Predicting Severity and Improving the Outcomes of Pediatric Pancreatitis

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Project Summary/Abstract The incidence of pediatric Acute Pancreatitis (AP) has been rising to 1/10,000 cases, close to adult incidence. AP in pediatrics remains understudied with outcomes poorly defined. Previous studies in pediatric AP are mostly single-centered and retrospective in nature, and thereby insufficient for understanding the natural history. A high percentage (15-30%) of patients develop severe acute pancreatitis (SAP) with increased morbidity, increased length of hospital stay and cost. To date, there is no pediatric AP study that examines progression prospectively like we plan through our design, there is no validated pediatric prognostic severity system to improve outcomes of AP. Diabetes can result from AP in a subset of patients, and that leads to increased morbidity especially if underdiagnosed, given that there is no current method for screening post AP. The primary goal of my proposed career development is to acquire additional comprehensive training in biostatistics, study design, epidemiology and outcome research through risk modeling, to acquire the skills necessary to build multicenter collaborations to study AP risk stratification and management that lead to the improved outcomes and decreased morbidity and mortality. I am an Assistant Professor of Pediatrics and a board certified Gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition in the Department of Pediatrics at Cincinnati Children’s Hospital Medical Center (CCHMC). CCHMC is committed to improving the health outcomes of children through innovative research. The exceptional environment at CCHMC facilitates the development of young investigators by having essential elements through core resources, expert mentorship, as well as the potential for internal collaboration. The pancreas Care Center at CCHMC is one of only a few pediatric pancreas centers in the United States and has an established referral pattern, with 70-90 new patients referred per year. My mentors Dr. Lee A. Denson- a nationally recognized leader in pediatric gastroenterology, Dr. Sohail Husain- a national expert and scientist in pediatric pancreatology, Dr. Woo- an expert in epidemiology and outcome research are invested in my training and guiding my path to be an independent investigators. The primary objective of this project is to improve outcomes of AP by decreasing SAP and improve screening for prediabetes. This will be accomplished through our prospective longitudinal study design. Specific Aim 1 to validate and optimize our previously generated SAP model by adding more factors, applying the new SAP definition, incorporating therapy effect, and incorporating MMPs and TIMPs as novel biomarkers. Specific Aim 2 to build a model to predict prediabetes post AP and understand the role of expanded gene testing in disease progression to prediabetes. Our proposal will help us better understand SAP and progression to prediabetes to fill the knowledge gap. Successful completion of this study has the potential to lead to improved outcomes by building clinical tools that facilitate management, and potentially lead to targeted therapies for AP in pediatrics.