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Matrix metalloproteinase-9 (MMP-9) is abundantly expressed by infiltrating leukocytes and contributes to the pathogenesis of hepatic ischemia and reperfusion injury (IRI). On the other hand, its physiological inhibitor, the tissue inhibitor of metalloproteinases-1 (TIMP-1), is available in insufficient levels to hamper MMP-9 activity during hepatic IRI. In this study, we generated recombinant adeno-associated virus type 8 vectors (rAAV8) encoding mouse TIMP-1 driven by a liver-specific thyroxine-binding globulin promoter as a strategy to increase the levels of TIMP-1 during liver IRI. Biodistribution analysis confirmed selective overexpression of TIMP-1 in livers of rAAV8-TIMP-1 vector treated C57BL/6 mice. rAAV8-TIMP-1-treated mice showed reduced MMP-9 activity, diminished leukocyte trafficking and activation, lowered transaminase levels, and improved histology after liver IRI. Moreover, the rAAV8-TIMP-1 vector therapy enhanced significantly the 7-day survival rate of TIMP-1 mice subjected to hepatic IRI. Neutrophils are the first cells recruited to inflamed tissues and, once activated, they release nuclear DNA-forming web-like structures, known as neutrophil extracellular traps. It was found that TIMP-1 has the ability to reduce formation of neutrophil extracellular traps and, consequently, limit the impact of neutrophil extracellular trap-mediated cytotoxicity in hepatic IRI. This is the first report demonstrating that TIMP-1 overexpression is hepatoprotective in ischemia and reperfusion injury. Hence, TIMP-1 may represent a promising molecule for drug development to treat liver IRI.

Objectives: The aim of the study was to evaluate feasibility and utility of an electronic health record (EHR) activity to assess transitional readiness, deliver services to meet individual needs, and to track patient progress. Methods: We developed a Transition EHR activity (TEA) to track patients through a standardized process where transition readiness is annually assessed and services distributed based on need. The process assesses transition skills starting at age 12 years and sets goals through shared decision-making, delivers resources according to need, reviews patients’ personal medical histories, and documents healthcare transfer to adult gastroenterology. We piloted TEA among patients with inflammatory bowel disease (IBD) ages ≥12 years. Distribution to patients was measured and tolerability assessed via patient self-report evaluations. Results: Since launch, TEA has been distributed to all eligible patients (N = 53) with a median age of 16 (14,18) years (median [IQR]), 62% male, 58% white, 26% Hispanic at our weekly dedicated IBD clinic. All have performed the transition skills’ self-assessment and practicum, and set transition goals with their healthcare provider. Of these individuals, 41 (77%) participated in survey feedback. On a utility rating scale of 0 (not helpful at all) to 10 (very helpful), patients reported median (IQR) utility scores of 8 (7,10) for the transition readiness assessment, 9 (7,10) for transition resources provided, and 9 (7,10) for the medical history summary. Most (91%) would recommend TEA to other patients. Conclusions: TEA standardized delivery of resources among pediatric IBD patients and was well received and friendly to clinical workflow.

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