RNA Expression Profiling in Pediatric Patients with Suspected Sepsis

疑似败血症儿科患者的 RNA 表达谱

• 批准号: 8967019
• 负责人: Frances B Balamuth
• 金额: $ 12.63万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967019
• 关键词: Accident and Emergency department; Acute; Adherence; Antigen Presentation; Applied Research; Basic Science; Benign; Biological Markers; Biology; Caring; Child; Childhood; Clinical; Clinical Oncology Supplement (K12); Clinical Practice Guideline; Complex; Convulsive therapy; Data; Decision Making; Development; Diagnostic; Discipline; Doctor of Philosophy; Electronics; Emergency Care; Emergency Department patient; Emergency Medicine; Emergency department visit; Enrollment; Ensure; Environment; Epidemiology; Etiology; Evaluation; Fever; Fingerprint; Functional disorder; Funding; Future; Gene Expression; Genes; Genetic Transcription; Goals; Health Expenditures; Hospitalization; Hospitals; Human Characteristics; Immunobiology; Immunology; Infant; Infection; Integrin Signaling Pathway; Integrins; Interferons; Intervention Trial; K-Series Research Career Programs; Lead; Liquid substance; Literature; Master of Science; Measures; Medical; Mentors; Methods; Microarray Analysis; Molecular Profiling; Morbidity - disease rate; Multicenter Studies; National Heart, Lung, and Blood Institute; Natural Immunity; Organ failure; Organism; Outcome; Pathway interactions; Patients; Pattern; Pediatric Hospitals; Pediatric Intensive Care Units; Pennsylvania; Philadelphia; Physicians; Population; Positioning Attribute; Principal Investigator; Prospective Studies; Protocols documentation; Regimen; Research; Research Training; Resources; Risk; Role; SECTM1 gene; Schools; Scientist; Sepsis; Septic Shock; Severities; Severity of illness; Shock; Signal Pathway; Signal Transduction; Signs and Symptoms; Source; Stratification; Techniques; Technology; Test Result; Testing; Time; Training; Training Programs; Translational Research; United States; United States National Institutes of Health; Universities; Vasoconstrictor Agents; Viral; Zinc; adaptive immunity; base; career; career development; clinical epidemiology; clinical predictors; experience; genetic epidemiology; improved; interest; medical schools; mortality; pathogen; patient oriented research; pediatric patients; personalized intervention; personalized medicine; programs; public health relevance; research and development; research study; response; skills; therapeutic target; tool; translational study

 DESCRIPTION (provided by applicant): Candidate: Dr. Balamuth has clinical training in pediatric emergency medicine, and research training both in immunobiology, having received a PhD through the Medical Scientist Training Program at Yale University, and epidemiology, as she is enrolled in the Masters of Science in Clinical Epidemiology program through the support of an NHLBI K12 award at the University of Pennsylvania. This proposal for a K23 Career Development Award will position the applicant to gain advanced skills in genetic epidemiology and high throughput gene expression studies through the conduct of a prospective study utilizing RNA expression profiling to improve pediatric sepsis recognition in the emergency department. Dr. Balamuth's mentors have expertise in epidemiology and immunology, and will ensure that both the career development and research plan are carried out successfully. The applicant's current objectives are to improve sepsis recognition in ED patients using both epidemiologic and biologic tools. With 75% of her time dedicated to patient oriented research and her career development, the applicant's short term goals are 1. To complete her K12 studies. These include a study which demonstrates improved outcomes for patients with severe sepsis or septic shock who were recognized rapidly in the ED and treated according to a clinical practice guideline and a study which evaluates a vital sign based electronic alert for sepsis in the emergency department and demonstrates that although the alert is sensitive for identifying sepsis, that it has a high false positive rate and 2. To carry out the studies described in the current proposal. The applicant's long term career goal is to become an independent academic physician-scientist with an established NIH-funded program to accurately identify pediatric patients with sepsis in the ED setting, and to risk stratify patients so that they receive appropriate and personalized interventions based on their underlying biology, with the ultimate goal of decreasing morbidity and mortality. She will achieve this through emergency medicine based research network sepsis intervention trials using risk stratification through personalized medicine techniques. Achieving these short and long term goals will develop Dr. Balamuth as a leader in the nascent field of translational research in the pediatric ED. Environment: The proposal takes advantage of the extensive resources available to Dr. Balamuth at The Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania Perelman School of Medicine (Penn) by bridging multiple disciplines, schools, and research centers to create a unique program aimed towards developing skills in advanced genetic epidemiology, and high throughput methods. Overall, CHOP and Penn provide a rich environment for research and training. The wealth and diversity of both formal didactic training and opportunities for mentored research experiences, combined with the high clinical volume of a quaternary pediatric emergency department is unique, and create an ideal environment for Dr. Balamuth's ongoing career development. Research: Severe sepsis is an important cause of morbidity and mortality in children. There have been significant advances over the past decade, which have demonstrated improved patient outcomes with timely, protocol-based therapies. However, identifying which children require these intensive therapies is challenging. Finding the children at risk for severe sepsis from among the thousands who present to emergency departments each year with common febrile illness is akin to finding a needle in a haystack. Although there have been many studies in the literature investigating candidate biomarkers as both diagnostic and therapeutic targets in sepsis, it has become clear that the complex nature of the human response to sepsis makes single marker strategies unlikely to succeed in facilitating sepsis recognition. RNA expression profiling provides a unique opportunity to gain a broad, high throughput picture in the complex and likely heterogeneous pathophysiology of sepsis, and several preliminary studies have yielded promising results using this technique in predicting both sepsis severity in pediatric intensive care unit (PICU) patients as well as etiology of infections in children with fever. The broad long-term objective of this line of research is to improve pediatric sepsis recognition in the emergency department using both clinical predictors and biomarker strategies. As a first step towards achieving this goal, the current proposal focuses on using RNA expression profiling to predict both illness severity and source pathogen in pediatric sepsis. The aims of this proposal are: 1. To determine association between the RNA expression profile and severity of illness during the initial 2 days of hospitalization in pediatri patients with suspected sepsis initially identified in the ED., and 2. To determine association between the RNA expression profile and sepsis source pathogen in pediatric ED patients with suspected sepsis.

 描述（由适用提供）：候选人：Balamuth博士在儿科急诊医学方面接受了临床培训，以及免疫生物学的研究培训，在耶鲁大学的医学科学培训计划和流行病学中获得了博士学位，因为她被纳入NHLBI K12奖的NHLBI K12奖的临床流行病学计划获得了临床科学硕士学位。 K23职业发展奖的提案将定位适用于获得遗传流行病学和高吞吐量基因表达研究的高级技能，并通过进行一项利用RNA表达分析的前瞻性研究来提高急诊科的小儿败血症的认可。 Balamuth博士的导师在流行病学和免疫学方面具有专业知识，并将确保成功执行职业发展和研究计划。申请人目前的目标是使用流行病学和生物学工具改善ED患者的败血症识别。申请人的短期目标为1.完成K12研究，因此有75％的时间致力于患者的研究和职业发展，因此申请人的短期目标为1。这些研究包括一项研究，该研究表明，严重败血症或败血性休克患者的结局得到改善，这些患者在ED中迅速被认可并根据临床实践指南和一项研究，该指南评估了急诊室中败血症的基于生命体征的电子警报，并证明，尽管该警报对识别sepsis的敏感性敏感，以确定sepsis的较高的效率率，并在当前的研究中进行了2次介绍。申请人的长期职业目标是通过既定的NIH资助计划成为独立的学术身体科学家，以准确地识别ED环境中败血症患者的儿科患者，并冒着分层患者的风险，以便根据其基本的生物学接受适当和个性化的干预措施，并具有降低疾病的最终目标。她将通过基于急诊医学的研究网络败血症干预试验使用个性化医学技术来实现这一目标。实现这些短期和长期目标将发展Balamuth博士，成为小儿Ed转化研究的新生领域的领导者。环境：该提案利用了费城儿童医院（CHOP）和宾夕法尼亚大学佩雷​​尔曼医学院（PENN）的大量资源，通过弥合多个学科，学校和研究中心，以创建一个独特的计划，以创建一个独特的计划，以发展高级遗传学流行病学方法，以及高级遗传学方法。总体而言，Chop和Penn为研究和培训提供了丰富的环境。正式的教学培训和指导研究经验的机会的财富和多样性，再加上Quaternary小儿急诊室的临床量是独一无二的，并为Balamuth博士持续的职业发展创造了理想的环境。研究：严重的败血症是儿童发病率和死亡率的重要原因。在过去的十年中，取得了重大进展，这表明了及时的基于方案的疗法的患者结局得到了改善。但是，确定孩子需要这些强化疗法是挑战的。在每年出现的成千上万到出现的患有普通高温疾病的人中，发现有严重败血症的孩子的风险类似于在干草堆中找到针头。尽管有许多RNA表达谱分析为败血症的复杂且可能异质的病理生理生理提供了一个独特的机会，并在败血症的复杂且可能是异质的病理生理学中获得了广泛的吞吐量，并且几项初步研究在预测这两种技术方面都在预测脓毒症的严重程度方面产生了令人鼓舞的结果，以预测儿童强化护理单位（PICU）患者（PICU）患者以及病学患者的病因。这项研究线的广泛长期目标是使用临床预测因子和生物标志物策略来改善急诊科的小儿脓毒症的识别。作为实现这一目标的第一步，当前的建议集中于使用RNA表达谱分析来预测小儿败血症中的疾病严重程度和源病原体。该提案的目的是：1。确定在住院的最初2天的RNA表达概况与疾病严重程度之间的关联，可疑的脓毒症最初在Ed。中鉴定出来，并确定2。确定RNA表达概况与可疑sepsis的儿科ED患者的RNA表达谱与脓毒症源病原体之间的关联。