Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas

Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)     

Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile

Digestive Diseases and Sciences - Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT)...     

Objectively‐measured sleep and its association with adiposity and physical activity in a sample of Canadian children

Cross‐sectional associations between objectively‐measured sleep duration, sleep efficiency and sleep timing with adiposity and physical activity were examined in a cohort of 567 children from Ottawa, Canada. Five‐hundred and fifteen children (58.8% female; age: 10.0 ± 0.4 years) had valid sleep measurements and were included in the present analyses. Physical activity, sedentary time and sleep parameters were assessed over 7 days (actigraphy). Height, weight and waist circumference were measured according to standardized procedures. Percentage body fat was assessed using bioelectric impedance analysis. Light physical activity and sedentary time were greater in children with the shortest sleep durations (P < 0.0001), whereas children with the highest sleep efficiencies had lower light physical activity and more sedentary time across tertiles (P < 0.0001). In multivariable linear regression analyses, and after adjusting for a number of covariates, sleep efficiency was inversely related to all adiposity indices (P < 0.05). However, sleep duration and sleep timing were not associated with adiposity indices after controlling for covariates. Inverse associations were noted between sleep duration and light physical activity and sedentary time (P < 0.0001). Sleep efficiency (P < 0.0001), wake time and sleep timing midpoint (P < 0.05) were negatively associated with light physical activity, but positively associated with sedentary time. In conclusion, only sleep efficiency was independently correlated with adiposity in this sample of children. Participants with the shortest sleep durations or highest sleep efficiencies had greater sedentary time. More research is needed to develop better sleep recommendations in children that are based on objective measures of sleep duration, sleep efficiency and sleep timing alike.     

Comparative Efficacies and Tolerabilities of Intravenous Azithromycin Plus Ceftriaxone and Intravenous Levofloxacin with Step-Down Oral Therapy for Hospitalized Patients with Moderate to Severe Community-Acquired Pneumonia

Objective: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP). Design: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting. Patients: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V. Interventions: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500mg daily or IV levofloxacin 500mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician’s discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented. Results: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI ?7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI ?6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin. Conclusions: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.     

Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule

Many factors have been shown to promote myelination, but few have been shown to be inhibitory. Here, we show that polysialylated-neural cell adhesion molecule (PSA-NCAM) can negatively regulate myelin formation. During development, PSA-NCAM is first expressed on all growing fibers; then, axonal expression is down-regulated and myelin deposition occurs only on PSA-NCAM-negative axons. Similarly, in cocultures of oligodendrocytes and neurons, PSA-NCAM expression on axons is initially high, but decreases as myelination proceeds. Importantly, if expression of PSA-NCAM is prematurely decreased in cultures, by either antibody-mediated internalization or enzymatic removal of the PSA moieties with endoneuraminidase N (endo-N), myelination increases 4- to 5-fold. In the optic nerve, premature cleavage of PSA moieties by intravitreous injection of endo-N also induces a transient increase in the number of myelinated internodes, but does not interfere with the onset of myelination. Previously, we showed that axonal electrical activity strongly induced myelination, which could be prevented by tetrodotoxin (TTX), an action potential blocker. Interestingly, removal of PSA moieties does not reverse the inhibition of myelination by TTX. Together, this suggests that myelination is tightly controlled by both positive (electrical activity) and negative (PSA-NCAM expression) regulatory signals.