Myocardial injury determination improves risk stratification and predicts mortality in COVID-19 patients

Background: Despite being associated with worse prognosis in patients with COVID-19, systematic determination of myocardial injury is not recommended. The aim of the study was to study the effect of myocardial injury assessment on risk stratification of COVID-19 patients.Methods: Seven hundred seven consecutive adult patients admitted to a large tertiary hospital with confirmed COVID-19 were included. Demographic data, comorbidities, laboratory results and clinical outcomes were recorded. Charlson comorbidity index (CCI) was calculated in order to quantify the degree of comorbidities. Independent association of cardiac troponin I (cTnI) increase with outcomes was evaluated by multivariate regression analyses and area under curve. In addition, propensity-score matching was performed to assemble a cohort of patients with similar baseline characteristics.Results: In the matched cohort (mean age 66.76 ± 15.7 years, 37.3% females), cTnI increase above the upper limit was present in 20.9% of the population and was associated with worse clinical outcomes, including all-cause mortality within 30 days (45.1% vs. 23.2%; p = 0.005). The addition of cTnI to a multivariate prediction model showed a significant improvement in the area under the time-dependent receiver operating characteristic curve (0.775 vs. 0.756, DC-statistic = 0.019; 95% confidence interval 0.001–0.037). Use of renin–angiotensin–aldosterone system inhibitors was not associated with mortality after adjusting by baseline risk factors.Conclusions: Myocardial injury is independently associated with adverse outcomes irrespective of baseline comorbidities and its addition to multivariate regression models significantly improves their performance in predicting mortality. The determination of myocardial injury biomarkers on hospital admission and its combination with CCI can classify patients in three risk groups (high, intermediate and low) with a clearly distinct 30-day mortality

Novel purine chemotypes with activity against Plasmodium 2 falciparum and Trypanosoma cruzi

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.SAF2016-76080-R (Spanish Ministry of Economy (AEI/FEDER, UE))PID2019-110810RB-I00 (Spanish Ministry of Science and Innovation)Generalitat of Catalonia Universities and Research Department, Spain (AGAUR; 2017SGR00924)Carlos III Health Institute (ISCIII)RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD12/0018/0010)Generalitat of Catalonia Department of Health (PERIS 2016–2010 SLT008/18/00132)Spanish Ministry of Education, Culture, and Sports (FPU grant ref. 14/00818)Spanish Ministry of Science, Innovation, and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S)CERCA Progra