Obtaining Samples from Human Subjects to Facilitate Basic, Translational and Clinical Research

该协议笼统地定义了NIH临床中心重症监护医学部成员和合作机构将从成人研究对象和健康志愿者那里收集血液、尿液和超滤液的目的，并建立了进行采样的一般条件。抽血将符合美国国立卫生研究院临床中心的指导方针。 重症监护医学部和我们的相关研究人员参与了新的转化性研究方案的开发和现有IRB批准的研究方案的维护。该方案将支持通过分析开发建立新的转译研究方案，并提供信息以指导新方案的有效实施以及维持现有方案的运作效率。 该方案于2017年8月由国家心肺和血液机构审查委员会(最近改为全科医学1 IRB)批准。在整个过程中，研究对象提供了用于炎症标志物研究的血液样本，以表征低密度粒细胞作为脓毒症患者新的治疗靶点的特征，用于肺动脉高压(PAH)的DNA基因测序，用于复发性多软骨炎的免疫表型鉴定，用于流式细胞仪的B细胞分离，用于PAH的游离DNA分离，血栓弹力成像(TEG)和其他凝血和纤溶的血液标记物，RNA分离用于测序，维生素C水平，从全血中分离的PBMC用于重新编程和产生诱导的多能干细胞(IPSC)系，并分离细胞和血浆以1)作为新冠肺炎患者的比较器或2)进行体外刺激以研究几种新冠肺炎的分子机制。 在本报告所述期间，新登记了12名受试者(9名健康志愿者和3名患者)。在该方案的有效期内(截至2023年9月)，共有114名受试者入选(65名健康志愿者和49名患者)。在本报告所述期间，向调查人员提供了189份血液样本，在议定书有效期内向调查人员提供了677份样本。 使用从该协议获得的样本提出了以下摘要。 布鲁塞尔SB、Elinoff JM、Jang MK、Demirkale CY、Valanta HA、所罗门MA和Agbor-Enoh St。血浆游离DNA作为肺动脉高压疾病严重程度的新标记物。美国心脏病学会第68届年度科学会议，《心脏杂志》，73(9，S1)：S1897,2019年。 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容肺动脉高压患者显示正常的血栓形成动力学。美国心脏协会科学会议，140：A10714,2019年 Becicka W、Garrad E、Berreby G、Wang J、Nghiem K、Ramos-Benitez M、Cowling B、Moitra J、Huffstutler R、Carney K、Ferrante E、Cudrici C、Brofferio A、Tourdot B、Jacobson K、Knight J、Kanthi Y和Boehm M。胞外酶CD73的遗传缺陷会增加ACDC患者中性粒细胞细胞外陷阱的形成。动脉硬化、血栓形成和血管生物学：2022年血管发现会议 王静、莫伊特拉·J、潘尼克·S、图尔多·贝、诺里斯·P、凯利·K、左翼、杜蒙·L、所罗门·马、奈特·杰森和康蒂·Y。新冠肺炎恢复期血浆中的抗磷脂抗体。动脉硬化、血栓形成和血管生物学：2022年AHA血管发现会议 Strich J，Chertow D，Ramos-Benitez，Marcos和Warner S.SYK抑制中性粒细胞对内毒素的过度激活。《重症监护医学》，51(1)：562,2023。 使用从该方案获得的样本发表了以下论文。 LU M、Blaine KP、Cuillinane A、Hall C、Dulau-Florea A、Sun J、Graninger GM、Harper BJ、布鲁塞尔SB、Elinoff JM和所罗门MA。肺动脉高压患者显示正常的血栓形成动力学。Pulm Circ，11(3)：1-9,2021 斯特里奇RJ，拉莫斯-贝尼特斯MJ，Randazzo D，Stein SR，Babyak A，Davey RT，Suffredini AF，Childs RW，Chertow DS。福斯塔替尼抑制新冠肺炎患者血浆诱导的中性粒细胞胞外陷阱：一种潜在的治疗方法。传染病杂志，223(6)：981984,2021年。 佩雷斯-巴伦西亚LJ，Vannella Km，Ramos-Benitez MJ，Sun J，Abu-Asab M，Dorward DW，Awad KS，Platt A，Jacobson E，Kindrachuk J，Chertow DS(2023)。埃博拉病毒脱落的糖蛋白对人类T、B和自然杀伤淋巴细胞具有毒性。IScience 26,107323。Https://doi.org/10.1016/j.isci.2023.107323

This protocol defines in general terms the purposes for which blood, urine and ultrafiltrate will be collected from adult research subjects and healthy volunteers by members of the NIH Clinical Center's Critical Care Medicine Department and collaborating institutions and establishes general conditions under which sampling will be performed. Blood drawing will be consistent with NIH Clinical Center guidelines. The Critical Care Medicine Department and our associated investigators are involved in the development of new translational research protocols and maintenance of existing IRB approved research protocols. This protocol will support the establishment of new translational research protocols through assay development and provide information to guide the effective implementation of new protocols as well as maintain efficiency in operations of existing protocols. The protocol was approved by the National Heart, Lung, and Blood Institutional Review Board (recently changed to General Medicine 1 IRB) in August 2017. Over the course of the protocol, research subjects have provided blood samples for inflammatory marker studies, to characterize low density granulocytes as a novel therapeutic target for patients with sepsis, DNA gene sequencing for Pulmonary Arterial Hypertension (PAH), immunophenotyping for relapsing polychondritis, isolation of B cells for flow cytometry, cell free DNA isolation for PAH, thrombelastography (TEG) and other blood markers of coagulation and fibrinolysis, RNA isolation for sequencing, vitamin C levels, PBMCs isolated from whole blood for reprogramming and generation of induced pluripotent stem cell (iPSC) lines, and to isolate cells and plasma to either 1) serve as a comparator for COVID-19 patients or 2) perform in-vitro stimulations to study several COVID-19 molecular mechanisms. During the current reporting period 12 subjects were newly enrolled (9 healthy volunteers and 3 patients). Over the life of the protocol (as of September 2023) a total of 114 subjects have enrolled (65 healthy volunteers and 49 patients). Over the current reporting period 189 blood samples were provided to investigators and over the life of the protocol 677 samples have been provided to investigators. The following abstract have been presented using samples obtained from this protocol. Brusca SB, Elinoff JM, Jang MK, Demirkale CY, Valantine HA, Solomon MA, and Agbor-Enoh ST. Plasma Cell-free DNA as a Novel Marker of Disease Severity in Pulmonary Arterial Hypertension. American College of Cardiology 68thAnnual Scientific Session, J Am Coll Cardiol, 73(9, S1): S1897, 2019. Lu M, Blaine K, Cullinane A, Hall C, Dulau-Florea ,A, Sun J, Chenwi H, Graninger G, Harper B, Elinoff JM, and Solomon MA. Pulmonary Arterial Hypertension Patients Display Normal Kinetics of Clot Formation. American Heart Association Scientific Sessions, 140: A10714, 2019 Becicka W, Garrad E, Berreby G, Wang J, Nghiem K, Ramos-Benitez M, Cowling B, Moitra J, Huffstutler R, Carney K, Ferrante E, Cudrici C, Brofferio A, Tourdot B, Jacobson K, Knight J, Kanthi Y, and Boehm M. Genetic Deficiency of the Ectoenzyme CD73 Increases Neutrophil Extracellular Trap Formation in Patients with ACDC. Arteriosclerosis, Thrombosis, and Vascular Biology: Vascular Discovery Conference 2022 Becicka W, Berreby G, Wang J, Moitra J, Panicker S, Tourdot BE, Norris P, Kelly K, Zuo Y, Dumont L, Solomon MA, Knight JS and Kanthi Y. Antiphospholipid antibodies in COVID-19 Convalescent Plasma. Arteriosclerosis, Thrombosis, and Vascular Biology: AHA Vascular Discovery Conference 2022 Strich J, Chertow D, Ramos-Benitez, Marcos, and Warner S. SYK Inhibition Abrogates Neutrophil Hyperactivation in Response to Lipopolysaccharides. Critical Care Medicine, 51(1): 562, 2023. The following papers have been published using samples obtained from this protocol. Lu M, Blaine KP, Cuillinane A, Hall C, Dulau-Florea A, Sun J, Graninger GM, Harper BJ, Brusca SB, Elinoff JM, and Solomon MA. Pulmonary Arterial Hypertension Patients Display Normal Kinetics of Clot Formation. Pulm Circ, 11(3): 1-9, 2021 Strich RJ, Ramos-Benitez MJ, Randazzo D, Stein SR, Babyak A, Davey RT, Suffredini AF, Childs RW, Chertow DS. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic. The Journal of Infectious Diseases, 223 (6): 981984, 2021. Perez-Valencia LJ, Vannella KM, Ramos-Benitez MJ, Sun J, Abu-Asab M, Dorward DW, Awad KS, Platt A, Jacobson E, Kindrachuk J, Chertow DS (2023). Ebola virus shed glycoprotein is toxic to human T, B, and natural killer lymphocytes. iScience 26, 107323. https://doi.org/10.1016/j.isci.2023.107323