The role of circulating biomarkers in predicting the 30-day mortality of immune checkpoint inhibitors-related myocarditis: a retrospective cohort study.

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.

Screening and Bioinformatics Analysis of Crucial Gene of Heart Failure and Atrial Fibrillation Based on GEO Database.

Background and objectives: In clinical practice, we observed that the prognoses of patients with heart failure and atrial fibrillation were worse than those of patients with only heart failure or atrial fibrillation. The study aims to get a better understanding of the common pathogenesis of the two diseases and find new therapeutic targets. Materials and Methods: We downloaded heart failure datasets and atrial fibrillation datasets from the gene expression omnibus database. The common DEGs (differentially expressed genes) in heart failure and atrial fibrillation were identified by a series of bioinformatics methods. To better understand the functions and possible pathways of DEGs, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We identified 22 up-regulated genes and 14 down-regulated genes in two datasets of heart failure and 475 up-regulated and 110 down-regulated genes in atrial fibrillation datasets. In addition, two co-upregulated (FRZB, SFRP4) and three co-downregulated genes (ENTPPL, AQP4, C1orf105) were identified. GO enrichment results showed that these common differentially expressed genes were mainly concentrated in the signal regulation of the Wnt pathway. Conclusions: We found five crucial genes in heart failure and atrial fibrillation, which may be potential therapeutic targets for patients with heart failure and atrial fibrillation.

A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/ß-TrCP/NRF2 Pathway.

Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/ß-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.