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Olfactory neuroblastoma (ON; Esthesioneuroblastoma) is a malignant tumor that arises from the olfactory neuroepithelium. Very rarely, ON can histologically display a biphenotypic pattern, with only 7 cases reported in the literature to date. We describe a case of this poorly understood entity and review the patient's histology, pathology, and treatment. An 85-year-old man presented with endoscopy and imaging findings of a sinonasal mass arising from the olfactory cleft. Biopsy and further pathological review established Hyams grade 3 and Kadish stage C tumor. The patient underwent combined endoscopic and open-approach resection due to the involvement of the nasal bone and subsequent adjuvant radiation therapy. Specimen contained Flexner-Wintersteiner rosettes and stained positive for the neuroendocrine marker synaptophysin consistent with ON. A second, epithelial component pattern of goblet cells and mucin was observed suggesting divergent differentiation. We are the first group to report next-generation sequencing of this tumor, which revealed a pathogenic mutation in PIK3CA and a likely pathogenic variant in RUNX1 (AML1). ON with divergent differentiation is very rare, and more robust studies characterizing molecular drivers and pathology may aid in clinical management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Key Points: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%., (© 2024 ARS‐AAOA, LLC.)

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures., Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient-reported outcome measures included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund-Kennedy endoscopic score (LKES)., Results: A total of 115 patients were clustered into type 2 inflammatory, non-type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT-22 (-28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between-group differences in SNOT-22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures., Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient-reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes., (© 2023 ARS‐AAOA, LLC.)

Objective: The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS)., Study Design: Cross-sectional questionnaire-based study with retrospective chart review., Setting: Tertiary Medical Center., Methods: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review., Results: Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow-up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow-up (77.3% vs 10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276)., Conclusion: Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: The purpose of this study was to investigate real-world adherence to intranasal corticosteroid irrigations using pharmacy data and assess factors associated with low adherence., Methods: Patients undergoing treatment with corticosteroid irrigations for any diagnosis during a 2-year period were prospectively recruited. Subjects completed a one-time set of questionnaires including the Barriers to Care Questionnaire (BCQ), 22-item Sino-Nasal Outcome Test (SNOT-22), and a questionnaire assessing their experience with corticosteroid irrigations. Pharmacy data was used to calculate the medication possession ratio (MPR), a measure of medication adherence graded from 0 to 1., Results: Seventy-one patients were enrolled. Patient diagnoses included chronic rhinosinusitis (CRS) without nasal polyps (n = 37), CRS with nasal polyps (n = 24), or a non-CRS diagnosis, most commonly chronic rhinitis (n = 10). The MPR for the overall group was 0.44 ± 0.33. Just 9.9% of patients had a perfect MPR of 1. Despite low MPR, only 19.7% of patients reported problems taking the medication when directly asked. Lower education resulted in lower MPR (unstandardized B = 0.065, p = 0.046). Increasing BCQ score, indicating higher barriers to care, was associated with lower MPR (unstandardized B = -0.010, p = 0.033). The lower the MPR, the worse the patient SNOT-22 scores (unstandardized B = -15.980, p = 0.036)., Conclusion: Adherence to corticosteroid irrigations was low and patients underreported issues with their medication. Education and barriers to care were associated with lower adherence, which, in turn, was associated with worse sinonasal quality of life., (© 2023 ARS-AAOA, LLC.)

Objective: Some previous studies have shown an increased prevalence of allergic fungal rhinosinusitis (AFRS) among young, black patients with poor access to health care; however, results have been mixed. The purpose of this study was to investigate the relationship between social determinants of health and AFRS., Data Sources: PubMed, Scopus, CINAHL., Review Methods: A systematic review was performed searching for articles published from date of inception to September 29, 2022. English language articles describing the relationship   between social determinants of health (i.e., race, insurance status) and AFRS as compared to chronic rhinosinusitis (CRS) were selected for inclusion. A Meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted., Results: A total of 21 articles with 1605 patients were selected for inclusion. The proportion of   black patients among AFRS, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic rhinosinusitis without nasal polyps (CRSsNP) groups was 58.0% [45.3%-70.1%], 23.8% [14.1%-35.2%], and 13.0% [5.1%-24.0%], respectively. This was significantly higher among the AFRS population compared to both the CRSwNP population (Δ34.2% [28.4%-39.6%], p < .0001) and the CRSsNP population (Δ44.9% [38.4%-50.6%], p < .0001). The proportion of patients who were either uninsured or covered by Medicaid among the AFRS, CRSwNP, and CRSsNP populations was 31.5% [25.4%-38.1%], 8.6% [0.7%-23.8%], and 5.0% [0.3%-14.8%], respectively. This was significantly higher among the AFRS group than the CRSwNP group (Δ22.9% [15.3%-31.1%], p < .0001) and the CRSsNP group (Δ26.5% [19.1%-33.4%], p < .0001)., Conclusion: This study confirms that AFRS patients are more likely to be Black and either uninsured or on subsidized insurance than their CRS counterparts., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Many studies have identified a higher degree of Olfactory Dysfunction (OD) in Black patients compared to White patients. This study aims to analyze olfactory outcomes in different races., Methods: The PubMed, Scopus, and CINAHL databases were searched from inception to September 5, 2022, for English-language articles documenting self-reported and psychophysical OD stratified by race. A meta-analysis of proportions, comparison of weighted proportions, and comparison of means were performed in MedCalc 20.218. In the quantitative analysis, 79,297 patients were included, comprising 79.3% Whites, 16.1% Blacks, and 4.6% Hispanics., Results: A total of 14 studies were meta-analyzed. The prevalence of self-reported OD in Hispanic, White, and Black patients was 19.5% (95% CI, 16.6% to 22.6%), 17.2% (95% CI, 10.5% to 25.0%), and 13.9% (95% CI, 9.3% to 19.2%), respectively (p < 0.0007). The prevalence of psychophysical OD in Black, White, and Hispanic patients was 30.3% (95% CI, 24.2% to 36.9%), 24.2% (95% CI, 20.1% to 28.5%), and 18.4% (95% CI, 16.3% to 20.7%), respectively (p < 0.0001). Blacks reported a greater extent of unrecognized OD compared to Whites, with a difference of 16.5% (95% CI, 15.0% to 17.9%) versus 5.8% (95% CI, 3.4% to 8.0%), respectively (p < 0.0001). Hispanic rates of self-reported OD and psychophysical OD were not statistically different., Conclusions: Our findings suggest that Blacks have the highest rate of psychophysical OD and are more likely to underreport their awareness compared to Whites., (© 2023 ARS-AAOA, LLC.)

Objective: To investigate novel methods of measuring intranasal trigeminal function and correlate to validated measures of trigeminal function., Study Design: Prospective cohort study., Setting: Tertiary medical center., Methods: Forty-one subjects without nasal congestion were assessed. The trigeminal temperature function of the cool/warmth detection threshold and cold/heat pain threshold was measured with the Thermal Sensory Analyzer (TSA) device, as previously validated at buccal mucosa and infraorbital skin. Identical temperature sensory function was assessed at the anterior septum and inferior turbinate. Lateralization of trigeminal odorants eucalyptol, isothiocyanate, and acetic acid was conducted. Visual analog scales (VAS) of trigeminal function were collected., Results: Extraoral cheek site and oral site thermal measures were moderately correlated, suggesting consistent assessment of trigeminal function. Nearly all intranasal thermal measures correlated between the septum and turbinate (significant correlations [ρ] ranged from .3 to .8). Oral and extraoral cheek sites had modest correlations to intranasal cold and heat pain (ρ = .4-.5). The oral site had modest correlations of cold and heat detection to intranasal sites, with turbinate appearing to have the most correlations. Isothiocyanate lateralization was the most closely correlated to intranasal thermal scores for cold and heat pain. Turbinate thermal measures had weak correlations with trigeminal VAS scores (ρ = .3-.4)., Conclusion: Intranasal trigeminal measures of thermal function correlate to validated extraoral and intraoral thermal measures. The turbinate appears to have stronger correlations to the septum than found in the mouth and face. TSA testing might provide a rapid, novel method of intranasal trigeminal function assessment., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives  Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design  Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results  The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion  Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) is a chronic inflammatory condition with significant patient morbidity and associated healthcare costs. While the economic burden of CRS overall has been previously described, the economic impact of CRSwNP has received less attention. Patients with CRSwNP have higher disease burden and healthcare resource utilization than those with CRS without nasal polyposis. Rapid evolution of medical management in recent years with the use of targeted biologics warrants further investigation into the economic burden of CRSwNP., Objective: Provide an updated review of the literature on the economic impact of CRSwNP., Methods: A literature review., Results: Research shows that patients with CRSwNP have higher direct costs and usage of ambulatory services compared to matched non-CRS controls. Patients undergoing functional endoscopic sinus surgery (FESS) incur roughly $13,000 in costs which is particularly relevant given the rate of disease recidivism and need for revision surgery associated with CRSwNP. Disease burden additionally leads to indirect costs through loss of wages and productivity due to work absenteeism and presenteeism, with estimates of up to roughly $10,000 lost in mean annual productivity cost in refractory CRSwNP. Several studies have shown FESS to be more cost-effective in intermediate and long-term management than medical therapy with biologics, despite similar long-term outcomes with respect to quality-of-life metrics., Conclusion: CRSwNP is a chronic condition with high recurrence rates making it a challenge to manage over time. Current research suggests that FESS is more cost-effective than medical management, including use of newer biologics. Further investigation into both direct and indirect costs associated with medical management is warranted to perform accurate cost-effectiveness analyses and allow for the best allocation of limited healthcare resources.

Background: Inflammatory patterns in chronic rhinosinusitis (CRS) may predict disease severity, need for multiple sinus surgeries, and treatment response. This study analyzes nasal mucus inflammatory cytokine patterns in patients with (CRSwNP) and without (CRSsNP) nasal polyposis and their association with revision sinus surgery., Methods: A total of 319 CRS patients who underwent sinus surgery were included. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Cytokine expression patterns in patients with 0, 1, and ≥2 previous surgeries were analyzed using Kruskal-Wallis and principal component (PC) regression analyses., Results: There were 122 (38%) patients with CRSsNP and 197 (62%) with CRSwNP. On univariate analysis, interleukin (IL)-1β, IL-6, IL-8, and IL-21 were associated with increasing number of sinus surgeries in CRSsNP, as were IL-2, IL-4, IL-5, IL-6, IL-9, IL-17A, and tumor necrosis factor (TNF)-α in CRSwNP. PC analysis with continuous Poisson regression in CRSwNP demonstrated that high IL-5 and IL-13 and low IL-1β, IL-12, and IL-21 were associated with more prior surgeries. In CRSsNP low IL-13 and high IL-5 and regulated-on-activation, normal T-cell-expressed and secreted (RANTES) were associated with more prior surgeries. Age remained a significant covariate in the full regression model for CRSsNP, but was nonsignificant in CRSwNP., Conclusion: In CRSwNP, elevated IL-5 and IL-13 levels were higher at time of surgery in patients with more prior surgeries. Type 2 cytokines in CRSsNP demonstrated mixed associations with revision surgery. For both phenotypes, IL-10, IL-12, and IL-21 were consistently lower as number of prior surgeries increased, suggesting that treatment-resistant disease may be modulated by impairment in these signaling pathways., (© 2022 ARS-AAOA, LLC.)

Sinonasal small cell neuroendocrine carcinoma (SNEC) is an extremely rare and aggressive neoplasm that can arise in the sinonasal region. These tumors are associated with high morbidity and mortality, are difficult to diagnose, and are hard to treat. We describe 2 cases of this poorly understood malignancy and review imaging, pathology, and treatment decisions. A 41-year-old male and a 64-year-old female presented to a tertiary center in 2019 after developing nasal obstruction and were found to have sinonasal masses on imaging. Both biopsies showed strong expression of pancytokeratin with dot-like reactivity and expression of neuroendocrine markers chromogranin and synaptophysin. The findings were diagnostic of SNEC. Staging positron emission tomography/computed tomography and brain MRI were performed, and patients were discussed at a multidisciplinary tumor board. Neither had distant metastatic disease at presentation. One patient had no intracranial or orbital disease and underwent a subtotal endoscopic resection with adjuvant chemoradiation. The other patient demonstrated middle cranial fossa, dural, and orbital involvement as well as cranial nerve V palsy. This patient was treated with induction chemotherapy, followed by concurrent chemoradiation. Both patients are presently alive at 4 months follow-up, but one with persistent local disease and the other distant metastasis. Sinonasal small cell neuroendocrine carcinoma is a rare and poorly understood malignancy with an aggressive clinical course. Continued careful review of pathology and study of molecular features are needed for improved understanding of SNEC, and particularly for head and neck SNEC, to establish a staging system and better formulate treatment protocols.

Chronic rhinosinusitis is characterized by persistent locoregional mucosal inflammation of the paranasal sinuses and upper airway that has substantial associated health care costs. Personalized approaches to care that incorporate use of molecular biomarkers, phenotypes, and inflammatory endotypes is a major focus of research at this time, and the concurrent rise of targeted therapeutics and biologic therapies has the potential to rapidly advance care and improve outcomes. Recent findings suggest that improved understanding of chronic rhinosinusitis phenotypic and endotypic heterogeneity, and incorporation of these characteristics into clinical care pathways, may facilitate more effective selection of surgical and/or therapeutic interventions. Ultimately, these personalized approaches have the potential to target specific inflammatory pathways, increase efficacy, reduce costs, and limit side effects. This review summarizes recent advances in the identification and characterization of chronic rhinosinusitis phenotypes, endotypes, and biomarkers and reviews potential implications for targeted therapeutics., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Neuroendocrine tumors of the head and neck are rare and arise either from epithelial or neuronal origin. Debate continues over the classification systems and appropriate management of these pathologies., Objective: By investigating a small set of cases of high grade epithelial-derived neuroendocrine tumors of the head and neck (neuroendocrine carcinomas or NEC) from one institution, we compare survival rates of NEC of the head and neck to pulmonary NEC., Methods: We identified patients from pathology records with neuroendocrine carcinomas of the head and neck and retrospectively collected clinical data as well as immunohistochemical (IHC) staining data., Results: We identified 14 patients with NEC, arising from the parotid (n = 5), nasal cavity (n = 4), larynx (n = 2), and other regions (n = 2). One additional patient had NEC arising in two sites simultaneously (parotid and nasal). Staining patterns using IHC were relatively consistent across specimens, showing reactivity to chromogranin and synaptophysin in 73% and 100% of specimens, respectively. Treatment courses varied across patients and included combinations of surgery, chemotherapy, and/or radiation. The overall survival rate at 1, 2, and 5 years of these patients was 56%, 56%, and 43% with a mean follow-up time of 2.12 years., Conclusion: Compared to NEC arising in the lung, this subset of patients had better survival rates, but worse survival rates than the more common squamous cell carcinoma of the head and neck., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Recent advances in molecular biology have enabled the identification of potential inflammatory endotypes of chronic rhinosinusitis (CRS), with prior work suggesting differential short-term surgical outcome trajectories based on cytokine signatures. However, there is a paucity of data assessing long-term treatment failure and need for revision surgery based on inflammatory biomarkers., Methods: Retrospective analysis of prospectively collected cross-sectional data from 231 patients electing surgical therapy for CRS. Intraoperative mucus specimens were quantitatively sampled for inflammatory cytokines using a multiplex flow cytometric bead assay. Univariate Spearman correlations between cytokine levels and prior number of surgeries were assessed. A stepwise adjusted multivariate Poisson regression analysis was used to model patient-reported prior sinus surgery counts as a function of cytokine levels., Results: Several cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, tumor necrosis factor α [TNF-α], interferon γ [IFN-γ], and eotaxin) demonstrated significant positive correlations with number of prior surgeries. However, only higher IL-17A levels were independently associated with a higher number of prior sinus surgeries (β = 0.345, p = 0.0003) after adjusting for the significant covariates of age (β = 0.018, p = 0.0036), Lund-Mackay score (β = -0.046, p = 0.02), history of aspirin-exacerbated respiratory disease (β = 1.01, p < 0.0001) and allergic fungal rhinosinusitis (β = 1.08, p < 0.0001). Higher levels of regulated on activation, normal T-cell expressed and secreted (RANTES) were conversely associated with a lower number of prior surgeries (β = -0.17, p = 0.048)., Conclusion: An IL-17A-predominant cytokine profile is linked to an increased number of prior sinus surgeries. Thus, type 3 inflammatory markers may indicate a particularly difficult-to-treat, recalcitrant CRS endotype., (© 2020 ARS-AAOA, LLC.)

Background: Sinonasal teratocarcinosarcoma (SNTCS) is a rare malignancy of the anterior skull base with only 127 cases described in the English literature. Given the rarity of this tumor, new cases and analysis of published reports may assist in future management of SNTCS., Objectives: 1) Describe findings from a systematic review of all available literature for malignant SNTCS including the clinical presentation, treatment modalities and outcomes. 2) Present two new cases of this rare anterior skull base tumor. 3) Compare treatment outcomes with respect to recurrence and mortality., Methods: A systematic review of all English literature available in 2 comprehensive databases was conducted by two independent reviewers using PRISMA guidelines. 85 publications were identified. Each case was reviewed for demographics, treatment and survival, and aggregate treatment outcomes were compared using Kaplan-Meier analysis., Results: A total of 64 articles meeting inclusion criteria were reported in the literature between 1977-2018. This represented a total of 127 patients, with a strong male predominance (83%) and mean age of 50 years (range 10-82). Mean follow-up was 21 months. Recurrence rate was 38%, with mean survival at 2 years of 55%. Almost all patients underwent surgery as a primary treatment modality (90%). The majority of cases were treated with multimodal therapy, with 55% receiving surgery and radiation and 20% receiving surgery with adjuvant chemoradiation. Kaplan-Meier analysis demonstrated a significant survival advantage for patients treated with combined therapy compared to surgery alone (p < 0.001) but did not show differences in recurrence (p = 0.085)., Conclusion: Two-year survival rates for SNTCS are 55%. Multimodality treatment outcomes appear to be superior to surgery alone based on the published data of this rare skull base tumor, although heterogeneity of treatment methods and reporting bias limits the generalizability of these findings.

Obtaining postoperative images of maxillofacial fractures does not affect the clinical management of asymptomatic patients; however, few studies have evaluated the role of postoperative imaging in the context of orbital floor fractures. In this study, we evaluate current practice techniques and the role of postoperative imaging in the management of orbital floor fractures in isolation and with concomitant facial fractures. Retrospective review of patients who underwent open reduction and internal fixation of orbital floor fractures between 2005 and 2015 at a single medical institution. Operative and perioperative records were reviewed to characterize postoperative imaging as routine or as indicated by concerning clinical symptoms, and to correlate clinical outcomes to postoperative imaging patterns across all identified orbital floor fractures. A total of 139 patients underwent open reduction and internal fixation of orbital floor fractures. Of these, 75 (54%) had zygomaticomaxillary (ZMC) involvement. The remaining 64 (46%) were isolated orbital floor fractures. Overall, 54 (39%) patients underwent postoperative imaging. Of these, 38 (70%) had postoperative imaging in the absence of concerning clinical symptoms. There was no observed difference in complication rates in those who underwent postoperative imaging, and those who did not. Patients with orbital + ZMC fractures underwent a significantly higher number of postoperative imaging studies ( p  < 0.001); however, there was no observed difference in complications between isolated orbital and orbital + ZMC fractures. Routine postoperative imaging is not warranted in the absence of persistent clinical symptoms following open reduction and internal fixation of orbital floor fractures.

Objective: Optical spectroscopy offers a noninvasive alternative to biopsy as a first-line screening tool for suspicious skin lesions. This study sought to define several optical parameters across malignant and benign tissue types., Study Design: Prospective pilot trial utilizing the Zenalux IM1 optical spectroscopy device from April 2016 to February 2017. For each skin lesion, provider pre-biopsy probability of malignancy was compared to histolopathologic diagnosis. Optical data were characterized across basal cell carcinoma (BCC; n = 9), squamous cell carcinoma (SCC; n = 5), actinic keratosis (AK; n = 4), scar tissue (n = 6), nevus (n = 2), and neurofibroma (NF; n = 1). Across all patients, agreement was determined between control measurements collected adjacent to the lesion and from the upper extremity., Methods: Prospective single center pilot study. The optical properties of 27 cutaneous lesions were collected from 18 adult patients presenting to Otolaryngology and Dermatology clinics with suspicious skin lesions warranting biopsy. Spectroscopy measurements were recorded for each lesion: two at the lesion site, two at an adjacent site (internal control), and one at the central medial upper extremity (arm control). Variables of interest included absolute oxygenated hemoglobin (Hb), Hb saturation, total Hb concentration, and Eumelanin concentration. For each lesion, internal control averages were subtracted from lesion averages to provide delta parameter values, and lesion averages were divided by internal control averages to provide ratio parameter values., Results: Mean percent difference between pre-biopsy probability of malignancy and histology was 29%, with a difference of 75% or greater seen in 5 of 25 lesions. Mean values for BCC, SCC, AK, and scar tissue varied most between extracted mean reduced scatter estimate (μa'; cm - ) delta values (BCC: -2.2 ± 3.8; SCC: -3.9 ± 2.0; AK: -3.3 ± 4.2, Scar: -1.7 ± 1.2) and total Hb (µM) ratio (BCC: 2.0 ± 3.3; SCC: 3.0 ± 1.3; AK: 1.1 ± 0.6; Scar: 1.4 ± 1.1). Agreement between local and arm controls was poor., Conclusion: This pilot trial utilizes optical spectroscopy as a noninvasive method for determining cutaneous lesion histology. Effect sizes observed across optical parameters for benign and malignant tissue types will guide larger prospective studies that may ultimately lead to prediction of lesional histology without need for invasive biopsy. Lasers Surg. Med. 50:246-252, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

The aim of this article is to determine hearing and mortality outcomes following temporal bone fractures. Retrospective chart review was performed of 152 patients diagnosed with a temporal bone fracture presenting to the emergency room at a tertiary care referral center over a 10-year period. Utilizing Patients' previously obtained temporal bone computed tomographic scans and audiograms, fractures were classified based on several classification schemes. Correlations between fracture patterns, mortality, and hearing outcomes were analyzed using χ 2 tests. Ossicular chain disruption was seen in 11.8% of patients, and otic capsule violation was seen in 5.9%; 22.7% of patients presented for audiologic follow-up. Seventeen patients with conductive hearing loss had air-bone gaps of 26 ± 7.5 dB (500 Hz), 27 ± 6.8 dB (1,000 Hz), 18 ± 6.2 dB (2,000 Hz), and 32 ± 7.7 dB (4,000 Hz). Two cases of profound sensorineural hearing loss were associated with otic capsule violation. No fracture classification scheme was predictive of hearing loss, although longitudinal fractures were statistically associated with ossicular chain disruption ( p  < 0.01). Temporal bone fractures in patients older than 60 years carried a relative risk of death of 3.15 compared with those younger than 60 years. The average magnitude of conductive hearing loss resulting from temporal bone fracture ranged from 18 to 32 dB in this cohort. Classification of fracture type was not predictive of hearing loss, despite the statistical association between ossicular chain disruption and longitudinal fractures. This finding may be due to the low follow-up rates of this patient population. Physicians should make a concerted effort to ensure that audiological monitoring is executed to prevent and manage long-term hearing impairment.

Background: Tumor necrosis factor alpha (TNF-α) inhibitors have revolutionized treatment of many inflammatory diseases. Sinusitis after initiation of TNF-α inhibitors has been observed, but has not been well described in the literature. We aim to characterize the clinical features of sinusitis in patients on anti-TNF-α therapy., Methods: This is a retrospective chart review of 28 patients on a TNF-α inhibitor diagnosed with sinusitis by otolaryngologists at Duke University. Patient demographics, sinusitis characteristics, and treatment course were studied by chart review., Results: The prevalence of sinusitis diagnosed and treated by an otolaryngologist was less than 1%. Of the 28 patients studied, 12 (42.9%) had a history of preexisting sinusitis and 16 (57.1%) had new-onset sinusitis. 71.4% were diagnosed with chronic rhinosinusitis without polyps (CRSsNP), with disease mainly involving the maxillary and ethmoid sinuses. No patients had major extrasinus complications or required hospital admission or intravenous (IV) antibiotics. 35.7% (n = 10), including 44% (7/16) of new-onset patients required a surgical intervention after initiating anti-TNF therapy. 14.3% (n = 4) of the cohort had improvement in sinonasal symptoms after stopping, changing, or holding doses of the TNF-α inhibitor., Conclusion: Anti-TNF-α therapy can be associated with new-onset sinusitis, mainly CRSsNP. Overall, the percentage of patients on a TNF-α inhibitor seeking consultation from an otolaryngologist is low. While some patients with new-onset sinusitis will require surgery, modification of anti-TNF-α therapy should be considered as an option in the medical management of these patients., (© 2016 ARS-AAOA, LLC.)

Objectives (1) Describe national patterns of chronic rhinosinusitis (CRS) care across academic and community practices. (2) Determine the prevalence of comorbid disorders in CRS patients, including nasal polyposis, allergic rhinitis, asthma, and cystic fibrosis. (3) Identify demographic, clinical, and practice type factors associated with endoscopic sinus surgery (ESS). Study Design Multisite cross-sectional study. Setting Otolaryngology's national research network CHEER (Creating Healthcare Excellence through Education and Research). Subjects and Methods A total of 17,828 adult patients with CRS were identified, of which 10,434 were seen at community practices (59%, n = 8 sites) and 7394 at academic practices (41%, n = 10 sites). Multivariate logistic regression was used to evaluate the association between demographic, practice type, and clinical factors and the odds of a patient undergoing ESS. Results The average age was 50.4 years; 59.5% of patients were female; and 88.3% were Caucasian. The prevalence of comorbid diseases was as follows: allergic rhinitis (35.1%), nasal polyposis (13.3%), asthma (4.4%), and cystic fibrosis (0.2%). In addition, 24.8% of patients at academic centers underwent ESS, as compared with 12.3% at community sites. In multivariate analyses, nasal polyposis (odds ratio [OR], 4.28), cystic fibrosis (OR, 2.42), and academic site type (OR, 1.86) were associated with ESS ( P < .001), while adjusting for other factors. Conclusions We describe practice patterns of CRS care, as well as demographic and clinical factors associated with ESS. This is the first study of practice patterns in CRS utilizing the CHEER network and may be used to guide future research.

Background: The retroantral ethmoid cell (RAEC) is defined as a posterior ethmoid cell that pneumatizes inferolaterally behind the posterior wall of the maxillary sinus. The RAEC can present a challenge to otolaryngologists during endoscopic ethmoidectomy due to its concealed location. It is also encountered during the endoscopic transpterygoid approach to the skull base, which requires dissection behind the posterior wall of the maxillary sinus. Because the RAEC is not described in the literature, this study aims to better characterize this anatomic variant., Methods: This is a retrospective review of 58 consecutive patients who underwent revision functional endoscopic sinus surgery (FESS) within a 2-year period at a tertiary referral center. Sinus computed tomography (CT) scans for this cohort (116 sides total) were reviewed independently by 3 authors to determine the incidence of the RAEC and the degree of surgical dissection during prior surgery., Results: Of the 116 sides included in the study, RAEC was identified in 19 (16%). Furthermore, 14 of 19 (74%) cells were diseased with evidence mucosal thickening or neo-osteogenesis. Of the 12 sides with RAEC that had evidence of previous posterior ethmoidectomy, 4 (33%) cells were not opened, 6 (50%) were partially opened, and only 2 (17%) were completely opened., Conclusion: This study demonstrates the relatively high prevalence of the RAEC in our patient population. The majority of RAECs showed both evidence of disease and that they were not completely opened during previous surgery. Recognition of this anatomic entity may allow for more thorough ethmoidectomy., Competing Interests: The authors have no conflicts of interests, financial or otherwise to disclose., (© 2016 ARS-AAOA, LLC.)

Objectives/hypothesis: To analyze cost and compare cholesteatoma recidivism and hearing outcomes with single-stage and second-look operative strategies., Study Design: Retrospective review and cost analysis., Methods: Adult and pediatric patients who underwent a tympanoplasty with mastoidectomy for cholesteatoma with a single-stage or second-look operative strategy were identified. Variables included procedure approach, residual or recurrent cholesteatoma, ossicular chain reconstruction frequency, and operative complications. Audiologic outcomes included pre-/postoperative air bone gap (ABG) and word recognition score (WRS). Cost analysis included charges for consultation and follow-up visits, surgical procedures, computed tomography temporal bone scans, and audiology visits., Results: One hundred and six patients had a tympanoplasty with mastoidectomy for cholesteatoma, with 80 canal wall-up procedures (CWU) as initial approach. Of these, 46 (57.5%) CWU patients had a planned second look. Two (4.3%) CWU patients had recurrent cholesteatoma and 20 (43.4%) had residual identified at second look. Four (11.7%) single-stage CWU strategy patients developed recurrent cholesteatoma. There was no significant difference in pre-/postoperative ABG and WRS between second look and single stage (P > 0.05). Compared to second-look patients, single-stage patients had significantly fewer postoperative visits (6.32 vs. 10.4; P = 0.007), and significantly lower overall charges for care ($23,529. vs. $41.411; P < 0.0001)., Conclusion: The goal of cholesteatoma surgery is to produce a safe ear, and a second-look strategy after CWU has historically been used to evaluate for recurrent or residual disease. The cholesteatoma recurrence rate at a second look after a CWU tympanoplasty-mastoidectomy is low. Costs of operative procedures are a significant proportion of healthcare resource expenditures. Considering the low rate of cholesteatoma recurrence and relatively high cost of care, implementation of a second-look strategy should be individually tailored and not universally performed., Level of Evidence: 4. Laryngoscope, 126:2574-2579, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Calcific aortic valve (AoV) disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. Enhanced cell-cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. Cadherin-11 (Cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. This study aims to elucidate the specific functions of Cad-11 and its downstream targets, RhoA and Sox9, in extracellular matrix remodeling and AoV calcification., Approach and Results: We conditionally overexpressed Cad-11 in murine heart valves using a novel double-transgenic Nfatc1(Cre);R26-Cad11(TglTg) mouse model. These mice developed hemodynamically significant aortic stenosis with prominent calcific lesions in the AoV leaflets. Cad-11 overexpression upregulated downstream targets, RhoA and Sox9, in the valve interstitial cells, causing calcification and extensive pathogenic extracellular matrix remodeling. AoV interstitial cells overexpressing Cad-11 in an osteogenic environment in vitro rapidly form calcific nodules analogous to in vivo lesions. Molecular analyses revealed upregulation of osteoblastic and myofibroblastic markers. Treatment with a Rho-associated protein kinase inhibitor attenuated nodule formation, further supporting that Cad-11-driven calcification acts through the small GTPase RhoA/Rho-associated protein kinase signaling pathway., Conclusions: This study identifies one of the underlying molecular mechanisms of heart valve calcification and demonstrates that overexpression of Cad-11 upregulates RhoA and Sox9 to induce calcification and extracellular matrix remodeling in adult AoV pathogenesis. The findings provide a potential molecular target for clinical treatment., (© 2016 American Heart Association, Inc.)

Objectives: (1) Compare postoperative bleeding in the CHEER network (Creating Healthcare Excellence through Education and Research) among age groups, diagnoses, and practice types. (2) Report the incidence of bleeding by individual CHEER practice site based on practice guidelines., Study Design: Retrospective data collection database review of the CHEER network based on ICD-9 and CPT codes related to tonsillectomy patients., Setting: Multisite practice-based network., Subjects and Methods: A total of 8347 subjects underwent tonsillectomy as determined by procedure code within the retrospective data collection database, and 107 had postoperative hemorrhage. These subjects had demographic information and related diagnoses based on the CPT and ICD-9 codes collected. Postoperative ICD-9 and CPT codes were used to identify patients who also had postoperative bleed. Variables included age (<12 vs ≥12 years), diagnoses (infectious vs noninfectious), and practice type (community vs academic). Statistical analysis included multivariate logistic regression variables predictive of postoperative bleeding, with P < .05 considered significant., Results: Thirteen sites contributed data to the study (7 academic, 6 community). There was postoperative bleeding for an overall bleed rate of 1.3%. Patients ≥12 years old had a significantly increased bleed rate when compared with the younger group (odds ratio, 5.98; 95% confidence interval: 3.79-9.44; P < .0001). There was no significant difference in bleed rates when practices or diagnoses were compared., Conclusion: A site descriptor database built to expedite clinical research can be used for practice assessment and quality improvement. These data were also useful to identify patient risk factors for posttonsillectomy bleed., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objectives: (1) Describe thyroid-related diagnoses and procedures in Creating Healthcare Excellence through Education and Research (CHEER) across academic and community sites. (2) Compare management of malignant thyroid disease across these sites. (3) Provide practice-based data related to flexible laryngoscopy vocal fold assessment before and after thyroid surgery based on the American Academy of Otolaryngology-Head and Neck Surgery Foundation's clinical practice guidelines., Study Design: Review of retrospective data collection (RDC) database of the CHEER network using ICD-9 and CPT codes related to thyroid conditions., Setting: Multisite practice-based network., Subjects and Methods: There were 3807 thyroid patients (1392 malignant, 2415 benign) with 10,160 unique visits identified from 1 year of patient data in the RDC. Analysis was performed for identified cohort of patients using demographics, site characteristics, and diagnostic and procedural distribution., Results: Mean number of patients with thyroid disease per site was 238 (range, 23-715). In community practices, 19% of patients with thyroid disease had cancer versus 45% in the academic setting (P < .001). While academic sites manage more cancer patients, community sites are also surgically treating thyroid cancer and performed more procedures per cancer patient (4.2 vs 3.5, P < .001). Vocal fold function was assessed by flexible laryngoscopy in 34.0% of preoperative patients and in 3.7% postoperatively., Conclusion: This is the first overview of malignant and benign thyroid disease through CHEER. It shows how the RDC can be used alone and with national guidelines to inform of clinical practice patterns in academic and community sites. This demonstrates the potential for future thyroid-related studies utilizing the otolaryngology-head and neck surgery practice-based research network., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objective. We aim to describe the first case in the literature of allergic fungal sinusitis (AFS) presenting with hyperprolactinemia due to compression of the pituitary gland. Case Presentation. A 37-year-old female presented with bilateral galactorrhea and occipital headaches of several weeks. Workup revealed elevated prolactin of 94.4, negative pregnancy test, and normal thyroid function. MRI and CT demonstrated a 5.0 × 2.7 × 2.5 cm heterogeneous expansile mass in the right sphenoid sinus with no pituitary adenoma as originally suspected. Patient was placed on cabergoline for symptomatic control until definitive treatment. Results. The patient underwent right endoscopic sphenoidotomy, which revealed nasal polyps and fungal debris in the sphenoid sinus, consistent with AFS. There was bony erosion of the sella and clivus. Pathology and microbiology were consistent with allergic fungal sinusitis caused by Curvularia species. Prolactin levels normalized four weeks after surgery with resolution of symptoms. Conclusion. Functional endoscopic sinus surgery alone was able to reverse the patient's pituitary dysfunction. To our knowledge, this is the first case of AFS presenting as hyperprolactinemia due to pituitary compression.

Laryngeal cysts are relatively rare benign lesions of the larynx. Congenital cysts can cause neonatal respiratory distress and death, but airway obstruction due to acquired cysts in adults is rare. We present a case report of 51-year-old male with dysphagia who was found to have a mobile pedunculated epiglottic cyst that intermittently caused partial obstruction of the laryngeal inlet. Patient was taken to operating room and following transoral fiberoptic intubation, endoscopic excision of this cyst was accomplished. Patient's postoperative course was uneventful., (Published by Elsevier Inc.)

Objective: To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells., Background: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC., Methods: Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing., Results: Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples., Conclusions: This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.