Utility of Survival Motor Neuron ELISA for Spinal Muscular Atrophy Clinical and Preclinical Analyses

Genetic defects leading to the reduction of the survival motor neuron protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there are a number of therapies under evaluation as potential treatments for SMA, there is a critical lack of a biomarker method for assessing efficacy of therapeutic interventions, particularly those targeting upregulation of SMN protein levels. Towards this end we have engaged in developing an immunoassay capable of accurately measuring SMN protein levels in blood, specifically in peripheral blood mononuclear cells (PBMCs), as a tool for validating SMN protein as a biomarker in SMA.A sandwich enzyme-linked immunosorbent assay (ELISA) was developed and validated for measuring SMN protein in human PBMCs and other cell lysates. Protocols for detection and extraction of SMN from transgenic SMA mouse tissues were also developed.The assay sensitivity for human SMN is 50 pg/mL. Initial analysis reveals that PBMCs yield enough SMN to analyze from blood volumes of less than 1 mL, and SMA Type I patients' PBMCs show ∼90% reduction of SMN protein compared to normal adults. The ELISA can reliably quantify SMN protein in human and mouse PBMCs and muscle, as well as brain, and spinal cord from a mouse model of severe SMA.This SMN ELISA assay enables the reliable, quantitative and rapid measurement of SMN in healthy human and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN ELISA has general translational applicability to both preclinical and clinical research efforts

Does biological therapy affect interferon-γ release assay response? A long-term follow-up of patients with psoriasis using QuantiFERON-TB

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HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland–bearing body sites. The negative impact of HS on patient’s quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. Objective The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. Methods A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment–General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). Results A total of 140 patients (59% women; mean age 34.9 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HSPGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test–retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. Conclusion Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practic

To what extent is quality of life impaired in vitiligo? A multicenter study on italian patients using the dermatology life quality index

BACKGROUND: It is believed that vitiligo has an impact on the overall patient quality of life (QoL). OBJECTIVE: To estimate QoL in a fairly large sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. METHODS: One hundred and sixty-one vitiligo patients referred to 9 dermatological centers were offered to participate by filling in the Italian version of the DLQI questionnaire. RESULTS: The mean total DLQI score was 4.3 (SD ±4.9; range: 0-22). In multivariate analysis, DLQI >5 was associated with female gender, stability of the disease over time and involvement of the face at disease onset. CONCLUSIONS: The impairment of QoL is overall limited in Italian vitiligo patients, especially if it is compared with results from other available studies. This could be due to cultural and ethnic characteristics of the sample. © 2014 S. Karger AG, Basel

Adult female acne and associated risk factors: Results of a multicenter case-control study in Italy.

BACKGROUND The reasons for the appearance of acne in adulthood are largely unknown. OBJECTIVE We explored the role of personal and environmental factors in adult female acne. METHODS We conducted a multicenter case-control study in the outpatient departments of 12 Italian cities. Cases (n = 248) were consecutive women ≥25 years of age with newly diagnosed acne of any grade. Controls (n = 270) were females diagnosed with conditions other than acne. RESULTS In multivariate analysis, a history of acne in parents (odds ratio [OR] = 3.02) or siblings (OR = 2.40), history of acne during adolescence (OR = 5.44), having no previous pregnancies (OR = 1.71), having hirsutism (OR = 3.50), being an office worker versus being unemployed or being a housewife (OR = 2.24), and having a high level of reported psychological stress (OR = 2.95) were all associated with acne. A low weekly intake of fruits or vegetables (OR = 2.33) and low consumption of fresh fish (OR = 2.76) were also associated with acne. LIMITATIONS We did not establish an onset date for acne. Some of our associations may reflect consequences of established acne. CONCLUSION Lifestyle factors may play an important role for acne development in adulthood, but their role should be further assessed in prospective studies

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

Background: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. Objective: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. Methods: Adult moderate-to-severe AD patients, referring to 39 Italian centres, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). Results: A total of 109 (71M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. Conclusions: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile