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.     

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.     

关节液分析对诊断假体周围感染价值的探讨

背景:假体周围感染(PJI)是人工关节置换术后最为严重的并发症之一.诊断PJI的各项实验室检查都存在一定的优劣性.目的:探讨血清C反应蛋白(CRP)、红细胞沉降率(ESR)、关节液白细胞计数及白细胞分类对PJI的诊断效力.方法:回顾性分析2017年1月至2019年12月接受人工髋、膝关节翻修术230例患者的临床资料,包...     

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

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

Synovial Fluid Calprotectin for the Preoperative Diagnosis of Chronic Periprosthetic Joint Infection

BackgroundThe diagnosis of periprosthetic joint infection (PJI) represents a challenge in clinical practice and the analysis of synovial fluid is a useful diagnostic tool. Calprotectin is an inflammatory biomarker widely used in the evaluation of chronic inflammatory diseases; however, little is known about its role in PJI. The purpose of this study is to determine the reliability of synovial calprotectin in the diagnosis of PJI.MethodsSeventy-six patients with painful knee arthroplasty were included in this prospective observational study. Synovial fluid was analyzed for cell count, percentage of polymorphonuclear neutrophils, microbiological culture, leukocyte esterase strip test, alpha-defensin rapid test, and calprotectin immunoassay dosage. The 2018 Consensus Statements criteria for PJI were used as standard reference to define the presence of infection. Sensitivity, specificity, positive and negative likelihood ratio, and receiver-operation characteristic curve were calculated for calprotectin immunoassay test.ResultsBy 2018 Consensus Statements criteria for PJI, 28 patients were considered infected, 44 patients were considered not infected, and 4 patients were classified as inconclusive. The calprotectin synovial fluid test resulted in 2 false-positive results and no false-negative results. The calprotectin synovial fluid test demonstrated a sensitivity of 100% (95% confidence interval [CI] 99.96-100) and specificity of 95% (95% CI 89.4-100) for the diagnosis of PJI. The positive likelihood ratio was 22 (95% CI 5.680-85.209) and the negative likelihood ratio was 0 (95% CI 0-0.292). The area under the receiver-operation characteristic curve was 0.996 (95% CI 94.3-100).ConclusionThe present study suggests that synovial calprotectin immunoassay test has a high sensitivity and specificity in the diagnosis of knee PJI. Moreover, it is easily applied, quick and valuable in clinical practice.     

Measurement of Serum Anti-staphylococcal Antibodies Increases Positive Predictive Value of Preoperative Aspiration for Hip Prosthetic Joint Infection

BackgroundPreoperative synovial fluid culture is pivotal in the early diagnosis of prosthetic joint infection (PJI) but may yield false-positive and false-negative results. We evaluated the predictive value of synovial fluid culture results combined with the measurement of serum anti-staphylococcal antibodies (SASA).Questions/purposes(1) For hip and knee PJI, does combining positive SASA results with preoperative synovial culture results improve the positive predictive value (PPV) of preoperative synovial fluid culture alone? (2) Does combining preoperative synovial fluid culture results with a positive cell count and differential result increase the PPV of preoperative synovial fluid culture alone? (3) What proportion of isolated organisms exhibit concordance in antibiotic susceptibility: preoperative aspiration versus intraoperative isolates?MethodsA prospective study was conducted at two French reference centers that manage bone and joint infections and included 481 adult patients who had a revision or resection arthroplasty between June 25, 2012 and June 23, 2014. Exclusion criteria including no serum sample available for immunoassay, the lack of microbiological documentation, and the absence of preoperative aspiration reduced the patient number to 353. Seven patients with an undetermined SASA result were excluded from the analysis. We also excluded patients with PJI involving more than one Staphylococcus species (polystaphylococcal infection) and those in whom more than one Staphylococcus species was recovered from the preoperative synovial fluid culture (polystaphylococcal synovial fluid culture). In total, 340 patients were included in the analysis (no infection, 67% [226 of 340]; staphylococcal infection, 21% [71 of 340]; other infection, 13% [43 of 340]). The preoperative synovial fluid analysis included a cell count and differential and bacterial culture. SASAs were measured using a multiplex immunoassay. The diagnosis of PJI was determined using the Infectious Diseases Society of America (IDSA) criteria [14] and intraoperative tissue culture at the time of revision surgery was used as the gold standard (at least one positive intraoperative sample for a “virulent” organism (such as S. aureus) or two positive samples for a “non-virulent” (for example S. epidermidis).ResultsSASA increased the PPV compared with synovial fluid culture alone (92% [95% CI 82 to 97] versus 79% [95% CI 68 to 87]; p = 0.04); when stratified by site, an increase in PPV was seen in hip infections (100% [95% CI 89 to 100] versus 77% [95% CI 63 to 88]; p = 0.01) but not in knee infections (84% [95% CI 66 to 95] versus 80% [95% CI 64 to 91]; p = 0.75). A positive cell count and differential result increased the PPV of staphylococcal synovial fluid cultures compared with synovial fluid culture alone (86% [95% CI 70 to 95] versus 79% [95% CI 68 to 87]; p = 0.36); when stratified by site, no difference in hip and knee infections was observed (86% [95% CI 67 to 96] versus 77% [95% CI 63 to 88]; p = 0.42) and 86% [95% CI 70 to 95] versus 80% [95% CI 64 to 91]; p = 0.74).ConclusionSASA measurement improves the predictive value of synovial fluid cultures of the hip for all staphylococcal organisms, including coagulase-negative staphylococci, but the PPV of SASA plus synovial fluid culture it is not superior to the PPV of synovial fluid cell count/differential plus synovial culture for the knee.Level of EvidenceLevel III, diagnostic study.     

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.     

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.     

Clinical Evaluation of Alpha Defensin Test Following Staged Treatment of Prosthetic Joint Infections

BackgroundDiagnosing persistent infection following staged treatment of prosthetic joint infection (PJI) is challenging. The alpha defensin (AD) test has been shown to be an accurate diagnostic test for the primary diagnosis PJI but has limited evaluation for use following a staged treatment of PJI. The goal of this study was to evaluate the diagnostic accuracy of AD testing following staged treatment of PJI before reimplantation surgery and to determine if negative AD test predicted success following reimplantation using Delphi Criteria at time of last follow-up.MethodsPatients who underwent AD testing prior to reimplantation after staged treatment of PJI (n = 52) were reviewed. Preoperative data (AD result, synovial fluid [SF], C-reactive protein level [mg/L], SF culture, SF white blood cell count, % of polymorphonuclear lymphocytes, serum C-reactive protein/erythrocyte sedimentation rate) and intraoperative data (purulence and tissue culture) were reviewed and used to classify patients using 2018 Musculoskeletal Infectious Disease Society criteria for infection, which was then used as a gold standard test to calculate diagnostic accuracy.Chart review was used to determine if patients who underwent reimplantation surgery would go on to treatment failure as defined by Delphi Criteria.ResultsThe sensitivity and specificity of AD test result as compared with Musculoskeletal Infectious Disease Society criteria in diagnosing PJI was calculated to be 71% and 97.78%. Positive predictive value was calculated to be 83.3%, and negative predictive value was calculated to be 95.65%.Patients who underwent reimplantation (46/52 patients) all had negative AD test results, and 9/46 or 19.5% would have treatment failure as defined by the Delphi Criteria with an average follow-up of 588 days.ConclusionAD demonstrates high specificity and negative predictive value, with low sensitivity when utilized after staged treatment of PJI. Further investigation of this and other diagnostic tests following staged treatment of PJI is needed. Additionally, validated criteria used to identify persistent infection following staged treatment of PJI are required.     

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.     

Laboratory Value Effectiveness in Predicting Early Postoperative Periprosthetic Joint Infection After Total Hip Arthroplasty

BackgroundDiagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution.MethodsWe retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values.ResultsBoth within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/μL, neutrophil percentage ≥74%, and ANC ≥3249 cells/μL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/μL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/μL.ConclusionEarly PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/μL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/μL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy.Level of EvidenceLevel IV Diagnostic.     

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

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

Utility of Synovial Fluid Aspirations in Failed Metal-On-Metal Total Hip Arthroplasty

White blood cell (WBC) count and neutrophil percentage from preoperative synovial fluid aspirations are used to help determine the presence or absence of periprosthetic joint infection (PJI) in failed total hip arthroplasty (THA). The clinical levels indicative of infection have not been delineated in metal-on-metal (MoM) bearings. We identified 39 patients who received a preoperative synovial fluid aspiration prior to MoM revision. Thirty-five of 39 cases were culture negative and 4 of 39 were culture positive. WBC count > 3000 cells/μL was 100% sensitive and 57.1% specific. Neutrophil percentage > 80% was 100% sensitive and 97.1% specific. Both CRP and ESR > 8.0 mg/L and > 22 mm/h, respectively were 75.0% sensitive and 67.6% specific. Our data suggest that synovial WBC count and serum ESR and CRP have poor predictive value in diagnosing PJI for failed MoM THA, whereas synovial neutrophil percentage is a highly accurate marker for diagnosing infection in this patient population.     

Increased Synovial Inflammatory Markers in Aseptic Total Hip Arthroplasty Dislocation

BackgroundIn cases of total hip arthroplasty (THA) dislocation, a synovial fluid aspiration is often performed to evaluate for periprosthetic joint infection (PJI). It is currently unclear how aseptic dislocation of a THA influences synovial fluid white blood cell (WBC) count and polymorphonuclear percentage (PMN%). The primary aim of this study is to investigate the influence of THA dislocation on synovial WBC count and PMN%.MethodsTwenty-eight patients who underwent a synovial aspiration of a THA between 2014 and 2019 were identified and enrolled in our case-control study. Patients with an aseptic THA dislocation and synovial hip aspiration were matched against patients without dislocation, patients undergoing hip aspiration before aseptic THA revision surgery, and patients undergoing hip aspiration before septic THA revision surgery.ResultsSynovial WBC count was significantly increased in the dislocation vs aseptic THA revision group (P = .015), as well as between the septic revision group vs dislocation and aseptic THA revision group (both P < .001). The PMN% did not differ significantly between the dislocation and aseptic revision groups (P = .294). Mean C-reactive protein values were 12.4 ± 14.9 mg/dL in THA dislocation, 24.1 ± 37.7 mg/dL in THA without infection compared to 85.7 ± 84.9 mg/dL in THA infection group (P < .001).ConclusionThis study shows that THA dislocation has a significant impact on synovial WBC count in joint aspiration. Our data suggest that in the setting of THA dislocation, synovial WBC and PMN% may not be the best method to evaluate for PJI. Further research should be performed to establish new thresholds for these synovial inflammatory markers in the setting of THA dislocation and PJI.Level of evidenceLevel III; retrospective trial.     

Synovial White Blood Cell Count and Differential to Predict Successful Infection Management in a Two-Stage Revision

BackgroundAn array of synovial white blood cell (WBC) count and polymorphonuclear differential (PMN%) thresholds have been reported using 2013 Musculoskeletal Infection Society (MSIS) definition which has a poor accuracy to confirm infection control before reimplantation. The workgroup of MSIS recently developed a comprehensive definition of successful infection management. Our objectives were to determine optimal thresholds for WBC count and PMN% associated with reimplantation success based on this new MSIS definition and assess if values above these thresholds indicate decreased survival time.MethodsA retrospective review was conducted on a consecutive series of 133 two-stage hip/knee arthroplasties performed by 15 surgeons (2014-2020) at 2 institutions. All surgeries had a minimum follow-up of 1 year. The inclusion criteria included reporting of preoperative synovial fluid aspiration results. Thus, 88 were finally included. Surgical success was defined by MSIS outcome reporting tool (Tiers 1-4). Receiver operating characteristic curve analyses were performed to estimate optimal thresholds of WBC count and PMN%. A Kaplan-Meier survival analyses with log-rank test were performed.ResultsWith area under the curve of 0.65, synovial PMN% showed superior accuracy than WBC count (area under the curve = 0.52) in determining outcome of reimplantation. The optimal PMN% threshold (62%) demonstrated sensitivity of 57% and specificity of 77%. The calculated WBC count threshold (2,733/μL) showed poor sensitivity (21%) but high specificity (95%). There was a significant difference in failure-free survival (24 months) between the cases with WBC count higher vs lower than 2,733/μL (P = .002). This was also true for PMN% at 5 months postoperatively (P = .009).ConclusionWBC count (2,733/μL) shows very high specificity to confirm successful reimplantation. Both WBC count and PMN% (62%) thresholds can significantly determine reimplantation survival.     

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.     

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 2018 New Definition of Periprosthetic Joint Infection is Valuable for Diagnosis of Persistent Infection at Reimplantation in Patients without Synovial Fluid

BackgroundDiagnosis of persistent infection at reimplantation of 2-stage exchange revision is a challenging problem. The aim of our study is to evaluate the performance of the 2018 new definition and Musculoskeletal Infection Society (MSIS) criteria in determining the persistent infection at reimplantation in patients without synovial fluid.MethodsWe retrospectively reviewed 150 patients who underwent 2-stage exchange revision from 2014 to 2018. Two models were used to define persistent infection—model 1: identical major criteria of the MSIS criteria and new definition and model 2: identical major criteria of 2 criteria and/or subsequent infection after reimplantation. The predictive accuracy of the new definition and MSIS criteria was compared by using receiver operating characteristic curves.ResultsThe receiver operating characteristic curves showed that the new definition had good performance in determining the persistent infection, with the area under the curve (AUC) of 0.871 in model 1 and 0.835 in model 2. The optimal threshold for aggregate scores in new definition was 4. The MSIS criteria had limited diagnostic value in both model 1 (AUC = 0.708) and model 2 (AUC = 0.664). In model 1, the sensitivity and specificity were 86.96% and 84.25% in new definition, and 47.83% and 93.70% in MSIS criteria in patients without synovial fluid. In model 2, the sensitivity and specificity were 78.57% and 85.25% in new definition, and 39.29% and 93.44% in MSIS criteria.ConclusionThe 2018 new definition of PJI is valuable in the diagnosis of persistent infection, which can improve diagnostic accuracy compared with the MSIS criteria in patients without synovial fluid.