Citations

Background Photophobia is experienced by most individuals with migraine, and it is frequently the most bothersome symptom other than headache. Light is not perceived uniformly; spectral composition and intensity influence discomfort and can exacerbate symptoms. While monochromatic green light shows therapeutic potential, it appears visually unnatural and is impractical for daily use. This study aimed to determine whether spectrally tailored white light, more visually acceptable in everyday environments, reduces light sensitivity among those with migraine. Methods Twenty adults (18–44 years) with episodic migraine completed two research sessions: one during an acute migraine attack and one between migraine attacks. Participants were exposed to four spectrally distinct white light conditions (red-, green-, cyan-, and blue-enriched) in a randomized order delivered at ten intensity levels (50–590 lux). After each exposure, visual discomfort was rated on a 0–10 scale. Pupil size was measured using a pupillometer. Repeated-measures ANOVAs examined the effects of light spectrum, intensity, and migraine state on visual discomfort and pupil response. Results Migraine attack status significantly increased visual discomfort ( F (1,19) = 25.84, p < .001, η 2 = .576). White light spectrum ( F (3,57) = 12.47, p < .001, η 2 = .396) and light intensity ( F (9171) = 124.30, p < .001, η 2 = .867) were associated with intensity of visual discomfort. Post-hoc analyses indicated that visual discomfort increased with increasing light intensity, especially at higher light intensities. Among all tested spectra, green-enriched white light resulted in the least visual discomfort; blue-, red-, and cyan-enriched white light produced significantly higher discomfort (all p < .001). Pupil size varied by spectrum ( F (3,57) = 14.13, p < .001, η 2 = .426), with green-enriched white light producing the largest pupil size. Conclusion Spectral composition, light intensity, and migraine state jointly influence both subjective and physiological responses to light. Across lighting spectra, lower light intensity was consistently associated with reduced visual discomfort, indicating greater visual comfort at lower intensities. These results identify green-enriched white light at lower intensities as a visually acceptable, migraine-conscious lighting option with potential for real-world application.

Objective We investigated potential racial disparities in the effects of audiometric hearing loss and its treatment on dementia and mortality among 3,602 older adults aged 68–89 years, 22% of whom were self-identified Black race. Methods Adjudicated all-cause dementia was determined using neurocognitive test data, proxy reports, and surveillance of hospital records and death certificates. Audiometric hearing loss, defined as the better-ear averaged pure-tone threshold (0.5–4 kHz), was categorized using clinical cutpoints. Multivariable-adjusted Cox proportional hazards models included hearing loss–race interaction terms. Results Dementia risk associated with moderate-to-severe hearing loss did not differ by race [Black participants: hazard ratio (HR): 1.66; 95% confidence interval (CI): 1.05, 2.61; White participants: HR: 1.71; 95% CI: 1.16, 2.51; P -interaction = 0.92]. However, moderate-to-severe hearing loss was associated with a 2.3-fold increase in mortality among Black participants only (95% CI: 1.17, 4.60). Conclusions Our findings emphasize the importance of including minoritized populations in hearing treatment research to build an evidence base for policy development and clinical decision-making. Hearing loss affects the health of both Black and White Americans. Racial disparities in hearing healthcare should be addressed to advance health equity for all older adults.

Abstract Introduction The evaluation of diastolic function in diabesity patients undergoing incretin-based therapy could facilitate early detection and help prevent progression to heart failure. Methodology A group of 15 diabesity cases with chest x-ray examinations (< 1 month) before and after ≥ 12 months of incretin-based therapy (absent ventricular/valvular dysfunction) were identified. Standard diabesity descriptors and predictions of pulmonary venous hypertension (aka “pulmonary congestion”) [None; Stage 1: vascular distention/redistribution but minimal interstitial edema; or Stage ≥ 2: vascular congestion with ≥ mild interstitial or alveolar edema] by validated AI-enabled chest x-ray staging, representing mean left atrial pressure in diastolic dysfunction, were evaluated pre- and post-therapy. Results By weight loss, cases clustered into equal-sized subgroups: 1. Significant Responders (9–30% decreases); 2. Insignificant Responders (0–2% decreases); and 3. Non-Responders (2–12% increases). Regarding hemoglobin A1c changes: 1. Significant Responders collectively decreased; 2. Insignificant Responders varied; and 3. Non-Responders were largely stable. Pre-therapy, all 15 cases demonstrated AI-enabled chest x-ray evidence of diastolic dysfunction; post-therapy, 4 improved (especially cases of greatest weight loss or hemoglobin A1c reduction), 5 were stable, and 6 worsened. Per subgroup, AI-enabled chest x-ray indications therapeutic response were: 1. Significant Responders (all demonstrating unequivocally decreased obesity and improved diabetes) collectively showed stable-decreased dysfunction; 2. Insignificant Responders (all demonstrating minimally decreased obesity but stable-worsening diabetes in most) reflected stable-increased dysfunction in 60%; and 3. Non-Responders (all demonstrating increased obesity but stable-improved diabetes) showed increased dysfunction in 80%. Conclusion AI-enabled CXR staging detects background subclinical diastolic dysfunction in diabesity and monitors its response to incretin-based therapy.

Abstract Introduction: Early relapse limits durable remissions in multiple myeloma (MM). Cell-free DNA (cfDNA) fragment patterns capture tumor burden and nucleosome positioning. We tested whether a fragmentomics signature trained at MRD time points stratifies progression-free survival (PFS) when applied to pretreatment plasma. Methods: We performed 30-40× whole-genome sequencing of plasma cfDNA from 43 newly diagnosed MM patients, with 65 additional MRD timepoint samples from 41 of those patients (post-ASCT n=30; 1-year maintenance n=30; other maintenance n=5) across eight Canadian sites (TFRIM4 and IMMAGINE studies) and one U.S. site (Mayo SPORE). MRD testing used multiparameter flow cytometry for all follow-up samples (n=65) and clonoSEQ in a subset (n=31). Logistic and elastic-net models were trained at MRD timepoints on fragmentomics features (short-fragment burden; a combined model integrating fragment-length distributions with inferred nucleosome positioning at MM-specific chromatin accessibility regions [Ordoñez et al., Genome Res. 2020]). A decision threshold was fixed by the Youden index during training and applied unchanged to diagnosis samples. PFS was analyzed by Kaplan-Meier, log-rank, and Cox models. Results: After a median follow-up of 49.1 months, 16 of 43 patients (37%) progressed. Using the prespecified locked threshold, patients classified as MRD+ by the proportion-of-short-fragments model had significantly shorter PFS than MRD- patients (HR = 5.12; 95% CI 1.16-22.57; log-rank p = 0.016), with median PFS of 49.2 months for MRD+ cases versus not reached for the MRD- group. Fixed-horizon PFS favored MRD- samples at 24/36/48 months (100/94/87% vs 85/81/53% for MRD+). A combined model integrating weighted fragment lengths with inferred nucleosome positioning also separated outcomes (log-rank p=0.054); the Cox HR was not estimable because no MRD- patients relapsed. At 24, 36, and 48 months, baseline MRD positivity by the short-fragment model identified 100%, 83%, and 86% of patients who relapsed within those intervals (specificity 44%, 43%, and 52%), while the combined model detected all early relapses across the same horizons (specificity 15-21%), indicating consistently high sensitivity but modest specificity for predicting early progression. Conclusions: A cfDNA fragmentomics signature trained at MRD time points stratified PFS when applied to diagnostic plasma, identifying patients at risk of early relapse. Short-fragment burden was most discriminative, and a combined model with nucleosome positioning recapitulated it with higher sensitivity, albeit lower specificity. These data support cfDNA fragmentomics as a practical liquid-biopsy risk biomarker in MM and suggest higher signals may proxy aggressive disease with greater tumor shedding and chromatin disorganization. Future work will validate findings in larger cohorts and integrate cytogenetic and immune features. Citation Format: Dor David Abelman, Jenna Eagles, Aimee Wong, Saumil Shah, Jeffrey Bruce, Stephanie Pedersen, David S. Scott, Cecilia Bonolo de Campos, Signy Chow, Darrell White, Irwindeed Sandhu, Kevin Song, Esteban Braggio, Shaji Kunnathu Kumar, Alli Murugesan, Tony Reiman, A. Keith Stewart, Suzanne Trudel, Trevor J. Pugh. Baseline cfDNA fragmentomics identifies multiple myeloma patients at risk of early progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2597.

Abstract Background and Aims Whether hemodynamic and symptomatic benefits of the APTURE left atrial-to-coronary sinus shunt translate into clinical outcome benefit in heart failure with left ventricular ejection fraction &gt;40% remains unknown. Methods In this post hoc analysis of ALT-FLOW EFS patients undergoing APTURE implantation, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score-predicted 1-year all-cause mortality was compared with observed mortality by Kaplan-Meier analysis of adjudicated events. Heart failure hospitalization (HFH) rates were compared for the 12 months before vs after implantation. Additional analyses included stratification by baseline sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and N-terminal pro-B-type natriuretic peptide (NT-proBNP), recurrent HFH cumulative hazard estimation (Nelson-Aalen), and H2FPEF score calculation. Results Among 95 patients (mean age 70.9 ± 8.5 years; 50% women; 93% New York Heart Association Class III; 85.9% with H2FPEF score &gt;3), MAGGIC-predicted 1-year mortality was 13.0%. Observed 1-year survival was significantly higher than predicted (94.7% vs 87.0%; P=0.04), consistent across SGLT2i subgroups (log-rank P=0.59). The proportion of patients with HFH declined from 37.9% pre implantation to 9.6% post implantation (P&lt;0.0001), with event rates falling from 0.61 to 0.21 per patient-year (P&lt;0.001) and a 1-year cumulative hazard of recurrent HFH of 0.19 (95% confidence interval, 0.12-0.31). HFHs were evenly distributed across NT-proBNP strata. Conclusions In ALT-FLOW EFS, observed 1-year mortality was lower than MAGGIC-predicted mortality, and post implantation HFH rates were lower than pre implantation rates. These hypothesis-generating findings will require confirmation in the randomized, sham-controlled ALT-FLOW II trial.

Background: Pancreatitis significantly alters the microbial composition of the oral and intestinal compartments, causing dysbiosis that may contribute to disease mechanisms and potentially serve as a basis for diagnosis or treatment. Objective: To determine whether the oral or gut microbial signature can classify chronic pancreatitis (CP). Methods: Stool samples (n=707) were collected from participants in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED). Samples were distributed among 200 healthy (HC), 310 CP, 49 acute pancreatitis (AP), and 148 recurrent acute pancreatitis (RAP). In addition, saliva samples were collected for a subset of participants (n=156). Whole genome sequencing was performed to assess microbiome composition. Machine learning algorithms were utilized to identify a signature with microbial features predictive of CP. Results: Gut alpha diversity was significantly decreased in AP, RAP, and CP compared with HC, with CP exhibiting the lowest diversity. In contrast, oral microbial diversity showed no significant variation across groups. Beta diversity analysis revealed distinct gut microbiome compositions between HC and pancreatitis subtypes, with CP showing the most pronounced differences. Random forest models using gut microbial species demonstrated robust predictive performance for CP using a minimum of 10 species (Area under the curve—AUC: 0.834; accuracy: 0.774). Despite similarities in gut microbiome composition across pancreatitis subtypes, a unique gut microbial signature for CP was identified highlighting the microbiome’s potential in CP diagnosis. Conclusion: Our study reveals a gut microbial signature predictive of CP using machine learning models in a large US multi-institutional cohort.

Abstract Background Robotic left pancreatectomy (RLP) is increasingly adopted worldwide. Current guidelines suggest a learning curve of 21 cases, yet its impact on major morbidity and oncological quality remains uncertain. Methods A retrospective multicentre international study was undertaken across 10 centres in the UK, Spain, Germany, the USA, and Australia (2014–2025). Consecutive patients undergoing RLP were categorised into competency (first 21 cases per centre) or proficiency phase (&gt;21). The primary outcome was major morbidity (Clavien–Dindo grade ≥ IIIa), and secondary outcome was the R1-margin rate. Mixed-effects logistic regression and risk-adjusted cumulative sum (RA-CUSUM) analyses were performed. Results 521 patients underwent RLP, including 200 (38.4%) in the competency phase and 321 (61.6%) in the proficiency phase. Median age was 63 years (IQR 54–73), and 56.4% were female. Rates of major morbidity were similar between phases (14.5% versus 14.0%, P = 0.981), as were R1 margin rates (21.6% versus 19.7%, P = 0.092). Independent predictors of major morbidity included male sex (OR 1.76, P = 0.037), preoperative pancreatitis (OR 2.23, P = 0.031), and multivisceral resection (OR 2.29, P = 0.034). Among patients with adenocarcinoma (n = 110), prolonged operative time (OR 1.39 per hour, P = 0.004) and nodal positivity (OR 2.62, P = 0.047) predicted R1 resection, while learning phase was not associated with margin status. RA-CUSUM demonstrated no excess morbidity over time in any centre. Conclusions In this first multicentre international analysis, the learning phase of RLP did not increase the risk of major morbidity or compromise oncological quality. These findings support the safe global adoption of RLP with appropriate training and case selection.

Abstract Background Minimally invasive left-sided pancreatectomy (MIS-LP) is increasingly adopted for pancreatic neuroendocrine tumours (PNETs), yet its oncological safety compared with open surgery (O-LP) remains debated. Robust population-level evidence is required to guide practice. Methods Patients ≥65 years with grade 1–2 PNETs undergoing left pancreatectomy were identified from the SEER-Medicare database (2010–2019). Overall and cancer-specific survival outcomes were analysed using multilevel Cox regression after propensity-score matching (PSM). Landmark analysis from 6 months excluded early postoperative deaths. Results 772 patients were included: 257 (33%) MIS-LP and 515 (67%) O-LP. Median age was 71 years; 87% had grade 1 and 13% grade 2 tumours. Before matching, MIS-LP patients had lower comorbidity (median Charlson Index 2 versus 3, P = 0.011) and fewer with metastatic disease (2.0% versus 5.7%, P = 0.019). After PSM (MIS-LP n = 248; O-LP n = 441), 5-year overall survival was higher with MIS-LP (88.1% versus 84.5%, P = 0.03), while 5-year cancer-specific survival was similar (95.2% versus 93.5%, P = 0.11). O-LP was associated with increased risk of death (HR 1.75, 95% c.i. 1.05–2.91, P = 0.030), though not cancer-specific death (HR 1.97, 95% c.i. 0.86–4.54, P = 0.110). Notably, all 90-day mortalities (n = 15, 1.9%) occurred in the O-LP group. In landmark analysis beyond 6 months, surgical approach was no longer predictive of OS or CSS. Conclusions MIS-LP confers an early survival advantage, driven by reduced perioperative mortality, without compromising long-term oncological outcomes. As the largest population-based analysis in this setting, these findings support MIS-LP as the standard surgical approach for older patients with low- to intermediate-grade PNETs.

Importance Adjuvant chemotherapy regimens may be administered after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMNs), although the evidence supporting their use is limited. Objective To evaluate the survival benefit associated with contemporary adjuvant chemotherapy regimens after resection in A-IPMNs between 2017 and 2023. Design, Setting, and Participants This retrospective cohort study was an international, multicenter study with 69 participating centers across Europe, North America, South America, and the Asia-Pacific region. Patients undergoing resection for A-IPMNs were included. Data were analyzed from May to August 2025. Intervention Contemporary adjuvant chemotherapy regimens, such as gemcitabine-capecitabine (GemCap); 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), modified FOLFIRINOX (mFOLFIRINOX), and S-1. Main Outcome and Measure Overall survival (months). Results Among 1321 patients (median [IQR] age 70 [63 to 76] years; 713 males [54.0%] and 608 females [46.0%]), 781 patients (59.1%) received adjuvant chemotherapy, while in 181 patients (13.7%) it was omitted due to poor patient fitness. Of patients who received adjuvant chemotherapy, 568 patients (72.6%) received contemporary regimens, including GemCap (232 patients [29.7%]), FOLFIRINOX (176 patients [22.5%]), mFOLFIRINOX (71 patients [9.1%]), and S-1 (70 patients [9.0%]). The median (IQR) follow-up for the cohort was 64.2 (40.4 to 85.0) months, and the median overall survival was 73.8 months (95% CI, 66.4 to 81.9 months). After 90-day landmark analysis and exclusion of patients ineligible for chemotherapy, adjuvant chemotherapy vs no adjuvant chemotherapy (propensity score–matched populations, 243:243 patients) was not associated with improved overall survival (median, 82.3 months; 95% CI, 78.2 months to not applicable [NA] vs not reached; 95% CI, 75.3 months to NA; P = .58). Contemporary regimens vs no adjuvant chemotherapy (propensity score–matched populations, 309:309 patients) was not associated with longer survival, and a mean survival benefit greater than 4.2 months over 5 years was excluded (difference in restricted mean survival, 1.26 months; 95%, −1.72 to 4.24 months). Treatment outcomes did not vary by chemotherapy regimen or disease characteristic (eg, N stage or carbohydrate antigen 19-9 level). Conclusions and Relevance In this study, contemporary adjuvant chemotherapy was not associated with improved overall survival in A-IPMNs, and a randomized clinical trial is indicated.