Schultz Blake J, Sweeney Timothy, DeBaun Malcolm R, Remmel Melissa, Midic Uros, Khatri Purvesh, Gardner Michael J
Department of Orthopedic Surgery, Stanford University, Redwood City, CA 94063, United States.
Inflammatix, Inc, 863 Mitten Road, Suite 104, Burlingame, CA 94010, United States.
World J Orthop. 2019 Dec 18;10(12):424-433. doi: 10.5312/wjo.v10.i12.424.
Septic arthritis is an orthopedic emergency requiring immediate surgical intervention. Current diagnostic standard of care is an invasive joint aspiration. Aspirations provide information about the inflammatory cells in the sample within a few hours, but there is often ambiguity about whether the source is infectious (. bacterial) or non-infectious (. gout). Cultures can take days to result, so decisions about surgery are often made with incomplete data. Novel diagnostics are thus needed. The "Sepsis MetaScore" (SMS) is an 11-mRNA host immune blood signature that can distinguish between infectious and non-infectious acute inflammation. It has been validated in multiple cohorts across heterogeneous clinical settings.
To study whether the SMS holds diagnostic validity in determining the etiology of acute arthritis.
We conducted a blinded, prospective, non-interventional clinical study of the SMS. All patients undergoing work-up for a septic primary joint were enrolled. Patients proceeded through the normal standard-of-care pathway, including joint aspiration and inflammatory labs [white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)]. Venous blood was also drawn into PAX gene RNA-stabilizing tubes and mRNAs were measured using Nano String nCounter™. SMS was calculated blinded to clinical results.
A total of 20 samples were included, of which 11 were infected based on aspiration or intra-operative cultures. The SMS had an area under the ROC curve (AUROC) of 0.87 for separating infectious from non-infectious conditions. For comparison, the AUROCs for ESR = 0.58, CRP = 0.6, and WBC = 0.59. At 100% sensitivity for infection, the specificity of the SMS was 40%, meaning nearly half of non-septic patients could have been ruled out for further intervention.
In this pilot study, SMS showed a high level of diagnostic accuracy in predicting septic joints compared to other diagnostic biomarkers. This quick blood test could be an important tool for early, accurate identification of acute septic joints and need for emergent surgery, improving clinical care and healthcare spending.
化脓性关节炎是一种需要立即进行手术干预的骨科急症。当前的诊断标准护理方法是侵入性关节穿刺抽吸术。穿刺抽吸术能在数小时内提供样本中炎症细胞的信息，但对于其来源是感染性（如细菌感染）还是非感染性（如痛风）往往存在不确定性。培养结果可能需要数天时间，因此关于手术的决策往往是在数据不完整的情况下做出的。因此需要新型诊断方法。“脓毒症Meta评分”（SMS）是一种由11种mRNA组成的宿主免疫血液标志物，可区分感染性和非感染性急性炎症。它已在多种不同临床环境的队列中得到验证。
研究SMS在确定急性关节炎病因方面是否具有诊断有效性。
我们对SMS进行了一项盲法、前瞻性、非干预性临床研究。纳入所有因原发性化脓性关节接受检查的患者。患者按照正常的标准护理流程进行，包括关节穿刺抽吸术和炎症实验室检查[白细胞（WBC）、红细胞沉降率（ESR）、C反应蛋白（CRP）]。同时采集静脉血至PAX基因RNA稳定管中，并使用Nano String nCounter™测量mRNA。在对临床结果不知情的情况下计算SMS。
共纳入20个样本，其中11个基于穿刺抽吸术或术中培养结果为感染性样本。SMS区分感染性和非感染性情况的ROC曲线下面积（AUROC）为0.87。相比之下，ESR的AUROC为0.58，CRP为0.6，WBC为0.59。在对感染具有100%敏感性时，SMS的特异性为40%，这意味着近一半的非脓毒症患者可以被排除进一步干预。
在这项初步研究中，与其他诊断生物标志物相比，SMS在预测化脓性关节方面显示出较高的诊断准确性。这种快速血液检测可能是早期、准确识别急性化脓性关节以及判断是否需要紧急手术的重要工具，可改善临床护理和医疗支出。
