Systems Engineering of Pheresis Intervention for Sepsis

脓毒症采血干预系统工程

• 批准号: 7682885
• 负责人: John A Kellum
• 金额: $ 157万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-28 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682885
• 关键词: Academia; Achievement; Acute; Algorithms; American; Animal Model; Animals; Back; Basic Science; Binding; Biocompatible; Biocompatible Materials; Biological Models; Biomedical Engineering; Blood; Blood Component Removal; Blood Platelets; Blood flow; Caliber; Cells; Characteristics; Chemical Engineering; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Communication; Complex; Critical Care; Critical Illness; Data; Development; Device Designs; Device or Instrument Development; Devices; Discipline; Disease; Engineering; Ensure; Excision; Experimental Designs; Fibrin; Figs - dietary; Functional disorder; Goals; Head; Health; Human; In Vitro; Industry; Infection; Inflammatory; Inflammatory Response; Institutes; Intervention; Laboratories; Laboratory Research; Lead; Length; Leukocytes; Ligation; Lipopolysaccharides; Mathematics; Medicine; Modeling; Modification; Monitor; Mus; Operative Surgical Procedures; Organ; Organ failure; Output; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Polymers; Porosity; Process; Property; Puncture procedure; Rattus; Regenerative Medicine; Research; Research Personnel; Rodent; Sepsis; Structure; Surface; System; Technology; Testing; Thrombosis; Toxicity Tests; Universities; Whole Blood; Work; base; biomaterial compatibility; complement pathway; cost; data modeling; density; design; feeding; implantation; in vivo Model; iterative design; killings; leukocyte activation; macrophage; mathematical model; model design; model development; models and simulation; preclinical study; prototype; research study; response; simulation; solute; therapeutic target; tool

In response to: PAR-04-023, we are proposing a Bioengineering Research Partnership to design and test an extracorporeal device for the treatment of severe sepsis, based on the principle of hemoadsorption. Our multi- disciplinary team comprises basic science and clinical researchers, bioengineering and biomaterials experts, and experts in complex systems modeling. Our proposal will carefully integrate this diverse group of researchers from both technical and biomedical fields, crossing the boundaries of multiple scientific disciplines and leveraging the capabilities of both industry and academia. Our project is entitled Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS). Severe sepsis (acute onset organ failure in the setting of infection) is a major health problem that kills nearly 250,000 Americans each year and costs billions of dollars. Available therapies for sepsis, including those recently approved, are suboptimal and new therapies are urgently needed. However, the complexities of the inflammatory response network and the high cost of clinical trials, particularly in the critically ill, renders the traditional drug/device development paradigm obsolete. We have previously developed and tested an extracorporeal blood purification device for treatment in chronic renal disease and have adapted this device for the treatment of acute inflammatory diseases. We have also developed and partially calibratedin both rodents and humansa mathematical model of sepsis. This project proposes to integrate these two achievements and, through an iterative design process, develop a device that can be used to treat severe sepsis. The goal of this proposal is to design an extracorporeal blood purification device for the treatment of severe sepsis. This proposal will bring together investigators from the following departments at the University of Pittsburgh: Bioengineering, Chemical Engineering, Critical Care Medicine, Surgery, Medicine, and Mathematics. We will also call on the expertise of two companies, one specializing in adsorbent polymer technology (MedaSorb Technologies, LLC) and the other in complex systems modeling (Immunetrics, Inc.).

为了回应：PAR-04-023，我们提议建立生物工程研究合作伙伴关系来设计和测试 基于血液吸附原理的用于治疗严重脓毒症的体外装置。我们的多 学科团队由基础科学和临床研究人员、生物工程和生物材料专家组成， 复杂系统建模专家。我们的提案将仔细整合来自不同领域的研究人员 技术和生物医学领域，跨越多个科学学科的界限，并利用 工业界和学术界的能力。我们的项目名为“血液分离干预的系统工程” 用于脓毒症（SEPsIS）。 严重脓毒症（感染时急性发生的器官衰竭）是一个主要的健康问题，导致近乎死亡 每年有 25 万美国人，花费数十亿美元。败血症的可用疗法，包括最近的疗法 已获批准，但效果欠佳，迫切需要新的疗法。然而，炎症的复杂性 反应网络和临床试验的高成本，特别是在危重病人中，使得传统的 药物/器械开发范式已经过时。我们之前开发并测试了体外血液 用于治疗慢性肾病的净化装置，并已将该装置改造用于治疗急性肾病 炎症性疾病。我们还开发了啮齿动物和人类并进行​​了部分校准 脓毒症的数学模型。该项目建议整合这两项成果，并通过 迭代设计过程，开发一种可用于治疗严重败血症的设备。 该提案的目标是设计一种体外血液净化装置，用于治疗 严重败血症。该提案将汇集来自大学以下部门的研究人员 匹兹堡：生物工程、化学工程、重症医学、外科、医学和数学。 我们还将利用两家公司的专业知识，其中一家专门从事吸附聚合物技术（MedaSorb Technologies, LLC）和复杂系统建模领域的另一个（Immunetrics, Inc.）。

项目成果

What blood temperature for an ex vivo extracorporeal circuit?

离体体外回路的血液温度是多少？

• 发表时间: 2011-06
• 影响因子: 2.4
• 作者: Rimmele, Thomas;Bishop, Jeffrey;Simon, Peter;Carter, Melinda;Kong, Lan;Lee, Minjae;Singbartl, Kai;Kellum, John A
• 通讯作者: Kellum, John A

Systems engineering medicine: engineering the inflammation response to infectious and traumatic challenges.

系统工程医学：设计针对感染和创伤挑战的炎症反应。

• 发表时间: 2010-07-06
• 作者: Parker, Robert S;Clermont, Gilles
• 通讯作者: Clermont, Gilles

A simple mathematical model of cytokine capture using a hemoadsorption device.

使用血液吸附装置捕获细胞因子的简单数学模型。

• 发表时间: 2009-01
• 影响因子: 3.8
• 作者: DiLeo, Morgan V;Kellum, John A;Federspiel, William J
• 通讯作者: Federspiel, William J

Ensemble models of neutrophil trafficking in severe sepsis.

严重脓毒症中性粒细胞运输的整体模型。

• 发表时间: 2012
• 影响因子: 4.3
• 作者: Song, Sang Ok;Song, Sang O K;Hogg, Justin;Peng, Zhi;Parker, Robert;Kellum, John A;Clermont, Gilles
• 通讯作者: Clermont, Gilles

Effects of hemoadsorption on cytokine removal and short-term survival in septic rats.

血液吸附对脓毒症大鼠细胞因子去除和短期生存的影响。

• 发表时间: 2008-05
• 影响因子: 8.8
• 作者: Peng, Zhi;Carter, Melinda J;Kellum, John A
• 通讯作者: Kellum, John A