Monomethylfumarate (MMF) is thought to be the bioactive ingredient of the drug Fumaderm (Biogen Idec, Cambridge, MA), licensed in Germany since 1994 for the treatment of moderate-tosevere psoriasis. Psoriasis is a common inflammatory hyperproliferative skin disorder that involves cross-talk between different cell types, including immune cells and keratinocytes. Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation, and inflammation, with the psoriatic cytokine network maintained by communication between immune cells and keratinocytes. Recently, there is increasing evidence regarding the pivotal role of keratinocytes in mediating the disease process, and these cells can be regarded as safe therapeutic targets. From the data available on human subjects treated with Fumaderm, MMF is an effective antipsoriatic agent with known effects on immune cells. However, little is known about its direct effects on keratinocytes. We hypothesized that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes. Indeed, MMF dose-dependently inhibited [ 3 H]thymidine incorporation into DNA, indicating a direct antiproliferative action on keratinocytes. MMF significantly increased the protein level of keratin 10, the early keratinocyte differentiation marker, and the activity of transglutaminase, a late differentiation marker. These results are consistent with an ability of MMF to promote keratinocyte differentiation and inhibit proliferation, thereby improving psoriatic lesions. In 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced keratinocytes, MMF significantly inhibited the expression of the proinflammatory cytokines, tumor necrosis factor-a (TNFa), interleukin-6, and interleukin-1a as well as the production of TNFa. Our results support the notion that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes, highlighting its potential use as a multifactorial antipsoriatic agent.

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This study provides direct evidence of aspiration of sinonasal secretions into the lungs of patients with CF and healthy adults in the recumbent position. The fact that both patients and controls aspirated secretions suggests that aspiration alone does not account for the pathogenesis of lung disease in CF patients.

Background:The purpose of this retrospective review was to determine how patient-related factors and culture data affect neo-osteogenesis in patients with chronic rhinosinusitis (CRS) and patients with cystic fibrosis (CF) with CRS. Methods:Information from a database associated with a large tertiary medical center was used to assess adult patients with CF CRS and non-CF CRS (total, n = 102; CF CRS, n = 31; non-CF CRS, n = 71). Radiologic evidence of neo-osteogenesis was measured using the Global Osteitis Scoring Scale (GOSS), and mucosal disease was assessed using the Lund-Mackay score (LMS) by 2 independent reviewers who were blinded to the patient's disease state. Bacterial cultures were obtained endoscopically. Multiple logistic regression models were used to evaluate the effect of age, sex, number of previous surgeries, CF, and culture species on the odds of neo-osteogenesis. Results:Fi y-one of the 102 patients (50%) met radiologic criteria for neo-osteogenesis. Sixty-nine patients (67.6%) with CF CRS and non-CF CRS had culture data. In the multiple logistic regression model, male gender was significantly associated with neo-osteogenesis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.68-17.86; p = 0.006). Pseudomonas aeruginosa was not associated with neoosteogenesis (OR, 3.12; 95% CI,; p = 0.097). Age, number of surgeries, CF, Staphylococcus aureus, and coagulase-negative Staphylococcus were not statistically significant. Conclusion:To our knowledge, this is the first study to assess risk factors associated with neo-osteogenesis and patients with CF CRS. Interestingly, male gender was the only significant predictor of neo-osteogenesis. C 2019 ARS-AAOA, LLC.

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Mycobacterium chelonae is an atypical mycobacterium that commonly affects young and immunocompromised populations. Cases of M chelonae have been reported in immunocompetent patients, and those involving the head and neck have always followed prior endoscopic procedures. We present the first report, to our knowledge, of an immunocompetent patient with no history of endoscopic procedures found to have M chelonae sinusitis causing overt nasal deformity.