Staphylococcus aureus plays an important role in skin and soft tissue infections and contributes to the pathophysiology of complex skin disorders such as atopic dermatitis. Bacterial resistance against commonly used antibiotics has increased considerably in the last decades demanding alternative treatment approaches. We present 3 cases where patients with chronic and recurrent S. aureus-related dermatoses were successfully treated with Staphefekt SA.100. Staphefekt SA.100 is a recombinant phage endolysin for topical skin application that specifically targets both methicillin-sensitive and methicillin-resistant S. aureus. As a consequence of its specific mechanism of action, bacterial resistance is unlikely to develop. In our 3 cases, resistance induction was not observed. Our results indicate that targeted treatment with Staphefekt might be an attractive alternative for (long-term) classical antibiotic therapy, and confirmatory randomized controlled trials are warranted to evaluate its clinical efficacy and safety.

Topical application of the commercially available solution of rapamycin (Rapamune 0.1%) as an adjuvant to PDL treatment does not appear to improve PWS blanching. Lasers Surg. Med. 49:104-109, 2017. © 2016 Wiley Periodicals, Inc.

Context:The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T 3 production.Objective: We determined D2 activity and D2 mRNA expression in human skeletal muscle biopsies under control conditions and during hypothyroidism, fasting, and hyperinsulinemia.Design: This was a prospective study. Setting:The study was conducted at a university hospital. Patients:We studied 11 thyroidectomized patients with differentiated thyroid carcinoma (DTC) on and after 4 wk off T 4 replacement and six healthy lean subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h of fasting.Mean Outcome Measures: D2 activity and D2 mRNA levels were measured in skeletal muscle samples.Results: No differences were observed in muscle D2 mRNA levels in DTC patients on and off T 4 replacement therapy. In healthy subjects, muscle D2 mRNA levels were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 activities were very low and not influenced by hypothyroidism and fasting. Conclusion:Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA modulation on the observed low D2 activities questions the physiological relevance of D2 activity in human skeletal muscle. (J Clin Endocrinol Metab 94: 2144 -2150, 2009) P eripheral thyroid hormone metabolism is mainly regulated by the iodothyronine deiodinases D1, D2, and D3 (1, 2). D1 is expressed in liver, kidney, thyroid, and at a lower level in the pituitary. This enzyme converts the prohormone T 4 to active T 3 and is very active in the breakdown of rT 3 (1, 3). Although D1 contributes significantly to peripheral T 4 to T 3 conversion, it is probably not the major source of extrathyroidal T 3 production in humans (1, 2, 4, 5). D2 also catalyzes the production of T 3

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition due to germline FLCN (folliculin) mutations, characterized by skin fibrofolliculomas, lung cysts, pneumothorax and renal cancer. We identified a de novo FLCN mutation, c.499C>T (p.Gln167X), in a patient who presented with spontaneous pneumothorax. Subsequently, typical skin features and asymptomatic renal cancer were diagnosed. Probably, de novo FLCN mutations are rare. However, they may be under-diagnosed if BHD is not considered in sporadic patients who present with one or more of the syndromic features. Genetic and immunohistochemical analysis of the renal tumour indicated features compatible with a tumour suppressor role of FLCN. The finding that mutant FLCN was expressed in the tumour might indicate residual functionality of mutant FLCN, a notion which will be explored in future studies.

BackgroundThe introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases.MethodsThis is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past.DiscussionOPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy.Trial registration NTR4499. Registered on 7 April 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1777-y) contains supplementary material, which is available to authorized users.