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Objective: There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Because of the rarity of pediatric AAV, randomized trials have not been feasible. The present study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) was undertaken to establish consensus treatment plans (CTPs) for severe pediatric AAV to enable the future study of comparative effectiveness and safety. Methods: A workgroup of CARRA members (rheumatologists and nephrologists) formed the AAV Workgroup. This group performed a literature review on existing evidence‐based treatments and guidelines for the management of AAV. They determined that the target population for CTP development was patients <18 years of age with new‐onset granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or renal‐limited AAV (eosinophilic GPA was excluded), with presentation confined to those with severe disease (i.e., organ‐ or life‐threatening). Face‐to‐face consensus conferences employed nominal group techniques to identify treatment strategies for remission induction and remission maintenance, data elements to be systematically collected, and outcomes to be measured over time. Results: The pediatric AAV Workgroup developed 2 CTPs for each of the remission induction and remission maintenance of severe AAV. A glucocorticoid‐weaning regimen for induction and maintenance, a core data set, and outcome measures were also defined. A random sample of CARRA membership voted acceptance of the CTPs for remission induction and remission maintenance, with a 94% (75 of 80) and 98% (78 of 80) approval rate, respectively. Conclusion: Consensus methodology established standardized CTPs for treating severe pediatric AAV. These CTPs were in principle accepted by CARRA‐wide membership for the evaluation of pragmatic comparative effectiveness in a long‐term registry. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate factors associated with extracutaneous involvement (ECI) in juvenile localized scleroderma (jLS). Methods A prospective, multicentre, 6-month observational study was performed. The data collected included disease features, global assessments, and subject symptoms. Bivariate and linear multilevel regression analyses were performed. Results A total of 86 jLS subjects (80% female, 80% Caucasian), median age of disease onset 7.7 years, were evaluated. Most had linear scleroderma or mixed morphea. Of the 86 subjects, 49 (57%) had 125 extracutaneous problems {median 2 [interquartile range (IQR) 1, 3] per subject} from nine organ systems. Most of these subjects had multiple musculoskeletal problems. ECI was associated with more extensive cutaneous involvement, higher number of symptoms, family history of autoimmunity, and ANA and RF positivity. Subjects with ECI had higher scores for physician global assessment of damage (PGA-D), and parental global assessment of disease impact, but not baseline physician global assessment of disease activity (PGA-A). Although subjects with ECI received more MTX and glucocorticoid treatment, they had a slower reduction in PGA-A scores and symptoms over time, suggesting a poorer response to treatment. In logistic regression modelling, female sex had the largest effect on parental impact scores. Conclusion ECI occurred in the majority of subjects with jLS, and was associated with more medication use, longer treatment duration, higher PGA-D scores, and higher parental assessment of disease impact. Our findings suggest that jLS subjects with ECI have greater overall disease burden, both cutaneous and extracutaneous, and poorer response to treatment. More study of the treatment needs of this population is warranted. [ABSTRACT FROM AUTHOR]

Abstract Background The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT). Methods The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as ≥ 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision. Results The panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for ≥ 3 days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined. Conclusion The expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.

Abstract Henoch-Schönlein purpura is one of the most common forms of systemic vasculitis of childhood. We report the response to anakinra, the interleukin-1 receptor antagonist, in a 9 year old girl without prior medical problems who developed life-threatening Henoch-Schönlein vasculitis that produced renal failure, pulmonary hemorrhage and vasculitis of the brain. Her response supports the theory that interleukin-1 may be an important mediator in this disease. Further study of interleukin-1 antagonists in severe Henoch-Schönlein purpura may be warranted.

A case of silent carditis (inflammation of the heart muscle) caused by poststreptococcal reactive arthritis (PSRA) in a pediatric patient shows the need for antibiotic treatment of PSRA to minimize damage to the heart. Previously, silent carditis had been associated with acute rheumatic fever (ARF) but not with PSRA. Carditis of ARF is one of the leading causes of acquired pediatric heart disease in North America, and can lead to congestive heart failure, the need for valve replacement, or death. Patients with PSRA may need to receive preventive antibiotic treatment to prevent recurrence of acute streptococcal infection, which can cause carditis. Patients who may have PSRA should be screened with Doppler-echocardiography so that silent carditis can be detected before much damage is done to the heart.

Objective: Endothelial dysfunction is central to the pathogenesis of many rheumatic diseases, typified by vascular inflammation and damage. Immunosuppressive drugs induce disease remission and lead to improved patient survival. However, there remains a higher incidence of cardiovascular disease in these patients even after adequate disease control. The purpose of this study was to determine the effect of mycophenolic acid (MPA), a commonly used immunosuppressive drug in rheumatology, on blood vessel or circulating endothelial colony forming cell number and function. Methods: We tested whether mycophenolic acid exerts an inhibitory effect on proliferation, clonogenic potential and vasculogenic function of endothelial colony forming cell. We also studied potential mechanisms involved in the observed effects. Results: Treatment with MPA decreased endothelial colony forming cell proliferation, clonogenic potential and vasculogenic function in a dose-dependent fashion. MPA increased senescence-associated β-galactosidase expression, p21 gene expression and p53 phosphorylation, indicative of activation of cellular senescence. Exogenous guanosine supplementation rescued diminished endothelial colony forming cell proliferation and indices of senescence, consistent with the known mechanism of action of MPA. Conclusion: Our findings show that clinically relevant doses of MPA have potent anti-angiogenic and pro-senescent effects on vascular precursor cells in vitro, thus indicating that treatment with MPA can potentially affect vascular repair and regeneration. This warrants further studies in vivo to determine how MPA therapy contributes to vascular dysfunction and increased cardiovascular disease seen in patients with inflammatory rheumatic disease. [ABSTRACT FROM AUTHOR]

Background: Because pediatric antineutrophil cytoplasmic antibody-associated vasculitis is rare, management generally relies on adult data. We assessed treatment practices, uptake of existing clinical assessment tools, and interest in pediatric treatment protocols among rheumatologists caring for children with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods: A needs-assessment survey developed by an international working group of pediatric rheumatologists and two nephrologists was circulated internationally. Data were summarized with descriptive statistics. Pearson's chi-square tests were used in inferential univariate analyses. Results: The 209 respondents from 36 countries had collectively seen ~1600 children with GPA/MPA; 144 had seen more than two in the preceding 5 years. Standardized and validated clinical assessment tools to score disease severity, activity, and damage were used by 59, 63, and 36%, respectively; barriers to use included lack of knowledge and limited perceived utility. Therapy varied significantly: use of rituximab rather than cyclophosphamide was more common among respondents from the USA (OR = 2.7 [1.3-5.5], p = 0.0190, n = 139), those with >5 years of independent practice experience (OR = 3.8 [1.3-12.5], p = 0.0279, n = 137), and those who had seen >10 children with GPA/MPA in their careers (OR = 4.39 [2.1-9.1], p = 0.0011, n = 133). Respondents who had treated >10 patients were also more likely to continue maintenance therapy for at least 24 months (OR = 3.0 [1.4-6.4], p = 0.0161, n = 127). Ninety six percent of respondents believed in a need for pediatric-specific treatment guidelines; 46% supported adaptation of adult guidelines while 69% favoured guidelines providing a limited range of treatment options to allow comparison of effectiveness through a registry. Conclusions: These data provide a rationale for developing pediatric-specific consensus treatment guidelines for GPA/MPA. While pediatric rheumatologist uptake of existing clinical tools has been limited, guideline uptake may be enhanced if outcomes of consensus-derived treatment options are evaluated within the framework of an international registry. [ABSTRACT FROM AUTHOR]

The first cases of acquired immunodeficiency syndrome (AIDS) in infants were reported in 1983, and that number has grown to a current population of over 1,300 cases of AIDS in children. In addition to children who can be presently classified as having AIDS, many more infants and children are infected with the human immunodeficiency virus (HIV, which causes AIDS) and have a high probability of developing AIDS at some time in the future. Obstetrical screening of newborns is now recommended for those who had fetal exposure to the virus, that is, screening of newborns with HIV-infected mothers. The current study explores the natural history of AIDS in children who belong to this high risk population. Women who were seen in a major center's gynecologic service, and identified as being at high risk for AIDS, were asked to participate in a study of AIDS risk for both themselves and their infants. All women who were identified as high-risk agreed to participate. Of these women, 25 percent were found to be infected with HIV as determined by blood testing (seropositive), but none had yet developed AIDS. Ninety percent of these mothers were Afro-American with an average age of 25.8 years. Approximately half continued to abuse drugs during pregnancy. The first 20 children born to HIV-infected mothers were evaluated at birth, and at 2, 4, 6, 9, 12, and 18 months of age by physical examination and blood testing. Of these children, eight were diagnosed with HIV infection. There was no significant difference between the infected children and the non-infected children on physical examination. The infected children suffered from opportunistic infections and failure-to-thrive. Six of the eight infected children produced antibodies against HIV that could be detected by blood testing; this may represent an important marker of the disease in young children. In this study, 8 of 20 young children at high risk for HIV infection became infected during the 18-month period of observation. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity.Methods: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined.Results: The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses.Conclusion: The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation. [ABSTRACT FROM AUTHOR]

Objectives This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). Methods The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. Results The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. Conclusions The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation. [ABSTRACT FROM AUTHOR]

Table of Contents P1 Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis Lampros Fotis, Nur Shaikh, Kevin Baszis, Anthony French, Phillip Tarr P2 Oral health and anti-citrullinated peptide antibodies (ACPA) in juvenile idiopathic arthritis Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newsom, Anne Stevens P3 Novel autoantigens for endothelial cell antibodies in pediatric rheumatic diseases identified by proteomics Rie Karasawa, Mayumi Tamaki, Megumi Tanaka, Toshiko Sato, Kazuo Yudoh, James N. Jarvis P4 Transcriptional profiling reveals monocyte signature associated with JIA patient poor response to methotrexate Halima Moncrieffe, Mark F. Bennett, Monica Tsoras, Lorie Luyrink, Huan Xu, Sampath Prahalad, Paula Morris, Jason Dare, Peter A. Nigrovic, Margalit Rosenkranz, Mara Becker, Kathleen M. O’Neil, Thomas Griffin, Daniel J. Lovell, Alexei A. Grom, Mario Medvedovic, Susan D. Thompson P5 A multi-dimensional genomic map for polyarticular juvenile idiopathic arthritis Lisha Zhu, Kaiyu Jiang, Laiping Wong, Michael J Buck, Yanmin Chen, Halima Moncrieffe, Laura Brungs, Tao Liu, Ting Wang, James N Jarvis P6 Tocilizumab for treatment of children with refractory JIA Khaled Alsaeid, Jasim Alfailakawi, Hamid Alenezi, Hazim Alsaeed P7 Clinical characteristics of the initial patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry Tim Beukelman, Marc Natter, Norm Ilowite, Kelly Mieszkalski, Grendel Burrell, Brian Best, Helen Bristow, Shannon Carr, Anne Dennos, Rachel Kaufmann, Yukiko Kimura, Laura Schanberg P8 Comparative performance of small and large clinical centers in a comprehensive pediatric rheumatology disease registry Peter R Blier P9 Clinical characteristics of children with membranous lupus nephritis: The Childhood Arthritis and Rheumatology Research Alliance Legacy Registry Alexis Boneparth, Scott E. Wenderfer, L. Nandini Moorthy, Suhas M. Radhakrishna, Anna Carmela P. Sagcal-Gironella, Emily von Scheven P10 Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome - a two center experience Kader Cetin Gedik, Salma Siddique, Cassyanne L. Aguiar, Doruk Erkan P11 Predictors of complementary and alternative medicine use and response in children with musculoskeletal conditions Ezra Cohen, Yvonne Lee, Michelle Dossett, Darshan Mehta, Roger Davis P12 Comparison of pediatric rheumatology and nephrology survey results for the treatment of refractory proliferative lupus nephritis and renal flare in juvenile SLE Mileka Gilbert, Beatrice Goilav, Esra Meidan, Joyce Hsu, Alexis Boneparth, Anabelle Chua, Stacy Ardoin, Scott E. Wenderfer, Emily Von Scheven, Natasha M. Ruth P13 Transitioning lupus patients from pediatric to adult rheumatology Joyce Hui-Yuen, Kader Cetin Gedik, Liza Bermudez, Ashlea Cook, Lisa Imundo, Amy Starr, Andrew Eichenfield, Anca Askanase P14 The systemic juvenile idiopathic arthritis cohort of the Childhood Arthritis & Rheumatology Research Alliance Registry Ginger Janow, Laura E. Schanberg, Soko Setoguchi, Victor Hasselblad, Elizabeth D. Mellins, Rayfel Schneider, Yukiko Kimura, The CARRA Legacy Registry Investigators P15 Results of the pilot study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, T Brent Graham, Maria Ibarra, Yonit Sterba Ruas, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E. Weiss, Pamela F. Weiss, Kelly Mieszkalski, Laura E. Schanberg P16 A systemic review of pain relief modalities in juvenile idiopathic arthritis: First step in developing a novel decision support intervention Timothy S. H. Kwok, Jacinthe Bisaillon, Christine Smith, Lucie Brosseau, Jennifer Stinson, Adam M. Huber, Ciaran M. Duffy, Karine Toupin April P17 Barriers and facilitators to care retention for pediatric systemic lupus erythematous patients in South Africa: A qualitative study Laura B Lewandowski, Christiaan Scott P18 Evaluating the feasibility of conducting comparative effectiveness studies in juvenile Localized Scleroderma (jLS) Suzanne C. Li, Kathryn S. Torok, C. Egla Rabinovich, Sandy D. Hong, Mara L Becker, Fatma Dedeoglu, Maria F. Ibarra, Polly J Ferguson, Rob C. Fuhbrigge, Katie G. Stewart, Elena Pope, Ronald M. Laxer, Thomas G. Mason, Gloria C. Higgins, Xiaohu Li, Marilynn G. Punaro, George Tomlinson, Eleanor Pullenayegum, John Matelski, Laura Schanberg, Brian M. Feldman P19 Tonsillar histology in patients with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome Kalpana Manthiram, Hernan Correa, Kathryn Edwards P20 Clinical course of juvenile dermatomyositis presenting as skin predominant disease Edward J. Oberle, Michelle Bayer, Dominic O. Co, Hatice Ezgi Baris, Yvonne Chiu, Adam Huber, Susan Kim P21 A Survey of musculoskeletal ultrasound practices of pediatric rheumatologists in North America Edward J Oberle, Timothy Beukelman P22 Assessment, classification and treatment of calcinosis as a complication of juvenile dermatomyositis: A survey of pediatric rheumatologists by the Childhood Arthritis and Rheumatology Research Alliance Amir B. Orandi, Kevin W. Baszis, Vikas Dharnidharka, Mark F. Hoeltzel, for the CARRA JDM Committee P23 CARRA dermatomyositis CTP pilot study Ann Reed, Adam Huber, George Tomlinson, Eleanor Pullenayegum, John Matelski, Y. Ingrid Goh, Laura Schanberg, Brian M. Feldman P24 Unexpectedly high incidences and prolonged disease activity in children with chronic non-bacterial osteomyelitis (CNO) as compared to bacterial osteomyelitis Anja Schnabel, Ursula Range, Gabriele Hahn, Timo Siepmann, Reinhard Berner, Christian Michael Hedrich P25 Juvenile systemic sclerosis cohort within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry: Follow up characteristics Brandi Stevens, Kathryn S. Torok, Suzanne Li, Nicole Hershey, Megan Curran, Gloria Higgins, Katharine Moore, Egla Rabinovich, Anne M. Stevens, for the CARRA Registry Investigators P26 Development and usability testing of an iPad and desktop psycho-educational game for children with Juvenile Idiopathic Arthritis and their parents Jennifer Stinson, Mark Connelly, Adam Huber, Nadia Luca, Lynn Spiegel, Argerie Tsimicalis, Stephanie Luca, Naweed Tajuddin, Roberta Berard, Julia Barsalou, Sarah Campillo, Paul Dancey, Ciaran Duffy, Brian Feldman, Nicole Johnson, Patrick McGrath, Natalie Shiff, Shirley Tse, Lori Tucker, Charles Victor P27 iCanCopeTM: User-centred design and development of a smartphone app to support self-management for youth with arthritis pain Jennifer Stinson, Chitra Lalloo, Lauren Harris, Joseph Cafazzo, Lynn Spiegel, Brian Feldman, Nadia Luca, Ronald Laxer P28 Accessing pediatric rheumatology care: Despite barriers, few parents prefer telemedicine Danielle R. Bullock, Richard K. Vehe, Lei Zhang, Colleen K. Correll1 P29 Exploration of factors contributing to time to achieve clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA): A preliminary report Suhas Ganguli, Max Shenberger, Ritesh Korumilli, Beth Gottlieb P30 Pediatric rheumatology referral patterns: Presenting complaints of new patients at a large, urban academic center Martha Rodriguez, Deirdre de Ranieri, Karen Onel, Linda Wagner-Weiner, Melissa Tesher P31 Quality improvement (QI) initiatives in childhood systemic lupus erythematosus (cSLE) Elizabeth Roth Wojcicki, Kristyn L. Maletta, Dominic O. Co, Marsha Malloy, Sarah Thomson, Judyann C. Olson P32 Proliferative lupus nephritis in juvenile SLE: Support from the pediatric nephrology community for the definitions of responsiveness and flare in the 2012 consensus treatment plans Scott E. Wenderfer, Mileka Gilbert, Joyce Hsu, Sangeeta Sule, Tamar B. Rubinstein, Beatrice Goilav, Daryl M. Okamura, Annabelle Chua, Laurence A. Greenbaum, Jerome C. Lane, Emily von Scheven, Stacy P. Ardoin, Natasha M. Ruth P33 The steroid taper app: Making of a mobile app Jennifer M. P. Woo, Marsha M. Malloy, James A. Jegers, Dustin J. Hahn, Mary K. Hintermeyer, Stacey M. Martinetti, Gretchen R. Heckel, Elizabeth L. Roth-Wojcicki, Dominic O. Co

Objective Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. Methods A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Results Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Conclusion Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS. [ABSTRACT FROM AUTHOR]

Objective To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Methods Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. Results By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 ( P = 0.053). There were no significant interarm differences in adverse events. Conclusion Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms. [ABSTRACT FROM AUTHOR]

Objective: To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE).Methods: Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL).Results: While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL.Conclusion: Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE. [ABSTRACT FROM AUTHOR]

The article presents two case studies related to hypertension. The first study is of 4-year-old boy, who was facing abdominal pain and emesis. After several examinations, he was diagnosed with hypertension. The second study is of 7-year-old boy, who was suffering from leg pain and red spots on his ankles and buttocks. He was diagnosed with proteinuria and hematuria along with hypertension.

Objectives To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. Methods The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, κ-agreement) using as ‘gold standard’ the final consensus classification or original treating physician diagnosis. Results A total of 1183/1398 (85%) samples collected were available for analysis: 827 HSP, 150 c-PAN, 60 c-WG, 87 c-TA and 59 c-other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c-vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with a κ-agreement of 0.96 for HSP (95% CI 0.84 to 1), 0.88 for c-WG (95% CI 0.76 to 0.99), 0.84 for c-TA (95% CI 0.73 to 0.96) and 0.73 for c-PAN (95% CI 0.62 to 0.84), with an overall κ of 0.79 (95% CI 0.73 to 0.84). Conclusion EULAR/PRINTO/PRES propose validated classification criteria for HSP, c-PAN, c-WG and c-TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis. [ABSTRACT FROM PUBLISHER]

The article focuses on the study that determines whether gene expression abnormalities persist in juvenile idiopathic arthritis (JIA) in remission. It is argued in the article that neutrophil gene profiling in polyarticular JIA depicts important roles for neutrophils in disease pathogenesis. The results also suggest the presence of complex interactions between innate and adaptive immunity which are not modeled easily in conventional, linear, reductionist systems.

The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation. [ABSTRACT FROM AUTHOR]