Developing the Biobehavioral Foundation for Self-Management of Psychoneurological Symptoms in Hematopoietic Cell Transplant (HCT) Survivors

项目摘要/摘要 我们的长期目标是阐明导致患者痛苦症状的生物行为机制 造血细胞移植(HCT)幸存者靶向治疗的开发和实施 以提高这一患者群体的生活质量。由于治疗的进步，HCT正在成为一种 对于危及生命的血液病患者和幸存者人数来说，越来越可行的选择 正在增加。因此，生存问题，如神经认知功能障碍的痛苦症状，疲劳， 焦虑和抑郁症状，以及统称为“精神神经学”(PN)症状的疼痛是一种 这是个大问题。到目前为止，人们对影响PN的可疑的共同生物基础知之甚少 症状。炎症是多种慢性疾病中PN症状的一种普遍接受的机制， 包括癌症。肠道微生物区系的新证据，通过微生物区系-肠道-脑轴，作为潜在的途径 因为启动炎症反应可能导致创新战略，包括饮食和营养 减少炎症的策略。了解饮食和肠道微生物区系之间的相互作用 炎症和PN症状可能会提供信息，从而有针对性地制定自我管理策略 减轻HCT后患者的PN症状。本研究的具体目的是：1)评价研究 数据收集的可行性、研究程序的可接受性，包括招聘和保留 数据缺失，2)表征基线(14-7天前)的关联强度(影响大小 患者因素、PN症状、炎症、GM和饮食 3)估计关联(效应大小)和随时间变化的模型(入院前14-7天 接受HCT调理，在HCT后30天和100天)原因：a)患者因素和PN症状 炎症b)患者因素，PN症状和炎症C)患者因素，PN症状， 炎症和GM与饮食d)患者因素、饮食、GM和炎症与PN症状。要实现 这些目标，我们将纵向检查50名成年(&gt；18岁)HCT受者从 佛罗里达大学骨髓移植中心。我们将描述患者的因素(年龄、性别、种族、 种族、体重指数、生活习惯和临床因素(癌症诊断、调理方案、移植类型)； 全身性炎症(细胞因子和C反应蛋白)；肠道微生物区系(丰富性和多样性)；饮食 和PN症状(神经认知功能障碍、疲劳、焦虑、抑郁、 基线(HCT前两周或更短时间)、HCT后30天和100天)。最先进的 将使用技术来分析生物样本，创新的贝叶斯统计方法将 用来检验研究变量的模型。这方面的知识对于为开发 有针对性的饮食自我管理干预，以解决这一主要生存问题，并改善HCT患者的生活质量 收件人。

Project Summary/Abstract Our long-term goal is to elucidate biobehavioral mechanisms contributing to distressing symptoms in hematopoietic cell transplantation (HCT) survivors for the development and implementation of targeted therapies to improve quality of life (QOL) in this patient population. Due to treatment advances, HCT is becoming an increasingly viable option for individuals with life-threatening hematologic disorders and the number of survivors is increasing. Thus, survivorship issues such as distressing symptoms of neurocognitive dysfunction, fatigue, anxiety and depressive symptoms, and pain collectively labeled as “psychoneurologic” (PN) symptoms are a major issue. To date, little is known about the suspected shared biological underpinnings influencing PN symptoms. Inflammation is a generally accepted mechanism of PN symptoms in multiple chronic illnesses, including cancer. Emerging evidence of gut microbiota, via the microbiota-gut-brain-axis, as a potential pathway for the initiation of an inflammatory response may lead to innovative strategies, including diet and nutrition strategies to reduce inflammation. Understanding the interplay among diet and the gut microbiota with inflammation and PN symptoms may provide information leading to targeted self-management strategies to mitigate PN symptoms in individuals following HCT. The specific aims of this study are to: 1) Evaluate study feasibility of data collection, acceptability of study procedures including recruitment and retention, and missingness of data, 2) Characterize the strength of the associations (effect sizes) at baseline (14-7 days prior to hospital admission for HCT conditioning) among patient factors, PN symptoms, inflammation, GM and diet and 3) Estimate associations (effect sizes) and models for change over time (14-7 days prior to hospital admission for HCT conditioning, 30 and 100 days after HCT) for: a) Patient factors and PN symptoms with Inflammation b) Patient factors, PN symptoms and Inflammation with GM c) Patient factors, PN symptoms, Inflammation and GM with Diet d) Patient factors, Diet, GM and Inflammation with PN symptoms. To achieve these aims, we will longitudinally examine 50 adult (> 18 years of age) HCT recipients recruited from the University of Florida Bone Marrow Transplant Center. We will characterize patient factors (age, sex, race, ethnicity, BMI, lifestyle habits, and clinical factors [cancer diagnosis, conditioning regimen, type of transplant]); systemic inflammation (cytokines and C-reactive protein); gut microbiota (richness and diversity); diet (consumption of macronutrients); and PN symptoms (neurocognitive dysfunction, fatigue, anxiety, depression, and pain) at baseline (two weeks or less prior to HCT), 30 and 100 days following HCT. State-of-the-art technology will be used to analyze the biological samples and innovative Bayesian statistical methodologies will be used to test the models of the study variables. This knowledge is critical to provide a foundation for developing a targeted diet self-management intervention to address this major survivorship issue and improve QOL for HCT recipients.