bluuebunny/crossref_metadata_2025_split huggingface dataset:
A63: Treatment of Arthritis in Animal Models of the Mucopolysaccharidoses Using a Novel Anti‐Inflammatory Drug, Pentosan Polysulfate
Authors: Simonaro Calogera , Frohbergh Michael , Ge Yi , Meng Fanli , Schuchman Edward 
Published: March 2014

Background/Purpose:The mucopolysaccharidoses (MPS) comprise a group of 11 lysosomal storage disorders (LSDs) due to inherited deficiencies of glycosaminoglycan (GAG) degrading enzymes. Naturally occurring animal models exist for most of these disorders, providing excellent systems in which to study disease pathogenesis and treatment. We have previously shown that GAG storage in MPS leads to activation of the TLR4/TNF‐alpha inflammatory pathway, and that inflammation is a major contributor to the degenerative cartilage disease occurring in MPS patients. The pattern of inflammatory changes in MPS closely resembles that occurring in arthritis, and the MPS animals also represent excellent, naturally occurring genetic models of arthritis. Various treatment approaches have been investigated for MPS, and we recently identified one FDA‐approved drug, pentosan polysulfate (PPS), that resulted in remarkable clinical improvements in a rat model of MPS type VI (Schuchman et al., PLoS One, 2013).Methods:In our previous work we reported the effects of daily oral PPS treatment in MPS VI rats, and here we compare these effects with weekly subcutaneous (subQ) injections. Four groups of MPS VI rats were treated with weekly subQ PPS at human equivalent doses of 1, 2 and 4 mg/kg, and with a combination of 2 mg/kg PPS and 1 mg/kg enzyme replacement therapy (ERT; Naglazyme®).Results:The most efficacious subQ PPS dose was 2 mg/kg. Among the four groups of treated rats the best results were found in animals treated with a combination of PPS and ERT. Treatment of all MPS VI rats with weekly subQ PPS for up to 6 months was safe.Conclusion:We propose that weekly subQ injections of PPS will be efficacious and safe in MPS patients, and a phase 1/2 clinical study is planned. We also propose that PPS could be effective in arthritis, and might provide a cost‐effective, safe alternative to existing TNF‐alpha drugs.
A67: Factors That Contribute to Classification of Children as Having Undifferentiated Juvenile Idiopathic Arthritis
Authors: Chan Mercedes O. , Petty Ross E. , Oen Kiem , Duffy Ciarán M. , Tucker Lori B. , Yeung Rae SM , Guzman Jaime ,   The ReACCh Out Investigators
Published: March 2014

Background/Purpose:According to the ILAR criteria, undifferentiated juvenile idiopathic arthritis (U‐JIA) includes children who fail to meet criteria for 1 of the other 6 categories or who meet criteria in more than 1 category. Classification requires category‐specific application of 5 exclusion criteria: 1. Psoriasis in the patient or a 1st degree relative; 2. Arthritis beginning after the 6th birthday in an HLA‐B27 + male; 3. HLAB27 associated disease in a 1st degree relative; 4. Rheumatoid factor positivity (RF+) on 2 occasions; and 5. The presence of systemic JIA (SoJIA).A pilot single‐centre study (n=21) revealed that psoriasis in a 1st degree relative was the most common reason for classifying patients as U‐JIA; disregarding this criterion would allow re‐classification of most U‐JIA patients and had no impact on the classification of JPsA patients (Chan et al., 2011). We aimed to determine the most frequent reasons for classifying children as U‐JIA from a large multicenter prospective cohort of children with JIA (n=1104).Methods:Two investigators reviewed data on patients diagnosed with UJIA extracted from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh‐Out) database. They identified by consensus the reasons for classifying patients as U‐JIA and the JIA category they would fall in if the following two changes were made: disregarding psoriasis in a 1st degree relative, considering patients as RF negative when only a single positive RF test was recorded.Results:84 patients (51 female), were classified as U‐JIA for the reasons shown in the .

Exclusion criteria
1st degree relative with psoriasis (n=57)
B27 male>6 years + arthritis (n=4)
RF+ on 2 occasions (n=1)
RF+ on 1 occasion only (n=17)
1st degree relative with B27 related disease (n=4)
SoJIA (n=0)
Fulfills criteria for 2 categories (n=2)

Revised category if exclusion criteria disregarded

Oligo
25

9
2

Poly RF−
13

2

Poly RF+
5 (1 RF+x2, 4 RF+x1)

ERA
12

5

Systemic
2

1

JPsA

4

1

U‐JIA

1
1

2 (JPsA + ERA)If the criterion of having a 1st degree relative with psoriasis was disregarded, 25 patients would be classified as oligo JIA, 13 poly RF−, 5 poly RF+, 12 ERA and 2 SoJIA. If a single positive RF test was considered to be insufficient to meet the ILAR criterion of RF positivity, 9 patients would be re‐classified as oligo JIA, 5 ERA, 1 SoJIA, 1 JPsA and 1 would remain U‐JIA.Conclusion:Psoriasis in a 1st degree relative is the most common factor contributing to the classification of a child as having U‐JIA and removing it from the existing criteria should be considered. The presence of a single positive test for RF was the second most common reason resulting in a classification of U‐JIA. Definitive RF testing (two tests) should be maintained to satisfy the criterion of “RF positivity”.
A69: Lupus Nephritis and Autoantibody Characteristics of a Single Center Cohort of Male Pediatric SLE Patients
Authors: Wenderfer Scott E. , Canter Debra , DeGuzman Marietta , Muscal Eyal 
Published: March 2014

Background/Purpose:Males represent 4–22% of all SLE patients, but it is unclear if gender should influence management. A number of studies of mostly adult patients suggest genetic, hormonal and environmental aspects of gender differences contribute to differences in presentation, clinical course and outcome, including a positive association between male gender and nephritis and a negative association with disease activity and outcome. While differences may exist, these findings are supported by limited evidence, particularly for children and adolescents with SLE.Methods:We retrospectively reviewed records of the nearly 200 pediatric SLE patients actively followed in the TCH rheumatology and renal clinics between 2011 and 2013 to identify males with SLE. Characteristic autoantibody features and renal disease were defined.Results:We identified 25 males (48% Hispanic, 16% Black, 16% Asian). The mean age of onset of disease was 11.5 ± 0.6 yo. Comorbid autoimmune diseases were identified in 46% of patients and 31% had a positive family history of autoimmune disease. Hypocomplementemia was seen at least once in 54% of patients. The cumulative incidence of positive autoantibodies included 50% anti‐dsDNA, 54% with antiphospholipid abs, 42% with anti‐RNP, 38% with anti‐Ro (SS‐A), 19% with anti‐Smith, 15% with anti‐La (SS‐B), and 8% with RF. Only 35% (9) of male SLE patients developed lupus nephritis (LN), the majority of whom had class IV lesions (77%). Class V lesions were seen in 3 patients, including one with mixed histopathology (IV/V). LN was a presenting symptom in all 9 patients. Of these, 33% had acute kidney injury and 22% had crescentic disease on biopsy. The proportion of boys with LN and anti‐dsDNA antibodies was not significantly different from boys without LN (66% vs. 50%, p = 0.67); however, a significantly higher proportion of boys with LN had anti‐RNP abs (77% vs. 29%, p = 0.04).Conclusion:Although SLE predominately affects females, males with SLE represent an important subset of patients about which little is known. In our male cohort, rates of autoantibody positivity were similar to those published for females, but rates of kidney invovlement seem lower than expected. In addition, autoantibody profiling may not be as useful in predicting kidney involvement in boys. Additional research is of upmost importance to improve the diagnosis, quality of care, and outcomes of male SLE patients.
A72: Predicting Progression From Oligoarticular to Polyarticular Juvenile Arthritis
Authors: Rumsey Dax , Rezaei Elham , Karunanayake Chandima , Oen Kiem , Rosenberg Alan M. , Shiff Natalie 
Published: March 2014

Background/Purpose:It has been previously shown that early involvement of wrist and ankle are risk factors for extension of oligoarticular onset juvenile arthritis (oligoJA). Our objective was to determine whether early wrist, ankle, upper limb, or lower limb involvement are risk factors for extension to a polyarticular course in a cohort of paediatric patients with oligoJA.Methods:This is a retrospective cohort study of children with oligoJA presenting to paediatric rheumatology clinics at the two Canadian paediatric centres from 1981 to 2010. OligoJA was defined as ≤4 joints at the first and 6 month visits. Risk factors for extension from oligoJA to polyarthritis (>5 joints) by 2 and 5 years after diagnosis were modelled using logistic regression while controlling for sex, ever having used DMARDs, or intraarticular corticosteroid injections. Time to extension was assessed using Cox proportional hazard analysis.Results:420 patients met eligibility criteria. 56% were female. The median time from disease onset to diagnosis was 136 days (IQR 55.5 days, 365.0 days); 15 patients in the logistic regression models extended by 2 years (n=280, of which 5.4% extended) and 27 by 5 years (n=339, of which 8.0% extended). At 2 years after diagnosis the odds of extension was 6.1 times higher (95% CI 1.9, 24.3) in those with initial wrist involvement than in those without, and at 5 years it was 3.1 times higher (95% CI 1.0, 8.0). The OR of extension in those with initial upper limb involvement versus those without was 7.0 (95% C.I. 2.3, 21.6) at 2 years and 6.3 (95% C.I. 2.5, 15.8) at 5 years. Cox proportional hazard modelling showed a HR of 2.3 (95% CI 1.2, 4.5) in patients with upper limb involvement compared to without upper limb involvement indicating that extension was 2.3 times more likely to occur in the former group. The likelihood ratio was 68.7, p value < 0.0001, degrees of freedom (d.f) = 4, and events per variable = 9.8.Conclusion:This study independently confirms previous published findings that wrist and upper limb arthritis in the first 6 months after diagnosis of oligoJA is a risk factor for extension. Unlike previous reports, we did not find an increased probability of extension in patients with early ankle arthritis. Patients with upper limb arthritis in the first 6 months after diagnosis were more likely to extend sooner than those without early upper limb arthritis.
A97: Endothelial Function in Children With a History of Henoch‐Schonlein Purpura
Authors: Aviel Yonatan butbul , Dafna Lotem , Brik Riva , Pilar Giora 
Published: March 2014

Background/Purpose:Few reports have focused on vascular endothelial function in children with Henoch‐Schönlein purpura (HSP). The purpose of the present study was to assess the long term effect of HSP on endothelial function, in children and adolescents.Methods:Patients between 6–20 years old, who were diagnosed as having HSP according to ACR Criteria, were included in the study. All patients were followed by the rheumatologic clinic at Meyer children's hospital Israel. The time interval between diagnosis of HSP and endothelial study was at least 6 months.Endothelial function evaluation was assessed by a noninvasive technology named peripheral arterial tonometry, using an ENDO_PAT device. The device measures blood flow in the limb, in response to arterial occlusion as an index of endothelial function, Reactive Hyperemic Index (RHI). Endothelial function was compared to known normal values of existing control group consisting of 23 healthy children and adolescents.Results:Nineteen children and adolescents (M:F 8/11) age (3.9 ± 13.5 years) with history of HSP were included in the study. Endothelial function was compared to that of a known control group comprising of 23 healthy children and adolescents of the same age group and M:F ratio.There was no difference in RHI levels between the children with diagnosis of HSP and the control group (1.8 ± 0.7 vs. 1.9 ± 0.35 p = 0.7).For patients with HSP we used multi variant regression models to evaluate relation between RHI and different variables the final model include smoking that have negative effect (β = (−1.042), P = 0.31) and, period of time from diagnosis to time of evaluation that have positive effect (β = 0.139, P = 0.003) (R2 = 0.476).When we excluded two patients with exceptional level of RHI from the study a higher correlation was found between those variables and RHI (R2 = 0.76).RHI levels were significantly higher in patients that endothelial function was measured more than 6 years after diagnosis of HSP compared to the rest of the group (1.98 ± 0.74 vs 1.38 ± 0.43 P = 0.037).Conclusion:These results suggest that HSP cause endothelial dysfunction that improves with time.The influence of the endothelial dysfunction on the long term chances of developing atherosclerosis has still to be determined.
A104: Aggressive Erosive Synovitis in Juvenile Idiopathic Arthritis
Authors: Chédeville Gaëlle , Azouz Michel , Scuccimarri Rosie 
Published: March 2014

Background/Purpose:Plain radiographs (x‐rays) are useful in the evaluation of children with JIA. Bone erosions are one of the finding that can be seen on x‐rays. However, they are most often reported in the polyarticular RF+ subtype of JIA and are rare in most other subtypes.Methods:Herein 3 patients with JIA are presented whose diagnoses were questioned after plain x‐rays were obtained. MRI later revealed significant erosive disease in these patients.Results:Case 1: A 14 yo male presented with a monoarthritis of the left wrist. Initial x‐rays were normal. His work‐up was unremarkable. His inflammatory markers were normal. He was thus diagnosed with JIA–oligoarthritis. After 6 months in remission, after the use of an NSAID, he flared in the same joint. Repeat x‐rays showed a radiolucent area with associated sclerosis in the scaphoid of unclear etiology. An MRI was thus requested. It revealed synovitis associated with erosive disease. Post gadolinium injection, a geode in the scaphoid bone with marked synovial enhancement visible within this erosion was detected. He underwent a joint injection which put him into remission. Repeat x‐rays one year later, revealed unchanged findings likely corresponding to the non‐healed erosion.Case 2: An 11 yo HLA B27 + male diagnosed with ERA with polyarthritis of the lower limbs and sacroiliac joints was treated with methotrexate and an NSAID. Investigations ruled out IBD and the arthritis was felt to be well controlled despite persistently elevated inflammatory markers of unclear etiology. He presented with a severe flare in his knees and ankles. X‐rays revealed well‐defined lytic lesions in the anterior aspect of the proximal tibial metaphysis just below the growth plate bilaterally. Given the concern of an infiltrative process, an MRI was obtained. Post gadolinium injection, a large erosion of the tibial plateau with marked synovial enhancement within this erosion was seen, as well as a knee synovitis. Etanercept was started.Case 3: An 8 yo male presented with a monoarthritis of the right wrist evolving for five months after an initial minor trauma. X‐rays revealed advanced bone maturation of the right wrist as well as a sclerotic lesion of the hamate. Given the initial trauma, an MRI was obtained which demonstrated very extensive bone marrow edema, synovitis, tenosynovitis and a large erosion within the hamate. A diagnosis of JIA–oligoarthritis was made. He underwent a joint injection with good disease control.Conclusion:Large erosions are not typical for some JIA subtypes such as oligoarthritis and ERA. Findings on x‐rays led the treating physicians to question the underlying diagnosis however, MRI revealed very aggressive synovitis of the wrist and knee in these patients. MRI was useful to demonstrate the presence of synovial enhancement within the eroded bone and helped rule out another diagnosis. Awareness of this type of aggressive arthritis is needed so that patients are not over‐investigated and prompt treatment can be offered.
A105: Late Cardiac Assessment in Children Who Were Diagnosed With Post Streptococcal Reactive Arthritis—A Long Term Study
Authors: Perl Liat , Kvint Ifat , Matityahu Avraham , Levi Alex , Uziel Yosef , Barash Judit 
Published: March 2014

Background/Purpose:In different from rheumatic fever (RF), the association of post streptococcal reactive arthritis (PSRA) and carditis is controversial. Currently the American Heart Association recommends anti‐streptococcal prophylaxis for PSRA for one year, repeat echocardiogram and discontinuation of prophylaxis if normal (level 2, C evidence).Aim—To examine whether there is late cardiac involvement in a cohort of children with PSRA.Methods:Children with defined PSRA who were followed at the pediatric rheumatology units in Meir and Kaplan hospitals had echocardiography, done by pediatric cardiologists, at least 1 year following diagnosis.Results:146 PSRA patients fulfilled the study criteria. Of these, 69 had undergone echocardiography 1–6.9 years from diagnosis. All had normal major parameters. 20 patients had minimal findings: 5 (7.2%) mild mitral insufficiency; 12 (17.4%) minimal mitral insufficiency; 2 (2.9%) mild tricuspid insufficiency and one patient (1.4%) had very mild aortic insufficiency. All were consistent as non significant findings. Of the 77 patients who did not complete echocardiography, 31 were randomly excluded from the study, 26 refused to undergo echocardiography, and 20 were lost to followup, all were asymptomatic according to their medical record or telephone questionnaire. There were no statistically significant differences between the group that had completed echocardiography to the group that had not.Conclusion:No late cardiac involvement was found in our pediatric PSRA patients. Therefore, different approaches to antibiotic prophylaxis for PSRA and RF are probably justified. A prospective, double blind placebo controlled study is needed to definitively assess the necessity of prophylaxis in PSRA.
A107: Dream Doctors—Medical Clowns Increase the Effect of Nitrous Oxide Sedation in Intra‐Articular Corticosteroid Injection for Juvenile Idiopathic Arthritis
Authors: Uziel Yosef , Weintraub Yael , Rabinowicz Noa , Hanuka Penny , Rothschild Michal , Kotzki Shulamit 
Published: March 2014

Background/Purpose:Intra‐articular corticosteroid injection (IASI), a common procedure in juvenile idiopathic arthritis (JIA), is usually associated with anxiety and pain.In previous study we concluded that nitrous oxide (NO) provides effective and safe sedation for such procedures. The efficacy in reducing pain was associated with the level of the child's anxiety even before starting the procedure.Following the introduction of “Dream Doctors” in our hospital, we added medical clown as an important integral part of the team doing IASI.Aim:To prospectively evaluate how a medical clown affects pain perception during IASI in JIA using NO conscious sedation.Methods:Patients scheduled for IASI first met and interacted with the medical clown. During the procedure, the rheumatologist and the medical clown worked in parallel to create distraction. NO was administered. The patient, parent, physician, medical clown and nurse completed a visual analog scale (VAS ‐ (0–10) for pain. Change in heart rate (HR) ≥15% was recorded to examine physiologic response to pain and stress.Results:46 procedures were performed in 32 children: 23 girls, 9 boys, with a mean age of 10.87 ± 3.58 yrs. The median VAS pain score for the patients, parents, physicians, medical clown and nurses was 2, 2, 1, 1, and 1, respectively. 5 patients had increased HR, and experienced increased pain. In our previous study using only NO, the median pain score was 3.Conclusion:Active participation of a medical clown during IASI with NO for JIA further decreasing pain, stress, and induces a pleasant patient experience.
A114: Methylprednisolone‐Induced Inhibition of miR‐155 Expression Increases SOCS1‐Driven Suppression of Cytokine Signaling
Authors: Davis Trevor E. , Kis‐Toth Katalin , Tsokos George C. 
Published: March 2014

Background/Purpose:MicroRNA (miRNA, miR) are short RNA species (20–23 nt) that act post‐transcriptionally modulating messenger RNA (mRNA) translation or stability. They control many biological processes including cell differentiation and homeostasis. Abnormal levels of miRNA have been implicated in cancers and autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Steroids are first line anti‐inflammatory medications that act through transcriptional or posttranscriptional gene regulation. In multiple instances steroids cause mRNA destabilization indicating a potential role for miRNA.Previously, using high‐throughput microarray analysis, we found that methylprednisolone (MP) decreased miR‐155 expression in CD4+ T cells in vitro. miR‐155 is highly expressed in immune cells and influential in cell differentiation. This influence may in part be mediated through suppression of cytokine signaling 1 (SOCS1), a known target of miR‐155. SOCS1 inhibits multiple JAK/STAT pathways, which may inhibit cell proliferation and differentiation. Steroids have also been shown to inhibit proliferation, differentiation and the JAK/STAT pathways. Steroids through blocking the IL‐12/STAT4 pathway inhibit Th1 differentiation. This pathway is in part controlled by SOCS1, which should be under the control of miR‐155. Following our previous work here we explore the potential mechanism of action of miR‐155 during MP treatment of T cells.Methods:Total or naive CD4+ T cells were isolated from peripheral blood of healthy donors and activated by anti‐CD3/anti‐CD28 antibodies for up to 5 days with or without Th1 polarizing conditions (10 nM IL‐12 and 5 mM anti‐IL‐4 neutralizing antibody) and with or without exposure to 10−6 M of methylprednisolone. Some cells were first transfected with mimic miR‐155, control mimic miR, anti‐miR‐155, or control anti‐miR by electroporation. Effects on miR‐155, SOCS1, STAT phosphorylation, IFNg production and Th1 differentiation were monitored using flow cytometry, RNA quantification by PCR, and protein quantification by ELISA or western blot analysis.Results:Activated T cells treated with MP decrease miR‐155 expression and increase SOCS1 expression. In turn, SOCS1 decreases JAK/STAT signaling and inhibits response to cytokines, notably IL‐12, resulting in decreased IFNg production by activated T cells.Conclusion:We found that the anti‐inflammatory effects of MP, at least in part, act through decreasing miR‐155 in T cells by inhibiting JAK/STAT signaling and cytokine production through modulating SOCS1 expression. Based on our findings we propose that miR‐155 inhibition could be utilized to suppress inflammation without the myriad of side effects currently inherent in chronic steroid therapy.