Patient Oriented Research in Solid Organ Transplantation

以患者为中心的实体器官移植研究

基本信息

批准号：
10616265
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
项目类别：
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/10616265
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 Provider Publishing Research Research Personnel Risk Scientist Short Interspersed Nucleotide Elements 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 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

项目摘要

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.

概括美国目前有超过10万名患者等待实体器官移植，但器官不足以挽救这些患者免于等待名单上的死亡，安全地扩大捐赠者库，并最佳地匹配捐赠者。正确的接受者对于移植至关重要，申请人的首要目标是指导临床决策。实体器官移植的制定和政策，特别是在艾滋病毒等新型扩张的背景下受感染的捐赠者和接受者、活体捐赠标准的扩大以及免疫不相容。这是为移植手术医师、医学博士、哲学博士 Dorri Segev 颁发 K24 职业生涯中期研究者奖的续签提案约翰·霍普金斯大学的外科医生和流行病学家，已发表 422 篇论文并获得 4 项 NIH 荣誉在他的 12 年教职生涯中，获得了 R01 和 2 个 NIH U01 奖项。 K24 的前 5 年提供了受保护的时间。 Segev 医生需要指导 11 名住院医师、16 名医学生、5 名研究生和 14 名初级教师在令人兴奋、富有成效的多学科环境中，这些学员撰写了 141 篇第一作者论文； Segev 博士的直接指导，并获得 31 项 NIH/AHRQ 拨款和 13 项基金会拨款。利用 Segev 博士通过 NIH 资助创建的精心设计的队列和数据驱动工具研究，包括 (1) 将国家移植捐献者和受者登记数据与保险和药房声明；(2) 超过 5500 名活体肾脏捐赠者的纵向多中心研究；具有颗粒 HLA 的不相容活体肾移植可带来长期结果和生存获益超过 2000 名接受者及其捐赠者的抗体数据；以及 (4) 一项关于虚弱的前瞻性多中心研究，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素，涉及 5000 多个肾脏此外，此次更新还将利用 U01 资助的两名新患者。 HIV 至 HIV 肾移植和肝移植的研究，包括 HIV 相关并发症的测量， HIV 相关肾病的表征、HIV 重复感染的测量以及潜伏感染的HIV原病毒群体的大小和遗传组成。这些国家数据和大型多中心队列研究为辅助研究提供了丰富的基础具体而言，本次会议的新目标 K24 是：(1) 为了更好地了解接受移植肝的 HIV+ 患者的生存获益，使用通过处方填写 HIV 特异性药物来识别 LT 候补名单上的 HIV 患者的新颖联系 (2) 描述长期捐赠后 eGFR 轨迹以及与后续的关联活体肾脏捐献者的结果；（3）确定近期致敏患者的适当治疗方法已故捐赠者分配和肾脏交换的时代；(4) 扩大 Segev 博士指导的能力实体器官移植领域的下一代临床医生科学家。