Faculty Bibliography

• 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.

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.

We present MelOD (Melanoma Omics Dashboard), a free, web-based interactive platform integrating preprocessed data from 16 melanoma studies, including eight bulk transcriptomics, six single-cell RNA-seq, and two proteomics datasets. MelOD provides user-friendly visualization and analysis tools, differential expression, dimensionality reduction, clustering, correlation, and survival analysis without requiring local computational resources. Several datasets include annotations for immunotherapy response, facilitating exploration of resistance and response signatures. Built on RShiny with optimized handling of large datasets, MelOD supports real-time hypothesis generation, cross-study validation, and community dataset contributions. Freely accessible online, MelOD lowers barriers to multi-omics research in melanoma and related fields.

In presynaptic nerve terminals, the endocytic apparatus rapidly restores synaptic vesicles after neurotransmitter release. Many endocytic proteins localize to the periactive zone, a loosely defined area adjacent to active zones. A prevailing model posits that recruitment of these endocytic proteins to the periactive zone is activity-dependent. We show that periactive zone targeting of endocytic proteins is largely independent of active zone machinery and synaptic activity. At mouse hippocampal synapses and Drosophila neuromuscular junctions, pharmacological or genetic silencing resulted in unchanged or increased levels of endocytic proteins including Dynamin, Amphiphysin, Nervous Wreck, Endophilin A, Dap160/Intersectin, PIPK1γ, and AP-180. Similarly, disruption of active zone assembly via genetic ablation of active zone scaffolds at each synapse did not impair the localization of endocytic proteins. Overall, our work indicates that endocytic proteins are constitutively deployed to the periactive zone and supports the existence of independent assembly pathways for active zones and periactive zones.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS:A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm3. Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS:A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION/CONCLUSIONS:VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

INTRODUCTION/BACKGROUND:Chronic traumatic encephalopathy (CTE) is a tauopathy linked to repetitive head impacts. Factors influencing brain regional susceptibility to tau deposition and spreading remain unclear. METHODS:We used three datasets: [18F]flortaucipir positron emission tomography (PET) in 157 former professional American football players and 53 controls (DIAGNOSE CTE); cortical myelin water fractions (MWF) in 50 healthy individuals (Myelin Water Atlas); and white matter (WM) tract MWF and functional connectivity (FC) in 100 healthy individuals (Human Connectome Project). We tested associations between tau-PET uptake and covariance in football players and typical cortical gray matter (GM) MWF, WM tract MWF, and FC. RESULTS:Cortical regions with lower typical GM MWF showed higher tau-PET uptake (β = -0.399, p = 0.001). WM tracts with lower typical MWF were associated with higher tau-PET covariance (β = -0.238, p < 0.001). Higher typical FC was associated with higher tau-PET covariance (β = 0.447, p < 0.001). DISCUSSION/CONCLUSIONS:In former football players at risk for CTE, regional susceptibility to tau deposition may be driven by low myelin and high FC.

BACKGROUND:Transcatheter aortic valve replacement (TAVR) has become a cornerstone in the management of aortic valve disease. However, delayed complications after hospital discharge and readmission remain in an issue following TAVR. We aimed to evaluate the impact of remote monitoring systems on clinical outcomes after TAVR. METHODS:All patients who underwent TAVR from September 2014 through January 2019 were included retrospectively. Additionally, all patients, clinically indicated for TAVR from 9/1/2018 through 8/30/2021, were screened, and patients who agreed were prospectively enrolled. Medtronic Care Management Service (MCMS) was used to monitor patients following TAVR after discharge (Medtronic, Minneapolis, MN). RESULTS:A total of 1078 patients were included. Among them, 843 (78.2 %) patients were discharged with MCMS (MCMS group) and 235 (21.8 %) patients were discharged without (non-MCMS group). Overall, the mean age was 81.5 years, and mean STS-PROM was 5.53 %. Baseline conduction defect was observed in 427 (39.6 %). Peripheral artery disease was more common in the MCMS group while a history of myocardial infarction was more likely seen in the non-MCMS group. After propensity-score matching, length of hospital stays was significantly shorter in the MCMS group (1.42 days vs. 1.82 days in the non-MCMS group, p < 0.001). Readmission rates and new permanent pacemaker insertion rates were similar between the two groups. All-cause mortality, 30-day and 90-day mortality were comparable between the groups. CONCLUSIONS:MCMS was easily applicable to a clinical practice and may reduce length of hospital stays in patients undergoing TAVR without increasing readmission or mortality.

BACKGROUND:Pediatric skin-limited discoid lupus erythematosus (DLE-only) is rare, with limited data on risk factors for progression to systemic lupus erythematosus (SLE). OBJECTIVE:To assess incidence, risk factors, and phenotype of pediatric DLE-only progression to SLE. METHODS:In this 17-site retrospective cohort of pediatric DLE, the primary outcome was time to SLE diagnosis (ACR classification criterion ≥4). Kaplan-Meier estimates for 1-, 2-, and 5-year progression to SLE were generated. Cox proportional hazards modeling identified baseline predictors of progression to SLE. RESULTS:The 1-year progression rate from DLE-only to SLE was 14.4% (95% CI: 9.6-18.9%). Progression to SLE was most strongly associated with baseline ANA positivity (HR 3.71) and older age (HR 1.11/yr). Antiphospholipid antibodies and cytopenias also predicted progression to SLE in multivariable analysis. The SLE phenotype was relatively mild, with most patients developing mucocutaneous and laboratory criteria (22/236, 9%) and few developing other end-organ disease (7/236, 3%). LIMITATIONS/CONCLUSIONS:Retrospective design, missing data. CONCLUSION/CONCLUSIONS:ANA-positive DLE-only patients warrant close monitoring for progression SLE, especially within the first year. Severe end-organ disease in DLE patients who progress to SLE is uncommon. Future studies should test whether early recognition and intervention in DLE-only slows progression to SLE.