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PurposeTo characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.Experimental designTumor RNA-sequencing data from over 800 patients with head and neck squamous cell carcinoma (HNSCC) and cervical cancer, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival (OS). A novel murine model of HPV+ HNSCC was used to study the effects of PD-1 blockade and radiotherapy on B-cell activation, differentiation, and clonality including analysis by single-cell RNA-sequencing and B-cell receptor (BCR)-sequencing. Human protein microarray was then used to quantify B-cell-mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade.ResultsRNA-sequencing identified CD19 and IGJ as novel B-cell prognostic biomarkers for 3-year OS (HR, 0.545; P < 0.001). PD-1 blockade and radiotherapy enhance development of memory B cells, plasma cells, and antigen-specific B cells. BCR-sequencing found that radiotherapy enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA-sequencing identified dramatic increases in B-cell germinal center formation after PD-1 blockade and radiotherapy. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade.ConclusionsThese findings establish a key role for B cells in patient outcomes and responses to PD-1 blockade in HPV-associated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B cells.

OBJECTIVE:The incidence and survivorship of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance. We also assessed the assay's applicability in screening for HPV+ OPSCC. STUDY DESIGN:Retrospective cohort study. SETTING:Two tertiary academic hospitals. SUBJECTS AND METHODS:Forty-nine patients with posttreatment OPSCC were enrolled. Separately, 21 treatment-naive patients and 40 controls were included in the screening analysis. Salivary rinses were obtained from these cohorts and biomarker levels were quantified. Receiver operative characteristic (ROC) curves and multivariate logistic models were used to assess performance of biomarker combinations. RESULTS:Eight patients (16.3%) in the posttreatment cohort developed locoregional recurrence. Recurrence was associated with alcohol use (odds ratio [OR], 6.12; 95% confidence interval [CI], 0.26-3.79) and advanced nodal disease (OR, 2.21; 95% CI, 1.52-3.01). A panel of HPV DNA and methylated EDNRB improved detection of recurrent disease (area under the curve [AUC], 0.88) compared to single markers (AUC, 0.69-0.78). Positive biomarkers preceded clinical detection by 2.4 ± 1.6 months and was associated with nearly 40-fold risk of recurrence (OR, 36.4; 95% CI, 1.15-45.22). Within the screening analysis, single biomarkers demonstrated moderate sensitivity and specificity (AUC, 0.59-0.83) in the detection of primary disease. A panel combining HPV DNA markers with methylated EDNRB and methylated PAX5 improved AUC to 0.93. CONCLUSION:Detection of high-risk HPV DNA or aberrant hypermethylation in oral rinses is associated with presence and recurrence of OPSCC. Targeting both markers in saliva may have utility in long-term surveillance.

Objective: Cochlear implants (CIs) are a well‐established treatment modality for hearing loss due to neurofibromatosis type 2 (NF2). Our aim is to investigate variables that affect longitudinal performance of CIs among patients with NF2. Study Design: Retrospective review at a single academic institution consisting of patients who have received cochlear implants following hearing loss due to NF2. Methods: The primary outcome examined was CI disuse or explantation. Associated clinical and surgical variables were analyzed using descriptive statistics. These included postoperative pure tone average (PTA) at 500, 1000, and 2000 Hz, tumor size, previous surgery, and comorbid depression. Results: A total of 12 patients and 14 cochlear implants received at our institution from 2001 to 2022 were included. Notably, 35.7% of CIs (5 out of 14 cases) resulted in disuse or explantation. The average interval until explant was 9.4 years (range 3–14 years). In explanted CI cases, 20% had previous surgery and 80% had a diagnosis of comorbid depression as compared to 22.2% and 22.2%, respectively, in intact CI cases. Maximum tumor diameter was the only variable found to impact CI usage outcome (p = 0.028). Long‐term data showed that on average, patients benefit from 13.85 years of CI utility and a maximum PTA improvement of 45.0 ± 29.0 dB. Conclusion: Despite the recurrent nature of NF2, patients continue to receive audiological benefit from cochlear implants. We found that larger tumor size may be associated with longitudinal CI failure. Level of Evidence: 4 Laryngoscope, 134:1847–1853, 2024 [ABSTRACT FROM AUTHOR]

Objective: This study aimed to estimate the size of the United States candidacy pool meeting expanded Center for Medicare Services criteria for cochlear implantation. Study Design: Retrospective cross‐sectional. Setting: Tertiary care center. Methods: Preimplantation audiometric data from 486 patients seen at a single academic medical center were collected retrospectively and used to generate a predictive model of AzBio score based on audiometric pure tone thresholds. This model was then used to estimate nationally representative cochlear implantation (CI)‐candidacy using pure tone averages included in the National Health and Nutrition Examination Survey. Qualitative and quantitative analyses were performed. Results: We find that the estimated prevalence of CI candidacy in individuals 65 years of age or older is expected to more than double with a change in the CI candidacy criteria from ≤40% to ≤60% (from 1.42%, 95% confidence interval [1.33, 1.63] to 3.73% [2.71, 6.56]) on speech testing. We also found the greatest absolute increase in candidacy in the 80+ age group, increasing from 4.14% [3.72, 5.1] of the population meeting the ≤40% criteria to 12.12% [9.19, 18.35] meeting the ≤60% criteria. Conclusion: The United States population size meeting expanded CMS audiologic criteria for cochlear implantation is estimated to be 2.5 million adults and 2.1 million age 65 or older. Changing the CI candidacy criteria from ≤40% to ≤60% on CI testing has the greatest effect on the eligible patient population in the >65‐year‐old age group. The determination of utilization rates in newly eligible patients will require further study. [ABSTRACT FROM AUTHOR]

Objectives: Accurate and reproducible measurements of the pediatric airway are critical for diagnostic evaluation and management of subglottic and tracheal stenosis. The endoluminal functional lumen imaging probe (EndoFLIP) is a catheter‐based imaging probe which utilizes impedance planimetry to calculate luminal parameters, including cross‐sectional area and compliance. Herein, we demonstrate the feasibility of this system for multidimensional evaluation of the pediatric airway. Methods: 3D‐printed pediatric laryngotracheal models were created based on computed tomography scans, then artificially deformed to simulate both circumferential and posterior subglottic stenosis. Two observers made six measurements of the minimum cross‐sectional area (MCSA) and length of stenosis of each model with EndoFLIP. Agreement between observer measurements and model dimensions was evaluated using Lin's concordance correlation coefficient; inter‐observer reliability was assessed using intraclass correlation. Results: Four models were created: two without pathology (MCSA: 132.4, 44.3 mm2) and two with subglottic stenosis (MCSA: 28.7, 59.7 mm2, stenotic length 27.8, 24.4 mm). Observer measurements of MCSA and length of stenosis demonstrated high concordance with the models (r = 0.99, 0.95, p < 0.001) with a mean error of 4.5% and 18.2% respectively. There was a low coefficient of variation (0.6%–2.8%) for measurements, indicating high precision. Interrater reliability was high for both MCSA and stenotic length (ICC: 0.99, 0.98). Conclusions: The EndoFLIP system allows for accurate and reproducible measurements of cross‐sectional area and stenotic length in pediatric airway models. This method may provide further advantages in the evaluation of airway distensibility, as well as measurements of asymmetric airway pathology. Level of Evidence: NA Laryngoscope, 134:108–112, 2024 [ABSTRACT FROM AUTHOR]

Objective: To assess the high-volume 2020 COVID-19-related surgical literature, with special attention to otolaryngology articles in regard to content, level of evidence, citations, and public attention. Study Design: A scoping literature review was performed with PubMed and Web of Science, including articles pertaining to COVID-19 and surgical specialties (March 20–May 19, 2020) or otolaryngologic subspecialties (March 20–December 31, 2020). Setting: Scoping literature review. Methods: Otolaryngology-specific COVID-19-related articles were reviewed for publication date, county of origin, subspecialty, content, level of evidence, and Altmetric Attention Score (a weighted approximation of online attention received). Data were analyzed with Pearson correlation coefficients, analysis of variance, independent t tests, and univariable and logistic regressions. Results: This review included 773 early COVID-19 surgical articles and 907 otolaryngology-specific COVID-19-related articles from 2020. Otolaryngology was the most represented surgical specialty within the early COVID-19-related surgical literature (30.4%). The otolaryngology-specific COVID-19 surgical literature responsively reflects the unique concerns within each otolaryngologic subspecialty. Although this literature was largely based on expert opinion (64.5%), articles with stronger levels of evidence received significantly more citations (on Web of Science and Google Scholar, P <.001 for both) and public attention (according to Altmetric Attention Scores, P <.001). Conclusion: Despite concerns of a surge in underrefereed publications during the COVID-19 pandemic, our review of the surgical literature offers some degree of reassurance. Specifically, the COVID-19 otolaryngology literature responsively reflects the unique concerns and needs of the field, and more scholarly citations and greater online attention have been given to articles offering stronger levels of scientific evidence. [ABSTRACT FROM AUTHOR]

Background: Endoscopic dacryocystorhinostomy (EN-DCR) is an increasingly common procedure performed by otolaryngologists. While EN-DCR has a high rate of success at relieving blockage of the lacrimal system, little is known regarding associated postoperative infection (POI) rates and risk factors. Objective: The purpose of this study was to identify factors associated with the occurrence of postoperative orbital and rhinologic infection in a large cohort of patients undergoing EN-DCR. Methods: A retrospective review of 582 patients who underwent EN-DCR was performed. All patients received antibiotic prophylaxis as a single intraoperative intravenous administration and a ten-day postoperative oral course. Clinical and demographic information was reviewed, including the occurrence of acute orbital or rhinologic infection within 30 days of surgery. Multivariable analysis was performed to identify risk factors associated with POI. Results: Fifteen of 582 patients (2.6%) developed POI following EN-DCR. The most common POI was acute rhinosinusitis (10/15, 66.7%), followed by acute dacryocystitis (2/15, 13.3%), preseptal cellulitis (2/15,13.3%), and acute bacterial conjunctivitis (1/15, 6.7%). The majority of patients (464/582, 79.7%) underwent concurrent endoscopic sinus surgery (ESS). In most cases (302/464, 65.1%), ESS was performed to address comorbid rhinosinusitis, whereas 7.8% (36/464) of patients underwent surgery to enhance surgical access to the lacrimal sac. Patients who underwent concurrent ESS were less likely to develop POI (OR: 0.17, CI: 0.04-0.80, p < 0.05). Evidence of mucopurulence at surgery increased the likelihood of POI (OR: 6.24, CI: 1.51-25.84, p < 0.05). Conclusion: Mucopurulence at the time of surgery significantly increased the risk of POI, whereas concurrent ESS, performed most commonly to address comorbid rhinosinusitis, significantly decreased the risk of POI. Awareness of risk factors for POI and appropriate surgical management of concurrent rhinosinusitis can lead to reduced infectious complications after EN-DCR. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: A subset of patients will undergo revision endoscopic sinus surgery (ESS) with a different otolaryngologist than the one who performed their primary surgery. The purpose of this study is to report the incidence of and clinicodemographic factors associated with a change in surgeon for revision ESS. Study Design: Retrospective cohort study. Methods: Adult patients who underwent at least two outpatient ESS procedures between 2009 and 2014 using the State Ambulatory Surgery Database for Florida were included in the study. Change in surgeon was defined by a change in a unique provider identifier for the revision procedure. Multivariable regression analysis was used to determine characteristics associated with a change in surgeon. Results: A total of 2,963 patients were included. For the revision procedure, 47.7% of patients changed their surgeon. On multivariable logistic regression, a medium‐ (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.53‐0.77) or high‐volume (OR: 0.50; 95% CI: 0.42‐0.61) surgeon performing the index surgery and advanced age (≥65 years) (OR: 0.79; 95% CI: 0.63‐0.99) were associated with decreased odds of surgeon change for revision ESS. Longer time elapsed between index and revision surgery (OR: 1.15; 95% CI: 1.13‐1.17) was associated with increased odds of surgeon change. Conclusions: Nearly half of patients who undergo revision ESS select a surgeon other than the one who performed their primary procedure. Surgeon volume, age, and time between surgeries affect the likelihood of a change in surgeon for revision ESS. These findings may provide introductory insights into patient preferences and decision making in the surgical management of recalcitrant chronic rhinosinusitis. Level of Evidence: 4 Laryngoscope, 131:E1049–E1053, 2021 [ABSTRACT FROM AUTHOR]

Introduction  Postoperative pain management and opioid use following endoscopic skull base surgery (ESBS) is not well understood. A subset of patients requires additional opioid prescription (AOP) in the postoperative period. The objective of this study is to describe the incidence of AOP, as well as evaluate patient and surgical characteristics that may predict additional pain management requirements following ESBS. Methods  A retrospective review of cases undergoing ESBS between November 2016 and August 2018 was performed. We reviewed patients' sociodemographic and clinical data, and Controlled Substance Utilization Review and Evaluation System (CURES) records. Stepwise multivariable logistic regressions were performed to evaluate the factors associated with AOP within 60 days following surgery. Results  A total of 42 patients were identified. Indications for ESBS included intracranial mass (64.2%), sinonasal malignancy (23.8%), and skull base reconstruction (9.5%). AOP were recorded in nine patients (21.4%). There were no significant differences in operative factors, including approach, lesion location, or perioperative analgesia between the two cohorts. On multivariable logistic regression, we found that younger age (odds ratio [OR]: 0.891, 95% confidence interval [CI]: 0.79–1.00, p  = 0.050), comorbid depression (OR: 86.48, 95% CI: 1.40–5,379.07, p  = 0.034), and preoperative opioid use (OR: 104.45, 95% CI: 1.41–7,751.10, p  = 0.034) were associated with additional prescriptions postoperatively. Conclusion  The requirement for extended postoperative opioid pain control is common after ESBS. Patient demographics including age and psychosocial factors, such as depression may predict the need for AOP after ESBS. These results suggest that patient-driven factors, rather than surgical characteristics, may determine the need for prolonged pain control requirements after ESBS. [ABSTRACT FROM AUTHOR]

Background: Concha bullosa (CB) is a prevalent anatomic variant and frequent surgical target in endoscopic sinus surgery (ESS). However, whether CB impacts quality-of-life (QOL) in chronic rhinosinusitis (CRS) is not well established. The purpose of this study was to investigate baseline and post-ESS QOL differences in patients with medically recalcitrant CRS with and without CB. Methods: Demographic and surgical characteristics, baseline and postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores for 137 patients with CRS who underwent primary ESS at our institution were recorded. Computed tomography (CT) scans were reviewed for Lund–Mackay score and presence of CB. Multiplanar CT was used to measure CB dimensions and estimate volume. Multivariable analysis was performed to identify differences in SNOT-22 overall and symptom-domain scores between patients with upper quartile (≥0.8 mL) CB and without CB. Results: CB was found in 37% of patients with mean volume of 0.67 mL. There were no significant differences in distribution of clinicodemographic variables by large CB status. At baseline, large CB was associated with higher SNOT-22 extranasal-rhinologic domain score (9.8 vs 6.0, P <.01). Following ESS, patients with large CB reported greater improvement in SNOT-22 extranasal-rhinologic domain score (multivariable mean absolute improvement 3.8, P =.01; relative 56% vs 30%). Conclusion: Patients with medically recalcitrant CRS and concomitant large CB have higher SNOT-22 extranasal-rhinologic domain scores at baseline, but also report greater intradomain improvement exceeding the subdomain's mean clinically important difference. To our knowledge, this is the first demonstration that CB has a clinically significant impact on QOL in CRS, and surgical intervention may be helpful to address these symptoms. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Socioeconomic and demographic factors have a significant impact on healthcare utilization and surgical outcomes. The effect of these variables on baseline symptom severity and quality of life (QOL) after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is not well established. Our goal was to investigate the association of sociodemographic factors on QOL before and after ESS, as reflected by the 22-item Sino-Nasal Outcome Test (SNOT-22) score.Study Design: Retrospective case series.Methods: From October 2016 to August 2018, 244 patients with chronic rhinosinusitis who underwent ESS were included. Socioeconomic and demographic data, surgical characteristics, and baseline and postoperative SNOT-22 scores were recorded. Univariate and multivariate regression were performed to identify determinants of baseline symptom severity and improvement following ESS.Results: Nonwhite patients reported worse baseline symptoms severity (SNOT-22, 52.06 vs. 43.76, P = .021) compared to white patients, yet lower CRS symptoms at follow-up (SNOT-22, 23.38 vs. 28.63, P = .035). Relative improvement was higher in nonwhite patients as well (41.2% vs. 36.5%, Mann-Whitney U = 1,747, P = .015). In an adjusted multivariate logistic regression model, below-median income ($71,805 [California]) was associated with worse baseline symptom severity (β = 7.72; 95% confidence interval [CI]: 1.10, 14.26). Nonmarried patients (β = 6.78; 95% CI: 2.22, 13.48) and white patients (β = 8.45; 95% CI: 0.40, 13.97) had worse QOL at follow-up.Conclusions: Nonwhite patients and those with below-median income present with more severe CRS symptoms at baseline. However, a greater degree of absolute and relative QOL improvement was found in nonwhite and married patients following ESS. Improved understanding of the significance of socioeconomic and demographic factors and attention to cultural differences/marital status could have a substantial impact on ESS outcomes.Level Of Evidence: 4 Laryngoscope, 130:297-302, 2020. [ABSTRACT FROM AUTHOR]

Efficient and minimally invasive drug delivery to the inner ear is a significant challenge. The round window membrane (RWM), being one of the few entry points to the inner ear, has become a vital focus of investigation. However, due to the complexities of isolating the RWM, our understanding of its pharmacokinetics remains limited. The RWM comprises three distinct layers: the outer epithelium, the middle connective tissue layer, and the inner epithelial layer, each potentially possessing unique delivery properties. Current models for investigating transport across the RWM utilize in vivo animal models or ex vivo RWM models which rely on cell cultures or membrane fragments. Guinea pigs serve as a validated preclinical model for the investigation of drug pharmacokinetics within the inner ear and are an important animal model for the translational development of delivery vehicles to the cochlea. In this study, we describe an approach for explantation of a guinea pig RWM with surrounding cochlear bone for benchtop drug delivery experiments. This method allows for preservation of native RWM architecture and may provide a more realistic representation of barriers to transport than current benchtop models.