Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Significance of serum protein electrophoresis in the diagnosis of Tsukayama type IV periprosthetic joint infection.

Objectives: To investigate the efficacy of serum protein electrophoresis (SPE) in the diagnosis of periprosthetic joint infection (PJI) after hip and knee arthroplasty. Methods: The medical records of patients undergoing hip and knee arthroplasty at a class A tertiary hospital between August 2013 and January 2021 were retrospectively investigated. A total of 179 patients were included and divided into two groups: 66 patients in the PJI group and 113 patients in the aseptic loosening (AL) group. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, Fibrinogen, Serum albumin and the proportion of serum protein in SPE were compared between the two groups. The diagnostic sensitivity and specificity were determined using the receiver operating characteristic (ROC) curve, and the diagnostic value was compared using the area under the ROC curve (AUC). Results: There was no significant difference in age, sex and body mass index (BMI) between PJI group and AL group (P>0.05), but there was significant difference in the ratio of hip to knee (X2 = 22.043, P<0.001). The CRP, ESR, D-dimer, Fibrinogen and the proportion of α1 globulin band in PJI group was 22.99(10.55,40.58) mg/L, 37.00(23.00,61.70) mm/h, 790.00(500.00,1500.00) ng/ml, 4.84(3.81,5.55) g/L and 5.80(5.00,7.73) % which was higher than that in AL group [1.89(0.50,4.12) mg/L, U=7.984, P<0.001; 10.10(7.00,16.90) mm/h, U=8.095, P<0.001; 570.00(372.50,780.00) ng/ml, U=3.448, P<0.001; 2.84(2.45,3.43) g/L, U=8.053, P<0.001 and 4.20(3.90,4.80) %, U=8.154, P<0.001]. The Serum albumin and the proportion of Albumin band in PJI group was 36.10(33.10,39.00) g/L and 49.00(44.95,52.20) % which was lower than that in AL group [38.10(34.00,41.10) g/L, U=-2.383, P=0.017 and 54.40(51.55,56.70) %, U=-6.162, P<0.001]. The proportion of In PJI group, the AUC of proportion of α1 globulin was 0.8654, which was equivalent to CRP (0.8698), ESR (0.8680) and outperformed that of fibrinogen (0.8025). Conclusions: Elevated proportion of α1 globulin in SPE presented with good diagnostic value for Tsukayama type IV PJI, and its accuracy was comparable to those of ESR and CRP. And α1 globulin can assist with CRP and ESR to determining the timing of second-stage revision.

Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC-MS/MS.

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 µg/ml for serum and 0.5-100 µg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Plasma D-Dimer Is Noninferior to Serum C-Reactive Protein in the Diagnosis of Periprosthetic Joint Infection.

BACKGROUND: No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Serological markers are often used as screening tools in the workup of patients with suspected PJI. This study aimed to determine the diagnostic utility of plasma D-dimer for PJI in a variety of clinical scenarios. METHODS: This prospective study enrolled 502 patients undergoing revision hip or knee arthroplasty. PJI was defined per a modified version of the 2018 International Consensus Meeting (ICM) criteria. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. Receiver operating characteristic curves were used to assess the utility of each biomarker in the diagnosis of PJI. Pairwise comparison with Bonferroni correction was performed to determine whether the differences in areas under the curve (AUCs) between the markers were significant. RESULTS: Of the 412 patients included, 317 (76.9%) did not have an infection (aseptic group) and 95 (23.1%) had an infection (PJI group). All 4 serological markers, D-dimer (AUC, 0.860; sensitivity, 81.3%; specificity, 81.7%), CRP (AUC, 0.862; sensitivity, 90.4%; specificity, 70.0%), ESR (AUC, 0.833; sensitivity, 73.9%; specificity, 85.2%), and fibrinogen (AUC, 0.798; sensitivity, 74.7%; specificity, 75.4%), demonstrated comparable accuracy for the diagnosis of PJI (all p > 0.05). When examining the performance of the different inflammatory markers in diagnosing infection caused by indolent organisms, D-dimer demonstrated the highest sensitivity at 93.8%. CONCLUSIONS: We found that plasma D-dimer was noninferior to serum CRP and ESR in the diagnosis of PJI and may be a useful adjunct when screening patients undergoing revision total joint arthroplasty. LEVEL OF EVIDENCE: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

The accuracy of D-dimer in the diagnosis of periprosthetic infections: a systematic review and meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication after total hip arthroplasty (THA) or total knee arthroplasty (TKA). It is scarce and contradicting evidence supporting the use of serum D-dimer to diagnose PJI in revision THA and TKA. This systematic review and meta-analysis aimed to investigate the accuracy of D-dimer in the diagnosis of periprosthetic infections. METHODS: The PubMed, Embase, Web of Science were systematically searched from the inception dates to August 15, 2020. We included all diagnostic studies of D-dimer in the diagnosis of periprosthetic infections. The literature's quality was evaluated by the QUADAS-2 tool, and Stata16 and Revman5.3 software carried out the meta-analysis. RESULTS: Of 115 citations identified by the search strategy, 10 studies (comprising 1756 participants) met the inclusion criteria. The literature quality assessment results show that most of the literature is low-risk bias literature. The combined sensitivity of D-dimer in diagnosing periprosthetic infections was 0.81 (95% confidence interval [CI] 0.71-0.88), combined specificity was 0.74 (95% CI 0.61-0.84), combined positive likelihood ratio was 3.1 (95% CI 2.0-5.0), combined negative likelihood ratio 0.26 (95% CI 0.16-0.41), combined diagnosis odds ratio 12 (95% CI 5-27), area under the Summary Receiver Operator Characteristic Curve (SROC) is 0.85 (95% CI 0.81-0.88). The data are statistically significant. CONCLUSION: D-dimer has a high diagnostic value in diagnosing PJI and has clinical significance in diagnosing periprosthetic infection. In addition, there are relatively few studies on the threshold of D-dimer, different sampling types, different laboratory detection methods, and different races, so more prospective trials with large samples, multi-centers, and scientific design should be carried out in the future.

Globulin and albumin to globulin ratio precisely diagnose periprosthetic joint infection and determine the timing of second-stage reimplantation.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications 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: A total of 206 patients who 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 ratio (PMR) and globulin-related markers such as globulin (GLB), 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.

Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. METHODS: We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. RESULTS: A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87-0.98), 0.93(95% CI 0.87-0.96), 13.65(95% CI 6.89-27.08), and 0.06(95% CI 0.02-0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52-941.11) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION: Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection.

BACKGROUND: The relationship of C-reactive protein (CRP)/interleukin-6 (IL-6) concentrations between serum and synovial fluid and whether synovial CRP/IL-6 testing in addition to serum CRP/IL-6 testing would result in a benefit in the diagnosis of periprosthetic joint infection (PJI) deserves to be investigated. METHODS: From June 2016 to July 2019, 139 patients were included in the study. Synovial CRP and IL-6 were tested by ELISA. The serum CRP and IL-6 were obtained from medical records. The definition of PJI was based on the modified Musculoskeletal Infection Society (MSIS) criteria. The relationship of serum and synovial CRP and IL-6 and the value of each index in the diagnosis of PJI were evaluated. RESULTS: The receiver operating characteristic (ROC) curves showed that synovial IL-6 had the highest area under the curve (AUC) at 0.935, which was followed by synovial CRP, serum IL-6 and serum CRP 0.861, 0.847 and 0.821, respectively. When combining serum CRP and synovial CRP to diagnose PJI, the AUC was 0.849, which was slightly higher than the result obtained when using serum CRP alone. In contrast, when combining serum IL-6 and synovial IL-6 to diagnose PJI, the AUC increased to 0.940, which was significantly higher than that obtained using serum IL-6 alone. CONCLUSION: The synovial IL-6 has the highest diagnostic accuracy for PJI. However, inferring the level of CRP/IL-6 in the synovial fluid from the serum level of CRP/IL-6 was not feasible. Synovial CRP testing did not offer an advantage when combined with an existing serum CRP result to diagnose PJI, while additional synovial IL-6 was worthy of testing even if there was an existing serum IL-6 result.

Combination of CRP with NLR is a sensitive tool for screening fixation-related infection in patients undergoing conversion total hip arthroplasty after failed internal fixation for femoral neck fracture.

AIMS: Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture. METHODS: We retrospectively included 340 patients who underwent conversion THA after internal fixation for femoral neck fracture from January 2008 to September 2020. Those patients constituted two groups: noninfected patients and patients diagnosed with FRI according to the 2013 International Consensus Meeting Criteria. Receiver operating characteristic (ROC) curves were used to determine maximum sensitivity and specificity of these two preoperative ratios. The diagnostic performance of the two ratios combined with preoperative CRP or ESR was also evaluated. RESULTS: The numbers of patients with and without FRI were 19 (5.6%) and 321 (94.4%), respectively. Areas under the ROC curve for diagnosing FRI were 0.763 for MLR, 0.686 for NLR, 0.905 for CRP, and 0.769 for ESR. Based on the Youden index, the optimal predictive cutoffs were 0.25 for MLR and 2.38 for NLR. Sensitivity and specificity were 78.9% and 71.0% for MLR, and 78.9% and 56.4% for NLR, respectively. The combination of CRP with MLR showed a sensitivity of 84.2% and specificity of 94.6%, while the corresponding values for the combination of CRP with NLR were 89.5% and 91.5%, respectively. CONCLUSION: The presence of preoperative FRI among patients undergoing conversion THA after internal fixation for femoral neck fracture should be determined. The combination of preoperative CRP with NLR is sensitive tool for screening FRI in those patients. Cite this article: Bone Joint J 2021;103-B(9):1534-1540.

Comparison of Demographic Profile, Laboratory, Epidemiology and Clinical Outcomes in Patients with Native Valve and Prosthetic Valve Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a heterogenous infection that affects the endothelial surface of the intracardiac structures and other implanted intracardiac devices. We aimed to compare demographical characteristics, causative microorganisms, treatment, and prognosis of prosthetic and native valve endocarditis diagnosed in two separate hospitals. MATERIAL AND METHODS: Between 2010 and 2020, patients admitted with the diagnosis of IE were retrospectively included in our multicenter study. Patients' demographic and epidemiological data, clinical characteristics, infected intracardiac structure and sort of valve, culprit microorganisms, laboratory findings, treatment manifestations and in-hospital outcomes with a period of 6 months were obtained from an electronic medical record system. RESULTS: A total of 173 consecutive patients had diagnosed IE, 60.1% (104 patients) of them native valve endocarditis (NVE) and 39.8 % (69 patients) of them prosthetic valve endocarditis (PVE).  Baseline demographic properties were not different except hypertension and atrial fibrillation. Patients with prior hypertension were 25% (26 patients) in NVE; 39.1% (27 patients) in PVE and the difference was statistically significant. Septic shock was significantly higher in the PVE group than the NVE group (7.4% versus 1%; P = .036), and also recurrent endocarditis occurred more frequently in the PVE group than the NVE group (8.8% versus 1%; P = .016). CONCLUSION: In our study, although we detected higher mean age, HT, RDW and atrial fibrillation rates compared with NVE, we did not detect a significant difference in mortality and morbidity.

The change of coagulation profile in two-staged arthroplasty for periprosthetic joint infection patients: a retrospective cohort study.

AIMS: Periprosthetic joint infection (PJI) is a serious complication of total joint arthroplasty. We performed a retrospective cohort study to evaluate (1) the change of coagulation profile in two-staged arthroplasty patients and (2) the relationship between coagulation profile and the outcomes of reimplantation. METHOD: Between January 2011 and December 2018, a total of 202 PJI patients who were operated on with two-staged arthroplasty were included in this study initially. This study continued for 2 years and the corresponding medical records were scrutinized to establish the diagnosis of PJI based on the 2014 MSIS criteria. The coagulation profile was recorded at two designed points, (1) preresection and (2) preimplantation. The difference of coagulation profile between preresection and preimplantation was evaluated. Receiver operating characteristic curves (ROC) were used to evaluate the diagnostic efficiency of the coagulation profile and change of coagulation profile for predicting persistent infection before reimplantation. RESULTS: The levels of APTT, INR, platelet count, PT, TT, and plasma fibrinogen before spacer implantation were significantly higher than before reimplantation. No significant difference was detected in the levels of D-dimer, ACT, and AT3 between the two groups. The AUC of the combined coagulation profile and the change of combined coagulation profile for predicting persistent infection before reimplantation was 0.667 (95% CI 0.511, 0.823) and 0.667 (95% CI 0.526, 0.808), respectively. CONCLUSION: The coagulation profile before preresection is different from before preimplantation in two-staged arthroplasty and the coagulation markers may play a role in predicting infection eradication before reimplantation when two-stage arthroplasty is performed. LEVEL OF EVIDENCE: Level III, diagnostic study.

Plasma D-dimer Does Not Anticipate the Fate of Reimplantation in Two-stage Exchange Arthroplasty for Periprosthetic Joint Infection: A Preliminary Investigation.

BACKGROUND: Inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels have always been a part of the diagnostic criteria for periprosthetic joint infection (PJI), but they perform poorly anticipating the outcome of reimplantation. D-dimer has been reported in a small series as a potential marker to measure infection control after single-stage revisions to treat PJI. Nonetheless, its use to confirm infection control and decide the proper timing of reimplantation remains uncertain. QUESTIONS/PURPOSES: (1) What is the best diagnostic threshold and accuracy values for plasma D-dimer levels compared with other inflammatory markers (ESR and CRP) or what varying combinations of these tests are associated with persistent infection after reimplantation? (2) Do D-dimer values above this threshold, ESR, CRP, and varying test combinations at the time of reimplantation indicate an increased risk of subsequent persistent infection after reimplantation? METHODS: We retrospectively studied the electronic medical records of all 53 patients who had two-stage revisions for PJI and who underwent plasma D-dimer testing before reimplantation at one of two academic institutions from November 22, 2017 to December 5, 2020. During that period, all patients undergoing two-stage revisions also had a D-dimer test drawn. The minimum follow-up duration was 1 year. We are reporting at this early interval (rather than the more typical 2-year time point) because of the poorer-than-expected performance of this diagnostic test. Of these 53 patients, 17% (9) were lost to follow-up before 1 year and could not be analyzed; the remaining 44 patients (17 hips and 27 knees) were studied here. The mean follow-up was 503 ± 135 days. Absence or persistence of infection after reimplantation were defined according to the Delphi criteria. The conditions included in these criteria were: (1) control of infection, as characterized by a healed wound without fistula, drainage, or pain; (2) no subsequent surgical intervention owing to infection after reimplantation; and (3) no occurrence of PJI-related mortality. The absence of any of the aforementioned conditions until the final follow-up examination was deemed a persistent infection after reimplantation. Baseline patient characteristics were not different between patients with persistent infection (n = 10) and those with absence of it after reimplantation (n = 34) as per the Delphi criteria. Baseline patient characteristics evaluated were age, gender, self-reported race (white/Black/other) or ethnicity (nonHispanic/Hispanic), BMI, American Society of Anesthesiologists (ASA) status, smoking status(smoker/nonsmoker), and joint type (hip/knee). The optimal D-dimer threshold to differentiate between persistence of infection or not after reimplantation was calculated using the Youden index. A receiver operating characteristic curve analysis was performed to test the accuracy of D-dimer, ESR, CRP, and their combinations to establish associations, if any, with persistent infection after reimplantation. A Kaplan-Meier survival analysis (free of infection after reimplantation) with a log-rank test was performed to investigate if D-dimer, ESR, and CRP were associated with absence of infection after reimplantation. Survival or being free of infection after reimplantation was determined as per Delphi criteria. Alpha was set at p < 0.05. RESULTS: In the receiver operating characteristic curve analysis, with an area under the curve of 0.62, D-dimer showed low accuracy and did not anticipate persistent infection after reimplantation. The optimal D-dimer threshold differentiating between persistence of infection or not after reimplantation was 3070 ng/mL. When using this threshold, D-dimer demonstrated a sensitivity of 90% (95% CI 55.5% to 99.7%) and negative predictive value of 94% (95% CI 70.7% to 99.1%), but low specificity (47% [95% CI 29.8% to 64.9%]) and positive predictive value (33% [95% CI 25.5% to 42.2%]). Although D-dimer showed the highest sensitivity, the combination of D-dimer with ESR and CRP showed the highest specificity (91% [95% CI 75.6% to 98%]) defining the persistence of infection after reimplantation. Based on plasma D-dimer levels, with the numbers available, there was no difference in survival free from infection after reimplantation (Kaplan-Meier survivorship free from infection at minimum 1 year in patients with D-dimer below 3070 ng/mL versus survivorship free from infection with D-dimer above 3070 ng/mL: 749 days [95% CI 665 to 833 days] versus 615 days [95% CI 471 to 759 days]; p = 0.052). Likewise, there were no associations between high ESR and CRP levels and persistent infection after reimplantation, but the number of events was very small, and insufficient power is a concern with this analysis. CONCLUSION: In this preliminary series, with the numbers available, D-dimer alone had poor accuracy and was not associated with survival free from infection after reimplantation in patients who underwent two-stage exchange arthroplasty. D-dimer alone might be used to establish that PJI is unlikely, and the combination of D-dimer, ESR, and CRP should be considered to confirm PJI diagnosis in the setting of reimplantation.Level of Evidence Level IV, diagnostic study.

Plasma fibrinogen in the diagnosis of periprosthetic joint infection.

Periprosthetic joint infections (PJIs) have become the most catastrophic complication for patients after arthroplasty. Although previous studies have found that many biomarkers have good performance for diagnosing PJI, early diagnosis remains challenging and a gold standard is lacking. This study aimed to investigate the diagnostic accuracy of plasma fibrinogen (FIB) in detecting PJI compared to other traditional biomarks (CRP, WBC and ESR). A total of 156 patients (including 57 PJI and 99 non-PJI patients) who underwent revision arthroplasty were retrospectively reviewed from 01/2014 to 01/2020. The diagnostic criteria of PJI were mainly based on the definition from the evidence-based definition for periprosthetic joint infection in 2018. The optimal plasma FIB predictive cutoff was 4.20 g/L, the sensitivity of the plasma fibrinogen was 0.860, the specificity was 0.900, the positive predictive value (PPV) was 0.831, and the negative predictive value (NPV) was 0.908. The area under the curve (AUC) value of plasma fibrinogen was 0.916 (95% CI 0.869-0.964), and the CRP, ESR and WBC levels had AUCs of 0.901, 0.822 and 0.647, respectively. Plasma FIB demonstrated better diagnostic strength compared with that of other serum biomarkers before revision arthroplasty. It represents a new horizon for the diagnosis of PJI due to the diagnosis values and cost-effective features.

Serum and Synovial Biomarkers for the Diagnosis of Implant-Associated Infection After Orthopedic Surgery.

Implant-associated infection is one of the most devastating complications following orthopedic surgery. Early identification is crucial for treatment. Currently, however, a reliable diagnostic tool is lacking, partly due to disparate bacteria colonies (virulent vs non-virulent), difficulty in distinguishing infection from inflammatory disease, and highly diverse diagnostic thresholds and testing methods. Given the importance of biomarkers in the initial screening for the infection, an extensive effort has been made to develop serum and synovial biomarkers. In this review, the authors summarize the results from the most relevant studies to provide comprehensive information on biomarkers for the diagnosis of implant-associated infection. [Orthopedics. 2021;44(2):e158-e166.].

Left ventricular assist device driveline infections in three contemporary devices.

Driveline infections (DLI) are common adverse events in left ventricular assist devices (LVADs), leading to severe complications and readmissions. The study aims to characterize risk factors for DLI readmission 2 years postimplant. This single-center study included 183 LVAD patients (43 HeartMate II [HMII], 29 HeartMate 3 [HM3], 111 HVAD) following hospital discharge between 2013 and 2017. Demographics, clinical parameters, and outcomes were retrospectively analyzed and 12.6% of patients were readmitted for DLI, 14.8% experienced DLI but were treated in the outpatient setting, and 72.7% had no DLI. Mean C-reactive protein (CRP), leukocytes and fibrinogen were higher in patients with DLI readmission (P < .02) than in outpatient DLI and patients without DLI, as early as 60 days before readmission. Freedom from DLI readmission was comparable for HMII and HVAD (98% vs. 87%; HR, 4.52; 95% CI, 0.58-35.02; P = .15) but significantly lower for HM3 (72%; HR, 10.82; 95% CI, 1.26-92.68; P = .03). DLI (HR, 1.001; 95% CI, 0.999-1.002; P = .16) or device type had no effect on mortality. DLI readmission remains a serious problem following LVAD implantation, where CRP, leukocytes, and fibrinogen might serve as risk factors already 60 days before. HM3 patients had a higher risk for DLI readmissions compared to HVAD or HMII, possibly because of device-specific driveline differences.

Revision total elbow arthroplasty: Is it safe to perform a single-stage revision for presumed aseptic loosening based on clinical assessment, normal inflammatory markers, and a negative aspiration?

BACKGROUND: Revision total elbow arthroplasty (TEA) is a challenging procedure that is becoming increasingly common. In our unit, we regard it as essential to exclude infection as the underlying cause of TEA loosening. In all patients with arthroplasty loosening, we undertake a careful history and examination, perform radiographs, monitor inflammatory markers, and undertake a joint aspiration. If any investigation suggests infection as the etiology, then a 2-stage revision is undertaken. Open biopsies are not routinely performed. The aim was to ascertain from our outcomes whether it is safe to perform a single-stage revision for presumed aseptic loosening using these criteria. METHODS: A retrospective review of a consecutive series of revision TEAs was performed in our unit over a 10-year period (2008-2018). Single-stage revisions performed for presumed aseptic loosening were identified. Case notes, radiographs, bloods, aspiration results, and microbiology of tissue samples taken at revision were reviewed. RESULTS: A total of 123 revision elbow arthroplasty cases were performed in the study period. Sixty cases were revised for preoperatively proven infection, instability, or implant failure and were excluded from this study. In 63 cases, aseptic loosening was diagnosed based on history, clinical examination, blood markers, and aspiration. There were 21 dual-component and 42 single-component revisions. In the dual-component revision group, tissue samples taken at the time of revision were positive in only 1 case (5%). In the single-component revision group, positive culture samples were present in 3 cases (7%). χ2 analysis showed no significant difference between single- and dual-component revisions (P = .76). No cases with positive culture samples from either group have required subsequent revision surgery. CONCLUSION: Given the results of this study, we conclude that is safe to perform single-stage revision arthroplasty for implant loosening based on history, examination, normal inflammatory markers, and negative aspiration results without the need for open biopsy.

Elevated plasma D-dimer concentration has higher efficacy for the diagnosis of periprosthetic joint infection of the knee than of the hip-A single-center, retrospective study.

The aim of this study is to evaluate the value of D-dimers in the diagnosis of periprosthetic joint infection (PJI). The analysis was performed for revision total hip (rTHA) and revision total knee arthroplasty (rTKA) together and separately with two thresholds, one calculated by statistical methods and the second adopted from the ICM 2018 definition. The study group comprised 133 patients who underwent rTHA or rTKA: 68 patients diagnosed according to the ICM 2018 definition (PJI group) and 65 with aseptic implant loosening, instability, malposition, or implant failure with the exclusion of infection (aseptic revision total joint arthroplasty or arTJA group). Mean D-dimer concentrations were 0.36 ± 0.25 µg/ml in the arTJA group and 0.87 ± 0.78 µg/ml in the PJI group (p < .001). For rTHA and rTKA together, the sensitivity and specificity of the evaluation were 75% and 73.8% according to the calculated cut-off value (0.45 µg/ml), and 33.8% and 95.4% based on the ICM 2018 threshold (0.85 µg/ml). Separately, for rTHA, sensitivity and specificity were 62.5% and 62.1% for the calculated value (0.43 µg/ml) and 6.3% and 96.6% for the ICM 2018 threshold; for rTKA, sensitivity was 86.1% and specificity was 88.9% for the calculated threshold (0.48 µg/ml) and 58.3% and 94.4% for the ICM 2018 value. Our findings indicate that plasma D-dimers have potential as markers of knee PJI, but moderate to low value for hip PJI.

The diagnostic effect of α-defensin, D-dimer, and IL-6 in periprosthetic joint infection: A systematic review and diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of α-defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice. METHOD: Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration. RESULTS: A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing α-defensin, D-dimer, and IL-6. The sensitivity and specificity of α-defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than α-defensin. CONCLUSION: The detection of α-defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.

Elevated HbA1c is not a risk factor for wound complications following total joint arthroplasty: a prospective study.

BACKGROUND: Controversies exist regarding the association of elevated serum glycated haemoglobin (HbA1c) levels and postoperative surgical site infection (SSI) or prosthetic joint infection (PJI) in the setting of total hip and knee arthroplasty (THA and TKA). The purpose of the current study was to determine the prevalence of unknown and uncontrolled diabetes mellitus (DM) in a consecutive series and to investigate the association between postoperative wound complications or SSI/PJI and elevated HbA1c in patients undergoing TJA. METHODS: In this prospective single-centre study, HbA1c was determined for patients undergoing elective primary, aseptic or septic revision THA and TKA, between September 2017 and March 2018. Prevalence of DM, unknown and uncontrolled diabetes were reported. Occurrence of 90-day wound healing disorders (WHD) as well as SSI or PJI were observed. Considering the HbA1c threshold ⩾6.5%, a comparative analysis between patients with and without WHD and SSI or PJI for the whole study cohort, as well as for each arthroplasty group, was performed. Receiver operating characteristic (ROC) curves were developed to quantify the predictive power of HbA1c with regard to WHD and infection complications. A total of 1488 patients were included for final analysis. There were 1127 primary THA and TKA (75.7%), 272 aseptic revisions (18.3%) and 89 septic revisions (6.0%). The known diabetic patients constituted 9.9% of the whole study cohort. RESULTS: The majority had uncontrolled DM (67%). Prevalence of unknown DM was 11.1%. The results reveal the prevalence for the German population and might be different in other regions. A total of 57 patients (3.7%) experienced postoperative wound or infectious complications. PJI occurred in only 5 patients (0.03%). There was no significant difference between patients with HbA1c <6.5% and patients with HbA1c ⩾6.5% (p = 0.092). CONCLUSIONS: We demonstrated that prevalence of unknown and uncontrolled DM in patients undergoing TJA is increasing, however; routine preoperative determination of the HbA1c value to prevent possible postoperative wound or infectious complications remains debatable. Larger studies investigating the optimal HbA1c level, as well as other predictors are required.

Meta-analysis of serum and/or plasma D-dimer in the diagnosis of periprosthetic joint infection.

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. CONCLUSIONS: 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.