Aims. Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90

Aims. To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration. Methods. We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map. Results. After screening of 5,660 articles, we included 166 studies reporting prognostic factors for outcomes after rTKA, with a median sample size of 319 patients (30 to 303,867). Overall, 50% of the studies reported prospectively collected data, and 61% of the studies were performed in a single centre. In some studies, multiple associations were reported; 180 different prognostic factors were reported in these studies. The three most frequently studied prognostic factors were reason for revision (213 times), sex (125 times), and BMI (117 times). Studies focusing on functional scores and patient-reported outcome measures as prognostic factor for the outcome after surgery were limited (n = 42). The studies reported 154 different outcomes. The most commonly reported outcomes after rTKA were: re-revision (155 times), readmission (88 times), and reinfection (85 times). Only five studies included costs as outcome. Conclusion. Outcomes and prognostic factors that are routinely registered as part of clinical practice (e.g. BMI, sex, complications) or in (inter)national registries are studied frequently. Studies on prognostic factors, such as functional and sociodemographic status, and outcomes as healthcare costs, cognitive and mental function, and psychosocial impact are scarce, while they have been shown to be important for patients with osteoarthritis. Cite this article: Bone Jt Open 2023;4(5):338–356

Aims. The principles of evidence-based medicine (EBM) are the foundation of modern medical practice. Surgeons are familiar with the commonly used statistical techniques to test hypotheses, summarize findings, and provide answers within a specified range of probability. Based on this knowledge, they are able to critically evaluate research before deciding whether or not to adopt the findings into practice. Recently, there has been an increased use of artificial intelligence (AI) to analyze information and derive findings in orthopaedic research. These techniques use a set of statistical tools that are increasingly complex and may be unfamiliar to the orthopaedic surgeon. It is unclear if this shift towards less familiar techniques is widely accepted in the orthopaedic community. This study aimed to provide an exploration of understanding and acceptance of AI use in research among orthopaedic surgeons. Methods. Semi-structured in-depth interviews were carried out on a sample of 12 orthopaedic surgeons. Inductive thematic analysis was used to identify key themes. Results. The four intersecting themes identified were: 1) validity in traditional research, 2) confusion around the definition of AI, 3) an inability to validate AI research, and 4) cautious optimism about AI research. Underpinning these themes is the notion of a validity heuristic that is strongly rooted in traditional research teaching and embedded in medical and surgical training. Conclusion. Research involving AI sometimes challenges the accepted traditional evidence-based framework. This can give rise to confusion among orthopaedic surgeons, who may be unable to confidently validate findings. In our study, the impact of this was mediated by cautious optimism based on an ingrained validity heuristic that orthopaedic surgeons develop through their medical training. Adding to this, the integration of AI into everyday life works to reduce suspicion and aid acceptance. Cite this article: Bone Jt Open 2023;4(9):696–703

Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95

Aims. The aim of this study was to inform the epidemiology and treatment of slipped capital femoral epiphysis (SCFE). Methods. This was an anonymized comprehensive cohort study, with a nested consented cohort, following the the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) framework. A total of 143 of 144 hospitals treating SCFE in Great Britain participated over an 18-month period. Patients were cross-checked against national administrative data and potential missing patients were identified. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants. Results. A total of 486 children (513 hips) were newly affected, with a median of two patients (interquartile range 0 to 4) per hospital. The annual incidence was 3.34 (95% confidence interval (CI) 3.01 to 3.67) per 100,000 six- to 18-year-olds. Time to diagnosis in stable disease was increased in severe deformity. There was considerable variation in surgical strategy among those unable to walk at diagnosis (66 urgent surgery vs 43 surgery after interval delay), those with severe radiological deformity (34 fixation with deformity correction vs 36 without correction) and those with unaffected opposite hips (120 prophylactic fixation vs 286 no fixation). Independent risk factors for avascular necrosis (AVN) were the inability of the child to walk at presentation to hospital (adjusted odds ratio (aOR) 4.4 (95% CI 1.7 to 11.4)) and surgical technique of open reduction and internal fixation (aOR 7.5 (95% CI 2.4 to 23.2)). Overall, 33 unaffected untreated opposite hips (11.5%) were treated for SCFE by two-year follow-up. Age was the only independent risk factor for contralateral SCFE, with age under 12.5 years the optimal cut-off to define ‘at risk’. Of hips treated with prophylactic fixation, none had SCFE, though complications included femoral fracture, AVN, and revision surgery. PROMs demonstrated the marked impact on quality of life on the child because of SCFE. Conclusion. The experience of individual hospitals is limited and mechanisms to consolidate learning may enhance care. Diagnostic delays were common and radiological severity worsened with increasing time to diagnosis. There was unexplained variation in treatment, some of which exposes children to significant risks that should be evaluated through randomized controlled trials. Cite this article: Bone Joint J 2022;104-B(4):519–528

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Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this.

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The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

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The evidence base within trauma and orthopaedics has traditionally favoured quantitative research methodologies. Qualitative research can provide unique insights which illuminate patient experiences and perceptions of care. Qualitative methods reveal the subjective narratives of patients that are not captured by quantitative data, providing a more comprehensive understanding of patient-centred care. The aim of this study is to quantify the level of qualitative research within the orthopaedic literature.

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To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design.

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Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB.

Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework – a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.

Cite this article: Bone Joint Res 2024;13(9):507–512.

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Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.

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Steroid injections are used for subacromial pain syndrome and can be administered via the anterolateral or posterior approach to the subacromial space. It is not currently known which approach is superior in terms of improving clinical symptoms and function. This is the protocol for a randomized controlled trial (RCT) to compare the clinical effectiveness of a steroid injection given via the anterolateral or the posterior approach to the subacromial space.

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The rate of day-case total knee arthroplasty (TKA) in the UK is currently approximately 0.5%. Reducing length of stay allows orthopaedic providers to improve efficiency, increase operative throughput, and tackle the rising demand for joint arthroplasty surgery and the COVID-19-related backlog. Here, we report safe delivery of day-case TKA in an NHS trust via inpatient wards with no additional resources.

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To review the evidence and reach consensus on recommendations for follow-up after total hip and knee arthroplasty.

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The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy.

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The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

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Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

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Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

The use of artificial intelligence (AI) is rapidly growing across many domains, of which the medical field is no exception. AI is an umbrella term defining the practical application of algorithms to generate useful output, without the need of human cognition. Owing to the expanding volume of patient information collected, known as ‘big data’, AI is showing promise as a useful tool in healthcare research and across all aspects of patient care pathways. Practical applications in orthopaedic surgery include: diagnostics, such as fracture recognition and tumour detection; predictive models of clinical and patient-reported outcome measures, such as calculating mortality rates and length of hospital stay; and real-time rehabilitation monitoring and surgical training. However, clinicians should remain cognizant of AI’s limitations, as the development of robust reporting and validation frameworks is of paramount importance to prevent avoidable errors and biases. The aim of this review article is to provide a comprehensive understanding of AI and its subfields, as well as to delineate its existing clinical applications in trauma and orthopaedic surgery. Furthermore, this narrative review expands upon the limitations of AI and future direction.

Cite this article: Bone Joint Res 2023;12(7):447–454.

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To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC).

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Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

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The evidence demonstrating the superiority of early MRI has led to increased use of MRI in clinical pathways for acute wrist trauma. The aim of this study was to describe the radiological characteristics and the inter-observer reliability of a new MRI based classification system for scaphoid injuries in a consecutive series of patients.

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This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

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The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques.

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Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

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We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

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In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method.

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The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD.

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To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

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To assess the cost-effectiveness of a two-layer compression bandage versus a standard wool and crepe bandage following total knee arthroplasty, using patient-level data from the Knee Replacement Bandage Study (KReBS).

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Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

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This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

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The aims of this study were to describe the epidemiology of metacarpal shaft fractures (MSFs), assess variation in treatment and complications following standard care, document hospital resource use, and explore factors associated with treatment modality.

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Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

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To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

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The management of mid-shaft clavicle fractures (MSCFs) has evolved over the last three decades. Controversy exists over which specific fracture patterns to treat and when. This review aims to synthesize the literature in order to formulate an appropriate management algorithm for these injuries in both adolescents and adults.

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This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

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The aim of this study was to develop and evaluate machine-learning-based computerized adaptive tests (CATs) for the Oxford Hip Score (OHS), Oxford Knee Score (OKS), Oxford Shoulder Score (OSS), and the Oxford Elbow Score (OES) and its subscales.

Cite this article: Bone Joint Res 2022;11(8):514–517.

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Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

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National joint registries under-report revisions for periprosthetic joint infection (PJI). We aimed to validate PJI reporting to the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) and the factors associated with its accuracy. We then applied these data to refine estimates of the total national burden of PJI.

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The aim of this study was to evaluate the epidemiology and treatment of Perthes’ disease of the hip.

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With increasing burden of revision hip arthroplasty (THA), one of the major challenges is the management of proximal femoral bone loss associated with previous multiple surgeries. Proximal femoral arthroplasty (PFA) has already been popularized for tumour surgeries. Our aim was to describe the outcome of using PFA in these demanding non-neoplastic cases.

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Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development.