REMISE study: REMnant biospecimen Investigation in SEpsis

项目摘要/摘要 每年有近200万美国人因脓毒症住院，近五分之一 活不下去了。减少败血症死亡的大多数努力都始于这样一个前提，即患者 在很大程度上是相似的，并且针对单一机制的治疗将会得到改进 结果。但脓毒症患者在病原体、生物学、转归等方面存在差异。 有治疗反应的内型。对脓毒症内型的更多研究 受限于昂贵的基础设施和不可扩展的生物样品收集。要解决 在这个挑战中，我们将使用临床残留物生物库来了解可行性， 完整性，以及对机械性脓毒症研究的科学价值。我们将评估传统的 生物标记物、定量蛋白质组学、代谢组学、类脂组学和病原体基因组学 对残留样本进行测序，并将成功的数据“层”按比例排列， 社区医院储藏室。这一交叉项目将由一名 外部顾问委员会，具有炎症、免疫学、计算机和 系统生物学、实验室和病理医学。这一方法将进一步 发展我们由NIGMS资助的临床-翻译实验室，创造新的假设 从一个多样化的、学术的和社区的医院残留物生物库中获得 脓毒症患者中内型丰富的人群。最后，我们将进一步整合 这些数据用多组学读出的方法对严重创伤患者进行探讨 危重疾病中的共享/非共享机制。

PROJECT SUMMARY / ABSTRACT Almost 2 million Americans are hospitalized with sepsis each year, and nearly one in five don’t survive. Most efforts to reduce sepsis deaths begin with the premise that patients are largely similar, and that targeting therapeutics to a single mechanism will improve outcomes. But sepsis patients differ in pathogen, biology, outcomes, and are proposed to have treatment responsive endotypes. Greater study of sepsis endotypes has been limited by costly infrastructure and biospecimen collection that is not scalable. To solve this challenge, we will use a clinical remnant biorepository to understand feasibility, integrity, and scientific value for mechanistic sepsis research. We will evaluate traditional biomarkers, quantitative proteomics, metabolomics, lipidomics, and pathogen genomic sequencing in remnant specimens and graduate successful data “layers” to a scaled, community hospital repository. This cross-cutting project will be supervised by an external advisory board with expertise in inflammation, immunology, computational and systems biology, and laboratory and pathology medicine. This approach will further develop our NIGMS-funded clinical-translational laboratory, creating new hypotheses from a diverse, academic and community hospital remnant biorepository acquired from an endotype-enriched population of sepsis patients. Finally, we will further integrate these data with multi-omics read-outs in severely injured trauma patients to explore shared/unshared mechanisms in critical illness.