Colorado APS Clinical Center

科罗拉多 APS 临床中心

• 批准号: 10645992
• 负责人: Neil Raj Aggarwal
• 金额: $ 17.36万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2029-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645992
• 关键词: Accident and Emergency department; Acute; Acute Respiratory Distress Syndrome; Acute respiratory failure; Advisory Committees; Alcohols; American; Biological Process; Black race; Blood; Caring; Cells; Clinic; Clinical; Clinical Research; Colorado; Communities; Community Hospitals; Complex; Critical Illness; Data Collection; Diagnosis; Disease; Endothelial Cells; Enrollment; Ensure; Epidemiology; Foundations; Functional disorder; Funding; Goals; Health; Heterogeneity; Hispanic; Hospitalization; Hospitals; Human Resources; Immune response; Immunophenotyping; Indigenous; Inflammatory Response; Infrastructure; Institution; Intensive Care Units; Interdisciplinary Study; Latinx; Leadership; Letters; Link; Location; Lung; Medical center; Modeling; Modification; Mononuclear; Morbidity - disease rate; Mosses; Outcome; Outpatients; Participant; Patient-Focused Outcomes; Patients; Phase; Phenotype; Pneumonia; Predisposition; Prospective cohort; Protocol Compliance; Protocols documentation; Publishing; Recording of previous events; Recovery; Reporting; Research; Research Infrastructure; Research Personnel; Rural; Rural Community; Science; Seminal; Sepsis; Severities; Sex Differences; Societies; Survivors; Techniques; Time; Translational Research; United States National Institutes of Health; Universities; alcohol effect; alcohol use disorder; clinical center; clinically relevant; cohort; commune; comorbidity; data acquisition; diagnostic criteria; drug of abuse; ethnic difference; experience; follower of religion Jewish; gender difference; improved; improved outcome; individual variation; injury recovery; innovation; member; mortality; multidisciplinary; nerve conduction study; neuromuscular; novel; participant enrollment; patient subsets; peripheral blood; personalized medicine; racial difference; recruit; research study; rural counties; sepsis induced ARDS; septic patients; survivorship; targeted treatment; transcriptome sequencing; urban area; ward

Colorado has a long and storied history of heterogeneity-related ARDS, pneumonia, and sepsis (APS) research. After the initial Lancet description of the acute respiratory distress syndrome (ARDS), Colorado investigators subsequently identified pneumonia and sepsis as diagnoses associated with an increased susceptibility for ARDS. Since that time, Colorado investigators (including many key personnel on this proposal) have reported seminal discoveries regarding heterogeneity of ARDS, pneumonia, and sepsis including identification of a) alcohol use disorders (AUDs) as the first co-morbid conditions that increase susceptibility to ARDS, b) AUDs deleterious impact on sepsis mortality, c) and sex, racial, and ethnic differences in ARDS and sepsis epidemiology. Simultaneously, Colorado investigators have been unraveling the basic mechanisms of APS focusing on heterogeneity in the host inflammatory response. As a higher proportion of patients began to survive APS, we expanded our research to examine survivorship focusing on neuromuscular dysfunction. These studies have resulted in enhanced ways to diagnose weakness and improve our understanding of the neuromuscular trajectory of recovery in APS survivors. We propose to conduct two clinical center-specific scientific projects demonstrating the breadth and depth of our research that spans acute APS severity and its recovery trajectory in survivors. The acute project will identify distinct mononuclear cell endotypes present in the lungs and blood of APS participants with acute respiratory failure using bulk RNA seq. The recovery project will establish whether neuromuscular endotypes, based primarily on a single time-point nerve conduction study, can identify distinct and clinically relevant trajectories of recovery. We will also explore the cross-cutting theme of how AUDs impact APS heterogeneity. Building upon a strong and persistent research foundation, we have the research infrastructure to achieve all the outlined goals and are poised to be a strong contributor to the national APS consortium. As an original and integral member of the ARDS and then PETAL Network (for over 28 consecutive years), our multi-disciplinary and collaborative research group is experienced in conducting high quality NIH-funded prospective cohort research. In 2021, the Colorado research group enrolled 554 APS participants into clinical and translational research studies. This number far exceeds the APS consortium requirement of 240 APS patients per year. We also have extensive expertise academic rural recruiting historically underrepresented communities (Latinx, Black, and Indigenous) from both and community hospitals. For this proposal, we will also enroll participants from the often overlooked community, ensuring their representation in the APS consortium.In summary, the Colorado APS Center plans to exceed our enrollment obligations; maintain excellence in the quality of protocol compliance, data acquisition, and regulatory responsibilities; actively contribute to the steering committee and other APS committees; and most importantly advance science and contribute to improving the care of APS patients.

科罗拉多州有着悠久的异质性ARDS、肺炎和败血症(APS)的历史。 研究。在《柳叶刀》最初对急性呼吸窘迫综合征(ARDS)进行描述后，科罗拉多州 研究人员随后发现肺炎和败血症是与肺炎和败血症相关的诊断 对ARDS的易感性。从那时起，科罗拉多州的调查人员(包括许多关键人员 提案)报告了关于ARDS、肺炎和败血症的异质性的开创性发现 包括确定a)酒精使用障碍(AUDS)是增加的第一种共病情况 对ARDS的易感性，b)AUDS对败血症死亡率的有害影响，c)以及性别、种族和民族 急性呼吸窘迫综合征和败血症流行病学的差异。与此同时，科罗拉多州的调查人员一直在解开 APS的基本机制侧重于宿主炎症反应的异质性。作为一名更高的 APS患者开始存活的比例，我们扩大了我们的研究以检查存活率，重点是 神经肌肉功能障碍。这些研究的结果是增强了诊断虚弱和 提高我们对APS幸存者神经肌肉恢复轨迹的理解。我们建议 开展两个特定于临床中心的科学项目，展示我们研究的广度和深度 存活者的急性APS严重程度及其恢复轨迹。急性项目将确定不同的 急性呼吸衰竭APS患者肺和血中单核细胞内型分布 使用批量RNA序列。恢复项目将确定神经肌肉内型，主要基于 单一的时间点神经传导研究，可以确定不同的和临床相关的康复轨迹。 我们还将探讨AUD如何影响APS异质性的交叉主题。建立在强大的 和坚持不懈的研究基础，我们有研究基础设施来实现所有概述的目标和 准备成为国家APS财团的强大贡献者。作为原始的和完整的成员 ARDS和花瓣网络(连续超过28年)，我们的多学科和协作性 研究小组在进行高质量的NIH资助的前瞻性队列研究方面经验丰富。2021年， 科罗拉多州研究小组招募了554名APS参与者参加临床和翻译研究。这 这一数字远远超过了APS联盟每年240名APS患者的要求。我们还有大量的 专业知识 学术 农村 招募历史上代表性不足的社区(拉丁裔、黑人和土著) 和社区医院。对于这项提案，我们还将招收经常被忽视的参与者 社区，确保他们在APS财团中的代表。总而言之，科罗拉多州APS中心 计划超出我们的注册义务；在协议遵从性、数据质量方面保持卓越 收购和监管职责；积极为指导委员会和其他AP作出贡献 委员会；最重要的是促进科学，并为改善对APS患者的护理做出贡献。