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

描述（由申请方提供）：婴儿和儿童的肠衰竭（IF）是一种破坏性疾病，可广义定义为肠道在没有补充肠外营养（PN）的情况下无法维持生命。损伤或切除后，肠道必须充分适应以实现不依赖PN，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。这些并发症在儿科人群中尤其普遍。目前的医学文献不足以确定IF患者预后的预测因素，因为在任何一个中心在足够短的时间内看到的患者太少，医疗，营养，手术和移植选择都是相似的。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，因此在我们对最佳治疗策略的理解方面存在相当大的知识差距。理解结局的一个主要障碍是在儿科IF领域没有全面的、多中心的研究，也没有大型的前瞻性研究。我们建议建立一个由对IF感兴趣的儿科中心组成的联盟。具体目标#1是研究可行性并计划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、流行病学和结局数据，包括来自血清、尿液、组织和DNA标本的信息。即将建立的前瞻性登记研究收集的临床数据将用于开发一个模型，以预测IF患者的三个关键结局，包括不依赖PN、胆汁淤积和死亡。我们将建议收集和储存生物样本，供我们联盟内外的临床和基础科学家使用，以增强我们对IF相关病理生理学状况（如肠适应、PN相关胆汁淤积、营养缺乏和粘膜免疫）的生理机制的理解。结合前瞻性登记研究，我们将提出确定、实施和完成适当的随机对照治疗试验，这些试验将为这些具有复杂临床状况的儿童的护理奠定循证实践模式的基础。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婴儿和儿童队列进行多中心回顾性审查，以确定此类研究能够识别人口统计学、临床和营养风险因素的可行性，这些因素将预测以下关键结局：（1）需要长期PN（> 360天），（2）停用PN，（3）发生胆汁淤积，（4）需要肠移植，（5）死亡。我们将使用收集的数据和从回顾性研究中获得的经验，以确定我们的联盟进行一项多中心的，前瞻性研究的儿童IF和进行随机，对照治疗试验的可行性。如果成功，这些数据将用于未来的RO 1应用。公共卫生相关性婴儿和儿童的肠衰竭（IF）是一种毁灭性的疾病，定义为肠道在没有补充营养的情况下无法维持生命，必须将补充营养注入大静脉，通常位于胸部。患有IF的儿童有营养缺乏、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预测儿童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）与全国各地的儿科中心建立有效的合作关系，这些中心被公认有能力照顾这些医学上复杂的儿童;（2）回顾过去七年，以确定那些不太可能从补充营养中移除的儿童的因素，谁可能需要肠道移植，或者谁可能会死。

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.