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Objectives: Many summer research programs (SRPs) for URiM students exist; however, only a few have been established by otolaryngology programs, who have a unique opportunity to provide a diverse experience. We sought to assess URiM undergraduate student perspectives on the most valuable program features that influence decision‐making and how this might be useful to otolaryngology programs seeking to establish pathway programs. Materials and Methods: An externally facing REDCap survey composed of 37 questions in scaled, multiple‐choice, and open‐ended form. The survey was delivered to applicants via email over two time periods in April 2021 and February 2022. All survey responses were analyzed using descriptive statistics and categorized according to demographic information, program features, and advertising mechanisms. Results: Seventy‐one percent of our applicants self‐identified as URiM. Over 60% experienced financial hardship, and 31% experienced educational hardship. The single most important feature when selecting a summer research program (SRP) was access to mentorship followed by clinical shadowing and research opportunities. When program features were aggregated into groups, institutional features were the most important, followed closely by funding features. Finally, students prefer to learn about SRPs through their university, followed by social media, despite many students learning about our program through other means. Conclusions: Paid programs with effective advertising, research, mentoring, and clinical shadowing are highly valued by URiM undergraduate students. Understanding student perspectives is critical for programs aiming to address the "leaky pipeline" while being deliberate in their support of underrepresented students. Level of Evidence: 5 Laryngoscope, 134:637–644, 2024 [ABSTRACT FROM AUTHOR]

Objective: Failure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC. Methods: Retrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care. Results: Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis. Conclusions: Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC. Level of Evidence: 4 Laryngoscope, 133:1394–1401, 2023 [ABSTRACT FROM AUTHOR]

Objectives: To identify the differences in sensitivity and accuracy between ultrasound-guided and palpation-guided fine needle aspirations (FNA) of suspicious lymph nodes in patients with human papillomavirus (HPV) (+) oropharyngeal squamous cell carcinoma (OPSCC). Additional objectives included identifying patient specific factors affecting biopsy accuracy and evaluating potential differences in accuracy between fine and core needle biopsies. Study Design: Retrospective chart review. Materials and Methods: A retrospective study of diagnostic sensitivity was completed at a single tertiary care center between 1/1/2006–12/31/2016. Participants included patients who underwent pretreatment FNA biopsy with HPV(+)OPSCC confirmed pathologically following neck dissection or excisional lymph node biopsy. A true positive (TP) on FNA biopsy was defined as an FNA biopsy concerning for squamous cell carcinoma (SCC) that was confirmed on excisional biopsy or neck dissection. A false negative (FN) was defined as a negative FNA but metastatic disease identified on excisional biopsy or neck dissection. Sensitivity was calculated as TPs/(TPs + FNs). Sensitivity was compared among techniques using chi-square and Fisher exact tests. Results: A total of 209 FNA biopsies among 198 patients were included in the study, including 31 (15%) palpationguided FNAs, 160 (77%) ultrasound-guided FNAs, and 18 (9%) ultrasound-guided FNA + core biopsies. Sensitivity was significantly different among palpation-guided FNA, ultrasound-guided FNA, and ultrasound-guided FNA + core biopsies (48% vs. 83% vs. 94%, respectively; P < .001) but there was no significant difference in sensitivity between ultrasound-guided FNA versus ultrasound-guided FNA + core biopsies (P = .31). Conclusion: The use of ultrasound guidance in FNA biopsies of nodal metastases in HPV(+)OPSCC improves sensitivity compared to palpation guidance alone. Ultrasound guided biopsies are preferred in patients with suspected nodal metastasis from HPV(+)OPSCC. [ABSTRACT FROM AUTHOR]

Objective: To describe and compare rates of metachronous and synchronous second primaries of the contralateral tonsil in patients with primary HPV(+) tonsillar squamous cell carcinoma (SCC). Study Design: Retrospective cohort study. Materials and Methods: This is a single tertiary care center retrospective case series, from 2006 to 2019, of HPV(+) tonsillar SCC patients who underwent primary surgical resection with unilateral wide‐field tonsillectomy or bilateral tonsillectomy for diagnostic or therapeutic purposes. A metachronous second primary is one diagnosed >6 months after completion of surgical treatment. A synchronous second primary is one diagnosed during bilateral tonsillectomy for unilateral HPV(+) tonsillar SCC. Rates of second primary and patient characteristics were compared using chi‐square tests. Results: About 303 patients underwent unilateral surgical resection +/− adjuvant therapy for HPV(+) tonsillar SCC. One (0.3%) developed a metachronous second primary in the contralateral tonsil 11.9 years following treatment. Fifty‐seven patients with HPV(+) tonsillar SCC underwent bilateral tonsillectomy, and 37/57 (65%) had no clinical signs for contralateral disease. Of these, only 1/37 (2.7%) was incidentally found to have a synchronous second primary. Twenty patients underwent bilateral tonsillectomy due to clinical concern for contralateral disease. Of these, 3/20 (15%) were found to have a synchronous HPV(+) SCC in the contralateral tonsil. Conclusions: The prevalence of metachronous second primary after appropriate treatment of HPV(+) tonsillar SCC is very low (0.3%) and so is the chance of incidentally discovering a synchronous second primary during bilateral tonsillectomy (2.7%). We do not recommend bilateral tonsillectomy as a part of the routine algorithm in the surgical management of these patients. Level of Evidence: 3 Laryngoscope, 132:332–338, 2022 [ABSTRACT FROM AUTHOR]

Objectives: The spine is the most common site of bone metastases in differentiated thyroid cancer (DTC). The role of surgery in the management of cervical spine (C‐spine) metastases (CSpM) has not been adequately explored. Methods: This is a retrospective cohort study at a tertiary referral center from 2002 to 2018. Inclusion criteria were pathologic diagnosis of DTC and imaging/pathologic diagnosis of CSpM. Statistical analysis utilized t tests for continuous variables and χ2 tests for categorical variables. Survival analysis was conducted using Kaplan–Meier curves with univariate and multivariate Cox regressions. Results: Fifty patients with DTC and CSpM were identified. Of those, 16 underwent surgical resection of the C‐spine, whereas 34 did not. The most common presenting symptom was neck pain (N = 37, 74%). Patients in the surgery group were more likely to report a subjective improvement of symptoms (P <.01) and to have local (P <.01) and systemic (P =.04) disease control. Five‐year overall survival was 44.7% for the surgery group (95% confidence interval [CI]: 17.1–69.3) and 11.1% (95% CI: 2.1–28.8) for the nonsurgery group (P =.01). The strongest risk factor for improved overall survival after C‐spine metastasis was local disease control at the C‐spine (multivariate hazard ratio [HR] = 0.32, 95% CI: 0.12–0.85, P =.02). Surgical intervention was significantly associated with improved survival on both univariate (HR = 0. 35, 95% CI: 0.15–0.82, P =.02) and multivariate (HR = 0.37, 95% CI: 0.14–0.98, P =.04) analysis. Conclusion: Surgical management of CSpM in differentiated thyroid cancers is associated with significantly improved local disease control and overall survival. Referral to spine surgeons should be considered after diagnosis. Level of Evidence: IV. Laryngoscope, 131:E1741–E1747, 2021 [ABSTRACT FROM AUTHOR]

Objective: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte‐derived M1 and M2 macrophages on normal airway and LTS‐derived fibroblasts (FBs) in vitro. Study Design: Comparative analysis; in vitro controlled study. Methods: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M‐CSF + Interferon‐gamma and lipopolysaccharide or Interleukin‐4, respectively. FBs isolated from laryngotracheal scar (LTS‐FBs) and normal tracheal airway (NA‐FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. Results: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P =.03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P =.001). In vitro, NA‐FBs cultured with M2 macrophages demonstrated a 2.41‐fold increase in collagen‐1 expression (P =.05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024–2.192, n = 8, P =.015). Conclusion: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. Level of Evidence: NA Laryngoscope, 131:E346–E353, 2021 [ABSTRACT FROM AUTHOR]

Objectives: Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy.Study Design: In vitro comparative study of human cells.Methods: Levels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre- and post-operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile.Results: Pulmonary function and voice and breathing outcome metrics demonstrated significant post-operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL-6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval.Conclusion: Pro-inflammatory and pro-fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers.Level Of Evidence: 4 Laryngoscope, 131:342-349, 2021. [ABSTRACT FROM AUTHOR]

Objectives: Determine the effect of endoscopic skull base surgery (ESBS) on long-term olfactory outcomes after surgery.Methods: An English-language search was conducted using the Cochrane, MEDLINE, Scopus, and Embase databases from January 2000 to October 2017 for adult patients undergoing ESBS with subjective and objective olfaction outcomes. Two authors independently examined articles to identify those meeting inclusion criteria. Studies examining objective olfactory outcomes after ESBS were included in the meta-analysis. A random-effects meta-analysis of patients undergoing sellar and parasellar ESBS was conducted to compare preoperative and postoperative olfactory outcomes using the University of Pennsylvania Smell Identification Test (UPSIT) and Cross-Cultural Smell Identification Test (CCSIT).Results: Among 339 eligible articles, 29 articles met inclusion criteria. Twenty-five of these focused on sellar and parasellar tumors. Individual articles not meeting criteria for meta-analysis were qualitatively reported. Meta-analysis showed there was no difference in preoperative and postoperative olfactory function after sellar and parasellar ESBS based on the UPSIT (five studies, mean difference [MD] = -1.03; 95% CI: -3.98, 1.93; P = .50) and the CCIST (three studies, MD = -0.77; 95% CI: -3.03, 1.49; P = .50). A pooled overall meta-analysis revealed similar results (eight studies, effect size = -0.30; 95% CI: -0.79, 0.18; P = .22). However, heterogeneity for all meta-analyses was high (I2 > 95%, P < .01), suggesting significant variation in the included studies.Conclusions: Based on published objective olfaction outcomes after sellar and parasellar ESBS, there was no significant difference between preoperative and postoperative olfaction. Further prospective studies using validated objective measures of olfaction are required to improve our understanding on this subject.Level Of Evidence: 2a Laryngoscope, 129:1998-2007, 2019. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV-positive and HPV-negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification STUDY DESIGN: Retrospective case series.Methods: A retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California-San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan-Meier and unadjusted and adjusted Cox regression models.Results: One hundred thirty-four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV-positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20-1.07; P = .06) but not HPV-negative (HR: 0.73, 95% CI: 0.43-1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV-positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12-0.96; P = .04). Survival did not vary significantly by race among HPV-positive patients. Among HPV-negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08-0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11-7.36; P = .94) analysis.Conclusions: Women with HPV-positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV-negative OPSCC. There are no differences in prognosis by race among HPV-positive or HPV-negative patients.Level Of Evidence: 4 Laryngoscope, E287-E295, 2018. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative fine needle aspiration (FNA) of parotid lesions often is used in the initial evaluation of parotid masses, but its role in guiding surgical decision making remains unclear, in part due to varying diagnostic accuracy reported. We sought to evaluate the role of preoperative FNA in detection of malignancy and impact on surgical management.Study Design: Retrospective study.Methods: The medical records of patients who underwent parotidectomy at a single tertiary medical center were reviewed from 2000 to 2015. Patients who had a preoperative FNA comprised the study cohort.Results: A total of 1,074 consecutive patients underwent parotidectomy during the study period; of those, 477 had a preoperative FNA. FNA was nondiagnostic in 26 cases. There were 29 false positives (6.4%), 26 false negatives (5.8%), 122 true positives (27.1%), and 274 true negatives (60.8%). The sensitivity and specificity of FNA were 82.4% and 90.4%, respectively, with a positive predictive value of 80.8% and a negative predictive value of 91.3%. The overall accuracy of preoperative FNA was 87.8%. The preoperative FNA resulted in a change in the surgical plan in 85 (18.9%) cases. In 66 of these cases (78%), surgery was extended to include neck dissection at time of resection. In 10 cases, FNA led to surgical management over surveillance. In 11 cases, FNA downgraded the extent of surgery planned to an excisional biopsy.Conclusion: Preoperative FNA is a valuable adjunct in the surgical management of parotid lesions, with high specificity for the detection of malignant disease.Level Of Evidence: 4. Laryngoscope, 128:398-402, 2018. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro. We hypothesize that LTS-derived fibroblasts will demonstrate aberrant behavior with faster proliferation, increased collagen production, and altered metabolic allocation compared with normal fibroblasts. Study Design In vitro comparative analysis. Methods Human biopsies of normal and iatrogenic LTS tissue (n = 7) were obtained, and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression, and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed. Results LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts. Conclusions Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed, suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general. Level of Evidence NA Laryngoscope, 127:E107-E113, 2017 [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Hereditary hemorrhagic telangiectasia (HHT) is a disease of abnormal angiogenesis, causing epistaxis in over 96% of patients. The Epistaxis Severity Score (ESS) was developed as a standardized measurement of nasal symptoms among HHT patients. The minimal important difference (MID) of a disease index estimates the smallest change that a patient and clinician would identify as important. This study aims to establish the MID of the ESS in a diverse population of HHT patients.Study Design: Retrospective cross-sectional study in patients with a diagnosis of HHT using Curacao criteria or genetic testing.Methods: The ESS questionnaire and Medical Outcomes Study 36-Item Short Form (SF-36) were administered to participants recruited through the HHT Foundation Web site. Demographics and relevant medical histories were collected from all participants. An anchor-based method using a change of 5 in the Physical Component Summary (PCS) of the SF-36 and a distributional method were used to estimate the MID.Results: A total of 604 subjects were recruited between April and August 2008. All participants reported epistaxis. An increasing ESS in the study cohort showed a significant negative correlation to the PCS (r = -0.43, P < 0.001). The MID was determined to be 0.41 via the anchor-based approach and 1.01 via the distribution-based approach, giving a mean MID of 0.71.Conclusion: Using both the anchor-based and distribution-based approaches, the estimated MID for the ESS in HHT is 0.71. Further implications include key metrics to help guide treatment responses in clinical care and essential information to calculate power and sample size for future clinical trials.Level Of Evidence: 4. Laryngoscope, 126:1029-1032, 2016. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To describe the pre-implant audiometric profile of adult cochlear implant (CI) recipients to investigate whether current binaural candidacy requirements prevent access to patients who could benefit from CI.Study Design: Retrospective case series.Methods: Retrospective review from 2016 to 2018 evaluating preoperative pure-tone thresholds and speech perception scores in the ipsilateral and contralateral ear.Results: A total of 252 adult CI recipients undergoing 270 implants were identified. Median age at time of implantation was 70.5 years (IQR 61.3-78.3) for those undergoing unilateral implantation and 59.0 (IQR 48.0-72.3) for those undergoing bilateral implantation (P < .01). For unilateral implantation, median pre-implantation speech perception performance in the ear to be implanted was 8.0% (IQR 0%-26.0%) for CNC word scores, and 9.0% (IQR 0%-34.0%) for AzBio sentence scores in quiet. Median speech perception performance in the contralateral ear was 36.0% (IQR 14.0%-60.0%) on CNC word scores, and 48.5% (IQR 17.5%-76.0%) on AzBio sentence tests. Speech perception scores were significantly different between ears for word and sentence tests (P < .01). Patients older than age 65 were significantly less likely to undergo bilateral implantation (P = .03).Conclusions: Adult CI recipients exhibit substantially poorer pre-implant speech perception scores than the commonly utilized ipsilateral qualifying threshold of 50% on sentence testing. Yet, existing insurance paradigms limit patients by excessively stringent binaural best-aided requirements. This limitation likely leads to worse device performance as patients often wait years for their binaural hearing to qualify while their ear to be implanted potentially experiences an unnecessarily extended duration of deafness. Older patients also experience a unique delay in referral for cochlear implantation.Level Of Evidence: 3- Retrospective review Laryngoscope, 131:E2007-E2012, 2021. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro. We hypothesize that LTS-derived fibroblasts will demonstrate aberrant behavior with faster proliferation, increased collagen production, and altered metabolic allocation compared with normal fibroblasts.Study Design: In vitro comparative analysis.Methods: Human biopsies of normal and iatrogenic LTS tissue (n = 7) were obtained, and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression, and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed.Results: LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts.Conclusions: Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed, suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general.Level Of Evidence: NA Laryngoscope, 127:E107-E113, 2017. [ABSTRACT FROM AUTHOR]