Aims. Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods. Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results. A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion. Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45

Aims. Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee. Methods. Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients’ mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14). Results. The median time to positive culture was five days (IQR 5 to 6) and median synovial fluid cell count was 22,583 cells (IQR 15,200 to 53,231). The median ESR was 25 mm/hr (IQR 7 to 37), and CRP was 15 mg/l (IQR 3 to 29). Of the 35 PJIs, 18 (51%) were treated with chronic antibiotic suppression without surgical intervention, and the remainder were treated with two-stage exchange arthroplasty. The two-year survival free of any revision was 94%. Four patients failed treatment due to symptomatic infection, with three treated with two-stage exchange and one treated with irrigation and debridement with modular component exchange for a survival rate of 89% and 83% at two and five years, respectively. Conclusion. Laboratory evidence of C. acnes PJI in this cohort was typical compared to more conventional organisms. Cultures grew more quickly than previously thought in patients with C. acnes PJI. Treatment with two-stage exchange or chronic antibiotic suppression alone both had few treatment failures at mid-term follow-up. Cite this article: Bone Joint J 2024;106-B(12):1426–1430

Aims. The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm. 3. and ≥ 65% for TKA and ≥ 3,000 cells/mm. 3. and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

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We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty.

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

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The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA).

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The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI).

Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion. Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51

We have investigated whether the use of laminar-flow theatres and space suits reduced the rate of revision for early deep infection after total hip (THR) and knee (TKR) replacement by reviewing the results of the New Zealand Joint Registry at ten years. Of the 51 485 primary THRs and 36 826 primary TKRs analysed, laminar-flow theatres were used in 35.5% and space suits in 23.5%. For THR there was a significant increase in early infection in those procedures performed with the use of a space suit compared with those without (p < 0.0001), in those carried out in a laminar-flow theatre compared with a conventional theatre (p < 0.003) and in those undertaken in a laminar-flow theatre with a space suit (p < 0.001) when compared with conventional theatres without such a suit. The results were similar for TKR with the use of a space suit (p < 0.001), in laminar-flow theatres (p < 0.019) and when space suits were used in those theatres (p < 0.001). These findings were independent of age, disease and operating time and were unchanged when the surgeons and hospital were analysed individually. The rate of revision for early deep infection has not been reduced by using laminar flow and space suits. Our results question the rationale for their increasing use in routine joint replacement, where the added cost to the health system seems to be unjustified

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Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative.

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The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid.

A new generation of knee prostheses has been introduced with the intention of improving post-operative knee flexion. In order to evaluate whether this goal has been achieved we performed a systematic review and meta-analysis. Systematic literature searches were conducted on MEDLINE and EMBASE from their inception to December 2007, and proceedings of scientific meetings were also searched. Only randomised, clinical trials were included in the meta-analysis. The mean difference in the maximum post-operative flexion between the ‘high-flex’ and conventional types of prosthesis was defined as the primary outcome measure. A total of five relevant articles was identified. Analysis of these trials suggested that no clinically relevant or statistically significant improvement was obtained in flexion with the ‘high-flex’ prostheses. The weighted mean difference was 2.1° (95% confidence interval −0.2 to +4.3; p = 0.07)

Between 1988 and 1998 we implanted 318 total hip replacements (THRs) in 287 patients using the Plasmacup (B. Braun Ltd, Sheffield, United Kingdom) and a conventional metal-on-polyethylene articulation. The main indications for THR were primary or secondary osteoarthritis. At follow-up after a mean 11.6 years (7.6 to 18.4) 17 patients had died and 20 could not be traced leaving a final series of 280 THRs in 250 patients. There were 62 revisions (22.1%) in 59 patients. A total of 43 acetabular shells (15.4%) had been revised and 13 (4.6%) had undergone exchange of the liner. The most frequent indications for revision were osteolysis and aseptic loosening, followed by polyethylene wear. The mean Kaplan-Meier survival of the Plasmacup was 91% at ten years and 58% at 14 years. Osteolysis was found around 36 (17.1%) of the 211 surviving shells. The median annual rate of linear wear in the surviving shells was 0.12 mm/year and 0.25 mm/year in those which had been revised (p < 0.001). Polyethylene wear was a strong independent risk factor for osteolysis and aseptic loosening. The percentage of patients with osteolysis increased proportionately with each quintile of wear-rate. There is a high late rate of failure of the Plasmacup. Patients with the combination of this prosthesis and bearing should be closely monitored after ten years

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Preoperative nasal Staphylococcus aureus screening and eradication reduces surgical site infections (SSIs) but its impact on reducing early prosthetic joint infection (PJI) remains controversial. This study aims to assess the effect of preoperative nasal S. aureus screening and eradication on the incidence of early PJI in general and S. aureus-induced early PJI.

We have developed a novel method of calculating the radiological magnification of the hip using two separate radio-opaque markers. We recruited 74 patients undergoing radiological assessment following total hip replacement. Both the new double marker and a conventional single marker were used by the radiographer at the time of x-ray. The predicted magnification according to each marker was calculated, as was the true radiological magnification of the components. The correlation between true and predicted magnification was good using the double marker (r = 0.90, n = 74, p < 0.001), but only moderate for the single marker (r = 0.50, n = 63, p < 0.001). The median error was significantly less for the double marker than for the single (1.1% vs 4.8%, p < 0.001). The double marker method demonstrated excellent validity (intraclass correlation coefficient = 0.89), in contrast to the single marker (0.32). The double marker method appears to be superior to the single marker method when used in the clinical environment

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To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI).

We describe the development and early clinical application of a ported, proximally-cemented titanium stem for cemented total hip arthroplasty. PMMA bone cement is delivered to the proximal femur under pressure after the stem has been positioned within the femoral canal. A mid-stem cement occluder contains the cement to the proximal stem only. A tapered body is incorporated in the design of the stem to reduce the structural stiffness and hence the degree of stress shielding within the reconstructed joint. We performed preclinical studies to measure the reduction in porosity and the pressurisation achieved. The porosity, as measured by the void percentage within the cured cement mantle, was reduced by more than 50% and there was an almost threefold increase in the mean pressure. Mechanical testing of the stem, using a three-point bend test, showed that the addition of cement injection ports on the anterior and posterior sides of the body of the proximal stem did not reduce its strength. Finite-element analysis indicated that, compared with a fully-cemented conventional stem, there was no change in the stresses within the cement mantle. In a series of 40 proximally-cemented stems followed for up to six years (mean 51 months) the mean Harris hip score was 91, and 85% of patients had good or excellent results. There was excellent pain relief, an increased level of activity and good patient satisfaction. One mechanical failure of the stem required revision at three years after implantation. The early results indicate that the clinical performance was equal to that achieved with other modern cemented stems. Radiological evaluation showed excellent results with no evidence of stress shielding. Further follow-up will determine if long-term stress shielding is reduced and if revision is made easier by the absence of a distal cement mantle

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The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level.

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The aim of this study was to establish the diagnostic accuracy of culture of joint aspirate with and without saline injection-reaspiration.