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Objectives: Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case‐dependent provider treatment preferences and identify factors which impact decision‐making in EGC. Methods: This cross‐sectional survey of laryngologists, head‐and‐neck surgeons, and radiation oncologists presented five diagrammatic cases of progressively advanced EGC (T1/2, N0). Respondents indicated preference for TLMS or XRT and ranked factors which influenced their recommendation for each case. Analysis utilized descriptive statistics, Fischer's exact tests, and Kruskal–Wallis tests for nonparametric data. Results: A total of 141 complete responses (69.5% laryngologists) were received. Most respondents practiced in academic settings (93.5%) and within multidisciplinary teams (94.0%). Anterior commissure involvement was the most important a priori tumor factor for case‐independent treatment recommendation (Likert Scale: 4.22/5), followed by Laterality (Likert Scale: 4.02/5). Across all specialties, TLMS was recommended for unilateral T1a lesions. Laryngologists continued recommending TLMS in T2 lesions (41.0%) more than head‐and‐neck surgeons (5.0%) and radiation oncologists (0.0%). Across all cases, survival and voice outcomes were the most important clinical factors impacting treatment decisions. Radiation oncologists weighed voice more heavily than laryngologists in more complex presentations of EGC (rank: 1.6 vs. 2.7, Kruskall–Wallis: p < 0.05). Conclusions: In more complex clinical presentations of EGC, preference for TLMS compared to XRT differed across specialists, despite similar rankings of factors driving these treatment recommendations. This may be driven by differing experiences and viewpoints on case‐dependent voice outcomes following TLMS versus XRT, suggesting a need for increased understanding of how tumor location and depth impact voice outcomes. Level of Evidence: 5 Laryngoscope, 134:3686–3694, 2024 [ABSTRACT FROM AUTHOR]

Introduction: The round window membrane (RWM) presents a significant barrier to the local application of therapeutics to the inner ear. We demonstrate a benchtop preclinical RWM model and evaluate superparamagnetic iron oxide nanoparticles (SPIONs) as vehicles for magnetically assisted drug delivery. Methods: Guinea pig RWM explants were inset into a 3D‐printed dual chamber benchtop device. Custom‐synthesized 7‐nm iron core nanoparticles were modified with different polyethylene glycol chains to yield two sizes of SPIONs (NP‐PEG600 and NP‐PEG3000) and applied to the benchtop model with and without a magnetic field. Histologic analysis of the RWM was performed using transmission electron microscopy (TEM) and confocal microscopy. Results: Over a 4‐h period, 19.5 ± 1.9% of NP‐PEG3000 and 14.6 ± 1.9% of NP‐PEG600 were transported across the guinea pig RWM. The overall transport increased by 1.45× to 28.4 ± 5.8% and 21.0 ± 2.0%, respectively, when a magnetic field was applied. Paraformaldehyde fixation of the RWM decreased transport significantly (NP‐PEG3000: 7.6 ± 1.5%; NP‐PEG600: 7.0 ± 1.6%). Confocal and electron microscopy analysis demonstrated nanoparticle localization throughout all cellular layers and layer‐specific transport characteristics within RWM. Conclusion: The guinea pig RWM explant benchtop model allows for targeted and practical investigations of transmembrane transport in the development of nanoparticle drug delivery vehicles. The presence of a magnetic field increases SPION delivery by 45%–50% in a nanoparticle size‐ and cellular layer‐dependent manner. Level of Evidence: NA Laryngoscope, 134:3355–3362, 2024 [ABSTRACT FROM AUTHOR]

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]

Introduction: Single sided deafness (SSD) results in profound cortical reorganization that presents clinically with a significant impact on sound localization and speech comprehension. Cochlear implantation (CI) has been approved for two manufacturers' devices in the United States to restore bilateral function in SSD patients with up to 10 years of auditory deprivation. However, there is great variability in auditory performance and it remains unclear how auditory deprivation affects CI benefits within this 10-year window. This prospective study explores how measured auditory performance relates to real-world experience and device use in a cohort of SSD-CI subjects who have between 0 and 10 years of auditory deprivation. Methods: Subjects were assessed before implantation and 3-, 6-, and 12-months post-CI activation via Consonant-Nucleus-Consonant (CNC) word recognition and Arizona Biomedical Institute (AzBio) sentence recognition in varying spatial speech and noise presentations that simulate head shadow, squelch, and summation effects (S0N0, SSSDNNH, SNHNSSD; 0 = front, SSD = impacted ear, NH = normal hearing ear). Patient-centered assessments were performed using Tinnitus Handicap Inventory (THI), Spatial Hearing Questionnaire (SHQ), and Health Utility Index Mark 3 (HUI3). Device use data was acquired from manufacturer software. Further subgroup analysis was performed on data stratified by <5 years and 5-10 years duration of deafness. Results: In the SSD ear, median (IQR) CNC word scores pre-implant and at 3-, 6-, and 12-months post-implant were 0% (0-0%), 24% (8-44%), 28% (4-44%), and 18% (7-33%), respectively. At 6months post-activation, AzBio scores in S0N0 and SSSDNNH configurations (n = 25) demonstrated statistically significant increases in performance by 5% (p = 0.03) and 20% (p = 0.005), respectively. The median HUI3 score was 0.56 pre-implant, lower than scores for common conditions such as anxiety (0.68) and diabetes (0.77), and comparable to stroke (0.58). Scores improved to 0.83 (0.71-0.91) by 3 months post-activation. These audiologic and subjective benefits were observed even in patients with longer durations of deafness. Discussion: By merging CI-associated changes in objective and patient-centered measures of auditory function, our findings implicate central mechanisms of auditory compensation and adaptation critical in auditory performance after SSD-CI and quantify the extent to which they affect the real-world experience reported by individuals. [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]

Objectives: Socioeconomic factors affect oncologic outcome in sinonasal squamous cell carcinoma (SNSCC). However, the relationship between these factors and stage at presentation (SAP)—a critical, early point in the care cycle—is not known. This study sought to determine the role of race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors in SAP and survival among patients with advanced SNSCC. Study Design: Retrospective cohort study. Methods: Using the National Cancer Database, 6,155 patients with SNSCC were identified and divided into those with "early" (Stage I or II; 2,212 (35.9%)) versus "advanced" (Stage III or IV; 3,943 (64.1%)) disease. Associations between sociodemographic and socioeconomic factors on SAP and survival were analyzed using multivariable logistic regression and Cox proportional hazard models. Results: Black (odds ratio [OR]: 2.18, CI: 1.74–2.76), Asian and Pacific Islander (API) (OR: 2.37, CI: 1.43–4.14), and Medicaid or uninsured (OR: 2.04, CI: 1.66–2.53) patients were more likely to present with advanced disease. Among patients with advanced disease, API patients demonstrated the highest 10‐year survival rate (30.2%), and Black patients had the lowest 2‐, 5‐, and 10‐year survival rates (47.7%, 31.9% and 19.2%, respectively). Older age (HR:1.03, CI:1.03–1.04), Black race (HR:1.39, CI:1.21–1.59), Medicaid or uninsured status (HR:1.48, CI:1.27–1.71), and treatment at a community hospital (HR:1.25, CI:1.14–1.37) were associated with poorer overall survival among patients with advanced disease. Conclusions: Factors including race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors influence SAP and survival in SNSCC. An improved understanding of how these factors relate to outcomes may elucidate opportunities to address gaps in education and access to care in vulnerable populations. Level of Evidence: 4 Laryngoscope, 131:2421–2428, 2021 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To conduct longitudinal postoperative follow‐up and discern health‐related quality‐of‐life (HR‐QoL) changes using a validated questionnaire among patients undergoing head and neck surgeries during a short‐term, global surgical trip in a resource‐limited setting. To identify clinicodemographic predictors of post‐operative HR‐QoL improvements in this setting. Study Design: Retrospective observational study with prospective follow‐up. Methods: Patients undergoing surgery at Moi Teaching and Referral Hospital in Eldoret, Kenya through the authors' short‐term surgical trip (STST) between 2016 and 2019 were asked to complete preoperative Short Form‐36 (SF‐36) HR‐QoL questionnaires, and postoperative SF‐36 questionnaires during subsequent follow‐up. Preoperative and postoperative SF‐36 domain scores, and two composite scores (mental component summary [MCS] and physical component summary [PCS]) were compared. Linear regression models were fit to identify clinicodemographic factors predictors of general health (GH), MCS, and PCS scores. Results: Among the 26 participating patients, significant improvements were seen in post‐operative GH (mean change = 19.8) and MCS (mean change = 11.2) scores. Lower pre‐operative GH, MCS, and PCS scores were predictive of greater improvement in the corresponding post‐operative scores. Longer time to follow‐up was associated with greater improvement in GH score. Mean follow‐up interval was 23.1 months (SD = 1.8 months). Conclusions: Utilizing the SF‐36 questionnaire, we found that patients' perception of their general and psychosocial health improved after undergoing head and neck surgeries through a global STST. This study provides important, preliminary evidence that that elective surgeries performed in low‐resource settings convey substantial benefit to patient QoL. Level of Evidence: 4 Laryngoscope, 131:2006–2010, 2021 [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]

Background: Clinical follow-up after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) allows for assessment of the sinonasal cavity, debridement, and tailoring of medical therapies. Frequency and timing of postoperative clinical visits is debated, but the impact of adherence on disease-specific outcomes is not well understood. In this longitudinal study, we assessed the association between follow-up adherence and quality of life (QOL) outcomes in the 12 months after ESS. Methods: A retrospective review of patients undergoing ambulatory ESS for CRS between 11/2016 and 1/2018 was performed. We assessed sociodemographic characteristics, radiographic severity, and QOL utilizing the 22-item sinonasal outcome test (SNOT-22). Patients were categorized as "non-adherent," "moderately-adherent," and "fully-adherent" to a 1-, 3- and 5-week postoperative visit schedule. Results: A total of 166 patients met the inclusion criteria. Of these, 55 (33.1%) were fully-adherent, 105 (63.2%) were moderately-adherent, and 6 (3.6%) were non-adherent within the 6 weeks following ESS. In the immediate postoperative period, fully-adherent patients demonstrated worse QOL (SNOT-22: 31.2 ± 23.1 vs 27.5 ± 17.6, P =.047). This cohort also had greater psychological dysfunction at baseline and 12-months (P <.05) after ESS. Extra-nasal symptom scores increased at a lower rate in the fully-adherent cohort (0.12 vs 1.29 points per 6 months, P =.038), as did ear/facial symptoms (1.17 vs 3.05 points per 6 months, P =.044). Conclusion: Despite worse symptom severity in the immediate postoperative period, patients who are more adherent to the follow-up schedule demonstrated slower return of symptoms in the extra-rhinological and ear-facial domains. These findings suggest that clinical adherence and management may impact the long-term evolution of ESS outcomes. [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]

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. [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]

Background: Sinonasal squamous cell carcinoma (SNSCC) is the most common malignancy of the paranasal sinuses. Surgery is the mainstay of treatment, yet positive surgical margins (PSM) are common and the prognostic impact on overall survival (OS) is mixed. Given the heterogeneity of impact of PSM on OS within the literature, we hypothesized that extent of tumor extirpation (microscopic PSM vs macroscopic PSM) may play a role in OS. Methods: Patients with SNSCC were identified in the National Cancer Database (NCDB, n = 7808). Of these, 4543 patients underwent surgery, 3265 patients underwent nonsurgical therapy. Kaplan‐Meier curves were used to compare OS between negative surgical margin (NSM), micro‐PSM, and macro‐PSM cohorts vs patients undergoing primary nonsurgical therapy in a propensity‐score‒matched analysis. Multivariable analysis of factors associated with macro‐PSM was also performed. Results: One thousand thirty‐three (22.0%) of the surgery patients had PSM, and approximately half (n = 521, 50.6%) of these had macro‐PSM. When compared with nonsurgical treatment, propensity‐score‒matched results demonstrated improved OS in patients with NSM and micro‐PSM (p < 0.001), but macro‐PSM patients did not demonstrate improvement (p = 0.20). Tumor within the paranasal sinuses and advanced nodal classification (N2/N3) (odds ratio [OR], 1.18; p = 0.02; and OR, 15.09; p = 005, respectively) was associated with increased odds of macro‐PSM on multivariable analysis. Conclusion: We demonstrate that the degree of tumor extirpation correlates with OS. Macro‐PSM did not confer a benefit to OS when compared with nonsurgical therapy, and factors including tumor location and advanced nodal status affect whether surgery will result in macro‐PSM. Given these findings, informed, shared decisionmaking between patient and surgeon regarding nonsurgical alternatives should occur before electing to proceed with surgery in SNSCC. [ABSTRACT FROM AUTHOR]

Background: Endoscopic sinus surgery (ESS) is generally well tolerated, yet a subset of patients require an additional opiate prescription in the postoperative period. The purpose of this study was to quantify differences in both preoperative and immediate postoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores between patients with a single prescription and those requiring additional opiate prescriptions (AOPs). Methods: Patients undergoing ESS between November 2016 and August 2017 were reviewed retrospectively. The Medical and Controlled Substance Utilization Review and Evaluation System (CURES) records were reviewed; patients requiring AOP within 60 days after surgery were identified. The primary and secondary outcomes of interest were the association of baseline and first postoperative visit SNOT‐22 total and domain scores with AOP. Results: A total of 121 patients were reviewed, 22 (18.2%) required AOP. Baseline SNOT‐22 scores were higher in aggregate (58.7 ± 16.0 vs 46.1 ± 22.5) and ear/facial domain (11.4 ± 4.8 vs 8.5 ± 5.4) in the AOP group (p < 0.01). AOP patients also demonstrated higher scores across all SNOT‐22 domains (p < 0.001) at the immediate preoperative visit. There was no difference in the absolute improvement between groups (15.5 ± 18.30 vs 12.3 ± 23.9, p = 0.54). AOP patients experienced less relative improvement (20.2% vs 34.8%, p < 0.05) and smaller mean effect size (0.57 vs 0.70, p < 0.001) after ESS. Conclusion: Patients reporting increased ear and facial symptoms at baseline have an increased risk of additional opiate prescription after surgery; preoperative SNOT‐22 scores may provide utility in identifying these patients. Subjects in both cohorts report symptomatic improvement after ESS; however, relative, not absolute, improvement in SNOT‐22 scores is more predictive of AOP. [ABSTRACT FROM AUTHOR]

Background: Excessive postoperative opioid prescription is a source of prescription diversion in the United States opioid crisis and may contribute to chronic opioid use. Efficient prescription by the surgeon can mitigate opioid abuse and improve postoperative pain control. In this study we sought to better characterize the incidence and predictive baseline characteristics associated with the need for additional opioid prescription after endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Methods: A retrospective review was performed on subjects undergoing ambulatory ESS between November 2016 and August 2017. The medical and Controlled Substance Utilization Review and Evaluation System (CURES) records were reviewed. Uni‐ and multivariable logistic regressions were performed to evaluate factors associated with additional opioid prescription within 60 days of surgery. Results: A total of 121 patients were included. Additional prescriptions were seen in 22 patients (18%). Surgical factors, including sinuses operated, septoplasty, revision, or extended procedure (Draf IIB/III), were not associated with additional prescription. On multivariate logistic regression, preoperative opioid use (odds ratio [OR], 23.45; 95% CI, 1.52‐362.63), greater number of prescribed tablets (OR, 1.13; 95% CI, 1.01‐1.26), and lower preoperative health status (ASA score) (OR, 11.21; 95% CI, 1.49‐84.30) were associated with additional prescription (p < 0.05). Conclusion: A need for extension of postoperative opioid pain control is not uncommon after ESS. Patient baseline clinical characteristics are predictive of a need for re‐prescription of opioids. Surgical extent is not associated with need for prolonged postoperative opioid pain management. [ABSTRACT FROM AUTHOR]

We have previously developed a glutamine synthetase (GS)-based mammalian recombinant protein expression system that is capable of producing 5–30 mg/L recombinant proteins. The over expression is based on multiple rounds of target gene amplification driven by methionine sulfoximine (MSX), an inhibitor of glutamine synthetase. However, like other stable mammalian over expression systems, a major shortcoming of the GS-based expression system is its lengthy turn-around time, typically taking 4–6 months to produce. To shorten the construction time, we replaced the multi-round target gene amplifications with single-round in situ amplifications, thereby shortening the cell line construction to 2 months. The single-round in situ amplification method resulted in highest recombinant CD62L expressing CHO cell lines producing ∼5 mg/L soluble CD62L, similar to those derived from the multi-round amplification and selection method. In addition, we developed a MSX resistance assay as an alternative to utilizing ELISA for evaluating the expression level of stable recombinant CHO cell lines. [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.

Objective: As exclusively endoscopic endonasal resection of benign orbital tumors has become more widespread, high-quality outcomes data are lacking regarding the decision of when and how to reconstruct the medial orbital wall following resection. The goal of this study was to systematically review pertinent literature to assess clinical outcomes relative to orbital reconstruction practices., Methods: Data Sources: PubMed, EMBASE, Web of Science. A systematic review of studies reporting exclusively endoscopic endonasal resections of benign orbital tumors was conducted. Articles not reporting orbital reconstruction details were excluded. Patient and tumor characteristics, operative details, and outcomes were recorded. Variables were compared using χ 2 , Fisher's exact, and independent t tests., Results: Of 60 patients included from 24 studies, 34 (56.7%) underwent orbital reconstruction following resection. The most common types of reconstruction were pedicled flaps ( n  = 15, 44.1%) and free mucosal grafts ( n  = 11, 32.4%). Rigid reconstruction was uncommon ( n  = 3, 8.8%). Performance of orbital reconstruction was associated with preoperative vision compromise ( p  < 0.01). The tendency to forego orbital reconstruction was associated with preoperative proptosis ( p  < 0.001), larger tumor size ( p  = 0.001), and operative exposure of orbital fat ( p  < 0.001) and extraocular muscle ( p  = 0.035). There were no statistically significant differences between the reconstruction and nonreconstruction groups in terms of short- or long-term outcomes when considering all patients. In patients with intraconal tumors, however, there was a higher rate of short-term postoperative diplopia when reconstruction was foregone ( p  = 0.041). This potential benefit of reconstruction did not persist: At an average of two years postoperatively, all patients for whom reconstruction was foregone either had improved or unchanged diplopia., Conclusion: Most outcomes assessed did not appear affected by orbital reconstruction status. This general equivalence may suggest that orbital reconstruction is not a necessity in these cases or that the decision to reconstruct was well-selected by surgeons in the reported cases included in this systematic review., Competing Interests: The authors declare that there are no conflict of interests., (© 2022 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Purpose: To 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 Design: Tumor 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., Results: RNA-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., Conclusions: These 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., (©2020 American Association for Cancer Research.)