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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]

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]

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

Background: 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]