Faculty Bibliography

BACKGROUND:Cardiac dysfunction is more common in people with HIV (PWH) than those without HIV (PWoH), with mitochondrial dysfunction implicated in pathogenesis. We investigated whether variations in mitochondrial DNA (mtDNA) and certain dideoxynucleoside analogs (D-drugs) relate to left ventricular diastolic dysfunction (LVDD) in PWH. METHODS:We included individuals with echocardiograms from the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. LVDD was defined using characterizing heart function on antiretroviral therapy criteria. mtDNA haplogroups were inferred using HaploGrep. Separate exploratory multivariable logistic regressions examined associations between LVDD and African (L0L1, L2, L3, or "other") or European haplogroups (UK, H, JT, or "other"), D-drugs, and their interactions. No adjustments were made for multiple comparisons. RESULTS:Among 842 men (455 PWH and 387 PWoH) and 898 women (620 PWH and 278 PWoH), LVDD prevalence was 29% in women and 24% in men. Among non-Hispanic White men with HIV, European haplogroup H was associated with lower odds of LVDD (odds ratio [OR], 0.50; 95% CI, 0.26-0.93), while haplogroup clade JT was associated with increased odds (OR, 2.09; 95% CI, 1.00-4.36). In men with HIV, D-drug exposure was associated with increased odds of LVDD (OR, 1.94; 95% CI, 1.21-3.13). No significant associations were observed between haplogroups and LVDD in women. HIV serostatus modified the association of haplogroup L2 (pinteraction = 0.036) and L3 (pinteraction = 0.045) with LVDD in women. CONCLUSIONS:Mitochondrial genetic variation and D-drug use were associated with altered LVDD risk in men with HIV, highlighting potential biological mechanisms that may be targeted for surveillance or therapeutic strategies.

STUDY OBJECTIVE/OBJECTIVE:Emergency department (ED) visits among older adults represent critical transition points in health care, often resulting in substantial downstream utilization. We aimed to quantify health care contact days in the 30 days following a treat-and-release ED visit among older adults and examine associations with demographic and clinical characteristics. METHODS:We conducted a pooled cross-sectional analysis of 2016-2021 Medicare Current Beneficiary Survey data. The sample included treat-and-release ED visits among beneficiaries ≥ 65 years. Health care contact days were categorized as institutional (ED, hospital, skilled nursing facility, hospice) and ambulatory (outpatient visits, labs, imaging, procedures, or treatments). We applied zero-inflated Poisson regression to estimate the likelihood and intensity of health care contact. RESULTS:The analytic sample comprised 10,964 treat-and-release ED visits. Within 30 days, 22.5% of visits resulted in institutional contact and 84.4% in ambulatory contact. On average, each ED visit was followed by 4.3 total contact days (3.0 ambulatory, 1.3 institutional) within 30 days. Having ≥ 2 chronic conditions was associated with greater odds of both institutional (OR: 1.46, 95% CI: 1.28-1.66) and ambulatory contact (OR: 1.44, 95% CI: 1.25-1.66). Dementia was associated with reduced odds of ambulatory contact (OR: 0.51, 95% CI: 0.37-0.72). CONCLUSIONS:Older adults experience frequent and sustained health care contact following treat-and-release ED visits, with particularly high intensity among those with multi-morbidity. Reduced ambulatory follow-up among patients with dementia highlights a potential gap in care coordination after ED discharge.

Xenotransplantation has been iteratively improved over the last decade in pre-clinical models, with first-in-human clinical trials underway. The 2025 IXA Congress in Geneva was held in parallel with meetings involving World Health Organization leaders to support the development of new guidance on xenotransplantation in this rapidly evolving field. Key scientific themes of the meeting included the introduction of multiple-gene edited pigs for xenotransplantation research and clinical trials, better characterization of innate and adaptive immune responses and xenograft preservation that optimizes ramifications of ischemia-reperfusion injury during implantation. This comes at a time when gene-edited pig organs are being used for human xenotransplantation, a development that demands safety, reproducibility, durability, and a clear mechanistic understanding of rejection and tolerance.

Allergic contact dermatitis (ACD) to personal care products (PCPs) represents a significant and growing clinical challenge, with increasing use of diverse PCPs and their expanding range of ingredients. Common allergenic components include fragrances, botanicals, preservatives, surfactants, emollients, emulsifiers, vitamins, and ultraviolet (UV) filters. Patch testing remains the gold standard for diagnosing ACD and identifying causative allergens, but traditional panels often fail to capture emerging PCP-related allergens. This review highlights key established and emerging PCP allergens, such as limonene and linalool hydroperoxides, sodium benzoate, octocrylene, and benzophenone-4. Strategies are discussed to optimize diagnostic accuracy through targeted series and repeated open application tests. Patient education about PCP labeling is paramount when assisting patients with allergen avoidance. Clinicians must balance precise allergen identification with practical management knowledge to improve outcomes in PCP-related ACD.

BACKGROUND AND IMPORTANCE/UNASSIGNED:Closed reduction is an important adjunct in the surgical management of traumatic cervical facet dislocations, particularly jumped and locked facets. By restoring normal spinal alignment, successful closed reduction allows the surgeon to proceed with surgical stabilization via an anterior-first approach, obviating the need to rotate a dislocated, biomechanically unstable cervical spine, thereby minimizing the risk of iatrogenic spinal cord injury. While closed reduction has traditionally been achieved with Gardner-Wells tongs and weights, this reduction method requires the patient to remain bedbound for prolonged periods of time, is not MRI-compatible, and is associated with inconsistent results. CLINICAL PRESENTATION/UNASSIGNED:We present two patients with bilaterally jumped and locked cervical facets, in whom a closed manual reduction technique was used, allowing rapid spinal realignment prior to surgical stabilization. We provide a detailed video illustration of this technique, emphasizing the steps involved and relevant technical nuances. While this technique might have been previously used and rarely reported, it has not, to the best of our knowledge, been described in a detailed, step-by-step fashion. CONCLUSION/UNASSIGNED:Closed manual reduction of traumatic cervical facet dislocations can be performed safely and effectively in the operating room prior to definitive surgical stabilization of the spine. This technique should not be attempted in patients with severe spinal cord compression or neurologic compromise. The importance of adequate muscle relaxation provided by general anesthesia and continuous intraoperative feedback provided by live fluoroscopy and neurophysiologic monitoring cannot be overemphasized.

BACKGROUND:CD19-directed chimeric antigen receptor T-cell (CAR T) therapy has significantly improved outcomes for patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) but is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS), a major cause of morbidity and mortality. Preclinical and early phase clinical studies suggest that interleukin-1 blockade with anakinra may mitigate ICANS without impairing CAR T efficacy. However, real-world data evaluating the efficacy and safety of prophylactic anakinra remain limited. OBJECTIVES/OBJECTIVE:We performed a retrospective analysis comparing CAR T toxicities and clinical outcomes among patients treated with prophylactic anakinra versus controls using inverse probability of treatment weighting (IPTW), hypothesizing that anakinra prophylaxis would be associated with decreased severe ICANS. STUDY DESIGN/METHODS:In 2023, our institution implemented a policy for anakinra prophylaxis for high-risk patients based on promising early phase data. We conducted a single-center retrospective cohort study of 176 adult patients with R/R B-NHL who received CD19 CAR T therapy between 2018 and 2025. The analysis was restricted to patients meeting institutional criteria for anakinra prophylaxis (age ≥65 years or receipt of a CD28 costimulatory domain CAR T product), excluding those with baseline ICE score <8. Patients treated with anakinra in the post-policy era were compared with patients treated prior to the implementation of the policy. Inverse probability of treatment weighting (IPTW) was used to balance baseline clinical and disease-related covariates between groups. RESULTS:After IPTW, patients receiving prophylactic anakinra had a higher incidence of any-grade ICANS compared with those who did not (40.0% vs 23.0%, p = 0.03), while rates of grade ≥3 ICANS were similar between groups (p = 0.62). In multivariate regression, anakinra prophylaxis was associated with increased odds of any-grade ICANS (aOR 3.22; 95% CI 1.39-7.46) but not grade ≥3 ICANS (aOR 1.84; 95% CI 0.61-5.5). Rates of all-grade CRS were comparable (p = 0.74); however, in multivariate regression, anakinra prophylaxis was associated with increased odds of grade ≥3 CRS (aOR 17.83; 95% CI 1.30-245.21), though the estimate was imprecise due to sparse events. Grade ≥3 infections were more common in the anakinra cohort (21.5% vs 7.3%; p = 0.01) by day 30 and by day 90 (27.1% vs 10.4%; p = 0.01). Grade ≥3 infections remained associated with use of anakinra in multivariate regression (day 30: aOR 7.08; 95% CI 1.90-26.30, p = 0.004) (day 90: (aOR 5.59; 95% CI 1.83-17.04; p = 0.003). No differences in response rates, event-free or overall survival were observed between groups. CONCLUSION/CONCLUSIONS:In this single-center historical comparison of high-risk patients receiving CD19 CAR T cells, prophylactic anakinra did not reduce severe ICANS and was associated with increased immune-mediated toxicities and infectious complications. Causal inference is limited by policy-driven treatment assignment, residual temporal confounding, and limited practical overlap. These findings suggest the need for caution in routine use of anakinra prophylaxis outside of clinical trials and underscore the importance of prospective studies to better define optimal toxicity mitigation strategies.

PURPOSE/OBJECTIVE:This study evaluates radiographic outcomes and reoperations in patients undergoing anterior vertebral body tethering (VBT) of the lumbar spine. METHODS:A retrospective review of an EOS database identified pediatric patients who underwent lumbar VBT. Demographic and surgical data were collected, as well as radiographic and clinical outcomes including complications, reoperations, and conversion to posterior spinal fusion (PSIF). Analyses included paired t-tests, Wilcoxon signed-rank tests and chi-square. RESULTS:Thirty-two patients with idiopathic scoliosis who underwent thoracolumbar VBT with 2-year follow-up were included. Mean age at surgery was 13.7 ± 1.8 years (mean follow-up 2.0 ± 0.2 years); median Sanders score was 3 (50% ≤ 3). Lumbar Cobb decreased from 48° ± 12 to 20° ± 10 postoperatively (p < 0.001) with correction loss to 29° ± 12 at 2 years (p < 0.001). Tethered Cobb decreased from 46° ± 8 to 13° ± 9 postoperatively (p < 0.001), with correction loss to 17° ± 12 at 2 years (p = 0.284). At 2 years, 31% had > 5° of correction loss and 84% had a tethered Cobb < 30°. Correction loss did not differ by Sanders stage (p = 0.92). Seven patients (23.3%) demonstrated > 5° of additional curve correction postoperatively. Four patients (12.5%) had unplanned reoperation and five others (15.6%) required PSIF: 28.1% total reoperation rate. CONCLUSIONS:Lumbar VBT provided substantial initial correction with maintenance of correction across the tethered levels at 2-year follow-up. While most patients maintained a tethered Cobb angle < 30° at 2 years, 28.1% of patients underwent reoperation (12.5% UPROR; 15.6% PSIF conversion). Longer follow-up in larger multicenter cohorts is required to more accurately define lumbar VBT durability and conversion-to-fusion risk. LEVEL OF EVIDENCE/METHODS:IV.

BACKGROUND/UNASSIGNED:Recent observational studies have suggested that early treatment (<12 hours from diagnosis) of intermediate risk pulmonary embolism (PE) with catheter-based therapies may reduce morbidity and mortality. However, the effect of early versus late mechanical thrombectomy on acute pulmonary hemodynamics and right ventricular mechanics is less well defined. METHODS/UNASSIGNED:Patients enrolled in SYMPHONY-PE were divided into one of 2 groups based on the time from baseline CT pulmonary angiography to mechanical thrombectomy: Early <12 hours versus late ≥12 hours. The primary safety end point was the rate of major adverse events within 48 hours, as adjudicated by an academic independent safety board. The primary efficacy end point was the core-lab assessed mean change in right ventricle-to-left ventricle ratio from baseline to 48 hours. RESULTS/UNASSIGNED:=0.431) between groups, and there were no mortalities. The differences in efficacy outcomes were greatest in higher-risk patients per the Composite Pulmonary Embolism Shock score. CONCLUSIONS/UNASSIGNED:Early mechanical thrombectomy was associated with larger reductions in right ventricle-to-left ventricle ratio and mean pulmonary artery pressure, with no significant differences in safety event rates compared with patients who underwent late thrombectomy. Randomized trials are needed to test these associations. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06062329.

This multinational cone-beam computed tomography (CBCT) study evaluated the root canal morphology of mandibular first premolars (M1Ps) from 21 countries and compared how well the Ahmed and Vertucci classification systems represented these patterns. A total of bilateral mandibular first premolars from eligible CBCT scans were assessed using both systems, and the data were analyzed with a hierarchical probabilistic approach to account for population and imaging-related variation. Across the overall dataset, a simple single-canal configuration was the dominant pattern, and this remained the most common finding in all populations despite limited but structured variation in less frequent subclasses. The Ahmed system classified all observed configurations, whereas the Vertucci system left approximately 10.2% of cases without an equivalent category. In addition, Ahmed preserved more anatomical detail, while Vertucci compressed several distinct configurations into broader groups. Demographic and imaging-related factors had modest effects, with voxel size showing the clearest technical influence on the detection of more complex patterns. Overall, M1P morphology showed a stable global pattern with secondary heterogeneity, and the Ahmed system provided a more complete and informative representation for CBCT-based morphology assessment across diverse populations.