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，这是我们匹兹堡儿童医院研究团队的主要研究重点，也是美国国家儿童健康与发展研究所(NICHD)儿科重症监护协作性研究网络(CPCCRN)的研究重点。这是一个续订申请，以继续参与NICHD-CPCCRN的第三个周期，目标是协作支持由儿科创伤和危重病分部网络开发的现有和新的研究，并扩展我们中心在CPCCRN内在创伤和脓毒症宿主-病原体相互作用方面的新工作。在过去的9年里，我们的中心已经为超过22项CPCCRN研究提供了2.4万名患者。我们中心的宿主-病原体相互作用研究计划已经导致了CPCCRN批准的三项研究。在第一个周期中，我们发现创伤患者发生医院感染和败血症的风险是非创伤患者的两倍。在第二个周期中，我们开始了正在进行的NIGMS-R01资助的儿科严重脓毒症炎症表型研究(PI：Carcillo)，该研究考察了创伤和非创伤患者中宿主炎症表型反应对医院感染和败血症结局的影响。在我们关于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，通过评估危重疾病中的微生物组扰动，提高对微生物组在健康和疾病中的作用的理解。在我们的单中心先导性研究中，我们发现危重儿童出现了微生物群多样性和部位特异性丧失的生物失调，有形成大量微生物(微生物群的30%)的趋势，这些微生物可以在医院感染发生前两天在病房和患者体内找到。如果我们证明这些发现可以在CPCCRN中推广，那么这将开启基于微生物组的药物预防和治疗危重儿童医院感染和败血症的新时代的可能性。

 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.