Association between BMI and Efficacy of SGLT2 Inhibitors in Patients with Heart Failure or at Risk of Heart Failure: A Meta-Analysis Based on Randomized Controlled Trials.

INTRODUCTION: This meta-analysis aimed to investigate the effect of SGLT2 inhibitors on the prognosis of patients with heart failure (HF) or at risk of HF across different body mass index (BMI). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials comparing SGLT2 inhibitors with placebo in patients with HF or at risk of HF and extracted relevant data up to April 2023 for meta-analysis. RESULTS: A total of 29,500 patients were enrolled in the selected five studies. The results showed that patients treated with SGLT2 inhibitors had lower HF hospitalization (HHF) or cardiovascular (CV) mortality compared to those taking placebo (hazard ratio [HR] = 0.73, p < 0.001). Patients taking SGLT2 inhibitors also had a lower all-cause mortality rate than those taking placebo (HR = 0.85, p = 0.017). In BMI subgroup analysis, the HHF rate in the experimental group was lower than that in the control group at BMI ≤24.9 kg/m2, 25.0-29.9 kg/m2, and ≥30.0 kg/m2. There was no significant difference in CV mortality between the two groups at BMI ≤24.9 kg/m2 (HR = 0.91, p = 0.331) and 25.0-29.9 kg/m2 (HR = 0.92, p = 0.307). However, when the BMI was ≥30.0 kg/m2, CV mortality with SGLT2 inhibitors was lower than in the control group (HR = 0.79, p = 0.002). When patients had a BMI ≤24.9 kg/m2 (HR = 0.85, p = 0.033) and 25.0-29.9 kg/m2 (HR = 0.83, p = 0.046), the all-cause mortality was lower in the experimental group than in the control group. However, there was no significant difference between the 2 groups in patients with a BMI ≥30.0 kg/m2 (HR = 0.87, p = 0.094). CONCLUSION: SGLT2 inhibitors improve the prognosis in patients with HF or at risk of HF. This effect is affected by BMI.

Development of a reporter gene assay for antibody dependent cellular cytotoxicity activity determination of anti-rabies virus glycoprotein antibodies.

Rabies is a viral disease that is nearly 100% fatal once clinical signs and symptoms develop. Post-exposure prophylaxis can efficiently prevent rabies, and antibody (Ab) induction by vaccination or passive immunization of human rabies immunoglobulin (HRIG) or monoclonal antibodies (mAbs) play an integral role in prevention against rabies. In addition to their capacity to neutralize viruses, antibodies exert their antiviral effects by antibody-dependent cellular cytotoxicity (ADCC), which plays an important role in antiviral immunity and clearance of viral infections. For antibodies against rabies virus (RABV), evaluation of ADCC activity was neglected. Here, we developed a robust cell-based reporter gene assay (RGA) for the determination of the ADCC activity of anti-RABV antibodies using CVS-N2c-293 cells, which stably express the glycoprotein (G) of RABV strain CVS-N2c as target cells, and Jurkat cells, which stably express FcγRⅢa and nuclear factor of activated T cells (NFAT) reporter gene as effector cells (Jurkat/NFAT-luc/FcγRⅢa cells). The experimental parameters were carefully optimized, and the established ADCC assay was systematically validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 guideline. We also evaluated the ADCC activity of anti-RABV antibodies, including mAbs, HRIG, and vaccine induced antisera, and found that all test antibodies exhibited ADCC activity with varied strengths. The established RGA provides a novel method for evaluating the ADCC of anti-RABV antibodies.

PD-1/L1 With or Without CTLA-4 Inhibitors Versus Chemotherapy in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. METHODS: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis's Prospero registration number is CRD42022323570. RESULTS: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. CONCLUSION: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.

Effect of HIV-1 Protease Inhibitor on IL-18 and IL-1ß in Rats with Insulinoma.

This study is aimed at investigating the treatment effectiveness of HIV-1 protease inhibitor for rats with insulinoma and its effects on interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). A total of 40 6-week-old nude mice were included in this study. We randomly assigned 20 rats for insulinoma modeling and divided them into model A and B groups. Another 20 rats were randomly divided into control A and B groups. Rats from the model A and control A groups were given HIV-1 protease inhibitors. The expression profiles of IL-18 and IL-1ß, clinical indicators, water maze test results, oxidative stress damage, and changes in neurological functions in rats from each group were recorded. The expression levels of IL-18 and IL-1ß, insulin level, the ratio of immunoreactive insulin to plasma glucose (IRI/G), escape latency, reactive oxygen species (ROS), and amyloid ß-protein (Aß) level were lower in the model A group than in the model B group while fasting blood glucose, platform crossing times, and superoxide dismutase (SOD) were higher in the model A group than in the model B group. The insulin level and hippocampus Aß level were lower in the control A group than in the control B group. In contrast, other indicators in the control A group were not significantly different from those in the model B group. HIV-1 protease inhibitor is effective in the treatment of insulinoma in rats. It can significantly reduce IL-18 and IL-1ß and protect the neurological functions in rats and has broad prospects for clinical application.

Assessment of Prophylactic Carbapenem Antibiotics Administration for Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. METHODS: This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. RESULTS: Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; p = 0.03) and complications (OR: 0.48; p = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; p = 0.24), mortality (OR: 0.69; p = 0.17), extrapancreatic infection (OR: 0.64, p = 0.54), pulmonary infection (OR: 1.23; p = 0.69), blood infection (OR: 0.60; p = 0.35), urinary tract infection (OR: 0.97; p = 0.97), pancreatic pseudocyst (OR: 0.59; p = 0.28), fluid collection (OR: 0.91; p = 0.76), organ failure (OR: 0.63; p = 0.19), acute respiratory distress syndrome (OR: 0.80; p = 0.61), surgical intervention (OR: 0.97; p = 0.93), dialysis (OR: 2.34; p = 0.57), use of respirator or ventilator (OR: 1.90; p = 0.40), intensive care unit treatment (OR: 2.97; p = 0.18), and additional antibiotics (OR: 0.59; p = 0.28) between the experimental and control groups. CONCLUSIONS: It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.