Synovial White Blood Cell Count Research Articles

Periprosthetic Joint Infection in Patients With Inflammatory Arthritis: Optimal Tests to Differentiate From Flares.

Diagnosis of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA) is challenging, as features of IA flares can mimic infection. We aimed to cross-sectionally determine if the optimal tests to diagnose PJI in osteoarthritis were present in patients with IA flares. We enrolled patients from October 2020 to July 2022 in 3 groups: (a) PJI-total joint arthroplasty patients undergoing revision for infection, (b) IA Flare-IA patients with a flaring native joint, and (c) IA Aseptic-total joint arthroplasty patients with IA undergoing aseptic arthroplasty revision. We compared blood and synovial fluid markers between the cohorts using Kruskal-Wallis and Fisher exact tests to assess marker sensitivity and specificity. Of 52 cases overall, 40% had rheumatoid arthritis, 20% psoriatic arthritis, and 11% osteoarthritis (in PJI group). PJI cases had higher C-reactive protein (CRP) and synovial fluid polymorphonuclear neutrophil percentage (%PMN). Alpha-defensin tested positive in 93% of PJI cases, 20% of IA Flares, and 6% of IA Aseptic (p < 0.01). Synovial white blood cell count >3000/μL and positive alpha-defensin were highly sensitive (100%) in diagnosing infection; however, specificity was 50% for white blood cell counts and 79% for alpha-defensin. PJI diagnosis was nearly 5 times more likely with positive alpha-defensin and almost 6 times more likely with %PMNs >80. Blood markers interleukin-6, procalcitonin, and d-dimer were neither sensitive nor specific, whereas erythrocyte sedimentation rate and CRP showed 80% sensitivity, but 47% and 58% respective specificities. Although synovial %PMNs, CRP, and alpha-defensin are sensitive tests for diagnosing PJI, they are less specific and may be positive in IA flares.

Evaluating the Diagnostic Utility of Serum Laboratory Studies and Synovial Fluid Analysis in Identifying Periprosthetic Joint Infection in Metal Hip Revisions.

Background Metal-on-metal (MoM) bearing surfaces have been implicated as a cause of increased complication rates in total hip arthroplasty (THA), with local and systemic reactions identified. These reactions may cause abnormal laboratory results in common tests that are used to diagnose periprosthetic joint infection (PJI). The purpose of this study was to evaluate the utility of common laboratory studies in the diagnosis of PJI in patients undergoing revision THA with MoM bearings. Methods A retrospective case series of 81 patients undergoing THA revision of MoM bearings from January 2010 to May 2023 at a single institution was performed. Patient data was extracted from the electronic medical record. All patients were evaluated using the 2018 International Consensus Meeting (ICM) definition of PJI. Descriptive statistics were calculated for the clinical characteristics of all patients. Univariate analyses were performed to compare patients who met the ICM criteria for infection with those deemed indeterminate. Results Fifty-one (63.0%) patients were deemed not infected according to ICM criteria, 19 (23.5%) were deemed indeterminate, and 11 (13.6%) were deemed infected. Clinically, four patients had two or more positive cultures and were formally treated for PJI; all patients were deemed inconclusive, and the remaining seven patients deemed infected were clinically treated as not infected, and all remained infection-free. There were significant differences between patients deemed inconclusive and those deemed infected in synovial WBC count (17,539 vs. 90,196 cells/μL, p = 0.049) and synovial polymorphonuclear (PMN) neutrophils (38 vs. 79%, p = 0.002). No other significant differences in laboratory values or outcomes were noted between groups. Conclusions Patients undergoing revision THA with MoM bearings may be more likely to present with a clinical picture that is concerning for infection and may benefit from a more aggressive preoperative workup. The synovial PMN neutrophil percentage may help differentiate between hips that are infected and those that are not.

Synovial Fluid White Blood Cell Count as a Potential Biomarker for the Clinical Severity of Knee Osteoarthritis: A Prospective Study

Knee osteoarthritis is categorized classically as a non-inflammatory arthropathy. However, there has been increasing evidence regarding the supplementary role of inflammation in the pathogenesis and disease progression of knee osteoarthritis. This study aims to identify a potential correlation between synovial fluid White Blood Cell (SF WBC) count and the severity of knee osteoarthritis clinical presentation. 200 knees (200 patients) were assessed through synovial fluid aspiration and cytology analysis for WBC count. All patients have filled out the Knee Injury and Osteoarthritis Outcome Score for clinical correlation. For the 200 knees, there was a statistically significant positive correlation between the severity of osteoarthritis clinical presentation as expressed by the KOOS and the synovial white blood cell count among the studied cases (p-value &lt; 0.001). There was no statistically significant correlation found between the patient’s age, sex, or side and KOOS or synovial fluid white cell count. The clinical severity of knee osteoarthritis is directly correlated with increased synovial fluid white cell count and hence, SF WBCs may play a role in identifying and grading osteoarthritis clinical severity. This may raise the interest in identifying the role of using specific disease-modifying drugs that deal with the WBC function in cases of osteoarthritis along with other modalities.

Aspirations Dashed: Conventional Synovial Fluid Analysis Is Superior to Synovial Fluid and Blood Neutrophil-to-Lymphocyte Ratios in Diagnosing Pediatric Septic Arthritis of the Hip and Knee.

Recent research suggests that synovial fluid neutrophil-to-lymphocyte ratio (SF-NLR) is a superior diagnostic for pyogenic septic arthritis (SA) in adults compared with synovial fluid white blood cell count (SF-WBC) ≥50,000 cells/μL or ≥90% polymorphonuclear leukocytes (SF-%PMN). Other research also indicates that the neutrophil-to-lymphocyte ratio in the blood (B-NLR) may be of diagnostic significance. However, it is not known whether these findings extend to the pediatric population. Medical records at a large urban tertiary-care children's hospital were queried for emergency department visits between 2012 and 2023, where synovial fluid (SF) analysis was performed to evaluate for SA of the hip or knee. Patients 18 years old and above were excluded. The "conventional composite test" (CCT) for SA was considered positive if SF analysis showed any of the following: (1) SF-WBC ≥50,000 cells/μL, (2) ≥90% PMNs, or (3) organisms reported on gram stain. Patients with aspirate and/or operating room (OR) cultures (or supplemental testing, ie, nucleic acid identification) revealing an offending organism were considered to have culture-positive septic arthritis (CPSA). The remaining patients were considered culture-negative (CN). Serum and SF test data were analyzed to assess their diagnostic utility in identifying CPSA. Receiver operating characteristic (ROC) curves were examined to compare the predictive value of SF-NLR and B-NLR versus conventional indicators of SA. A total of 394 patients met the inclusion criteria. In all, 58.6% (n=231) were male, 67.5% (n=266) involved the knee, and 20.1% (n=79) had CPSA. Those with CPSA had higher ESR and CRP compared with CN patients (P<0.01). Bivariate testing did not show a difference in SF-NLR or B-NLR between those with CPSA and CN patients (P=0.93 and 0.37, respectively). The CCT showed 91% sensitivity and 35% specificity using conventional thresholds. ROC analysis showed that SF-WBC was superior to SF-NLR and B-NLR in the diagnosis of CPSA (AUC=0.71 vs. 0.50 and 0.53, respectively; both P<0.01). Among CCT (+) patients who ended up culture negative, Lyme testing was positive in 48.8% (100/205). In contrast to adults, SF-NLR and B-NLR were not found to be strong diagnostic indicators of SA of the hip or knee in pediatric patients. This may be because competing diagnoses in children come with systemic inflammatory responses similar to that seen in pyogenic SA, while noninfectious conditions that might represent the major alternate diagnoses in adults do not increase systemic inflammatory markers as significantly. Given the high incidence of Lyme disease seen among patients in this study, this topic should be further studied at pediatric centers outside Lyme-endemic areas to better understand the generalizability of these findings. Despite excitement regarding SF-NLR and B-NLR as diagnostics for adult SA, these criteria appear less useful in the diagnosis of pyogenic SA in pediatric patients in Lyme-endemic areas.

The predictive value and reliability of ultrasound-guided synovial aspiration and biopsies for diagnosing periprosthetic shoulder infections.

Preoperative diagnosis of periprosthetic shoulder infections (PSI) is difficult. Infections are mostly caused by low virulence bacteria and patients do not show typical signs of infection. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination with multiplex polymerase chain reaction (mPCR), serum markers, and/or synovial markers for the preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. A prospective explorative diagnostic cohort study was performed including 55 patients undergoing revision shoulder replacement surgery. A shoulder puncture was performed preoperatively before incision to collect synovial fluid for mPCR analysis and for measurement of interleukin-6, calprotectin, white blood cell count (WBC), and polymorphonuclear cells. Also prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two for mPCR analysis. A blood sample was obtained to determine serum C-reactive protein, WBC, and erythrocyte sedimentation rate. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; the primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, blood and synovial markers, mPCR, and combinations thereof. Routine tissue cultures were positive for infection in 24 patients. Cultures from ultrasound-guided biopsies diagnosed infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. The best diagnostic value was found for the combination of ultrasound-guided biopsies for culture, synovial WBC, and calprotectin with a sensitivity of 69.2%, specificity of 80.0%, PPV of 69.2%, and NPV of 80.0%. Ultrasound-guided biopsies for cultures alone and in combination with mPCR, and/or blood and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of PSI. Diagnostic study level II.

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.