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.     

Plasma Fibrinogen Performs Better Than Plasma d-Dimer and Fibrin Degradation Product in the Diagnosis of Periprosthetic Joint Infection and Determination of Reimplantation Timing

BackgroundThe accurate and timely diagnosis of periprosthetic joint infection (PJI) is challenging, and no single biomarker can definitively confirm infection before revision arthroplasty. The coagulation cascade has been linked closely to infection. This study was performed to determine the value of plasma d-dimer, plasma fibrinogen, and plasma fibrin degradation product (FDP) for the diagnosis of PJI and timing of reimplantation.MethodsWe retrospectively enrolled 136 patients who underwent revision surgery from January 2008 to December 2019. They were assigned to 3 groups: aseptic failure (group A), PJI (group B), and reimplantation (group C). Receiver operating characteristic curves were constructed to estimate the value of plasma fibrinogen, plasma d-dimer, plasma FDP, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP) for PJI diagnosis and reimplantation timing.ResultsAll biomarker levels were significantly higher in group B than in group A (P < .05), and plasma fibrinogen, CRP, and ESR values were significantly higher in group B than in group C (all P < .05). The receiver operating characteristic curves showed that the areas under the curve of plasma fibrinogen, plasma d-dimer, plasma FDP, CRP, and ESR were 0.848, 0.914, 0.728, 0.737, and 0.868, respectively, and the threshold values for plasma fibrinogen, plasma d-dimer, and plasma FDP were 3.61 g/L, 0.41 mg/L, and 3.55 mg/L, respectively.ConclusionPlasma fibrinogen exhibits good value for the diagnosis of PJI and can be an indicator of residual infection before reimplantation in 2-stage arthroplasty. Plasma d-dimer and FDP are of limited value for PJI diagnosis and cannot be used to determine the timing of reimplantation.     

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.     

Plasma Fibrinogen and Platelet Count Are Referable Tools for Diagnosing Periprosthetic Joint Infection: A Single-Center Retrospective Cohort Study

BackgroundAlthough the MusculoSkeletal Infection Society has suggested a series of markers to diagnose periprosthetic joint infection (PJI), no single marker can accurately identify infection before revision hip or knee arthroplasty, and exploring promising markers to easily and reliably diagnose PJI is ongoing. The aim of this study was to evaluate the diagnostic value of plasma fibrinogen and platelet count for diagnosing PJI.MethodsWe retrospectively included 439 patients who underwent revision arthroplasty from January 2008 to December 2018; 79 patients with coagulation-related comorbidities were evaluated separately. The remaining 360 patients constituted 153 PJI and 207 non-PJI patients. Receiver operating characteristic curves were used to evaluate the maximum sensitivity and specificity of the tested markers.ResultsThe receiver operating characteristic curves showed that the areas under the curve for plasma fibrinogen, platelet count, and serum C-reactive protein and erythrocyte sedimentation rate were 0.834, 0.746, 0.887, and 0.842, respectively. Based on Youden's index, the optimal predictive cutoffs for fibrinogen and platelet count were 3.57 g/L and 221 × 10⁹/L, respectively. The sensitivity and specificity, respectively, were 68.6% and 86.0% (fibrinogen) and 57.5% and 83.1% (platelet count) for diagnosing PJI. The sensitivity and specificity, respectively, were 76.7% and 72.2% (fibrinogen) and 48.8% and 63.9% (platelet count) for diagnosing PJI in patients with coagulation-related comorbidities.ConclusionPlasma fibrinogen performed well for diagnosing PJI before revision arthroplasty, and its value neared that of traditional inflammatory markers. Although the diagnostic value of the platelet count was inferior to traditional markers, its diagnostic value was fair for diagnosing PJI. Fibrinogen also may be useful for diagnosing PJI in patients with coagulation-related comorbidities.     

D-Dimer,Erythrocyte Sedimentation Rate,and C-Reactive Protein Sensitivities for Periprosthetic Joint Infection Diagnosis

BackgroundThere is contradicting evidence on the diagnostic value of inflammatory biomarkers for periprosthetic joint infection (PJI). We sought to quantify the sensitivity of D-dimer for acute and chronic PJI diagnosis and evaluate D-dimer lab values in the 90-day postoperative window in a control cohort of primary joint arthroplasty patients for comparison.MethodsAn institutional database was queried for patients undergoing revision procedures for PJI after total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2014 to present. CRP, ESR, and D-dimer were collected within 90 days pre and postoperatively and sensitivities for the diagnosis of PJI were calculated. The control group included patients who underwent a negative diagnostic workup for deep venous thrombosis (DVT) or pulmonary embolus (PE) and had a D-dimer lab collected within 90 days postoperatively from primary total joint arthroplasty (TJA).ResultsA total of 604 PJI patients were identified, and 81 patients had D-dimer, ESR, and CRP collected. There were 50/81 acute PJI patients and 31/81 chronic PJI patients who had median D-dimer values of 2,136.5 ng/mL [interquartile range (IQR): 1,642-3,966.5] and 3,336 ng/mL [IQR: 1,976-5,594]. Only the chronic PJI group had significantly higher D-dimer values when compared to the control cohort (P = .009). The sensitivity of D-dimer was calculated to be 92% and 93.5% in the acute and chronic PJI groups, respectively.ConclusionSerum D-dimer may not have high diagnostic utility for acute PJI, especially in the setting of recent surgery; however, it still may be useful for patients who have chronic PJI.     

Sensitivity and Specificity of Serum and Synovial Fluid Markers in Diagnosis of Infection in Head-Neck Taper Corrosion of Metal-On-Polyethylene Total Hip Arthroplasty

BackgroundThe accurate diagnosis of periprosthetic joint infection (PJI) in the setting of adverse local tissue reactions in patients with metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper junction corrosion is challenging as it frequently has the appearance of purulence. The aim of this study is to evaluate the utility of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial fluid markers in diagnosing PJI in failed MoP THA due to head-neck taper corrosion.MethodsA total of 89 consecutive patients with MoP THA with head-neck taper corrosion in 2 groups was evaluated: (1) infection group (n = 11) and (2) noninfection group (n = 78). All patients had highly crossed polyethylene with cobalt chromium femoral heads and had preoperative synovial fluid aspiration. In addition, serum cobalt and chromium levels were analyzed.ResultsThe optimal cutoff value for synovial white blood cell was 2144 with 93% sensitivity and 84% specificity. Neutrophil count optimal cutoff value was 82% with 93% sensitivity and 82% specificity. Receiver operating characteristic analysis of ESR and CRP determined optimal cutoff at 57 mm/h and 35 mg/L with 57% sensitivity and 94% specificity and 93% sensitivity and 76% specificity, respectively. There were no significant differences in metal ion levels between the infected and noninfected groups.ConclusionThe results of this study suggest that ESR and CRP are useful in excluding PJI, whereas both synovial white blood cell count and neutrophil percentage in hip aspirate are useful markers for diagnosing infection in MoP THA patients with head-neck taper corrosion associated adverse local tissue reaction.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Can the Leukocyte Esterase Strip Test Predict Persistence of Periprosthetic Joint Infection at Second-Stage Reimplantation?

BackgroundWe evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR.MethodsThe records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated.ResultsSensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively.ConclusionThe LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.     

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.     

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.     

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.     

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.     

Development and Validation of an Evidence-Based Algorithm for Diagnosing Periprosthetic Joint Infection

BackgroundThe guidelines for diagnosis of periprosthetic joint infection (PJI) introduced by the American Academy of Orthopaedic Surgeons served the orthopedic community well. However, they have never been validated and do not account for newer diagnostic modalities. Our aim was to update current guidelines and develop an evidence-based and validated diagnostic algorithm.MethodsThis multi-institutional study examined total joint arthroplasty patients from 3 institutions. Patients fulfilling major criteria for infection as defined by Musculoskeletal Infection Society were considered infected (n = 684). Patients undergoing aseptic revision for a noninfective indication and did not show evidence of PJI or undergo reoperation within 2 years served as a noninfected control group (n = 820). The algorithm was validated on a separate cohort of 422 cases.ResultsThe first step in evaluating PJI should include a physical examination, followed by serum C-reactive protein, erythrocyte sedimentation rate, and D-dimer. If at least one of these tests are elevated, or if high clinical suspicion exists, joint aspiration should be performed, sending the fluid for a white blood cell count, leukocyte esterase, polymorphonuclear percentage, and culture. Alpha defensin did not show added benefit as a routine diagnostic test. In inconclusive cases, intraoperative findings including gross purulence, histology, and next-generation sequencing or a single positive culture can aid in making the diagnosis. The proposed algorithm demonstrated a high sensitivity (96.9%) and specificity (99.5%).ConclusionThis validated, evidence-based algorithm for diagnosing PJI should guide clinicians in the workup of patients undergoing revision arthroplasty and improve clinical practice. It also has the potential to reduce cost.