Predicting Severity and Improving the Outcomes of Pediatric Pancreatitis

预测小儿胰腺炎的严重程度并改善预后

• 批准号: 10415235
• 负责人: Maisam Abu-El-Haija
• 金额: $ 18.93万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415235
• 关键词: Admission activity; Adult; Albumins; Biological Markers; Biometry; Caring; Categories; Characteristics; Child; Childhood; Clinical; Collaborations; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Development; Diabetes Mellitus; Disease; Disease Progression; Elements; Endocrine; Environment; Evaluation; Foundations; Funding; Future; Gastroenterologist; Gastroenterology; Generations; Genes; Genetic; Genetic Markers; Genetic Models; Genetic study; Glucose Intolerance; Goals; Grant; Health; Hepatology; Heritability; High-Throughput Nucleotide Sequencing; Hospital Costs; IV Fluid; Incidence; Institution; Investigation; Knowledge; Laboratories; Lead; Length of Stay; Link; Lipase; Longitudinal prospective study; Matrix Metalloproteinases; Medical Genetics; Medical center; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Nature; Outcome; Outcomes Research; Pancreas; Pancreatitis; Patients; Pattern; Pediatric Hospitals; Pediatrics; Performance; Plasma; Population; Prediabetes syndrome; Prevention therapy; Prospective Studies; Public Health; Registries; Research; Research Design; Research Personnel; Resources; Retrospective cohort; Risk; Risk Management; Role; SPINK1 gene; Scientist; Severities; Severity of illness; Small Business Innovation Research Grant; System; Testing; Time; Tissues; Training; United States; Validation; Variant; Work; acute pancreatitis; adverse outcome; base; biobank; career; career development; clinical predictors; cohort; design; disease phenotype; epidemiology study; follow-up; gene panel; genetic analysis; genetic predictors; genetic testing; high risk; improved; improved outcome; indexing; inhibitor; innovation; mortality; novel; novel marker; novel therapeutics; nutrition; optimal treatments; patient subsets; pediatric department; predictive modeling; prevent; professor; prognostic; prognostic model; prognostic performance; prognostic tool; prospective; risk prediction; risk stratification; screening; skills; targeted treatment; tool

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.

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。 儿科中的 AP 仍未得到充分研究，其结果尚不明确。先前关于儿科 AP 的研究是 本质上大多是单中心和回顾性的，因此不足以理解自然 历史。很大比例 (15-30%) 的患者会出现重症急性胰腺炎 (SAP)，且病情加重 发病率、住院时间和费用增加。迄今为止，还没有儿科 AP 研究检查 正如我们通过设计所计划的那样，前瞻性进展，没有经过验证的儿科预后严重程度 系统以改善 AP 的结果。部分患者可能因 AP 导致糖尿病，这会导致 发病率增加，特别是在诊断不足的情况下，因为目前没有用于 AP 后筛查的方法。 我提出的职业发展的主要目标是获得以下方面的额外综合培训 通过风险建模进行生物统计学、研究设计、流行病学和结果研究，以获得技能 有必要建立多中心合作来研究 AP 风险分层和管理，从而导致 改善结果并降低发病率和死亡率。 我是儿科助理教授和委员会认证的胃肠病学家 辛辛那提儿童医院儿科胃肠病学、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优越的环境有利于年轻人的发展 通过核心资源、专家指导以及潜力来掌握必要要素 用于内部协作。 CCHMC 胰腺护理中心是为数不多的儿科胰腺中心之一 在美国，有既定的转诊模式，每年转诊 70-90 名新患者。我的 导师 Lee A. Denson 博士（全国公认的儿科胃肠病学领军人物），Sohail Husain 博士（美国儿科胃肠病学领域公认的领导者） 国家儿科胰腺学专家和科学家，流行病学和结果专家吴博士 研究投入到我的培训和指导我成为一名独立调查员的道路上。初级 该项目的目标是通过减少 SAP 和改进筛选来改善 AP 的结果 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 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，纳入治疗效果，并将 MMP 和 TIMP 纳入新的生物标志物。具体目标 2 建立模型来预测 AP 后糖尿病前期并了解扩展基因检测在疾病中的作用 进展为糖尿病前期。我们的提案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。成功完成这项研究有可能通过以下方式改善结果： 构建促进管理的临床工具，并有可能为儿科 AP 提供靶向治疗。

项目成果

Pancreatitis in the Complex Care Population: Presentation, Incidence, and Severity.

• DOI: 10.1097/mpg.0000000000003610
• 发表时间: 2022-12-01
• 期刊: JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
• 影响因子: 2.9
• 作者: Hawa, Kathryn;Corker, Lisa;Hornung, Lindsey;Noritz, Garey;Gariepy, Cheryl;Shaikhkhalil, Ala;Abu-El-Haija, Maisam
• 通讯作者: Abu-El-Haija, Maisam

Ultrasound findings of acute pancreatitis in children.

• DOI: 10.1007/s00247-022-05381-z
• 发表时间: 2022-11
• 期刊: Pediatric radiology
• 影响因子: 2.3

Menstruation-Associated Acute Pancreatitis in Patients with Hereditary Pancreatitis.

• DOI: 10.1016/j.jpeds.2020.11.024
• 发表时间: 2021-03
• 期刊: The Journal of pediatrics
• 作者: Khalaf R;Narkewicz M;El-Haija MA
• 通讯作者: El-Haija MA

A Practical Approach to Management of Acute Pancreatitis: Similarities and Dissimilarities of Disease in Children and Adults.

• DOI: 10.3390/jcm10122545
• 发表时间: 2021-06-08
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Sellers ZM;Barakat MT;Abu-El-Haija M
• 通讯作者: Abu-El-Haija M

Continuous Glucose Monitoring in the Intensive Care Unit Following Total Pancreatectomy with Islet Autotransplantation in Children: Establishing Accuracy of the Dexcom G6 Model.

• DOI: 10.3390/jcm10091893
• 发表时间: 2021-04-27
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Segev N;Hornung LN;Tellez SE;Courter JD;Lawson SA;Nathan JD;Abu-El-Haija M;Elder DA
• 通讯作者: Elder DA