PDE5A-Positive Cancer-Associated Fibroblasts Drive Immune Exclusion in Gastric Cancer — Therapeutic Rationale for Combining PDE5 Inhibition with LAG3 Blockade
Posted inGastroenterology news Oncology

PDE5A-Positive Cancer-Associated Fibroblasts Drive Immune Exclusion in Gastric Cancer — Therapeutic Rationale for Combining PDE5 Inhibition with LAG3 Blockade

Single‑cell and spatial profiling identify a PDE5A+ CAF subset that remodels stroma, activates PI3K/AKT/mTOR–CXCL12 signaling, and recruits exhausted LAG3+ CD8 T cells, promoting immune exclusion in gastric cancer. Vardenafil plus LAG3 blockade restores antitumour immunity in preclinical models, supporting biomarker‑driven combination trials.
GLP‑1 Receptor Agonists Provide Greatest MACE Reduction in Type 2 Diabetes — Evidence from a Large US Comparative-Effectiveness Study
Posted inCardiology Diabetes & Endocrinology news

GLP‑1 Receptor Agonists Provide Greatest MACE Reduction in Type 2 Diabetes — Evidence from a Large US Comparative-Effectiveness Study

In a 241,981-patient emulated trial using modern causal methods, sustained GLP‑1RA use yielded the lowest 2.5‑year MACE risk, followed by SGLT2is, sulfonylureas, and DPP4is; the GLP‑1RA advantage over SGLT2is was greatest in older adults and those with ASCVD, HF, or kidney impairment.
Baseline SGLT2 Inhibitor Use Associated with Lower Risk of Sepsis-Induced Cardiomyopathy and Improved Outcomes in Type 2 Diabetes: Insights from a Large Propensity-Matched Cohort
Posted inCardiology Critical Care news

Baseline SGLT2 Inhibitor Use Associated with Lower Risk of Sepsis-Induced Cardiomyopathy and Improved Outcomes in Type 2 Diabetes: Insights from a Large Propensity-Matched Cohort

A large propensity-matched cohort study found that baseline SGLT2 inhibitor use versus DPP4 inhibitor therapy in adults with type 2 diabetes and infection was associated with lower 30-day sepsis-induced cardiomyopathy and improved 1-year mortality and cardiovascular outcomes; residual confounding and safety considerations warrant prospective trials.
Peginterferon Add‑On to siRNA JNJ‑73763989 Yields Deep HBsAg Declines but Not Durable Off‑Therapy Cure in HBeAg‑Positive CHB: Phase 2 REEF‑IT Results
Posted inGastroenterology Infectious Diseases news

Peginterferon Add‑On to siRNA JNJ‑73763989 Yields Deep HBsAg Declines but Not Durable Off‑Therapy Cure in HBeAg‑Positive CHB: Phase 2 REEF‑IT Results

In the phase 2 REEF‑IT trial, pegylated interferon‑α2a added to siRNA JNJ‑73763989 produced large HBsAg reductions and transient seroclearance in some untreated HBeAg‑positive patients, but no participant reached the prespecified sustained off‑therapy HBsAg loss endpoint at 24 weeks.
Not All ‘Indeterminate’ HBV Is Equal: Specific Indeterminate Types Carry Markedly Higher Long‑Term HCC Risk
Posted inGastroenterology Infectious Diseases news

Not All ‘Indeterminate’ HBV Is Equal: Specific Indeterminate Types Carry Markedly Higher Long‑Term HCC Risk

A multinational cohort study of 1,986 patients with indeterminate chronic hepatitis B (CHB) shows large differences in long‑term hepatocellular carcinoma (HCC) risk by baseline indeterminate subtype and by phase transition, identifying subgroups that may benefit from earlier antiviral therapy and intensified surveillance.
Immune-related adverse events strongly predict early graft rejection after liver transplant in HCC patients treated with checkpoint inhibitors
Posted inGastroenterology news Oncology Transplantation

Immune-related adverse events strongly predict early graft rejection after liver transplant in HCC patients treated with checkpoint inhibitors

A multicentre retrospective cohort found that pretransplant immune-related adverse events (irAEs) markedly increase the risk of early liver allograft rejection after liver transplantation for hepatocellular carcinoma (HCC). IrAEs, short ICI washout, and younger recipient age were independent predictors.
Lactate Predicts Citrate Accumulation During Continuous Kidney Replacement Therapy: incidence, severity, and clinical implications
Posted inCritical Care Nephrology news

Lactate Predicts Citrate Accumulation During Continuous Kidney Replacement Therapy: incidence, severity, and clinical implications

In 911 critically ill patients on RCA-CKRT, citrate accumulation occurred in 17%. Pre-CKRT lactate strongly predicted accumulation (OR 2.34 per 1-unit increase on log scale); VIS was less discriminatory. Accumulation linked to liver dysfunction but not to shock and—after adjustment—did not increase mortality.