414 research outputs found

    Effects of eight neuropsychiatric copy number variants on human brain structure

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    peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

    Target molecules for future hidradenitis suppurativa treatment

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    The registration of the tumour necrosis factor-α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti- interleukin (IL)-17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL-1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better-defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

    Anti-COVID-19 measurements for hidradenitis suppurativa patients

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    The reported incidence of COVID-19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID-19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID-19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti-COVID-19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS-CoV2 and patients affected by metabolic syndrome constitute a high-risk group for COVID-19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non-living virus anti-SARS-CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

    Cutaneous manifestations in patients with COVID-19 : a preliminary review of an emerging issue

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    Background: The infection caused by the recently identified SARS-CoV-2, called COronaVIrus Disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in COVID-19 patients. Objectives: To provide a brief overview of the COVID-19-associated cutaneous lesions. Methods: Literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding clinical and histological features of COVID-19-associated skin manifestations. Results: Literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the role of hyperactive immune response, complement activation and microvascular injury has been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: i) urticarial rash, ii) confluent erythematous/maculo-papular/morbilliform rash, iii) papulovesicular exanthem, iv) chilblain-like acral pattern, v) livedo reticularis/racemosa-like pattern, vi) purpuric "vasculitic" pattern. These six patterns can be merged into two main settings: the first one - inflammatory/exanthematous - including the first three groups cited above and the second one including the vasculopathic/vasculitic lesions of the last three aforementioned groups. Conclusions: The possible presence of cutaneous findings leading to suspect COVID-19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic value of such cutaneous manifestations

    Treatment of Autoimmune Bullous Diseases During Pregnancy and Lactation : A Review Focusing on Pemphigus and Pemphigoid Gestationis

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    Pregnancy may induce the onset or exacerbation of autoimmune bullous diseases such as pemphigus or pemphigoid gestationis. A shift toward T helper (Th) 2 immune response and the influence of hormonal changes have been evoked as possible triggering factors. Therapeutic management of this setting of patients may represent a challenge, mainly due to safety concerns of some immunosuppressive drugs during pregnancy and lactation. In this narrative review, we provided a comprehensive overview of the therapeutic management of autoimmune bullous diseases in pregnant and breastfeeding women, focusing on pemphigus and pemphigoid gestationis

    Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey

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    BACKGROUND: The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. OBJECTIVES: This cross-sectional survey was aimed at evaluating physicians\u2019 attitudes regarding therapeutic management of CSU on clinical practice. METHODS: A study-specific questionnaire was administered to a group of physicians (n=21) with a specialist interest in CSU from different areas of Italy (Group A) and also to other physicians (n=25) who manage CSU only occasionally in their clinical activity (Group B). RESULTS: In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. CONCLUSIONS: These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work

    A unified concept of acne in the papa spectrum disorders

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    Background:Acne is a common condition. Sometimes acne or acne-like features are a part of autoinflammatory diseases such as PAPA spectrum disorders. Our objective wasto determine whether acne in PAPA spectrum disorders has specific phenotypic traits. Summary: This is aliterature review on reported cases of patients with PAPA, PAMI, PASH, PAPASH, PsAPASH, PAC or PASS syndrome. Acne was classified into four categories: moderate, severe, nodulocystic, acne fulminans.One hundred patients were included. Age of onset of acne and topography were the same as in acne vulgaris. Acne's phenotype was at least severe (including acne fulminans, nodulocystic and severe) in 83% of cases. Genetic mutations or variants with potential pathological significance were reported in 49 patients. The addition of isotretinoin to biotherapies was required to control acne in several patients