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.

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.

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.

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.

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.

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies. METHODS: Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients. RESULTS: Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza. CONCLUSION: Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.

Associação entre capacidade funcional e força de preensão manual em pessoas com diabetes mellitus / Association between functional capacity and handgrip strength in people with diabetes mellitus / Asociación entre la capacidad funcional y la fuerza de prensión manual en personas con diabetes mellitus

RESUMO Objetivo: investigar a associação entre força de preensão manual e capacidade funcional de pessoas com diabetes. Método: estudo observacional de corte transversal com 168 participantes atendidos num ambulatório de Curitiba, Brasil, em 2019. Coletaram-se dados clínicos, sociodemográficos, socioeconômicos e aplicados os protocolos: World Health Organization Disability Assessment Schedule; Timed Up and Go e dinamometria. Para a análise, foram ajustados modelos de regressão linear múltipla para as variáveis dependentes relativas à capacidade funcional. Resultados: observou-se incapacidade leve, mobilidade funcional limítrofe, e maior correlação entre a escala de mobilidade funcional e força de preensão manual (r=-0,384; p < 0,01). A força de preensão manual com outras covariáveis explicaram menos de 30% da variabilidade funcional. Conclusão: esses resultados contribuem para a resolutividade da prática clínica na medida em que evidenciam que a força muscular e a capacidade funcional devem ser consideradas na avaliação do paciente de forma combinada, tornando-a mais clara e abrangente.

ABSTRACT Objective: to investigate the association between handgrip strength and functional capacity in people with diabetes. Method: observational cross-sectional study with 168 participants seen at an outpatient clinic in Curitiba, Brazil, in 2019. Clinical, sociodemographic, and socioeconomic data were collected, and the following protocols were applied: World Health Organization Disability Assessment Schedule; Timed Up and Go; and dynamometry. For the analysis, multiple linear regression models were adjusted for the dependent variables related to functional capacity. Results: we observed mild disability, borderline functional mobility, and higher correlation between functional mobility scale and handgrip strength (r=-0.384; p < 0.01). Handgrip strength with other covariates explained less than 30% of the functional variability. Conclusion: these results contribute to the problem-solving of clinical practice in that they show that muscle strength and functional capacity should be considered in the evaluation of the patient in combination, making it clearer and more comprehensive.

RESUMEN Objetivo: investigar la asociación entre la fuerza de prensión manual y la capacidad funcional en personas con diabetes. Método: estudio observacional transversal con 168 participantes atendidos en una clínica ambulatoria en Curitiba, Brasil, en 2019. Se recogieron datos clínicos, sociodemográficos y socioeconómicos, y se aplicaron los siguientes protocolos: World Health Organization Disability Assessment Schedule; Timed Up and Go y dinamometría. Para el análisis, se ajustaron modelos de regresión lineal múltiple para las variables dependientes relacionadas con la capacidad funcional. Resultados: se observó una discapacidad leve, una movilidad funcional limítrofe y una mayor correlación entre la escala de movilidad funcional y la fuerza de prensión manual (r=-0,384; p < 0,01). La fuerza de prensión manual con otras covariables explicó menos del 30% de la variabilidad funcional. Conclusión: estos resultados contribuyen a la resolución de la práctica clínica, ya que muestran que la fuerza muscular y la capacidad funcional deben considerarse en la evaluación del paciente de forma combinada, haciéndola más clara y completa.

COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease. Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines. Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status. Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

Lung Neutrophilic Recruitment and IL-8/IL-17A Tissue Expression in COVID-19.

The new SARS-CoV-2 virus differs from the pandemic Influenza A virus H1N1 subtype (H1N1pmd09) how it induces a pro-inflammatory response in infected patients. This study aims to evaluate the involvement of SNPs and tissue expression of IL-17A and the neutrophils recruitment in post-mortem lung samples from patients who died of severe forms of COVID-19 comparing to those who died by H1N1pdm09. Twenty lung samples from patients SARS-CoV-2 infected (COVID-19 group) and 10 lung samples from adults who died from a severe respiratory H1N1pdm09 infection (H1N1 group) were tested. The tissue expression of IL-8/IL-17A was identified by immunohistochemistry, and hematoxylin and eosin (H&E) stain slides were used for neutrophil scoring. DNA was extracted from paraffin blocks, and genotyping was done in real time-PCR for two IL17A target polymorphisms. Tissue expression increasing of IL-8/IL-17A and a higher number of neutrophils were identified in samples from the H1N1 group compared to the COVID-19 group. The distribution of genotype frequencies in the IL17A gene was not statistically significant between groups. However, the G allele (GG and GA) of rs3819025 was correlated with higher tissue expression of IL-17A in the COVID-19 group. SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 infection since the IL-8/IL-17A tissue expression, and lung neutrophilic recruitment may be decreased. In SNP rs3819025 (G/A), the G allele may be considered a risk allele in the patients who died for COVID-19.

Active surveillance of carbapenem-resistant Gram-negative healthcare-associated infections in a low-middle-income country city.

BACKGROUND: Carbapenem-resistance in healthcare-associated infections (HCAIs) is of great concern, and it is urgent to improve surveillance. We aimed to describe and analyze HCAIs trends on Gram-negative antimicrobial susceptibility in a city from a developing country, following the implementation of an active surveillance program. METHODS: This is an aggregated study describing data from 24 hospitals with intensive care units, including a trend analysis by Joinpoint regression between January 2012 and December 2017. RESULTS: There were 23,578 pathogens in 39,832 HCAIs, from which 16,225 were Gram-negatives (68.8%). Carbapenem susceptibility was lowest in A. baumannii (15.4-25.9%), K. pneumoniae (51.0-55.9%), and P. aeruginosa (64.9-84.1%) and highest in E. coli (96.5-99.2%). Only K. pneumoniae showed a significant Joinpoint at 95% confidence interval: -10.71% (-18.02; -2.75) from 2012 to 2014, p=0.02, and 6.54% (-2.00; 15.83) from 2015 to 2017, p=0.12, which was most influenced by urinary tract infections: -9.98% (-16.02; -3.48) from 2012 to 2014, p=0.01, and 9.66% (-1.75; 22.39) from 2015 to 2017, p=0.09. CONCLUSION: Although we found a significant change toward an improvement in carbapenem susceptibility in K. pneumoniae, resistance is high for most pathogens. These data should encourage health institutions to improve their prevention and control strategies.

Hepatorenal index for grading liver steatosis with concomitant fibrosis.

INTRODUCTION: Ultrasonography is widely used as the first tool to evaluate fatty liver disease, and the hepatorenal index is a semi-quantitative method that improves its performance. Fibrosis can co-exist with steatosis or even replace it during disease progression. This study aimed to evaluate the influence of fibrosis on the measurement of steatosis using the hepatorenal index. MATERIALS AND METHODS: This cross-sectional study included 89 patients with nonalcoholic fatty liver disease and in whom liver fibrosis was determined by ultrasound elastography. The Pearson's correlation coefficient was used to compare between the results of the sonographic hepatorenal index and the quantification of steatosis using magnetic resonance spectroscopy as well the accuracy of detecting moderate to severe steatosis using sonography in two groups of patients: (A) without advanced fibrosis and (B) with advanced fibrosis. Advanced fibrosis was defined as a shear wave speed ≥ 1.78 m/s on ultrasound elastography. We calculated the area under the curve (AUC-ROC) to detect the ability of the hepatorenal index to differentiate light from moderate to severe steatosis in both groups. Moderate to severe steatosis was defined as a fat fraction > 15% on the magnetic resonance spectroscopy. The intra-observer variability was assessed using the Bland-Altman plot. RESULTS: Among patients, the mean age was 54.6 years and 59.6% were women, 50.6% had a body mass index ≥ 30 kg/m2, 29.2% had moderate to severe steatosis, and 27.2% had advanced fibrosis. There was a correlation between steatosis grading by ultrasonography and magnetic resonance in group A (0.73; P < 0.001), but not in Group B (0.33; P = 0.058). The AUC-ROC for detecting a steatosis fraction ≥ 15% was 0.90 and 0.74 in group A and group B, respectively. The intra-observer variability for the hepatorenal index measurements was not significant (-0.036; P = 0.242). CONCLUSION: The hepatorenal index is not appropriate for estimating steatosis in livers with advanced fibrosis.

Active surveillance of carbapenem-resistant Gram-negative healthcare-associated infections in a low-middle-income country city

ABSTRACT Background: Carbapenem-resistance in healthcare-associated infections (HCAIs) is of great concern, and it is urgent to improve surveillance. We aimed to describe and analyze HCAIs trends on Gram-negative antimicrobial susceptibility in a city from a developing country, following the implementation of an active surveillance program. Methods: This is an aggregated study describing data from 24 hospitals with intensive care units, including a trend analysis by Joinpoint regression between January 2012 and December 2017. Results: There were 23,578 pathogens in 39,832 HCAIs, from which 16,225 were Gram-negatives (68.8%). Carbapenem susceptibility was lowest in A. baumannii (15.4-25.9%), K. pneumoniae (51.0-55.9%), and P. aeruginosa (64.9-84.1%) and highest in E. coli (96.5-99.2%). Only K. pneumoniae showed a significant Joinpoint at 95% confidence interval: −10.71% (−18.02; −2.75) from 2012 to 2014, p = 0.02, and 6.54% (−2.00; 15.83) from 2015 to 2017, p = 0.12, which was most influenced by urinary tract infections: −9.98% (−16.02; −3.48) from 2012 to 2014, p = 0.01, and 9.66% (−1.75; 22.39) from 2015 to 2017, p = 0.09. Conclusion: Although we found a significant change toward an improvement in carbapenem susceptibility in K. pneumoniae, resistance is high for most pathogens. These data should encourage health institutions to improve their prevention and control strategies.