Faculty Bibliography
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school:SOM
Department/Unit:Otolaryngology
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7611
A Novel Method for Thyroarytenoid Myofiber Culture
OBJECTIVES/HYPOTHESIS/OBJECTIVE:Myofiber culture has been employed to investigate muscle physiology in vitro and is well-established in the rodent hind limb. Thyroarytenoid (TA) myofiber culture has not been described, providing an opportunity to employ this method to investigate distinct TA myofiber functions. The purpose of this study was to assess the feasibility of a TA myofiber culture model. STUDY DESIGN/METHODS:In vitro. METHODS:for 2 h. Myofiber specificity was determined via immunolabeling for desmin and myosin heavy chain (MHC). Myofibers viability was assessed over 7 days via esterase assay. Additional myofibers were immunolabeled for satellite cell marker Pax-7. Glucocorticoid (GC) receptor (GR) was immunolabeled following GC treatment. RESULTS:The harvest technique yielded ~120 myofibers per larynx. By day 7, ~60% of the fibers remained attached and were calcein AM-positive/ethidium homodimer-negative, indicating viability. Myofibers were positive for desmin and MHC, indicating muscle specificity. Cells surrounding myofibers were positive for Pax-7, indicating the presence of myogenic satellite cells. Myofibers also responded to GC treatment as determined by GR nuclear translocation. CONCLUSION/CONCLUSIONS:TA myofibers remained viable in culture for at least 7 days with a predictable response to exogenous stimuli. This technique provides novel investigative opportunities regarding TA structure and function. LEVEL OF EVIDENCE/METHODS:N/A Laryngoscope, 2023.
PMID: 37227163
ISSN: 1531-4995
CID: 5543832
Oral surgery, oral medicine, oral pathology & oral radiology. 2023:136(5):584-594.DOI: 10.1016/j.oooo.2023.06.013
World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey
OBJECTIVES:To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS:Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS:Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION:The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.
PMID: 37574377
ISSN: 2212-4411
CID: 5635022
Radiographic Magnification on Videofluoroscopy: An Important Variable to Consider for Scaled Analyses of Swallowing
PURPOSE/OBJECTIVE:Traditionally, kinematic measures on videofluoroscopy require the use of an external scalar (such as a penny) to transform pixels to absolute distances. Videofluoroscopy is subject to image magnification based on the distance of the feature of interest to the X-ray source. However, the impact of the position/location of the external scalar on swallowing measures is unknown. Our goal was to systematically investigate the accuracy of various common external scalar locations in lateral and anterior-posterior (A-P) view. METHOD/METHODS:U.S. pennies were taped to a styrofoam head in three positions (on the left and right lateral neck and in midline submentally). Locations were measured to ensure equal left and right, as well as midline, placement. A metal screwdriver (6 mm in diameter) was inserted into the premanufactured hole that is centrally located at the bottom of the styrofoam head. The head was centered on a medical tray and placed in the middle of a Siemens Alpha C-arm Fluoroscope field. ImageJ was used to measure penny length in pixels (three locations) in both lateral and A-P views. Penny length was known (19.05 mm), and, therefore, used to derive screwdriver size (for each location) for comparison to the actual screwdriver size. RESULTS:All scalars overestimated the screwdriver size ranging from 6.55 to 7.87 mm, representing a 9%-31% inflation. Scalars closer to the X-ray source had the largest magnification. CONCLUSIONS:Our results confirm that image magnification of external scalars is a significant source of variability that is currently unaccounted for in the swallowing literature. Recommendations for future research design/measurement methods are provided.
PMID: 37889234
ISSN: 1558-9102
CID: 5607422
Molecular Profiling of 50,734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management
CONTEXT/BACKGROUND:Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine-needle aspiration (FNA) samples has not been reported. OBJECTIVE:To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. DESIGN/METHODS:Retrospective analysis of FNA samples tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier. SETTING/METHODS:UPMC MGP laboratory. PARTICIPANTS/METHODS:A total of 50,734 BCIII-VI nodules from 48,225 patients. INTERVENTION/METHODS:None. MAIN OUTCOME MEASURES/METHODS:Prevalence of diagnostic, prognostic, and targetable genetic alterations. RESULTS:Among 50,734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alteration. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.2% of cases. CONCLUSIONS:In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutationsand targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.
PMID: 37071871
ISSN: 1945-7197
CID: 5466102
Virtual Tumor Boards for Remote Learning in Head and Neck Surgical Oncology
IMPORTANCE/UNASSIGNED:In addition to their patient management value, multidisciplinary tumor boards have been recognized as effective learning tools. However, the value of using a virtual tumor board as a learning tool for head and neck surgical oncology fellows has not been studied. OBJECTIVE/UNASSIGNED:To describe the structure and content of the American Head and Neck Society (AHNS) Virtual Tumor Board and assess its educational value as perceived by attendees. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:All sessions of the AHNS Virtual Tumor Board from April 8, 2020, to June 1, 2022, were reviewed. Topics, presenters, participants, and viewership data were collected as of October 15, 2022, from session recordings posted to an online video sharing and social media platform. Additionally, an anonymous, 14-question online survey was designed to elicit feedback from head and neck surgery trainees on virtual tumor board engagement, strengths, and weaknesses. The survey was electronically distributed in June and July 2022 to the 101 fellows enrolled in AHNS-accredited programs between July 1, 2020, and June 30, 2022. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary aim was to tabulate online viewership of the sessions. The secondary aim was to qualitatively assess the experience of head and neck trainees with the AHNS Virtual Tumor Board using a survey. RESULTS/UNASSIGNED:Forty-two sessions of the virtual tumor board were held between April 8, 2020, and June 1, 2022. Almost all sessions (41 [98%]) were case based. One hundred and sixteen cases were presented, representing 2 to 3 cases per session, by 75 unique faculty members. Each session was viewed a mean of 217 times (range, 64-2216 views). In the 2021 to 2022 academic year, a mean of 60 viewers (range, 30-92 viewers) attended each live session. In all, 29 survey responses were collected from 101 fellows in AHNS-accredited programs (29% response rate). Most respondents felt the format allowed for excellent teaching (18 of 26 respondents [69%]) and discussion (19 of 26 respondents [73%]). Most respondents (22 of 29 respondents [76%]) believed that practicing head and neck surgeons would benefit from the sessions. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This survey study found that the AHNS Virtual Tumor Board was well-attended and well-reviewed by head and neck surgical oncology trainees. The virtual tumor board format could be used as model of remote learning for other organizations.
PMCID:10450583
PMID: 37615974
ISSN: 2168-619x
CID: 5599382
The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019
IMPORTANCE/UNASSIGNED:Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. OBJECTIVE/UNASSIGNED:To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. EVIDENCE REVIEW/UNASSIGNED:The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. FINDINGS/UNASSIGNED:In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
PMCID:10485745
PMID: 37676656
ISSN: 2374-2445
CID: 5611702
Private Payer-Negotiated Rates for FDA-Approved Head and Neck Cancer Immunotherapy and Chemotherapy Agents
OBJECTIVE:To quantify the price that private payers pay hospitals for head and neck squamous cell carcinoma (HNSCC) treatments and identify hospital-level factors associated with price variation. STUDY DESIGN:Cross-sectional study. SETTING:Price transparency files. METHODS:Files from the top 50 hospitals in otolaryngology according to the US News and World Report were analyzed between December 2021 and June 2022. This study analyzed the following Food and Drug Administration-approved HNSCC therapies: pembrolizumab, nivolumab, cetuximab, cisplatin, carboplatin, and paclitaxel. RESULTS:Twenty-four (48%) hospitals reported prices for at least 1 medication in our sample. Newer biologics were significantly more expensive than traditional chemotherapeutic agents. Given approved medication regimens, all biologics in our sample have similar annual costs. Price markups over acquisition costs ranged between 109% (pembrolizumab, nivolumab) and 530% for carboplatin. Across hospitals, prices varied the most for paclitaxel, the cheapest medication in our sample, and prices varied the least for pembrolizumab the most expensive medication in our sample. Hospital 340B status and geographic location in the northeast/west are associated with lower price markups. CONCLUSION:Price nondisclosure remains a significant problem among hospitals. Newer biological medications are more expensive when compared to traditional chemotherapeutic agents. Prices vary significantly across hospitals, with lower price markups observed in 340B hospitals as well as hospitals located in the geographic northeast and west. It remains to be seen if price transparency will lead to more uniform pricing or lower costs of treatments.
PMID: 36856039
ISSN: 1097-6817
CID: 5707882
Paralysis Versus Non-Paralysis Anesthesia for Operative Laryngoscopy: A Randomized Controlled Trial
OBJECTIVE:To compare outcomes between two standard-of-care anesthesia regimens for operative laryngoscopy: general anesthesia with a neuromuscular blocking agent (NMBA) versus remifentanil and propofol (non-NMBA). METHODS:This was a prospective, single-blinded, randomized controlled trial at a tertiary care center. Patients were randomized to either anesthesia using rocuronium (NMBA) or with remifentanil/propofol infusion alone (non-NMBA). Intraoperative impressions, anesthesia data, and post-operative patient surveys were collected. RESULTS:Sixty-one patients who underwent suspension laryngoscopy from 2020 to 2022 were included (25 female, 36 male, ranging 20-81 years). Thirty patients were enrolled in the NMBA arm and 31 patients in the non-NMBA arm. Heart rate and mean arterial pressure were higher in the NMBA (p < 0.01). Patients in the non-NMBA group were more likely to require vasopressors (p = 0.04, RR = 3.08 [0.86-11.05]). Surgeons were more frequently satisfied with conditions in the NMBA group (86.7%) compared to the non-NMBA group (58.1%, p < 0.01). Procedures were more likely to be paused due to movement in the non-NMBA group (45.1%) compared to the NMBA group (16.6%, p < 0.03, RR = 2.26 [1.02-4.99]). Patients in the non-NMBA group were more likely to endorse myalgia the week after surgery (44%) compared to the NMBA group (8.3%, p < 0.01) and reported higher average pain levels on a 0-10 pain scale (3.7) compared to the paralysis group (2.0). CONCLUSIONS:Anesthesia with rocuronium was associated with better intraoperative conditions and postoperative pain compared to anesthesia with remifentanil/propofol. Remifentanil/propofol were associated with lower blood pressure and suppression of laryngoscopy-associated tachycardia. LEVEL OF EVIDENCE/METHODS:Level 2 Laryngoscope, 2023.
PMID: 36715102
ISSN: 1531-4995
CID: 5419902
Dose-Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages
OBJECTIVE:Variable outcomes of glucocorticoid (GC) therapy for laryngeal disease are putatively due to diverse interactions of the GC receptor (GR) with cell signaling pathways, limited consideration regarding concentration-dependent effects, and inconsistent selection of GCs. In the current study, we evaluated the concentration-dependent effects of three frequently administered GCs on transcription factors with an emphasis on the phosphorylation of GR at Ser203 and Ser211 regulating the nuclear translocation of GR. This study provides foundational data regarding the diverse functions of GCs to optimize therapeutic approaches. STUDY DESIGN:In vitro. METHODS:Human vocal fold fibroblasts and THP1-derived macrophages were treated with different concentrations of dexamethasone, methylprednisolone, and triamcinolone in combination with IFN-γ, TNF-α, or IL4. Phosphorylated STAT1, NF-κB family molecules, and phosphorylated STAT6 were analyzed by Western blotting. Ser211-phosphorylated GR (S211-pGR) levels relative to GAPDH and Ser203-phosphorylated GR (S203-pGR) were also analyzed. RESULTS:GCs differentially altered phosphorylated STAT1 and NF-κB family molecules in different cell types under IFN-γ and TNF-α stimuli. GCs did not alter phosphorylated STAT6 in IL4-treated macrophages. The three GCs were nearly equivalent. A lower concentration of dexamethasone increased S211-pGR/GAPDH ratios relative to increased S211-pGR/S203-pGR ratios regardless of cell type and treatment. CONCLUSION:The three GCs employed in two cell lines had nearly equivalent effects on transcription factor regulation. Relatively high levels of Ser203-phosphorylation at low GC concentrations may be related to concentration-dependent differential effects of GCs in the two cell lines. LEVEL OF EVIDENCE:NA Laryngoscope, 133:2704-2711, 2023.
PMCID:10406972
PMID: 36752581
ISSN: 1531-4995
CID: 5735082
General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement
PMCID:10611977
PMID: 37642289
ISSN: 1557-9077
CID: 5609202
