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.     

Synovial-Based Tests Outperform Serum Markers to Rule Out Infection in Total Knee Arthroplasty and Total Hip Arthroplasty: A Systematic Review and Meta-Analysis

BackgroundTotal knee arthroplasty (TKA) provides successful results in most patients. Periprosthetic joint infection (PJI) accounts for up to 25% of failed TKAs needing revision. In clinical practice, consensus in diagnostic strategy for excluding or diagnosing PJI is still lacking. In this systematic review and meta-analysis, we aim to provide a simplified data-driven diagnostic strategy for aseptic knee and hip revision surgeons to rule out PJI in the outpatient clinic phase.MethodsA literature search in EMBASE, MEDLINE, PubMed, and Cochrane was conducted. Studies involving the diagnosis of PJI in patients with failed TKAs and total hip arthroplasties needing revision were identified. Only studies using the Musculoskeletal Infection Society criteria were included. Quality was assessed using MINORS criteria. Meta-analysis was performed for each diagnostic test identified in the included studies. Pooled estimates of diagnostic accuracy measures were calculated using a bivariate model and plotted in summary receiver–operator characteristic curves. Positive and negative predictive values were calculated in a hypothetical sample of patients with a given disease prevalence.ResultsTwenty-four studies met the inclusion criteria, describing a total of 2974 patients. Quality scores ranged from 13 to 19. Meta-analysis could be performed on 7 unique diagnostic tests. Highest pooled sensitivity and specificity were demonstrated for α-defensin with values of 86% and 96.6%, respectively. α-defensin and white blood cell count in synovial fluid demonstrate highest negative predictive value values.ConclusionsWe recommend, in a clinical setting with low–intermediate prevalence of PJI, performing arthrocentesis and joint fluid analysis using α-defensin and/or white blood cell count before revision TKA and revision total hip arthroplasty surgery to rule out 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.     

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 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.     

Diagnostic Accuracy of the Alpha-Defensin Test for Periprosthetic Joint Infection in Patients With Inflammatory Diseases

BackgroundThe alpha-defensin test has been reported to have high accuracy to diagnose periprosthetic joint infection (PJI). There are remaining concerns about the utility of the test in patients with inflammatory diseases. The purpose of this study is to determine sensitivity and specificity of laboratory-based alpha-defensin in diagnosing PJI in patients with systemic inflammatory disease in revision total hip/knee arthroplasty.MethodsA retrospective review was conducted of 1374 cases who underwent revision total hip/knee arthroplasty at a single healthcare system from 2014 to 2017. Cases with inflammatory diseases who received a 1-stage revision arthroplasty, the first stage of 2-stage revision arthroplasty, or irrigation and debridement with available preoperative alpha-defensin results were included. Patients who received a second-stage procedure, spacer exchange, who had insufficient Musculoskeletal Infection Society criteria, or with early postoperative PJI were excluded from this study. Cases were classified as infected or not according to Musculoskeletal Infection Society criteria. A total of 41 cases met the inclusion criteria. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of alpha-defensin to diagnose PJI were calculated.ResultsThe alpha-defensin test demonstrated a sensitivity of 93%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 96%, and an accuracy of 97% for diagnosing PJI. There was 1 patient with polymyositis who had a false-negative result.ConclusionAlpha-defensin had high accuracy for diagnosing PJI even in inflammatory diseases. The alpha-defensin test provides useful information with high accuracy in diagnosing PJI in patients with inflammatory diseases.     

The Potential Value of Monocyte to Lymphocyte Ratio,Platelet to Mean Platelet Volume Ratio in the Diagnosis of Periprosthetic Joint Infections

ObjectiveTo explore the possibility of obtaining more accurate information from routine blood tests for the diagnosis of periprosthetic joint infection (PJI).MethodsThis is a retrospective study. Between 2017 and 2018, a total of 246 patients who underwent total hip or knee revision surgery were included in this study. There were 146 females and 100 males, and the mean age of the patients was 62.1 ± 12.75 years. Laboratory parameters erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), D‐dimer, plasma fibrinogen, serum white blood cell (WBC), and calculable ratio markers were collected. Based on leukocytes (monocyte count, neutrophil count, lymphocyte count), platelet count, and mean platelet volume Inflammation‐related ratio markers were calculated, which including monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and platelet to mean platelet volume ratio (PMR). Follow‐up of all studied cases for at least 1 year. The diagnostic value of the markers based on the receiver operating characteristic (ROC) analysis. The most optimal combinations of blood markers were selected by the prediction models. Statistical analyses and prediction models were performed using R software.ResultsOf the 246 patients, 125 were diagnosed with PJI and 121 with aseptic loosening. A higher rate of patients underwent revision surgery due to hip prosthesis loosening in the aseptic loosening group (74.4%) compared to the PJI group (45.6%, P < 0.001). ROC curves showed that the area under the curve (AUC) for classical markers, fibrinogen was 0.853 (95% confidence interval [CI], 0.805–0.901), ESR was 0.836 (95% CI, 0.785–0.887) and CRP was 0.825 (95% CI, 0.773–0.878). Followed by the PMR, PLR, NLR and MLR, which showed promising diagnostic performance with AUCs of 0.791, 0.785, 0.736, and 0.733. The AUCs of the ratio markers were higher than those of D‐dimer (0.691;95% CI, 0.6243–0.7584) and serum WBC (0.622; 95% CI, 0.552–0.691). After the predictive model calculation, AUC was up to 0.923 (95% CI, 0.891–0.951) when plasma fibrinogen combined with MLR and PMR and interpreted excellent discriminatory capacity with a sensitivity of 86.40% and a specificity of 84.17%. The new combination significantly increases the accuracy and reliability of the diagnosis of PJI (P < 0.001). The AUC increased to 0.899 (95% CI, 0.861–0.931; P = 0.007) and 0.916 (95% CI, 0.880–0.946; P < 0.001), followed by CRP and ESR, respectively. All plasma fibrinogen, ESR, and CRP combined with both PMR and MLR achieved the highest specificity (89.17%) and PPV (85.34%).ConclusionThe diagnostic performance greatly improved when plasma fibrinogen, ESR, and CRP combined with ratio markers.     

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.     

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.     

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.     

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.     

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.     

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.     

Which International Consensus Meeting Preoperative Minor Criteria is the Most Accurate Marker for the Diagnosis of Periprosthetic Joint Infection in Hip and Knee Arthroplasty?

BackgroundThe accurate preoperative diagnosis of periprosthetic joint infection (PJI) is critical. The aim of this study was to evaluate the diagnostic accuracy and performance of the 2018 International Consensus Meeting (ICM) preoperative minor criteria for the diagnosis of chronic PJI in total hip and knee arthroplasty.MethodsWe retrospectively reviewed 260 patients that underwent a revision knee or hip arthroplasty at our institution between 2015 and 2017. All major and minor 2018 ICM criteria (except erythrocyte sedimentation rate, D-dimer) were available for all patients included. Cases with at least 1 major criterion were considered as infected. Receiver operative characteristic curve analysis was performed for preoperative minor criteria.ResultsThe diagnostic performance of the preoperative minor criteria ranked as per the area under the curve was PMN% (0.926), alpha defensin (0.922), white blood cell count (0.916), leukocyte esterase (0.861), and serum C-reactive protein (0.860). Increasing the PMN % cutoff from 70% to 77.8% improves the diagnostic accuracy (86.5% vs 90.8%). The highest diagnostic performance was achieved by combining all 5 preoperative parameters, and at current ICM thresholds, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive were 93.5%, 95.4%, 92.1%, 89.7%, and 96.5%, respectively.ConclusionThe diagnostic performance of preoperative minor criteria was outstanding (PMN%, alpha defensin, white blood cell count) or excellent (leukocyte esterase, serum C-reactive protein). PMN% showed the best diagnostic utility (area under the curve) and should have an increased weight-adjusted score in the ICM scoring system.     

The Utility of Frozen Section Histology in Diagnosing Periprosthetic Joint Infection in Revision Total Joint Arthroplasty

BackgroundSurgeons utilize a combination of preoperative tests and intraoperative findings to diagnose periprosthetic joint infection (PJI); however, there is currently no reliable diagnostic marker that can be used in isolation. The purpose of our study is to evaluate the utility of frozen section histology in diagnosis of PJI.MethodsRetrospective analysis of 614 patients undergoing revision total joint arthroplasty with frozen section histology from a single institution was performed. Discriminatory value of frozen section histology was assessed using univariate analysis and evaluation of area under the curve (AUC) of a receiver operating characteristic curve comparing frozen section histology results to the 2018 International Consensus Meeting (ICM) PJI criteria modified to exclude the histology component.ResultsThe sensitivity of the frozen section histology was 53.6% and the specificity was 95.2%. There was 99.2% concordance between the permanent section and frozen section results. The receiver operating characteristic curve for frozen section yielded an AUC of 0.744 (95% confidence interval 0.627-0.860) and the modified ICM score yielded an AUC of 0.912 (95% confidence interval 0.836-0.988) when compared to the full score. The addition of frozen section histology changed the decision to infected in 20% of “inconclusive” cases but less than 1% of total cases.ConclusionIn comparison to the modified ICM criteria, intraoperative frozen section histology has poor sensitivity, strong specificity, and acceptable overall discrimination for diagnosing PJI. This test appears to be of particular value for patients deemed “inconclusive” for infection using the remaining ICM criteria.     

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.     

The Screening of Fixation‐Related Infection in Patients Undergoing Conversion Total Hip Arthroplasty after Failed Internal Fixation of Hip Fractures: A Single‐Central Retrospective Study

ObjectiveTo evaluate the diagnostic values of preoperative plasma fibrinogen and platelet count for screening fixation‐related infection (FRI) in patients undergoing conversion total hip arthroplasty (cTHA) after failed internal fixation of hip fractures.MethodThis was a single‐center retrospective study. Data were retrospectively analyzed for 435 patients who underwent cTHA in our hospital from January 2008 to September 2020. They were divided into infected (n = 30) and non‐infected groups (n = 405) according to the 2013 International Consensus Meeting (ICM) criteria. The diagnostic sensitivity and specificity of plasma fibrinogen and platelet count were determined using receiver operating characteristic (ROC) curves. Optimal predictive cutoffs of these two markers were determined based on the Youden index. In addition, the diagnostic value of preoperative serum C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for screening FRI were also evaluated based on the cutoffs recommended by the 2013 ICM Criteria. Finally, the diagnostic ability of various combinations of the plasma fibrinogen and platelet count as well as serum CRP and ESR was re‐assessed.ResultsThe numbers of patients with and without FRI were 30 (6.9%) and 405 (93.1%), respectively. Areas under the ROC curves were 0.770 for fibrinogen, 0.606 for platelet, 0.844 for CRP and 0.749 for ESR. The optimal predictive cutoff of fibrinogen was 3.73 g/L, which gave sensitivity of 60.0% and specificity of 90.5%. The optimal predictive cutoff for platelet was 241.5 × 10⁹/L, which gave sensitivity of 46.7% and specificity of 83.7%. The CRP gave sensitivity of 66.7% and specificity of 92.5% with the predetermined cutoff of 10 mg/L, while the ESR gave sensitivity of 67.5% and specificity of 72.4% % with the predetermined cutoff of 30 mm/h. The combination of CRP and ESR showed high specificity of 93.2% but low sensitivity of 66.7%, while the corresponding values for CRP with fibrinogen were satisfied both for sensitivity of 80.0% and specificity of 78.7%. The combination of these four biomarkers gave sensitivity of 73.3% and specificity of 85.7%.ConclusionPreoperative serum CRP, ESR, plasma fibrinogen and platelet count have low sensitivity on their own for screening FRI in patients, but the combination of CRP with fibrinogen shows promise for that.     

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.     

Synovial Fluid d-Lactate—A Novel Pathogen-Specific Biomarker for the Diagnosis of Periprosthetic Joint Infection

BackgroundSynovial fluid d-lactate may be useful for diagnosing periprosthetic joint infection (PJI) as this biomarker is exclusively produced by bacteria. We evaluated the performance of synovial fluid d-lactate using 2 definition criteria and determined its optimal cutoff value for diagnosing PJI.MethodsConsecutive patients undergoing joint aspiration before prosthesis revision were prospectively included. Synovial fluid was collected for culture, leukocyte count, and d-lactate concentration (by spectrophotometry). Youden's J statistic was used for determining optimal d-lactate cutoff value on the receiver operating characteristic curve by maximizing sensitivity and specificity.ResultsA total of 224 patients were included. Using Musculoskeletal Infection Society criteria, 71 patients (32%) were diagnosed with PJI and 153 (68%) with aseptic failure (AF), whereas using institutional criteria, 92 patients (41%) were diagnosed with PJI and 132 (59%) with AF. The optimal cutoff of synovial fluid d-lactate to differentiate PJI from AF was 1.3 mmol/L, independent of the used definition criteria. Synovial fluid d-lactate had a sensitivity of 94.3% (95% confidence interval [95% CI], 86.2-98.4) and specificity of 78.4% (95% CI, 66.8-81.2) using Musculoskeletal Infection Society criteria, whereas its sensitivity was 92.4% (95% CI, 84.9-96.9) and specificity 88.6% (95% CI, 81.9-93.5) using institutional criteria. The concentration of d-lactate was higher in infections caused by Staphylococcus aureus (P < .001) and streptococci (P = .016) than by coagulase-negative staphylococci or in culture-negative PJI.ConclusionThe synovial fluid d-lactate showed high sensitivity (>90%) for diagnosis of PJI using both definition criteria and correlated with the pathogen virulence. The high sensitivity makes this biomarker useful as a point-of-care screening test for PJI.Level of EvidenceDiagnostic level I.