Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Otolaryngology
Total Results:
7588
Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis
OBJECTIVE:To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). METHODS:Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses. RESULTS:An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. CONCLUSION/CONCLUSIONS:The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2023.
PMID: 37204106
ISSN: 1531-4995
CID: 5503642
Discharge Disposition After Head and Neck Reconstruction: Effect on Adjuvant Therapy and Outcomes
OBJECTIVES/OBJECTIVE:Head and neck cancer patients that require major reconstruction often have advanced-stage disease. Discharge disposition of patients can vary and impact time to adjuvant treatment. We sought to examine outcomes in patients discharged to skilled nursing facilities (SNF) compared to those discharged home, including the impact on adjuvant therapy initiation and treatment package time (TPT). METHODS:Patients with head and neck squamous cell carcinoma treated with surgical resection and microvascular free flap reconstruction from 2019 to 2022 were included. Retrospective review was conducted to evaluate the impact of disposition on time to radiation (RT) and TPT. RESULTS:230 patients were included, with 165 (71.7%) discharged to home and 65 (28.3%) discharged to SNF. 79.1% of patients were recommended adjuvant therapy. Average time to RT was 59 days for patients discharged to home compared to 70.1 days for patients discharged to SNF. Disposition was an independent risk factor for delays to starting RT (p = 0.03). TPT was 101.7 days for patients discharged to home versus 112.3 days for those who discharged to SNF. Patients discharged to SNF had higher rates of readmission (p < 0.005) compared to patients discharged home in an adjusted multivariate logistic regression. CONCLUSIONS:Patients discharged to an SNF had significantly delayed time to initiation of adjuvant treatment and higher rates of readmission. Timeliness to adjuvant treatment has recently been established as a quality measure, thus identifying delays to adjuvant treatment initiation should be a priority. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2023.
PMID: 36896866
ISSN: 1531-4995
CID: 5482492
Characterization of Vocal Fold Pathology in Military Drill Instructors
OBJECTIVE:Military drill instructors have extreme vocal demands that place them at risk for phonotrauma. Characterization of laryngeal pathology and vibratory characteristics among drill instructors presenting for specialized voice care is lacking. METHODS:A retrospective review in a specialized voice clinic over a two-year period was conducted. Patients identified as current drill instructors between the ages of 28-43 with a diagnosis of dysphonia were included. Laryngeal pathology was diagnosed by a fellowship trained laryngologist and vibratory characteristics were evaluated utilizing the Voice-Vibratory Assessment with Laryngeal Imaging (VALI) rating form. All patients were also evaluated by a speech-language pathologist. Patient reported outcome measures were collected along with perceptual voice evaluations utilizing the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). RESULTS:Twelve current drill instructors were identified, and all had phonotraumatic lesions. Lesions were categorized as vocal fold hemorrhage (8%), ectasia (25%), unilateral epithelial thickening (33.3%), bilateral epithelial thickening (58.3%), ventricular cyst (8%), polyp (25%), and sulcus vocalis (25%). Vibratory abnormalities were assessed with the VALI rating scale and correlated to CAPE-V perceptual ratings with 83% having reduced mucosal wave, 75% reduced amplitude of lateral excursion, 50% aperiodic vibrations, 50% asymmetric or chasing wave, 58% glottal insufficiency, 100% supraglottic hyperfunction, and an average CAPE-V overall severity of 50% with severe perceptual dysphonia. The average Voice Handicap Index (VHI-10) and Reflux Symptom Index (RSI) score was 15.5 and 14.7, respectively. CONCLUSION/CONCLUSIONS:Phonotraumatic lesions were universally present in drill instructors complaining of hoarseness, suggesting early referral, and intervention may be warranted in this population. LEVEL OF EVIDENCE/METHODS:4.
PMID: 34256981
ISSN: 1873-4588
CID: 4938452
A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism
OBJECTIVE:Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS:A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS:Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION/CONCLUSIONS:Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.
PMID: 37678470
ISSN: 1530-891x
CID: 5708602
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
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
