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

• 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
• 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

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）：婴儿和儿童中的肠道衰竭（如果）是一种毁灭性的疾病，可以广泛定义为肠道无法维持生命而无需补充肠胃外营养（PN）。受伤或切除后，肠道必须足够适应以使其与PN独立，否则患者有营养缺乏，终末期肝病，血管血栓形成，败血症和死亡的风险。这些并发症在小儿人群中尤为普遍。当前的医学文献不足以确定能够预测患者预后的因素，因为在短时间内，任何一个中心都在医疗，营养，外科手术和移植选择相似的患者中看到了很少的患者。目前接受的疗法基于轶事经验和小型不受控制的研究的报告，从而在我们对最佳治疗策略的理解中造成了巨大的知识差距。理解结果的一个主要障碍是，没有全面的，多中心的研究，也没有大量的前瞻性研究。我们建议建立一个由小儿中心组成的财团，对IF具有公认的兴趣。具体目的1是研究可行性并计划一个前瞻性，多中心财团，该联盟将收集，维护，分析和报告临床，营养，外科手术，流行病学和结果数据，其中IF的儿童，包括源自血清，尿液，组织和DNA标本的信息。为了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，以预测三个关键结果，即IF包括脱离PN的患者，胆汁淤积的发展和死亡。我们将建议收集和存储我们财团内外的临床和基础科学家使用的生物样品，以增强我们对与肠道适应性相关的病理生理状况的理解，例如肠道适应，PN相关的胆固醇，营养缺乏症和粘膜免疫。结合前瞻性注册表，我们将提议识别，进行和完成适当的随机，对照治疗试验，这将构成基于循证实践模型的基础，以照顾这些患有复杂临床状况的儿童。为了确保我们建立富有成效的合作能力，我们提出了特定的目标＃2，即对当代的婴儿和儿童进行多中心的回顾性回顾，以确定该研究能够确定能够确定人口统计学，临床和营养风险因素的可行性，以预测以下关键成果：胆汁淤积的发展，（4）需要肠道移植和（5）死亡。我们将使用收集的数据以及回顾性研究中获得的经验来确定我们的财团的可行性，以对具有IF的儿童进行以上为中心的前瞻性研究并进行随机，对照治疗试验。如果成功，这些数据将用于将来的RO1应用程序。婴儿和儿童中的公共卫生相关性肠道衰竭（IF）是一种毁灭性的疾病，被定义为肠道无法维持生命而没有补充营养，必须将其注入大静脉，通常位于胸部。患有IF的儿童有患营养缺乏，肝硬化，血凝块，血液感染和死亡的风险；然而，当前的医学文献不足以识别那些将使医生能够预测孩子是否会恢复还是需要肠道移植的因素。要解决与孩子有关的重要问题，我们建议（1）与全国各地的许多儿科中心建立有效的，协作的关系，他们因照顾这些医学上复杂的孩子而受到认可，并且（2）回顾过去的七年来，以确定那些不太可能从补充营养中被遗忘的因素，这些因素可能会识别那些可能会造成替代性营养的孩子，或者可能会遭受更高的态度。

项目成果

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.