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Purpose:Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti–PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.Patients and Methods:This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling.Results:Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%–84%) and 75% (51%–88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells.Conclusions:Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.

T cell gating

Purpose: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome.Experimental Design: XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1).Results: Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037).Conclusions: In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment. Clin Cancer Res; 17(20); 6542–52. ©2011 AACR.

PFS and OS by AJCC 8

B cell gating

Supplementary Table 2 from Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-κB Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma

Supplementary Table 1 from Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-κB Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma

Gene expression signatures generated from DNA microarray analyses have shown promise as predictive biomarkers of clinical outcome. In this study, we determined a high-risk signature for disease recurrence using formalin-fixed head and neck squamous cell carcinoma (HNSCC) tumors and compared the results with an independent data set obtained from fresh frozen tumors. We also showed that genes involved in epithelial-to-mesenchymal transition (EMT) and nuclear factor-κB (NF-κB) signaling deregulation are the most prominent molecular characteristics of the high-risk tumors. Gene expression was determined in 40 samples, including 34 formalin-fixed tissues and 6 matched frozen tissues, from 29 HNSCC patients. A 75-gene list predictive of disease recurrence was determined by training on the formalin-fixed tumor data set and tested on data from the independent frozen tumor set from 60 HNSCC patients. The difference in recurrence-free survival (RFS) between the high-risk versus low-risk groups in the training and test sets was statistically significant (P = 0.002 and 0.03, respectively, log-rank test). In addition, the gene expression data was interrogated using Gene Set Enrichment Analysis to determine biological significance. The most significant sets of genes enriched in the high-risk tumors were genes involving EMT, NF-κB activation, and cell adhesion. In conclusion, global gene expression analysis is feasible using formalin-fixed tissue. The 75-gene list can be used as a prognostic biomarker of recurrence, and our data suggest that the molecular determinants of EMT and NF-κB activation can be targeted as the novel therapy in the identified high-risk patients. (Cancer Res 2006; 66(16): 8210-8)

Objectives The frequency of endoscopic skull base surgery in pediatric patients is increasing. This study aims to systematically review the literature for endoscopic skull base surgery outcomes in children/adolescents aged 0 to 18 years. Design A systematic review of the literature was performed in PubMed and SCOPUS databases querying studies from 2000 to 2020 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Final inclusion criteria included: case series with more than 10 patients with pediatric patients aged ≤18 years, endoscopic or endoscopic-assisted skull base surgery, and outcomes reported. Setting This study was conducted at a tertiary care medical center. Participants Children/adolescents aged 0 to 18 years who underwent endoscopic skull base surgery were participated in this study. Main Outcome Measures Patient demographics, pathology, reconstructive technique, intraoperative findings, intraoperative, and postoperative surgical complications were measured through this study. Results Systematic literature search yielded 287 publications. Of these, 12 studies discussing a total of 399 patients aged 0 to 18 years met inclusion criteria for final analysis. Seven of the 12 studies discussed a single pathology. The most common pathology was a skull base defect causing cerebrospinal fluid (CSF) leak. The majority of skull base repairs were made with free tissue grafts. The most common postoperative complication was CSF leak (n = 40). Twelve cases of meningitis occurred postoperatively with two of these episodes resulting in death. Conclusion Endoscopic skull base surgery has been performed recently in the pediatric population in a variety of disease states. Inconsistent individual-level data and reporting standards are present in existing studies posing challenges for comparative analysis. Standardized reporting will aid future reviews and meta-analysis for rare skull base pathology.

Background There is a paucity of data on financial toxicity among patients with head and neck squamous cell carcinoma (HNSCC). Materials This was a retrospective, cross-sectional study of patients with HNSCC surveyed at an outpatient oncology clinic. Results The sample included 202 patients with HNSCC with a mean age of 59.6 years (SD 10.0). There were 53 patients (26%) with self-reported financial burden. Education of high school or less was a significant predictor of self-reported financial burden (OR 2.52, 95% CI 1.03-6.14, p = 0.042). Patients reporting financial burden had significantly worse physical (p = 0.003), mental (p = 0.003), and functional (p = 0.036) health-related quality of life (HRQOL). Patients reporting financial burden appeared to have lower 5-year overall survival (74.3% vs. 83.9%, p = 0.165), but this association did not reach statistical significance. Conclusion Financial burden or toxicity may affect approximately a quarter of patients with HNSCC and appears to be associated with worse HRQOL outcomes.

OBJECTIVES: To date, there is still a significant debate on the role of human papilloma virus (HPV) infection in transformation of inverted papillomas (IPs) to squamous cell carcinoma (SCC). This study was designed to determine if the presence of HPV in a sinonasal IP increases the risk of malignant transformation to IPSCC. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 19 high-quality case-control and cohort studies with tissue-diagnosed IP or IPSCC and HPV diagnosis were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method with correction for random effects. Subgroup, publication bias and a sensitivity analyses were also performed. RESULTS: Nineteen studies with minimal bias met the inclusion criteria for quality and identified HPV infection in an IP. The pooled data revealed a strong association with progression to malignancy with an unweighted, pooled OR of 2.38 (CI(95) 1.47 to 3.83) and a weighted OR of 2.80 (CI(95) 1.42 to 5.51). Sensitivity analysis revealed that no single study contributed significantly to our pooled OR calculations (ORs 2.52 to 3.57). Subgroup analyses stratified by publication date, nucleic acid target, HPV detection method and type, sample size, and region all demonstrated a positive association of HPV with IPSCC. CONCLUSIONS: There appears to be a significant association between HPV infection and malignant transformation of IPs. While HPV testing is not currently the standard of care for IPs, these data suggest a link between the two and suggest further studies should be performed to identify a link between the virus and malignant transformation.

Objectives To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma. Methods Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta-analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1. Results Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta-analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n = 13) and SLIT versus placebo (n = 33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD] = 0.40; 95% confidence interval [CI] = 0.31-0.49), MS (SMD = 0.26; 95% CI = 0.14-0.39), CSMS (SMD = 0.42; 95% CI = 0.17-0.67), and RQLQ (MD = 0.24; 95% CI = 0.04-0.44). Statistically significant results favoring SLIT were found for SS (SMD = 0.42; 95% CI = 0.32-0.53), MS (SMD = 0.40; 95% CI = 0.28-0.53), CSMS (SMD = 0.37; 95% CI = 0.29-0.45), and RQLQ (MD = 0.32; 95% CI = 0.20-0.43). No significant differences were found between SCIT and SLIT for SS (SMD = -0.02; 95% CI = -0.15 to 0.11), MS (SMD = -0.14; 95% CI = -0.31 to 0.03), CSMS (SMD = 0.05; 95% CI = -0.21 to 0.31), or RQLQ (MD = -0.08; 95% CI = -0.31 to 0.15). Conclusion SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two. Laryngoscope, 2021.

INTRODUCTION: Intranasal corticosteroids sprays (INCS) are first line treatment for allergic rhinitis and are frequently used for chronic rhinosinusitis. Improperly aiming INCS increases the risk of epistaxis and may decrease the efficacy of the medication. The goal of this study was to determine how patients position INCS for drug delivery and if verbal or written instructions improve their positioning. METHODS: Patients in rhinology clinics were photographed while administering a generic spray bottle. The angle of the spray bot- tle relative to the patients’ head and a fixed background was determined. RESULTS: A total of 46 participants were included. The average spray angle for the right naris was 10.1o towards the septum and 67.2o below the Frankfurt Horizontal plane. The average spray angle for the left naris was 4.5o towards the septum and 62.2o below the Frankfurt horizontal plane. The angle of the spray bottle ranged from 50o toward the septum to 43o away from the sep- tum. Only 8 patients aimed away from the septum for both nares. Patients who recalled receiving verbal and written instructions aimed the INCS bottle at the lateral wall and inferior turbinate in contrast to patients who only received one form of instruction or no instructions. CONCLUSIONS: Most patients (83%) incorrectly aim INCS when compared to current guidelines. There was statistically significant improvement in the positioning of patients who reported receiving both verbal and written instruction; however, this study high- lights a greater need for patient education.

To compare oncologic outcomes in sinonasal squamous cell carcinoma (SNSCC) treated with standard of care (SOC) definitive therapy, consisting of surgery or chemoradiotherapy, vs induction therapy followed by definitive therapy.Retrospective review.Academic tertiary care hospital.The medical records of patients with biopsy-proven SNSCC treated between 2000 and 2020 were reviewed for demographics, tumor characteristics, staging, treatment details, and oncologic outcomes. Patients were matched 1-to-1 by age, sex, and cancer stage according to treatment received. Time-to-event analyses were conducted.The analysis included 26 patients with locally advanced SNSCC who received either induction therapy (n = 13) or SOC (n = 13). Baseline demographics, Charlson Comorbidity Index, and median follow-up time were well balanced. Weekly cetuximab, carboplatin, and paclitaxel were the most common induction regimen utilized. Tolerance and safety to induction were excellent. Objective responses were observed in 11 of 13 patients receiving induction. No difference in disease-free survival was found between the induction and SOC groups at 1 or 3 years. However, when compared with SOC, induction therapy resulted in significant improvement in overall survival at 2 years (100% vs 65.3%,Induction therapy was safe and effective. When compared with SOC, induction therapy improved 3-year overall survival.

Background Recent indirect evidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission during endoscopic endonasal procedures has highlighted the dearth of knowledge surrounding aerosol generation with these procedures. As we adapt to function in the era of Coronavirus Disease 2019 (COVID-19) a better understanding of how surgical techniques generate potentially infectious aerosolized particles will enhance the safety of operating room (OR) staff and learners. Objective To provide greater understanding of possible SARS-CoV-2 exposure risk during endonasal surgeries by quantifying increases in airborne particle concentrations during endoscopic sinonasal surgery. Methods Aerosol concentrations were measured during live-patient endoscopic endonasal surgeries in ORs with an optical particle sizer. Measurements were taken throughout the procedure at six time points: 1) before patient entered the OR, 2) before pre-incision timeout during OR setup, 3) during cold instrumentation with suction, 4) during microdebrider use, 5) during drill use and, 6) at the end of the case prior to extubation. Measurements were taken at three different OR position: surgeon, circulating nurse, and anesthesia provider. Results Significant increases in airborne particle concentration were measured at the surgeon position with both the microdebrider (p = 0.001) and drill (p = 0.001), but not for cold instrumentation with suction (p = 0.340). Particle concentration did not significantly increase at the anesthesia position or the circulator position with any form of instrumentation. Overall, the surgeon position had a mean increase in particle concentration of 2445 particles/ft3 (95% CI 881 to 3955; p = 0.001) during drill use and 1825 particles/ft3 (95% CI 641 to 3009; p = 0.001) during microdebrider use. Conclusion Drilling and microdebrider use during endonasal surgery in a standard operating room is associated with a significant increase in airborne particle concentrations. Fortunately, this increase in aerosol concentration is localized to the area of the operating surgeon, with no detectable increase in aerosol particles at other OR positions.

The incidence of oral tongue squamous cell carcinoma has been increasing in young patients (≤45 years) without a clear etiologic driver. It is unknown if younger patients have an increased risk of recurrence compared to older patients. A literature search was conducted through January 2020 using PubMed/MEDLINE, Embase, Cochrane, Scopus, Science Direct, and clinicaltrials.gov. This review was registered with PROSPERO (ID: CRD42020167498) and the PRISMA statement was followed. Studies were eligible for inclusion if they assessed risk of recurrence by age using a time-to-event analysis, used an age cutoff of ≤45 years or less for the younger cohort, and limited the analysis to the oral tongue subsite. Data were extracted independently by two reviewers using a form with a prespecified list of variables. There were 13 articles that met criteria for the qualitative synthesis (n = 1763 patients). The reported 5-year rates of disease-free survival ranged from 30% to 72% for the younger cohorts and 42% to 81% for the older cohorts. Three studies reported a statistically significant increased risk of recurrence in younger patients, three studies reported a nonsignificant increased risk in younger patients, and seven studies reported a similar risk in younger patients based on the time-to-event analyses. There may be an increased risk of recurrence for younger patients with oral tongue cancer. A definitive conclusion is precluded by limitations among individual studies, and additional research is warranted to examine this question.

Background Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature. Objective The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model. Methods Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically. Results Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time. Conclusions While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

Background Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms. Methods We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified. Results The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17–53 years old. The volumes for all thee sinus cavities were significantly smaller (p Conclusions Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group.

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare., Comment: 24 pages, 8 figures, 5 tables

Purpose: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti–PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC. Patients and Methods: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling. Results: Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%–84%) and 75% (51%–88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells. Conclusions: Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.

Background Allergic rhinitis is a widespread disease that has significant quality-of-life ramifications. Symptoms include rhinorrhea, nasal obstruction, cough, and postnasal drip. Intranasal corticosteroids are a hallmark of treatment of allergic rhinitis. However, the benefits of treatment are dependent on correct nasal spray technique, of which many patients are not aware. Patient instructions are included with the purchase of these medications. The readability and understandability for these educational materials has been minimally assessed in the medical literature. The aim of this study was to evaluate the readability and understandability of commonly used intranasal steroids. Methods Three readability measures (Gunning Fog, Simple Measure of Gobbledygook [SMOG], and FORCAST) and an understandability assessment (Patient Education Materials Assessment Tool for Printable Materials [PEMAT-P]) were used to evaluate the instructions for use of commonly prescribed intranasal steroids. Instructions with 6th grade readability level or lower were considered to meet health literacy experts' recommendations. Higher understandability values correlate to easier understandability. Results Instructions for 10 intranasal corticosteroid brands were reviewed. Gunning Fog consistently estimated easiest readability, whereas FORCAST estimated most difficult readability. Twenty percent (20%) of analyzed instructions met National Institutes of Health and health literacy experts' recommended reading levels. Understandability of instructions ranged from 33% to 90%, with an average of 66%. Conclusion The benefit of intranasal corticosteroids is contingent on correct use by patients. However, the prepackaged instructions provided are most often above recommended reading levels and are difficult to understand. Future development of intranasal steroid instructions should meet recommended readability levels and be understandable to maximize their utility.

Our objectives were to analyze the recent trends in applicants of otolaryngology-head and neck surgery (Oto-HNS) residency programs, including evolutions in sex and racial/ethnic distribution within the applicant pool and subsequent residency cohort.Retrospective database and literature review. Data regarding applicants to Oto-HNS programs as well as Oto-HNS residents in the United States from 2008 to 2017 were analyzed from the Electronic Residency Application Service, National Resident Matching Program, and Journal of the American Medical Association.Between 2008 and 2018, the number of Oto-HNS residency programs and residency positions offered increased from 105 to 112 and from 273 to 315, respectively. There was no statistically significant difference between applicant sex in 2008 to 2012 compared to 2013 to 2018 (P .05), but significantly more females made up the residency workforce from 2013 to 2018 compared to 2008 to 2012 (P .001). However, the percentage increase in female residents from 2008 to 2017 was only 6.1% (29.8% to 35.9%). No statistically significant difference was present between applicant race in 2008 to 2012 compared to 2013 to 2018 (P .05), but significantly more minority residents made up the residency workforce from 2013 to 2018 compared to 2008 to 2012 (P .0001). However, the percentage increase in minority residents from 2008 to 2017 was only 4.9% (35.1% to 40%).Women and minority racial and ethnic groups continue to be underrepresented among Oto-HNS applicants. However, the presence of these groups among current residents has increased. Understanding and tracking these national trends yearly is critical for training a diverse future otolaryngology workforce.VI Laryngoscope, 131:277-281, 2021.

PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHODS AND MATERIALS A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance. RESULTS One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months). CONCLUSION Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.

BACKGROUND Care coordination for cystic fibrosis (CF) is essential. The objectives of this study were to: (1) compare otolaryngologists' and pulmonlogists' understanding of long-term chronic rhinosinusitis (CRS) management; and (2) query patient perceptions of otolaryngologic care and CRS. METHODS A cross-sectional survey was administered by the Cystic Fibrosis Foundation in 2018 to patients with CF or their caregivers, otolaryngologists, and pulmonologists. Statistical analysis was performed comparing specialists. Descriptive statistics were computed for patient/caregiver-reported data. RESULTS Respondents included 126 otolaryngologists, 115 pulmonologists, and 186 patients with CF or their caregivers. Pulmonologists had greater experience caring for CF patients compared with otolaryngologists (66.7% vs 43.2% with 13+ years of experience, respectively), but more otolaryngologists cared for both adult and pediatric CF patients (39.2% vs 10.4%, respectively). Significantly more otolaryngologists advocated for establishing otolaryngologic care at time of CF diagnosis (64.8%) compared with pulmonologists (14.4%, p < 0.001), of whom 60.4% recommended otolaryngologist referral when sinonasal symptoms affect quality of life. More otolaryngologists perceived sinus surgery as beneficial for pulmonary function (74.5% vs 57.7%, p = 0.009); 60.8% of patients first sought otolaryngologic care in infancy or childhood (

BACKGROUND: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. METHODS: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance) and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. RESULTS: We identified 3 latent classes. Advanced T-stage was higher for Black (RFD=(+)20.2%; 95% CI: (−)4.6–44.9) than White patients (RFD=(+)10.7%; 95% CI: 2.1–19.3) in the low-SES/high-access/high-behavioral risk class and higher for both Black (RFD=(+)29.6%; 95% CI: 4.7–54.5) and White patients (RFD=(+)23.9%; 95% CI: 15.2–32.6) in the low-SES/low-access/high-behavioral risk class. CONCLUSION: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation.

Objectives Pain management remains a point of emphasis given the ongoing opioid crisis. There are no studies in the literature interrogating opioid prescribing and use following endoscopic pituitary surgery. This study investigates provider prescribing tendency, patient utilization of analgesics, and patient outcomes regarding pain management after endoscopic pituitary surgery. Methods We identified 100 patients undergoing endoscopic pituitary surgery at one institution from 2016 to 2018 in the electronic medical record (EMR) and state narcotic database to determine postoperative analgesic regimens. A telephone survey was used to characterize postoperative analgesic use and satisfaction with prescribed regimen. Results Fifty-two different pain control regimens were prescribed to the study patients. Also, 93% of study patients were prescribed an opioid postoperatively. The average quantity of opioids prescribed per patient in morphine milligram equivalents (MMEs) was 625 (equivalent 83 oxycodone 5-mg tablets) with an average MME/day of 59 (equivalent 8 oxycodone 5-mg tablets). A total of 71% survey respondents who used opioids reported using 50% of their postoperative opioid intake in the first 24 to 48 hours after discharge. There were no significant differences in pain outcome between opioid users and nonopioid users. Conclusion Vast heterogeneity exists in narcotic prescribing by providers at our institution following endoscopic pituitary surgery. Narcotic prescribing patterns exceeded most patients' analgesic needs. Opioid analgesics were not superior to nonopioids regimens in patient-reported pain outcomes in this study population.

Introduction: The coronavirus 2019 pandemic has altered how modern healthcare is delivered to patients. Concerns have been raised that masks may hinder effective communication, particularly in patients with hearing loss. The purpose of this study is to determine the effect of masks on speech recognition in adult patients with and without self-reported hearing loss in a clinical setting. Methods: Adult patients presenting to an otolaryngology clinic were recruited. A digital recording of 36 spondaic words was presented to each participant in a standard clinical exam room. Each word was recorded in 1 of 3 conditions: no mask, surgical mask, or N95 mask. Participants were instructed to repeat back the word. The word recognition score was determined by the percent correctly repeated. Results: A total of 45 participants were included in this study. Overall, the mean word recognition score was 87% without a mask, 78% with a surgical mask, and 61% with an N95 mask. Among the 23 subjects (51.1%) with self-reported hearing loss, the average word recognition score was 46% with an N95 mask compared to 79% in patients who reported normal hearing (p < 0.001). Conclusion: Our results suggest that masks significantly decrease word recognition, and this effect is exacerbated with N95 masks, particularly in patients with hearing loss. As masks are essential to allow for safe patient-physician interactions, it is imperative that clinicians are aware they may create a barrier to effective communication.

Background NUT carcinoma is an aggressive malignancy characterized by translocations in the NUTM1 gene. There are currently no consensus treatment recommendations for NUT carcinomas. Methods Here, we describe the case of a previously healthy male diagnosed with NUT carcinoma after presenting with sinus pressure, found to have a sinonasal mass and distant metastatic disease in the lungs. While pathologic evaluation and immunohistochemistry were consistent with NUT carcinoma, initial genomic profiling did not demonstrate a NUTM1 translocation. Results Whole transcriptomic RNA sequencing of the tumor revealed a YAP1‐NUTM1 fusion. Based on an in vitro drug sensitivity screen, the patient was treated with gemcitabine and nab‐paclitaxel, achieving a partial response that persisted for 9 months. Conclusions Unbiased transcriptomic sequencing may identify previously uncharacterized NUTM1 fusion partners. Gemcitabine and nab‐paclitaxel is a well‐tolerated combination chemotherapy regimen and could offer a novel treatment approach for NUT carcinoma., Unbiased transcriptome sequencing may identify previously uncharacterized NUTM1 fusion partners. Gemcitabine and nab‐paclitaxel is a well‐tolerated combination chemotherapy regimen and could offer a novel treatment approach for NUT carcinoma.

Background Endoscopic craniofacial resections (CFR) are performed for extensive anterior skull base lesions. This surgery involves removal of multiple intranasal structures, potentially leading to empty nose syndrome (ENS). However, many patients remain asymptomatic postoperatively. Our objective was to analyze the impact of CFR on nasal physiology and airflow using computational fluid dynamics (CFD). This is the first CFD analysis of post-CFR patients. Methods Three-dimensional sinonasal models were constructed from 3 postoperative images using MimicsTM . Hybrid computational meshes were created. Steady inspiratory airflow and heat transport were simulated at patient-specific flow rates using shear stress transport k-omega turbulent flow modeling in FluentTM . Simulated average heat flux (HF) and surface area where HF exceeded 50 W/m2 (SAHF50) were compared with laminar simulations in 9 radiographically normal adults. Results Three adults underwent CFR without developing ENS. Average HF (W/m2 ) were 132.70, 134.84, and 142.60 in the CFR group, ranging from 156.24 to 234.95 in the nonoperative cohort. SAHF50 (m2 ) values were 0.0087, 0.0120, and 0.0110 in the CFR group, ranging from 0.0082 to 0.0114 in the radiographically normal cohort. SAHF50 was distributed throughout the CFR cavities, with increased HF at the roof and walls compared with the nonoperative cohort. Conclusion Average HF was low in the CFR group compared with the nonoperative group. However, absence of ENS in most CFR patients may be due to large stimulated mucosal surface area, commensurate with the nonoperative cohort. Diffuse distribution of stimulated area may result from turbulent mixing after CFR. To better understand heat transport post-CFR, a larger cohort is necessary.

Background Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Methods Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Results Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Conclusion Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.

OBJECTIVES/HYPOTHESIS Recent studies revealed sex bias in surgical research. Although many diseases exhibit sex-based clinically relevant differences, otolaryngology research has not been evaluated for sex reporting and sex-based analysis. We postulate that a similar bias is prevalent in otolaryngology literature. STUDY DESIGN Literature review. METHODS Articles published from 2016 to 2017 in The Laryngoscope, Otolaryngology-Head and Neck Surgery, and JAMA Otolaryngology-Head and Neck Surgery were reviewed. Articles with animal subjects, human subject cells, or commercial cell lines were included. Data collected included study type, cell/animal sex, and sex-based data analysis. RESULTS One hundred forty-four basic/translational research articles were identified. Sixty-nine (47.9%) of those lacked sex reporting. Of 75 studies that reported sex, 22 (29.3%) included both sexes, and 11 (14.7%) analyzed data by sex. One hundred five (72.9%) used animal subjects, of which 54 (51.9%) lacked sex breakdown. Among animal studies, 48/105 included only one sex, and three articles analyzed data by sex. Fifty-four studies used commercial cell lines (N = 23) or human/animal subject cells (N = 31). Among cell groups, 28/54 (51.9%) were of unknown sex, and seven were single sex. Eight (14.8%) studies included data analysis by sex. Domestic studies exhibited a lower rate of sex reporting in both animal and cell studies, and a lower rate of sex-based analysis in cell studies. CONCLUSIONS Sex may influence outcomes significantly but is underreported and underanalyzed in basic/translational otolaryngology research. Because this research frequently lays the groundwork for clinical trials and standards of care, future research must address these sex-based discrepancies. LEVEL OF EVIDENCE NA Laryngoscope, 129:613-618, 2019.