Citations

AbstractObjectiveTo determine whether the complaint of cough in chronic rhinosinusitis (CRS) patients is associated with asthma and if there is a potential predictive value for asthma diagnosis.MethodConsecutive patients presenting for initial evaluation at a tertiary rhinology clinic who were diagnosed with CRS were considered for inclusion in a cross‐sectional study. The presence and severity of cough was determined using the 22‐item Sinonasal Outcome Test (SNOT‐22). Subgroup analysis included asthma diagnosis confirmed by pulmonary function testing (PFT) in our institution, and for chronic rhinosinusitis patients with (CRSwNP) and without nasal polyps (CRSsNP).ResultsThe total study population included 297 patients with a diagnosis of CRS, with 63.9% of patients reporting cough. Physician‐confirmed diagnosis of asthma was made in 38.7% of patients, and confirmed in 69.6% by PFT. Cough was more frequently reported by CRS patients diagnosed with asthma (relative risk [RR] = 1.60, 95% confidence interval [CI], 1.13‐2.25), with sensitivity of 73.9% (95% CI, 65.0%‐81.1%). This remained significant in the CRSsNP subgroup (RR = 2.65, 95% CI, 1.32‐5.30), with sensitivity of 83.3% (95% CI, 70.4%‐91.3%) and specificity of 41.2% (95% CI, 33.2%‐49.8%). Cough was not associated with asthma in CRSwNP patients (RR = 1.26, 95% CI, 0.89‐1.79). Cough severity had poor predication for asthma diagnosis (AUC = 0.60, 95% CI, 0.54‐0.65).ConclusionsComplaint of cough is associated with diagnosis of asthma in CRS patients. In CRSsNP, complaint of cough was sensitive for asthma diagnosis, although specificity was low. Cough in CRS patients can be multifactorial and asthma may be an important diagnostic consideration.Level of evidence4.

Abstract Glioblastoma multiforme (GBM) and other solid malignancies are heterogeneous and contain subpopulations of tumor cells that exhibit stem-like features. Our recent findings point to a dedifferentiation mechanism by which reprogramming transcription factors Oct4 and Sox2 drive the stem-like phenotype in glioblastoma, in part, by differentially regulating subsets of miRNAs. Currently, the molecular mechanisms by which reprogramming transcription factors and miRNAs coordinate cancer stem cell tumor-propagating capacity are unclear. In this study, we identified miR-486-5p as a Sox2-induced miRNA that targets the tumor suppressor genes PTEN and FoxO1 and regulates the GBM stem-like cells. miR-486-5p associated with the GBM stem cell phenotype and Sox2 expression and was directly induced by Sox2 in glioma cell lines and patient-derived neurospheres. Forced expression of miR-486-5p enhanced the self-renewal capacity of GBM neurospheres, and inhibition of endogenous miR-486-5p activated PTEN and FoxO1 and induced cell death by upregulating proapoptotic protein BIM via a PTEN-dependent mechanism. Furthermore, delivery of miR-486-5p antagomirs to preestablished orthotopic GBM neurosphere-derived xenografts using advanced nanoparticle formulations reduced tumor sizes in vivo and enhanced the cytotoxic response to ionizing radiation. These results define a previously unrecognized and therapeutically targetable Sox2:miR-486-5p axis that enhances the survival of GBM stem cells by repressing tumor suppressor pathways. Significance: This study identifies a novel axis that links core transcriptional drivers of cancer cell stemness to miR-486-5p–dependent modulation of tumor suppressor genes that feeds back to regulate glioma stem cell survival.

AbstractObjectiveThe histopathological characteristics of primary vs recurrent nasal polyps in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been studied comprehensively. Identification of these features may be helpful for prognostication, postoperative management, and consideration of novel eosinophil‐targeting biologic therapy. This study investigates the histopathological differences in primary vs recurrent CRSwNP tissue.MethodsPatients undergoing endoscopic sinus surgery for CRSwNP were included if all 13 histopathological and mucin characteristics on a standardized report were available. Histopathology parameters were compared in surgical tissue and mucin from primary vs recurrent CRSwNP.ResultsComplete structured histopathology reports were available for 96 patients (39 primary polyps and 57 recurrent polyps). Compared to primary polyp tissue, recurrent CRSwNP mucin was significantly more likely to feature eosinophil aggregates (57.9% vs 35.9%; P = .047). Tissue eosinophilia (using a threshold >10 per high power field [HPF]) was not significantly different in primary and recurrent CRSwNP tissue. Other histopathologic parameters and clinical characteristics were similar.ConclusionEosinophil aggregates on histopathology are significantly more likely to be present in recurrent CRSwNP. In the limited series, tissue eosinophilia (>10 per HPF) was not significantly different in primary and recurrent CRSwNP. Therefore, in addition to the study of tissue eosinophilia levels, Rhinologic surgeons should also direct attention to CRSwNP mucin. Mucin eosinophilic aggregates are an independent marker of severe inflammation that is associated more likely with recurrent vs primary polyposis. Further study of this marker may help determine its role of choice of postoperative medical therapies, including anti‐eosinophilic biologics.Level of Evidence4