Attenuating Inflammation via Protein-Calorie Restriction

通过限制蛋白质热量减轻炎症

• 批准号: 7294344
• 负责人: TODD W RICE
• 金额: $ 15.11万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294344
• 关键词: Abdomen; Academic Medical Centers; Acute respiratory failure; Address; Adherence; Advanced Development; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Arginine; Aspiration Pneumonia; Atrophic; Attenuated; Bacteremia; Bacteria; Bacterial Translocation; Benefits and Risks; Biochemical; Biometry; Blood flow; Bolus Infusion; Burn Trauma; C-reactive protein; Caloric Restriction; Clinical; Clinical Research; Clinical Trials; Closed head injuries; Collaborations; Communities; Complication; Conduct Clinical Trials; Conflict (Psychology); Coupled; Critical Care; Critical Illness; Data; Development; Disruption; Doctor of Medicine; Enrollment; Enteral; Enteral Feeding; Enteral Nutrition; Enterobacteriaceae; Epidemiology; Epithelial; Epithelial Cells; Equilibrium; Feeds; Foundations; Functional disorder; Future; Gastrointestinal Motility; Glutamine; Growth; Homeostasis; Hyperglycemia; IL8 gene; Immune; Immunoglobulin A; Immunosuppression; Incidence; Infection; Inflammation; Inflammatory; Inflammatory Response; Inflammatory Response Pathway; Intensive Care; Intensive Care Units; Interleukin-1; Interleukin-10; Interleukin-4; Interleukin-6; Intestinal Mucosa; Intestines; Invasive; Ischemic Bowel Disease; Laboratories; Length of Stay; Leukotrienes; Measures; Mechanical ventilation; Mediator of activation protein; Medical; Mentors; Messenger RNA; Nausea and Vomiting; Nosocomial Infections; Nosocomial pneumonia; Numbers; Nutritional Support; Omega-3 Fatty Acids; Operative Surgical Procedures; Organ; Organ failure; Outcome; Parenteral Nutrition; Patient Recruitments; Patients; Physicians; Physiology; Population; Population Heterogeneity; Procedures; Production; Prostaglandins; Proteins; Purpose; Randomized; Randomized Controlled Trials; Rate; Reporting; Research; Research Personnel; Residual state; Residual volume; Resolution; Resources; Rice; Risk; Safety; Serum; Stimulus; Stomach; Structure; Systemic infection; Techniques; Therapeutic immunosuppression; Tight Junctions; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Upper arm; Ventilator; Weaning; aging population; bile salts; career; cellular microvillus; concept; cost; cytokine; day; design; feeding; gastrointestinal; gastrointestinal microvillus; human TNF protein; improved; in vivo; lipid metabolism; nutrition; outcome forecast; prevent; prognostic; prospective; response; skills; trial comparing

DESCRIPTION (provided by applicant): The purpose of this proposal is to cultivate the scientific development and advance the skills of Dr. Todd W. Rice in the design and conduct of clinical trials, so that he may become an independent investigator in conducting clinical research. Vanderbilt University Medical Center, through its several intensive care units, will provide Dr. Rice with the necessary patient population to conduct a prospective, randomized clinical trial comparing the effects of trophic nutrition versus advancement to full-calorie rates in mechanically ventilated, critically ill patients. Laboratory resources are available to investigate changes in biochemical responses, including pro- and anti-inflammatory cytokine responses. Differences in clinical outcomes, including weaning patients from the ventilator, will be assessed. Through collaboration with his clinical mentor, Dr. Arthur P. Wheeler, Dr. Rice will become adept at trial design, biostatistics, epidemiology, patient recruitment, and reporting of results to the scientific community. These skills will provide the foundation for Dr. Rice to pursue an independent academic career in critical care research. Many mechanically ventilated patients, unable to nourish themselves, are provided with nutrition, either enterally or parenterally. Enteral nutrition has been shown to reduce inflammation and improve clinical outcomes by preserving the intestinal mucosa, decreasing bacterial translocation, and reducing systemic infections. Although these improvements have been observed with full enteral feedings, very low rates of enteral feedings show similar protection in animals. We hypothesize that these low-level feedings also preserve the intestinal mucosa in ventilated patients, while reducing the pro- and anti-inflammatory cytokine responses seen in these patients along with the gastrointestinal complications, resulting in improved clinical outcomes compared to full-calorie feeds. The specific aims of this proposal are to demonstrate that low-level as compared to full-calorie enteral feedings will: 1) decrease the early pro-inflammatory and compensatory anti-inflammatory cytokine responses; 2) decrease the incidence of feeding complications, and thus, 3) improve clinical outcomes, such as ventilator-free days and other organ-failure free days. The aging population, increasing immunosuppression, and rising use of invasive procedures will result in the continued growth of critical care. Many mechanically ventilated, critically ill patients are supported with enteral nutrition. Despite widespread use, data on optimal delivery of enteral nutrition to such patients is lacking. This proposal will help weigh the benefits and risks, establish a cost-efficient means of reducing feeding complications, and provide the foundation for future studies of enteral feeds in patients with acute respiratory failure requiring mechanical ventilation.

描述（由申请人提供）： 该建议的目的是培养科学发展，并提高托德·赖斯博士在临床试验的设计和行为中的技能，以便他可以成为进行临床研究的独立研究者。范德比尔特大学医学中心通过其多个重症监护病房，将为赖斯博士提供必要的患者人群，以进行一项前瞻性，随机的临床试验，以比较营养营养与进步与机械通风，重症患者的全热量率的影响。实验室资源可用于研究生化反应的变化，包括促炎和抗炎细胞因子反应。将评估临床结局的差异，包括呼吸机的断奶患者。通过与他的临床导师Arthur P. Wheeler博士的合作，赖斯博士将擅长试验设计，生物统计学，流行病学，患者招聘以及向科学界报告结果。这些技能将为赖斯博士从事重症监护研究的独立学术生涯奠定基础。许多机械通风的患者无法滋养自己，在肠胃外或肠胃外提供营养。肠内营养已被证明可以通过保留肠粘膜，减少细菌易位并减少全身感染来减少炎症并改善临床结果。尽管已经通过完整的肠内喂养观察到了这些改进，但是肠内喂养的速率非常低，在动物中显示出相似的保护。我们假设这些低水平的喂养还可以保留通风患者的肠粘膜，同时减少了这些患者和胃肠道并发症的促疾病和抗炎细胞因子反应，从而改善了临床效果，从而改善了临床成果。该提案的具体目的是证明，与全热量肠内饲料相比，低水平将：1）减少早期促炎和补偿性抗炎细胞因子反应； 2）降低喂养并发症的发生率，因此3） 改善临床结果，例如无呼吸机的日子和其他器官无效的日子。老化 人口，免疫抑制的增加以及对侵入性程序的使用增加将导致重症监护的持续增长。许多机械通风，重症患者受到肠内营养的支持。尽管使用了广泛使用，但仍缺乏有关将肠内营养最佳分娩到此类患者的数据。该建议将有助于权衡收益和风险，建立一种减少喂养并发症的成本效益手段，并为未来的急性呼吸衰竭患者的肠内饲料研究提供基础，需要机械通气。