Periprosthetic Joint Infection Group Research Articles

Risk factors of periprosthetic joint infection after hemiarthroplasty for displaced femoral neck fracture in the elderly: Analysis of 1619 cases in the multicenter database

PurposeThis multicenter retrospective study focuses on understanding the incidence, causative bacteria, and risk factors for Periprosthetic Joint Infection (PJI) following hemiarthroplasty in elderly patients with displaced femoral neck fractures (FNF). MethodsFrom 2016 to 2020, 1,619 patients were diagnosed with displaced FNFs and treated surgically across 11 centers. After exclusions, 1,438 patients (399 men and 1,039 women) were included in the study, averaging 82.1 years in age and 20.2 kg/m² in BMI, observed over 25.7 months on average. Data on demographics, medical history, surgical details, and complications were described. ResultsPJI occurred in 20 of the 1438 patients (1.4%). The causative organism was methicillin-susceptible Staphylococcus aureus in 6 patients and methicillin-resistant S. aureus in 6 patients. In patients' backgrounds, the average age was slightly higher in the non-PJI group (82.1 years) compared to the PJI group (80.4 years). There was a higher percentage of males in the PJI group (45%) than in the non-PJI group (27.5%). Drug history showed that the prevalence of anticoagulant use in the PJI group was 25%. Peripheral vascular disease and diabetes mellitus were more prevalent in the PJI group. Most patients in both groups were independent in daily activities. The blood transfusion rate was significantly higher in the PJI group (50%) than in the non-PJI group (23.8%). Notably, the incidence of hematoma was higher in the PJI group (40%). ConclusionThis multicenter retrospective study demonstrates a low incidence (1.4%) of PJI in elderly patients undergoing hemiarthroplasty for FNF, primarily due to Staphylococcus aureus. Increased usage of antiplatelets and anticoagulants, as well as comorbidities related to atherosclerosis, like peripheral vascular disease and diabetes mellitus, were observed in patients with PJI. Additionally, these patients experienced higher rates of blood transfusion and postoperative hematomas, highlighting the need for careful management. It should be noted, however, that this finding is a conclusion limited by study design issues, including the retrospective design, small PJI sample size, and variability in treatment approaches.

Diagnosing periprosthetic hip joint infection with new-generation 0.55 T MRI

PurposeTo assess the accuracy of 0.55 T MRI in diagnosing periprosthetic joint infection (PJI) in patients with symptomatic total hip arthroplasty (THA). Material and methods0.55 T MRI of patients with THA PJI (Group A) and noninfected THA (Group B), including aseptic loosening (Group C, subgroup of B) performed between May 2021 and July 2023 were analysed retrospectively.Two musculoskeletal fellowship-trained radiologists independently identified MRI bone and soft tissue changes including: marrow oedema, periosteal reaction, osteolysis, joint effusion, capsule oedema and thickening, fluid collections, muscle oedema, bursitis, inguinal adenopathy, and muscle tears. The diagnostic performance of MRI discriminators of PJI was evaluated using Fisher’s exact test (p < 0.05) and interrater reliability was determined. 61 MRI scans from 60 THA patients (34 female, median age 68, range 41–93 years) in Group A (n = 9; female 4; median age 69, range 56–82 years), B (n = 51; 30; 67.5, 41–93 years), and C (10; 6; 67; 41–82 years) were included. ResultsCapsule oedema (sensitivity 89 %, specificity 92 %,), intramuscular oedema (89 %, 82 %) and joint effusion (89 %, 73 %) were the best performing discriminators for PJI diagnosis (p ≤ 0.001), when viewed individually and had combined 70 % sensitivity and 100 % specificity for PJI diagnosis in parallel testing. For the differentiation between PJI and aseptic loosening, intramuscular oedema (89 %, 80 %) and capsule oedema (89 %, 80 %) were significant discriminators (p ≤ 0.001) with combined 64 % sensitivity and 96 % specificity for PJI. ConclusionsNew generation 0.55 T MRI may aid in the detection of PJI in symptomatic patients. Oedema of the joint capsule, adjacent muscles as well as joint effusion were indicative of the presence of PJI.

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

To investigate the efficacy of serum protein electrophoresis (SPE) in the diagnosis of periprosthetic joint infection (PJI) after hip and knee arthroplasty. 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). 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). 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.

Diagnostic and Predictive Efficacy of Synovial Fluid Versus Serum C-Reactive Protein Levels for Periprosthetic Joint Infection and Reimplantation Success

IntroductionA two-stage exchange revision for periprosthetic joint infection (PJI) is associated with major risks for reinfection. Although serum markers are frequently used for diagnosis, their effectiveness remains debatable. Synovial fluid markers may offer a more accurate diagnosis of PJI; however, the importance of these biomarkers, notably synovial fluid C-reactive protein (syCRP), remains controversial, particularly in the context of reimplantation. The present study aimed to clarify these diagnostic uncertainties by evaluating the diagnostic efficacy of syCRP versus serum CRP (seCRP) levels in the context of PJI and recurring or persisting infections before reimplantation. MethodsA total of 186 patients were enrolled and divided into two groups: aseptic revision (n = 112) and PJI revision (n = 74). Of the PJI group, 65 were categorized as success and 9 as failure, based on the presence of recurrent or persistent infection before reimplantation. The syCRP and seCRP levels and their changes were assessed preoperatively and in the first- and second-stage revisions. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were analyzed. ResultsBoth seCRP and syCRP levels were significantly elevated in the PJI group compared with the aseptic group (P < 0.001). The ROC curve analysis highlighted the enhanced diagnostic accuracy of syCRP for PJI, with an AUC of 0.93 versus 0.80 for seCRP. Furthermore, syCRP proved to be more reliable in predicting reimplantation success, exhibiting an AUC of 0.86 versus 0.63 for seCRP. In evaluating trends in CRP levels to determine reimplantation timing, changes in syCRP levels demonstrated superior diagnostic utility, exhibiting an AUC of 0.79 versus 0.63 for changes in seCRP levels. ConclusionIn assessing PJI and infections before reimplantation, syCRP may offer enhanced accuracy compared with seCRP. Nevertheless, variations in both syCRP and seCRP levels did not consistently predict the outcome of reimplantation.

Two-Stage Exchange Arthroplasty for Periprosthetic Reverse Shoulder Arthroplasty Infection Provides Comparable Functional Outcomes to Primary Reverse Shoulder Arthroplasty

This study aimed to compare functional outcomes after two-stage revision reverse shoulder arthroplasty (RSA) for periprosthetic joint infection (PJI) with the results of primary RSA. Patients affected by PJI and treated by means of two-stage revision RSA were 1:1 matched with a group of patients who were treated electively with RSA without developing any complications. Out of 1477 RSAs performed between 2009 and 2021, 16 patients developed a PJI. Each matched cohort comprised 16 patients (3 females, 13 males). The mean age was 69.13 ± 5.43 years old in the PJI group and 70.28 ± 5.04 (p = 0.543) in the matched cohort. The mean follow-up was 41.23 ± 26.9 months in the PJI group and 28.5 ± 20.2 (p = 0.142) in the matched group. Only one patient showed recurrent PJI five years after revision RSA. Comparison between the PJI patients and matched patients did not show any significant differences at the latest follow-up, nor for subjective shoulder value (SSV) (p = 0.101) or Constant score (p = 0.134). Two-stage exchange RSA for PJI allows for appropriate control of the disease and good functional outcomes. Comparison with an age- and sex-matched cohort of uninfected patients showed no significant differences, thus confirming the idea that revision surgeries may lead to satisfactory functional outcomes, as expected after primary surgery.

Limited value of platelet-related markers in diagnosing periprosthetic joint infection

ObjectiveTo evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI).MethodsThe medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC).ResultsThe PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively.ConclusionsThe results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.

Comparison of outcomes between fungal and non-fungal periprosthetic joint infections in total knee arthroplasty.

Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs.

Serum procalcitonin has no significance in the diagnosis of periprosthesis joint infection before total hip and knee replacement.

Currently, there is no "gold standard" for early diagnosing PJI. The diagnosis of periprosthetic joint infection (PJI) is a challenging problem in the clinic. As we know, many serum markers have been used in the early diagnosis of PJI. The aim of this study was to validate the value of PCT in the diagnosis of PJI. A retrospective review of 77 patients with revision arthroplasties from January 2013 to July 2020 was conducted. PJI was defined using the modified Musculoskeletal Infection Society (MSIS) criteria combined with follow-up results. Besides medical history, clinical and laboratory data was gathered. Preoperative blood was taken for serum PCT and other biomarkers measurement. Receiver operating characteristic (ROC) curves were generated to evaluate the biomarkers' diagnostic performance and optimal cut-off value. Forty-one patients were identified as the PJI group (27 hips and 14 knees), while thirty-six patients were identified as the aseptic loosening (AL) group (33 hips and 3 knees). The AUCs for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Platelets (PLT), Fibrinogen (FIB), and Procalcitonin (PCT) were 0.845 (95% CI 0.755-0.936, p < 0.001), 0.817 (95% CI 0.718-0.916, p < 0.001), 0.728 (95% CI 0.613-0.843, p < 0.001), 0.810 (95% CI 0.710-0.910, p < 0.001) and 0.504 (95% CI 0.373-0.635, p = 0.950), respectively. Higher Area under the Curve (AUC) values were obtained for the combinations of PCT and CRP (AUC = 0.870) (95% CI, 0.774-0.936), PCT and ESR (AUC = 0.817) (95% CI, 0.712-0.896), PCT and PLT (AUC = 0.731) (95% CI, 0.617-0.825), PCT and FIB (AUC = 0.815) (95% CI, 0.710-0.894). The serum PCT indicated a sensitivity of 19.51% and a specificity of 83.33% for diagnosing PJI. When the optimal cut-off value for PCT was set as 0.05 ng/ml, its positive and negative likelihood ratios were 57.1% and 47.6%, respectively. In conclusion, serum PCT appeared to be no reliable biomarker in differentiating PJI from aseptic loosening before revision arthroplasties. However, PCT combined with other biomarkers further increases the diagnostic accuracy.

Can Platelets/Mean Platelet Volume Accurately Diagnose Periprosthetic Joint Infection? Revealing Their Actual Diagnostic Efficacy.

Currently, there is no single test indicator for diagnosing periprosthetic joint infection (PJI) with an acceptable level of sensitivity. Therefore, ratio indicators have been introduced to improve the accuracy of diagnostic algorithms. Platelet count /mean platelet volume (PMR) is reported to be a potential PJI diagnostic biomarker, but its clinical value for diagnosing PJI is still uncertain. This study aims to provide additional evidence to support the effectiveness of PMR in accurately diagnosing PJI. This study recruited 116 patients with PJI and 137 patients with aseptic loosening, divided them into PJI group and AL group. Collect subjects' preoperative laboratory indicators such as ESR, CRP, PLT, MPV, etc. The area under the curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve to determine the diagnostic efficacy of PMR. ESR, CRP, PLT, and PLT/MPV were significantly increased in the PJI group, while MPV levels were decreased (both P< 0.001). The AUC of the PMR was 0.752, and the optimal cut-off value for diagnosing chronic PJI was determined to be 27.8 based on the Youden index. The sensitivity and specificity for diagnosing PJI were 79.3% and 47.9%, respectively, with a positive predictive value of 68.27%, a negative predictive value of 69.80%, and a diagnostic odds ratio of 4.97. The AUC (0.752) of the ratio biomarker was lower than that of ESR (0.825) and CRP (0.900). After predictive model calculation, the combination of PMR, CRP, and ESR had an AUC value of 0.910, with a sensitivity of 84.5% and a specificity of 84.7%, showing good discriminative ability. Compared with traditional biomarkers ESR and CRP, the value of the PMR for diagnosing PJI is not significant, but it can be used as an auxiliary indicator for PJI diagnosis in combination with other indicators (P<0.001).

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections.

The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. Level II, diagnostic study.

Increased mortality after total hip prosthetic joint infection is mainly caused by the comorbidities rather than the infection itself.

Periprosthetic joint infection (PJI) is a feared complication of arthroplasty surgery. There is controversy as to whether PJI also correlates with increased mortality. Our aim was to investigate in a nationwide cohort if PJI is an independent risk factor for dying. We performed a retrospective cohort study based on data from the Swedish Hip Arthroplasty Register (SHAR). All patients with a revision THA performed between 1998 and 2017 were included. The outcome is mortality; exposure is PJI according to SHAR. The control group was study participants who underwent aseptic revision. Confounders were age, sex, diagnosis, and comorbidity according to the Elixhauser index. The outcome was analyzed with a Cox proportional hazards model. 4,943 PJI revisions and 12,529 non-infected revisions were included in the analysis. The median follow-up time was 4.1 years. In the PJI group, 1,972 patients died and in the control group, 4,512. The incidence rate ratio was 1.19 (95% confidence interval [CI] 1.13-1.25), the crude hazard ratio (HR) 1.19 (CI 1.13-1.25), and the adjusted HR 1.05 (CI 0.99-1.12) for the exposed versus the unexposed group. The strongest confounder was comorbidity. The increased mortality risk after revision due to PJI is mainly caused by the comorbidity of the patient, rather than by the infection itself.

Diagnostic Value of Synovial Fluid Biomarkers for Periprosthetic Joint Infection: A Prospective, Double-blind Trial.

BACKGROUND This prospective, double-blind study investigated the clinical diagnostic value of synovial fluid S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) in periprosthetic joint infection (PJI) and investigated the subtypes of a-defensin that have diagnostic value for PJI. MATERIAL AND METHODS Synovial fluid samples were collected from 82 patients with suspected PJI after total joint arthroplasty. Patients were divided into a PJI group (n=39) and non-PJI group (n=43). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to determine S100A8, S100A9, alpha-defensin, and internal reference standards in synovial fluid. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of S100A8, S100A9, and alpha-defensin for PJI, as well as the diagnostic value in combination with common biomarkers of infection. RESULTS S100A8, 3 variants of S100A9, and 3 alpha-defensins (human neutrophil peptides [HNP]1-3) in synovial fluid were significantly higher in the PJI group than in the non-PJI group (P<0.001). The sensitivity, specificity, and the area under ROC curve (AUC) for diagnosing PJI were 97.4%, 86.0%, and 0.964 (95% CI: 0.929-0.998), respectively, for synovial fluid S100A8; 87.2%, 88.4% and 0.902 (95% CI: 0.823-0.980), respectively, for S100A9; and 89.7%, 83.7%, and 0.933 (95% CI: 0.884-0.982), respectively, for HNP1-3. The diagnostic efficiency was improved when combined with synovial fluid white blood cell count and percentage of polymorphonuclear neutrophils. CONCLUSIONS Synovial fluid S100A8, S100A9, and HNP1-3 have satisfactory diagnostic efficiency for the diagnosis of PJI, which will help clinicians to accurately diagnose PJI.

An Exciting Performance of Established and Novel Biomarkers in Diagnosing Periprosthetic Joint Infections: A Single-center Retrospective Cohort Study.

Significant progress has been made in recent years in the diagnosis of periprosthetic joint infections (PJI). However, the lack of a gold standard test for the diagnosis of PJI remains a challenge.The aim of this study was to evaluate the diagnostic values of the albumin/fibrinogen ratio (AFR), the C-reactive protein/albumin ratio (CAR), and the levels of fibrinogen (FIB) and albumin (ALB) in the diagnosis of PJI. The medical records of 158 patients who had undergone hip or knee revisions from January 2018 to May 2022 were retrospectively analyzed. Of these patients, 79 were diagnosed with PJI, while 79 were diagnosed with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of C-reactive protein (CRP), ALB, and FIB; the erythrocyte sedimentation rate (ESR); and the AFR and CAR in the two groups were recorded and analyzed. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator; the diagnostic value for each indicator was calculated as the area under the curve (AUC). The ESR, CRP, FIB, and CAR values in the PJI group were significantly higher than those in the AL group, and the ALB and AFR values were significantly lower than those in the AL group (p < 0.001). The AUC values of AFR and fibrinogen were 0.851 and 0.848, respectively, which were slightly higher than those of CRP (0.826) and ESR (0.846). The AUC of CAR was 0.831 which was slightly lower than that of CRP (0.846). ALB had an AUC of 0.727. The optimal threshold, sensitivity, and specificity, respectively, were 10.05, 84.81%, and 82.28% for AFR; 4.03 μg/mL, 77.22%, and 86.08% for FIB; 0.23, 72.15%, and 82.28% for CAR; and 37.30 g/L, 65.82%, and 73.42% for ALB. AFR, CAR, and FIB are good new auxiliary diagnostic indicators of PJI, while ALB is of fair value for the diagnosis of PJI.

Joint fluid interleukin-6 combined with the neutral polymorphonuclear leukocyte ratio (PMN%) as a diagnostic index for chronic periprosthesis infection after arthroplasty

BackgroundThe diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty.Materials and methodsSixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve).ResultsThe diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%.ConclusionsJoint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty.Level of evidencePatients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included.Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.

Immune modulation as a potential treatment strategy to salvage the bone metabolism after periprosthetic joint infection

Background: In arthroplasty, periprosthetic joint infection (PJI) is one of the most disastrous postoperative complications with high long-term failure rates despite successful revision surgery. PJI causes a pro-inflammatory environment in the surrounding bone stock that subsequently results in compromised bone metabolism. This increases the risk for unstructured bone-resorption potentially leading to aseptic loosening. We hypothesize that PD-1-positive monocytes and monocyte-derived osteoclasts play a significant role in this pathology. In this study, we assessed the presence of PD-1-positive monocytes and their osteoclastogenic differentiation potential, as well as resulting osteoclast activity in PJI. We also investigated anti-PD-1-antibody as a potential salvage therapy. Material and Methods: Peripheral blood specimens were collected from 15 patients undergoing knee arthroplasty (ctrl) or prosthesis explantation due to PJI. Peripheral blood mononuclear cells were isolated and stained for CD33, CD11b, and CD14. Osteoclastic differentiation was induced ± PD-L1 and ± anti-PD-1-antibody. Osteoclast number and function were determined by pit assay, TRAP staining and qPCR. Results: Monocyte cell count (0.86±0.35 v 0.21±0.03/nl, p=.02) and PD-1 expression on monocytes (92.50±6.83 v 35.34±15.43%, p&lt;.01) waselevated in patients with PJI. After differentiation, in PJI, total osteoclast surface area was larger (47.40±3.19% v 26.75±3.49%, p&lt;.01) and increased significantly further (+64.04±1.72%, p&lt;.01) after PD-L1 stimulation. Addition of PD-1 inhibitor reduced osteoclast surface area in PJI (36.51±3.95 v 64.04±1.72%, p&lt;.01). Expression of osteoclast differentiation marker Nfatc1 and Ctsk were higher in the PJI group ( Nfatc1: 1.09±0.20 v 0.45±0.06, p&lt;.01; Ctsk: 2.27±1.00 v 0.73±0.23, p=.02), but did not differ in Mmp9 and Acp5 expression. In PJI, the expression of all four genes were upregulated after PD-L1 stimulation, while PD-1 inhibitor treatment reversed this effect. PD-L1 stimulation led to increased osteoclast bone resorption compared to without stimulation (7.65±3.15 v 2.49±0.67%, p=.05), while addition of PD-1 inhibitor showed no influence in the ctrl group. In PJI, osteoclast surface resorption was increased after PD-L1 stimulation (20.69±6.54 v 8.06±1.54, p=.01). Conversely, osteoclast function was reduced after treatment with PD-1 inhibitor (4.23±0.55 v 8.06±1.54, p=.03). Conclusion: Elevated numbers of monocytic osteoclast-progenitor cells and increased osteoclastic differentiation and function may contribute to decreased bone volume and impact prosthesis osseointegration in patients with PJI. Our results show PD-L1 can stimulate osteoclast generation and function and that this can be reversed by PD-1 inhibitor. This effect is particularly prominent in PJI. Targeting PD-1 can be a potential therapy to inhibit monocyte-mediated osteoclastogenesis while retaining anti-microbial activity of macrophages to limit the impact of PJI on the bone stock. Dr. Arne Kienzle is participant in the BIH-Charité Junior Clinician Scientist Program funded by the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health. The authors wish to acknowledge the support of the non-profit German Arthritis Society (Deutsche Arthrose-Hilfe e.V.) and its president Helmut H. Huberti, MD by grant P482. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Detection of inguinal lymph nodes is promising for the diagnosis of periprosthetic joint infection.

Localized inguinal lymphadenopathy often represents lower extremity pathogen infection, while normalized lymphadenopathy is associated with infection regression. We hypothesized that inguinal lymph nodes (LNs) were enlarged in Periprosthetic Joint Infection (PJI) patients and that normalized inguinal LNs would be a promising way to determine the timing of reimplantation. We prospectively enrolled 176 patients undergoing primary and revision hip or knee arthroplasty. All patients underwent ultrasound examination of inguinal LNs preoperatively. The diagnostic value of inguinal LNs in PJI was evaluated by the receiver operating characteristic (ROC) curve. The median level of inguinal LNs was 26mm in the revision for PJI group compared with 12mm in the aseptic revision group (p< 0.0001). The size of the inguinal LNs well distinguishes PJI from aseptic failure (AUC= 0.978) compare with ESR (AUC= 0.707) and CRP (AUC= 0.760). A size of 19mm was determined as the optimal threshold value of the inguinal LNs for the diagnosis of PJI, with a sensitivity of 92% and specificity of 96%. Ultrasonic analysis of inguinal LNs is a valuable piece of evidence for the diagnosis of PJI and evaluation of persistent infection.

Alteration of m6A-Tagged RNA Profiles in Bone Originated from Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N6-methyladenine (m6A) modification in PJI. Synovium, synovial fluid, sonication fluid and bone samples were collected intraoperatively from Staphylococcus aureus PJI and aseptic failure (AF) patients. The overall m6A level was detected by the m6A RNA methylation quantification kit, and the expression of m6A-related genes was quantified by real-time PCR and Western blot. Finally, an epitranscriptomic microarray and bioinformatics analysis were performed. We showed that there was a significant difference in overall m6A level between the PJI group and the AF group (PJI group had a higher overall m6A level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential m6A-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential m6A-modified mRNAs were significantly enriched in the NOD-like receptor signaling pathway, Th17 cell differentiation and the IL-17 signaling pathway, which indicates that the m6A modification might be involved in the processes of infection and immune response, bone metabolism and programmed cell death in PJI. In summary, the present work demonstrated that m6A modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.

What is the Safe Distance Between Hip and Knee Implants to Reduce the Risk of Ipsilateral Metachronous Periprosthetic Joint Infection?

Periprosthetic joint infection (PJI), the most common cause of revision after TKA and THA, is a devastating complication for patients that is difficult to diagnose and treat. An increase in the number of patients with multiple joint arthroplasties in the same extremity will result in an increased risk of ipsilateral PJI. However, there is no definition of risk factors, micro-organism patterns, and safe distance between knee and hip implants for this patient group. (1) In patients with hip and knee arthroplasties on the same side who experience a PJI of one implant, are there factors associated with the development of subsequent PJI of the other implant? (2) In this patient group, how often is the same organism responsible for both PJIs? (3) Is a shorter distance from an infected prosthetic joint to an ipsilateral prosthetic joint associated with greater odds of subsequent infection of the second joint? We designed a retrospective study of a longitudinally maintained institutional database that identified all one-stage and two-stage procedures performed for chronic PJI of the hip and knee at our tertiary referral arthroplasty center between January 2010 and December 2018 (n = 2352). Of these patients, 6.8% (161 of 2352) had an ipsilateral hip or knee implant in situ at the time of receiving surgical treatment for a PJI of the hip or knee. The following criteria led to the exclusion of 39% (63 of 161) of these patients: 4.3% (seven of 161) for incomplete documentation, 30% (48 of 161) for unavailability of full-leg radiographs, and 5% (eight of 161) for synchronous infection. With regard to the latter, per internal protocol, all artificial joints were aspirated before septic surgery, allowing us to differentiate between synchronous and metachronous infection. The remaining 98 patients were included in the final analysis. Twenty patients experienced ipsilateral metachronous PJI during the study period (Group 1) and 78 patients did not experience a same-side PJI (Group 2). We analyzed the microbiological characteristics of bacteria during the first PJI and ipsilateral metachronous PJI. Calibrated, full-length plain radiographs were evaluated. Receiver operating characteristic curves were analyzed to determine the optimal cutoff for the stem-to-stem and empty native bone distance. The mean time between the initial PJI and ipsilateral metachronous PJI was 8 ± 14 months. Patients were followed for a minimum of 24 months for any complications. The risk of ipsilateral metachronous PJI in the other joint secondary to a joint implant in which PJI develops can increase up to 20% in the first 2 years after the procedure. There was no difference between the two groups in age, sex, initial joint replacement (knee or hip), and BMI. However, patients in the ipsilateral metachronous PJI group were shorter and had a lower weight (1.6 ± 0.1 m and 76 ± 16 kg). An analysis of the microbiological characteristics of bacteria at the time of the initial PJI showed no differences in the proportions of difficult-to-treat, high virulence, and polymicrobial infections between the two groups (20% [20 of 98] versus 80% [78 of 98]). Our findings showed that the ipsilateral metachronous PJI group had a shorter stem-to-stem distance, shorter empty native bone distance, and a higher risk of cement restrictor failure (p < 0.01) than the 78 patients who did not experience ipsilateral metachronous PJI during the study period. An analysis of the receiver operating characteristic curve showed a cutoff of 7 cm for the empty native bone distance (p < 0.01), with a sensitivity of 72% and a specificity of 75%. The risk of ipsilateral metachronous PJI in patients with multiple joint arthroplasties is associated with shorter stature and stem-to-stem distance. Appropriate position of the cement restrictor and native bone distance are important in reducing the risk of ipsilateral metachronous PJI in these patients. Future studies might evaluate the risk of ipsilateral metachronous PJI owing to bone adjacency. Level III, therapeutic study.

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

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. 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. 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%. 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. Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Synovial fluid neutrophil extracellular traps could improve the diagnosis of periprosthetic joint infection.

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%). 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. 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. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly.Cite this article: Bone Joint Res2023;12(2):113-120.