Long-term topical management of psoriasis: the road ahead

AbstractTopical therapies have been available for the treatment of psoriasis for several decades. Despite this and the availability of several types of topicals, with varying potency, and numerous ..

Use of systemic therapies in adults with atopic dermatitis:12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD)

Background The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. Methods Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. Results 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. Conclusion The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines

The Treat-to-Target Project in Atopic Dermatitis: One Year On

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been deve loped previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development

Seeing the way: visual sociology and the distance runner's perspective

Employing visual and autoethnographic data from a two‐year research project on distance runners, this article seeks to examine the activity of seeing in relation to the activity of distance running. One of its methodological aims is to develop the linkage between visual and autoethnographic data in combining an observation‐based narrative and sociological analysis with photographs. This combination aims to convey to the reader not only some of the specific subcultural knowledge and particular ways of seeing, but also something of the runner's embodied feelings and experience of momentum en route. Via the combination of narrative and photographs we seek a more effective way of communicating just how distance runners see and experience their training terrain. The importance of subjecting mundane everyday practices to detailed sociological analysis has been highlighted by many sociologists, including those of an ethnomethodological perspective. Indeed, without the competence of social actors in accomplishing these mundane, routine understandings and practices, it is argued, there would in fact be no social order

Assembly and characterisation of a unique onion diversity set identifies resistance to Fusarium basal rot and improved seedling vigour

Conserving biodiversity is critical for safeguarding future crop production. Onion (Allium cepa L.) is a globally important crop with a very large (16 Gb per 1C) genome which has not been sequenced. While onions are self-fertile, they suffer from severe inbreeding depression and as such are highly heterozygous as a result of out-crossing. Bulb formation is driven by daylength, and accessions are adapted to the local photoperiod. Onion seed is often directly sown in the field, and hence seedling establishment is a critical trait for production. Furthermore, onion yield losses regularly occur worldwide due to Fusarium basal rot caused by Fusarium oxysporum f. sp. cepae. A globally relevant onion diversity set, consisting of 10 half-sib families for each of 95 accessions, was assembled and genotyping carried out using 892 SNP markers. A moderate level of heterozygosity (30–35%) was observed, reflecting the outbreeding nature of the crop. Using inferred phylogenies, population structure and principal component analyses, most accessions grouped according to local daylength. A high level of intra-accession diversity was observed, but this was less than inter-accession diversity. Accessions with strong basal rot resistance and increased seedling vigour were identified along with associated markers, confirming the utility of the diversity set for discovering beneficial traits. The onion diversity set and associated trait data therefore provide a valuable resource for future germplasm selection and onion breeding

Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis.

Importance: Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied. Objective: To examine the factors associated with PPP severity. Design, Setting, and Participants: An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020. Main Outcomes and Measures: Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). Results: Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 [43%]) compared with men (5 of 25 [20%]) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with nonsmokers (6 of 24 [25%]) (P = .14). Conclusions and Relevance: The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial

Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne

Damaging alleles affecting multiple CARD14 domains are associated with palmoplantar pustulosis

No abstract available

Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3–10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD