Background The results obtained with the novel biologic agents have increased the expectations of benefit of treatment of juvenile idiopathic arthritis (JIA), with disease remission being now the therapeutic goal in all patients. However, the assessment of remission has seldom been incorporated in clinical trials of biologics in JIA. Moreover, little information exists on the prediction of the efficacy of biologic medications. Objectives To evaluate the proportion of children with JIA treated with etanercept (ETN) who achieved the state of inactive disease (ID) and to search for predictors of ID. Methods The clinical chart of all consecutive JIA patients who were given ETN between 2002 and 2011, and had a follow-up of at least 6 months after ETN start were reviewed. The achievement of ID, defined by the Wallace criteria (J Rheum 2004;31:2290-4), was assessed at each visit from the start of ETN. The primary study outcomes were: 1) proportion of patients who had ID at last follow-up visit while still on ETN; 2) time to achievement of ID after ETN start. Predictors of treatment outcomes included demographic data, JIA subset, type of affected joints, medications received before and during ETN administration, and JIA activity measures at ETN start. The search for predictors was conducted by means of univariate and multivariate analyses. Results A total of 187 patients were given ETN at the standard dose of 0.8 mg/kg/week in the study period. The disease duration at ETN start ranged from 3 months to 21.2 years (median 5.0 years). Fourteen patients had received ETN for less than 6 months or were lost to follow-up. In the remaining 173 patients, treatment duration from baseline to last follow-up visit ranged from 6 months to 10.5 years (median 2.4 years). At last follow-up visit, 87 (50.3%) patients had ID. The time to ID ranged from 2 months to 6.3 years (median 0.7 years). An age at disease onset <3.6 years and the lack of involvement of the wrist joint at treatment start were the strongest predictors of both the achievement of ID at last follow-up visit (adjusted odds ratio of 2.1 and 2.7, respectively, in logistic regression analysis) and a shorter time to the attainment of ID (adjusted odds ratio of 1.6 and 2.2, respectively, in Cox regression analysis). Conclusions Around half of our children with JIA treated with ETN achieved ID. Early disease onset and lack of involvement of the wrist joint at treatment baseline were associated with a greater likelihood and rapidity of achieving ID References Wallace criteria for inactive disease (J Rheum 2004;31:2290-4). Disclosure of Interest None Declared

Background In the last decade, there have been major advances in the management of juvenile idiopathic arthritis (JIA). A reliable documentation of these progresses creates the need for validated criteria that describe precisely patient states. We recently, developed the cut-off values for remission, minimal disease activity and acceptable symptom states in JIA based on the JADAS (1). Objectives To determine the JADAS cut-offs for high disease activity (HDA) in JIA. Methods For the selection of cut-offs, data from a clinical database including 618 children with JIA were used. Patients were defined as having HDA when the physician made one of the following therapeutic interventions: 1) start of methotrexate (MTX); 2) intra-articular corticosteroid injection; 3) start of a biologic medication; 4) start of systemic corticosteroids. Patients were defined as having low disease activity (LDA) when they were receiving no therapy or had therapy discontinued, tapered or left unchanged for >1 year. For each patient, 1 visit in HDA and 1 visit in LDA was retained for the analyses. “Optimal” JADAS cut-offs were determined by calculating the 25th percentile of cumulative score distribution in patients with HDA and by assessing their ability to discriminate between HDA and LDA through ROC curve analysis (including calculation of Youden index and fixed 90% specificity). Cross-validation of cut-offs was performed in 490 JIA patients enrolled in the PRINTO MTX trial (2) and was based on assessment of discriminant validity. Results The cut-offs were calculated separately for patients with oligoarticular and polyarticular course of joint disease (irrespective of ILAR category) owing to the different severity of these 2 JIA phenotypes. The table shows the cut-offs for HDA for JADAS-71 version, defined according to the different statistical methods. The cut-offs that showed the best trade-off between sensitivity and specificity were selected for cross-validation analyses. These analyses showed that at baseline visit of MTX trial 94.7% of patients had a JADAS-71 higher than the HDA cut-off for polyarthritis. At 6-month visit, the percentage of patients with a JADAS-71 higher than the cut-off was 85.6% among nonresponders and 23.8% among responders. Conclusions We developed the JADAS cut-offs for HDA in JIA. The cut-offs revealed strong discriminant ability in a clinical trial and are, therefore, potentially applicable in clinical practice, observational investigations, and therapeutic studies. References Consolaro A et al. A&R, in press. Ruperto et al. A&R 2004;50:2191-201 Disclosure of Interest None Declared

Recent advances in the management of juvenile idiopathic arthritis (JIA) render disease remission an attainable goal in many, if not most, patients. This has led to suggestions that future treatment guidelines include an overriding goal to achieve clinical remission or, at least, minimal disease activity. Furthermore, implementation of treatment strategies aimed at achieving and maintaining tight disease control in standard paediatric rheumatology practice has been proposed. A compelling argument is available at this time to suggest that the incorporation of treat-to-target approach in the management of children with JIA may improve disease outcome. Recently, descriptions of disease states that represent suitable therapeutic targets, such as inactive disease, minimal disease activity, or parent- or child-acceptable symptom states, have been developed. In addition, criteria for these states based on the Juvenile Arthritis Disease Activity Score (JADAS) have been identified. Future studies will clarify whether the addition of an imaging assessment to the management of children with JIA will improve the prediction of clinical outcomes.

Recently, great research interest has been focused on immunological mechanisms of lung graft rejection in particular of Bronchiolitis Obliterans Syndrome (BOS). A systematic evaluation of BAL fluid (BALf) proteome in BOS has been previously attempted by means of 2-DE and MALDI-TOF analysis and possible predictive markers of disease were identified (Surfactant protein A=SP-A, Clara Cell protein 16=CCP-16 whose expression decreased significantly in BOS patients with respect to stable lung recipients=SLRs; human alpha-defensins and lysozyme which were found increased in BOS). In addition, several pro-inflammatory factors have been evaluated in BALf and found to vary significantly in BOS (IL10,IL12, CXCL10, CXCL9, CXCL8, γ-IFN and TNF-α). Aim of this study was to evaluate previously identified markers in BALf obtained from 16 lung recipients who developed BOS (both pre-BOS and BOS) and a group of 14 SLRs (mean follow-up 14.5±6.7 months).

Soil fungal diversity plays a fundamental role in delivering key ecosystem goods and services. This article assesses diversity of saprobic soil and litter microfungi, as taxonomical and functional components which affect above- and below-ground relationships within Alpine and Mediterranean regions of Italy. We highlighted biodiversity high spots focusing on four research topics that have been developed over time and are currently in progress in Italy. Preliminary quantitative data concerning soil microfungi in the Raethian Alps showed a strong reduction of Colony Forming Unit (CFU)s with altitude. Keratinophilic microfungi in natural and anthropogenic environments were widespread among filamentous fungi and 121 species have been isolated in Italy since 1960. Heat stimulated microfungi in Mediterranean region soils showed high values both in abundance and species density even two years after the experimental fire, with Neosartorya spp. playing a pivotal role. The diversity of microfungi of Quercus ilex (150 species), in the Mediterranean region, higher than that in leaf litter of other species, was explained mainly by different forms of growth and the phytoclimatic characters of the areas under study.

Background In juvenile idiopathic arthritis (JIA), substantial disagreement between physicians, parents and children over disease remission can lead to difficulty in assessing the efficacy of treatments. It is, therefore, important to ascertain whether clinicians’, parents’ and children’s opinions converge and diverge and whether the recently developed criteria for inactive disease (ID) or minimal disease activity (MDA) may help enhance concordance. Objective

Recent reports provided an evidence of some clinical efficacy for extracorporeal photopheresis in improving/stabilizing graft function in nearly 60% of treated BOS patients (overall 49 BOS pts reported). The purpose of this study was to evaluate clinical and immunological effects of ECP in a cohort of lung recipients with macrolide non-responsive BOS: 8 with BOS grade 1, 6 with BOS 2, 2 with BOS 3.

OBJECTIVEThe pathophysiology of the lung fibrotic process in systemic sclerosis (SSc) is not fully elucidated. Since this pattern represents the leading cause of death in SSc, the knowledge of its actual pathophysiology is basic to prevent and stage pulmonary damage. In this study, we aimed to further investigate the relationship between the functional profiles of bronchoalveolar lavage (BAL) T cells and the pulmonary manifestation of the disease.METHODSWith this aim, we assessed the frequency of Th1, Th2 and Th17 producing T-lymphocytes and their effector cytokines in BAL of SSc patients without signs or symptoms of lung interstitial involvement (SScFib-) and with interstitial lung fibrosis (SScFib+). We also study as control groups: patients with usual interstitial pneumonia (UIP), patients with sarcoidosis and 9 healthy controls (NHCs).RESULTSSScFib- showed an increase in BAL Th1/Th2 balance compared to NHCs, which was even higher than that observed in sarcoidosis. SScFib+ showed a shift towards a lower Th1/Th2 ratio as compared to SScFib-. The frequency of Th17 BAL T cells did not change among study groups.CONCLUSIONOur data confirm the Th1/Th2 imbalance hypothesis on the pathogenesis of interstitial fibrosis in SSc patients, and suggest a possible utility in the assessment of BAL Th1/Th2 ratio.

BOS is the leading cause of morbidity and late mortality after lung transplant recipients (LTRs). Recent studies demonstrated that azithromycin (AZI) induced an improvement in the forced expiratory volume in 1 sec (FEV1) in patients with BOS by reducing airway inflammation. We aimed to examine the effects of long-term AZI treatment on pulmonary function and inflammatory parameters in a cohort of LTRs with different stages of BOS.

OBJECTIVE:To identify a set of clinical parameters that can predict the probability of carrying mutations in one of the genes associated with hereditary autoinflammatory syndromes.METHODS:A total of 228 consecutive patients with a clinical history of periodic fever were screened for mutations in the MVK, TNFRSF1A, and MEFV genes, and detailed clinical information was collected. A diagnostic score was formulated based on univariate and multivariate analyses in genetically positive and negative patients (training set). The diagnostic score was validated in an independent set of 77 patients (validation set).RESULTS:Young age at onset (odds ratio [OR] 0.94, P = 0.003), positive family history of periodic fever (OR 4.1, P = 0.039), thoracic pain (OR 4.6, P = 0.05), abdominal pain (OR 33.1, P < 0.001), diarrhea (OR 3.3, P = 0.028), and oral aphthosis (OR 0.2, P = 0.007) were found to be independently correlated with a positive genetic test result. These variables were combined in a linear score whose ability to predict a positive result on genetic testing was validated in an independent data set. In this latter set, the diagnostic score revealed high sensitivity (82%) and specificity (72%) for discriminating patients who were genetically positive from those who were negative. In patients with a high probability of having a positive result on genetic testing, a regression tree analysis provided the most reasonable order in which the genes should be screened.CONCLUSION:The proposed approach in patients with periodic fever will increase the probability of obtaining positive results on genetic testing, with good specificity and sensitivity. Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened.

Results More than 4000 determinations of ferritin requested by the study unit were performed between January 2004 and December 2007 by the central laboratory of the study hospital. Hyperferritinemia was found in 408 determinations in 87 patients. The most common specific diagnoses in patients with hyperferritinemia were the following: systemic juvenile idiopathic arthritis (sJIA) (48.3%), systemic lupus erythematosus (SLE) (5.7%), protein intolerance with lysinuria (4.6%), virus-associated haemophagocytic syndrome (3.4%), hematologic disorders (3.4%), juvenile dermatomyositis (2.3%), polyarticular JIA (2.3%), systemic vasculitis (2.3%), autoinflammatory syndrome (2.3%). Twelve patients (13.8%) had a nonspecific systemic inflammatory syndrome. Twenty-seven (31%) of the 87 patients with hyperferritinemia developed features consistent with MAS.