Cincinnati Multidisciplinary Clinical Research Center

这项申请来自辛辛那提儿童医院医疗中心，是我们现有P60多学科临床研究中心资助的竞争性延续，是对我们正在进行的P30辛辛那提风湿病核心中心资助的补充。该中心的主要关注点是更好地了解儿童风湿病的机制及其治疗。特别强调跨学科互动和利用资源，以实现协同增效。提出了四个项目(没有一个是试点项目)。每本书的标题和重点如下所示。 1)改进了儿童神经精神系统性红斑狼疮(NPSLE)的诊断和高级磁共振成像。该项目的主要目的是开发一种简单易用的神经认知功能障碍(NCD)筛查工具，可在常规临床环境中使用，并确定先进成像技术的效用，以提高我们对儿童SLE如何影响CMS，导致NCD的理解。 2)提高了对幼年特发性关节炎(JIA)的生物学和肿瘤坏死因子抑制作用的认识。这项研究的主要目标是开发方法，准确地识别哪些儿童在良好反应后可以安全地停止抗肿瘤坏死因子治疗，而不会有快速疾病发作的风险。这项研究将有助于更好地了解肿瘤坏死因子拮抗剂治疗对JIA生物学的影响，并为这些极其重要的新疗法的使用提供更安全和更具成本效益的方法。 3)系统性JIA中的巨噬细胞激活综合征(MAS)生物标志物。这个项目将调查MUNC 13-4基因的多态是否与MAS的易感性有关，从而帮助识别MAS风险增加的儿童。初步证据表明，血清sL2Ra和sCD163水平可反映MAS患者T细胞和巨噬细胞的活化和扩增程度，可作为MAS的早期诊断指标。此外，我们将研究这些可溶性受体水平的升高是否能够可靠地区分显性和亚临床MAS与常规sJIA病情的患者。我们将确定那些增加MAS风险的人是否代表了在sJIA发病时可以识别的sJIA的一个独特的亚型。 4)JIA儿童健康相关生活质量的影响因素。这个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治疗的儿童的HRQOL的途径。 一个成熟的方法核心将服务于MCRC的所有四个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进行行政和业务监督。

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.