PJI is a very serious complication that can occur after total joint arthroplasty, which leads to a devastating consequence if not diagnosed properly. Thus, the MSIS initially proposed criteria for diagnosis of PJI, and modified these criteria during the International Consensus Meeting (ICM) in 2013 [6]. However, it is still difficult to diagnose PJI pre-operatively because synovial fluid can be difficult to obtain via joint aspiration and bacterial cultures may take a long time to yield results. In an effort to accurately diagnose PJI in a more timely manner, several previous studies examined the potential use of novel biomarkers such as CD4+ blood monocytes [17], α-defensin [18], leukocyte esterase [8], and calprotectin [19] and found that they had greater diagnostic value than traditional biomarkers, including CRP and ESR. But, measurement of these novel parameters can be expensive and unavailable in some institutions. Our purpose was to identify simple and practical biomarkers for the early diagnosis of PJI. Thus, we assessed the diagnostic performance of NLR, PLR, and PVR, the biomarkers that are easily obtained from routine blood tests, and then compared their diagnostic performance with the traditional biomarkers.
We first compared the diagnostic performance of NLR, PLR, PVR in distinguishing patients in the PJI and the aseptic failure groups. Each of these three biomarkers was significantly elevated in PJI patients compared with aseptic failure patients, similar to the traditional biomarkers. Our ROC analysis indicated the optimal cut-off values were 2.71 for NLR, 132.67 for PLR, and 34.31 for PVR. NLR had the best diagnostic performance (AUC: 0.740, 95% CI: 0.666–0.805), with a sensitivity of 68.09% and a specificity of 70.09%, followed by PLR (AUC: 0.721, 95% CI: 0.646–0.788) and PVR (AUC: 0.668, 95% CI: 0.590–0.739). Notably, PLR had the highest sensitivity (85.11%) among all five tested biomarkers, and its sensitivity was even greater than that of CRP (82.98%) and ESR (63.83%). However, CRP (AUC: 0.896) and ESR (AUC: 0.829) provided better overall diagnostic performance than NLR, PLR, and PVR. Thus, we also tested the diagnostic performance of the combined use of CRP with each of the other markers. The combination of CRP + NLR had a diagnostic performance similar to that of CRP + ESR, the combination widely used in clinical practice.
Besides the convenience and minimal expense necessary for measuring the three biomarkers examined here, previous studies reported that these three biomarkers are generally useful for the diagnosis of infection. For example, Zareifar et al. [20] reported that an elevated platelet count and mean platelet volume (MPV) were decreased in patients with infectious and inflammatory processes. A retrospective study by Paziuk et al. [13] demonstrated that the PVR had acceptable performance in diagnosing PJI, with an AUC of 0.69 (48.10% sensitivity, 80.85% specificity) at the cut-off value of 31.70, similar to our cutoff value (34.31). They also reported that the combined application of PVR, CRP, and ESR significantly improved diagnostic performance. Sigmund et al. [16] evaluated the diagnostic value of PVR in a cohort of 177 patients who required revision surgery after THA (n = 91) and TKA (n = 86). They found that the individual use of PVR only had a sensitivity of 43% and a specificity of 81%, significantly inferior to that of CRP. They also found that the combined use of CRP + PVR did not improve the diagnostic performance relative to CRP alone. Our results are consistent with those of Sigmund et al [16]. We therefore conclude that PVR should not be considered as a reliable test for the diagnosis of PJI.
Other studies also considered the use of NLR and PLR as biomarkers for inflammatory responses and infections. For example, Qu et al. [21] measured the NLR in 2160 patients with bloodstream infections (BSIs) and 2523 healthy controls and found that the NLR was significantly higher in the BSI group. They concluded that NLR had a strong association with BSIs caused by Gram-negative bacteria, Gram-positive bacteria, and fungi. Shen et al. [22] demonstrated that an elevated PLR was related to increased risk of mortality based on analysis of the clinical data of 5537 patients with sepsis. Some other recent studies found that NLR and PLR had potential use for predicting PJI. In particular, the retrospective study by Zhao et al. [23] demonstrated that the NLR and PLR were significantly higher in an early PJI group than in a non-PJI group, and that NLR might be more valuable than PLR based on ROC analysis. They used an NLR cutoff of 2.77, similar to our cutoff (2.71). Similarly, Yu et al. [14] found that the NLR was effective in diagnosing PJI (AUC: 0.802, 85% sensitivity, 68.3% specificity, 34.7% PPV, 95.8% NPV) with a cut-off value of 2.13. However, Zhao et al. [23] and Yu et al. [14] demonstrated that NLR and PLR had greater predictive value for diagnosis of PJI than ESR and CRP, in stark contrast to our results. Our further analysis indicated that this was most likely due to differences in the characteristics of the enrolled patients; in our study, examined patients were diagnosed as chronic PJI, but the other two studies [14, 23] examined patients who had acute PJI .
To improve the accuracy of PJI diagnosis, many researchers have examined the effect of the combined use of several biomarkers. In particular, Tirumala et al. [15] found that the sensitivity and specificity for diagnosing PJI was near-perfect when PLR or PVR was combined with CRP, ESR, and synovial biomarkers. The present study showed that that only CRP + NLR provided better diagnostic performance than CRP + ESR (the most widely used combination in clinical practice) for PJI diagnosis, and that the difference was not statistically significant. Therefore, we consider NLR to be potentially valuable for the diagnosis of PJI.
There are several limitations in our study. First, this is a retrospective study and therefore has all of the limitations inherent to studies with this design. Our exclusion of patients with missing critical data or complicated with autoimmune diseases might have led to some bias. Second, there is no gold standard for the diagnosis of PJI. However, the MSIS criteria are considered the best method for its diagnosis, although this standard has low sensitivity in patients with low-virulence bacterial infections [17, 24]. To reduce the possibility of misdiagnosis, we excluded patients who underwent second-stage reimplantation due to the difficulty of determining their infection status. Finally, we examined 164 cases from a single institution, thus the small sample limited the generalizability of our conclusions. Therefore, well-designed multicenter studies with larger samples are needed to evaluate the value of NLR, PLR, and PVR for the diagnosis of PJI.