Resubmission: Elucidating Pediatric Sepsis by Defining Comprehensive Signatures for Diagnosis and Outcome

重新提交：通过定义诊断和结果的综合特征来阐明儿童败血症

• 批准号: 10364419
• 负责人: Prashant Mahajan
• 金额: $ 59.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364419
• 关键词: 18 year old; Accident and Emergency department; Address; Age; Antibiotics; Antimicrobial Resistance; Area; Bacteria; Bioinformatics; Biological Markers; Blood; Blood specimen; Cessation of life; Child; Childhood; Clinical; Clinical Data; Consent; Custom; Data; Data Set; Diagnosis; Diagnostic; Disease; Electronic Health Record; Emergency Department patient; Emergency department visit; Enrollment; Etiology; Functional disorder; Future; Goals; Guidelines; Heart Rate; Hour; Immune; Immune response; Immunoassay; Immunologics; Infection; Inpatients; Intervention; Knowledge; Laboratories; Life; Liquid substance; Measures; Medical; Methods; Modeling; Molecular; Morbidity - disease rate; Multicenter Studies; Nucleic Acids; Observational Study; Organ; Organ failure; Outcome; Patient Monitoring; Patient-Focused Outcomes; Patients; Pediatric Hospitals; Physiological; Process; Provider; Recommendation; Research Personnel; Resources; Resuscitation; Ribosomes; Risk; Sampling; Science; Sepsis; Septic Shock; Shock; Speed; Subgroup; Syndrome; Technology; Temperature; Testing; Time; Viral; Viremia; Virus; Work; accurate diagnosis; clinical decision-making; detection assay; evidence base; experience; improved; mortality; multidisciplinary; nanorod; nucleic acid detection; outcome prediction; pathogen; patient response; pediatric emergency; pediatric patients; pediatric sepsis; precision medicine; prospective; rapid diagnosis; risk stratification; septic patients; tertiary care; tissue culture; tool; transcriptomics; working group

PROJECT SUMMARY: Sepsis, defined as life-threatening organ dysfunction resulting from a dysregulated immune response of the patient to infection, is a major cause of pediatric morbidity and mortality. Annually, sepsis accounts for ~100,000 emergency department (ED) and ~25-50% of children with sepsis will die due to complications that include shock and multiple organ dysfunction. These unacceptably high bad outcomes are mostly because of our limited understanding of the fundamental underlying immune response processes at the cellular level that are involved in pediatric sepsis. There is an urgent need for generating high quality evidence using multidisciplinary teams to rapidly and accurately diagnoses sepsis so that appropriate therapies can be initiated in the ED to reduce morbidity and mortality in children. We believe that the patient has a unique “sepsis” signature when they first present to the ED and we can define this signature by studying the changes in the vital signs (such as temperature, heart rate) and initial laboratory tests, i.e. physiologic profile along with tests that measure the immune response i.e. the immunologic profile and their changes in the ribosomal nucleic acids (RNA) at the cellular level i.e. transcriptomic profile. We will also be able to better identify the cause of sepsis i.e. bacteria or non-bacteria (for e.g. viruses) using a more sensitive and faster turnaround test called nanorod PCR, which will help the ED provider in initiating appropriate treatments. We also believe that the changes in the sepsis signature over time will allow us to reliably predict which child is more at risk for developing complications and death very early in the disease course to help reduce sepsis related mortality. In order to achieve our aims, we will conduct a prospective, observational study in children (3 months ≤ 18 years of age) with suspected sepsis in the ED at a tertiary care Children’s Hospital and monitor patients through their inpatient stay (ICU, general unit). We have assembled a team of experienced investigators and have the necessary resources and expertise to achieve the goals of our project that are directly aligned with the NOSI to Advance Understanding and Management of MODS in Children. Our project is the first step towards precision medicine to improve diagnosis, guide appropriate therapies, and reliably prognosticate patient outcomes in children with sepsis.

项目概要： 脓毒症，定义为由于免疫系统的免疫反应失调而导致的危及生命的器官功能障碍。 患者感染，是儿科发病率和死亡率的主要原因。每年败血症 约100，000名急诊科（艾德）和约25-50%的脓毒症儿童将死于并发症， 包括休克和多器官功能障碍。这些令人无法接受的高不良结果主要是因为 我们对细胞水平的基本免疫应答过程的理解有限， 与小儿败血症有关迫切需要使用以下方法生成高质量证据 多学科团队快速准确地诊断脓毒症， 在艾德发起，以降低儿童的发病率和死亡率。 我们认为，当病人第一次到艾德就诊时，他们有一个独特的“脓毒症”特征，我们可以 通过研究生命体征（如体温、心率）的变化来定义此签名， 实验室测试，即生理特征沿着测量免疫应答的测试，即 免疫概况及其在细胞水平上核糖体核酸（RNA）的变化，即 转录组学特征。我们还将能够更好地识别脓毒症的原因，即细菌或非细菌（对于 例如病毒）使用更灵敏和更快的周转测试称为纳米棒PCR，这将有助于艾德 提供者提供适当的治疗。我们还认为脓毒症特征随时间的变化 这将使我们能够可靠地预测哪个孩子更容易出现并发症和死亡， 有助于降低脓毒症相关死亡率。 为了实现我们的目标，我们将在儿童（3个月≤ 18岁）中进行一项前瞻性、观察性研究 年龄30岁）在三级儿童医院的艾德急诊室疑似脓毒症，并监测患者 通过他们的住院治疗（ICU，普通病房）。我们已经召集了一队经验丰富的调查员， 拥有必要的资源和专业知识来实现我们项目的目标，这些目标与 NOSI旨在促进对儿童MODS的理解和管理。我们的项目是第一步 精确医学，以改善诊断，指导适当的治疗，并可靠地 脓毒症儿童的患者结局。