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Importance Accurate prediction of patient mortality after kidney transplant is an unmet need. Objective To develop and validate an integrative prediction model that predicts short- and long-term patient mortality for kidney recipients. Design, Setting, and Participants This international cohort study included patients who underwent transplants between 2004 and 2023 from 14 academic medical centers from Europe and the US. The derivation cohort consisted of 1566 consecutive adult kidney recipients in a deeply phenotyped cohort prospectively recruited in 1 French center between 2004 and 2014. External validation cohorts consisted of 10 951 kidney recipients from 7 centers in France, 3 centers in Europe, and 3 centers in North America who underwent kidney transplants between 2006 and 2023. Data were analyzed from January 2023 to June 2025. Main Outcome and Measures All-cause mortality was assessed, and 121 candidate prognostic factors, comprising demographics and clinical, biological, imaging, and immunological parameters, were collected. Results Among 12 517 kidney transplant recipients, including 1566 in the derivation cohort (mean [SD] age, 50.05 [14.31] years; 942 male [60.15%]) and 10 951 in validation cohorts (mean [SD] age, 53.32 [13.97] years; 6766 male [61.78%]), 2486 patients (19.9%) died after a median (IQR) follow-up of 5.08 (2.97-7.00) years. Fourteen prognostic factors (including clinical, biological, and imaging risk factors) were independently associated with patient death (eg, patient age: hazard ratio per 1-year increase in age, 1.07 [95% CI, 1.06-1.08]; P < .001) and were combined into a risk prediction model (mBox). The model exhibited accurate calibration and discrimination in the derivation cohort, with C statistics of 0.82 (95% CI, 0.77-0.87) and 0.80 (95% CI, 0.78-0.82) at 1 and 10 years, respectively, after the transplant. Abbreviated models were developed and validated to ensure model generalizability. Performance of abbreviated models was confirmed in external validation cohorts from France (C statistic, 0.76 [95% CI, 0.73-0.78]), Europe (C statistic, 0.74 [95% CI, 0.72-0.76]), the US (C statistic, 0.74 [95% CI, 0.70-0.78]), the Greater Paris University Hospital database (C statistic, 0.79 [95% CI, 0.77-0.81]), and the University of California at San Francisco database (C statistic, 0.70 [95% CI, 0.65-0.74]). The model was also validated in a series of subpopulations (eg, women vs men: C statistic, 0.81 [95% CI, 0.77-0.84] vs 0.79 [95% CI, 0.77-0.82]) and clinical scenarios (eg, before COVID-19 era: C statistic, 0.79 [95% CI, 0.77-0.81]) with good and stable performance. Conclusions and Relevance In this study, an accurate prediction model for mortality among kidney recipients, computable at the time of transplant, was developed and externally validated. Results suggest that this model may help stratify patient risk of death, allowing for improved medical decisions.

Abstract Context The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting. Objective To describe the maternal characteristics associated with GDM in twin pregnancies and to assess the associated pregnancy outcomes compared to twin pregnancies unaffected by GDM. Methods A retrospective cohort study was conducted at Mayo Clinic, Rochester, Minnesota, USA, and included predominantly Causasian women aged 18 to 45 years who received prenatal care for a twin pregnancy from 2017-2022. Maternal characteristics and a broad spectrum of pregnancy outcomes were evaluated. Universal GDM screening involved a 50 g oral glucose challenge test +/− a 100 g oral glucose tolerance test. Results GDM was diagnosed in 23% pregnancies (n = 104/452). Compared to those without, women with GDM had known risk factors including a higher prepregnancy body mass index (31.1vs 26.3 kg/m2; P < .01) and a prior history of GDM (21.7 vs 5.9%; P < .01). There were no differences in maternal pregnancy complications or neonatal outcomes between groups. Attendance at postpartum glucose testing among women with GDM was poor at 27.9% (29/104). Conclusion These data suggest that women with twin pregnancies share a similar GDM risk profile to those with singleton pregnancies and provide reassuring evidence that current management for GDM twin pregnancies produces similar outcomes to twin pregnancies without GDM.

68 Background: While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their high cost and limited global supply pose major challenges. Optimizing ICI dosing to achieve a minimum effective dose that has shown to maintain clinical benefit may be a potential solution with significant savings to the health system. We investigated potential savings in Medicare that could be attained from alternative ICI dosing. Methods: We conducted a literature review including original Phase 1/2 trials describing the minimal effective dose of three commonly used ICIs: Pembrolizumab (P), Nivolumab (N) and Atezolizumab (A). Alternate dosing strategies based on existing data for Pembrolizumab (2 mg/kg), Nivolumab (1 mg/kg) and Atezolizumab (4 mg/kg) were proposed. Publicly available CMS data on Medicare Part B expenditure for these therapies was utilized to obtain average cost per dosage unit, mg/dosage unit, and number of Medicare beneficiaries between 2018-2021. Average cost per dose and total cost per ICI was calculated based on current FDA approved dosing and alternate dosing strategies. Results: The average wholesale cost per fixed dose for P (200 mg), N (480 mg), and A were $9,242.00, $12,460.80, and $8,616.00, respectively. Implementing the proposed alternate dosing strategies led to a substantial reduction in drug costs: P ($7,393.60), N ($2,076.80), and A ($2,297.60). The ensuing cost savings were calculated based on the annual number of Medicare beneficiaries. From 2018-2021, the average total savings were estimated to be $95,545,182 for Pembrolizumab, $294,734,264 for Nivolumab, and $62,937,582 for Atezolizumab (Table). The cumulative average total cost savings from 2018-2021 exceeded $453 million. Conclusions: We demonstrate potential savings in Medicare with implementation of an alternative ICI dosing strategy. Our study underscores an urgent need to better understand clinical efficacy and cost savings from a patient perspective, and feasibility from a regulatory standpoint. This perspective may hold considerable global implications, providing a roadmap for cost-effective care in the domain of immunotherapy. [Table: see text]

9037 Background: The clinical outcomes for patients with NSCLC remain suboptimal despite recent advancements in anti-PD-1/PD-L1 immunotherapies. Thus, identification of rational combinations of novel immune checkpoint (IC) strategies is imperative. This study aimed to comprehensively characterize the expression of IC targets to inform drug development and design effective combinatorial strategies, to advance the search for optimized therapies for NSCLC. Methods: We analyzed the differential gene expression of IC targets in 537 primary lung adenocarcinoma (LUAD) samples and 59 normal lung tissue samples pre-immunotherapy receipt using RNA-sequencing data from The Cancer Genome Atlas. Gene expression of IC-targets including PDCD1 (PD-1), CD274 (PD-L1), CTLA4, TIGIT, LAG3, HAVCR2 (TIM-3), VSIR (VISTA), ICOS, CD276 (B7-H3), BTLA, IDO1, KLRD1 (CD94/NKG2A), NT5E (CD73), TNFRSF4 (OX-40), TNFRSF18 (GITR), and TNFRSF9 (4-1BB) were obtained. Differential gene expression was determined intra-tumorally by comparison of transcripts per million and inter-tumorally using the DESeq2 algorithm. Log2 fold change >0.5 and false discovery rate adjusted P<0.05 were used as criteria for significant differential expression. Hierarchical clustering was used to identify subsets of tumors with similar profiles of IC-targetable gene expression. Results: Tumors showed significantly increased expression of TNFRSF18 (GITR), NT5E (CD73), TNFRSF9 (4-1BB), LAG3, TIGIT, CTLA4, PD-1, BTLA, B7-H3, and OX-40 (Table 1). On the other hand, tumors exhibited significant downregulation of CD274 (PD-L1), HAVCR2 (TIM-3), ICOS, KLRD1 (CD94/NKG2A), and VSIR (VISTA). Hierarchical clustering revealed recurrent patterns of IC gene overexpression which were characterized by: 1) IDO1-hi, 2) CD276-mid + TNFRSF18-mid, 3) VSIR-hi, 4) CD276-hi, 5) NT5E-hi, and 6) CD276-mid + NT5E-mid. Interestingly, patterns of IC gene expression distinguish tumors from controls. Of note, high VSIR expression was specific to normal tissue rather than tumors. Conclusions: Our study identified many IC targetable genes that were significantly overexpressed in tumors. However, subsets of tumors showed distinct and segregable combinations of overexpressed IC genes. These results suggest heterogeneous mechanisms of immune evasion in NSCLC, which may explain suboptimal outcomes with anti-PD-1/PD-L1 based strategies in this patient population. Our findings emphasize the importance of biomarker-guided approaches for the optimal selection of ICs and the development of rational combinatorial immunotherapies in NSCLC.

OBJECTIVES Few medical schools incorporate formal education on human trafficking (HT) and sex trafficking (ST) into their curriculum. Our objective was to develop, implement, and evaluate education on HT and ST in the first-year medical student curriculum. METHODS The curriculum included a standardized patient (SP) experience and lecture. As part of their mandatory sexual health course, students interviewed an SP who presented with red flags for ST and then participated in a discussion led by a physician-facilitator in an observed small group setting. A multiple-choice survey to assess knowledge about HT and ST was developed and administered to students before and after the SP interview. RESULTS Of the 50 first-year medical students, 29 (58%) participated in the survey. Compared with the students’ baseline scores (according to the percentage of correct responses), scores after the educational intervention showed a significant increase in percentage correct on questions related to trafficking definition and scope (elder care, P = .01; landscaping, P = .03); victim identification ( P < .001); referral to services ( P < .001); legal issues ( P = .01); and security ( P < .001). On the basis of the feedback, a 2-hour lecture, which was adapted from the American Medical Women's Association–Physicians Against the Trafficking of Humans “Learn to Identify and Fight Trafficking” training, was presented the next year to all first-year medical students as part of their longitudinal clinical skills course and before the SP case. Curriculum objectives included learning trafficking definitions, victim/survivor identification, intersections with health care, the local impact of HT, and available resources. CONCLUSION This curriculum fulfills course objectives and could be replicated at other institutions. Further evaluation of this pilot curriculum is necessary to evaluate its effectiveness.

Introduction Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. Project aim The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. Design This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Results Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications ( P = .11). There were no differences in patient ( P = .88) or graft survival ( P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Conclusion Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

AbstractDual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien‐Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1‐year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1‐ (P = .004) and 2‐years post‐transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5‐3.3, P = .58) or graft (HR 1.1, 95% CI .5‐2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.

Abstract Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non‐TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End‐Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow‐up, approximately half of those requiring endoscopy were undergoing a stent‐free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re‐LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76–5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98–4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.