Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms.

Chronic rhinosinusitis (CRS) is a multifaceted disease with variable clinical courses and outcomes. We aimed to determine CRS-associated nasal-tissue transcriptome in clinically well-characterized and phenotyped individuals, to gain a novel insight into the biological pathways of the disease. RNA-sequencing of tissue samples of patients with CRS with polyps (CRSwNP), without polyps (CRSsNP), and controls were performed. Characterization of differently expressed genes (DEGs) and functional and pathway analysis was undertaken. We identified 782 common CRS-associated nasal-tissue DEGs, while 375 and 328 DEGs were CRSwNP- and CRSsNP-specific, respectively. Common key DEGs were found to be involved in dendritic cell maturation, the neuroinflammation pathway, and the inhibition of the matrix metalloproteinases. Distinct CRSwNP-specific DEGs were involved in NF-kß canonical pathways, Toll-like receptor signaling, HIF1α regulation, and the Th2 pathway. CRSsNP involved the NFAT pathway and changes in the calcium pathway. Our findings offer new insights into the common and distinct molecular mechanisms underlying CRSwNP and CRSsNP, providing further understanding of the complex pathophysiology of the CRS, with future research directions for novel treatment strategies.

Pharyngocutaneous fistula: the incidence and the risk factors.

A pharyngocutaneous fistula is the most common complication following laryngectomy. A wide range of potential risk factors has been suggested. The purpose of this study was to determine the incidence and risk factors for the fistula at the Department of Otorhinolaryngology and Head and Neck Surgery in Ljubljana, Slovenia between 2007 and 2012. Charts from patients treated for head and neck cancer by laryngectomy were retrospectively reviewed. Comprehensive clinicopathologic data were collected including potential risk factors related to the patient, disease, surgery and postoperative period. The patients were categorised into the group with the fistula (a study group) and without it (a control group). The incidence of the fistula was calculated and the groups were statistically compared according to potential risk factors using the Chi square test, Fisher exact test, T test, Mann-Whitney U test and binary logistic regression analysis. Hundred fifty-eight patients were included. The incidence of the fistula was 30.4 %. In the primary laryngectomy group the incidence was 22.6 %, whereas in the salvage laryngectomy group 44.6 % (p = 0.006). The independent predictors for the fistula were history of head and neck cancer (p = 0.001), invasion of piriform sinus (p = 0.020) and surgical wound infection (p < 0.001). The timing of surgical wound infection could be of some importance. In the PCF group, it started on the 5th postoperative day, whereas in the control group on the 7th postoperative day (p = 0.063). Decreasing the rate of surgical wound infection could diminish the fistula rate.

Transcription factors gene expression in chronic rhinosinusitis with and without nasal polyps.

Background Chronic rhinosinusitis (CRS) current therapeutic approaches still fail in some patients with severe persistent symptoms and recurrences after surgery. We aimed to evaluate the master transcription factors gene expression levels of T cell subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) that could represent new, up-stream targets for topical DNAzyme treatment. Patients and methods Twenty-two newly diagnosed CRS patients (14 CRSwNP and 8 CRSsNP) were prospectively biopsied and examined histopathologically. Gene expression levels of T-box transcription factor (T-bet, TBX21), GATA binding protein 3 (GATA3), Retinoic acid-related orphan receptor C (RORC) and Forkhead box P3 (FOXP3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results Eosinophilic CRSwNP was characterized by higher level of GATA3 gene expression compared to noneosinophilic CRSwNP, whereas there was no difference in T-bet, RORC and FOXP3 between eosinophilic and noneosinophilic CRSwNP. In CRSsNP, we found simultaneous upregulation of T-bet, GATA3 and RORC gene expression levels in comparison to CRSwNP; meanwhile, there was no difference in FOXP3 gene expression between CRSwNP and CRSsNP. Conclusions In eosinophilic CRSwNP, we confirmed the type 2 inflammation by elevated GATA3 gene expression level. In CRSsNP, we unexpectedly found simultaneous upregulation of T-bet and GATA3 that is currently unexplained; however, it might originate from activated CD8+ cells, abundant in nasal mucosa of CRSsNP patients. The elevated RORC in CRSsNP could be part of homeostatic nasal immune response that might be better preserved in CRSsNP patients compared to CRSwNP patients. Further data on transcription factors expression rates in CRS phenotypes are needed.