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 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 Existing studies are limited by small sample sizes and using outdated criteria for periprosthetic joint infection (PJI).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 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.     

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.     

Diagnostic Utility of Platelet Count/Lymphocyte Count Ratio and Platelet Count/Mean Platelet Volume Ratio in Periprosthetic Joint Infection Following Total Knee Arthroplasty

BackgroundDiagnosing a periprosthetic joint infection (PJI) can be challenging and often requires a combination of clinical and laboratory findings. Monocyte/lymphocyte ratio, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio (PLR), and platelet/mean platelet volume ratio (PVR) are simple predictors for inflammation that can be readily obtained from complete blood count. The aim of this study is to evaluate the diagnostic utility of these markers in predicting PJI in total knee arthroplasty (TKA) patients.MethodsA total of 538 patients who underwent revision TKA with calculable marker ratios prerevision in 2 groups were evaluated: (1) 206 patients with a preoperative diagnosis of PJI (group I) and (2) 332 patients treated for revision TKA for aseptic failures (group II). The diagnostic abilities of the markers were assessed via receiver operator characteristic curve analysis.ResultsThe optimal threshold of PVR at 30.82 had the highest sensitivity of 87.7%, while the optimal threshold of PLR at 234.13 had the highest specificity of 82.5%. Both PLR and PVR, when combined with Musculoskeletal Infection Society thresholds for erythrocyte sedimentation rate, C-reactive protein, synovial WBC, and PMN%, achieve significantly higher sensitivity and specificity rates for PJI at or above 97% (PLR: 99.03%; 98.80%; PVR: 98.54%;97.89%).ConclusionOur study demonstrates that PVR and PLR, which are readily available and inexpensive to obtain from complete blood counts, when combined with serum and synovial fluid markers have increased sensitivity and specificity comparable to that of alpha defensin. This suggests that PVR and PLR can be used together with other hematologic and aspirate markers to increase the accuracy of PJI diagnosis in TKA patients.     

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.     

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.     

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.     

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 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.     

Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study

BackgroundInflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.MethodsThis prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively.ResultsAn increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%.ConclusionCurrent serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.     

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.     

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.     

Periprosthetic joint infection diagnosis: a complete understanding of white blood cell count and differential

Recent research has raised doubts regarding the utility of serum white blood cell count (WBC) for diagnosis of periprosthetic joint infection (PJI). As synovial WBC and neutrophil (PMN) percentage have been adopted as accurate markers of PJI, this study investigated the correlation of WBC in serum versus joint fluid and diagnostic value of all WBC levels for failed arthroplasty patients. 153 patients (73 PJI) undergoing revision knee arthroplasty were identified. Weak correlations between joint fluid and serum for WBC (R = 0.19), PMN count (R = 0.31), and lymphocyte count (R = -0.22) were observed. Diagnostic accuracy of PMN (93%) and WBC (93%) synovial count relative to serum was similar to synovial WBC (93%) and PMN% (95%) alone. Serum WBC analysis does little to improve the accurate diagnosis of PJI.     

Reevaluating Current Cutoffs for Acute Periprosthetic Joint Infection: Current Thresholds Are Insensitive

BackgroundDiagnosing acute periprosthetic joint infection remains a challenge. Several studies have proposed different acute cutoffs resulting in the International Consensus Meeting recommending a cutoff of 100 mg/L, 10,000 cell/μL and 90% for serum C-reactive protein (CRP), synovial white blood cell count (WBC), and polymorphonuclear percentage (PMN%), respectively. However, establishing cutoffs are difficult as the control group is limited to rare early aseptic revisions, and performing aspiration in asymptomatic patients is difficult because of a fear of seeding a well-functioning joint arthroplasty. This study (1) assessed the sensitivity of current thresholds for acute periprosthetic joint infection (PJI) and (2) identified associated factors for false negatives.MethodsWe retrospectively reviewed patients with acute PJIs (n = 218), defined as less than 6 weeks from index arthroplasty, treated between 2000 and 2017. Diagnosis of PJI was based on 2 positive cultures of the same pathogen from the periprosthetic tissue or synovial fluid samples. Sensitivities of International Consensus Meeting cutoff values of CRP, synovial WBC, and PMN% were evaluated according to organism type. Multiple logistic regression analysis was performed to determine associated factors for false negatives.ResultsOverall, the sensitivity of CRP, synovial WBC, and PMN% for acute PJI was 55.3%, 59.6%, and 50.5%, respectively. Coagulase-negative Staphylococcus (CNS) demonstrated the lowest sensitivity for both CRP (37.5%) and WBC (55.6%). CNS infection was identified as an independent risk factor for false-negative CRP.ConclusionsCurrent thresholds for acute PJI may be missing approximately half of PJIs. Low virulent organisms, such as CNS, may be responsible for these false negatives. Current thresholds for acute PJI must be reexamined.     

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.     

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.     

Diagnostic Value of Synovial White Blood Cell Count and Serum C-Reactive Protein for Acute Periprosthetic Joint Infection After Knee Arthroplasty

Background

The diagnosis of periprosthetic joint infection (PJI) remains difficult, particularly in acute postoperative stage. The purpose of this study was to investigate the optimal cutoff value of synovial white blood cell (WBC) count, percentage of polymorphonuclear cells, erythrocyte sedimentation rate, and C-reactive protein (CRP) for diagnosing early postoperative infection after knee joint arthroplasty.

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.     

Utility of Synovial White Blood Cell Count and Differential Before Reimplantation Surgery

BackgroundDetermining optimal timing of reimplantation during 2-stage exchange for periprosthetic joint infection (PJI) remains elusive. Joint aspiration for synovial white blood cell (WBC) count and neutrophil percentage (PMN%) before reimplantation is widely performed; yet, the implications are rarely understood. Therefore, this study investigates (1) the diagnostic yield of synovial WBC count and differential analysis and (2) the calculated thresholds for persistent infection.MethodsInstitutional PJI databases identified 129 patients undergoing 2-stage exchange arthroplasty who had joint aspiration before reimplantation between February 2005 and May 2014. Persistent infection was defined as a positive aspirate culture, positive intraoperative cultures, or persistent symptoms of PJI—including subsequent PJI-related surgery. Receiver-operating characteristic curve was used to calculate thresholds maximizing sensitivity and specificity.ResultsThirty-three cases (33 of 129; 25.6%) were classified with persistent PJI. Compared with infection-free patients, these patients had significantly elevated PMN% (62.2% vs 48.9%; P = .03) and WBC count (1804 vs 954 cells/μL; P = .04). The receiver-operating characteristic curve provided thresholds of 62% and 640 cells/μL for synovial PMN% and WBC count, respectively. These thresholds provided sensitivity of 63% and 54.5% and specificity of 62% and 60.0%, respectively. The risk of persistent PJI for patients with PMN% >90% was 46.7% (7 of 15).ConclusionSynovial fluid analysis before reimplantation has unclear utility. Although statistically significant elevations in synovial WBC count and PMN% are observed for patients with persistent PJI, this did not translate into useful thresholds with clinical importance. However, with little other guidance regarding the timing of reimplantation, severely elevated WBC count and differential analysis may be of use.