Midwest Children's Consortium

描述(由申请人提供)： 儿童肝病研究和教育网络(CHIELS)提供了前所未有的 在全球范围内改善儿童肝病预后的机会。拟建的临床中心 提交建立在患者登记、临床和BASE研究方面的强大机构记录，以及 圣路易斯儿童医院/华盛顿大学医学院的诊断技术 (SLCH/WUSTL)，通过扩大阿肯色州儿童医院/阿肯色大学医学科学(ACH/UAMS)的招生人数，与华盛顿大学临床与翻译科学奖和昆士兰医学研究所的资源互动，以及与儿科初级保健网络(吴儿童/青少年非卧床研究联盟)合作。我们将把先进的成像、病理学和人口分析应用到解决儿科肝病所需的复杂的多学科项目中。我们的目标体现在以下具体目标中：AIM I(临床登记、数据积累和标本(收集))将高效的SLCH/WUSTL登记工作扩展到ACH/UAMS的活动计划，在美国中部产生一个大型转诊基础，每年将从70名患者收集数据、血清、病理样本和复杂的图像。我们预计将加强对所有议定书的贡献。AIM 2(为儿童疾病制定新的诊断和预后策略)测试了以下假设：可识别的、可能可修改的导致肝纤维化的机制，以及系统和严格的生物标记物发现研究将阐明这些过程，以及相互竞争的结果和神经网络 分析将进一步确定病程。目标3(加强实践质量和教育)仔细审查初级保健做法和实验室利用，试图加快胆汁淤积症婴儿的识别和转诊，重点放在围绕表现的关键事件上，目的是确定然后减少阻碍及时转诊为胆道闭锁的因素。AIM 4(将成像方法应用于儿童疾病)将SLCH/WUSTL的先进肝脏成像能力融合到儿童肝病研究中，并将这些提供给网络。这些高度综合的目标将建立在我们的招生战略基础上，由这笔赠款资助，加上现有和预期的竞争性资金，以及专门的WUSTL机构支持。通过研究得出结论， 我们打算产生的知识将改善儿童疾病的诊断、预测结果、指导干预和改进提供者的做法。 相关性：患有肝病的儿童面临重大挑战。这些疾病具有很高的发病率、死亡率和对公共卫生的影响，因此具有集体重要性。治疗往往是无效的，肝硬变、肝功能衰竭和肝移植是常见的终点。诊断和发现肝硬变的原因和决定因素的能力的进步为影响这些结果提供了希望和潜在的影响。为了实现这一点，通过合作研究联盟将研究和临床护理整合在一起是至关重要的。

DESCRIPTION (provided by applicant): The Children's Liver Disease Research and Education Network (ChiLDREN) provides unprecedented opportunities to improve outcomes of pediatric liver diseases worldwide. This proposed Clinical Center submission builds on a strong institutional record in patient enrollment, clinical and bench research, and diagnostic technology at the St. Louis Children's Hospital/Washington University School of Medicine (SLCH/WUSTL) by expanding enrollments to Arkansas Children's Hospital/University of Arkansas for Medical Sciences (ACH/UAMS), interacting with the resources of the Washington University Clinical and Translational Science Award and Queensland Institute for Medical Research, and collaborating with a pediatric primary care network (WU Pediatric/Adolescent Ambulatory Research Consortium). We will apply advanced imaging, pathology, and population analyses to the sophisticated multidisciplinary project required to tackle pediatric liver diseases. Our goals are embodied in the following Specific Aims: Aim I (Clinical Enrollment, Data Accrual, and Specimen (Collection) extends the highly effective SLCH/WUSTL enrollment effort to the active program at ACH/UAMS, generating a large referral base across the central US, that will collect data, sera, pathology samples and sophisticated images from >70 patients annually. We anticipate enhanced contribution to all protocols. Aim 2 (Develop Novel Diagnostic and Prognostic Strategies for ChiLDREN Diseases) tests the hypotheses that identifiable, possibly modifiable mechanisms leading to hepatic fibrosis, and that systematic and rigorous biomarker discovery studies will elucidate these processes, and that competing outcomes and neural network analyses will further define disease course. Aim 3 (Enhance practice quality, and Education) scrutinizes primary care practices and laboratory utilization in an attempt to accelerate identification and referral of infants with cholestasis, focussing on the critical events surrounding presentation, with the goal of defining, then reducing, the factors that hinder timely referral for biliary atresia. Aim 4 (Apply imaging methodologies to ChiLDREN diseases) amalgamates SLCH/WUSTL's advanced liver imaging capabilities to the study of childhood liver diseases, offering these to the Network. These highly matrixed Aims will be built on our enrollment strategies funded by this grant, augmented by existing and anticipated competitive funding, and dedicated WUSTL institutional support. By study conclusion, we intend to generate knowledge that will improve diagnosis, predict outcomes, guide intervention and improve provider practices in ChiLDREN diseases. Relevance: Children with liver disease present major challenges. These diseases are collectively important because of high morbidity, mortality, and public health impact. Management is often ineffective, with cirrhosis, liver failure and liver transplantation as common end-points. Advances in ability to diagnose, and discover causes and determinants of cirrhosis offer hope and potential to impact these outcomes. To achieve this, integration of research and clinical care via a collaborative research consortium is essential.