The Intermountain West-Atlantic Center (InterACT) for the APS Phenotyping Consortium

项目摘要 该提案介绍了山间西大西洋中心(InterAct)，该中心汇集了四个强大的 参与APS表型联盟的调查网站。InterAct建议使用Robust 急性呼吸窘迫综合征表型患者的统计和机器学习方法 (ARDS)、肺炎和脓毒症在两个广泛的提案中。在整个财团的第一个提案中，我们将 在标准化治疗轨迹的设置中使用多重细胞因子阵列和临床变量 通过考虑治疗所起的作用来提高表型的准确性。此方法创建 表型将在模拟临床试验中得到确认，着眼于治疗意义。在 中心的第二项建议具体而言，我们将把我们的统计方法集中在新的工作调查上 组织损伤和修复的模式，重点是透明质酸和晚期糖基化的可溶性受体 终产物(SRAGE)作为组织损伤生物标志物和失调炎症的预测因子。这项工作将 在对调节组织损伤的病理后果的新型制剂的模拟试验中达到高潮。 这些高度创新的提案共同承诺了可操作的、对治疗敏感的患者表型 未来的临床试验。

Project Summary This proposal presents the Intermountain West-Atlantic Center (InterACT), which brings together four robust investigative sites to participate in the APS Phenotypes Consortium. InterACT proposes to use robust statistical and machine learning methods to phenotype patients with Acute Respiratory Distress Syndrome (ARDS), pneumonia, and sepsis in two broad proposals. In the first proposal for the entire Consortium, we will use multiplex cytokine arrays and clinical variables in the setting of normalized treatment trajectories to improve the accuracy of phenotyping by accounting for the role treatment plays. This method creates phenotypes that will be confirmed, with an eye toward therapeutic implications, in emulated clinical trials. In the second proposal for the Center specifically, we will focus our statistical methodology on new work investigating the pattern of tissue injury and repair, with a focus on hyaluronan and soluble Receptor for Advanced Glycation Endproducts (sRAGE) as tissue injury biomarkers and predictors of dysregulated inflammation. This work will culminate in emulated trials of novel agents that modulate the pathologic consequences of tissue injury. Together these highly innovative proposals promise actionable, treatment-responsive patient phenotypes for future clinical trials.