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

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

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

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