Effectiveness of Systemic Therapies in Patients with Obesity and Psoriasis: A Single-center Retrospective Study

This retrospective study included 63 patients with obesity (Body Mass Index; BMI ≥ 30) and psoriasis. Our aim was to verify the effectiveness of different systemic therapies administered to the above cohort of subjects over a period of 1 year. Improvements of 75%, 90%. and 100% compared with the baseline Psoriasis Area Severity Index (PASI 75, PASI 90, and PASI 100, respectively) were used as clinical outcome measures. In a median time of 16 weeks, 85.7%, 68.2%, and 38.0% of patients achieved PASI 75, PASI 90, and PASI 100, respectively. In parallel, the Dermatology Life Quality Index (DLQI) and the visual analog score for measuring itch intensity (VAS itch) decreased significantly (P<0.0001 for both parameters). At the achievement of PASI 75, BMI increased as compared to baseline (P=0.02) and did not significantly vary at the attainment of PASI 90 and PASI 100 (P= 0.07 for both outcomes). Logistic multivariate regression analysis showed that treatment with biologic drugs was a positive predictor for achieving PASI 75, PASI 90, and PASI 100. BMI >31.7 and the presence of psoriatic arthritis were negative predictors for the achievement of PASI 90, while having a DLQI >6 was a positive predicto

Effectiveness of Systemic Therapies in Patients with Obesity and Psoriasis: A Single-center Retrospective Study

This retrospective study included 63 patients with obesity (Body Mass Index; BMI ≥ 30) and psoriasis. Our aim was to verify the effectiveness of different systemic therapies administered to the above cohort of subjects over a period of 1 year. Improvements of 75%, 90%. and 100% compared with the baseline Psoriasis Area Severity Index (PASI 75, PASI 90, and PASI 100, respectively) were used as clinical outcome measures. In a median time of 16 weeks, 85.7%, 68.2%, and 38.0% of patients achieved PASI 75, PASI 90, and PASI 100, respectively. In parallel, the Dermatology Life Quality Index (DLQI) and the visual analog score for measuring itch intensity (VAS itch) decreased significantly (P<0.0001 for both parameters). At the achievement of PASI 75, BMI increased as compared to baseline (P=0.02) and did not significantly vary at the attainment of PASI 90 and PASI 100 (P= 0.07 for both outcomes). Logistic multivariate regression analysis showed that treatment with biologic drugs was a positive predictor for achieving PASI 75, PASI 90, and PASI 100. BMI >31.7 and the presence of psoriatic arthritis were negative predictors for the achievement of PASI 90, while having a DLQI >6 was a positive predicto

Endothelin-1 Levels Are Increased in Sera and Lesional Skin Extracts of Psoriatic Patients and Correlate with Disease Severity

Endothelins (ETs), in addition to their systematical activities, exert important functions at the skin level, such as increase of keratinocyte proliferation, neo-angiogenesis and leukocyte chemotaxis, which are among the main characteristics of psoriasis. To assess a possible ET-1 involvement in plaque-type psoriasis, ET-1 determinations were carried out in 15 sera and 8 lesional and non-lesional biopsy skin extracts from psoriatic patients and in 15 sera and 5 biopsy skin extracts from healthy volunteers, sex- and age-matched, using commercially available ELISA kits. A statistical analysis of the results showed that ET-1 levels were increased in sera of psoriatic patients, as compared to normal subjects (p = 0.04). In addition, there was a significant correlation between both serum (r = 0.60, p = 0.02) and lesional skin (r = 0.80, p = 0.03) ET-1 values versus the Psoriasis Area and Severity Index scores. Significant increases of the lesional versus the non-lesional (p = 0.01) and versus the normal (p = 0.04) ET-1 skin extract values were observed, together with a significant correlation between lesional and non-lesional ET-1 skin levels (r = 0.79, p = 0.03). These findings were also confirmed at the mRNA level, using RT-PCR analysis, where increased ET-1 mRNA levels, densitometrically measured, were found in the lesional samples versus non-lesional and normal skin. Since interleukin-8 is involved in psoriasis and shares some biological properties with ET-1, we further evaluated the levels of this cytokine in skin extracts. The behaviour of interleukin-8 paralleled that of ET-1, and a significant correlation between these two molecules was observed in the lesional skin (r = 0.76, p = 0.05). Taken together, these data stress that, as previously described for interleukin-8, ET-1 may be involved in inflammatory processes associated with psoriasis

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLACw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

Can hydradenitis suppurativa be associated with inflammatory joint involvement? Report of a case series and review of the literature.

Dear Editor, Hidradenitis suppurativa (HS) or acne inversus, is a chronic inflammatory cutaneous disease with a significant negative impact on the patient's quality of life, from a psychological, social and occupational point of view. The disease mainly affects the female sex and occurs between puberty and 40 years of age. It is estimated that in Europe the prevalence of the disease in the general population is 1%.1 Recent studies have shown a high incidence of inflammatory arthritis, in particular spondyloarthritis, in patients with HS.2 In this report, we present 18 cases of patients with hidradenitis suppurativa, visited at the San Gallicano Dermatological Institute, who presented joint symptoms. [...

Magnetic resonance spectroscopy in Parkinson's disease and parkinsonian syndromes

This paper looks at the use of magnetic resonance spectroscopy (MRS) for diagnostic and research purposes in Parkinson’s disease and parkinsonian syndromes. The review considers both proton MRS (1H MRS) and phosphorus MRS (31 P MRS) studies. MRS is useful for diagnostic purposes, helping to differentiate Parkinson’s disease from other parkinsonian syndromes. Even more usefully, MRS can be used for non invasive in vivo human researc

Ataxia in posterior circulation stroke: Clinical-MRI correlations

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