Predicting Severity and Improving the Outcomes of Pediatric Pancreatitis

项目摘要/摘要 儿童急性胰腺炎(AP)的发病率已上升至1/万，接近成人发病率。 儿科的急性胰腺炎仍未得到充分的研究，其结果也不明确。以前在儿科AP上的研究是 大多是单一中心的，具有追溯性，因此不足以理解自然 历史。发生重症急性胰腺炎(SAP)的患者比例很高(15%-30%)，而且 发病率、住院时间和费用增加。到目前为止，还没有儿科AP研究检查 像我们在设计中计划的那样，没有经过验证的儿科预后严重程度 改善急性胰腺炎预后的系统。糖尿病可由AP在部分患者中引起，这会导致 发病率增加，尤其是在诊断不足的情况下，因为目前还没有筛查AP后的方法。 我提出的职业发展的主要目标是在以下方面获得额外的全面培训 通过风险建模的生物统计学、研究设计、流行病学和结果研究，以获得技能 有必要建立多中心协作来研究AP风险分层和管理，从而 改善结果，降低发病率和死亡率。 我是一名儿科学助理教授和一名委员会认证的胃肠病专家 辛辛那提儿童医院儿科的胃肠病、肝病和营养学 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特殊的环境促进了YOUNG的发展 调查人员通过核心资源、专家指导以及潜力拥有基本要素 用于内部协作。CCHMC的胰腺护理中心是为数不多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名新患者被转诊。我的 导师Lee A.Denson博士-全国公认的儿科胃肠病学领导者Sohail Husain-a博士 国家儿科胰腺科专家和科学家，吴医生-流行病学和结果专家 研究被投入到我的培训和指导我成为一名独立调查人员的道路上。初级阶段 该项目的目标是通过降低SAP和改善筛查来改善AP的预后 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、应用新的SAP来验证和优化我们之前生成的SAP模型 定义，纳入治疗作用，并纳入MMPs和TIMPs作为新的生物标志物。特定目标 2建立预测急性胰腺炎后糖尿病前期的模型，并了解扩展基因检测在疾病中的作用。 进展为糖尿病前期。我们的建议将帮助我们更好地了解SAP和进展到糖尿病前期 填补知识空白。这项研究的成功完成有可能通过以下方式改善结果 建立便于管理的临床工具，并有可能导致儿科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.