Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient’s surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (. sd. 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion. The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery

Ceramic-on-metal (CoM) is a relatively new bearing combination for total hip arthroplasty (THA) with few reported outcomes. A total of 287 CoM THAs were carried out in 271 patients (mean age 55.6 years (20 to 77), 150 THAs in female patients, 137 in male) under the care of a single surgeon between October 2007 and October 2009. With the issues surrounding metal-on-metal bearings the decision was taken to review these patients between March and November 2011, at a mean follow-up of 34 months (23 to 45) and to record pain, outcome scores, radiological analysis and blood ion levels. The mean Oxford Hip Score was 19.2 (12 to 53), 254 patients with 268 hips (95%) had mild/very mild/no pain, the mean angle of inclination of the acetabular component was 44.8. o. (28. o. to 63. o. ), 82 stems (29%) had evidence of radiolucent lines of > 1 mm in at least one Gruen zone and the median levels of cobalt and chromium ions in the blood were 0.83 μg/L (0.24 μg/L to 27.56 μg/L) and 0.78 μg/L (0.21 μg/L to 8.84 μg/L), respectively. The five-year survival rate is 96.9% (95% confidence interval 94.7% to 99%). Due to the presence of radiolucent lines and the higher than expected levels of metal ions in the blood, we would not recommend the use of CoM THA without further long-term follow-up. We plan to monitor all these patients regularly. Cite this article: Bone Joint J 2015;97-B:300–5

Aims. Displaced, comminuted acetabular fractures in the elderly are increasingly common, but there is no consensus on whether they should be treated non-surgically, surgically with open reduction and internal fixation (ORIF), or with acute total hip arthroplasty (THA). A combination of ORIF and acute THA, an approach called ’combined hip procedure’ (CHP), has been advocated and our aim was to compare the outcome after CHP or ORIF alone. Patients and Methods. A total of 27 patients with similar acetabular fractures (severe acetabular impaction with or without concomitant femoral head injury) with a mean age of 72.2 years (50 to 89) were prospectively followed for a minimum of two years. In all, 14 were treated with ORIF alone and 13 were treated with a CHP. Hip joint and patient survival were estimated. Operating times, blood loss, radiological outcomes, and patient-reported outcomes were assessed. Results. No patient in the CHP group required further hip surgery, giving THA a survival rate of 100% (95% confidence interval (CI) 100 to 100) after three years, compared with 28.6% hip joint survival in the ORIF group (95% CI 12.5 to 65.4; p = 0.001). No dislocations or deep infections occurred in the CHP group. No patient died within the first year after index surgery, but patient survival was lower in the CHP group after three years. There were no relevant differences in patient-reported outcomes. Conclusion. The CHP confers a considerably reduced need of further surgery when compared with ORIF alone in elderly patients with complex acetabular fractures. These findings encourage both further use of, and larger prospective studies on, the CHP. Cite this article: Bone Joint J 2019;101-B:478–483

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The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

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Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism.

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.

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Total knee arthroplasty (TKA) is a common and safe orthopaedic procedure. Zimmer Biomet's NexGen is the second most popular brand of implant used in the UK. The primary cause of revision after the first year is aseptic loosening. We present our experience of using this implant, with significant concerns around its performance with regards early aseptic loosening of the tibial component.

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One of the main causes of tibial revision surgery for total knee arthroplasty is aseptic loosening. Therefore, stable fixation between the tibial component and the cement, and between the tibial component and the bone, is essential. A factor that could influence the implant stability is the implant design, with its different variations. In an existing implant system, the tibial component was modified by adding cement pockets. The aim of this experimental in vitro study was to investigate whether additional cement pockets on the underside of the tibial component could improve implant stability. The relative motion between implant and bone, the maximum pull-out force, the tibial cement mantle, and a possible path from the bone marrow to the metal-cement interface were determined.

Aims. HIV predisposes patients to opportunistic infections. However, with the establishment of Highly Active Anti-Retroviral Therapy (HAART), patients’ CD4 counts are maintained, as is a near normal life expectancy. This study aimed to establish the impact of HIV on the bacteriology of spondylodiscitis in a region in which tuberculosis (TB) is endemic, and to identify factors that might distinguish between them. Patients and Methods. Between January 2014 and December 2015, 63 consecutive cases of spontaneous spondylodiscitis were identified from a single-centre, prospectively maintained database. Demographics, presenting symptoms, blood results, HIV status, bacteriology, imaging, and procedure undertaken were reviewed and comparisons made of TB, non-TB, and HIV groups. There were 63 patients (22 male, 41 female) with a mean age of 42.0 years (11 to 78; . sd. 15.0). Results. In total, 53 patients had tuberculous, nine bacterial, and one cryptococcal spondylodiscitis. There were 29 HIV-positive patients, 29 HIV-negative patients, and five patients with unknown HIV status. The local incidence of TB spondylodiscitis was 1.54/100 000 and that of non-TB spondylodiscitis was 0.29/100 000 per annum. TB patients were younger with similar clinical presentation and infective markers, but were more likely to have a paraspinal abscess. They were also less likely to have a hyperintense disc on MRI. There was no difference between the two HIV groups. Conclusion. In areas of endemic TB and HIV, TB remains the most common cause of spondylodiscitis at five times the rate of non-tuberculous causes. HIV managed with HAART increases the rate of infection but does not influence the bacteriology unless there is a low CD4. There was little to differentiate the groups. TB /HIV co-infected patients were younger than non-TB and HIV-negative patients. Non-TB patients were more likely to have disc hyperintensity on MRI and TB patients were more likely to have abscess formation, but as both groups exhibited these features, neither was diagnostic. Culture confirmation remains necessary. Cite this article: Bone Joint J 2019;101-B:617–620

Aims. A variety of surgical approaches are used for total hip arthroplasty (THA), all with reported advantages and disadvantages. A number of common complications can occur following THA regardless of the approach used. The purpose of this study was to compare five commonly used surgical approaches with respect to the incidence of surgery-related complications. Patients and Methods. The electronic medical records of all patients who underwent primary elective THA at a single large-volume arthroplasty centre, between 2011 and 2016, with at least two years of follow-up, were reviewed. After exclusion, 3574 consecutive patients were included in the study. There were 1571 men (44.0%) and 2003 women (56.0%). Their mean age and body mass index (BMI) was 63.0 years (. sd. 11.8) and 29.1 kg/m. 2. (. sd. 6.1), respectively. Data gathered included the age of the patient, BMI, the American Society of Anesthesiologists (ASA) score, estimated blood loss (EBL), length of stay (LOS), operating time, the presence of intra- or postoperative complications, type of complication, and the surgical approach. The approaches used during the study were posterior, anterior, direct lateral, anterolateral, and the northern approach. The complications that were recorded included prolonged wound drainage without infection, superficial infection, deep infection, dislocation, aseptic loosening, and periprosthetic fracture. Finally, the need for re-operation was recorded. Means were compared using analysis of variance (ANOVA) and Student’s t-tests where appropriate and proportions were compared using the chi-squared test. Results. A total of 248 patients had 263 complications related to the surgery, with an incidence of 6.94%. The anterior approach had the highest incidence of complications (8.5% (113/1329)) and the posterior approach had the lowest, at 5.85% (97/1657; p = 0.006). Most complications were due to deep infection (22.8%), periprosthetic fracture (22.4%), and prolonged wound drainage (21.3%). The rate of dislocation was 0.84% (14/1657) with the posterior approach and 1.28% (17/1329) with the anterior approach (p = 0.32). Conclusion. Overall, THA has a relatively low complication rate. However, the surgical approach plays a role in the incidence of complications. We found that the posterior approach had a significantly lower overall complication rate compared with the anterior approach, with an equal dislocation rate. Periprosthetic fracture and surgical site infection contributed most to the early complication rates. Cite this article: Bone Joint J 2019;101-B:646–651

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Tranexamic acid (TEA), an inhibitor of fibrinolysis, reduces blood loss after routine total knee replacement (TKR). However, controversy persists regarding the dosage and timing of administration of this drug during surgery. We performed a prospective randomised controlled study to examine the optimum blood-saving effect of TEA in minimally invasive TKR. We randomly assigned 151 patients who underwent unilateral minimally invasive TKR to three groups: 1) a placebo group (50 patients); 2) a one-dose TEA group (52 patients), who received one injection of TEA (10 mg/kg) intra-operatively on deflation of the tourniquet; and 3) a two-dose TEA group (49 patients), who received two injections of TEA (10 mg/kg) given pre-operatively and intra-operatively. Total blood loss was calculated from the maximum loss of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism (VTE). The mean total blood loss was significantly higher in the placebo group than in the other two groups (1222 ml (845 to 2043) versus 1035 ml (397 to 1934) and 986 ml (542 to 1811), respectively (both p < 0.0001)). The mean blood loss was not significantly different between the one- and two-TEA groups (p = 0.148). The mean transfusion rate was higher in the placebo group than in the other two groups (22% versus 3.8% (p = 0.006) and 6.1% (p = 0.041), respectively) and there was no statistically significant difference in the mean transfusion rate between the one- and two-TEA groups (p = 0.672). Only one patient, in the two-dose group, had a radiologically confirmed deep venous thrombosis. Our prospective randomised controlled study showed that one intra-operative injection of TEA is effective for blood conservation after minimally invasive TKR

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1

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Surgical reconstruction of deformed Charcot feet carries a high risk of nonunion, metalwork failure, and deformity recurrence. The primary aim of this study was to identify the factors contributing to these complications following hindfoot Charcot reconstructions.

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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

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Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive.

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The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases.