Redox Trapping for Biospecimen Preservation and Innovation in Sepsis Care

摘要 我们的目标是通过引入一种新的氧化还原捕获制剂， 保存血液标本。新配方预期：1）防止人为氧化和损失 2）使氧化还原代谢的研究，强调失调， 脓毒症中的免疫代谢反应，以及3）改善区分氧化还原分子标志物的分析 与人口统计学特征（年龄、性别和种族）相关。我们的氧化还原专业知识 专利氧化还原化学试剂的生物化学和创新，败血症机制，试验设计和临床 将首先应用专业知识来验证新的氧化还原捕集配方（R21阶段），然后进行规模放大 通过在参与嵌入式精确急症护理的研究中心部署该系统采集血液样本 试验（EMPACT）网络（R33阶段）。这是一个新成立的网络总理重症监护临床试验网站 旨在对败血症进行精确的临床试验和发现研究。成功完成我们的 目的是改善脓毒症患者的分期和临床精确研究，以发现新的治疗方法。 治疗败血症的靶点。更具体地说，在R21阶段，我们将研究 新的氧化还原配方与高端质谱和单电池技术，以评估其 测量氧化还原和其他生物标志物的性能。新配方将与现有配方进行比较。 用于临床和研究目的的血液采集护理程序标准（黄金标准）。进一步 在败血症患者中验证该公式，然后我们将在试点中评估其对标准临床实验室测试的影响 使用前瞻性收集的来自败血症重症患者的配对单个时间点样本的研究。我们将 通过将测量结果与生理学和生物学特性联系起来， 通过维克森林重症监护数据分析平台被动收集的结局数据。后 为了在R21阶段完成时实现关键指标，我们将与EMPACT网络合作， R33阶段，在疾病连续体的3个时间点采集150例患者的血液标本 使用标准方法和新的氧化还原配方的进展。使用高端组学进行分析 技术将产生信息丰富和特定于氧化还原的数据集，这些数据集将使用 生物信息学方法，并与通过EMPACT数据仓库被动捕获的临床数据相关联， 为脓毒症研究提出新的假设。最后，我们包括一个共享冷冻保存标本的计划， 临床和分子数据与研究者在该机构，以支持发现或假设驱动的研究 通过氧化还原生物学和医学以及危重疾病、伤害和 研究恢复研究中心分别由MPI Furdui和Files指导，并与外部 调查人员通过EMPACT。

ABSTRACT We aim to advance sepsis research and clinical diagnosis by introducing a new redox trapping formulation for preservation of blood specimens. The new formulation is anticipated: 1) to prevent artifactual oxidation and loss of specimen integrity during storage, 2) to enable studies of redox metabolism which underlines the dysregulated immunometabolic response in sepsis, and 3) to improve analysis of differentiating redox molecular markers associated with demographic features (age, gender and racial ethnicity). Our combined expertise of redox biochemistry and innovation in patented redox chemical reagents, sepsis mechanisms, trial design and clinical expertise will be applied first to validate the new redox trapping formulation (R21 Phase) and then to scale-up by deploying this for collection of blood specimens at sites participating in the EMbedded Precision in Acute Care Trials (EMPACT) Network (R33 Phase). This is a newly formed network of premier critical care clinical trials sites designed to conduct precision clinical trials and discovery research in sepsis. Successful accomplishment of our aims will improve staging of septic patients and clinical precision research for discovery of new therapeutic targets for treatment of sepsis. More specifically, during the R21 Phase we will investigate the compatibility of the new redox formulation with high-end mass spectrometry and single cell technologies to evaluate its performance for measurement of redox and other biomarkers. The new formulation will be compared with current standard of care procedures for blood collection for clinical and research purposes (gold standard). To further validate this formula in sepsis patients, we will then evaluate its effects on standard clinical lab tests in a pilot study using prospectively collected paired single timepoint samples from critically ill patients with sepsis. We will further determine the advantage of redox trapping formulation by linking the measurements to physiologic and outcome data collected passively through the Wake Forest Critical Care Data Analytic Platform. Upon accomplishment of key metrics at the completion of R21 Phase, we will work with the EMPACT Network in the R33 Phase to collect blood specimens from 150 patients at 3 timepoints across the continuum of their disease progression using the standard methods and the new redox formulation. Analysis using high-end omics technologies will produce information-rich and redox-specific datasets, which will be integrated using bioinformatics approaches and linked to clinical data captured passively via the EMPACT data warehouse to generate new hypotheses for sepsis research. Lastly, we include a plan to share cryopreserved specimens, clinical and molecular data with investigators at the institution to support discovery or hypothesis-driven research through pilot mechanisms under the Center for Redox Biology and Medicine and Critical Illness, Injury and Research Recovery Research Center directed by MPIs Furdui and Files, respectively, and with outside investigators via EMPACT.