Anyi Xu

Background According to previous studies, the efficacy of xanthine oxidase inhibitors (XOIs) in patients with chronic heart failure (CHF) is still controversial. Therefore, the purpose of this study was to investigate the efficacy of XOIs in patients with CHF. Methods Up to July 2024, we searched PubMed, EMBASE, Medline, Web of Science, and Cochrane Library for studies on the efficacy of XOI in patients with CHF. The main results included all-cause mortality, cardiovascular (CV) mortality, and heart failure (HF) hospitalization rates. The results were evaluated by hazard ratio (HR) and 95% confidence interval (95% CI). Results A total of eight studies were included in this meta-analysis, of which five were cohort studies and three were randomized controlled trials (RCTs). The total sample size was 301,345. The experimental group was exposed to allopurinol or hydroxypurinol. The all-cause mortality (HR = 1.26, 95% CI 1.05–1.51, p = 0.013) and CV mortality (HR = 1.58, 95% CI 1.17–2.14, p = 0.03) in the experimental group were higher than those in the control group. In terms of HF hospitalization, there was no difference between both groups (HR = 1.21, p = 0.292). Subgroup analysis showed that the CV hospitalization rate of the experimental group was higher than that of the control group, regardless of frequency and dose levels. The all-cause mortality in the low-dose group was higher than that in the control group (HR = 1.39, p = 0.033). The CV mortality of the low-dose group (HR = 1.55, p = 0.006) and the prevalent group (HR = 1.50, p = 0.042) was higher than that of the control group. Conclusion Purine XOI exposure may be unfavorable for the prognosis of CHF patients and is affected by the frequency and dose of use.

Background: This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC). Methods: Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival. Results: A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04). Conclusions: This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.

Background This study aims to investigate the effect of PD-1/PD-L1 immunotherapy on cardiac-related adverse events in patients with advanced or metastatic lung cancer. Methods We conducted a detailed search in PubMed, Web of Science, Cochran, and Embase for articles on the application of immunotherapy for lung cancer and report cardiac-related adverse events with respect to myocardial ischemia, pericardial effusion, myocarditis, and electrophysiology. The dichotomous variables were assessed by relative risk (RR) and 95% confidence intervals (CI). Results A total of 7132 subjects were included in 12 phase III randomized controlled trials (RCTs). The results showed that under the fixed effects model, the probability of cardiac-related adverse events in pericardial effusion was higher in the experimental group than in the control group (RR 2.30, 95% CI 1.01–5.21, P = 0.05). Under the random effects model, there was no statistical difference between the two groups (RR 2.03, 95% CI 0.81–5.12, P = 0.13). No statistical difference is observed between the experimental group and the control group (under the fixed effects model and the random effects model) for other cardiac-related adverse events, including myocarditis, acute coronary syndrome, myocardial infarction, acute myocardial infarction, myocardial ischemia, unstable angina, ventricular tachycardia, supraventricular tachycardia, tachycardia, bradycardia, atrial flutter, atrial fibrillation, cardiac failure, cardiac arrest, cardiopulmonary failure, acute heart failure, cardiac arrest (all P > 0.05). Conclusions PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer is generally safe for cardiac-related adverse events.