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The COVID-19 pandemic has caused delays in the diagnosis, treatment and follow-up of patients with malignant neoplasms (MN). To analyze the distribution pattern of MN cases in Brazil, we collected data in August 2022, provided by the Department of Informatics of the Brazilian Ministry of Health, from 2013 to 2021. The data were organized in Microsoft Excel, the analysis and presentation of the data were made using ggplot and Reshape packages, and temporal patterns and forecast models were obtained by ARIMA method together with aTSA. The results show that the COVID-19 pandemic did not directly impact the notifications of MN cases, but changed the profile of notifications, as in 2018 there was an increase in the diversity of notified neoplasms, and a change in the number of cases in 2019 and 2020. In addition, the distribution between the evaluations of neoplasms was not proportional, showing conversion in 12 (32.4%), decrease in 24 (64.9%) and increase in 1 neoplasm (2.7%). The findings help to understand the new behavior of notifications, demonstrating a pattern similar to the seasonal forecast model, with random or linear trending patterns. This distribution, with a seasonal pattern, shows variability in certain periods of the year, providing important information for early diagnosis and better planning. Data from this research reinforce the need for active screening methods and incentives for preliminary screening for better detection and management of this malignancy. (AU)

A pandemia de COVID-19 causou atrasos no diagnóstico, tratamento e acompanhamento de pacientes com neoplasias malignas (NM). Para analisar o padrão de distribuição dos casos de MN no Brasil, coletamos dados em agosto de 2022 disponibilizados pelo Departamento de Informática do Ministério da Saúde do Brasil de 2013 a 2021. Os dados foram organizados no Microsoft Excel, a análise e apresentação dos dados foram feitas usando os pacotes ggplot e Reshape, e os padrões temporais e modelos de previsão foram obtidos pelo método ARIMA junto com o aTSA. Os resultados mostram que a pandemia de COVID-19 não impactou diretamente nas notificações dos casos de NM, mas mudou o perfil das notificações, pois em 2018 houve aumento na diversidade de neoplasias notificadas, e mudança no número de casos em 2019 e 2020. Além disso, a distribuição entre as avaliações das neoplasias não foi proporcional, mostrando conversão em 12 (32,4%), diminuição em 24 (64,9%) e aumento em 1 neoplasia (2,7%). As descobertas ajudam a entender o novo comportamento das notificações demonstrando um padrão semelhante ao modelo de previsão sazonal, com padrões de tendência aleatórios ou lineares. Essa distribuição com padrão sazonal, apresenta variabilidade em determinados períodos do ano, fornecendo informações importantes para o diagnóstico precoce e melhor planejamento. Os dados desta pesquisa reforçam a necessidade de métodos de triagem ativa e incentivos à triagem preliminar para melhor detecção e manejo dessa malignidade. (AU)

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Obesity alters the capacity of effective immune responses in infections. To further address this phenomenon in the context of COVID-19, this study investigated how the immunophenotype of leukocytes was altered in individuals with obesity in severe COVID-19. This cross-sectional study enrolled 27 ICU COVID-19 patients (67% women, 56.33 ± 19.55 years) that were assigned to obese (BMI ≥ 30 kg/m2, n = 9) or non-obese (BMI < 30kg/m2, n = 18) groups. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples, and surface receptors' frequency and expression patterns were analyzed by flow cytometry. Clinical status and biochemical data were additionally evaluated. The frequency of monocytes was negatively correlated with BMI, while NK cells and HD neutrophils were positively associated (p < 0.05). Patients with obesity showed a significant reduction of monocytes, and these cells expressed high levels of PD-L1 (p < 0.05). A higher frequency of NK cells and increased expression of TREM-1+ on HD neutrophils were detected in obese patients (p < 0.05). The expression of receptors related to antigen-presentation, phagocytosis, chemotaxis, inflammation and suppression were strongly correlated with clinical markers only in obese patients (p < 0.05). Collectively, these outcomes revealed that obesity differentially affected, and largely depressed, innate immune response in severe COVID-19.

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The Apgar score is applied immediately after birth to clinically evaluate the newborn, at the first and fifth minutes of life. The Apgar score can help diagnose scenarios of neonatal anoxia or hypoxia. This is a retrospective, descriptive, and analytical study that used secondary data from DATASUS (Department of Informatics of the Unified Health System), from 1994 to 2018. The studied population includes all live births in Brazil during this period. The inclusion criteria were pregnant women over 15 years old, and the exclusion criteria were multiple pregnancies, pregnancies lasting less than 37 weeks, and newborns with congenital anomalies. These criteria were established to reduce potential confounding factors in the analysis that could lead to errors in interpretation of the results. The variables studied were place of delivery, type of delivery, and number of prenatal consultations. As results, having 7 or more prenatal consultations is a protective factor for alterations in the Apgar score, as well as cesarean delivery and hospital delivery. It was observed that pregnancy care, regarding the studied variables, influences the Apgar score. However, future studies in different populations are necessary to confirm these results.(AU)

O índice de Apgar é aplicado imediatamente após o nascimento, para avaliação clínica do recém-nascido, no primeiro e quinto minutos de vida. O índice de apgar é capaz de ajuda a diagnosticar cenários de anóxia ou hipóxia neonatal. Trata-se de um estudo retrospectivo, descritivo e analítico, que utilizou dados secundários do DATASUS (Departamento de Informática do Sistema Único de Saúde), de 1994 a 2018. A população estudada compreende todos os nascidos vivos no Brasil nesse período. Cujo critérios de inclusão foram: gestantes maiores de 15 anos e os critérios para a excluídas das gestantes, foram: gestações duplas, triplas e mais, gestações com menos de 37 semanas e recém-nascidos com anomalias congênitas, taís critérios foram estabelcidos afim de diminuir potenciais fatores de confusão a análise, que possam direcionar a discussão dos resultados ao erro de interpretação. As variáveis estudadas foram: local de parto, tipo de parto e número de consultas de pré-natal. Como resultados, possuir 7 ou mais consultas pré-natais, é um fator protetor para alterações no índice de Apgar, assim como parto cesáreo e parto hospitalar. Observou-se que os cuidados com a gravidez, no que diz respeito às variáveis estudadas, têm influência no escore de Apgar, entretanto futuros estudos em diferentes populações se torna necessário para confirmação desse resultado.(AU)

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Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, with or without diabetes mellitus (DM) from sites in Brazil and India. RNA sequencing (RNAseq) performed at baseline and during TB treatment. Publicly available baseline RNAseq data from South Africa and Romania reported by the TANDEM Consortium were also analyzed. Across the sites, differentially expressed genes varied for each condition (DM, TB, and TBDM) and no pattern classified any one group across all sites. A concise signature of TB disease was identified but this was expressed equally in TB and TBDM. Pathway enrichment analysis failed to distinguish TB from TBDM, although there was a trend for greater neutrophil and innate immune pathway activation in TBDM participants. Pathways associated with insulin resistance, metabolic dysfunction, diabetic complications, and chromosomal instability were positively correlated with glycohemoglobin. The immune response to pulmonary TB as reflected by whole blood gene expression is substantially similar with or without comorbid DM. Gene expression pathways associated with the microvascular and macrovascular complications of DM are upregulated during TB, supporting a syndemic interaction between these coprevalent diseases.

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SARS-CoV-2 has caused a high number of deaths in several countries. In Brazil, there were 37 million confirmed cases of COVID-19 and 700,000 deaths caused by the disease. The population size and heterogeneity of the Brazilian population should be considered in epidemiological surveillance due to the varied tropism of the virus. As such, municipalities and states must be factored in for their unique specificities, such as socioeconomic conditions and population distribution. Here, we investigate the spatiotemporal dispersion of emerging SARS-CoV-2 lineages and their dynamics in each microregion from Sergipe state, northeastern Brazil, in the first 3 years of the pandemic. We analyzed 586 genomes sequenced between March 2020 and November 2022 extracted from the GISAID database. Phylogenetic analyses were carried out for each data set to reconstruct evolutionary history. Finally, the existence of a correlation between the number of lineages and infection cases by SARS-CoV-2 was evaluated. Aracaju, the largest city in northeastern Brazil, had the highest number of samples sequenced. This represented 54.6% (320) of the genomes, and consequently, the largest number of lineages identified. Studies also analyzed the relationship between mean lineage distributions and mean monthly infections, daily cases, daily deaths, and hospitalizations of vaccinated and unvaccinated patients. For this, a correlation matrix was created. Results revealed that the increase in the average number of SARS-CoV-2 variants was related to the average number of SARS-CoV-2 cases in both unvaccinated and vaccinated individuals. Thus, our data indicate that it is necessary to maintain epidemiological surveillance, especially in capital cities, since they have a high rate of circulation of resident and non-resident inhabitants, which contributes to the dynamics of the virus.

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Objective: To assess the Simplified Acute Physiology Score 3 (SAPS3) prognostic score performance across different body mass index categories. Methods: A retrospective cohort study in a general ICU in Brazil. A secondary analysis of medical records was performed with clinical and epidemiological data. Patients were stratified according to their body mass index (BMI) category, and a binary logistic regression was then performed to identify factors independently associated with mortality. SAPS3 accuracy was determined using the area under the receiver operating characteristics curve and the Hosmer-Lemeshow test. A modified Kaplan-Meyer plot was employed to evaluate death probability according to BMI. ICU mortality was evaluated as the primary outcome. Results: A total of 2,179 patients (mean age of 67.9 years and female predominance (53.1%)) were enrolled. SAPS3 was found accurate in all groups except in the underweight (AUC: 0.694 95% CI 0.616-0.773; HL = 0.042). The patients in the underweight group tended to be older, have longer hospital stay, have worse functional status, and have a higher value on prognostic scores. After the adjustments, no statistically significant difference between the BMI groups was noted in relation to mortality, except for the low weight that presented a likelihood of death of 3.50 (95% CI, 1.43-8.58, p = 0.006). Conclusion: This research showed that SAPS3 had poor accuracy in predicting ICU mortality in underweight patients. This group was shown to be an independent risk factor for worse clinical outcomes.

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Visceral leishmaniasis (VL) is a systemic chronic and potentially fatal disease for humans. Mechanisms related to the dysregulation of the inflammatory response may be involved in both the pathogenesis and prognosis of VL. Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) is a receptor constitutively expressed on neutrophils and monocyte subsets. The protein serves to regulate and amplify inflammatory responses. This study aimed to evaluate the expression profile of TREM-1 on the surface of neutrophils from patients with VL at varying time points during leishmanicidal treatment. For this purpose, neutrophils were isolated from the peripheral blood of patients with VL at different stages of treatment, which include 0, 7, and 30 days after treatment. Surface TREM-1 expression was assessed by immunophenotyping neutrophil populations. In addition, the association of TREM-1 expression on the surface of neutrophils with clinical and laboratory parameters and serum levels of inflammatory mediators was also evaluated. Results demonstrate a lower surface expression of TREM-1 in VL patients in the absence of treatment. However, increased levels of TREM-1 expression were observed 7 and 30 days after the start of treatment, with levels similar to those of healthy controls. TREM-1 expression was directly correlated with lymphocyte and erythrocyte count and indirectly correlated with spleen and liver size. Furthermore, elevated levels of TREM-1 expression were also correlated with lower serum levels of interleukin (IL)-22. Taken together, these results suggest that infection by Leishmania infantum leads to depressed TREM-1 expression on the neutrophil surface and may contribute to the inflammatory imbalance that characterizes active VL disease.

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Homeostatic perturbation caused by infection fosters two major defense strategies, resistance and tolerance, which promote the host's survival. Resistance relates to the ability of the host to restrict the pathogen load. Tolerance minimizes collateral tissue damage without directly affecting pathogen fitness. These concepts have been explored mechanistically in murine models of malaria but only superficially in human disease. Indeed, individuals infected with Plasmodium vivax may present with asymptomatic malaria, only mild symptoms, or be severely ill. We and others have reported a diverse repertoire of immunopathological events that potentially underly susceptibility to disease severity in vivax malaria. Nevertheless, the combined epidemiologic, clinical, parasitological, and immunologic features associated with defining the disease outcomes are still not fully understood. In the present study, we perform an extensive outlining of cytokines and inflammatory proteins in plasma samples from a cohort of individuals from the Brazilian Amazon infected with P. vivax and presenting with asymptomatic (n = 108) or symptomatic (n = 134) disease (106 with mild presentation and 28 with severe malaria), as well as from uninfected endemic controls (n = 128) to elucidate these gaps further. We employ highly multidimensional Systems Immunology analyses using the molecular degree of perturbation to reveal nuances of a unique profile of systemic inflammation and imbalanced immune activation directly linked to disease severity as well as with other clinical and epidemiologic characteristics. Additionally, our findings reveal that the main factor associated with severe cases of P. vivax infection was the number of symptoms, despite of a lower global inflammatory perturbation and parasitemia. In these participants, the number of symptoms directly correlated with perturbation of markers of inflammation and tissue damage. On the other hand, the main factor associated with non-severe infections was the parasitemia values, that correlated only with perturbation of inflammatory markers, such as IL-4 and IL-1ß, with a relatively lower number of symptoms. These observations suggest that some persons present severe vivax regardless of pathogen burden and global inflammatory perturbation. Such patients are thus little tolerant to P. vivax infection and show higher susceptibility to disrupt homeostasis and consequently exhibit more clinical manifestations. Other persons are capable to tolerate higher parasitemia with lower inflammatory perturbation and fewer symptoms, developing non-severe malaria. The analytical approach presented here has capability to define in more details the determinants of disease tolerance in vivax malaria.

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Coronavirus disease 19 (COVID-19) has struck the world since the ending of 2019. Tools for pandemic control were scarce, limited only to social distance and face mask usage. Today, upto 12 vaccines were approved and the rapid development raises questions about the vaccine efficiency. We accessed the public database provided by each country and the number of death, active cases, and tests in order to evaluate how the vaccine is influencing the COVID-19 pandemic. We observed distinct profiles across the countries and it was related to the vaccination start date and we are proposing a new way to manage the vaccination.

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BACKGROUND: Severity stratification scores developed in intensive care units (ICUs) are used in interventional studies to identify the most critically ill. Studies that evaluate accuracy of these scores in ICU patients admitted with pneumonia are lacking. This study aims to determine performance of severity scores as predictors of mortality in critically ill patients admitted with pneumonia. METHODS: Prospective cohort study in a general ICU in Brazil. ICU severity scores (Simplified Acute Physiology Score 3 [SAPS 3] and Sepsis-Related Organ Failure Assessment [qSOFA]), prognostic scores of pneumonia (CURB-65 [confusion, urea, respiratory rate, blood pressure, age] and CRB-65 [confusion, respiratory rate, blood pressure, age]), and clinical and epidemiological variables in the first 6 hours of hospitalization were analyzed. RESULTS: Two hundred patients were included between 2015 and 2018, with a median age of 81 years (interquartile range, 67-90 years) and female predominance (52%), primarily admitted from the emergency department (65%) with community-acquired pneumonia (CAP, 80.5%). SAPS 3, CURB-65, CRB-65,and qSOFA all exhibited poor performance in predicting mortality. Multivariate regression identified variables independently associated with mortality that were used to develop a novel pneumonia-specific ICU severity score (Pneumonia Shock score) that outperformed SAPS 3, CURB-65, and CRB-65. The Shock score was validated in an external multicenter cohort of critically ill patients admitted with CAP. CONCLUSIONS: We created a parsimonious score that accurately identifies patients with pneumonia at highest risk of ICU death. These findings are critical to accurately stratify patients with severe pneumonia in therapeutic trials that aim to reduce mortality.

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