Exploratory Study Of Synovial Biomakers In The Diagnosis Of Chronic Periprosthetic Joint Infection After Total Joint Arthroplasty

Periprosthetic joint infection(PJI)is a common and potentially catastrophic complication after total hip and knee arthroplasty and is a challenge that surgeons must face.However,in some cases,periprosthetic joint infection and aseptic failure after total joint arthroplasty can be indistinguishable,especially when the infection is chronic and occult.Since the clinical symptoms and signs of patients with chronic PJI are atypical,and most of the levels of common serum inflammatory markers are not significantly abnormal,patients with chronic PJI often develop delayed healing of infection,severe bone defects and joint dysfunction,and even a higher risk of short-term death.To date,there is still no "gold standard" test or protocol for diagnosing chronic PJI.In addition,there are significant differences in the treatment of periprosthetic joint infection and aseptic failure after total joint arthroplasty,and the treatment based on misdiagnosis may result in serious adverse consequences for patients.Therefore,it is of great importance to accurately identify chronic periprosthetic joint infection and aseptic loosening after total joint arthroplasty.At present,there are diagnostic criteria of PJI established by Musculoskeletal Infection Society,and recommended threshold of a series of tests,but the sensitivity and specificity of these tests cannot still meet the need of clinical practice and the researchers have been working to develop an accurate biomarkers or diagnostic methods to improve the efficacy of diagnosis.Therefore,this study investigated the role of IL-β in the diagnosis of chronic periprosthetic joint infection after total joint arthroplasty,the diagnostic value of combined serum and synovial CRP in the detection of PJI,and the diagnostic value of multiple synovial cytokines in chronic periprosthetic infection and active rheumatoid arthritis.PART I DIAGNOSTIC VALUE OF SYNOVIAL INFLAMMATORY CELLULAR MOLECULE IN CHRONIC PERIPROSTHETIC JOINT INFECTIONCHAPTER I APPLICATION OF SYNOVIAL IL-1β IN DIAGNOSIS OF CHRONIC PERIPROSTHETIC JOINT INFECTIONPurpose The purpose of this study was to investigate the role of synovial interleukin(IL)-1β in diagnosing chronic periprosthetic joint infection(PJI)and to identify the optimal threshold of synovial IL-1β for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties.Methods Between January 2019 and December 2020,we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty.We measured synovial IL-1βadditionally along with routine preoperative diagnostic serum and synovial biomarkers.The receiver operating characteristic(ROC)curves and area under the curve(AUC)were calculated for each biomarker.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/m L vs.34.49 pg/m L,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-1βwas 312.7 pg/m L,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.CHAPTER II APPLICATION OF COMBINED SYNOVIAL AND SERUM C-REACTIVE PROTEIN IN DIAGNOSIS OF CHRONIC PERIPROSTHETIC JOINT INFECTIONBackground Diagnosis of periprosthetic joint infection(PJI),especially chronic PJI,is very confusing and challenging.The value of C-reactive protein(CRP)in infectious diseases has been recognized,but the diagnostic value of CRP in chronic PJI is unknown.Our aim was to investigate the diagnostic value of synovial CRP in chronic PJI and to explore the role of combined serum and synovial CRP in distinguishing chronic PJI from aseptic failure after knee and hip arthroplasties.Methods We prospectively enrolled patients scheduled to have a revision surgery for chronic PJI or aseptic loosening from January 2019 to December 2020,in which synovial CRP was additionally measured along with routine preoperative diagnostic serum((ESR,CRP)and synovial(PMN%)biomarkers.We calculated the receiver operating characteristic(ROC)curves and area under the curve(AUC)for each biomarker.Results Statistically significant differences between the infection(n=39)and aseptic(n=58)groups were not shown,including 61 hips and 36 knees.The synovial CRP levels in the infection group were significantly higher than in the aseptic group(median: 9.93mg/l vs 3.58mg/l;P<.001).The optimal cut-off value for detecting chronic PJI of Synovial fluid(SF)CRP was of 7.26mg/l with a sensitivity of 84.62%,a specificity of 93.10%.The combined model I(Serum CRP>10.2mg/l OR SF CRP>7.26mg/l)had a negative predictive value(NPV)of 96.67%,and a sensitivity of 97.44%.The combined model II(Serum CRP>10.2mg/l AND Synovial CRP>7.26mg/l)led to a specificity of 1,and a positive predictive value(PPV)of 1.Conclusions The present study demonstrated that the combination of serum and synovial CRP can be used as an adjunct to the diagnosis of chronic PJI.Synovial CRP is a valuable test that can well exclude chronic PJI through a combination of serum and synovial CRP(Serum CRP ≤ 10.2 mg/l ANDSynovial CRP ≤ 7.26 mg/l).And we recommend that the synovial CRP test be considered for all patients suspected of PJI.PART II DIAGNOSTIC VALUE OF SYNOVIAL BIOMAKERS IN CHRONIC PERIPROSTHETIC JOINT INFECTION WITH ACTIVE RHEUMATOID ARTHRITISBackground Inflammatory responses in patients with active rheumatoid arthritis(RA)may lead to the current serum and synovial biomarkers that misidentify chronic periprosthetic joint infection(PJI).We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.Methods This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021,and30 patients with active RA cumulative knee from August 2020 to March2021.The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected.Serum D-dimer,erythrocyte sedimentation rate,C-reactive protein,and interleukin-6(IL-6),as well as synovial IL-6,percentage of polymorphonuclear neutrophils,and CD64 index level were measured preoperatively.Results An increase in biomarker concentrations were observed in group C (active RA).Synovial fluid CD64 index exhibited good discriminatory power between group B(chronic PJI)and group C with an area under curve of 0.930.For diagnosis of chronic PJI with active RA,the optimal threshold of synovial CD64 index was 0.87,with a sensitivity of 82.86%and a specificity of 93.33%.Conclusion Synovial fluid biomarkers(IL-6,CD64,PMN%)can be used to distinguish between PJI and active RA,and satisfactory results can be achieved by adjusting their thresholds.