Periprosthetic joint infection (PJI) is a catastrophic complication after total joint arthroplasty (TJA). Timely and accurate diagnosis is important for the management of PJI. Currently, many biomarkers are available for the diagnosis of PJI, but which inflammatory biomarker combination has the best diagnostic value has not been reported.We retrospectively analyzed 244 patients who underwent revision knee or hip arthroplasty in our institution. They were divided into two groups: 87 in the PJI group and 157 in the aseptic failure (AF) group. The preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-to-albumin ratio (CAR), CRP-to-lymphocyte ratio (CLR), neutrophil-to-albumin ratio (NAR) and platelet-to-albumin ratio (PAR) were determined and compared between the two groups. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to assess the diagnostic value of all biomarkers, and the optimal cut-off value, positive predictive value (PPV) and negative predictive value (NPV) were further calculated by the Youden index.The NLR, PLR, CAR, CLR, NAR and PAR of the PJI group were significantly higher than those of the AF group (P<0.001). According to the ROC and AUC results, the diagnostic value of CAR and CLR was considered excellent with AUCs of 0.931 and 0.935, respectively. The diagnostic value of NAR (0.739) and PAR (0.785) were fair, the diagnostic value of NLR (0.694) was poor, and PLR (0.535) had no diagnostic ability. Subgroup analysis showed no significant differences in combined inflammatory biomarkers between the two groups.CAR and CLR are valuable combined inflammatory biomarkers for diagnosing PJI, while other markers were of limited value for the diagnosis of PJI. 

https://www.dovepress.com/getfile.php?fileID=87077

C-Reactive Protein-to-Albumin Ratio (CAR) and C-Reactive Protein-to-Lymphocyte Ratio (CLR) are Valuable Inflammatory Biomarker Combination for the Accurate Prediction of Periprosthetic Joint Infection

The current literature on the diagnosis of periprosthetic joint infection provides controversial evidence on the diagnostic accuracy of MLR, NLR, PVR, and PLR. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of these biomarkers for the diagnosis of hip and knee prosthetic infection. According to the PRISMA flowchart, we searched MEDLINE, Scopus, and Web of Science, for studies on these ratios for diagnosing PJI. Sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and AUC were analyzed. We included 11 articles in our meta-analysis, including 7537 patients who underwent total hip and knee arthroplasties; among these, 1974 (26%) patients reported a joint infection. The pooled sensitivity and specificity were 0.72 and 0.74, respectively, for NLR, 0.72 and 0.77 for PVR, and 0.77 and 0.75 for PLR. The sensitivity of MLR ranges from 0.54 to 0.81, while the specificity ranges from 0.78 to 0.81. Regarding the evaluation of AUCs, the best diagnostic performance was achieved by MLR (AUC = 0.77) followed by PLR (AUC = 0.75), NLR (AUC = 0.73), and PVR (AUC = 0.70). This meta-analysis demonstrates a fair diagnostic accuracy of these ratios, thus not being useful as a screening tool.

/pdf/diagnostic-performance-of-neutrophil-to-lymphocyte-ratio-3vj4fdtz.pdf

Diagnostic Performance of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Platelet to Mean Platelet Volume Ratio in Periprosthetic Hip and Knee Infections: A Systematic Review and Meta-Analysis

The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and unify their diagnostic accuracy and the threshold selection of serum and synovial routine tests for PJI at an early stage.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/os.13500

Reliable Diagnostic Tests and Thresholds for Preoperative Diagnosis of Non‐Inflammatory Arthritis Periprosthetic Joint Infection: A Meta‐analysis and Systematic Review

Serum and synovial biomarkers are currently used to diagnose periprosthetic joint infection (PJI). Serum neutrophil-to-lymphocyte ratio (NLR) has shown promise as an inexpensive test in diagnosing infection, but there are no reports of synovial NLR or absolute neutrophil count (ANC) for diagnosing chronic PJI. The purpose of this study was to investigate the diagnostic potential of both markers.A retrospective review of 730 patients who underwent total joint arthroplasty and subsequent aspiration was conducted. Synovial white blood cell (WBC) count, synovial polymorphonuclear percentage (PMN%), synovial NLR, synovial ANC, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), serum WBC, serum PMN%, serum NLR, and serum ANC had their utility in diagnosing PJI examined by area-under-the-curve analyses (AUC). Pairwise comparisons of AUCs were performed.The AUCs for synovial WBC, PMN%, NLR, and ANC were 0.84, 0.84, 0.83, and 0.85, respectively. Synovial fluid ANC was a superior marker to synovial NLR (P = .027) and synovial WBC (P = .003) but not PMN% (P = .365). Synovial NLR was inferior to PMN% (P = .006) but not different from synovial WBC (P > .05). The AUCs for serum ESR, CRP, WBC, PMN%, NLR, and ANC were 0.70, 0.79, 0.63, 0.72, 0.74, and 0.67, respectively. Serum CRP outperformed all other serum markers (P < .05) except for PMN% and NLR (P > .05). Serum PMN% and NLR were similar to serum ESR (P > .05).Synovial ANC had similar performance to PMN% in diagnosing chronic PJI, whereas synovial NLR was a worse diagnostic marker. The lack of superiority to synovial PMN% limits the utility of these tests compared to established criteria. 

Synovial Fluid Absolute Neutrophil Count and Neutrophil-to-Lymphocyte Ratio are not Superior to Polymorphonuclear Percentage in Detecting Periprosthetic Joint Infection.

<h2>Abstract</h2><h3>Background</h3> The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. <h3>Methods</h3> We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. <h3>Results</h3> Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, <i>P</i> < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, <i>P</i> < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, <i>P</i> < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, <i>P</i> < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, <i>P</i> < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. <h3>Conclusion</h3> In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI. 

Neutrophil to lymphocyte ratio and periprosthetic joint infection: a systematic review and meta-analysis.

BACKGROUND Diagnosing chronic periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the serum neutrophil-to-lymphocyte ratio (NLR) in aiding the diagnosis of chronic PJI. MATERIALS AND METHODS We retrospectively evaluated the medical records of 158 patients who had undergone revision arthroplasty (104 with aseptic mechanic failure and 54 with chronic PJI) from July 2011 to July 2020. Univariate analysis followed by multivariate logistic regression was applied to compare NLR, C-reactive protein (CRP), and erythrocyte sedimentation ratio (ESR) between the two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with CRP and ESR. RESULTS NLR, CRP, and ESR were significantly higher in patients with chronic PJI than in the aseptic revision group (p < 0.05). ROC curve analysis revealed that NLR had a sensitivity of 57.41% and a specificity of 77.88% with an optimal threshold of 2.56. The optimal threshold for CRP and ESR was 7.00 mg/L (sensitivity 62.50% and specificity 83.12%) and 43 mm/h (sensitivity 59.38% and specificity 80.52%), respectively. The combined diagnostic value of NLR with CRP and ESR was shown to have no additional diagnostic value in predicting chronic PJI. CONCLUSION Compared with traditional inflammatory biomarkers (ESR and CRP), the value of serum NLR alone or combined with CRP and ESR for diagnosing chronic PJI is limited. LEVEL OF EVIDENCE Level 3.

/pdf/limited-value-of-serum-neutrophil-to-lymphocyte-ratio-in-the-1a2dcme46l.pdf

Limited value of serum neutrophil-to-lymphocyte ratio in the diagnosis of chronic periprosthetic joint infection.

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Limited value of serum neutrophil-to-lymphocyte ratio in the diagnosis of chronic periprosthetic joint infection.