Faculty Bibliography

DNA methylation-based classification is now central to contemporary neuro-oncology, as highlighted by the World Health Organization (WHO) classification of central nervous system (CNS) tumors. We present the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.8), trained on 7,495 methylation profiles, which expands recognized entities from 91 classes in version 11 (v11) to 184 subclasses. This expansion is a result of newly identified tumor types discovered through our large online repository and global collaborations, underscoring CNS tumor heterogeneity. The random forest-based classifier achieves 95% subclass-level accuracy, with its well-calibrated probabilistic scores providing a reliable measure of confidence for each classification. Its hierarchical output structure enables interpretation across subclass, class, family, and superfamily levels, thereby supporting clinical decisions at multiple granularities. Comparative analyses demonstrate that v12.8 surpasses previous versions and conventional WHO-based approaches. These advances highlight the improved precision and practical utility of the updated classifier in personalized neuro-oncology.

Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM ('calcium bioluminescence activity monitor'), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.

PURPOSE/OBJECTIVE:Dysphagia is a commonly occurring medical condition estimated to occur in between and 10% adults in the US. Despite this relatively high prevalence, the general population's understanding of this condition is currently unknown. Our aims were to (a) conduct a large-scale survey to determine the public's awareness and understanding of dysphagia in comparison to other three other health conditions and (b) compare this knowledge to relative prevalence rates of the conditions. METHODS:The survey was designed to measure four constructs of interest comparing dysphagia with insomnia, vertigo and ataxia. Constructs included: (1) Knowledge of the Condition, (2) Source of Knowledge, (3) Health Impact, (4) Treating Medical Professionals. The survey was launched via Qualtrics™ software and participants were recruited and paid using Prolific™. Descriptive statistics were used to compare participants knowledge of dysphagia with the other conditions. To obtain relative prevalence rates, Cosmos was used to quantify the number of Epic-based patient encounters with any ICD-10 code for each condition in 2023 and expressed as a percent of all patient encounters in the US in 2023. RESULTS:2000 adults (n = 1030 female) aged 18-95 (median 49, IQR = 33-62) completed our survey. When asked, 'Do you know what ____ is'? participants expressed higher familiarity with insomnia (99%) and vertigo (87%) in comparison to dysphagia (25%) and ataxia (18%). From a list of 8 options, 99% and 94% participants selected the correct impairment for insomnia and vertigo respectively, compared with 44% correct for dysphagia and 22% for ataxia. Participants selected an appropriate healthcare provider for dysphagia 47% of the time compared with 74% for insomnia, 56% for vertigo and 36% for ataxia. When asked to identify up to 3 sequelae (from a list of 9), only 4% of participants were able to correctly identify all three for dysphagia, in comparison to 16% for ataxia, 27% for vertigo and 60% for insomnia. The Cosmos analysis revealed that while insomnia had the highest prevalence in 2023 (5.5% of patient encounters), dysphagia occurred much more frequently (2.4%) than vertigo (0.68%) and ataxia (0.24%). CONCLUSIONS:These discrepancies highlight a notable gap in public awareness between dysphagia and more recognized conditions of insomnia and vertigo, even though the prevalence of dysphagia is higher than vertigo. Increasing public awareness of dysphagia is vital for early intervention, increasing quality of life, and advocating for equitable access to healthcare resources.

INTRODUCTION/BACKGROUND:Differentiated thyroid cancer is the most common endocrine malignancy and has an excellent 5-year survival rate after appropriate management. Current management guidelines state that thyroid lobectomy is adequate resection for papillary thyroid cancer (PTC) without preoperative evidence of high-risk features. However, the extent of surgery for PTC in the thyroid isthmus remains controversial, given the unclear lymphatic drainage and retrospective studies suggesting higher rates of lymphatic metastasis. The aim of this study was to examine the surgical management and outcomes of patients with isthmus PTC. METHODS:A retrospective review was performed at two high-volume centers of 138 patients who underwent thyroidectomy between 2013 and 2021 with isthmus PTC on final pathology. Preoperative tumor characteristics, surgical pathology, and postoperative outcomes were compared. RESULTS:There were 138 patients treated for isthmus PTC. Total thyroidectomy (TT) was most frequently performed (70.0 ​%), followed by lobectomy (TL, 17.1 ​%) and isthmusectomy (TI, 12.9 ​%). Among the 106 patients with Bethesda V/VI nodules, most underwent TT (75.5 ​%), followed by TL (13.2 ​%), and TI (11.3 ​%). Patients with Bethesda III/IV nodules most frequently had TI (44.4 ​%) or TL (44.4 ​%), then followed by TT (11.1 ​%). Patients who underwent TT more frequently had suspicious lymph nodes on preoperative imaging (n ​= ​30, n ​= ​1, n ​= ​0, p ​< ​0.001) and/or multiple nodules than TL and TI respectively (73.5 ​%, 70.8 ​%, 16.7 ​%, p ​< ​0.001). Of TT patients, 48 had central neck dissections (29 prophylactic and 19 therapeutic) and 20 had both therapeutic CND and lateral neck dissections. TT patients had larger median tumor size (1.5 ​cm; TL 1.1 ​cm; TI 1.0 ​cm; p ​= ​0.008). PTC variants were identified in 26.1 ​% of patients. Completion thyroidectomy was performed in 4 patients (TL, n ​= ​2; TI, n ​= ​2, p ​= ​0.41). Of 99 patients with lymph nodes sampled, 62 patients had metastatic lymph nodes (TT 58.2 ​%; TL, 16.7 ​%; TI: 11.1 ​%; p ​= ​0.02). At the last follow-up, 10 patients had persistent/recurrent disease (TT: 8, TI: 2, TL: 0). At one year, among patients who did not undergo TT, 10 patients required thyroid hormone replacement (TL: 56 ​%; TI: 10 ​%; p ​= ​0.018). CONCLUSION/CONCLUSIONS:Isthmus PTC may present with high-risk pathologic variants and positive nodes in 2 out of 3 patients. TI may be an appropriate management strategy in small, low-risk tumors, with similar reoperation rates as TL and lower rates of needing thyroid hormone replacement.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Neurosurgical clinical research depends on medical data collection and evaluation that is often laborious, time consuming, and inefficient. The goal of this work was to implement and evaluate a novel departmental data infrastructure (Neuro Data Hub) designed to provide specialized data services for neurosurgical research. Data acquisition would become available purely by request. METHODS:through collaboration between Department Leadership and Medical Center Information Technology, integrating it with Institutional Review Board workflows and an existing Epic electronic health record Datalake infrastructure. The system implementation included monthly departmental meetings and an asynchronous Research Electronic Data Capture-based request system. Data requests submitted between August 2023 and November 2024 were analyzed and categorized as basic, complex, or Natural Language Processing (NLP)-augmented, with optional visualization and database creation services. Request volumes, types, and execution times were assessed. RESULTS:The Hub processed 39 research data requests (2.6/month), comprising 3 basic, 22 complex, and 14 NLP-augmented requests. Two complex requests included visualization services, and one NLP request included database creation. Average request execution time was 36.5 days, with NLP-augmented requests showing increasing adoption over time. CONCLUSION/CONCLUSIONS:The Neuro Data Hub represents a paradigm shift from centralized to department-level data services, providing specialized support for neurosurgical research and democratizing access to institutional data. While effective, implementation may be limited by institutional information technology infrastructure requirements. This model could serve as a template for any form of medical-clinical research program seeking to improve data accessibility and research capabilities.

OBJECTIVE:To characterize patient outcomes after primary stereotactic radiosurgery (SRS) for the management of sporadic facial nerve schwannoma. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Six tertiary referral centers across the United States and United Kingdom. PATIENTS/METHODS:Adults undergoing SRS from 2000 through 2023 for sporadic facial nerve schwannoma along any segment of the facial nerve were included. Patients with NF2-related schwannomatosis were excluded. INTERVENTION/METHODS:Stereotactic radiosurgery. MAIN OUTCOME MEASURE/METHODS:Long-term tumor control. RESULTS:Among 60 patients meeting inclusion, the median age at SRS was 52 years (IQR: 41 to 64) with a median tumor size of 19.5 mm (IQR: 14.7 to 22.8). Tumors commonly involved the internal auditory canal (73%), cisternal (49%), geniculate/labyrinthine (47%), and tympanic segments (22%). Two patients experienced SRS failure and underwent salvage treatment; salvage-free survival rates (95% CI; number still at risk) at 1, 3, 5, and 10 years after SRS were 100% (100 to 100; 55), 100% (100 to 100; 36), 100% (100 to 100; 18), and 87% (72 to 100; 9), respectively. Among 31 (52%) patients with House-Brackmann (HB) grade I facial function at presentation, only 6 demonstrated worse facial function at a median of 3.2 years (IQR: 1.7 to 6.6) after SRS. Of 18 patients with serviceable hearing (AAO-HNS class A/B) at SRS, 13 maintained serviceable hearing at a median of 1.0 years (IQR: 0.5 to 4.9) of post-SRS audiometric follow-up. CONCLUSIONS:Durable tumor control after primary SRS for sporadic facial nerve schwannoma is achieved in most patients. Among those with HB grade I facial function at presentation, treatment with SRS harbors limited additional risk of facial paresis beyond observation alone.