Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Aim. D-dimer is a widely available serum test that detects fibrinolytic activities that occur during infection. Prior studies have explored its utility for diagnosis of chronic periprosthetic joint infections (PJI), but not explored its prognostic value for prediction of subsequent treatment failure. The purpose of this study was to: (1) assess the ability of serum D-dimer and other standard-of-care serum biomarkers to predict failure following reimplantation, and (2) establish a new cutoff value for serum D-dimer for prognostic use prior to reimplantation. Method. This prospective study enrolled 92 patients undergoing reimplantation between April 2015 and March 2019 who had previously undergone total hip/knee resection arthroplasty with placement of an antibiotic spacer for treatment of chronic PJI. Serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured preoperatively for all patients. Failure following implantation was defined per the Delphi consensus criteria. Optimal cutoffs for D-dimer, ESR, and CRP were calculated based on ROC curves and compared in their association with failure following reimplantation criteria at minimum 1-year follow-up. Results. 15/92(16.3%) patients failed reimplantation surgery at mean follow up of 2.9 years (range 1.0–4.8). Optimal thresholds for D-Dimer, ESR and CRP were determined to be 1300ng/mL, 30mm/hr, and 1mg/L, respectively. The failure rate in patient with positive D-dimer was significantly higher at 32.0% (8/25) compared to those with negative D-dimer 10.6% (7/66); p=0.024. In comparison, 17.8% (8/45) of patients with ESR above threshold failed, compared to 13.89% (5/41) below (p=0.555) and 16.0% (4/25) of patients with CRP above threshold failed, compared to 16.1% (10/62) below (p=1.000). Conclusions. Patients with elevated D-Dimer appear to be at higher risk of failure after reimplantation surgery. This serum marker may be used to generate an additional data point in patients undergoing reimplantation surgery, especially in circumstances when optimal timing of reimplantation cannot be determined based on clinical circumstances

Background. Preoperative diagnosis of fracture related infections can be challenging, especially when confirmatory criteria such as sinus tract and purulent discharge are absent. Although serum parameters, such as CRP and white blood cell count (WBC), showed poor accuracy in the literature, they are still often used in clinical practice. The European Bone and Joint Infection Society (EBJIS) defined evidence-based criteria for fracture related infection. Elevated serum inflammatory markers were regarded as suggestive criteria only, as the literature was of limited quality. This study assessed the diagnostic value of the serum parameters CRP, WBC and differential cell count in the diagnosis of fracture related infections defined by the EBJIS-criteria for fracture related infections. Methods. In this retrospective cohort study, 94 patients who underwent surgical treatment for suspected infected non unions after failed fracture fixation were included. Preoperatively, blood samples including serum inflammatory markers were taken. For this study, cut-offs of 5 mg/L for CRP, 10×10⁁9 cells/L for WBC, and >70% for the percentage of neutrophils were regarded as positive for infection. All patients had intraoperative samples taken for microbiology and histology. Analysis of diagnostic accuracy was based on the receiver-operating characteristic (ROC). Results. Based on the EBJIS criteria, 40 patients (43%) were diagnosed with a fracture related infection. 11/94 (12%) patients had an elevated serum WBC count, 13/94 (14%) an increased percentage of neutrophils, and 43/82 (52%) an elevated serum CRP. The mean values of CRP concentration, WBC count, and percentage of neutrophils in the infection group were 7.9 mg/L (IQR:6.4 – 9.7), 18.3 G/l (IQR: 3.9 – 24.9), and 63% (IQR: 58 – 67%), respectively. The sensitivity, specificity, and area under the curve of serum WBC count were 20% (95% CI: 10 −35%), 94.4% (84 −99%), and 0.57 (0.50 – 0.64), respectively; of percentage of neutrophils 12.5% (5 – 27%), 85.2% (73 −93%), and 0.49 (0.42 – 0.56); and of serum CRP 67.6% (51 – 90%), 60.0% (45 – 73%), and 0.64 (0.53 – 0.74), respectively. A statistically significant difference between the AUCs of all three serum parameters and AUC of tissue culture as well as AUC of histology was shown (p <0.0001). A simple decision tree approach using only low WBC and CRP may allow identification of aseptic cases. Conclusion. Based on the standardized and evidence-based EBJIS criteria, the three inflammatory serum markers showed an insufficient accuracy for the diagnosis of fracture related infections. They also correlate poorly with culture or histological diagnosis. Therefore, they should not be used alone as a confirmatory test

Aim. Despite the availability of numerous tests, the diagnosis of periprosthetic infection (PJI) continues to be complex. Although several studies have suggested that coagulation-related markers, such as D-dimer and fibrinogen, may be promising tools in the diagnosis of prosthetic infections, their role is still controversial. The aim of this study is to evaluate the diagnostic accuracy of serum D-dimer and fibrinogen in patients with painful total knee replacement. Method. 83 patients with painful total knee replacement and suspected peri-prosthetic infection were included. All patients underwent pre-operative blood tests to evaluate inflammation indices (ESR and CRP) and serum D-Dimer and Fibrinogen levels. The diagnostic performance of the tests was assessed using the ICM definition as the gold standard. The diagnostic accuracy of the D-dimer and fibrinogen was measured by assessing sensitivity, specificity and by calculating the area under the ROC curve. Results. The definition of prosthetic infection based on the ICM criteria has made it possible to classify 40 peri-prosthetic infections and 43 aseptic failures. The mean value of fibrinogen, D-Dimer, VES and PCR observed in patients with prosthetic infection was significantly higher than in patients with aseptic failure [fibrinogen 468 mg / dl vs 331 mg / dl, p <0.001; D-Dimero 2177 ng/mL vs. 875 ng / mL, p <0.005], ESR 49 mm / hr vs 24 mm/h, p <0.001; PCR 25.5 mg /L vs 8.9 mg/L, p <0.001]. The optimal threshold value of the fibrinogen indicative of the presence of infection was 418 mg/dl, with a sensitivity of 72% and a specificity of 88%. The serum concentration of d-dimer greater than 945 ng / ml showed a sensitivity of 72.5% and a specificity of 76.7%. Conclusions. Although in this multicenter prospective study we found that serum D-dimer may have significantly higher statistical values in PJI than aseptic failures, its diagnostic power appears however limited when compared with other markers including plasma fibrinogen. Fibrinogen is regularly analyzed before surgery, the evaluation of this marker does not involve additional costs. The diagnostic accuracy appears to be similar to that of classic markers such as the level of PCR and VES. Plasma D-dimer may have a limited value in the diagnosis of PJI unlike plasma fibrinogen which has shown moderate sensitivity and excellent specificity. However, in our limited series of cases, both tests cannot be used alone in the diagnosis of infection but could contribute to the diagnosis if contextualized to ves and pcr

Aim. Diagnosis of periprosthetic joint infection (PJI) is challenging given the limitations of available diagnostic tests. Recently, several studies have shown a role of the long pentraxin PTX3 as a biomarker in inflammatory diseases and infections. This single-center prospective diagnostic study evaluated the diagnostic ability of synovial fluid and serum PTX3 for the infection of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Method. Consecutive patients undergoing revision surgery for painful THA or TKA were enrolled. Patients with antibiotic therapy suspended for less than 2 weeks prior to surgery and patients eligible for metal-on-metal implant revision or spacer removal and prosthesis re-implantation were excluded. Quantitative assessment of synovial fluid and serum PTX3 was performed with ELISA method. Musculoskeletal Infection Society (MSIS) criteria were used as reference standard for diagnosis of PJI. Continuous data values were compared for statistical significance with univariate unpaired, 2-tailed Student's t-tests. Receiver operating characteristic (ROC) curve analyses was performed to assess the ability of serum and synovial fluid PTX3 concentration to determine the presence of PJI. Youden's J statistic was used to determine optimum threshold values for the diagnosis of infection. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative (LR-) likelihood ratio, area under the ROC curve (AUC) were calculated. Results. One-hundred fifteen patients (M:F=49:66) with a mean age of 62 years (40–79) underwent revision of THA (n=99) or TKA (n=16). According with MSIS criteria, 18 cases were categorized as septic and 97 as aseptic revisions. The average synovial fluid concentration of PTX3 was significantly higher in patients with PJI compared to patients undergoing aseptic revision (24,3 ng/dL vs 3,64 ng/dL; P=0.002). There was no significant difference in terms of serum concentration of PTX3 between the two groups. Synovial fluid PTX3 demonstrated an AUC of 0.96 (95%IC 0.89–0.98) with Se 94%, Sp 90%, PPV 67%, NPV 100%, LR+ 9.4 and LR- 0.06 for a threshold value of 4.5 ng/dL. Serum PTX3 demonstrated an AUC of 0.70 (95%IC 0.51–0.87) with Se 72%, Sp 67%, PPV 30%, NPV 93%, LR+ 2.2 and LR- 0.42 for a threshold value of 4.5 ng/dL. Conclusions. In patients undergoing revision surgery for painful THA or TKA, synovial PTX3 demonstrated a strong diagnostic ability for PJI. Synovial PTX3 could represent a more useful biomarker for detection of PJI compared with serum PTX3

Background. Recent clinical studies have suggested that systemic metal ion levels are significantly elevated at midterm follow-up after ceramic-on-metal (COM) bearing. However, it is not clear whether there is a correlation between patient- and surgical-related factors including the lifestyle and elevated levels of serum metal ions following COM total hip arthroplsty (THA). Material and Methods. Two hundred and one patients (234 hips) including 121 COM patients (140 hips) and 80 non-COM patients (94 hips) were enrolled in accordance with the inclusion criteria. The patients were divided into three groups based on the type of surgical bearings used. The Harris Hip Score (HHS), University of California, Los Angeles (UCLA) activity scale score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were measured, and radiographs were obtained for the analysis. Serum metal ion levels of cobalt and chromium were measured using a high-resolution inductively coupled plasma mass spectrometry. Patient- and surgical-related factors were analyzed to determine which group of patients is at a high risk of metal ion-related problems. Results. Significantly higher serum levels of Co and Cr were detected in the serum of the COM THA group (Co: 1.86±4.0 µg/L, range: 0.30 to 34.20 µg/L; Cr: 1.81±2.87 µg/L, range: 0.10 to 27.80 µg/L) than in the serum of the non-COM THA group (Co: 0.27±0.14 µg/L, range: 0.15 to 0.90 µg/L; Cr: 0.19±0.25 µg/L, range; 0.10 to 2.30 µg/L) (p<0.001). The HHS in the COM group was significantly better than that in the non-COM group (p=0.013). The total ROM of the THAs was significantly greater in the 36-mm COM THA group (272.7°, range: 200°–345°) than in the non-COM group (248.5°, range: 135°–300°) (p<0.001). No radiolucency, osteolysis, or loosening was found during the follow-up radiographic examination. The serum Co levels of patients who achieved the squatting position were significantly higher than those of patients who could not squat (Co: p=0.033; Cr: p=0.074). The serum Co and Cr levels of patients who achieved the kneeling position were significantly higher than those of patients who could not kneel (Co: p=0.049; Cr: p=0.031). There was no significant difference between the two groups in the cross-legged sitting position. The metal ion levels of the COM THA group correlated with the total ROM (Co: p=0.0293; Cr: p=0.0399), and those of the patients who were capable of squatting and kneeling were significantly higher than those of the patients who were unable (p<0.05). However, age, BMI, acetabular cup position and patient activity did not show significant correlations with the serum metal ion levels. Conclusions. Patients who underwent a 36-mm COM THA had good clinical outcomes with an excellent hip function at the short and midterm follow-up intervals. However, high levels of metal ions were detected in the serum of COM THA patients. We found that COM THA patients who were capable of greater ROMs, squatting, and kneeling are at risk of metal ion-related problems

The purpose of this study was to prospectively measure serum cobalt and chromium ion levels in patients who had MITCH Resurfacing (Stryker) and to correlate these with acetabular component orientation (anteversion and inclination). Twenty-seven patients were enrolled in the study. Serum ion levels were measured pre-operatively, six weeks, six months, twelve months and twenty-four months post-operatively. Axial CT scans of the pelvis were used to measure cup anteversion and plain radiographs used to measure cup inclination. The median serum cobalt and chromium levels at one year were 14.5 nmol/l (range, 6 nmol/l to 59 nmol/l) and 36 nmol/l (range, 17nmol/l to 63 nmol/l) respectively. The median serum cobalt and chromium levels at two years were 16.5 nmol/l (range, 6 nmol/l to 75 nmol/l) and 37.5 nmol/l (range, 13 nmol/l to 109 nmol/l) respectively. The mean cup inclination was 43° (range, 30° to 60°). The mean cup anteversion was 19° (range, 1° to 47°). There was no clear correlation with cup position and serum ion levels. There was one outlier with slightly elevated chromium (109 nmol/l) in a female with a small head size. All patients at all time points showed serum cobalt and chromium levels below the level indicating a high-risk implant (7 parts per billion or chromium >134 nmol/l and cobalt > 119 nmol/l). Our results show no clear relationship between cup position and serum metal ions in this group of patients with relatively well-positioned components

Background. Periprosthetic joint infection (PJI) remains challenging as a “gold standard” for diagnosis has not yet been established. The aim of this study was to evaluate the accuracy of synovial fluid procalcitonin (SF-PCT) and serum procalcitonin as diagnostic biomarker for PJI and compared their accuracy with standard methods. Materials and Methods. A single-centered prospective cohort study was conducted between 2015–2017 in 32 patients with painful hip or knee arthroplasty underwent revision surgery. Relevant clinical and laboratory data were collected. PJI was diagnosed based on the 2013 international consensus criteria. Preoperative blood sample and intraoperatively acquired joint fluid were taken for PCT measurement with a standard assay. Diagnostic accuracy was analyzed by the receiver-operating characteristic (ROC) curve and the area under the curve (AUC). Results. Twenty patients (62.5%) were classified as PJI, and 12 of them (37.5%) were classified as aseptic loosening group. The median age was 68 years (range 38–87 years). The median values of SF-PCT and serum PCT in PJI group were both significant higher than those in aseptic loosening group: the median serum PCT levels (interquartile range: IQR) were 0.33 ng/mL (0.08–2.79 ng/mL) in PJI group compared with 0.04 ng/mL (0.03–0.06 ng/mL), and the median SF-PCT levels (IQR) were 0.16 ng/mL (0.12–0.26 ng/mL) in PJI group compared with 0.00 (0.00–0.00 ng/mL) (p<0.001 both) (Fig 1). SF-PCT, with a cut-off level as 0.08 ng/mL, had a AUC of 0.87, a sensitivity of 90.0% and a specificity of 83.3%, and a negative likelihood ratio (LR-) of 0.12. Whereas serum PCT, with a standard cut-off level as 0.5 ng/mL, had a AUC of 0.70, a sensitivity of 40.0% and a specificity of 100.0%, and a LR- of 0.60. (Fig 2–3). Conclusion. SF-PCT appears to be a reliable test and could be useful as an alternative indicator or in combination for the diagnosis of PJI

Introduction. The MHRA guidelines for metal on metal (MOM) suggest cobalt and chromium levels of more than 7ppb as potential for soft tissue reaction. However, in some patients soft tissue reaction is seen even in the presence of normal serum metal ions levels. Methods. A prospective review of all patients who had metal-on-metal hip arthroplasty was done. Patients who had both serum metal ion levels and MARS MRI scan were included in this study. Results. There were 574 patients with 319 females and 255 males. 240 patients had both MARS MRI scan and serum metal ions. Fifty nine (24.5%) patients with normal metal ions had metallosis/pseudo tumour on MRI scans, and 17 (7%) patients with increased metal ions had normal MRI scans. Conclusion. This study confirms that there is poor correlation between serum metal ions and soft tissue reaction. Nearly a quarter of patients with normal serum metal ions had evidence of metallosis on MRI scan. Clinicians should be aware of the potential for soft tissue reaction even in the presence of normal metal ions. Hence, consideration should be given to further imaging where appropriate, to ensure early metallosis is picked up and further complications of pseudo tumour prevented

Introduction. In a recent study we evaluated the clinical and radiographic long-term results as well as the serum metal concentrations of 105 cementless primary total hip prosthesis, performed between November 1992 and May 1994 with a 28-mm high-carbide-concentration metal-on-metal articulating surfaces. Forty-one patients who had had a total of forty-four arthroplasties were available for follow-up evaluation at a minimum of seventeen years postoperatively. The median serum cobalt concentration of the patients with their hip replacement as the only source of cobalt was 0.7 µg/L (range 0.4–5.1µg/L), showing no significant difference to the previous study after a minimum of 10 years follow-up. We were investigating the systemic dissemination, which in turn, did not show more severe effects, such as carcinogenicity or renal failure. There are many complex issues associated with the analysis of metal ions, including collecting technique, analysis and reporting of the results. At the AAOS in March 2013, the Hip Society mentioned, that systemic ion levels are just one factor in the evaluation and should not be relied upon solely to determine the need for revision surgery. Furthermore, the correlation between cobalt or chromium serum, urin or synovial fluid levels and adverse local tissue reactions is incompletely understood. Patients and Methods. In our present study we evaluated the serum, urin as well as the joint aspirate metal concentrations, of cementless total hip arthroplasties with a high-carbon, metal-on-metal bearing (Metasul®) at a mean of eighteen-years follow-up. We performed a correlation analysis to evaluate the relationship between these values and to determine whether elevated serum metal concentrations are associated with elevated and local metal concentrations and with early failure of metal-on-metal articulations. Results. Spearman correlations evaluated that there was no significant relationship between the serum cobalt or chromium level and the joint aspirate cobalt (r= 0.60, p=0.15) or chromium (r=0.39, p=0.38) concentration, and the urin cobalt (r=0.21, p=0.62) or chromium (r=0.27, p=0.51) level. Additionally we evaluated a positive correlation between the local chromium concentration and the BMI (r=0.53, p= 0.21) and the cup inclination (r=0.24, p=0.64), a negative correlation between the local chrom concentration and the UCLA (r=0.25, p=0.59) and the Harris hip score (r=0.16, p= 0.73), but without a significance. Conclusion. We evaluated the regional dissemination and the local determination in the synovial fluid, which offers better information about wear and local reactions at the components level prior to the occurrence of marked adverse local tissue and therefore is the best predictor for wear related tissue reaction in MOM articulations, even in asymptomatic patients

Purpose. There is a postulated association between increased serum metal ions and pseudotumour formation in patients with metal-on-metal hip replacements. The primary aim of this study was to assess the prevalence of pseudotumour in 31 asymptomatic patients with a large femoral head (LFH) metal-on-metal hip implant. This was compared to the prevalence of pseudotumour in 20 matched asymptomatic patients with a hip resurfacing (HRA) and 24 matched asymptomatic patients with a standard metal-on-polyethylene (MOP) total hip. A secondary objective was to assess possible correlation between increased serum metal ions and pseudotumour formation. Method. Ultrasound examination of the three groups was performed at a minimum follow up of two years. Serum metal ions were measured in the metal-on-metal LFH and HRA groups at a minimum of two years. Results. There were 10 (32%) solid or cystic masses in the LFH group with a mean size of 89.3 (8 to 437) cm3. In the HRA group there were five (25%) masses with a mean size of 41.6 (6 to 119) cm3. In the MOP group there was one cystic mass measuring 9.8 cm3. Median serum cobalt and chromium ion levels in the LFH group were 4.50 gL (interquartile range, 2.38 to 7.47) and 2.82 gL (interquartile range, 1.48 to 3.18) compared to 0.83 gL (interquartile range, 0.65 to 1.12) and 1.08 gL (interquartile range, 0.78 to 1.31) in the HRA group. Conclusion. This study demonstrates a significantly higher prevalence of pseudotumours in patients with large head metal-on-metal total hips. The higher levels of metal ions in this group suggest that elevated metal ions may lead to pseudotumour formation

Introduction. Antibiotic-loaded acrylic cement (ALAC) is employed in the treatment or prevention of infected total hip arthroplasty (THA). We have administered vancomycin (VCM) as the ALAC for the treatment of THAs with methicillin-resistant Staphylococcus aureus, or for the prevention of THAs with high risks. This study aimed to evaluate the serum concentration of VCM from ALAC in THA or cement beads. Methods. Between December 2013 and February 2014, 16 hips (16 patients) underwent application of the ALAC including VCM at our institution. Two hips were used for the treatment of infection, in the first stage of two-staged revision THAs (i.e., cement beads). Two hips were used for the both treatment and prevention of infection, in one-staged revision THAs. Twelve hips were used for the prevention of infection, in aseptic revision THAs or primary THAs with high risks. Patients were classified into two groups depending on the VCM concentration of ALAC, as follows: high-dose group (2 hips), average 4.4% (3.8–5.0%); low-dose group (14 hips), average 1.6% (1.3–2.5%). The amount of VCM placed as ALAC into the hip was calculated by using the remaining ALAC. The serum concentration of VCM was evaluated at 1 day, 4 days, 7 days, and 28 days after surgery. Statistical analysis was performed by using the t-test, and the differences were considered significant when the p value was <0.05. Results. Average amount of VCM placed as ALAC was 3.5 g (3.1–4.0 g) and 0.9 g (0.3–2.0 g) in the high- and low-dose groups, respectively. The average serum concentration of VCM (μg/mL) was 2.5 and 1.1 on day 1, 2.8 and 1.2 on day 4, 2.3 and 1.1 on day 7, and 1.9 and 1.0 on day 28, in the high- and low-dose groups, respectively. There were significant differences in the high- and low-dose groups on all days. Conclusions. Although the serum concentration of VCM in the high-dose group is significantly increased compared to that in the low-dose group, it is always under the effective blood concentration (5–10 μg/mL) and seem to be clinically safe. Further, we confirmed the continuous effect of ALAC, including VCM, because they were detected at 28 days. However, careful continued follow-up and further evaluation will be required

Introduction. Higher concentrations of metal ion levels after Metal-on-metal (MoM) THA are a cause for concern. Elevated cobalt (Co) and chromium (Cr) ion levels in the blood indicate metal wear, and may predict secondary soft-tissue damage (adverse reaction to metal debris; ARMD). Although, it is well known that concentrations of metal ion levels are elevated in the short term after MoM, the long-term consequences in ion concentration and risk factors for increased ion levels are not clarified. We sequentially investigated the postoperative Co and Cr ion levels after MoM THA and the relationship between the metal ion levels and several risk factors. Materials and Methods. We reviewed the data on one hundred and eighty six patients of two hundred ninety one MoM THA cases. The one hundred eighty six patients were measured at least three times after a MoM THA surgery over a five year (2005–2010) period in our institution. Serum cobalt and chromium levels were measured by inductor coupled plasma – mass spectrometry at several times in follow-up period, (measured at the preoperative period, the third month, the sixth month, the first year, the second year, and the fourth year after MoM THA). Furthermore, we investigated the correlation between the metal ion levels and various factors which might influence the release of metal ions, such as Body mass index (BMI), renal function, femoral head size, unilateral or bilateral THA, the cup position, and postoperative activity. The renal function was evaluated by measuring estimated glomerular filtration ratio (GFR) at preoperative examination. A postoperative activity was assessed with a pedometer measurement counting number of steps a day. A cup position was evaluated by lateral inclination measured by X-ray or computed tomography. Results. Average serum Co and Cr concentrations in preoperative period were 0.69 and 0.05 mg/ ml, respectively. Postoperative serum Co and Cr ion levels were significantly increased compared with preoperative value throughout the postoperative period. There was no significant correlation with regards to BMI, renal function, femoral head size tothe metal ion level measurement. In bilateral THA cases, Co and Cr ion concentrations were significantly increased compared with unilateral THA cases. In addition, in cases that its cup inclination was more than 50 degrees, Co and Cr ion concentration were significantly increased compared with cases less than 50 degrees in the first year after surgery. There was a trend for higher metal ion levels in the group of patients who walked more than 7000 steps a day, but this did not reach statistical significance. Conclusion. Metal ion concentrations of almost patients were increased after MoM THA surgery. Side effects related to elevation of serum Co or Cr concentration were currently not identified and overall clinical results were good. However, Longer follow-up would be necessary if the patients have overlapping risk factors, because those patients may experience elevation of the level in postoperative late stage

Various reports confirm that elevations in serum markers associated with skeletal muscle injury exist and can occur after orthopaedic surgery in the absence of overt clinical manifestations of myocardial injury. The purpose of this study is to measure the influence surgical approach on these serum markers following primary Minimally Invasive THA. Consecutive enrollment of 30 patients into three different groups of 10 was performed. The MIS Modified Watson Jones THA is an approach using an inter-muscular plane, the Mini Posterior is a trans-muscular approach with some muscle detachment and repair, while the MIS II Incision THA is an inter-muscular approach anteriorly and a trans-muscular approach posteriorly. Blood samples for total creatine kinase (CK), creatine phospho-kinase (CPK), and serum myoglobin were obtained at screening and the morning before surgery as a baseline, immediately post-operatively in the recovery room and 8, 16, 24, 36, 48, and 72 hours post-operatively. Hemoglobin and hematocrit was obtained pre-operatively, 16, 36, and 72 hours (±6 hours) post-operatively. Cardiac troponin-I was measured the morning before surgery (pre-operatively) and 16 hours following surgery to monitor any contributory effect of myocardial injury. We report measurable and reproducible trends in serum enzyme levels consistent with skeletal muscle damage due to THA. Troponin-I remained normal in all but one case throughout the entire study indicating no myocardial contribution to measured serum enzyme levels. While these trends may have slight correlation with surgical approach, they were not statistically significant. We conclude that all three procedures do affect serum enzyme markers and are safe from this standpoint, but no surgical approach appears to affect the degree of muscle trauma more or less than another

Background and Purpose. Serum lactate has been shown to be an indicator of adverse clinical outcomes in patients admitted secondary to general trauma or sepsis. We retrospectively investigated whether admission serum venous lactate can predict in-hospital mortality in patients with hip fractures. Method and Results. Over a 38-month period the admission venous lactate of 807 patients with hip fractures was collated. Mean age was 82 years. The overall in-hospital mortality for this cohort was 9.4%. Mortality was not influenced by the fracture pattern or the type of surgery - be it internal fixation or arthroplasty (p = 0.7). A critical threshold of 3 mmol/L with respect to the influence of venous lactate level on mortality was identified. Mortality rate in those with a lactate level of less than 3 mmol/L was 8.6% and 14.2% for those whose level was 3 mmol/L or greater. A 1 mmol/L increase in venous lactate was associated with a 1.2 (1.02–1.41) increased risk of in-hospital mortality. Patients with a venous lactate of 3 mmol/L or higher had twice the odds of death in hospital compared to matched individuals. There was no statistically significant difference in ASA distribution between those with a lactate of less than or greater than 3 mmol/L. Conclusions. Patients with an elevated venous lactate following hip trauma should be identified as being at increased risk of death and may benefit from targeted medical therapy

To identify the differences in inflammatory profiles between hip OA, knee OA and non-OA control cohorts and investigate the association between cytokine expression and clinical outcome measurements, specifically pain. A total of 250 individuals were recruited in three cohorts (100 knee OA, 50 hip OA, 100 control). Serum was collected and inflammatory profiles analysed using the Multiplex Human Cytokine Panel (Millipore) on the Luminex 100 platform (Luminex Corp., Austin, TX). The pain, physical function and activity limitations of hip OA cohort were scored using the WOMAC, SF-36, HHS and UCLA scores. All cytokine levels were compared between cohorts individually using Mann–Whitney–Wilcoxon (MWW) test with Bonferroni multiple comparison correction. Within hip OA cohorts, the effect of hip alignment (impingement and dysplasia) and radiographic grade (Kellgren and Lawrence grade, K/L grade) on cytokine levels were accessed by MWW test. Spearman's rank correlation test used to assess the association between cytokines and pain levels. The three cohorts showed distinct inflammatory profiles. Specifically, EGF, FGF-2, MCP-3, MIP-1a, IL-8 were significant different between knee and hip OA; FGF-2, GRO, IL-8, MCP-1, VEGF were significant different between hip OA and control; Eotaxin, GRO, MCP-1, MIP-1b, VEGF were significant different between knee OA and control (p-value < 0.0012). For hip OA cohorts, cytokines do not differ between K/L grade three and K/L grade four or between patients that displayed either impingement or dysplasia. Three cytokines were significant associated with pain: IL-6 (p-value = 0.045), MDC (p-value = 0.032) and IP-10 (p-value = 0.038). We have demonstrated that differences in serum inflammatory profiles exist between hip and knee OA patients. These differences suggest that OA may include different inflammatory subtypes according to affected joints. We also identified that the cytokine IL-6, MDC and IP-10 are associated with pain level in hip OA patients. These cytokines might help explain the inconsistent of presentation of pain with radiographical severity of OA joints. Future studies are needed to validate our findings and then to understand the following questions: (1) how differently affected joints are reflected in systematic biomarkers; (2) how these cytokines are biologically involved in the OA pain pathway

Background. Polyethylene (PE) wear is known as a limiting factor for total knee replacements (TKR). Thus, preclinical wear testing is an important tool to assess the suitability of new designs and new materials. However, standardized testing (e.g. according to ISO 14243) does not cover the individual situation in the patient. Consequentially, this study investigates the following two parameters:. a). Testing-Frequency: Patients with TKR's show a humiliated walking frequency (down to 0,5Hz) compared to standardized testing (1Hz±0.1). In the first part of this study, the influence of a decreased test frequency on the PE wear behavior is investigated. b). Interval of lubricant replacement: For in-vitro testing bovine serum is used as a substitute for the synovial fluid. Physiologically a continuous regeneration and removement of destructed components is taking place. In contrast, for simulator testing the bovine serum is typically changed completely every 500.000 cycles/steps. Therefore the goal of the second part of this study was to test if the serum replacing interval affects the PE wear behavior. Material and Methods. Wear tests were conducted on an AMTI force controlled knee simulator. A cruciate substituting (ultracongruent) implant design (TC Plus, Smith & Nephew, Rotkreuz, Switzerland) was used. First, a reference wear study with a test frequency of 1Hz and a lubricant replacement interval (RI) of 500.000 cycles according to ISO 14243-1:2009 was carried out. Tests were run to a total of 5 million cycles. A second wear test was run with a reduced frequency of 0.5 Hz. The reduced frequency resulted in an extended testing period for the same number of cycles. To exclude an influence of the extended time period, the lubricant was changed, in the first half of testing every 500.000 cycles corresponding to 12 days (cycle depending (CD)), and in the second part every 250.000 cycles corresponding to 6 days (time depending (TD)). Tests were run to a total of 3 million cycles. A third test was run with a frequency of 1 Hz. For this test a reduced serum RI of 150.000 cycles was choosen. This test was run to a total of 1.500.000 cycles. Results. The results of wear testing are given in Fig. 1 & 2. There was no difference for testing at a lower frequency in the case, that the serum replacement occurred at the same time interval (p=0.234). However, if the replacement interval is extended or reduced, the wear rate decreases (2.69mg/Mc) or increases respectively (15.87mg/Mc) (p=0.001;p≤0.001). There is a great time depending influence of the serum RI. This influence is shown in Fig. 3, comparing the wear rates in dependency to the time period of lubricant change. Conclusion. This study shows that there is no influence of the reduced testing frequency in a TKR wear simulator study on the PE wear rate. However, there is a massive influence of the lubricant replacement interval. Thus the interval of replacing is of crucial importance for the interpretation of wear simulator studies. The reasons for the changes in the tribological behavior of the bovine serum have to be investigated in further studies

Background. Previous studies have indicated poor outcomes and high complication rate in patients having revision of metal-on-metal (MoM) hip implants resulting from adverse local tissue reactions. Metal ions released by MoM bearings may potentially increase infection occurrence in patients with failed implants. Questions/purposes. We reviewed all patients at our institution who sustained revision of a failed large-head metal-on-metal hip implant to determine if infection-related complications are associated with the elevation of serum metal ions concentration. Methods. From December 2005 to April 2013, we performed 44 revisions of large-head MoM total hip arthroplasty (THA) and resurfacing in 44 patients. In all revision procedures MoM couplings (ASR XL Acetabular System and DePuy ASR Hip Resurfacing System) were explanted. Preoperative diagnosis were: aseptic loosening in 21 hips, hip pain with high serum metal ions levels in 7 hips, high serum metal ions levels without hip pain in 9 hips, deep infections in 4 hips, unexplained hip pain in 2 hips and periprosthetic fracture in 1 hip. Serum cobalt and chromium analysis were preoperatively conducted in 25 patients. Intraoperative fluid aspiration was performed in all cases to determine the presence or absence of periprosthetic joint infection. Results. Fluid analysis for bacteria reported that 35 of 45 cases were culture negative and 10 of 45 cases (22%) were culture positive to Staphylococcus (St) Aureus (4), St Capitis (2), St Epidermidis (2), St Hominis (1), Streptococcus Mitis (1). All preoperative diagnoses of deep infection were confirmed. Within patients evaluated with serum metal ions analysis (mean Co and Cr, 78 μg/l and 39 μg/l, respectively), five cultures resulted positive (20%). The infection rate within patients with higher (> 20 μg/l) metal ions levels (4 positive cultures of 18, 22%) was not significantly higher than infection rate within patients with lower (≤ 20 μg/l) metal ions levels (1 positive culture of 7, 14%). Conclusions. We observed a high rate of periprosthetic joint infection among our revision cases. High metal ions concentrations released by MoM bearings might promote bacterial infections in patients with MoM THA and resurfacing. When evaluating patients with failed MoM hip devices, there may be an increased incidence of co-infection in these patients

Introduction:. The clinical significance of serum metal ion levels alone in patients with stemmed MoM hip arthroplasty remains uncertain. This study aims to measure the metal ion levels in patients with unilateral and bilateral hip arthroplasty to see whether or not the patients with bilateral hips have higher metal ions. Patients and Methods. All the patients with bilateral MoM hip arthroplasty were identified from the research database. These patients were then matched with those in a similar age group who had a unilateral hip arthroplasty, but same University of California Los Angeles (UCLA) activity score. The UCLA activity scores along with other hip scores have been previously gathered for all the patients. Both sets of patients then had measurement of serum cobalt and chromium levels. The results were analyzed and compared. Results:. There were a total of 53 patients with bilateral hips and 53 matched patients with unilateral hips. The average serum Cobalt and Chromium levels were 34 nmol/L (range <10–76) and 23 nmol/L (range <10–104) respectively in the bilateral group; and 14 nmol/L (range <10–45) and 21 nmol/L (range <10–57) in the unilateral group. Given that the MHRA (UK) threshold levels deemed clinically significant are 120 nmol/L and 135 nmol/L for Cobalt and Chromium respectively; the results obtained here are not clinically significant. Conclusions:. One would normally expect, with mathematical reasoning, a patient with bilateral hip arthroplasty to have higher serum metal ion levels than a patient with unilateral arthroplasty. However, this study goes to show that it is not the case