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.     

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

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

Plasma 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.     

Normal CRP and WBC values in total hip arthroplasty (THA) with signs of loosening. Do we need a joint aspiration?

PurposeOverall Total hip arthroplasty (THA) is a very successful procedure. However, in case of complication dedicated management is required. Two major complications of THA failures are aseptic loosening (AL) and periprosthetic joint infection (PJI). The primary hypothesis of this study was that joint aspirations in patients with signs of loosening after THA are capable to detect PJI in suspected AL with negative serologic testing.MethodsIn this study a total of 108 symptomatic patients with radiographic signs of prosthetic loosening and hip pain in THA were included. Based on a standardized algorithm all patients underwent serological testing followed by joint aspiration preoperatively. Intraoperatively harvested samples were subjected to microbiological testing and served as the gold standard in differential diagnosis. Demographics, as well as the results of serologic and microbiological testing were collected from the medical records.ResultsOf the included patients 85 were finally diagnosed with an AL and 23 with PJI. Within the patients with PJI 13 (56%) patients demonstrated elevated CRP and WBC counts, as well as positive synovial cultures after joint aspiration. In ten patients (44%) diagnosed with PJI neither CRP nor WBC were abnormal.ConclusionThe diagnosis of PJI can be difficult in THA with radiographic signs of loosening. Clinical features including pain, fever, and local sings of infection are uncommon especially a long period after index operation. First-line screening testing relies on serological evaluation of CRP and WBC. However, normal CRP and WBC values cannot rule out a PJI. These cases can be detected by joint aspiration and synovial cultures reliably.     

An Exciting Performance of Established and Novel Biomarkers in Diagnosing Periprosthetic Joint Infections: A Single-center Retrospective Cohort Study

Objective

Significant progress has been made in recent years in the diagnosis of periprosthetic joint infections (PJI). However, the lack of a gold standard test for the diagnosis of PJI remains a challenge.The aim of this study was to evaluate the diagnostic values of the albumin/fibrinogen ratio (AFR), the C-reactive protein/albumin ratio (CAR), and the levels of fibrinogen (FIB) and albumin (ALB) in the diagnosis of PJI.

Methods

The medical records of 158 patients who had undergone hip or knee revisions from January 2018 to May 2022 were retrospectively analyzed. Of these patients, 79 were diagnosed with PJI, while 79 were diagnosed with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of C-reactive protein (CRP), ALB, and FIB; the erythrocyte sedimentation rate (ESR); and the AFR and CAR in the two groups were recorded and analyzed. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator; the diagnostic value for each indicator was calculated as the area under the curve (AUC).

Results

The ESR, CRP, FIB, and CAR values in the PJI group were significantly higher than those in the AL group, and the ALB and AFR values were significantly lower than those in the AL group (p < 0.001). The AUC values of AFR and fibrinogen were 0.851 and 0.848, respectively, which were slightly higher than those of CRP (0.826) and ESR (0.846). The AUC of CAR was 0.831 which was slightly lower than that of CRP (0.846). ALB had an AUC of 0.727. The optimal threshold, sensitivity, and specificity, respectively, were 10.05, 84.81%, and 82.28% for AFR; 4.03 μg/mL, 77.22%, and 86.08% for FIB; 0.23, 72.15%, and 82.28% for CAR; and 37.30 g/L, 65.82%, and 73.42% for ALB.

Conclusions

AFR, CAR, and FIB are good new auxiliary diagnostic indicators of PJI, while ALB is of fair value for the diagnosis of PJI.     

Lipopolysaccharide-binding protein: A valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?

Purpose

The pre-operative differentiation between periprosthetic joint infection (PJI) and aseptic loosening after total hip (THA) or knee (TKA) arthroplasty is essential for successful therapy and relies in part on the use of molecular markers. The objective of this study was to assess serum levels of lipopolysaccharide-binding protein (LBP) as a diagnostic tool for PJI and to compare its accuracy with standard tests.

Methods

One hundred and twenty patients presenting with a painful TKA or TKA with indication for surgical revision were included in this prospective, controlled, clinical trial at a single centre. Pre-operative blood and serum samples were collected and analysed for white blood cell (WBC) count, C-reactive protein (CRP) and LBP. The definite diagnosis of periprosthetic joint infection was determined on the basis of clinical, microbiological and histopathological examination.

Results

LBP showed significantly higher values in PJI compared with aseptic loosening (p?p?7 ng/ml. In combination with CRP, the positive predictive value for PJI was at 0.67; negative predictive value with both negative was at 0.77.

Discussion

Patients with PJI have elevated serum levels of LBP when compared with patients with aseptic loosening. The use of LBP in serum appears not to be a more accurate marker than CRP level in serum for detecting PJI. On the basis of these results, we cannot recommend the sole use of LBP for differentiating PJI and aseptic loosening following THA and TKA.     

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.     

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.     

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.     

Preoperative Opioid Use Is Associated With Higher Revision Rates in Total Joint Arthroplasty: A Systematic Review

BackgroundAlthough preoperative opioid use has been associated with poor postoperative patient-reported outcome measures and delayed return to work in patients undergoing total joint arthroplasty, direct surgery-related complications in patients on chronic opioids are still not clear. Thus, we sought to perform a systematic review of the literature to evaluate the influence of preoperative opioid use on postoperative complications and revision following primary total joint arthroplasty.MethodsFollowing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we queried PubMed, EMBASE, the Cochrane Library, and the ISI Web of Science for studies investigating the influence of preoperative opioid use on postoperative complications following total hip arthroplasty and total knee arthroplasty up to May 2020.ResultsAfter applying exclusion criteria, 10 studies were included in the analysis which represented 87,165 opioid users (OU) and 5,214,010 nonopioid users (NOU). The overall revision rate in the OU group was 4.79% (3846 of 80,303 patients) compared to 1.21% in the NOU group (43,719 of 3,613,211 patients). There was a higher risk of aseptic loosening (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.11-1.53, P = .002), periprosthetic fractures (OR 1.89, 95% CI 1.53-2.34, P < .00001), and dislocations (OR 1.26, 95% CI 1.14-1.39, P < .00001) in the OU group compared to the NOU group. Overall, 5 of 6 studies reporting on periprosthetic joint infection (PJI) rates showed statistically significant correlation between preoperative opioid use and higher PJI rates.ConclusionThere is strong evidence that preoperative opioid use is associated with a higher overall revision rate for aseptic loosening, periprosthetic fractures, and dislocation, and an increased risk for PJI.Level of EvidenceLevel III, systematic review.     

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.     

Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection

Purpose

The purpose of this study was to evaluate the diagnostic value of interleukin-6 (IL-6) and other inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) in diagnosis of PJI.

Methods

The study group included 40 patients (21 males, 19 females) admitted for surgical intervention after knee or hip arthroplasties. Patients were subjected to careful history taking, thorough clinical examination and pre-operative laboratory investigations including serum IL-6, CRP, WCC and ESR. Peri-implant tissue specimens were subjected to microbiological culture and histopathological examination.

Results

The mean age of patients was 58.4 years (range, 38–72 years). Intra-operative cultures and histopathological examination revealed 11 patients had been infected (PJI) and 29 patients were aseptic failure of prosthesis. Four presumed markers of infection were tested preoperatively: ESR, CRP, WCC, and IL-6. ESR (p?=?0.0001), CRP (p?=?0.004), WCC (0.0001), and IL-6 (p?=?0.0001) were significantly higher in patients with septic revision than those with aseptic failure of the prosthesis. Serum IL-6 (>10.4 pg/ml) reportedly had a sensitivity of 100 %, a specificity of 90.9 %, a PPV of 79 %, a NPV of 100 %, and accuracy of 92.5 %.

Conclusions

The present study demonstrated that IL-6 has been found to be the most accurate laboratory marker for diagnosing PJI when compared to ESR, CRP, and WCC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/L will identify all patients with PJI and the combination of CRP?+?IL-6 is an excellent screening test to identify all such patients (sensitivity 100 %, NPV 100 %).     

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.     

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.     

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.     

Aseptic Reoperations Within 1 Year of Primary Total Knee Arthroplasty Markedly Increase the Risk of Later Periprosthetic Joint Infection

BackgroundDespite the high rate of success of primary total knee arthroplasty (TKA), some patients are candidates for early aseptic reoperation. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients treated with an aseptic reoperation within 1 year of primary TKA.MethodsA retrospective review of our total joint registry compared 249 primary TKAs requiring an aseptic reoperation within 1 year following index arthroplasty to a control group of 17,867 TKAs not requiring reoperation within 1 year. Patients were divided into groups based on time from index TKA: (1) 90 days or less (114 TKAs) and (2) 91 to 365 days (135 TKAs). Mean age was 68 years with 57% female. Mean follow-up was 7 years.ResultsAt 2 years postoperatively, patients undergoing an aseptic reoperation within 90 days subsequently had a 9% PJI rate, while patients undergoing an aseptic reoperation between 91 and 365 days subsequently had a 3% PJI rate. The control group had a 0.4% PJI rate. Compared to the control group, patients undergoing an aseptic reoperation within 90 days had an elevated risk of PJI (hazard ratio, 9; P < .0001), as did patients who had a reoperation between 91 and 365 days (hazard ratio, 4; P < .0001).ConclusionAseptic reoperation within 1 year of primary TKA was associated with a notably increased risk of subsequent PJI.     

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.     

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.