the true incidence of diagnostic errors, and the harm associated with these events.

 

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27 Kostopoulou O, Oudhoff J, Nath R, et al. Predictors of diagnostic accuracy and safe management in difficult diagnostic problems in family medicine. Med Decis Making 2008;28:668-80.

28 Fitzgerald R. Error in radiology. Clin Radiol 2001;56:938-46.

29 Foucar E. Error in anatomic pathology. Am J Clin Pathol 2001;116(Suppl):S34-46.

30 Westra WH, Kronz JD, Eisele DW. The impact of second opinion surgical pathology on the practice of head and neck surgery: a decade experience at a large referral hospital. Head Neck 2002;24:684-93.

31 Raab SS GD. Quality in Cancer Diagnosis. CA Cancer J Clin 2010;60:27.

32 Singh H, Arora HS, Vij MS, et al. Communication outcomes of critical imaging results in a computerized notification  system. JAMIA 2007;14:459-66.

33 Singh H, Thomas EJ, Mani S, et al. Timely follow-up of abnormal diagnostic imaging test results in an outpatient setting: are electronic medical records achieving their potential? Arch Intern Med 2009;169:1578-86.

34 Fenn P, Gray A, Rivero-Arias O, et al. The epidemiology of error: an analysis of databases of clinical negligence litigation. Manchester, UK: Manchester Centre for Healthcare Management, University of Manchester, 2004.

35 Tehrani A, Lee H, Mathews S, et al. 25-year summary of US malpractice claims for diagnostic errors 1986-2010; An analysis from the National Practitioner Data Bank. BMJ Qual Saf 2013.

36 Newman-Toker D, Robinson K, Edlow J. Frontline misdiagnosis of cerebrovascular events in the era of modern neuro-imaging: a systematic review. Ann Neurol 2008;64(Suppl 12):S17-18.

37 Kostopoulou O, Delaney BC, Munro CW. Diagnostic difficulty and error in primary care-a systematic review. Fam Pract 2008;25:400-13.

38 Singh H, Daci K, Petersen LA, et al. Missed opportunities to initiate endoscopic evaluation for colorectal cancer diagnosis. Am J Gastroenterol 2009;104:2543-54.

39 Singh H, Hirani K, Kadiyala H, et al. Characteristics and predictors of missed opportunities in lung cancer diagnosis. J Clinical Oncology 2010;28:3307-15.

40 Kostopoulou O, Delaney B. Confidential reporting of patient safety events in primary care: results from a multilevel classification of cognitive and system factors. Qual Saf Health Care 2007;16:95-100.

41 Graber ML. Taking steps towards a safer future: measures to promote timely and accurate medical diagnosis. Am J Med 2008;121(Suppl 5):S43-6.

42 Tsang C, Majeed A, Avlin P. Routinely recorded patient safety events in primary care: a literature review. Fam Pract 2012;29:8-15.

43 Levinson D. Adverse events in hospitals: national incidence among medicare beneficiaries. Department of Health and Human Services-Office of Inspector General, 2012.

44 Resar RK, Rozich JD, Classen D. Methodology and rationale for the measurement of harm with trigger tools. Qual Saf Health Care 2003;12(Suppl 2):ii39-45.

45 Classen D, Resar R, Griffin F, et al. Global Trigger Tool shows that adverse events in hospitals may be ten times greater than previously measured. Health Affairs 2011;30:581-89.

46 Schildmeijer K, Nilsson L, Arestedt K, et al. Assessment of adverse events in medical care: lack of consistency between experienced teams using the global trigger tool. BMJ Qual Saf 2012;31:307-14.

47 Singh H, Thomas EJ, Khan MM, et al. Identifying diagnostic errors in primary care using an electronic screening algorithm. Arch Intern Med 2007;167:302-8.

48 Singh H, Giardina T, Forjuoh S, et al. Electronic health record-based surveillance of diagnostic errors in primary care. BMJ Qual Saf 2011.

49 Singh H, Traber D,Meyer A, et al. Types and origins of diagnostic errors in primary care settings. JAMA Internal Med 2013.

50 Newman-Toker D, Moy E, Valente E, et al. Missed and delayed diagnosis of stroke in emergency department patients with headache or dizziness. Poster presentation: ISPOR 17th Annual Meeting. Washington, DC, 2012.

51 Schiff GD, Kim S, Krosnjar N, et al. Missed hypothyroidism diagnosis uncovered by linking laboratory and pharmacy data. Arch Intern Med 2005;165:574-7.

52 Schiff G. Finding and fixing diagnosis errors: can triggers help? BMJ Qual Saf 2012;21:89-92.

53 Burroughs TE, Waterman AD, Gallagher TH, et al. Patient concerns about medical errors in emergency departments. Acad Emerg Med 2005;23:57-64.

54 Schiff GD. Minimizing diagnostic error: the importance of follow-up and feedback. Am J Med 2008;121(5 Suppl):S38-42.

55 Graber ML. Reducing diagnostic error in medicine-there's a job for everyone. NPSF Focus Patient Saf 2009;12:6-7.

56 Shrier I, Green S, Solin J, et al. Knowledge of and attitude toward patient confidentiality within three family medicine teaching units. Acad Med 1998;73:710-12.

57 Weingart S, Pagovich O, DZ S, et al. What can hospitalized patients tell us about adverse events? Learning from patient-reported incidents. J Gen Intern Med 2005;20:7.

58 Pear R. New system for patients to report medical mistakes. New York Times, 2012.

59 Hasegawa T, Fujita S, Seto K, et al. Patient identification and reporting of unsafe events at six hospitals in Japan. Jt Comm J Qual Patient Saf 2011;37:502-08.

60 Ohrn A, Elfstrom J, Liedgren C, et al. Reporting of sentinel events in Swedish hospitals: a comparison of severe adverse events reported by patients and providers. Jt Comm J Qual Patient Saf 2011;37:495-501.

61 Tierney WM. Adverse outpatient drug events - a problem and an opportunity. N Engl J Med 2003;348:1587-89.

62 Phillips RL Jr., Bartholomew LA, Dovey SM, et al. Learning from malpractice claims about negligent, adverse events in primary care in the United States. Qual Saf Health Care 2004;13:121-26.

63 Trowbridge R, Salvador O. Addressing diagnostic errors: an institutional approach. Focus Patient Saf Newsletter National Patient Saf Found 2010;13:1-5.

64 Leape L, Berwick D, Bates D. Counting deaths from medical errors. JAMA 2002;288:2405.

65 Winters B, Custer J, Galvagno S, et al. Diagnostic errors in the intensive care unit: a systematic review of autopsy studies. BMJ Qual Saf 2012;21:894-902.

66 Shojania K. Deaths due to medical error: jumbo jets or just small propeller planes? BMJ Qual Saf 2012;21:709-12.

67 Zwaan L, de Bruijne M, Wagner C, et al. Patient record review of the incidence, consequences, and causes of diagnostic adverse events. Arch Intern Med 2010;170:1015-21.

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Interation of Acid-Base and Electrolyte Disorders - REVIEWFecha: 3/1/2016

 

 

Interation of Acid-Base and Electrolyte Disorders

REVIEW ARTICLE

 

                                                                                           Julian L. Seifter, M.D.

                                                                                N Engl J Med 2014; 371:1821-1831

 

This review describes a method of analyzing acid-base disorders that incorporates insights from the traditional, bicarbonate-centered model and the Stewart (or strong ion) model.1-6 Acid-base balance and electrolyte homeostasis are intricately connected at the cellular level and in clinical disorders. This article emphasizes the integration of the principles of mass balance and electroneutrality - which are prominently featured in the strong ion model (also known as the physicochemical model) - for interpretation of acid-base phenomena. Most acid-base abnormalities can be diagnosed and interpreted with the use of the traditional approach. Why, then, should the strong ion theory be incorporated into teaching about acid-base balance? Although the Stewart model is not primarily a mathematical expression of a confirmed reality, it is relevant because it is a powerful construct that can shed light on an important biologic system.

Included in this article are several case vignettes that show the explanatory power of the strong ion approach in clinical practice. Some of these examples have been presented in a companion article on the physiological approach to acid-base balance by Audemars Piguet Replica Berend et al.7 . The more complex chemistry of the hydrogen-ion concentration in intracellular and extracellular fluid compartments is beyond the scope of this article.

BICARBONATE-CENTERED AND STRONG ION APPROACHES

The traditional model uses easily measured concentrations of blood carbon dioxide [CO2] and bicarbonate [HCO3 -].6 It is the basis of the Henderson-Hasselbalch equation:

                 

where pK is the acid dissociation constant, PaCO2 the partial pressure of arterial carbon dioxide, and 0.03 the solubility of CO2 in blood.

The overall equilibrium between carbon dioxide and bicarbonate is shown below:

(2) CO2+H2O←→H2CO3←→H++HCO3 -,       where H2CO3 denotes carbonic acid, and H+ hydrogen.

In a teaching model, this relationship shows how alterations in the partial pressure of carbon dioxide (PCO2) or levels of hydrogen or bicarbonate affect the other variables through mass balance. The fact that the hydrogen ion concentration is more than a million times lower than the bicarbonate level indicates that other forces are at work in the regulation of pH.

As in any chemical reaction in equilibrium, a change in the concentration of the reactant or product will move the reaction in the direction that would reestablish equilibrium (Le Châtelier's principle). If this principle is applied to equation 2, metabolic acidosis may be attributed to either the addition of hydrogen, with the consumption of bicarbonate as the reaction shifts to the left, or the removal of bicarbonate from the body, resulting in increased hydrogen as the reaction shifts to the right (from carbon dioxide) to replace lost bicarbonate. The observed relation between arterial PCO2 (PaCO2) and bicarbonate effectively predicts the direction but not the magnitude or time course of respiratory and renal compensations. Only empirical observations can determine the appropriate degree of compensation.

The anion gap, consisting of the sum total of all unmeasured charged species (predominantly albumin) in plasma, is calculated below as

(3) anion gap=[Na+]-([Cl-]+[HCO3 -]).

The anion gap is used in the differential diagnosis of metabolic acidosis.8-10 It can suggest a cause for unmeasured anions. Possible causes include lactic acidosis, ketoacidosis, and uremic acidosis; ingestion of salicylate, methanol, ethylene glycol, or propylene glycol; and many inborn errors of metabolism. It is assumed that the unmeasured anion is added as the protonated acid (such as lactic acid). However, a severe form of metabolic acidosis results from treatment with sodium thiosulfate, a compound that has no hydrogen.11

In contrast to the anion gap shown in equation 3 above, the physicochemical model emphasizes that all cation and anion concentrations must balance, according to the laws of electroneutrality.3The independent balance of each ion, when disrupted, provides a mechanism for the acid-base condition. In their classic article, Peters and Van Slyke defined acid-base balance in the blood as the chemical state resulting from the balance between cations and anions.12 Carrying this idea to the extreme, one could view metabolic acid-base disorders as the predicted consequences of primary fluid and electrolyte imbalance.

Strong ions such as sodium and chloride are assumed to be completely dissociated in body water but can be lost or gained disproportionately. When the sum of all negatively charged ions (predominantly chloride) is subtracted from the sum of all positively charged strong ions, a value known as the strong ion difference (in millimoles per liter) is introduced. The strong ion difference is calculated as shown below:

(4) strong ion difference=[Na+]+[K+]+[Ca2+]+[Mg2+]-[Cl-],       where Ca2+ denotes calcium, and Mg2+ magnesium.

As shown in equation 5 below, the total content of albumin, phosphate, and circulating nonvolatile weak acids [HA] and their dissociated anions [A-] is referred to as [Atot] in the Stewart model:

(5) [Atot]=[HA]+[A-].

As shown in equation 6 below, in which CO3 -2 denotes carbonate and OH- hydroxide, an expression for remaining charged species, considered to be the dependent variables, is

(6) [strong ion difference]-[A-]=[HCO3 -]+[CO3 -2]+[(OH-)]-[H+],

in which the levels of carbonate, hydroxide, and hydrogen are much lower than the levels of bicarbonate. Any developed difference in the ionic charge, or strong ion difference, determines the bicarbonate concentration. Essential to this argument is that any difference in an unbalanced charge will immediately result in the appearance or disappearance of bicarbonate formed from ubiquitous and neutral carbon dioxide and water. It is also expected that the changes in the bicarbonate concentration will begin to occur at a very minimal strong ion difference, since large charge separations are not possible. We can assume that electrostatic forces come into play until changes in bicarbonate concentrations match the charge separations among other ionic species. Clearly, electroneutrality in the macroenvironment always exists.

One drawback of using equation 6 in a clinical calculation of the hydrogen concentration is that the error in measurements of electrolytes in the millimolar range cannot allow for an accurate determination of the hydrogen level in nanomolar concentrations.

The Stewart (or physicochemical) model of acid-base balance is quantitatively based on the view that the hydrogen and bicarbonate concentrations are not independently determined. Instead, they are dependent on the following: carbon dioxide (PaCO2) and its spontaneous relationship with hydrogen and bicarbonate, the dissociation of water (the abundant source of hydrogen within body fluids), the dissolved strong ions, the strong ion difference, and Atot, which is the sum of all buffer pairs (mostly weak acids) that move toward equilibrium with a dissociated anion [A-] according to the dissociation constant for each (e.g., albumin with its net negative charge under physiological conditions).13

In keeping with the laws of electroneutrality, all charged species must balance. This requires that any change in the concentration of one of the charged variables (the strong ion difference) must be matched by a change in the concentration of another charged species. According to constraints in this internal system, the hydrogen and bicarbonate concentrations are dependent on the other variables, the total mass of which is conserved.

The simultaneous mathematical solution of these reactions is complex and is not required to diagnose acid-base disorders. Furthermore, both experimental and clinical observations can be explained with the use of either model. Yet the physicochemical model is useful in revealing individual processes in the development of an acid-base disturbance because it associates the abnormality with specific electrolyte disturbances. The traditional model uses the calculated, and useful, anion gap to elucidate the pathophysiology of metabolic disorders. The usual calculation for the anion gap is shown in equation 3. For this equality to hold true, for electroneutrality purposes, the anion gap must be the net value for a complex mixture of all ionic species not included in the calculation, such as albumin, other proteins, calcium, magnesium, potassium, and phosphate, plus any additional anions such as lactate or acetoacetate. To illustrate the usefulness of a more inclusive approach in separating out various components of the anion gap, an anion gap hypothetically could be calculated as simply [Na+]-[HCO3 -]. From a charge point of view, it works out, but obviously, hyperchloremic acidosis could not be distinguished from an "anion gap" acidosis.

The anion-gap equation could be rearranged to solve for the bicarbonate concentration instead of unmeasured anions:

[Na+]-([Cl-]+[AG])=[HCO3 -],                          where AG denotes the anion gap.

This is analogous to the strong ion difference. The anion gap, which is usually calculated with the use of plasma bicarbonate, is useful clinically. If every charged species were known and measured, the equation could be rearranged to calculate the bicarbonate concentration, but often the unmeasured ion is unknown. How, then, does the strong ion difference increase or decrease? The answer lies in specific gains or losses of electrolytes such as sodium and chloride in a different proportion to each other than the proportion in the normal extracellular fluid. The first step in understanding how an acid-base disorder develops is to know or assume the specific electrolyte content of any gained fluids (e.g., intravenous fluids) or lost fluids (e.g., gastrointestinal fluids, sweat, or urinary fluids).

Since the normal concentration ratio of sodium to chloride in extracellular fluid is approximately 140:100, an increase in the sodium level, a decrease in the chloride level, or both will increase the strong ion difference and the bicarbonate concentration will increase (metabolic alkalosis), according to electroneutrality requirements.3 When the strong ion difference decreases, pH and the bicarbonate level will decrease (metabolic acidosis). The electroneutrality relationship in equation 6 can be useful in diagnosing the causes of metabolic alkalosis and metabolic acidosis.

 

METABOLIC DISTURBANCES AND STRONG IONS

Acid-base balance is dependent on strong ions in the macroscopic sense because the same cellular mechanisms regulate acid-base homeostasis and electrolyte homeostasis. The following case vignette illustrates this point:

A 31-year-old woman with gastroenteritis had been vomiting for 2 days. She was weak and hypotensive. Laboratory tests revealed a sodium concentration of 125 mmol per liter, potassium 2.6 mmol per liter, chloride 72 mmol per liter, and bicarbonate 40 mmol per liter. The arterial pH was 7.54, the PaCO2 48 mm Hg, and the urinary pH 5.0.

Depletion of the extracellular fluid from vomiting creates profound needs to conserve sodium and water and preserve potassium balance; these mechanisms are clearly obstacles to maintaining a normal blood pH and bicarbonate concentration. With volume and potassium depletion, metabolic alkalosis is maintained, not corrected, by the kidneys.14,15 Low extracellular fluid volume and low blood pressure increase angiotensin II and aldosterone levels. Increased sodium reabsorption through proximal tubular sodium-hydrogen exchange and the collecting-duct sodium channel, accompanied by hydrogen secretion by the hydrogen ATPase and the potassium-hydrogen ATPase, in turn increases bicarbonate reabsorption until the urinary pH decreases as it becomes free of bicarbonate. This paradoxical aciduria in the midst of alkalemia is evidence that blood pH depends on strong ion balance. The alkalemia will be corrected only with sufficient replacement of sodium, chloride, and potassium. In this patient, after the administration of 0.9% normal saline with potassium chloride, the electrolyte status improved, and the urinary pH increased to 8.0 with the prompt excretion of sodium, potassium, and bicarbonate. In this clinical situation, the interdependency of acid-base and electrolyte balance is self-evident. If this were not the case, and kidney function instead focused on maintaining a normal acid-base balance, the bicarbonate generated by vomiting would result in the urinary loss of even larger quantities of sodium, potassium, and water, leading to life-threatening volume and potassium depletion.

The traditional acid-base approach tacitly overlaps with aspects of the strong ion theory Consider the familiar concept known as the "delta-delta" (Δ-Δ), the increase (Δ) in the anion gap versus the decrease (Δ) in the bicarbonate level.8,9

All metabolic acid-base disorders are associated with either a change in the concentration of sodium, potassium, calcium, chloride, hydrogen phosphate, or albumin or a change in the anion gap. The normal anion gap can be adjusted for hypoalbuminemia by allowing for 2.5 mmol per liter of negative charge for each 1 g per deciliter of albumin concentration.13 The relative change in the bicarbonate level and the anion gap (Δ-Δ) is only part of the electroneutrality requirement. The net sum of all cation and anion electrolyte charge gaps must cancel out. In the search for a "Δ-Δ-Δ-Δ-Δ-Δ," clues about any acid-base disorder will emerge.

A finding of an increase in the anion gap above the normal concentration (the Δ anion gap) that exceeds the decrease in the bicarbonate concentration (Δ bicarbonate) may indicate mixed metabolic acidosis and metabolic alkalosis. The following case shows that a ratio other than 1:1 is not pathognomonic for a mixed acid-base disturbance:

Before a cardiac arrest, a 67-year-old man with an acute myocardial infarction had normal levels of serum electrolytes (level of sodium 140 mmol per liter, potassium 4.0 mmol per liter, chloride 103 mmol per liter, and bicarbonate 25 mmol per liter). While he was anuric after the cardiac arrest, his laboratory tests showed a sodium level of 140 mmol per liter, potassium 5.0 mmol per liter, chloride 62 mmol per liter, and bicarbonate 5 mmol per liter. The arterial pH was 7.10, and the PaCO2 was 16 mm Hg. The lactate level was 60 mmol per liter, and the anion gap was 73 mmol per liter.

This patient had severe anion-gap metabolic acidosis due to lactate overproduction from tissue hypoperfusion. Since lactate production can result in blood lactate concentrations greater than a normal bicarbonate concentration, what happens when the bicarbonate concentration decreases almost to zero? Hydrogen might be preferentially reactive with other tissue buffer systems, but a decrease in the chloride level is often observed, yielding a hypochloremic anion-gap acidosis.16,17With lactate acting as a strong ion, the strong ion difference [Na+]-[Cl-]-[lactate-] is decreased and the bicarbonate concentration decreases to achieve electroneutrality. Chloride moves into cells, probably in exchange for lactate or bicarbonate. In this case, there was no clinical evidence of superimposed metabolic alkalosis:

Δ [HCO3 -]+Δ [Cl-]=Δ [AG]=[lactate].

Also, consider examples of metabolic alkalosis in which the increase in a strong cation is balanced by an increase in the bicarbonate concentration, as in the following case, which was also described by Berend et al.7:

A 50-year-old woman with a recent onset of hypertension had the following laboratory results: sodium level 150 mmol per liter, potassium 2.2 mmol per liter, chloride 103 mmol per liter, and bicarbonate 32 mmol per liter. The arterial pH was 7.50, and the PaCO2 was 43 mm Hg. She was found to have an aldosterone-secreting adrenal adenoma.

In this case, the change in the bicarbonate level was associated with an increased sodium concentration, which is often seen in primary hyperaldosteronism and is attributable to increased function of epithelial sodium channels in renal cortical collecting-duct principal cells. Mild hypernatremia probably occurred as a result of extracellular fluid expansion that decreased vasopressin release, with a consequent decrease in renal reabsorption of water. The plasma chloride level was not increased in proportion to the sodium level, which is consistent with less chloride than sodium retention in primary hyperaldosteronism.18 Loss of chloride, a feature of "aldosterone escape from edema," is linked to decreased sodium-chloride cotransport in the distal renal tubule.19 Hypokalemia in turn is associated with increased loss of urinary chloride. Thus,

Δ [HCO3 -]=Δ [Na+]+Δ [K+]-Δ [Cl-],

with changes in each of these strong ions contributing to the alkalosis.

Treatment of the alkalosis in this patient with hyperaldosteronism will require replacement with potassium chloride. Administering chloride in the form of saline would worsen the hypokalemia, and administering potassium without chloride would not correct it; thus, the term "saline unresponsive" is more accurate than "chloride unresponsive" as a description of this type of alkalosis.

Hypercalcemia will increase the strong ion difference and is associated with metabolic alkalosis.20The milk alkali syndrome, which is often caused by excessive ingestion of calcium-containing antacids, is characterized by alkalosis and hypercalcemia. In contrast, hypercalcemia in primary hyperparathyroidism is associated with a proximal renal tubular metabolic acidosis rather than metabolic alkalosis. This observation may be explained by the decrease in the strong ion difference due to losses of urinary sodium resulting from inhibition of proximal tubular sodium-hydrogen exchange by parathyroid hormone.21

 

GASTROINTESTINAL LOSSES OF STRONG IONS

Losses of ions due to diarrhea are associated with the development of metabolic acidosis22 or metabolic alkalosis. Since depletion of extracellular volume can occur in cases of acidosis or alkalosis and may be initiated by losses of sodium and chloride in any ratio, the term "contraction alkalosis" is a misnomer. As shown in the following case, the relative content of the strong ions lost (sodium and potassium vs. chloride),23 not the site of the loss, determines the acid-base disorder:

A 40-year-old woman who underwent a colonic resection for ulcerative colitis had excessive liquid drainage from an ileostomy. Her laboratory results revealed a plasma sodium level of 138 mmol per liter, potassium 5.0 mmol per liter, chloride 110 mmol per liter, and bicarbonate 15 mmol per liter. The arterial pH was 7.30, and the PaCO2 was 32 mm Hg.

In this case, the loss of watery small-intestinal and pancreatic secretions, which have high sodium and bicarbonate levels and very low chloride levels, would result in the relative retention of more chloride than sodium in the extracellular fluid, causing hyperchloremic acidosis. In cases of colonic diarrhea, hyperchloremic acidosis may develop because of loss of sodium and potassium with organic anions of bacterial origin, such as acetate, rather than bicarbonate per se.23

When diarrhea is the cause of metabolic alkalosis, rather than acidosis, the mechanism is determined by measuring the electrolyte content in stool. Large losses of chloride may occur in patients who have villous adenomas or other secretory diarrheas that cause depletion of chloride, as shown in the following case, described by Berend et al.7:

Large volumes of watery diarrhea from infectious gastroenteritis developed in a 22-year-old man. Laboratory tests revealed a plasma sodium concentration of 140 mmol per liter, potassium 3.0 mmol per liter, chloride 86 mmol per liter, and bicarbonate 38 mmol per liter. The arterial pH was 7.60, and the PaCO2 was 40 mm Hg.

In this case, the electrolyte concentrations in liquid stool, if measured, would probably show a charge gap, in which (Na++K+)-Cl- would be less than the normal plasma bicarbonate concentration. High losses of chloride in stool, like losses of chloride from vomiting or after the use of loop diuretics, cause hypochloremic alkalosis.

 

URINARY CHARGE GAP AND STRONG IONS

Measurements of urinary electrolyte concentrations and flow rate indicate renal acid-base function even without measurement of urinary bicarbonate. As shown in equation 7, the urinary net charge compares the loss of measured strong cations (sodium and potassium) with the loss of chloride24:

(7) Urinary net charge gap=[UNa +]+[UK +]-[UCl -].

Negative Urinary Charge Gap

A negative value for the urinary net charge gap indicates the presence of the unmeasured cation, ammonium (excretion of ammonium chloride). The loss of ammonium chloride in the urine of a patient with metabolic acidosis is an appropriate compensation, since the very process of excreting acid in this way has an alkalinizing effect on body fluids. The loss of net acid in the form of ammonium chloride is a normal renal response to nonrenal causes of metabolic acidosis, such as severe watery diarrhea. The losses of urinary chloride result in an increased plasma strong ion difference, which in turn permits the formation of more bicarbonate.

However, in a patient with metabolic alkalosis, a relative excess of chloride in the urine strongly suggests that the losses of urinary chloride cause the metabolic alkalosis by increasing the plasma strong ion difference. In the following case, such losses of urinary chloride led to hypochloremic alkalosis:

An 80-year-old man with congestive heart failure received furosemide until all peripheral edema disappeared. Laboratory tests revealed a sodium level of 130 mmol per liter, potassium 2.5 mmol per liter, chloride 80 mmol per liter, and bicarbonate 40 mmol per liter. The arterial pH was 7.50, and the PaCO2 was 53 mm Hg.

In this patient, the sodium-potassium-chloride cotransporter was inhibited by furosemide (in the thick ascending limb of the loop of Henle). Under these circumstances, the stoichiometric balance of sodium, potassium, and chloride was 1:1:2, and proportionately more chloride than sodium was lost in the urine. Thus, there is a direct explanation for the hypochloremic metabolic alkalosis in this patient. Inhibition of the sodium-chloride cotransporter of the distal tubule by thiazides (stoichiometric balance between sodium and chloride, 1:1) is also predictive of metabolic alkalosis because of the greater loss of chloride than sodium from the extracellular fluid. In addition to chloride-wasting diuretics, many hereditary disorders of sodium and chloride transport by the renal tubules (so-called channelopathies) may cause acid-base disorders

 Urinary Charge Gap

A positive value for the urinary net charge gap indicates excretion of an unmeasured anion. The lost, unmeasured anion may be bicarbonate or nonbicarbonate anions such as ketones, lactate, L-lactate, D-lactate, and hippurate in persons who sniff glue. Such loss of anions will decrease the plasma strong ion difference and acidify the extracellular fluid as the process returns chloride to the circulation.10,25 If the urinary clearance of these nonchloride anions is high enough that they do not accumulate as a plasma anion gap, then the hyperchloremia may be mistaken for renal tubular acidosis.24 Without those nonbicarbonate anions, metabolic acidosis with the loss of urinary sodium and potassium and retention of chloride (the positive-charge gap) will result in a decreased plasma strong ion difference, constituting a renal cause of acidosis (e.g., carbonic anhydrase inhibition or renal tubular acidosis).

If metabolic alkalosis is present, a positive urinary gap suggests that the renal loss of strong cations (sodium and potassium) and conservation of chloride will acidify the extracellular fluid because of a decrease in the plasma strong ion difference and in the bicarbonate concentration.

The excretion patterns of urinary electrolytes reflect the ability of the kidney to counteract nonrenal acid-base disorders. The capacity of the kidney to excrete ammonium chloride in acidosis allows for elimination of anions with conservation of sodium for volume and potassium for potassium balance. This potassium-sparing effect of urinary ammonium is evident in hypokalemic stimulation of ammoniagenesis.

The traditional physiological approach interprets the urine electrolytes to deduce the presence of ammonium and bicarbonate with less emphasis on the strong ion pathogenesis of acid-base disorders. The physicochemical model emphasizes the relative losses of the actual measured quantities to determine the cause of the disturbance. Both perspectives are enlightening.

COMPENSATION FOR RESPIRATORY DISORDERS AND URINARY STRONG IONS

The ratio of bicarbonate to PaCO2 in the Henderson-Hasselbalch equation (equation 1) is a simple way to illustrate the initial disturbance and then the modulating effect of the compensatory response on pH. In respiratory conditions, the PaCO2 is the initial abnormality leading to sharp, sudden changes in pH, with little change in strong ion

concentrations. Over time, however, the change in the level of chloride and reciprocal changes in the level of bicarbonate are the major factors that allow pH to return toward normal values. The hyperchloremic renal compensation for respiratory alkalosis is the excretion of filtered sodium and potassium with bicarbonate, because low PaCO2 decreases proximal and distal hydrogen secretion. As the plasma strong ion difference decreases, the plasma bicarbonate concentration will decrease.

In respiratory acidosis, high PaCO2 increases production of ammonia by the kidney, and the excretion of ammonium chloride with a negative urinary net charge, shown in equation 7, results in hypochloremia, an increased plasma strong ion difference, and an elevated plasma bicarbonate concentration. The elevated PaCO2 increases the renal reabsorption of sodium and bicarbonate, so the compensation is maintained. If the PaCO2 is abruptly lowered by means of a ventilator, the compensatory response transitions to posthypercapnic hypochloremic metabolic alkalosis, which will not resolve until the chloride that is lost as ammonium chloride is replenished.

INTRAVENOUS FLUIDS AND CONTENT OF STRONG IONS

The gain of fluids containing strong ions in ratios dissimilar to those in the extracellular fluid also affects acid-base balance, as shown in the following case, which was also described by Berend et al.7 in their article about the physiological approach:

A 22-year-old woman who had been injured in an accident received 6 liters of isotonic saline, after which the level of sodium was 135 mmol per liter, potassium 3.8 mmol per liter, chloride 115 mmol per liter, and bicarbonate 18 mmol per liter. The arterial pH was 7.28, and the PaCO2 was 39 mm Hg. The urinary sodium level was 65 mmol per liter, potassium 15 mmol per liter, and chloride 110 mmol per liter.

This is an example of saline-induced acidosis,26 which develops because the infusion of a proportionately high sodium chloride-containing solution, one with a sodium-to-chloride ratio of less than 140:100, will decrease the plasma strong ion difference and the bicarbonate concentration. The insufficient urinary excretion of the extra chloride as ammonium chloride leads to metabolic acidosis. The infusion of saline with its 1:1 sodium-to-chloride ratio, resulting in hyperchloremic acidosis, is the converse of inhibition of the 1:1 sodium-to-chloride transport ratio in thiazide-induced diuresis and hypochloremic metabolic alkalosis.

Even Ringer's lactate, with a level of sodium of 130 mmol per liter, chloride 109 mmol per liter, and lactate 28 mmol per liter, can cause hyperchloremic acidosis because the ratio of sodium to chloride is smaller than the ratio of sodium to chloride in the normal extracellular fluid.26,27 Thus, what matters is the content and amount of infused fluids.

 

CONCLUSIONS

Clinical evidence can be interpreted with the use of both the strong ion theory and the traditional bicarbonate-centered approach to provide an optimal understanding of acid-base disorders. Electrolyte concentrations of plasma may be altered by the gains and losses associated with intravenous fluids and with urinary, intestinal, or sweat-gland secretions. An understanding of the consequences of these disturbances helps in the diagnosis and treatment of the associated acid-base disorders.

The evidence connecting acid-base balance with electrolyte balance is apparent at the cellular level (i.e., ion transporters, their stoichiometric balance, and the hormones that regulate them) and in clinical practice. The fact that transporters often couple a strong ion such as sodium or potassium with hydrogen, or chloride with bicarbonate,28-30 suggests an ultimate coherence between the two approaches. As more is learned about the molecular nature of disorders of epithelial-cell transport as well as about intracellular pH, it will become more important to understand interactions between carbon dioxide and bicarbonate with strong ions and cellular buffers in the body.31

 

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1. Am J Cardiol. 2014 Sep 1;114(5):737-42. doi: 10.1016/j.amjcard.2014.05.062. Epub 2014 Jun 19.
Effect of spironolactone on 30-day death and heart failure rehospitalization(from the COACH Study).
Maisel A(1), Xue Y(2), van Veldhuisen DJ(3), Voors AA(3), Jaarsma T(4), PangPS(5), Butler J(6), Pitt B(7), Clopton P(2), de Boer RA(3).
Author information: (1)Division of Cardiology, University of California San Diego, San Diego,California. Electronic address: amaisel@ucsd.edu. (2)Division of Cardiology,University of California San Diego, San Diego, California. (3)Department ofCardiology, University of Groningen, University Medical Center Groningen, TheNetherlands. (4)Division of Health, Activity and Care, Department of Social- and Welfare Studies, Linköping University, Norrköping, Sweden. (5)Department ofEmergency Medicine, Northwestern University Feinberg School of Medicine, Chicago,Illinois. (6)Division of Cardiology, Emory University, Atlanta, Georgia.(7)Division of Cardiology, University of Michigan, Ann Arbor, Michigan.
Erratum in    Am J Cardiol. 2014 Nov 15;114(10):1628.
The aim of our study is to investigate the effect of spironolactone on 30-dayoutcomes in patients with acute heart failure (AHF) and the association betweentreatment and outcomes stratified by biomarkers. We conducted a secondaryanalysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactonetherapy was initiated and terminated at the discretion of the treating physician;30-day outcomes were compared between patients who were treated withspironolactone and those who were not. Outcomes with spironolactone therapy were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, andcreatinine levels. Spironolactone was prescribed to 297 (55.6%) patients atdischarge (158 new and 139 continued). There were 19 deaths and 30 HFrehospitalizations among 46 patients by 30 days. Patients discharged onspironolactone had significantly less 30-day event (hazard ratio 0.538, p =0.039) after adjustment for multiple risk factors. Initiation of spironolactonein patients who were not on spironolactone before admission was associated with asignificant reduction in replica watches event rate (hazard ratio 0.362, p = 0.027). The survivalbenefit of spironolactone was more prominent in patient groups with elevations ofcreatinine, N-terminal pro-B-type natriuretic peptide, ST2, or galectin-3. Inconclusion, AHF patients who received spironolactone during hospitalization hadsignificantly fewer 30-day mortality and HF rehospitalizations, especially inhigh-risk patients.
Copyright © 2014 Elsevier Inc. All rights reserved.
PMID: 25129066  [PubMed - indexed for MEDLINE]

2. Heart Fail Clin. 2014 Jul;10(3):471-9. doi: 10.1016/j.hfc.2014.04.005.
Novel biomarkers in heart failure with preserved ejection fraction.
Shah KS(1), Maisel AS(2).
Author information: (1)Department of Internal Medicine, University of California, San Diego, 402Dickinson Street, Suite 380, San Diego, CA 92103-8425, USA. (2)Cardiology Section(9111-A), VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego,CA 92161, USA. Electronic address: amaisel@ucsd.edu.
Heart failure with preserved ejection fraction (HFPEF) is a common subtype ofheart failure with morbidity and mortality similar to that of heart failure with systolic dysfunction. This article discusses the numerous biomarkers that promiseto play a substantial role in terms of our ability to understand the mechanismsof HFPEF and discern possible phenotypes that respond to targeted therapies:natriuretic peptides, high-sensitivity troponins, galectin-3, soluble ST2,neutrophil gelatinase-associated lipocalin, and cystatin C.
Published by Elsevier Inc.
PMID: 24975910  [PubMed - indexed for MEDLINE]

3. JACC Heart Fail. 2014 Jun;2(3):260-8. doi: 10.1016/j.jchf.2013.12.004.
Biomarkers of myocardial stress and fibrosis as predictors of mode of death inpatients with chronic heart failure.
Ahmad T(1), Fiuzat M(1), Neely B(2), Neely ML(2), Pencina MJ(2), Kraus WE(3),Zannad F(4), Whellan DJ(5), Donahue MP(3), Piña IL(6), Adams KF(7), KitzmanDW(8), O'Connor CM(1), Felker GM(9).
Author information: (1)Division of Cardiology, Duke University Medical Center, Durham, NorthCarolina; Duke Clinical Research Institute, Durham, North Carolina. (2)DukeClinical Research Institute, Durham, North Carolina. (3)Division of Cardiology,Duke University Medical Center, Durham, North Carolina. (4)Nancy University,Nancy, France. (5)Thomas Jefferson University, Philadelphia, Pennsylvania.(6)Montefiore Medical Center, Bronx, New York. (7)University of North Carolina,Chapel Hill, North Carolina. (8)Wake Forest University, Winston-Salem, NorthCarolina. (9)Division of Cardiology, Duke University Medical Center, Durham,North Carolina; Duke Clinical Research Institute, Durham, North Carolina.Electronic address: michael.felker@duke.edu.
Comment in    JACC Heart Fail. 2014 Dec;2(6):672-3.    JACC Heart Fail. 2014 Dec;2(6):673.
OBJECTIVES: The aim of this study was to determine whether biomarkers ofmyocardial stress and fibrosis improve prediction of the mode of death inpatients with chronic heart failure.BACKGROUND: The 2 most common modes of death in patients with chronic heartfailure are pump failure and sudden cardiac death. Prediction of the mode ofdeath may facilitate treatment decisions. The relationship between amino-terminalpro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers thatreflect different pathogenic pathways in heart failure (myocardial stress andfibrosis), and mode of death is unknown.METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes ofExercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricularsystolic dysfunction (left ventricular ejection fraction ≤35%). An independentclinical events committee prospectively adjudicated mode of death. NT-proBNP,galectin-3, and ST2 levels were assessed at baseline in 813 subjects.Associations between biomarkers and mode of death were assessed usingcause-specific Cox proportional hazards modeling, and interaction testing wasused to measure differential associations between biomarkers and pump failureversus sudden cardiac death. Discrimination and risk reclassification metricswere used to assess the added value of galectin-3 and ST2 in predicting mode ofdeath risk beyond a clinical model that included NT-proBNP.RESULTS: After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes.Elevations in all biomarkers were associated with increased risk for both pumpfailure and sudden cardiac death in both adjusted and unadjusted analyses. Ineach case, increases in the biomarker had a stronger association with pumpfailure than sudden cardiac death, but this relationship was attenuated afteradjustment for clinical risk factors. Clinical variables along with NT-proBNPlevels were stronger predictors of pump failure (C statistic: 0.87) than suddencardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improvednet risk classification of 11% for sudden cardiac death, but not pump failure.CONCLUSIONS: Clinical predictors along with NT-proBNP levels were strongpredictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less best replica watches robustand enhanced by information provided by novel biomarkers.
Copyright © 2014 American College of Cardiology Foundation. Published by ElsevierInc. All rights reserved.
PMCID: PMC4224312PMID: 24952693  [PubMed - indexed for MEDLINE]

4. Curr Opin Cardiol. 2014 Jul;29(4):312-8. doi: 10.1097/HCO.0000000000000077.
Emerging biomarkers for acute heart conditions.
Vasile VC(1), Jaffe AS.
Author information: (1)aDivision of Cardiovascular Diseases, Department of Medicine bDepartment ofLaboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester,Minnesota, USA.
PURPOSE OF REVIEW: Acute cardiac conditions such as acute myocardial infarctionand heart failure are associated with significant morbidity and mortality. Rapid diagnosis allows risk stratification and initiation of treatment in a timelymanner. Numerous novel biomarkers have been identified to predict outcomes. Thesemay assist in tailoring of appropriate therapy to high-risk patients.RECENT FINDINGS: This study reviews several novel biomarkers - galectin-3, ST2and copeptin. The scope of this review is to identify and underline the clini