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Avoiding the use of mathematical formalism, this essay exposes the quantum mechanics phenomenon of nonlocality in terms of a metaphor involving human twins, focused on their hands' dexterity attribute.
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OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/terapia , Enfermedad Crítica , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Respiración Artificial , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Introducción: La insuficiencia renal aguda (IRA) es una enfermedad grave y causante de disfunciones de órganos distantes que incrementan su mortalidad. Objetivo: Identificar disfunción hemodinámica y respiratoria gatillada por IRA en un modelo pediátrico animal de isquemia-reperfusión renal. Método: Doce cerdos anestesiados (11,9 +/- 1,0 kg). En seis animales se indujo lesión renal bilateral por isquemia-reperfusión: 45 min de isquemia y 240 min de reperfusión, mientras que los seis animales restantes fueron grupo control. En condiciones basales y posterior a lesión renal se realizó monitorización hemodinámica convencional y termodilución transpulmonar. Paralelamente se midió gasometría arterial y análisis de mecánica pulmonar. Resultados: Hubo un incremento de la precarga volumétrica en 29 por ciento (221 +/- 22 ml/m² vs 286 +/- 16 ml/m², p = 0,04) y de la presión arterial media en 58 por ciento (71 +/- 6 mmHg vs 112 +/- 17 mmHg, p = 0,04) respecto a controles, sin cambios en frecuencia cardíaca, presión venosa central ni gasto cardíaco. Además ocurrió un aumento del agua extravascular pulmonar en 86 por ciento (7,6 +/- 0,6 ml/kg vs 14,1 +/- 1,4 ml/kg, p = 0,02), sin cambios en intercambio gaseoso ni mecánica pulmonar. Simultáneamente hubo un leve deterioro de la creatinina sérica (1,12 +/- 0,07 mg/dL vs 1,45 +/- 0,10 mg/dL, p = 0,03). Discusión: En este modelo experimental se pudo apreciar el desarrollo temprano de disfunción hemodinámica y pulmonar. Se evidenció un aumento de la precarga volumétrica y de la presión arterial, asociado a un incremento substancial del agua extravascular pulmonar. Creemos que es fundamental monitorizar de forma seriada la función hemodinámica y respiratoria en sujetos con una lesión renal aguda, aún sin una IRA urémica.
Background: Acute kidney injury (AKI) is a serious disease that can cause distant organ injuries and is associated with high mortality rates. Objective: To identify the hemodynamic and respiratory dysfunction triggered by AKI, in an animal model of renal ischemia-reperfusion. Method: Twelve anesthetized juvenile pigs (11.9 +/- 1.0 kg). Six animals underwent ischemia/reperfusion-induced AKI: 45 min of ischemia and 240 minutes of reperfusion, while the remaining six animals were the control group. In basal conditions and after AKI, a conventional hemodynamic monitoring and transpulmonary thermodilution were performed. At the same time, arterial blood gases and lung mechanics were measured. Results: There was a 29 percent increase in volumetric preload (221 +/- 22 ml/m² vs 286 +/- 16 ml/m², p = 0.04) and a 58 percent mean arterial pressure increase (71 +/- 6 mmHg vs 112 +/- 17 mmHg, p = 0.04) compared to controls, without changes in heart rate, central venous pressure and cardiac output. In addition, an increase of 86 percent in extravascular lung water (7.6 +/- 0.6 ml/kg vs 14.1 +/- 1.4 ml/ kg, p = 0.02) was reported, without changes in gas exchange and lung mechanics. Simultaneously, a slight increase in serum creatinine (1.12 +/- 0.07 mg/dl vs 1.45 +/- 0.10 mg/dl, p = 0.03) was described. Discussion: An early development of hemodynamic and pulmonary dysfunction was observed in this experimental reperfusion model. An increase in volumetric preload and blood pressure associated with a substantial increase in the extravascular lung water were also reported. It is essential serially monitor the hemodynamic and respiratory functions in AKI, including nonuremic subjects.
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Animales , Daño por Reperfusión/complicaciones , Enfermedades Pulmonares/etiología , Lesión Renal Aguda/complicaciones , Análisis de los Gases de la Sangre , Gasto Cardíaco , Modelos Animales de Enfermedad , Enfermedades Pulmonares/fisiopatología , Hemodinámica , Pulmón/fisiopatología , Mecánica Respiratoria , Riñón/fisiopatología , PorcinosRESUMEN
Introduction: Abdominal compartment syndrome (ACS) is a severe and under-reported condition among the pediatric population due to inadequate warning and recognition. It can be caused by medical and surgical reasons, resulting in a high mortality rate. objective: To determine the magnitude of the initial hemodynamic and respiratory consequences triggered by the induction of ACS in an experimental model. Methods: The model consisted of twelve anesthetized pigs (4.8 +/- 0.1 kg). The ACS was induced by instillation of colloid solution in the peritoneal cavity to obtain an intra-abdominal pressure (IAP) of 24.9 +/- 0.6 mmHg. In basal conditions and after the ACS induction, a conventional hemodynamic monitoring and transpulmonary thermodilution were performed. At the same time, arterial blood gases and lung mechanics analysis were measured. results: There was a reduction of cardiac output by 16 percent (5.19 +/- 0.33 to 4.34 +/- 0.28 l/min/m², p = 0.01) and abdominal perfusion pressure by 20 percent (72.3 +/- 3.2 to 57.3 +/- 4.0 mmHg, p <0.001) without changes in heart rate, arterial or central venous pressure. In addition there was an approximately 50 percent worsening of respiratory system compliance (1.28 +/- 0.09 to 0.62 +/- 0.04 ml/cmH2O/kg, p = 0.002) associated with a significant increase in intrathoracic pressure and slight decrease in oxygenation. Discussion: In this experimental model, the early development of hemodynamic and pulmonary dysfunction could be observed. A reduction of cardiac output that was not detected by conventional monitoring and a substantial deterioration of lung mechanics, characteristic of restrictive disease, associated with mild alterations in gas exchange were reported. It is essential then to monitor the IAP in patients predisposed to develop ACS, especially in the case of organ dysfunction deterioration, as severe hypotension and hypoxemia are late signs of this complication.
Introducción: El síndrome compartimental abdominal (SCA) es una entidad grave, de escaso reporte en población pediátrica por una inadecuada alerta y reconocimiento. Puede ser originado por causas médicas y quirúrgicas, presentando una elevada mortalidad. objetivo: Determinar la magnitud de las consecuencias hemodinámicas y respiratorias iniciales desencadenadas por la inducción de un SCA en un modelo experimental. Método: Doce cerdos anestesiados (4,8 +/- 0,1 kg). El SCA fue inducido con instilación de solución coloide en cavidad peritoneal para obtener una presión intra-abdominal (PIA) de 25 +/- 5 mmHg. En condiciones basales y posterior a inducción del SCA se realizó monitorización hemodinámica convencional y termodilución transpulmonar. Paralelamente se midió gasometría arterial y análisis de mecánica pulmonar. resultados: Hubo una reducción del gasto cardíaco en 16 por ciento (5,19 +/- 0,33 a 4,34 +/- 0,28 l/min/m², p = 0,01) y de la presión de perfusión abdominal en 20 por ciento (72,3 +/- 3,2 a 57,3 +/- 4,0 mmHg, p < 0,001) sin cambios en frecuencia cardiaca, presión arterial y venosa central. Además ocurrió un deterioro de la compliance del sistema respiratorio cercana al 50 por ciento (1,28 +/- 0,09 a 0,62 +/- 0,04 ml/cmH2O/kg, p = 0,002) asociado a un incremento significativo en las presiones intratorácicas y disminución leve de la oxigenación. Discusión: En este modelo experimental se pudo apreciar el desarrollo temprano de disfunción hemodinámica y pulmonar. Se evidenció una reducción de gasto cardiaco no detectado por la monitorización convencional y un deterioro substancial de la mecánica pulmonar, propia de una enfermedad restrictiva, asociado a alteraciones leves del intercambio gaseoso. Creemos que es fundamental monitorizar la PIA en pacientes predispuestos a desarrollar un SCA, más aún ante empeoramiento de disfunciones orgánicas dado que la hipotensión e hipoxemia grave son signos tardíos de esta complicación.
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Animales , Hipertensión Intraabdominal/fisiopatología , Pulmón/fisiopatología , Modelos Animales de Enfermedad , Gasto Cardíaco Bajo/fisiopatología , Hemodinámica , Presión , Porcinos , Sistema Respiratorio/fisiopatologíaRESUMEN
We describe four pregnant patients with distal renal tubular acidosis (type I) (DRTA) whose initial presentation was rhabdomyolysis (RML) secondary to severe hypokalemia. We draw attention to the unusual presentation of DRTA during pregnancy, the low frequency of DRTA in adult patients and RML as initial manifestation. In one case the DRTA was secondary to Sjögren Syndrome and the etiology was unknown in the rest of the cases. We discuss the potential pathogenic mechanisms to explain hypokalemic RML and the various causes of DRTA in adult patients.
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Acidosis Tubular Renal/diagnóstico , Túbulos Renales Distales/fisiopatología , Complicaciones del Embarazo/diagnóstico , Rabdomiólisis/etiología , Acidosis Tubular Renal/sangre , Acidosis Tubular Renal/clasificación , Acidosis Tubular Renal/complicaciones , Adulto , Enfermedades Autoinmunes/complicaciones , Bacteriemia/complicaciones , Bacteriemia/microbiología , Femenino , Humanos , Hipopotasemia/etiología , Hipotiroidismo/complicaciones , Recién Nacido , Transporte Iónico , Túbulos Renales Distales/metabolismo , Infecciones por Klebsiella/complicaciones , Klebsiella pneumoniae/aislamiento & purificación , Embarazo , Resultado del Embarazo , Cuadriplejía/etiología , Rabdomiólisis/sangre , Síndrome de Sjögren/complicaciones , Vómitos/etiologíaRESUMEN
Disseminated Gonococcal Infection (DGI) is very unusual in elderly patients and its association with Rhabdomyolysis (RML) has not been published for which reason we are presenting a case of RML secondary to DGI in an elderly women. We presume that the muscle damage was directly related with the gonococcal infection through toxin generation and release of endogenous mediators from mononuclear phagocytes and neutrophils and/or with ischemic injury due to altered tissue perfusion evidenced in this case by the presence of hypotension, oliguria and acidosis. We suggest that DGI be added to the RML infectious etiologies and considered in the initial differential diagnosis of all patients with polyarthritis and RML in order to facilitate an optimal treatment.
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Gonorrea/complicaciones , Rabdomiólisis/etiología , Anciano , Femenino , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Humanos , Rabdomiólisis/diagnóstico , Rabdomiólisis/tratamiento farmacológico , SíndromeRESUMEN
Entre janeiro de 1979 e dezembro de 1989, foram realizadas 85 operaçoes para o tratamento da dissecçao da aorta, sendo 50 na fase aguda e 35 na fase crônica. A mortalidade imediata (hospitalar) foi de 21,1 por cento (18 pacientes), tendo como causa principal a síndrome de baixo débito cardíaco. Foi maior nos pacientes operados na fase aguda. Dentre quatro pacientes reoperados por recidiva ou dissecçao em outro local, dois faleceram. Com relaçao à morbidade, uma paciente, reoperada por aneurisma tóraco-abdominal, apresentou paraplegia no período de pós-operatório. O seguimento tardio mostrou boa evoluçao dos 63 sobreviventes.