Tag: pubmed

Ann Surg. 2026 Jul 20. doi: 10.1097/SLA.0000000000007152. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of CYP2A6 genetic polymorphisms on survival outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) receiving perioperative S-1 therapy.

BACKGROUND: S-1, an oral fluoropyrimidine containing tegafur, is widely used for perioperative treatment of PDAC in Japan. Tegafur requires metabolic activation to 5-fluorouracil, primarily by CYP2A6. Given the high prevalence of reduced-function CYP2A6 variants in East Asian populations, their clinical significance in PDAC remains unclear.

METHODS: This retrospective study included 145 patients with PDAC who underwent curative resection and received adjuvant S-1, including 78 patients who had received S-1-containing neoadjuvant therapy. Germline CYP2A6 variants were identified using whole-exome sequencing of peripheral blood samples. Decreased-function alleles (*4, *7, *9) and the rare nonsense allele *48 were evaluated. Patients were classified into poor, intermediate, and normal metabolizer groups. Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.

RESULTS: Decreased-function CYP2A6 genotypes were identified in 82 patients (56.6%), including 6 poor metabolizers (4.1%). These patients had a higher frequency of lymph node metastasis than those with normal genotypes (78.0% vs. 52.4%, P=0.001). Recurrence-free survival (RFS) was significantly shorter (median, 19.2 vs. 32.3 mo; P=0.040), whereas overall survival (OS) was shorter but not statistically significant (47.9 vs. 62.2 mo; P=0.104). In multivariable analysis, CYP2A6 poor metabolizer status was independently associated with OS (HR, 3.17; 95% CI, 1.06-9.46; P=0.039). Among the 78 patients who received S-1-containing neoadjuvant therapy, both OS and RFS were significantly worse in those with decreased-function genotypes.

CONCLUSIONS: Decreased CYP2A6 functional genotypes were associated with poorer oncological outcomes in patients with PDAC receiving perioperative S-1 therapy, suggesting that the CYP2A6 genotype may serve as a biomarker for optimizing treatment strategies.

PMID:42475636 | DOI:10.1097/SLA.0000000000007152

JCO Clin Cancer Inform. 2026 Jul-Sep;10(3):e2500385. doi: 10.1200/CCI-25-00385. Epub 2026 Jul 20.

ABSTRACT

PURPOSE: Guidelines recommend germline testing in advanced prostate cancer (PCa) to inform treatment and personal/familial cancer risk, yet Black patients are less likely than White patients to complete testing. Artificial intelligence (AI) tools are increasingly used in pretest education to improve access but remain unevaluated for racial bias.

MATERIALS AND METHODS: We developed ProGene, a secure, generative AI chatbot for PCa germline testing education in Black patients. We prompted ProGene with seven questions about testing types, personal benefits, family benefits, drawbacks, logistics, costs, and privacy. Each question was asked nine times across three patient vignettes (Black, non-Hispanic White, race-agnostic), in triplicate. Two blinded reviewers assessed responses across five domains: (1) comprehensiveness (0%-100%), (2) accuracy (presence/absence of inaccuracies), (3) readability (grade level via Simple Measure of Gobbledygook [SMOG] and Flesch-Kincaid), (4) actionability (0%-100% via Patient Education Materials Assessment Tool), and (5) quality (1-18 via DISCERN-AI). Outcomes were compared by race and question using two-sample t-tests or Wilcoxon rank-sum tests for continuous measures and chi-square or proportion tests for categorical measures; ANOVA was used for question-level comparisons.

RESULTS: The mean comprehensiveness was 67% and did not vary by race, although responses for question-1 (genetic testing types) were less comprehensive for Black versus race-agnostic vignette (60% v 93%, P < .01). Inaccuracies appeared in 32% of responses, primarily related to sample collection and cost/insurance, and did not vary by race. The mean readability were 10th (SMOG) and 13th (Flesch-Kincaid) grades, actionability 92%, and DISCERN score 14/18 (good quality); none varied by race.

CONCLUSION: We identified no statistically significant racial disparities across the five evaluation domains in ProGene. Responses were generally good quality and actionable. Although AI may facilitate equity in PCa genetic education, deficiencies in comprehensiveness, accuracy, and readability highlight the need for refinement and/or human oversight with implementation.

PMID:42475635 | DOI:10.1200/CCI-25-00385

J Am Coll Health. 2026 Jul 20:1-11. doi: 10.1080/07448481.2026.2693666. Online ahead of print.

ABSTRACT

Objective: This study aimed to measure the effect of a Social Cognitive Theory (SCT)-based, urban gardening, cooking, and nutrition education intervention on health behavior mediators and fruit and vegetable intake in food-insecure college students. Methods: In a 6-week, randomized controlled trial, 89 food-insecure students at a southeastern university (86% female, 59% Hispanic), randomized into a controlled 107 (n = 42) or intervention group (n = 47), attended once a week, cooking/gardening sessions, that incorporated nutrition education, recipes, and at home garden materials. Outcome measures were assessed at baseline and post intervention and included anthropometrics, health behavior mediators such as nutrition knowledge (Dickson-Spillmann Consumer Oriented Nutrition Knowledge Survey), Dewar’s SCT construct subscales: self-efficacy, outcome expectations, reciprocal determinism, and fruit and vegetable intake using the National Cancer Institute’s Fruit and Vegetable Screener. Linear regressions and ANOVA’s were conducted. Results: Intervention participants increased fruit and vegetable intake (F = 19.19, p < .001) and health behavior mediators: self-efficacy (F = 17.65, p < .001), reciprocal determinism (F = 4.16, p = .045), An increase in reciprocal determinism was significantly associated with an increase in self-efficacy (β = .392, t = 2.66, p = .011). Intervention mediators did not have a significant effect on change in fruit and vegetable intake (F = . 580, p = .679, R2 = . 061). Conclusions: An SCT-based cooking and gardening nutrition program tailored to food-insecure college students improved health behavior mediators and increased fruit and vegetable intake. A nutrition education program that utilizes a hands-on, interactive approach may be an effective intervention to promote fruit and vegetable intake and health behaviors among food insecure college students.

PMID:42475621 | DOI:10.1080/07448481.2026.2693666

J Med Internet Res. 2026 Jul 20;28:e93347. doi: 10.2196/93347.

ABSTRACT

BACKGROUND: Patients with atrial fibrillation (AF) face significant bleeding risks, particularly those receiving oral anticoagulation; however, existing risk scores such as HAS-BLED and ORBIT demonstrate limited predictive accuracy. Pulse pressure (PP), calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure, is a noninvasive marker of arterial stiffness that has been associated with cardiovascular outcomes. However, PP has not been evaluated as a predictor of bleeding in this population.

OBJECTIVE: This study evaluated whether elevated PP independently predicts major bleeding events, overall and by subtype, in patients with AF after adjusting for established clinical risk factors.

METHODS: We conducted a retrospective cohort study using electronic health records from REACHnet, a PCORnet-affiliated clinical data network in Louisiana. A total of 4935 adults (mean age 63.7, SD 11.0 y; n=1606, 32.5% female) with AF between 2010 and 2019 were included via consecutive sampling of all eligible patients. PP was derived from outpatient blood pressure measurements closest to AF diagnosis and analyzed in tertiles (low: <46, middle: 46-62, high: >62 mm Hg) and continuously per 10 mm Hg. The primary outcome was time to the first bleeding event, a composite of gastrointestinal bleeding, intracranial hemorrhage, and other clinically significant bleeding, identified using ICD-9/ICD-10 codes. Kaplan-Meier survival curves with log-rank testing were used for univariable analysis. Multivariable Cox proportional hazards regression was adjusted for age, sex, race, comorbidities, medications, and the ORBIT score. A sensitivity analysis applied multivariable logistic regression additionally incorporating SBP. Statistical significance was set at P<.05.

RESULTS: Over a 5-year follow-up, 677 out of 4935 (13.7%) patients experienced a bleeding event (intracranial hemorrhage: n=60, 1.2%; gastrointestinal bleeding: n=195, 4.0%; and other bleeding: n=149, 3.0%). Gastrointestinal bleeding differed significantly across PP tertiles (P=.007). Kaplan-Meier analysis confirmed lower gastrointestinal bleeding-free survival in the highest tertile (log-rank P=.004). No significant differences were observed for intracranial (P=.08), other (P=.58), or composite bleeding (P=.22). In multivariable Cox regression, each 1 mm Hg increase in PP was independently associated with a 1.4% higher gastrointestinal bleeding risk (hazard ratio 1.014, 95% CI 1.001-1.028; P=.04), approximately 15% per 10 mm Hg. This remained significant after adjusting for SBP and ORBIT score (odds ratio 1.013/mm Hg, 95% CI 1.001-1.025; P=.03), while SBP was not independently significant (P=.13).

CONCLUSIONS: PP independently predicts gastrointestinal bleeding risk in patients with AF beyond established clinical risk factors and validated bleeding risk scores. Unlike prior investigations that examined SBP or diastolic blood pressure components in isolation, this is the first study to identify PP as a predictor of gastrointestinal bleeding in this population. As a readily available, low-cost hemodynamic parameter derived from routine clinical measurements, PP could enhance existing risk stratification tools and inform more personalized bleeding risk management strategies in patients with AF.

PMID:42475619 | DOI:10.2196/93347

Otolaryngol Head Neck Surg. 2026 Jul 20. doi: 10.1002/ohn.70342. Online ahead of print.

ABSTRACT

OBJECTIVE: Given health system limitations, access to timely Auditory Brainstem Response (ABR) testing in infants is often challenging. The purpose of this study is to identify common barriers that may affect the number of ABRs needed to establish a definitive diagnosis of hearing loss in infants.

STUDY DESIGN: Retrospective review of variables impacting definitive diagnosis in infants who underwent ABRs from 2019 to 2024.

SETTING: Tertiary free-standing children’s hospital.

METHODS: Univariate and multivariable regression analyses were used to explore potential barriers with delays in time to definitive hearing loss diagnosis and management. All statistical tests were two-sided and performed at the 0.05 level of significance.

RESULTS: 630 patients met inclusion criteria. Of these, 579 (92%) had received a definitive diagnosis through ABR, 322 (55.6%) of which required only one ABR. 172 (29.7%) required two ABRs and 85 (14.7%) needed three or more. Time to hearing aid fitting was significantly influenced by time to definitive diagnosis. Patients diagnosed after 3 months of age were fit with a hearing aid at a significantly older age than those diagnosed by 3 months (11.2 vs 5.9 months, P = <.001). In the univariate analysis, otolaryngology consultation was associated with definitive hearing diagnosis at >3 months of age (386 vs 193, P = <.001). This association held true when controlling for other variables in multivariable analysis (aHR: 0.46, 95% CI: 0.38-0.55, P = <.001).

CONCLUSION: Primary common barriers impacting appropriate and timely EHDI guidelines: Infant sleep state, coordination with other providers, middle ear dysfunction, distance to facility, and scheduling constraints.

PMID:42475156 | DOI:10.1002/ohn.70342

Plast Reconstr Surg. 2026 Jul 20. doi: 10.1097/PRS.0000000000013328. Online ahead of print.

ABSTRACT

BACKGROUND: Immediate lymphatic reconstruction (ILR) following axillary lymph node dissection (ALND) has emerged as a potential strategy to mitigate breast cancer-related lymphedema (BCRL). This present study aims to evaluate the impact of ILR on lymphedema incidence in breast cancer patients undergoing ALND and identify potential risk factors for lymphedema despite ILR.

METHODS: A comprehensive search was performed using PubMed, Embase, Scopus, Ovid and Google Scholar databases. Thirty studies met inclusion criteria for the meta-analysis, comprised of seventeen comparative studies and thirteen non-comparative studies. The primary outcome was the incidence of lymphedema.

RESULTS: Overall, there was a 63% reduction in lymphedema risk with ILR. Among 1030 patients who underwent ILR, 14.5% developed lymphedema, compared to 25% of the 1260 patients in the control group. When pooling all ILR patients (including non comparative studies) across studies (n = 2080), 11% developed lymphedema. While BMI and the number of lymph nodes removed showed trends toward increased lymphedema risk in the ILR group, neither reached statistical significance (p > 0.05). There was significant variability among studies in terms of follow-up, post-operative management, and metrics for determining lymphedema. Notably, studies with longer follow-up reported higher lymphedema rates.

CONCLUSION: ILR is associated with a reduction in BCRL risk following ALND. Despite heterogeneity and risk of bias across studies, the meta-analysis suggests a favorable effect of ILR. Future studies should adopt standardized diagnostic criteria and assessment tools for lymphedema to enhance comparability and reduce heterogeneity.

PMID:42475134 | DOI:10.1097/PRS.0000000000013328

J Med Internet Res. 2026 Jul 20;28:e89780. doi: 10.2196/89780.

ABSTRACT

BACKGROUND: Digital health interventions can improve access to and outreach of evidence-based support for people living with chronic pain. How best to deliver such interventions remains unclear, however, and although guided or blended care models show promise, digital interventions are primarily delivered without support or follow-up.

OBJECTIVE: This study aimed to compare the use and effect of the evidence-based digital pain self-management intervention EPIO when (1) delivered through digital download without follow-up (ie, EPIO_NoFollowUp), compared with (2) delivery through a simple blended-care model (ie, EPIO_BlendedCare), or care-as-usual controls.

METHODS: People (n=73) with chronic pain received access to the EPIO program through individual download (EPIO_NoFollowUp). Program use and outcome measures were collected over 12 months and compared with findings from a separate randomized controlled trial in which people with chronic pain (n=266) were assigned to receive EPIO through a simple blended care model (EPIO_BlendedCare) or to a care-as-usual control group. Outcome measures were collected at baseline and at 3, 6, and 12 months and included pain interference (Brief Pain Inventory [BPI]; primary outcome), pain severity (BPI), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue Scale-18), health-related quality of life (HRQoL; RAND 36-Item Health Survey), pain catastrophizing (Pain Catastrophizing Scale), and pain acceptance (Chronic Pain Acceptance Questionnaire-8). Generalized linear models for repeated measures were fitted to explore between-group differences over time. Interviews with the EPIO_NoFollowUp group (n=15) exploring perceived program experiences were analyzed using rapid analysis.

RESULTS: Participants (N=332) had a median age of 49 (IQR 39-55) years, were primarily women (271/332, 82%), and had a variety of pain conditions. Statistically significant between-group differences in favor of the EPIO_NoFollowUp group compared with the control group included improved HRQoL and pain acceptance and reduced pain catastrophizing. Intervention group comparison revealed only 1 significant between-group difference, for self-regulation, in favor of EPIO_BlendedCare. Participants receiving the EPIO_NoFollowUp delivery model displayed lower program use, averaging 10 (IQR 3-24) days of use vs 30 (IQR 13-44) days for EPIO_BlendedCare. Similarly, 23% (17/73) of the EPIO_NoFollowUp group participants completed ≥7 of 9 modules, compared with 62% (78/125) in EPIO_BlendedCare. Higher education level was associated with significant improvements in pain severity, anxiety, HRQoL, and pain catastrophizing, as well as higher module completion, in the EPIO_NoFollowUp group but not in the EPIO_BlendedCare group. Qualitative findings identified a preference for more follow-up, as well as positive changes in awareness, acceptance, and coping in the EPIO_NoFollowUp group.

CONCLUSIONS: The delivery model should be considered when providing access to digital self-management, and models with guidance appear to be the most helpful. When health care resources are limited, blended care delivery should likely be chosen for those who need it most, for example, those with lower education.

PMID:42475133 | DOI:10.2196/89780

J Am Acad Orthop Surg Glob Res Rev. 2026 Jul 20;10(7). doi: 10.5435/JAAOSGlobal-D-25-00201. eCollection 2026 Jul 1.

ABSTRACT

BACKGROUND: Women have a higher prevalence of osteoarthritis and report worse symptoms, yet they undergo joint replacement surgery (JRS) at lower rates than men. Studies suggest that cultural norms, healthcare access, physician biases, and patient preferences may contribute to disparities, but consensus on gender-specific barriers in JRS utilization remain unclear.

METHODS: From a database of JRS candidates seen in 2022 at two tertiary academic centers, patients who were offered but declined surgery were invited to participate in focus groups (FGs). Demographics, Kellgren-Lawrence grades, symptom duration, visual analog pain score, Charlson Comorbidity Index, and nonsurgical treatments were collected. Statistical analysis included chi-square, analysis of variance, and t-tests. FGs explored patient treatment experiences using code-based qualitative analysis.

RESULTS: The database cohort included 976 patients (140 shoulder, 493 hip, and 343 knee), with 60% female. No notable sex differences were found in JRS utilization. FG participants (n = 24) included 12 women and 12 men. Women were younger than men (70.9 ± 9.6 vs. 73.4 ± 6.1). Both men and women reported negative physician interactions and identified return to lifestyle as key in influencing surgery decisions. Men expressed concerns about hobbies, recovery support, and felt encouraged to undergo surgical treatment. Women prioritized household responsibilities, cosmetic outcomes, and trialed alternative treatments more often and endorsed age- and gender-based biases in care.

CONCLUSION: Gender-based differences influence patient experiences and decision making regarding JRS. Although men felt supported in pursuing surgery, women perceived bias and exhausted conservative treatments first. These findings highlight the need for shared decision-making frameworks that address gender-based disparities in surgical care.

PMID:42475122 | DOI:10.5435/JAAOSGlobal-D-25-00201

JAMA Netw Open. 2026 Jul 1;9(7):e2623265. doi: 10.1001/jamanetworkopen.2026.23265.

ABSTRACT

IMPORTANCE: Relapse limits survival after allogeneic hematopoietic cell transplant. Although human leukocyte antigen-matched related donors (MRDs) are traditionally preferred, mismatched unrelated donors (MMUDs) using posttransplant cyclophosphamide may provide stronger graft-vs-leukemia effects, potentially altering donor selection strategies.

OBJECTIVE: To compare outcomes between MRD and MMUD transplant in the posttransplant cyclophosphamide era and assess whether MMUD grafts are associated with lower relapse rates.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study (January 1, 2017, to August 31, 2024) assessed 1038 patients with acute leukemia or myelodysplastic syndromes and/or myeloproliferative neoplasms undergoing their first peripheral blood hematopoietic cell transplant using posttransplant cyclophosphamide. The MRD cohort was from a single tertiary center, and the MMUD cohort was from the Center for International Blood and Marrow Transplant Research. Data were analyzed between January 19, 2026, and April 2, 2026.

EXPOSURE: Transplant from MRD (n = 306) vs MMUD (n = 732).

MAIN OUTCOMES AND MEASURES: Disease-free survival (DFS), overall survival (OS), relapse, nonrelapse mortality, and graft-vs-host disease (GVHD). The study used inverse probability of treatment weighting with overlap weights and bootstrapping to address structural confounding, particularly donor age. Cox proportional hazard models were used to compare outcomes between groups and confirm that phrasing with the author.

RESULTS: Among 1038 patients (526 [50.7%] female), donors in the MRD group were older (median [IQR] age, 57 [45-64] years) than in the MMUD group (median [IQR] age, 28 [24-35] years) (P < .001). Recipient age was similar (median [IQR] age, 60 [47-66] vs 58 [47-65] years; P = .40). In patients with a high or very high Disease Risk Index (DRI), MMUD transplant was associated with significantly lower relapse hazard vs MRD (weighted hazard ratio [HR], 0.56; 95% CI, 0.33-0.94; P = .03), although DFS (HR, 0.71; 95% CI, 0.46-1.11; P = .14) and OS (HR, 0.85; 95% CI, 0.53-1.37; P = .51) were similar. Conversely, in patients with low to intermediate DRIs, hazard estimates for DFS (HR, 1.24; 95% CI, 0.92-1.66; P = .16) and OS (HR, 1.36; 95% CI, 0.99-1.88; P = .06) lacked precision. MMUD was associated with lower risk of grade III to IV acute GVHD (HR, 0.56; 95% CI, 0.32-0.98; P = .04) but higher chronic GVHD (HR, 2.82; 95% CI, 2.02-3.95; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, MMUD transplant was associated with lower relapse rates compared with MRD in patients with high-risk malignant tumors, potentially reflecting enhanced alloreactivity, although accompanied by increased chronic GVHD. These findings indicated that the immunologic role of human leukocyte antigen mismatch varies by disease risk, suggesting that MMUD grafts offered a distinct risk-benefit profile that warrants further investigation.

PMID:42475099 | DOI:10.1001/jamanetworkopen.2026.23265

JAMA Netw Open. 2026 Jul 1;9(7):e2623622. doi: 10.1001/jamanetworkopen.2026.23622.

ABSTRACT

IMPORTANCE: Radical cystectomy for bladder cancer is associated with high complication rates. Evidence supporting perioperative specialized immunonutrition for reducing complications is limited.

OBJECTIVE: To determine whether perioperative specialized immunonutrition reduces 30-day complications compared with standard oral nutrition support among adults undergoing radical cystectomy.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, phase 3 clinical trial (SWOG S1600) conducted at 13 US academic and community sites within the National Cancer Institute National Clinical Trials Network and National Community Oncology Research Program enrolled patients from March 5, 2019, through October 19, 2023, with 30-day complications assessed through day 90 and survival outcomes through 2 years. Participants included adults with bladder cancer scheduled for radical cystectomy who could swallow oral liquids and did not have severe malnutrition. Statistical analysis was performed from January 2024 to December 2026.

INTERVENTIONS: Participants consumed drinks 3 times daily for 5 days before and after surgery. Both drinks used the same base formula. The immunonutrition product contained added l-arginine, ω-3 fatty acids, and dietary nucleotides. Adherence was 94.5% (52 of 55), measured using the plasma arachidonic acid to eicosapentaenoic acid biomarker.

MAIN OUTCOMES AND MEASURES: Analysis was performed on a modified intent-to-treat basis. The primary outcome was any 30-day complication (Clavien-Dindo grade ≥1). A 65% complication rate and a 35% relative reduction were prespecified. Secondary outcomes included high-grade complications at 30 and 90 days, adverse events, and 2-year disease-free and overall survival.

RESULTS: Of the 203 participants enrolled, the median age was 68.8 years (range 32.0-95.2 years) and 162 (79.8%) were male. Of 203 randomized (99 immunonutrition, 104 standard), 17 withdrew, and 8 lacked 30-day data, yielding 178 evaluable participants (90 immunonutrition, 88 standard). Any 30-day complication occurred in 62.2% of patients (56 of 90) receiving immunonutrition and 58.0% of patients (51 of 88) receiving standard nutrition (odds ratio [OR], 1.18; 95% CI, 0.64-2.18). High-grade 30-day complications occurred in 11.1% of patients (10 of 90) receiving immunonutrition vs 12.5% of patients (11 of 88) receiving standard nutrition (OR, 0.86; 95% CI, 0.34-2.17). Two-year overall survival was 87.4% among patients receiving immunonutrition vs 78.2% among patients receiving standard nutrition, and disease-free survival was 77.0% among patients receiving immunonutrition vs 67.5% among patients receiving standard nutrition. Adverse events occurred for 34.1% of patients (31 of 91) receiving immunonutrition and 20.5% of patients (18 of 88) receiving standard nutrition, with nausea most common.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of adults undergoing radical cystectomy, perioperative specialized immunonutrition did not reduce 30-day complications compared with standard oral nutrition. Differences in 2-year survival favored immunonutrition but were not statistically significant. Further mechanistic evaluation and subgroup analyses are warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03757949.

PMID:42475098 | DOI:10.1001/jamanetworkopen.2026.23622