Developing strategies for effective debridement in patients for venous leg ulcers

制定对腿部静脉溃疡患者进行有效清创的策略

• 批准号: 10311083
• 负责人: Robert Scott Kirsner
• 金额: $ 53.47万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311083
• 关键词: Biological; Biological Markers; Biopsy; Bone callus; CAV1 gene; Candidate Disease Gene; Caring; Cell Therapy; Cells; Characteristics; Chronic; Clinic; Clinical; Clinical Data; Clinical Trials; Coupled; Data; Debridement; Development; Diabetic Foot Ulcer; Diagnostic tests; Epidermal Growth Factor Receptor; Evaluation; Exhibits; GATA3 gene; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; Genetic Transcription; Genomic approach; Genomics; Goals; Growth Factor; Histopathology; Hypertrophy; Impaired healing; Individual; Intervention; Leg Ulcer; Messenger RNA; Methods; Molecular; Morbidity - disease rate; Morphology; Operative Surgical Procedures; Outcome; Patients; Pattern; Phenotype; Procollagen; Proteins; Protocols documentation; Randomized Clinical Trials; Research; Role; Specialist; Specimen; Stimulus; Subgroup; Testing; Therapeutic; Tissues; Treatment Cost; Venous; acute wound; base; beta catenin; c-myc Genes; compression therapy; diagnostic tool; efficacy testing; genomic profiles; healing; improved; intervention cost; migration; minimally invasive; mortality; point-of-care diagnostics; post intervention; protein expression; response; skin fibrosis; skin ulcer; standard of care; tool; transcriptome sequencing; treatment arm; wound; wound bed; wound care

Project Summary The goal of this research is to use gene and protein expression patterns to develop point of care diagnostic tool that can serve as a guiding tool to optimize debridement for non-healing venous leg ulcers (VLUs). Thus, it will identify objective and reliable biomarkers that will guide wound practitioners to make informed decision when wound edge debridement is adequate. We have shown that biopsies obtained from the non- healing edges of VLUs before/after debridement have distinct morphologies and distinguishable gene and protein expression patterns. Cells generated from pre-debridement edge biopsies exhibit a non-healing phenotype as evidenced by loss of migration and loss of ability to respond to growth factors, suggesting a loss of healing potential whereas cells genrated from post-debridement biopsy are migratiory and responsive to growth factors. Some clinical data show a positive response in VLUs wound size reduction following wound bed debridemet. However, wound bed debridement is not always considered standard of care for VLUs. Therefore we aim to compare effectivnes of two therapeutic approaches: standard of care (i.e. compression therapy) and wound bed debridement coupled to standard of care. The intervention arm will consit of two subgroups, a) one that utilizes gene/protein expression-guidaded debridement protocol, and b) uses standard clinical debridement protocol for VLUs. We hypothesize that gene/protein expression patterns can be utilized to guide wound edge debridement in VLUs and further that such biomarker-guided debridement will improve healing outcome in patients suffering from chronic non-healing VLUs. Also, based on genomic profiles we plan to develop specific PCR- and immunostain-based methods to serve as a simplified diagnostic test to guide the extent of debridment. Thus, we will conduct a randomized clinical trial to test if gene expression patterns can be utilized as a guiding tool for the debridement extent and to test the effect of wound edge debridement on healing progression (Aim 1) and develop PCR- and/or immunostain-based complementary assessment method and validate it for guiding surgical debridement (Aim 2). We will proceed with genomic profiling and compare gene expression patterns of specimens obtained before and after debridement. Next, expression patterns will be correlated with healing outcomes comparing patients with wounds that progressed to healing with those that did not at 4 weeks post intervention. The proposed study is the first step in incorporating gene/protein wound signatures as a clinical tool. Successful completion of this study will provide objective biological markers to guide wound edge debridement in patients suffering from VLUs. Incorporation of molecular tools into armory of intervention will result in a paradigm shift that will alter the course of healing, decrease morbidity, mortality, and lower associated treatment costs.

项目摘要 本研究的目的是利用基因和蛋白质表达模式来开发护理点诊断 该工具可作为指导工具，用于优化不愈合下肢静脉溃疡（VLU）的清创术。 因此，它将确定客观和可靠的生物标志物，这将指导伤口从业者作出知情的 决定何时进行伤口边缘清创术。我们已经证明，从非- 清创前后VLU的愈合边缘具有不同的形态和可区分的基因， 蛋白质表达模式。从清创前边缘活检产生的细胞表现出不愈合 表型的丧失，表现为迁移能力的丧失和对生长因子反应能力的丧失，表明 而从清创后活检产生的细胞是迁移性的， 生长因子一些临床数据显示，创伤后VLU伤口尺寸缩小有积极反应 床上清创。然而，伤口床清创术并不总是被认为是VLU的护理标准。 因此，我们的目的是比较两种治疗方法的有效性：标准治疗（即压迫 治疗）和结合标准护理的创床清创术。干预机构将由两个 亚组，a）利用基因/蛋白质表达指导的清创方案，和B）使用标准的 VLU的临床清创方案。我们假设基因/蛋白质表达模式可以用于 以引导VLU中的伤口边缘清创术，并且进一步地，这种生物标记引导的清创术将改善 慢性非愈合性VLU患者的愈合结果。此外，根据基因组图谱，我们计划 开发特异性PCR和免疫染色方法，作为一种简化的诊断测试，以指导 清创程度。因此，我们将进行一项随机临床试验，以测试基因表达模式是否可以 用作清创范围的指导工具，并测试伤口边缘清创对 愈合进展（目标1），并开发基于PCR和/或免疫染色的补充评估 方法，并验证其用于指导外科清创术（目标2）。我们将继续进行基因组分析， 比较清创前后标本的基因表达模式。接下来，表达式 模式将与愈合结果相关，比较伤口进展至愈合的患者 与干预后4周未接受治疗的受试者进行比较。这项拟议中的研究是将 基因/蛋白质伤口签名作为临床工具。成功完成本研究将提供客观的 用于指导患有VLU的患者的伤口边缘清创的生物标记物。掺入 分子工具进入干预军械库将导致一个范式转变，这将改变疗愈的过程， 降低发病率、死亡率和相关治疗费用。