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To define the prevalence of subclinical synovitis on magnetic resonance imaging (MRI) in a large cohort of patients with juvenile idiopathic arthritis (JIA) in clinical remission and to evaluate its predictive value in terms of disease flare and joint deterioration.Ninety patients with clinically inactive JIA who underwent a contrast-enhanced (CE)-MRI of a previously affected joint were retrospectively included. Each joint was evaluated for synovitis, tenosynovitis, and bone marrow edema. Baseline and follow-up radiographs were assessed to evaluate structural damage progression.CE-MRI was acquired in 45 wrists, 30 hips, 13 ankles, and 2 knees. Subclinical synovitis was detected in 59 (65.5%) of 90 patients and bone marrow edema in 42 (46.7%) of 90 patients. Fifty-seven of 90 (63.3%) patients experienced a disease flare during follow-up. Forty-four of 59 (74.6%) patients with subclinical synovitis experienced a disease flare versus 13 (41.9%) of 31 patients with no residual synovitis on MRI (P = 0.002). The presence of subclinical synovitis was the best predictor of disease flare on multivariable regression analysis (hazard ratio [HR] 2.45, P = 0.003). Baseline and follow-up radiographs were available for 54 patients, and 17 (31.5%) of 54 patients experienced radiographic damage progression. The presence of bone marrow edema (HR 4.40, P = 0.045) and being17 years old (HR 3.51, P = 0.04) were strong predictors of joint damage progression in the multivariable analysis.MRI-detected subclinical inflammation was present in a large proportion of patients with JIA despite clinical remission. Subclinical synovitis and bone marrow edema have been shown to play a role in predicting the risk of disease relapse and joint deterioration, with potential implications for patients' management of the disease.

Background Functional variants of the cytotoxic T-lymphocyte antigen-4 (CTLA4) could contribute to the pathogenesis of disorders characterized by abnormal T-cell responses. Case presentation We report a case of a 13-year-old girl who first presented with polyarticular juvenile idiopathic arthritis poorly responsive to treatment. During the following years the patient developed cytopenias, chronic lymphoproliferation, high values of T-cell receptor αβ+ CD4- CD8- double-negative T cells and defective Fas-mediated T cells apoptosis. Autoimmune lymphoproliferative syndrome was diagnosed and therapy with mycophenolate mofetil was started, with good hematological control. Due to the persistence of active polyarthritis, mycophenolate mofetil was replaced with sirolimus. In the following months the patient developed hypogammaglobulinemia and started having severe diarrhea. Histologically, duodenitis and chronic gastritis were present. Using the next generation sequencing-based gene panel screening, a CTLA4 mutation was detected (p.Cys58Serfs*13). At the age of 21 the patient developed acute autoimmune hemolytic anemia; steroid treatment in combination with abatacept were started with clinical remission of all symptoms, even arthritis. Conclusions Targeted immunologic screening and appropriate genetic tests could help in the diagnosis of a specific genetically mediated immune dysregulation syndrome, allowing to select those patients who can take advantage of target therapy, as in the case of abatacept in CTLA4 deficiency.

Flash-induced absorption changes in the Soret region arising from the [PD1PD2]+ state, the chlorophyll cation radical formed upon excitation of Photosystem II (PSII), were obtained using Mn-depleted PSII cores at pH 8.6. Under these conditions, TyrD is reduced before the first flash but oxidised before subsequent flashes. When TyrD• is present, an additional signal in the [PD1PD2]+-minus-[PD1PD2] difference spectrum was observed when compared to the first flash. The additional feature was W-shaped with troughs at 434 nm and 446 nm. This feature was absent when TyrD was reduced, but was present when TyrD was physically absent (and replaced by phenylalanine) or when its H-bonding histidine (D2-His190) was physically absent (replaced by a Leucine),. Thus, the simple difference spectrum without the double trough feature at 434 nm and 446 nm, required the native structural environment around the reduced TyrD and its H bonding partners to be present. A range of PSII variants were surveyed, and we found no evidence of involvement of PD1, ChlD1, PheD1, PheD2, TyrZ, and the Cytb559 heme in difference spectrum. Direct data ruling out the participation of PD2 is lacking. It seems possible that the specific H-bonding environment of around reduced TyrD allows a more homogenous electrostatic environment for [PD1PD2]+. A role for PD2 in the double-trough Soret signal may be tested using mutants of PD2 axial His ligand D2-His197.

Many cyanobacteria species can use both plastocyanin and cytochrome c

Many cyanobacteria species can use both plastocyanin and cytochrome c6 as lumenal electron carriers to shuttle electrons from the cytochrome b6f to either photosystem I or the respiratory cytochrome c oxidase. In Synechocystis sp. PCC6803 placed in darkness, about 60% of the active PSI centres are bound to a reduced electron donor which is responsible for the fast re-reduction of P700in vivo after a single charge separation. Here, we show that both cytochrome c6 and plastocyanin can bind to PSI in the dark and participate to the fast phase of P700 reduction, but the fraction of pre-bound PSI is smaller in the case of cytochrome c6 than with plastocyanin. Because of the inter-connection of respiration and photosynthesis in cyanobacteria, the inhibition of the cytochrome c oxidase results in the over-reduction of the photosynthetic electron transfer chain in the dark that translates into a lag in the kinetics of P700 oxidation at the onset of light. We show that this is true both with plastocyanin and cytochrome c6, indicating that the partitioning of electron transport between respiration and photosynthesis is regulated in the same way independently of which of the two lumenal electron carriers is present, although the mechanisms of such regulation are yet to be understood.

Background: remission is becoming a realistic target in JIA, but clinical remission (CR) may not accurately reflect real absence of synovitis. It would be desirable to have instruments to predict the risk of relapse in patients in CR in order to establish the most appropriate therapeutic strategy. Despite in RA the role of imaging to predict disease flare is established, this field has remained almost unexplored in JIA. Objectives: 1) to investigate the prevalence of musculoskeletal ultrasound (MSUS)-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare; 5) MSUS data will be integrated with serum levels of inflammatory biomarkers to develop a multidimensional measure of remission. Methods: it is a longitudinal prospective 4 years study started on November 2017. So far we have enrolled 99 consecutive JIA patients who met the Wallace criteria for CR. For each patient 46 joints were scanned for synovial hyperplasia/joint effusion and PD signal, all graded semiquantitatively on a 0–3 scale independently by 2 expert ultrasonographers. Subclinical synovitis was defined when total synovitis score for each joint was ≥2. MSUS was performed at baseline and at 6 month follow up visit. At inclusion serum assays have been stored to determine levels of inflammatory biomarkers (S100A8/9-A12, bFGF, IL-6, IL-10, CXCL9-10, VEGF, YKL40). A flare of synovitis was defined as a recurrence of clinically active arthritis. Results: 99 patients (79.8% F; median age 11.3 y; median disease duration 5.3 y; median CR duration 1.6 y) were included. Thirty-eight/99 (38.4%) patients had persistent oligoarthiritis; 34/99 (34.3%) extended oligoarthiritis; 22/99 (22.2%) polyarthiritis; 5/99 (5.1%) systemic arthritis. Fifty-nine/99 (59.6%) patients were in CR on medication. Subclinical synovitis was detected in 54/99 (54.5%; 95% CI: 45.2 – 65.5%) patients, PD in 18/99 (18.2%; 95% CI: 11.1 – 27.2%) patients; subclinical tenosynovitis in 7/99 (7.1%; 95% CI: 2.9 – 14%) patients. Subclinical synovitis was found more frequently in the ankle [31/54 (57.4%) patients] and wrist joints [17/54 (31.5%) patients]. No patients had subclinical synovitis in the hip. A 14-joint reduced count including bilateral knee, ankle (tibiotalar, subtalar and talonavicular joints), wrist (radiocarpal and intercarpal joints) and elbow joints, detected 92.6% of children with subclinical synovitis. Twenty-five/99 (25.2%) patients in persistent CR were reassessed with MSUS at a follow up visit (median follow up duration 7 months): 82.3% of patients showed persistent subclinical synovitis. Sixty-four/99 (64.6%) patients had a clinically follow up of at least 6 months and 9/64 (14%) patients experienced a disease flare (median time to flare 6.6 months). Six/9 (66.7%) patients who experienced a relapse had subclinical synovitis at baseline. Conclusion: our preliminary results confirm the discrepancy between clinical and imaging remission and that clinical evaluation may not sensitive to detect an inflammation-free state. Bilateral US assessment of the elbow, wrist, knee and ankle joints is reliable to detect subclinical synovitis. So far, patients who have relapsed are a small percentage, but to extend follow up is crucial to test predictive value of MSUS. Imaging findings will be combined with serum biomarkers leading to the construction of a predictive model. References: [1] De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018Oct;77(10):1426-1431. Disclosure of Interests: Marta Mazzoni: None declared, Silvia Merlo: None declared, Angela Pistorio: None declared, Stefania Viola: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Clara Malattia: None declared

In Chlamydomonas reinhardtii, chloroplast gene expression is tightly regulated post-transcriptionally by gene-specific trans-acting protein factors. Here, we report the molecular identification of an OctotricoPeptide Repeat (OPR) protein, MDA1, which governs the maturation and accumulation of the atpA transcript, encoding subunit α of the chloroplast ATP synthase. As does TDA1, another OPR protein required for the translation of the atpA mRNA, MDA1 targets the atpA 5'-untranslated region (UTR). Unexpectedly, it binds within a region of approximately 100 nt in the middle of the atpA 5'-UTR, at variance with the stabilization factors characterized so far, which bind to the 5'-end of their target mRNA to protect it from 5' → 3' exonucleases. It binds the same region as TDA1, with which it forms a high-molecular-weight complex that also comprises the atpA mRNA. This complex dissociates upon translation, promoting degradation of the atpA mRNA. We suggest that atpA transcripts, once translated, enter the degradation pathway because they cannot reassemble with MDA1 and TDA1, which preferentially bind to de novo transcribed mRNAs.

In plants, algae, and some photosynthetic bacteria, the ElectroChromic Shift (ECS) of photosynthetic pigments, which senses the electric field across photosynthetic membranes, is widely used to quantify the activity of the photosynthetic chain. In cyanobacteria, ECS signals have never been used for physiological studies, although they can provide a unique tool to study the architecture and function of the respiratory and photosynthetic electron transfer chains, entangled in the thylakoid membranes. Here, we identified bona fide ECS signals, likely corresponding to carotenoid band shifts, in the model cyanobacteria Synechococcus elongatus PCC7942 and Synechocystis sp. PCC6803. These band shifts, most likely originating from pigments located in photosystem I, have highly similar spectra in the 2 species and can be best measured as the difference between the absorption changes at 500 to 505 nm and the ones at 480 to 485 nm. These signals respond linearly to the electric field and display the basic kinetic features of ECS as characterized in other organisms. We demonstrate that these probes are an ideal tool to study photosynthetic physiology in vivo, e.g., the fraction of PSI centers that are prebound by plastocyanin/cytochrome c(6) in darkness (about 60% in both cyanobacteria, in our experiments), the conductivity of the thylakoid membrane (largely reflecting the activity of the ATP synthase), or the steady-state rates of the photosynthetic electron transport pathways.

Background:The accurate assessment of remission status in JIA patients is of utmost relevance to taper medications and prevent side effects from their long-term administration. In RA patients in clinical remission (CR), musculoskeletal ultrasound (MSUS) allows to detect persistent joint inflammation (subclinical synovitis), which predicts disease flare and structural damage progression. Although subclinical synovitis has been reported in a substantial proportion of JIA patients with inactive disease, its prognostic value is still being defined.Objectives:1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare and whether it should affect the therapeutic strategy.Methods:135 consecutive JIA patients who met the Wallace criteria for CR were included in this 3-years prospective study. All patients underwent MSUS assessment of 56 joints at study entry and at 6 months follow-up visit. Joints were scanned for synovial hyperplasia, joint effusion and Power Doppler (PD) signal by two independent ultrasonographers. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis. The association between clinical and MSUS variables with flare, was evaluated by adjusted logistic regression models.Results:135 patients (78.5% F; median age 11.3 y; median disease duration 5.7 y; median CR duration 1.4 y) were included. Fifty-seven/135 (42.2%) patients had persistent oligoarthiritis; 41/135 (30.4%) extended oligoarthiritis; 32/135 (23.7%) polyarthiritis; 5/135 (3.7%) systemic arthritis. Seventy-eight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 32/135 (23.7%) patients and in 53/7560 (0.7%) joints. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. Subclinical synovitis was found more frequently in the ankle and wrist joints. 58.6% of patients showed persistent subclinical synovitis at 6 month follow up MSUS examination. During the 3-year follow up 45/135 (33.3%) patients experienced a disease flare (median survival time 2.2 y). PD positivity in tendons was the stronger independent risk factor of flare on multivariable regression analysis (HR: 4.8; P=0.04). Other predictors of flare were the JIA subtype (oligo-extended form: HR: 2.3; P=0.031) and the status of CR on medication (HR: 3.7; P=0.002).Conclusion:our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients. Subclinical tenosynovitis was the best predictor of disease flare. To date, the role of tenosynovitis in the diagnosis and prognosis of JIA has been poorly investigated. Our results further support the role of MSUS, especially of the wrist and the ankle, in monitoring JIA patients in clinical remission and to predict disease flare.References:[1]De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431.[2]Filippou G, et al. The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study. Ann Rheum Dis 2018;77:1283-9.Disclosure of Interests:None declared

Objective To investigate the frequency of ultrasound (US)–detectable involvement of the subtalar joint (STJ), to compare clinical versus US assessment of the STJ, and to compare different scanning approaches to the STJ in juvenile idiopathic arthritis (JIA). Methods Clinical and US assessments were performed independently in 50 ankles with clinically active JIA. US abnormalities of the STJ were investigated using a lateral, medial, and posterior scanning approach and scored semiquantitatively. Agreement was tested using kappa statistics. A control group of 10 healthy subjects was examined. Results Clinical and US evaluations detected synovitis in 24 of 50 (48.0%) and 27 of 50 (54.0%) of STJs, respectively. US detected synovitis in 10 of 26 STJs (38.5%) recorded as normal on clinical evaluation, but was negative in 7 of 24 STJs (29.2%) diagnosed as having involvement on clinical examination. Agreement between clinical and US assessments was fair (κ = 0.32). US abnormalities were more frequently detectable using the lateral scanning approach. All patients with US abnormalities in the medial and/or posterior side of the STJ had also US abnormalities on the lateral scanning approach, but the reverse was not true. Intra- and interobserver agreements for the lateral scanning approach were satisfactory for both detecting involvement and scoring US abnormalities. None of the 17 STJs of healthy controls showed US abnormalities. Conclusion US may increase the precision of the evaluation of the STJ in JIA. The observed high frequency of STJ involvement on US suggests to include this joint in US scanning protocols devised for children with JIA. Synovitis is more frequently detected using the lateral scanning approach.

Photosynthesis occurs in thylakoids, a highly specialized membrane system. In the cyanobacterium Synechocystis sp PCC 6803 (hereafter Synechocystis 6803), the thylakoids are arranged parallel to the plasma membrane and occasionally converge toward it to form biogenesis centers. The initial steps in PSII assembly are thought to take place in these regions, which contain a membrane subcompartment harboring the early assembly factor PratA and are referred to as PratA-defined membranes (PDMs). Loss of CurT, the Synechocystis 6803 homolog of Arabidopsis thaliana grana-shaping proteins of the CURVATURE THYLAKOID1 family, results in disrupted thylakoid organization and the absence of biogenesis centers. As a consequence, PSII is less efficiently assembled and accumulates to only 50% of wild-type levels. CurT induces membrane curvature in vitro and is distributed all over the thylakoids, with local concentrations at biogenesis centers. There it forms a sophisticated tubular network at the cell periphery, as revealed by live-cell imaging. CurT is part of several high molecular mass complexes, and Blue Native/SDS-PAGE and isoelectric focusing demonstrated that different isoforms associate with PDMs and thylakoids. Moreover, CurT deficiency enhances sensitivity to osmotic stress, adding a level of complexity to CurT function. We propose that CurT is crucial for the differentiation of membrane architecture, including the formation of PSII-related biogenesis centers, in Synechocystis 6803.

To investigate the capacity of ultrasound (US) to detect improvement of synovial abnormalities induced by treatment in juvenile idiopathic arthritis (JIA).Eighty-three joints (33 knees, 22 tibiotalar, 10 wrists, 9 elbows, 9 subtalar joints) of 33 patients with new-onset JIA were assessed by US at study entry and 6 months after a therapeutic intervention. Each joint was scored for grey-scale (GS) and power Doppler (PD) abnormalities according to a 4-point semiquantitative scale. Pre- and post-treatment US scores were compared and the sensitivity to change of GSUS and PDUS was estimated. Clinical response was assessed using the ACR paediatric (ACRp) response criteria.Seventeen patients (51.5%) underwent intra-articular corticosteroid injection (IACI) only, 15 (45.5%) were given IACI and systemic medications, and 1 (3.0%) was started with systemic therapy alone. Both GSUS and PDUS scores improved significantly (p0.0001) from baseline to follow-up. US revealed strong sensitivity to change with standardised response mean for GSUS and PDUS of 2.44 and 1.23, respectively. At the follow-up visit, 13/20 (65.0%) joints with residual US abnormalities were judged in remission on clinical grounds. Six/21 (28.6%) patients who were ACRp90 responders did not display complete resolution of synovial abnormalities on US.US is a sensitive tool to assess therapeutic response in patients with JIA. Subclinical disease on US is common in joints with clinically-defined remission. An ACRp90 response may not be coupled with complete resolution of synovial abnormalities on US. Further studies are needed to establish the impact of US on therapeutic decision-making in JIA.

Summary Background Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy. Methods We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m 2 ; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70. Findings Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event. Interpretation Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis. Funding Italian Agency of Drug Evaluation.

Objective To evaluate agreement among musculoskeletal pediatric specialists in assessing radiographic joint damage in juvenile idiopathic arthritis (JIA). Methods Two pediatric rheumatologists, 2 pediatric radiologists, and 2 pediatric orthopedic surgeons evaluated independently 60 radiographs of both wrists and hands of children with polyarticular-course JIA. Films were scored using an adapted and simplified version of the Larsen score, ranging from 0–5. Study radiographs were selected from 568 films used in a previous study aimed to validate an adapted pediatric version of the Sharp/van der Heijde (SHS) score. To enable comparison of specialists' scores with the adapted SHS score, the 60 radiographs were divided into 6 classes of severity of damage based on quintiles of the adapted SHS score. Agreement was evaluated in terms of absolute agreement and through weighted kappa statistics. Results The pediatric radiologists tended to assign lower scores and to provide more frequently scores of 0 than did the other specialists. Weighted kappa for the 3 pairs of specialists ranged from 0.67–0.69, indicating substantial agreement. Absolute agreement ranged from 51.3–55.7%, depending on the pair of specialists examined. Both absolute and weighted kappa concordance between specialists' scores and the adapted SHS score were poorer for the pediatric radiologist than for the other specialists. Conclusion We observed fair agreement in the assessment of radiographic damage among pediatric specialists involved in the care of children with JIA. The radiologists tended to be more reserved than the rheumatologists and orthopedic surgeons in labeling radiographs as damaged or in considering changes as important.

Chloroplasts of land plants characteristically contain grana, cylindrical stacks of thylakoid membranes. A granum consists of a core of appressed membranes, two stroma-exposed end membranes, and margins, which connect pairs of grana membranes at their lumenal sides. Multiple forces contribute to grana stacking, but it is not known how the extreme curvature at margins is generated and maintained. We report the identification of the CURVATURE THYLAKOID1 (CURT1) protein family, conserved in plants and cyanobacteria. The four Arabidopsis thaliana CURT1 proteins (CURT1A, B, C, and D) oligomerize and are highly enriched at grana margins. Grana architecture is correlated with the CURT1 protein level, ranging from flat lobe-like thylakoids with considerably fewer grana margins in plants without CURT1 proteins to an increased number of membrane layers (and margins) in grana at the expense of grana diameter in overexpressors of CURT1A. The endogenous CURT1 protein in the cyanobacterium Synechocystis sp PCC6803 can be partially replaced by its Arabidopsis counterpart, indicating that the function of CURT1 proteins is evolutionary conserved. In vitro, Arabidopsis CURT1A proteins oligomerize and induce tubulation of liposomes, implying that CURT1 proteins suffice to induce membrane curvature. We therefore propose that CURT1 proteins modify thylakoid architecture by inducing membrane curvature at grana margins.

CurT is required for shaping the thylakoid membrane architecture in Synechocystis and mediates osmotic stress responses.

To investigate the frequency of ultrasound (US)-detectable involvement of the subtalar joint (STJ), to compare clinical versus US assessment of the STJ, and to compare different scanning approaches to the STJ in juvenile idiopathic arthritis (JIA).Clinical and US assessments were performed independently in 50 ankles with clinically active JIA. US abnormalities of the STJ were investigated using a lateral, medial, and posterior scanning approach and scored semiquantitatively. Agreement was tested using kappa statistics. A control group of 10 healthy subjects was examined.Clinical and US evaluations detected synovitis in 24 of 50 (48.0%) and 27 of 50 (54.0%) of STJs, respectively. US detected synovitis in 10 of 26 STJs (38.5%) recorded as normal on clinical evaluation, but was negative in 7 of 24 STJs (29.2%) diagnosed as having involvement on clinical examination. Agreement between clinical and US assessments was fair (κ = 0.32). US abnormalities were more frequently detectable using the lateral scanning approach. All patients with US abnormalities in the medial and/or posterior side of the STJ had also US abnormalities on the lateral scanning approach, but the reverse was not true. Intra- and interobserver agreements for the lateral scanning approach were satisfactory for both detecting involvement and scoring US abnormalities. None of the 17 STJs of healthy controls showed US abnormalities.US may increase the precision of the evaluation of the STJ in JIA. The observed high frequency of STJ involvement on US suggests to include this joint in US scanning protocols devised for children with JIA. Synovitis is more frequently detected using the lateral scanning approach.

Objective.To develop and test a new multidimensional questionnaire for assessment of children with juvenile idiopathic arthritis (JIA) in standard clinical care.Methods.The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) includes 15 parent or patient-centered measures or items that assess well-being, pain, functional status, health-related quality of life, morning stiffness, disease activity, disease status and course, joint disease, extraarticular symptoms, side effects of medications, therapeutic compliance, and satisfaction with illness outcome. The JAMAR is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 7–18 years for use as a self-report. From March 2007 to September 2009, the questionnaire was completed by the parents of 618 children with JIA in 1814 visits and by 332 children in 749 visits.Results.The JAMAR was found to be feasible and to possess face and content validity. All parents and children reported that the questionnaire was simple and easy to understand. Completion and scoring appeared to be quick, requiring < 15 minutes. There were very few missing data. Parents’ proxy-reported and children’s self-reported data were remarkably concordant. The JAMAR provided thorough information for the study patients about recent medical history and current health status. It performed similarly across different children’s ages and characterized the level of disease activity and disability well.Conclusion.The development of the JAMAR introduces a new approach in pediatric rheumatology practice. This new questionnaire may help enhance the quality of care of children with JIA.

Objective. To determine the capability and reliability of dynamic contrast-enhanced MRI (DCE-MRI) in the assessment of disease activity in juvenile idiopathic arthritis (JIA). Methods. DCE-MRI of the clinically more affected wrist or hip joints was undertaken in 21 patients, coupled with standard clinical assessment and biochemical analysis. Synovial inflammation was assessed by computing the maximum level of synovial enhancement (ME), the maximum rate of enhancement (MV) and the rate of early enhancement (REE) from the enhancement curves generated from region of interest independently delineated by two readers in the area of the ME. Correlations between dynamic parameters and clinical measures of disease activity, and static MRI synovitis score were investigated. Results. In patients with wrist arthritis, REE correlated with the wrist swelling score (r s = 0.72), ESR (r s = 0.69), pain assessment scale (r s = 0.63) and childhood HAQ (r s = 0.60). In patients with hip arthritis, ME correlated with the hip limitation of motion (r s = 0.69). Static MRI synovitis score based on post-gadolinium enhancement correlated with MV (r s = 0.63) in patients with wrist arthritis and with ME (r=0.68) in those with hip arthritis. The inter-reader agreement assessed by intra-class correlation coefficient (ICC) for ME, MV and REE (ICC = 0.98, 0.97 and 0.84, respectively) was excellent. Conclusions. DCE-MRI represents a promising method for the assessment of disease activity in JIA, especially in patients with wrist arthritis. As far as we know, this study is the first to demonstrate the feasibility, reliability and construct validity of DCE-MRI in JIA. These results should be confirmed in large-scale longitudinal studies in view of its further application in therapeutic decision making and in clinical trials.

ObjectiveTo develop and test reduced joint counts in children with juvenile idiopathic arthritis (JIA).MethodsFour reduced joint counts including 45, 35, 27, and 10 joints were devised by a panel of experienced pediatric rheumatologists, who selected the joints to be included based on the ease of technical assessment, functional relevance, and frequency of involvement. Three large samples of patients with JIA (total n = 4353) who had a detailed joint assessment available were used to develop and test reduced joint counts. Performance of reduced counts was examined by comparing their Spearman correlation with the standard (i.e., complete) joint count. Construct validity was evaluated by calculating Spearman correlation with other JIA outcome measures. Responsiveness to clinical change was determined through the standardized response mean (SRM).ResultsSpearman correlations of reduced joint counts with the whole joint count and with the other JIA outcome measures were comparable, revealing that they had similar ability to serve as surrogate for the whole joint count and construct validity. Responsiveness to clinical change was also comparable across reduced counts (SRM 0.83–1.09 for active joint counts and 0.63–0.81 for restricted joint counts). Based on these results and considering the relative feasibility of the different counts, the 27-joint reduced count is proposed for use in JIA. This joint count includes the cervical spine and the elbow, wrist, metacarpophalangeal (from first to third), proximal interphalangeal, hip, knee, and ankle joints.ConclusionReduced joint counts appear to be as reliable as standard joint counts in assessment of the severity of joint disease and its change over time in children with JIA.

Objective To develop and validate a new short and simple measure of physical function in children with juvenile idiopathic arthritis (JIA). Methods The Juvenile Arthritis Functionality Scale (JAFS) is a 15-item questionnaire that explores physical function in 3 body areas (lower limbs, hand/wrist, and upper segment). Validation of the Italian version of the instrument was accomplished by evaluating 211 consecutive JIA patients ages 2.2–18 years. The instrument's feasibility, face and content validity, construct and discriminative ability, internal consistency, interrater reliability, and responsiveness to clinical change were examined. JAFS psychometric properties were compared with those of the Childhood Health Assessment Questionnaire (C-HAQ). Results The JAFS was found to be feasible and to possess both face and content validity. The JAFS score correlated with most of the other JIA outcome measures in the range predicted, thereby demonstrating good construct validity, and discriminated well among different levels of disability. The internal consistency (Cronbach's alpha) was 0.82. The intraclass correlation coefficients between raters (mothers, fathers, and children) and between reported and observed level of function ranged from 0.65 to 0.84. The JAFS revealed fair responsiveness, with a standardized response mean ranging from 0.42 to 0.56. Comparison with the C-HAQ indicated that the JAFS may be superior in terms of construct validity and reliability, and at least as good in terms of discriminant validity and responsiveness. Conclusion The JAFS exhibited good reliability, construct validity, and discriminative ability and fair responsiveness, and is therefore a valid instrument for the assessment of physical function in children with JIA.

Objective To investigate the rate of radiographic progression and identify prognostic factors of radiographic progression, radiographic damage, and physical disability in juvenile idiopathic arthritis (JIA). Methods Ninety-four JIA patients with a median disease duration of 1.1 years were followed up prospectively for a median of 4.5 years. Bilateral wrist radiographs were obtained at baseline, at 1 year, and at the last followup visit. Radiographic damage was assessed by the carpal length (Poznanski score), and physical disability by the Childhood Health Assessment Questionnaire (C-HAQ). Yearly radiographic progression, the Poznanski score at the final visit, and the C-HAQ score at the final visit were used as outcome measures. Baseline parameters included demographic, clinical, laboratory, and radiographic data. Results The mean ± SD Poznanski score was −1.2 ± 1.3 at baseline, −1.7 ± 1.8 at the 1-year visit, and −1.9 ± 2.2 at the final visit (P < 0.0001). Radiographic progression was greater during the first year (mean ± SD −0.5 ± 1.1) than between the 1-year visit and the final visit (−0.2 ± 1.3). The mean yearly radiographic progression during the entire study period was −0.1 ± 0.4. Logistic regression analysis revealed that radiographic progression during the first year was the only baseline parameter that was predictive of all 3 study outcomes. The final Poznanski score was also predicted by the baseline Poznanski score, whereas female sex was protective against radiographic progression. Conclusion We identified the prognostic factors for poorer outcome in polyarticular-course JIA. The changes in the early Poznanski score can be used to predict long-term joint damage and physical disability.

Objective To evaluate whether abnormal T cell recognition may be generated by exposure to exogenous antigens presenting sequence homology with epitopes contained in self HLA alleles, and if such recognition may be part of the mechanisms that fuel inflammation in autoimmune diseases associated with certain HLA alleles. Methods Cytotoxic responses of peripheral blood mononuclear cells to 9-mer peptides derived from HLA molecules (DRB1*1101, DRB1*0801, or DPB1*0201) associated with oligoarticular juvenile idiopathic arthritis (JIA) or homologous peptides derived from Epstein-Barr virus (EBV) proteins (Bolf1 or Balf2) were analyzed in patients with oligoarticular JIA and in healthy controls matched for HLA–DRB1*1101, DRB1*0801, or DPB1*0201. Production of proinflammatory cytokines in culture supernatants was determined by enzyme-linked immunosorbent assay. Results T cell cytotoxic responses and production of proinflammatory cytokines in response to stimulation with self HLA–derived peptides were found only in patients with oligoarticular JIA, and not in controls. Patients with oligoarticular JIA, but none of the healthy controls, had EBV–self HLA cross-reactive T cells. Conclusion Our data suggest a disease- and allele-specific mechanism of autoimmunity in oligoarticular JIA. This mechanism may be part of the pathogenesis of the disease, and could be the basis of one of the likely multiple candidates for antigen-specific immunotherapy approaches in the future.

Over the last decade the use of musculoskeletal ultrasound (MSUS) for the assessment of juvenile idiopathic arthritis (JIA) has increased considerably. However, little is known about the potential of MSUS in supporting the clinical management of JIA, when compared to magnetic resonance (MR).

In contrast with the numerous controlled trials conducted in polyarticular or systemic juvenile idiopathic arthritis (JIA), little evidence-based information is available for oligoarticular JIA. As a result, the management of children with this subtype, which is the most prevalent in Western countries, is largely empiric. Intra-articular corticosteroid (IAC) injection is the therapy of first choice for oligoarthritis in many pediatric rheumatology centers. However, although IAC injections are usually highly efficacious, relapses of synovitis are common and sometimes occur only a few months after the procedure. It is still unclear whether concomitant administration of methotrexate (MTX) may increase and prolong the effectiveness of IAC injections.

The chloroplast F1Fo-ATP synthase/ATPase (cpATPase) couples ATP synthesis to the light-driven electrochemical proton gradient. The cpATPase is a multiprotein complex and consists of a membrane-spanning protein channel (comprising subunit types a, b, b', and c) and a peripheral domain (subunits α, β, γ, δ, and ε). We report the characterization of the Arabidopsis (Arabidopsis thaliana) CONSERVED ONLY IN THE GREEN LINEAGE160 (AtCGL160) protein (AtCGL160), conserved in green algae and plants. AtCGL160 is an integral thylakoid protein, and its carboxyl-terminal portion is distantly related to prokaryotic ATP SYNTHASE PROTEIN1 (Atp1/UncI) proteins that are thought to function in ATP synthase assembly. Plants without AtCGL160 display an increase in xanthophyll cycle activity and energy-dependent nonphotochemical quenching. These photosynthetic perturbations can be attributed to a severe reduction in cpATPase levels that result in increased acidification of the thylakoid lumen. AtCGL160 is not an integral cpATPase component but is specifically required for the efficient incorporation of the c-subunit into the cpATPase. AtCGL160, as well as a chimeric protein containing the amino-terminal part of AtCGL160 and Synechocystis sp. PCC6803 Atp1, physically interact with the c-subunit. We conclude that AtCGL160 and Atp1 facilitate the assembly of the membranous part of the cpATPase in their hosts, but loss of their functions provokes a unique compensatory response in each organism.

None of the controls showed US STJ synovitis. US detected synovitis in 27 (54%) STJs of patients. Agreement between clinical and US assessment for presence and absence of STJ involvement was found in 17 (34%) and 16 (32%) ankles, respectively. In 10 (20%) STJs not considered to be clinically affected, synovitis was found on US. In 7 (14%) ankles labelled as having STJ involvement on clinical examination US was negative for STJ, but showed the involvement of different anatomical sites (midfoot, tibiotalar joint, tendons). Overall, the concordance between clinical and US evaluation was poor (k=0.32). The Cohen-kappa value for inter-observer reliability of STJ involvement on US was high (k= 0.92). All patients having US findings in the medial and/or posterior side of STJ presented also with US findings using the lateral scanning approach, but the reverse was not true. Conclusion US is more sensitive than clinical evaluation in the assessment of STJ in ankles with active disease. The high frequency of its involvement may suggest to include the assessment of STJ in US scanning protocols. In this perspective, the lateral approach to the joint seems to be more appropriate for US evaluation of STJ involvement.

Objective. To determine the level of agreement between parents and clinicians in rating dysfunction in children with juvenile idiopathic arthritis (JIA). Methods. A parent of each patient completed the Italian version of the Childhood Health Assessment Questionnaire (CHAQ). Subsequently, an examiner assessed, in a specially equipped room, the child’s performance of tasks as described by the CHAQ. Demographic and clinical variables were recorded for all patients. Results. Seventy consecutive JIA patients and their parents were included. The mean proxyreported and observed CHAQ score was 0.64 " 0.53 and 0.47 " 0.62 respectively, the difference ranging from 21.75 to 1.5. There were 30 cases (43%) of agreement (difference (0.25 CHAQ units) between the parent’s and clinician’s ratings, whereas in 40 cases (57%) there was discordance (difference >0.25 CHAQ units). In 30 cases the parent rated the child’s functional ability as worse than that observed by the clinician (i.e. the parent underestimated the child’s function), whereas in 10 cases the parent rated the child’s functional ability as better than that observed by the clinician (i.e. overestimated the child’s function). Multivariate regression analysis showed that children’s functional ability was overestimated by parents with increasing erythrocyte sedimentation rate and global articular severity score and underestimated with increasing level of pain. Among the functional areas of the CHAQ, the level of agreement was poorest in the areas of eating and hygiene and was best for activities. Conclusions. Discordance between proxy-reported and observed functional ability was frequent in our patients with JIA. The children’s functional ability was overestimated by parents as the severity of arthritis increased and underestimated as the level of pain increased.

Objective: To determine whether demographic, clinical, and laboratory variables measurable at baseline predict the clinical efficacy or major toxic effects of methotrexate (MTX) therapy in children with chronic arthritis. Study design: Patient eligibility criteria: (1) monitored in our unit between 1986 and 1996 with a diagnosis of chronic arthritis and (2) treatment with MTX as the sole second-line agent and for at least 6 months. Outcomes investigated: (1) short-term (6-month) clinical response, (2) complete disease control, (3) disease relapse after MTX discontinuation after complete disease control, (4) aminotransferase elevation, (5) gastrointestinal toxicity. Independent variables that showed significant results with univariate tests or were clinically relevant for each outcome underwent multiple logistic or Poisson regression analyses. Results: Eighty patients were available for analysis. The disease onset subtype was systemic in 37 patients, polyarticular in 20 patients, and oligoarticular in 23 patients (all with polyarticular course: extended oligoarticular subtype). The extended oligoarticular subtype was the best predictor for both the short-term clinical response (odds ratio 6.80, P = .02) and, together with a better functional ability, the complete disease control (rate ratio 3.85, P = .03 and rate ratio 3.29, P = .006, respectively). Patients with this subtype of chronic arthritis tended to have earlier, and more frequently, a disease relapse after MTX discontinuation. Thrombocytosis was the only significant risk factor for liver biochemical abnormalities (rate ratio 2.94, P = .008), whereas no variable yielded significant results for gastrointestinal toxicity. Conclusion: Patients with extended oligoarticular chronic arthritis were more likely to benefit from MTX therapy and to have a relapse after treatment discontinuation, suggesting that MTX is distinctly more effective in this subset of chronic arthritis. (J Pediatr 1999;135:316-20)

OBJECTIVE—To investigate the performance of the core set of outcome measures and the preliminary definition of improvement (PDI) in the assessment of response to methotrexate (MTX) treatment in children with juvenile chronic arthritis (JCA). METHODS—Data were obtained from an open label, non-controlled trial designed to investigate the efficacy of MTX in children with JCA. All patients had the core set of variables assessed at baseline and after six months of treatment. Variables in the core set are: (1) physician global assessment of disease activity; (2) parent or patient (if appropriate in age) global assessment of overall well being; (3) functional ability; (4) number of joints with active arthritis; (5) number of joints with limited range of motion; (6) erythrocyte sedimentation rate. The PDI specifies that to be classified as improved, a patient must show at least 30% improvement from baseline in three of any six variables in the core set, with no more than one of the remaining variables worsening by more than 30%. RESULTS—A total of 111 JCA patients were included in the study. According to the PDI, after six months of MTX treatment 73 patients (66%) were classified as improved and 38 (34%) as not improved. Among the core set variables, parent assessment detected the highest percentage of patients improved (72%) and functional assessment the lowest (37%). CONCLUSION—The PDI identifies about two thirds of patients with JCA treated with low dose MTX as improved. This proportion is similar to that expected to improve based upon a previous controlled study of low dose, oral MTX and provides preliminary evidence of the definition's validity. Keywords: juvenile chronic arthritis; methotrexate; outcome measures; definition of improvement

Objective To compare whole-body MRI (WB-MRI) with clinical examination in the assessment of disease activity in juvenile dermatomyositis (JDM). Methods WB-MR images were obtained from 41 JDM patients and 41 controls using a 1.5 T MRI scanner and short τ inversion recovery sequences. 18 patients had follow-up WB-MRI. Muscle, subcutaneous tissue and myofascial signal abnormalities were scored in 36 muscular groups and on proximal and distal extremities. WB-MRI and clinical assessments were performed concurrently and results compared. Validation procedures included analysis of feasibility, reliability, construct validity, discriminative ability and responsiveness. Results WB-MRI revealed distal legs (26/41 patients) and forearm (19/41 patients) muscle inflammation undetected during clinical examination and allowed an accurate assessment of subcutaneous (23/41 patients) and myofascial involvement (13/41 patients). 27 patients showed a patchy distribution of muscle inflammation while in seven the abnormal hyperintense areas tended to be homogeneously distributed. The inter-reader agreement for muscular, subcutaneous and myofascial WB-MRI scores was excellent. Correlations between WB-MRI muscle score and disease activity measures were excellent (Manual Muscle Test: rs=−0.84, Childhood Myositis Assessment Scale: rs=−0.81). WB-MRI score was higher in JDM active patients when compared with the control group (p B B =0.004), and showed an excellent responsiveness (standardised response mean=1.65). Follow-up WB-MRI showed resolution of inflammation in nine patients whereas clinical criteria for remission were satisfied in five. Conclusions WB-MRI provides additional information to clinical evaluation and represents a promising tool to estimate total inflammatory burden, tailor treatment and monitor its efficacy.

Objective.To evaluate the rate of inactive disease in children with juvenile idiopathic arthritis (JIA) treated with etanercept, and to identify clinical characteristics associated with attainment of inactive disease.Methods.Clinical charts of patients who were given etanercept between January 2002 and January 2011 were evaluated retrospectively. For each patient, all visits from initiation of etanercept to the last followup evaluation in which the patient was still receiving etanercept were examined to establish whether the patient had reached the state of inactive disease and to identify the first visit in which inactive disease was documented. Clinical characteristics associated with achievement of inactive disease were determined through univariate analyses and Cox regression procedures.Results.A total of 173 patients who received etanercept for a median of 2.2 years (range 0.5–10.5 yrs) were studied. Eighty-seven patients (50.3%) achieved inactive disease after a median of 0.6 years (range 0.1–2.5 yrs) of therapy. At last followup evaluation, 85 patients (49.1%) still had inactive disease and 70 (40.5%) were in clinical remission on medication. The probability of achievement of inactive disease after 6, 12, and 24 months of therapy was 24%, 46% and 57%, respectively. On Cox regression analysis, the attainment of inactive disease was associated with lack of wrist involvement and an age at disease onset < 3.6 years.Conclusion.Around half of our patients with JIA treated with etanercept achieved a state of inactive disease. Children who lacked wrist involvement and were younger at disease onset had a greater likelihood of achieving inactive disease.

Objective.To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU).Methods.Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications.Results.Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-α agents were recorded in the NIR and data from 91, with at least 12 months’ followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%) maintained a chronic course. A higher remission rate was observed with ADA (67.4% vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with ADA).Conclusion.IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

In juvenile chronic arthritis (JCA) the indices of disease activity, such as joint swelling, pain, tenderness, and limitation of motion, may poorly correlate with the degree of functional impairment. Since the improvement of functional capacity is one of the main objectives of treatment, we evaluated the effect of methotrexate (MTX) in 29 children with JCA by assessing both the articular indices and a functional status measure. After 6 months of therapy, 15 of the 29 patients had a significant (or = 50%) reduction in the number of joints with active arthritis and/or the articular severity score and were then judged as responders, while 14 did not respond to MTX. In the responder group, the median functional index score decreased from 17 (range: 13-27) at baseline to 13 (range: 13-15) at 6 months (p0.001); the median score of the non-responder group was 20 both at baseline and at 6 months (ranges: 14-27, and 13-36, respectively). These results show an improvement of functional impairment in those patients who respond to MTX according to the conventional indices of articular inflammation.

ObjectivesTo develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials—Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested.MethodsIn 66 patients with JIA the clinically more affected wrist was studied. Thirty-nine patients had a 1-year MRI follow-up. Two readers independently assigned the paediatric score and the RAMRIS to all studies. Validation procedures included analysis of reliability, construct validity and responsiveness to change. A reduced version of the bone erosion score was also developed and tested.ResultsThe paediatric score showed an excellent reproducibility (interclass correlation coefficient >0.9). The interobserver agreement of RAMRIS was moderate for bone erosions and excellent for bone marrow oedema (BMO). The paediatric score and RAMRIS provided similar results for construct validity. The responsiveness to change of the paediatric score was moderate for synovitis and bone erosion, and poor for BMO and did not improve when RAMRIS was applied. The reduced version of the bone erosion was valuable for the assessment of joint damage, and provided time-saving advantages.ConclusionThe results demonstrate that the paediatric MRI score is a reliable and valid method for assessing disease activity and damage in JIA. Unexpectedly, the RAMRIS provides acceptable suitability for use in the paediatric age group. Further work, especially in a longitudinal setting, is required before defining the most suitable MRI scale for assessing growing joints.

An adult patient had a syndrome associating the features of juvenile dermatomyositis and cutaneous polyarteritis nodosa that followed a cyclic course from childhood; recurrences were always associated with a rise of serum antistreptococcal antibodies. Regions of homology between streptococcal type 5 M protein and skeletal myosin were found. These findings suggest that streptococcal infection, possibly through a molecular mimicry mechanism, played a role in the pathogenesis of the disease in our patient.

Objective.To develop and validate a radiographic scoring system for the assessment of radiographic damage in the hip joint in patients with juvenile idiopathic arthritis (JIA).Methods.The Childhood Arthritis Radiographic Score of the Hip (CARSH) assesses and scores these radiographic abnormalities: joint space narrowing (JSN), erosion, growth abnormalities, subchondral cysts, malalignment, sclerosis of the acetabulum, and avascular necrosis of the femoral head. Score validation was accomplished by evaluating reliability and correlational, construct, and predictive validity in 148 JIA patients with hip disease who had a total of 381 hip radiographs available for study.Results.JSN was the most frequently observed radiographic abnormality, followed by erosion and sclerosis of the acetabulum. The least common abnormalities were avascular necrosis, growth abnormalities, and malalignment. Interobserver and intraobserver reliability on baseline and longitudinal score values and on score changes was good, with intraclass correlation coefficients ranging from 0.76 to 0.98. Early score changes, but not absolute baseline score values, were moderately correlated (rs> 0.4) with clinical indicators of disease damage at last followup observation, thereby demonstrating that the CARSH has good construct and predictive validity. The amount of structural damage in the hip radiograph at last followup observation was predicted better by baseline to 1-year score change (rs= 0.66; p < 0.0001) than by absolute baseline score values (rs= 0.40; p = 0.002).Conclusion.Our results show that the CARSH is reliable and valid for the assessment of radiographic hip damage and its progression in patients with JIA.

Objective:To assess whether the removal of aids/devices and/or help from another person in the Childhood Health Assessment Questionnaire (C-HAQ) leads to a significant change in the disability index (DI) score and responsiveness in juvenile idiopathic arthritis (JIA).Methods:Changes in the C-HAQ DI score in a cross-sectional sample of 2663 children with JIA and in 530 active patients with JIA in a trial of methotrexate (MTX) were compared.Results:Patients in the MTX trial had higher disease activity and disability than the cross-sectional sample. The frequency of aids/devices (range 1.2–10.2%) was similar between the two samples, while help (range 5.3–38.1%) was more frequently used in the MTX group. Correlation between disease severity variables and the two different C-HAQ DI scoring methods did not change substantially. There was a decrease in the C-HAQ DI score for both the cross-sectional (mean score from 0.64 with the original method to 0.54 without aids/devices and help, pConclusion:The removal of aids/devices and help from the C-HAQ does not alter the interpretation of disability at a group level. The simplified C-HAQ is a more feasible and valid alternative for the evaluation of disability in patients with JIA.

Objective To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). Methods The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0–101), 27-joint (range 0–57), or 10-joint (range 0–40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). Results The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. Conclusion The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.

Objective To compare magnetic resonance imaging (MRI), conventional radiography, and ultrasonography in identifying bone erosions in patients with juvenile idiopathic arthritis (JIA), and to determine the validity and reliability of an MRI scale in detecting and grading joint damage. Methods In 26 JIA patients, the clinically more affected wrist was studied with MRI, radiography, and ultrasonography, coupled with standard clinical assessment and biochemical analysis. MR images were assessed independently by 2 readers according to an apposite devised scoring system. Results Of 26 patients, 25 (96.1%) had 1 or more erosions as detected by MRI, whereas conventional radiography and ultrasonography revealed erosions in 13 (50%) of 26 and 12 (50%) of 24 patients, respectively. The ability of MRI to detect erosive changes was significantly higher with respect to conventional radiography (P = 0.002 with Bonferroni correction [PB]) and ultrasonography (PB = 0.0002) in the group of patients with

Objective To investigate the disease outcomes of a cross-sectional sample of children with longstanding juvenile idiopathic arthritis (JIA) seen between September 2002 and December 2006, and to provide a benchmarking of outcomes obtained with current treatment. Methods All consecutive patients were included if they met the following criteria: diagnosis of JIA, disease duration ≥5 years, and informed consent. Outcome assessments included disease activity, inactive disease, minimal disease activity, pain, physical function, health-related quality of life (HRQOL), auxometric measurements, and articular and extraarticular damage. Results A total of 310 patients were included. At study visit, patients had on average a low level of disease activity. However, only 21.8% met the criteria for inactive disease, and less than 50% met the definition of minimal disease activity. Additionally, 19.2% had moderate to severe Childhood Health Assessment Questionnaire disability and 3.6% were in Steinbrocker class III–IV. Approximately 10% had major impairment in HRQOL. A total of 34.2% had damage in ≥1 joint or joint group and 26.1% showed extraarticular damage. Of the 125 patients who underwent a wrist radiograph, 35.2% had significant structural damage and 8.7% had growth retardation. Conclusion Our patients had on average a low level of disease activity, little or no physical disability, and a satisfactory HRQOL. However, a sizable proportion of patients had persistently active disease, impaired function, and damage. These findings underscore the critical need for treatments and treatment strategies that have the ability to better control disease activity and to reduce the development of disease-related morbidities.

Methods The Pediatric Rheumatology Quality of Life (PRQL) includes 10 questions, each scored from 0 (normal) to 3 (worst). Score range is 0–30. The PRQL contains two subscales, each composed of 5 questions (score range 0–15), that assess physical (PhH) and psychosocial (PsH) health. Validation of PRQL included evaluation of feasibility, face and content validity. Construct validity was assessed by calculating Spearman's correlation with JIA outcome measures in 723 visits (403 patients) made between 2007 and 2008. Construct validity of PRQL was compared with that of Child Health Questionnaire (CHQ) by assessing the same correlations of in a historical sample of 501 visits (448 patients) made between 2002 and 2006 who had CHQ completed.

Background Chronic isolated inflammatory coxitis (CIIC) is characterized by exclusive involvement of coxo-femoral joints and an aggressive course leading to permanent structural damage, often requiring surgical treatment. Early commencement of disease-modifying or corticosteroid therapy has been suggested. To date, treatment with biological agents has not been reported. We describe the favourable response to etanercept in two girls with CIIC.

Methods 369 parents completed a multidimensional questionnaire (the JAMAR), including Juvenile Arthritis Functionality Scale (JAFS) (score 0–30), Pediatric Rheumatology Quality of Life (PRQL) questionnaire (score 0–30) and traditional JIA outcome measures, and stated whether they considered their children's status satisfactory or not. PASS thresholds were estimated based on parent opinion and targeting the 75th percentile of cumulative distribution. Stepwise logistic regression was used to assess contributors to PASS. PASS was validated by analyzing proportions of patients who were judged by parent or physician in remission, flare or continued activity.

Although it is well known that some dietary measures are able to beneficially affect blood pressure (BP) levels, hypertensive patients find it very difficult to definitively change their nutritional habits. The aim of this study was to evaluate the effects on BP of a return to the habitual diet following a dietary intervention period. Three hundred and seven hypertensive patients (149 females, 158 males) with a mean age of 52+/-12 years were included in the study. All enrolled patients had reported having reverted to their habitual diet after a period of at least 6 months on a prescribed low-energy and/or low-sodium diet. Nutritional habits were investigated by a simple semiquantitative 24-item food-frequency questionnaire. Patients were divided into tertiles according to their systolic BP. The groups differed in regard to their body mass index (27.6+/-4, 28.7+/-4, and 30.4+/-6 kg/m(2), respectively, for the low- to high-systolic BP groups, but were similar in regard to the number of antihypertensive pills taken (2.1+/-0.9, 2.2+/-1.2, 2.2+/-1.3) and metabolic parameters. Patients in the lowest tertile consumed a diet significantly lower in the percentage of energy from saturated fats and sodium content and significantly higher in the percentage of energy from carbohydrate, and the fiber and potassium content in comparison to the highest tertile. The number of servings of legumes, fish and cooked vegetables was higher and that of salami and cheese lower in the 1st tertile. Definitively changing a habitual diet to a healthier one is a difficult task for hypertensive patients. However, those who return to a diet richer in vegetables, legumes and fish and poorer in saturated fat and salt achieve better control of their BP, without increasing the number of antihypertensive pills.