Background Chronic Chagas Cardiomyopathy (CCM) is a unique form of cardiomyopathy compared to other etiologies of heart failure. In CCM, risk prediction based on biomarkers has not been well-studied. ...We assessed the prognostic value of a biomarker panel to predict a composite outcome (CO), including the need for heart transplantation, use of left ventricular assist devices, and mortality. Methods Prospective cohort study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Survival analyses were performed using Cox proportional hazard models. Results During a median follow-up of 52 months, the mortality rate was 20%, while the CO was observed in 25% of the patients. Four biomarkers (NT-proBNP, hs-cTnT, sST2, and Cys-C) were associated with the CO; concentrations of NT-proBNP and hs-cTnT were associated with the highest AUC (85.1 and 85.8, respectively). Combining these two biomarkers above their selected cut-off values significantly increased risk for the CO (HR 3.18; 95%CI 1.31-7.79). No events were reported in the patients in whom the two biomarkers were under the cut-off values, and when both levels were above cut-off values, the CO was observed in 60.71%. Conclusion The combination of NT-proBNP and hs-TnT above their selected cut-off values is associated with a 3-fold increase in the risk of the composite outcome among CCM patients. The use of cardiac biomarkers may improve prognostic evaluation of patients with CCM.
Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these approaches is the use of lytic ...bacterial viruses known as phage therapy. We aimed to assess the efficacy of phage therapy in preclinical animal models of bacterial infection.
In this systematic review and meta-analysis, MEDLINE/Ovid, Embase/Ovid, CINAHL/EbscoHOST, Web of Science/Wiley, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar were searched from inception to Sept 30, 2021. Studies assessing phage efficacy in animal models were included. Only studies that assessed the efficacy of phage therapy in treating established bacterial infections in terms of survival and bacterial abundance or density were included. Studies reporting only in-vitro or ex-vivo results and those with incomplete information were excluded. Risk-of-bias assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation tool. The main endpoints were animal survival and tissue bacterial burden, which were reported using pooled odds ratios (ORs) and mean differences with random-effects models. The I2 measure and its 95% CI were also calculated. This study is registered with PROSPERO, CRD42022311309.
Of the 5084 references screened, 124 studies fulfilled the selection criteria. Risk of bias was high for 70 (56%) of the 124 included studies; therefore, only studies classified as having a low-to-moderate risk of bias were considered for quantitative data synthesis (n=32). Phage therapy was associated with significantly improved survival at 24 h in systemic infection models (OR 0·08 95% CI 0·03 to 0·20; I2=55% 95% CI 8 to 77), skin infection (OR 0·08 0·04 to 0·19; I2 = 0% 0 to 79), and pneumonia models (OR 0·13 0·06 to 0·31; I2=0% 0 to 68) when compared with placebo. Animals with skin infections (mean difference –2·66 95% CI –3·17 to –2·16; I2 = 95% 90 to 96) and those with pneumonia (mean difference –3·35 –6·00 to –0·69; I2 = 99% 98 to 99) treated with phage therapy had significantly lower tissue bacterial loads at 5 ± 2 days of follow-up compared with placebo.
Phage therapy significantly improved animal survival and reduced organ bacterial loads compared with placebo in preclinical animal models. However, high heterogeneity was observed in some comparisons. More evidence is needed to identify the factors influencing phage therapy performance to improve future clinical application.
Swiss National Foundation and Swiss Heart Foundation.
BackgroundChronic Chagas Cardiomyopathy (CCM) is a unique form of cardiomyopathy compared to other etiologies of heart failure. In CCM, risk prediction based on biomarkers has not been well-studied. ...We assessed the prognostic value of a biomarker panel to predict a composite outcome (CO), including the need for heart transplantation, use of left ventricular assist devices, and mortality.MethodsProspective cohort study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Survival analyses were performed using Cox proportional hazard models.ResultsDuring a median follow-up of 52 months, the mortality rate was 20%, while the CO was observed in 25% of the patients. Four biomarkers (NT-proBNP, hs-cTnT, sST2, and Cys-C) were associated with the CO; concentrations of NT-proBNP and hs-cTnT were associated with the highest AUC (85.1 and 85.8, respectively). Combining these two biomarkers above their selected cut-off values significantly increased risk for the CO (HR 3.18; 95%CI 1.31-7.79). No events were reported in the patients in whom the two biomarkers were under the cut-off values, and when both levels were above cut-off values, the CO was observed in 60.71%.ConclusionThe combination of NT-proBNP and hs-TnT above their selected cut-off values is associated with a 3-fold increase in the risk of the composite outcome among CCM patients. The use of cardiac biomarkers may improve prognostic evaluation of patients with CCM.
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