Left ventricular thrombus in the multisystem inflammatory syndrome in children associated with COVID-19.

A 3-year-old girl presenting with fever, mucocutaneous inflammation, and acute gastrointestinal symptoms met criteria for the multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). Echocardiography showed severely decreased left ventricular (LV) function with an apical mass. After treatment with intravenous (IV) immunoglobulin, IV steroids, anakinra, milrinone, and systemic anticoagulation, her LV function rapidly improved and the mass became increasingly mobile. Given the risk of systemic embolization, the mass was excised through left ventriculotomy and pathology confirmed a thrombus.

Emergent high fatality lung disease in systemic juvenile arthritis.

OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

An i2b2-based, generalizable, open source, self-scaling chronic disease registry.

OBJECTIVE: Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. MATERIALS AND METHODS: Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. RESULTS: The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. DISCUSSION: We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. CONCLUSIONS: The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.

Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma.

OBJECTIVE: Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. METHODS: A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. RESULTS: Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. CONCLUSION: Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS.