Objective: To challenge the validity of using biomarker concentrations in synovial fluid for the assessment of joint pathology. Hypothesis: Synovial fluid biomarker concentrations are influenced by both cartilage and synovial fluid volumes. Methods: Synovial fluid volumes were determined from the equine metacarpophalangeal (MCP), proximal inter-phalangeal (PIP) and distal interphalangeal (DIP) joints, which have different disease prevalences. Chondrocyte density was calculated from a defined site in each joint. Cartilage volume was measured by novel application of Peripheral Quantitative Computed Tomography (pQCT). Cartilage oligomeric matrix protein (COMP), glycos-aminoglycans (GAG) and total protein (TP) concentrations were measured and then adjusted for cartilage and synovial fluid volume and compared between joints. Results: Mean synovial fluid volume was significantly greater in the MCP than the distal joints (p< 0.0001) (3.2 ±0.5ml, 0.5 ±0.1ml and 0.6 ±0.1ml respectively). In contrast, the DIP had the greatest cartilage volume compared to the proximal joints (5360 ±667mm3 2640mm3, 1940 ±331mm3 respectively). There was no significant difference in the cartilage cellularity between all joints. The DIP had higher TP, COMP and GAG concentrations, however, when values were expressed per unit cartilage volume the opposite was found, with the MCP then exhibiting significantly higher concentrations. Conclusions: These data show the joint with the highest prevalence to osteoarthritis has the lowest biomarker synovial fluid concentrations but the highest biomarker levels per unit cartilage, suggesting a higher release. These results indicate that meaningful interpretation of biomarkers in synovial fluid require consideration of both fluid and cartilage volume

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

Aims. 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%). Methods. 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. Results. 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. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

INTRODUCTION:. The diagnosis of periprosthetic joint infection (PJI) remains a serious challenge. Based on previous work, we believe that biomarkers will become the mainstay of diagnosing PJI in the future. We report on completion of our 8 year comprehensive biomarker program, evaluating the diagnostic profile of the 15 most promising synovial fluid biomarkers. METHODS:. Synovial fluid was prospectively collected from 99 patients being evaluated for infection in the setting of revision hip or knee arthroplasty. All synovial fluid samples were tested by immunoassay for 15 putative biomarkers that were developed and optimized specifically for use in synovial fluid. Sensitivity, specificity and receiver operating Characteristic (ROC) curve analysis were performed for all biomarkers. RESULTS:. The MSIS criteria, including cultures, CRP, ESR, fluid WBC, PMN%, and histology, was used to classify 30 PJIs and 69 cases of aseptic failure. Four synovial fluid biomarkers (alpha-defensin, bactericidal/permeability increasing protein, neutrophil gelatinase-associated lipocalin, and resistin) correctly predicted the MSIS classification of all patients in this study, exhibiting an AUC of 1.0 with >98% sensitivity and specificity for the diagnosis of PJI. Eight other biomarkers exhibited an AUC of >0.9. These results all outperformed the tests for serum CRP (specificity 87%, sensitivity 96%) and ESR (specificity 80%, sensitivity 93%). Interestingly, the Pearson correlations comparing the biomarkers to each other and to the synovial fluid WBC in the group of infected samples revealed only weak correlations, demonstrating that these biomarkers are not simply inflammatory biomarkers. DISCUSSION AND CONCLUSION:. A comprehensive biomarker program has led to the identification of several synovial fluid biomarkers that appear to be diagnostic for PJI. The four top biomarkers are proteins that have known functional roles in the cellular response to pathogens. These biomarkers outperform our currently utilized serum tests and can be used to develop rapid bedside immunoassays for PJI

Aim. Several options to standardize the definition of periprosthetic joint infection (PJI) have been created including the 2013 Musculoskeletal Infection Society (MSIS), 2018 Intentional Consensus Meeting (ICM), and the 2019 proposed European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid biomarkers have been investigated in an effort to simplify and improve the diagnosis of PJI. The aim of this study was to test the sensitivity, specificity, positive, and negative predicted values (PPV and NPV, respectively) of a calprotectin point of care (POC) test for diagnosing PJI in revision total knee arthroplasty (TKA) patients comparing different sets of criteria (2013 MSIS, 2018 ICM, and 2019 EBJIS criteria) used to define patients as with or without infection. Method. From October 2018 to January 2020 and under IRB approval 123 intraoperative samples of synovial fluid were prospectively collected at two academic hospitals in the same institution from revision TKA patients. All patients underwent standard clinical and laboratory evaluation for PJI at our institution, allowing for categorization using the 3 criteria. Patients were adjudicated by 2 blinded and independent reviewers for the 3 sets of criteria. The 3 criteria agreed 91.8% of the time. Four likely cases by the 2019 proposed EBJIS were considered unlikely and 1 inconclusive case by the 2018 ICM was considered not infected for the purposes of analysis. Calprotectin POC testing followed manufacturer's instructions using a threshold of >50 mg/L to indicate PJI. Sensitivities, specificities, PPV, NPV, and areas under the curve (AUC) were calculated for the 3 sets of criteria. Results. Using 2013 MSIS criteria the calprotectin POC test demonstrated a sensitivity, specificity, PPV, NPV AUC of 98.1%, 95.7%, 94.5%, 98.5%, and 0.969, respectively. Using 2018 ICM the POC test demonstrated a sensitivity, specificity, PPV, NPV and (AUC) of 98.2%, 98.5%, 98.2%, 98.5%, and 0.984, respectively. Using the 2019 proposed EBJIS criteria the POC test demonstrated a sensitivity, specificity, PPV, NPV and area under the curve (AUC) of 93.2%, 100.0%, 100.0%, 94.2%, and 0.966, respectively. Conclusions. The calprotectin lateral flow POC test has an excellent sensitivity and specificity regardless of the set of criteria used to define PJI. These results are promising and suggest that the calprotectin lateral flow test may be used as a rule out test in a cost-conscious health care model or when conventional diagnostic tools may not be available. Further investigations of the calprotectin PCO test must be completed to validate these results

Aim. Despite several synovial fluid biomarkers for diagnosis of periprosthetic joint infection (PJI) have being investigated, point-of-care (POC) tests using these biomarkers are not widely available. Synovial calprotectin has recently been reported to effectively exclude diagnosis of PJI and a novel lateral flow POC test using it has shown potential to be effective. Thus, the aims of this study were to 1) validate calprotectin POC with enzyme linked immunosorbet assay (ELISA) 2) at 2 separate thresholds for PJI diagnosis in total knee arthroplasty (TKA) patients using the 2013 Musculoskeletal Infection Society (MSIS) PJI diagnosis criteria as the gold standard. Method. Intraoperative synovial fluid samples were prospectively collected from 123 patients who underwent revision TKAs (rTKA) at two academic hospitals within the same healthcare system from October 2018 to January 2020. The study was conducted under IRB approval. Included patients followed the hospital standard for their PJI diagnostic work-up. Data collection included demographic, clinical, and laboratory data in compliance with MSIS criteria. Synovial fluid samples were analysed by calprotectin POC and ELISA tests in accordance with manufacturer's instructions. Patients were categorized as septic or aseptic using MSIS criteria by two independent reviewers blinded to calprotectin assay results. The calprotectin POC and ELISA test performance characteristics were calculated with sensitivities, specificities, positive, and negative predicted values (PPV and NPV, respectively) and areas under the curve (AUC) for 2 different PJI diagnosis scenarios: (1) a threshold of >50 mg/L and (2) a threshold of >14 mg/L. Results. According to MSIS criteria, 53 rTKAs were septic while 70 rTKA were aseptic. In the (1) >50 mg/mL threshold scenario, the calprotectin POC and ELISA performance showed 100% agreement with sensitivity, specificity, PPV, NPV, and AUC, respectively, of 98.1%, 95.7%, 94.5%, 98.5%, and 0.969. In the (2) >14 mg/mL threshold scenario, the POC slightly outperformed the ELISA with sensitivity, specificity, PPV, NPV and AUC of 98.1%, 87.1%, 85.2%, 98.4%, and 0.926, respectively (ELISA values were 98.1%, 82.9%, 81.3%, 98.3%, and 0.905, respectively). Conclusions. The calprotectin POC test performed as well as the ELISA at the >50mg/L threshold and was slightly better at the >14 mg/L threshold. The >50 mg/L threshold had a better specificity while maintaining the same sensitivity as the >14 mg/L threshold. This test could be effectively implemented as a rule out test. However, further investigations with larger cohorts are necessary to validate these results

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared. 9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies. This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context

Aim. To evaluate a panel of peripheral blood and synovial fluid biomarkers for the identification of periprosthetic joint infection PJI. Method. Peripheral blood and synovial fluid measurements of CD64, IL-1a, IL-1b, IL-6, IL-8, IL-10, IL-17, Alpha Defensin and CRP were made on samples collected from patients with suspected PJI using a combination of flow cytometry (CD64), ELISA (Alpha Defensin) and MSD Electrochemiluminescence (IL-1a, IL-1b, IL-6, IL-8, IL-10, IL-17). Receiver operating characteristic (ROC) curves which combine sensitivity and specificity were created for each marker using GraphPad PRISM statistical software. The diagnosis of infection was based on MSIS major criteria. Results. A total of 35 infections were identified (12 acute, 23 chronic). The best performing peripheral blood biomarker in both acute and chronic PJI was CRP with an area under the curve (AUC) of 0.88 (sensitivity 83%, specificity 94%) in acute infection and 0.82 in chronic infection (sensitivity 80%, specificity 85%). In synovial fluid the best performing acute infection marker was CRP with an AUC of 0.94 (sensitivity 87.5%, specificity 95%) and in chronic cases was Alpha defensin with an AUC of 0.98 (sensitivity 100%, specificity 85%). Conclusions. CRP measured in peripheral blood shows excellent diagnostic characteristics in both acute and chronic cases. This is also replicated in synovial fluid from acute PJIs but not in chronic infection where Alpha defensin showed the best performance

The number of shoulder arthroplasty procedures performed in the United States continues to rise. Currently, the number of procedures performed per year ranges from 55,000–80,000 and is expected to increase more than 300% in the coming years. Periprosthetic joint infection (PJI) is one of the most serious complications associated with arthroplasty surgery, leading to poor outcomes, increased cost, and technically difficult revision surgery. The incidence of infection following primary shoulder arthroplasty has been reported between 0.7% and 4%, representing 2.9–4.6% of all complications. Prosthetic shoulder joint infections are unlike prosthetic joint infections of the hip and knee. Shoulder PJIs are primarily indolent in nature and difficult to diagnose using traditional methods that have been shown to be accurate for periprosthetic infections of the hip and knee. The majority of infected revision shoulder arthroplasties are associated with growth of Propionibacterium acnes (P. Acnes). This slow-growing, anaerobic organism requires longer than normal incubation times for culture (7–21 days), and typically demonstrates a subtle, non-specific clinical presentation that can make the presence of infection difficult to identify. In the reported literature, P. Acnes accounts for about 70% of cases with positive cultures associated with revision for treatment of a painful shoulder arthroplasty and due to the bacteria's slow growing nature and virulence profile, the rate of infection following shoulder arthroplasty may often be underestimated. A more recent and promising tool for evaluation of periprosthetic infection has been analysis of synovial fluid. Synovial fluid biomarkers have been identified as part of the innate response to pathogens, and include pro-inflammatory cytokines and anti-microbial peptides, and marker levels have shown promise for improved diagnostic efficacy in hip and knee PJI. Currently, no highly predictive clinical test for diagnosis of PJI in the shoulder exists, however, several of these synovial biomarkers have recently been analyzed for their diagnostic capacity in the setting of periprosthetic shoulder infection. Synovial fluid cytokine analysis shows the potential to improve diagnosis of infection in revision shoulder arthroplasty. This information can help to guide decision-making in the management of PJI of the shoulder, including the decision to perform a single- vs. two-stage revision surgery, and the need for post-operative antibiotics following an unexpected positive culture result after revision surgery. However, there are still challenges to broader use of these synovial biomarkers. Synovial α-defensin (Synovsure, CD Diagnostic) is the only marker currently available as a commercial test, and no point-of-care test is currently available for any of the biomarkers to allow for intraoperative decision-making. While a preoperative synovial aspirate is possible to send for α-defensin analysis currently, with results back in approximately 24 hours, dry fluid aspirations are frequent in the shoulder because of the predominance of indolent pathogens and may limit utility of the test. In summary, indolent infection associated with P. acnes is a common cause for the painful total shoulder arthroplasty. Pre-operative diagnosis of infection is difficult as a result of the poor diagnostic accuracy of traditional methods of testing. Synovial biomarker testing may ultimately improve our ability to more accurately diagnosis and treat prosthetic shoulder joint infections

While advances in laboratory and imaging modalities facilitate the diagnosis of periprosthetic joint infection (PJI), clinical suspicion and a thorough history and physical remain the basis of evaluation. If clinical suspicion is high, the evaluation should be more vigorous, and vice versa. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inexpensive as well as ubiquitous, and should be obtained as a preliminary screening tool. These tests have been found to be cost-effective and highly sensitive. If both tests are negative, there is a low risk of periprosthetic joint infection (i.e., good negative predictive value). Positive results on both tests, in contrast, are not as specific but again raise suspicion. When either the ESR or CRP is elevated, or if the clinical suspicion for infection is high, aspiration of the knee joint is suggested. Synovial fluid should be sent for a synovial fluid white blood cell count (WBC), differential and culture. Given the ability to get three data points from one intervention, arthrocentesis, is the best single maneuver the physician can perform to rule in or out PJI. The synovial fluid WBC count has demonstrated in multiple studies excellent specificity and sensitivity in the diagnosis of infection. Based on multiple recent studies, the proceedings of the International Consensus on PJI recommend cut-offs for the synovial fluid WBC count as >3000 cells/mL and > 80% neutrophils for the differential. Synovial fluid biomarkers represent an expanding area of clinical interests based on the unique cascade of gene expression that occurs in white blood cells in response to pathogens. Deirmegian et al. described the unique gene expression and biomarker production by neutrophils in response to bacteria that are detectable in synovial fluid. Specifically, alpha-defensin is one such antimicrobial peptide. Along with synovial CRP, alpha-defensin can be measured in a currently commercially-available immunoassays. The diagnosis of PJI can be difficult to make in spite of the variety of tests available. That being said, the diagnosis is easily made in our experience in 90% of patients by getting an ESR and CRP followed by selective aspiration of the joint if these values are elevated or if the clinical suspicion is high. Synovial fluid obtained should be sent for a synovial fluid WBC count, differential and cultures

Aim. Alpha-defensin is a new synovial fluid biomarker for the diagnosis of periprosthetic joint infections (PJI). We compared the performance of two different alpha-defensin assays: quantitative ELISA test and qualitative lateral flow test. Method. In this prospective cohort study, consecutive patients with a painful prosthesis of the lower limb were eligible for inclusion. In addition to standard diagnostics of PJI, alpha-defensin was determined in the aspirated synovial fluid between October 2016 and April 2017. PJI was defined according to the modified Zimmerli criteria, the Musculoskeletal Infection Society (MSIS) criteria and the Infectious Disease Society of America (IDSA) criteria. A positive quantitative alpha-defensin test was defined at a cut-off value of 5.2 mg/L. The sensitivity, specificity, accuracy and area under the curve of each test were determined and the AUCs were compared among each other. Results. We included 72 patients (55 knee, 27 hip prosthesis) with a median age of 70 years (range: 41 – 85 years). Based on the modified Zimmerli criteria, 23 cases (32%) were categorized as septic and 49 (68%) as aseptic prosthesis failure. The sensitivity, specificity, accuracy, and AUC of quantitative alpha-Defensin were 48%, 98%, 82%, and 0.73, respectively; for qualitative alpha-Defensin, results were 48%, 100%, 83%, and 0.74, respectively. When the IDSA criteria were applied, the sensitivity of the quantitative and qualitative alpha-defensin test was 83% and 75%, respectively; when the MSIS criteria were applied, the sensitivity of the quantitative and qualitative alpha-Defensin was 92% and 83%, respectively. The comparison between the qualitative and quantitative alpha-defensin tests showed no statistically significant difference regardless of the used infection classification (modified Zimmerli: [difference AUC −0.01; p = 0.792], IDSA: [difference AUC 0.04; p = 0.317], MSIS: [difference AUC 0.04; p = 0.264]). Conclusions. The sensitivity of the alpha-defensin test in synovial fluid showed poor sensitivity (48%) for diagnosing PJI when modified Zimmerli criteria were used. No difference were observed between the qualitative and quantitative alpha-defensin test

Peri-prosthetic joint infection (PJI) can be both a diagnostic and therapeutic challenge in shoulder arthroplasty, due to the indolent nature of the common infecting organisms. Proprionobacterium acnes (P. acnes) is the most common pathogen cultured in revision shoulder arthroplasty. It is a slow growing, anaerobic organism – requires longer incubation period (7–21 days). Coagulase-negative Staphylococcus species (CNSS) is also a common organism responsible for PJI. Established diagnostic tests for hip and knee PJI are often negative in the shoulder despite post-operative growth of intra-operative cultures. Pre-operative synovial aspiration often low volume due to indolent pathogens and successful aspiration is often reported to be 50% or less with Dilisio et al, JBJS 2014: reporting 16.7% sensitivity, 100% specificity. Variable culture length for P. acnes culture protocols are reported from 7–28 days with most groups recommending 14 days. From our research, we demonstrated time to culture growth was significantly shorter in probable true positive culture group (median, 5 vs. 9 days, p=0.002). Frozen section analysis may help intra-operative decision-making (one- vs. two-stage reimplantation) yet the reported sensitivity and specificity in shoulder arthroplasty is far less than in hip and knee arthroplasty. Synovial fluid biomarkers have been identified as part of the innate response to pathogens include pro-inflammatory cytokines and antimicrobial peptides. In a series of prospective studies of revision shoulder arthroplasty, synovial fluid analysis reported by Frangiamore et al, JBJS 2015: IL-6, Frangiamore et al, JSES 2015: α-defensin (Synovasure. TM. ), Frangiamore et al, AAOS 2015: Broader cytokine analysis it was demonstrated that these markers are much more predictive of infection than synovial fluid cultures, frozen section or serum markers

Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly

Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease. However, the Periprosthetic Joint Infection (PJI) remains one of the biggest challenges facing orthopaedics today. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

INTRODUCTION. Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. However, infection of these implants, called Periprosthetic Joint Infection (PJI), remains one of the biggest challenges facing orthopaedics today. PJI can lead to additional surgeries, revision, fusion and amputation. Diagnosis of PJI. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The Synovasure® Test for Periprosthetic Joint Infection (PJI). The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. These biomarkers include inflammatory proteins, cytokines, and microbicidal peptides / proteins that are known to be involved in the host response to infection. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. DISCUSSION. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. CONCLUSIONS. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.

Aims

The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid.

Aims

Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).

Aims

This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI).

Aim. Our goal is to increase diagnostic accuracy of synovial fluid testing in differentiating prosthetic joint infection(PJI) by more exhaustively studying simple and inexpensive biomarkers. For that purpose, we sought to determine: 1) if synovial fluid C-reactive protein(CRP), alpha-2-macrogloblulin(A2M), procalcitonin and adenosine deaminase(ADA) concentrations are different between infected and aseptic cases; 2) performance and optimal cutoff values of each marker; 3) whether any such test may help improve diagnostic performance of traditional leukocyte count. Method. Between January/2013 and December/2015 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples as well as the implant for sonication were gathered for microbiological study. Definitive diagnosis was classified as infection or aseptic on the basis of the recent International Consensus Meeting definition of PJI. Using receiver operating characteristic curves, we determined cutoff values as well as sensitivity and specificity for each marker. Results. Fifty-five out of 143 revision arthroplasties fully respected the inclusion criteria. Two supposedly aseptic cases were ultimately classified as infected resulting in 32 aseptic and 23 infected cases available for analysis. Total leukocyte count, proportion of PMN, C-reactive protein, ADA and alpha-2-macroglobulin but not procalcitonin were significantly different between both groups. Cutoff values for optimal performance in the diagnosis of infection were: total leukocyte count >1,463 cells/μL; proportion of PMN >81%; CRP >6.7mg/L and ADA >61U/L. Conclusions. Synovial fluid leukocyte count offers great negative predictive value and interpreting it together with other more specific markers such as C-reactive protein and ADA is helpful in improving its positive predictive value. These simple and inexpensive markers may reduce the number of equivocal synovial fluid results requiring more expensive investigation