Renewal Application for the Childrens Hospital of Pittsburgh Collaborative Pediatric Critical Care Research Network Site

 描述（由申请人提供）：在美国，儿童死亡率最常见的原因是创伤和败血症，这是我们在美国国立儿童健康与发展研究院（NICHD）合作儿科重症监护研究网络（CPCCRN）匹兹堡儿童医院研究中心的研究团队的主要研究重点。这是一份延续申请，旨在继续参与NICHD-CPCCRN的第三个周期，目的是合作支持儿科创伤和危重病分支网络开发的现有和新研究，并扩展我们中心在创伤和脓毒症中宿主-病原体相互作用的CPCCRN内的新工作。在过去的9年里，我们中心为22项CPCCRN研究提供了24，000例患者。我们中心在宿主-病原体相互作用方面的研究计划已经导致了三项CPCCRN批准的研究。在第一个周期中，我们发现与非创伤患者相比，创伤患者发生医院感染和败血症的风险增加了两倍。在第二个周期中，我们开始了正在进行的NIGMS-R 01资助的儿科严重脓毒症炎症表型研究（PI：Carcillo），该研究检查了创伤和非创伤患者中宿主炎症表型反应对医院感染和脓毒症结局的影响。在我们的第三个周期的新概念提案中，我们响应了NIH路线图倡议的呼吁，即通过评估危重疾病中的微生物组扰动来提高对微生物组在健康和疾病中的作用的理解。在我们的单中心初步研究中，我们发现重症儿童患有微生物多样性和位点特异性丧失的“生态失调”，倾向于形成大量微生物（> 30%的微生物组），这些微生物可以在医院感染发生前两天在患者的房间和患者体内发现。如果我们证明这些发现在CPCCRN中是可推广的，那么这将开启一个基于微生物组的医学新时代的可能性，用于预防和治疗严重受伤儿童的医院感染和败血症。

 DESCRIPTION (provided by applicant): Child mortality in the United States is most commonly attributed to trauma and sepsis, the major research focus of our research team at the Children's Hospital of Pittsburgh Site of the National Institutes of Child Health and Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN). This is a renewal application to continue participation in the third cycle of the NICHD-CPCCRN with the goals of collaboratively supporting existing and new studies developed by the Pediatric Trauma and Critical Illness Branch network and also extending our center's novel work within the CPCCRN in host-pathogen interactions in trauma and sepsis. Over the past 9 years our center has provided 24,000 patients to over 22 CPCCRN studies. Our center's program of research in host-pathogen interactions has led to three CPCCRN approved studies. In the first cycle we showed that trauma patients have a two-fold increased risk of developing nosocomial infection and sepsis compared to non-trauma patients. In the second cycle we commenced the ongoing NIGMS-R01 funded Inflammation Phenotypes in Pediatric Severe Sepsis study (PI: Carcillo) which examines the influence of host inflammation phenotype response on nosocomial infection and sepsis outcomes in trauma and non-trauma patients. In our new concept proposal for this third cycle we respond to the NIH roadmap initiative's call for improved understanding of the role of the microbiome in health and disease by evaluating microbiome perturbations in critical illness. In our single center pilot study we found that critically ill children suffered `dysbiosis with loss of microbiome diversity and site specificity with a tendency to formation of an abundant microorganism (> 30% of the microbiome) which could be found in the patient's room and in the patient two days before the onset of nosocomial infection. If we demonstrate that these findings are generalizable across the CPCCRN then this will open the possibility of a new era of microbiome based medicine for prevention and treatment of nosocomial infection and sepsis in critically injured children.