Randomized, Placebo-Controlled Phase 1/2 Study to Determine the Appropriate ATX-101 Concentration for Reduction of Submental Fat.

BACKGROUND: ATX-101 is indicated for submental fat treatment. OBJECTIVE: Evaluate ATX-101 versus placebo for reducing submental fat. MATERIALS AND METHODS: Adults with unwanted submental fat across 6 global sites were randomized to ATX-101 (0.5%, 1.0%, or 2.0%) or placebo for ≤4 treatments every 28 days. Outcomes included safety (adverse events and pain visual analog scale) throughout the study and efficacy (submental fat rating, patient satisfaction, and submental fat improvements) at Week 16. RESULTS: Eighty-four of 85 enrolled patients received ≥1 ATX-101 treatment (0.5% [n = 20], 1.0% [n = 20], 2.0% [n = 22] or placebo [n = 22]). Most patients (n = 82) experienced adverse events, which were mostly mild/moderate, seemed to be dose-related, and led to no study discontinuations. The mean pain scores were highest in the ATX-101 1.0% and 2.0% groups. Week-16 change from baseline in the submental fat rating scale was significantly greater for ATX-101 0.5% and 1.0% versus placebo (p ≤ .05). At Week 16, 71%, 74%, 53%, and 40% of patients in the ATX-101 0.5%, 1.0%, 2.0%, and placebo groups, respectively, achieved a ≥1-grade reduction in submental fat from baseline. Satisfaction with appearance and patient-assessed global improvement ratings increased in all ATX-101 treatment groups versus placebo. CONCLUSION: All ATX-101 concentrations were safe and efficacious for moderate/severe submental fat reduction.

Debunking the Myth of Wool Allergy: Reviewing the Evidence for Immune and Non-immune Cutaneous Reactions.

Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30-32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.

Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata.

Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL.