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Department/Unit:Otolaryngology

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Clinical Features Associated With Malignant Transformation of Low-Grade Dysplasia

Laronde, Denise M; Berkowitz, Matt; Kerr, A Ross; Hade, Erinn M; Siriruchatanon, Mutita; Rosin, Miriam P; Kang, Stella K
BACKGROUND:Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions. METHODS:We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use. RESULTS:Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression). CONCLUSION/CONCLUSIONS:Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.
PMID: 41054281
ISSN: 1600-0714
CID: 5951652

Smad2/3 Signaling Mediates the Atrophic Response in Vocal Fold Myoblasts In Vitro

Yoshimatsu, Masayoshi; Nakamura, Ryosuke; Bing, Renjie; Gartling, Gary J; Branski, Ryan C
BACKGROUND/OBJECTIVES/OBJECTIVE:Vocal fold (VF) muscle atrophy, often associated with neuromuscular disorders and aging, can lead to voice-related disability. Myostatin is well-known to mediate skeletal muscle atrophy via Smad2/3 signaling, whereas TGF-β1, a potent inducer of Smad2/3 signaling, is upregulated following VF injury. However, the impact of Smad2/3 signaling on laryngeal muscles remains unclear. This study provides foundational insight regarding Smad2/3-dependent atrophic responses of VF skeletal muscle cells, to ultimately develop novel therapeutic strategies for VF muscle atrophy. STUDY DESIGN/METHODS:In vitro. METHODS:Myoblasts isolated from the rat thyroarytenoid muscle were differentiated into myotubes in myogenic differentiation medium ±500 ng/mL myostatin or 10 ng/mL TGF-β1, in the presence or absence of an ALK4/5 inhibitor or siRNA targeting Smad2 and Smad3. Myotube formation and activation of Smad2/3 (nuclear localization of Smad2/3) were assessed via immunofluorescence. Transcription related to myotube differentiation and Smad2/3 signaling was quantified by qRT-PCR. RESULTS:Both myostatin and TGF-β1 suppressed myogenic differentiation, increased Smad2/3 nuclear intensity, downregulated Myh2, and upregulated downstream targets of Smad2/3 (Ccn2 and Serpine1) and Fbox32, an atrophy-related gene. These effects were more pronounced with TGF-β1 than with myostatin and were reversed by inhibition of ALK4/5. Furthermore, Smad2/3 knockdown via siRNA promoted myogenic differentiation, further supporting the role of Smad2/3 signaling in the atrophic response in VF myoblasts. CONCLUSIONS:Smad2/3 signaling mediates differentiation of VF myoblasts and TGF-β1, a potent mediator of fibrosis, elicited a more pronounced atrophic response than myostatin. Smad2/3 may be an attractive therapeutic target for VF muscle atrophy. LEVEL OF EVIDENCE/METHODS:NA.
PMID: 40735858
ISSN: 1531-4995
CID: 5903452

Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain

Peach, Chloe J.; Tu, Nguyen Huu; Lewis, Parker K.; Pollard, Rachel E.; Sokrat, Badr; Nicholson, Sam; Trevett, Kai; Barrett, Naomi; De Logu, Francesco; Zhu, Jiaqi; Latorre, Rocco; Teng, Shavonne; Therien, Michael J.; Jensen, Dane D.; Schmidt, Brian L.; Bunnett, Nigel W.; Pinkerton, Nathalie M.
ISI:001597018400001
ISSN: 0142-9612
CID: 5966152

How Changing Signaling Volume Impacts the Importance of Away Rotations in the Otolaryngology Match

Hatley, Maya G; Wang, Ronald S; Garcia Morales, Emmanuel; Yang, Wenqing; Santacatterina, Michele; Mihalic, Angela P; April, Max M
OBJECTIVE/UNASSIGNED:Signaling was introduced to the otolaryngology match in 2021, with 5 signals allotted to applicants in 2021, 4 in 2022, 7 in 2023, and 25 in 2024. This study investigated the modifying effect of signaling volume on the relationship between away rotations and matching in otolaryngology from 2018 to 2024. STUDY DESIGN/UNASSIGNED:Cross-sectional. SETTING/UNASSIGNED:National survey of US medical students. METHODS/UNASSIGNED:We used the Texas Seeking Transparency in Application to Residency (STAR) survey responses of otolaryngology applicants from 2018 to 2024. Using multivariate logistic regression, we determined the odds of matching where away rotations were performed and how these odds varied across the pre-volume (2018-2020), low-volume (2021-2023), and high-volume (2024) signaling eras. RESULTS/UNASSIGNED: < .001). CONCLUSION/UNASSIGNED:The introduction of signaling and the recent increase in signal number are associated with decreased likelihood of matching at a program where an away rotation was performed compared to the pre-signaling era. LEVEL OF EVIDENCE/UNASSIGNED:V.
PMCID:12780956
PMID: 41523886
ISSN: 2473-974x
CID: 5985932

Implementing the NYU Electronic Patient Visit Assessment (ePVA)© for head and neck cancer in rural and urban populations: a study protocol for a type 1 hybrid effectiveness-implementation clinical trial

Van Cleave, Janet H; Brody, Abraham A; Schulman-Green, Dena; Hu, Kenneth S; Li, Zujun; Johnson, Stephen B; Major, Vincent J; Lominska, Christopher E; Bauman, Jessica R; Hanania, Alexander N; Tatlonghari, Ghia V; Tsikis, Marcely; Egleston, Brian L
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.
PMCID:12690913
PMID: 41366462
ISSN: 1745-6215
CID: 5977322

Transmuscular vocal fold injury reduces frequency complexity of rat ultrasonic vocalizations

Gould, Marilla; Nakamura, Ryosuke; Yang, Wenqing; Branski, Ryan C; Johnson, Aaron M
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.
PMID: 41371504
ISSN: 1872-7549
CID: 5977482

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification

Sill, Martin; Schrimpf, Daniel; Patel, Areeba; Sturm, Dominik; Jäger, Natalie; Sievers, Philipp; Schweizer, Leonille; Banan, Rouzbeh; Reuss, David; Suwala, Abigail; Korshunov, Andrey; Stichel, Damian; Wefers, Annika K; Hau, Ann-Christin; Boldt, Henning; Harter, Patrick N; Abdullaev, Zied; Benhamida, Jamal; Teichmann, Daniel; Koch, Arend; Hench, Jürgen; Frank, Stephan; Hasselblatt, Martin; Mansouri, Sheila; Díaz de Ståhl, Theresita; Serrano, Jonathan; Ecker, Jonas; Selt, Florian; Taylor, Michael; Ramaswamy, Vijay; Cavalli, Florence; Berghoff, Anna S; Bison, Brigitte; Blattner-Johnson, Mirjam; Buchhalter, Ivo; Buslei, Rolf; Calaminus, Gabriele; Dikow, Nicola; Dohmen, Hildegard; Euskirchen, Philipp; Fleischhack, Gudrun; Gajjar, Amar; Gerber, Nicolas U; Gessi, Marco; Gielen, Gerrit H; Gnekow, Astrid; Gottardo, Nicholas G; Haberler, Christine; Hamelmann, Stefan; Hans, Volkmar; Hansford, Jordan R; Hartmann, Christian; Heppner, Frank L; Driever, Pablo Hernaiz; von Hoff, Katja; Thomale, Ulrich W; Tippelt, Stephan; Frühwald, Michael C; Kramm, Christof M; Schüller, Ulrich; Schittenhelm, Jens; Schuhmann, Martin U; Stein, Marco; Ketteler, Petra; Ladanyi, Marc; Jabado, Nada; Jones, Barbara C; Jones, Chris; Karajannis, Matthias A; Ketter, Ralf; Kohlhof, Patricia; Kordes, Uwe; Reinhardt, Annekathrin; Kölsche, Christian; Lamszus, Katrin; Lichter, Peter; Maas, Sybren L N; Mawrin, Christian; Milde, Till; Mittelbronn, Michel; Monoranu, Camelia-Maria; Mueller, Wolf; Mynarek, Martin; Northcott, Paul A; Pajtler, Kristian W; Paulus, Werner; Perry, Arie; Blümcke, Ingmar; Plate, Karl H; Platten, Michael; Preusser, Matthias; Pietsch, Torsten; Prinz, Marco; Reifenberger, Guido; Kristensen, Bjarne W; Kool, Marcel; Hovestadt, Volker; Ellison, David W; Jacques, Thomas S; Varlet, Pascale; Etminan, Nima; Acker, Till; Weller, Michael; White, Christine L; Witt, Olaf; Herold-Mende, Christel; Debus, Jürgen; Krieg, Sandro; Wick, Wolfgang; Snuderl, Matija; Aldape, Ken; Brandner, Sebastian; Hawkins, Cynthia; Horbinski, Craig; Thomas, Christian; Wesseling, Pieter; von Deimling, Andreas; Capper, David; Pfister, Stefan M; Jones, David T W; Sahm, Felix
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.
PMID: 41349541
ISSN: 1878-3686
CID: 5975372

How We Do It: Neuromodulators for Optimization of Blepharoplasty and Brow Lift Procedures

von Csiky-Sessoms, Stephanie; Husain, Solomon; Abraham, Manoj T; Marmur, Ellen
PMID: 40433963
ISSN: 1524-4725
CID: 5855342

An Observational Study of the Prevalence of Oral Human Papilloma Virus Infection in Laryngologists

Lackey, Taylor G; Gartling, Gary; Nakamura, Ryosuke; Maria, Chloe Santa; Johns, Michael; Branski, Ryan C; Amin, Milan R
OBJECTIVE:Surgical treatment of recurrent respiratory papillomatosis (RRP) has been shown to aerosolize human papillomavirus (HPV), putting healthcare workers at risk for exposure, infection, and disease. Knowledge of HPV infection risk among otolaryngologists who treat HPV-related diseases is limited. We sought to characterize the prevalence of oral HPV infection in otolaryngologists treating RRP. METHODS:This observational cohort study enrolled otolaryngologists at a national meeting. Participants completed a survey concerning HPV vaccination, disease history, and practice techniques for patients with RRP. An oral rinse was collected from participants; DNA was extracted and analyzed using commercially available kits. RESULTS:laser (N = 78), microdebrider (N = 80), and cold steel (N = 21). Oral rinses from three participants (2.2%) tested positive for HPV, including Subtypes 6 (N = 2) and 16 (N = 1). All three were male with no history of HPV vaccination. CONCLUSION/CONCLUSIONS:Otolaryngologists treating HPV-related diseases do not seem to be at a higher risk of HPV infection compared to the general adult population. Vaccination, the use of N95 masks, and minimizing aerosol-generating techniques are likely protective for healthcare workers dealing with HPV-related conditions.
PMID: 40735902
ISSN: 1531-4995
CID: 5903462

Neuro Data Hub: A New Approach for Streamlining Medical Clinical Research

Han, Xu; Alyakin, Anton; Ciprut, Shannon; Lapierre, Cathryn; Stryker, Jaden; Golfinos, John; Kondziolka, Douglas; Oermann, Eric Karl
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.
PMCID:12560744
PMID: 41163737
ISSN: 2834-4383
CID: 5961452