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Background: The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small‐molecule Akt activator SC79 induces nasal cell NO production and suppresses IL‐8 via the transcription factor Nrf‐2. We hypothesized that SC79 NO production may additionally have antibacterial effects. Methods: NO production was measured using fluorescent dye DAF‐FM. We tested effects of SC79 during co‐culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live–dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79‐induced NO production and tested dependence on Akt. Results: SC79 induced dose‐dependent, Akt‐dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h. Conclusions: Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small‐molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies. [ABSTRACT FROM AUTHOR]

Background: Inadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS. Methods: This was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed. Results: Of 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by −21.5 and −21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade. Conclusion: Over 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition. [ABSTRACT FROM AUTHOR]

Background After sinus surgery, patients are commonly instructed to irrigate with saline irrigations with their heads over a sink and noses directed inferiorly (nose-to-floor). Although irrigations can penetrate the sinuses in this head position, no study has assessed whether sphenoid sinus penetration can be improved by irrigating with the nose directed superiorly (nose-to-ceiling). The purpose of this study was to use a validated computational fluid dynamics (CFD) model of sinus irrigations to assess the difference in sphenoid sinus delivery of irrigations after irrigating in a nose-to-floor vs nose-to-ceiling head position. Methods Bilateral maxillary antrostomies, total ethmoidectomies, wide sphenoidotomies, and a Draf III frontal sinusotomy were performed on a single fresh cadaver head. CFD models were created from postoperative computed tomography maxillofacial scans. CFD modeling software was used to simulate a 120-mL irrigation to the left nasal cavity with the following parameters: flow rate 30 mL/second, angle of irrigation 20 degrees to the nasal floor, and either nose-to-floor or nose-to-ceiling head positioning. Results In the postoperative CFD models, the sphenoid sinuses were completely penetrated by the irrigation while in a nose-to-ceiling head position. However, no sphenoid sinus penetration occurred in the nose-to-floor position. Other sinuses were similarly penetrated in both head positions, although the ipsilateral maxillary sinus was less penetrated in the nose-to-ceiling position. Conclusion CFD modeling demonstrated that the nose-to-ceiling head position was superior to the nose-to-floor position in delivering a 120-mL irrigation to the sphenoid sinuses. [ABSTRACT FROM AUTHOR]

Background Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS). Methods This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed. Results Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences. Conclusion Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome. [ABSTRACT FROM AUTHOR]

Key points: We created a LangChain/OpenAI API‐powered chatbot based solely on International Consensus Statement of Allergy and Rhinology: Rhinosinusitis (ICAR‐RS).The ICAR‐RS chatbot is able to provide direct and actionable recommendations.Utilization of consensus statements provides an opportunity for AI applications in healthcare. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22‐item Sinonasal Outcomes Test (SNOT‐22) has been shown to improve with treatment. This study aims to characterize SNOT‐22 subdomain outcomes in SNM.Patients diagnosed with SNM were prospectively enrolled in a multi‐center patient registry. SNOT‐22 scores were collected at the time of diagnosis and through the post‐treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT‐22 subdomains.Note that 234 patients were reviewed, with a mean follow‐up of 22 months (3 months–64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow‐up at all timepoints showed statistically significant improvement in rhinologic, extra‐nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69–8.66])), extra‐nasal (2.21 [0.22–4.17]) and ear/facial (5.53 [2.10–8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54–5.93]) and ear/facial (2.97 [0.32–5.65]) subdomains. Positive margins (5.74 [2.17–9.29]) and surgical approach—combined versus endoscopic (3.41 [0.78–6.05])—were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18–4.40]) was associated with worse sleep outcomes.Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra‐nasal, psychological, and sleep subdomains. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) are adverse effects after surgery, which may increase the risk of complications. Aprepitant is a neurokinin‐1 receptor blocker and has been shown to reduce chemotherapy‐related nausea and vomiting and PONV. However, its role in endoscopic skull base surgery remains unclear. The purpose of this study was to evaluate the effect of aprepitant in reducing PONV in endoscopic transsphenoidal (TSA) pituitary surgery. Methods: A retrospective chart review between July 2021 and January 2023 of 127 consecutive patients who underwent TSA was performed at a tertiary academic institution. Patients were divided into 2 groups based on preoperative aprepitant use. Two groups were matched based on known risk factors of PONV (age, sex, nonsmoking, and history of PONV). The primary outcome was the incidence of PONV. Secondary outcome measures included the number of anti‐emetic use, length of stay, and postoperative cererebrospinal fluid (CSF) leak. Results: After matching, 48 patients were included in each group. The aprepitant group demonstrated a significantly lower incidence of vomiting than the non‐aprepitant group (2.1% vs 22.9%, p = 0.002). The number of nausea episodes and anti‐emetic use decreased with aprepitant use (p < 0.05). There was no difference in the incidence of nausea, length of stay, or postoperative CSF leak. Multivariate analysis demonstrated that aprepitant decreased the incidence of postoperative vomiting with odds ratio of 0.107. Conclusion: Aprepitant may serve as a useful preoperative treatment to reduce PONV in patients undergoing TSA. Further studies are needed to evaluate its impact in other arenas of endoscopic skull base surgery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). Methods: This was a multi‐institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan‐Meier tests were used to evaluate disease‐free survival (DFS), overall survival (OS), and post‐recurrence survival (PRS) reported with standard errors (SE) and log‐rank testing used for comparison. Cox‐regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. Results: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60‐month DFS (SE) was 15.5% (2.9%), 60‐month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60‐month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60‐month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12‐month PRS (HR = 0.32, 95% CI = 0.11–0.92, p = 0.034), and no treatment group was associated with improved 24‐ or 60‐month PRS (p > 0.05). Conclusion: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12‐month PRS. [ABSTRACT FROM AUTHOR]

Introduction: Inverted papilloma (IP) is a sinonasal tumor with a well‐known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma. Methods: To determine the HPV‐specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP‐associated squamous cell carcinoma (IPSCC). Paired with next‐generation sequencing, 48 types of HPV with 857 region‐specific probes were interrogated against the tumors. Results: The prevalence of HPV‐16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV‐18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region‐specific analysis, which identified the only oncogenic HPV‐18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV‐18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC. Conclusions: There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high‐risk. Our study demonstrated a trend of increasing prevalence of HPV‐18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP. [ABSTRACT FROM AUTHOR]

This article discusses the long-term effects of aspirin desensitization on the inflammatory response in patients with aspirin-exacerbated respiratory disease (AERD). The study found that after long-term aspirin desensitization, there were significant increases in interferon-gamma (IFN-γ) and interleukin-10 (IL-10), suggesting a shift in the inflammatory response. These cytokines are associated with immune tolerance and may play a role in the mechanism of aspirin desensitization. However, the specific cells producing these cytokines and the role of lipid mediators in aspirin desensitization were not addressed in this study. Further research is needed to understand the cellular context and mechanisms associated with these cytokine shifts. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Methods: Data from 1252 adult CRS patients electing to undergo ESS (2007‐2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT‐22 scores at 0, 3, and 6 months after surgery. Changes in SNOT‐22 scores were analyzed using a mixed models analysis. Results: After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre‐ESS SNOT‐22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT‐22 scores declined by 20.7 points at 3 months post‐ESS and 16.1 points at 6 months post‐ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post‐ESS (p = 0.7952 and p = 0.1057, respectively). Conclusion: Both age groups showed significant and durable improvement in SNOT‐22 scores after ESS. Patients younger than 50 years of age have higher pre‐ESS SNOT‐22 scores, but converge to the same SNOT‐22 scores by 3 months post‐ESS. The rate of change of SNOT‐22 scores is not different between those younger than 50 years and those of at least 50 years. [ABSTRACT FROM AUTHOR]

Background: Non‐steroidal anti‐inflammatory drugs (NSAIDs) have emerged as an alternative to opioids for optimal postoperative pain management. However, the adoption of NSAIDs in sinonasal surgery has been impeded by a theoretical concern for postoperative bleeding. Our objective is to systematically review the efficacy and safety of NSAIDs for patients undergoing sinonasal surgery. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO International Clinical Trials Registry Platform were searched from inception to January 27, 2022. Randomized controlled trials (RCTs) and comparative observational studies in any language were considered. Screening, data extraction, and risk of bias assessment were performed in duplicate. Our outcomes were postoperative pain scores, requirement for rescue analgesia, and postoperative adverse events (epistaxis, nausea/vomiting). Results: Out of 4661 records, 15 RCTs (enrolling 1210 patients) and two observational studies were included. Following endoscopic sinus surgery, there was no difference in pain scores between NSAIDs and non‐NSAIDs groups (standardized mean differences [SMD] 0.44 units better, 95% CI –0.18 to 1.05). Following septorhinoplasty, NSAIDs decreased pain scores compared to non‐NSAID regimens (SMD 1.14 units better, 95% CI 0.61 to 1.67 units better). Overall, NSAIDs reduced the need for rescue medication with a relative risk (RR) of 0.45 (95% CI 0.24 to 0.84). In addition, NSAIDs decreased the risk of nausea with an RR of 0.62 (95% CI 0.42 to 0.91) and did not increase the risk of epistaxis (RR 0.72, 95% CI 0.23‐2.22). Conclusion: Among patients undergoing sinonasal surgery, NSAIDs are beneficial in postoperative pain management and avoidance of postoperative nausea without increasing the risk of postoperative epistaxis. [ABSTRACT FROM AUTHOR]

METHODS Patient selection Institutional review board approval was obtained from the University of Pennsylvania for a retrospective chart review of patients receiving dupilumab for CRSwNP at a tertiary rhinology/allergy clinic between November 2018 and February 2022. Reasons for discontinuation All patients had undergone prior sinus surgery and were receiving dupilumab for CRSwNP with or without asthma treatment. DISCUSSION Although there was a recent database-based publication on adverse events of dupilumab,[7] our study is the first to report on a large real-world case series of patients who were treated with dupilumab for CRSwNP and experienced AEs significant enough to discontinue the medication. [Extracted from the article]

Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin‐25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma. Methods: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air‐liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium. Results: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium‐mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta‐defensin 2, an antimicrobial peptide, compared to treatment with a control solution. Conclusion: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS. [ABSTRACT FROM AUTHOR]

Background: Sinonasal lymphoma (SL) is a heterogeneous, underrecognized neoplastic disorder with limited outcomes data. We sought to better define outcomes by subtype and treatment at 2 referral centers over the past 2 decades. Methods: Demographics, clinicopathologic data, and treatment outcomes for patients treated for SL were queried from January 1, 2000 to December 31, 2021 at 2 tertiary academic medical centers. Results: Eighty‐four patients were included, with an average age at diagnosis of 63.4 ± 15 years. There were 34 females (40.5%). The majority of patients had an Eastern Cooperative Oncology Group (ECOG) score of <2 (76.2%) and the most common presenting symptom was facial swelling/pain (26.2%). The most common primary site was the nasal cavity (36.9%). Diffuse large B‐cell lymphoma was the most common subtype (46.4%), followed by extranodal NK/T‐cell lymphoma (17.9%). Chemotherapy was the most common treatment strategy (n = 59, 70.2%), followed by radiation therapy (n = 35, 41.7%) and immunotherapy (n = 24, 28.6%). Disease‐specific survival rates at 1, 5, and 10 years were 85.7%, 73.6%, and 58.6%, respectively. Eighteen patients (21.4%) developed recurrence. On multivariate analysis, higher ECOG score (p < 0.0001) and history of head and neck radiation (p = 0.048) were associated with worse survival. Younger age was associated with greater risk of recurrence (p = 0.022) and male sex was associated with more treatment side effects (p = 0.012). Conclusion: This is the largest multi‐institutional analysis of SL characteristics and outcomes. Our work suggests that, although disease control in the first 5 years is reasonable, 10‐year outcomes remain challenging. Further studies are needed to investigate new treatment paradigms and risk stratification. [ABSTRACT FROM AUTHOR]

KEY POINTS: Patients are increasingly turning to online education materials to aid with disease management.Patient education materials on aspirin‐exacerbated respiratory disease are of poor readability with significant room for improvement. [ABSTRACT FROM AUTHOR]

AERD subjects demonstrated increased sensitivity to DB ( I p i < 0.01) and sucrose ( I p i < 0.01) compared with CRSsNP, while CRSsNP subjects demonstrated a reduced sensitivity to DB ( I p i < 0.05) and sucrose ( I p i < 0.05) compared with controls (Figure 1). It was anticipated that in AERD, unique genetic polymorphisms in DB-responsive T2Rs may result in upregulation of the receptors and resulting type-2 inflammation. Keywords: aspirin-exacerbated respiratory disease; bitter; chronic rhinosinusitis; gene; open array; sensory; taste EN aspirin-exacerbated respiratory disease bitter chronic rhinosinusitis gene open array sensory taste 269 272 4 02/21/23 20230301 NES 230301 INTRODUCTION Chronic rhinosinusitis (CRS), a disease of long-standing sinonasal inflammation, is divided into two phenotypes: CRS with and without nasal polyposis (CRSwNP, CRSsNP). [Extracted from the article]

Taste receptors in the oral cavity guide our preferences for foods, preventing toxic ingestions and encouraging proper nutrient consumption. More recently, expression of taste receptors has been demonstrated in other locations throughout the body, including the airway, gastrointestinal tract, pancreas, and brain. The extent and specific roles of extraoral taste receptors are largely unknown, but a growing body of evidence suggests that taste receptors in the airway serve a critical role in sensing bacteria and regulating innate immunity. This review will focus on the function of bitter and sweet taste receptors in the human airway, with particular emphasis on T2R38, a bitter taste receptor found in sinonasal ciliated cells, and the bitter and sweet receptors found on specialized sinonasal solitary chemosensory cells. The importance of these novel taste receptor-immune circuits in the human airway and their clinical relevance in airway disease will also be reviewed. [ABSTRACT FROM AUTHOR]

Background: Postoperative management strategies for endoscopic skull base surgery (ESBS) vary widely because of limited evidence‐based guidance. Methods: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from January 1990 through February 2022 to examine 18 postoperative considerations for ESBS. Nonhuman studies, articles written in a language other than English, and case reports were excluded. Studies were assessed for levels of evidence, and each topic's aggregate grade of evidence was evaluated. Results: A total of 74 studies reporting on 18 postoperative practices were reviewed. Postoperative pain management, prophylactic antibiotics, and lumbar drain use had the highest grades of evidence (B). The literature currently lacks high quality evidence for a majority of the reviewed ESBS precautions. There were no relevant studies to address postoperative urinary catheter use and medical intracranial pressure reduction. Conclusion: The evidence for postoperative ESBS precautions is heterogeneous, scarce, and generally of low quality. Although this review identified the best evidence available in the literature, it suggests the urgent need for more robust evidence. Therefore, additional high‐quality studies are needed in order to devise optimal postoperative ESBS protocols. [ABSTRACT FROM AUTHOR]

Background: Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recent, endoscopic endonasal approaches have been increasingly used; however, there has been limited evaluation of long‐term outcomes for this approach. Methods: A retrospective review was performed to analyze patients with pediatric craniopharyngioma undergoing endonasal endoscopic resection from 2012 to 2020. Demographic information, clinicopathologic factors, and outcomes including follow‐up and recurrences were analyzed. Results: All 42 patients, with a mean age of 8.0 years, were included. The median follow‐up time was 49 months. Mean tumor diameter was 3.6 cm. All of the tumors had sellar and suprasellar components. The most common presenting symptoms were headaches (64.3%), visual changes (59.5%), and nausea/vomiting (38.1%). Most patients (73.3%) had resolution of their presenting symptoms by their first postoperative visit. Vision improved or remained normal in 69.0% of patients. Postoperatively, incidence of panhypopituitarism or diabetes insipidus developed in 89.7% and 77.8% of patients, respectively. The postoperative cerebrospinal fluid leak rate was 7.1%. The recurrence rate was 9.5%. Conclusion: Endoscopic endonasal resection for pediatric craniopharyngiomas can achieve high rates of resection with low rates of disease recurrence when compared with the outcomes of open transcranial resection reported in the literature. However, hypothalamic‐pituitary dysfunction remains a significant postoperative morbidity in both approaches. [ABSTRACT FROM AUTHOR]

CRSwNP can be further subcategorized into endotypes including aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and, recently, central compartment atopic disease (CCAD) has been proposed as a novel endotype.2 There is a complex relationship between allergic rhinitis (AR) and CRS3; one potential link may be CCAD. Keywords: allergens; allergic rhinitis; chronic rhinosinusitis; skin prick testing EN allergens allergic rhinitis chronic rhinosinusitis skin prick testing 1299 1302 4 09/30/22 20221001 NES 221001 INTRODUCTION Chronic rhinosinusitis (CRS) is an inflammatory condition of the nose and paranasal sinuses that persists for greater than 12 weeks.1 CRS has traditionally been categorized based on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. There was no statistically significant difference in the inhalant allergen sensitization profiles of patients with AR and CCAD, except for a higher prevalence of weed allergy in the CCAD group, which barely reached statistical significance. [Extracted from the article]

Background: Patients with aspirin‐exacerbated respiratory disease (AERD) are among the most challenging rhinologic patients to treat. AERD has a complex inflammatory milieu of lipid mediators and cytokines. In this study we evaluated cytokine differences in the complex AERD environment at the mucus, epithelial, and tissue levels. Methods: Samples were acquired at the time of sinus surgery from 21 patients (seven steroid‐treated, 14 untreated) with aspirin challenge‐confirmed AERD. Three methods (sponge adsorption, epithelial brushing, tissue biopsy) were used to acquire samples from the respective sinus sampling sites (mucus, polyp epithelium, and full‐thickness polyp) of each patient. We measured and compared 16 cytokine concentrations in AERD patients with or without prednisone treatment using the Luminex platform. Results: In most sampling sites, IL‐5, IL‐6, IL‐10, IL‐13, IL‐33, CCL20, and TNF‐α were detected at higher concentrations than IFN‐γ, IL‐1β, IL‐17A, IL‐4, IL‐22, IL‐17E/IL25, and GM‐CSF. Each sampling site had a different pattern of cytokine levels, and except for IL‐5 and IL‐25 there was no correlation among sampling methods for each cytokine tested. The most notable and significant decreases in cytokines from those treated with prednisone were observed in the epithelium for IL‐5, IL‐10, IL‐33, and IFN‐γ. Conclusions: In the epithelial samples, type 2‐associated cytokines IL‐5 and IL‐33, the anti‐inflammatory cytokine IL‐10, and IFN‐γ were lower in AERD patients treated with prednisone. This work serves as a basis to assess therapeutic‐induced mucosal cytokine responses in AERD and indicates that the site of cytokine measurement is an important consideration when assessing results. [ABSTRACT FROM AUTHOR]

Background: Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP‐SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these 2 entities, but no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP‐SCC. We explored a deep learning approach, using 3‐dimensional convolutional neural networks (CNNs), to address this challenge. Methods: Retrospective chart reviews were performed at 2 institutions to create a data set of preoperative MRIs with corresponding surgical pathology reports. The MRI data set included all available MRI sequences in the axial plane, which were used to train, validate, and test 3 CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions. Results: A total of 90 patients with IP (n = 64) or IP‐SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP‐SCC (n = 117). The best CNN model, All‐Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and receiver‐operating characteristic area under the curve of 0.80 (95% confidence interval, 0.682‐0.898) for test classification performance. The other 2 models, Small‐All‐Net and Elastic‐All‐Net, showed similar performance levels. Conclusion: A deep learning approach with 3‐dimensional CNNs can distinguish IP and IP‐SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP‐SCC using MRIs, more data are needed before they can reach the predictive value already established by human MRI evaluation. [ABSTRACT FROM AUTHOR]

Background Over 550,000 sinus surgeries are performed annually in the United States on patients with chronic rhinosinusitis (CRS). Although the results of sinus surgery vary widely, no known genetic factor has been identified to predict surgical outcomes. The bitter taste receptor T2R38 has recently been demonstrated to regulate upper airway innate defense and may affect patient responses to therapy. Our goal was to determine whether TAS2R38 genetics predicts outcomes in CRS patients following sinus surgery. Methods A prospective study of patients undergoing sinus surgery evaluating postoperative outcomes through the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were genotyped for TAS2R38. Results A total of 123 patients with CRS were initially analyzed; 82 patients showed nasal polyps (CRSwNP) and 41 patients were without nasal polyps (CRSsNP). Six months after surgery, the overall SNOT-22 improvement was 25 ± 23 points. The TAS2R38 genotype was found to significantly correlate with surgical outcomes in patients without polyps; homozygotes for the functional receptor had a mean improvement of 38 ± 21, whereas heterozygotes or homozygotes for the nonfunctional receptor had a mean improvement of 12 ± 22 ( p = 0.006). This result was confirmed with a multivariate regression that incorporated further patients with 1-month and 3-month scores (n = 207). Conclusion In patients undergoing sinus surgery for CRS, we have identified a genetic polymorphism that predicts variability in quality of life improvement following surgery at 6 months in nonpolypoid CRS. This is the first genetic polymorphism identified that has demonstrated to predict surgical outcome for a select group of CRS patients. [ABSTRACT FROM AUTHOR]

We tracked patient SNOT-22 and ACT scores at the following time-points: post-FESS/pre-desensitization; 1 to 3 months post-desensitization; 4 to 6 months post-desensitization; 7 to 12 months post-desensitization; and 13 to 24 months post-desensitization. Values for age, daily prednisone dose, and pre-desensitization SNOT-22 were recorded after FESS and before aspirin treatment after aspirin desensitization. Keywords: chronic rhinosinusitis; endoscopic sinus surgery; eosinophilic rhinitis and nasal polyposis; FESS; SNOT-22 EN chronic rhinosinusitis endoscopic sinus surgery eosinophilic rhinitis and nasal polyposis FESS SNOT-22 872 875 4 05/17/22 20220601 NES 220601 Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory condition characterized by the triad of eosinophilic asthma, chronic rhinosinusitis with nasal polyposis, and a non-IgE-mediated hypersensitivity to nonsteroidal anti-inflammatory drugs.1 The "gold standard" treatment of AERD consists of debulking of nasal polyps via complete functional endoscopic sinus surgery (FESS) of all 8 sinuses followed by aspirin treatment after aspirin desensitization (ATAD).2 The treatment protocol has been shown to lead to improved score on the 22-item Sino-Nasal Outcome Test (SNOT-22), decreased overall corticosteroid use, lower rate of revision surgery, and improved control of asthma.3,4 In this study, we seek to compare the outcomes of ATAD between men and women with AERD. [Extracted from the article]

Background The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population. Methods A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive. Results Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were 'supertasters,' experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections ( p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables. Conclusion This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals. [ABSTRACT FROM AUTHOR]

Background Spontaneous cerebrospinal fluid (CSF) leaks/encephaloceles are proven to be associated with intracranial hypertension by objective measurements of CSF pressure during or following endoscopic repair. A common area of involvement is a pneumatized lateral recess of the sphenoid (LRS) sinus, where prolonged intracranial pressures lead to arachnoid pits and subsequent development of skull-base defects. Even though the LRS is never present at birth, a 'congenital' cause of these leaks due to a persistent Sternberg's (lateral craniopharyngeal) canal continues to be erroneously perpetuated in the literature. The objective of this study was to eliminate the myths defining these leaks as congenital in nature. Methods Evaluation of LRS CSF leaks present within a multiinstitutional case series was performed. Data regarding demographics, body mass index (BMI), radiologic evaluation of intracranial hypertension, and direct intracranial pressure measurements (when available) were collected. Results Data evaluation identified 77 LRS CSF leaks in 59 patients (mean age 52 years). Obesity was present in 83% of individuals (mean BMI 36) and 81% were females. Radiologic evidence of intracranial hypertension (eg, empty sella, dilated optic nerve sheaths, and scalloped/attenuated bone) was present on 96% of preoperative computed tomography (CT) and/or magnetic resonance imaging (MRI) scans. Opening or postsurgical lumbar drain or ventriculostomy pressure measurements were elevated in 95% of patients (mean 27.7; range, 9-50 cmH2O). Conclusion This study provides objective evidence that LRS CSF leaks are secondary to erosions from intracranial hypertension and refutes the myth regarding a congenital origin from Sternberg's canal. [ABSTRACT FROM AUTHOR]

Background The bitter taste receptor T2R38 was recently described to play a role in upper airway innate mucosal defense. When activated by bacterial quorum-sensing molecules, T2R38 stimulates the ciliated epithelial cells to produce nitric oxide (NO), resulting in bactericidal activity and an increase in mucociliary clearance (MCC). Polymorphisms within the T2R38 gene ( TAS2R38) confer variability in activation of the receptor yielding dramatic differences in upper airway defensive responses (NO production and accelerated MCC) to microbial stimulation based on genotype. Our objective was to determine whether the nonprotective TAS2R38 polymorphisms, which render the receptor inactive, correlate with medically recalcitrant chronic rhinosinusitis (CRS) necessitating surgical intervention in the context of known risk factors, and thus identify whether the TAS2R38 genotype is an independent risk factor for patients undergoing functional endoscopic sinus surgery (FESS). Methods CRS patients undergoing primary FESS were prospectively genotyped for TAS2R38. Chi-square analysis was performed on the genotype distribution with respect to other risk factors, including allergies, asthma, nasal polyposis, aspirin sensitivity, diabetes, and smoking exposure. Results Seventy primary FESS patients were genotyped demonstrating a statistically significant skewing from the expected distribution of the general population ( p < 0.0383). CRS patients with a particular polymorphism seemed less likely to have allergies, asthma, nasal polyposis, aspirin sensitivity, and diabetes, but this did not demonstrate statistical significance. Conclusion Our investigation suggests that TAS2R38 genotype is an independent risk factor for patients failing medical therapy, necessitating surgical intervention. [ABSTRACT FROM AUTHOR]

Image-guided surgery (IGS) has become a mainstay of modern endoscopic sinus and skull base surgery (ESS) and has been shown to improve surgical outcomes and reduce complication rates.[[1]] A variety of registration techniques exist, including paired-point and contour-map registration. GLO:BDB7/01dec22:alr23046-fig-0001.jpg PHOTO (COLOR): 1 Non-contrast-enhanced computed tomography of the sinuses with TruDi fast anatomic mapping (FAM) after resident surgeon involvement in the procedure (red) and attending rhinologist completion of the case (green). [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co‐occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)‐associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case‐control study. Methods: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta‐analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend. Results: A meta‐analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16–1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23–2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02–1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS. Conclusion: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease. [ABSTRACT FROM AUTHOR]

Background: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment‐related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. Methods: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi‐institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. Results: Overall, 142 patients met the inclusion criteria. Twenty‐three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T‐stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06‐11.19). Conclusions: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings. [ABSTRACT FROM AUTHOR]

Background We recently demonstrated the bitter taste receptor T2R38 upregulates sinonasal mucosal innate defense in response to gram-negative quorum-sensing molecules through increased nitric oxide production and mucociliary clearance. T2R38 was initially identified in the quest to understand the variability in bitter taste perception to the compound phenylthiocarbamide (PTC) and demonstrated to have polymorphisms generating diplotypes dividing people into PTC supertasters, heterozygotes (with variable PTC detection), and nontasters. We have further demonstrated that sinonasal epithelial cultures derived from supertasters significantly increase innate defenses in response to gram-negative quorum-sensing molecules compared with sinonasal cultures derived from heterozygotes and nontaster individuals. Based on this data, we hypothesize that supertasters are less likely to require sinus surgery compared with heterozygous or nontasters and that supertasters have improved surgical outcomes. Methods Banked sinonasal tissue samples from patients who had undergone primary functional endoscopic sinus surgery at the University of Pennsylvania or the Philadelphia Veterans Affairs Medical Center were genotyped for T2R38 and compared to the expected population distribution. Necessity for additional antibiotic therapy following the postoperative healing time frame was evaluated. Results A total of 28 patients were included in the study. Only 1 supertaster was identified (expected 5.6, p < 0.043). Additionally, 14 heterozygous and 13 nontaster patients were identified. Conclusion This pilot study investigating the genetics of the bitter taste receptor T2R38 in the context of primary sinonasal surgery demonstrates supertaster patients are less likely to need surgical intervention for chronic rhinosinusitis. Additional study is necessary to ascertain postsurgical outcomes. [ABSTRACT FROM AUTHOR]

Background: This study evaluated 1-year outcomes in patients with chronic rhinosinusitis (CRS) who were considered surgical candidates by study criteria and elected either medical management or endoscopic sinus surgery (ESS). In addition, some patients initially enrolled in the medical treatment arm crossed over to the surgery arm during the study period and their respective outcomes are evaluated. Methods: Adult subjects with CRS who failed initial medical therapy were prospectively enrolled into a nonrandomized, multi-institutional cohort. Subjects were included in 1 of 3 cohorts: medically managed, surgically managed, or crossover (from medical to surgical). The primary outcome measure was disease-specific quality-of-life (QOL). Bivariate and multivariate analyses compared QOL improvement between cohort groups. Results: Baseline comorbidity, QOL, and other disease severity measures were not different between the 3 cohorts. With 1-year follow up, surgical patients (n = 65) reported significantly more improvement than medically managed patients (n = 33; Rhinosinusitis Disability Index (RSDI), p = 0.039; Chronic Sinusitis Survey (CSS), p = 0.018). Seventeen subjects who had initially elected medical management crossed over to surgery during the follow-up period. QOL in the crossover cohort was initially stagnant or worsening followed by improvement after ESS (RSDI, p = 0.035; CSS, p = 0.070). At 1-year follow-up, higher frequency of improvement was found in the surgical cohort vs medical cohort for several outcomes (total CSS: 70.8% vs 45.5%; odds ratio [OR], 3.37; 95% confidence interval [CI], 1.27-8.90; p = 0.014). Conclusion: With 1 year of follow-up, patients electing ESS experienced significantly higher levels of improvement in outcomes compared to patients managed by medication alone. In addition, a crossover cohort who initially elected medical management experienced improvement in several outcomes after crossing over to ESS. © 2013 ARS-AAOA, LLC. [ABSTRACT FROM AUTHOR]

Keywords: chronic rhinosinusitis; human leukocyte antigen; rhinosinusitis; sinusitis EN chronic rhinosinusitis human leukocyte antigen rhinosinusitis sinusitis 1075 1077 3 07/27/22 20220801 NES 220801 INTRODUCTION Chronic rhinosinusitis (CRS), an extremely common chronic condition, is defined as symptomatic and objective inflammation of the sinonasal mucosa lasting more than 12 weeks.1,2 Treatment for CRS remains a challenge despite our evolving understanding of the underlying mechanisms. RESULTS The 550 patients comprised 317 CRS patients (208 CRSwNP, 109 CRSsNP) and 233 controls (Table 1), all self-identified as white/Caucasian and middle-aged. In summary, we have determined that heterozygous carriers of the rs1391371 T allele are at significantly increased risk for developing CRSwNP, which further supports the potential contribution of this HLA region to CRS. [Extracted from the article]

Keywords: anosmia; COVID-19; dysgeusia; hyposmia; olfaction disorders; risk for hospitalization; UPSIT EN anosmia COVID-19 dysgeusia hyposmia olfaction disorders risk for hospitalization UPSIT 1273 1277 5 07/28/21 20210801 NES 210801 INTRODUCTION Variable prevalence of smell and taste dysfunction caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has been reported worldwide.1,2 Although South American countries have been listed in the top ten of coronavirus disease 2019 (COVID-19) case numbers,3,4 psychophysical data has not been reported in these regions. The present study has the following limitations: (1) patients with smell impairment could have been more prone to participate; and (2) outpatients had greater smell loss and were tested with the UPSIT earlier than hospitalized patients. Outpatients versus hospitalized condition Hospitalized patients were significantly older than outpatients (51.1 ± 14.6 vs. 34.6 ± 11.5 years, 95% CI, 11.6-22.3; I t i = 6.301; I p i < 0.001). Anosmia, COVID-19, dysgeusia, hyposmia, olfaction disorders, risk for hospitalization, UPSIT. [Extracted from the article]

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin‐exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL‐25) in upper airways, leading to type 2 inflammation, and are activated by bitter‐tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. Methods: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL‐25 via flow cytometry. Results: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10–9M, 1.00 × 10–8M, 1.78 × 10–8M, 3.16 × 10–8M, 5.62 × 10–8M, and 1.00 × 10–7M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10–8M and 3.16 × 10–8M (p < 0.0083). In vitro data demonstrated significant increase in IL‐25–positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). Conclusion: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL‐25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10–8M for future study of clinical utility. [ABSTRACT FROM AUTHOR]

Background: Solitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)‐25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs). However, the SCC‐trigeminal synapse has yet to be demonstrated in human sinonasal epithelium. Methods: Immunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (nChR), and SCC markers was performed in vibratome sections from polyp and healthy turbinate tissue. Quantitative polymerase chain reaction and immunofluorescence of cultured epithelial cells were used to evaluate the expansion of SCCs. Last, intracellular calcium imaging was used to demonstrate cholinergic signaling in sinonasal epithelial cells. Results: Calcitonin gene‒related peptide (CGRP) immunostaining was used to identify cholinergic nerve endings, which were only evident in sections from the inferior turbinate and intertwined with SCCs (α‐gustducin‒positive cells). CGRP‐positive nerve endings were not identified in sections from NPs. Human SCCs expressed nChR as well as the ACh synthetic enzyme choline acetyltransferase. Live cell calcium imaging demonstrated functionally active cholinergic signaling in discrete sinonasal epithelial cells, consistent with SCCs. Finally, SCC‐specific genes were dramatically upregulated with pretreatment with IL‐13 and nicotinic agonists. Conclusion: SCCs are innervated by trigeminal nerve endings in healthy turbinate tissue but not in NPs. SCCs express ACh receptors as well as choline acetyltransferase and, in the setting of a type 2 inflammatory environment, denervated SCCs dramatically expand with nicotinic stimulation. [ABSTRACT FROM AUTHOR]

Background: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses. Methods: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt. Results: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small. Conclusion: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients. [ABSTRACT FROM AUTHOR]

Background: Treatment of aspirin‐exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy. Methods: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression. Results: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36). Conclusion: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications. [ABSTRACT FROM AUTHOR]

Keywords: cerebrospinal fluid rhinorrhea; natural orifice endoscopic surgery; skull base; therapeutics EN cerebrospinal fluid rhinorrhea natural orifice endoscopic surgery skull base therapeutics 321 323 3 02/22/22 20220301 NES 220301 INTRODUCTION The last decade has seen the utilization of endoscopic endonasal approach (EEA) in resection of tumors with intradural components.1 EEA for intracranial masses is both possible and effective.2-4 When compared to transcranial approach, EEA has demonstrated superior vision outcomes, equivalent rates of total resection and complication, and stable quality of life outcomes.5,6 Successful EEA requires adequate skull base closure to prevent cerebrospinal fluid (CSF) leaks. There was no significant difference in postoperative CSF leak rates between pediatric and adult groups, underscoring EEA with NSF repair as a successful and safe technique in the surgical resection of pediatric anterior skull base tumors. One recent study examined NSF skull base reconstruction in a cohort of 12 post-EEA pediatric patients.9 Complications included one CSF leak, with a leak rate of 8.33%. [Extracted from the article]

Background: Aspirin‐exacerbated respiratory disease (AERD) is an aggressive respiratory tract inflammatory disorder manifesting as asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory sensitivity to aspirin and nonsteroidal anti‐inflammatory drugs (NSAIDs). Corticosteroids, both systemic and topical/inhaled, are used to treat inflammation of the upper and lower airways. Our objective was to examine the potential impact of complete endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on short‐term and long‐term corticosteroid use. Methods: For this pilot study, a retrospective chart review of all patients with AERD who underwent ESS followed by AD was performed. Daily prednisone use, average daily prednisone dose, and inhaled corticosteroid use were analyzed at the following time points: preoperative, postoperative/pre‐AD, and 2 to 3 months, 4 to 6 months, 7 to 12 months, and 13 to 24 months following AD. Results: A total of 125 patients underwent ESS followed by AD. Compared to preoperatively, patients who underwent ESS and AD were less likely to be on daily prednisone at all time points and upon long‐term follow‐up (32% preoperatively vs 10% at 13 to 24 months, McNemar's test = 9.00, p = 0.009). Average daily prednisone dose decreased from 10.6 ± 7.9 mg preoperatively to 3.8 ± 2.6 mg at 13 to 24 months following AD (Mann‐Whitney U; W = 122, p = 0.01). Similarly, high‐dose and medium‐dose inhaled corticosteroid use decreased from 18% to 7% and from 36% to 22% respectively (Pearson's chi‐square = 8.06, p = 0.05). Conclusion: In our AERD cohort who underwent ESS followed by AD, there was an observed decrease in overall systemic and topical/inhaled corticosteroid use. These findings can have implications for treatment given the potentially hazardous side effects of corticosteroid use. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull‐base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement. Methods: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty‐three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund‐Mackay (LM) scores, and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Results: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre‐SBS and post‐SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre‐SBS and post‐SBS SNOT‐22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013). Conclusion: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of inverted papilloma (IP) has not been fully elucidated. However, chronic paranasal sinus inflammation has been anecdotally observed in sites distant from tumor obstruction in IP patients, suggesting an association between inflammation and IP tumorigenesis. This study assesses the association between sinonasal inflammation found in IP and compares this to the level of inflammation observed in other sinonasal tumors. Methods: A retrospective chart review was performed identifying patients with unilateral IP. Pertinent clinical data was obtained and comparative analysis of preoperative computed tomography (CT) imaging and histopathology was performed. A sample of unilateral, sinonasal, non‐IP and non–squamous cell tumors was used as the control. The Lund‐Mackay scoring system was used to assess radiologic sinonasal inflammation both ipsilateral and contralateral to the tumor. Results: Seventy‐one patients were included; 58.9% of patients with IP had evidence of contralateral sinusitis at the time of presentation. In the control group, 26.7% had evidence of contralateral inflammation. When comparing contralateral sinus inflammation between the 2 study groups, the IP patients had significantly higher Lund‐Mackay scores than the control group (1.9 vs 0.26, p < 0.001). When comparing ipsilateral sinus inflammation, no significant difference was found in Lund‐Mackay scores (5.44 vs 4.00, p < 0.184). Conclusion: In this study, unilateral IPs were associated with a higher level of contralateral sinonasal inflammation when compared to control. This suggests that IP may be associated with inflammation that is independent of obstruction by the tumor. Further studies are needed to better understand the temporal relationship between chronic inflammation and tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Ketotifen is a second‐generation noncompetitive H1‐antihistamine and mast‐cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast‐cell, and other allergic‐type disorders. However, it has never been studied in aspirin‐exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis. Methods: Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long‐term cellular toxicity. Results: Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures. Conclusion: Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long‐term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process. Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients. Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot‐Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high‐power field (44.4% vs 73.6%, p < 0.017). Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide‐based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management. [ABSTRACT FROM AUTHOR]

Background: Primary sinonasal mucoepidermoid carcinoma (SN‐MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large‐scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN‐MEC leveraging the National Cancer Database (NCDB). Methods: This was a retrospective, population‐based cohort study of patients diagnosed with SN‐MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS). Results: A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio [HR], 7.29; 95% confidence interval [CI], 1.74‐30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19‐20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66‐54.23; N2B: HR, 19.3; 95% CI, 1.07‐350.64) were associated with worse OS. Conclusion: Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5‐year survival for SN‐MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival. [ABSTRACT FROM AUTHOR]

Background: Inverted papilloma (IP) is a benign sinonasal tumor with a well‐known propensity to recur, especially at its bony attachment site. Anecdotal evidence suggests lower rate of recurrence in primary resection. We also aimed to evaluate the effect of multifocal vs single focus of attachment in disease control. Methods: This work is a retrospective review of 535 IP resections performed during the period from 2006 to 2016 at a tertiary‐care center. Demographic data, tumor location and attachment sites, and follow‐up duration data were obtained. Results: Two hundred ten patients were eligible for analysis. The mean age was 57 years, with an average postoperative surveillance of 36.4 months. Patients who had a previous procedure at an outside institution have a recurrence rate of 22.3%, compared with 12.4% for patients who had primary surgery at our institution. The most common site of attachment was maxillary sinus (47.6%), followed by ethmoid sinus (39%). Individual tumor review showed 50% of the patients to have multifocal attachment disease, of which there is a higher prevalence in secondary cases when compared with primary cases (53.7% vs 44.9%). Multiple tumor attachment sites had a significant effect on recurrence (odds ratio, 3.5; 95% confidence interval, 1.6‐7.6; p = 0.002). Conclusion: Primary resection and single‐focus attachment of inverted papilloma are associated with lower recurrence rates at 3‐year follow‐up. [ABSTRACT FROM AUTHOR]

Keywords: cystic fibrosis; CFTR modulator; elexacaftor; tezacaftor; ivacaftor; chronic rhinosinusitis; sinus surgery; SNOT-22 EN cystic fibrosis CFTR modulator elexacaftor tezacaftor ivacaftor chronic rhinosinusitis sinus surgery SNOT-22 201 203 3 02/24/21 20210201 NES 210201 Cystic fibrosis (CF) is a genetic condition caused by an abnormality in the cystic fibrosis transmembrane conductance regulator (CFTR) causing recurrent pulmonary infections, pancreatic insufficiency, and, from an otolaryngology perspective, chronic rhinosinusitis (CRS).1 Symptoms are recalcitrant to medical therapies, and over 20% of CF patients require endoscopic sinus surgery (ESS) to address sinonasal complaints. All patients on CFTR modulators before ELX/TEZ/IVA were DF508 homozygotes on either TEZ/IVA or LUM/IVA. In summary, the novel highly-effective CFTR modulator ELX/TEZ/IVA leads to significantly improved sinonasal QoL in CF adults as measured by the SNOT-22 questionnaire. [Extracted from the article]

Background: Solitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin‐25 (IL‐25), an innate cytokine eliciting T‐helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation. Methods: Multicolor flow cytometry, immunofluorescence, and enzyme‐linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL‐25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry. Results: SCCs producing IL‐25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL‐25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki‐67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls. Conclusion: Although fungal antigens are known to potentiate immune response through innate cytokines, including IL‐25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention. [ABSTRACT FROM AUTHOR]