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Importance Patients with cancer have high utilization of health care services, and many have high financial burdens from care. High-deductible health plans (HDHPs), which offer lower premiums at the expense of higher deductibles and possibly higher out-of-pocket costs, are associated with decreased care utilization among survivors of cancer. However, it is unclear whether HDHPs are associated with cancer outcomes. Objective To determine whether HDHP status is associated with survival among cancer survivors and individuals without history of cancer and whether financial barriers to care mediate associations between HDHP status and survival. Design, Setting, and Participants This cross-sectional study included US adults ages 18 to 84 years who participated in the National Health Interview Survey from 2011 to 2018. Data were analyzed from December 14, 2023, to December 1, 2025. Exposure HDHP status. Main Outcomes and Measures Outcomes of interest were overall survival (OS) and cancer-specific survival (CSS). Analyses were adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, and cancer site and time since cancer diagnosis (if applicable). Results A total of 147 254 respondents (mean [SD] age, 45.7 [16.4] years; 79 261 [50.9%] female) were identified, including 9799 (5.9%) with history of cancer. A total of 2331 cancer survivors (25.6%) and 37 473 individuals without history of cancer (28.5%) reported an HDHP at the time of NHIS participation. HDHP status was associated with worse OS (hazard ratio [HR], 1.46; 95% CI, 1.19-1.79) and CSS (HR, 1.34; 95% CI, 1.01-1.77) among cancer survivors. In contrast, among adults without history of cancer, HDHP status was not significantly associated with OS (HR, 1.08; 95% CI, 0.96-1.21; P for interaction = .001). In mediation analyses, HDHP status among cancer survivors was associated with increased financial barriers to care, which mediated approximately 30% to 70% of the total association of HDHP with survival. Conclusions and Relevance In this cross-sectional study of nationwide population-based data, HDHPs were associated with worse OS and CSS among cancer survivors. However, HDHPs were not associated with mortality in adults without history of cancer. These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes.

Abstract INTRODUCTION The vascular endothelial growth factor (VEGF) signaling family plays a role in neurodegenerative diseases, including Alzheimer's disease (AD). Previous work has shown widespread effects of the members FLT1 , FLT4 , and VEGFB on AD outcomes. However, these analyses have focused within the non‐Hispanic White (NHW) population. METHODS The goal of this study was to analyze the effects of the VEGF family in underrepresented populations, leveraging large and diverse bulk RNA sequencing and tandem mass tag–mass spectrometry (TMT‐MS) proteomic data. Outcomes included measures of AD pathology and diagnosis. RESULTS Within underrepresented populations, we replicated previously reported effects of FLT1 and FLT4 , whereby higher protein abundance was observed in the AD brain and was associated with higher neuropathology burden. In stratified analyses, these associations were largely consistent across race and ethnicity. DISCUSSION This multi‐omic study on the role of the VEGF family in AD emphasizes the need for more representative studies focused on therapeutic targets for AD. Highlights Vascular endothelial growth factor (VEGF) genes and proteins were quantified in four different brain regions. Samples included participants from four different populations. Previously observed effects were replicated in diverse populations. This study is the largest multi‐omic study of the vascular endothelial growth factor (VEGF) genes among Alzheimer's disease (AD) participants from diverse populations.

Abstract Background There is an unmet need for ulcerative colitis (UC) treatments that show improved effectiveness while maintaining safety profiles comparable with existing advanced therapies. Dual targeted therapy (DTT) has been proposed as a strategy to combine benefits of different advanced therapies to improve outcomes. The ExiGem study (NCT06095128) aims to assess the efficacy and safety of combined therapy with vedolizumab (VDZ) and tofacitinib (TOF) in adults with UC. We report results for the induction phase from the first 24 patients. Methods ExiGem is an ongoing phase 4, single-arm, multicentre study including adults with moderately to severely active UC (complete Mayo [cMayo] score of 6–12 with a rectal bleeding subscore ≥ 1 and centrally read endoscopic subscore ≥ 2). Eligible patients have previously had an inadequate response, loss of response, or intolerance to 1 or 2 anti-tumour necrosis factor α treatments. Patients receive induction therapy with intravenous (IV) VDZ 300 mg at weeks 0, 2, and 6 plus twice-daily oral TOF 10 mg for 8 weeks and then VDZ 300 mg IV monotherapy as maintenance from week 14. The primary endpoint is the proportion of patients in clinical remission by cMayo score at week 8. Secondary endpoints include clinical response and clinical remission by modified Mayo (mMayo) score at week 8. Changes in faecal calprotectin (FCP) levels and endoscopic improvement were evaluated. Efficacy data were analysed using non-responder imputation. For the final analysis a pre-specified Bayesian approach will be used. The safety profile of DTT was evaluated. Results Patient baseline characteristics are shown in Table 1. At week 8, 12/24 patients (50%) and 14/24 patients (58%) had clinical remission assessed by cMayo and mMayo scores, respectively; these rates were higher than pre-specified benchmark rates (Figure 1). Clinical response was observed in 21/24 patients (88%). At week 8, 14/24 patients (58%) showed endoscopic improvement, and 12/21 patients (57%) had normalization of FCP levels (< 250 µg/g). Treatment-emergent adverse events (TEAEs) were experienced by 10 patients (42%), and 1 serious TEAE was reported (suspected viral infection). One severe adverse event (AE; cough) and 2 moderate AEs (herpes zoster, drug intolerance) were considered related to TOF. No moderate or severe AEs were considered related to VDZ. One patient withdrew from the study before week 8 owing to intolerance to TOF. Conclusion Initial data suggest that induction with a combination of VDZ and TOF can produce improved rates of response and remission in patients with UC with a comparable safety profile to existing advanced monotherapies. Further data, including outcomes of VDZ maintenance as monotherapy, are pending. Conflict of interest: Prof. Dr. Yarur, Andres: Andres Yarur has served as an advisory board member for Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Roche/Genentech, and Takeda. This study was funded by Takeda Pharmaceuticals U.S.A., Inc. Medical writing support was provided by Adam Errington PhD of PharmaGenesis Cardiff, Cardiff, UK, and funded by Takeda Pharmaceuticals U.S.A., Inc. Barnes, Edward: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI. Ha, Christina: Christina Ha has served as an advisory board member for AbbVie, Bausch Health, Johnson & Johnson, Lilly, Merck, Takeda, and Sanofi has received educational programming support from AbbVie, Celltrion, Johnson & Johnson, Lilly, Pfizer, and Takeda and has received consulting fees from AbbVie. Hudesman, David: Consultant: Abbvie, Abivax, BMS, Biocon, Eli Lilly, Fresenius Kabi, Pfizer, Prometheus, CorEvitas, Takeda, Johnson and Johnson, Sanofi Research Support: Johnson and Johnson, Pfizer Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Lukin, Dana: Dana Lukin has served as a consultant/advisory board member for AbbVie, AltruBio, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Palatin, Pfizer, Prime, PSI, Takeda, and Vedanta has received grants from Boehringer Ingelheim and Johnson & Johnson and serves as a speaker for AbbVie and Johnson & Johnson. Rubin, David T.: Grant support: Takeda Pharmaceuticals. Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Schreiber, Stefan Wolfgang: Stefan Schreiber has received consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring, Fresenius, Galapagos, Genentech, Gilead, GlaxoSmithKline, I-MAB Biopharma, Janssen, Merck, Novartis/Sandoz, Pfizer, Protagonist, Takeda, and Ventyx Biosciences. Gower, Megan: Megan Gower is an employee and hold stock/stock options at Takeda Pharmaceuticals U.S.A., Inc. Jones, Stephen: Stephen Jones is an independent medical consultant who provides services for Takeda Pharmaceuticals U.S.A., Inc. Robinson, Ian: Ian Robinson is an employee and hold stock/stock options at Takeda Pharmaceuticals U.S.A., Inc. Sanchirico, Marie: Marie Sanchirico is an employee and hold stock/stock options at Takeda Pharmaceuticals U.S.A., Inc. Yajnik, Vijay: Vijay Yajnik is an employee and hold stock/stock options at Takeda Pharmaceuticals U.S.A., Inc.

Abstract Background Global data demonstrate an inverse relationship between hospital ileoanal pouch volume and adverse outcomes, highlighting the need for quality metrics for this technically demanding procedure.1-4 Currently, there are no standardised quality indicators to define high-quality pouch surgery. This study aimed to establish international consensus on key performance indicators (KPIs) in pouch surgery. Methods A modified Delphi process was conducted among an international, multidisciplinary panel of experts. Participants were identified through professional networks, literature review, and direct email invitation; additional participants recruited via a snowball sampling approach over one month. Candidate KPIs were generated from literature review and expert input across 5 domains. Each item was rated on a 9-point Likert scale (1 = not important, 9 = critically important); consensus was predefined as ≥ 80% of respondents rating an item 7–9. Items not reaching consensus were re-rated in a second round following anonymized group feedback. Results Round 1 included 312 participants from 37 countries. Demographics (Table 1): 53% were age 45 years, 35.2% were female, and included surgeons (68.6%) and gastroenterologists (31.1%). Most (76.6%) practice at academic or university hospitals, with a median of 11 (5–17) years in practise; 78.9% perform >1 pouchoscopy per month, and 39.5% of surgeons perform 5 pouches/year. Respondents’ regions included North America (51%), Europe (26%), Oceania (9%), Asia (6%), Latin America (4%), and the Middle East/Africa (4%). Seven (18%) countries (Denmark, Lithuania, Malaysia, Norway, United Arab Emirates, Sweden, and Switzerland) reported pouch surgery is already centralised, while 70.6% agreed pouch centralisation should be implemented. Cost/logistics and professional autonomy were the most important barriers to centralisation, whereas capacity and training exposure were least important. Overall, 37/59 (62.7%) candidate KPIs reached consensus after Round 1. The Round 2 response rate was 61%, and 2 additional KPIs reached consensus (preop ileitis and long-term risk of pouchitis). Additionally, 14 of 25 (56%) informed consent items reached consensus, and 64% of respondents felt informed consent for pouch surgery requires 2 or more office visits. Consensus items were used to populate a KPIPS Checklist (Figure 1). Conclusion Through an international Delphi process, the KPIPS study identified a consensus-derived set of key performance indicators to measure quality in pouch surgery. These quality metrics provide a foundation for benchmarking outcomes and represent a critical step towards centralization and the development of designated pouch centres of excellence to improve global standards of care for pouch patients. References: 1. Worley GHT, Fearnhead NS, Brown SR, et al. Review of current practice and outcomes following ileoanal pouch surgery: Lessons learned from the ileoanal pouch registry and the 2017 ileoanal pouch report. Colorectal Dis 2018;20:913–22. 2. Giddings HL, Yang PF, Steffens D, Solomon MJ, Ng KS. Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: Systematic review. Br J Surg 2024;111. 3. Hoang CM, Maykel JA, Davids JS, et al. Distribution of elective ileal pouch-anal anastomosis cases for ulcerative colitis: A study utilizing the university health system consortium database. J Gastrointest Surg 2020;24:2613–9. 4. Moojen TB, Visser E, Reijntjes MA, et al. One-year stoma-free survival of ileoanal pouches for uc in european centers: The miracle project. Ann Surg Open 2025;6:e596. Conflict of interest: Prof. Holubar, Stefan: No conflict of interest Soop, Mattias: No conflict of interest Poskus, Tomas: No conflict of interest Neary, Peter: No conflict of interest Uchino, Tairin: No conflict of interest Yang, Song-soo: No conflict of interest Adamina, Michel: No conflict of interest Avellaneda, Nicolas Luis: No conflict of interest Barnes, Edward: No conflict of interest Brouquet, Antoine: No conflict of interest Brown, Steven Ross: No conflict of interest De Buck Van Overstraeten, Anthony: No conflict of interest Buskens, Christianne J.: No conflict of interest Chiorean, Michael: No conflict of interest Clark, David: No conflict of interest Cohen, Benjamin: No conflict of interest El Ouali, Sara: No conflict of interest Faiz, Omar Darius: No conflict of interest Fichera, Alessandro: No conflict of interest Hahnloser, Dieter: No conflict of interest Hancock, Laura: No conflict of interest Herfarth, Hans: No conflict of interest Johnston, Michael: No conflict of interest Kayal, Maia: No conflict of interest Laharie, David: No conflict of interest Liberman, Sender: No conflict of interest Loftus, Jr, Edward: No conflict of interest Moeslein, Gabriela: No conflict of interest Myrelid, Pär: No conflict of interest Poylin, Vitaliy: No conflict of interest Qazi, Taha: No conflict of interest Raffals, Laura: No conflict of interest Rubin, David T.: No conflict of interest Spinelli, Antonino: No conflict of interest Steinhagen, Emily: No conflict of interest Tozer, Philip: No conflict of interest Verstockt, Bram: No conflict of interest Warusavitarne, Janindra: No conflict of interest Wexner, Steven: No conflict of interest Winter, Desmond: No conflict of interest

Background Costosternal cartilages and the costal margin, collectively termed costal cartilage, are hyaline cartilage connecting ribs to the sternum and to adjacent ribs, respectively. Presence of intact costal cartilage is essential for elasticity of the chest wall. Anecdotally, costal cartilage injuries are underdiagnosed on trauma CT scan in patients with rib fractures. Our aim was to determine a baseline frequency of acute costal cartilage injury among patients presenting with rib fractures. Methods We performed a retrospective cohort study of injured adult patients admitted to Level I/II trauma centers with rib fractures from January 2020 to July 2024. CT images obtained at admission were manually reviewed by chest wall surgeons for presence of costal cartilage injury. Concordance with the original radiology report was obtained. Multivariable regression was used to analyze factors associated with costal cartilage injury and missed cartilage fractures. Results 1441 patients were identified; 197 (14%) had a costal cartilage fracture. A plurality of injuries included falls (n=667, 46%). Median ISS (Injury Severity Score) was 13 (IQR: 9 to 21), median Abbreviated Injury Scale thorax score was 3 (IQR: 3 to 3), and median number of fractured ribs was 3 (IQR: 3 to 7). 294 (21%) patients had radiographic flail segments, and 136 (9%) had sternal fractures. 172 (87%) patients had a costal cartilage fracture missed on initial trauma chest CT. On multivariable analysis, ISS (adjusted OR (aOR) 1.02 (95% CI 1.01 to 1.04), radiographic flail segment (aOR 1.6 (95% CI 1.10 to 2.31)) and presence of sternal fracture (aOR 1.85 (95% CI 1.19 to 2.89)) were associated with costal cartilage fractures. Only the total number of rib fractures was associated with a missed costal cartilage fracture on univariate analysis (OR 1.17 (95% CI 1.01 to 1.36)). Conclusions Costal cartilage injuries are common and frequently are not identified during interpretation of the initial trauma CT. A higher index of suspicion is warranted for costal cartilage fractures among patients with greater injury burden, radiographic flail segment, and sternal fractures. Level of evidence Level III.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer provide recommendations for diagnostic workup, staging, and treatment. These NCCN Guidelines Insights highlight recent updates, with a particular focus on changes to systemic therapies and radiation treatment in the NCCN Guidelines for Small Cell Lung Cancer.

Lay Summary This multicenter study evaluated clinical outcomes in pregnancy for women with ulcerative colitis and an ileal pouch-anal anastomosis. Close monitoring is needed with a multidisciplinary team for management of inflammatory complications of the pouch such as pouchitis in pregnancy and postpartum.

The treatment landscape for soft tissue sarcomas (STS) is evolving constantly. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for STS specific to surgical management and systemic therapy recommendations for various subtypes.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer provide diagnostic workup, staging, and various treatment recommendations for cervical cancer based on clinical and surgical staging. This selection from the NCCN Guidelines for cervical cancer specifically focuses on diagnosis and workup, principles of staging and surgery, and primary treatment recommendations for early-stage and advanced disease and provides a detailed overview of systemic therapy recommendations for cervical cancer.

Purpose of the review Perioperative pain management continues to evolve as we see the pendulum of opioid use swinging back from highly restrictive administration towards more balanced intraoperative dosing strategies. Striking the optimal balance between nonopioid multimodal pain regimens and thoughtful opioid use has been at the forefront of cardiac surgical enhanced recovery protocols for several years. Herein, we review the history of methadone as a long-acting opioid and its resurgence with pleiotropic benefits in cardiac surgery patients. Recent findings Despite barriers to use and potential adverse effects, methadone is a proven agent for long-lasting analgesia, potentially reducing both short- and long-term opioid consumption. Multiple studies have demonstrated safety and efficacy in cardiac surgery. Dosing (0.1–0.3 mg/kg) and timing vary slightly in published studies and protocols; however, through standardization and clinical judgement regarding patient selection, methadone can safely be used to reduce opioid use and improve analgesia for cardiac surgery. Summary Further studies are needed to explore the mechanisms and ideal protocols for incorporating methadone into routine use as part of existing enhanced recover protocols. Long-term treatment effects extending beyond the immediate postoperative period, outcomes when included with adjuncts, and broader dose-response analysis are needed to guide future implementation.