Collaborative Pediatric Critical Care Research Network - Clinical Site

项目摘要/摘要-费城儿童医院 儿科重症监护协作性研究网络(CPCCRN)是推动科学发展的关键 和儿科重症监护医学的实践。这一选址方案的总体目标是为 费城(CHOP)，在雅典娜·祖帕和罗伯特·伯格的继续领导下，继续担任 在新的和扩大的CPCCRN中的临床站点。Zuppa博士和Berg博士，过去11年的现场PI，是 具有丰富的临床和转化性研究经验的儿科强化治疗师，他们成功地 指导了许多初级调查人员，并为CPCCRN出版了大量科学出版物。印章是 位于费城的一家独立的、三级护理的学术儿童医院，为儿童和 具有不同种族、民族和社会经济背景的家庭。Chop，最大的儿童餐厅之一 全国医院，是一家拥有559张床位的儿童医院，设有49个儿科内外科专科， 员工超过14,585人，教职员工860人，年度运营预算为32亿美元。Chop是其中之一的家园 全国最大的儿科研究项目，联邦奖励总额超过1.47亿美元， 年度预算超过4.04亿美元(19财年)。脓毒症中的个性化免疫调节 本申请中提出的“多器官功能障碍综合征(MODS)”试验是一项大型的 脓毒症所致多器官功能障碍儿童的个体化、针对性免疫功能管理。这场审判 解决了免疫抑制儿童将受益于粒细胞-巨噬细胞集落的假设 刺激因子(GM-CSF)和高度炎症的儿童将受益于靶向抗炎 使用Anakinra(重组IL-1受体拮抗剂)或tocilizumab(IL-6受体阻断抗体)治疗。 效益将根据与健康相关的短期和长期生活质量进行评估。这项研究建立在 CPCCRN的研究表明，儿童中存在特定的免疫表型 脓毒症诱导的MODS，并通过应用GM-CSF成功逆转免疫抑制。它 也是对正在进行的NICHD R01资助的研究的补充，该研究调查了 儿科多器官功能障碍，祖帕医生是其中的一员。这项研究提出了一种变革性的个性化方法 免疫--针对败血症儿童的护理。Zuppa博士和Berg博士以及他们的研究团队对 与本试验所依据的CPCCRN研究，包括样本收集和处理方法 用于免疫表型、GM-CSF的剂量和给药，以及收集短期和长期脓毒症- 相关结果。Zuppa博士和Berg博士以及辅助站点Pi Neal Thomas博士得到了他们的全力支持 各机构参加CPCCRN，并坚定地致力于与其他 CPCCRN网站和数据协调中心，以及初级调查人员的纳入和指导 在CPCCRN活动中。

PROJECT SUMMARY/ABSTRACT – Children’s Hospital of Philadelphia The Collaborative Pediatric Critical Care Research Network (CPCCRN) is essential to advancing the science and practice of pediatric critical care medicine. The overall aim of this site proposal is for Children’s Hospital of Philadelphia (CHOP), under the continued leadership of Athena Zuppa and Robert Berg, to continue as a clinical site in the new and expanded CPCCRN. Drs. Zuppa and Berg, site-PIs for the past 11 years, are pediatric intensivists with a wealth of clinical and translational research experience, who have successfully mentored many junior investigators and produced numerous scientific publications for the CPCCRN. CHOP is a free-standing, tertiary care, academic children’s hospital located in Philadelphia that serves children and families with diverse racial, ethnic, and socioeconomic backgrounds. CHOP, one of the largest children’s hospitals in the country, is a 559-bed children’s hospital with 49 pediatric medical and surgical subspecialties, a staff of over 14,585, a faculty of 860, and an annual operating budget of $3.2 billion. CHOP is home to one of the largest pediatric research programs in the country with more than $147 million in total federal awards and an annual budget of more than $404 million (FY19). The “Personalized Immunomodulation in Sepsis-Induced Multiple Organ Dysfunction Syndrome (MODS)” trial proposed in this application is a large RCT of personalized, targeted management of immune function in children with sepsis-induced MODS. The trial addresses the hypothesis that immunosuppressed children will benefit from granulocyte macrophage-colony stimulating factor (GM-CSF), and children with hyperinflammation will benefit from targeted anti-inflammatory therapy with anakinra (recombinant IL-1 receptor antagonist) or tocilizumab (IL-6 receptor blocking antibody). Benefit will be evaluated in terms of short- and long-term health-related quality of life. This study builds on CPCCRN studies that have demonstrated the existence of specific immune phenotypes among children with sepsis-induced MODS, and successful reversal of immune suppression by administration of the GM-CSF. It also complements the ongoing NICHD R01-funded study investigating the risk factors for immunoparalysis in pediatric MODS, of which Dr. Zuppa is a co-PI. This study proposes a transformative approach to personalized immune-targeted care of the septic child. Drs. Zuppa and Berg and their research team are thoroughly familiar with the CPCCRN studies on which this trial is based including methods of sample collection and processing for immunophenotyping, dosing and administration of GM-CSF, and collection of short- and long-term sepsis- related outcomes. Drs. Zuppa and Berg, and the ancillary site PI Dr. Neal Thomas have the full support of their respective institutions to participate in the CPCCRN, and are strongly committed to collaboration with other CPCCRN sites and the Data Coordinating Center, as well as the inclusion and mentoring of junior investigators in CPCCRN activities.