Developing a molecular tool to stratify the acute joint presentation: facilitating early diagnosis of septic arthritis.

开发一种分子工具来对急性关节表现进行分层：促进化脓性关节炎的早期诊断。

• 批准号: 1651836
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1651836
• 关键词: Developing; molecular; tool; stratify; acute

Keywords: Sepsis, biomarker, arthritis, diagnosisAbstract:Atraumatic acute joint swelling, a limping child or a child unwilling to weight-bear/move a joint due to pain are common presentations to the Emergency Department. The key diagnostic differential is between septic arthritis, which is defined as inflammation of a joint secondary to bacterial infection, and non-infectious causes of inflammation e.g. gout and transient synovitis. However, distinguishing between infectious and non-infectious arthritis represents a diagnostic challenge as clinical signs and symptoms may be subtle with considerable overlap between the two groups and screening laboratory/imaging studies and synovial fluid/blood cultures are relatively insensitive. Previous work has demonstrated that bacteria and their toxins are highly destructive to joint tissues such as bone and cartilage and therefore a delay in diagnosis and initiation of treatment, which typically involves a combination of intravenous antibiotics coupled with joint irrigation, may have severe clinical consequences. Septic arthritis however comprises only a minority of acute joint presentations, yet almost all such patients are admitted to hospital, undergo potentially invasive procedures and universally receive anti-infective therapeutics, with their attendant risks in the context of expanding antibiotic resistance, overuse and expense. The rapid and accurate clinical stratification of the acute joint presentation would thus be extremely desirable. This may be achieved through the identification of novel blood, synovial fluid and urinary biomarkers unique to infectious arthritis. In addition, for those patients with microbiologically confirmed septic arthritis, genome sequencing of isolated bacteria may identify unique molecular signatures associated with poor structural or systemic prognosis, which could be utilised ultimately to develop novel antimicrobial treatments to improve clinical outcome in such patients. This studentship therefore proposes to analyse blood, synovial fluid and urine samples of patients presenting with suspected septic arthritis utilising established metabolomic, proteomic and transcriptomic techniques coupled with advanced bioinformatic approaches for dataset analysis. Samples from patients recruited to this study will be collected during routine investigations and treatments (joint aspiration/surgical washout) and thus no patients will undergo invasive procedures solely for the purpose of the study. Genome sequencing will be conducted on all bacteria isolated from routine synovial fluid and blood cultures. In addition the studentship will provide hands on training in cell culture and ex vivo infection model development to enhance the skill set and breadth of training on offer.

保留字：脓毒症，生物标志物，关节炎，diagnosisAbstract：非创伤性急性关节肿胀，一个跛行的孩子或一个孩子不愿意承担/移动关节由于疼痛是常见的急诊科介绍。关键的诊断差异是脓毒性关节炎（定义为继发于细菌感染的关节炎症）与非感染性炎症原因（如痛风和一过性滑膜炎）之间的差异。然而，区分感染性和非感染性关节炎是一项诊断挑战，因为临床体征和症状可能很微妙，两组之间有相当大的重叠，筛选实验室/成像研究和滑液/血培养相对不敏感。以前的工作已经证明，细菌及其毒素对关节组织（如骨和软骨）具有高度破坏性，因此诊断和治疗开始的延迟（通常涉及静脉注射抗生素与关节冲洗的组合）可能会产生严重的临床后果。然而，脓毒性关节炎仅包括少数急性关节表现，但几乎所有此类患者都被收治入院，经历潜在的侵入性手术并普遍接受抗感染治疗，伴随着抗生素耐药性扩大、过度使用和费用增加的风险。因此，对急性关节表现进行快速准确的临床分层是非常必要的。这可以通过鉴定感染性关节炎特有的新的血液、滑液和尿液生物标志物来实现。此外，对于那些微生物学证实的脓毒性关节炎患者，分离细菌的基因组测序可以识别与不良结构或全身预后相关的独特分子特征，最终可以用于开发新的抗菌治疗方法，以改善此类患者的临床结局。因此，该研究计划利用已建立的代谢组学，蛋白质组学和转录组学技术，结合先进的生物信息学方法对疑似脓毒性关节炎患者的血液，滑液和尿液样本进行分析。将在常规检查和治疗（关节抽吸/手术洗脱）期间采集本研究招募患者的样本，因此，患者不会仅出于研究目的接受侵入性手术。将对从常规滑液和血液培养物中分离的所有细菌进行基因组测序。此外，该奖学金将提供细胞培养和体外感染模型开发方面的实践培训，以提高所提供培训的技能和广度。