First year of COVID-19 in Brazil: Factors associated with the spread of COVID-19 in small and large cities.

AIM: To test the association between sociodemographic and social characteristics with COVID-19 cases and deaths in small and large Brazilian cities. METHODS: This ecological study included COVID-19 data available in State Health Secretaries (managed by brasil.io API) and three national databases (IBGE, DATASUS and Embrapa). Temporal spread of COVID-19 in Brazil during the first year considered as outcome: a) days until 1st case in each city since 1st in the country; b) days until 1,000 cases/100,000 inhabitants since 1st case in each city; c) days until 1st death until 50 deaths/100,000 inhabitants. Covariates included geographic region, city social and environmental characteristics, housing conditions, job characteristics, socioeconomic and inequalities characteristics, and health services and coverage. The analysis were stratified by city size into small (<100,000 inhabitants) and large cities (≥100,00 inhabitants). Multiple linear regressions were performed to test associations of all covariates to adjust to potential confounders. RESULTS: In small cities, the first cases were reported after 82.2 days and 1,000 cases/100,000 were reported after 117.8 days, whereas in large cities these milestones were reported after 32.1 and 127.7 days, respectively. For first death, small and large cities took 121.6 and 36.0 days, respectively. However, small cities were associated with more vulnerability factors to first case arrival in 1,000 cases/100,000 inhabitants, first death and 50 deaths/100,000 inhabitants. North and Northeast regions positively associated with faster COVID-19 incidence, whereas South and Southeast were least. CONCLUSION: Social and built environment characteristics and inequalities were associated with COVID-19 cases spread and mortality incidence in Brazilian cities.

Fever as a Predictor of COVID-19 Outcomes in Hospitalized Patients.

INTRODUCTION: With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. OBJECTIVE: To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. METHODOLOGY: This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1] The study evaluated [LG2] the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). RESULTS: Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. CONCLUSION: Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability. / Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade.

BACKGROUND: Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability Association of ischemic heart disease (adjusted for traditional risk factors and socioeconomics variables) and income level (A), and walkability z-score (B), and association of walkability z-score and income level (C). BACKGROUND: Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. OBJECTIVES: To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. METHODS: This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. RESULTS: From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = -0.3%). CONCLUSIONS: Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Association between inpatient glycemic variability and COVID-19 mortality: a prospective study.

BACKGROUND: This study aimed to determine the association between glycemic variability (GV) and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We prospectively analyzed data from inpatients (> 18 years old) with RT-PCR confirmed COVID-19 admitted between March 2020 and July 2021. All patients were hospitalized for more than 48 h and had at least six point-of-care capillary glucose tests obtained three times daily in the pre-prandial period during hospitalization. GV was measured using the glucose standard deviation (SD) and coefficient of variation (CV). ROC curve was adjusted to determine the SD and CV cutoff values associated with mortality (44.7 mg/dL and 27.5%, respectively); values above these were considered indicative of high GV. Logistic regression models were fitted to explore the association between GV and mortality in patients with and without diabetes. RESULTS: A total of 628 patients were stratified into SD < 44.7 mg/dL (n = 357) versus ≥ 44.7 mg/dL (n = 271) and CV < 27.5% (n = 318) versus ≥ 27.5% (n = 310) groups. After controlling for age, sex, presence of diabetes mellitus (DM) and cardiovascular disease, we found a significant association between high GV and mortality (odds ratio 2.99 [1.88-4.77] for SD and 2.43 [1.54-3.85] for CV; p values < 0.001). The mortality rate was higher with SD ≥ 44.7 mg/dL and CV ≥ 27.5% compared to that with SD < 44.7 mg/dL and CV < 27.5%, regardless of DM (p < 0.001 for all). CONCLUSION: High glycemic variability was independently associated with mortality in patients with and without DM, who were hospitalized with COVID-19.

A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

Tricuspid Regurgitation and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis. / Insuficiência Tricúspide e Mortalidade em Pacientes Submetidos à Troca da Valva Aórtica Transcateter: Uma Revisão Sistemática e Metanálise.

BACKGROUND: The extent of cardiac damage associated with aortic stenosis has important prognostic implications after transcatheter aortic valve replacement (TAVR). However, the role of tricuspid regurgitation (TR) in this clinical setting is still unclear. OBJECTIVES: To explore the association between TR and mortality in patients undergoing TAVR and assess changes in TR severity post TAVR and its relationship with short and mid-term mortality. METHODS: Relevant databases were searched for articles published from inception until August 2020. Out of 414 screened studies, we selected 24 that reported the degree of TR pre or post TAVR. The primary outcome was all-cause mortality, and random effects meta-analysis models were conducted (at a significance level of 5%). RESULTS: Seventeen studies reported associations between pre-TAVR TR and all-cause mortality (> 45,000 participants) and thirteen accessed TR severity post TAVR (709 participants). Moderate/severe baseline TR was associated to higher all-cause mortality both at 30 days (HR 1.65; 95% CI, 1.20-2.29) and 1.2 years (HR 1.56; 95% CI, 1.31-1.84). After TAVR, 43% of patients presented a decrease of at least one grade in TR (30 days, 95% CI, 30-56%), sustained at 12.5 months in 44% of participants (95% CI, 35-52%). Persistence of significant TR was associated with a two-fold increase in all-cause mortality (HR 2.12; 95% CI, 1.53-2.92). CONCLUSIONS: Significant TR pre TAVR is associated with higher mortality. Although TR severity may improve, the persistence of significant TR post TAVR is strongly associated with increased mortality. Our findings highlight the importance of a detailed assessment of TR pre and post TAVR and might help identify patients who may benefit from more careful surveillance in this scenario.

FUNDAMENTO: A extensão do dano cardíaco associada à estenose aórtica tem importantes implicações prognósticas após a substituição da valva aórtica transcateter (TAVR). Contudo, ainda não está claro qual é o papel da insuficiência tricúspide (IT) nesse cenário clínico. OBJETIVOS: Explorar a associação entre IT e mortalidade em pacientes submetidos a TAVR e avaliar as alterações na gravidade da IT após a TAVR e sua relação com mortalidade de curto e médio prazo. MÉTODOS: Foram feitas pesquisas em bases de dados relevantes de artigos publicados do início até agosto de 2020. Dos 414 estudos triados, selecionamos 24 que relataram o grau de IT pré- ou pós-TAVR. O desfecho primário foi mortalidade por todas as causas, e foram conduzidos modelos de metanálise de efeitos aleatórios (a um nível de significância de 5%). RESULTADOS: Dezessete estudos relataram associações entre IT pré-TAVR e mortalidade por todas as causas (> 45.000 participantes), e 13 avaliaram a gravidade da IT pós-TAVR (709 participantes). A IT basal moderada/grave foi associada a maior mortalidade por todas as causas em 30 dias [razão de risco (RR) 1,65; intervalo de confiança (IC) 95% 1,20-2,29] e 1,2 ano (RR 1,56; IC95% 1,31-1,84). Após a TAVR, 43% dos pacientes apresentaram redução de pelo menos um grau na IT (30 dias, IC95% 30-56%), que se sustentou em 12,5 meses em 44% dos participantes (IC95% 35-52%).A persistência de IT significativa foi associada a um aumento de duas vezes na mortalidade por todas as causas (RR 2,12; IC95% 1,53-2,92). CONCLUSÕES: A IT significativa pré-TAVR está associada a maior mortalidade. Ainda que a gravidade da IT possa melhorar, a persistência de IT significativa após a TAVR está fortemente associada ao aumento da mortalidade. Nossos achados destacam a importância de uma avaliação detalhada da IT pré- e pós-TAVR e podem ajudar a identificar pacientes que possam se beneficiar de uma vigilância mais cuidadosa nesse cenário.

Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of South Brazil: Have they changed through the first year of the pandemic?

The Coronavirus Disease 2019 (COVID-19) pandemic posed various challenges to the healthcare system and disease management. This study aimed to describe changes in the clinical characteristics and outcomes of hospitalized patients during the first year of the COVID-19 pandemic in a city in southern Brazil. This prospective study was carried out in two tertiary care private hospitals in Curitiba. A total of 1151 patients hospitalized between March 2020 and March 2021 were included. We identified three epidemiological critical periods of the pandemic and compared patients' characteristics and the frequencies of oral intubation, intensive care unit (ICU) admission and mortality. Continuous variables were analyzed by variance analysis model (ANOVA) or the Kruskal-Wallis nonparametric test and categorical variables by the chi-square or Fisher's exact test. Models for univariate and multivariate logistic regression analysis were adjusted to identify the factors associated with mortality. All p-values were two-tailed and p<0.05 was considered statistically significant. The average age of the patients was 58 years and 60.9% (n = 701) were males. The most prevalent comorbidities were systemic arterial hypertension, diabetes and obesity. There were no significant variations in the demographic characteristics and previous comorbidities of the patients for the different periods of analysis. Mortality was positively associated with the age ≥65 years and the presence of one or more cardiometabolic comorbidities (p<0.001). March 2021 was the most important critical period of the pandemic since there were higher frequencies of patients admitted later in the course of the disease, with desaturation and more symptoms at hospital admission (p<0.001). There was also an increase in the duration of hospital stay (p<0.001) and the frequencies of all critical outcomes for this period: oral intubation (p<0.001), ICU admission (p = 0.606) and mortality (p = 0.001). Our key findings revealed that, although there were no statistically significant differences between the subgroups of hospitalized patients over time in terms of demographic characteristics and comorbidities, the course of COVID-19 was significantly more severe for patients admitted to the hospital at the end of the first year of the pandemic in Brazil.

Longitudinal Relationship Between Handgrip Strength and Cognitive Function in a European Multicentric Population Older Than 50 Years.

OBJECTIVE: The aim of this study was to analyze the bidirectional association between handgrip strength (HGS) and cognitive performance in different cognitive functions in a European population and to evaluate the predictive validity of HGS for the risk of future cognitive impairment in aging individuals. METHODS: This was a prospective cohort study conducted using data on individuals over 50 years of age from the Survey of Health, Aging and Retirement in Europe (SHARE). HGS measures and scores in numeracy, recall, and verbal fluency were repeated and analyzed biannually for 4 years and were used in generalized estimating equations to test the bidirectional association, categorized by sex. RESULTS: Of the 8236 individuals included, 55.73% were women with a mean age of 67.55 (standard deviation [SD] = 8.4) years and 44.27% were men with a mean age of 68.42 (SD = 7.7) years. HGS predicted cognitive decline in both sexes, except for numeracy in men, even after adjustments. The strongest association with HGS in women was in verbal fluency (ß = .094; 95% CI = 0.039 to 0.151), whereas the strongest association with HGS in men was in delayed verbal recall (ß = .095; 95% CI = 0.039 to 0.151). Conversely, the greatest cognitive predictor of HGS decline was verbal fluency in men (ß = .796; 95% CI = 0.464 to 1.128), and in women (ß = .801; 95% CI= 0.567 to 1.109). CONCLUSION: There is a significant and bidirectional association between HGS and different cognitive functions in a European multicentric population. This bidirectional association differed between sexes. IMPACT: Both men and women who presented with cognitive decline also showed early changes in their HGS measures, and vice versa, but there still were differences between the sexes. These findings reinforce that HGS may be a simple and inexpensive method to identify early signs of cognitive decline, and that studies and rehabilitation strategies should be more sex specific.

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis.

Backgroud: Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS. Methods: We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality. Results: Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low. Conclusions: These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Aging and the COVID-19 pandemic: The inter-related roles of biology, physical wellbeing, social norms and global health systems.

The coronavirus disease 2019 (COVID-19) pandemic has had a devastating and disproportionate impact on the elderly population. As the virus has swept through the world, already vulnerable elderly populations worldwide have faced a far greater burden of deaths and severe disease, crippling isolation, widespread societal stigma, and wide-ranging practical difficulties in maintaining access to basic health care and social services - all of which have had significant detrimental effects on their mental and physical wellbeing. In this paper, we present an overview of aging and COVID-19 from the interrelated perspectives of underlying biological mechanisms, physical manifestations, societal aspects, and health services related to the excess risk observed among the elderly population. We conclude that to tackle future pandemics in an efficient manner, it is essential to reform national health systems and response strategies from an age perspective. As the global population continues to age, elderly-focused health services should be integrated into the global health systems and global strategies, especially in low- and middle-income countries with historically underfunded public health infrastructure and insufficient gerontological care.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

Cognitive Performance and Diabetic Retinopathy: What Your Eyes Can Reveal About Your Brain.

BACKGROUND: Diabetic retinopathy (DR) is a chronic diabetes complication. People with Type 2 Diabetes Mellitus (T2DM) have two times the risk for dementia, suggesting it is a new chronic diabetes complication. OBJECTIVE: Evaluate the association of DR with cognitive performance in a T2DM population. METHODS: Cross-sectional study with 400 T2DM adults from whom socio-demographic, clinical, laboratory data were collected, and screening test for depression symptoms (Patient Health Questionaire- 9 (PHQ-9)), Mini-Mental State Examination (MMSE), Semantic Verbal Fluency Test, Trail Making Test A and B, Word Memory test were performed. All cognitive test scores were converted into Global Cognition z-Score (GCS(z)). The association between GCS(z) < 0 with DR was performed using a multivariate binary logistic regression model adjusted for age ≥ 65 years, school years ≤ 6 years, DM duration ≥ 10 years, depression symptoms score > 9 at PHQ-9, arterial hypertension, physical activity, diabetic retinopathy, macular edema, and cardiovascular disease. RESULTS: After exclusions, the 251 eligible patients were 56.6% female, with a mean age of 61.1 (±9.8) years, DM duration of 12.6 (±8.9) years, and 7.6 (±4.2) years of school education. DR prevalence was 46.5%. Multivariate Logistic Regression Model showed an association between DR and GCS(z) < 0, with odds ratio (CI95%) of 2.50 (1.18-5.34), adjusted for age, low education level, arterial hypertension and depression symptoms (OD and CI95% respectively: 5.46(2.42-12.34); 12.19 (5.62-26.46); 2.55 (0.88-7.39); 3.53 (1.55-8.07)). CONCLUSION: In this T2DM population, having DR increased the chance for worse cognitive performance even when adjusted for age, low education level, presence of arterial hypertension, and depression symptoms.

Associação de Nível de Renda e Doença Isquêmica do Coração: Papel Potencial da Caminhabilidade / Association of Income Level and Ischemic Heart Disease: Potential Role of Walkability

Resumo Fundamento O nível socioeconômico tem sido associado à doença isquêmica do coração (DIC). Bairros de alta renda podem expor os indivíduos a um ambiente construído que promova caminhadas para atividades diárias (caminhabilidade). Faltam dados sobre a associação entre renda e DIC em países de renda média. Também é incerto se a caminhabilidade medeia essa associação. Objetivos Investigar se a renda está associada à DIC em um país de renda média e se a caminhabilidade dos bairros medeia a associação entre renda e DIC. Métodos O presente estudo transversal avaliou 44.589 pacientes encaminhados para imagem de perfusão miocárdica (SPECT-MPI). A renda e a caminhabilidade foram derivadas do setor censitário residencial dos participantes. A pontuação quantitativa da caminhabilidade combinou as seguintes 4 variáveis: conectividade viária, densidade residencial, densidade comercial e uso misto do solo. A DIC foi definida pela presença de perfusão miocárdica anormal durante um estudo SPECT-MPI. Utilizamos modelos ajustados com efeitos mistos para avaliar a associação entre nível de renda e DIC e realizamos uma análise de mediação para medir o percentual da associação entre renda e DIC mediada pela caminhabilidade. Consideramos valores de p abaixo de 0,01 como estatisticamente significativos. Resultados Dos 26.415 participantes, aqueles que residiam no setor censitário do tercil de menor renda eram mais fisicamente inativos (79,1% versus 75,8% versus 72,7%) quando comparados aos setores censitários do tercil de maior renda (p < 0,001). A renda foi associada à DIC (odds ratio: 0,91 [intervalo de confiança de 95%: 0,87 a 0,96] para cada aumento de 1000,00 dólares internacionais na renda), para homens e mulheres igualmente (p para interação = 0,47). Os setores censitários com maior renda estiveram associados a uma melhor caminhabilidade (p < 0,001); no entanto, a caminhabilidade não mediou a associação entre renda e DIC (porcentagem mediada = −0,3%). Conclusões A renda foi independentemente associada a maior prevalência de DIC em um país de renda média, independentemente de gênero. Embora a caminhabilidade tenha sido associada à renda do setor censitário, ela não mediou a associação entre renda e DIC.

Abstract Background Socioeconomic status has been linked to ischemic heart disease (IHD). High-income neighborhoods may expose individuals to a walking-promoting built environment for daily activities (walkability). Data from the association between income and IHD is lacking in middle-income countries. It is also uncertain whether walkability mediates this association. Objectives To investigate whether income is associated with IHD in a middle-income country and whether neighborhood walkability mediates the income-IHD association. Methods This cross-sectional study evaluated 44,589 patients referred for myocardial perfusion imaging (SPECT-MPI). Income and walkability were derived from participants' residential census tract. Walkability quantitative score combined 4 variables: street connectivity, residential density, commercial density, and mixed land use. IHD was defined by abnormal myocardial perfusion during a SPECT-MPI study. We used adjusted mixed effects models to evaluate the association between income level and IHD, and we performed a mediation analysis to measure the percentage of the income-IHD association mediated by walkability. We considered p values below 0.01 as statistically significant. Results From 26,415 participants, those living in the lowest-income tertile census tract were more physically inactive (79.1% versus 75.8% versus 72.7%) when compared to higher-income tertile census tracts (p < 0.001). Income was associated with IHD (odds ratio: 0.91 [95% confidence interval: 0.87 to 0.96] for each 1,000.00 international dollars increase in income) for both men and women equally (p for interaction = 0.47). Census tracts with a higher income were associated with better walkability (p < 0.001); however, walkability did not mediate the income-IHD association (percent mediated = −0.3%). Conclusions Income was independently associated with higher prevalence of IHD in a middle-income country irrespective of gender. Although walkability was associated with census tract income, it did not mediate the income-IHD association.

Insuficiência Tricúspide e Mortalidade em Pacientes Submetidos à Troca da Valva Aórtica Transcateter: Uma Revisão Sistemática e Metanálise / Tricuspid Regurgitation and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Resumo Fundamento A extensão do dano cardíaco associada à estenose aórtica tem importantes implicações prognósticas após a substituição da valva aórtica transcateter (TAVR). Contudo, ainda não está claro qual é o papel da insuficiência tricúspide (IT) nesse cenário clínico. Objetivos Explorar a associação entre IT e mortalidade em pacientes submetidos a TAVR e avaliar as alterações na gravidade da IT após a TAVR e sua relação com mortalidade de curto e médio prazo. Métodos Foram feitas pesquisas em bases de dados relevantes de artigos publicados do início até agosto de 2020. Dos 414 estudos triados, selecionamos 24 que relataram o grau de IT pré- ou pós-TAVR. O desfecho primário foi mortalidade por todas as causas, e foram conduzidos modelos de metanálise de efeitos aleatórios (a um nível de significância de 5%). Resultados Dezessete estudos relataram associações entre IT pré-TAVR e mortalidade por todas as causas (> 45.000 participantes), e 13 avaliaram a gravidade da IT pós-TAVR (709 participantes). A IT basal moderada/grave foi associada a maior mortalidade por todas as causas em 30 dias [razão de risco (RR) 1,65; intervalo de confiança (IC) 95% 1,20-2,29] e 1,2 ano (RR 1,56; IC95% 1,31-1,84). Após a TAVR, 43% dos pacientes apresentaram redução de pelo menos um grau na IT (30 dias, IC95% 30-56%), que se sustentou em 12,5 meses em 44% dos participantes (IC95% 35-52%).A persistência de IT significativa foi associada a um aumento de duas vezes na mortalidade por todas as causas (RR 2,12; IC95% 1,53-2,92). Conclusões A IT significativa pré-TAVR está associada a maior mortalidade. Ainda que a gravidade da IT possa melhorar, a persistência de IT significativa após a TAVR está fortemente associada ao aumento da mortalidade. Nossos achados destacam a importância de uma avaliação detalhada da IT pré- e pós-TAVR e podem ajudar a identificar pacientes que possam se beneficiar de uma vigilância mais cuidadosa nesse cenário.

Abstract Background The extent of cardiac damage associated with aortic stenosis has important prognostic implications after transcatheter aortic valve replacement (TAVR). However, the role of tricuspid regurgitation (TR) in this clinical setting is still unclear. Objectives To explore the association between TR and mortality in patients undergoing TAVR and assess changes in TR severity post TAVR and its relationship with short and mid-term mortality. Methods Relevant databases were searched for articles published from inception until August 2020. Out of 414 screened studies, we selected 24 that reported the degree of TR pre or post TAVR. The primary outcome was all-cause mortality, and random effects meta-analysis models were conducted (at a significance level of 5%). Results Seventeen studies reported associations between pre-TAVR TR and all-cause mortality (> 45,000 participants) and thirteen accessed TR severity post TAVR (709 participants). Moderate/severe baseline TR was associated to higher all-cause mortality both at 30 days (HR 1.65; 95% CI, 1.20-2.29) and 1.2 years (HR 1.56; 95% CI, 1.31-1.84). After TAVR, 43% of patients presented a decrease of at least one grade in TR (30 days, 95% CI, 30-56%), sustained at 12.5 months in 44% of participants (95% CI, 35-52%). Persistence of significant TR was associated with a two-fold increase in all-cause mortality (HR 2.12; 95% CI, 1.53-2.92). Conclusions Significant TR pre TAVR is associated with higher mortality. Although TR severity may improve, the persistence of significant TR post TAVR is strongly associated with increased mortality. Our findings highlight the importance of a detailed assessment of TR pre and post TAVR and might help identify patients who may benefit from more careful surveillance in this scenario.

Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.

The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease's mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1ß, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.

Risk factors for cognitive decline in type 2 diabetes mellitus patients in Brazil: a prospective observational study.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) patients are twice as likely to develop dementia. The study's goal was to evaluate cognitive performance and risk factors for cognitive decline in this population. METHODS: Prospective observational study was conducted with 400 T2DM adults, of whom, during routine baseline and follow-up appointments, had socio-demographic, clinical, and laboratory data collected, and underwent physical examination, screening for depression symptoms (Patient Health Questionaire-9-PHQ-9), and cognitive tests: Mini-Mental State Examination (MMSE), Semantic Verbal Fluency Test, Trail Making Test A/B, and Word Memory Tests. Each cognitive test score was converted to a z-score and its average resulted in a new variable called Global Cognitive z-Score [GCS(z)]. Averages of the cognitive test scores and GCS(z) at both moments were compared by the Student's T-Test for paired samples. Multivariate binary logistic regression models were built to assess the association of GCS(z) < zero with risk factors for cognitive decline at the baseline and follow-up. RESULTS: After exclusions, 251 patients were eligible, being 56.6% female, mean age of 61.1 (± 9.8) years, 12.6 (± 8.9) years of DM duration, and 7.6 (± 4.2) years of school education. Follow-up had 134 patients reevaluated and took place after a mean of 18.4(± 5.0) months. Eleven (14%) patients with a GCS(z) ≥ 0 at baseline turned into a GCS(z) < 0 at follow-up. There were no significant differences between the means of cognitive test scores and GCS(z) at the two evaluation moments. At the baseline, the multivariate logistic regression model identified five risk factors associated with GCS(z) < zero: age ≥ 65 years, schooling ≤ 6 years, arterial hypertension, depression symptoms, and diabetic retinopathy (DR), with odds ratio (OR) and 95% confidence interval (CI95%) respectively: 5.46 (2.42-12.34); 12.19 (5.62-26.46); 2.55 (0.88-7.39); 3.53 (1.55-8.07) e 2.50 (1.18-5.34). At follow-up, the risk factors for GCS(z) < zero were: schooling ≤ 6 years, DM duration ≥ 10 years, depression symptoms, arterial hypertension, and cardiovascular disease (CVD), OR and CI95% respectively: 10.15 (3.68-28.01); 2.68 (0.96-7.48); 4.92 (1.77-13.70); 7.21 (1.38-35.71) e 5.76 (1.93-17.18). CONCLUSIONS: Based on our results, cognitive evaluation and follow-up should be incorporated on the routine of T2DM patients, especially for those with advanced age, low education level, prolonged DM duration, arterial hypertension, depression symptoms, CVD, and DR.

Achievement of LDL-Cholesterol Goals after Acute Myocardial Infarction: Real-World Data from the City of Curitiba Public Health System. / Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba.

BACKGROUND: Reduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries. OBJECTIVE: To evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI). METHODS: This retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05. RESULTS: Of 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70-99, 50-69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases. CONCLUSION: In the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.

FUNDAMENTO: A redução dos níveis de colesterol LDL é a pedra angular na redução de risco, mas muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas, mesmo em países de alta renda. OBJETIVO: Avaliar se os pacientes atendidos na rede pública de saúde da cidade de Curitiba estão atingindo as metas de colesterol LDL após infarto agudo do miocárdio (IAM). MÉTODOS: Esta coorte retrospectiva explorou os dados de pacientes internados com IAM entre 2008 e 2015 em hospitais públicos da cidade de Curitiba. Para avaliar o atingimento da meta de colesterol LDL, utilizamos o último valor registrado no banco de dados para cada paciente até o ano de 2016. Para aqueles que tinham pelo menos um valor de colesterol LDL registrado no ano anterior ao IAM, calculou-se o percentual de redução. O nível de significância adotado para a análise estatística foi p<0,05. RESULTADOS: Dos 7.066 pacientes internados por IAM, 1.451 foram acompanhados em ambiente ambulatorial e tiveram pelo menos uma avaliação de colesterol LDL. A média de idade foi 60,8±11,4 anos e 35,8%, 35,2%, 21,5% e 7,4% dos pacientes apresentavam níveis de colesterol LDL≥100, 70­99, 50­69 e <50 mg/dL, respectivamente. Destes, 377 pacientes também tiveram pelo menos uma avaliação de colesterol LDL antes do IAM. As concentrações médias de colesterol LDL foram 128,0 e 92,2 mg/dL antes e após o IAM, com redução média de 24,3% (35,7 mg/dL). Os níveis de colesterol LDL foram reduzidos em mais de 50% em apenas 18,3% dos casos. CONCLUSÃO: Na cidade de Curitiba, pacientes do sistema público de saúde, após infarto do miocárdio, não estão atingindo níveis adequados de colesterol LDL após IAM.

Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba / Achievement of LDL-Cholesterol Goals after Acute Myocardial Infarction: Real-World Data from the City of Curitiba Public Health System

Resumo Fundamento A redução dos níveis de colesterol LDL é a pedra angular na redução de risco, mas muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas, mesmo em países de alta renda. Objetivo Avaliar se os pacientes atendidos na rede pública de saúde da cidade de Curitiba estão atingindo as metas de colesterol LDL após infarto agudo do miocárdio (IAM). Métodos Esta coorte retrospectiva explorou os dados de pacientes internados com IAM entre 2008 e 2015 em hospitais públicos da cidade de Curitiba. Para avaliar o atingimento da meta de colesterol LDL, utilizamos o último valor registrado no banco de dados para cada paciente até o ano de 2016. Para aqueles que tinham pelo menos um valor de colesterol LDL registrado no ano anterior ao IAM, calculou-se o percentual de redução. O nível de significância adotado para a análise estatística foi p<0,05. Resultados Dos 7.066 pacientes internados por IAM, 1.451 foram acompanhados em ambiente ambulatorial e tiveram pelo menos uma avaliação de colesterol LDL. A média de idade foi 60,8±11,4 anos e 35,8%, 35,2%, 21,5% e 7,4% dos pacientes apresentavam níveis de colesterol LDL≥100, 70-99, 50-69 e <50 mg/dL, respectivamente. Destes, 377 pacientes também tiveram pelo menos uma avaliação de colesterol LDL antes do IAM. As concentrações médias de colesterol LDL foram 128,0 e 92,2 mg/dL antes e após o IAM, com redução média de 24,3% (35,7 mg/dL). Os níveis de colesterol LDL foram reduzidos em mais de 50% em apenas 18,3% dos casos. Conclusão Na cidade de Curitiba, pacientes do sistema público de saúde, após infarto do miocárdio, não estão atingindo níveis adequados de colesterol LDL após IAM.

Abstract Background Reduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries. Objective To evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI). Methods This retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05. Results Of 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70-99, 50-69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases. Conclusion In the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.

COVID-19 and Lung Mast Cells: The Kallikrein-Kinin Activation Pathway.

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.