Objective
There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the ...diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies.
Methods
Case‐based surveys were administered to CARRA members to identify prevailing treatments for new‐onset systemic JIA. A 2‐day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Followup surveys were employed to refine the plans and assess clinical acceptability.
Results
The initial case‐based survey identified significant variability among current treatment approaches for new‐onset systemic JIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed 4 consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The 4 treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra, or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of the CARRA membership.
Conclusion
Four standardized treatment plans were developed for new‐onset systemic JIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of systemic JIA.
Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA). In particular, diminished fecal ...abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified.
We obtained fecal specimens from 30 children with treatment-naïve enthesitis-related arthritis (ERA) and 19 healthy controls, as well as specimens from 11 adult patients with longstanding SpA and 10 adult healthy controls. All of the samples underwent sequencing of the 16S ribosomal DNA. A subset of the pediatric fecal samples was subjected to shotgun metagenomics sequencing.
ERA patients had decreased abundance of the anti-inflammatory F. prausnitzii A2-165 strain (41 ± 28% versus 54 ± 20% of all sequences matching F. prausnitzii, p = 0.084) and an increased abundance of the control F. prausnitzii L2/6 strain (28 ± 28% versus 15 ± 15%, p = 0.038). Similar trends were observed in adults with longstanding SpA (n = 11) and controls (n = 10). In contrast, the fecal abundance of Bacteroides fragilis was increased in ERA subjects (2.0 ± 4.0% versus 0.45 ± 0.7% of all sequences, p = 0.045), yet was diminished in adult subjects (0.2 ± % versus 1.0 ± % of all sequences, p = 0.106). Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects revealed diminished coverage of the butanoate pathway (abundance normalized to controls of 1 ± 0.48 versus 0.72 ± 0.33 in ERA, p = 0.037).
The anti-inflammatory F. prausnitzii A2-165 strain appears to be depleted in both pediatric and adult SpA. In contrast, B. fragilis may be depleted in adult disease yet abundant in pediatric SpA, suggesting developmental effects on the immune system.
Chronic musculoskeletal pain (CMP) is one of the main reasons for referral to a pediatric rheumatologist and is the third most common cause of chronic pain in children and adolescents. Causes of CMP ...include amplified musculoskeletal pain, benign limb pain of childhood, hypermobility, overuse syndromes, and back pain. CMP can negatively affect physical, social, academic, and psychological function so it is essential that clinicians know how to diagnose and treat these conditions. This article provides an overview of the epidemiology and impact of CMP, the steps in a comprehensive pain assessment, and the management of the most common CMPs.
Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent role for cohesin in the expression of genes that facilitate ...neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in mouse primary cortical neurons. Immediate early genes (IEGs) remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the IEGs
formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterized by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend on cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts.
Objective
Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin‐1 (IL‐1) and IL‐6 inhibitors appear to be effective treatments. Pulmonary ...arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients.
Methods
Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.
Results
The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL‐1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti–IL‐1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications.
Conclusion
PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.
MIS-C After ARDS Associated With SARS-CoV-2 Clouser, Katharine; Baer, Aryeh; Bhavsar, Sejal ...
The Pediatric infectious disease journal,
2020-November, 2020-11-00, 20201101, Letnik:
39, Številka:
11
Journal Article
Recenzirano
Odprti dostop
This is a case of an 11-year-old female who was admitted with respiratory failure, requiring intubation while testing positive for SARS-CoV-2. During her recovery, she had new onset fevers and ...uptrending inflammatory markers. After an evaluation of infectious causes, the diagnosis of MIS-C was made approximately 1 month after her initial symptoms.
Climate variability and its response to increasing greenhouse gases are important considerations for impacts and adaptation. Modeling studies commonly assess projected changes in variability in terms ...of changes in the variance of climate variables. Despite the distant and impactful covariations that climate variables can exhibit, the covariance response has received much less attention. Here, a novel ensemble framework is developed that facilitates a unified assessment of the response of the regional variances and covariances of a climate variable to imposed external forcings and their time of emergence from an unforced climate state.
Illustrating the framework, the response of variability and covariability of land and ocean temperatures is assessed in the Community Earth System Model Large Ensemble under historical and RCP8.5 forcing. The results reveal that land temperature variance emerges from its preindustrial state in the 1950s and, by the end of the twenty-first century, grows to 1.5 times its preindustrial level. Demonstrating the importance of covariances for variability projections, the covariance between land and ocean temperature is considerably enhanced by 2100, reaching 1.4 times its preindustrial estimate. The framework is also applied to assess changes in monthly temperature variability associated with the Arctic region and the Northern Hemisphere midlatitudes. Consistent with previous studies and coinciding with sea ice loss, Arctic temperature variance decreases in most months, emerging from its preindustrial state in the late twentieth century. Overall, these results demonstrate the utility of the framework in enabling a comprehensive assessment of variability and its response to external climate forcings.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To evaluate the proportion of children with juvenile idiopathic arthritis (JIA) who met criteria for comorbid juvenile fibromyalgia (FM) using the Pain and Symptom Assessment Tool (PSAT), ...and to identify clinical and demographic differences among JIA patients with and without juvenile FM.
Methods
Patients ages 11–17 years with JIA were recruited from 4 North American pediatric rheumatology centers. Each patient completed the PSAT. Additional clinical and disease activity measures included pain visual analog scale, patient global assessment of disease activity (PtGA) and physician global assessment of disease activity (PhGA), the Functional Disability Inventory (FDI), and the Pain Catastrophizing Scale in children.
Results
Of 129 patients, 11 met criteria for juvenile FM. FDI scores were markedly higher in patients who tested positive for juvenile FM, with a mean of 24.8 compared to 6.9 in patients without juvenile FM (P < 0.001). Pain catastrophizing scores were also significantly higher, by ~14 points, in patients with juvenile FM. There was a significant tendency for patients to give higher disease activity scores than physicians, which was more marked among patients with juvenile FM. In patients with juvenile FM, PtGA scores exceeded PhGA scores by a mean of 3.7, compared to a mean of 0.7 among patients without juvenile FM (P < 0.001).
Conclusion
A minority of JIA patients (8.5%) met criteria for juvenile FM. This group demonstrated markedly more functional impairment. PtGA scores were strikingly higher than PhGA scores among patients with JIA who met juvenile FM criteria, suggesting that providers might consider a more expansive approach to chronic pain and non‐musculoskeletal symptom assessment and treatment in JIA patients.
Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with ...spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.
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