Faculty Bibliography

BACKGROUND:The diagnosis and treatment of tumors often depend on molecular-genetic data. However, rapid and iterative access to molecular data is not currently feasible during surgery, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins to guide resections. METHODS:Here, we introduce Ultra-Rapid droplet digital PCR (UR-ddPCR), a technology that achieves the fastest measurement, to date, of mutation burdens in tissue samples, from tissue to result in 15 min. Our workflow substantially reduces the time from tissue biopsy to molecular diagnosis and provides a highly accurate means of quantifying residual tumor infiltration at surgical margins. FINDINGS/RESULTS: = 0.995). CONCLUSIONS:The technology and workflow developed here enable intraoperative molecular-genetic assays with unprecedented speed and sensitivity. We anticipate that our method will facilitate novel point-of-care diagnostics and molecularly guided surgeries that improve clinical outcomes. FUNDING/BACKGROUND:This study was funded by the National Institutes of Health and NYU Grossman School of Medicine institutional funds. Reagents and instruments were provided in kind by Bio-Rad.

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

Inhibitory interneurons are highly heterogeneous circuit elements often characterized by cell biological properties, but how these factors relate to specific roles underlying complex behavior remains poorly understood. Using chronic silicon probe recordings, we demonstrate that distinct interneuron groups perform different inhibitory roles within HVC, a song production circuit in the zebra finch forebrain. To link these functional subtypes to molecular identity, we performed two-photon targeted electrophysiological recordings of HVC interneurons followed by post hoc immunohistochemistry of subtype-specific markers. We find that parvalbumin-expressing interneurons are highly modulated by sensory input and likely mediate auditory gating, whereas a more heterogeneous set of somatostatin-expressing interneurons can strongly regulate activity based on arousal. Using this strategy, we uncover important cell-type-specific network functions in the context of an ethologically relevant motor skill.

Current models of eye movement control propose that motor neurons responsible for moving the eyes contribute to all eye movements, regardless of context. A recent study in larval zebrafish has instead identified specialized neural circuits, including subtypes of motor neurons, for two different types of fast eye movement, one for exploration and the other for hunting.

OBJECTIVES/OBJECTIVE:Recent studies suggest that hearing loss is associated with balance dysfunction and an increased risk of falls. The purpose of this study was to investigate whether adults with unilateral hearing loss (UHL) have an underlying vestibular dysfunction and whether vestibular testing explains balance function and fall risk. STUDY DESIGN/METHODS:Cross-sectional. SETTING/METHODS:Urban otology practice and a human motion laboratory. PATIENTS/METHODS:We recruited 41 healthy controls (mean age, 52 years; range, 22-78 years) and 29 adults with stable UHL (mean age, 53 years; range, 18-80 years) who denied symptoms of dizziness (Dizziness Handicap Inventory average, 1.86; range, 0-14). UHL occurred an average of 4 years (range from sudden loss, 4 months to 27.5 years) prior to testing. INTERVENTIONS/METHODS:We conducted the caloric portion of the videonystagmography test, video head impulse test (vHIT), and a battery of balance tests: standing on foam with eyes closed, timed up and go test, four square step test, 10-meter walk, and a virtual reality (VR) assessment of postural control. MAIN OUTCOME MEASURES/METHODS:Hearing was quantified by four-frequency pure-tone average (PTA). Caloric weakness was defined as asymmetry greater than 25%. Participants self-reported falls over the past 12 months and history of vertigo. Performance on balance tests was quantified by time to completion or duration of hold. Performance on the VR assessment was quantified by root-mean-square velocity of head sway. RESULTS:Proportion of unilateral caloric weakness was significantly higher in the UHL group (25%) than the control group (12%). Five participants with UHL refused caloric testing. vHIT gains of lateral canals were normal in both groups. The majority of participants in the UHL group experienced vertigo at the onset of hearing loss (72%). There were five fallers in the UHL group (17%) and three in the control group (7%). Participants with caloric weakness or vertigo at onset did not differ from those without in age or in any of the balance tests. Participants with history of falls differed in head sway and duration of hold standing on foam with eyes closed. CONCLUSIONS:Individuals with UHL are more likely to have caloric weakness than healthy controls; however, these findings are not correlated with functional outcomes or history of falls. Postural control testing using virtual reality or standing on foam with eyes closed may help detect those at a risk for falls.

OBJECTIVE:To investigate the effect of heated-cigarette smoking on voice. METHODS:Participants completed a survey including three sections: section-1 comprised demographic data, section-2 comprised visual analogue scale grading of voice changes and fatigue and section-3 consisted of the voice handicap index-10. RESULTS:< 0.05). CONCLUSION/CONCLUSIONS:Smokers of heated cigarettes have a significantly higher mean voice handicap index-10 score compared to non-smokers and higher grade of voice changes and fatigue.

The endoscopic transsphenoidal approach (ETSA) is a commonly used technique that allows for the minimally invasive removal of sellar and parasellar lesions. Augmented reality (AR) applications in ETSA are hypothesized to enhance intraoperative visualization by integrating a 3D-reconstructed model into the operative field. This study describes the workflow and surgical outcomes associated with the Endoscopic Surgical Navigation Advanced Platform (EndoSNAP, Surgical Theater, Cleveland, OH, USA), an AR platform designed for surgical planning and intraoperative navigation in ETSA for sellar and parasellar lesions. We analyzed a cohort of patients who underwent ETSA tumor resection using EndoSNAP. Preoperative MRI and CT scans were reconstructed and merged into a single 360° AR model using the Surgical Rehearsal Platform software. The model was then imported into EndoSNAP, which was integrated with the endoscope and neuronavigation system for real-time intraoperative use. Patient demographics, tumor characteristics, extent of resection (EOR), and endocrinologic and neurologic outcomes were recorded. Eighteen adult patients with newly diagnosed (83%) and recurrent (17%) tumors were included. Pathologies consisted of pituitary adenoma (72%), craniopharyngioma (11%), meningioma (11%), and chordoma (6%). Optic compression was present in 56% of patients, with preoperative visual deficits in 70% of them. Cavernous sinus invasion was observed in 17% of tumors. Preoperative hormonal excess and insufficiency were noted in 56% and 28% of cases, respectively. The mean preoperative tumor volume was 21.4 ± 17 cm³, which decreased to 0.4 ± 0.3 cm³ postoperatively. The mean EOR was 93.6 ± 3.6%. Postoperative complications included CSF leaks requiring surgical repair (17%), seizures related to pre-existing hemispheric trauma (6%), pulmonary embolism (6%), deep venous thrombosis (6%), and sinusitis (6%). These findings suggest that AR-enhanced visualization through EndoSNAP is a feasible and potentially beneficial adjunct in ETSA for sellar and parasellar tumor resection.

The adoption of large language models (LLMs) in healthcare demands a careful analysis of their potential to spread false medical knowledge. Because LLMs ingest massive volumes of data from the open Internet during training, they are potentially exposed to unverified medical knowledge that may include deliberately planted misinformation. Here, we perform a threat assessment that simulates a data-poisoning attack against The Pile, a popular dataset used for LLM development. We find that replacement of just 0.001% of training tokens with medical misinformation results in harmful models more likely to propagate medical errors. Furthermore, we discover that corrupted models match the performance of their corruption-free counterparts on open-source benchmarks routinely used to evaluate medical LLMs. Using biomedical knowledge graphs to screen medical LLM outputs, we propose a harm mitigation strategy that captures 91.9% of harmful content (F1 = 85.7%). Our algorithm provides a unique method to validate stochastically generated LLM outputs against hard-coded relationships in knowledge graphs. In view of current calls for improved data provenance and transparent LLM development, we hope to raise awareness of emergent risks from LLMs trained indiscriminately on web-scraped data, particularly in healthcare where misinformation can potentially compromise patient safety.

INTRODUCTION/BACKGROUND:Tracheostomy is a commonly performed procedure in Otolaryngology and can be performed in different settings. We evaluate patient characteristics and cost efficacy of tracheostomy at the bedside versus operating room (OR). MATERIALS AND METHODS/METHODS:Retrospective chart review was performed for adult intensive care unit (ICU) patients who underwent tracheostomy from 2020 to 2023. Data and cost of procedures were analyzed using descriptive statistics. RESULTS:One hundred and sixty-five patients were included. One hundred and thirty-four (81.2%) patients underwent bedside tracheostomy. Age, sex, and BMI were not significantly different. Average time from consult to procedure and operative time was significantly shorter (p = 0.03; 0.008). There were no differences in postoperative complications, 30-day mortality, ICU length of stay (LOS), or overall LOS. Tracheostomy at the bedside offered a 73.1% cost reduction compared with performed in the OR. CONCLUSION/CONCLUSIONS:Advantages of bedside tracheostomy include decreased operative time, time from consult to procedure, and cost reduction for the hospital system. We advocate for consideration of bedside tracheostomy when appropriate.