Citations

Abstract Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity. Methods Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests. Results In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC. Conclusions Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

ABSTRACT Objectives Patients requiring long‐term enteral nutrition or continuous infusion of carbidopa/levodopa can benefit from jejunostomy tube placement. Recently, directly placed percutaneous transgastric jejunal tubes (TGJs) have been used instead of gastrostomy tubes with jejunal extensions (PEG‐Js) for enteral access. We aim to compare patient characteristics and outcomes after placement of TGJs placed via the introducer technique compared to PEG‐Js. Methods We performed a retrospective study of 141 patients (TGJ = 58, PEG‐J = 83) assessed at Mayo Clinic between 2010 and 2024. Patients were identified using a prospectively maintained procedure data registry. Demographic data, patient characteristics, procedural indications, complications, and first‐replacement date were gathered. Statistical analysis included the Wilcoxon rank sum test, chi‐square test, Fisher's exact test, and Kaplan‐Meier estimates. Patients receiving carbidopa/levodopa were excluded from complications analysis due to the carbidopa/levodopa tube's proprietary structure. A p ‐value of <0.05 was set as a threshold for significance. Results Our results demonstrated no difference in cumulative incidence of complications within 1 year for TGJs and PEG‐Js, p ‐value 0.48. Regarding time to first replacement, treating death as a competing risk factor, there was no statistically significant difference in cumulative incidence of replacement within 1 year for TGJs and PEG‐Js, p ‐value 0.389. Conclusions Our study demonstrates that both direct TGJs and PEG‐Js are safe options for long‐term jejunal feeding. More studies are needed to compare endoscopic to radiologically placed percutaneous transgastric jejunal feeding tubes.

Objective Despite promising outcomes from pilot initiatives, the transition to widespread adoption and upscaling of eHealth solutions in the hospital context remains challenging. This study aims to explore the barriers and facilitators influencing the implementation of eCoaches from the perspective of professionals. Methods A qualitative research design was employed, involving individual semi-structured interviews with management and healthcare professionals ( n = 10) who were involved with an eCoach either for heart failure (HF) or inflammatory bowel disease (IBD). Both eCoaches supported remote monitoring, advisory, educational, and interactive care activities. Interview topics were guided by the Consolidated Framework for Implementation Research (CFIR), including the original five domains and the added domain Patients′ needs and Resources. Data were analyzed thematically. Results Barriers and facilitators were identified across all CFIR domains: eCoach design and licensing costs (Intervention Characteristics); financial compensation (Outer Setting); integration into care pathways, Information and Communication Technology (ICT) infrastructure, team dynamics, and task reallocation (Inner Setting); intrinsic motivation, beliefs, and competencies of professionals (Characteristics of Individuals); patient resources and digital literacy (Patients’ Needs and Resources); and availability of evidence and management information (Process of Implementation). Conclusion This study underscores the complex nature of implementing eCoaches within the hospital setting, where barriers and facilitators span multiple interrelated domains. To overcome “pilotitis” and achieve the sustainable integration of blended care for patients with chronic conditions, comprehensive implementation strategies that concurrently address all relevant domains are essential. By illuminating the experiences of healthcare professionals, this study offers actionable insights to guide the design, implementation, and upscaling of eCoaches and related eHealth technologies.

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.

Abstract Background Opioid stewardship policies could adversely affect pain management for patients with cancer. Yet patients with cancer are also at risk for opioid‐related harms. This study sought to determine trends in opioid prescribing by clinical stratum and pain for patients with cancer from 2016 to 2020. Methods A retrospective study was conducted of opioid‐naive adults with newly diagnosed cancer from 2016 to 2020 ( N = 10,232) in a large Connecticut health system. Logistic regression was used to calculate changes in the predicted probability of opioid prescribing from 2016 to 2020. Two subpopulations were examined: patients treated surgically ( n = 4405) and patients with metastatic cancer ( n = 2158). Flowsheet pain scores for patients with metastatic cancer were used to stratify by no pain (all scores, 0) versus any pain. The main outcomes were new (≥1 prescription in the 0–6 months after diagnosis) and additional (0–6 and 7–9 months) opioid prescriptions. Results A decline was observed in the predicted probability of new (71.1% to 64.6%; p < .001) and additional prescribing (27.2% to 24.2%; p = .07 [not significant]) declined. Among surgical patients, the predicted probability of new opioid prescribing fell (96.0% to 88.6%; p < .001), whereas additional prescribing was stable (13%). For patients with metastatic cancer with pain, new opioid prescribing was stable (56%). For those reporting no pain, the predicted probability of new opioid prescribing declined from 61.6% to 36.1% ( p < .001). Conclusions In the context of widespread policy changes, this study showed a modest decline in new and additional opioid prescribing for patients with cancer. In metastatic cancer, prescribing remained stable for patients reporting pain and declined steeply for those reporting no pain.

Background: Estimating operative time with low accuracy and precision leads to suboptimal scheduling of available operating rooms (ORs) and waste of healthcare resources. We aimed to develop a predictive machine learning (ML) model for operative time using our institutional data to improve the scheduling of neurosurgical ORs, minimize waste, and maximize resource utilization. Methods: We developed a predictive model using our institution’s multicenter registry, which included diverse neurosurgical cases across three tertiary hospitals. We applied multiple ML techniques, including linear regression, support vector regression, deep neural networks, and extreme gradient boosting regression (XGBR). The best model was combined with the first fit decreasing bin-packing algorithm to create a practical OR scheduling system based on prior data. Results: The XGBR model exhibited the best performance, with lower mean absolute errors (MAEs) (root mean squared error: 52.24, MAE: 37.25) and higher R2 (0.76) values than other models. Implementing this model in a simulated OR scheduling scenario using institutional data, we successfully scheduled 30 random procedures with minimal residual time, such that the model ran out of procedures for the week with 86 and 171 min remaining in the cranial and spinal ORs, respectively, demonstrating potential efficiency gains. The cranial procedures were scheduled over 4 days and spinal procedures over 6 days, optimizing available OR time. Conclusion: Integrating ML models into operative time prediction can significantly improve the accuracy and efficiency of surgical schedules. This approach minimizes wasted OR time and enhances resource allocation, potentially improving patient outcomes and satisfaction by reducing waiting times.

Background: Prophylactic antimicrobials for pediatric patients requiring extracorporeal membrane oxygenation (ECMO) support are not well delineated; there are no consistent guidelines nationally or internationally. We analyzed antimicrobial use before and after implementing a narrow-spectra ECMO antimicrobial prophylaxis protocol intended to standardize prophylaxis by risk related to ECMO type and configuration. Methods: This retrospective, single-center study included children under 18 years old requiring ECMO between May 2018 and December 2021. Medical and cardiac surgical patients requiring open-chested (central) or peripheral veno-venous or veno-arterial ECMO were included. We evaluated the impact of an ECMO antimicrobial prophylaxis protocol by comparing the appropriateness of antimicrobial use as well as nosocomial infections in the pre versus post protocol. Results: Our study included 55 children with 58 individual ECMO episodes. More than 50% of the patients were open-chested during ECMO support, and the majority of ECMO support was veno-arterial. In the post protocol period, patients were 4 times as likely to have appropriate antimicrobial prescribing (Odds ratio 4.4; 95% confidence interval: 1.1–19; P = 0.036), including both prophylactic (per protocol) and therapeutic (chart documentation of an infection with appropriate therapeutic antimicrobials, including drug and duration). There was no difference in the odds of nosocomial infection occurring during ECMO pre protocol versus post protocol (pre vs. post protocol, P = 0.71 for invasive infections, P = 0.73 for all infections including potential colonization). Conclusions: After implementation of a standardized narrow-spectra ECMO antimicrobial prophylaxis protocol, we observed an increase in appropriate and standardized antimicrobial prescribing without concomitant increase in nosocomial infections.

Abstract Background: Black women continue to face disproportionate mortality and long-term challenges after breast cancer treatment, including gaps in follow-up care, culturally relevant support, and access to survivorship resources. Digital tools designed with Black survivors in mind remain limited, despite their potential to reduce disparities in post-treatment engagement. Objective: To address these gaps, we developed HERCaRE (Health Equity Resources for Breast Cancer Responsive Education), a progressive web application (PWA) designed to deliver culturally responsive survivorship education and engagement tools to Black breast cancer survivors. HERCaRE was designed to meet the need for a culturally responsive, easily accessible resource that empowers survivors to engage more confidently in their post-treatment care. Methods: The concept for HERCaRE was informed by a previous pilot study on virtual breast health education, in which participants expressed the need for more sustained and accessible support for survivors. Building on that insight, the platform was developed with advisory input from Black breast cancer survivors and community advocates through informal, discussion-based feedback. While not a formal co-design process, this input helped ensure cultural relevance in tone, structure, and visual language. HERCaRE includes three core features: educational modules on key survivorship topics, interactive behavior-prompting activities, and a notes section for self-reflection and goal tracking. The platform is grounded in the Health Promotion Model and RE-AIM framework, providing a foundation for future implementation and evaluation. The platform is currently being prepared for pilot testing, which will assess usability, perceived relevance, and engagement frequency among Black breast cancer survivors. Mixed-method surveys and platform analytics will guide refinement ahead of broader implementation. Preliminary Insights: Early input emphasized the importance of affirming, plain-language content and simple navigation. Activities were designed to promote exploration of the educational material and personal health behaviors through simple, self-guided prompts. Current efforts are focused on content finalization, participant recruitment, and platform readiness for testing. Conclusion: HERCaRE offers a responsive, theory-informed approach to digital survivorship support for Black women. While still in the pre-implementation phase, its development reflects a commitment to accessible design, cultural alignment, and future scalability. The platform lays important groundwork for reducing disparities in survivorship care and expanding digital health tools that center the needs of historically underserved populations. HERCaRE’s modular design and emphasis on user experience position it for adaptation across diverse clinical and community settings, including integration into survivorship programs serving other medically underserved populations. Citation Format: Manisha Salinas, Timethia Bonner, Laura Pacheco-Spann, Oluwadamilola Oladeru, Dianne Townsend, Che Ngufor. A culturally tailored digital health platform to improve breast cancer survivorship for Black women: HERCaRE [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B048.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

ABSTRACT Objective The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. Methods Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post‐contrast gadolinium enhancement resolution at 6 months post‐treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow‐up. Results Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39–55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2–3) and 4 (IQR 2.5–6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A 1 ), 36 (17.8%) received corticosteroids < 4 weeks (B 1 ), 21 (10.4%) received corticosteroids plus sarcoidosis‐directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non‐sarcoidosis‐directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A 1 27/106 (25.5%), B 1 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal–Wallis p = 0.69 and 0.63, respectively) after median follow‐up of 46.5 months (IQR 18–91.3). Interpretation Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.