Soluble CD137 as a potential biomarker for severe COVID-19.

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic infection responsible for the world pandemic in 2020. COVID-19 is characterized by an increased number of critically ill patients with a high risk of health care system collapse. Therefore, the search for severity biomarkers and potential therapies is crucial. In this study, we evaluated SARS-CoV-2 -induced cytokines, cytokines receptors and growth factors profile, in critical COVID-19 patients admitted in intensive care unit (ICU) aiming to identify potential biomarkers and therapeutic targets. We designed a prospective study enrolling 62 adults with severe COVID-19 during the first two Brazilian COVID-19 waves (from May to July 2020 and December 2020 to May 2021), convenience samples recruitment in first 24 hours and then, every 4 days until day 20 of ICU admission from a tertiary hospital in São Paulo, Brazil. Controls were healthy blood donors. Whole blood was used to evaluate 17 cytokines, cytokines receptors and growth factors. Due to low mortality rate, we used the need of mechanical ventilation as primary endpoint. In our analysis, we found a different pattern in soluble CD137 (sCD137) in critically ill patients with COVID-19, with a direct relationship between increased levels and worse clinical outcome. sCD137 was related with increased risk of mechanical ventilation and World Health Organization (WHO) clinical score for disease severity. CD137 is a tumor necrosis factor receptor (TNF) family member, mainly responsible for T-cell activation. Soluble isoforms of immune checkpoints competitively regulate function of their membrane-bound counterparts. Our study demonstrated the onward increase in sCD137 levels during severe SARS-CoV-2 infection and its correlation with worse outcomes, suggesting sCD137 as a potential reliable severity biomarker.

Acute Kidney Injury Due to COVID-19 in Intensive Care Unit: An Analysis From a Latin-American Center.

Introduction: The kidney may be affected by coronavirus (COVID-19) in the setting of acute kidney injury (AKI). Data about AKI in intensive care unit (ICU) patients in Latin America are scarce. We aimed to evaluate the risk of AKI, dialysis (HD), and death in ICU COVID-19 patients in a Brazilian center. Methods: Analysis from medical records of COVID-19 patients in a Brazilian center. Results: A total of 95 patients were analyzed. There was male predominance (64.2%), median age: 64.9 years, and previous history of hypertension and diabetes in 51.6 and 27.4%, respectively. AKI was diagnosed in 54 (56.8%) patients, and 32 (59.2%) of them required HD. Mortality rate was 17.9%. AKI patients when compared with no-AKI were more frequently hypertensive/diabetic and more often needed organ support therapies. Workups depicted more anemia, lymphopenia, and higher levels of inflammatory markers and higher mortality. Comparing patients who had undergone death to survivors, they were older, more frequently diabetic, and had worse SAPS3 and SOFA scores and need for organ support therapies, AKI, and HD. Multinomial logistic regression revealed that hypertension (p = 0.018) and mechanical ventilation (p = 0.002) were associated with AKI; hypertension (p = 0.002), mechanical ventilation (p = 0.008), and use of vasopressor (p = 0.027) to HD patients; and age >65 years (p = 0.03) and AKI (p = 0.04) were risk factors for death. Conclusions: AKI was a common complication of ICU COVID-19 patients, and it was more frequent in patients with hypertension and need of organ support therapies. As well as age >65 years, AKI was an independent risk factor for death.

Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology

Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.

Há diversas terapias sendo utilizadas, consideradas ou propostas para o tratamento da COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é fornecer recomendações baseadas nas evidências científicas disponíveis e em sua interpretação transparente, para subsidiar decisões sobre o tratamento farmacológico da COVID-19 no Brasil. Um grupo de 27 especialistas e metodologistas integraram a força-tarefa formada pela Associação de Medicina Intensiva Brasileira (AMIB), pela Sociedade Brasileira de Infectologia (SBI) e pela Sociedade Brasileira de Pneumologia e Tisiologia (SBPT). Foram realizadas revisões sistemáticas rápidas, atualizadas até 28 de abril de 2020. A qualidade das evidências e a elaboração das recomendações seguiram o sistema GRADE. As recomendações foram elaboradas nos dias 5, 8 e 13 de maio de 2020. Foram geradas 11 recomendações, embasadas em evidência de nível baixo ou muito baixo. Não há indicação para uso de rotina de hidroxicloroquina, cloroquina, azitromicina, lopinavir/ritonavir, corticosteroides ou tocilizumabe no tratamento da COVID-19. Heparina deve ser utilizada em doses profiláticas no paciente hospitalizado, mas não deve ser realizada anticoagulação na ausência de indicação clínica específica. Antibacterianos e oseltamivir devem ser considerados somente nos pacientes em suspeita de coinfecção bacteriana ou por influenza, respectivamente. Até o momento, não há intervenções farmacológicas com efetividade e segurança comprovada que justifiquem seu uso de rotina no tratamento da COVID-19, devendo os pacientes serem tratados preferencialmente no contexto de pesquisa clínica. As recomendações serão revisadas continuamente, de forma a capturar a geração de novas evidências

Diretrizes para o tratamento farmacológico da COVID-19. Consenso da Associação de Medicina Intensiva Brasileira, da Sociedade Brasileira de Infectologia e da Sociedade Brasileira de Pneumologia e Tisiologia / Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology

RESUMO Introdução: Há diversas terapias sendo utilizadas, consideradas ou propostas para o tratamento da COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é fornecer recomendações baseadas nas evidências científicas disponíveis e em sua interpretação transparente, para subsidiar decisões sobre o tratamento farmacológico da COVID-19 no Brasil. Métodos: Um grupo de 27 especialistas e metodologistas integraram a força-tarefa formada pela Associação de Medicina Intensiva Brasileira (AMIB), pela Sociedade Brasileira de Infectologia (SBI) e pela Sociedade Brasileira de Pneumologia e Tisiologia (SBPT). Foram realizadas revisões sistemáticas rápidas, atualizadas até 28 de abril de 2020. A qualidade das evidências e a elaboração das recomendações seguiram o sistema GRADE. As recomendações foram elaboradas nos dias 5, 8 e 13 de maio de 2020. Resultados: Foram geradas 11 recomendações, embasadas em evidência de nível baixo ou muito baixo. Não há indicação para uso de rotina de hidroxicloroquina, cloroquina, azitromicina, lopinavir/ritonavir, corticosteroides ou tocilizumabe no tratamento da COVID-19. Heparina deve ser utilizada em doses profiláticas no paciente hospitalizado, mas não deve ser realizada anticoagulação na ausência de indicação clínica específica. Antibacterianos e oseltamivir devem ser considerados somente nos pacientes em suspeita de coinfecção bacteriana ou por influenza, respectivamente. Conclusão: Até o momento, não há intervenções farmacológicas com efetividade e segurança comprovada que justifiquem seu uso de rotina no tratamento da COVID-19, devendo os pacientes serem tratados preferencialmente no contexto de pesquisa clínica. As recomendações serão revisadas continuamente, de forma a capturar a geração de novas evidências.

ABSTRACT Introduction: Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. Methods: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. Results: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. Conclusion: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.

[Echocardiographic assessment of cardiac resynchronization therapy: two-year follow-up period]. / Avaliação ecocardiográfica da terapia de ressincronização cardíaca: dois anos de seguimento.

BACKGROUND: The cardiac resynchronization therapy (CRT) is an effective option for patients with advanced heart failure (HF). Clinical, electrocardiographic and echocardiographic criteria have been studied in an attempt to find the patients that will benefit from the CRT, considering that the echocardiogram is the method that is used both in the selection and in the assessment of such therapy. OBJECTIVE: The objective of this work is to analyze the use of echocardiogram to assess the CRT, in a ten-day follow-up period and after two years of evolution. METHODS: The assessment considered 20 patients subjected to CRT, for a period of two years, 80% of which were male. The Minnesota Living with Heart Failure Questionnaire (MLWHF) was filled out. Patients underwent a six-minute walking test. Then, the two-dimensional echo-Doppler-cardiogram was performed. The initial assessment was repeated ten days after and two year after the implantation of the biventricular pacemaker. RESULTS: In two years, 5 patients (25%) died; 4 had cardiomyopathy caused by the Chagas's disease. There was no statistically significant change in the ejection fraction between the pre-operation period and the following ten days, but there was a significant change between the pre-operation period and two years after that, and the ten-day period and two years after that. In the ten-day follow-up period, there was the worsening of the intraventricular dyssynchrony, as evaluated by the tissue Doppler method, and the 'living with heart failure' score was higher in the group of deaths. CONCLUSION: Out of the echocardiographic parameters assessed, only the intraventricular dyssynchrony assessment through the tissue Doppler method, after the procedure, was capable of predict the CRT efficiency with respect to the death rate.

Avaliação ecocardiográfica da terapia de ressincronização cardíaca: dois anos de seguimento / Echocardiographic assessment of cardiac resynchronization therapy: two-year follow-up period / Evaluación ecocardiográfica de la terapia de resincronización cardiaca: dos años de seguimiento

Fundamento: A terapia de ressincronização cardíaca (TRC) é uma opção efetiva para os pacientes com insuficiência cardíaca (IC) avançada. Critérios clínicos, eletrocardiográficos e ecocardiográficos têm sido estudados na tentativa de selecionar os pacientes que serão beneficiados com a TRC, sendo o ecocardiograma um método utilizado tanto na seleção quanto na avaliação desta terapêutica. Objetivo: O objetivo deste trabalho é analisar a utilização do ecocardiograma na avaliação da TRC, no seguimento de dez dias e após dois anos de evolução. Métodos: Foram avaliados 20 pacientes submetidos à TRC, por um período de dois anos, sendo 80 por cento do sexo masculino. Foi aplicado o Questionário de Qualidade de Vida de Minnesota, o teste de caminhada de seis minutos e realizado o ecodopplercardiograma bidimensional. Dez dias após o implante do marca-passo biventricular, bem como dois anos depois, foi repetida a avaliação inicial. Resultados: Em dois anos, 5 pacientes (25 por cento) foram a óbito; 4 apresentavam cardiomiopatia de etiologia chagásica. Não houve alteração estatisticamente significante da fração de ejeção entre o período pré-operatório e os dez dias seguintes, mas sim uma alteração significante nos períodos de pré-operatório e dois anos e de dez dias e dois anos. No seguimento de dez dias, houve piora da dissincronia intraventricular avaliada pelo Doppler tecidual, assim como a pontuação no escore de qualidade de vida foi maior no grupo óbito. Conclusão: Dos parâmetros ecocardiográficos avaliados, somente a avaliação da dissincronia intraventricular pelo Doppler tecidual após o procedimento foi capaz de predizer a eficácia da TRC em relação à mortalidade.

Background: The cardiac resynchronization therapy (CRT) is an effective option for patients with advanced heart failure (HF). Clinical, electrocardiographic and echocardiographic criteria have been studied in an attempt to find the patients that will benefit from the CRT, considering that the echocardiogram is the method that is used both in the selection and in the assessment of such therapy. Objective: The objective of this work is to analyze the use of echocardiogram to assess the CRT, in a ten-day follow-up period and after two years of evolution. Methods: The assessment considered 20 patients subjected to CRT, for a period of two years, 80 percent of which were male. The Minnesota Living with Heart Failure Questionnaire (MLWHF) was filled out. Patients underwent a six-minute walking test. Then, the two-dimensional echo-Doppler-cardiogram was performed. The initial assessment was repeated ten days after and two year after the implantation of the biventricular pacemaker. Results: In two years, 5 patients (25 percent) died; 4 had cardiomyopathy caused by the Chagas's disease. There was no statistically significant change in the ejection fraction between the pre-operation period and the following ten days, but there was a significant change between the pre-operation period and two years after that, and the ten-day period and two years after that. In the ten-day follow-up period, there was the worsening of the intraventricular dyssynchrony, as evaluated by the tissue Doppler method, and the "living with heart failure" score was higher in the group of deaths. Conclusion: Out of the echocardiographic parameters assessed, only the intraventricular dyssynchrony assessment through the tissue Doppler method, after the procedure, was capable of predict the CRT efficiency with respect to the death rate.

Fundamento: La terapia de resincronización cardiaca (TRC) es una opción efectiva para los pacientes con insuficiencia cardiaca (IC) avanzada. Se vienen estudiando criterios clínicos, electrocardiográficos y ecocardiográficos en el intento de seleccionar a los pacientes que serán beneficiados con la TRC, siendo el ecocardiograma un método utilizado tanto en la selección como en la evaluación de este tratamiento. Objetivo: El objetivo de este trabajo es analizar la utilización del ecocardiograma en la evaluación de la TRC, en el seguimiento de diez días y luego de dos años de evolución. Métodos: Fueron evaluados 20 pacientes sometidos a la TRC, por un período de dos años, siendo el 80 por ciento de sexo masculino. Se aplicó el Cuestionario de Calidad de Vida de Minnesota, el test de caminata de 6 minutos y se realizó el ecodopplercardiograma bidimensional. Diez días tras el implante del marcapasos biventricular, así como dos años después, se repitió la evaluación inicial. Resultados: En dos años, 5 pacientes (25 por ciento) obitaron; 4 presentaban miocardiopatía de etiología chagásica. No hubo alteración estadísticamente significativa de la fracción de eyección entre el período preoperatorio y los diez días siguientes, pero sí una alteración significativa en los períodos de preoperatorio, dos años y diez días y dos años. En el seguimiento de diez días, hubo un empeoramiento de la disincronía intraventricular evaluada por doppler tisular, así como la puntuación en el escore de calidad de vida fue mayor en el grupo óbito. Conclusión: De los parámetros ecocardiográficos evaluados, solamente la evaluación de la disincronía intraventricular por doppler tisular tras el procedimiento fue capaz de predecir la eficacia de la TRC en relación a la mortalidad.

Left atrial appendage aneurysm: echocardiographic diagnostic.

The left atrial appendage aneurysm is a rare condition that frequently manifests itself by heart arrhythmias or thromboembolism. We report the case of a patient with left atrial appendage aneurysm, diagnosed by echocardiography and submitted to surgical resection.

Aneurisma de apêndice atrial esquerdo: diagnóstico ecocardiográfico / Left atrial appendage aneurysm: echocardiografic diagnostic

O aneurisma de apêndice atrial esquerdo é condição rara que se manifesta freqüentemente por arritmias cardíacas ou tromboembolismo. Relatamos um caso de paciente portador de aneurisma de apêndice atrial esquerdo, diagnosticado pela ecocardiografia e submetido a ressecção cirúrgica.

The left atrial appendage aneurysm is a rare condition that frequently manifests itself by heart arrhythmias or thromboembolism. We report the case of a patient with left atrial appendage aneurysm, diagnosed by echocardiography and submitted to surgical resection.

Endocardite em válvula de Eustáquio / Eustachian valve endocarditis

A endocardite em válvula de Eustáquio é uma condição rara, que ocorre geralmente em usuários de drogas injetáveis e em portadores de marcapasso ou cateter venoso central. Apresentamos um caso de paciente que, em pós-operatório de cirurgia de revascularização do miocárdio com circulação extracorpórea, apresentou endocardite em válvula de Eustáquio diagnosticada pela ecocardiografia, sendo identificada Klebsiella pneumoniae à hemocultura. O paciente foi tratado com antibioticoterapia apropriada, apresentando resolução do quadro em quatro semanas.

Eustachian valve endocarditis is a rare condition that affects mostly injectable drug users and patients using pacemakers or central venous catheter. We describe the case of a patient who underwent myocardial revascularization with extracorporeal circulation and who presented Eustachian valve endocarditis in the postoperative period, diagnosed by echocardiogram. The blood culture identified Klebsiella pneumoniae. He received appropriate antibiotic therapy and presented resolution of the condition within four weeks.

Defeito do anel fibroso mitral posterior com aneurisma de átrio esquerdo e insuficiência mitral: tratamento cirúrgico com sucesso / Defect of the posterior mitral fibrous ring with left atrial aneurysm and mitral insufficiency: successful surgical treatment

Aneurismas em átrio esquerdo são pouco comuns, podendo ocorrer na aurícula ou na parede do átrio esquerdo. Freqüentemente, são assintomáticos, podendo ocorrer arritmias, fenômenos tromboembólicos ou insuficiência cardíaca como complicação da sua evolução. Apresentamos paciente de 39 anos, do sexo feminino, com defeito do anel posterior da valva mitral levando a grande dilatação aneurismática da parede posterior do átrio esquerdo com insuficiência mitral. O diagnóstico foi feito pela radiografia de tórax (abaulamento de silhueta cardíaca esquerda) e ecocardiograma (grande aneurisma do átrio esquerdo posteriormente à parede posterior do ventrículo esquerdo com insuficiência mitral). O estudo hemodinâmico sugeriu pseudo-aneurisma de ventrículo esquerdo. Submetida a tratamento cirúrgico com auxílio da circulação extracorpórea, realizou-se anuloplastia mitral e exclusão do aneurisma com reconstrução do assoalho do átrio esquerdo com retalho de pericárdio bovino. A paciente apresentou boa evolução pós-operatória, recebendo alta hospitalar no oitavo dia em boas condições clínicas