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捉剂来促进败血症的研究和临床诊断 血液标本的保存。新配方预计：1)防止人工氧化和损失 样品在储存过程中的完整性，2)使氧化还原代谢的研究能够强调失调的 脓毒症的免疫代谢反应，以及3)改进氧化还原分子标志物的鉴别分析 与人口统计特征(年龄、性别和种族)相关。我们在氧化还原方面的专业知识 生物化学和专利氧化还原化学试剂创新、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获配方(R21阶段)，然后进行放大 通过在参与Embedded Precision在急性护理中参与的地点将其用于采集血液样本 试验(Empact)网络(R33阶段)。这是一个新形成的首屈一指的重症监护临床试验站点网络。 旨在对脓毒症进行精确的临床试验和发现研究。成功地完成了我们的 AIMS将改善脓毒症患者的分期和临床精确度研究，以发现新的治疗方法 脓毒症的治疗靶点。更具体地说，在R21阶段，我们将调查 采用高端质谱学和单细胞技术的新氧化还原配方 用于测量氧化还原和其他生物标志物的性能。新提法将与目前的提法进行比较 临床和研究用采血护理程序标准(金标准)。为了进一步 在脓毒症患者中验证该配方，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重症脓毒症患者的配对单一时间点样本进行研究。我们会 进一步确定氧化还原捕集配方的优势，通过将测量与生理和 通过维克森林重症监护数据分析平台被动收集的结果数据。vt.在.的基础上 完成R21阶段的关键指标，我们将与Empact Network在 R33期，在3个时间点采集150名患者的血液样本 使用标准方法和新的氧化还原配方。使用高端组学进行分析 技术将产生信息丰富的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，并链接到通过Empact数据仓库被动捕获的临床数据，以 为脓毒症研究产生新的假说。最后，我们包括一项共享超低温保存标本的计划， 临床和分子数据与该机构的研究人员一起支持发现或假说驱动的研究 通过氧化还原生物和医学中心下的试点机制以及危重疾病、伤害和 研究恢复研究中心，分别由MPIS 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.