Administrative Core

骨感染，主要由金黄色葡萄球菌引起，仍然是骨科手术的祸根。 虽然初次全关节置换术(TJR)后感染的发生率很低(~1%)，但再次感染 发病率非常高(15%-40%)，这导致了骨科领域的金黄色葡萄球菌感染是 不治之症。此外，假体关节感染(PJI)是已知的非随机事件，在很大程度上 由患者特定的因素决定。为了解决这个问题，我们提出了最初的研究中心 翻译骨感染的骨免疫学(CoRTOBI)以检验以下假设：1)存在 金黄色葡萄球菌的蓄水池不受标准护理治疗的影响，以及2)患者的免疫力 针对金黄色葡萄球菌抗原的蛋白质组影响骨感染的发生率和结局。我们在这方面的工作 已经产生了33种出版物，6项专利技术，正在被行业转化为临床 合作伙伴，以及几项开创性的发现，这些仍然是这次更新的重点。这些包括：1)金黄色葡萄球菌 活骨的骨细胞陷窝管网络(OLCN)的定植，2)新型抗生素佐剂， 专门针对这些可以3D打印到定制垫片中的机械装置，3)定制多路复用器 免疫分析以阐明金黄色葡萄球菌的免疫蛋白质组，4)活体成像以量化“竞争 5)将抗ISDB反应识别为敏感免疫与抗-ISDB GMD反应作为保护性免疫在小鼠和患者的培养中证实金黄色葡萄球菌骨感染。 在这次更新中，行政核心将提供CoRTOBI的业务和财务管理。会的 还支持临床研究和生物统计需求，促进沟通，运行浓缩 计划，并维护试点和可行性项目计划(PFPP)。《公约》的具体目标 管理核心是：目标1.管理整个CoRTOBI，包括人事管理， 通过如期评估对服务和研究进展进行财务监督和质量控制 开会。目标2.促进CoRTOBI项目和核心调查人员、IAC和EAC、我们的 NIH资助的CTSA、NIH/NIAMS计划工作人员以及更大的科学界。目标3.协调成本- 有效访问研究核心。目标4.维护我们成功的试点和可行性项目计划 (PFPP)在骨感染中的作用。目标5.为新的知识产权申请专利，并与行业合作伙伴合作。 以及，目标6.为CoRTOBI调查人员、骨感染研究人员、 整形外科医生，以及更大的科学界和非科学界。在更新后的P50结束时 我们将有：1)阐明金黄色葡萄球菌在骨骼上定植的新机制；2)鉴定新的 抗生素佐剂，并展示了它们在3D打印间隔物中的用途，用于1阶段修订，3)定义了 易感免疫蛋白质组的发生机制及研制攻克的mRNA型纳米疫苗 它，以及4)生成了一个全面的算法来预测感染和临床结果。

Bone infection, primarily caused by Staphylococcus aureus, remains the bane of orthopaedic surgery. Although the incidence of infection following primary total joint replacement (TJR) is low (~1%), reinfection rates are very high (15-40%), which has led to the orthopaedic paradigm that S. aureus infection of bone is incurable. Additionally, prosthetic joint infection (PJI) is known to be a non-random event that is largely determined by patient-specific factors. To address this, we proposed the original Center of Research Translation on the Osteoimmunology of Bone Infection (CoRTOBI) to test the hypotheses that: 1) there are reservoirs of S. aureus that are not affected by standard of care treatments, and 2) the patient’s immune proteome against S. aureus antigens impacts the incidence and outcome of bone infection. Our work on this has resulted in 33 publications, 6 patented technologies that are being translated to the clinic by industry partners, and several seminal discoveries that remain the focus of this renewal. These, include: 1) S. aureus colonization of the osteocyte lacuno-canalicular network (OLCN) of live bone, 2) novel antibiotic adjuvants that specifically target these mechanisms that can be 3D-printed into custom spacers, 3) custom multiplex immunoassays to elucidate the immune proteome of S. aureus, 4) in vivo imaging to quantify “the race for the surface” of implants in real time, and 5) identification of anti-IsdB responses as susceptible immunity vs. anti- Gmd responses as protective immunity in mice and patients with culture confirmed S. aureus bone infection. In this renewal, the Administrative Core will provide operational and fiscal management of the CoRTOBI. It will also support clinical research and biostatistical needs, facilitate communications, run the Enrichment Programs, and maintain the Pilot and Feasibility Project Program (PFPP). The Specific Aims of the Administrative Core are to: Aim 1. Govern the entire CoRTOBI, which includes administration of personnel, financial oversight, and quality controls on services and research progress through evaluations at scheduled meetings. Aim 2. Foster communications between CoRTOBI Project & Core investigators, the IAC & EAC, our NIH-funded CTSAs, NIH/NIAMS Program staff, and the greater scientific community. Aim 3. Coordinate cost- effective access to the Research Cores. Aim 4. Maintain our successful Pilot and Feasibility Project Program (PFPP) in Bone Infection. Aim 5. Patent new intellectual property and collaborate with industry partners. And, Aim 6. Provide enrichment opportunities for CoRTOBI investigators, bone infection researchers, orthopaedic surgeons, and the larger scientific and lay communities. At the conclusion of this renewed P50 CoRTOBI, we will have: 1) elucidated novel mechanisms of S. aureus colonization of bone, 2) identified novel antibiotic adjuvants, and demonstrate their use in 3D-printing spacers for 1-stage revision, 3) defined the mechanism of susceptible immune proteome genesis, and develop mRNA nanoparticle vaccines to overcome it, and 4) generated a comprehensive algorithm to predict infection and clinical outcomes.