Faculty Bibliography

BACKGROUND:Carpal tunnel syndrome (CTS) and cubital tunnel syndrome (CuTS) are the most common upper extremity compressive neuropathies. Although often considered isolated conditions, they may occur concomitantly, and the clinical significance of dual compression remains poorly defined. This study evaluated whether concomitant CTS/CuTS represents a distinct clinical subgroup characterized by greater objective motor impairment compared with isolated entrapment syndromes. METHODS:Eighty-six adults evaluated between 2021 and 2025 were prospectively enrolled, including isolated CTS (n = 32), isolated CuTS (n = 26), and concomitant CTS/CuTS (n = 28). Standardized examinations assessed sensory findings and intrinsic motor strength using Medical Research Council grading. Multivariable logistic and ordinal regression analyses identified predictors of decreased intrinsic muscle strength. RESULTS: = .0471). CONCLUSIONS:Concomitant CTS/CuTS is associated with greater baseline intrinsic motor impairment despite similar sensory findings, suggesting that dual-site compression reflects greater motor involvement rather than the incidental coexistence of 2 isolated entrapment syndromes.

The organization of diverse mesenchymal populations during human small intestinal development is critical for tissue architecture and function yet remains poorly defined. Here, to construct a comprehensive, tissue-scale map of the developing human small intestine at single cell resolution, we leveraged single-cell RNA-sequencing data to build a Xenium spatial transcriptomics gene panel covering the cell diversity of the human small intestine. We defined five subpopulations occupying discrete anatomical locations within the lamina propria and submucosa-the subepithelial cells, lamina propria fibroblasts, submucosal fibroblasts, smooth muscle cells and CXCL13⁺ fibroblasts. Our data establish molecular markers to distinguish these populations in both sequencing and imaging data. We leverage this high-resolution atlas to interrogate cell-cell signalling, benchmark pluripotent stem cell-derived human intestinal organoids and to demonstrate how this resource can incorporate relative spatial organization into tissue analysis, with broad implications for modelling development, regeneration and disease.

INTRODUCTION/BACKGROUND:Emergency department (ED) care transitions are particularly challenging for persons living with cognitive impairment (PLWCI) and their care partners. Existing measures overlook care partners' unique experiences. We developed and validated the Caregiver-reported Outcome Measure for Emergency care Transitions (COMET) tool to assess these transitions. METHODS:We enrolled 170 care partners from four EDs in a multiphase process including qualitative interviews, item development, member checking, cognitive debriefing, expert review, and psychometric testing. RESULTS:= 0.85). Factor analysis supported a clear structure, and correlations with the Care Transitions Measure-3 supported validity. DISCUSSION/CONCLUSIONS:COMET is a feasible, reliable, and valid tool for evaluating ED care transitions for PLWCI and their care partners.

Structural inequities, including historical redlining, have created compounding climate-related vulnerabilities in marginalized communities, with potential implications for pediatric cardiometabolic diseases (CMD). However, the joint effects of redlining, climate risk, and urban heat on pediatric CMD remain poorly understood. Using New York State hospital administrative data (2018-2022), we examined associations between neighborhood redlining, climate risk, urban heat, and CMD-related emergency department (ED) and outpatient visits among children aged < 18 years. Exposures included historical redlining (Home Owners' Loan Corporation grades C/D vs. A/B), climate risk (high vs. low, based on the Climate Vulnerability Index), and urban heat (high vs. low, based on satellite-derived land surface temperature). Associations were estimated using Poisson regression with interaction terms and subtype-specific analyses. Among 342,220 CMD-related visits in the climate-risk cohort and 9,195 in the urban-heat cohort (mean age, 7.4 years; 49% female), residence in historically redlined neighborhoods was associated with increased rates of CMD-related ED visits (rate ratios [RRs] = 1.15; 95% CI, 1.12-1.18) and outpatient visits (RR = 1.18; 95% CI, 1.17-1.20), with the strongest associations observed for comorbidity, hypertension, and type 1 diabetes (T1D). High-climate risk was associated with modestly lower overall rates of CMD-related ED visits (RR = 0.95; 95% CI, 0.94-0.96) and outpatient visits (RR = 0.96; 95% CI, 0.96-0.97), although elevated risks remained evident for selected CMD subtypes (e.g., hypertension, obesity, T1D). In the urban-heat cohort, most associations were not statistically significant (RRs = 1.00-1.03), except for outpatient visits for T1D, where higher urban heat exposure was associated with increased risk (RR = 1.28; 95% CI, 1.04-1.57). Co-exposure to historical redlining and high-climate-risk was associated with a modest increase in CMD-related ED visits (RR = 1.04; 95% CI, 1.01-1.07), whereas no significant associations were observed for co-exposure to redlining and urban heat (RR = 1.08; 95% CI, 0.78-1.49). Associations for outpatient visits were attenuated in both analyses. These findings suggest that redlining may be a stronger determinant of pediatric CMD healthcare utilization than climate-related hazards alone, highlighting the enduring health consequences of structural inequities and underscoring the need for targeted, climate-adaptive interventions, especially in historically redlined communities.

Type 2 diabetes (T2D) prevention efforts have largely focused on intervening when dysglycemia is already established. We propose that T2D prevention be reframed around prediabetes remission, with preservation and restoration of normoglycemia as the optimal clinical goal. The transition from normoglycemia through increasing dysglycemia to T2D is progressive and cumulatively shaped by biological, behavioral and environmental exposures across the life course. Prediabetes (intermediate hyperglycemia) remission is an achievable, pragmatic and measurable prevention target. Here we provide a life-course risk architecture for T2D integrating developmental, transitional and contextual determinants, defining critical windows of amplified metabolic vulnerability and potential restoration of normoglycemia. Precision prevention should target mechanistic heterogeneity, with aligned interventions that remain scalable, affordable and adaptable across socioeconomic settings. Our framework identifies ten priorities in T2D prevention, moving beyond traditional approaches toward context-specific, actionable interventions capable of altering the natural history of disease early in the life course and restoring metabolic health.

BACKGROUND:Major depressive disorder and generalized anxiety disorder frequently co-occur, leading to heterogeneous presentations that complicate diagnosis and treatment. While diagnostic categories often obscure symptom variability, network approaches offer a powerful way to examine how symptoms relate to one another within and across conditions. By identifying symptom clusters, these methods can provide insights into potential mechanisms of comorbidity and symptom maintenance and may ultimately help guide more personalized treatment. METHODS: = 10,718), we examined the relationship between baseline cluster probabilities and three outcome trajectories over 12 weeks of treatment. RESULTS:We found four baseline symptom clusters relating to Affective Dysregulation, Worries, Neurovegetative symptoms, and Hyperarousal. Affective Dysregulation and Neurovegetative clusters were associated with poorer outcomes, whereas Worries and Hyperarousal were associated with recovery over partial improvement; Hyperarousal also differentiated recovery from non-response. CONCLUSIONS:Symptom clusters derived from standard screening measures were associated with differential treatment trajectories. Targeting these symptom configurations may be particularly effective at disrupting multiple symptom pathways. Future research should examine whether personalized treatment strategies that consider symptom clusters based on simple screening in practice settings yield greater clinical improvement than traditional diagnostic categories.

IMPORTANCE/UNASSIGNED:Retest effects can inflate longitudinal cognitive test performance and complicate estimation of cognitive change. Whether retest effects influence estimated intervention effects in randomized clinical trials remains unclear. OBJECTIVE/UNASSIGNED:To quantify the magnitude and heterogeneity of differences associated with retesting in longitudinal cognitive testing and examine whether accounting for retesting alters estimated treatment effects in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was an ad hoc secondary analysis of ACHIEVE, a multicenter phase 3 randomized clinical trial conducted from 2017 to 2022 with 3-year follow-up. Community-dwelling older adults with untreated hearing loss were enrolled at 4 US community sites: Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland. Analyses were completed in November 2025. EXPOSURE/UNASSIGNED:Cognitive retesting, defined as a binary indicator (0 for baseline visit; 1 for follow-up visits). MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was a global cognitive factor score derived from a neurocognitive battery. Secondary outcomes included domain-specific factor scores (language, executive function, memory) and individual test scores. Retest differences were estimated using linear mixed-effects models adjusted for covariates consistent with the main ACHIEVE analysis. Interactions tested whether retest differences varied by key factors. Model-based trajectories and intervention-control estimates were compared with and without retest adjustment. RESULTS/UNASSIGNED:A total of 977 older adults (mean [SD] baseline age, 76.3 [4.0] years; 523 [54%] female) contributed 2571 in-person cognitive assessments , including 552 adults (57%) with mild hearing loss and 739 adults (76%) recruited de novo. Retest differences were significant for global cognition (β = 0.11; 95% CI, 0.07 to 0.15), executive function (β = 0.15; 95% CI, 0.10 to 0.20), and memory (β = 0.12; 95% CI, 0.06 to 0.18), approximately offsetting 1 year of model-estimated age-related cognitive decline. Language showed minimal retest differences (β = -0.03; 95% CI, -0.08 to 0.02). Retest differences did not meaningfully vary by hearing loss severity, trial intervention, or recruitment source. Retest adjustment altered estimated cognitive trajectories but did not meaningfully alter intervention outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study found that retest differences were substantial for global cognition, executive function, and memory but did not meaningfully alter estimated hearing intervention outcomes. Adjustment for retest differences is recommended to improve interpretation and intervention estimation in longitudinal cognitive studies.

INTRODUCTION/BACKGROUND:This study aimed to evaluate the impact of the COVID-19 pandemic on screening patterns from a large, diverse, nationally representative breast cancer screening registry and to perform microsimulation modeling of breast cancer outcomes. METHODS:Retrospective breast imaging and outcomes data from the National Mammography Database (NMD) from January 2017 through December 2022 were collected and partitioned into pre-COVID, peak-COVID, and post-COVID time periods. Microsimulation modeling was performed to predict breast cancer outcomes, including the cancer stage distribution, excess breast cancer deaths, and years of life lost from 2020 to 2065. RESULTS:There were 12,118,324 screening exams, 1,211,754 screening recalls, 194,096 biopsies, and 55,732 cancer diagnoses included for analysis. There was an acute drop in all metrics in 2020, and these metrics did not approach pre-COVID levels until 2022. This corresponded with a significant increase in the time interval between screening exams between the pre-COVID and post-COVID periods (16.3±7.7 vs. 17.8±9.3 months respectively; p<0.001). Simulations predicted that, by 2030, 12% more late-stage cancers would be diagnosed. The estimated cumulative excess deaths following peak-COVID were 6.7 per 100,000 women by 2030, an increase of 0.40%, increasing to 16.8 (0.51%) excess deaths by 2040. The corresponding number of years of life lost by 2065 was 565 per 100,000 women screened. CONCLUSIONS:The interruption in screening during peak-COVID and the slow return to pre-COVID screening levels may have resulted in an increase in late-stage cancers, excess cancer deaths, and years of life lost.

BACKGROUND:Clofazimine is commonly included in multidrug regimens for children with multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB), but accurate pediatric dosing has been limited by 100-mg soft-gel capsules that cannot be reliably divided. We evaluated the exposure and safety of a novel 50-mg clofazimine tablet using revised once-daily weight-banded dosing informed by a previous study (Clofazimine PK1). METHODS:Children <18 years weighing <30 kg receiving MDR/RR-TB treatment, including clofazimine, were enrolled. Sparse and semi-intensive pharmacokinetic sampling was completed at baseline and at weeks 2 and 12. Model-predicted weekly steady-state area-under-the-curve (wAUCss) was compared with an adult target of 111.79 mg·h/L. Safety monitoring included clinical, laboratory, and electrocardiogram (ECG) monitoring. RESULTS:Twelve children were included (median age 2.8 years; range 0.6-8.2). Median predicted wAUCss was 106 mg·h/L (range 76.9-274), within 25% of target. Two grade 3 adverse events (drug-induced liver injury and skin hyperpigmentation) possibly related to clofazimine, but no other clofazimine-related serious adverse events, were observed, The Fridericia corrected QT (QTcF) interval typically increased with 0.042 ms per1-µg/L increase in clofazimine concentration; five QTcF prolongations (>460-480 ms) occurred in three participants. CONCLUSIONS:The revised once-daily dosing with the 50-mg clofazimine tablet achieved the predefined exposure target. Clinically important adverse events support cautious use with ECG and laboratory monitoring and further evaluation before broad adoption. CLINICAL TRIALS REGISTRATION/BACKGROUND:South African National Clinical Trials Register (https://sanctr.samrc.ac.za/; DOH-27-0620-6415).