Aims . Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. Patients and Methods. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. . Results. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. . Conclusion . Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. . Cite this article: Bone Joint J 2017;99-B:660–5

Aim. The analysis of synovial fluid has proved to be of crucial importance in the diagnostic process of prosthetic joint infections (PJI), suggesting the presence of an infection before the microbiological culture results. In this context, several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI [1, 2]. However, several testing methods have been explored to detect synovial calprotectin levels, emphasizing the need to use a standardized, rapid and rapid test. In this study, synovial calprotectin was analyzed by means of a commercial stool test [3] to explore whether the detected levels might predict PJIs and, therefore, being a promising tool for the fast and reliable diagnosis of this complication. Method. The synovial fluid of 55 patients underwent to revision of the prosthetic implant were analyzed. The measurement of calprotectin was carried out by of commercial stool test, following the protocol for liquid samples. Calprotectin levels were then compared to other synovial biomarkers of PJI such as leucocyte esterase and count and percentage of polymorphonuclear cells. Data analysis were performed using R software v4.1.1 (R Core Team) and package “pROC” [4]. Receiver operator characteristics curves were designed using culture test as gold standard to evaluate the area under curve (AUC) of each method (with DeLong method for confidence-interval calculation). Thresholds were calculated to maximize Youden's index; sensitivity and specificity were reported. One-to-one Pearson's correlations coefficient were calculated for each pair of methods. P value <0.05 were considered statistically significant. Results. Of the 55 synovial fluids analyzed, 13 patients were diagnosed with PJI and 42 with an aseptic failure of the implant. The specificity, sensitivity, and AUC of calprotectin resulted 0.90, 0.85, and 0.86 (95%CI: 0.72–0.99), respectively with a set threshold of 226.5 µg/g. The values of calprotectin had a moderate and statistically relevant correlation with the synovial leucocyte counts (r. s. = 0.54, p = 0.0003) and the percentage of polymorphonuclear cells (r. s. = 0.68, p = 0.0000). Conclusions. From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicator of local infection, delivering a rapid and reliable results and supporting the diagnostic process of PJI

Introduction. In the last couple of years, several synovial biomarkers have been introduced in the diagnostic algorithm for a prosthetic joint infection (PJI). Alpha defensin-1 proved to be one of the most promising, with a high sensitivity and specificity. However, a major disadvantage of this biomarker is the high costs. Calprotectin is a protein that is present in the cytoplasm of neutrophils, and is released upon neutrophil activation. Its value has been established for decades as a (fecal) marker for inflammatory bowel disease. Aim. To determine the efficacy of synovial calprotectin in the diagnosis of a prosthetic joint infection. Methods. We prospectively collected synovial fluid (from hip, knee and shoulder) from patients with a proven PJI (n=15) and from patients that underwent a revision surgery without signs of a PJI (n=19). Patients with an active rheumatoid arthritis and/or gout were excluded from the study. Synovial fluid was centrifuged and the supernatant was used to measure calprotectin, by using a rapid, point of care test. This test was validated for synovial fluid analysis of calprotectin using an ELISA. A Mann-Whitney U test was used to calculate the difference between both patient groups. Results. The median calprotectin level was 899 mg/L (range 28–2120) for PJI versus 22 mg/L (range 0–202) for controls (p < 0.0001). With a cut-off value of 50 mg/L, synovial calprotectin has a high sensitivity of 93%, and a specificity of 84%. The positive and negative predictive values are 82% and 94%, respectively. Conclusions. Synovial calprotectin is a potentially valuable biomarker in the diagnosis of a PJI. With a point of care test, a rapid quantative diagnosis can be made within the operating room (results are obtained within 20 minutes), and could help in the decision making process to re-implant a prosthesis in a one stage procedure. In comparison to the currently available test (to measure alpha defensin-1), the measurement of calprotectin test is much cheaper (500 euro versus 20 euro per sample) and easily to implement in hospitals where this test is already available. Its diagnostic efficacy for exclusively low-grade PJI should be further elaborated

Aim. Synovial calprotectin point-of-care test (POC) has shown promising clinical value in diagnosing periprosthetic joint infections (PJIs). However, limited data are available in unclear cases. Moreover, cut-off values for calprotectin lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) need to be adapted. The aim of this study was to evaluate the performance of an upgraded and more sensitive version of a synovial calprotectin LFA along with ELISA immunoassay in patients with septic, aseptic, and unclear cases. Methods. Overall, 206 prospectively collected periprosthetic synovial fluid samples from 169 patients (106f/63m; 38 hip/131 knee) who underwent revision surgeries were retrospectively evaluated for calprotectin concentration. The following groups were analyzed: unexpected negative cultures (UNC; 32/206), unexpected positive cultures (UPC; 28/206), and unclear cases (65/206) with conflicting clinical results. In addition, we added a true aseptic (40/206), and true septic (41/206) control groups according to the international consensus meeting (ICM) 2018 PJI classification. Calprotectin concentration was determined by a rapid quantitative LFA (n=206) (Lyfstone®, Norway), and compared to calprotectin ELISA immunoassay (171/206). For the determination of a new calprotectin cut-off value, analysis of the area under the curve (AUC) followed by Youden's J statistic were performed using the calproctectin values from clear septic and aseptic cases. Sensitivity and specificity for calprotectin were calculated. All statistical analyses were performed using IBM-SPSS® version 25 (Armonk, NY, USA). Results. An absolute calprotectin value of 43 mg/ml, and 40.15 mg/ml was determined to be the optimal cut-off for PJI diagnosis using the new version of the LFA and ELISA, respectively. With this cut-off, the sensitivity and specificity of synovial calprotectin concentration for PJI were 88.1% (95% CI 77.8 to 94.7) and 76.6% (95% CI 61.9 to 87.7) for LFA, and 97.06% (95% CI 89.8 to 99.64) and 93.6% (95% CI 82.5 to 98.66) for ELISA, respectively. Of the evaluated groups, UNC 30/32 (93.8%) vs 26/27 (96.3%), UPC 6/28 (21.4%) vs 4/21 (19%), and unclear samples 45/65 (69.2%) vs 30/56 (53.6%) displayed a high likelihood of infection by using LFA, and ELISA, respectively. Conclusion. The upgraded version of the calprotectin quantitative LFA with a new suggested cut-off for infected samples showed additional clinical value in identifying cases at high risk of infection in unclear PJI revisions. Additionally, calprotectin ELISA immunoassay had a better performance than LFA. Further large sample-size validation studies are warranted

Aims

Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320

Background. The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice and the analysis of synovial fluid (SF) is a useful diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase (LE) strip test, alpha-defensin (AD)) have been introduced into the MSIS (MusculoSkeletal Infection Society) algorithm for the diagnosis of PJI. AD, although promising with high sensitivity and specificity, remains expensive. Calprotectin is another protein released upon activation of articular neutrophils. The determination of calprotectin and joint CRP is feasible in a routine laboratory practice with low cost. Purpose. Our objective was to evaluate different synovial biomarkers (calprotectin, LE, CRP) for the diagnosis of PJI. Methods. In this monocentric study, we collected SF from hip, knee, ankle and shoulder joints of 42 patients who underwent revision or puncture for diagnostic purposes. Exclusion criteria included a joint surgery in the previous 3 months and a diagnosis of a systemic inflammatory disease. PJI was diagnosed in a multidisciplinary consultation meeting (RCP) of the Reference Centers for Osteoarticular Infections of the Great West (CRIOGO). SF was analysed for LE, CRP and calprotectin. The cut-off values used were 50 mg/L for calprotectin, 8.8 mg/L for CRP and 125 WBC/µL for LE. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for these different synovial markers. Results. Of the 42 patients included, 28 were considered as infected and 14 uninfected. The statistical parameters are presented in Table 1. Conclusion. The present study shows that the synovial calprotectin assay has an excellent sensitivity and a 100% NPV for the diagnosis of PJI, suggesting that a result < 50 mg/L could exclude PJI. This promising study suggests that calprotectin should be included with synovial CRP in a new decision algorithm for the diagnosis of PJI. For any tables or figures, please contact the authors directly

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

Aims

This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) .

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This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint?

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This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients.