RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

[Postpartum pulmonary hypertension]. / Hipertensión pulmonar postparto.

Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery.

Hipertensión pulmonar postparto / Postpartum pulmonary hypertension

La presencia de hipertensión pulmonar (HP) en el embarazo es poco frecuente y conlleva un alto riesgo para madres e hijos. Existe escasa bibliografía relacionada al diagnóstico de la misma luego del parto. Se describen tres pacientes a quienes se diagnostica HP luego de cursar sus embarazos y partos libres de eventos. A pesar de desconocerse las causas, son varios los mecanismos propuestos, como la hipercoagulabilidad, la hipoxia placentaria o la embolia de líquido amniótico. Resulta difícil definir si la HP diagnosticada en el puerperio, corresponde a una HP en período asintomático que fue desenmascarada por el estrés fisiológico del parto o es una condición de reciente comienzo. A pesar de la falta de datos que avalen la ausencia de HP previa al embarazo en nuestras tres casos, el curso libre de eventos en sus embarazos, sin síntomas y con partos normales, indican que no padecían esta enfermedad hasta el momento del parto, y que la desarrollaron posteriormente. De haberla padecido antes se hubieran presentado síntomas previos al parto o en el puerperio inmediato, ya que las demandas hemodinámicas deterioran gravemente a un ventrículo con poca reserva.

Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery.

Cirurgia coronária com condutos arteriais múltiplos sem circulação extracorpórea / Off-pump coronary artery bypass with multiple arterial conduits

Objetivo: abalisar os resultados, em 30 dias, em pacientes submetidos de forma eletiva à revascularização arterial total do miocárdio sem circulação extracorpórea(CEC), e identificar preditores de morbimortalidade com esta estratégia cirúrgica.Método: Entre maio de 1999 e fevereiro de 2004, efetuaram-se 203 cirurgias de revascularização miocárdica(CRM) com revascularização arterial total sem CEC, em pacientes com doença de múltiplos vasos (três vasos 81,7 por cento, doença de uma vaso excluído). Reportaram-se variáveis pré-operatórias e comorbidade: média de idade 63,9 anos, homens 182(89,5 por cento), hipertensão 132(65 por cento), tabagismo 125(61 por cento), hipercolesterolemia 152(74,8 por cento), infarto agudo do miocárdio prévio(mais de 30 dias) 73(35 por cento), disfunção ventricular moderada a grave 31(15 por cento), reoperação cinco(2,5 por cento). a revascularização arterial total incluiu anastomoses em T e sequenciais com artéria torácica interna esquerda(100 por cento), torácica interna direita(56,6 por cento) e artéria radial(63 por cento). O número total de anastomoses foi de 576(méida de três pontes/paciente), todas efetuadas com estabilizadores mecânicos externos. Não foram realizadas anastomoses proximais na aorta. Cirurgia com CEC foi realizada em três(1,5 por cento) pacientes. Noventa por cento dos pacientes foram extubados na sala de operações. Para a análise estatística, utilizou-se teste de regressão logística múltipla.Resultados: A incidência de fibrilação atrial pós-operatória foi de 12,8 por cento(26), insuficiência renal oligoanúrica 3 por cento(seis), diálise 0,49 por cento(um), infarto de miocárdio pós-operatório 1,47 por cento(três), baixo débito cardíaco 4 por cento(oito), reoperação por sangramento 1,47 por cento(três), mediastinite 1,47 por cento(três), acidente vascular cerebral 1,47 por cento(três). A mortalidade intra-hospitalar foi de 2,45 por cento(cinco). O únco preditor independente de morbidade em 30 dias foi a idade(p igual 0,033; OR 1,04; IC 95 por cento:1-1,08).Conclusão: A cirurgia de revascularização miocárdica sem circulação extracorpórea utilizando condutos arteriais para a doença de múltiplos vasos é factível com baixa morbimortalidade em 30 dias

Cirugía coronaria con conductos arteriales múltiples sin circulación extracorpórea / Total coronary artery revascularization on beating hearts

Objetivo: Analizar los resultados intrahospitalarios en pacientes sometidos en forma electiva a revascularización arterial total sin circulación extracorpórea (sin CEC) e identificar predictores de morbimortalidad con esta estrategia quirúrgica. Material y métodos: Entre mayo de 1999 y febrero de 2004 se realizaron 203 cirugías de revascularización miocárdica (CRM) con revascularización arterial total sin CEC, en pacientes con enfermedad de múltiples vasos (tres vasos 81,7 por ciento, enfermedad de 1 vaso excluída). Se comunican variables preoperatorias y comorbilidad: edad promedio 63,9 ± 9,13 años, hombres 182 (89,5 por ciento), hipertensión 132 (65 por ciento), tabaquismo 125 (61 por ciento), hipercolesterolemia 152 (74,8 por ciento), IAM previo (más de 30 días) 73 (35 por ciento), disfunción ventricular moderada a severa 31 (15 por ciento), reoperación 5 (2,5 por ciento). La revascularización arterial total incluyó anastomosis en T y secuenciales con mamaria interna izquierda (100 por ciento), mamaria interna derecha (56,6 por ciento) y arteria radial (63 por ciento). El número total de anastomosis distales fue de 576 (mediana de 3 puentes/paciente), todas realizadas con estabilizadores mecánicos externos. No se realizaron anastomosis proximales en la aorta. Se convirtieron a cirugía con CEC 3 pacientes (1,5 por ciento). El 90 por ciento de los pacientes fueron extubados en la sala de operaciones. Para el análisis estadístico se utilizó la prueba de regresión logística múltiple. Resultados: La incidencia de fibrilación auricular posoperatoria fue del 12,8 por ciento (26), insuficiencia renal oligoanúrica 3 por ciento (6), diálisis 0,49 por ciento (1), infarto de miocardio posoperatorio 1,47 (3), bajo gasto cardíaco 4 por ciento (8), reoperación por sangrado 1,47 por ciento (3), mediastinitis 1,47 por ciento (3), bajo gasto cardíaco 4 por ciento (8), reoperación por sangrado 1,47 por ciento (3), mediastinitis 1,47 por ciento (3), accidente cerebrovascular 1,47 por ciento (3). La mortalidad intrahospitalaria fue del 2,45 por ciento (5). El único predictor independiente de morbilidad a los 30 días fue la edad (p = 0,033; OR 1,04; IC 95 por ciento: 1-1,08). Conclusión: La cirugía de revascularización miocárdica sin circulación extracorpórea utilizando conductos arteriales para la enfermedad de múltiples vasos es factible con baja morbimortalidad a los 30 días.

Registro Nacional de internación por insuficiencia cardíaca 2002-2003 / National survey of hospitalization of patients with heart failure, 2002-2003

Objetivos: Describir el perfil de una cohorte de pacientes internados por insuficiencia cardíaca (IC), evaluar patrones de presentación, modalidades diagnósticas y terapéuticas, utilización de recursos y evolución hospitalaria. Comparar con el registro del Área de Investigación de la SAC 1999. Materiales y métodos: Se incluyeron prospectivamente 615 pacientes mayores de 18 años internados por IC descompensada en 36 centros participantes entre mayo de 2002 y marzo de 2003. Se recabaron datos de filiación, socioeconómicos, antecedentes patológicos y relativos a la evolución hospitalaria. Resultados: La media de edad fue de 70 años, predominio masculino. Se observó un alto porcentaje de comorbilidades (40,3 por ciento), antecedentes de IC (72,8 por ciento) y factores desencadenantes (73,8 por ciento). Predominaron las formas leves de presentación (67,2 por ciento), con alto porcentaje de ingreso en cuidados intensivos (57,7 por ciento). La mortalidad hospitalaria fue del 9,94 por ciento. Formas de presentación severas y el grado de cobertura médica predijeron en forma independiente internación en cuidados críticos e internación prolongada, mientras que variables clínicas como edad avanzada, diabetes, urea elevada, hipotensión sistólica, tercer ruido e hiponatremia se asociaron independientemente con mayor mortalidad. Una mayor utilización de betabloqueantes y antagonistas de angiotensina II se asoció independientemente a pertenecer a la cohorte de 2002. Conclusiones: La población internada por IC es añosa, con elevada prevalencia de IC previa y comorbilidades. Existen factores predisponentes potencialmente prevenibles y muchos pacientes no graves internados en cuidados intensivos. La ausencia de cobertura médica define independientemente la no internación en cuidados críticos así como una internación prolongada. Variables clínicas simples fueron predictoras de mayor mortalidad.

Assessment of bronchodilator response through changes in lung volumes in chronic airflow obstruction.

Although FEV1 improvement is routinely used to define bronchodilator (BD) response, it correlates poorly with clinical effects. Changes in lung volumes (LV) have shown better correlation with exercise tolerance and might be more sensitive to detect BD effects. We assessed the additional contribution of measuring LV before and after BD to detect acute improvement in lung function not demonstrated by FEV1, and the influence of the response criteria selected on this contribution. We analyzed 98 spirometries and plethismographies performed pre and post BD in patients with airflow obstruction (FEV1/FVC < 70%). BD response was defined for FEV1 and FVC as per ATS guidelines and for other LV as delta > or = 10% of baseline (delta > or = 5 and > or = 15% were also analyzed). FEV1 identified as responders 32% of patients. Greater proportions were uncovered by slow vital capacity (51%, p < 0.001), inspiratory capacity (43%, p < 0.05) and residual volume (54%, p < 0.001). Slow spirometry identified 11% of responders additional to those detected by FEV1 and FVC. Plethismography added 9% more. The magnitude of volume responses correlated with the degree of baseline hyperinflation. Percentages of responders varied greatly using different thresholds (delta > or = 5 and > or = 15%). Mean change and proportions of responders for each LV varied significantly (p < 0.05) whether change was expressed as percent of baseline or predicted values. A considerable proportion of patients with airflow obstruction shows acute response to bronchodilators identified by changes in lung volumes but not detected by an improvement in FEV1. The selection of LV response criteria has important influence on the magnitude of this additional detection.

Assessment of bronchodilator response through changes in lung volumes in chronic airflow obstruction

Although FEV, improvement is routinely used to define bronchodilator (BD) response, it correlates poorly with clinical effects. Changes in lung volumes (LV) have shown better correlation with exercise tolerance and might be more sensitive to detect BD effects. We assessed the additional contribution of measuring LV before and after BD to detect acute improvement in lung function not demonstrated by FEV, and the influence of the response criteria selected on this contribution. We analyzed 98 spirometries and plethismographies performed pre and post BD in patients with airflow obstruction (FEV,/FVC < 70%). BD response was defined for FEV, and FVC as per ATS guidelines and for other LV as o>_10% of baseline (4>_5 and >_15% were also analyzed). FEV, identified as responders 32% of patients. Greater proportions were uncovered by slow vital capacity (51 %, p<0.001), inspiratory capacity (43%, p<0.05) and residual volume (54%, p<0.001). Slow spirometry identified 11% of responders additional to those detected by FEV, and FVC. Plethismography added 9% more. The magnitude of volume responses correlated with the degree of baseline yperinflation. Percentages of responders varied greatly using different thresholds (A>5 and >_15%). Mean change and proportions of responders for each LV varied significantly (p<0.05) whether change was expressed as percent of baseline or predicted values. A considerable proportion of patients with airflow obstruction shows acute response to bronchodilato rs identified by changes in lung volumes but not detected by an improvement in FEV, The selection of LV response criteria has important influence on the magnitude of this additional detectìon.