User-Centered Design to Develop Automated Short Message Service Messaging for Patient Support of Rheumatic Heart Disease Secondary Antibiotic Prophylaxis.

Background: The Active Community Case Management Platform is a cloud-based technology developed to facilitate rheumatic heart disease case management by health care providers. This study aimed to design and pilot an automated short message service (SMS) intervention to support secondary prophylaxis adherence.

Methods And Results: We developed a concise library of messages to support secondary antibiotic prophylaxis.

Development and User Testing of a Dynamic Tool for Rheumatic Heart Disease Management.

Objective: Most rheumatic heart disease (RHD) registries are static and centralized, collecting epidemiological and clinical data without providing tools to improve care. We developed a dynamic cloud-based RHD case management application with the goal of improving care for patients with RHD in Uganda.

Methods: The Active Community Case Management Tool (ACT) was designed to improve community-based case management for chronic disease, with RHD as the first test case.

Comparison of approaches to determine echocardiographic outcomes for children with latent rheumatic heart disease.

Background: Screening programmes using echocardiography offer opportunity for intervention through identification and treatment of early (latent) rheumatic heart disease (RHD). We aimed to compare two methods for classifying progression or regression of latent RHD: serial review method and blinded, side-by-side review.

Methods: A four-member expert panel reviewed 799 enrolment (in 2018) and completion (in 2020) echocardiograms from the GOAL Trial of latent RHD in Uganda to make consensus determination of normal, borderline RHD or definite RHD.

Definition and validation of serum biomarkers for optimal differentiation of hyperferritinaemic cytokine storm conditions in children: a retrospective cohort study.

Background: Cytokine storm syndromes are life-threatening complications that can occur in children with rheumatic conditions (macrophage activation syndrome [MAS]), inherited cytotoxicity defects (ie, primary haemophagocytic lymphohistiocytosis [HLH]), or as a result of infection or malignancies (ie, secondary HLH). To adequately steer treatment, an early and clear discrimination of these entities is essential. We aimed to define and validate serum biomarker profiles that can differentiate between primary HLH, secondary HLH (predominantly infection-associated), and MAS associated with systemic juvenile idiopathic arthritis (systemic JIA-MAS).

Diagnoses during the First Three Years of Life for Children with Prenatal Opioid Exposure and Neonatal Abstinence Syndrome Using a Large Maternal Infant Data Hub.

Purpose: The purpose of this study was to examine patterns of health and developmental outcomes in children with prenatal opioid exposure (POE) and neonatal abstinence syndrome (NAS) compared to children without exposure during the first three years of life.

Design And Methods: This was a secondary data analysis of the Maternal and Infant Data Hub (MIDH), a de-identified dataset originating from the Midwest region of the United States, consisting of newborn billing records and corresponding maternal and child electronic medical records. For these analyses, the repository included data on more than 20,000 children born between 2013 and 2019.

Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal TRIM8 as a mediator of IFN-γ hyper-responsiveness and risk for macrophage activation syndrome.

Objectives: Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening cytokine storm driven by interferon (IFN)-γ. SJIA monocytes display IFN-γ hyper-responsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte and bone marrow macrophage (BMM) polarisation phenotypes in SJIA including molecular features contributing to IFN response.

IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome.

Objectives: Systemic juvenile idiopathic arthritis (sJIA) is a childhood arthritis with features of autoinflammation and high risk of macrophage activation syndrome (MAS). IL-18 has been shown to have key roles in sJIA and MAS. We aimed to examine IL-18 levels in sJIA in relation to disease activity and history of MAS and other disease biomarkers namely S100 proteins and CXCL9.

Discovery of tear biomarkers in children with chronic non-infectious anterior uveitis: a pilot study.

Background: Biomarkers in easily obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. Aqueous humor has been studied for biomarkers, but is not routinely available. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor.

Brief Report: Novel UNC13D Intronic Variant Disrupting an NF-κB Enhancer in a Patient With Recurrent Macrophage Activation Syndrome and Systemic Juvenile Idiopathic Arthritis.

Objective: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (JIA) and has pathologic similarity to hemophagocytic lymphohistiocytosis (HLH). Intronic variants in UNC13D are found in patients with familial HLH type 3 (FHLH3), but the role of noncoding variants in MAS is unknown. The objective of this study was to identify deep intronic UNC13D variants in patients with MAS.

Urine S100 proteins as potential biomarkers of lupus nephritis activity.

Background: Improved, noninvasive biomarkers are needed to accurately detect lupus nephritis (LN) activity. The purpose of this study was to evaluate five S100 proteins (S100A4, S100A6, S100A8/9, and S100A12) in both serum and urine as potential biomarkers of global and renal system-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE).

Methods: In this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy control subjects using commercial enzyme-linked immunosorbent assays.

Proinflammatory Cytokine Environments Can Drive Interleukin-17 Overexpression by γ/δ T Cells in Systemic Juvenile Idiopathic Arthritis.

Objective: Systemic-onset juvenile idiopathic arthritis (JIA) is speculated to follow a biphasic course, with an initial systemic disease phase driven by innate immune mechanisms and interleukin-1β (IL-1β) as a key cytokine and a second chronic arthritic phase that may be dominated by adaptive immunity and cytokines such as IL-17A. Although a recent mouse model points to a critical role of IL-17-expressing γ/δ T cells in disease pathology, in humans, both the prevalence of IL-17 and the role of IL-17-producing cells are still unclear.

Methods: Serum samples from systemic JIA patients and healthy pediatric controls were analyzed for the levels of IL-17A and related cytokines.

Monocyte MicroRNA Expression in Active Systemic Juvenile Idiopathic Arthritis Implicates MicroRNA-125a-5p in Polarized Monocyte Phenotypes.

Objective: Systemic juvenile idiopathic arthritis (JIA) is an inflammatory disease of childhood in which cells of the monomyelocytoid lineage are thought to be key effector cells. Monocytes from patients with systemic JIA have a distinct phenotype, with features of both M1 and M2 alternative activation. MicroRNAs are critical regulators of monocyte polarization and function, but cellular microRNAs in systemic JIA have not been examined systematically.

Relationship of cell-free urine MicroRNA with lupus nephritis in children.

Background: MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of genes. The objective of this study was to investigate whether select urinary cell-free microRNA's may serve as biomarkers in children with active lupus nephritis (LN) and to assess their relationship to the recently identified combinatorial urine biomarkers, a.k.

Whole-Exome Sequencing Reveals Mutations in Genes Linked to Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome in Fatal Cases of H1N1 Influenza.

Background: Severe H1N1 influenza can be lethal in otherwise healthy individuals and can have features of reactive hemophagocytic lymphohistiocytosis (HLH). HLH is associated with mutations in lymphocyte cytolytic pathway genes, which have not been previously explored in H1N1 influenza.

Methods: Sixteen cases of fatal influenza A(H1N1) infection, 81% with histopathologic hemophagocytosis, were identified and analyzed for clinical and laboratory features of HLH, using modified HLH-2004 and macrophage activation syndrome (MAS) criteria.

Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis.

Objective: Macrophage activation syndrome (MAS), a life-threatening complication of systemic juvenile idiopathic arthritis (JIA), resembles familial hemophagocytic lymphohistiocytosis (HLH), a constellation of autosomal-recessive immune disorders resulting from deficiency in cytolytic pathway proteins. We undertook this study to test our hypothesis that MAS predisposition in systemic JIA could be attributed to rare gene sequence variants affecting the cytotolytic pathway.

Methods: Whole-exome sequencing was used in 14 patients with systemic JIA and MAS and in their parents to identify protein-altering single-nucleotide polymorphisms/indels in known HLH-associated genes.

Follistatin-like protein 1 and the ferritin/erythrocyte sedimentation rate ratio are potential biomarkers for dysregulated gene expression and macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Objective: Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS).

Methods: FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls.

Short-term stability study of RNA at room temperature.

The quality of RNA preserved in different stabilization matrices was investigated after 2 weeks of storage at room temperature. RNA samples in RNAstable (Biomatrica), GenTegra (IntegenX), and RNAshell (Imagene) were compared to RNA stored at -80°C (the current gold standard for RNA preservation) and with liquid or dried RNA stored at room temperature without additives in this multi-center study. One center prepared all of the RNA samples, and five participating laboratories applied the samples to the matrices and stored them for 2 weeks at room temperature.

The limited role of interferon-γ in systemic juvenile idiopathic arthritis cannot be explained by cellular hyporesponsiveness.

Objective: Systemic juvenile idiopathic arthritis (JIA) is an autoinflammatory syndrome in which the myelomonocytic lineage appears to play a pivotal role. Inflammatory macrophages are driven by interferon-γ (IFNγ), but studies have failed to demonstrate an IFN- induced gene signature in active systemic JIA. This study sought to characterize the status of an IFN-induced signature within affected tissue and to gauge the integrity of IFN signaling pathways within peripheral monocytes from patients with systemic JIA.

Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis.

Introduction: Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene-expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared with related conditions.

Methods: The 199 patients with JIA (23 sJIA and 176 non-sJIA) and 38 controls were studied.

Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis.

Objective: To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA prior to treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents.

Methods: Peripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis-related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF]-negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG-U133 Plus 2.

In vivo evidence that Sarcoptes scabiei (Acari: Sarcoptidae) is the source of molecules that modulate splenic gene expression.

The clinical signs of a Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae) infestation are initially delayed, which suggests that the mites can depress the immune/inflammatory response. The purpose of this study was to investigate the modulatory properties of scabies mites in vivo at the gene expression level in a secondary lymphoid organ that is involved in initiating an immune response to the parasite. We found that substances from scabies mites influenced the expression of mRNA for molecules that participate in the sequestering of lymphocytes in the periarteriolar lymphoid sheath, primary follicle, and marginal zone of the spleen.

Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome.

Objective: Systemic juvenile idiopathic arthritis (JIA) is frequently associated with the development of macrophage activation syndrome. This study was undertaken to better understand the relationship between systemic JIA and macrophage activation syndrome.

Methods: Gene expression profiles were examined in 17 patients with untreated new-onset systemic JIA, 5 of whom showed evidence of subclinical macrophage activation syndrome (of whom 2 eventually developed overt macrophage activation syndrome).

Association between lack of angiogenic response in muscle tissue and high expression of angiostatic ELR-negative CXC chemokines in patients with juvenile dermatomyositis: possible link to vasculopathy.

Objective: To investigate the relationship between the vasculopathy of juvenile dermatomyositis (juvenile DM) and the balance between the angiostatic ELR- and angiogenic ELR+ CXC chemokines in the muscle of patients with the disease.

Methods: The expression of 3 ELR- CXC chemokines (interferon-inducible protein 10 [IP-10], monokine induced by interferon-gamma, and interferon-inducible T cell alpha-chemoattractant) and 2 ELR+ CXC chemokines was quantitated in muscle biopsy samples from 7 patients with juvenile DM and 7 healthy children, by real-time polymerase chain reaction. The findings were correlated with various histopathologic features, with particular emphasis on the degree of vasculopathy.