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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 Methods Results Conclusions 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.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.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.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: 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]

Background: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient's forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. Methods: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. Results: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. Conclusion: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS. [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: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic‐based staging system was developed. Methods: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. Results: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. Conclusion: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high‐quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH. [ABSTRACT FROM AUTHOR]

Background: In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin‐exacerbated respiratory disease (AERD). Methods: A retrospective chart review was conducted for patients with aspirin challenge–proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality‐of‐life measures using the 22‐item Sino‐Nasal Outcomes Test (SNOT‐22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post‐desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed‐effects model was used for data analysis. Results: Thirty‐four patients met the inclusion criteria for this study. Thirty‐two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow‐up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT‐22 scores. Our results demonstrate that total SNOT‐22 scores remained statistically unchanged from immediate post‐desensitization throughout the 30‐month follow‐up period. Conclusion: Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long‐term management of sinus disease in patients with AERD. [ABSTRACT FROM AUTHOR]

Background The gold standard of treatment for esthesioneuroblastoma consists of en bloc craniofacial resection with postoperative therapy dictated by histology and tumor extent. Numerous studies have shown fully endoscopic approaches to provide comparable survival and recurrence rates with decreased patient morbidity. Here we report the first multi-institutional series assessing smell outcomes of patients who underwent unilateral endoscopic resection of esthesioneuroblastoma with preservation of the contralateral olfactory bulb. Methods A multi-institutional retrospective review was performed identifying patients who underwent endoscopic unilateral resection of esthesioneuroblastoma with preservation of 1 olfactory bulb between 2003 and 2015. After completion of postoperative radiation, patients were administered the University of Pennsylvania Smell Identification Test (UPSIT) to assess olfactory function. Results Fourteen patients (7 males, 7 females) were identified and tested for posttreatment olfactory function. All 14 patients received postoperative radiotherapy and 4 patients received additional chemotherapy. Mean follow-up time was 51.7 months. There was no disease recurrence. Six patients (43%) were found to have residual smell function with 2 patients (14%) having normal or mildly reduced smell function. Conclusion Here we report the first multi-institutional series demonstrating smell preservation after unilateral endoscopic resection of esthesioneuroblastoma. In carefully selected patients, this approach can yield comparable survival with decreased patient morbidity. [ABSTRACT FROM AUTHOR]

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 Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed. Methods Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients. Results Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings ( p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients ( p = 0.0026). Conclusion In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients. Methods ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment. Results A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05). Conclusion Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients. [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]

Background Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS. Methods Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed. Results A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions. Conclusion S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes. [ABSTRACT FROM AUTHOR]

Background It remains unclear how much chronic rhinosinusitis (CRS) patients with bacterial biofilms can benefit from functional endoscopic sinus surgery (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with quality of life (QOL) improvement after FESS. Methods This retrospective cohort study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus samples were taken to evaluate for biofilm-formation in vitro using a modified Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3-month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Patients' characteristics and medications were collected. Clinical significant QOL change was defined as a difference of at least 0.5 standard deviation (SD) of baseline SNOT-22 score in the reference group. Results A total of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24). Patients with biofilm-forming bacteria had significantly worse preoperative SNOT-22 scores compared to patients without biofilm-forming bacteria (48 ± 20 vs 38 ± 23, p = 0.048). Both groups had clinically significant QOL improvement after FESS, and the differences in their 1-month (23 ± 19 vs 17 ± 20) and 3-month (27 ± 18 vs 18 ± 19) post-FESS SNOT-22 scores were not significant. However, patients with biofilm-forming bacteria demonstrated significantly less QOL improvement than patients without biofilm-forming bacteria from pre-FESS to 6-month post-FESS visits after adjusting for clinical factors (35 ± 25 vs 14 ± 15; β-coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p = 0.016). Conclusion CRS patients with biofilm-forming bacteria demonstrated clinically significant QOL improvement following FESS, but the degree of improvement was decreased overtime and became significantly worse than patients without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was independent of other risk factors for CRS. [ABSTRACT FROM AUTHOR]

Background Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity. Methods Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture. Results A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034). Conclusion Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates. [ABSTRACT FROM AUTHOR]

Background It is unclear whether chronic rhinosinusitis (CRS) patients with both nasal polyps and asthma have different quality of life (QOL) improvement after functional endoscopic sinus surgery (FESS). We aimed to determine whether CRS patients with asthma and nasal polyps had a greater QOL improvement after FESS compared to patients without asthma or polyps. Methods This retrospective analysis included adult CRS patients who underwent FESS between 2007 and 2011. QOL was measured using the 22-item Sino-Nasal Outcome Test (SNOT-22). Variables collected included baseline demographics, clinical factors, SNOT-22 scores before FESS, and 1 month, 3 months, and 6 months post-FESS. Groups tested were asthma alone, polyps alone, asthma and polyps, and no asthma or polyps. Linear mixed-effects regression model was performed to calculate β-coefficients, which represent the adjusted mean QOL differences. Results Among the 376 patients included, 40.16% had both asthma and polyps (n = 151), 14.36% had asthma alone (n = 54), 19.45% had polyps alone (n = 75), and 25.53% had no asthma or polyps (n = 96). After adjusting for all factors, there were significantly more QOL improvements in patients with both asthma and nasal polyps from baseline to 1-month (β-coefficient = −10.05; 95% CI, −15.86 to −4.23; p = 0.001) and 3-month follow-up (β-coefficient = −8.27; 95% CI, −14.98 to −1.56; p = 0.016), and patients with asthma alone from baseline to 6-month follow-up (β-coefficient = −8.78; 95% CI, −17.45 to −0.11; p = 0.047), when compared to patients without asthma or nasal polyps. Conclusion CRS patients with both asthma and nasal polyps or asthma alone experience a larger QOL benefit from FESS immediately after FESS compared to CRS patients without asthma or polyps. [ABSTRACT FROM AUTHOR]

Background Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS). Methods We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis. Results Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p = 0.004) and Gram-negative rods (26.32% vs 8.96%; p = 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS. Conclusion DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM. [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]

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]

Abstract: Introduction: Postoperative CSF leak is the most common complication of endoscopic endonasal approach (EEA) to skull base lesions. Endoscopic multilayer closure of skull base defect using pedicled nasoseptal flaps (NSF) based off the sphenopalatine artery reduces CSF leaks. EEA robustly expands in surgical arena, yet postoperative imaging evaluation remains poorly studied. This work illustrates normal MR imaging appearance of skull base reconstruction utilizing NSFs during immediate postoperative period. Methods: We retrospectively identified patients who had skull base reconstructions utilizing NSFs following EEAs and immediate postoperative-enhanced brain MRI. NSFs and free grafts were evaluated for signal intensity, thickness, configuration, enhancement, vascular pedicle of NSF, relationship in multilayer reconstruction, and defect coverage. Imaging findings were correlated with surgical technique and CSF leaks. Results: Twenty-eight patients had 26 multilayer reconstructions and 34 NSFs. Twenty-nine NSFs showed enhancing C-shaped arc at the skull base. Of those, 26 flaps (90%) were confidently identified by visualization of their vascular pedicles, 3 were not distinguishable from adjacent mucosa and pedicles were not identified. Five NSFs showed no enhancement (1 CSF leak). Twenty-seven enhancing NSFs approximated defects with close abutment to free grafts. One flap was displaced; one incompletely covered the defect (2 CSF leaks). Fisher exact test demonstrated an association between incomplete defect coverage and displacement of NSFs with CSF leak (P =0.05). Conclusion: Endoscopic skull base reconstruction utilizing NSF has characteristic MR imaging appearance. Non-enhancing mucosal gap or displacement of NSF may indicate incomplete defect coverage, identifying patients at risk for CSF leak. [Copyright &y& Elsevier]

Background: Topical surfactant therapy has been found to be effective in the management of recalcitrant chronic rhinosinusitis. Objective: To determine in vitro the antibacterial potential of SinuSurf™, a previously commercially available sinonasal surfactant. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) cultures were grown in the presence or absence of serial dilutions of mupirocin or gentamicin with and without SinuSurf and quantified by colony-forming units (CFUs). Biofilm formation was also assessed. Finally, bacterial growth was evaluated in sinus irrigation bottles inoculated with MRSA or PA and rinsed daily with SinuSurf. Results: SinuSurf alone evinced a 3-log (1,000-fold) and 6-log (106-fold) reduction in CFUs for MRSA and PA, respectively. The combination of SinuSurf with a 1:10 dilution mupirocin and 1:100 dilution gentamicin demonstrated complete bacterial eradication. Similar concentrations of antibiotic dilutions alone demonstrated bacterial growth. SinuSurf averaged an 83% MRSA and 76% PA reduction in biofilm formation. Bottle contamination evaluation demonstrated reduction of MRSA and PA (p < 0.05) with SinuSurf. Conclusion: Biofilms have been demonstrated in chronic rhinosinusitis patients and implicated in recalcitrant disease. Our in vitro data demonstrates the addition of SinuSurf improved the effectiveness of a lower concentration of topical antibiotics in biofilm mass and viability. Copyright © 2012 S. Karger AG, Basel [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]

The article discusses about the study conducted on Chronic maxillary sinus discomfort.

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]

Background: Sinonasal posttransplant lymphoproliferative disorder (PTLD) is a serious but uncommon complication of solid organ and hematopoietic stem cell transplantation that can overlap in many features with invasive fungal sinusitis (IFS).Objective: To identify clinical, laboratory, and radiographic features that may help to differentiate sinonasal IFS and PTLD in the posttransplant population.Methods: We performed a retrospective chart review of patients with posttransplant sinonasal PTLD and IFS to evaluate for clinical, laboratory, and imaging characteristics.Results: A total of 4 patients with sinonasal PTLD and 10 posttransplant IFS patients were evaluated. A total of 2 of 4 PTLD patients presented with a symptom duration of greater than 3 months compared to none in the IFS group (p = 0.07). Mean absolute neutrophil count (ANC) was 2,976 per mm3 (range 2,488-3,462) in the PTLD group compared to 773 per mm3 (range 0.0-2,744) in the IFS group (p = 0.01). Both PTLD lesions with available diffusion-weighted imaging demonstrated diffusion restriction on magnetic resonance im-aging (MRI) compared to zero of the IFS lesions (p = 0.10). No PTLD lesions demonstrated mucosal infarcts compared to three of seven IFS lesions (p = 0.23).Conclusion: IFS was associated with a significantly lower ANC at the time of diagnosis compared to PTLD. Additionally, three other measures trend towards association with their respective pathology. PTLD typically has a more chronic time course than IFS, diffusion restriction on MRI is predominantly associated with PTLD patients, and mucosal infarct on MRI is more suggestive of IFS. Additionally, all cases of sinonasal PTLD arose following solid organ transplantation. These factors may assist clinicians during diagnosis. [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]