Faculty Bibliography

OBJECTIVE:The relationship between physical activity and sleep with inflammatory arthritis (IA) is understudied, and existing research has relied largely on self-report or short-term assessments. The NIH All of Us database provides long-term accelerometry data, enabling more precise estimation of the association between lifestyle behaviors and IA. METHODS:Participants from the All of Us database who shared electronic health record and Fitbit data were included. Daily activity and sleep metrics were compared between individuals with and without IA using multiple linear regression. Cox proportional hazards regression was used to examine the association of activity and sleep patterns with incident IA in a 10-year follow-up period. RESULTS:A total of 23,855 participants were included, 200 of whom had IA. Participants with IA took fewer daily steps (P < 0.001) and had greater sleep variability (P < 0.001) compared to those without IA. 122 individuals had incident IA. Every 1,000 extra daily steps were associated with a 7% lower risk of IA (hazard ratio [HR] 0.93 [95% confidence interval (CI) 0.87-0.99], P = 0.02). Compared to those who walked <5,000 steps daily, those who walked 5,000 to 10,000 steps and 10,000+ steps had a 41% (HR 0.59 [95% CI 0.39-0.91], P = 0.02) and 50% (HR 0.50 [95% CI 0.29-0.86], P = 0.01) reduction in risk of IA. CONCLUSION/CONCLUSIONS:Individuals with IA had reduced step counts and more sleep variability compared to those without IA, highlighting how physical activity and sleep contribute to IA. Additionally, increased daily step count was associated with decreased risk of incident IA, suggesting a possible research intervention for those at high risk of IA.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with marked clinical heterogeneity and a multifactorial pathogenesis. Environmental and lifestyle factors, including obesity, tobacco exposure, microbiome dysbiosis, dietary patterns, and plastic-associated endocrine disruptors, have all been linked to HS risk or disease severity. However, these exposures alone do not fully explain why only some individuals develop HS, why age at onset and severity vary substantially, or why disease occurs in patients without major identifiable environmental burden. In parallel, genetic studies have demonstrated that inherited susceptibility is a central component of HS pathogenesis. Rare loss-of-function variants in γ-secretase complex genes cause a small subset of familial, autosomal dominant HS, while genome-wide association studies have shown that population-level risk implicates pathways involved in epithelial differentiation, follicular biology, immune signaling, and cutaneous inflammation. Recent work further suggests that common and rare genetic risk may converge on shared biological mechanisms, including γ-secretase-related signaling. While nature vs. nurture arguments dichotomize genetic constitution and environmental exposures, current evidence supports a model in which genetic susceptibility interacts with environmental exposures to shape HS risk, clinical expression, and disease progression. In this review, we examine the evidence supporting both exposomic and genomic contributions to HS and argue that the disease is best understood as arising from their intersection rather than from either domain alone.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Circumferential minimally invasive surgery (cMIS) techniques in adult spinal deformity (ASD) surgery may reduce physiological burden compared with open technique, but their utility in octogenarians has not been previously assessed. METHODS:Operative ASD patients aged 80 years or older with complete baseline (BL) and 2-year postoperative radiographic and health-related quality of life data were assessed and compared by surgical technique: open vs cMIS. Propensity score matching aligned groups by BL Charlson Comorbidity Index (CCI), C7-S1 sagittal vertical axis, pelvic incidence minus lumbar lordosis mismatch, and C7 plumb line. BL and peri/postoperative factors were assessed using analysis of variance and Bonferroni-adjusted analysis of covariance while controlling for BL CCI and posterior fusion length. RESULTS:Thirty-four octogenarian ASD patients met inclusion criteria, of whom 29.4% underwent cMIS and 70.6% underwent open correction. cMIS patients were less likely to require surgical intensive care unit (10% vs 75%, P < .001) and had shorter hospital stays (4.6 vs 10.1 days, P = .013). Open patients reported higher Scoliosis Research Society-22 Appearance and Mental domain scores (both P < .005) and more frequently reached minimal clinically important difference in both domains by 2 years (P = .025, .024). cMIS patients more often required reoperation for radiographic sagittal imbalance by 2 years when controlling for CCI and levels fused (20.0% vs 8.3%, P < .001). No deaths occurred in either group by 2 years. CONCLUSION/CONCLUSIONS:In octogenarians undergoing ASD surgery, cMIS reduced physiological burden but had higher reoperation rates, whereas open surgery showed greater durability.

PURPOSE/UNASSIGNED:To determine whether exposure to antibiotics is associated with new-onset International Classification of Diseases (ICD) coding of geographic atrophy (GA). METHODS/UNASSIGNED:This case-control study of patients ages sixty and older used health insurance claims data from the Merative MarketScan Research Databases. A total of 3254 cases with new-onset ICD coding of GA between 2019 and 2021 were matched by year to 3249 controls without GA using propensity scores estimated by age, hypertension, U.S. Census Bureau region, and Charlson Comorbidity Index. For cases, we analyzed prescription drug claims of antibiotics in the two years before GA diagnosis. For controls, we analyzed claims in the two years before a randomly selected eye examination. We calculated the odds of new-onset ICD coding of GA controlling for age-related macular degeneration risk factors. RESULTS/UNASSIGNED:Exposure to any antibiotics (OR = 1.25; 95% confidence interval [CI], 1.11-1.41; P < 0.001), tetracyclines (OR = 1.18; 95% CI, 1.03-1.36; P = 0.021), quinolones (OR = 1.16; 95% CI, 1.03-1.31; P = 0.017), or broad-spectrum antibiotics (OR = 1.20; 95% CI, 1.07-1.34; P = 0.003) was associated with increased odds of new-onset ICD coding of GA. Greater cumulative day supply was associated with increasing odds, suggesting a dose-dependent relationship. CONCLUSIONS/UNASSIGNED:Exposure to antibiotics is associated with increased odds of new-onset ICD coding of GA. This association may be dose dependent. These findings suggest that antibiotic exposure could be a novel modifiable risk factor for GA, although this conclusion is tempered by potential confounding by health status or misclassification of GA and by multiple comparisons. Further investigation will be needed to validate these findings.

AIM/OBJECTIVE:The "2026 HRS Expert Consensus Statement Update on Cardiovascular Implantable Electronic Device Lead Management and Extraction" provides updated recommendations to guide clinicians in the management of cardiovascular implantable electronic device (CIED) leads. BACKGROUND:Since the publication of the "2017 HRS Expert Consensus Statement on Cardiovascular Implantable Electronic Device Lead Management and Extraction," the field has evolved quickly. New evidence on CIED lead management and the blooming development of new CIED technologies, including leadless pacing and implantable cardioverter-defibrillator leads implanted outside the vascular system and new lumenless pacing leads and lead extraction tools, have contributed to the field's rapid evolution. METHODS AND RESULTS/RESULTS:A comprehensive literature search was conducted in accordance with the Institute of Medicine standards. The writing committee reviewed evidence gathered through electronic literature searches encompassing clinical trials, original studies, and meta-analyses conducted on human subjects published in English from MEDLINE, PubMed, Embase, and the Cochrane Library up to December 2024. The comprehensive literature review supports each evidence-based recommendation and is compiled in the evidence tables. A predefined threshold of >70% approval for each recommendation was required, with a quorum of two-thirds of the writing committee. The final mean consensus of 108 recommendations was 93.61%. DISCUSSION/CONCLUSIONS:The recommendations from the "2017 Expert Consensus Statement on Cardiovascular Implantable Electronic Device Lead Management and Extraction" have been updated with new evidence to guide clinicians. The new recommendations address the latest CIED technologies with the advantages over transvenous leads; new evidence supporting diagnosis, treatment, and prevention for CIED infection; appropriate lead management in transcatheter tricuspid valve replacement for tricuspid regurgitation; and standardization of transvenous lead extraction approach, protocol, and facilities to improve the outcomes of CIED lead management and extraction.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Working memory (WM), the transient storage and manipulation of information, is a cognitive function that can improve with training. Accumulating evidence suggests that sleep, particularly slow oscillations (SOs) that occur during nonrapid eye movement sleep, supports this improvement. Yet, how sleep and SOs in particular relate to neural processes supporting WM remains poorly understood. In this study, we investigated how WM-related neural activity evolves across nocturnal sleep and how these changes relate to neural processing during SOs. Participants performed a WM task during fMRI before and after sleep, with simultaneous EEG-fMRI capturing neural activity during the first 2.5 hr of sleep. Our results showed significant overnight changes in WM-related activity, characterized by reduced recruitment of the dorsal precuneus during WM encoding/maintenance phases and frontal regions during the retrieval phase of WM. In addition, sleep increased item-specific reinstatement in a sensory processing region during WM. This pattern of results suggests a combined influence of sleep on enhancing sensory reinstatement while reducing potential top-down control (i.e., reduced parietal and frontal activity). Critically, SO-related activity was directly linked to overnight activity changes: Stronger SO activation in the premotor cortex and ventromedial pFC predicted greater overnight reductions in WM-related activity, and multivoxel analyses in the ventral attention network revealed a parallel relationship. These findings suggest that SOs play a critical role in WM function by facilitating the reorganization of WM-related processing.