Biomarkers for pressure injury risk following spinal cord injury: Development of a multi-scalar predictive model for personalized preventive health care

脊髓损伤后压力性损伤风险的生物标志物：开发用于个性化预防保健的多标量预测模型

• 批准号: 10043836
• 负责人: KATH BOGIE
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043836
• 关键词: 3-Dimensional; Activities of Daily Living; Address; Adipose tissue; Affect; Anterior; Area; Automobile Driving; Biological Assay; Biological Markers; Blood; Blood Tests; Blood specimen; Candidate Disease Gene; Caregivers; Caring; Cessation of life; Classification; Clinical; Cohort Studies; Complication; DNA; Data; Deposition; Development; Dose; Drug or chemical Tissue Distribution; Early identification; Exclusion Criteria; Exhibits; Freezing; Genes; Genetic; Genetic Markers; Genetic Variation; Head; Health; Health Care Costs; Health Status; Health behavior; Hospitalization; Image; Incidence; Individual; Inferior; Inflammation; Institutes; Intramuscular; Investigation; Measures; Medical center; Metabolism; Modeling; Monitor; Muscle; Output; Participant; Pelvis; Performance; Persons; Phase; Prevention; Preventive healthcare; Procedures; Process; Protocols documentation; Quality Control; Quality of life; Questionnaires; Recording of previous events; Recurrence; Research; Research Design; Risk; Risk Assessment; Risk Factors; Sacral vertebra structure; Sacroiliac joint structure; Sampling; Scanning; Site; Skin; Slice; Spinal cord injury; Standardization; Supination; Surveys; Systemic disease; Telephone; Testing; Thinness; Time; Tissues; Underrepresented Populations; Update; Validation; Variant; Veterans; Whole Blood; X-Ray Computed Tomography; base; biomarker validation; clinically significant; cohort; cost; decubitus ulcer; early detection biomarkers; economic cost; genetic profiling; genome analysis; improved; next generation sequencing; personalized care; predictive modeling; pressure; programs; reconstruction; recruit; tool

Pressure injures (PrI) are a major secondary complication for far too many people with spinal cord injury (SCI). Development and/or recurrence of a PrI limits activities of daily living, often leading to hospitalization and even death. In addition to the devastating impact on affected individuals and their caregivers, PrI management has a significant effect on Veterans Heath Administration healthcare costs, which provides lifetime care for our Veterans with SCI. The proposed study will address the conundrum of why some Veterans with SCI suffer from a continuous cycle of recurring PrI, while others remain PrI free. The research strategy will build on the model developed by the Bogie lab of Biomarkers for Early Identification of Pressure Injury Risk (BEIPIR) for persons with SCI. BEIPIR unifies hierarchical relationships between clinical factors, health behaviors and muscle composition. We have shown that intramuscular adipose tissue (IMAT) is a critical clinically significant risk factor for PrI development. IMAT levels and accumulation rates vary greatly in this cohort. Some people exhibit rapid IMAT accumulation following SCI, while others do not. It is important to explain what is driving these changes. Our preliminary findings provide the basis for the central hypothesis: DNA variants predispose some individuals to increased deposition of IMAT following SCI, and resultant increased PrI risk. The proposed study will update the BEIPIR model by examining IMAT in conjunction with investigation of DNA variants associated with accelerated and/or higher levels of IMAT deposition. The TruSight™ One Expanded Sequencing panel (Illumina, San Diego CA) will be applied for Next Generation Sequencing of 50 existing blood samples from 38 persons with complete or incomplete SCI (AIS A-D) for whom gluteal muscle composition over time has already been evaluated. Genetic profile information, specifically DNA variants which are differentially active between persons with and without a history of PrI at a statistically significant level of p<0.05, will be selected and incorporated into the multi-scalar BEIPIR model for early identification of PrI risk. The updated BEIPIR model will be internally and externally validated to establish predicative efficacy. Internal validation of the BEIPIR model will be provided by testing the model with the genetic biomarkers identified. Split bootstrap procedures will be employed in order to derive stable estimations with low bias. A four year repeated measures study will be carried out to externally validate the BEIPIR model. A stratified study design will be employed to achieve a study cohort of 100 Veterans with SCI (AIS A-D) including participants with and without a history of PrI. Study participants will be recruited from Louis Stokes Cleveland VA Medical Center and the James J. Peters VA Medical Center (Site PI: Dr. Galea). Whole blood will be collected from study participants and DNA extracted prior to processing using the TruSight™ One Expanded Sequencing panel. Very low dose transverse pelvic region CT scans with contrast will be carried out based on our established protocol. Muscle composition and cross-sectional area will be determined using our established Hounsfield Unit scale classification protocol to determine relative lean muscle and IMAT content. 3D reconstruction will be applied to show IMAT distribution throughout the muscle. Study participants will be surveyed monthly by phone using our standardized skin status questionnaire to determine tissue health status. Incidences of tissue compromise or breakdown will be monitored and data applied to refine the BEIPIR model. Blood draw and CT scans will be repeated annually or when a PrI occurs. Longitudinal repeated measures of the de novo study cohort will be used to evaluate BEIPIR model performance and provide external validation of the model. Update and validation of the BEIPIR model will provide a clinical tool to optimize personalized care, recognizing that every person with SCI is an individual. Our proposed study has great potential to improve PrI risk assessment, enhance health status and quality of life for Veterans with SCI and reduce VHA costs. In the longer term, the BEIPIR model may provide the basis for development of a blood test kit for PrI risk. This research will also expand the de-identified genetic data publicly available for this underrepresented population.

压力性损伤(PRI)是太多脊髓损伤(SCI)患者的主要继发性并发症。 PRI的发展和/或复发限制了日常生活活动，通常导致住院甚至 死亡。除了对受影响的个人及其照顾者造成的破坏性影响外，PRI管理层还 显著影响退伍军人健康管理局的医疗成本，为我们的 患有SCI的退伍军人。这项拟议的研究将解决为什么一些患有脊髓损伤的退伍军人患有 持续循环的PRI，而其他的则保持无PRI。研究策略将建立在模型的基础上 由Bogie生物标记物实验室开发，用于人员压力损伤风险的早期识别(BEIPIR) 和SCI一起。BEIPIR统一了临床因素、健康行为和肌肉之间的等级关系 组成。我们已经证明，肌肉内脂肪组织(IMAT)是一个重要的临床危险因素。 用于PRI开发。IMAT水平和积累率在这组人群中差异很大。有些人表现得很快 脊髓损伤后的IMAT积聚，而其他的则不是。重要的是要解释是什么在推动这些变化。 我们的初步发现为中心假说提供了基础：DNA变异倾向于某些个体 脊髓损伤后IMAT沉积增加，导致PRI风险增加。拟议的研究将更新 通过检查IMAT和研究与以下相关的DNA变异来建立BEIPIR模型 加速和/或更高水平的IMAT沉积。TruSight™One扩展测序面板(Illumina， 加州圣地亚哥)将对38个人的50个现有血液样本进行下一代测序 伴有完全性或不完全性脊髓损伤(AISA-D)，随着时间的推移，臀肌成分已经 已评估。遗传概况信息，特别是在人与人之间具有不同活性的DNA变体 具有和不具有P&lt；0.05统计显著水平的PRI的历史将被选择并纳入 用于早期识别PRI风险的多标度BEIPIR模型。更新的BEIPIR模型将在内部和 外部验证以建立预测性疗效。BEIPIR模型的内部验证将由 用识别出的遗传生物标记物测试模型。将采用拆分引导程序，以便 得出具有低偏差的稳定估计。将对外部进行为期四年的重复措施研究 验证BEIPIR模型。将采用分层研究设计，以实现100名退伍军人的研究队列 有脊髓损伤(AIS A-D)的参与者包括有和没有PRI病史的参与者。研究参与者将从以下地点招募 路易斯·斯托克斯克利夫兰退伍军人医疗中心和詹姆斯·J·彼得斯退伍军人医疗中心(网站：Dr.Galea)。 将从研究参与者身上采集全血，并在使用TruSight™进行处理之前提取DNA 一个扩展的测序面板。将进行极低剂量的盆腔横断CT增强扫描 根据我们已制定的协议。肌肉成分和横截面积将使用我们的 建立了Hounsfield单位量表分类方案，以确定相对瘦肉和IMAT含量。3D 将进行重建以显示IMAT在肌肉中的分布。研究参与者将是 每月通过电话进行调查，使用我们的标准化皮肤状况问卷来确定组织的健康状况。 将监测组织受损或破裂的发生率，并应用数据来完善BEIPIR模型。 每年或当PRI发生时，将重复抽血和CT扫描。纵向重复测量 新的研究队列将用于评估BEIPIR模型的性能，并提供外部验证 模特。BEIPIR模型的更新和验证将提供优化个性化护理的临床工具， 认识到每一个SCI患者都是一个个体。我们提议的研究具有提高PRI的巨大潜力 风险评估，提高SCI退伍军人的健康状况和生活质量，降低VHA成本。在 从长远来看，BEIPIR模型可能会为PRI风险血液检测试剂盒的开发提供基础。这 研究还将扩大为这一代表性不足的人群公开提供的未识别的基因数据。