The Impact of Frailty on Liver Transplant Outcomes in Older Adults with Hepatocellular Carcinoma

虚弱对老年肝细胞癌肝移植结果的影响

• 批准号: 10570786
• 负责人: Jennifer C. Lai
• 金额: $ 18.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570786
• 关键词: Acceleration; Accounting; Adipose tissue; Age; Aging; Alzheimer' s disease risk; Award; Cancer Etiology; Caring; Categories; Cessation of life; Chronic; Chronology; Cirrhosis; Classification; Clinical; Clinical Research; Communities; Data; Data Set; Databases; Decision Making; Dedications; Discipline; Disease; Dropout; Educational Curriculum; Elderly; Eligibility Determination; Endowment; Ensure; Exclusion; Faculty; Financial Support; Funding; Gastroenterology; Geriatrics; Habilitation; Health; Hepatology; Hospitalization; Impaired cognition; Improve Access; Industry; Infrastructure; Intervention; Intuition; Knowledge; Laboratories; Leadership; Liver; Liver Failure; Liver diseases; Living Donor Liver Transplantation; MRI Scans; Measurement; Medical; Medicine; Mentors; Mentorship; Modeling; Muscle; Natural History; Older Population; Oncology; Operative Surgical Procedures; Organ; Organ Transplantation; Outcome; Pathway interactions; Patients; Pattern; Perioperative; Physiological; Population; Positioning Attribute; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Quality of life; Recurrence; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Risk Assessment; Risk Factors; Role; Severity of illness; Skeletal Muscle; Solid; Stage at Diagnosis; Standardization; Structure; Surgical Specialties; Testing; Time; Training; Transplant Recipients; Transplantation; Tumor Burden; Waiting Lists; Work; abdominal CT; age effect; aging demographic; aging demography; alpha-Fetoproteins; career; career development; chronic liver disease; cohort; comorbidity; curative treatments; demographics; disability; experience; fitness; frailty; functional status; human old age (65+); improved; indexing; interest; liver function; liver transplantation; mid-career faculty; mortality; muscle form; next generation; novel; patient oriented; patient oriented research; post-transplant; prognostic; programs; skill acquisition; skills; transplant centers; tumor progression

PROJECT ABSTRACT I am a transplant hepatologist on faculty as Associate Professor of Medicine in the Division of Gastroenterology & Hepatology, who has developed a nationally recognized clinical research program focused on the application of aging research and geriatric principles of care to the management of patients with cirrhosis awaiting and undergoing liver transplantation. Support for my current activities involving aging research and mentorship include a diverse pool of resources: 1) a NIA R01 to understand the role of frailty on global functional health in patients after liver transplantation, 2) a NIA R21 to develop a laboratory frailty index for patients with cirrhosis, 3) a NIA supplement to characterize cognitive impairment and Alzheimers Disease risk factors in liver transplant recipients, 4) several industry-supported investigator-initiated studies to evaluate aging-related factors in cirrhosis patients, 5) philanthropy-supported research in patients with chronic liver disease, and 6) an endowed professorship. My research grants leverage the data and infrastructure of the Functional Assessment in Liver Transplantation (FrAILT) Study, which I founded in 2012 and is currently the largest cohort worldwide dedicated to investigating the effect of aging—both chronologic (i.e., age) and physiologic (i.e., frailty)—on outcomes in patients with cirrhosis. For the new research proposed in this K24, I will expand my research program to older adults with hepatocellular carcinoma (HCC) who are eligible for liver transplantation by enriching our current data with granular HCC metrics and additional aging-related metrics to: characterize distinct groups of patients by frailty trajectories and identify novel predictors of frailty trajectory group membership (Aim 1), and investigate the association between frailty trajectories and waitlist dropout (Aim 2) or post-transplant global functional health (Aim 3). In so doing, I will create a unique multi-center dataset that is representative of the U.S. HCC population and combines aging-, liver-, HCC-, and transplant-related factors that will not only expand my research portfolio but also enable me to train new mentees interested in pursuing patient-oriented research at the intersection of aging research, hepatology, oncology, and transplantation. This scientific proposal leverages my current skills, clinical and research knowledge, and my established cohort to offer me the opportunity to develop new research skills and approaches in this under-studied population of older adults with HCC awaiting and undergoing liver transplantation. During this K24, I plan additional training in professional leadership and mentorship skills development, and will create for my mentees a formal research/career curriculum to ensure a structured and sustainable mentoring program for years to come. Given my own career as a medical subspecialist (hepatology) in a surgically-oriented discipline (transplant) with long-standing intellectual and financial support from the geriatric and aging research communities, I am particularly well-positioned to support trainees and early stage investigators in medical and surgical subspecialties who can further promote aging research and geriatric principles of care within their subspecialities.

项目摘要 我是胃肠病学系副教授的教师的移植肝病学家 ＆Hepatology，他开发了一项针对该应用的全国认可的临床研究计划 衰老研究和老年护理原理，肝硬化患者的管理等待和 接受肝移植。支持我当前涉及衰老研究和精神训练的活动 包括潜水员资源库：1）NIA R01了解脆弱的作用在全球功能健康中的作用 肝移植后的患者，2）A NIA R21为肝硬化患者开发实验室脆弱指数， 3）肝移植中认知障碍和阿尔茨海默氏病风险因素的NIA补充 接受者，4）几项行业支持的研究者发起的研究，以评估与衰老相关的因素 肝硬化患者，5）在慢性肝病患者中慈善研究的研究和6） 教授职位。我的研究授予了肝脏功能评估的数据和基础架构 我于2012年成立的移植（Frailt）研究目前是全球最大的队列 调查衰老的影响（年龄（即年龄）和生理学（即脆弱））的结果 肝硬化患者。对于此K24中提出的新研究，我将把我的研究计划扩展到较旧 患有肝细胞癌（HCC）的成年人通过丰富我们的当前数据有资格进行肝移植 具有颗粒状HCC指标和其他与衰老相关的指标：以：通过 脆弱的轨迹并确定弱势轨迹群体成员资格的新颖预测指标（AIM 1），并研究 脆弱的轨迹与候补辍学（AIM 2）或移植后全球功能健康之间的关联 （目标3）。这样，我将创建一个独特的多中心数据集，该数据集代表美国HCC人群 并结合衰老，肝，HCC和移植相关的因素，不仅会扩大我的研究组合 但也使我能够训练有兴趣在与患者进行研究的新月 衰老研究，肝病学，肿瘤学和移植。这项科学建议利用了我当前的技能， 临床和研究知识，以及我既定的队列，为我提供了开发新研究的机会 在这一研究不足的老年人中，HCC等待和肝脏的技能和方法 移植。在此K24期间，我计划在专业领导和精神技能方面进行其他培训 开发，并将为我的改装创建正式的研究/职业课程，以确保结构化和 可持续的心理计划已有几年。鉴于我自己作为医学专科医生（Hepatology）的职业 在以外科手术为导向的学科（移植）中，并具有长期的智力和财政支持 老年和老化的研究社区，我在支持培训和早期阶段特别有利 可以进一步促进衰老研究和老年医学和外科手术的研究人员 其亚科中的护理原则。