Administrative Core

主要由金黄色葡萄球菌引起的骨感染仍然是骨科手术的祸根。 尽管初次全关节置换术（TJR）后感染的发生率较低（~1%）， 率非常高（15-40%），这导致了S。金黄色葡萄球菌感染的骨是 无法治愈此外，已知人工关节感染（PJI）是一种非随机事件， 取决于患者的具体因素。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） 是S.金黄色葡萄球菌，不受护理治疗标准的影响，和2）患者的免疫 抗S.金黄色葡萄球菌抗原影响骨感染的发生率和结果。我们在这方面的工作 已经有33篇出版物，6项专利技术正在被工业界转化为临床应用 合作伙伴，和几个开创性的发现，仍然是这个更新的重点。包括：1）S.金黄色 活骨的骨细胞腔隙-小管网络（OLCN）的定殖，2） 特别针对这些可以3D打印到定制间隔区中机制，3）定制多路复用 免疫分析，以阐明免疫蛋白质组的S。金黄色葡萄球菌，4）体内成像，以量化“竞争的 真实的时间的植入物的“表面”，以及5）将抗IsdB应答识别为易感免疫与抗 Gmd反应作为保护性免疫在小鼠和患者与培养证实S。金黄色葡萄球菌骨感染。 在这次更新中，行政核心将提供CoRTOBI的业务和财政管理。它将 还支持临床研究和生物统计需求，促进通信，运行富集 计划，并保持试点和可行性项目计划（PFPP）。的具体目标 行政核心是：目标1。管理整个CoRTOBI，包括人事管理， 通过定期评估，对服务和研究进展进行财务监督和质量控制 会议.目标2.促进CoRTOBI项目和核心调查员、IAC和EAC、我们的 NIH资助的CTSA，NIH/NIAMS计划工作人员和更大的科学界。目标3.协调成本- 有效地访问研究核心。目标4。保持我们成功的试点和可行性项目计划 （PFPP）骨感染。目标5。为新的知识产权申请专利，并与行业合作伙伴合作。 目标6为CoRTOBI研究者、骨感染研究者、 整形外科医生，以及更大的科学和外行社区。在这次更新的P50会议结束时， CoRTOBI，我们将有：1）阐明新的机制，S。骨金黄色葡萄球菌定植，2）确定为新 抗生素佐剂，并证明它们在3D打印间隔物中用于一期翻修，3）定义了 易感免疫蛋白质组发生的机制，并开发mRNA纳米颗粒疫苗，以克服 它，和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.