TGFβ2 Induces the Soluble Isoform of CTLA-4 - Implications for CTLA-4 Based Checkpoint Inhibitor Antibodies in Malignant Melanoma.

Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on immune responses from volunteer healthy or melanoma patient PBMC samples.

Low-Dose Vitamin D Supplementation Does Not Affect Natural Regulatory T Cell Population but Attenuates Seasonal Changes in T Cell-Produced IFN-γ: Results From the D-SIRe2 Randomized Controlled Trial.

Background: Seasonal variations have been reported for immune markers. However, the relative contributions of sunlight and vitamin D variability on such seasonal changes are unknown.

Objective: This double-blind, randomized, placebo-controlled trial tested whether daily 400 IU vitamin D supplementation affected short-term (12 weeks) and long-term (43 weeks) natural regulatory T cell (nTreg) populations in healthy participants.

Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts.

Importance: Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition not compatible with clinical decision making or inclusion for clinical trials.

Objective: To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum.

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort.

Is speed of healing a good predictor of eventual healing of pyoderma gangrenosum?

Background: Pyoderma gangrenosum is a rare inflammatory skin condition. Two prospective studies have evaluated treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks.

Objective: Using data from both studies we assessed the predictive value of 3 early predictors for healing at 6 months: speed of healing, Investigator Global Assessment (IGA), and resolution of inflammation, recorded at 2 and 6 weeks.

Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: A prospective cohort study.

Background: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment.

Objective: We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG.

Methods: This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012).

Interventions for hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by recurrent painful boils in flexural sites, such as the axillae and groin, that affects about 1% of the population, with onset in early adulthood.

Objectives: To assess the effects of interventions for HS in people of all ages.

Search Methods: We searched the following databases up to 13 August 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982).

Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.

Objective: To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management.

Design: Multicentre, parallel group, observer blind, randomised controlled trial.

Setting: 39 UK hospitals, recruiting from June 2009 to November 2012.

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model.

Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.

Importance: Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs.

Objective: To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite.

Design, Setting, And Participants: A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003.

Treatment of acne in children.

Acne is a common skin condition in adolescents. It is not uncommon in childhood and it persists into adulthood. A broad range of acne treatments are available and have been shown to be safe and effective in adolescents and adults.

The management of acne vulgaris in pregnancy.

Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy.

Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn's Disease.

Background: Cutaneous Crohn's Disease is a notoriously difficult condition to treat and causes significant morbidity, impacting heavily on quality of life. This is the first study in adults examining the effect of topical tacrolimus on the different cutaneous manifestations of Crohn's Disease.

Methods: This open label observational study of 20 patients with heterogeneous forms of cutaneous Crohn's disease used topical tacrolimus 0.

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

Background: Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment.

Effects of ultraviolet light on human serum 25-hydroxyvitamin D and systemic immune function.

Background: Many immune-mediated diseases are associated with low levels of vitamin D and sunlight. UV light or supplementation with vitamin D can increase regulatory T-cell activity and prevent animal models of autoimmune disease. Increasing population vitamin D levels may therefore alleviate the burden of human immune-mediated disease.

Patient preferences for psoriasis treatment: process characteristics considered more important than outcome attributes.

In a recent paper by Schaarschmidt et al., patients with moderate-to-severe psoriasis completed a conjoint analysis survey (discrete choice experiment) to determine which factors had influenced their choice of treatment, and the relative importance of each factor. They also assessed how socioeconomic and demographic factors affected patient choice.

Influence of isotretinoin on hippocampal-based learning in human subjects.

Rationale: The acne drug isotretinoin has 13-cis retinoic acid as its active agent. Adverse effects that have been described include severe depression. Animal studies indicate that the hippocampus is particularly sensitive to retinoic acid.

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds.

Background: Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.

Factors affecting adherence to treatment of psoriasis: comparing biologic therapy to other modalities.

Objectives: This study evaluated self-reported patient adherence to different types of treatment in psoriasis and factors that affect adherence.

Patients And Methods: Patients attending a Dermatology Department for treatments of psoriasis completed a questionnaire about adherence to each of their therapies, Self-assessed Psoriasis Area and Severity Index (SAPASI) and Dermatology Life Quality Index (DLQI).

Results: Hundred and six patients participated, 98 on topical treatments, 43 on oral systemic therapies, 39 on phototherapy and 29 were on biologic therapies.