Citations

Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background Traumatic injury is the fourth leading cause of death nationally; rural residents are twice as likely to die from injury as urban counterparts. On-scene mortality coverage gaps across regional trauma systems remain poorly characterized. Objective To identify geographic blind spots and time-critical, spatially advantageous on-scene deaths (2019-2023) that fall outside modeled 10-minute drive-time service areas across seven North Central state trauma regions. Methods This retrospective analysis geocoded death certificate records to ZIP Code Tabulation Areas and modeled 10-minute drive-time service areas in ArcGIS Online. EMS agency headquarters and staffing classification (volunteer, mixed, paid) were obtained from the DHS EMS Service Map. Candidate sites were identified by maximizing coverage of weighted, uncovered death centroids per region. Results Of 11,868 decedents (60.7% male; mean age 64.4 years [SD 25.6]; 49.9% fall, 26.4% firearm), 7815 had geocodable addresses. Coverage ranged from 53.5% (Western) to 87.0% (North Central); 5492 (70.3%) fell within a 10-minute service area. One candidate site per region could extend modeled coverage to 4-321 additional death locations (480 combined). Volunteer-dominant regions, where 63% of agencies reported scheduling gaps, had the lowest coverage, suggesting headquarters presence overstates availability. Conclusion Geospatial analysis identified actionable blind spots where one additional EMS resource per region could extend modeled coverage to hundreds of death locations. Because these are modeled coverage gains, not demonstrated mortality reductions, and depend in volunteer-dominant regions on staffing reliability that placement alone cannot resolve, the identified locations warrant further evaluation, not presumed survival benefit.

OBJECTIVE Craniopharyngiomas are benign intracranial tumors that can be difficult to manage operatively and often result in postoperative complications and prolonged recovery. Understanding the factors that influence length of stay (LOS), discharge disposition, and readmission can guide perioperative planning and patient counseling. The authors examined the clinical, radiographic, and surgical predictors of extended LOS (eLOS), nonhome discharge, 90-day readmission, and hospitalization ratio (HR) after craniopharyngioma resection using a large, multicenter cohort. METHODS A retrospective analysis was conducted using the Registry of Adenomas of the Pituitary and Related Disorders database, encompassing 469 patients who underwent craniopharyngioma resection at 14 US academic centers from 2011 to 2025. Patients were stratified by 4 outcomes: eLOS (> 75th percentile), discharge to home versus skilled nursing facility/rehabilitation, 90-day hospital readmission, and hospitalization ratio (i.e., integration of initial and readmission LOS). Multivariable logistic regression models identified independent predictors for each outcome among patient and surgical variables. RESULTS An eLOS (> 10 days) was independently associated with preoperative memory loss (OR 3.75, 95% CI 1.95–7.21), gait imbalance (OR 5.90, 95% CI 1.53–22.70), and postoperative complications (OR 4.07, 95% CI 2.34–7.06). The use of a nasoseptal flap was protective against an eLOS (OR 0.52, 95% CI 0.28–0.93). Discharge to home was predicted by an endoscopic approach (OR 3.87, 95% CI 1.78–8.44) and postoperative intact thirst (OR 2.22, 95% CI 1.05–4.66) and negatively predicted by preoperative diabetes mellitus (OR 0.21, 95% CI 0.09–0.50), LOS (OR 0.87, 95% CI 0.84–0.91), and postoperative cognitive dysfunction (OR 0.30, 95% CI 0.13–0.72). Among 385 patients with follow-up data, a 90-day readmission was independently associated with postoperative complications (OR 5.62, 95% CI 3.12–10.13), preexisting coronary artery disease (OR 4.30, 95% CI 1.46–12.69), and postoperative cognitive dysfunction (OR 3.33, 95% CI 1.76–6.44). A higher HR was associated with diabetes mellitus (unstandardized B 0.059, 95% CI 0.010–0.108, p = 0.02), postoperative complications (unstandardized B 0.054, 95% CI 0.021–0.086, p = 0.001), and postoperative cognitive dysfunction (unstandardized B 0.049, 95% CI 0.006–0.092, p = 0.02). Tumor pathologic subtype and size, prior treatment, extent of resection, and surgeon experience were not directly predictive of outcomes. CONCLUSIONS Cognitive and functional status, systemic comorbidities, and postoperative complications, in addition to surgical approach, are important predictors of the early clinical course after craniopharyngioma surgery. Early identification of high-risk patients may help to guide treatment decisions, improve discharge planning, and reduce healthcare utilization.

The 2025 Annual Congress of the International Liver Transplantation Society (ILTS), themed “ Advancing Liver Transplantation: Embracing Innovation for the Future ,” was held from May 28 to 31 in Singapore. The meeting offered a comprehensive scientific program, featuring 92 sessions and 7 pre-congress workshops spanning living donor liver transplantation, advanced surgery, anesthesia and critical care, transplant oncology and immunology, basic science, pediatrics, and more. The program emphasized collaboration and innovation to advance patient outcomes in liver transplantation. In this report, the ILTS Vanguard Committee summarizes the key proceedings of the congress.

The success of living donor liver transplantation (LDLT) has bridged the growing gap between organ demand and availability in patients with liver failure or liver cancer. Safety of the living liver donor (LLD) is paramount, and astute intraoperative management plays a critical role in ensuring optimal outcomes for them. Given that intraoperative surgical and anesthesia practices vary widely across centers, the International Liver Transplantation Society (ILTS) and the International Living Donor Liver Transplantation Group (iLDLT Group) convened a global consensus conference in Toronto in March 2025 to develop guidelines for intraoperative management of the LLD. This manuscript details the recommendations on intraoperative considerations for the safety of LLD developed by Working Group II of the Consensus Scientific Committee, using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for assessment of recommendations, and the Danish model of consensus. Working Group II focused on intraoperative monitoring, fluid and ventilation strategies, surgical techniques for vascular and biliary division, surgeon and center-specific experience, and intraoperative crises planning. These guidelines aim to support both established and emerging LDLT teams to ensure high-quality and safe intraoperative care for the LLD.

406 Background: Anxiety is highly prevalent among oncology patients, often arising from uncertainty around diagnosis, treatment options, and prognosis. Elevated anxiety can impair decision-making, reduce treatment adherence, and diminish overall quality of life. Effective second opinion consultations may help mitigate anxiety and increase patients’ confidence in recommending healthcare services to others. Our study evaluates the impact of oncology second opinion (OSO) consultations on anxiety level (AL) and confidence in the organization (CIO) providing the second opinion, i.e., Cincinnati Cancer Advisors (CCA) and Naples Cancer Advisors (NCA). Methods: The study included patients with cancer diagnoses, age ≥18 years, who were served in person for OSO at CCA and NCA. A survey was used before and after consultation, measuring AL (scale 1- 10) and CIO level (scale 1 - 10), assessed by asking patients how likely they would refer loved ones to the organization. After the content and face validation, patients completed the survey anonymously, put it in a sealed envelope, and dropped it in a dedicated box. Data was analyzed using paired t-tests to compare the change from pre- to post-consultation scores. Spearman’s correlation test was used to assess the relation between the changes in AL and CIO. Statistical significance was assessed using an alpha-level of 0.05. Analyses were conducted via R and R Studio (version 2025.5.1.513). Results: Overall, 46 consecutive patients participated (45 completed AL pre and post visit survey and 43 completed the CIO pre and post visit survey). The mean pre-consultation anxiety score was 5.92 (SD = 2.58), and the post-consultation score was 3.87 (SD = 2.10), demonstrating a significant reduction (mean paired difference = -2.05; p < 0.0001). The mean pre-consult CIO was 8.21 (SD = 2.03), increasing to 9.73 post-consultation (SD = 0.53), indicating a significant improvement (mean paired difference = 1.66; p < 0.0001). The correlation between changes in AL and CIO was not statistically significant, which may be attributed to the high baseline CIO scores (ceiling effect) and the small sample size. Conclusions: Oncology second opinion was associated with a marked decrease in patient AL and a significant increase in CIO. The patient survey will continue to recruit additional participants to increase the sample size and explore the correlation between changes in AL and CIO. Studying the downstream impact on patient experience and outcome is warranted.

This consensus by the Society of Abdominal Radiology Inflammatory Bowel Disease Disease Focused Panel provides an updated imaging-based definition of small bowel Crohn disease stricture for CT and MR enterography.