Diabetic Foot Ulcer Wound Fluid Biomarker

CDC 2020年全国糖尿病统计报告指出，3420万美国人，即10.5%的美国人 2018年人口患有糖尿病。据估计，在他们的一生中，多达三分之一的人 患有糖尿病的人会发展成糖尿病足溃疡(DFU)。五年死亡率和人们护理的直接成本 糖尿病足的并发症与癌症相当。约40%-60%的非创伤性肢体 世界各地的截肢手术都是由糖尿病并发症引起的，其中80%的截肢手术是在DFU之后进行的。在……里面 患有难以治愈的DFU的患者，通常需要采用多种治疗方法来管理顽固 伤口。当前的DFU治疗算法使用四次失败后改善(&gt；50%伤口面积减少) 数周的标准护理(SOC)治疗，以做出改变治疗的临床决定。缺乏 目的创面愈合结果的早期指标阻碍了DFU的护理策略。生物标志物可以预测非 治愈(即SOC的难治性)将为合理采用替代治疗提供客观依据 及时向伤口护理人员提供养生方案。这项提议基于我们的前提，即无法治愈的糖尿病患者 伤口会遭受代谢损伤，而代谢损伤又会通过代谢产物的变化反映出来。 包含在伤口液(WF)中。使用代谢组学方法从161名WF中筛选出578种代谢物 来自慢性伤口患者。在所有这些代谢物中，有一个参数是非 愈合：低半胱氨酸(Cys)/半胱氨酸(CysS)。一项对24例DFU患者的前瞻性初步研究显示 WF中低的Cys/CysS预示着无法愈合。医疗点微量试板(标准医院化验平台) 采用基于实验的测试方法。因为拟议的工作旨在将半胱氨酸氧化还原确立为非 无论是愈合还是开放创伤，这项研究被命名为CREDO。R61准备阶段被命名为2CREDO(朝向 CREDO)，R33阶段称为CREDO。目的1：验证DFU创面液低半胱氨酸/半胱氨酸的使用 Ratio(&lt；3.43截断值)作为预测DFU无法愈合的主要生物标志物。目标2：建立一个完整的临床 验证伤口液中Cys/CysS比率预测成人DFU愈合的方案。目标3：行为 一项对糖尿病足溃疡患者进行伤口液详细验证的多中心临床研究 Cys/CysS比值作为预测糖尿病足溃疡愈合的生物标志物。目标4：发起与FDA的讨论以 建立Cys/CysS作为预测DFU愈合的临床生物标志物。拟议的工作将按以下方式进行 目前NIDDK糖尿病足联盟(DFC)已批准我们的可行性的辅助研究 协议。

The 2020 CDC national diabetes statistics report identified that 34.2 million Americans, or 10.5% of the population had diabetes in 2018. It is estimated that over the course of their lifetime up to a third of these people with diabetes will develop a diabetic foot ulcer (DFU). The five-year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. Approximately 40-60% of nontraumatic lower limb amputations worldwide are caused by diabetic complications, and 80% of these amputations follow DFU. In patients with hard-to-heal DFUs, treatment with multiple therapies is often necessary to manage stubborn wounds. The current DFU treatment algorithm uses failure to improve (>50% wound area reduction) after four weeks of standard of care (SoC) therapy to make a clinical decision on changing the therapy. The lack of objective early indicators of wound healing outcomes handicaps DFU care strategy. Biomarkers that predict non- healing (i.e., refractory to SoC) would provide an objective basis for rationally adopting alternate treatment regimen to wound care providers in a timely manner. This proposal rests on our premise that non-healing diabetic wounds would suffer from metabolic impairments which in turn would be reflected by changes in metabolites contained in wound fluids (WF). A metabolomics approach was used to screen 578 metabolites from 161 WF from chronic wound patients. Of all these metabolites, ONE PARAMETER emerged as a robust predictor of non- healing: low Cysteine (Cys)/Cystine (CysS). A prospective preliminary study on DFU patients (N=24) showed that low Cys/CysS in WF predicts non-healing. A point-of-care microtiter-plate (standard hospital assay platform) based test was used. Because the proposed work seeks to establish Cysteine Redox as a biomarker of non- healing or Open wound, the study is named CREDO. The R61 preparatory phase is named 2CREDO (towards CREDO), and the R33 phase is referred to as CREDO. Aim 1: Validate the use DFU wound fluid low Cys/CysS ratio (<3.43 cut-off) as a primary biomarker to predict non-healing of DFU. Aim 2: Develop a complete clinical protocol to validate the use of Cys/CysS ratio in wound fluids to predict the healing of adult DFU. Aim 3: Conduct a multi-center clinical study of diabetic foot ulcer patients to perform detailed validation of wound fluid based Cys/CysS ratio as a biomarker to predict diabetic foot ulcer healing. Aim 4: Initiate discussions with FDA to establish Cys/CysS as a clinical biomarker to predict DFU healing. The proposed work will be conducted as ancillary Study of the current NIDDK Diabetic Foot Consortium (DFC) who have approved feasibility of our protocol.