Faculty Bibliography

BACKGROUND:Guidelines do not recommend routine screening for thyroid nodules when starting a glucagon-like peptide-1 receptor agonist. Patients, however, increasingly present with incidental nodules from imaging ordered at glucagon-like peptide-1 receptor agonist initiation. METHODS:This retrospective case-control study examined patients in a single academic health system from 1 January 2019 to 31 December, 2024 who underwent thyroid ultrasound, fine-needle aspiration biopsy, molecular testing, and/or surgery with glucagon-like peptide-1 receptor agonist initiation compared with patients not prescribed a glucagon-like peptide-1 receptor agonist. Patient, prescription, and intervention data were collected. Chart review was also performed for a subset of patients. RESULTS:From 2019 to 2024, 2,523 patients prescribed a glucagon-like peptide-1 receptor agonist underwent thyroid ultrasound; from 2020 to 2023, there was a higher growth rate of ultrasound scans ordered for them. A random sample of 415 patients prescribed a glucagon-like peptide-1 receptor agonist showed that most ultrasounds were ordered for "thyroid nodules" by the endocrinologist who prescribed glucagon-like peptide-1 receptor agonist. In this subset, 757 nodules were detected on ultrasound; 10.6% (80/757) had fine-needle aspiration biopsy. Cytology showed 3.8% were Bethesda I (3/80), 72.5% Bethesda II (58/80), 15% Bethesda III (12/80), 0% Bethesda IV (0/80), 2.5% Bethesda V (2/80), and 6.6% Bethesda VI (5/80). Of 15 indeterminate nodules, 11 had molecular testing: 5 were positive or suspicious, including fusions, alterations, RAS and BRAF mutations. Sixteen patients had thyroid surgery after glucagon-like peptide-1 receptor agonist initiation (8 total thyroidectomies, 8 hemithyroidectomies, 1 completion). Final pathology demonstrated 6 benign, 10 malignant, 1 NIFTP. The rate of malignancy in the subset was 2.4% (10/415). CONCLUSION/CONCLUSIONS:The malignancy rate in patients prescribed a glucagon-like peptide-1 receptor agonist remains low, but ultrasound screening rates increased for a period. Strong clinical suspicion should govern screening.

BACKGROUND:for HNC as a digital patient-reported symptom monitoring system that enables early symptom detection and real-time interventions at the point of care. With this study protocol, we aim to test the effectiveness of the ePVA in improving HNC outcomes in real-world settings and to identify implementation strategies optimizing its effectiveness. METHODS:We will conduct a longitudinal mixed-methods hybrid type I study at four National Cancer Institute-designated Comprehensive Cancer Centers serving diverse populations in rural and urban settings (New York University, the University of Kansas Cancer Center, Fox Chase Cancer Center, and Baylor College of Medicine) guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Patient eligibility criteria include having histologically diagnosed HNC and undergoing radiation therapy with or without chemotherapy for curative intent. We will also interview clinicians caring for patients with HNC at the participating institutions regarding facilitators and barriers to implementing the ePVA. The accrual goal is 270 patients. Aim 1 is to determine the effect of the ePVA on HNC symptoms in a two-arm (usual care vs. ePVA + usual care) trial. The study's primary outcomes are patients' self-reported social function, senses of taste and smell, and swallowing, measured by the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35. For Aim 2, we will interview patients (n = 40) as well as clinicians (n = 30) caring for patients with HNC at the participating institutions regarding facilitators and barriers to implementing the ePVA. In Aim 3, we will integrate Aims 1 and 2 data to identify strategies that optimize the use of the ePVA. DISCUSSION/CONCLUSIONS:The overarching goal of this research is to advance cancer care by identifying implementation standards for effective, widespread use of the ePVA that apply to all patient-reported outcomes in cancer care. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT06030011. Registered on 8 September 2023.

Rapid and precise activation of the laryngeal musculature, particularly the thyroarytenoid (TA), is required for the production of rat ultrasonic vocalizations (USVs). Although the role of the TA in USV production has been established through denervation and excised larynx studies, how TA muscle dysfunction affects USV acoustics remains unknown. This study examined how iatrogenic, transmuscular vocal fold injury influences USV production by comparing acoustic parameters between rats receiving bilateral transmuscular vocal fold injury (including the TA muscle) versus sham surgery. Twenty adult male rats were randomly assigned to injury or sham groups and assessed at 30 or 60 days post-surgery. USVs were recorded at each timepoint (pre- and post-surgery) and analyzed for changes in principal frequency, frequency complexity (standard deviation and sinuosity), power (intensity of the USV), tonality, and duration. Injury significantly decreased USV frequency complexity and reduced the likelihood of producing frequency-modulated vocalizations in both post-surgical time groups. These findings demonstrate that while TA muscle integrity is crucial for frequency modulation, it is not necessary for basic USV production, offering new insights into the biomechanical role of the TA muscle in rat vocalization and laying the groundwork for investigating therapeutic interventions targeting laryngeal muscle function.

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.