Collaborative Pediatric Critical Care Research Network At Children's Hospital of

描述（由申请人提供）：脓毒症引起的多器官衰竭（MOF）仍然是儿童发病和死亡的重要原因。在十多年的机制研究中，我们已经报道了器官衰竭与炎症和凝血增加以及免疫功能降低有关。我们已经表征了三种儿科败血症诱导的MOF综合征表型; 1）病毒/淋巴组织增生性疾病相关的顺序性多器官衰竭综合征，2）代偿性抗炎反应/延长的淋巴细胞减少/免疫麻痹综合征，和3）微血管血栓形成相关的血小板减少相关的多器官衰竭综合征。在我们的单中心，当表型特异性治疗策略分别针对恢复免疫和凝血系统功能时，这些患者可以有92%的存活率，而当不使用这些特异性治疗时，存活率仅为63%。由于这些表型的诊断需要专门的诊断测试，这些MOF表型的表征和特定疗法的使用尚未在儿科重症监护病房进行系统研究，除了我们自己的。我们的建议的目的是确定这些败血症诱导的MOF表型的发生率和结果在合作儿科重症监护研究网络（CPCCRN）的人口。该提案将确定这些表型的发生率和结局，这些表型已经在我们的东北部和主要是高加索人群中观察到，在种族和地理上多样化的CPCCRN人群中观察到。这些知识将使我们能够确定未来在CPCCRN中对儿科败血症诱导的MOF进行表型特异性治疗策略试验的可行性。 在过去的四年里，我们一直是六个有幸参加CPPCRN的网站之一。在此期间，我们的主要研究是危重病应激诱导的免疫抑制试验，该试验测试预防策略预防应激诱导的淋巴细胞凋亡和随后的医院感染/败血症的能力。我们目前的建议代表了下一步的调查免疫抑制的作用，在不断流行的医院感染和感染引起的发病率和死亡率 公共卫生相关性：感染性和耐药菌败血症是一个重要的公共卫生问题。我们目前的建议旨在对脓毒症患者进行表型分析，以确定设计新的表型特异性预防和治疗试验的可行性，这些试验可能会减少儿童医院感染和耐药微生物脓毒症的国家和全球负担。

DESCRIPTION (provided by applicant): Sepsis-induced multiple organ failure (MOF) remains an important cause of child morbidity and death. In over ten years of mechanistic investigation we have reported that organ failure is associated with increased inflammation and coagulation, and reduced immune function. We have characterized three pediatric sepsis- induced MOF syndrome phenotypes; 1) the virus / lymphoproliferative disease associated Sequential Multiple Organ Failure Syndrome, 2) the Compensatory Anti-inflammatory Response / Prolonged Lymphopenia / Immuneparalysis Syndrome, and 3) the microvascular thrombosis related Thrombocytopenia Associated Multiple Organ Failure Syndrome. In our single center, these patients can have a 92% survival when phenotype specific therapeutic strategies are directed to restoring immune and coagulation system function respectively, compared to only a 63% survival when these specific therapies are not used. Because diagnosis of these phenotypes requires specialized diagnostic tests, the characterization of these MOF phenotypes and the use of specific therapies have not been systematically investigated in Pediatric Intensive Care Units, other than our own. The purpose of our proposal is to determine the incidence and outcome of these sepsis induced MOF phenotypes in the Collaborative Pediatric Critical Care Research Network (CPCCRN) population. This proposal will establish the incidence and outcome of these phenotypes, already observed in our Northeastern and predominantly Caucasian population, across the ethnically and geographically diverse CPCCRN population. This knowledge will allow us to determine the feasibility of future trials of phenotype specific therapeutic strategies for pediatric sepsis induced MOF in the CPCCRN. For the past four years we have been one of 6 sites privileged to participate in the CPPCRN. Our principal study during this time was the Critical Illness Stress Induced Immune Suppression Trial which tests the ability of a prophylaxis strategy to prevent stress induced lymphocyte apoptosis and consequent nosocomial infection / sepsis. Our present proposal represents the next step in investigation into the role of immune depression in the ongoing epidemic of nosocomial sepsis and sepsis induced morbidity and mortality PUBLIC HEALTH RELEVANCE: Noscomial and resistant organism sepsis is a signifcant public health problem. Our present proposal aims to phenotype patients with sepsis to determine the feasibility of designing novel phenotype specific prophylaxis and treatment trials which can potentially decrease the national and global burden of nosocomial and drug resistant organism sepsis in chidlren.