Faculty Bibliography

BACKGROUND:Long-term effect of COVID-19 (Long COVID) may persist for months or years after SARS-CoV-2 infection, but longer-term cardiopulmonary manifestations have not been previously reported. OBJECTIVES/OBJECTIVE:The objective of the study was to characterize cardiopulmonary function after SARS-CoV-2 infection in a digital health substudy of the nationwide Researching COVID-19 to Enhance Recovery Adult Cohort Study. METHODS:Associations between wearable sensor device measures of cardiopulmonary fitness and survey-derived Long COVID symptoms were estimated over a 6-month window at least 6 months after infection using linear regression models adjusted for wear time, age, sex, race/ethnicity, and body mass index. RESULTS:Among 1,475 participants (72% female, 65% non-Hispanic White) a median of 21 months (IQR: 15-31 months) after infection, 498 (34%) had high symptom burden as characterized by the Researching COVID-19 to Enhance Recovery Long COVID Research Index (LCRI). High LCRI (vs low LCRI) was associated with significantly lower heart rate variability (-4.4 ms; 95% CI: -6.5 to -2.4; P < 0.001), higher resting heart rate (+1.5 beats/min [+0.7 to +2.4]; P < 0.001), fewer metabolic equivalent of task minutes (-96.3 [-128.8 to -63.8]; P < 0.001), lower step counts (-1,624 steps/day [-1,952 to -1,296]; P < 0.001), and lower activity levels (-7.9 minutes/day very or fairly active [-10.9 to -5.0]; P < 0.001). Hierarchal clustering analysis identified two subphenotypes with abnormal cardiovascular measures associated with low quality of life scores. CONCLUSIONS:Long COVID is associated with worse cardiovascular fitness. Additional studies are needed to determine if Long COVID is a novel risk factor for incident cardiovascular disease.

Diffusion magnetic resonance imaging (dMRI) is a non-invasive neuroimaging technique that enables in vivo assessment of white matter microstructure and is highly sensitive to tissue alterations associated with disease. Although substantial evidence links diffusion-derived metrics to underlying white matter tissue properties, the presence of complex within-voxel axonal configurations complicates their biological interpretation. Several methods have been proposed to assess diffusion properties of individual crossing axonal populations, but their validation and clinical applicability remain limited. Glaucoma, the second leading cause of blindness worldwide, is characterized by progressive loss of retinal ganglion cells and axonal damage in the optic nerve, leading to degeneration along the entire visual pathway. This degeneration includes secondary effects on fiber crossings within the optic chiasm, which are challenging to characterize with conventional diffusion methods. Here, we evaluated whether advanced diffusion metrics can detect microstructural alterations in these complex white matter configurations and whether these measures correlate with clinical markers of glaucoma severity. In this study, we evaluated 31 patients with asymmetric glaucoma and 31 healthy controls using advanced diffusion magnetic resonance imaging methods, including Diffusion Tensor Imaging, Constrained Spherical Deconvolution, multi-tensor fit via Multi-Resolution Discrete Search method, and Fixel-Based Analysis. We found significant differences of diffusion metrics in white matter tracts of the visual system, including the optic nerve, optic chiasm, optic tracts, and optic radiations. Moreover, diffusion metrics correlated with clinical ophthalmological parameters such as cup-to-disc ratio, visual field mean deviation, and retinal nerve fiber layer thickness. These findings support the use of advanced diffusion magnetic resonance imaging models as sensitive tools for detecting Wallerian degeneration and resolving complex white matter architecture in the human visual pathway, and demonstrate their utility to study other fiber-crossing regions throughout the brain.

BACKGROUND/UNASSIGNED:The practice of living donor kidney transplantation has evolved through innovations in logistics, technology, and clinical practice. In the United States, Good Samaritan donation, a historical label exclusive to nondirected donors, now incorporates voucher-based models. METHODS/UNASSIGNED:To determine how voucher-based nondirected living kidney donation has influenced the volume and practice of Good Samaritan living kidney donation in the United States, we analyzed living donor kidney transplants from 2000 to 2024 using data from the National Kidney Registry (103 transplant centers) and the Scientific Registry of Transplant Recipients. Temporal trends were derived by linear regression. RESULTS/UNASSIGNED:We identified 4662 Good Samaritan living donor kidney transplants, defined as historical nondirected and novel voucher-based nondirected donations. Of 2131 Good Samaritan living donor kidney transplants facilitated by the National Kidney Registry, donors had a median age of 43 y, were predominantly of White race (93%), and were women (60%). Recipients had a median age of 52 y and were racially and ethnically diverse (63% White, 14% Black, and 10% Hispanic). Annual Good Samaritan donation counts in the United States increased from 17 in 2000 to 439 in 2024, corresponding to a growth rate of 14.5%. Voucher-based nondirected donations increased from 2 in 2015 to 314 in 2024, comprising 72% of all Good Samaritan donations in that year. CONCLUSIONS/UNASSIGNED:The advent of voucher-based nondirected donation correlated with growth in Good Samaritan donation volume. Given the prevalence of voucher-based donations, connecting local kidney paired donation practices to voucher-based nondirected donation may improve access to and participation in living kidney donation.

Recurrent patellar instability is a complex condition influenced by both soft tissue insufficiency and a spectrum of bony abnormalities. Although medial patellofemoral ligament reconstruction is the cornerstone of treatment, it may not address all contributing factors-particularly in patients with malalignment, trochlear dysplasia, or abnormal patellar height. This study explores the indications, techniques, and outcomes of adjunctive bony procedures including tibial tubercle osteotomy, trochleoplasty, and derotational distal femoral osteotomies. Ultimately, the goal is to integrate soft tissue and bony procedures in a patient-specific manner to reduce recurrence and preserve long-term joint function. This synthesis aims to offer an up-to-date framework for approaching a challenging condition with growing treatment complexity.

OBJECTIVE:To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND:Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown. METHODS:, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit. RESULTS:= 1.36, 95% CI [0.78-1.93]).Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response. CONCLUSIONS:In this preliminary study, CBD was well tolerated; AEs were mild-moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier NCT03900923.

BACKGROUND/UNASSIGNED:Differentiated service delivery (DSD) is increasingly available for HIV treatment. DSD has been shown to improve treatment retention, but DSD modalities incur higher costs than the clinic-based standard-of-care (SoC). We conducted a cost-effectiveness (CE) analysis to assess what DSD modalities, in what settings, would constitute an efficient use of limited HIV program resources. METHODS/UNASSIGNED:) to project HIV trends (incidence, prevalence, mortality), disability-adjusted life years (DALYs), and costs (2021 USD) arising from DSD versus SoC over 2022-2062 in four settings: South Africa, Malawi, Zambia, and a collective representation of African low- and middle-income countries (LMICs). We compared three DSD modalities: healthcare worker-managed community adherence groups (CAG), client-managed urban adherence group (UAG), and home ART delivery (HomeART). We calculated incremental cost-effectiveness ratios (ICERs) of DSD versus SoC from the health system perspective using country-specific CE thresholds, and performed one-way sensitivity analyses for key assumptions. RESULTS/UNASSIGNED:Community adherence groups (ICER: $274-$604/DALY averted) and UAG (ICER: $590-$720/DALY averted) were cost-effective for all country/model settings. HomeART was dominated by UAG in all settings. In nearly all settings, CE estimates of CAG were robust to uncertainty in DSD effectiveness (except Zambia), DSD costs, CE threshold (except South Africa), HIV-associated disability weights, and discount rates. Cost-effectiveness of UAG was highly sensitive to uncertainty in DSD effectiveness in all settings. CONCLUSIONS/UNASSIGNED:Community adherence groups and UAG can provide cost-effective alternatives to the clinic-based SoC in multiple African settings.

BACKGROUND:Almost 75% of patients with relapsing multiple sclerosis (pwRMS) with suboptimal response to other disease-modifying therapies (DMTs) showed no evidence of disease activity (NEDA-3) when treated with ocrelizumab in a large single-arm multicentre trial over 2 years. We aimed to assess the 4-year effectiveness and safety of ocrelizumab in pwRMS who entered a 2-year extension trial. METHODS:PwRMS completing CASTING were eligible to rollover into LIBERTO if available in the country of residence. PwRMS received ocrelizumab every 24 weeks; the same frequency was used for clinical assessments. Primary endpoint was the proportion of patients who had NEDA-3 over 4 years. Safety was assessed by rate and nature of adverse events (AEs). RESULTS:A total of 439 pwRMS rolled over to LIBERTO, of which 68.1% completed the study; most patients discontinued from LIBERTO due to country-specific changes in reimbursement but most remained on ocrelizumab outside the trial. Over 4 years, 79.5% of patients showed no 24-week confirmed disability progression, 87.5% no relapses, and 90.0% no radiological activity. A total of 65.6% of patients (n = 290) showed NEDA-3, with the proportion of patients achieving NEDA-3 yearly remaining above 84.8%. Over 4 years, infections (72.9% of patients) and infusion-related reactions (44.2%) were the most reported AEs. Serious AEs were reported in 9.3% of patients. Five (1.1%) patients discontinued due to AEs. CONCLUSIONS:Findings suggest that switching to ocrelizumab is safe for patients with early RRMS and suboptimal response to previous DMTs, resulting in significant and durable control of disease activity. TRIAL REGISTRATION/BACKGROUND:LIBERTO (NCT03599245), extension study to CASTING (NCT02861014); first patient enrolled 12.07.2018; https://clinicaltrials.gov/study/NCT03599245. CHORDS (NCT02637856), ENSEMBLE (NCT03085810).

INTRODUCTION/UNASSIGNED:Facet-mediated lumbar pain is commonly treated with radiofrequency neurotomy (RFN) following confirmatory medial branch blocks. Because RFN generates electrical current, concerns exist regarding electromagnetic interference (EMI) in patients with cardiac implantable electronic devices, particularly leadless pacemakers, for which limited procedural guidance is available. CASE REPORT/UNASSIGNED:We present the case of an 81-year-old man with chronic low back pain and a right ventricular leadless pacemaker (Medtronic Micra) who underwent lumbar RFN after successful diagnostic blocks. Pre-procedural electrophysiology evaluation confirmed he was not pacemaker dependent, and the device was interrogated without reprogramming. Bipolar lesioning was performed with continuous cardiac monitoring. The procedure was completed without complication, and post-procedural interrogation demonstrated normal device function. The patient reported significant pain relief at follow-up. DISCUSSION/UNASSIGNED:This case highlights that lumbar RFN can be safely performed in patients with a leadless pacemaker when a multidisciplinary approach is utilized. Key considerations include confirmation of device type and pacemaker dependency, pre-procedural interrogation, use of bipolar lesioning to reduce EMI risk, and continuous peri-procedural monitoring. As leadless pacemakers become increasingly prevalent, further research is needed to guide specialty-specific recommendations for interventional pain procedures involving radiofrequency-based therapies.