Synovial White Blood Cell Count Research Articles

The Effect of Crystal Arthropathy on the Diagnostic Criteria of Native Septic Arthritis.

Distinguishing between septic arthritis and crystal arthropathy flares can be challenging. The purpose of this study was to determine how the presence of synovial crystals affects the diagnostic criteria of septic arthritis. A retrospective review identified patients undergoing joint aspirations to rule out native septic arthritis. Differences between septic arthritis presenting with and without synovial crystals were analyzed. A receiver-operating characteristic curve was plotted for laboratory markers to determine the area under the curve, or diagnostic accuracy, for septic arthritis and to evaluate thresholds that maximized sensitivity and specificity. There were 302 joint aspirations in 267 patients. Septic arthritis was diagnosed in 17.9% (54/302). Patients with synovial crystals were less likely to have septic arthritis (4.2% [5/119] vs. 26.8% [49/183], P < 0.0001). Septic arthritis in patients with no synovial crystals was associated with fever and a higher synovial white blood cell (WBC) count, synovial polymorphonuclear cell percentage (PMN%), serum WBC, and C-reactive protein (CRP) (P < 0.05). Septic arthritis in patients with synovial crystals was only associated with inability to bear weight and a higher synovial WBC and CRP (P < 0.05). Synovial PMN% was considered nondiagnostic of septic arthritis (area under the curve 0.56) in patients with crystals while synovial WBC and CRP had acceptable (0.76) and excellent (0.83) diagnostic utility, respectively. The WBC and CRP value thresholds that maximized sensitivity and specificity for septic arthritis were greater in patients with crystals (21,600 vs. 17,954 cells/μL and 125 vs. 69 mg/L, respectively). The presence of synovial crystals reduced the likelihood of septic arthritis and altered the laboratory diagnostic criteria. PMN% was nondiagnostic in the setting of synovial crystals.

Utility of Synovial Fluid Biomarkers for Culture-Positive Septic Arthritis in a Lyme Disease-Endemic Region.

To evaluate the performance of synovial fluid biomarkers to identify children with culture-positive septic arthritis. We identified children 6 months to 18 years old presenting to a single emergency department between 2007 and 2022 undergoing evaluation for septic arthritis defined by having a synovial fluid culture obtained. Our primary outcome was septic arthritis defined by a positive synovial fluid culture. We evaluated the ability of synovial fluid biomarkers to identify children with septic arthritis using area under the receiver operating characteristic curve (AUC) analyses. We measured the sensitivity and specificity of commonly used synovial fluid biomarkers. We included 796 children, of whom 79 (10%) had septic arthritis. Compared with synovial white blood cell count (AUC, 0.72; 95% confidence interval [CI], 0.65-0.78), absolute neutrophil count (AUC, 0.72; 95% CI, 0.66-0.79; P = 0.09), percent neutrophils (AUC, 0.66; 95% CI, 0.60-0.71; P = 0.12), and glucose (AUC, 0.78; 95% CI, 0.67-0.90; P = 0.33) performed similarly, whereas protein (AUC, 0.52; 95% CI, 0.40-0.63, P = 0.04) had lower diagnostic accuracy. Synovial fluid white blood cell count ≥50,000 cells/μL had a sensitivity of 62.0% (95% CI, 50.4%-72.7%) and a specificity of 67.0% (95% CI, 63.4%-70.4%), whereas a positive synovial fluid Gram stain had a sensitivity of 48.1% (95% CI, 36.5%-59.7%) and specificity of 99.1% (95% CI, 98.1%-99.7%) for septic arthritis. None of the routinely available synovial fluid biomarkers had sufficient accuracy to be used in isolation in the identification of children with septic arthritis. New approaches including multivariate clinical prediction rules and novel biomarkers are needed.

Laboratory workflow for optimizing leukocyte count and differential in synovial fluids on Sysmex XN-1000.

Falsely elevated synovial white blood cell (WBC) counts using automated hematology analyzers have been reported particularly in the setting of joint arthroplasty. We evaluated the implementation of a laboratory workflow based on Sysmex XN-1000-automated cell counting and scattergram interpretation. WBC and differential were measured for 76 synovial fluid samples (29 native joints and 47 with joint arthroplasties) with Sysmex XN-1000 and manual methods. All scattergrams were evaluated for possible incorrect WBC and/or differential according to our implemented workflow. A specific finding was the "banana-shape" scattergram, which indicates possible interferences. The European Bone & Joint Infection Society (EBJIS) criteria were applied to identify possible prosthetic joint infections (PJIs) in patients with joint arthroplasties. Correlation between automated and manual WBC counts, calculated for samples with WBC count <50 000/μL, was higher for native joints (r = 0.938) compared with patients known with arthroplasty (r = 0.906). Scattergrams classified as OK showed overall a higher correlation compared with scattergrams, which were interpreted as NOT OK. "Banana-shape" scattergrams (n = 19) showed falsely elevated automated WBC count, and the patterns were mainly seen in prosthesis patients (17/19 [89%]). Six of 47 (13%) patients with joint arthroplasties were reclassified from "confirmed" to "unlikely" PJI according to the EBJIS criteria. Our workflow based on scattergram interpretation resulted in accurate WBC counts in synovial fluid using automated/and or manual methods. It is important to identify the presence of "banana-shape" scattergrams to avoid overestimated automated WBC counts. Overall, automated synovial WBC count can be used, even for patients with arthroplasty, but after visual inspection of the scattergram to exclude possible interferences.

Evaluation of predictive factors of septic wrist to avoid overdiagnosis

BackgroundThe existing diagnostic criteria for septic wrist are nonspecific, exposing patients with noninfectious etiologies to surgical morbidity. This study aimed to identify predictors differentiating septic wrist from other etiologies. MethodsAn institutional review board-approved retrospective review was conducted on patients with a presumed diagnosis of septic wrist (2003–2022). Bivariate and multiple regression analyses were performed to identify correlation between confirmed septic wrist and comorbidities (autoimmune diseases, immunosuppression, crystalline arthropathy, intravenous [IV] drug use, smoking), penetrating trauma, fever, multi-joint involvement, inflammatory markers (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP]/white blood cells [WBC]), serum uric acid level, blood cultures, imaging findings, and synovial fluid analysis. Categorical data were reported as median [interquartile range]. ResultsHundred and sixty-eight (58 females and 110 males) patients were included. The median length of hospitalization and follow-up were 6[7] days and 1[3] months. Eighty-nine (53%) patients had septic wrist confirmed with Gram stain/culture, 48 (29%) patients received alternative diagnoses, and 31 (18%) patients had undetermined diagnoses. Concomitant septic wrist and crystalline arthropathy were identified in 9 patients (6.6% of total patients). Out of the 48 patients who received alternative diagnoses, 12 (25%) underwent open drainage. Elevated synovial WBC count (95,409.4 ± 85,926.2) showed a trend of association with septic wrist (p = 0.08). Negative synovial crystals (p = 0.01), positive blood culture (p = 0.04), negative history of crystalline arthropathy (p = 0.08), and multi-joint involvement (p = 0.05) were identified as predictors of septic wrist with a combined sensitivity of 87.5%, specificity of 86.2%, and area under the curve 0.93. ConclusionsCurrent diagnostic criteria for septic wrist have low specificity. Negative history of crystalline arthropathy, multi-joint involvement, absence of synovial crystals, and positive blood culture are helpful indicators for predicting septic wrist in patients presenting with a painful, erythematous, and swollen wrist.

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange: A Diagnostic Scoring System.

This study evaluated appropriate thresholds for serum biomarkers, synovial fluid white blood cell (SF-WBC) count, and synovial fluid neutrophil (polymorphonuclear leukocyte [PMN]) percentage to predict infection in a patient group who underwent definitive reimplantation after receiving a continuous course of antibiotic therapy for chronic knee periprosthetic joint infection (PJI). These thresholds were then used to generate a scoring system to predict recurrence (or persistence) of infection. The study included 153 patients with a median age of 73 years (range, 46 to 91 years) who underwent 2-stage revision for chronic knee PJI. Staphylococci were identified at baseline in 107 (70%) of the patients. After the 96-week follow-up period, 12% (19) of the 153 patients had recurrence of the PJI. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of common serum biomarkers and SF aspiration before reimplantation, and the area under the curve (AUC) was evaluated. Variables that were significantly different between patients with and without infection recurrence were evaluated using a multivariable logistic regression model. A half-integer-point scoring system was created based on the final beta coefficients. Regarding the prediction of recurrent infection, a D-dimer level of >1110 ng/mL yielded a sensitivity of 74%, specificity of 61%, and AUC of 0.69; an SF-WBC count of >934 cells/µL showed a sensitivity of 68%, specificity of 90%, and AUC of 0.79; and an SF-PMN percentage of >52% showed a sensitivity of 73%, specificity of 90%, and AUC of 0.82. The beta coefficients were approximated to 1.5 for the D-dimer level and to 2 for the SF-WBC count and SF-PMN percentage. A total score of >2 was used to classify patients with a high risk of infection recurrence. The ability to discriminate infection recurrence was demonstrated by an AUC of 0.90 (95% confidence interval: 0.82 to 0.99). Patients with a score of >2 on our proposed scoring system based on serum biomarkers, SF-WBC count, and SF-PMN percentage should not undergo reimplantation, as they are at a high risk for recurrent PJI. Patients with a score of ≤2 can undergo definitive reimplantation with the lowest risk of recurrence. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of Antibiotic Administration Before Joint Aspiration on Synovial Fluid White Blood Cell Count in Native Joint Septic Arthritis.

This study was performed to assess the impact of preaspiration antibiotics on synovial fluid analysis and timing of operative treatment in native-joint septic arthritis. We performed a retrospective record review of adult patients from an urban level 1 trauma center with native joint septic arthritis in 2015-2019, identified by means of codes from the International Classification of Diseases (Ninth Revision and Tenth Revision). Univariate and multivariate analyses were performed to determine whether antibiotics were associated with lower synovial fluid white blood cell counts (WBCs), the percentage of polymorphonuclear neutrophil (PMNs), and rate of culture positivity. Secondary analysis included time elapsed from aspiration to surgery. Of the 126 patients with septic joints included, nearly two-thirds (n = 80 [63.5%]) received antibiotics before joint aspiration. The synovial fluid WBC count, percentage of PMNs, and rate of culture positivity were significantly lower in patients who received preaspiration antibiotics than in those who did not (mean WBC count, 51 379.1/μL [standard deviation, 52 576.3/μL] vs 92 162.7/μL [59 330.6/μL], respectively [P < .001]; PMN percentage, 83.6% [20.5%] vs 91.9% [6.0%; P = .01]; and culture positivity, 32.5% vs 59.1% [P = .008]). Multivariable analyses revealed that these associations remained after controlling for potential confounders (change in PMNs, -42 784.60/μL [95% confidence interval, -65 355/μL to -20 213.90/μL [P < .001]; change in PMNs, -7.8% [-13.7% to -1.8%] [P = .01]; odds ratio, 0.39 [.18-.87; P = .02). Patients with a synovial fluid WBC count ≤50 000/μL experienced significant delay in time from joint aspiration to operative intervention (mean [standard deviation], 10.5 [11.3] vs 17.9 [17.2] hours; P = .02). The administration of antibiotics before joint aspiration for suspected septic arthritis appears to decrease the synovial fluid WBC count, the percentage of PMNs, and the rate of culture positivity. Efforts to limit antibiotic administration before joint aspiration are important to minimize diagnostic dilemmas and circumvent treatment delays.

Diagnosing periprosthetic joint infection.

The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties.

How Reliable Is the Absolute Synovial Polymorphonuclear Neutrophil Cell Count in Diagnosing Periprosthetic Joint Infection?

BackgroundDiagnosing periprosthetic joint infection (PJI) is a daunting task for even the most experienced orthopedic surgeons, as there is currently no test available that can provide absolute accuracy. Utilizing an established synovial indicator for detecting PJI without incurring additional costs or resources would be the optimal solution for predicting the presence of infection. Therefore, we hypothesized that synovial absolute neutrophil count (ANC) would improve the diagnostic accuracy of chronic knee and hip PJI. MethodsThe study included 260 patients (134 men and 126 women, mean age of 70 years [range, 26 to 89]) who underwent aspiration during preoperative workup. Of these, 109 patients (41.9%) were diagnosed with chronic PJI (50 knees, 59 hips), and 151 patients (58.1%) were diagnosed as aseptic (94 knees, 57 hips). Data obtained from all patients included age, sex, procedure type (total hip or total knee arthroplasty), operation side, synovial white blood cell count (cells/μL), synovial polymorphonuclear cells percentage, and synovial α-defensin immunoassay value at the admission were retrieved from the electronic medical record. ResultsThe calculated optimal threshold for synovial ANC of 1,415.5 cells/μL was associated with an area under the receiver operating characteristic curve (AUC) of 0.930 for chronic knee PJI diagnosis. The calculated optimal threshold for synovial ANC of 2,247 cells/μL was associated with an AUC of 0.905 for chronic hip PJI diagnosis. ConclusionsThis study has conclusively shown that the synovial ANC serves as a valuable marker in the complicated diagnosis of PJI. This highly effective and efficient approach should be utilized for obtaining further information through standard tests, thereby ruling out the possibility of PJI. Level of evidenceIII.

Administering Antibiotics for Less Than Four Weeks Increases the Risk of Relapse in Culture-Positive Septic Arthritis of Native Joints.

(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57-412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74-175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis.

Utility of Blood Cell Ratio Combinations for Diagnosis of Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) is a serious complication following joint replacement surgery, and its diagnosis can be challenging due to the similarity of symptoms to other conditions and the lack of confirmatory imaging tests. Platelet/mean platelet volume ratio (PVR), platelet/lymphocyte ratio, monocyte/lymphocyte ratio, and neutrophil/lymphocyte ratio have been proposed as potential markers to aid in the diagnosis of PJI. This study aimed to further assess the utility of these blood cell ratio combinations for the diagnosis of PJI. A retrospective chart review was conducted on patients who presented to a university hospital for evaluation for PJI or underwent aseptic revision surgery. All patients were reviewed for inclusion in the study. Data were collected on several markers, including complete blood counts, synovial fluid white blood cell count, and polymorphonuclear percentage. Receiver operator characteristic curve analysis was used to evaluate the diagnostic capabilities of the markers and marker combinations. The combination of erythrocyte sedimentation rate, C-reactive protein, synovial white blood cell count, and synovial polymorphonuclear percentage, with PVR, had the highest area under the curve of 0.97, with a sensitivity of 94.3% and a specificity of 88.9%, and a positive predictive value of 97.1% and a negative predictive value of 80.0%. This study further supports the use of PVR calculated from complete blood count commonly ordered laboratory values obtained during routine complete blood counts when combined with established serum and synovial markers to increase the diagnostic accuracy for diagnosing PJI.

Diagnosis of periprosthetic joint infections in patients who have rheumatoid arthritis.

To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI.

Are Synovial Inflammatory Markers Increased in Patients Who Have Aseptic Total Hip Arthroplasty Dislocation Indicated for Revision?

BackgroundPrevious studies have speculated on elevated synovial inflammatory markers in patients undergoing surgical revision for total hip arthroplasty (THA) dislocation. However, this assumption is based on small patient series and a full investigation according to International Consensus Meeting (ICM) criteria has not yet been performed. MethodsPatients who had aseptic THA dislocation indicated for revision surgery were identified retrospectively. Only patients who had available diagnostic workup according to ICM 2018 criteria, including preoperative and intraoperative parameters, were included. For comparison, we analyzed a matched cohort of patients indicated for aseptic THA revision for other conditions. The 2 cohorts each consisted of 55 patients and were not different regarding age, sex, BMI, or implant fixation. ResultsThere was no difference in synovial white blood cell count (2,238 ± 2,544 versus 2,533 ± 3,448 c/μL; P = .601), alpha-defensin quotient (0.14 ± 0.11 versus 0.19 ± 0.28; P = .207), or polymorphonuclear neutrophil percentage (% PMN) (36.7 ± 22.6 versus 31.3 ± 24.5%; P = .312) between the groups. In the dislocation cohort, 20% of patients had a synovial white blood cell count of 3,000 c/μL or higher, compared with 18% in the control cohort. However, all patients in the dislocation cohort were below the cutoff for alpha-defensin or % PMN. ConclusionIn patients who have aseptic THA dislocation, synovial inflammatory markers are not elevated compared with patients undergoing aseptic revision for other complications. A detailed preoperative analysis of synovial inflammatory markers using ICM criteria appears critical in patients who have a THA dislocation to exclude periprosthetic joint infection. Level of EvidenceLevel III, retrospective, comparative study.

How reliable are the synovial cell count and blood parameters in the diagnosis of septic arthritis?

This study aims to investigate the reliability of the joint fluid cell count and blood parameters compared to the culture results in the diagnosis of septic arthritis (SA). A total of 192 patients (112 males, 80 females, mean age: 60.3±19.2 years; range, 18 to 98 years) who presented with SA between January 2018 and July 2022 were evaluated retrospectively. The recorded joint fluid cell count, complete blood count (CBC), white blood cell (WBC) count, serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) and culture results were analyzed comparatively according to SA diagnosis. The most commonly involved joint was the knee joint (82.3%), which was affected in 158 patients. Thirty-six (18.8%) of the patients who underwent joint aspiration had positive culture result. The cultures were positive in 10 (35.7%) of 28 patients with synovial WBC value greater than 50,000/mm3, while 26 (15.9%) of 164 patients with a synovial WBC value less than 50,000/mm3 had positive culture results (p=0.013). Patients with SA may present variable blood and synovial parameters. Making decision based on the commonly used synovial WBC count cut-off value of 50,000/mm3 may lead to misdiagnosis. To avoid misdiagnosis or delay in treatment, it is of utmost importance not to exclude the diagnosis acutely, and suspicion of SA should remain even with unlikely values.

It can be unnecessary to combine common synovial fluid analysis and alpha-defensin tests for periprosthetic joint infection diagnosis

BackgroundPeriprosthetic joint infection is a serious complication after total joint arthroplasty. Despite that alpha-defensin was used as diagnostic test in the 2018 ICM (international consensus meeting) criteria, its position in the PJI diagnostic pipeline was controversial. Therefore, we performed a retrospective pilot study to identify whether synovial fluid alpha-defensin test was necessary when corresponding synovial fluid analysis (WBC count, PMN% and LE tests) was performed.MethodsBetween May 2015 and October 2018, a total of 90 suspected PJI patients who underwent revisions after TJA were included in this study. Based on the 2018 ICM criteria, the interobserver agreements between preoperative diagnostic results and postoperative diagnostic results and the interobserver reliability between preoperative diagnostic results and postoperative diagnostic results with or without synovial fluid alpha-defensin tests were calculated. After that, the ROC analysis, and the direct cost-effectiveness of adding alpha-defensin was performed.ResultsThere were 48,16 and 26 patients in the PJI group, inconclusive group and non-PJI group, respectively. Adding the alpha-defensin tests into 2018 ICM criteria can’t change the preoperative diagnostic results, postoperative diagnostic results, and the concordance between preoperative and postoperative diagnostic results. Moreover, the Risk–benefit Ratio is over 90 per changed decision and the direct cost-effectiveness of alpha-defensin was more than $8370($93*90) per case.ConclusionsAlpha-defensin assay exhibit high sensitivity and specificity for PJI detection as a standalone test based on the 2018 ICM criteria. However, the additional order of Alpha-defensin can’t offer additional evidence for PJI diagnosis when corresponding synovial fluid analysis was performed (synovial fluid WBC count, PMN% and LE strip tests).Evidence levelLevel II, Diagnostic study.

Simple and inexpensive synovial fluid biomarkers for the diagnosis of prosthetic joint infection according to the new EBJIS definition.

Introduction: diagnosis of periprosthetic joint infection (PJI) is challenging, as no single test has absolute accuracy. The purpose of this study was to assess the utility of different simple synovial biomarkers in the diagnosis of PJI as defined by the European Bone and Joint Infection Society (EBJIS). Methods: we retrospectively identified all patients undergoing revision hip or knee arthroplasty from 2013 to 2019 on our prospectively maintained database. Only patients with minimum required infection diagnostic workup were included in the study. Patients with comorbidities that may influence the accuracy of synovial biomarkers were excluded. Receiver operator characteristic (ROC) curves were utilised to assess the diagnostic utility of synovial fluid white blood cell (WBC) count, polymorphonuclear leukocyte percentage (PMN %), C-reactive protein (CRP), adenosine deaminase (ADA), and alpha-2-microglobulin (A2M). Results: in total, 102 patients met the inclusion criteria. Of these, 58 were classified as infection unlikely, 8 as infection likely, and 36 as infection confirmed. Synovial WBC count (area under the curve (AUC) 0.94) demonstrated the best utility for the diagnosis of PJI, followed by PMN % (AUC 0.91), synovial CRP (AUC 0.90), ADA (AUC 0.82), and A2M (AUC 0.76). We found added value in the combined interpretation of different biomarkers. We calculated high sensitivity and negative predictive value if at least two of them are negative and high specificity and positive predictive value if at least two are elevated. Conclusion: current results show that synovial fluid investigation is a useful tool for the diagnosis of PJI, and the combined interpretation of simple and inexpensive biomarkers demonstrated improved diagnostic accuracy.

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.

Utility of Diagnostic Tests Before Reimplantation in Patients Undergoing 2-Stage Revision Total Joint Arthroplasty

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty (TJA), with treatment failure occurring in 12% to 28% after 2-stage revision. It is vital to identify diagnostic tools indicative of persistent infection or treatment failure after 2-stage revision for PJI. The Cochrane Library, PubMed (MEDLINE), and EMBASE were searched for randomized controlled trials and comparative observational studies published before October 3, 2021, which evaluated the utility of serum/plasma biomarkers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], interleukin-6 [IL-6], fibrinogen, D-dimer), synovial biomarkers (white blood cell [WBC] count, neutrophil percentage [PMN %], alpha-defensin [AD], leukocyte esterase [LE]), tissue frozen section, tissue culture, synovial fluid culture, or sonicated spacer fluid culture indicative of persistent infection before the second stage of 2-stage revision for PJI or treatment failure after 2-stage revision for PJI. A total of 47 studies including 6,605 diagnostic tests among 3,781 2-stage revisions for PJI were analyzed. Among those cases, 723 (19.1%) experienced persistent infection or treatment failure. Synovial LE (sensitivity 0.25 [0.10-0.47], specificity 0.99 [0.93-1.00], positive likelihood ratio 14.0 [1.45-135.58]) and serum IL-6 (sensitivity 0.52 [0.33-0.70], specificity 0.92 [0.85-0.96], positive likelihood ratio 7.90 [0.86-72.61]) had the highest diagnostic accuracy. However, no biomarker was associated with a clinically useful negative likelihood ratio. In subgroup analysis, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP had limited utility for detecting persistent infection before reimplantation (positive likelihood ratios ranging 2.33-3.74; negative likelihood ratios ranging 0.31-0.9) and no utility for predicting failure after the second stage of 2-stage revision. Synovial WBC count, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP have modest sensitivity and specificity for predicting persistent infection during the second stage of 2-stage revision, suggesting some combination of these diagnostic tests might be useful before reimplantation. No biomarker or culture accurately predicted treatment failure after reimplantation. Level III. See Instructions for Authors for a complete description of levels of evidence.

Synovial fluid neutrophil extracellular traps could improve the diagnosis of periprosthetic joint infection.

This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly.Cite this article: Bone Joint Res2023;12(2):113-120.

Identifying Inflammation in Knee Osteoarthritis: Relationship of Synovial Fluid White Blood Cell Count to Effusion-Synovitis on Magnetic Resonance Imaging.

Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on magnetic resonance imaging (MRI) and by synovial fluid white blood cell count (WBC). However, the performance characteristics of synovial fluid WBC for the detection of synovitis have not been established. This study was undertaken to determine the sensitivity and specificity of synovial fluid WBC in identifying inflammation in knee OA using MRI effusion-synovitis as the gold standard. We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration, and a laboratory order for synovial fluid WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion-synovitis using the MRI OA Knee Score (MOAKS). We dichotomized effusion-synovitis as 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of synovial fluid WBC using MRI effusion-synovitis (medium/large) as the gold standard. We used the Youden index to identify the best cut point. We included 75 patients. Mean ± SD age was 63 ± 12 years, and 69% were female. The synovial fluid WBC was higher in the medium/large effusion-synovitis group (median 335 [interquartile range (IQR) 312]) than in the none/small group (median 194 [IQR 272]). The optimal cut point was 242, yielding a sensitivity of 71% (95% confidence interval [95% CI] 56-83%) and specificity of 63% (95% CI 41-81%). The sensitivity and specificity of synovial fluid WBC in identifying effusion-synovitis on MRI were limited. Further research is needed to better understand the association between MRI and effusion-synovitis measured by synovial fluid and to determine which measure more strongly relates to synovial histopathology and patient outcomes.

Efficacy of Lavage by Tube under Local Anesthesia versus Arthroscopic Treatment of Acute Septic Arthritis of Native Knee.

Although arthroscopic treatment is a minimally invasive surgery that effectively treats septic arthritis of the knee joint, it requires general or regional anesthesia. This study aimed to compare the clinical results of lavage after tube insertion versus arthroscopic treatment. Patients treated with arthroscopic treatment were included in group I (n = 76), while those treated with lavage by tube were included in group II (n = 34). We investigated the following in all patients: demographics, underlying disorders, initial serum white blood cell (WBC) count, C-reactive protein (CRP) level, synovial fluid WBC and polymorphonuclear cell counts, causative organism, initial Kellgren-Lawrence grade, lavage number, interventional delay, hospitalization days, CRP normalization time, and Western Ontario McMaster Universities Osteoarthritis index scores for clinical outcomes at 3 months postoperative. The mean interventional delay was significantly greater in group I (23.6 ± 15.6 h vs. 8.7 ± 9.3 h, p < 0.001). The lavage by tube featured a significantly shorter interventional delay time than arthroscopy, while the CRP decrease rate did not differ between groups. Moreover, lavage by tube showed no significant differences in outcomes, including laboratory results and functional outcomes at 3 months postoperative.