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Chronic Chagas cardiomyopathy (CCC) is a major public health issue in endemic areas of Latin America, representing one of the leading causes of heart failure and sudden death. The hallmark histopathological lesion of CCC is low-intensity, persistent myocarditis associated with cytokine production. Long-term use of pentoxifylline (PTX) may serve as an effective pharmacological intervention for immunomodulation, reducing inflammation and, consequently, diminishing myocardial perfusion abnormalities and thus preserving left ventricular systolic function. We investigated 38 patients with CCC, randomly assigned to PTX (n = 19), 400 mg 3 times a day for 6 months, or placebo (PLC) (n = 19). At baseline and post-treatment, patients underwent cytokine measurements, quality of life assessment, 2D echocardiography, and myocardial perfusion scintigraphy. After treatment, TNF-α levels in the PTX group decreased from 10.14 ± 5.5 to 8.32 ± 3.6 and from 9.12 ± 4.4 to 10.32 ± 8.5 in the PLC group (p = 0.06). Additionally, IL-10 levels increased from 2.74 ± 0.7 to 5.61 ± 8.6 in the PTX group, while in the placebo group, they decreased from 6.96 ± 11.8 to 5.50 ± 8.3 (p = 0.09); neither of these findings reached statistical significance. Also, no significant changes were observed in the echocardiographic variables after treatment. LVEF showed a modest change from 46.2% ± 7.9 to 47.4% ± 7.0 in the PTX group and from 48.2% ± 6.6 to 48.0% ± 6.9 in the PLC group (p = 0.37). No significant positive effects on myocardial perfusion were noted. However, the quality-of-life assessment documented a significant improvement of functional capacity in the PTX group. The results of this study suggest a potential positive effect of PTX in modulating the inflammatory profile of CCC patients. However, use of pentoxifylline in these patients did not attenuate the degree of ventricular dysfunction or reduce myocardial perfusion defects.

BackgroundMyocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters.Methods and resultsWe investigated female hamsters 6-months after T. cruzi infection (baseline condition) and control animals, divided into T. cruzi-infected animals treated with DIPY (CH + DIPY) or placebo (CH + PLB); and uninfected animals treated with DIPY (CO + DIPY) or placebo (CO + PLB). The animals were submitted to echocardiogram and rest SPECT-Sestamibi-Tc99m myocardial perfusion scintigraphy. Next, the animals were treated with DIPY (4 mg/kg bid, intraperitoneal) or saline for 30 days, and reevaluated with the same imaging methods. At baseline, the CH + PLB and CH + DIPY groups showed larger areas of perfusion defect (13.2 ± 13.2% and 17.3 ± 13.2%, respectively) compared with CO + PLB and CO + DIPY (3.8 ± 2.2% e 3.5 ± 2.7%, respectively), P < .05. After treatment, we observed: reduction of perfusion defects only in the CH + DIPY group (17.3 ± 13.2% to 6.8 ± 7.6%, P = .001) and reduction of LVEF in CH + DIPY and CH + PLB groups (from 65.3 ± 9.0% to 53.6 ± 6.9% and from 69.3 ± 5.0% to 54.4 ± 8.6%, respectively, P < .001). Quantitative histology revealed greater extents of inflammation and interstitial fibrosis in both Chagas groups, compared with control group (P < .001), but no difference between Chagas groups (P > .05).ConclusionsThe prolonged use of DIPY in this experimental model of CCC has reduced the rest myocardial perfusion defects, supporting the notion that those areas correspond to viable hypoperfused myocardium.

Neurohormonal benefits of Chronic Chagas’ Cardiomyopathy (CCC) remain controversial. This study aimed to assess therapeutic interventions on CCC evolution in T. cruzi -infected hamsters at pre and post-treatment (2 months with beta-blocker (CH + BB) or ACE inhibitor (CH + ACEI)). Echocardiography was performed through evolution and compared to histopathological myocardial analysis. At post-treatment, a significant reduction of LV global systolic function and segmental function was observed between the control group and all Chagas’ groups. Compared to the Control, a reduction in LV regional strain was observed in three LV segments, regardless of treatment. No differences were observed in apoptosis, myocardial fibrosis, and the number of inflammatory cells among the groups. In an experimental model of CCC, LV global and regional function is compromised, and the treatment with ACEi and BB did not change LV remodeling. Regional LV function was slightly better in animals treated with BB, and this difference was not observed in the CH + ACEi group.

Speckle tracking echocardiography (STE) enables early diagnosis of myocardial damage by evaluating myocardial strain. We aimed to study sequential changes in structural and ventricular functional parameters during Chagas disease (CD) natural history in an animal model. 37 Syrian hamsters were inoculated intraperitoneally with Trypanosoma cruzi (Chagas) and 20 with saline (Control). Echocardiography was performed before the infection (baseline), at 1 month (acute phase), 4, 6, and 8 months (chronic phase) using Vevo 2100 (Fujifilm Inc.) ultrasound system. Left ventricular end-diastolic diameter, Left ventricular end-systolic diameter (LVESD), Left ventricular ejection fraction (LVEF), Global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were evaluated. Tricuspid annular plane systolic excursion (TAPSE) was used to assess right ventricular function. At 8 months, animals were euthanized and LV myocardial samples were analyzed for quantitation of inflammation and fibrosis. LVEF decreased over time in Chagas group and a difference from Control was detected at 6 months (p-value of groups#time interaction = 0.005). There was a pronounced decrease in GLS, GCS and TAPSE in Chagas group (p-value of groups#time interaction = 0.003 for GLS, < 0.001 for GCS and < 0.009 for TAPSE vs Control) since the first month. LVESD, LVEF and GLS were significantly correlated to the number of inflammatory cells (r = 0.41, p = 0.046; r = − 0.42, p = 0.042; r = 0.41, p = 0.047) but not to fibrosis. In the Syrian hamster model of CD STE parameters (GLS and GCS) showed an early decrease. Changes in LVEF, LVESD, and GLS were correlated to myocardial inflammation but not to fibrosis.

Mandacaru ( Cereus jamacaru ) is a species of cactus known to possess various health-beneficial compounds, making it a viable option for consumption. However, to preserve these compounds during storage, appropriate techniques are necessary. Thus, the present study aimed to evaluate the effectiveness of hydrocooling as a preservation method on the quality and bioactive compounds of mandacaru. A completely randomized experimental design was adopted, in a factorial arrangement of 3 (no hydrocooling (control, hydrocooling at 30 °C, and at 60 °C) × 6 (storage times—0, 3, 6, 9, 12, and 15 days), with four replicates. Colorimetry, pulp firmness, soluble solids, pH, titratable acidity, firmness, total soluble sugars, and chlorophyll and carotenoid levels were evaluated. It was observed that the storage of mandacaru fruits resulted in significant changes in their physical and chemical characteristics over the analyzed period. Hydrocooling proved effective in improving some characteristics, such as sugar contents. However, even with this conservation technique, there was still a decrease observed in some properties over time.

IntroductionPost-COVID-19 conditions (PCC) may include pulmonary sequelae, fatigue and other symptoms, but its mechanisms are not fully elucidated.ObjectiveThis study investigated the correlation between fatigue and the presence of pulmonary abnormalities in PCC patients with respiratory involvement 6–12 months after hospitalisation.DesignCross-sectional study.SettingA tertiary hospital in Brazil.Participants315 patients, aged ≥18 years, were considered eligible based on SARS-CoV-2 infection confirmed by reverse transcription-PCR.MethodsPulmonary function tests (PFT), cardiopulmonary exercise tests (CPET), chest CT and hand grip were performed. The following scales were applied: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, Euroqol 5 Dimensions quality of life (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Participants were divided between the fatigue group (FACIT-F≤30) and the non-fatigue group (FACIT-F>30). For the statistical analysis, the primary outcome was the difference in the diffusing capacity of the lungs for carbon monoxide (DLCO) between groups. Considered secondary outcomes were differences in PFT, CPET, chest CT, hand grip, EQ-5D and HADS.ResultsThe fatigue group had 81 patients (25.7%) against 234 (74.3%). PFT and CPET showed no significant difference in DLCO and oxygen consumption peak values between groups. The fatigue group had a lower workload (mean 55.3±21.3 watts vs 66.5±23.2 watts, p=0.003), higher breathing reserve (median 41.9% (33.8–52.5) vs 37.7% (28.9–47.1), p=0.028) and lower prevalence of ground glass opacity (60.8% vs 77.7%, p=0.003) and reticulation (36.7% vs 54.9%, p=0.005) in chest CT. The fatigue group had higher anxiety (57% vs 24%, p<0.001), depression (50.6% vs 13.6%, p<0.001), lower health-related quality of life (median 50 (32–63) vs 80 (61.3–88.3), p<0.001) and lower hand grip strength (median 15.8 (6–21) kgf vs 21 (12.1–30) kgf, p<0.001).ConclusionFatigue in patients with PCC 6–12 months after hospitalisation is relatively common and had weak correlation with pulmonary disorders. Our results suggested fatigue could be strongly related with peripheral disorders such as reduced musculoskeletal strength or psychosocial limitations.

CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.

ObjectiveThis study aimed to propose a simple, accessible and low-cost predictive clinical model to detect lung lesions due to COVID-19 infection.DesignThis prospective cohort study included COVID-19 survivors hospitalised between 30 March 2020 and 31 August 2020 followed-up 6 months after hospital discharge. The pulmonary function was assessed using the modified Medical Research Council (mMRC) dyspnoea scale, oximetry (SpO2), spirometry (forced vital capacity (FVC)) and chest X-ray (CXR) during an in-person consultation. Patients with abnormalities in at least one of these parameters underwent chest CT. mMRC scale, SpO2, FVC and CXR findings were used to build a machine learning model for lung lesion detection on CT.SettingA tertiary hospital in Sao Paulo, Brazil.Participants749 eligible RT-PCR-confirmed SARS-CoV-2-infected patients aged ≥18 years.Primary outcome measureA predictive clinical model for lung lesion detection on chest CT.ResultsThere were 470 patients (63%) that had at least one sign of pulmonary involvement and were eligible for CT. Almost half of them (48%) had significant pulmonary abnormalities, including ground-glass opacities, parenchymal bands, reticulation, traction bronchiectasis and architectural distortion. The machine learning model, including the results of 257 patients with complete data on mMRC, SpO2, FVC, CXR and CT, accurately detected pulmonary lesions by the joint data of CXR, mMRC scale, SpO2 and FVC (sensitivity, 0.85±0.08; specificity, 0.70±0.06; F1-score, 0.79±0.06 and area under the curve, 0.80±0.07).ConclusionA predictive clinical model based on CXR, mMRC, oximetry and spirometry data can accurately screen patients with lung lesions after SARS-CoV-2 infection. Given that these examinations are highly accessible and low cost, this protocol can be automated and implemented in different countries for early detection of COVID-19 sequelae.

Kidney involvement appears to be frequent in coronavirus disease 2019 (COVID-19). Despite this, information concerning renal involvement in COVID-19 is still scarce. Several mechanisms appear to be involved in the complex relationship between the virus and the kidney. Also, different morphological patterns have been described in the kidneys of patients with COVID-19. For some authors, however, this association may be just a coincidence. To investigate this issue, we propose assessing renal morphology associated with COVID-19 at the renal pathology reference center of federal university hospitals in Brazil. Data will come from a consortium involving 17 federal university hospitals belonging to (EBSERH) network, as well as some state hospitals and an autopsy center. All biopsies will be sent to the referral center for renal pathology of the EBSERH network. The data will include patients who had coronavirus disease, both alive and deceased, with or without pre-existing kidney disease. Kidney biopsies will be analyzed by light, fluorescence, and electron microscopy. Furthermore, immunohistochemical (IHC) staining for various inflammatory cells (i.e., cells expressing CD3, CD20, CD4, CD8, CD138, CD68, and CD57) as well as angiotensin-converting enzyme 2 (ACE2) will be performed on paraffinized tissue sections. In addition to ultrastructural assays, hybridization (ISH), IHC and reverse transcription-polymerase chain reaction (RT-PCR) will be used to detect Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in renal tissue. For the patients diagnosed with Collapsing Glomerulopathy, peripheral blood will be collected for apolipoprotein L-1 (APOL1) genotyping. For patients with thrombotic microangiopathy, thrombospondin type 1 motif, member 13 (ADAMTS13), antiphospholipid, and complement panel will be performed. The setting of this study is Brazil, which is second behind the United States in highest confirmed cases and deaths. With this complete approach, we hope to help define the spectrum and impact, whether immediate or long-term, of kidney injury caused by SARS-CoV-2.