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Summary: The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accuracy, which was similar for diabetics and nondiabetics. Notably, direct NHE1 blockade by empagliflozin ameliorated cardiomyocyte cell death by restoring expression of X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing protein 5 (BIRC5). These results were independent of diabetes mellitus comorbidity, suggesting that empagliflozin may emerge as a new treatment in HFrEF. Key Words: empagliflozin, heart failure, machine learning

Myocardial infarction (MI) remains a dreadful disease around the world, causing irreversible sequelae that shorten life expectancy and reduce quality of life despite current treatment. Here, the authors engineered a cell-enriched myocardial graft, composed of a decellularized myocardial matrix refilled with adipose tissue-derived progenitor cells (EMG-ATDPC). Once applied over the infarcted area in the swine MI model, the EMG-ATDPC improved cardiac function, reduced infarct size, attenuated fibrosis progression, and promoted neovascularization of the ischemic myocardium. The beneficial effects exerted by the EMG-ATDPC and the absence of identified adverse side effects should facilitate its clinical translation as a novel MI therapy in humans.

Objectives: The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia., Methods: We performed a severity matched case-control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed., Results: Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9-20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65-4.07; p < 0.001)., Discussion: Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk., (Copyright © 2021. Published by Elsevier Ltd.)

Although bloodstream infection (BSI) is a major cause of mortality after solid organ transplantation, information regarding its prognostic factors is scarce. To identify risk factors for 30-day mortality in solid organ transplant (SOT) recipients with BSI, we prospectively recorded all episodes of BSI occurring in adult SOT recipients from January 2007 to October 2014 at a university hospital. We identified 361 consecutive episodes of BSI involving 246 patients. The 30-day case-fatality rate from the onset of BSI was 11.4%. Factors independently associated with 30-day mortality in a logistic regression analysis were shock at presentation (OR 13.658; 95% CI 5.985-31.168), acute graft rejection in the previous 6 months (OR 3.681; 95% CI 1.059-12.795), and a platelet count of <50,000 × 10(9)/L (OR 3.070; 95% CI 1.173-8.038). Kidney recipients were the patients with the best prognosis (OR 0.375; 95% CI 0.156-0.900). Our findings may help to identify SOT recipients with BSI who are at the highest risk of death., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)