IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis.

BACKGROUND: The CARD14 gene encodes a protein that enhances nuclear factor (NF)-κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis. OBJECTIVES: To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis. METHODS: DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments. RESULTS: A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04). CONCLUSIONS: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.

Dermoscopy in general dermatology: practical tips for the clinician.

In addition to its well-documented value in improving the diagnosis of skin tumours, dermoscopy is continually gaining appreciation in the field of general dermatology. Dermoscopy has been shown to facilitate the clinical recognition of several inflammatory and infectious diseases, as well as their discrimination from skin tumours. Moreover, recent data indicate that it might also be profitable in assessing the outcome and adverse effects of various treatments. Application of dermoscopy should follow the standard procedure of acquiring information from patient history and clinically evaluating the number, location and morphology of the lesion(s). Four parameters should be assessed when applying dermoscopy in the realm of inflammatory and infectious diseases: (i) morphological vascular patterns; (ii) arrangement of vascular structures; (iii) colours; and (iv) follicular abnormalities, while the presence of other specific features (clues) should also be evaluated. It must be underlined that dermoscopic findings should always be interpreted within the overall clinical context of the patient, integrated with information from the history and the macroscopic examination. With new evidence continuously being gathered, the dermatoscope gradually acquires a role similar to the stethoscope of general practitioners, becoming an irreplaceable clinical tool for dermatologists. In this article, we provide a succinct summary of existing data on dermoscopy in general dermatology. Practical tips are suggested, which can assist clinicians in profitably utilizing and applying the available knowledge in their everyday practice.

Cold-induced sweating syndrome type 1, with a CRLF1 level mutation, previously associated with Crisponi syndrome.

INTRODUCTION: Cold-induced sweating syndrome type 1 (CISS1) is a rare autosomal recessive genodermatosis caused by mutations in the CRLF1 gene, characterized by profuse sweating when the ambient temperature is below 22°C and morphological alterations. CRLF1 mutations also cause Crisponi syndrome (CS), which presents neonatal muscle contractions, morphological disorders and alterations in the autonomous nervous system. CASE REPORT: A 30-year-old man sought treatment for profuse sweating. His medical record included neonatal admission for generalized hypertonicity. Clinical examination revealed morphological alterations. A genetic study was requested, detecting a c.713dupC mutation in homozygosity in the CRLF1 gene. CONCLUSIONS: We report the case of a male with clinical and genetic diagnosis of CISS1 who in childhood presented clinical characteristics of CS. The mutation detected in CRLF1 has not been described in patients with CISS1, but in one with CS. These data seem to support the theory that CS and CISS1 are variants of the same disorder.

Heavy rains control the floating macroplastic inputs into the sea from coastal Mediterranean rivers: A case study on the Têt River (NW Mediterranean Sea).

This study focuses on the relevance of small watersheds in the macroplastic pollution of coastal environments. It aims to identify and quantify in terms of composition, number and mass, current riverine flows of floating macroplastics (>2.5 cm). Estimates are based on 66 visual monitoring of total litter over a 4-year-period (2016-2019) in a small coastal Mediterranean river, the Têt River (NW Mediterranean Sea). The plastic fraction represented 97 % of the observed litter, mainly cigarette butts (20.5 %), polystyrene fragments (18.8 %) and light packaging (16.3 %). The Tet River is characterized by frequent flash-flood events caused by heavy rain, that can induce a sudden rise of the water discharge. Such hydroclimatic forcing greatly influence macroplastic flows, both in terms of their average compositions and loads. We have estimated that 354,000 macroplastic items, corresponding to 0.65 tons, are discharged annually from the Tet River into the sea, and that 73 % of them are released during rain events (∼6 % of the year). The short observation distance from the water surface allowed to exhibit the great abundance of small litter (80 % of them were < 10 cm) and to evaluate to 1.8 g the average mass of floating plastics. Our results suggest that remediation actions must be taken on rainy days and target small litter in order to significantly limit macroplastic inputs from rivers to the sea. Moreover, the large share of cigarette butts in macrolitter inputs demonstrates that reducing ocean pollution cannot be achieved solely by improving waste management, but that changes in social behavior are also needed to stem waste production at the source.

Floating marine macro litter in the Black Sea: Toward baselines for large scale assessment.

The Black Sea is a semi-enclosed basin subject to major anthropogenic pressures, including marine litter and plastic pollution. Due to numerous large rivers draining into the basin and a population settled along the coast, the region could accumulate significant amounts of floating litter over time. Until now, only limited field data were available, and litter quantities and distribution remained unknown. In this study, floating marine macro litter (FMML) was assessed at the regional Black Sea scale for the first time, showing relatively high litter densities across the basin that reached a weighted mean of 81.5 items/km2. Monitoring data revealed an accumulation of floating items offshore in the eastern part of the basin, resembling on a small scale a 'garbage patch', where litter items were trapped, showing elevated densities in comparison to their surrounding areas. Most of these items were made of plastic materials (ca. 96%) and included large numbers of plastic and polystyrene fragments of small size ranges (2.5-10 cm). Harmonised field data collection through consistent and regular monitoring programmes across the region is essential to establish baselines and thresholds for large scale assessment at international level.

Patient and Physician Satisfaction with Calcipotriol and Betamethasone Dipropionate Aerosol Foam in the Treatment of Plaque Psoriasis on the Body. / Satisfacción del paciente y el médico con la espuma en aerosol de calcipotriol y dipropionato de betametasona para el tratamiento de la psoriasis vulgar en el cuerpo.

BACKGROUND AND OBJECTIVE: Calcipotriol and betamethasone dipropionate (Cal/BD) aerosol foam is more effective in the treatment of plaque psoriasis than earlier formulations incorporating this combination of active ingredients. The aim of this study was to evaluate patient and physician satisfaction with Cal/BD aerosol foam in the treatment of plaque psoriasis on the body. MATERIAL AND METHODS: Retrospective observational study of 446 patients with plaque psoriasis affecting no more than 30% of the body surface area who had received treatment with Cal/BD aerosol foam for 4 weeks. The patients rated their satisfaction with the treatment using the TSQM-9 (Treatment Satisfaction Questionnaire for Medication) and the physicians on a 5-point Likert scale. RESULTS: Patients were highly satisfied with Cal/BD aerosol in terms of its ability to treat their condition (84%), relieve their symptoms (84.4%), and act rapidly (82.8%). With respect to convenience, the patients gave high ratings to ease of use (91.8%), ease of planning (93.9%), and ease of following instructions (89.9%). Global satisfaction was also high, with 85% of patients expressing that they were satisfied, very satisfied, or extremely satisfied with the treatment. Of the physicians, 85.7% stated that they were quite or very satisfied with the treatment. CONCLUSION: Both patients and physicians expressed high satisfaction with the use of Cal/BD aerosol foam for the treatment of plaque psoriasis on the body.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

Fecal pollution in coastal marine sediments from a semi-enclosed deep embayment subjected to anthropogenic activities: an issue to be considered in environmental quality management frameworks development.

Sewage discharge is a major source of pollution in marine environments. Urban wastewaters can directly enter marine environments carrying pathogen organisms, organic loads, and nutrients. Because marine sediments can act as the ultimate fate of a wide range of pollutants, environmental quality assessment in this compartment can help to identify pollution problems in coastal areas. In the present study, characterization of surficial marine sediments allowed assessment of fecal pollution in a semi-enclosed deep embayment that is subjected to anthropogenic activities. Physicochemical parameters and fecal indicators presented a great spatial heterogeneity. Fecal coliform and Clostridium perfringens showed accumulation in an extensive area, not only in proximity to sewage discharge points, but also in sediments at 100 meters depth. Results included herein demonstrated that, in coastal areas, urban wastewater discharge can affect the whole ecosystem through accumulation of fecal matter in bottom sediments. Application of multivariate techniques provided useful information with applicability for management of coastal areas in such complex systems. Environmental implications of wastewater discharge in coastal areas indicate the need to implement and include sediment quality control strategies in legislative frameworks.