bluuebunny/crossref_metadata_2025_split huggingface dataset:
A93: Childhood Granulomatosis With Polyangiitis: Standardized Disease Assessment in 6 Czech Children
Authors: Böhm Marek , Nemcová Dana , Dallos Tomáš , Lád Václav , Suláková Terezie , Jancová Eva , Dolezalová Pavla 
Published: March 2014

Background/Purpose:Granulomatosis with polyangiitis is a rare primary systemic vasculitis affecting small blood vessels with predilection for the respiratory tract and kidneys. We describe clinical outcome of a small patient cohort as captured by the recently developed tools the Paediatric Vasculitis Activity Score (PVAS) and the Paediatric Vasculitis Damage Index (PVDI).Methods:A retrospective and prospective analysis of data gathered from 2006 to 2013 on patients fulfilling the EULAR/PRINTO/PRES criteria for GPA. Disease activity and damage items have been systematically recorded, data from the time of diagnosis and from the last follow‐up (F/U) are presented.Results:Characteristics of the 6 girls identified are summarized in the . The median F/U was 4 years. Disease manifestations were recorded under PVAS and PVDI sections with 6/9 and 8/10 systems affected with active disease or damage, respectively. General, ENT and pulmonary manifestations were observed in 4/6 patients. Nephritis developed in 2/6 patients. Cumulative damage was noted in all cases with ENT region most commonly affected. Persistent remission was achieved in one case with limited disease, in the other one subglottic stenosis caused an episode of airway obstruction and cerebral ischemia leading to apalic syndrome and later to death. Clinical inactivity on treatment was achieved in 2 girls.
Patient characteristics

Patient
1
2
3
4
5
6

Age at onset (years)
14
14
13
12
15
14

F/U (years)
5
2
5
5
3
0.2

ANCA
Atypical IF
c‐ANCA
p‐ANCA
Atypical IF
c‐ANCA
c‐ANCA

Treatment
CS, CP, MMF
CS, MTX
CS, MTX
CS, MTX, CP, AZA
CS, CP, MMF, RTX
CS, CP, RTX

PVAS category (section score)
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U

General
0
0
3
0
1
0
0
0
3
0
2
N/A

Cutaneous
0
0
0
0
0
0
0
0
3
0
5
N/A

Mucous memb./Eyes
0
0
0
0
6
0
2
0
0
0
0
N/A

ENT
0
0
6
0
0
0
6
0
4
0
6
N/A

Chest
3
0
0
0
0
0
6
0
6
0
6
N/A

Renal
12
4
0
0
0
0
0
0
12
0
0
N/A

PVAS total
15
4
9
0
7
0
14
0
28
0
19
N/A

PVDI category (section score)
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U
Onset
F/U

Musculoskeletal
0
0
0
0
0
0
0
0
0
2
0
N/A

Skin/Mucous memb.
0
0
0
0
0
0
0
1
0
0
1
N/A

Ocular
0
0
0
0
0
1
0
1
0
0
0
N/A

ENT
0
0
0
3
0
1
0
2
0
1
1
N/A

Chest
0
0
0
0
0
0
0
3
0
1
1
N/A

Renal
0
1
0
0
0
0
0
0
0
1
0
N/A

Nervous system
0
0
0
0
0
0
0
2
0
0
0
N/A

Other
0
1
0
1
0
0
0
3
0
0
1
N/A

PVDI total
0
2
0
4
0
2
0
12
0
5
4
N/A

F/U–follow‐up, N/A‐non–available, CS‐Corticosteroids, CP‐Cyclophosphamide, MTX‐Methotrexate, MMFMycophenolate mofetil, AZA‐Azathioprine, RTX‐RituximabConclusion:This small series of patients illustrates a variety of GPA outcomes. A standardized scoring of disease activity and damage enables systematic patient F/U and drives appropriate treatment decision‐making.
A103: Childhood Onset Takayasu Arteritis—Experience From a Tertiary Care Centre in South India
Authors: Kumar Sathish , Goel Ruchika , Danda Debashish , Surin Ajith Kumar , Bacon Paul A 
Published: March 2014

Background/Purpose:Takayasu Arteritis (TA) is a chronic granulomatous vasculitis of autoimmune etiology characterized by narrowing of aorta and its main branches. It is one of the rarest diseases but the third common cause of vasculitis in pediatric age group. Mortality in juvenile onset TA has been reported to range from 8% to 35%. The outcome of disease has improved recently with interdisciplinary treatment including immunosuppressants and cardiovascular interventional procedures. We aimed to study the clinical features, angiographic findings and outcome of children with TA referred to a single centre in South India over a 9 year period.Methods:Records of TA patients, with symptom onset prior to 16 years of age were studied. Disease Extent Index‐Takayasu (DEI.TAK), Indian Takayasu Arteritis Score 2010, and Takayasu Arteritis Damage Score (TADS) were calculated retrospectively using clinical information in electronic records. Cumulative incidence of sustained remission was estimated using Kaplan Meir curveResults:Forty patients with childhood onset TA with median age of onset of 12.5 (range 1–16) years presented at a median diagnostic delay of 11.3 (range 1–60) months. Commonest presenting features were hypertension, headache, malaise and fever. Pulse‐less disease was observed in 25 (62.5%) cases. Majority (n = 28) had active disease with raised inflammatory markers, high baseline DEI.TAK score of 10 (3–24) and high median TADS of 7 (3–14).Of the 34 patients, followed up for 21.5 (range 3–192) months, remission was attained in 30, however cumulative sustained remission was achieved in only 29% of them at 5 years. Median period of sustained remission was 22.5 months (95% CI 17.1–26.8). New areas of vessel involvement were observed in 13 patients. Disease progression was arrested in majority (n= 20) with aggressive medical management and endovascular intervention. All 11 patients with an increment in TADS of ≥4 units during follow up had persistently active or relapsing disease. There was single case with fatality.Conclusion:Corticosteroids and immunosuppressive therapy were effective in the control of disease activity. Progression of damage was associated with persistent inflammation. Continued surveillance by clinical instruments and imaging is warranted.
A117: Demonstration of Antibodies to Multiple Citrullinated Epitopes in the Sera of Patients With Juvenile Idiopathic Arthritis
Authors: Feller Lance , Gilliam Brooke , Cleland Esperanza , Syed Reema H. , Pepmueller Peri H. , Moore Terry L. 
Published: March 2014

Background/Purpose:IgG anti‐cyclic citrullinated peptide (anti‐CCP) antibodies have been identified in the sera of juvenile idiopathic arthritis (JIA) patients and have been associated with more destructive disease. The identity of the target proteins of the citrullinated modification has remained elusive. We attempted to determine the prevalence and significance of different citrullinated epitopes.Methods:We evaluated serum from 96 patients with various subtypes of JIA for the presence of antideiminated (citrullinated) fibrinogen, anti‐citrullinated α‐enolase, anti‐citrullinated and native type II collagen, and anti‐vimentin (vim1–16 and vim 59–74) antibodies by enzyme‐linked immunosorbent assays. We correlated the presence of the antibodies with anti‐CCP and rheumatoid factor (RF) isotypes, erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP) levels.Results:31 JIA patients (32%) demonstrated reactivity to anti‐citrullinated fibrinogen, 23 (24%) to anti‐citrullinated type II collagen, 10 (10.5%) to anticitrullinated vimentin I‐16, 9 (9%) to anti‐citrullinated α‐enolase, and 7 (7.4%) to anti‐citrullinated vimentin 59–74 antibodies. One IgM RF positive JIA patient was positive for all 6 of the citrullinated autobodies assayed. The reactivity was higher in those JIA patients positive for IgM RF and IgG/IgM anti‐CCP antibodies.Conclusion:The study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with JIA. A higher percentage of antibodies reacted with citrullinated fibrinogen and citrullinated type II collagen. The more widespread the positivity correlates with more severe disease.
A129: Unlike Fibroblast‐like Synoviocytes from Oligoarticular Juvenile Idiopathic Arthritis, Fibroblast‐like Synoviocytes From Polyarticular Subtype Do Not Display a Chondrocyte Phenotype
Authors: Brescia AnneMarie C. , Simonds Megan , McCahan Suzanne , Fawcett Paul T. , Rose Carlos D. 
Published: March 2014

Background/Purpose:Condylar bony hypertrophy is functionally detrimental for children with JIA. Through gene expression profiling, we have identified dysregulated TGFb‐signaling when fibroblast‐like synoviocytes (FLS) from persistent oligoarticular JIA was compared to controls (heatmap). JIA FLS have a chondrocyte phenotype and may contribute to bony hypertrophy. In the current work, we have expanded the study to determine if FLS from extended oligoarticular (ext) and polyarticular (poly) subtypes also display a chondrocyte phenotype.Methods:Synovial fluid was obtained from our IRB‐approved repository. Appropriate samples from steroid‐naïve knee joints were identified by chart review and JIA subtype classification. Control samples were obtained from remnant synovial fluid/tissue obtained from orthopedic procedures performed on non‐arthritic joints. Both ext patients were on naprosyn and the first was also on methotrexate (mtx). Both poly patients were taking mtx and the first one was also taking naprosyn. Synovial fluid/tissue was plated in 6‐well plates with 15% FBS DMEM media and passaged 3–6 times to obtain a pure sample of FLS. We examined secreted proteins in the cell culture supernatants from JIA and control FLS using western blot and ELISA.Results:FLS from ext (O) secrete increased amounts of BMP4, BMP2, aggrecan, collagen II and COMP when compared to both FLS from controls (C) and from poly (P) (western blot). By ELISA, the ext samples (Oligo) secreted more BMP4 protein than the controls (Ctrl) (p = 0.012) and the poly (Poly) (p < 0.001). COMP was significantly more highly secreted by the ext than the controls (p = 0.038) and the poly (p < 0.001).
imageConclusion:Characterization of proteins expressed in cell culture media supernatants reveals that JIA FLS from oligoarticular subtype, either persistent or ext, but not from poly subtype, secrete chondrocyte differentiation markers. The difference more likely is related to differences in underlying disease pathogenesis between the subtypes rather than a medication effect since ¾ JIA patients were on mtx and no patients were on biologic agents at the time the synovial fluid was obtained. These characteristics may have implications for endochondral bone formation and local growth disturbances that are more prominent in oligoarticular than in poly JIA.
A141: Active Engagement of Teens with Juvenile Idiopathic Arthritis in Medical Education: What Do They Think Their Contribution Might Be?
Authors: Morin Marie‐Paule , Schneider Rayfel , Martimianakis Tina , Bowen Francois , Mylopoulos Maria 
Published: March 2014

Background/Purpose:The unique expertise and contributions to teaching of patients with chronic diseases is increasingly recognized and valued in medical education. Specifically in rheumatology, patient educators (also referred as patients partners) programs have been developed and shown to be effective for MSK exam teaching. To our knowledge, this educational strategy has never been adapted to pediatrics. We believe adolescents with juvenile idiopathic arthritis (JIA) might benefit from participation in such educational programs. Since little is known about how teens with JIA could actively be engaged in medical education, the main aim of the study was to explore and develop a detailed understanding of their perspective about potential contributions as patient educators.Methods:Using a qualitative approach, nineteen individual semi‐structured interviews were conducted with adolescents diagnosed with JIA. A purposeful critical case sampling was realized and participants were recruited at two tertiary pediatric hospitals. Consistent with qualitative research analysis, interviews were conducted until theme saturation. A thematic analysis of the transcripts was achieved using a constant comparative approach. In order to facilitate the data analysis, NVivo qualitative research software was utilized.Results:Motivational factors for teens' involvement and main barriers for engagement in patient partners programs were identified. Beyond teaching components of the pediatric musculoskeletal exam, adolescents brought to light other competencies, such as teaching of communication skills, which they valued as important elements to incorporate in the educational program. They also recognized their unique form of knowledge, referred as experiential knowledge, and expressed how it may complement the trainees' biomedical knowledge.Conclusion:Our work demonstrates that adolescents with juvenile idiopathic arthritis express a strong desire to be engaged as patient educators, manifest a clear understanding of what their potential contributions to the teaching might be and vocalize their desire to share with trainees their unique experiential knowledge. This study represents the first step toward the development of patient‐centered arthritis educational programs actively and effectively involving teens with JIA as teachers in medical education.
A143: Barriers to Referral to Pediatric Rheumatology among General Pediatricians in the Upper Midwest
Authors: Correll Colleen K. , Spector Logan G. , Zhang Lei , Binstadt Bryce A. , Vehe Richard K. 
Published: March 2014

Background/Purpose:Access to pediatric rheumatology (PR) care is limited. An average of 28 fellows graduate from PR training programs annually, and there are 224 board‐certified pediatric rheumatologists in the United States. Eleven states have no pediatric rheumatologist and 24 states have two or fewer. Furthermore, the mean distance to a certified pediatric rheumatologist is 60 miles. The impact that limited access to PR has on general pediatricians has not been studied.Methods:A web‐based survey was emailed to general pediatricians practicing in Minnesota (MN), North Dakota (ND), and South Dakota (SD). The email databases were obtained from the MN and ND state medical licensing boards and from the SD chapter of the American Academy of Pediatrics. The goal of the survey was to define barriers to access to PR care and the consequences of limited access. Basic descriptive analysis was performed and responses were summarized.Results:The overall response rate was 15.3% (93/609). Responders were younger than non‐responders (mean age 48 yo versus 53 yo, p = 0.0006) and had been in practice a shorter period of time (mean 22 y versus 27 y, p = 0.0051). Forty percent (37/92) of the clinics were urban, 40% (37/92) suburban, and 20% (18/92) rural. Twenty‐nine percent (27/92) of respondents' clinics were at least two hours by car from a pediatric rheumatologist, and 9% (8/92) were more than 6 hours away. Ninety‐two percent (85/92) had referred a patient to PR at least once, but 89% (83/93) had experienced a situation at least once in which they considered a referral to PR but ultimately did not. Reasons for not referring varied. When asked, “In cases in which you considered a PR referral but did not refer a patient to a pediatric rheumatologist, please indicate your reasons for doing so. (Select all that apply),” many had referred to other subspecialists instead: 29% (24/83) to pediatric infectious disease, 20% (17/83) to adult rheumatology, and 12% (10/83) to pediatric orthopedics, while 34% (28/83) managed the patient themselves. Although not a pre‐specified choice in the survey, 9% (3/32) of pediatricians added wait‐time as the reason for not referring to PR. Thirty‐five percent (32/60) had referred a pediatric patient to an adult rheumatologist, most commonly for distance (47%), while physician preference was never selected as a reason.Conclusion:Pediatricians often refer children with possible rheumatic disease to specialists other than PR due to reasons of distance and wait‐time. Referral to adult rheumatologists occurs, but not based on pediatrician preference. These findings suggest that the PR workforce is inadequate to meet demand, at least in the Upper Midwest. Interventions are needed to improve access to care in PR.
A147: Engaging Patients and Families in the Pediatric Rheumatology Care and Outcomes Improvement Network
Authors: DeWitt Esi Morgan , Fricke Kay , Bergheger Lindsey , Griffin Nancy , Laxer Ronald M. , Jones Karla B. , Gottlieb Beth S. , Taylor Janalee , Mims Catherine C. , Robbins Lisa M. , Lovell Daniel J. , Noonan Laura 
Published: March 2014

Background/Purpose:The Pediatric Rheumatology Care and Outcomes Improvement Network (PR‐COIN) is a multi‐site quality improvement learning network that aims to improve outcomes for children and adolescents with juvenile idiopathic arthritis. In addition to addressing variations in care practices, PR‐COIN has incorporated guidance and tangible contributions from patients and families to its national organizational and governance structure to drive improvement in JIA outcomes. PR‐COIN aims to grow this initiative to bring care providers, patients and family members together as co‐producers in improving care and outcomes.Methods:Various methods supporting family engagement are employed. PR‐COIN teams invite interested parents at their respective clinical sites to bring the parent perspective and priorities into local improvement work. To assure a reliable structure, a parent engagement specialist was employed to develop a platform for bringing families and care providers together. National conference calls facilitated by the specialist establish relationships across site representatives and begin goal setting for this group. Parents contribute to shared decision making project efforts. PR‐COIN's public website encourages family awareness and involvement in the network's improvement efforts.Results:7 of 11 sites have welcomed parent contributions to their improvement efforts (e.g. focus groups, advisory activities, etc.). Parents and patients have participated in PR‐COIN's biannual conferences, sharing the family perspective and needs associated with JIA care. One parent brings a unique background and skillset as both a pediatrician with QI experience and the parent of a teen with JIA. This distinction prompted appointment to PR‐COIN's governing body. We incorporate patient perspectives into clinic process improvements (e.g. pain management, optimizing physical functioning), enhanced and refined PR‐COIN's Shared Decision Making tool, supporting stronger, more informed medication choice, and are developing best practices optimizing use of these materials in clinic. Finally our engaged parents are encouraging others to contribute ideas supportive of PR‐COIN structure, growth, strategy and improvement efforts.Conclusion:Parents and patients bring unique talents, insight and skills to the operation of quality improvement networks making efforts more relevant to the self‐identified needs of JIA families.
A155: Development of an Intensive Interdisciplinary Pediatric Pain Rehabilitation Program: Improving Pain, Functioning, and Psychological Outcomes
Authors: Hoffart Cara , Anderson Rawni , Wallace Dustin 
Published: March 2014

Background/Purpose:We examined functional, psychological, and pain‐related outcomes among children with amplified pain syndromes completing an intensive interdisciplinary pediatric pain rehabilitation program. We hypothesized that baseline psychological measures and disability would predict a longer treatment course.Methods:This outpatient program provides 5–6 hours of daily intensive physical and occupational therapy in addition to yoga, self‐regulation, and behavioral health intervention. All pain medications are discontinued, and no invasive therapeutic procedures are utilized. 30 patients (26 female) aged 11–18 with chronic musculoskeletal pain completed Functional Disability Inventory, 100mm Visual Analog Scale, PROMIS Anxiety, Depression, and PRCQ‐catastrophizing at baseline and the end of each week; 22 have completed a one‐month follow‐up, and 6 completed six‐month follow‐up. The mean program duration was 3.7 (SD 0.91) weeks, determined by achievement of functional goals. Analyses were conducted with SPSS and supplemented with hierarchical linear modeling (HLM7) for time‐series analyses of pain and functioning.Results:There is linear improvement in parent‐reported FDI (25.2 to 7.3, P < .001) and patient‐reported FDI (27.5 to 13.9, P < .001) between baseline and program end. Patient‐reported function showed additional significant gains at 1 and 6‐month follow‐up with FDI of 7.2 and 2.8, respectively (P < .001). Patient‐reported pain did not consistently change during the program (P = .975); however, longitudinal patterns demonstrated significant decrease in pain between program end and follow‐up (P < .001). Pain is significantly affected by conversion symptoms, which are associated with higher levels of pain (P = .005) but did not affect the pattern of pain resolution. Patient reported anxiety and depression decline significantly (P = 0.004 and P = 0.001, respectively) as does patient catastrophizing following treatment (P = .001). Duration of treatment correlated with baseline functional disability (FDI r = .664; P = .001), and presence of conversion symptoms (r = .548; P = .008). imageConclusion:Children with amplified pain syndromes successfully restore and maintain function and improve pain without pharmacotherapy. Baseline functional disability and psychological factors correlate with treatment program duration. Prospective studies are warranted to determine long‐term efficacy and effectiveness of this interdisciplinary program.
A157: Macrophage Activation Syndrome‐like Illness Due to an Activating Mutation in NLRC4
Authors: Canna Scott , de Jesus Adriana Almeida , Deng Zuoming , Gouni Sushanth , Marrero Bernadette , Brooks Stephen , Dimattia Michael , Liu Yin , Huang Yan , Plass Nicole , Chapelle Dawn C. , Montealegre Gina , Benseler Susanne , Laxer Ronald M. , Goldbach‐Mansky Raphaela 
Published: March 2014

Background/Purpose:Macrophage Activation Syndrome (MAS) is a life‐threatening systemic inflammatory disorder of unknown etiology. While MAS has no known genetic basis, clinical similarity with a genetic disorder of impaired cytotoxicity known as primary Hemophagocytic Lymphohistiocytosis (HLH) has suggested shared pathogenesis. In contrast, other investigations have suggested innate immune dysregulation drives MAS.Methods:We performed detailed clinical, genetic, and immunologic evaluation of a patient with early onset, recurrent MAS‐like disease including whole exome sequencing and analyses of serum cytokines, whole blood transcription, and stimulated monocyte and macrophage responses. We subsequently tested the effects of a de novo mutation in transfection experiments with a monocytic cell line.Results:We identified a 7 year‐old female with recurrent episodes of fever, splenomegaly, transaminitis, pancytopenia, occasional evanescent rash, and massive hyperferritinemia since 6 months of age. Her Natural Killer cell function was normal, and she had no mutations in genes associated with HLH or hereditary periodic fever syndromes. Whole exome sequencing identified a de novo missense mutation in a highly conserved area in the nucleotide‐binding region of the inflammasome component NLRC4. Interleukin (IL)‐1b, Interferon a2, and particularly IL‐18 were elevated in the patient's peripheral blood even during clinical quiescence. The patient's monocytes produced more of a number of inflammatory cytokines in response to stimulation than controls, while monocyte‐derived macrophages specifically over‐produced IL‐1b and IL‐18. Transfection of THP1 monocytes with a plasmid bearing a mutant NLRC4 construct resulted in increased cell death and IL‐1b production versus a wild‐type plasmid. The patient showed short‐term clinical improvement and ability to wean steroids with recombinant IL‐1 receptor antagonist (IL‐1ra) therapy.Conclusion:While NLRP3 inflammasome hyperactivity has been implicated in the pathogenesis of a variety of autoinflammatory conditions, our data suggest that a mutation in the ADP binding domain of NLRC4 can result in MAS‐like disease. This mutation may destabilize NLRC4's auto‐inhibited conformation by altering ADP binding (), resulting in enhanced/spontaneous activation and pathogenic production of IL‐1b and IL‐18. NLRC4 hyperactivity represents a novel mechanism of MAS/HLH pathogenesis.