A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata.

Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA.

Diagnosis and novel clinical treatment strategies for pyoderma gangrenosum.

Introduction: Pyoderma gangrenosum (PG) is a noninfectious, reactive inflammatory neutrophilic dermatosis that is commonly associated with autoimmune and neoplastic disorders. There are emerging diagnostic tools and treatment options for PG.Area covered: The diagnosis of PG should be seriously considered when managing ulcers to avoid unnecessary medical and surgical complications with prompt and suitable treatment. There are no standardized treatment guidelines for PG, and current therapy largely depends on the severity and progression of the disease. Systemic corticosteroids, immunosuppressant therapy, and biologic agents remain mainstay therapies. In this article, we present a literature review of recent diagnostic and novel treatment options for the management of PG. The literature research considered clinical studies or scientific reviews. Studies were identified by searching electronic databases and reference lists of respective articles till August 2019.Expert opinion: The true diagnosis of PG is challenging, as there is no diagnostic gold standard. PARACELSUS is a novel diagnostic tool. Biologics and small molecules are emerging systemic therapy options that are relatively new in treatment of PG.

What Ethical Issues Really Arise in Practice at an Academic Medical Center? A Quantitative and Qualitative Analysis of Clinical Ethics Consultations from 2008 to 2013.

As the field of clinical ethics consultation sets standards and moves forward with the Quality Attestation process, questions should be raised about what ethical issues really do arise in practice. There is limited data on the type and number of ethics consultations conducted across different settings. At Loyola University Medical Center, we conducted a retrospective review of our ethics consultations from 2008 through 2013. One hundred fifty-six cases met the eligibility criteria. We analyzed demographic data on these patients and conducted a content analysis of the ethics consultation write-ups coding both the frequency of ethical issues and most significant, or key, ethical issue per case. Patients for whom ethics consultation was requested were typically male (55.8 %), white (57.1 %), between 50 and 69 years old (38.5 %), of non-Hispanic origin (85.9 %), and of Roman Catholic faith (43.6 %). Nearly half (47.4 %) were in the intensive care unit and 44.2 % died in the hospital. The most frequent broad ethical categories were decision-making (93.6 %), goals of care/treatment (80.8 %), and end-of-life (73.1 %). More specifically, capacity (57.1 %), patient's wishes/autonomy (54.5 %), and surrogate decision maker (51.3 %) were the most frequent particular ethical issues. The most common key ethical issues were withdrawing/withholding treatment (12.8 %), patient wishes/autonomy (12.2 %), and capacity (11.5 %). Our findings provide additional data to inform the training of clinical ethics consultants regarding the ethical issues that arise in practice. A wider research agenda should be formed to collect and compare data across institutions to improve education and training in our field.

Light-emitting Diodes: A Brief Review and Clinical Experience.

BACKGROUND: In the early 1990s, the biological significance of light-emitting diodes was realized. Since this discovery, various light sources have been investigated for their cutaneous effects. STUDY DESIGN: A Medline search was performed on light-emitting diode lights and their therapeutic effects between 1996 and 2010. Additionally, an open-label, investigator-blinded study was performed using a yellow light-emitting diode device to treat acne, rosacea, photoaging, alopecia areata, and androgenetic alopecia. RESULTS: The authors identified several case-based reports, small case series, and a few randomized controlled trials evaluating the use of four different wavelengths of light-emitting diodes. These devices were classified as red, blue, yellow, or infrared, and covered a wide range of clinical applications. The 21 patients the authors treated had mixed results regarding patient satisfaction and pre- and post-treatment evaluation of improvement in clinical appearance. CONCLUSION: Review of the literature revealed that differing wavelengths of light-emitting diode devices have many beneficial effects, including wound healing, acne treatment, sunburn prevention, phototherapy for facial rhytides, and skin rejuvenation. The authors' clinical experience with a specific yellow light-emitting diode device was mixed, depending on the condition being treated, and was likely influenced by the device parameters.

Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden.

BACKGROUND: Disease burden should be an important component for guiding research funding. OBJECTIVE: We sought to examine the relationship between dermatologic research funded from 2012 to 2013 by the National Institutes of Health (NIH) and US skin disease burden as measured by disability-adjusted life years in the Global Burden of Disease 2010 study. METHODS: A cross-sectional analysis was independently performed by 2 researchers who matched projects from the 2012 to 2013 NIH Research Portfolio Online Reporting Tools with 15 skin conditions and their respective disability-adjusted life years from Global Burden of Disease 2010. RESULTS: The NIH funded 1108 projects spanning the 15 skin conditions. Melanoma received almost half of the total skin condition budget (49.5%). Melanoma, nonmelanoma skin cancer, and leprosy were funded above what would be suggested by their disease burden, whereas dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared underfunded. Bacterial skin diseases, viral skin diseases, and psoriasis were well matched with disease burden. LIMITATIONS: Disease burden is one of many factors that may be used to guide priority-setting decisions. CONCLUSION: Skin disease burden measured by disability-adjusted life year metrics partially correlates with NIH funding prioritization. Comparing US disease burden with NIH funding suggests possible underfunded and overfunded skin diseases.