Intestinal failure in children: A contemporary retrospective review by the Pediat

儿童肠衰竭：Pediat 的当代回顾性评论

基本信息

批准号：
7633321
负责人：
ROBERT H SQUIRES
金额：
$ 21.44万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-15 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7633321
关键词：
Address Age Back Biological Blood Blood Clot Blood Vessels Blood coagulation Caring Cessation of life Chest Child Child Care Childhood Cholestasis Cirrhosis Classification Clinical Clinical Data Collaborations Collection Country DNA Data Dependence Development Diagnosis Ensure Epidemiology Evidence based practice Excision Failure Fatty acid glycerol esters Foundations Frequencies Future Goals Ileocecal Valve Incidence Infant Infection Injury Intestines Intravenous Knowledge Length Life Literature Liver diseases Low Birth Weight Infant Malnutrition Medical Modeling Morbidity - disease rate Mucosal Immunity Nutritional Operative Surgical Procedures Outcome Parenteral Nutrition Patient Monitoring Patients Pattern Physiological Population Procedures Process Prospective Studies Randomized Registries Reporting Research Personnel Residual state Retrospective Studies Risk Risk Factors Sampling Scientist Sepsis Serum Site Small Intestines Specimen Staging Testing Therapy Clinical Trials Thrombosis Time Tissues Transplantation Uncontrolled Study Urine Veins Waiting Lists Weaning base cohort cost design experience infant outcome interest mortality nutrition prospective public health relevance treatment strategy treatment trial

项目摘要

DESCRIPTION (provided by applicant): Intestinal failure (IF) in infants and children is a devastating condition that can be broadly defined as the inability of the intestinal tract to sustain life without supplemental parenteral nutrition (PN). Following injury or resection, the intestinal tract must adapt sufficiently to achieve independence from PN, or the patient is at risk for nutritional deficiencies, end-stage liver disease, vascular thrombosis, sepsis, and death. These complications are particularly prevalent in the pediatric population. The current medical literature is insufficient to determine factors that predict outcome in patients with IF as too few patients are seen at any one center in a short enough time that medical, nutritional, surgical, and transplant options are similar. Currently accepted therapies are based on anecdotal experience and reports of small uncontrolled studies, thus creating a sizeable knowledge gap in our understanding of optimal treatment strategies. A major obstacle to understanding outcomes is that there are no comprehensive, multi-center studies, nor large prospective studies in the field of pediatric IF. We propose to establish a consortium comprised of pediatric centers with a recognized interest in IF. Specific Aim #1 is to investigate the feasibility and plan a prospective, multi-center consortium that will collect, maintain, analyze, and report clinical, nutritional, surgical, epidemiological, and outcome data in children with IF, including information derived from serum, urine, tissue, and DNA specimens. The clinical data compiled by the to-be-established prospective registry will be used to develop a model to predict three critical outcomes in IF patients that include independence from PN, development of cholestasis, and death. We will propose to collect and store biological samples to be used by clinical and basic scientists, within and outside our consortium, to enhance our understanding of the physiological mechanisms that underlie pathophysiological conditions associated with IF such as intestinal adaptation, PN related cholestasis, nutritional deficiencies, and mucosal immunity. In conjunction with the prospective registry, we will propose to identify, conduct, and complete appropriately powered randomized, controlled treatment trials that will form the foundation of an evidence-based practice model in the care of these children with complicated clinical conditions. To ensure our ability to create a productive collaboration, we propose Specific Aim #2 which is to perform a multi-center, retrospective review of a contemporary cohort of infants and children with IF to determine the feasibility that such a study will be able to identify demographic, clinical, and nutritional risk factors that will predict the following critical outcomes: (1) need for long-term PN (> 360 days), (2) discontinuation of PN, (3) development of cholestasis, (4) need for intestinal transplant, and (5) death. We will use the data collected and the experiences gained from the retrospective study to determine the feasibility of our consortium to conduct a multi-centered, prospective study of children with IF and to conduct randomized, controlled therapeutic trials. If successful, these data will be utilized for a future RO1 application. PUBLIC HEALTH RELEVANCE Intestinal failure (IF) in infants and children is a devastating condition that is defined as the inability of the intestinal tract to sustain life without supplemental nutrition that must be infused into a large vein, usually one located in the chest. Children with IF are at risk for developing nutritional deficiencies, cirrhosis, blood clots, blood infections, and death; yet the current medical literature is not sufficient to identify factors that that will allow doctors to predict whether the child will recover or need an intestinal transplant. To address the important problems related to children with IF, we propose to (1) establish an effective, collaborative relationship with a number of pediatric centers around the country who are recognized for their ability to care for these medically complicated children and (2) to look back over the last seven years to identify factors that will identify those children who are not likely to be removed from supplemental nutrition, who will likely require an intestinal transplant, or who is likely to die.

描述（由申请人提供）：婴儿和儿童的肠衰竭（IF）是一种毁灭性的疾病，可以广泛地定义为在没有补充肠外营养（PN）的情况下肠道无法维持生命。损伤或切除后，肠道必须充分适应以实现独立于 PN，否则患者面临营养缺乏、终末期肝病、血管血栓形成、败血症和死亡的风险。这些并发症在儿科人群中尤其普遍。目前的医学文献不足以确定预测 IF 患者预后的因素，因为在足够短的时间内在任何一个中心接诊的患者都太少，医疗、营养、手术和移植选择都相似。目前接受的疗法是基于轶事经验和小型非对照研究的报告，从而在我们对最佳治疗策略的理解上造成了相当大的知识差距。了解结果的一个主要障碍是儿科 IF 领域没有全面的多中心研究，也没有大型前瞻性研究。我们建议建立一个由对 IF 具有公认兴趣的儿科中心组成的联盟。具体目标#1是调查可行性并计划建立一个前瞻性的多中心联盟，该联盟将收集、维护、分析和报告 IF 儿童的临床、营养、手术、流行病学和结果数据，包括来自血清、尿液、组织和 DNA 样本。即将建立的前瞻性注册中心编制的临床数据将用于开发一个模型来预测 IF 患者的三个关键结局，包括独立于 PN、胆汁淤积的发展和死亡。我们将建议收集和储存生物样本，供我们联盟内部和外部的临床和基础科学家使用，以增强我们对 IF 相关病理生理条件的生理机制的理解，例如肠道适应、PN 相关胆汁淤积、营养缺乏和粘膜免疫。与前瞻性登记相结合，我们将建议确定、开展和完成适当的随机对照治疗试验，这些试验将构成护理这些患有复杂临床病症的儿童的循证实践模型的基础。为了确保我们能够建立富有成效的合作，我们提出了具体目标 #2，即对当代 IF 婴儿和儿童群体进行多中心回顾性审查，以确定此类研究能够确定的可行性人口统计学、临床和营养风险因素将预测以下关键结果：(1) 需要长期 PN（> 360 天），(2) 停止 PN，(3) 发生胆汁淤积，(4) 需要肠移植，以及（5）死亡。我们将利用收集到的数据和回顾性研究中获得的经验来确定我们的联盟对 IF 儿童进行多中心、前瞻性研究并进行随机、对照治疗试验的可行性。如果成功，这些数据将用于未来的 RO1 应用。公共卫生相关性婴儿和儿童的肠衰竭 (IF) 是一种破坏性病症，其定义为如果没有必须将补充营养注入大静脉（通常位于胸部）的情况下，肠道就无法维持生命。患有 IF 的儿童面临营养缺乏、肝硬化、血栓、血液感染和死亡的风险；然而，目前的医学文献不足以确定医生可以预测孩子是否会康复或需要肠道移植的因素。为了解决与 IF 儿童相关的重要问题，我们建议 (1) 与全国各地的一些儿科中心建立有效的合作关系，这些中心因照顾这些患有复杂疾病的儿童的能力而受到认可，以及 (2)回顾过去七年，找出一些因素，确定那些不太可能脱离补充营养的儿童、可能需要肠道移植的儿童或可能死亡的儿童。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Race affects outcome among infants with intestinal failure.

DOI：
10.1097/mpg.0000000000000456
发表时间：
2014-10
期刊：
Journal of pediatric gastroenterology and nutrition
影响因子：
2.9
作者：
Squires RH;Balint J;Horslen S;Wales PW;Soden J;Duggan C;Li R;Belle SH;Pediatric Intestinal Failure Consortium
通讯作者：
Pediatric Intestinal Failure Consortium

Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.

DOI：
10.1016/j.jpeds.2012.03.062
发表时间：
2012-10
期刊：
JOURNAL OF PEDIATRICS
影响因子：
5.1
作者：
Squires, Robert H.;Duggan, Christopher;Teitelbaum, Daniel H.;Wales, Paul W.;Balint, Jane;Venick, Robert;Rhee, Susan;Sudan, Debra;Mercer, David;Martinez, J. Andres;Carter, Beth A.;Soden, Jason;Horslen, Simon;Rudolph, Jeffrey A.;Kocoshis, Samuel;Superina, Riccardo;Lawlor, Sharon;Haller, Tamara;Kurs-Lasky, Marcia;Belle, Steven H.
通讯作者：
Belle, Steven H.