Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Do the provisional PRINTO Enthesitis/Spondylitis-Related JIA criteria capture youth with axial spondyloarthritis?

Background: The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria amongst youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.

Prologue: Spondyloarthritis Unmet Research Needs Conference IV.

The Spondylitis Association of America (SAA) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) convened a conference on the campus of the National Institutes of Health (NIH) on September 28 and 29, 2023, to identify unmet needs in spondyloarthritis (SpA) research. The conference featured presentations by experts in areas of disease endotypes, pain, innovative imaging in SpA, health disparities in rheumatic diseases, and therapeutics. Members of the conference planning committee moderated the sessions and led the development of manuscripts summarizing recommendations to address unmet research needs.

Classification Criteria for Axial Disease in Youth With Juvenile Spondyloarthritis.

Objective: The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA).

Methods: This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort.

Results: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected.

Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis.

Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform.

VEGF Secretion Drives Bone Formation in Classical MAP2K1+ Melorheostosis.

Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most patients have somatic, mosaic mutations in MAP2K1 (encoding the MEK1 protein) in osteoblasts and overlying skin. As with most rare bone diseases, lack of affected tissue has limited the opportunity to understand how the mutation results in excess bone formation.

Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

Objective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.

Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA.

Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.

Objective: We undertook this study to examine the functional basis for epistasis between endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 in experimental spondyloarthritis (SpA).

Methods: ERAP1-knockout rats were created using genome editing and bred with HLA-B27/human β -microglobulin-transgenic (HLA-B27-Tg) rats and HLA-B7-Tg rats. The effects of ERAP1 deficiency on HLA allotypes were determined using immunoprecipitation and immunoblotting, flow cytometry, allogeneic T cell proliferation assays, and gene expression analyses.

Modified Juvenile Spondyloarthritis Disease Activity Index in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

Objective: To validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), and modified versions thereof, in a North American cohort of patients with enthesitis-related arthritis (ERA).

Methods: We utilized the Childhood Arthritis and Rheumatology Research Alliance Registry database ERA cohort to validate the JSpADA and its modifications (JSpADA6-no Schober, no C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR]; JSpADA7-no Schober; and JSpADA7-no CRP/ESR) using the Outcome Measures in Rheumatology principles of face validity, discriminative validity, and responsiveness to change.

Results: There were 51 subjects (64 visits) with complete JSpADA data with a mean age of 13.

Acute cytokine treatment stimulates glucose uptake and glycolysis in human keratinocytes.

During inflammation, cellular glucose uptake and glycolysis are upregulated to meet an increased energy demand. For example, keratinocyte glycolysis is essential for progression of psoriasis. Therefore, understanding the regulation of glucose metabolism in keratinocytes is of importance.

Fibroblasts from Patients with Melorheostosis Promote Angiogenesis in Healthy Endothelial Cells through Secreted Factors.

Melorheostosis is a rare sclerosing bone disease with associated vascular abnormalities in skin and bone, which is caused by somatic mosaic single nucleotide variations in the MAP2K1 gene, which encodes MAPK/extracellular signal‒regulated kinase (ERK) kinase 1. However, disease pathogenesis is poorly understood. Using patient-derived cells, we found that affected skin fibroblasts carrying the single nucleotide variations have increased activation of ERK1/2, which results in increased expression and secretion of proangiogenic factors, including VEGF.

Evenings with Molly: Adult Couples' Use of MDMA for Relationship Enhancement.

Within the modern resurgence of psychedelics as medicinal agents for a range of conditions, the story of MDMA (Ecstasy, Molly) has been re-narrated from a dangerous street drug to a breakthrough mental health therapy. Even still, the story of MDMA remains incomplete within a binary discourse of deviant recreational use versus psychotherapeutic-medical use. The present research aimed to uncover an emerging model of MDMA use grounded in the experiences of adult couples using MDMA privately and in the context of their committed relationships.

Cutaneous Kaposi's sarcoma in an HIV-negative patient with Crohn's disease on thiopurine immunosuppression.

We present the rare case of a 61-year-old man with Crohn's disease who developed a cutaneous Kaposi's sarcoma in the setting of long-term treatment with 6-mercaptopurine. Deciding on the best course of management provided a clinical challenge in an 'evidence-light' area. Relevant case reports and guidelines were reviewed.

Recent Updates in Juvenile Spondyloarthritis.

Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint involvement is usually asymmetric.

Consensus-driven conceptual development of a standardized whole body-MRI scoring system for assessment of disease activity in juvenile idiopathic arthritis: MRI in JIA OMERACT working group.

Objectives: Whole body-MRI is helpful in directing diagnostic and treatment approaches, and as a research outcome measure. We describe our initial consensus-driven phase towards developing a whole body-MRI scoring system for juvenile idiopathic arthritis.

Methods: An iterative approach using three rounds of anonymous Delphi surveys followed by a consensus meeting was used to draft the structure of the whole body-MRI scoring system, including the relevant anatomic joints and entheses for assessment, diagnostic item selection, definition and grading, and selection of appropriate MRI planes and sequences.

JAK1: Number one in the family; number one in inflammation?

Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine.