Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.
Statistical Bioinformatics Department, University of Regensburg, Am BioPark 9, 93053, Regensburg, Germany.
Int Orthop. 2020 Dec;44(12):2515-2520. doi: 10.1007/s00264-020-04731-6. Epub 2020 Jul 25.
In many cases, the diagnosis of a periprosthetic joint infection (PJI) consisting of the clinical appearance, laboratory tests, and other diagnostic tools remains a difficult task. Single serum biomarkers are easy to collect, are suitable for periodical assessment, and are a crucial tool in PJI diagnosis, but limited sensitivity or specificity is reported in literature. The aim of this study was to combine the best-performing single serum biomarkers into a multi-biomarker model aiming to improve the diagnostic properties.
Within a 27-month period, 124 surgical procedures (aseptic or septic revision total knee arthroplasty (TKA) or total hip arthroplasty (THA)) were prospectively included. The serum leukocyte count, C-reactive protein (CRP), interleukin-6, procalcitonin, interferon alpha, and fibrinogen were assessed 1 day prior to surgery. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. After randomly splitting the data into a training (75%) and a test set (25%), the multi-biomarker model was calculated and validated in a cross-validation approach.
CRP (AUC 0.91, specificity 0.67, sensitivity 0.90, p value 0.03) and fibrinogen (AUC 0.93, specificity 0.73, sensitivity 0.94, p value 0.02) had the best single-biomarker performances. The multi-biomarker model including fibrinogen, CRP, the ratio of fibrinogen to CRP, and the ratio of serum thrombocytes to CRP showed a similar performance (AUC 0.95, specificity 0.91, sensitivity 0.72, p value 0.01).
In this study, multiple biomarkers were tested for their diagnostic performance, with CRP and fibrinogen showing the best results regarding the AUC, accuracy, sensitivity, and specificity. It was not possible to further increase the diagnostic accuracy by combining multiple biomarkers using sophisticated statistical methods.
在许多情况下,由临床症状、实验室检查和其他诊断工具组成的假体周围关节感染(PJI)的诊断仍然是一项艰巨的任务。单一的血清生物标志物易于采集,适合定期评估,是 PJI 诊断的重要工具,但文献报道其敏感性或特异性有限。本研究的目的是将表现最佳的单一血清生物标志物组合成一个多生物标志物模型,以提高诊断性能。
在 27 个月的时间内,前瞻性纳入 124 例手术(无菌或感染性翻修全膝关节置换术(TKA)或全髋关节置换术(THA))。在手术前一天评估白细胞计数、C 反应蛋白(CRP)、白细胞介素 6、降钙素原、干扰素-α和纤维蛋白原。使用带有 lasso 正则化的逻辑回归对生物标志物及其所有比值进行分析。将数据随机分为训练集(75%)和测试集(25%)后,在交叉验证方法中计算和验证多生物标志物模型。
CRP(AUC 0.91,特异性 0.67,敏感性 0.90,p 值 0.03)和纤维蛋白原(AUC 0.93,特异性 0.73,敏感性 0.94,p 值 0.02)具有最佳的单生物标志物表现。包括纤维蛋白原、CRP、纤维蛋白原与 CRP 的比值以及血小板与 CRP 的比值的多生物标志物模型表现相似(AUC 0.95,特异性 0.91,敏感性 0.72,p 值 0.01)。
在这项研究中,测试了多种生物标志物的诊断性能,CRP 和纤维蛋白原在 AUC、准确性、敏感性和特异性方面表现最佳。使用复杂的统计方法将多个生物标志物结合起来,无法进一步提高诊断准确性。