The association between variables of cardiopulmonary exercise test and quality of life in patients with chronic Chagas cardiomyopathy (Insights from the PEACH STUDY).

Studies investigating the association between functional capacity and quality of life (QoL) in individuals with chronic Chagas cardiomyopathy (CCC) usually do not include a gold-standard evaluation of functional capacity, limiting the validity and the interpretation of the results. The present study is a cross-section analysis aiming to evaluate the association between functional capacity (quantified by cardiopulmonary exercise test [CPET]) and QoL in individuals with CCC. QoL was assessed using the SF-36 questionnaire. Sociodemographic, anthropometric, clinical, cardiac function and maximal progressive CPET variables were obtained from PEACH study. Generalized linear models adjusted for age, sex, and left ventricular ejection fraction were performed to evaluate the association between CPET variables and QoL. After adjustments, VO2 peak and VO2 AT were both associated with physical functioning (ß = +0.05 and ß = +0.05, respectively) and physical component summary (ß = +0.03 and ß = +0.03, respectively). Double product was associated with physical functioning (ß = +0.003), general health perceptions (ß = +0.003), physical component summary (ß = +0.002), and vitality (ß = +0.004). HRR≤12bpm was associated with physical functioning (ß = -0.32), role limitations due to physical problems (ß = -0.87), bodily pain (ß = -0.26), physical component summary (ß = -0.21), vitality (ß = -0.38), and mental health (ß = -0.19). VE/VCO2 slope presented association with all mental scales of SF-36: vitality (ß = -0.028), social functioning (ß = -0.024), role limitations due to emotional problems (ß = -0.06), mental health (ß = -0.04), and mental component summary (ß = -0.02). The associations between CPET variables and QoL demonstrate the importance of CPET inclusion for a more comprehensive evaluation of individuals with CCC. In this setting, intervention strategies aiming to improve functional capacity may also promote additional benefits on QoL and should be incorporated as a treatment strategy for patients with CCC.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience.

BACKGROUND: We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. METHODS: This was an observational retrospective study with clinical data retrieved from medical records. RESULTS: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. CONCLUSIONS: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

Gene expression profile of Mycobacterium leprae contribution in the pathology of leprosy neuropathy

Peripheral neuropathy is the main cause of physical disability in leprosy patients.Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges.

Covid-19 is a novel infectious disease whose spectrum of presentation ranges from absence of symptoms to widespread interstitial pneumonia associated with severe acute respiratory syndrome (SARS), leading to significant mortality. Given the systemic pattern of Covid-19, there are many factors that can influence patient's functional capacity after acute infection and the identification of such factors can contribute to the development of specific rehabilitation strategies. Pulmonary impairment is the primary cause of hospitalization due to Covid-19, and can progress to SARS as well as increase length of hospitalization. Moreover, cardiac involvement is observed in approximately 30% of hospitalized patients, with an increased risk of acute myocarditis, myocardial injury, and heart failure, which may compromise functional capacity in the long-term. Thromboembolic complications have also been reported in some patients with Covid-19 and are associated with a poor prognosis. Musculoskeletal complications may result from long periods of hospitalization and immobility, and can include fatigue, muscle weakness and polyneuropathy. Studies that address the functional capacity of patients after Covid-19 infection are still scarce. However, based on knowledge from the multiple systemic complications associated with Covid-19, it is reasonable to suggest that most patients, especially those who underwent prolonged hospitalization, will need a multiprofessional rehabilitation program. Further studies are needed to evaluate the functional impact and the rehabilitation strategies for patients affected by Covid-19.

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Abstract Covid-19 is a novel infectious disease whose spectrum of presentation ranges from absence of symptoms to widespread interstitial pneumonia associated with severe acute respiratory syndrome (SARS), leading to significant mortality. Given the systemic pattern of Covid-19, there are many factors that can influence patient's functional capacity after acute infection and the identification of such factors can contribute to the development of specific rehabilitation strategies. Pulmonary impairment is the primary cause of hospitalization due to Covid-19, and can progress to SARS as well as increase length of hospitalization. Moreover, cardiac involvement is observed in approximately 30% of hospitalized patients, with an increased risk of acute myocarditis, myocardial injury, and heart failure, which may compromise functional capacity in the long-term. Thromboembolic complications have also been reported in some patients with Covid-19 and are associated with a poor prognosis. Musculoskeletal complications may result from long periods of hospitalization and immobility, and can include fatigue, muscle weakness and polyneuropathy. Studies that address the functional capacity of patients after Covid-19 infection are still scarce. However, based on knowledge from the multiple systemic complications associated with Covid-19, it is reasonable to suggest that most patients, especially those who underwent prolonged hospitalization, will need a multiprofessional rehabilitation program. Further studies are needed to evaluate the functional impact and the rehabilitation strategies for patients affected by Covid-19.

Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. METHODS: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. RESULTS: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 4 8 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). CONCLUSION: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Adverse drug events and the associated factors in patients with chronic Chagas disease.

INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Adverse drug events and the associated factors in patients with chronic Chagas disease

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Agreement between upper endoscopy and esophagography in the diagnosis of megaesophagus in Chagas disease.

INTRODUCTION: The diagnosis and classification of megaesophagus can be challenging in patients with Chagas disease. The present study aimed to evaluate the agreement between upper endoscopies and esophagographies for the diagnosis and classification of megaesophagus in Chagas disease. METHODS: A cross-sectional study of 50 patients with Chagas disease with upper digestive symptoms was undertaken. Esophagography and upper endoscopy exams were performed to compare diagnoses. Statistical analysis included sensitivity and specificity used to evaluate the diagnostic accuracy of upper endoscopies, and measures of agreement: linearly weighted Kappa (κw) and Cohen`s classical Kappa (κ) coefficients with 95% confidence intervals (95% CI). RESULTS: Twenty-three patients (46%) were diagnosed with megaesophagus by esophagography. The upper endoscopy sensitivity and specificity for megaesophagus diagnosis were 100% and 33.3%, respectively. Regarding megaesophagus classifications, there was a substantial agreement between the two exams (κw = 0.622; 95% CI: 0.498 to 0.746). Within megaesophagus groups, agreement for group I was slight (κ = 0.096; 95% CI: 0.000 to 0.403); for group II, substantial (κ = 0.703; 95% CI: 0.456 to 0.950); and for groups III and IV, inconclusive (κ = 0.457; 95% CI: 0.000 to 0.967; κ = 0.540; 95% CI: 0.035 to 1.000, respectively). CONCLUSIONS: Upper endoscopy has a high sensitivity, but a low specificity to diagnose megaesophagus. Agreement between the two exams varies depending on the megaesophagus grade. Thus, upper endoscopy can be used in the diagnostic workup of a possible Chagas disease megaesophagus, but all identified cases should undergo esophagography.

Agreement between upper endoscopy and esophagography in the diagnosis of megaesophagus in Chagas disease

Abstract INTRODUCTION The diagnosis and classification of megaesophagus can be challenging in patients with Chagas disease. The present study aimed to evaluate the agreement between upper endoscopies and esophagographies for the diagnosis and classification of megaesophagus in Chagas disease. METHODS: A cross-sectional study of 50 patients with Chagas disease with upper digestive symptoms was undertaken. Esophagography and upper endoscopy exams were performed to compare diagnoses. Statistical analysis included sensitivity and specificity used to evaluate the diagnostic accuracy of upper endoscopies, and measures of agreement: linearly weighted Kappa (κw) and Cohen`s classical Kappa (κ) coefficients with 95% confidence intervals (95% CI). RESULTS: Twenty-three patients (46%) were diagnosed with megaesophagus by esophagography. The upper endoscopy sensitivity and specificity for megaesophagus diagnosis were 100% and 33.3%, respectively. Regarding megaesophagus classifications, there was a substantial agreement between the two exams (κw = 0.622; 95% CI: 0.498 to 0.746). Within megaesophagus groups, agreement for group I was slight (κ = 0.096; 95% CI: 0.000 to 0.403); for group II, substantial (κ = 0.703; 95% CI: 0.456 to 0.950); and for groups III and IV, inconclusive (κ = 0.457; 95% CI: 0.000 to 0.967; κ = 0.540; 95% CI: 0.035 to 1.000, respectively). CONCLUSIONS Upper endoscopy has a high sensitivity, but a low specificity to diagnose megaesophagus. Agreement between the two exams varies depending on the megaesophagus grade. Thus, upper endoscopy can be used in the diagnostic workup of a possible Chagas disease megaesophagus, but all identified cases should undergo esophagography.

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study.

BACKGROUND: Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients. METHODS: The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated. RESULTS: Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups. CONCLUSION: Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary. TRIAL REGISTRATION: NCT01863576.

Autophagy is an innate mechanism associated with leprosy polarization

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study.

INTRODUCTION: The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS: A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS: Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS: CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.