Citations

Background: While tobacco use is a well-known risk factor for adverse outcomes after carpal tunnel release (CTR), the impact of non-tobacco nicotine products remains unclear. This study evaluated complications in CTR patients with non-tobacco nicotine dependence (NTND) compared with tobacco users and controls. Methods: Patients who underwent CTR with ≥2-year follow-up were identified using a large national database. After 1:1 propensity score matching, patients with NTND (n = 6319) were matched to controls, tobacco users (n = 86 430) were matched to controls, and patients with NTND (n = 6325) were matched to tobacco users. Matching was based on age, gender, Charlson comorbidity index, and comorbidities. Outcomes including 90-day medical complications, infection, emergency department (ED) visits, readmissions, and 2-year revision rates were compared using multivariable logistic regression. Results: Compared with controls, patients with NTND demonstrated higher 90-day medical complication rates (2.4% vs 1.7%; odds ratio [OR], 1.35; 95% CI, 1.04-1.77) and ED visits (10.3% vs 8.1%; OR, 1.16; 95% CI, 1.02-1.32). Compared with tobacco users, patients with NTND had decreased ED visits (10.4% vs 14.2%; OR, 0.74; 95% CI, 0.66-0.83) and revision surgery (1.9% vs 2.5%; OR, 0.78; 95% CI, 0.62-0.99), with no significant differences in medical complications, infection, or readmissions. Conclusions: Non-tobacco nicotine dependence was associated with increased medical complications and ED visits compared with controls, but decreased ED visits and revision surgery compared with tobacco users. There were no significant differences in medical complications, infections, or readmissions between tobacco users and patients with NTND. These findings underscore the importance of screening for non-tobacco nicotine use during preoperative evaluations for CTR.

Traditional home-call managing after-hours pager communications remains a common component of hematology-oncology fellowship and modern practice. Little is known about these patient-related interactions and implications. This project aimed to characterize after-hours pager volumes and evaluate perceived impacts on care, physician wellbeing, and trainee education. We performed a mixed-methods study at a tertiary academic center, analyzing after-hours pager activity from 2020-2024 across Hematology Consult (HCP), Hematology Outpatient (HOP), and Medical Oncology (MOP) pagers. A survey of hematology-oncology fellows evaluated perceptions and attitudes toward the home-call experience using free-text responses and a 5-point Likert scale. After-hours pager burden was substantial and sustained. The MOP received >3,000 pages annually, with medians of 5-6 per weekday and 15-15.5 per weekend day. The HOP volume nearly doubled over the study period (960 to 1,721 annually) with median pager volumes of 1-3 per weekday and 2-7 per weekend day. The HCP volume ranged from 594-768 pages annually. Survey response rate was 58% (19/33). Only 16% of fellows endorsed educational value from patient calls on MOP or HOP, and ≤5% agreed that call tasks required physician-level expertise. Respondents reported that the pager resulted in fatigue, anxiety, and social disruptions. Free text responses revealed themes of low educational value, high non-urgent call volume, and system inefficiencies. Contemporary home-call had substantial pager burdens with limited actionability, adverse effects on wellbeing, and low educational value. Systems engineering, including triage processes and augmented patient education, could help optimize patient care, physician wellbeing, and trainee education.

Peripheral impairment: a novel therapeutic target in Fontan physiology? Exercise intolerance is nearly universal in adults post-Fontan procedure. This exercise catheterization study showed that two-thirds of adults with Fontan circulation exhibited peripheral limitation to exercise, alongside established central hemodynamic constraints. Moreover, peripheral oxygen extraction was an independent determinant of exercise capacity in multivariable analyses. As demonstrated in HFpEF, peripheral oxygen extraction may represent a modifiable therapeutic target in Fontan physiology.

BACKGROUND: Hemorrhoids are common and relief anchors on symptom improvement. Despite several available treatment options, the optimal patient-reported outcome measure for contemporary clinical trials is not established. OBJECTIVE: We aimed to systematically assess patient-reported outcome measures that measure hemorrhoid symptom severity and/or health-related quality of life. DATA SOURCES: A systematic review was performed using PubMed and Embase (1980-2025). STUDY SELECTION: Prospective development/validation studies evaluating patient-reported outcome measures relevant to hemorrhoidal disease. MAIN OUTCOME MEASURES: Patient-reported outcome measures were evaluated on key measurement properties of reliability, internal consistency, construct validity, and responsiveness according to COSMIN v2.0 criteria. RESULTS: Of the 1,266 total studies reviewed, nine patient-reported outcome measures were identified: seven measure symptom severity and six measure health-related quality-of-life. Three demonstrated reliability, internal consistency, construct validity, and responsiveness. The Patient Reported Outcome Measure-Haemorrhoidal Impact And Satisfaction Score comprehensively measures symptom severity, health-related quality-of-life, and treatment satisfaction. The Hemorrhoidal Disease Symptom Score classifies patients with high or low symptom load, and when used in combination with Short Health Scale-Hemorrhoidal Disease, also measures impact on health-related quality of life. LIMITATIONS: Preference toward specific measures may differ between clinical trials and clinical practice. CONCLUSIONS: We identify two viable patient-reported outcome measures for use in future clinical trials that evaluate hemorrhoid interventions.

BET bromodomain inhibitors are efficacious as anti-inflammatory compounds, but clinical translation is hampered by dose-limiting toxicities from non-selective inhibition. We herein report compounds 16 and 26, based on previously reported 4-methyl-1,2,3-triazole-based inhibitor, DW34. 16 has a BRD4 BD1 Ki of 10 nM, and up to 13–38-fold selectivity for BRD4 BD1 over other BD2 domains, and an improved hERG affinity of 4.24 µM over DW34. 26, A biscyclopropyl analog of 16 showed further enhancement of BD1 selectivity over BD2 (26–203-fold), but exhibited more potent hERG inhibition. Compound 16 had improved liver and plasma clearance over DW34, with good biodistribution to the liver, and had an intracellular target-engagement affinity Ki of 92 nM, with reduction of Ccl2, Cxcl1, AST, and ALT in in vitro and in vivo mouse models of liver inflammation. 16 represents a useful lead for treating inflammatory liver diseases, with improved specificity, drug-like properties, and reduced hERG affinity.

BACKGROUND: The right ventricular (RV) response to pressure overload is a crucial determinant of outcomes in pulmonary arterial (PA) hypertension. Sotatercept improves clinical outcomes, but its effects on the right ventricle have been inconsistent. We evaluated the effects of sotatercept on load-independent measures of RV contractility, RV–PA coupling, and right heart deformation at rest and exertion in patients with PA hypertension. METHODS: In this prospective trial among participants with PA hypertension recruited between July 2024 and May 2025, we performed simultaneous echocardiography and invasive pressure measurements during rest and exercise to evaluate changes in RV contractility (end-systolic elastance [Ees]), afterload (PA elastance [Ea]), RV–PA coupling (ratio of arterial Ea to Ees), and right heart deformation, including RV and right atrial strain, before and after 24 weeks of sotatercept using mixed models. RESULTS: Among 30 participants (n=21; 70% female; mean age, 49.3 years [SD 13.5]), sotatercept decreased PA Ea. These changes were associated with reduced RV contractility, PA pulsatility index, and the maximal rate of RV pressure increase over time (dP/dt max ; P <0.001 for all). The decrease in Ees was associated with a decrease in PA Ea (r=+0.70 [95% CI, +0.44 to +0.85]; P <0.0001) with preserved RV–PA coupling (mean difference, +0.08 [95% CI, −0.11 to +0.26]; P =0.42). Although systolic indices measured at the base of the right ventricle (tricuspid annular plane systolic excursion and systolic velocity of the lateral tricuspid annulus) decreased after sotatercept use, there was an increase in RV free wall–dependent systolic indices, including resting and exercise RV free wall strain (mean difference, +6.2% [95% CI, +4.5 to +7.8]; P <0.0001) and fractional area change ( P =0.0001). Beyond the right ventricle, there was also improved right atrial filling and contractile performance across rest and exercise ( P <0.0001 for all). CONCLUSIONS: Sotatercept decreases RV contractility in proportion to reduced afterload, while preserving the RV–PA coupling relationship. Despite decreased RV contractility, global measures of right heart performance, such as RV free wall strain and RA strain, improve, alongside redistribution of RV deformation from annular motion to free wall shortening. These data suggest that sotatercept causes an energetically favorable reduction in resting RV contractility to match the lower afterload, which does not appear physiologically detrimental when considering the concurrent improvement in RV free wall contractile mechanics and exertional right heart reserve. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06409026.

Introduction: Frontotemporal lobar degeneration (FTLD) is a devastating disease that commonly results in early onset dementia, yet its rarity and heterogeneity limit large-scale research and clinical trials. Remote monitoring via low-burden digital health tools may overcome these barriers. We evaluated clinical utility of passive smartphone monitoring in FTLD using a multi-domain mobile assessment platform. Methods: Participants were 567 adults (53% clinically normal, 21% prodromal FTLD, 26% symptomatic FTLD) who completed an in-person study visit and downloaded the ALLFTD Mobile App on their personal smartphones. The app delivered unsupervised cognitive tests and passively collected continuous data on battery percentage (proxy for smartphone use) and step count. Longitudinal follow-up included smartphone monitoring and annual in-person study visits. Primary analyses examined associations between passive smartphone features and markers of disease severity at baseline and longitudinally, and tested whether passive features added incremental value beyond app-based cognitive testing. Results: Passive smartphone features were feasible to collect and showed excellent reliability with <2 weeks of monitoring (ICCs>0.9). Features capturing smartphone use and movement demonstrated sensitivity to gold-standard clinical measures of disease severity both at baseline and longitudinally. A classification model combining passive features, the app-based cognitive composite score, and demographics detected longitudinal functional decline (AUC=0.89); passive features alone (AUC=0.84) performed comparably to a cognitive screener (AUC=0.85). Discussion: Passive smartphone monitoring is a valid, zero-burden measure of disease severity and progression in FTLD that adds modest incremental value beyond app-based cognitive testing. Findings support its use as a scalable digital endpoint in longitudinal FTLD research.

ABSTRACT Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the intestine’s integrated vascular, immune, and metabolic complexity. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37°C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

ABSTRACT Patients with newly‐diagnosed acute myeloid leukemia (ND‐AML) derive variable survival benefit from venetoclax (Ven) plus hypomethylating agent (HMA) therapy, and the optimal Ven duration across genetic risk groups remains undefined. Among 540 ND‐AML patients receiving Ven‐HMA at Mayo Clinic, outcomes were compared across Ven 7‐ ( n = 33), 14‐ ( n = 117), 21‐ ( n = 96), and 28‐day ( n = 294) schedules during Cycle 1 and stratified by ELN 2024 and Mayo genetic risk groups. At a median follow‐up of 37.7 months, allogeneic stem cell transplant (ASCT) rates were similar across Ven duration groups (15%, 18%, 18%, and 20% for 7‐, 14‐, 21‐, and 28‐day; p = 0.86). Median transplant‐censored survival was comparable across Ven durations (13.3, 11.9, 16.8, and 13.2 months for 7, 14, 21, 28 days, respectively; p = 0.65), with outcomes driven by ELN risk (6.3, 11.5, 18.3 months for high, intermediate, low; p < 0.01) and Mayo genetic risk (6.9, 17.8 months, not reached; p < 0.01). Survival was comparable across Ven durations within ELN intermediate/low‐risk and all Mayo risk groups. Among ELN high‐risk patients, 14‐day Ven was associated with inferior transplant‐censored survival compared to 21‐ and 28‐day schedules ( p < 0.01). Notably, 30‐ and 60‐day mortality were higher with shorter Ven schedules (7‐day: 9%/18%; 14‐day: 7%/15%) versus 28‐day (2%/6%), which likely reflects treatment selection bias. In ND‐AML, no significant difference in transplant‐censored survival was observed across the 7‐, 14‐, 21‐, and 28‐day Ven schedules; prognosis was determined primarily by Mayo and ELN 2024 genetic risk rather than by Ven duration. Prospective trials are needed to establish risk‐adapted Ven dosing strategies.