14.2 Causes of early death in juvenile onset systemic lupus erythematosus (JSLE)

PubMe

Ordered mesoporous silica materials for protein adsorption

Lysozyme and BSA were used, as model proteins of considerably different dimensions, in order to evaluate the influence of the distinct pore structural characteristics of three types of ordered mesoporous silica materials (MCF, SBA-15 and MCM-41) on protein adsorption. Characterisation by X ray diffraction and nitrogen adsorption at 77K revealed the typical pore structural features of each type of material. The maximum of the pore size distributions indicated that the width of the windows of MCF (2) (mesitylene/P123 of 2) was larger than the pore diameter of the unidirectional tubular pores of SBA-15. All the materials presented similar small external surface areas but high pore volumes, with that of MCF (2) being the highest. The adsorption of lysozyme at pH=8 increased in the order MCM-41<< SBA-15< MCF (2), and the uptakes were well above those of BSA at pH=5. Although BSA is not completely excluded from the mesopores of SBA-15 and MCF (2), as happens with MCM-41, the adsorption occurs to a very limited extent. The overall behaviour of these SBA-15 and MCF (2) samples was not significantly different and both revealed potential for the separation of these proteins

Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com

OBJECTIVES: To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (jSSc) patients in the international Juvenile SSc Inception Cohort (jSScC), compare these characteristics between the classically defined diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes, and among those with overlap features. METHODS: A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, treatment, and patient and physician reported outcomes were extracted and summary statistics applied. Comparisons between dcjSSc and lcSSc subtypes and patients with and without overlap features were performed using Chi-square and Mann Whitney U-tests. RESULTS: At data extraction 150 jSSc patients were enrolled across 42 centers, 83% were Caucasian, 80% female, dcjSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between dcjSSc and lcjSSc regarding the modified Rodnan Skin Score, presence of Gottron's papules, digital tip ulceration, 6 Minute walk test, composite pulmonary and cardiac involvement. All more frequent in dcSSc except for cardiac involvement. DcjSSc patients had significantly worse scores for physician rated disease activity and damage. A significantly higher occurrence of Gottron's papules, musculoskeletal involvement and composite pulmonary involvement, and significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION: Results from a large international jSSc cohort demonstrate significant differences between dcjSSc and lcjSSc patients including more globally severe disease and increased frequency of ILD in dcjSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease

Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. Conclusion The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice

Are diffuse and limited juvenile systemic sclerosis different in clinical presentation? Clinical characteristics of a juvenile systemic sclerosis cohort

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies