Determination of the Th1, Th2, Th17, and Treg cytokine profile in patients with chronic Chagas heart disease and systemic arterial hypertension.

Chronic Chagas heart disease (CCHD affects about 30% of patients with chronic Chagas disease (CCD). Systemic arterial hypertension (SAH) afflicts about 25% of patients with CCD. The association of CCHD with SAH (CCHD-SAH) predisposes patients to develop chronic heart failure. The role of cytokines in disease progression in patients with CCHD-SAH is unknown. Accordingly, the aim of this study was to evaluate the plasma levels of cytokines expressing the Th1, Th2, Th17 pattern, as well as Treg cytokines, TNF-alpha, IL-1ß, IL-8, IL-7 in patients with SAH-CCHD to get insight into the immunomodulation process in patients with this condition. Fifteen patients with CCHD, 22 patients with CCHD-SAH, and 28 controls were studied. All patients underwent history-taking, physical examination, 12-lead resting ECG, chest X-ray, and Doppler-echocardiogram. Ten of 15 (66%) patients with CCHD, and 16 of 22 (73%) patients with CCHD-SAH had decreased left ventricular ejection fraction (p > 0.05). Cytokines levels were performed on plasma samples using the ELISA method. Overall, proinflammatory, anti-inflammatory, and regulatory cytokine levels were increased in patients with CCHD-SAH in comparison to patients with CCHD and controls. However, such a difference was higher regarding IL-2, IL-5, IL-17, IL-12, and TNF-alpha cytokine levels, respectively. Cytokine levels were higher in CCHD patients in comparison to controls. Patients with CCHD-SAH have increased plasma levels of pro-inflammatory, anti-inflammatory, and regulatory cytokines in comparison with CCHD patients, thus suggesting a higher level of immunomodulation in patients with CCHD-SAH.

Prevalence and clinical course of patients with chronic heart failure secondary to chronic Chagas heart disease associated with obstructive coronary artery disease.

BACKGROUND: The prevalence and the outcomes of patients with chronic Chagas heart disease with obstructive coronary artery disease (CCHD-CAD) and chronic heart failure (CHF) with precordial chest pain are unsettled. Accordingly, the aim of this study was to determine the prevalence and clinical course of patients with CHF secondary to CCHD-CAD. METHODS: Patients with positive serology for Chagas disease and systolic CHF were included; those with precordial chest pain and at least two risk factors for CAD underwent coronary arteriogram. RESULTS: In total 262 patients were included in the investigation; 234 (89%) had CHF secondary to CCHD alone, and 28 (11%) with CHF secondary to CCHD-CAD, as observed at coronary arteriogram. The survival probability of patients with CHF secondary to CCHD alone at 12, 24, 36, 48 and 72 mo was 79%, 64%, 54%, 44% and 33%, respectively, whereas survival probability for patients with CHF secondary to CCHD-CAD at 12, 24, 36, 48 and 72 mo was 96%, 80%, 71%, 66% and 57%, respectively (p=0.04). CONCLUSIONS: In patients with CCHD with CHF, the prevalence of CAD of 11% is not neglectable in those with precordial chest pain. The outcome for patients with precordial chest pain with CHF secondary to CCHD-CAD is better than that observed in patients with CHF secondary to CCHD alone.

Plasma Levels of Matrix Metalloproteinases 2 and 9 in Patients with Chronic Chagas Heart Disease and Systemic Arterial Hypertension: Correlation with TGF-Beta Plasma Levels.

Background: Chronic Chagas heart disease (CCHD) and systemic arterial hypertension (SAH) frequently coexists in areas where Chagas disease is endemic. The effects of the association of both conditions (CCHD-SAH) on the extracellular matrix (ECM) remodeling are unknown. Matrix metalloproteinases (MMP) 2 and 9 are involved in ECM remodeling. The aim of this study was to evaluate MMP 2 and MMP9 in CCHD-SAH patients and to correlate their levels with those of the profibrogenic cytokine TGF-beta. Methods: We included 19 patients with CCHD-SAH, 14 patients with CCHD alone, and 19 controls matched by sex and age. MMP-2 and MMP-9 plasma levels were studied by gel zymography and showed as optical densities (OD). TGF-beta plasma levels were measured by double-ligand ELISA and expressed as pg/mL. Results: Median (5th, 95th) MMP-2 plasma levels were 1224.7 OD (1160, 1433.5) in patients with CCHD alone, 1424.1 OD (1267.5, 1561) in patients with CCHD-SAH, and 940 OD (898.1, 1000.8) in controls (p=0.001). MMP-9 plasma levels were 1870 OD (1740, 1904.1) in patients with CCHD alone, 1754.6 OD (1650, 2049) in those with CCHD-SAH and 89.7 OD (80, 96) in controls (p=0.0003). MMP-9 plasma levels were higher than those of MMP 2 in patients with CCHD-SAH (p=0.01). No correlation was found between TGF-beta plasma levels with MMP-2 serum levels (r = 0.12; p=0.7), but a moderate negative correlation (r = -0.46; p=0.048) was observed between TGF-beta and MMP-9 plasma levels. Conclusions: MMP-2 and especially MMP-9 may play a role in the ECM remodeling process in patients with CCHD-SAH. TGF-Beta may counteract the MMP effect on the ECM remodeling process in patients with CCHD-SAH.

Nonpharmaceutical public health interventions to curb the COVID-19 pandemic: a narrative review.

Nonpharmaceutical Interventions (NPI) consist of compulsory (isolation, quarantine, stay-at-home orders, banning public gatherings, nonessential business closures, school closures), and voluntary (social distancing, handwashing, respiratory etiquette, and universal mask wearing) measures. The aim of this narrative review is to evaluate the different forms of NPI and their effectiveness in combating the pandemic. Isolation can be indicated for symptomatic and asymptomatic infected people at home or at hospitals depending on the patient's clinical picture. Quarantine is a social distancing intervention in asymptomatic uninfected people who had contact with SARS-CoV-2 infected individuals. Stay-at-home orders refer to statewide mandates imposing nonessential business closures, prohibition of public events and gatherings, and travel restrictions. Studies have suggested that stay-at-home orders may be associated with a reduction in the incidence of COVID-19 in some countries. Mask wearing decreases the risk of COVID-19 in the community, especially when the surgical masks are used for vulnerable people. N-95 respirators protect health workers from COVID-19. NPI may be helpful to curb the COVID-19 pandemic while mass vaccination worldwide is not attainable, and the threat of SARS-COV-2 variants remain on the horizon.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.

Massive right-sided cardiac thrombosis in Chagas' heart disease without left ventricular dysfunction.

A 63-year-old woman with the diagnosis of mega-oesophagus secondary to chronic Chagas' disease and no past cardiac history was referred for cardiac evaluation. The resting ECG showed right bundle-branch block, whereas a 2-D echocardiogram revealed marked right ventricular dilatation with hypokinesia, right atrial dilatation, normal pulmonary artery pressure, and normal left ventricular ejection fraction. A large, irregularly shaped mass, arising from the right atrium and protruding into the right ventricle through the tricuspid valve, with several different bizarre forms inside the right atrium during systole and/or diastole was seen on 2-D echocardiogram. Therefore, massive right-sided thrombosis can be detected in Chagas' disease patients with no overt right- and left-sided ventricular failure.

Pharmacological Treatment of Patients with Mild to Moderate COVID-19: A Comprehensive Review.

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.

The history of the evolution of the knowledge about the diagnosis and the pathogenetic aspects of heart failure: From the Egyptians to James Mackenzie.

The recognition of the syndrome of heart failure (HF) dates back to the Egyptians, although it is still a mystery how they did that because they had an erroneous notion of the blood flow. Some cardinal aspects of the clinical picture of HF were associated with cardiac disease 1600 years later. Dyspnea was associated with cardiac disease in 1000 CE by Avicenna; pedal edema was associated with cardiac disease by Pawl in 1615. Lower associated dyspnea with pedal edema in 1669, and Bonet associated ascites with cardiac disease in 1679. Lancisi associated the jugular venous distention with right ventricular dilatation in 1728. However, it was only in 1748 that Albertini associated pedal edema and dyspnea with the myocardial disease. The evolution of the understanding that myocardial contractility abnormality was the mechanism behind HF partially started with Lower in 1669, it was clearly pointed out by Albertini in 1748 and refined by Mackenzie in 1908. At that time, it was clear that the exhausted myocardial would lead to the appearance of HF. However, the full understanding of the pathogenesis of HF had to wait for the hemodynamic studies which would appear in the second decade of the 20th century, and for the neurohormonal theory of the 90's.

Kinins and nitric oxide in patients with chronic chagas disease and systemic arterial hypertension.

BACKGROUND: Chronic Chagas disease (CCHD) associated with Systemic Arterial Hypertension (SAH) is frequently found in areas where the disease is endemic. The pathogenesis of patients with both pathologies (CCHD-SAH) is unsettled. Nitric Oxide (NO) and Kinins are important players in the myocardial inflammation process in experimental CCHD. No previous study has addressed this question in patients with CCHD, particularly in those with CCHD-SAH. Accordingly, this study was undertaken in an attempt to contribute to the understanding of the pathogenesis of patients with CCHD-SAH. METHODS: Thirty-seven patients with a positive serology for Chagas disease were enrolled; 15 had CCHD alone, 22 had CCHD-SAH (abnormal ECG/Doppler echocardiogram plus a systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on admission), and 11 had SAH alone. Thirty healthy individuals matched by age and sex served as controls. Plasma High-molecular (Hkg) and low-molecular weight (LKg) kininogens, plasma kallikrein levels (Pkal and Tcal), Kininase II, and plasma NO were measured. RESULTS: HKg and LKg were lower in CCHD-SAH patients in comparison with other groups (P < .0001). Pkal and Tcal were higher in CCHD-SAH patients in comparison with the other groups (P< .0001). Kininase II levels were similar in SAH, CCHD, and CCHD-SAH patients, but lower in comparison with controls (P< .0001). NO levels were similar in CCHD and CCHD-SAH patients, but higher in comparison with SAH patients and controls (P > .0001). CONCLUSION: Such findings suggest increased Kinin and NO activity in patients with CCHD-SAH, thus contributing to the understanding of the pathogenesis of this condition.

University Admission Test Associates with Academic Performance at the End of Medical Course in a PBL Medical Hybrid Curriculum.

PURPOSE: Most studies assessing the value of the university admissions test (UAT) to predict academic performance at the end of a medical course were carried out on lecture-based medical courses. However, the association between performance in the UAT with academic achievement at the end of medical course in a problem-based learning (PBL) medical hybrid curriculum remains controversial. The aim of this study was to correlate marks in the UAT with those obtained in the Organized Structured Clinical Examination (OSCE), in the progress testing (PT), and in the final marks of the clerkship (FMC). METHODS: We used data from 48 medical students. A single and a multiple dependency studies were performed to assess bivariate and multiple correlation between the UAT or the essay scores (dependent variables) and the OSCE, PT, and FMC (independent variables). Pearson test, multiple linear regression, and ANOVA tests were used and a p-value < 0.05 was considered significant. RESULTS: In the bivariate analysis, only the UAT and FMC marks were correlated (r=0.34; p=0.02). However, the multiple dependency study showed a moderate correlation among UAT, OSCE, PT, and FMC marks (r=0.46; p=0.01). No correlation was found between the essay scores and PT, FMC, and OSCE scores. CONCLUSION: Our study shows that UAT marks, but not essay scores, can predict academic achievement, particularly in terms of clinical competence (FMC) at the end of a medical course in a PBL hybrid curriculum.

A systematic review of studies on heart transplantation for patients with end-stage Chagas' heart disease.

BACKGROUND: Uncertainties regarding indications for the procedure, proper immunosuppressive regimen, and the fear of Trypanosoma cruzi infection reactivation are major concerns regarding heart transplantation (HTx) for patients with end-stage Chagas' heart disease. METHODS AND RESULTS: To review indications for HTx, current immunosuppressive therapy, posttransplant morbidities, and outcome in Chagas' heart transplant recipients. Review of articles linking HTx and Chagas' disease at PubMed and Scielo database from 1966 onward. HTx can reasonably be indicated in patients with an annual probability of death of 70%. HTx has been associated with a similar incidence of rejection episodes in Chagas' and non-Chagas' heart transplant recipients. A lower incidence of infection episodes has been observed in Chagas' in comparison to non-Chagas' heart transplant recipients. T. cruzi infection reactivation is easily treated with either benznidazole or allopurinol and portends a very low mortality rate. Other posttransplant morbidities have a similar incidence in Chagas' and in non-Chagas' patients. Survival probability for Chagas' HTx recipients at 1 month, 1 year, 4 years, and 10 years follow-up is 83%, 71%, 57%, and 46%, respectively. Such an outcome is better than that seen in non-Chagas' heart transplant recipients. CONCLUSIONS: HTx is safe and efficacious for patients with end-stage Chagas' heart disease.