Bringing Best Practice Care to Children with Pediatric Rheumatic Diseases

The PR-COIN (Pediatric Rheumatology Care and Outcomes Improvement Network) is dedicated to improving remission rates in children with juvenile idiopathic arthritis, and focuses on identifying and spreading best practice care amongst the 18 participating hospitals. Esi Morgan, MD, MSCE, working with the Learning Networks Program of the James M. Anderson Center for Health Systems Excellence, has led PR-COIN and, demonstrated improvement in processes of care delivery and patient outcomes; more children now have inactive disease or lower disease activity thanks to the work of PR-COIN. The PR-COIN cohort consists of over 4,700 children with juvenile idiopathic arthritis (JIA). Further, PR-COIN expanded and now includes children with lupus.

Data from patient visits are entered into a shared registry and used for clinical care, quality improvement and research. Network teams review data and then share progress during monthly webinars. Cincinnati Children's care providers also share advance quality improvement initiatives with other PR-COIN teams during semiannual two-day learning sessions. Parent volunteers are very involved as co-producers in the PR-COIN improvement work, interacting closely with the rheumatology provider teams. PR-COIN has focused on self-management assessment and interventions during 2015-2016 including creating a new version of a “Helping Hands” book of materials for newly diagnosed families in partnership with parents, funded by AHRQ (PI Carole Lannon). In the past year, PR-COIN has transitioned to a new registry platform, and has partnered with Epic Corporation to develop standardized medical records template to enable a “data-in-once” strategy to allow clinical data to be efficiently re-purposed for quality improvement and research in the PR-COIN registry. The network has received grant funding (Current Opinion in Rheumatology) from AHRQ, PCORI, Pfizer and Novartis.

Research Flow Cytometry Core Provides Novel Technologies for Cincinnati Children's Investigators

Directed by Sherry Thornton, PhD, the Division of Rheumatology houses the Research Flow Cytometry Core (RFCC) and provides state-of-the-art equipment to over 140 research investigators to perform single cell analysis. In the last year, funding from the Research Foundation enabled the core to increase the capacity for highly multi-parametric flow cytometry that provides capability for more detailed cellular analysis. Furthermore, researchers developed an educational program for this technology, and offered it to our users. Three NIH center grants supports the core, the Cincinnati Rheumatic Disease Core Center (now funded for years 16-20 of the grant), the Center for Excellence in Molecular Hematology and the Digestive Health Center. To enhance the research of Cincinnati Children's investigators, the RFCC works closely with other core facilities-collaborations with Cincinnati Children's Gene Expression Core and its DNA Sequencing and Genotyping Core have improved the workflow of combining cell sorting and single cell analysis for RNA sequencing. Such innovative activities of the RFCC were presented at a workshop on "Bridging Flow Cytometry with New Technologies" at the 2015 Annual Meeting of the International Society for the Advancement of Cytometry in Glasgow, Scotland.

MicroRNA may serve as key regulators of inflammation in systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder of childhood associated with potentially destructive arthritis and high risk of life-threatening complications. MicroRNA serve as key epigenetic regulators during inflammation, “fine-tuning” cellular responses including monocyte activation and polarization. In systemic JIA, innate immune cells including monocytes are thought to be key effectors, but the function and regulation of these cells remains largely unknown. In this study, Dr. Grant Schulert, and colleagues, identified significantly altered microRNA expression profiles in monocytes from children with active systemic JIA, including elevated miR-125a-5p which correlated with clinical and laboratory features of inflammation. Additionally, in vitro manipulation of miR-125a-5p levels altered polarized monocyte phenotypes, with overexpression enhancing features observed in systemic JIA. Together, these findings suggest that microRNA alterations impact the phenotype of monocytes in systemic JIA, and could represent novel targets for immune regulation.

Imaging Research in Neuro-Psychiatric Lupus

Supported by funding from the Lupus Foundation of America, collaborative research by Dr. Mark DiFrancesco, the Division of Radiology, and Dr. Hermine Brunner, the Division of Rheumatology, used advanced magnetic resonance imaging techniques to delineate the effects of lupus on the brain of children.

The team of researchers showed that impaired cognition in children with lupus associates with a significant decrease in global streamline density, depicted by diffusion tensor imaging (p = 0.002). This finding suggests that neuropsychiatric lupus associates with a breakdown of the structural neuronal network. Further, using arterial spin labeling interleaved with diffusion-weighted imaging, Drs. DiFrancesco and Brunner developed a new imaging method to non-invasively depict the integrity of the blood-brain barrier.

In a pilot study, researchers found children with lupus, and clinically normal cognitive ability, experienced a significant regional “leakiness” of their blood-brain barrier, thought to be the basis for pathological antibodies and inflammatory cytokines to reach the brain tissue resulting in degenerative changes to the brain. Taken together, changes in streamline density and blood-brain-barrier function measurement appear to be excellent candidates to serve as imaging biomarkers for neuropsychiatric lupus therapies.