The use of the 4-subdomain structure for SNOT-22 (reflecting sleep, nasal, otologic/facial pain, and emotional symptoms of CRS) was validated as the most appropriate to calculate SNOT-22 subdomain scores for patients from different geographic regions using CFA.
Fibroblast growth factor 2 (FGF2) induces endothelial cell migration and angiogenesis through two classes of receptors: receptor tyrosine kinases, such as FGF receptor 1 (FGFR1), and heparan sulfate proteoglycans, such as syndecan 4 (S4). We examined the distinct contributions of FGFR1 and S4 in shaping the endothelial response to FGF2. S4 determined the kinetics and magnitude of FGF2-induced mitogen-activated protein kinase (MAPK) signaling by promoting the macropinocytosis of the FGFR1-S4-FGF2 signaling complex. Internalization of the S4 receptor complex was independent of clathrin and dynamin, proceeded from lipid raft–enriched membranes, and required activation of the guanosine triphosphatases RhoG and Rab5. Genetic knockout of S4, disruption of S4 function, or inhibition of Rab5 led to increased endocytosis and MAPK signaling. These data define the mechanism by which FGFR1 and S4 coordinate downstream signaling upon FGF2 stimulation: FGFR1 initiates MAPK signaling, whereas S4-dependent FGFR1 macropinocytosis modulates the kinetics of MAPK activation. Our studies identify S4 as a regulator of MAPK signaling and address the question of how distinct classes of FGFRs individually contribute to signal transduction in endothelial cells.
Objective: We sought to establish the significance of querying chronic rhinosinusitis (CRS) patients about their past CRS-related oral antibiotic and corticosteroid usage by determining the association between these metrics and patients' quality of life (QoL).Study Design: Cross-sectional study.Methods: A total of 157 patients with CRS were prospectively recruited. CRS-specific QoL was measured using the 22-item Sinonasal Outcome Test . General health-related QoL was measured using the EuroQoL five-dimensional questionnaire visual analog scale. Associations were sought between these measures of QoL and frequency of CRS-related oral antibiotic and corticosteroid usage reported by the participants in the prior 3 and 12 months.Results: More frequent antibiotic and corticosteroid use was significantly associated with worse CRS-specific and general health-related QoL, whether querying medication use over the prior 3 months or over the prior 12 months (P < 0.001 in all cases). The effect size of CRS-related antibiotic use during the prior 3 months on CRS-specific QoL (SNOT-22 score) was significantly greater than for use during the prior 12 months. However, there was no other statistically significant difference in effect size for association between QoL and CRS-related antibiotic or corticosteroid use in the prior 3 months versus prior 12 months. These results were independent of the presence or absence of polyps.Conclusion: More frequent past CRS-related oral antibiotic and corticosteroid use, regardless of time period queried (3 months or 12 months) is associated with significant decrease in CRS-specific and general health-related QoL. CRS-related systemic medication use is an important indicator of CRS patients' QOL that easily can be queried and utilized in both clinical and research settings.
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