Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

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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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To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture.

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

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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.

Aims. 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. Methods. We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results. BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion. BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38

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Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).

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The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition.

Aims. The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods. Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results. Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion. The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977

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Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection.

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The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI).

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Smoking is associated with post-operative complications but smokers often under-report the amount they smoke. Our objective was to determine whether a urine dipstick test could be used as a substitute for quantitative cotinine assays to determine smoking status in patients.

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Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs.

Aims. Chronic conditions of the wrist may be difficult to manage because pain and psychiatric conditions are correlated with abnormal function of the hand. Additionally, intra-articular inflammatory cytokines may cause pain. We aimed to validate the measurement of inflammatory cytokines in these conditions and identify features associated with symptoms. Patients and Methods. The study included 38 patients (18 men, 20 women, mean age 43 years) with a chronic condition of the wrist who underwent arthroscopy. Before surgery, the Self-Rating Depression Scale (SDS), Hand20 questionnaire and a visual analogue scale (VAS) for pain were used. Cytokine and chemokine levels in the synovial fluid of the wrist were measured using enzyme-linked immunosorbent assays and correlations between the levels with pain were analysed. Gene expression profiles of the synovial membranes were assessed using quantitative polymerase chain reaction. Results. Older patients had high pre-operative Hand20 scores. One-year post-operative Hand20 and VAS scores and pre-operative VAS scores correlated with SDS scores. Post-operative VAS scores negatively correlated with the expression of nerve growth factor and SDS scores positively correlated with the expression of tumour necrosis factor-alpha and negatively correlated with the expression of tumour necrosis factor-converting enzyme. Conclusion. There was a positive correlation between depression and chronic conditions of the wrist. Levels of some cytokines correlate with pain and depression. Additionally, cytokines may be important in the assessment and treatment of chronic conditions of the wrist and depression. Cite this article: Bone Joint J 2016;98-B:961–8

The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life.

A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post-treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection.

At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action.

This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.

Cite this article: Bone Joint J 2015;97-B:924–32.

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay.

The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group.

This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder.

Cite this article: Bone Joint J 2015;97-B:824–9.

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression.

These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement.

Cite this article: Bone Joint J 2014; 96-B:1172–7.

We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery.

Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p < 0.001) and functional score (p < 0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml (sd 53.4) versus 201 pg/ml (sd 49.4) for groups I and II, respectively) and CRP (91 mg/L (sd 24.1) versus 88 mg/L (sd 23.4), respectively) on the first post-operative day, returning to pre-operative values at two and six weeks, respectively. The mean peak level of ESR for the respective two groups was 46 mm/hr versus 48 mm/hr at two weeks, which had still not returned to its pre-operative mean value at 26 weeks. The elevation in the skin temperature appeared to mirror the peak elevation of the ESR, with a range of 2.5° C to 4.5° C with some reduction at 26 weeks but still exceeding the pre-operative value.

We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery.

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP.

After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks.

Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.

Lyme disease is a vector-borne multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi sensu lato. This disease is frequently seen in North America and to a lesser degree in Europe. However, its presence in England is uncommon and we present a case in which the patient developed a palsy of the common peroneal nerve