Lung adenocarcinoma (LUAD) shows marked outcome heterogeneity within clinicopathological stage groups. This study developed and externally validated a ferroptosis-linked transcriptomic risk model using a leakage-controlled multi- cohort survival-learning framework and characterized its immune context.

Background and Objectives: The modified Glasgow Prognostic Score (mGPS)-a composite of serum C-reactive protein (CRP) and albumin-simultaneously reflects systemic inflammatory activity and nutritional reserve. Its specific prognostic role in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab in the second-line setting has not previously been examined in a large multicentre cohort. The aims of this study are to determine whether baseline mGPS independently predicts overall survival (OS) and progression-free survival (PFS) in this population and whether its discriminatory capacity compares favourably with the International Metastatic RCC Database Consortium (IMDC) risk score. Methods: This multicentre retrospective cohort study included 174 consecutive patients with histopathologically confirmed mRCC who progressed on first-line VEGF-targeted tyrosine kinase inhibitor (TKI) therapy and subsequently received nivolumab monotherapy at six oncology centres in Türkiye between January 2015 and December 2023. Baseline mGPS was calculated from serum albumin and CRP measured within four weeks before treatment initiation. Kaplan-Meier analysis with log-rank testing and Cox proportional-hazards regression were used for survival analyses; discriminatory capacity was quantified using Uno's concordance (C) statistic. Results: The median follow-up was 24.2 months. The median OS was 44.5, 15.3, and 10.0 months for the mGPS 0, 1, and 2 groups, respectively (log-rank p < 0.0001); the median PFS was 6.7, 4.2, and 2.6 months (p = 0.022). On multivariable analysis, mGPS 2 independently predicted inferior OS (hazard ratio [HR] 3.61, 95% confidence interval [CI] 1.78-7.31; p < 0.001) and PFS (HR 1.87, 95% CI 1.17-2.97; p = 0.008). Uno's C-statistic for OS was numerically higher for the combined mGPS + IMDC model (0.70) than for either the mGPS (0.66) or IMDC (0.63) alone; these differences were not formally tested and are presented descriptively. Conclusions: Baseline mGPS is a simple, inexpensive, and independent prognostic biomarker in mRCC patients treated with second-line nivolumab, providing discriminatory information that may be complementary alongside IMDC risk stratification. Prospective validation in randomised trials is warranted.

Introduction: Changes in the United Network for Organ Sharing (UNOS) allocation system, coupled with declining donor availability, have contributed to a rising proportion of durable left ventricular assist device (LVAD) implantations, particularly among patients with prior cardiac surgeries and those requiring multiple concomitant intracardiac procedures. As the complexity of LVAD candidates increases, understanding peri/postoperative determinants of survival becomes critical. We sought to identify risk factors associated with short- and long-term mortality following LVAD implantation. Methods: We analyzed 22,467 adults (18-80 years) who underwent LVAD implantation between January 2013 and June 2023 using data from the INTERMACS registry. A FasterRisk-derived risk score was developed for 90-day mortality prediction, and a Cox proportional hazards model was constructed to evaluate long-term post-implant survival. Results: Predictors of 90-day mortality included advanced age, preoperative extracorporeal membrane oxygenation (ECMO), LVAD exchange, prior cardiac surgery, and concomitant surgery. A 90-day mortality score incorporating pre-implant ECMO, prior cardiac surgery, concomitant surgery, and age demonstrated c-statistic 0.69 in training and 0.67 in testing. The Cox regression model identified advanced age, preoperative ECMO, previous cardiac surgery, planned concomitant RVAD, concomitant surgery, IABP, CVA and postoperative dialysis as significant predictors of long-term mortality (c-index 0.72 training; 0.70 testing). Conclusions: A cross-validated machine learning-based risk model for 90-day mortality following LVAD implantation and a Cox regression model for long-term survival may support improved risk stratification and perioperative management in LVAD patients.

Early liver transplantation (LT) is increasingly being adopted as a treatment for alcohol-associated hepatitis (AAH), but the optimal strategy for incorporating AAH into the existing organ allocation framework remains unclear. This retrospective cohort study used the United Network for Organ Sharing database (January 1, 2018 to December 31, 2024) to compare adults waitlisted for first-time, single-organ LT for AAH with those with other alcohol-associated liver disease (ALD) and non-ALD. During the study period, waitlisting and LT for AAH increased more than 6-fold, with 98.2% of centers performing LT for this indication. Compared with other ALD and non-ALD, patients with AAH experienced lower waitlist mortality (8.2% vs. 12.6% and 19.3%, respectively; p <0.001) and higher LT rates (81.2% vs. 69.0% and 67.0%, respectively; p <0.001). After adjusting for clinical and demographic characteristics for patients on the initial waitlist application, both other ALD and non-ALD were associated with higher waitlist mortality relative to AAH (adjusted HR=1.23 with p =0.003 and adjusted HR=1.86 with p <0.001, respectively). Among patients with AAH, waitlist mortality was not associated with MELD scores <40 (p =0.66). Across all MELD categories, non-ALD was associated with higher waitlist mortality than AAH (HR 1.83-3.23; all p ≤0.005), while other ALD was associated with higher mortality in most MELD strata (p <0.05 at MELD 20-24 and ≥30). Of individual MELD components, serum sodium was not associated with AAH waitlist mortality (HR=1.01; p =0.53), while international normalized ratio was a stronger predictor of mortality in AAH than other LT indications (HR=1.95 for AAH vs. HR=1.14 for other ALD vs. HR=1.23 for non-ALD; all p <0.001). Patients with AAH are disproportionately prioritized under the current organ allocation system, underscoring the need to revise the allocation practices to ensure equitable LT access.

Organs from donors with positive blood cultures (BCx) have been shown to increase the risk of donor-derived infections. However, the percentage of BCx positivity in donors remains uncertain.