BACKGROUND: Neutrophils present as major inflammatory cells in refractory chronic rhinosinusitis with nasal polyps (CRSwNP), regardless of the endotype. However, their role in the pathophysiology of CRSwNP remains poorly understood. We investigated factors predicting the surgical outcomes of CRSwNP patients with focus on neutrophilic localization. METHODS: We employed machine-learning methods such as the decision tree and random forest models to predict the surgical outcomes of CRSwNP. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE), Bcl-2, and Ki-67 in NP tissues. We counted the immunofluorescence-positive cells and divided them into three groups based on the infiltrated area, namely, epithelial, subepithelial, and perivascular groups. RESULTS: On machine learning, the decision tree algorithm demonstrated that the number of subepithelial HNE-positive cells, Lund-Mackay (LM) scores, and endotype (eosinophilic or non-eosinophilic) were the most important predictors of surgical outcomes in CRSwNP patients. Additionally, the random forest algorithm showed that, after ranking the mean decrease in the Gini index or the accuracy of each factor, the top three ranking factors associated with surgical outcomes were the LM score, age, and number of subepithelial HNE-positive cells. In terms of cellular proliferation, immunofluorescence analysis revealed that Ki-67/HNE-double positive and Bcl-2/HNE-double positive cells were significantly increased in the subepithelial area in refractory CRSwNP. CONCLUSION: Our machine-learning approach and immunofluorescence analysis demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.

Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction. Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a systematic review. The overall pooled prevalences of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalences of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalences of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment. The regional and chronological differences in the prevalences of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.

Background: Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 . However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear. Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction. Methods: Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a Freeman-Tukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively. Results: The overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment. Conclusion: The regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.