Faculty Bibliography

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.

Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows^1,2. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies.

INTRODUCTION/UNASSIGNED:Few populations face more disadvantage than those with lifelong intellectual and developmental disabilities (IDD) and those with serious mental illness (SMI). People with IDD may face unique challenges in the manifestation and treatment of SMI; little is known about these challenges during the widespread expansion of telehealth mental health services during the COVID-19 pandemic which disrupted service availability. METHODS/UNASSIGNED:Using Medicaid claims from Kansas, Massachusetts, New York and South Carolina, mental health service utilization patterns for three cohorts of people ages 1-45 years were studied: those with IDD, those with SMI, and those with SMI and IDD. Utilization was examined before (2018-2019) and during (2020-2021) the emergence of telehealth services for each cohort. Meta-analysis was used to compare odds of mental health service utilization by demographic subgroups. RESULTS/UNASSIGNED:The prevalence of mental health service utilization was approximately 75% for the IDD/SMI cohort, 60% for the SMI cohort, and 30% of the IDD cohort in 2018. Teens 13-17 years and young adults tended to have the highest levels of service utilization. Service utilization was driven by different diagnoses for the groups. The SMI cohort utilized services significantly more for mood and anxiety disorders, and the IDD cohort utilized services significantly more for comorbid neurodevelopmental conditions, anxiety, and trauma-related disorders. The IDD/SMI cohort utilized services more bipolar and related disorders and had a younger median age of service utilizers for trauma- and stress-related disorders than the SMI cohort. DISCUSSION/UNASSIGNED:The IDD/SMI cohort had the highest mental health service utilization rates compared to the other two cohorts, with minimal urban-rural differences, suggesting mental health services may be reaching those at the highest levels of risk for adverse outcomes. People with IDD demonstrated substantially lower rates of telehealth utilization for mental health needs; however, people in the cohort with IDD and SMI demonstrated similar or higher rates (in adults) of telehealth utilization compared to people with SMI only. Even with expanded telehealth services, the COVID-19 pandemic appeared to partially disrupt utilization across all cohorts and age groups. Findings suggest that people with IDD and SMI experience trauma- and stressor-related disorders that require treatment at younger ages than people with SMI only.

BACKGROUND:Traumatic encephalopathy syndrome (TES) is a clinical research construct used to identify individuals at risk for chronic traumatic encephalopathy (CTE) following exposure to repetitive head impacts (RHI). Adjudication of TES relies on clinical features such as progressive cognitive impairment and neurobehavioral dysregulation. Blood-based biomarkers and structural neuroimaging abnormalities have been associated with TES but are not part of the criteria. This study evaluated whether TES identification was associated with the combined contribution of cognitive performance, blood biomarkers, and structural neuroimaging measures across two well-characterized cohorts. METHODS:Participants included 158 professional fighters from the Professional Athletes Brain Health Study and 149 former American football players from The DIAGNOSE CTE Research Project. Three indices were constructed representing complementary domains: a cognitive index reflecting cohort-specific cognitive features, a blood biomarker index including plasma neurofilament light chain, glial fibrillary acidic protein, total tau, tau phosphorylated at amino acid 231, and APOE-ε4 carrier status, and an imaging index comprising volumetric MRI measures of subcortical structures, ventricles, and corpus callosum subregions. Grouped weighted quantile sum regression models were estimated within each cohort to evaluate associations between these indices and TES while adjusting for age, race, competition status, and RHI exposure. RESULTS:Multidomain models demonstrated improved model performance compared with single-domain models in both cohorts (PABHS: AUC = 0.91, PPV = 0.80; DIAGNOSE CTE: AUC = 0.84, PPV = 0.85). Biomarker and imaging indices contributed additional information across cohorts, although imaging contributions were more prominent in fighters whereas blood biomarker associations were stronger in football players. CONCLUSION/CONCLUSIONS:TES in RHI-exposed athletes was associated with a convergent clinicobiological profile observed across two independent cohorts with distinct exposure patterns. These findings support multidomain analytic frameworks for evaluating correlated biological signals in RHI-exposed populations and may inform future studies of TES and CTE.

• The authors present supravalvular stenosis from congenital and iatrogenic etiologies. • Multimodality imaging is essential for diagnosing supravalvular stenosis. • Echocardiography assesses severity, while CCT provides diagnostic clarity.

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.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through August 2024 for articles related to endoscopic submucosal dissection. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

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.

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.