Collaborative Pediatric Critical Care Research Network - Clinical Site

项目概要/摘要-费城儿童医院 协作儿科重症监护研究网络（CPCCRN）对于推进科学至关重要 和儿科重症监护医学的实践。本选址建议书的总体目标是： 费城（CHOP），在雅典娜祖帕和罗伯特贝格的继续领导下，继续作为一个 新的和扩展的CPCCRN的临床站点。Zuppa博士和贝格博士是过去11年的研究中心PI， 儿科重症监护医师具有丰富的临床和转化研究经验，他们成功地 指导了许多初级研究人员，并为CPCCRN制作了许多科学出版物。斩波 一个独立的，三级保健，学术儿童医院位于费城，为儿童和 不同种族、民族和社会经济背景的家庭。CHOP是世界上最大的儿童 医院在该国，是一个559张病床的儿童医院，49个儿科内科和外科专科， 员工人数超过14，585人，教职员工860人，年度运营预算为32亿美元。CHOP是一个 全国最大的儿科研究项目，联邦拨款总额超过1.47亿美元， 年度预算超过4.04亿美元（FY 19）。“脓毒症诱导的个性化免疫调节” 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RCT， 个性化的，有针对性的管理免疫功能在脓毒症引起的MODS儿童。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），和儿童与炎症将受益于有针对性的抗炎 阿那白滞素（重组IL-1受体拮抗剂）或托珠单抗（IL-6受体阻断抗体）治疗。 将根据短期和长期健康相关生活质量评价获益。这项研究建立在 CPCCRN的研究表明，在儿童中存在特异性免疫表型， 脓毒症诱导的MODS，以及通过给予GM-CSF成功逆转免疫抑制。它 也补充了正在进行的NICHD R 01资助的研究，调查免疫麻痹的风险因素， 儿科多器官功能不全综合征祖帕医生是其中的共同主要研究者这项研究提出了一种变革性的方法， 对脓毒症患儿进行免疫靶向治疗。祖帕博士和贝格博士以及他们的研究团队 本试验所基于的CPCCRN研究，包括样本采集和处理方法 用于免疫表型分析、GM-CSF给药和给药，以及收集短期和长期脓毒症- 相关成果。Zuppa和贝格博士以及辅助研究中心PI Neal托马斯博士得到了他们的全力支持。 各机构参与CPCCRN，并坚定地致力于与其他机构合作 CPCCRN研究中心和数据协调中心，以及初级研究者的纳入和指导 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.