bluuebunny/crossref_metadata_2025_split huggingface dataset:
A9: Exploring Systemic Lupus Erythematosus from the Molecular Level and Dissecting the Disease Mechanism by Molecular Imaging
Authors: Hu Shaofan , Ke Shi , Wang Wei , Ran Henry , Chen Meipu , Zhang Fujun , Qiu Xiuchun , Jiang Ming , Zou Chaoxia , Zhang Rufeng , Cao Li , Fu Rui , Chen Chaoying 
Published: March 2014

Background/Purpose:One and a half million Americans suffer from systemic lupus erythematosus (SLE), with increased death rate in the 15–44 year age group. SLE has a wide range of symptoms and affects multiple organs and tissues. SLE affects each person differently over time. Treatment options are limited with potential serious side effects. There is no cure currently due to the lack of understanding of the mechanism of disease at molecular levels. However, recent developments in the field of molecular imaging provide a tool for noninvasive, target‐specific and longitudinal study of multiple disease components at the same time as well as understanding the dynamic change of the disease. We hypothesize genetic differences play a role in development and severity of the disease. In addition, multiple different disease molecules in different organs at one time point make SLE difficult to treat by standard regiments.Methods:We tested our hypothesis in animal models with two different genetic backgrounds and three target‐specific molecular imaging agents. Two groups of mice carrying normal or mutant Fas gene with SLE were utilized in the study. Optical imaging agents that specifically target to pro‐inflammatory cytokine (IL‐11), cytokine from T‐cells (CXCR4), or disease stroma (matrix metalloproteinase, MMP) were injected through the tail vein. Mice were imaged immediately after injection and for as long as 48 hours afterward. SAS software was used to analyze data by one‐way‐ANOVA or the general linear model. Data comparison was presented in notched box‐and whisker plots. The significant level was set at 0.05 with two‐tailed test.Results:Mice with a normal Fas gene have statistical higher signal intensities for all agents in the joint regions than the Fas mutant mice (P = 0.0139). Target‐specific agents have different organ distributions in Fas mutant mice. The MMP signals are in the kidney (Fig. 1A) and IL‐11 signals are in the lung (Fig. 1B). Both agents have statistical low signal intensities in the same organs in the control mice with normal Fas gene (P<0.0002). The animal with normal Fas gene has high IL‐11 signal intensity in the knee (Fig. 1C). On contrary, CXCR4 has significantly low signal intensity in the Fas mutant mice. Fas mutant mice also have enlarged spleen and kidney by either size or weight than control mice (P<0.0001). imageConclusion:We found that different genetic backgrounds predispose to different disease manifestations. Each organ has different disease components even with same the genetic background at the same disease stage The method we developed here can be used as a tool to better understand genetic and disease components and improve the treatment plan for individual patient needs.
A13: The Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh Out) Cohort: Prospective Determination of the Incidence of New Onset Uveitis in Juvenile Idiopathic Arthritis
Authors: Watanabe Duffy Karen N , Lee Jennifer , Guzman Jaime , Barrowman Nick , Morishita Kimberly , Spiegel Lynn R. , Stringer Elizabeth , Gibbon Michele , Yeung Rae SM , Tucker Lori B. , Oen Kiem , Duffy Ciarán M. ,   ReACChOut Investigators
Published: March 2014

Background/Purpose:Previous studies of uveitis in Juvenile Idiopathic Arthritis (JIA) patients have reported prevalence and not incidence. The ReACCh Out cohort, a large inception cohort of newly diagnosed JIA patients provided the opportunity to prospectively ascertain the true incidence of new onset uveitis. The objectives of this study were to determine the overall incidence rate and its trajectory over time.Methods:ReACCh Out recruited newly diagnosed JIA patients between January 2005 and December 2010, from 16 Canadian centres across the country. Prospective data was collected every 6 months for the first 2 years, then yearly. Data was collected on numerous clinical and laboratory measures including the diagnosis of uveitis and its complications, determined by an ophthalmologist. A Poisson model was used to estimate the overall incidence rate. A Kaplan‐Meier plot was used to evaluate the time from diagnosis of JIA to the time of diagnosis of new onset uveitis.Results:1104 patients with newly diagnosed (≤6 months) JIA with ≥1 follow‐up visit were reviewed. Patients were predominantly female (63%), age at diagnosis was 9.3 (3.9, 13.0) years. Time from diagnosis to enrollment was 0.3 (0, 1.6) months. Follow‐up to last visit or study end was 34.2 (21.5, 48) months. 23 patients whose uveitis status was not available, were excluded. 77 patients with new onset uveitis were identified during the study period. The overall incidence rate of new cases of uveitis following the diagnosis of JIA was 2.9% per year (95% confidence interval 2.3–3.6). Following the trajectory of new cases of uveitis over time, the incidence of new cases showed a slow decline over time (Figure ). Importantly, new cases of uveitis occurred as far out from diagnosis as the end of the study period. Kaplan‐Meier plots were also used to evaluate age at diagnosis of new onset uveitis and gender. Results support previously identified risk factors for uveitis including younger age (<5 years) and female gender. The frequency of uveitis occurred in the JIA patients in the following distribution according to subtype: oligoarthritis (43, 56%), polyarthritis RF negative (18, 23%), polyarthritis RF positive (1, 1%), psoriatic (4, 5%), ERA (1, 1%), systemic (1, 1%) and undifferentiated (9, 12%).Time (confidence intervals) from diagnosis of JIA to diagnosis of new onset uveitisimageConclusion:In a large inception cohort of newly diagnosed JIA patients followed prospectively, the overall incidence rate of new cases of uveitis was 2.9% per year. The slow decrease in incidence over time and the development of new cases of uveitis years later, highlight the importance of ongoing and long term surveillance.
A15: Predicting Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus Patients at Diagnosis
Authors: Gerstein Maya , Sukhdeo Sharon , Levy Deborah M. , Feldman Brian M. , Benseler Susanne M. , Ng Lawrence W.K. , Abdelhaleem Mohamed , Silverman Earl D. , Hiraki Linda 
Published: March 2014

Background/Purpose:Macrophage activation syndrome (MAS), a life‐threatening inflammatory emergency of children with rheumatic diseases, is increasingly recognized in pediatric systemic lupus erythematosus (pSLE). The challenge is to differentiate active pSLE from MAS in order to make correct treatment decisions. The purpose of this study is to generate a decision tree for the recognition of MAS in newly diagnosed pSLE and test the performance of these proposed criteria in an independent pSLE cohort.Methods:A retrospective cohort study of consecutive patients requiring admission to SickKids Hospital with newly diagnosed, active pSLE between January 2002 and July 2007 (training cohort) was performed. All patients met ≥4/11 ACR criteria. Data collection on: 1) Clinical features including fever, CNS dysfunction, splenomegaly, hepatomegaly and hemorrhage; 2) laboratory parameters; CBC, ESR, CRP, C3, C4, ferritin, AST, ALT, LDH, albumin, bilirubin, triglycerides, LDL, HDL, urea, creatinine, sodium, coagulation parameters including INR, PTT, fibrinogen and D‐Dimer, and soluble IL‐2 receptor (sIL‐2R) and CD163. Patients were assigned to one of 2 cohorts exclusively (MAS/non‐MAS). Putative predictor variables were compared between cohorts. A decision tree analysis for diagnosis of MAS in pSLE was constructed using recursive partitioning, and decision rules were subsequently applied to an independent cohort of newly diagnosed, active pSLE diagnosed and admitted to SickKids between July 2007 and July 2013 (testing cohort) to determine the sensitivity and specificity of the proposed criteria.Results:The training cohort consisted of 56 pSLE patients: 9 (16%) diagnosed with MAS and 47 non‐MAS patients. Splenomegaly was more common in the non‐MAS cohort, with no other differences in clinical characteristics between cohorts. Of all the available laboratory data, ALT ≥ 45 units/L, neutrophils < 1.65 × 103/mm3 and ferritin < 836 µg/L identified 56% of the patients with MAS (R2 = 0.75) with 100% specificity. The testing cohort consisted of 9 (20%) MAS and 37 non‐MAS pSLE patients. The proposed thresholds for ALT, neutrophil count and ferritin demonstrated a sensitivity of 11% and specificity of 97%.Conclusion:MAS is a life threatening complication of pSLE. Early recognition is challenging yet critical for appropriate therapy. PSLE patient with and without MAS have many similar clinical and laboratory features. Using statistical modeling, the initial criteria developed maintained excellent specificity but poor sensitivity for distinguishing MAS from active SLE at diagnosis in the testing cohort. Hence, new validated models are required for the early recognition of MAS among pSLE patients. Future analyses are planned to address these issues.
A16: Long‐term follow‐up of 36 Pediatric Antiphospholipid Syndrome Patients: A Retrospective Study
Authors: Gomes Francisco Hugo , Carvalho Luciana , Pinheiro Paola , Resende Tamara , Ferriani Virgínia 
Published: March 2014

Background/Purpose:Antiphospholipid syndrome (APS) is a multisystem autoimmune disease characterized by arterial and/or venous thrombosis and persistent presence of antiphospholipid antibodies. Long term follow‐up studies in children are still scarce. The aim of this study was to evaluate clinical data and long‐term outcome of patients with confirmed antiphospholipid syndrome in childhood.Methods:Between 1993 and 2013, 36 patients with confirmed pediatric antiphospholipid syndrome (22 female; aged 8 months‐18 years, mean 9 years) were followed at the Pediatric Rheumatology Unit of the University Hospital of USP‐RP. Clinical data and long‐term outcome of these patients were reviewed retrospectively.Results:The median follow‐up period was 8.5 years (0.6–20 years), fourteen (38.8%) had underlying autoimmune diseases (30% systemic lupus erytematosous, 5% Behcet's disease and 2.5% systemic juvenile idiopathic arthritis). Venous and arterial thrombosis on the first episode occurred in 14 (38%) and 22 (61%) patients, respectively. Ischemic stroke was the most frequent thrombotic event (50%). Three patients had thrombosis in two different sites on the first episode (inferior vena cava and cerebral sinus vein; lower extremities deep vein thrombosis and pulmonary thromboembolism; portal vein and jugular vein thrombosis). The most frequent associated nonthrombotic clinical manifestations were hematologic manifestations (27%), hypertension (22%), and valvulopaties, identified in 10/27 echocardiograms performed (37%), including one case of Libmann‐Sachs endocarditis. The frequency of antiphospholipid antibodies identified were: IgG anticardiolipin in 24/35 (68%) patients, IgM anticardiolipin in 21/35 (60%), IgG anti‐beta(2)‐glycoprotein I in 6/31 (19%), IgM anti‐beta(2)‐glycoprotein I in 7/31(22%), and lupus anticoagulant in 17/35 (48%). Six patients were positive for all antiphospholipid antibodies investigated. During the follow‐up period new thrombotic events occurred in 9 patients (25%), with catastrophic antiphospholipid syndrome in one of these patients. One patient had two new events (jugular vein thrombosis and pulmonary thromboembolism). Major hemorrhagic events, including intracranial hemorrhage and minor hemorrhagic events, including epistaxis, hematomas and hypermenorrhea occurred in 47% of the patients during the use of oral anticoagulants.Conclusion:Despite of prophylaxis with anticoagulants, new thrombotic events occurred in 25% of the patients and reaching the ideal prothrombin time to prevent thrombotic episodes was the major challenge, as nearly half of the patients had hemorrhagic events. Studies are necessary to identify ideal parameters for treating and monitoring children with antiphospholipid syndrome.
A23: Favorable Response to Belimumab in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Hui‐Yuen Joyce S , Bermudez‐Santiago Liza Mariel , Isgro Josephine , Eichenfield Andrew H. , Starr Amy J. , Imundo Lisa F. , Askanase Anca 
Published: March 2014

Background/Purpose:Belimumab (Benlysta) is a human monoclonal antibody inhibiting soluble B‐lymphocyte stimulator that was approved by the Food and Drug Administration in 2011 for treatment of active, autoantibody‐positive, systemic lupus erythematosus (SLE) in adults. To date, there have been no published data on the use of belimumab in childhood‐onset SLE.Methods:This is a case series of patients with childhood‐onset SLE treated with belimumab at our institution. Data were collected on demographic and disease characteristics, clinical manifestations requiring treatment, concomitant medications, disease course, and treatment outcomes. Descriptive statistics were used when appropriate.Results:We describe 7 patients with childhood‐onset SLE treated with belimumab, 5 of whom are still receiving belimumab infusions at our institution, with a mean follow‐up of 9.3 months on belimumab. The mean age was 18.5 years old, mean disease duration 5.8 years at initiation of belimumab. Eighty‐six percent of the patients were female, 57% African American, 28% Hispanic, and 14% Caucasian. All patients were taking other background medications prior to initiation of belimumab (hydroxychloroquine 7/7, prednisone 7/7, azathioprine 2/7, mycophenolate mofetil 3/7). The most common indications for initiation of therapy were the inability to taper steroids (100%, mean prednisone equivalent dose 0.54mg/kg/day), rash (43%), fatigue (29%), and arthritis (14%), accompanied by worsening serologic activity (increasing anti‐dsDNA titers and hypocomplementemia). At the last follow‐up (mean 9.3 months after initiation of belimumab), average SLEDAI decreased from 6.4 to 4. We were able to taper steroids in 57% of patients, with 3/7 (43%) able to completely discontinue steroids. The average complement levels increased from 71 to 74 (lower limit of normal 83) for C3 and 8 to 10 (lower limit of normal 16) for C4. Six of the seven patients clinically responded to belimumab within three months, with marked improvement in rash, arthritis, and fatigue. Six of seven patients tolerated infusions well, with 1 patient who discontinued treatment due to recurrent vaginal moniliasis.Conclusion:This is the first study investigating the use of belimumab in childhood‐onset SLE across major ethnic groups. Our data demonstrate favorable clinical outcomes including the discontinuation of steroids in 3/7 (43%) of our patients, and improvement in C3 and C4 as early as 3 months after the initiation of belimumab, suggesting a quicker onset of action for belimumab in children than that observed in adult studies, which may support a larger role for belimumab in childhood‐onset SLE.
A43: Juvenile Idiopathic Arthritis in Relation to Maternal Prenatal Smoking
Authors: Shenoi Susan , Bell Samantha , Wallace Carol , Mueller Beth 
Published: March 2014

Background/Purpose:Cigarette smoking increases the risk of seropositive adult Rheumatoid arthritis. Juveinile idiopathic arthritis (JIA) is a heterogenous group of 7 mutually exclusive categories of chronic childhood inflammatory arthritides.Objectives:To determine the association between JIA and its categories with maternal prenatal smoking.Methods:This case‐control study used ICD‐9 codes from hospital records to identify 1196 JIA cases born in Washington State and diagnosed at a tertiary pediatric center during 1997—2010. Controls (n = 5618) were randomly selected from birth records of children without JIA, frequency matched on birth year. Prenatal smoking exposure was assessed from subjects' birth certificates. Chart review categorized JIA into ILAR categories. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression adjusted for maternal age and marital status.Results:We did not observe an increased risk of JIA in relation to maternal prenatal smoking. Prenatal smoking was reported less often among mothers of JIA cases (11%), than among control mothers (17%, OR 0.71, 95% CI: 0.58—0.87), a relationship somewhat more marked for oligoarticular/ extended oligoarticular JIA. Although the inverse relationship persisted after adjustment for maternal education or health insurance status, we cannot rule out the possibility that this effect may have been at least partially due to residual confounding by socio‐economic status.Conclusion:We did not observe an increased risk of JIA with maternal prenatal smoking.
A57: Four Prolonged Cases of Eosinophilic Fasciitis in Children
Authors: Hui‐Yuen Joyce S , Lauren Christine , Garzon Maria , Starr Amy J. , Imundo Lisa F. 
Published: March 2014

Background/Purpose:Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by a progressive inflammatory thickening of skin and soft tissues. Diagnosis is often based on characteristic clinical and biopsy findings, and treatment remains challenging. Pediatric data describing clinical course and treatment recommendations remain scarce.Methods:This is a case series of all patients diagnosed with EF at our institution in the last 8 years. A retrospective chart review was conducted and data collected on clinical signs and symptoms and laboratory data at diagnosis, disease course, and treatment outcomes. Descriptive statistics were used when appropriate.Results:We describe four pediatric patients with EF, with a mean follow‐up of 54 months. Three of the four patients had preceding diagnoses before beginning treatment for EF. All patients had peripheral eosinophilia at diagnosis, two had positive anti‐thyroid antibodies, and two had high levels of total cholesterol. Treatment induction in all patients consisted of intravenous methylprednisone (30mg/kg/day to a maximum of 1g daily for 3 days). All patients required at least one steroid‐sparing agent (methotrexate at 15mg/m2/dose and/or mycophenolate mofetil (MMF) at 600mg/m2/dose) for disease maintenance post‐induction. The mean length of treatment with methotrexate was 23 months, discontinued in only one patient. The mean length of treatment with MMF was 8.3 months. All patients had improvement in skin findings, and all abnormal laboratory findings normalized after treatment with intravenous corticosteroid. One patient had a disease flare less than 12 months after being weaned off cortico‐steroids and methotrexate. Another patient developed a second autoimmune disease five years after treatment for EF. All patients had residual skin changes, and 3 patients had signs of lipodystrophy and/or subcutaneous fat atrophy after treatment.Conclusion:EF is often difficult to diagnose and has a variable course in children. We report four cases of prolonged EF, the only four EF patients diagnosed in our practice. Our data suggest a more severe course at earlier age of onset, with higher likelihood of recurrence. Our data also confirm the efficacy of corticosteroid treatment as first‐line therapy, and suggest a role for methotrexate as a promising steroid‐sparing agent. This is the first case series to describe successful treatment of EF with the addition of mycophenolate mofetil to a treatment course of methotrexate and corticosteroid therapy. Three of our four patients required triple therapy for disease control, which may be suggestive of a more severe disease course in the pediatric population.
A62: GO‐KIDS Imaging Substudy: MRI Treatment Response to 30 mg/m2 Q4W Subcutaneous (SC) Injections of Golimumab (GLM) and Placebo in Children With Polyarticular JIA (pJIA)—Preliminary Results of the Placebo Controlled Portion (Week 48)
Authors: Tzaribachev Nikolay , Tzaribachev Catrin , Mehrwald Marret , Koos Bernd 
Published: March 2014

Background/Purpose:The GO‐KIDS trial is a double blind placebo controlled Phase III trial, where patients 2–17 yrs of age with pJIA received open label SC GLM 30 mg/m2 every 4 weeks until W16, followed by 1:1 randomization to placebo or GLM from W16 to W48 for children achieving ACR Pedi 30 response at W16 with resumption of GLM in PBO randomized subjects upon flare. Primary endpoint is % of children who did not experience flares of JIA between W16 and 48. 173 patients were enrolled globally.Methods:Patients participating in the GO‐KIDS trial at a single center could voluntarily participate in the GO‐KIDS Imaging substudy after obtaining separate informed consent. Gadolinium enhanced MRI examinations of a reference peripheral joint region were obtained at Weeks 0, 16, 28, 48 (primary endpoint). MRI was scored (grade 0–3) for synovitis (S) and synovial hypertrophy (SH). Statistical analysis used Shapiro‐Wilk‐W‐test, non‐parametric Wilcoxon rank‐sum test.Results:From the 17 children with complete data sets at W16 (10 female) with a median age of 9 (7–17) years at study inclusion in the Imaging substudy, 14 of the 17 children reached W48 in the substudy (8 GLM, 6 PBO). Discontinuations through W48 were due to 2 clinical non‐responders at W16 and 1 possible allergic reaction to GLM before W48. At W16 and W48 the MRI was significantly improved compared to W0 both for S and SH (p < 0.001 for W16, p < 0.0001 for W48) for the peripheral joints.After unblinding, 6 patients were on placebo (PBO) where 4 demonstrated through W48 both inactive disease on MRI and clinical improvement above ACR Ped 30 compared to baseline. One of the 4 patients flared after W48, while the remaining 3 do not show residual disease activity on MRI beyond W72. The remaining 2 patients, who were randomized to PBO at W16, flared and resumed GLM treatment. MRI at W28 predicted clinical flare in both patients with evidence of recurrent synovitis. One of the 2 patients responded to reintroduction of GLM showing inactive disease on MRI at W48. The other patient did not respond clinically or by MRI to GLM reintroduction.
Changes in synovitis (S) on Gd enhanced MRI were a significant. Data presented as mean, mininal and maximal values.imageConclusion:At the primary endpoint of the GO‐KIDS trial, overall, children with pJIA demonstrated significant improvement on MRI measurements of synovitis and synovial hypertrophy between W0 and W48 during the GO‐KIDS Imaging substudy, particularly children randomized to continued GLM between W16 and W48. In 4/6 patients randomized to placebo at W16, GLM treatment from W0 to W12 alone induced inactivity on MRI through W48. MRI predicted clinical flare in 2 patients randomized to PBO.