Faculty Bibliography

Human pluripotent stem cells (hPSCs) are a valuable tool for disease modeling. Further stem cells can be reprogrammed from adult somatic cells, called induced pluripotent stem cells (iPSC). iPSC technology allows for the evaluation of specific study participants and populations and ventures into personalized medicine. Blood is routinely taken and cryopreserved for research purposes. These samples are processed either as buffy coats, a blood sample containing white blood cells and platelets, or as peripheral blood mononuclear cells (PBMCs), which represent a more purified population of white blood cells without eosinophils, basophils, platelets, or red blood cells. Both are a readily available and relatively non-invasive source for reprogrammable somatic cells. Several reports detail reprogramming from PBMCs, whereas only one describes this process from frozen buffy coats. Recent experience revealed PBMC reprogramming protocols available in the literature and from manufacturers to be unsuccessful when applied to frozen buffy coat samples, necessitating the adaptations and troubleshooting strategies described here. For many researchers, who employ iPSC technologies, it is imperative to have thorough protocols with a high success rate, especially in cases, where patient samples may contain only few cells, are obtained in wide time intervals, are from limited participant pool, or are otherwise highly valuable. Here, checkpoints and troubleshooting strategies are identified to increase the chance of reprogramming human frozen buffy coats or purified PBMCs. Ultimately, this protocol will allow researchers to identify predictors of reprogramming success and strategize alternative approaches to improve the chances of successful iPSC derivation.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Traditional medical board examinations present clinical information in static vignettes with multiple-choices (MC), fundamentally different from how physicians gather and integrate data in practice. Recent advances in large language models (LLMs) offer promising approaches to creating more realistic clinical interactive conversations. However, these approaches are limited in neurosurgery, where patient communication capacity varies significantly and diagnosis heavily relies on objective data such as imaging and neurological examinations. We aimed to develop and evaluate a multi-artificial intelligence (AI) agent conversation framework for neurosurgical case assessment that enables realistic clinical interactions through simulated patients and structured access to objective clinical data. METHODS:We developed a framework to convert 608 Self-Assessment in Neurological Surgery first-order diagnosis questions into conversation sessions using 3 specialized AI agents: patient AI for subjective information, system AI for objective data, and clinical AI for diagnostic reasoning. We evaluated generative pretrained transformer 4o's (GPT-4o's) diagnostic accuracy across traditional vignettes, patient-only conversations, and patient + system AI interactions, with human benchmark testing from 10 neurosurgery residents. RESULTS:= .0030) using fewer interactions and reported high educational value of the interactive format. CONCLUSION/CONCLUSIONS:This multi-AI agent framework provides both a more challenging evaluation method for LLMs and an engaging educational tool for neurosurgical training. The significant performance drops in conversational formats suggest that traditional MC testing may overestimate LLMs' clinical reasoning capabilities, while the framework's interactive nature offers promising applications for enhancing medical education.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The rapid rise of electric and mechanical bikes and scooters has transformed urban transportation, but their neurosurgical consequences remain underexplored. This study aimed to evaluate micromobility-related injuries over time, examining mechanisms of injury, patient risk factors, injury patterns, and associated clinical outcomes at a Level-1 trauma center over a 5-year period. METHODS:We performed a retrospective review of patients who sustained micromobility-related injuries and presented to the Bellevue Hospital Center between 2018 and 2023. The cohort included riders of electric or mechanical bikes and scooters, as well as pedestrians struck by these devices. Key clinical variables and outcomes were compared across device types, both before and after propensity score matching. Unlike national database studies, this hospital-based analysis provides detailed clinical and neurosurgical outcome data. RESULTS:A total of 914 patients presented with micromobility-related injuries, accounting for 6.9% of all trauma admissions. Annual case volume and electric device involvement increased over time. The most common mechanism was collision with a motor vehicle (49.9%). Most patients (68.7%) required admission; 30.2% required intensive care. The median length of hospital stay was 3 days [IQR 1-5]. Half underwent a surgical intervention or procedure, and the overall mortality was 1.2%. Helmet use was low (31.7%). Pedestrians experienced the most severe outcomes, particularly when struck by electric devices. Injuries clustered during evening hours, suggesting modifiable environmental and behavioral risk factors. CONCLUSION/CONCLUSIONS:Micromobility-related trauma imposes a substantial neurosurgical burden, with frequent traumatic brain injury, intensive care unit utilization, and operative intervention. Unlike previous database studies, this hospital-based analysis provides detailed neurosurgical outcome data and identifies prevention targets-including helmet use, intoxication, and urban infrastructure-to reduce morbidity and resource utilization.

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer's disease (AD) research. We evaluated the test-retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant volumes of entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test-retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15-50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Implementation of telemedicine expanded options for outpatient neurology care. It remains uncertain which new neurology patients can be appropriately evaluated virtually. We compared subsequent health care utilization after virtual vs in-person new patient neurology visits across 3 academic medical centers. METHODS:We conducted a retrospective multicenter cohort study of adults with a new outpatient neurology visit from September 2020 through December 2021 using the Vizient Clinical Data Base and Clinical Practice Solutions Center databases. Virtual and in-person patients were matched 1:1 using propensity scores incorporating demographics, clinical characteristics, time period, and previous health care utilization. Outcomes were analyzed overall and stratified by neurologic chief complaint category and institution. We compared rates of subsequent neurologic clinic follow-up, emergency department (ED) visits, and hospitalizations after virtual and in-person encounters. Testing and all-cause ED visits/hospitalizations were also assessed. RESULTS:= 0.13, respectively). Analyses by chief complaint found that 90-day follow-up was higher after in-person visits for dementia, whereas 30- and 90-day follow-up was higher after virtual visits for Parkinson disease and multiple sclerosis, and 90-day follow-up was higher after virtual visits for headache. Testing was more frequent after in-person visits for certain chief complaints. DISCUSSION/CONCLUSIONS:In this propensity score-matched multicenter cohort, new neurology patients seen virtually had similar downstream utilization as those seen in-person, including comparable 90-day follow-up and similar neurologic and all-cause ED visits and hospitalizations. Although follow-up varied modestly by chief complaint and testing was more frequent after some in-person visits, no major differences emerged overall.

Historically hindered by a lack of access to academic, political, financial, technological, scientific, and social resources, most people living with disability have been unable to successfully merge their lived experience with the traditional research process. The lack of this community's perspective has been an ongoing missed opportunity for the broadening and relevance of research around disability. Patient-scientists, however, bridge the gap. They are individuals who act as patient research partners (PRPs) with the valuable addition of a research and/or medical degree. Their embodied expertise, combined with their academic accreditation, seamlessly positions them to work within the academic system. With a foot in both worlds, they are equipped to generate real change for themselves and others living with their condition. Patients are encouraged to participate in their own clinical care, although PRPs remain relatively uncommon. Even more scarce are patient-scientists, who serve as intellectual peers with expertise in technical and experiential domains. Their research training gives them an invaluable role: to act as both scientist and patient at once. This special communication builds on ongoing efforts to bolster patient participation in rehabilitation research by focusing on patient-scientists and highlighting their potential to enhance rehabilitation research processes.

BACKGROUND:Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an established treatment for medication-refractory tremor with limited evidence in patients aged >80 years. OBJECTIVE:To retrospectively compare safety and efficacy of MRgFUS in under-80 versus over-80 patients without prior balance disturbances or unstable comorbidities. METHODS:One hundred thirty five consecutive patients with essential tremor or tremor-predominant Parkinson's disease underwent unilateral MRgFUS thalamotomy. Patients were stratified into under-80 (n: 97, median age 71 years) and over-80 (n: 38, median age 82 years). Tremor severity was scored with the Fahn-Tolosa-Marin Clinical Rating Scale. Outcomes included intraoperative tremor suppression and SE occurrence, resolution, and improvement. RESULTS:Older patients showed higher baseline tremor severity (U: 383.5; p: 0.02). Tremor reduction >50% occurred in 95.6% of cases, with complete resolution in 77.0%. Higher target temperature predicted better tremor control (OR [95% CI]: 4.03 [1.39-11.65]; p: 0.01), whereas greater baseline tremor (OR [95% CI]: 0.90 [0.83-0.99]; p: 0.02) and SDR <0.4 (OR [95% CI]: 0.14 [0.02-0.85]; p: 0.03) predicted poorer outcomes. Age ≥ 80 did not affect intraprocedural tremor control (OR [95% CI]: 0.83 [0.15-4.70]; p: 0.83) and longitudinal mixed-effects analysis confirmed sustained 1-year tremor control, unaffected by advanced age. SEs occurred in 71.1%, mostly balance disturbances. After a mean follow-up of 43.7 weeks, 60.4% improved and 46.9% fully resolved, with only 1.5% severe persistent SEs. Age ≥ 80 did not influence SE rates (OR [95% CI]: 0.60 [0.27-1.33]; p: 0.20), resolution (OR [95% CI]: 0.56 [0.25-1.26]; p: 0.16), or improvement (OR [95% CI]: 0.60 [0.28-1.30]; p: 0.19). CONCLUSIONS:MRgFUS thalamotomy yields comparable outcomes in carefully selected patients aged >80 years and in younger individuals.