SUMMARYClinically, corticosteroids (CS) are among the first line drugs in the therapy of autoimmune and allergic diseases and potently inhibit the activation of immune cells. However, due to their pleiotropic mode of action, the prolonged use of CS is generally associated with a range of undesirable side-effects. In this study, we compared the activity of pimecrolimus, a novel immunomodulatory drug for the treatment of inflammatory skin disorders, and the CS dexamethasone (Dex) and beta-methasone-valerate ( b -MSV) in different in vitro assays addressing the cytokine-induced differentiation and maturation of monocytederived dendritic cells (M-DC), the susceptibility of M-DC to drug-induced apoptosis and the potency of differentiated M-DC to induce primary T cell activation. In contrast to pimecrolimus, Dex and b -MSV strongly induced apoptosis of M-DC precursors if added at the start of the DC differentiation culture. Flow cytometric analysis of surviving cells on day 6 of culture showed that the expression of several DC-specific antigens such as CD1a, CD40 and CD80 was inhibited by 50% to 80% at concentrations between 1 n M and 10 n M of either Dex or b -MSV. Furthermore, the presence of CS during the final maturation of M-DC inhibited the synthesis of IL-12p70, the expression of critical DC costimulatory molecules, such as CD83 and CD86 and impaired their ability to activate primary CD4 + T cell proliferation. In contrast, pimecrolimus did not inhibit the LPS-induced secretion of IL-12, surface expression of costimulatory molecules or the maturation of M-DC into potent stimulators of T cells. Taken together, these data indicate that pimecrolimus does not interfere with the differentiation and viability of dendritic cells and their precursors or with the function of mature M-DC to prime naïve T lymphocytes, and thus may have a lower potential than CS to interfere with DC-mediated immunosurveillance.

Objective To compare surgical outcomes of transcanal endoscopic ear surgery (TEES) for congenital ossicular anomalies with those of conventional microscopic surgery. Study Design Retrospective case review. Setting Tertiary referral academic center. Subjects and Methods From March 2012 to November 2018, 42 consecutive ears in 40 patients with congenital ossicular anomaly who underwent ossiculoplasty or stapes surgery using either ear endoscopes (TEES group) or an operating microscope (microscopic group) were included. Postoperative audiometric results, operation time, switch of approach, and complications were compared between the 2 groups. Results Twenty-four ears (66.1%) were in the microscopic group and 18 ears (33.9%) were in the TEES group. The mean (SD) preoperative air-bone gap was 31.8 (10.0) dB in the microscopic group and 35.2 (11.1) dB in the TEES group. The mean (SD) postoperative air-bone gap was 7.4 (6.5) dB in the microscopic group and 5.6 (5.0) dB in the TEES group. The differences in the preoperative and postoperative air-bone gaps between the 2 groups were not statistically significant ( P = .316 and P = .412, respectively). Average operation time in the TEES group was 24.6 minutes shorter than that in the microscopic group, which was statistically significant ( P = .019). None of patients in the TEES group did require a switch of approach. There was no significant difference in complication incidence between the 2 groups. Conclusions TEES for congenital ossicular anomaly has comparable audiometric results and complication rates to conventional microscopic surgery. TEES appears to have the advantages of shorter operation times.

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Povidone-iodine (PVP-I) is an antiseptic and a disinfectant with broad-spectrum antimicrobial activity against various pathogens. However, it is unclear whether PVP-I nasal instillation can suppress mucosal inflammation in non-eosinophilic chronic rhinosinusitis (CRS) mice. This study aimed to explore the anti-inflammatory effects and underlying molecular mechanism of PVP-I on lipopolysaccharide-stimulated airway epithelial cells and investigate whether nasal instillation of PVP-I can suppress mucosal inflammation in non-eosinophilic CRS mice. Inflammation-related molecules in the nasal epithelial cells and non-eosinophilic CRS mice were measured by enzyme-linked immunosorbent assay, western blotting, quantitative real-time polymerase chain reaction, immunoprecipitation, and histopathological analysis. PVP-I blocked expressions of various inflammation-related molecules, such as NLRP3, NF-κB-p65, caspase-1, and IL-1β. Translocation of NF-κB to the nucleus, and assembly of NLRP3/ASC complexes in the nasal epithelial cells and non-eosinophilic CRS mice were also restricted. Notably, PVP-I strongly blocked the receptor co-localization of TLR4 and MyD88 in the epithelial cells of nasal mucosa. We demonstrated that PVP-I significantly attenuated inflammatory molecules and cytokines via blocking the formation of TLR4 and MyD88 complexes during LPS-induced mucosal inflammation in non-eosinophilic CRS.