Association between several immune response-related genes and the effectiveness of biological treatments in patients with moderate-to-severe psoriasis.

Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.

Treatment of Behçet disease with oral roflumilast, an observational study.

INTRODUCTION: Mucocutaneous Behcet's disease is often a therapeutic challenge. Roflumilast has shown promise in other inflammatory dermatological conditions. The objective of this study is to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet's Disease-associated aphthosis in routine clinical practice. METHODS: Single cohort ambispective observational study. 11 patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period with the previous treatment. RESULTS: During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared to the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the Whitout treatment period and the Roflumilast treatment period.Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patient withdrew treatment. DISCUSSION: Roflumilast appears a promising option in the treatment of Behçet's disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet's Disease-associated aphthosis, which could improve patients' quality of life and address unmet therapeutic needs.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Soil Water Content Prediction Using Electrical Resistivity Tomography (ERT) in Mediterranean Tree Orchard Soils.

Water scarcity in arid and semiarid regions poses problems for agricultural systems, awakening special interest in the development of deficit irrigation strategies to improve water conservation. Toward this purpose, farmers and technicians must monitor soil water and soluble nutrient contents in real time using simple, rapid and economical techniques through time and space. Thus, this study aimed to achieve the following: (i) create a model that predicts water and soluble nutrient contents in soil profiles using electrical resistivity tomography (ERT); and (ii) apply the model to different woody crops under different irrigation regimes (full irrigation and regulated deficit irrigation (RDI)) to assess the efficiency of the model. Simple nonlinear regression analysis was carried out on water content and on different ion contents using electrical resistivity data as the dependent variable. A predictive model for soil water content was calibrated and validated with the datasets based on exponential decay of a three-parameter equation. Nonetheless, no accurate model was achieved to predict any soluble nutrient. Electrical resistivity images were replaced by soil water images after application of the predictive model for all studied crops. They showed that under RDI situations, soil profiles became drier at depth while plant roots seemed to uptake more water, contributing to reductions in soil water content by the creation of desiccation bulbs. Therefore, the use of ERT combined with application of the validated predictive model could be a sustainable strategy to monitor soil water evolution in soil profiles under irrigated fields, facilitating land irrigation management.

Performance of Coronary Artery Calcium Testing in Patients With Severe Psoriasis: Risk Assessment and Reclassification Potential in a Low Cardiovascular Risk Population.

BACKGROUND: Patients with severe psoriasis have an increased cardiovascular (CV) risk and prevalence of subclinical coronary artery disease (CAD). Coronary artery calcium (CAC) testing can detect subclinical CAD and improve cardiovascular risk assessment beyond clinical scores. OBJECTIVES: Evaluate the presence and magnitude of subclinical CAD determined by CAC score among the different ESC/EAS CV risk categories, as well as the potential for risk reclassification, in patients with severe psoriasis from a low CV risk population. METHODS: Unicentric cross-sectional study in 111 patients with severe chronic plaque psoriasis from a low CV risk population in the Mediterranean region. Patients were classified into four CV risk categories according to the ESC/EAS guideline recommendations and HeartScore/SCORE calibrated charts. Patients underwent coronary computed tomography to determine their CAC scores. Patients in the moderate-risk category with a CAC score of ≥100 were considered to be reclassified as recommended by the 2019 ESC/EAS guidelines. Reclassification was also considered for patients in the low-risk category with a CAC score>0. RESULTS: Presence of subclinical CAD was detected in 46 (41.4%) patients. These accounted for 86.2% of patients in high/very-high-risk categories and 25.6% of patients in non-high-risk categories. Fourteen (17.1%) of the patients in non-high-risk categories were reclassifiable due to their CAC score. This percentage was higher (25%) when considering the moderate-risk category alone and lower (13.8%) in the low-risk category. Age was the only variable associated with presence of subclinical CAD and reclassification. CONCLUSIONS: Over 40% of patients with severe psoriasis from a low-risk region and up to 25% of those in non-high-risk categories have subclinical CAD. CAC appears to be useful for reclassification purposes in CV risk assessment of patients with severe psoriasis. Further research is required to elucidate how CAC could be implemented in everyday practice at outpatient dermatology clinics dedicated to severe psoriasis.

Irriman Platform: Enhancing Farming Sustainability through Cloud Computing Techniques for Irrigation Management.

Crop sustainability is essential for balancing economic development and environmental care, mainly in strong and very competitive regions in the agri-food sector, such as the Region of Murcia in Spain, considered to be the orchard of Europe, despite being a semi-arid area with an important scarcity of fresh water. In this region, farmers apply efficient techniques to minimize supplies and maximize quality and productivity; however, the effects of climate change and the degradation of significant natural environments, such as, the "Mar Menor", the most extent saltwater lagoon of Europe, threatened by resources overexploitation, lead to the search of even better irrigation management techniques to avoid certain effects which could damage the quaternary aquifer connected to such lagoon. This paper describes the Irriman Platform, a system based on Cloud Computing techniques, which includes low-cost wireless data loggers, capable of acquiring data from a wide range of agronomic sensors, and a novel software architecture for safely storing and processing such information, making crop monitoring and irrigation management easier. The proposed platform helps agronomists to optimize irrigation procedures through a usable web-based tool which allows them to elaborate irrigation plans and to evaluate their effectiveness over crops. The system has been deployed in a large number of representative crops, located along near 50,000 ha of the surface, during several phenological cycles. Results demonstrate that the system enables crop monitoring and irrigation optimization, and makes interaction between farmers and agronomists easier.

Drug holiday approach for Vismodegib treatment in patients with nevoid basal cell carcinoma syndrome: Three cases from real clinical practice.

Sonic hedgehog pathway inhibitor Vismodegib is the first systemic treatment to be approved for metastatic or locally advanced basal cell carcinoma non-subsidiary of surgical treatment, and appears to be a promising treatment option for patients with nevoid basal cell carcinoma syndrome. In these patients, where repeated or prolonged treatment may be necessary, the psychological exhaustion caused by the chronicity of less severe adverse effects appears as the main limiting factor in the persistence of the drug in the long term and in the willingness of patients to take the drug again after its suspension. We report our experience with three cases where a drug holiday approach was effective in decreasing the intensity of adverse effects or improving the patient's subjective tolerance to the drug while maintaining clinical response.

Novel PTEN mutation in Cowden syndrome: case report with late diagnosis and non-malignant course.

Cowden syndrome (CS) is an infrequent genodermatosis caused by mutations in the phosphatase and tensin homolog (PTEN) gene in the majority of cases. As such, it belongs to the PTEN hamartoma tumor syndrome spectrum. This disease has a variable clinical expression characterized by the development of multiple hamartomatous tumors in different organs, usually during the second and third decades of life, and a high cumulative risk of several malignancies. We present a case of Cowden syndrome with late diagnosis presenting with a florid dermatological expression and multiple benign tumors, but no malignancies. A novel PTEN mutation was identified.

Digital ulcerative lichenoid dermatitis in a patient receiving anti-PD-1 therapy.

Programmed cell death receptor 1 inhibitors (anti-PD-1) constitute a form of immunotherapy for the treatment of several cancers. They are associated with cutaneous immune-related adverse events (irAE), occurring in up to 50% of patients. Lichenoid dermatitis is frequent and several presentations have been described. Although attempts have been made to study these reactions, they are yet to be fully characterized and the relationship with tumor response is unclear. We describe a case of digital ulcerative lichenoid dermatitis resembling ulcerative cutaneous lichen planus that occurred during pembrolizumab therapy for oral squamous cell carcinoma. The patient developed a painful ulcer on his index finger 18 months into therapy. Biopsy revealed epidermal ulceration with intense lichenoid dermatitis. Immunohistochemical study revealed intense CD8 positivity at the ulcer's edges and marked CD163 positivity at its base. Although idiopathic forms of this type of lichenoid dermatitis are particularly recalcitrant, our case was successfully managed with topical therapy and oncologic treatment did not require modification. One year after ending treatment the patient remains free of disease progression. It is unclear if this reaction is associated with his favorable oncologic response. This report adds an undescribed reaction to the increasing diversity of cutaneous irAE associated with anti-PD-1 therapy.

Long-term impact of deficit irrigation on the physical quality of berries in 'Crimson Seedless' table grapes.

BACKGROUND: In table grapes, berry firmness influences consumer acceptance so it is important to avoid berry shattering and dehydration during their post-harvest life. Since studies of irrigation effects on table grape quality are comparatively rare, sensory evaluation aimed to identify high-quality berries obtained under different deficit irrigation treatments. A 3-year study examined the effects of deficit irrigation strategies on some physical quality attributes at harvest, after 28 days of cold storage at 0 °C and after an additional shelf-life period of 3 days at 15 °C. Control vines were irrigated to ensure non-limiting water conditions (110% of crop evapo-transpiration), while both regulated deficit irrigation treatment (RDI) and partial root-zone drying (PRD) treatments applied 35% less water post-veraison. The null irrigation treatment (NI) only received natural precipitation (72% less water than control vines). RESULTS: Total yield and physical quality at harvest were not significantly affected by RDI or PRD. Only severe deficit (NI) decreased berry size, and this treatment had the most dehydrated berries and the worst sensory scores post-harvest. After cold storage, increased berry shattering of the PRD treatment was correlated with lower leaf xylem abscisic acid (ABA) concentration at the time of harvest. Overall quality, especially stem browning, determined the shelf-life, and longer storage duration tended to diminish treatment differences. CONCLUSIONS: Only NI clusters showed lower quality than their irrigated counterparts. Neither RDI nor PRD had any noticeable effect on berry quality at the end of cold storage and shelf-life, with the slight differences detected between these treatments related to stem browning and dehydration. Sensory results were similar in RDI and PRD, which provided grapes that were more acceptable to consumers than the control. Thus, it is possible to decrease irrigation of table grapes without adversely affecting the physical quality of the berries.

Psoriasis and ischemic coronary artery disease.

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with an increased risk of ischemic coronary artery disease (CAD) in some populations. We aimed to determine the association between these 2 diseases in our geographic area. MATERIAL AND METHOD: We performed a cross-sectional study of patient records between 2005 and 2012 in the database (Abucacis, Datamart) that contains all medical case histories in the province of Castellón, Spain. Patients diagnosed with psoriasis were compared with a control group of patients diagnosed with melanocytic nevus. The prevalence of CAD and the presence or absence of the main cardiovascular risk factors were analyzed in each group. RESULTS: A total of 9181 patients with psoriasis and 21925 with melanocytic nevus were studied. Univariate logistic regression analysis showed that CAD was significantly associated with psoriasis, age (in years), sex, hypertension, diabetes mellitus, dyslipidemia, and obesity (P<.05). On adjustment for age, sex, and the other cardiovascular risk factors, multivariate regression analysis established that psoriasis was independently associated with CAD (P<.029). CONCLUSION: Our findings in a large sample of patients in a Mediterranean area support the hypothesis that patients in this population have an increased risk of ischemic CAD.