Cardiovascular Mortality During the COVID-19 Pandemics in a Large Brazilian City: A Comprehensive Analysis.

Introduction: The impact of COVID-19 pandemics on cardiovascular diseases (CVD) may be caused by health system reorganization and/or collapse, or from changes in the behaviour of individuals. In Brazil, municipalities were empowered to define regulatory measures, potentially resulting in diverse effects on CVD morbimortality. Objective: To analyse the impact of COVID-19 pandemics on CVD outcomes in Belo Horizonte (BH), the sixth greater capital city in Brazil, including: mortality, mortality at home, hospitalizations, intensive care unit utilization, and in-hospital mortality; and the differential effect according to sex, age range, social vulnerability, and pandemic's phase. Methods: Ecological study analysing data from the Mortality and Hospital Information System of BH residents aged ≥30 years. CVD was defined as in Chapter IX from ICD-10. Social vulnerability was classified by a composite socioeconomic index as high, medium and low. The observed age-standardized rates for epidemiological weeks 10-48, 2020, were compared to the expected rates (mean of 2015-2019). Risk ratios (RiR) were analysed and 95% confidence intervals were calculated for all estimates. Population projected to 2020 for BH and its census tracts were used to calculate rates. Results: We found no changes in CVD mortality rates (RiR 1.01, 95%CI 0.96-1.06). However, CVD deaths occurred more at homes (RiR 1.32, 95%CI 1.20-1.46) than in hospitals (RiR 0.89, 95%CI 0.79-0.99), as a result of a substantial decline in hospitalization rates, even though proportional in-hospital deaths increased. The rise in home deaths was greater in older adults and in had an increasing gradient in those more socially vulnerable (RiR 1.45); for high (RiR 1.45), medium (RiR 1.32) and low vulnerability (RiR 1.21). Conclusion: The greater occurrence of CVD deaths at home, in parallel with lower hospitalization rates, suggests that CVD care was disrupted during the COVID-19 pandemics, which more adversely affected older and more socially vulnerable individuals, exacerbating health inequities in BH.

Higher mortality during COVID-19 pandemic in socially vulnerable areas in Belo Horizonte: implications for vaccination prioriti / Maior mortalidade durante a pandemia de COVID-19 em áreas socialmente vulneráveis em Belo Horizonte: implicações para priorização da vacinação

Objective: To assess mortality during the COVID-19 pandemic according to social vulnerability by areas of Belo Horizonte (BH), aiming at strategies for vaccination. Methods: Ecological study with mortality analysis, according to census tracts classified by the Health Vulnerability Index, a composite indicator that includes socioeconomic and sanitation variables. Deaths due to natural causes and COVID-19 were obtained from the "Mortality Information System", between the 10th and 43rd epidemiological weeks (EW) of 2020. Excess mortality was calculated by a time series model, considering observed deaths by EW, between 2015 and 2019, for census tracts. Mortality rates (MR) were calculated and age-standardized =using population estimates from 2010 census. Results: Excess mortality in BH was 16.1% (n =1524): 11.0%, 18.8% and 17.3% in the low, intermediate and high vulnerability areas, respectively. The differences between observed and expected age-standardized MR by natural causes were equal to 59/100,000 inhabitants in BH, increasing from 31 to 77 and 95/100,000 inhabitants, in the areas of low, intermediate and high vulnerability, respectively. There was an aging gradient in COVID-19 MR, ranging from 4 to 611/100,000 inhabitants among individuals of 20-39 years and 75+ years. The COVID-19 MR per 100,000 elderly (60+ years) was 292 in BH, increasing from 179 to 354 and 476, in the low, intermediate and high vulnerability areas, respectively. Conclusion: Inequalities in mortality, particularly among the elderly, combined with the limited supply of doses, demonstrate the importance of prioritizing socially vulnerable areas during vaccination against COVID-19.

Objetivo: Avaliar a mortalidade por áreas de Belo Horizonte (BH) durante a pandemia de COVID-19 conforme vulnerabilidade social, visando estratégia de vacinação. Métodos: Estudo ecológico com análise de mortalidade, segundo setores censitários classificados pelo Índice de Vulnerabilidade da Saúde, composto por indicadores de saneamento e socioeconômicos. Óbitos por causas naturais e COVID-19 foram obtidos do Sistema de Informação sobre Mortalidade, entre a 10ª e 43ª semana epidemiológica (SE) de 2020. Calculou-se o excesso de mortalidade por modelo de série temporal, considerando as mortes observadas por SE, entre 2015 e 2019, por setor censitário. Taxas de mortalidade (TM) foram calculadas e padronizadas por idade a partir de estimativas populacionais do IBGE. Resultados: Houve 16,1% (n=1524) de excesso de mortalidade em BH: 11,0%, 18,8% e 17,3% nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. As diferenças entre TM observadas e esperadas por causas naturais, padronizadas por idade, foi igual a 59/100.000 habitantes em BH, aumentando de 31 para 77 e 95/100.000, nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. Houve gradiente de aumento com a idade nas TM por COVID-19, variando de 4 a 611/100.000 habitantes entre as idades de 20-39 anos e 75+ anos. A TM por COVID-19 por 100.000 idosos (60+ anos) foi igual a 292, aumentando de 179 para 354 e 476, nos setores de baixa, média e elevada vulnerabilidade, respectivamente. Conclusão: Desigualdades na mortalidade, mesmo entre idosos, aliadas à baixa oferta de doses, demonstram importância de priorizar áreas socialmente vulneráveis durante a vacinação contra COVID-19.

The impact of COVID-19 pandemic course in the number and severity of hospitalizations for other natural causes in a large urban center in Brazil.

The COVID-19 pandemic may indirectly impact hospitalizations for other natural causes. Belo Horizonte is a city with 2.5 million inhabitants in Brazil, one of the most hardly-hit countries by the pandemic, where local authorities monitored hospitalizations daily to guide regulatory measures. In an ecological, time-series study, we investigated how the pandemic impacted the number and severity of public hospitalizations by other natural causes in the city, during 2020. We assessed the number and proportion of intensive care unit (ICU) admissions and in-hospital deaths for all-natural causes, COVID-19, non-COVID-19 natural causes, and four disease groups: infectious, respiratory, cardiovascular, and neoplasms. Observed data from epidemiological week (EW) 9 (first diagnosis of COVID-19) to EW 48, 2020, was compared to the mean for the same EW of 2015-2019 and differences were tested by Wilcoxon rank-sum test. The five-week moving averages of the studied variables in 2020 were compared to that of 2015-2019 to describe the influence of regulatory measures on the indicators. During the studied period, there was 54,722 hospitalizations by non-COVID-19 natural causes, representing a 28% decline compared to the previous five years (p<0.001). There was a concurrent significant increase in the proportion of ICU admissions and deaths. The greater reductions were simultaneous to the first social distancing decree or occurred in the peak of COVID-19 hospitalizations, suggesting different drivers. Hospitalizations by specific causes decreased significantly, with greater increase in ICU admissions and deaths for infectious, cardiovascular, and respiratory diseases than for neoplasms. While the first reduction may have resulted from avoidance of contact with healthcare facilities, the second reduction may represent competing causes for hospital beds with COVID-19 after reopening of activities. Health policies must include protocols to address hospitalizations by other causes during this or future pandemics, and a plan to face the rebound effect for elective deferred procedures.

Predicting reintubation, prolonged mechanical ventilation and death in post-coronary artery bypass graft surgery: a comparison between artificial neural networks and logistic regression models.

INTRODUCTION: In coronary artery bypass (CABG) surgery, the common complications are the need for reintubation, prolonged mechanical ventilation (PMV) and death. Thus, a reliable model for the prognostic evaluation of those particular outcomes is a worthwhile pursuit. The existence of such a system would lead to better resource planning, cost reductions and an increased ability to guide preventive strategies. The aim of this study was to compare different methods - logistic regression (LR) and artificial neural networks (ANNs) - in accomplishing this goal. MATERIAL AND METHODS: Subjects undergoing CABG (n = 1315) were divided into training (n = 1053) and validation (n = 262) groups. The set of independent variables consisted of age, gender, weight, height, body mass index, diabetes, creatinine level, cardiopulmonary bypass, presence of preserved ventricular function, moderate and severe ventricular dysfunction and total number of grafts. The PMV was also an input for the prediction of death. The ability of ANN to discriminate outcomes was assessed using receiver-operating characteristic (ROC) analysis and the results were compared using a multivariate LR. RESULTS: The ROC curve areas for LR and ANN models, respectively, were: for reintubation 0.62 (CI: 0.50-0.75) and 0.65 (CI: 0.53-0.77); for PMV 0.67 (CI: 0.57-0.78) and 0.72 (CI: 0.64-0.81); and for death 0.86 (CI: 0.79-0.93) and 0.85 (CI: 0.80-0.91). No differences were observed between models. CONCLUSIONS: The ANN has similar discriminating power in predicting reintubation, PMV and death outcomes. Thus, both models may be applicable as a predictor for these outcomes in subjects undergoing CABG.

Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase.

Alcohol's deleterious effects on memory are well known. Acute alcohol-induced memory loss is thought to occur via inhibition of NMDA receptor (NMDAR)-dependent long-term potentiation in the hippocampus. We reported previously that ethanol inhibition of NMDAR function and long-term potentiation is correlated with a reduction in the phosphorylation of Tyr(1472) on the NR2B subunit and ethanol's inhibition of the NMDAR field excitatory postsynaptic potential was attenuated by a broad spectrum tyrosine phosphatase inhibitor. These data suggested that ethanol's inhibitory effect may involve protein tyrosine phosphatases. Here we demonstrate that the loss of striatal-enriched protein tyrosine phosphatase (STEP) renders NMDAR function, phosphorylation, and long-term potentiation, as well as fear conditioning, less sensitive to ethanol inhibition. Moreover, the ethanol inhibition was "rescued" when the active STEP protein was reintroduced into the cells. Taken together, our data suggest that STEP contributes to ethanol inhibition of NMDAR function via dephosphorylation of tyrosine sites on NR2B receptors and lend support to the hypothesis that STEP may be required for ethanol's amnesic effects.

Sera of chagasic patients react with antigens from the tomato parasite Phytomonas serpens.

The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These flagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identified, resulting in 22 different putative proteins. The identified proteins were classified into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies.

Sera of Chagasic patients react with antigens from the tomato parasite Phytomonas serpens

The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These fagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identifed, resulting in 22 different putative proteins. The identifed proteins were classifed into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies.

Avaliação do nível da pressão positiva expiratória como recurso fisioterapêutico no pós-operatório de transplante cardíaco / Evaluation of the level of expiratory positive pressure as physiotherapeutical

Introdução: O transplante cardíaco (TC) é considerado última alternativa para pacientes com grande comprometimento por insuficiência cardíaca (IC) com classes funcionais III e IV. Pacientes submetidos a TC apresentam alterações nas respostas das variáveis cardiovasculares e ocorre elevação da sobrevida com qualidade de vida retornando à classe funcional I. A fisioterapia respiratória deverá ser realizada tão logo o paciente se apresente hemodinamicamente estável, a fim de evitar complicações pulmonares. Objetivo: Relatar um método utilizado para eleger valor adequado de PEEP (Positive End-Expiratory Pressure) em um caso de pós-operatório de TC. Materiais e Metodologia: Para escolha do nível de valor pressórico ideal, foram observadas as respostas hemodinâmicas e respiratórias em três níveis de valores pressóricos diferentes: 5 cmH2O, 10 cmH2O e 15 cmH2O, com duração de 2 a 3 minutos, tendo intervalo de 10 minutos entre elas. Conclusão: Deste modo observou-se que os valores pressóricos 5 cmH2O e 10 cmH2O apresentaram resposta positiva; enquanto que 15 cmH2O provocaram alterações hemodinâmicas e respiratórias como: redução da pressão arterial, aumento da pressão da artéria pulmonar e diminuição da saturação de oxigênio e aumento da freqüência respiratória.

Introduction: The Heart Transplant (HT) is considered the last alternative for patients with serious impairments due to Heart Failure (HF) with functional classes III and IV. The patients submitted to HT have modifications in the responses of cardiovascular variables and survival elevation, resulting in improvement of life quality and return of functional class I. The respiratory physiotherapy should be performed as soon as the patient is hemodynamically stable, in order to avoid lung complications . Objective: To report a method to find an adequate level of PEEP (Positive End-Expiratory Pressure) pressure value in a case of a postoperative HT. Materials and Methods: To select the ideal pressure value level, the hemodynamics and respiratory responses were observed in 3 different pressure value levels: 5 cmH2O, 10 cmH2O and 15 cmH2O, during 2 to 3 minutes with an interval of 10 minutes between them. Conclusions: Therefore, it was observed that the 5 cmH2O and 10 cmH2O pressure values have produced positive responses. However, the 15 cmH2O produced respiratory and hemodynamic alterations such as: decrease of blood pressure, increase of pulmonary artery pressure, decrease of O2 blood concentration and increase of respiratory rate.

Molecular basis for calcium signaling in hepatic stellate cells.

Progressive liver fibrosis (with the resultant cirrhosis) is the primary cause of chronic liver failure. Hepatic stellate cells (HSCs) are critically important mediators of liver fibrosis. In the healthy liver, HSCs are quiescent lipid-storing cells limited to the perisinusoidal endothelium. However, in the injured liver, HSCs undergo myofibroblastic transdifferentiation (activation), which is a critical step in the development of organ fibrosis. HSCs express P2Y receptors linking extracellular ATP to inositol (1,4,5)-trisphosphate-mediated cytosolic Ca(2+) signals. Here, we report that HSCs express only the type I inositol (1,4,5)-trisphosphate receptor and that the receptor shifts into the nucleus and cell extensions upon activation. These cell extensions, furthermore, express sufficient machinery to enable local application of ATP to evoke highly localized Ca(2+) signals that induce localized contractions. These autonomous units of subcellular signaling and response reveal a new level of subcellular organization, which, in turn, establishes a novel paradigm for the local control of fibrogenesis in the liver.

Relevância da análise do comportamento dinâmico não-linear (Teoria do Caos) como elemento prognóstico de morbidade e mortalidade em pacientes submetidos à cirurgia de revascularização miocárdica / The relevance of nonlinear dynamic analysis (Chaos Theory) to predict morbidity and mortality in patients undergoing surgical myocardial revascularization

Objetivo: Estudos recentes mostram que uma variabilidade da freqüência cardíaca baixa (VFC) é uma indicação clara de aumento no risco de arritmia ventricular grave e morte cardíaca súbita. No entanto, as técnicas tradicionais de análise de dados no domínio da freqüência e do tempo não são suficientes para caracterizar as dinâmicas complexas da geração dos batimentos cardíacos. Portanto, o objetivo do presente estudo foi avaliar a importância da análise dinâmica não-linear (Teoria do Caos), para prever a morbidade a mortalidade em um grupo de pacientes submetidos à cirurgia de revascularização miocárdica. Método: Foram incluídos no estudo 51 pacientes não-selecionados (média de idade de 60,4 ± 10,1 anos), cujo único critério de inclusão era presença de doença arterial coronariana com indicação para cirurgia eletiva. Comparou-se a ocorrência de eventos importantes durante a duração da permanência pós-cirúrgica. A Análise da Variabilidade da Freqüência Cardíaca no Domínio do Caos: Os dados eletrocardiográficos (1.000 intervalos RR) foram testados digitalmente(Polar Advanced S810) e transferidos para um microcomputador, para quantificar a dinâmica da FC no domínio do caos com as variáveis da Análise Destendenciada da Flutuação, Expoente de Lyapunov, Expoente de Hurst Autocorrelação e Dimensão Fractal. Resultados: Os pacientes com alterações simultâneas nas cinco variáveis não-lineares apresentaram morbidade e mortalidade significativamente maiores no período póscirúrgico(Relação de possibilidades 21,500; IC 95 2,533 a 182,47; Razão de Verossimilhança Positiva (RVP)= 9,200; valor de P = 0,0087) para morte versus zero para três eventos adversos, considerados como eventos neurológicos, complicações infecciosas ou renais e a presença de arritmias potencialmente letais. Conclusão:Pacientes com redução no comportamento caótico apresentaram morbidade e mortalidade mais significativasdo que seus pares. Acreditamos que esta pode ser uma nova abordagem como ferramenta de prognóstico na avaliação pré-cirúrgica de pacientes submetidos à cirurgia de revascularização miocárdica eletiva.

[Is it possible to identify dengue in children on the basis of Ministry of Health criteria for suspected dengue cases?]. / E possível identificar a dengue em crianças a partir do critério de caso suspeito preconizado pelo Ministério da Saúde?

OBJECTIVES: To identify clinical characteristics indicative of dengue and to evaluate the applicability to children of the Health Ministry criteria for suspected cases. METHODS: A cross-sectional study undertaken at the General Pediatrics Center of the Fundação Hospitalar de Minas Gerais. Children were enrolled if presenting acute febrile conditions with no definite etiology, lasting > 24 hours and < or = 7 days and if resident in the Metropolitan Region of Belo Horizonte. Clinical variables were investigated, specific tests were performed and aspartate-aminotransferase assayed, during a period considered both endemic and epidemic for the disease. The subset of children who did have dengue was compared with the subset of nonspecific acute febrile diseases. The Health Ministry criteria for suspected cases was evaluated. RESULTS: Dengue was diagnosed in 50.4% of the 117 children studied. There were no statistically significant associations between the disease and the majority of the symptoms analyzed. Only exanthema was more often associated with dengue (Prevalence Ratio = 1.49; 95% CI: 1.05-2.11). The criteria for suspected cases of dengue had a sensitivity of just 50.8% and a positive predictive value of 62.5%. These values were greater among schoolchildren and during the period of greater disease incidence. CONCLUSIONS: Dengue is common among febrile diseases of childhood, with prevalence that varies according to the epidemiological situation. The clinical status of children with dengue was very similar to that of children with other nonspecific diseases. The Health Ministry criteria for suspected cases was shown to be of little use, particularly with smaller children and during periods of reduced incidence.

É possível identificar a dengue em crianças a partir do critério de caso suspeito preconizado pelo Ministério da Saúde? / Is it possible to identify dengue in children on the basis of Ministry of Health criteria for suspected dengue cases?

OBJETIVOS: Identificar características clínicas indicativas de dengue e avaliar a aplicabilidade, na criança, do critério de caso suspeito do Ministério da Saúde. MÉTODOS: Estudo transversal, realizado no Centro Geral de Pediatria, Fundação Hospitalar de Minas Gerais. Foram incluídas crianças com doença febril aguda sem etiologia definida, com duração > 24 horas e < 7 dias, procedentes da Região Metropolitana de Belo Horizonte. Foram investigadas variáveis clínicas, realizados exames específicos e dosagem de aspartato-aminotransferase, em período considerado endêmico e epidêmico da doença. O grupo de crianças com dengue foi comparado com o grupo com doenças febris agudas inespecíficas. O critério de caso suspeito do Ministério da Saúde foi avaliado. RESULTADOS: O diagnóstico de dengue foi feito em 50,4 por cento das 117 crianças incluídas no estudo. Não houve associação estatisticamente significativa entre a doença e a maioria dos sintomas analisados. Somente o exantema associou-se mais à dengue (Razão de Prevalência = 1,49; IC a 95 por cento: 1,05-2,11). A sensibilidade do critério de caso suspeito de dengue foi de somente 50,8 por cento, e o valor preditivo positivo de 62,5 por cento. Esses valores foram maiores nos escolares e no período de maior incidência da doença. CONCLUSÕES: A dengue é freqüente entre as doenças febris na infância, com prevalência variando de acordo com a situação epidemiológica. A clínica das crianças com dengue foi muito semelhante à das crianças com outras doenças inespecíficas. O critério de caso suspeito do Ministério da Saúde mostrou-se de pouca utilidade, principalmente nas crianças menores e em períodos de menor incidência.

Endotoxin unmasks the role of gap junctions in the liver.

Gap junctions are thought to be necessary for proper tissue function. However, no clear hepatic phenotype has been described in patients lacking connexin 32 (Cx32), the principal gap junction in liver. To determine the physiological role of Cx32 in liver, we compared the response of wild type and Cx32-deficient mice to endotoxin, since this stress increases serum levels of hormones that bind to receptors that are asymmetrically distributed across the hepatic lobule. In hepatocyte couplets isolated from wild type mice, most hepatocytes could transfer microinjected dye to their neighbor even after treatment with endotoxin. Dye transfer was not observed in Cx32-deficient couplets. Treatment of hepatocyte couplets from wild type mice with vasopressin induced calcium (Ca(2+)) waves that crossed the couplets in a concentration-dependent fashion, but the delay in transmission was markedly prolonged at all concentrations in Cx32-deficient couplets. Expression of the vasopressin receptor and the inositol 1,4,5-trisphosphate receptor was not decreased by endotoxin or in Cx32-deficient couplets. Finally, endotoxin caused transient hypoglycemia and cholestasis in wild type animals, but hypoglycemia was slightly prolonged and cholestasis was much worse in Cx32-deficient mice treated with endotoxin. The hepatic response to endotoxin is markedly impaired in the absence of Cx32. Thus, an important role of gap junctions in the liver is to assure integrated and uniform tissue response in times of stress.