Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis.

Introduction: Understanding compartmentalized immune responses in target organs is crucial for elucidating the pathogenesis of various diseases. However, obtaining samples from affected vital organs often poses safety challenges. In this study, we aimed to investigate potential correlations between the levels of disease-associated immune molecules in the bloodstream with their gene expression profiles in the hearts of patients suffering from Chagas Cardiomyopathy (CCC). This debilitating and often fatal condition is caused by infection with the protozoan Trypanosoma cruzi. Methods: Blood samples were analyzed using the Bio-Plex platform. Gene Expression Omnibus (GEO) database was used to determine gene expression profile in heart tissue from CCC and non-Chagas controls (CTRL). Results: Elevated levels of inflammatory cytokines were detected in the plasma of CCC patients, and these levels correlated with clinical indicators of deteriorating cardiac function. Notably, 75% of the soluble factors assessed in the plasma exhibited a consistent relationship with their gene expression levels in the cardiac tissue of CCC patients. Analysis of interactions and signaling pathways related to these molecules revealed an overrepresentation of inflammatory pathways in both blood and heart compartments. Moreover, we identified that differentially expressed genes in CCC cardiac tissue were primarily associated with T-cell signaling pathways and correlated with the presence of CD8+ T cells in the myocardium. Discussion: Our findings establish a strong correlation between relevant immune molecules and their signaling pathways in both the blood and heart tissue in CCC. This validates the use of blood as a non-invasive medium for understanding immunopathology and identifying markers for cardiac dysfunction in Chagas disease.

Accuracy of Transthoracic Echocardiogram as a Screening Method in the Clinical Practice of Pulmonary Hypertension Investigation. / Acurácia do Ecocardiograma Transtorácico como Método de Triagem na Prática Clínica da Investigação da Hipertensão Pulmonar.

BACKGROUND: The transthoracic echocardiogram (TTE) plays a screening role in the diagnostic algorithm of pulmonary hypertension (PH). Studies have shown a significant disagreement between TTE measurements of the systolic pulmonary artery pressure (sPAP) and right atrial pressure (RAP) and those obtained by right heart catheterization (RHC). OBJECTIVE: To compare TTE measurements of sPAP and RAP with those obtained by RHC in patients being investigated for PH. METHODS: Patients referred to a PH reference center with a high or intermediate TTE probability of PH upon admission were submitted to RHC. The agreement between sPAP and RAP from both procedures was assessed through the Bland-Altman test. Differences of up to 10 mmHg for sPAP and 5 mmHg for RAP were considered within the variability of the test. Receiver Operating Characteristic (ROC) curve was constructed to determine the most accurate sPAP and Tricuspid regurgitation maximal velocity (TRV)values associated with the diagnosis of PH by RHC. The adopted level of statistical significance was 5%. RESULTS: Ninety-five patients were included. The Bland-Altman analysis showed a bias of 8.03 mmHg (95% CI:-34.9-50.9) for sPAP and -3.30 mmHg (95% CI:-15.9-9.3) for RAP. AUC for sPAP and TRV measured by TTE for discrimination of probable PH were 0.936 (95% CI: 0.836-1.0) and 0.919 (95% CI: 0.837-1.0), respectively. However, only 33.4% of the echocardiographic estimate of sPAP and 55.1% of RAP were accurate, as compared to the measurements obtained by RHC. CONCLUSION: TTE has a high discriminatory power as a screening diagnostic method for PH despite presenting disagreements between sPAP and RAP absolute values when compared to RHC measurements.

FUNDAMENTO: O ecocardiograma transtorácico (ETT) tem um papel de triagem no algoritmo diagnóstico da hipertensão pulmonar (HP). Estudos demonstraram uma discordância significativa entre as medições do ETT da pressão arterial pulmonar sistólica (PAPs) e da pressão atrial direita (PAD) e as obtidas pelo cateterismo do coração direito (CCD). OBJETIVO: Comparar as medições do ETT da PAPs e da PAD com as obtidas pelo CCD em pacientes com suspeita de HP. MÉTODOS: Pacientes encaminhados a um centro de referência com probabilidade alta ou intermediária de PH ao ETT na admissão hospitalar passaram por CCD. A concordância entre a PAPs e a PAD em ambos os procedimentos foi avaliada pelo teste de Bland-Altman. Diferenças de até 10 mmHg na PAPs e de até 5 mmHg na PAD foram consideradas dentro da variabilidade do teste. A curva de característica de operação do receptor (ROC) foi construída para determinar os valores mais precisos de PAPs e VRT associados ao diagnóstico de HP pelo CCD. O nível de significância estatística adotado foi 5%. RESULTADOS: Foram incluídos noventa e cinco pacientes. A análise de Bland-Altman análise revelou um viés de 8,03 mmHg (IC 95%: -34,9 a 50,9) na PAPs e -3,30 mmHg (IC 95%: -15,9 a 9,3) na PAD. AUC da PAPs e VRT medidas pelo ETT para a discriminação de provável HP foram de 0,936 (IC 95%: 0,836 a 1,0) e 0,919 (IC 95%: 0,837 a 1,0), respectivamente. Entretanto, apenas 33,4% da estimativa ecocardiográfica da PAPs e 55,1% da PAD foram precisas, em comparação às medições obtidas pelo CCD. CONCLUSÃO: O ETT tem um alto poder discriminatório como método diagnóstico de triagem para HP, apesar de apresentar discordâncias entre os valores absolutos de PAPs e PAD, em comparação às medições por CCD.

Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

Acurácia do Ecocardiograma Transtorácico como Método de Triagem na Prática Clínica da Investigação da Hipertensão Pulmonar / Accuracy of Transthoracic Echocardiogram as a Screening Method in the Clinical Practice of Pulmonary Hypertension Investigation

Resumo Fundamento O ecocardiograma transtorácico (ETT) tem um papel de triagem no algoritmo diagnóstico da hipertensão pulmonar (HP). Estudos demonstraram uma discordância significativa entre as medições do ETT da pressão arterial pulmonar sistólica (PAPs) e da pressão atrial direita (PAD) e as obtidas pelo cateterismo do coração direito (CCD). Objetivo Comparar as medições do ETT da PAPs e da PAD com as obtidas pelo CCD em pacientes com suspeita de HP. Métodos Pacientes encaminhados a um centro de referência com probabilidade alta ou intermediária de PH ao ETT na admissão hospitalar passaram por CCD. A concordância entre a PAPs e a PAD em ambos os procedimentos foi avaliada pelo teste de Bland-Altman. Diferenças de até 10 mmHg na PAPs e de até 5 mmHg na PAD foram consideradas dentro da variabilidade do teste. A curva de característica de operação do receptor (ROC) foi construída para determinar os valores mais precisos de PAPs e VRT associados ao diagnóstico de HP pelo CCD. O nível de significância estatística adotado foi 5%. Resultados Foram incluídos noventa e cinco pacientes. A análise de Bland-Altman análise revelou um viés de 8,03 mmHg (IC 95%: -34,9 a 50,9) na PAPs e -3,30 mmHg (IC 95%: -15,9 a 9,3) na PAD. AUC da PAPs e VRT medidas pelo ETT para a discriminação de provável HP foram de 0,936 (IC 95%: 0,836 a 1,0) e 0,919 (IC 95%: 0,837 a 1,0), respectivamente. Entretanto, apenas 33,4% da estimativa ecocardiográfica da PAPs e 55,1% da PAD foram precisas, em comparação às medições obtidas pelo CCD. Conclusão O ETT tem um alto poder discriminatório como método diagnóstico de triagem para HP, apesar de apresentar discordâncias entre os valores absolutos de PAPs e PAD, em comparação às medições por CCD.

Abstract Background The transthoracic echocardiogram (TTE) plays a screening role in the diagnostic algorithm of pulmonary hypertension (PH). Studies have shown a significant disagreement between TTE measurements of the systolic pulmonary artery pressure (sPAP) and right atrial pressure (RAP) and those obtained by right heart catheterization (RHC). Objective To compare TTE measurements of sPAP and RAP with those obtained by RHC in patients being investigated for PH. Methods Patients referred to a PH reference center with a high or intermediate TTE probability of PH upon admission were submitted to RHC. The agreement between sPAP and RAP from both procedures was assessed through the Bland-Altman test. Differences of up to 10 mmHg for sPAP and 5 mmHg for RAP were considered within the variability of the test. Receiver Operating Characteristic (ROC) curve was constructed to determine the most accurate sPAP and Tricuspid regurgitation maximal velocity (TRV)values associated with the diagnosis of PH by RHC. The adopted level of statistical significance was 5%. Results Ninety-five patients were included. The Bland-Altman analysis showed a bias of 8.03 mmHg (95% CI:-34.9-50.9) for sPAP and -3.30 mmHg (95% CI:-15.9-9.3) for RAP. AUC for sPAP and TRV measured by TTE for discrimination of probable PH were 0.936 (95% CI: 0.836-1.0) and 0.919 (95% CI: 0.837-1.0), respectively. However, only 33.4% of the echocardiographic estimate of sPAP and 55.1% of RAP were accurate, as compared to the measurements obtained by RHC. Conclusion TTE has a high discriminatory power as a screening diagnostic method for PH despite presenting disagreements between sPAP and RAP absolute values when compared to RHC measurements.

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature.

BACKGROUND: Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10-9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.

Hospitalizations due to gastrointestinal Chagas disease: National registry.

OBJECTIVES: Analyze the hospitalizations of patients admitted for Chagas disease with gastro-intestinal involvement (CD-GI) in the Brazilian Unified Health System, describe the epidemiological profile, mortality and costs. METHODS: This is an observational study that uses secondary data from the National Hospital Information System (SIH-SUS) for the years 2017-2019. CD-GI admissions were defined by specific ICD-10 codes that identify the main diagnosis. RESULTS: From 2017 to 2019, there were 4,407 hospitalizations for CD-GI in Brazil, considering only public hospitals and those associated with the SUS. This corresponds to an average of 1,470 hospitalizations per year, or 0.6 per 100,000 inhabitants, with significant regional variation. Hospitalizations increased with age and were slightly higher in men. More than 60% were emergencies and in 50% the procedure performed was surgical. The most used code was the one for megaesophagus followed by megacolon. In-hospital mortality was 5.8% and 17.2% went to intensive care units. The median cost was USD$ 553.15 per hospitalization, and an overall cost of USD$ 812,579.98 per year to the SUS budget. CONCLUSION: The numbers, rates and costs presented here are possibly underestimated but they give us an idea of the overall profile of hospitalizations due to CD-GI, which are not rare and are related to significant in-hospital mortality. CD-GI is a neglected manifestation of a neglected disease.

Biomakers in Chronic Chagas Cardiomyopathy.

The primary objective was to observe the relationship between serum levels of BNP, Ca-125, C-reactive protein and uric acid as prognostic and functional markers in patients with chronic Chagas cardiomyopathy (CCC). Circulating levels of cytokines: IL-1ß, TNFα, IL-10, IL6, IL-8 and IL-12 were determined and investigated regarding their association with hemodynamic parameters, clinical signs of heart failure and outcome. Chagas is still a neglected disease that affects numerous individuals, many of them in their most productive years. CCC with left ventricular dysfunction is the most severe presentation of Chagas Disease. BNP is a well-recognized prognostic and clinical biomarker, not only in chronic heart failure patients but also in patients with CCC. Previous studies have shown Ca-125, C-reactive protein, and uric acid to be potentially good prognostic markers in heart failure (HF). Fifty patients with left ventricular fraction less (LVEF) than 55% were selected and followed for a mean period of 18 ± 8.3 months. Patient's mean age was 43.42 ± 10.3 years (32 male), their BNP was 293 (160-530) pg/mL, Ca-125 8.5 (5.5-16.75) U/mL, uric acid 6.2 ± 2 mg/dL, and C- reactive protein 4.5 (4.5-7.3) mg/L. Patients who had LVEF less than 35% had higher BNP (p = 0.0023), Ca-125 (p = 0.027) and uric acid (p = 0.01) serum levels. Patients who died also showed higher BNP (p = 0.01), uric acid (p = 0.05) and a trend towards higher Ca-125 serum levels (p = 0.056). All markers: BNP, Ca-125, uric acid and C-reactive had good predictability of death in Cox-regression univariate analysis, however, not on the final multivariate model. Of the inflammatory cytokines, IL-8 and IL-12 showed a relation to LVEF of less than 35%. IL-12 was related to adverse cardiovascular events and non-survival. IL-1ß was a good predictor of mortality in the final Cox regression model. Determination of Ca-125, uric acid levels and C-reactive protein may add useful clinical and prognostic information and may help clinical decision making for patients with CCC.

Prognosis of chronic Chagas heart disease and other pending clinical challenges.

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Contextual influence on poor self-rated health in patients with Chagas disease: multilevel study.

Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

Two-year death prediction models among patients with Chagas Disease using machine learning-based methods.

Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases. More than 80% of people affected by CD will not have access to diagnosis and continued treatment, which partly supports the high morbidity and mortality rate. Machine Learning (ML) can identify patterns in data that can be used to increase our understanding of a specific problem or make predictions about the future. Thus, the aim of this study was to evaluate different models of ML to predict death in two years of patients with CD. ML models were developed using different techniques and configurations. The techniques used were: Random Forests, Adaptive Boosting, Decision Tree, Support Vector Machine, and Artificial Neural Networks. The adopted settings considered only interview variables, only complementary exam variables, and finally, both mixed. Data from a cohort study with CD patients called SaMi-Trop were analyzed. The predictor variables came from the baseline; and the outcome, which was death, came from the first follow-up. All models were evaluated in terms of Sensitivity, Specificity and G-mean. Among the 1694 individuals with CD considered, 134 (7.9%) died within two years of follow-up. Using only the predictor variables from the interview, the different techniques achieved a maximum G-mean of 0.64 in predicting death. Using only the variables from complementary exams, the G-mean was up to 0.77. In this configuration, the protagonism of NT-proBNP was evident, where it was possible to observe that an ML model using only this single variable reached G-mean of 0.76. The configuration that mixed interview variables and complementary exams achieved G-mean of 0.75. ML can be used as a useful tool with the potential to contribute to the management of patients with CD, by identifying patients with the highest probability of death. Trial Registration: This trial is registered with ClinicalTrials.gov, Trial ID: NCT02646943.

Contextual influence on poor self-rated health in patients with Chagas disease: multilevel study / Influência contextual na pior autopercepção em saúde de portadores de Doença de Chagas: estudo multinível

Abstract Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

Resumo A Doença de Chagas (DC) é reconhecida pela Organização Mundial da Saúde como uma das treze doenças tropicais mais negligenciadas do mundo. A autopercepção de saúde é considerada um melhor preditor de mortalidade do que medidas objetivas do estado de saúde, e o contexto em que se vive influencia esse preditor. O objetivo deste estudo foi avaliar a prevalência e os fatores individuais e contextuais associados à pior autopercepção em saúde de pacientes com DC de uma região endêmica do Brasil. É um estudo transversal multinível. Os dados individuais vêm de um corte transversal de um estudo de coorte denominado SaMi-Trop. Os dados contextuais foram coletados a partir de plataformas e sistemas de informações institucionais acessíveis ao público. A variável dependente foi a autopercepção de saúde. A análise foi realizada por meio de regressão logística binária multinível. Participaram do estudo 1.513 pacientes com DC, sendo 335 (22,1%) com pior autopercepção de saúde. Este estudo revelou a influência da organização/oferta do serviço público de saúde brasileiro e de características individuais na autopercepção de saúde de pacientes com DC.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Distinct CD4-CD8- (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease.

CD4-CD8- (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form-IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.

Cohort profile update: the main and new findings from the SaMi-Trop Chagas cohort.

The SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic areas of Chagas disease, including 1,959 patients with chronic Chagas cardiomyopathy. In this article we updated the results of the project, adding information from the second cohort visit. Trypanosoma cruzi-seropositive patients were enrolled from the primary care Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for the second visit was the participation in the baseline evaluation. Of 1,959 participants at the baseline assessment, 1,585 (79.9%) returned after two years for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to 18.2% when it was stratified by certain clinical characteristics. A lower age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment were associated with lower mortality. There was an improvement in most quality of life domain scores. Participants have also reported fewer signs and symptoms and greater use of medication. The second follow-up visit will be complete in Oct 2021.

Sydenham's chorea: from pathophysiology to therapeutics.

Sydenham's chorea is an autoimmune chorea emerging after a group A beta-hemolytic streptococcal (GABHS) infection, i.e. a rheumatic chorea with or without the presence of carditis or arthritis. The disorder, defined by the presence of chorea, is also associated with cognitive and behavioral symptoms, including emotional lability, anxiety, depressive and obsessive-compulsive symptoms. The authors review the pathophysiology, clinical characteristics, and available evidence on therapeutic strategies, the latter including the secondary prevention of GABHS infections, reduction of chorea, and immune modulation. Sydenham's chorea has been regarded as a model for pediatric autoimmune neuropsychiatric disorders, however, the field is marked by conflicting results and controversies. Regarding therapeutics, there are limited high-quality interventional studies and the selection of treatment strategy often relies on the clinician's experience. A serial treatment algorithm is presented based upon the severity of clinical presentation and response to symptomatic pharmacotherapy.

Artificial Inteligence-Based Decision for the Prediction of Cardioembolism in Patients with Chagas Disease and Ischemic Stroke.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. AIMS: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. MATERIALS AND METHODS: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. RESULTS: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. CONCLUSIONS: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.