Background. Presbyosmia, or aging related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction, and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis.Methods. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single cell RNA-sequencing (scRNA-seq), and culture studies.Results. We identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress, or the regulation of proliferation and differentiation.Using a culture model, cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation. Conclusions.Our data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia, via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction.

Objective To determine whether treatment of sinonasal squamous cell carcinoma (SCC) at a high-volume facility affects survival. Study Design Retrospective database analysis. Setting National Cancer Database (2004-2014). Subjects and Methods The National Cancer Database was queried for sinonasal SCC from 2004 to 2014. Patient demographics, tumor characteristics and classification, resection margins, treatment regimen, and facility case-specific volume—averaged per year and grouped in tertiles as low (0%-33%), medium (34%-66%), and high (67%-100%)—were compared. Overall survival was compared with Cox proportional hazards regression analysis. Results A total of 3835 patients treated for sinonasal SCC between 2004 and 2014 were identified. Therapeutic options included surgery alone (18.6%), radiotherapy (RT) alone (29.1%), definitive chemoradiation (15.4%), surgery with adjuvant RT (22.8%), and combinations (14.1%) of the aforementioned treatments. Patients who underwent surgery with adjuvant RT had better overall survival (hazard ratio [HR], 0.74; P < .001; 95% CI, 0.63-0.86). As for treatment volume per facility, 7.4% of patients were treated at a low-volume center, 17.5% at a medium-volume center, and 75.1% at a high-volume center. Univariate analysis showed that treatment at a high-volume facility conferred a significantly better overall survival (HR, 0.77; P = .002). Multivariable Cox proportional hazards regression analysis, adjusting for age, sex, tumor classification, and treatment regimen, demonstrated that patients who underwent treatment at a high-volume facility (HR, 0.81; P < .001) had significantly improved survival. Conclusion This study shows a better overall survival for sinonasal SCC treated at high-volume centers. Further study may be needed to understand the effect of case volume on the paradigms of sinonasal SCC management.

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