Veronika Vargová

Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis : a randomised trial

BACKGROUND Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. METHODS We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedmans test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. FINDINGS Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study. INTERPRETATION Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate. FUNDING Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Electrochemical sensing of concanavalin A and ovalbumin interaction in solution

In an attempt to develop a label- and reagent-free electrochemical method for the detection of lectin-glycoprotein interactions, we tested lectin-concanavalin A (ConA), glycoprotein-ovalbumin (Ova) and their complex using chronopotentiometric stripping (CPS) analysis and a hanging mercury drop electrode. Incubation of ConA with Ova resulted in an increase of the CPS peak H of the complex as compared to the CPS peaks of individual Ova and ConA proteins. Qualitatively similar results were obtained with other glycoprotein-lectin couples (ConA-RNase B and lectin from Sambucus nigra-fetuin). Using the CPS method, we were able to follow the course of complex formation in solution. Comparable responses of Ova, ConA and ConA-Ova complex were obtained not only at the mercury electrode but also with solid amalgam electrodes, which are more suitable for parallel analysis. It can be anticipated that electrochemical methods, namely CPS, will find application in glycomics and proteomics.

A52: the impact of adalimumab on growth in patients with juvenile idiopathic arthritis.

Children with juvenile idiopathic arthritis (JIA) often exhibit growth impairments. Treatment with adalimumab (ADA) has been shown to be safe and effective in JIA patients (pts) when dosed every other week (eow) for up to 3 years, but the effect of ADA on growth is not known. The purpose of this post hoc analysis is to describe growth parameters in pts with JIA treated with ADA in a clinical trial setting.

PReS-FINAL-2001: The impact of adalimumab on growth in patients with juvenile idiopathic arthritis

Children with juvenile idiopathic arthritis (JIA) often exhibit growth impairments. Treatment with adalimumab (ADA) has been shown to be safe and effective in JIA patients (pts) when dosed every other week (eow) for up to 3 years [1], but the effect of ADA on growth is not known.

The Slovak version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Slovak language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 108 JIA patients (5.6% systemic, 38.9% oligoarticular, 30.5% RF-negative polyarthritis, 25% other categories) and 100 healthy children were enrolled in two centres. Notably, none of the enrolled JIA patients is affected with psoriatic arthritis. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Slovak version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways

Objective Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Methods Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. Results STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Conclusions Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars.

First report on Giardia duodenalis assemblage F in Slovakian children living in poor environmental conditions

BACKGROUND Giardiasis is one of the most common gastrointestinal infections of humans and animals attributable to complex of eight morphologically identical genetic assemblages, further divided into sub-assemblages. Disease is common for a wide range of hosts and genetic characterization is needed for better understanding of multifaceted epidemiology for this protozoan parasite. The aim of this study was to identify genetic heterogeneity in assemblages and sub-assemblages of Giardiaduodenalis circulating among the children population living in deprived socioeconomic conditions. METHODS A total of 333 stool samples from children in eastern Slovakia were collected during the period of 2015-2016 and analysed by molecular methods. Molecular characterization of G. duodenalis was performed by sequence analysis of triose phosphate isomerase gene (tpi) and glutamate dehydrogenase gene (gdh). RESULTS G. duodenalis DNA was detected in 21 samples (6.3%), out of which 14 isolates (66.7%) belonged to assemblage B, 4 isolates (19.0%) to sub-assemblage AII and 3 isolates (14.3%) corresponded to assemblage F. As regards the determination of sub-assemblages of assemblage B, 4 isolates were characterized as sub-assemblage BIII and 6 isolates as sub-assemblage BIV. CONCLUSION This study is the first finding of cat specific assemblage F in man not only in Slovakia, but also in Europe. The absence of molecular data about G. duodenalis in companion animals in Slovakia establishes a strong need for further investigation for potential sources of giardiasis and understanding the epidemiology will help to improve the preventive strategies in eradication of infection in this population.

Efficacy of TNF blockers from the perspective of growth velocity: slovak experience

In patients with polyarticular course of juvenile idiopathic arthritis (JIA) both, ongoing chronic inflammation with high levels of pro-inflammatory cytokines and corticosteroid treatment, may affect linear growth adversely, potentially leading to irreversible growth retardation. Biologic treatment of JIA may have the potential to enable normal growth in children with JIA.

Absence of Arthritis as a Sign of Sine Syndrome in Still’s Disease in Adulthood

The authors of this chapter discuss the atypical course of Still’s disease in adulthood. It is a sine syndrome (skin changes, itchy, linear urticarial rash or other skin manifestations, periorbital edema and erythema of eyelids; organ manifestations were not present in the patient) with arthritis – in the form of monoarthritis of the right knee – that occurred after 23 years of the disease. The most pronounced feature was five attacks of fever associated with chills and high inflammatory activity. Therapy with corticosteroids, cyclosporine and methotrexate suppressed and reduced relapses of the disease. An attempt to discontinue basal therapy led to the last relapse of the disease. Differential diagnostic procedures for nosographic demarcation of Still’s disease in adulthood associated with sine syndrome are discussed, as well as the options for future treatment with biologics.