Faculty Bibliography

OBJECTIVE:Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, meta-analyses were performed estimating age-specific incidence of SLE by sex, race, and ethnicity. METHODS:The CDC network of SLE registries includes five state-based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002-2018. Registries provided age-specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person-years, stratified by sex, race, and ethnicity for the meta-analyses. RESULTS:Incidence rates among women were highest for those aged 30-39 (12.7, 95%CI: 9.5-16.8), while rates among men were highest for those aged 60-69 (2.1, 95%CI: 1.3-3.4). Black women aged 20-39 had the highest SLE incidence rates (23.6, 95%CI: 20.7-26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8-15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4-15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30-39 years. CONCLUSIONS:This study provides comprehensive sex- and race-specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

BACKGROUND:Risk assessment in high-risk cutaneous squamous cell carcinoma (HRcSCC) uses several clinicopathologic staging system tools, yet under- and over-treatment often occur. Integration of tumor biology as an independent predictor via gene expression profile (GEP) may improve risk stratification and tailor adjuvant care. OBJECTIVE:Integrate clinicopathologic risk factors with 40-GEP testing to refine risk stratification. METHODS:Integrated 40-GEP (i40-GEP) combines optimized nested predictive models and five clinicopathologic features (immunosuppression, location, differentiation, tumor diameter, and perineural invasion) with the validated 40-GEP, and reports results: Class 1A (Low Risk), Class 1B (Moderate Risk), Class 2A (High Risk), and Class 2B (Highest Risk). RESULTS:i40-GEP significantly stratifies metastatic and local recurrence (LR) risk (p<0.001) in a validation cohort (n=572), with >95% NPV for Class 1A across National Comprehensive Cancer Network subsets. The i40-GEP identified 12.9% of patients as Class 2B, with the lowest 3-year metastasis-free survival (66.2%) and a demonstrated benefit from adjuvant radiation treatment (ART). Multivariable analysis showed i40-GEP results significantly predict metastatic and LR risk more than individual clinicopathologic factors. LIMITATIONS/CONCLUSIONS:Retrospective study. CONCLUSIONS:I40-GEP accurately stratifies metastatic and LR risk in patients with HRcSCC, leading to improved clinical decision-making. Class 2B i40-GEP identifies patients most likely to benefit from ART.

OBJECTIVE:Belting is a vocal quality commonly used across contemporary singing genres. Despite its ubiquity, belting production and perception are highly debated. Variable methodologies and terminology used to discuss, teach, and study belting limit our understanding of underlying mechanisms and restrict the development of science-informed voice pedagogy. We systematically examined the published literature on belting to identify commonalities, disagreements, and directions for future research. METHODS:We conducted a scoping review surveying English-language peer-reviewed scientific studies and pedagogical publications on belting in adult singers that were published between January 1978 and November 2025. Data were extracted and grouped into the following categories: perception, acoustics, physiology, and pedagogy. RESULTS:In total, 2018 publications were reviewed. 472 underwent full-text review, and 112 met inclusion criteria, comprising 58 scientific studies and 54 pedagogical publications. Most scientific studies were cross-sectional comparing the same group or population across variable tasks (n = 25), and pedagogical publications were largely expert commentary (n = 32). Perceptually, belting was characterized as having "bright" or "forward" resonance and increased loudness. Acoustic findings included higher first and second formant frequencies, with the first formant tuned to the second harmonic. Physiologically, belting was associated with an elevated laryngeal position, pharyngeal narrowing, closed quotient >50%, high subglottal pressure, and "megaphone" mouth shape. High individual variability was a hallmark of all findings. Terminology was highly variable, with over 100 words and phrases used to describe belting. CONCLUSIONS:High variability of findings suggests that belting is better understood as a family of related vocal behaviors than as a single, homogeneous phenomenon. We propose three tenets for future work: (1) use of objective acoustic and physiological terminology to define belting, (2) inclusion of multiple terminologies where appropriate to reflect the diversity of learning styles and individual physicality, and (3) use of auditory anchors to supplement written definitions and reduce perceptual ambiguity.

IMPORTANCE/UNASSIGNED:The 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline newly recommends selective use of coronary artery calcium (CAC) scoring based on a 10-year risk of 3% to less than 10% estimated with the Predicting Risk of Cardiovascular Disease EVENTS (PREVENT) atherosclerotic cardiovascular disease (ASCVD) equations. However, the utility of CAC scoring alongside the PREVENT equations for ASCVD risk estimation is not known. OBJECTIVE/UNASSIGNED:To determine the change in predictive utility when adding CAC scores to the PREVENT-ASCVD equations. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Longitudinal observational cohort study conducted at 6 sites in the United States and enrolling adult participants aged 45 to 79 years without ASCVD at baseline in the Multi-Ethnic Study of Atherosclerosis. EXPOSURES/UNASSIGNED:Ten-year ASCVD risk with the PREVENT-ASCVD equations before and after adding CAC scores. MAIN OUTCOMES/UNASSIGNED:Performance metrics for estimation of risk of fatal and nonfatal ASCVD, assessed using the Harrell C statistic, calibration, and net reclassification improvement (NRI) for newly defined ASCVD risk categories: low (<3%); borderline (3% to <5%); intermediate (5% to <10%); and high (≥10%). RESULTS/UNASSIGNED:A total of 6098 participants were included. At baseline, participant mean age was 61.4 (SD, 9.6) years, 52% were female, mean estimated 10-year ASCVD risk was 6.4% (SD, 4.8%) with the PREVENT-ASCVD base equations, and 49% had a CAC score greater than 0. During 10 years of follow-up, 366 (6%) experienced an ASCVD event. The Harrell C statistic for the PREVENT-ASCVD base equations was 0.73 (95% CI, 0.70-0.75). After adding CAC to the PREVENT-ASCVD base equations, the change in Harrell C statistic was 0.02 (95% CI, 0.01-0.03), and the categorical NRI was 0.095 (95% CI, 0.053-0.137). The calibration slope for the PREVENT-ASCVD base equations was 1.09 (95% CI, 0.93-1.25), and for the PREVENT-ASCVD base plus CAC equations was 0.92 (95% CI, 0.81-1.03). Among those at borderline risk, incident ASCVD occurred in 1.9% of those with CAC score of 0, 3.9% with CAC greater than 0 and less than 100, 7.4% with CAC 100 or greater and less than 300, and 14.3% with CAC 300 or greater. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among US adults aged 45 to 79 years, addition of CAC score to the PREVENT-ASCVD equations across all risk groups overall only modestly improved and, in some groups, did not change model discrimination and reclassification. Reclassification results support selective use of CAC in those with borderline to intermediate risk estimated by the PREVENT-ASCVD equations.

Multimodal large language models are increasingly used for dermatologic queries, but whether Fitzpatrick skin type (FST) labels affect diagnostic accuracy is unknown. We evaluated 656 biopsy-confirmed photographs from the Diverse Dermatology Images (DDI) dataset under no-FST, DDI-concordant FST, and two DDI-discordant FST conditions using ChatGPT 5.2 Edu and Gemini 3.1 Pro browser configurations (5248 evaluations). Confirmed malignant diagnosis omission from the top three differential diagnoses ("lethal miss") was a prespecified exploratory outcome. Gemini had higher ordinal accuracy than ChatGPT (odds ratio 2.32; 95% confidence interval 2.01-2.67; false discovery rate-adjusted p < 0.001). No FST prompt condition significantly improved accuracy over no-FST prompting; an equal-image-weighted sensitivity analysis yielded similar results. Among malignant images eligible for extreme discordance, extreme DDI-discordant prompting was associated with more ChatGPT lethal misses than no-FST prompting (paired odds ratio 5.0; p = 0.043); Gemini showed no significant paired shift (p = 1.00). Post hoc binary malignancy detection showed low no-FST specificity for ChatGPT (42.5%) and Gemini (22.9%), indicating frequent overcalling. Gemini showed lower no-FST accuracy for malignant FST V-VI images than for FST I-II and III-IV images. FST prompting provided no measurable diagnostic benefit. Neither configuration supports autonomous dermatologic use.

BACKGROUND:Prosthetic joint infection (PJI) following total ankle arthroplasty (TAA) is a rare but devastating complication associated with high rates of reoperation and poor functional outcomes. The purpose of this study was to identify risk factors for PJI following primary TAA and to characterize associated treatment approaches and clinical outcomes. METHODS:A single-institution retrospective cohort study was conducted, including 1008 primary TAAs performed between 2010 and 2023. PJI was defined using established microbiologic and clinical criteria consistent with prior literature. Patient demographics, comorbidities, preoperative functional status, and operative characteristics were collected. Infected patients were compared with non-infected controls using 2:1 propensity score matching based on age and sex. Associations with PJI were evaluated using penalized logistic regression (Firth method). Microbiologic profiles, surgical management strategies, and outcomes were analyzed for the infection cohort. RESULTS:was the most frequently identified organism (36.7%). Eight (29.6%) PJIs were considered chronic (>4 weeks). Two-stage revision TAA was the predominant surgical strategy (59.3%), with limb salvage achieved in 96.2% of cases and arthroplasty retention maintained in 69.2% at a mean follow-up of 4.07 years. CONCLUSION/CONCLUSIONS:PJI following primary TAA occurred at a rate of 2.7%, with calcaneal displacement osteotomies identified as a significant associated procedural risk factor. Despite the severity of this complication, high rates of limb salvage and arthroplasty retention were observed with contemporary treatment strategies at midterm follow-up. LEVEL OF EVIDENCE/METHODS:Level III, retrospective cohort study.

BACKGROUND/UNASSIGNED:The potential of methadone maintenance treatment (MMT) to address the opioid crisis has been limited by restrictive federal and local policies that require frequent clinic visits for medication. Unprecedented federal regulatory changes started in early COVID-19 and were made permanent in 2024, allowing clinics increased flexibility in granting take-home medication to patients. Medicaid payment policies can profoundly shape provider behaviors but may not align with regulatory changes. METHODS/UNASSIGNED:We conducted a systematic synthesis of Medicaid MMT payment and billing policies among 40 states over March 2020-July 2025. RESULTS/UNASSIGNED:More than half of the states continued to adopt a per-dose or per-diem approach to paying for methadone dosing and a per-service approach to paying for addiction counseling, thus tying Medicaid revenue closely to clinic visits. More than one-quarter maintained a flat bundled payment dating back to prepandemic era that provided little incentive for granting patients more than 1 week of take-home medication. Adoption of a 2-tiered bundled payment modeled after Medicare's payment increased over time but remained limited. CONCLUSION/UNASSIGNED:Medicaid payment policies for MMT saw limited changes over the 5 years following initial federal regulatory changes. Practice changes toward more flexible and patient-centered care may be hindered without compatible changes in payment approaches.

BACKGROUND/UNASSIGNED:Lower extremity peripheral artery disease (PAD) is a major contributor to cardiovascular morbidity and mortality; however, the metabolic pathways underlying disease development and progression are poorly understood. METHODS/UNASSIGNED:We conducted a prospective cohort study of 3759 participants from the ARIC study (Atherosclerosis Risk in Communities; mean age, 53.5 years; 60% women; 62% Black participants) with untargeted metabolomic profiling at baseline (1987-1989). Incident PAD (458 cases) and its severe form with rest pain or tissue loss, critical limb ischemia (CLI; 135 cases), were identified through hospitalization codes over a median follow-up of 27 years. We used Cox regression with adjustment for traditional risk factors and accounted for multiple testing using a false discovery rate correction at a threshold of 0.05. Risk prediction improvement was evaluated using Harrell C statistics and the net reclassification improvement. RESULTS/UNASSIGNED:Thirteen metabolites were significantly associated with incident PAD and primarily reflected dysregulated glycemic control, impaired redox balance, and altered lipid remodeling (eg, higher levels of mannose and lower levels of 1,5-anhydroglucitol, gamma-glutamyl dipeptides, and lysophospholipids). For CLI, 18 metabolites were identified, 11 of which were unique to CLI and reflected intensified oxidative and bioenergetic stress (eg, homocitrulline, arabonate, and 1-linoleoylglycerol). Metabolites significantly improved risk prediction for PAD beyond traditional risk factors (∆C statistic, 0.017 [95% CI, 0.008-0.025] from a base C statistic of 0.770; net reclassification improvement, 0.053 [95% CI, 0.018-0.083]) and particularly CLI (∆C statistic, 0.041 [95% CI, 0.018-0.064] from a base C statistic of 0.823; net reclassification improvement, 0.176 [95% CI, 0.085-0.268]). CONCLUSIONS/UNASSIGNED:Distinct metabolomic profiles were associated with incident PAD and CLI years before clinical onset, highlighting dysregulated glycemic control, impaired redox balance, and altered lipid remodeling as key underlying pathways. These findings suggest that circulating metabolites may serve as early indicators of metabolic health relevant to PAD risk identification and progression to advanced disease.