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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]

Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies. [ABSTRACT FROM AUTHOR]

Background: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. Methods: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi‐squared or Fisher's exact tests. The Cochrane‐Armitage test for trend was used to analyze outcomes by class. Results: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). Conclusion: Endoscopic treatment of PBOTs is an effective approach, with favorable short‐term and long‐term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic‐based framework that effectively facilitates high‐quality outcomes reporting for all PBOTs. [ABSTRACT FROM AUTHOR]

This article discusses the use of plasma circulating tumor DNA (ctDNA) testing in the management of HPV-associated sinonasal and nasopharyngeal tumors. The incidence of HPV-associated head and neck cancer has been increasing, and HPV-driven tumors commonly occur in the oropharynx and sinonasal tract. The management of HPV+ sinonasal carcinoma and HPV+ nasopharyngeal carcinoma is challenging, and better diagnostics are needed. Plasma ctDNA testing, also known as liquid biopsy, has shown promise in detecting the presence and recurrence of virus-induced tumors. It has been used successfully in the management of HPV+ oropharyngeal cancer and has the potential to improve the diagnosis and surveillance of HPV+ sinonasal and nasopharyngeal tumors. However, more research is needed to assess its efficacy in these specific tumor types. The article also discusses the methodology and cost analysis of plasma ctDNA testing and encourages clinicians to incorporate it into routine management of HPV+ sinonasal and nasopharyngeal tumors. [Extracted from the article]

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase‐11 (MMP‐11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP‐11 in IP epithelial migration and invasion.Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP‐derived epithelial cultures and normal mucosa‐derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP‐11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti‐MMP‐11 antibody on IP and control epithelial cultures.IP‐derived cultures demonstrated strong MMP‐11 expression compared to controls. Treatment with anti‐MMP‐11 blocking antibody significantly reduced epithelial migration only in IP‐derived cells compared to non‐treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP‐11 reduced IP epithelia's ability to invade through collagen‐coated transwells, suggesting that MMP‐11 plays a role in invasion.We established an in vitro model to study IP‐derived epithelial cells. MMP‐11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP‐11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP‐11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP‐11 has a role in malignant transformation of IP. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Sinonasal malignancies (SNMs) adversely impact patients’ quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients.In this prospective, multi‐institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease‐related factors that influence each of the 12 UWQOL subdomains from baseline to 5 ‐years post‐treatment.Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI −10.8, −2.4, p = 0.01) and pain (CI −17.0, −4.0, p < 0.001). Neck dissection predicted worse swallow (CI −14.8, −2.8, p < 0.001), taste (CI −31.7, −1.5, p = 0.02), and salivary symptoms (CI −28.4, −8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI −21.8, −5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI −13.0, −2.0, p = 0.03).Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course. [ABSTRACT FROM AUTHOR]

Background Sinonasal debridement is typically performed in the weeks following endonasal skull base surgery (ESBS). In the pediatric population, this second-look procedure may require general anesthesia; however, there is currently little evidence assessing the benefit of this practice. Methods This was a multicenter retrospective study of pediatric patients (age <18 years) undergoing a planned second-look debridement under general anesthesia following ESBS. Intraoperative findings, interventions performed, and perioperative complications were reviewed. Multivariate regression analysis was performed to identify associations between intraoperative findings and clinical factors. Results We reviewed 69 cases of second-look debridements (age mean 8.6 ± 4.2 years, range: 2–18 years), occurring a mean of 18.3 ± 10.3 days following ESBS. All abnormal findings were noted in patients age ≤12 years. Synechiae were noted in 8.7% of cases, bacterial rhinosinusitis in 2.9%, and failed reconstruction with cerebrospinal fluid leak in 4.5% (two cases of flap malposition and one case of flap necrosis). All failed reconstructions were noted following expanded endonasal cases for craniopharyngioma, and in each case, a revision reconstruction was performed during the second-look surgery. Synechiae were not significantly associated with younger age, revision cases, or cases with reconstructive flaps. There were no perioperative complications. Conclusion Second-look debridement under general anesthesia may be useful in the identification and intervention of sinonasal pathology following endoscopic skull base surgery, particularly in children ≤12 years old or those with pedicled flap reconstructions. Larger controlled studies are warranted to validate this practice and refine indications and timing of this second procedure. [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]

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two innate immune cell types are activated by bitter products, including those secreted by Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO enhances mucociliary clearance and has direct antibacterial effects in ciliated epithelial cells. NO also increases phagocytosis by macrophages. Using biochemistry and live-cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). Immunofluorescence showed that H441 cells express eNOS and T2Rs and that the bitter agonist denatonium benzoate activates NO production in a Ca2+- and HSP90-dependent manner in cells grown either as submerged cultures or at the air–liquid interface. In primary sinonasal epithelial cells, we determined that HSP90 inhibition reduces T2R-stimulated NO production and ciliary beating, which likely limits pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves as an innate immune modulator by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream Ca2+ signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases such as chronic rhinosinusitis, asthma, or cystic fibrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Inverted papillomas are benign sinonasal tumors that can recur or become cancerous. The mainstay of treatment is surgical resection. We summarize the biology of inverted papillomas and review surgical outcomes in an effort to define the current treatment strategy. Inverted papillomas (IP) are the most common sinonasal tumor with a tendency for recurrence, potential attachment to the orbit and skull base, and risk of malignant degeneration into squamous cell carcinoma (SCC). While the overall rate of recurrence has decreased with the widespread adoption of high-definition endoscopic optics and advanced surgical tools, there remain challenges in managing tumors that are multiply recurrent or involve vital neurovascular structures. Here, we review the state-of-the-art diagnostic tools for IP and IP-degenerated SCC, contemporary surgical management, and propose a surveillance protocol. [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: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT‐22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling. Methods: Patients with previously untreated SNMs were prospectively enrolled (2015–2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT‐22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL. Results: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT‐22 QOL in patients with skull base erosion (p = 0.02). SNOT‐rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005). Conclusions: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex‐specific and symptom‐related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T‐staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL. [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]

This article discusses the secondary repair of iatrogenic cerebrospinal fluid (CSF) leaks during functional endoscopic sinus surgery (FESS) in a tertiary-care center. The study included 12 patients who underwent secondary repair of CSF leaks. The average time from initial surgery to presentation at the institution was 8.25 days, and CSF leaks were recognized intraoperatively in 33.3% of cases. The management included updated CT scans, intravenous ceftriaxone, and operative repair tailored to each patient. Acetazolamide was started postoperatively for patients with a BMI greater than 40, and there were no cases of persistent CSF leaks or meningitis. [Extracted from the article]

This article discusses the use of an endoscopic endonasal approach (EEA) for the resection of anterior skull base tumors in young children. Traditionally, these tumors have been treated with open craniotomy, but the EEA has become more common in pediatric patients. The article reviews a retrospective study of ten patients aged 5 or younger who underwent EEA for tumor resection. The results showed that the EEA was safe and effective, with successful reconstruction of the skull base in all cases. Further research is needed to evaluate the EEA in this population. [Extracted from the article]

This article explores the impact of patient demographics and socioeconomic status on surgical outcomes in endonasal endoscopic pituitary surgery. The study reviewed 187 patients who underwent this surgery between 2017 and 2019. The findings revealed that male patients were more likely to have larger tumors and higher comorbidity scores, while Hispanic patients had smaller tumors and lower comorbidity scores. Black patients experienced longer hospital stays, higher costs, and higher rates of readmission, regardless of income. These results suggest that racial health disparities are not solely due to socioeconomic status and emphasize the importance of considering social determinants of health in clinical practice. [Extracted from the article]

Background: The non-cancerous functions of Akt in the airway are understudied. In some tissues, Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) to produce nitric oxide (NO) that has anti-inflammatory effects. NO production has antibacterial and antiviral effects in the airway, and increasing NO may be a useful anti-pathogen strategy. Akt also stimulates the nuclear factor erythroid 2-related factor 2 (Nrf-2) transcription factor, which transcribes antioxidant genes. Therefore, we hypothesized that activation of the Akt/eNOS pathway, which also activates Nrf-2, may have protective effects in human airway cells against injury.Methods: To directly test the effects of Akt signaling in the airway, we treated A549 and 16HBE cells as well as primary bronchial, nasal, and type II alveolar epithelial cells with small molecule Akt activator SC79. We examined the effects of SC79 on eNOS activation, NO production, Nrf-2 target levels, and interleukin-8 (IL-8) transcription during exposure to TNF-α or Pseudomonas flagellin (TLR5 agonist). Additionally, air-liquid interface bronchial cultures were treated with cadmium, an oxidative stressor that causes airway barrier breakdown.Results: SC79 induced a ~ twofold induction of p-eNOS and Nrf-2 protein levels blocked by PI3K inhibitor LY294002. Live cell imaging revealed SC79 increased acute NO production. Quantitative RT-PCR showed a ~ twofold increase in Nrf-2 target gene transcription. TNF-α or flagellin-induced IL-8 levels were also significantly reduced with SC79 treatment. Moreover, the transepithelial electrical resistance decrease observed with cadmium was ameliorated by SC79, likely by an acute increase in tight junction protein ZO-1 levels.Conclusions: Together, the data presented here demonstrate SC79 activation of Akt induces potentially anti-pathogenic NO production, antioxidant gene transcription, reduces IL-8 transcription, and may protect against oxidative barrier dysfunction in a wide range of airway epithelial cells. [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]

Background: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under‐studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal‐specific and generalized QOL using validated metrics in a large cohort over a 5‐year posttreatment time frame. Methods: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow‐ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease‐specific and generalized physical and social/emotional function QOL. Results: One hundred ninety‐four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT‐22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT‐22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease‐specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01). Conclusion: Disease‐specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment. [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: 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]

Background Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with a poor prognosis, and multimodal therapy is the standard of care. We sought to characterize treatment delays in SNUC managed with surgery and adjuvant radiation and to determine the impact on survival using the National Cancer Database (NCDB). Methods This was a retrospective, population-based cohort study of patients with SNUC between 2004 and 2016 in the NCDB. The intervals of diagnosis to surgery (DTS), surgery to radiation (SRT), and radiation duration (RTD) were examined. Recursive partitioning analysis (RPA) was performed to identify the variables with the greatest impact on survival. The association between treatment delay and overall survival (OS) was then assessed using multivariate Cox proportional hazards regression. Results Of 173 patients who met inclusion criteria, 65.9% were male, average age at diagnosis was 56.6 years, and 5-year OS was 48.1%. Median durations of DTS, SRT, and RTD were 18, 43, and 46 days, respectively. Predictors of treatment delay included Black race, government insurance excluding Medicare/Medicaid, and positive margins. RPA-derived optimal thresholds were 29, 28, and 38 days for DTS, SRT and RTD, respectively. On multivariate analysis, positive margins (hazard ratio [HR]: 4.82; 95% confidence interval [CI]: 2.28–10.2) and DTS less than 29 days (HR: 2.41; 95% CI: 1.23–4.73) were associated with worse OS. Conclusion Our results likely reflect the aggressive nature of the disease with surgeons taking more invasive disease to the operating room more quickly. Median treatment intervals described may serve as relevant national benchmarks. [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]

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84–6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6–97.1), 83.0 months (95% CI: 74.9–98.2), and 63.6 months (95% CI: 37.3–101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69–1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex. [ABSTRACT FROM AUTHOR]

We implemented a streamlined care pathway for patients undergoing endoscopic transsphenoidal (TSA) pituitary surgery. Select patients are recovered in the postanesthesia care unit and transferred to a step-down unit for intermediate neurologic care (INCU), with clinicians trained to manage cerebrospinal fluid leak, diabetes insipidus (DI), and other complications. We evaluated all TSA surgeries performed at 1 academic medical center from 7th January, 2017 to 30th March, 2020, collecting patient factors, tumor characteristics, cost variables, and outcomes. The INCU pathway was implemented on 7th January 2018. Pathway patients were compared with nonpathway patients across the study period. Outcomes were assessed using multivariate regression, adjusting for patient and surgical characteristics, including intraoperative cerebrospinal fluid leak, postoperative DI, and tumor dimensions. One hundred eighty-seven patients were identified. Seventy-nine were on the INCU pathway. Mean age was 53.5 years. Most patients were male (66%), privately insured (62%), and white (66%). Mean total cost of admission was $27,276. Mean length of stay (LOS) was 3.97 days. Use of the INCU pathway was associated with total cost reduction of $6376.33 (P < 0.001, 95% confidence interval [CI]: $3698.21–$9054.45) and LOS reduction by 1.27 days (P = 0.008, 95% CI: 0.33–2.20). In-hospital costs were reduced across all domains, including $1964.87 in variable direct labor costs (P < 0.001, 95% CI: $1142.08–$2787.64) and $1206.52 in variable direct supply costs (P < 0.001, 95% CI: $762.54–$1650.51). Pathway patients were discharged earlier despite a higher rate of postoperative DI (25% vs. 11%, P = 0.011), with fewer readmissions (0% vs. 6%, P = 0.021). A streamlined care pathway following TSA surgery can reduce in-hospital costs and LOS without compromising patient outcomes. [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]

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]

Rathke cleft cysts (RCCs) arise from the development of the Rathke pouch. Recurrence is common after either drainage or cyst removal. The endoscopic endonasal approach (EEA) is increasingly utilized for the management of RCC. Various techniques have been described to try to reduce the rates of recurrence. We studied the effect of fenestration with a nasoseptal flap (NSF) on recurrence rates by comparing a cohort of patients undergoing this technique to a cohort of patients undergoing conventional drainage. Patients who underwent EEA for RCC between 2011 and 2020 were identified and divided into 2 cohorts: conventional fenestration versus fenestration with NSF. Surgical approach, reconstructive method, and recurrences were recorded. Primary end point was symptomatic or radiographic recurrence. 21 patients were identified undergoing EEA. An NSF was used to line the cyst cavity in 11 cases. Conventional fenestration without mucosal reconstruction was performed in the remaining 10 cases. In the cases without NSF, 5 (50%) developed recurrence requiring revision surgery, while there was only one recurrence in the NSF group (P < 0.05). In patients requiring revision, all had an NSF placed and none had a second recurrence of their RCC. NSF placement into a fenestrated RCC is useful to prevent cyst reaccumulation and reoperation. Typical fenestration carries an unacceptably high rate of recurrence. [ABSTRACT FROM AUTHOR]

Objective: To determine in-hospital costs associated with performing an EEA to anterior skull base pathology and to identify drivers of cost variability for patients undergoing endoscopic anterior skull base surgery. Methods: All endoscopic anterior skull base surgeries performed over a period from January 1st, 2015 to October 24th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using Stata software. Results: An EEA was associated with an average total in-hospital cost of $44 545. Compared to patients undergoing a transsphenoidal approach to pituitary tumor resection, EEA patients incurred higher in-hospital costs across all variables including a total cost increase of $15 921 (95% confidence interval $5720-26 122, P =.002). Univariate analysis of all endoscopic anterior skull base surgery patients showed a cost increase of $30 616 associated with post-operative cerebrospinal fluid (CSF) leak ($10 420-50 811, P =.004), $14 610 with post-operative diabetes insipidus (DI) ($4610-24 609, P =.004), and $11 522 with African-American patients relative to Caucasian patients ($3049-19 995, P =.008). Conclusions: Patients who undergo endoscopic EEA for resection of anterior skull base tumors typically incur greater in-hospital costs than patients undergoing a standard TSA. Post-operative complications such as CSF leak and DI, as well as ethnicity, are significant drivers of cost-variability. [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]

Objective  This study aimed to provide information regarding the prognosis of patients presenting with metastatic anterior skull base malignancies based upon histology and site of distant metastasis (DM). Patients and Methods  The National Cancer Database was queried for patients with anterior skull base malignant neoplasms with DM. Outcomes  Prognosis was compared between site of DM and tumor histologies. A multivariable Cox proportional hazards model was used to identify prognostic factors for overall survival (OS). Results  A total of 481 patients were identified. Lung was the most common site of DM (24.9%), followed by bone (22.2%), liver (5.6%), and brain (2.5%). Lung was the most common site for squamous cell carcinoma (SCCa) (28.3%), melanoma (37.7%), and adenoid cystic carcinoma (ACC; 31.4%). The median survival for patients presenting with metastatic disease regardless of tumor histology was 9.0 months (95% confidence interval [CI]: 8.2–10.3), and patients with metastasis to the liver had the best median survival at 15.5 months (95% CI: 10.5–25.6). The median survivals for the most common histologies, SCCa, melanoma, and ACC were 8.2 months (95% CI: 5.5–10.2), 10.5 months (95% CI: 8.7–14.1), and 15.0 months (95% CI: 11.1–61.1), respectively. Multivariable analysis demonstrated worse overall survival (OS) for older patients, higher Charlson-Deyo comorbidity scores, and tumors with higher grade and T stage. Compared with metastasis to bone, lung metastasis had better OS on multivariable analysis (hazard ratio [HR]: 0.70, 95% CI: 0.51–97). Adenoid cystic carcinoma had improved OS compared with SCCa (HR: 0.62, 95% CI: 0.39–99). Conclusion  Tumor histology, metastatic sites, and several disease factors affected prognosis in anterior skull base malignancies with DM. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced‐based review with recommendations (EBRR) for fundamental management principles of CF CRS. Methods: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence. Results: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS). Conclusion: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder. [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]

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]

T2R bitter taste receptors in airway motile cilia increase ciliary beat frequency (CBF) and nitric oxide (NO) production. Polymorphisms in some T2Rs are linked to disease outcomes in chronic rhinosinusitis (CRS) and cystic fibrosis (CF). We examined the expression of cilia T2Rs during the differentiation of human nasal epithelial cells grown at air–liquid interface (ALI). The T2R expression increased with differentiation but did not vary between CF and non-CF cultures. Treatment with Pseudomonas aeruginosa flagellin decreased the expression of diphenhydramine-responsive T2R14 and 40, among others. Diphenhydramine increased both NO production, measured by fluorescent dye DAF-FM, and CBF, measured via high-speed imaging. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired the growth of lab and clinical strains of P. aeruginosa, a major pathogen in CF and CF-related CRS. Diphenhydramine impaired biofilm formation of P. aeruginosa, measured via crystal violet staining, as well as the surface attachment of P. aeruginosa to CF airway epithelial cells, measured using colony-forming unit counting. Because the T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, diphenhydramine-derived compounds may have potential clinical usefulness in CF-related CRS as a topical therapy. However, utilizing T2R agonists as therapeutics within the context of P. aeruginosa infection may require co-treatment with anti-inflammatories to enhance T2R expression. [ABSTRACT FROM AUTHOR]

Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence‐based review, or evidence‐based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further. [ABSTRACT FROM AUTHOR]

Chondrosarcomas of the skull base are rare tumors most commonly treated surgically with or without adjuvant radiation therapy. Using the National Cancer Database (NCDB), we analyzed overall survival (OS), treatment modalities, and prognosticators. The NCDB was queried for all cases of histologically confirmed skull base chondrosarcoma treated between 2004 and 2015, excluding patients with more than 1 malignant tumor, on palliative care, receiving unrelated concurrent treatments, or having less than 1 month of follow-up. The χ2 test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with the use of adjuvant radiation, OS, and survival time. A total of 498 patients with skull base chondrosarcoma were identified in the NCDB. Of them, 224 (45.0%) and 198 (39.8%) were treated with either surgery alone or surgery with adjuvant radiation therapy, respectively. Patients more likely to undergo surgery with adjuvant radiation had higher tumor grade (P = 0.008), later year of diagnosis (P = 0.002), positive surgical margins (P < 0.001), and treatment at an academic institution (P = 0.02). Patient, tumor, and socioeconomic factors associated with worse OS on multivariate analysis included the Charlson/Deyo Comorbidity Score ≥2 (P = 0.017), as well as clear cell (P = 0.02) and dedifferentiated (P = 0.006) histology. Age, tumor grade, tumor size, treatment modality, insurance status, facility type, and urban/rural population did not show a statistically significant impact on OS. The mainstay of treatment for skull base chondrosarcoma is surgery, with consideration of adjuvant radiation. This study demonstrated worse overall survival associated with more frail patients and aggressive histology types. It is important to consider these factors when planning the clinical management of these patients. [ABSTRACT FROM AUTHOR]

Background: Inverted papilloma (IP) is a sinonasal tumor with a well‐known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma‐in‐situ and invasive carcinoma. Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma‐in‐situ, and 13 squamous cell carcinoma ex‐IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next‐generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma‐in‐situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma‐in‐situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification. [ABSTRACT FROM AUTHOR]