Faculty Bibliography

INTRODUCTION/BACKGROUND:Progression Independent of Relapse Activity (PIRA) is a critical measure of disability progression in multiple sclerosis (MS) independent of relapses but lacks a standardized definition. Current reliance on the Expanded Disability Status Scale (EDSS) limits sensitivity to non-motor domains, necessitating a stratified framework to enhance detection and guide management. OBJECTIVES/OBJECTIVE:To develop a novel seven-level stratified PIRA definition and assess its validity, enhanced sensitivity, clinical relevance, and feasibility through expert consensus, and propose a simplified framework based on feedback. METHODS:A two-stage study: (1) A four-expert panel developed a seven-level PIRA framework (PIRA 1: EDSS-based; PIRA 2: EDSS-plus measures; PIRA 3: stress tests; PIRA 4: patient-reported outcomes [PROs]; PIRA 5: conventional MRI; PIRA 6: advanced MRI; PIRA 7: biomarkers) via literature synthesis. (2) A survey of 90 MS experts (26 responded, 28.9%) from nine countries evaluated each level's validity, sensitivity (vs. EDSS), relevance, and feasibility (1-5 scale), with open-ended comments on barriers and suggestions. High agreement was defined as a score ≥ 4. Qualitative feedback on barriers and improvement suggestions was thematically analyzed. RESULTS:Strong support (24/26; 92.3%) endorsed a stratified PIRA definition. Respondents included primarily clinician-researchers (22/26; 84.6%), with 11/26 (42.3%) reporting more than 20 years of MS experience. High agreement for validity ranged from 15/26 (57.7%) for PIRA 1-23/26 (88.5%) for PIRA 6. Agreement regarding enhanced sensitivity was highest for PIRA 2 (25/26; 96.2%), followed by PIRA 6 (22/26; 84.6%) and PIRA 5 (19/26; 73.1%). Clinical relevance was rated highly for PIRA 1, PIRA 2, and PIRA 6 (each 25/26; 96.2%). Feasibility was highest for PIRA 1 (24/26; 92.3%) and declined for higher levels, particularly PIRA 7. Barriers included inter-rater variability (PIRA 1, 30.8%), subjectivity (PIRA 4, 23.1%), and cost/expertise (PIRA 6-7, 26.9% each). Suggestions included digital tools (PIRA 2-3), AI for MRI (PIRA 5-6), biomarker validation (PIRA 7), and combining PIRA 5-6. PIRA 1-2 were preferred for clinical practice, PIRA 5-7 for research. A three-tier framework was proposed: Probable PIRA (clinical), Definite PIRA (clinical + MRI), and Definite PIRA Plus (clinical + MRI + biomarkers). CONCLUSIONS:The proposed seven-level PIRA framework demonstrates strong expert support for its conceptual validity and clinical relevance but highlights feasibility challenges for advanced assessments. A simplified three-tier model may provide a practical structure for standardized evaluation of relapse-independent progression in MS. Further empirical validation in diverse clinical cohorts is required.

OBJECTIVE/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:-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/UNASSIGNED: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.

Pericarditis is the most frequent manifestation of pericardial disease and accounts for up to 5% of emergency department visits for chest pain. Although traditionally considered a benign and self-limited condition, it is a heterogeneous syndrome with a broad aetiological spectrum and potentially significant morbidity. While mortality is low, the burden of complications like recurrent disease, cardiac tamponade or constrictive pericarditis, and the frequent need for hospitalisation underscore its clinical relevance. The growing availability of multimodality imaging and the publication of updated international guidelines in 2025 have recently renewed attention to pericardial diseases, refining diagnostic criteria, risk stratification and therapeutic approaches. In high-income settings, idiopathic or presumed viral pericarditis remains the most common presentation. However, a substantial proportion of patients harbour alternative aetiologies that carry distinct prognostic implications and require tailored diagnostic and management strategies. In this review, we use the ABCDE mnemonic as a pragmatic framework to highlight five clinically important and often under-recognised forms of pericardial disease. Pericarditis associated with autoimmune and systemic inflammatory diseases is typically characterised by recurrent or refractory inflammatory courses and frequent extracardiac involvement. Bacterial pericarditis, although rare, represents a life-threatening condition requiring rapid aetiological identification and aggressive therapy. Cancer-related pericardial disease often presents with large pericardial effusions or cardiac tamponade and is associated with a poor prognosis largely determined by the underlying malignancy. Damage-related and drug-related pericarditis encompasses postcardiac injury syndromes and pharmacological toxicity. Finally, endocrine and metabolic disorders, including uraemia, hypothyroidism and infiltrative conditions such as amyloidosis, are associated with pericardial disease that manifests with atypical features and effusion. Early recognition of these entities is critical, as management extends beyond standard anti-inflammatory therapy and often requires correction of the underlying cause and close multidisciplinary collaboration. This ABCDE approach can aid clinicians in identifying these uncommon high-risk forms of pericarditis and optimising patient-centred care.

IMPORTANCE/UNASSIGNED:Syringe services programs (SSPs) are evidence-based interventions that reduce bloodborne infections and injection-related harms among people who inject drugs, yet access remains limited and geographically uneven across the US. OBJECTIVE/UNASSIGNED:To quantify the travel time, distance, and cost required to reach the nearest SSP from population-weighted census tracts nationwide and to examine differences by urbanicity, state, and SSP legality. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional geospatial study linked all known SSP locations as of August 2024 to the population-weighted centroids of census tracts in the 50 US states and the District of Columbia. Analyses were conducted between December 2024 and February 2026. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Population-weighted mean and median driving time, distance, and cost to access the nearest SSP, stratified by National Center for Health Statistics urban-rural county category and SSP legal status. Costs were estimated using 2024 Internal Revenue Service (IRS) medical mileage deduction rates and 2022 state-specific gasoline prices. RESULTS/UNASSIGNED:In 1338 SSPs across 83 780 census tracts, the population-weighted mean 1-way driving time to the nearest SSP was 46.1 minutes (95% CI, 45.7-46.5 minutes) and the median was 23.3 minutes (IQR, 12.2-58.5 minutes). Altogether, 23.1% of the population lived more than 60 minutes from an SSP and 12.6% lived over 120 minutes away. The mean 1-way driving distance was 41.8 miles (95% CI, 41.3-42.2 miles). The mean 1-way driving cost was $8.77 (95% CI, $8.68-$8.86) using the 2024 IRS mileage rate and $6.91 (95% CI, $6.84-$6.98) using state mean gasoline prices in 2022. In states where SSPs were legal, mean driving time was 30.1 minutes (95% CI, 29.8-30.4 minutes) and mean cost by IRS mileage rates was $4.94 (IQR, $4.88-$5.00), compared with 110.7 minutes (95% CI, 109.6-111.8 minutes) and $24.19 (IQR, $23.92-$24.46) in states where SSPs were illegal. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cross-sectional study of travel burden to SSPs found substantial geographic and financial barriers to accessing SSPs across the US, particularly in nonmetropolitan areas. Targeting new SSPs to areas with the greatest travel burden could improve utilization and reduce drug-related morbidity.

Minimally invasive surgery (MIS) has revolutionized foot and ankle care by emphasizing delicate tissue handling, reduced postoperative pain, and faster recovery through small incisions and precise instrumentation. The evolution of MIS spans 4 distinct historical "seasons," from its early development in the mid-20th century to its global resurgence in the 2010s, driven by improved techniques, education, and international collaboration. Today, MIS extends beyond hallux valgus correction to include complex procedures such as first metatarsophalangeal joint, subtalar joint, tibiotalar joint, and tibiotalocalcaneal arthrodesis, with evidence demonstrating comparable or superior outcomes to open approaches. This review details the history of MIS in foot and ankle orthopedics and how this paradigm shift continues to redefine standards and improves outcomes in foot and ankle surgery.

INTRODUCTION/BACKGROUND:A 2021 federal rule permits opioid treatment programs (OTPs) to provide methadone through mobile medication units (MMUs), creating an opportunity to provide medication for people in residential care facilities. We used simulations to quantify the potential of MMUs to expand methadone access to people residing in residential substance use treatment facilities (RTF), skilled nursing facilities (SNF), and nursing facilities (NF) in New York State under different scenarios. METHODS:For each facility (RTF, SNF, and NF), a need score was created using three items: facility opioid use disorder (OUD) population, driving distance to nearest OTP, and county overdose mortality rate. We then demonstrated potential patient reach following the launch of 50 hypothetical MMUs making one stop per day to the highest need facilities. In refinements, we examined three additional scenarios involving more daily stops and prioritizing rural areas. RESULTS:Our sample included 3214 people with OUD estimated to be housed in 1052 facilities in New York, with the majority in RTFs (51.5%). The demonstrated percentage of OUD population served ranged from 23.5% to 35.8%, and the percentage of facilities served ranged from 23.8% to 37.4%. Each scenario reached a large percentage of rural facilities (73-76%). Prioritizing rural facilities decreased the proportion of OUD population served (10% reduction) but did not substantially increase driving time. Allowing multiple stops increased the proportion of OUD population served (32-36% vs. 24-26%). CONCLUSIONS:Using methods based on location information and spatial relationships, state officials can develop priorities and assess tradeoffs of MMU deployment and distribution strategies.

Autoimmune diseases rise steeply with biological aging, reflecting progressive failure of immune regulation. Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) represents a unique lifelong viral exposure in which the viral genome is embedded within host telomeres, potentially altering leukocyte telomere length (LTL), a core biomarker of immune aging. Circulating metabolites may further modify these viral-telomeric interactions. We analyzed 156,927 UK Biobank participants free of autoimmune disease at baseline. Baseline iciHHV-6 carrier status, LTL, and plasma metabolomic profiles were related to incident autoimmune disease during follow-up. Mediation and interaction models were used to test whether LTL and various metabolomic pathways mediated or modified viral effects. Over follow-up, 7.8% of participants developed autoimmune disease and 1.3% were iciHHV-6 carriers. iciHHV-6 was not directly associated with autoimmune disease despite higher baseline comorbidity. Longer LTL was independently protective overall, especially for rheumatoid arthritis, although it was positively associated with multiple sclerosis. iciHHV-6 carriers had longer LTL, yielding a small but significant indirect protective effect on autoimmune risk. LTL also modified viral effects, with stronger protection among iciHHV-6-positive individuals, suggesting telomere length buffers adverse viral-immune interactions. Metabolomic analyses showed that triglyceride-rich lipoproteins and proinflammatory lipids were associated with shorter LTL and higher autoimmune risk, whereas omega-3 fatty acids, albumin, and HDL phospholipids were protective. Lipidomic pathways mediated a substantial portion of the LTL-autoimmune association and modified viral effects. These findings identify a telomere-lipid-immunity axis linking lifelong viral integration, metabolic aging, and autoimmune susceptibility, highlighting biological aging pathways as targets for autoimmune disease prevention.