A novel model for predicting a composite outcome of major complications after valve surgery.

Background: On-pump valve surgeries are associated with high morbidity and mortality. The present study aimed to reliably predict a composite outcome of postoperative complications using a minimum of easily accessible clinical parameters. Methods: A total of 7,441 patients who underwent valve surgery were retrospectively analyzed. Data for 6,220 patients at West China Hospital of Sichuan University were used to develop a predictive model, which was validated using data from 1,221 patients at the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary outcome was a composite of major complications: all-cause death in hospital, stroke, myocardial infarction, and severe acute kidney injury. The predictive model was constructed using the least absolute shrinkage and selection operator as well as multivariable logistic regression. The model was assessed in terms of the areas under receiver operating characteristic curves, calibration, and decision curve analysis. Results: The primary outcome occurred in 129 patients (2.1%) in the development cohort and 71 (5.8%) in the validation cohort. Six variables were retained in the predictive model: New York Heart Association class, diabetes, glucose, blood urea nitrogen, operation time, and red blood cell transfusion during surgery. The C-statistics were 0.735 (95% CI, 0.686-0.784) in the development cohort and 0.761 (95% CI, 0.694-0.828) in the validation cohort. For both cohorts, calibration plots showed good agreement between predicted and actual observations, and ecision curve analysis showed clinical usefulness. In contrast, the well-established SinoSCORE did not accurately predict the primary outcome in either cohort. Conclusions: This predictive nomogram based on six easily accessible variables may serve as an "early warning" system to identify patients at high risk of major complications after valve surgery. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04476134].

Palmitic acid methyl ester induces cardiac hypertrophy through activating the GPR receptor-mediated changes of intracellular calcium concentrations and mitochondrial functions.

Myocardial hypertrophy is associated with a significant increase in intracellular Ca2+ , which can be induced by long-chain fatty acid. Palmitic acid methyl ester (PAME), a fatty acid ester released from adipose tissue, superior cervical ganglion, and retina, has been found to have anti-inflammation, antifibrosis, and peripheral vasodilation effects. However, the effects of PAME on cardiomyocytes are still unclear. The aim of this study was to determine whether PAME could disrupt the intracellular Ca2+ balance, leading to cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were treated with various concentrations (10-100 µM) of PAME for 1-4 days. Cytosolic Ca2+ and mitochondrial Ca2+ concentrations were examined using Fura-2 AM and Rhod-2, respectively. After treatment with PAME for 4 days, mitochondrial Ca2+ , an indicator of the state of mitochondrial permeability transition pore (MPTP), and cell death were monitored by flow cytometric analysis. ATP levels were detected using the ATP assay kit. Cardiomyocyte hypertrophy was analyzed by measuring the cardiac hypertrophy biomarker and cell area using quantitative real time-polymerase chain reaction, Western Blot analysis and immunofluorescence analysis. Our results show that PAME concentration- and time-dependently increased cytosolic and mitochondria Ca2+ through the mitochondrial calcium uniporter. Moreover, treatment with PAME for 4 days caused MPTP opening, thereby reducing ATP production and enhancing reactive oxygen species (ROS) generation, and finally led to cardiomyocyte hypertrophy. These effects caused by PAME treatment were attenuated by the G-protein coupled receptor 40 (GPR40) inhibitor. In conclusion, PAME impaired mitochondrial function, which in turn led to cardiomyocyte hypertrophy through increasing the mitochondrial Ca2+ levels mediated by activating the GPR40 signaling pathway.

Comparative effects of different types of cardioplegia in cardiac surgery: A network meta-analysis.

Objective: To compare the outcomes of four types of cardioplegia during cardiac surgery: del Nido (DN), blood cardioplegia (BC), histidine-tryptophan-ketoglutarate (HTK) and St. Thomas. Methods: Randomized controlled trials (RCTs) and observational cohort studies from 2005 to 2021 were identified in PubMed, Embase, and Cochrane databases. Data were extracted for the primary endpoint of perioperative mortality as well as the following secondary endpoints: atrial fibrillation, renal failure, stroke, use of an intra-aortic balloon pump, re-exploration, intensive care unit stay and hospital stay. A network meta-analysis comparing all four types of cardioplegia was performed, as well as direct meta-analysis comparing pairs of cardioplegia types. Results: Data were extracted from 18 RCTs and 49 observational cohort studies involving 18,191 adult patients (55 studies) and 1,634 children (12 studies). Among adult patients, risk of mortality was significantly higher for HTK (1.89, 95% CI 1.10, 3.52) and BC (RR 1.73, 95% CI 1.22, 2.79) than for DN. Risk of atrial fibrillation was significantly higher for BC (RR 1.41, 95% CI 1.09, 1.86) and DN (RR 1.51, 95% CI 1.15, 2.03) than for HTK. Among pediatric patients, no significant differences in endpoints were observed among the four types of cardioplegia. Conclusions: This network meta-analysis suggests that among adult patients undergoing cardiac surgery, DN may be associated with lower perioperative mortality than HTK or BC, while risk of atrial fibrillation may be lower with HTK than with BC or DN.

The nomograms to predict early death among metastatic small-cell lung cancer patients: a retrospective study based on SEER database.

Background: This study aims to discriminate risk factors associated with early death (died within 3 months) in metastatic small-cell lung cancer (SCLC) patients, and construct predictive nomograms to help physicians in guiding individual treatment. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to obtain records of deceased metastatic SCLC patients. The univariate and multivariate logistic regression methods were managed to identify risk factors for early death in overall patients and chemotherapy recipients. Predictive nomograms were developed and then validated by receiver operating characteristics curve (ROC) and calibration plots to verify its' precision. Results: A total of 13,229 patients were collected of which 5,832 of them encountered early death. The univariate and multivariate logistic regression analysis identified variables that were negatively associated with early death include sex, age, race, sequence, T stage, N stage, organ metastasis. Chemotherapy and radiotherapy implementation significantly decreased the odds of early death. For the chemotherapy recipients, white male patients with advanced age (over 80 years old), T4 stage, multiple organ metastasis, and without radiotherapy most likely died within 3 months. The area under the curve (AUC) of the nomograms for overall population and chemotherapy recipients' early death prediction was 0.839 and 0.653. Conclusions: Early death among metastatic SCLC patients was extremely common in clinical practice. The nomograms constructed were able to assist clinical physicians in discriminating high-risk SCLC patients for targeted intervention, and elderly white male patients diagnosed with advanced T stage and multiple organ metastasis might be exempted from systemic treatment to receive palliative care.

Genetics of the glutamate-mediated methylamine utilization pathway in the facultative methylotrophic beta-proteobacterium Methyloversatilis universalis FAM5.

The ability of some microbial species to oxidize monomethylamine via glutamate-mediated pathways was proposed in the 1960s; however, genetic determinants of the pathways have never been described. In the present study we describe a gene cluster essential for operation of the N-methylglutamate pathway in the methylotrophic beta-proteobacterium Methyloversatilis universalis FAM5. Four major polypeptides from protein fractions displaying high activities of N-methylglutamate synthetase, N-methylglutamate dehydrogenase and gamma-glutamylmethylamide synthetase were selected for mass spectrometry-based identification. The activities of enzymes were associated with the presence of peptides identified as ferredoxin-dependent glutamate synthase (GltB2), large subunit of putative heterotetrameric sarcosine oxidase (SoxA) and glutamine synthetase type III (GSIII) respectively. A gene cluster (8.3 kb) harbouring gltB2, soxA and gsIII-like genes was amplified from M. universalis FAM5, sequenced and assembled. Two partial and six complete open reading frames arranged in the order soxBDAG-gsIII-gltB132 were identified and subjected to mutational analysis, functional and metabolic profiling. We demonstrated that gltB-like and sox-like genes play a key role in methylamine utilization and encode N-methylglutamate synthetase and N-methylglutamate dehydrogenase respectively. Metabolic, enzymatic and mutational analyses showed that the gsIII-like gene encodes gamma-glutamylmethylamide synthetase; however, this enzyme is not essential for oxidation of methylamine.