Red Cell Transfusion, Severe Anemia and Necrotizing Enterocolitis

红细胞输注、严重贫血和坏死性小肠结肠炎

• 批准号: 9109818
• 负责人: Ravi Mangal Patel
• 金额: $ 16.62万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9109818
• 关键词: Adverse effects; Affect; Amines; Anemia; Biometry; Birth; Blood; Blood Banks; Blood Flow Velocity; Blood Transfusion; Blood Vessels; Blood donor; Bronchopulmonary Dysplasia; Caring; Case Fatality Rates; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Cohort Studies; Complex; Complication; Coupled; Data; Data Analyses; Development; Diet; Disease; Emergency Situation; Enrollment; Epidemiology; Erythrocyte Transfusion; Erythrocytes; Etiology; Evaluation; Event; Exposure to; Funding; Goals; Healthcare; Incidence; Infant; Infection; Inflammatory disease of the intestine; Intervention; Intestines; Knowledge; Lactobacillus casei rhamnosus; Master of Science; Measures; Medicine; Mentors; Mesentery; Meta-Analysis; Methodology; Methods; Monitor; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Near-Infrared Spectroscopy; Necrosis; Necrotizing Enterocolitis; Neonatal; Neonatal Mortality; Observational Study; Onset of illness; Pathogenesis; Physiological; Premature Infant; Prevention strategy; Preventive Intervention; Preventive therapy; Probiotics; Production; Prospective Studies; Public Health; Relative Risks; Relaxation; Reporting; Research; Research Personnel; Research Training; Resources; Retinopathy of Prematurity; Risk; Risk Factors; Role; Stratification; Subgroup; Symptoms; Testing; Transfusion; United States; United States National Institutes of Health; Ursidae Family; Very Low Birth Weight Infant; aged; career; clinical investigation; cohort; cost; design; effective therapy; experience; gastrointestinal; high risk; improved; metabolomics; modifiable risk; mortality; neonatal care; neonatal morbidity; novel; patient oriented research; premature; prevent; probiotic therapy; prospective; public health relevance; skills; therapy development; treatment effect

 DESCRIPTION (provided by applicant): Transfusion Related Necrotizing Enterocolitis in Premature Infants Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality with a poorly understood pathogenesis. The disease is characterized by the rapid development of intestinal inflammation, often leading to intestinal necrosis. Currently, there is n safe and effective treatment to prevent NEC. Multiple recent studies have identified red blood cell (RBC) transfusion, a common therapy in very low birth weight (VLBW) premature infants for the treatment of anemia, as an important risk factor and potential causative factor in the development of NEC. While a compelling factor in the etiology of NEC, the clinical determinants of RBC transfusion-related NEC remain poorly understood. The applicant, Dr. Ravi Mangal Patel, will bring to bear expertise from national leaders in transfusion medicine (primary mentor: Dr. Cassandra Josephson), neonatal medicine (co-mentor: Dr. David Carlton) and necrotizing enterocolitis (co-mentor: Dr. Patricia Denning) to better understand how donor RBC factors contribute to NEC and how probiotic therapy may protect against NEC. Specifically, this proposal aims to determine the effect of Lactobacillus rhamnosus GG on intestinal oxygenation in transfused VLBW infants using near infrared spectroscopy and understand if repeated RBC transfusions from the same single blood unit is a risk factor for NEC. This proposal will capitaliz on the unique opportunity provided by recently collected data from a completed prospective, multicenter birth cohort study and an upcoming prospective study, both funded by the NHLBI and led by Dr. Josephson (primary mentor). This mentored research experience will allow Dr. Patel, a neonatologist with a strong commitment to patient- oriented research who received a Master of Science in Clinical Research as a NIH KL2 scholar, to pursue additional advanced mentored clinical research training pertaining to the execution of large, complex clinical studies. Dr. Patel's long-term career goal is to advance public health and neonatal care through clinical investigation into prevention strategies and interventions to decrease morbidity and mortality caused by NEC. Dr. Patel plans to achieve this through multicenter, collaborative clinical trials coupled with investigator initiated observational studies (R01/U01). The candidate's short-term career goals are to: 1) develop broad expertise in neonatal transfusion medicine; 2) develop expertise in conducting prospective observational research; 3) obtain the skills necessary to successfully develop, design and execute a multicenter clinical trial; 4) become proficient in the use of near infrared spectroscopy; 5) develop skills in longitudinal data analysis and clinical tril methodology. The mentored research training will provide Dr. Patel with new expertise in transfusion medicine and new skills in advanced biostatistics, epidemiology and clinical trial design. This will prepare him for an independent clinical research career focused on developing interventions to reduce NEC and other devastating complications of prematurity.

 描述（由申请方提供）：早产儿输血相关坏死性小肠结肠炎（NEC）是新生儿发病和死亡的主要原因，其发病机制尚不清楚。这种疾病的特点是肠道炎症迅速发展，往往导致肠坏死。目前，没有安全有效的治疗方法来预防NEC。最近的多项研究已经确定红细胞（RBC）输注是极低出生体重（VLBW）早产儿治疗贫血的常见疗法，是NEC发展的重要风险因素和潜在致病因素。虽然NEC的病因学中的一个令人信服的因素，红细胞输注相关NEC的临床决定因素仍然知之甚少。申请人Ravi Mangal Patel博士将带来输血医学（主要导师：Cassandra Josephson博士）、新生儿医学（共同导师：大卫卡尔顿博士）和坏死性小肠结肠炎（共同导师：帕特里夏·丹宁博士）国家领导人的专业知识，以更好地了解供体RBC因子如何导致NEC以及益生菌疗法如何预防NEC。具体而言，该提案旨在使用近红外光谱法确定鼠李糖乳杆菌GG对输血VLBW婴儿肠道氧合的影响，并了解重复输注来自同一血液单位的RBC是否是NEC的风险因素。该提案将利用最近从一项已完成的前瞻性、多中心出生队列研究和一项即将进行的前瞻性研究中收集的数据提供的独特机会，这两项研究均由NHLBI资助，由Josephson博士（主要导师）领导。Patel博士是一位对以患者为导向的研究有着坚定承诺的医学专家，他作为NIH KL 2学者获得了临床研究理学硕士学位，他将能够继续进行与执行大型复杂临床研究有关的高级指导临床研究培训。 博士Patel的长期职业目标是通过临床研究预防策略和干预措施来促进公共卫生和新生儿护理，以降低NEC引起的发病率和死亡率。Patel博士计划通过多中心、协作临床试验以及研究者发起的观察性研究（R 01/U 01）来实现这一目标。候选人的短期职业目标是：1）发展新生儿输血医学的广泛专业知识; 2）发展进行前瞻性观察性研究的专业知识; 3）获得成功开发，设计和执行多中心临床试验所需的技能; 4）精通近红外光谱的使用; 5）发展纵向数据分析和临床试验方法的技能。指导性研究培训将为帕特尔博士提供输血医学方面的新专业知识以及先进生物统计学、流行病学和临床试验设计方面的新技能。这将为他的独立临床研究生涯做好准备，专注于开发干预措施，以减少NEC和其他破坏性的早产并发症。