Comparison of a Comprehensive Set of Fibrinolytic Markers With C-Reactive Protein and Erythrocyte Sedimentation Rate for the Diagnosis of Periprosthetic Joint Infection

BackgroundThe diagnosis of periprosthetic joint infection (PJI), a serious complication after primary total joint arthroplasty, remains challenging. Recently, fibrinolytic activities have been shown to be closely related to infections and inflammation. However, data assessing the value of fibrinolytic markers for the diagnosis of PJI have been sparse until now.MethodsWe retrospectively enrolled 157 patients undergoing revision for aseptic loosening (n = 106, group A) or revision for chronic PJI (n = 51, group B) from January 2014 to August 2019. PJI was defined using the Musculoskeletal Infection Society criteria. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, fibrin degradation product (FDP), and fibrinogen were measured preoperatively. The diagnostic values of each biomarker were analyzed and compared using receiver operating characteristic curves, sensitivity, and specificity.ResultsCompared with group A, group B had significantly higher levels of CRP, ESR, D-dimer, FDP, and fibrinogen (P < .001). The area under the curve of fibrinogen was 0.914, which was slightly lower than that of CRP (0.924). FDP and D-dimer had area under the curve values of 0.808 and 0.784, respectively. The optimal threshold, sensitivity, and specificity were 3.56 g/L, 86.27%, and 83.96% for fibrinogen; 1.22 mg/L, 66.67%, and 85.85% for D-dimer; and 3.98 μg/mL, 72.55%, and 80.19% for FDP, respectively.ConclusionFibrinolytic markers provided promising diagnostic support for PJI, especially fibrinogen, which had a diagnostic efficiency similar to that of CRP and ESR.     

Elevated ESR/CRP Ratio Is Associated With Reinfection After Debridement,Antibiotics, and Implant Retention in Chronic Periprosthetic Joint Infections

BackgroundRatios of established inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), have been used for diagnostic purposes in the surgical field; however, the ESR:CRP ratio (ECR) has not been evaluated as a marker for predicting infection resolution in patients with periprosthetic joint infections (PJIs). This study aimed to evaluate the diagnostic accuracy of ECR in predicting postoperative reinfection in patients who underwent debridement, antibiotics, and implant retention (DAIR).MethodsThis is a retrospective review of 179 consecutive patients who underwent DAIR revision total joint arthroplasty for PJI. Patients were stratified by acuity of their infection: acute PJI, acute hematogenous PJI, and chronic PJI. The area under the receiver operating characteristic curve was calculated to evaluate ECR as diagnostic marker for predicting postoperative reinfection in patients who underwent DAIR.ResultsStatistically significant differences in ECR were found in patients who underwent DAIR revision total joint arthroplasty for chronic infection (1.23 vs 2.33; P = .04). There was no significant difference in ECR in patients who underwent DAIR for acute infection (P = .70) and acute hematogenous infection (P = .56). In patients who underwent DAIR for chronic PJI, ECR demonstrated a sensitivity and specificity of 75% and 84%, respectively, for the prediction of postoperative reinfection, which was significantly higher than that of ESR (sensitivity, 67%; specificity, 47%; P < .001) and CRP (sensitivity, 50%; specificity, 26%; P < .001).ConclusionElevated ECR was associated with an increased reinfection risk in patients who underwent DAIR for chronic PJI, suggesting that preoperative ECR may be a useful predictor to identify patients at increased risk of reinfection after DAIR for chronic PJIs.     

The Natural Course of Serum D-Dimer,C-Reactive Protein,and Erythrocyte Sedimentation Rate Levels After Uneventful Primary Total Joint Arthroplasty

BackgroundThis study aimed to assess the baseline levels of D-dimer, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) and monitor the natural course of these serum markers after uneventful primary total joint arthroplasty.MethodsThis prospective study enrolled 81 patients undergoing primary total knee arthroplasty or total hip arthroplasty. The level of serum D-dimer, CRP, and ESR was measured preoperatively and on postoperative days 1, 3, 5, 15, and 45. Mean peak values, peak times, and distribution were compared between D-Dimer, CRP, and ESR.ResultsThe mean preoperative serum D-dimer, CRP, and ESR level was 412 ± 260 (range 200-980) ng/mL, 2.93 ± 2.1 (range 1-18) mg/L, and 22.88 ± 17.5 (range 3-102) mm/h, respectively. The highest mean peak for D-dimer, CRP, and ESR was at postoperative day 1, 3, and 5, respectively.ConclusionD-dimer levels reached peak levels on postoperative day 1 and then declined rapidly to a plateau level by postoperative day 3. A second, albeit small, peak in the level of D-dimer occurred on postoperative day 15. The level of CRP and ESR remained elevated for much longer with CRP returning to baseline on postoperative day 45 and the level of ESR had not returned back to normal on postoperative day 45.     

Plasma Fibrin Degradation Product and D-Dimer Are of Limited Value for Diagnosing Periprosthetic Joint Infection

BackgroundAlthough the Musculoskeletal Infection Society introduced the use of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers for diagnosing periprosthetic joint infection (PJI), no single blood marker reliably detects infection before revision arthroplasty. We therefore posed 2 questions: (1) Are fibrin degradation product (FDP) and D-dimer of value for diagnosing PJI before revision arthroplasty? (2) What are their sensitivity and specificity for that purpose?MethodsTo answer these questions, we retrospectively enrolled 318 patients (129 with PJI [group A], 189 with aseptic mechanical failure [group B]) who underwent revision arthroplasty during 2013-2018. Receiver operating characteristic curves were used to determine maximum sensitivity and specificity of the 2 markers. Inflammatory and fibrinolytic markers were evaluated based on (1) the Tsukayama-type infection present and (2) the 3 most common PJI-related pathogens.ResultsFDP and D-dimer levels were higher in group A than in group B: 4.97 ± 2.83 vs 4.14 ± 2.67 mg/L and 2.14 ± 2.01 vs 1.51 ± 1.37 mg/L fibrinogen equivalent units (FEU), respectively (both P < .05). Based on the Youden index, 2.95 mg/L and 1.02 mg/L FEU are the optimal FDP and D-dimer predictive cutoffs, respectively, for diagnosing PJI. Sensitivity and specificity, respectively, were 65.12% and 60.33% (FDP) and 68.29% and 50.70% (D-dimer). ESR, CRP, and interleukin-6 values were diagnostically superior to those of FDP and D-dimer.ConclusionThe value of plasma FDP and D-dimer for diagnosing PJI is limited compared with traditional inflammatory markers (ESR, CRP, interleukin-6) before revision arthroplasty.     

Combined Measurement of D-Dimer and C-Reactive Protein Levels: Highly Accurate for Diagnosing Chronic Periprosthetic Joint Infection

BackgroundDiagnosis of chronic periprosthetic joint infection (PJI) can be challenging and elusive in the absence of a gold standard. D-dimer plays an important role in inflammation that occurs during infections and therefore could be a valuable biomarker for PJI. This study aims to investigate the sensitivity and specificity of D-dimer in detecting chronic PJI and to improve the accuracy of chronic PJI diagnosis through combined measurement of serum D-dimer with C-reactive protein (CRP)/erythrocyte sedimentation rate.MethodsOne hundred twenty-two patients presenting with a painful knee or hip after total hip or total knee arthroplasty for surgical revision were included in this prospective trial. Our cohort consisted of 55 patients undergoing revision for chronic PJI and 67 patients undergoing revision for aseptic failure. PJI was defined using the Musculoskeletal Infection Society criteria. Receiver operating characteristic curves and area under the curve were analyzed for each biomarker.ResultsThe area under the curve for D-dimer was 0.915 and was more accurate than serum erythrocyte sedimentation rate 0.719 and CRP 0.761. 1170 ng/mL was determined to be the optimal threshold value of D-dimer for the diagnosis of chronic PJI, with a sensitivity of 92.73% and a specificity of 74.63% in the diagnosis of chronic PJI. The combination of D-dimer and CRP tests demonstrated a sensitivity of 98.11% and negative predictive value of 96.55% for the diagnosis of chronic PJI.ConclusionThe present study identified the D-dimer is a valuable biomarker in detecting chronic PJI. The combinations of serum D-dimer and CRP led to the improvement of sensitivity compared with those of the single-index test.     

Utility of D-dimer in total joint arthroplasty

As the number of patients receiving total joint replacements continues to rise, considerable attention has been directed towards the early detection and prevention of postoperative complications. While D-dimer has long been studied as a diagnostic tool in venous thromboembolism (VTE), this assay has recently received considerable attention in the diagnosis of periprosthetic joint infection (PJI). D-dimer values are substantially elevated in the acute postoperative period after total joint arthroplasty, with levels often exceeding the standard institutional cutoff for VTE (500 µg/L). The utility of D-dimer in detecting VTE after total joint replacement is currently limited, and more research to assess its value in the setting of contemporary prophylaxis protocols is warranted. Recent literature supports D-dimer as a good to excellent biomarker for the diagnosis of chronic PJI, especially when using serum sample technique. Providers should exercise caution when interpreting D-dimer levels in patients with inflammatory and hypercoagulability disorders, as the diagnostic value is decreased. The updated 2018 Musculoskeletal Infection Society criteria, which includes D-dimer levels > 860 µg/L as a minor criterion, may be the most accurate for diagnosing chronic PJI to date. Larger prospective trials with transparent lab testing protocols are needed to establish best assay practices and optimal cutoff values for D-dimer in the diagnosis of PJI. This review summarizes the most current literature on the value of D-dimer in total joint arthroplasty and elucidates areas for future progress.     

Utility of Diagnostic Markers in Late Periprosthetic Joint Infection Workup for Total Knee Arthroplasty Patients Who Received Antibiotics 48 Hours Before Aspiration

BackgroundDiagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI.MethodsPatients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group.ResultsThe immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82).ConclusionAntibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients.Level of EvidenceLevel III, retrospective comparative study.     

Variation in Inflammatory Biomarkers Among Demographic Groups Significantly Affects Their Accuracy in Diagnosing Periprosthetic Joint Infection

BackgroundDiagnosis of periprosthetic joint infection (PJI) is a multistep process that involves performing various tests including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The latter two tests, despite being used at all times for PJI diagnosis, are known to be nonspecific and substantially affected by demographic characteristics, including age, gender, race, and body mass index. It is unknown how these variations affect the diagnostic utility of serological markers for PJI.MethodsInstitutional databases were queried to identify patients undergoing revision arthroplasty between 2010 and 2018, in whom preoperative serum ESR and CRP was performed. Patient demographics were collected, and patients were cross-referenced with an internal database to determine their infection status. Analyses were performed to determine how ESR and CRP varied with respect to demographic factors, including age, gender, race, and infection status. Given that patient infection status was known at the time of revision, conclusions were drawn about the effect of these variations in inflammatory markers on the diagnostic utility of ESR and CRP.ResultsThe value of ESR increased by age was higher in females and African American race. No significant differences were observed in the value of CRP among the demographic factors, although a slight positive trend was observed with respect to age. The variation in inflammatory markers significantly affected the sensitivity, specificity, and accuracy of ESR and CRP for PJI diagnosis.ConclusionUnderstanding how the accuracy of diagnostic tests varies with respect to demographic factors can help physicians avoid subjecting patients to unnecessary additional testing and reach more accurate diagnoses of PJI.     

Do Pre-Reimplantation Erythrocyte Sedimentation Rate/C-Reactive Protein Cutoffs Guide Decision-Making in Prosthetic Joint Infection? Are We Flying Blind?

BackgroundTwo-stage exchange is a commonly used approach for treating chronic periprosthetic joint infections (PJI). A pre-reimplantation threshold value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to determine infection eradication and the proper timing of reimplantation remains ill-defined.MethodsWe retrospectively reviewed 483 potential patients for eligibility. In total, 178 patients were excluded. In addition, 305 joints were eligible who underwent 2-stage revision for prosthetic hip or knee joint infection (PJI). Serum ESR and CRP were recorded at 8 weeks post resection prior to stage 2 reimplantation. ESR and CRP were analyzed with receiver operating characteristic curves (ROC) for response failure.ResultsIn total, 252 patients had resections for chronic infections while 53 septic patients had resections for acute infections. Forty-one of 252 (16.3%) patients failed reimplantation. Median ESR at the time of reimplantation was 17 (normal less than 20 mm/h). Median CRP was 0.6 (normal less than 0.5 mg/dL). ROC plot for response failure in analyzing ESR found an area under the curve (AUC) of 0.47. ROC plot analyzing CRP found an AUC of 0.57. The ratio of ESR/CRP was also utilized and found an AUC of 0.60. All of the AUC data are in the “fail to discriminate category.”ConclusionAlthough improvements in serology can be somewhat reassuring, there are no statistically significant values of ESR or CRP that would predict failure of reimplantation in the 2-stage treatment of PJI. Because we are flying blind consideration should be made for mandatory pre-reimplantation aspirates.Level of EvidenceLevel IV, Retrospective Case Series.     

Serum Fibrinogen Test Performs Well for the Diagnosis of Periprosthetic Joint Infection

BackgroundSerum fibrinogen (FIB) is an acute-phase glycoprotein in the infection response that may stop excessive bleeding. The purposes of this study are to determine the value of FIB that can be used to differentiate between periprosthetic joint infection (PJI) and aseptic loosening of the prosthesis, and to determine the clinical significance of FIB for analyzing infection outcomes after first-stage surgery.MethodsThis retrospective study included 90 patients undergoing total knee arthroplasty or total hip arthroplasty revision from January 2015 to August 2019. PJI was confirmed in 53 patients (group A), and the other 37 patients were diagnosed with aseptic loosening of the prosthesis (group B). Only 21 patients in group A documented the results for serum FIB, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) after spacer insertion, so the postoperative serological marker levels of the these patients were also assessed.ResultsThe FIB, CRP, and ESR levels were significantly higher in group A than in group B (P < .001). The area under the receiver operating characteristic curve was highest for FIB at 0.928. Analyses of FIB levels revealed a sensitivity of 79.25% and a specificity of 94.59%. FIB levels were significantly lower in patients with PJI after spacer insertion (P < .001).ConclusionFIB is an adequate test to aid in diagnosing PJI, and it is not inferior to CRP and ESR in distinguishing between PJI and aseptic loosening of the prosthesis. It is an especially useful tool in assessing infection outcomes after first-stage surgery.     

Concomitant Hip and Knee Periprosthetic Joint Infection in Periprosthetic Fracture: Diagnostic Utility of Serum and Synovial Fluid Markers

BackgroundDiagnosing periprosthetic joint infection (PJI) in patients with a periprosthetic fracture can be challenging due to concerns regarding the reliability of commonly used serum and synovial fluid markers. This study aimed at determining the diagnostic performance of serum and synovial fluid markers for diagnosing PJI in patients with a periprosthetic fracture of a total joint arthroplasty.MethodsA total of 144 consecutive patients were included: (1) 41 patients with concomitant PJI and periprosthetic fracture and (2) 103 patients with periprosthetic fracture alone. Serum markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and synovial markers white blood cell (WBC) count and polymorphonuclear percentage were assessed.ResultsESR demonstrated 87% sensitivity and 48% specificity at the Musculoskeletal Infection Society threshold, area under the curve (AUC) of 0.74, and optimal threshold of 45.5 mm/h (76% sensitivity, 68% specificity). CRP showed 94% sensitivity and 40% specificity, AUC of 0.68 with optimal threshold of 16.7 mg/L (84% sensitivity, 51% specificity). Synovial WBC count demonstrated 87% sensitivity and 78% specificity, AUC of 0.90 with optimal threshold of 4552 cells/μL (86% sensitivity, 85% specificity). Polymorphonuclear percentage showed 79% sensitivity and 63% specificity, AUC of 0.70 with optimal threshold of 79.5% (74% sensitivity, 63% specificity). The AUC of all combined markers was 0.90 with 84% sensitivity and 79% specificity.ConclusionThe diagnostic utility of the serum and synovial markers for diagnosing PJI was lower in the setting of concomitant periprosthetic fracture compared to PJI alone. Using the Musculoskeletal Infection Society thresholds, ESR, CRP, and WBC count showed high sensitivity, yet low specificity, thus higher thresholds and utilizing all serum and synovial markers in combination should be considered.     

Diagnostic Utility and Thresholds for Commonly Obtained Serum and Synovial Markers Prior to Reimplantation in Periprosthetic Joint Infection

BackgroundAccurate diagnosis of persistent periprosthetic joint infection (PJI) during 2-stage exchange remains a challenge. This study evaluated the diagnostic performance and thresholds of several commonly obtained serum and synovial markers to better guide reimplantation timing.MethodsThis was a retrospective review of 249 patients who underwent 2-stage exchange with antibiotic spacers for PJI. Serum and synovial markers analyzed included white blood cell (WBC) count, polymorphonuclear percentage (PMN%), neutrophil-to-lymphocyte ratio (NLR), and absolute neutrophil count (ANC). Serum markers analyzed were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as percentage change in ESR and CRP from initial diagnosis to reimplantation. Area under the curve (AUC) analyses were performed to determine diagnostic accuracy of detecting PJI.ResultsIn TKAs, synovial ANC and WBC had the highest AUCs (0.76), with thresholds of 2,952 and 3,800 cells/μL, respectively. The next best marker was serum CRP (0.73) with a threshold of 5.2 mg/dL. In THAs, serum CRP had the highest AUC (0.84) with a threshold of 4.3 mg/dL, followed by synovial PMN% (0.80) with a threshold of 77%. Percentage change in serum ESR or CRP provided low diagnostic value overall.ConclusionRegarding serum markers, CRP consistently performed well in detecting persistent PJI in patients with antibiotic spacers. Absolute values of serum CRP and ESR had better diagnostic value than trends for guiding reimplantation timing. Diagnostic performance differed with joint type; however, synovial markers outperformed serum counterparts. No marker alone can be utilized to diagnose residual PJI in these patients, and further work is needed in this domain.     

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

BackgroundSerum 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.MethodsA 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.ResultsThe 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).ConclusionSynovial 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.     

Evaluation of Serum Albumin and Globulin in Combination With C-Reactive Protein Improves Serum Diagnostic Accuracy for Low-Grade Periprosthetic Joint Infection

BackgroundSerum immune markers can be useful in the diagnosis of periprosthetic joint infection (PJI) by detecting long-lasting abnormal immunological conditions. The purpose of this study was to examine whether serum immune markers can improve the diagnostic accuracy of PJI.MethodsWe enrolled 51 PJI, 45 aseptic loosening, and 334 osteoarthritis patients for assessment of the discriminatory accuracy of serum markers including white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer, total protein, albumin (Alb), globulin (Glb), neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, albumin-globulin ratio (AGR), CRP-albumin ratio (CAR), and CRP-AGR ratio (CAGR). These diagnostic accuracies for low-grade PJI were also calculated in patients who had serum CRP levels < 10 mg/L.ResultsAmong serum markers, Alb, Glb, AGR, CRP, ESR, CAR, and CAGR had highly accurate diagnostic accuracy for PJI, with area under the curve of 0.92, 0.90, 0.96, 0.97, 0.92, 0.97, and 0.98, respectively. In low-grade PJI patients, area under the curve of CRP, ESR, CAR, and CAGR (0.69, 0.80, 0.65, and 0.82, respectively) was decreased but that of Alb, Glb, and AGR (0.90, 0.88, and 0.95, respectively) remained high, indicating the diagnostic utility of these immune markers. The sensitivity and specificity of AGR with cutoff value of 1.1 were demonstrated as 0.92 and 0.89, respectively, and with cutoff value of 1.2, 1.00, and 0.79, respectively, in the diagnosis of low-grade infection.ConclusionOur results demonstrate the potential value of Alb, Glb, AGR, and combination indices of these immune makers with CRP in improving preoperative serum diagnosis for PJI, especially in low-grade PJI.Level of EvidenceDiagnostic- Level II.     

Screening for Periprosthetic Joint Infections With ESR and CRP: The Ideal Cutoffs

BackgroundThe purpose of this study was to (1) determine the sensitivity and specificity of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) when screening for a periprosthetic joint infection (PJI) using the standard MSIS cutoff of 30 mm/h and 10 mg/L, respectively, and (2) determine the optimal ESR and CRP cutoff to achieve a sensitivity ≥95%.MethodsWe retrospectively analyzed 81 PJI patients and 83 noninfected arthroplasty patients. We calculated the sensitivity and specificity (and 95% confidence intervals) for ESR and CRP at thresholds of 30 mm/h and 10 mg/L, respectively. We determined the optimal cutoff for both ESR and CRP to yield a sensitivity greater than or equal to 95%.ResultsThe ESR cutoff that resulted in a sensitivity ≥ to 95% (95% CI: 85.2-97.6%) was 10 mm/h, and the CRP cutoff that resulted in a sensitivity ≥ to 95% (95% CI: 87.1-98.4%) was 5 mg/L. The sensitivity and specificity with a combined ESR and CRP of 10 mm/h and 5 mg/L was 100% (95% CI: 94.1-100%) and 54.7% (95% CI: 46.4-62.3%).ConclusionWhen using ESR and CRP as a screening tool with the accepted cutoffs of 30 mm/h and 10 mg/L, there is an unacceptably low sensitivity and a high number of false negatives. Therefore, further recommendation must be given to lowering these thresholds to avoid the devastating morbidity of a missed PJI.Level of EvidenceIII.     

Plasma Viscosity Has a Role in the Diagnosis of Prosthetic Joint Infection After Total Knee Arthroplasty

BackgroundThe diagnosis of prosthetic joint infection (PJI) is challenging because no single test has consistently demonstrated an adequate discriminative potential. The combination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with adequate thresholds is well established. This study sought to investigate the role of plasma viscosity (PV) in the diagnosis of PJI following painful total knee arthroplasty.MethodsThe medical notes, and hematological and microbiology results of 310 patients who underwent revision for a painful total knee arthroplasty were evaluated. Infection was confirmed using Musculoskeletal Infection Society criteria in 102 patients (32.9%), whereas 208 patients (67.1%) were classified as noninfected. Serum investigations including ESR, CRP, and PV were analyzed using receiver observer curves and optimal cutoff points identified.ResultsThere was a strong correlation between PV and both ESR and CRP. The area under curve was 0.814 for PV and 0.812 for ESR. Statistical analysis showed noninferiority of PV as compared to ESR in diagnosing PJI. A PV value of ≥ 1.81 mPa.s. had the best efficiency of 82.1%. Combining a CRP ≥ 13.5 mg/L with a PV ≥ 1.81 mPa.s. in a serial test approach yielded the highest specificity of 97.9% and positive likelihood ratio of 22.8. Sensitivity was 47.9% and a negative likelihood ratio of 0.53.ConclusionPV is noninferior to ESR in diagnosing PJI. Its use is justified in clinical practice. It is cheaper, quicker, more efficient, and not influenced by hematocrit levels or medication. In this cohort, a PV value ≥ 1.81 mPa.s. would be an adequate cutoff to diagnose PJI in combination with CRP ≥ 13.5 mg/L.     

Synovial C-Reactive Protein is a Useful Adjunct for Diagnosis of Periprosthetic Joint Infection

BackgroundThe diagnostic utility of synovial C-reactive protein (CRP) has been debated for a while. Existing studies are limited by small sample sizes and using outdated criteria for periprosthetic joint infection (PJI). Furthermore, the relationship between synovial and serum CRP has rarely been investigated in the setting of PJI. This study aimed to evaluate the diagnostic utility of synovial CRP and to assess its relationship with serum CRP and other common biomarkers.MethodsWe reviewed 621 patients who underwent evaluation for PJI prior to revision arthroplasty from 2014 to 2021. Biomarkers, including serum CRP and erythrocyte sedimentation rate, synovial CRP, polymorphonuclear leukocyte percentage, white blood cell count, and alpha-defensin, were evaluated using the 2018 International Consensus Meeting criteria.ResultsIn total, 194 patients had a PJI; 394 were considered aseptic failures and 33 were inconclusive. Synovial CRP showed an area under the curve (AUC) of 0.951 (95% CI, 0.932-0.970) with 74.2% sensitivity and 98.0% specificity, whereas, serum CRP had an AUC of 0.926 (95% CI, 0.903-0.949) with 83.5% sensitivity and 88.3% specificity. There was a good correlation between synovial and serum CRP (R = 0.703; 95% CI, 0.604-0.785). The combination of serum and synovial CRP yielded a significantly higher AUC than that obtained when using serum CRP alone (AUC 0.964 versus 0.926, P = .016).ConclusionSynovial CRP demonstrated excellent accuracy when used to determine the presence of PJI. There was a good correlation between serum and synovial CRP levels in revision arthroplasty patients and the combined use of serum and synovial CRP proved to be more accurate than the serum test alone. These findings support the use of synovial CRP as an adjunct in the workup of PJI.     

Synovial Fluid Viscosity Test is Promising for the Diagnosis of Periprosthetic Joint Infection

BackgroundSo far there is no “gold standard” test for the diagnosis of periprosthetic joint infection (PJI), compelling clinicians to rely on several serological and synovial fluid tests with no 100% accuracy. Synovial fluid viscosity is one of the parameters defining the rheology properties of synovial fluid. We hypothesized that patients with PJI may have a different level of synovial fluid viscosity and aimed to investigate the sensitivity and specificity of synovial fluid viscosity in detecting PJI.MethodsThis prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 45 patients undergoing revision for PJI (n = 15), revision for aseptic failure (n = 15), and primary arthroplasty (n = 15). PJI was defined using the Musculoskeletal Infection Society criteria. In all patients, synovial fluid viscosity, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma d-dimer levels were measured preoperatively.ResultsThe synovial fluid viscosity level was significantly lower (P = .0011) in patients with PJI (7.93 mPa·s, range 3.0-15.0) than in patients with aseptic failure (13.11 mPa·s, range 6.3-20.4). Using Youden’s index, 11.80 mPa·s was determined as the optimal threshold value for synovial fluid viscosity for the diagnosis of PJI. Synovial fluid viscosity outperformed CRP, ESR, and plasma d-dimer, with a sensitivity of 93.33% and a specificity of 66.67%.ConclusionSynovial fluid viscosity seems to be on the same level of accuracy with CRP, ESR, and d-dimer regarding PJI detection and to be a promising marker for the diagnosis of PJI.     

Plasma D-dimer Does Not Anticipate the Fate of Reimplantation in Two-stage Exchange Arthroplasty for Periprosthetic Joint Infection: A Preliminary Investigation

BackgroundInflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels have always been a part of the diagnostic criteria for periprosthetic joint infection (PJI), but they perform poorly anticipating the outcome of reimplantation. D-dimer has been reported in a small series as a potential marker to measure infection control after single-stage revisions to treat PJI. Nonetheless, its use to confirm infection control and decide the proper timing of reimplantation remains uncertain.Questions/purposes(1) What is the best diagnostic threshold and accuracy values for plasma D-dimer levels compared with other inflammatory markers (ESR and CRP) or what varying combinations of these tests are associated with persistent infection after reimplantation? (2) Do D-dimer values above this threshold, ESR, CRP, and varying test combinations at the time of reimplantation indicate an increased risk of subsequent persistent infection after reimplantation?MethodsWe retrospectively studied the electronic medical records of all 53 patients who had two-stage revisions for PJI and who underwent plasma D-dimer testing before reimplantation at one of two academic institutions from November 22, 2017 to December 5, 2020. During that period, all patients undergoing two-stage revisions also had a D-dimer test drawn. The minimum follow-up duration was 1 year. We are reporting at this early interval (rather than the more typical 2-year time point) because of the poorer-than-expected performance of this diagnostic test. Of these 53 patients, 17% (9) were lost to follow-up before 1 year and could not be analyzed; the remaining 44 patients (17 hips and 27 knees) were studied here. The mean follow-up was 503 ± 135 days. Absence or persistence of infection after reimplantation were defined according to the Delphi criteria. The conditions included in these criteria were: (1) control of infection, as characterized by a healed wound without fistula, drainage, or pain; (2) no subsequent surgical intervention owing to infection after reimplantation; and (3) no occurrence of PJI-related mortality. The absence of any of the aforementioned conditions until the final follow-up examination was deemed a persistent infection after reimplantation. Baseline patient characteristics were not different between patients with persistent infection (n = 10) and those with absence of it after reimplantation (n = 34) as per the Delphi criteria. Baseline patient characteristics evaluated were age, gender, self-reported race (white/Black/other) or ethnicity (nonHispanic/Hispanic), BMI, American Society of Anesthesiologists (ASA) status, smoking status(smoker/nonsmoker), and joint type (hip/knee). The optimal D-dimer threshold to differentiate between persistence of infection or not after reimplantation was calculated using the Youden index. A receiver operating characteristic curve analysis was performed to test the accuracy of D-dimer, ESR, CRP, and their combinations to establish associations, if any, with persistent infection after reimplantation. A Kaplan-Meier survival analysis (free of infection after reimplantation) with a log-rank test was performed to investigate if D-dimer, ESR, and CRP were associated with absence of infection after reimplantation. Survival or being free of infection after reimplantation was determined as per Delphi criteria. Alpha was set at p < 0.05.ResultsIn the receiver operating characteristic curve analysis, with an area under the curve of 0.62, D-dimer showed low accuracy and did not anticipate persistent infection after reimplantation. The optimal D-dimer threshold differentiating between persistence of infection or not after reimplantation was 3070 ng/mL. When using this threshold, D-dimer demonstrated a sensitivity of 90% (95% CI 55.5% to 99.7%) and negative predictive value of 94% (95% CI 70.7% to 99.1%), but low specificity (47% [95% CI 29.8% to 64.9%]) and positive predictive value (33% [95% CI 25.5% to 42.2%]). Although D-dimer showed the highest sensitivity, the combination of D-dimer with ESR and CRP showed the highest specificity (91% [95% CI 75.6% to 98%]) defining the persistence of infection after reimplantation. Based on plasma D-dimer levels, with the numbers available, there was no difference in survival free from infection after reimplantation (Kaplan-Meier survivorship free from infection at minimum 1 year in patients with D-dimer below 3070 ng/mL versus survivorship free from infection with D-dimer above 3070 ng/mL: 749 days [95% CI 665 to 833 days] versus 615 days [95% CI 471 to 759 days]; p = 0.052). Likewise, there were no associations between high ESR and CRP levels and persistent infection after reimplantation, but the number of events was very small, and insufficient power is a concern with this analysis.ConclusionIn this preliminary series, with the numbers available, D-dimer alone had poor accuracy and was not associated with survival free from infection after reimplantation in patients who underwent two-stage exchange arthroplasty. D-dimer alone might be used to establish that PJI is unlikely, and the combination of D-dimer, ESR, and CRP should be considered to confirm PJI diagnosis in the setting of reimplantation.Level of Evidence Level IV, diagnostic study.     

A Novel Adjunct Indicator of Periprosthetic Joint Infection: Platelet Count and Mean Platelet Volume

BackgroundDiagnosing a periprosthetic joint infection (PJI) is difficult and often requires a combination of objective findings. The purpose of this study is to determine whether platelets, a known acute phase reactant, would be able to further aid in the diagnosis of PJI.MethodsA single-institution retrospective review study was performed on all revision total hip and knee arthroplasties done between 2000 and 2016 (n = 4939). PJI was defined by Musculoskeletal Infection Society criteria (n = 949). Platelet count and mean platelet volume were assessed from each patient’s preoperative complete blood count. These values were then assessed as a ratio via receiver operating characteristic (ROC) curve analysis.ResultsThe platelet count to mean platelet volume ratio for PJI patients was 33.45 compared to 25.68 for patients in the aseptic revision cohort (P < .001). ROC curve analysis demonstrates that a ratio of 31.70 has a sensitivity of 48.10 (95% confidence interval 44.9-51.4) and a specificity of 80.85 (95% confidence interval 79.6-82.1). This specificity was higher than that of both estimated sedimentation ratio (ESR) and C-reactive protein (CRP) for the same cohorts using optimal values determined via ROC curve analysis. When used in conjunction with ESR and CRP, there was a statistically significant increase in the diagnostic performance of the model used to assess PJI relative to the model that just employed ESR and CRP (P < .05).ConclusionOur study demonstrates that platelets and their associated serum biomarkers are associated with PJI and warrant consideration in patients who are being evaluated for potential PJI.