Citations

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work using human organoids found that dietary glucose hyperabsorption is a steadfast trait in cultures derived from some obese subjects, but detailed transcriptional or epigenomic features of the intestinal epithelia associated with this persistent phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as non-obese, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subject organoids have significantly upregulated dietary nutrient absorption transcripts and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting predicted that enhanced HNF4G binding may promote the obese hyperabsorption phenotype. Quantitative RT-PCR assessment in organoids representing a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, SLC5A11, and SLC2A5 were highly correlated with hyperabsorption. Thus, the obese hyperabsorption phenotype was characterized by transcriptional changes that support increased nutrient uptake by intestinal epithelia, potentially driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides a new perspective in considering therapeutic targets and options with which to manage the disease.

230 Background: The burden of symptoms and financial toxicity are well-documented adverse effects of cancer treatments. Recently, logistic toxicity has emerged, referring to the detrimental impact of logistical demands associated with cancer treatment on patient well-being. For non- English speaking patients, language barriers can affect their treatment experience, increasing logistic burdens. Methods: Between September 2024 and May 2025, semi-structured qualitative interviews were conducted with 21 low English proficiency (LEP)/non-English speaking adults with cancer. The interviews explored logistic challenges faced due to LEP and its impact on patients' cancer care experience. Transcripts were analyzed using an inductive thematic analysis approach. Results: Of the 39 identified eligible individuals, 26 provided consent, and 21 (81%) completed the interview. The most common primary language of the participants was Spanish (9, 43%), followed by Somali (3, 14%), Arabic and Korean (2, 9%), and Amharic, Mandarin, Hmong, Russian, and Vietnamese (1, 5%). Seven major themes emerged regarding the logistic burdens of cancer care: (1) communication challenges, (2) navigating healthcare systems, (3) emotional distress from diagnosis and communication barriers, (4) financial toxicity, (5) transportation challenges, (6) adverse treatment effects, and (7) concerns about the political climate and its impact on resources. Conclusions: The increase in non-English languages in the U.S. highlights the need to understand the unique challenges faced by these patients. This study identified logistic toxicity themes consistent with previous research, while also revealing unique challenges. Further research is necessary to explore strategies to mitigate logistic burdens among those with LEP. Theme Illustrative Quotes Communication challenges “Communication with the psychologist was challenging … I couldn’t express myself effectively and it left me unsatisfied with the interaction.” Navigating healthcare systems “dealing with the insurance, it has been difficult … I have to depend on another person to help me” Emotional distress from diagnosis and communication barriers “In addition to my sickness, the lack of communication and understanding… makes me very sad.” Financial toxicity “...there's no income. There is nothing to feed our children.” Transportation challenges “I have to leave home 2 or 3 hours in advance because people will help me, not within my time, but within their own time.” Adverse treatment effects “I noticed weird feelings in my limbs. I'm not able to write down or hold anything. It makes everything difficult.” Concerns about current political climate and its impact on existing resources “… that they don't want Spanish spoken in the United States. They're not going to provide help for people like me at the hospitals…”

98 Background: Prior authorization (PA) purports to control costs and ensure adherence to evidence-based guidelines but negatively impacts cancer care. Radiation oncology (RO) represents a minority of overall cancer spending yet bears a disproportionately high PA burden. Limited research exists on the effects of PA on patient outcomes and administrative workload within RO clinics. Methods: From 9/2024 to 10/2024, an online survey was open to U.S. members of the American Society for Radiation Oncology assessing experiences with PA including disposition (approval/denial/appeal including peer-to-peer [P2P] review) and perceived impact on patient care and administrative workload. Outcomes included treatment delays, changes from recommended treatment, and patient event including hospitalization, ED visits, permanent disability, or death. Descriptive statistics evaluated responses. Results: Of 736 responding radiation oncologists (16% response rate), 83% reported a rise in PA over the past three years, with 58% noting the burden has increased greatly. In the past year, 50% reported that more than half of their cases required PA, with a median approval rate of 75% and median overturn rate of 82% for denials. For more than half of their cases, nearly half of physicians (43%) noted that P2P was a futile effort to overturn PA denials due to insurance policies. Most (75%) reported that PA resulted in their practice needing to reallocate staff; 91% reported worsening burnout due to PA. P2P reviews were particularly burdensome, averaging 1.65 hours per week. A third (30%) reported that PA requirements had caused serious complications for their patients, including 7% who reported PA had contributed to patient death. Almost all (91%) reported PA-related treatment delays for some of their patients, with 58% indicating average delays of ≥5 days. Most (81%) reported that at times they had to use radiation techniques they considered less optimal due to PA, including 58% who were forced to deviate from national guidelines. The most common reasons for not appealing a PA denial were anticipated delays (73%), perceived futility based on prior PA experiences (62%), and administrative burden (45%). Conclusions: The administrative and clinical burdens associated with PA have significant implications for patient care, physician well-being, and healthcare resource allocation in RO. Treatment delays, compromised therapies, and adverse patient outcomes are commonly reported and underscore the need for PA reform to improve patient outcomes, reduce physician burnout, and improve efficiency.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal resurfacing (DMR), offer minimally invasive interventions that target metabolic dysfunction and weight loss. This review synthesizes current evidence on the mechanisms and hepatic outcomes of EBTs in MASLD, highlighting improvements in hepatic steatosis, liver stiffness, and fibrosis biomarkers across multiple modalities. ESG is consistently associated with reductions in hepatic steatosis and fibrosis scores across multiple studies. IGB therapy improves liver stiffness and reduces hepatic fat as assessed by imaging modalities such as MRI- Proton Density Fat Fraction and ultrasound. DJBL lowers liver enzymes and improves non-invasive markers of steatohepatitis like the Fibroscan-AST score, although its effect on fibrosis appears limited. DMR demonstrates reductions in liver fat, particularly in patients with type 2 diabetes, but evidence for histological improvement in MASLD remains inconsistent. Despite their promise, most EBT studies remain limited by small sample sizes and short follow-up. Further randomized trials are needed to validate long-term efficacy and position EBTs alongside or as alternatives to surgical interventions for MASLD.

Purpose To evaluate the proportion of patients with choroidal nevus in an ocular oncology practice who would be suitable candidates for monitoring via a virtual photoscreening model, wherein imaging is asynchronously reviewed and longitudinally managed by an ocular oncologist. Methods Data were abstracted from the Prospective Ocular Tumor Study Database for all patients diagnosed with choroidal nevus from July 2019-October 2024. A stratification model for identification of virtual pathway candidates was defined and implemented as follows: good virtual pathway candidates included those with posteriorly located lesions for adequate photographic capture and no more than two high-risk features. Risk factors, outlined by the TFSOM-DIM acronym, included thickness >2 mm, presence of subretinal fluid, visual acuity 20/50 or worse, presence of orange pigment, low internal reflectivity, and basal diameter >5 mm. Of posteriorly located lesions, those with 0–2 risk factors were defined as good virtual pathway candidates, 3 risk factors as acceptable in select cases, and 4 or more as poor candidates. Results There were 614 choroidal nevi in 586 patients diagnosed during the study period. Mean patient age at initial visit was 63.5 years old (median 66.1, range 5.8–94.8), with 59.4% female and 98.8% white. Analysis identified 436 (71%) nevi in 408 (69.6%) patients as good virtual pathway candidates, 53 (8.6%) nevi in 53 (9%) patients as potential candidates in select cases, and 125 (20.4%) nevi in 125 (21.3%) patients as poor candidates. Conclusion Nearly 70% of patients with choroidal nevi followed by Mayo Clinic Ocular Oncology were identified as good candidates for follow-up via virtual photoscreening. This highlights the potential for improved clinical efficiency through virtual frameworks in ocular oncology.

Abstract Objective This study aimed to understand the factors limiting access to medications for the preventive treatment of migraine and to improve access to evidence‐based preventive care. Background For decades, the effective use of medication for the preventive treatment of migraine was limited by slow onset, slow and complex dose titration schedules, modest benefits, drug interactions, frequent side effects, and very low long‐term adherence. The calcitonin gene‐related peptide (CGRP) targeted preventive medications mitigate some of these limitations and demonstrated substantial therapeutic benefits in a significant proportion of adults with migraine. The American Headache Society considers these medications among the first‐line options for migraine prevention, although access to them remains limited. The American Migraine Foundation hosted a single‐day, multidisciplinary expert panel discussion to identify barriers to optimal preventive care and developed recommendations to address them. Methods Participants identified and prioritized barriers and used a modified nominal group technique to achieve consensus on them. A series of moderated discussions in plenary and breakout sessions was used to create possible solutions. Modified nominal group technique was also employed to achieve consensus on the priorities among these barriers and to achieve whole‐group consensus on the recommendations. Ethical issues that inform access were discussed. Results Participants included eight neurologists and board‐certified headache specialists, six representatives of reimbursement decision‐makers, six employees of life sciences companies, four patient advocates with lived experience with migraine, and a medical ethicist. Among those who have consulted healthcare professionals and received a diagnosis of migraine, we identified four main barriers to accessing preventive treatment: restrictive prior authorization requirements, the perceived lack of real‐world evidence and treatment guidelines, the need for clinician education, and the need for patient education. Consensus recommendations for eliminating barriers centered on using new evidence to evaluate policies that restrict the selection of first‐line therapies, initiating/improving collaboration among stakeholders, sharing of data and best practices, and increased training. Participants agreed to explore novel definitions of the value of preventive treatment and to establish the Migraine Prevention Network to facilitate ongoing cooperation and collective action. However, due to financial limitations, staffing changes, and time constraints, post‐meeting discussions led to a shift from establishing a broad Migraine Prevention Network to forming smaller task forces focused on the top‐priority barriers (real‐world evidence and The Patient Playbook ) identified through collaborative voting among American Headache Society, American Migraine Foundation, and industry stakeholders. Conclusions Adults with migraine face multiple barriers in accessing novel migraine‐specific, CGRP‐targeted preventive treatment. Stakeholders in the delivery of care, including clinicians, reimbursement decision‐makers, life sciences companies, and patient and clinician advocates, may be able to overcome many of these barriers and improve access by working with and on behalf of patients.

Importance The definition of cure in stage II to III colon cancer (CC) remains unclear due to limitations in conventional end points, which include deaths and second primary tumors as events. These can complicate communication with patients regarding long-term outcomes. Objective To distinguish relapses from competing health-related events to classify long-term outcomes years after surgery and explore when the incidence of true relapses of the initial CC approaches 0% to define cure in this disease. Design, Setting, and Participants This pooled analysis of individual patient–level data from 15 phase 3 randomized clinical trials assessed time to CC-related relapse using Kaplan-Meier and Aalen-Johansen methods, with death and second primary tumors treated as competing risks. Cox regression models evaluated prognostic associations, stratified by sex, stage, and tumor. Patients with stage II to III CC who underwent adjuvant chemotherapy were included. All patients had undergone radical surgery for CC and received adjuvant chemotherapy with a median follow-up of at least 6 years. The Adjuvant Colon Cancer Endpoints (ACCENT) and the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) databases included adjuvant studies conducted between 1996 and 2015. Data were analyzed from February 2022 to June 2025. Exposures Adjuvant chemotherapy regimens varied across trials, including fluoropyrimidines alone or in combination with oxaliplatin or biologic agents. Main Outcomes and Measures The primary outcome was time to CC-related recurrence. The predefined threshold for cure was a recurrence risk below 0.5%. Results Of 35 213 included patients, 19 346 (54.9%) were male, and the mean (SD) age was 60.2 (10.8) years. The incidence rate of recurrence peaked at 6.4% (1993 of 31 373) between month 6 and month 12 and decreased continuously until year 10 of follow-up never exceeding 0.5%. Recurrence rate appeared to increase again after year 10 and peaked at 2.0% during year 12.5 to year 13, a pattern observed exclusively in the MOSAIC trial. Competing-event analysis revealed that death and second primary tumors inflated the apparent recurrence rate, especially for older patients. The overall cumulative incidence of relapse with death as competing risk was lower among female patients (hazard ratio, 0.58; 95% CI, 0.45-0.76; P < .001). Conclusions and Relevance In this pooled analysis of phase 3 randomized clinical trials, a recurrence rate less than 0.5% occurred after 6 years from surgery, supporting a practical definition of cure. Recognizing this milestone may improve patient communication, guide follow-up duration, and reduce unnecessary long-term surveillance.

Background: Variable terminology is used in the literature to describe facial synkinesis and hypertonicity following incomplete recovery from facial paralysis and its associated medical and surgical treatments. Study Objectives: Establish a nomenclature consensus for this condition among a group of facial nerve experts. Design Type: Consensus study. Methods: Using modified Delphi methodology, an international, multidisciplinary group of facial nerve experts reviewed the terminology for the name of the clinical condition and treatments of interest. Online surveys and a virtual discussion were performed to establish consensus, defined a priori as agreement by 80% of the group. Results: Twenty-five facial nerve experts established consensus after three Delphi rounds. Consensus terminology for the condition is “facial synkinesis” with 84% agreement. Medical treatment is termed “chemodenervation” with 100% agreement. Surgical treatments including “selective facial neurectomy,” “selective facial neurotomy,” “selective facial myectomy,” and “selective facial myotomy,” were defined and reached agreement of 100%. Conclusions: This international group of facial nerve experts has recommended standardized nomenclature for the condition of facial synkinesis and its various treatments. While “facial synkinesis” reached consensus as the preferred term, some experts noted it may insufficiently describe the full clinical spectrum, which includes muscle hypertonicity, weakness, and spontaneous twitching.

Purpose Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. Methods The systematic review used in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The EPC synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 articles evaluating 46 nonhormonal interventions were described in an evidence map. Results Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and nonhormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. Conclusion The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making, considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

Abstract Introduction The rapidly ageing population and multimorbidity are associated with increased emergency department (ED) visits by older adults. In the ED, older adults have higher risk of hospitalization, functional and cognitive decline, and mortality. Boarding, holding admitted patients in the ED awaiting a hospital bed, exacerbates these negative outcomes, which disproportionately affect older adults. Methods We conducted a cross-sectional analysis to investigate US boarding trends by age using clinical administrative data from 5 health systems and publicly available NHAMCS data from 2018 to 2024. Results Boarding ≥3 h in the ED has increased across diverse hospital types, with oldest adults (85+) facing the greatest risk (System 4: IRR [95% CI] = 1.18 [1.15-1.20], System 5: IRR [95% CI] = 1.20 [1.17-1.23], System 3 [Community Hospital]: IRR [95% CI] = 1.25 [1.19-1.33]). These results were recapitulated at the national level in NHAMCS (IRR [95% CI] = 1.30 [1.05-1.61]). Discussion The trend of increased boarding has serious implications for patients, caregivers, and health systems. The 2025 CMS Age-Friendly Hospital Measure offers opportunities to improve processes and procedures to mitigate the negative effects of hospital boarding on older patients. We highlight opportunities to address this challenge, including ongoing quality improvement initiatives, bed prioritization algorithms, and alternate admission pathways.