What is the performance of novel synovial biomarkers for detecting periprosthetic joint infection in the presence of inflammatory joint disease?

2021 ◽  
Vol 103-B (1) ◽  
pp. 32-38
Author(s):  
Rui Li ◽  
Xiang Li ◽  
Ming Ni ◽  
Jun Fu ◽  
Chi Xu ◽  
...  

Aims The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid. Methods We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38.

2018 ◽  
Vol 20 (11) ◽  
Author(s):  
Ajay Premkumar ◽  
Kyle Morse ◽  
Ashley E. Levack ◽  
Mathias P. Bostrom ◽  
Alberto V. Carli

2020 ◽  
Author(s):  
Cheng Li ◽  
Donara Margaryan ◽  
Cristina Ojeda-Thies ◽  
Carsten Perka ◽  
Andrej Trampuz

Abstract Background The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI). Methods A systematic search and screen of relevant studies was performed in the PubMed, Web of Science and Embase databases using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Then, the data were analysed and processed by Meta-Disc software. Results A total of 7 studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.75 (95% confidence interval [CI]: 0.70 to 0.79), 0.69 (95% CI: 0.66 to 0.72), 3.01 (95% CI: 1.84 to 4.93), 0.32 (95% CI: 0.19 to 0.53) and 10.20 (95% CI: 3.63 to 28.64), respectively. Subgroup analyses showed that use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI (0.86, 0.84 vs. 0.67, 0.60, respectively). Conclusion Serum D-dimer had a better diagnostic value than plasma D-dimer for the diagnosis of PJI.


2020 ◽  
Author(s):  
Cheng Li ◽  
Donara Margaryan ◽  
Cristina Ojeda-Thies ◽  
Carsten Perka ◽  
Andrej Trampuz

Abstract Background The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI). Methods A systematic search and screening of relevant studies was performed in the databases PubMed, Web of Science, and Embase using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Data were subsequently analysed and processed using Meta-Disc. Results Seven studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.75 (95% confidence interval [CI]: 0.70–0.79), 0.69 (95% CI: 0.66–0.72), 3.01 (95% CI: 1.84–4.93), 0.32 (95% CI: 0.19–0.53), and 10.20 (95% CI: 3.63–28.64), respectively. Subgroup analyses showed that the use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI . Conclusion Serum D-dimer was shown to have a better diagnostic value than plasma D-dimer for the diagnosis of PJI. Further research is required for clarification.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xi Chen ◽  
Wenwei Qian ◽  
Xisheng Weng ◽  
Jin Lin ◽  
Jin Jin ◽  
...  

Abstract Background Fibrinogen (Fbg) and D-dimer have been used as biomarkers for the diagnosis of periprosthetic joint infection (PJI). However, previous research has reported conflicting results on the diagnostic value of D-dimer in comparison to Fbg, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Aim This study aimed to: (1) determine the optimal threshold of plasma Fbg and D-dimer in the diagnosis of PJI and compare their diagnostic value to that of CRP and ESR; and (2) investigate whether Fbg and D-dimer perform differently than CRP and ESR as diagnostic indicators for different types of PJI. Methods A total of 115 revision cases after total hip arthroplasty (THA) and total knee arthroplasty (TKA) were identified. Based on demographic characteristics, 25 culture-positive cases were matched to 50 culture-negative cases using propensity score matching. Sensitivity, specificity, receiver operating characteristics (ROC), negative predictive value (NPV), and positive predictive value (PPV) were calculated and compared. Results The optimal thresholds were 2.72 mg/L for D-dimer, 3.655 g/L for Fbg, 12.64 mg/L for CRP, and 27 mm/h for ESR. Levels of plasma Fbg, D-dimer, CRP, and ESR were significantly higher in the culture-positive group than the culture-negative group. Fbg, D-dimer, CRP, and ESR showed sensitivity of 0.92, 0.56, 0.92, and 0.88, respectively, and showed specificity of 0.84, 0.96, 0.94, and 0.80, respectively. The ROC curve showed that CRP has the highest area under the curve (AUC) (0.94), followed by Fbg (0.90), ESR (0.87), and D-dimer (0.81). Conclusions Plasma Fbg exhibited a similar diagnostic performance compared to CRP and ESR in predicting culture-positive results in PJI. Plasma D-dimer showed high specificity but low sensitivity. In our study, Fbg and D-dimer did not show better diagnostic performance with different pathogens and different types of PJI. Further studies are required to investigate the difference between serum D-dimer and plasma D-dimer in the arthroplasty population.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Han Yin ◽  
Duliang Xu ◽  
Dawei Wang

Abstract Background We herein compared the diagnostic value of next-generation sequencing (NGS), bacterial culture, and serological biomarkers to detect periprosthetic joint infection (PJI) after joint replacement. Methods According to the diagnostic criteria of the Musculoskeletal Infection Society, 35 patients who underwent joint revision surgery were divided into infection (15 cases) and non-infection (20 cases) groups, and were routinely examined preoperatively for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and D-dimer levels. All patients underwent arthrocentesis preoperatively. Synovial fluid was used for white blood cell count, white blood cell classification, bacterial culture, and NGS. Furthermore, we calculated the area under the curve (AUC) of the receiver operating characteristic curve (ROC) for ESR, CRP, PCT, IL-6, and D-dimer. Data were assessed by comparing diagnostic accuracy, sensitivity, and specificity. Results Fourteen patients showed positive results by NGS and seven showed positive bacterial culture results in the infection group; further, 18 showed negative results by NGS in the non-infection group. The AUC of ESR, D-dimer, CRP, IL-6, and PCT was 0.667, 0.572, 0.827, 0.767, and 0.808, respectively. The accuracy of NGS, bacterial culture, CRP, IL-6, and PCT was 0.91, 0.74, 0.77, 0.74, and 0.83, respectively. When comparing NGS with CRP, IL-6, PCT, and bacterial culture, differences in overall test results and those in sensitivity were statistically significant, and compared with CRP, differences in specificity were also statistically significant. In comparison with IL-6, PCT, and bacterial culture, the specificity of NGS was statistically insignificant. Conclusions Our results indicated that NGS had higher accuracy and sensitivity than the bacterial culture method and commonly used serological biomarkers for diagnosing PJI.


2021 ◽  
Author(s):  
Hai Wang ◽  
LeiLei Qin ◽  
Jiawei Wang ◽  
Wei Huang

Abstract Purpose The purpose of this study was to investigate the role of synovial fluid interleukin (IL)-1β in diagnosing chronic periprosthetic joint infection (PJI) and to identify the optimal threshold of synovial fluid IL-1β for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties.Methods Between January 2019 and December 2019, we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty. Then synovial IL-1β was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy.Results Of the 93 patients included, their demographic data were not found to be statistically significant. The median synovial IL-1β levels were significantly higher in the chronic PJI group than in the aseptic group (894.73 pg/mL vs. 34.49 pg/mL, P<0.01). The AUC for synovial fluid IL-1β was 0.991, which was higher than serum ESR (0.627) and CRP (0.712). The optimal threshold value for detecting chronic PJI of synovial IL-1β was 312.7 pg/mL, with a sensitivity of 97.3% and a specificity of 94.64%. And the combined measurement of synovial fluid IL-1β and synovial fluid PMN% can led to a specificity of 1, and a negative predictive value (NPV) of 1.Conclusions The present study demonstrated that synovial fluid IL-1β is a valuable biomarker for detection of chronic PJI. The combination of synovial fluid IL-1β and PMN% led to an improvement in specificity compared with evaluation of each single index.


2021 ◽  
Author(s):  
Guangqian Shang ◽  
Zhixuan Fei ◽  
Hao Xu ◽  
Yingzhen Wang ◽  
Shuai Xiang

Abstract Background Periprosthetic joint infection (PJI) is one of the most challenging complication of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated with better treatment outcomes. However, whether the platelet-related markers and globulin-related markers can be used to assist the diagnosis of PJI remains elusive. Methods 206 patients underwent revision hip or knee arthroplasty in our institution were divided into two groups: 79 patients in PJI group and 127 patients in aseptic failure group. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet-related markers including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT) and PLT to MPV raito (PMR) and globulin-related markers, such as globulin, albumin to globulin ratio (AGR), and PLT to AGR ratio were compared. The diagnostic value was measured using area under the curve (AUC) after constructing receiver operating characteristic (ROC) curves. The potential of each marker for determining the timing of second-staged reimplantation was also evaluated. Results Significantly increased levels of ESR, CRP, PLT, PCT, PMR, GLB, and PLT to AGR ratio were identified in PJI group, while decreased levels of MPV and AGR were also found. The diagnostic values of all platelet-related markers and GLB were considered as fair, and good diagnostic values of AGR and PLT to AGR ratio were found, which were comparable to those of ESR and CRP. The levels of GLB and AGR can also be used to predict negative culture result and the timing of second-stage reimplantation. Conclusions Globulin and albumin to globulin ratio were found to have good diagnostic values for PJI, and they can precisely predict the culture results and persistent infection.


2020 ◽  
Vol 9 (10) ◽  
pp. 701-708
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian

Aims The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP. Methods PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR. Results Six studies with 1,255 cases were included (374 PJI cases and 881 non-PJI cases). Overall D-dimer showed sensitivity of 0.80 (95% confidence interval (CI) 0.69 to 0.87) and specificity of 0.76 (95% CI 0.63 to 0.86). Sub-group analysis by excluding patients with thrombosis and hyper-coagulation disorders showed sensitivity of 0.82 (95% CI 0.70 to 0.90) and specificity of 0.80 (95% CI 0.70 to 0.88). Serum D-dimer showed sensitivity of 0.85 (95% CI 0.76 to 0.92), specificity of 0.83 (95% CI 0.74 to 0.90). Plasma D-dimer showed sensitivity of 0.67 (95% CI 0.60 to 0.73), specificity of 0.58 (95% CI 0.45 to 0.72). CRP showed sensitivity of 0.78 (95% CI 0.72 to 0.83), specificity of 0.81 (95% CI 0.72 to 0.87). ESR showed sensitivity of 0.68 (95% CI 0.63 to 0.73), specificity of 0.83 (95% CI 0.78 to 0.87). Conclusion In patients without thrombosis or a hyper-coagulation disorder, D-dimer has a higher diagnostic value compared to CRP and ESR. In patients with the aforementioned conditions, D-dimer has higher sensitivity but lower specificity compared to ESR and CRP. We do not recommend the use of serum D-dimer in patients with thrombosis and hyper-coagulation disorders for diagnosing PJI. Serum D-dimer may perform better than plasma D-dimer. Further studies are needed to compare serum D-dimer and plasma D-dimer in arthroplasty patients. Cite this article: Bone Joint Res 2020;9(10):701–708.


2021 ◽  
Author(s):  
Jiaxing Huang ◽  
Jiawei wang ◽  
Lei lei Qin ◽  
Bo Zhu ◽  
Sizheng Zhu ◽  
...  

Abstract Background: Synovial fluid biomarkers have been confirmed with promising diagnostic value for chronic periprosthetic joint infection (PJI), even there was still no “gold standard”. Interleukin-4 (IL-4) and polymorphonuclear cells (neutrophil) count in synovial fluid play a crucial role in mediating local inflammation of bacterial infections and therefore could be valuable biomarkers for PJI. Methods: The purpose of this study was to investigate the diagnostic capacity of synovial fluid IL4 (SF-IL4) and polymorphonuclear cell percentage(SF-PMN%) for chronic PJI. According to the 2013 Musculoskeletal Infections Society(MSIS 2013) criteria, chronic PJI is defined as occurred more than 6 weeks after the primary arthroplasty. A total of 110 patients who scheduled to undergo revision arthroplasty from January 2019 to October 2020 were enrolled. 11 patients were eliminated by exclusion criteria. 43 of 99 patients were classified as infected and 56 as not infected. In all patients, SF-IL4 and SF-PMN% were measured in synovial fluid, serum CRP, ESR levels were measured preoperatively. The area under the curve(AUC) for each biomarker was analyzed, the diagnostic value and optimal cutoff values were calculated. Results: The demographic data was not statistically different. The SF-IL4 and SF-PMN% showed a great diagnostic accuracy of chronic PJI from aseptic failure patients with AUC of 0.97(95% confidence interval (CI), 0.92-0.99) and 0.89(95%CI, 0.82-0.95) separately, which was higher than the serum ESR (0.72), and serum CRP (0.83). We set 1.7 pg/mL and 75% as the optimal cut-off values of SF-IL4 and SF-PMN% individually. Combination of SF-IL4 and SF-PMN% improved the diagnostic ability for chronic PJI with a specificity of 97.0%, and 96.0% accuracy.Conclusion: Synovial fluid IL-4 was a valuable biomarker for chronic PJI detection. Combination of SF-IL4 and SF-PMN% provided higher specificity and accuracy when met the cut-off values of 1.7 pg/mL and 75% simultaneously.


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