Cincinnati Multidisciplinary Clinical Research Center

辛辛那提多学科临床研究中心

• 批准号: 7932754
• 负责人: DANIEL Joe LOVELL
• 金额: $ 117.77万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932754
• 关键词: Cincinnati; Multidisciplinary; Clinical; Research; Center

This application, from Cincinnati Children's Hospital Medical Center, is a competing continuation of our existing P60 Multidisciplinary Clinical Research Center grant and is complementary to our ongoing P30 Cincinnati Rheumatic Diseases Core Center grant. The Center's chief focus is a greater understanding of the mechanisms of the rheumatic illnesses of childhood and their treatment. Special emphasis is given to cross-disciplinary interactions, and leveraging of resources such that synergism is realized. Four projects (none of which are pilot projects) are proposed. The titles and chief foci of each are given below. 1) Improved Diagnostic and Advanced Magnetic Resonance Imaging for Pediatric Neuro-Psychiatric SLE (NPSLE). Chief aims of this project are to develop an easy-to-use screening tool for neuro-cognitive dysfunction (NCD) that can be utilized in the routine clinic setting, and to determine the utility of advanced imaging techniques to heighten our understanding of how pediatric SLE affects the CMS, resulting in NCD. 2) Improved Understanding of the Biology and Use of TNF Inhibition in juvenile idiopathic arthritis (JIA). The primary goal of this study is to develop methods to accurately identify those children in whom anti-TNF therapies can be safely stopped after a favorable response, without risk of a rapid disease flare. This study will result in a better understanding of the effect of TNF antagonist therapy on the biology of JIA and a safer and more cost effective approach to the use of these profoundly important new therapies. 3) Macrophage Activation Syndrome (MAS) Biomarkers in Systemic JIA (sJIA). This project will investigate whether polymorphisms in the MUNC 13-4 gene contribute to the predisposition to MAS, thereby helping to identify children at an elevated increased risk of MAS. Preliminary evidence suggests that serum levels of slL2Ra and sCD163 may reflect the degree of activation and expansion of T cells and macrophages in MAS, and thus serve as early diagnostic markers. Further, we will investigate whether elevated levels of these soluble receptors can distinguish reliably between those with overt and sub-clinical MAS from those with conventional sJIA flare. We will determine if those at increased risk of MAS represent a distinct subtype of sJIA which can be recognized at onset of sJIA. 4) Determinants of Health-Related Quality of Life in Children with JIA. The chief aim of this project is to determine the pathways by which medical variables (biological, physiological, clinical) and non-medical variables (child, family, environmental) predict the HRQOL in children being treated for JIA. A well-matured Methodology Core will serve all four MCRC projects, as well as many projects in the research base, and serves as a national and international resource. An Administrative Unit, composed of several internal and external advisory boards, will exercise administrative and operational oversight.

这项申请，从辛辛那提儿童医院医疗中心，是我们现有的P60多学科临床研究中心赠款的竞争延续，是我们正在进行的P30辛辛那提风湿病核心中心赠款的补充。该中心的主要重点是更好地了解儿童风湿性疾病及其治疗的机制。特别强调跨学科的互动，并利用资源，从而实现协同作用。提出了四个项目（均不是试点项目）。下文列出了每一个项目的标题和主要重点。 1)儿童神经精神系统性红斑狼疮（NPSLE）的改进诊断和高级磁共振成像。该项目的主要目的是开发一种易于使用的神经认知功能障碍（NCD）筛查工具，可用于常规临床设置，并确定先进的成像技术的实用性，以提高我们对儿童SLE如何影响CMS，导致NCD的理解。 2)提高对幼年特发性关节炎（JIA）中TNF抑制的生物学和用途的理解。本研究的主要目的是开发方法，以准确地识别那些在良好反应后可以安全停止抗TNF治疗的儿童，而没有快速疾病发作的风险。这项研究将导致更好地了解TNF拮抗剂治疗对JIA生物学的影响，以及使用这些非常重要的新疗法的更安全，更具成本效益的方法。 3)巨噬细胞活化综合征（MAS）生物标志物在系统性JIA（sJIA）。该项目将研究MMP 13-4基因的多态性是否有助于MAS的易感性，从而帮助识别MAS风险升高的儿童。初步证据表明，血清sIL 2 Ra和sCD 163水平可能反映MAS中T细胞和巨噬细胞的活化和扩增程度，从而可作为早期诊断标志物。此外，我们将研究这些可溶性受体水平的升高是否可以可靠地区分那些与传统的sJIA耀斑明显和亚临床MAS。我们将确定那些MAS风险增加的患者是否代表sJIA的一种独特亚型，这种亚型在sJIA发作时就可以识别。 4)JIA儿童健康相关生活质量的决定因素该项目的主要目的是确定医学变量（生物、生理、临床）和非医学变量（儿童、家庭、环境）预测接受JIA治疗的儿童HRQOL的途径。 一个成熟的方法核心将服务于所有四个MCRC项目，以及研究基地的许多项目，并作为国家和国际资源。一个由若干内部和外部咨询委员会组成的行政股将行使行政和业务监督。