Patient Oriented Research in Solid Organ Transplantation

以患者为中心的实体器官移植研究

• 批准号: 10582518
• 负责人: DORRY L. SEGEV
• 金额: $ 19.12万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582518
• 关键词: Ancillary Study; Antibodies; Area; Atmosphere; Award; Biological Markers; Clinical Research; Clinical Trials; Cohort Studies; Communication; Country; Data; Data Linkages; Doctor of Philosophy; Donor person; Educational Curriculum; Educational process of instructing; Environment; Epidemiologist; Evaluation; Faculty; Fellowship; First Name; Foundations; Funding; Genetic; Goals; Grant; HIV; Health; Immunologics; Impaired cognition; Individual; Infrastructure; Insurance; K-Series Research Career Programs; Kidney; Kidney Diseases; Kidney Transplantation; Leadership; Learning; Liver; Liver Fibrosis; Living Donors; Longitudinal Studies; Measurement; Medical Students; Mentors; Mentorship; Methodology; Modality; Modeling; Multicenter Studies; Operative Surgical Procedures; Organ; Organ Transplantation; Outcome; Paper; Patients; Pharmaceutical Preparations; Pharmacy facility; Physicians; Policies; Population; Positioning Attribute; Process; Productivity; Provider; Publishing; Research; Research Personnel; Risk Marker; Scientist; Solid; Structure; Surgeon; System; Time; Training; Transplant Recipients; Transplant Surgeon; Transplantation; Transplantation Surgery; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; Universities; Waiting Lists; Writing; career; clinical decision-making; cohort; data registry; design; evidence base; fatty liver disease; frailty; graduate student; health literacy; improved; liver transplantation; living kidney donor; mortality; multidisciplinary; next generation; novel; organ transplant recipient; patient oriented research; post-transplant; prospective; public health relevance; superinfection; tool; Ancillary Study; Antibodies; Area; Atmosphere; Award; Biological Markers; Clinical Research; Clinical Trials; Cohort Studies; Communication; Country; Data; Data Linkages; Doctor of Philosophy; Donor person; Educational Curriculum; Educational process of instructing; Environment; Epidemiologist; Evaluation; Faculty; Fellowship; First Name; Foundations; Funding; Genetic; Goals; Grant; HIV; Health; Immunologics; Impaired cognition; Individual; Infrastructure; Insurance; K-Series Research Career Programs; Kidney; Kidney Diseases; Kidney Transplantation; Leadership; Learning; Liver; Liver Fibrosis; Living Donors; Longitudinal Studies; Measurement; Medical Students; Mentors; Mentorship; Methodology; Modality; Modeling; Multicenter Studies; Operative Surgical Procedures; Organ; Organ Transplantation; Outcome; Paper; Patients; Pharmaceutical Preparations; Pharmacy facility; Physicians; Policies; Population; Positioning Attribute; Process; Productivity; Provider; Publishing; Research; Research Personnel; Risk Marker; Scientist; Solid; Structure; Surgeon; System; Time; Training; Transplant Recipients; Transplant Surgeon; Transplantation; Transplantation Surgery; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; Universities; Waiting Lists; Writing; career; clinical decision-making; cohort; data registry; design; evidence base; fatty liver disease; frailty; graduate student; health literacy; improved; liver transplantation; living kidney donor; mortality; multidisciplinary; next generation; novel; organ transplant recipient; patient oriented research; post-transplant; prospective; public health relevance; superinfection; tool

Summary Over 100,000 patients in the US currently await solid organ transplantation, with inadequate organs to save these patients from waitlist mortality. Safely expanding the donor pool, and optimally matching donors to the right recipient, is essential to transplantation. The overarching goal of the applicant is to guide clinical decision- making and policy in solid organ transplantation, particularly in the context of novel expansions such as HIV- infected donors and recipients, expanded criteria for living donation, and immunological incompatibility. This is a renewal proposal for a K24 Midcareer Investigator Award for Dorry Segev, MD, PhD, a transplant surgeon and epidemiologist at Johns Hopkins University who has published 422 papers and received 4 NIH R01 and 2 NIH U01 awards in his 12 years on faculty. The first 5 years of this K24 provided the protected time that Dr. Segev needed to mentor 11 residents, 16 medical students, 5 graduate students, and 14 junior faculty in an exciting, productive multidisciplinary environment; these mentees wrote 141 first-authored papers under Dr. Segev’s direct mentorship, and received 31 NIH/AHRQ grants and 13 foundation grants. This renewal will leverage carefully designed cohorts and data-driven tools that Dr. Segev has generated through NIH-funded studies, including (1) a linkage of national transplant donor and recipient registry data to insurance and pharmacy claims; (2) a longitudinal multicenter study of over 5500 living kidney donors; (3) multicenter study of long-term outcomes and survival benefit from incompatible live donor kidney transplantation, with granular HLA and antibody data on over 2000 recipients and their donors; and (4) a prospective multicenter study of frailty, health literacy, cognitive dysfunction, biomarkers, and other novel risk predictors, with over 5000 kidney transplant and 2000 liver transplant patients. In addition, this renewal will leverage two new U01-funded studies of HIV-to-HIV kidney and liver transplantation, including measurement of HIV-related complications, characterization of HIV-related kidney disease, measurement of HIV superinfection, and examination of the size and genetic composition of the latently infected HIV proviral population. These national data and large multicenter cohort studies provide rich substrate for ancillary studies by mentees, as well as many opportunities for advanced methodologic training. Specifically, the new aims of this K24 are: (1) to better understand survival benefit in HIV+ patients undergoing liver transplantation, using a novel linkage to identify patients with HIV on the LT waitlist by prescription fills of medications specific to HIV treatment; (2) to characterize long-term post-donation eGFR trajectories and associations with subsequent outcomes in living kidney donors; (3) to identify the appropriate treatment for sensitized patients in the recent era of deceased donor allocation and kidney exchange; and (4) to expand Dr. Segev’s capacity to mentor the next generation of clinician-scientists in solid organ transplantation.

概括 美国目前有100,000多名患者正在等待固体器官移植，并且器官不足以保存 这些患者来自等待名单死亡率。安全地扩展供体池，并最佳地匹配捐助者 正确的接受者，对于移植至关重要。申请人的总体目标是指导临床决策 - 固体器官移植中的制定和政策，特别是在新的扩张的背景下，例如HIV- 受感染的捐助者和接受者，扩大生活捐赠的标准以及免疫学不相容。 这是K24中级职业研究员Dorry Segev，MD，PhD的续签提案， 约翰·霍普金斯大学（Johns Hopkins University）的外科医生和流行病学家，曾发表422篇论文并收到4份NIH R01和2 NIH U01在他担任教职员工的12年中颁奖。该K24的前5年提供了受保护的时间 Segev博士需要指导11名居民，16名医学生，5名研究生和14名初级教师 在令人兴奋的产品多学科环境中；这些受训者在 Segev博士的直接精神训练，并获得了31名NIH/AHRQ补助金和13个基金会赠款。这个更新的意愿 利用Segev博士通过NIH资助生成的精心设计的队列和数据驱动工具 研究，包括（1）国家移植捐赠者和接收者注册表数据与保险和 药房主张； （2）一项超过5500个活肾脏供体的纵向多中心研究； （3）多中心研究 不兼容的活供体肾移植带有颗粒HLA的长期结局和生存受益 以及有关2000多名接受者及其捐助者的抗体数据； （4）一项预期的多中心研究， 健康素养，认知功能障碍，生物标志物和其他新型风险预测因子，有5000多个肾脏 移植和2000个肝移植患者。此外，此续约将利用两个新的U01资助 HIV至HIV肾脏和肝移植的研究，包括测量与HIV相关并发症的测量 艾滋病毒相关肾脏疾病的表征，艾滋病毒近次感染的测量和检查 潜在感染的HIV病毒种群的大小和遗传组成。 这些国家数据和大型多中心队列研究为通过 Menees，以及许多高级方法论培训的机会。具体而言，新目标 K24是：（1）更好地了解接受肝移植的HIV+患者的生存益处 通过处方填充艾滋病毒的药物，在LT候补名单上识别HIV患者的新型联系 治疗; （2）表征长期演讲后EGFR轨迹和随后的关联 活肾脏捐赠者的结果； （3）在最近的 已故捐赠者分配和肾脏交换的时代； （4）扩大Segev博士指导的能力 固体器官移植中的下一代临床科学家。