Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO/ROS imbalance.

Aims: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs).

Methods And Results: Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used.

Priors and decision thresholds in phase 2 and phase 3 randomized controlled trials evaluating drug efficacy using Bayesian methods: a systematic review.

Objective: To describe the priors and decision thresholds in phase 2 and 3 RCTs evaluating drug efficacy using Bayesian methods.

Study Design And Setting: A systematic review of phase 2 and 3 RCTs evaluating drug efficacy through Bayesian inference was conducted across the MEDLINE, EMBASE and Cochrane databases, with no date restrictions until September 2022. The type of prior used for the analysis of the primary endpoint and its characteristics (type and parameters of the distribution, justification, sensitivity analysis), the use of a posterior probability decision threshold defined a priori, and its value, were extracted.