Predicting Severity and Improving the Outcomes of Pediatric Pancreatitis

项目概要/摘要 儿童急性胰腺炎（AP）的发病率已上升至1/10，000例，接近成人发病率。 儿科AP的研究仍然不足，结局定义不明确。先前在儿科AP中的研究是 大多是单中心的和回顾性的性质，从而不足以理解自然的 历史高比例（15-30%）的患者发生重症急性胰腺炎（SAP）， 发病率、住院时间和费用增加。到目前为止，还没有儿科AP研究， 前瞻性进展，如我们通过我们的设计计划，没有经过验证的儿科预后严重程度 改善AP的结果。糖尿病可由AP在一部分患者中引起，这导致 发病率增加，特别是在诊断不足的情况下，因为目前没有筛查AP后的方法。 我所建议的职业发展的主要目标是获得更多的全面培训， 生物统计学，研究设计，流行病学和通过风险建模的结果研究，以获得技能 有必要建立多中心合作，研究AP风险分层和管理， 改善结果并降低发病率和死亡率。 我是一名儿科助理教授，也是一名委员会认证的胃肠病学家， 辛辛那提儿童医院儿科的胃肠病学、肝病学和营养学 医疗中心（CCHMC）。CCHMC致力于通过以下方式改善儿童的健康状况： 创新研究。CCHMC的特殊环境促进了年轻人的发展 通过核心资源、专家指导以及潜在的 内部合作。CCHMC的胰腺护理中心是仅有的几个儿科胰腺中心之一 在美国，有一个既定的转诊模式，每年有70-90名新患者转诊。我 导师李博士A. Denson-全国公认的儿科胃肠病学领导者，Sohail Husain博士- a 国家儿科胰腺病学专家和科学家，吴博士-流行病学和结果专家 研究投资于我的培训和指导我成为独立调查员的道路。主 本项目的目的是通过减少SAP和改善对 糖尿病前期这将通过我们的前瞻性纵向研究设计来实现。具体目标1至 通过添加更多因素，应用新SAP，验证和优化我们以前生成的SAP模型 定义，纳入治疗效果，并纳入MMP和TIMP作为新的生物标志物。具体目标 2建立一个模型来预测AP后的前驱糖尿病，并了解扩展基因检测在疾病中的作用 进展为前驱糖尿病。我们的建议将帮助我们更好地了解SAP和糖尿病前期的进展， 填补知识空白。成功完成本研究有可能通过以下方式改善结局： 建立有助于管理的临床工具，并可能导致儿科AP的靶向治疗。

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.