Desenvolvimento de uma metodologia de microanálise electromediada (EMMA) para avaliação da actividade de carboxilesterases

O interesse crescente no estudo das carboxilesterases (CES) deve-se ao seu importante papel no metabolismo de fármacos e pró-fármacos, em especial no campo da oncologia. Os métodos convencionais apresentam limitações na avaliação da actividade específica das diferentes isoformas (CES-1 ou CES-2) em amostras complexas. A microanálise electromediada (EMMA) tem sido utilizada com sucesso em ensaios de actividade enzimática, estudos cinéticos e estudo de inibidores, mas nunca para avaliação de carboxilesterases. Objectivo do estudo: desenvolver uma metodologia de EMMA para avaliar a actividade de CES em amostras biológicas complexas

COVID-19 in Brazilian children and adolescents: findings from 21 hospitals / COVID-19 em crianças e adolescentes brasileiros: registros de 21 hospitais

Introdução: Crianças e adolescentes com Covid-19 apresentam menor mortalidade e sintomas menos intensos quando comparados aos adultos. Os estudos no Brasil baseiam-se apenas no sistema de notificação compulsória. Objetivo: Analisar as características clínicas, laboratoriais, radiológicas e desfechos de pacientes hospitalizados com menos de 20 anos de idade com Covid-19. Métodos: Série de casos de pacientes internados com Covid-19, confirmado, com idade inferior a 20 anos, obtida em estudo de coorte em 21 hospitais de cinco estados brasileiros. Resultados: Dos 36 pacientes, 20 (55,5%) eram adolescentes, 20 (55,5%) eram do sexo masculino, 18 (50,0%) apresentavam comorbidades, 2 estavam grávidas; e em 7 (19,4%) os sintomas iniciais ocorreram durante a internação por outras causas, dos quais 3 foram possivelmente infectados no hospital. Febre (61,1%), dispneia (33,3%) e sintomas neurológicos (33,0%) foram as queixas mais comuns. A proteína C reativa estava acima de 50mg / L em 16,7% e o dímero-D estava acima do limite de referência em 22,2%. Radiografias de tórax foram realizadas em 20 (55,5%) pacientes, 9 apresentavam anormalidades; e tomografias computadorizadas de tórax em 5. O tempo de internação variou de 1-40 dias (mediana 5 [intervalo interquartil 3-10]), 16 (44,4%) necessitaram de cuidados intensivos, 6 (16,7%) necessitaram de ventilação mecânica e um paciente (2,8%) faleceu. Conclusão: Em uma amostra de pacientes menores de 20 anos, procedentes de hospitais de 5 estados do Brasil, as comorbidades foram frequentes e os sintomas mais comuns foram febre, dispneia e sintomas neurológicos. Quarenta e quatro por cento dos pacientes necessitaram de cuidados intensivos, mostrando que na amostra avaliada a doença não era tão leve quanto o esperado, e um paciente morreu. 

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score

Abstract Background The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. Methods This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. Results From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641–0.944) and 0.704 (95% IC: 0.617–0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). Conclusions The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians

ABSTRACT: Objectives: To analyze the clinical characteristics and outcomes of admitted patients with the hospital- versus community-manifested COVID-19 and to evaluate the risk factors related to mortality in the first population. Methods: This retrospective cohort included consecutive adult patients with COVID-19, hospitalized between March and September 2020. The demographic data, clinical characteristics, and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. Results: Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while admitted for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs 10.8%) and alcoholism (8.8% vs 2.8%) than patients with community-manifested COVID-19 and also had a higher rate of intensive care unit requirement (45.1% vs 35.2%), sepsis (23.8% vs 14.5%), and death (35.8% vs 22.5%) (P <0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. Conclusion: Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested COVID-19 disease

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients

Abstract Background Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. Methods This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results The median age of the model-derivation cohort was 59 (IQR 47–70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918–0.939) and validation (temporal AUROC 0.927, 95% CI 0.911–0.941; geographic AUROC 0.819, 95% CI 0.792–0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). Conclusions The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation