Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific genetic mechanisms underlying OA remain only partially understood, hindering the development of targeted therapeutic strategies. A transcriptome-wide association study (TWAS) was conducted for site-specific OA phenotypes using functional summary-based imputation (FUSION). High-confidence candidate genes were identified through rigorous quality control measures, including joint/conditional analysis, permutation tests, best model evaluation, and colocalization analysis. Co-expression network analysis was performed to elucidate the functional biology of these candidate genes. Druggable gene targets and their structural models were retrieved from the DrugBank and SWISS-MODEL databases. Finally, the enrichment of mitogen-activated protein kinase 3 (Aims
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The effectiveness of total hip arthroplasty (THA) for patients with no or minimal radiological signs of osteoarthritis (OA) is unclear. In this study, we aimed to: 1) assess the outcome of such patients; 2) identify patient comorbidities and CT or MRI findings which predicted outcome; and 3) compare their outcome to the expected outcome of THA for hip OA. Adult patients undergoing THA for hip pain, with no or minimal radiological features of OA (Tönnis grading scale ≤ 1), were identified from a consecutive series of 1,925 THAs. Exclusion criteria were: inflammatory arthritis; osteonecrosis of the femoral head; prior trauma or infection; and patients without minimum one-year follow-up and patient-reported outcome measures (PROMs). The primary outcome measure was the Oxford Hip Score (OHS). Secondary outcome measures were EuroQol-visual analogue scale (EQ-VAS), University of California and Los Angeles (UCLA) scale, and patient satisfaction on a validated three-point ‘better’, ‘same’, or ‘worse’ scale.Aims
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Periprosthetic joint infections (PJIs) pose significant challenges to patients and healthcare systems worldwide. The aim of this study was to estimate the health-economic burden of reimbursement payment in Europe for PJIs following primary hip and knee arthroplasty. The calculation was based on health-economic modelling using data on primary hip and knee arthroplasties for the year 2019 from the Statistical Office of the European Union (Eurostat) and published infection rates to estimate the total number of hip and knee PJIs in 30 European countries. Revision procedures were stratified into: 1) debridement, antibiotics, and implant retention (DAIR); 2) one-stage exchange; and 3) two-stage revision procedures. The cases were then multiplied by the respective healthcare system reimbursement payments. Payment data were acquired from a survey of 13 countries (Austria, Croatia, France, Germany, Italy, Lithuania, Netherlands, Norway, Portugal, Slovenia, Switzerland, Turkey, and the UK) and extrapolated for the remaining countries.Aims
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Aims. Prevalence of artificial intelligence (AI) algorithms within the Trauma & Orthopaedics (T&O) literature has greatly increased over the last ten years. One increasingly explored aspect of AI is the automated interpretation of free-text data often prevalent in electronic medical records (known as natural language processing (NLP)). We set out to review the current evidence for applications of NLP methodology in T&O, including assessment of study design and reporting. Methods. MEDLINE, Allied and Complementary Medicine (AMED), Excerpta Medica Database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were screened for studies pertaining to NLP in T&O from database inception to 31 December 2023. An additional grey literature search was performed. NLP quality assessment followed the criteria outlined by Farrow et al in 2021 with two independent reviewers (classification as absent, incomplete, or complete). Reporting was performed according to the Synthesis-Without Meta-Analysis (SWiM) guidelines. The review protocol was registered on the Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42022291714). Results. The final review included 31 articles (published between 2012 and 2021). The most common subspeciality areas included trauma,
Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article:
The diagnosis of periprosthetic joint infection (PJI) remains a challenge, as no single diagnostic test shows high diagnostic accuracy. Recently, the measurement of synovial biomarkers has shown promising results. The aim of this study was to present a novel multiplex micro-enzyme-linked immunosorbent assay (ELISA) method for the rapid and simultaneous measurement of alpha-defensin, interleukin (IL)-6, and calprotectin developed in a model buffer system and human spiked synovial fluid. A microfluidics- and chemiluminescence-based multiplex micro-ELISA point-of-care testing system was employed for the rapid and simultaneous measurement of alpha-defensin, calprotectin, and IL-6 developed in a model buffer system and spiked human synovial fluid. Cut-off values of 1.56 µg/ml for alpha-defensin, 50 µg/ml for calprotectin, and 0.031 µg/ml for IL-6 were extracted from the literature as optimal cut-off values for the diagnosis of PJI, and were used for comparison.Aims
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The risk of mortality after a hip fracture has been extensively investigated, but there is little high-quality information available dealing with the overall risk of complications. The aim of this study was to report the risk of complications in the first 120 days after a hip fracture. This was a multicentre, prospective cohort study of patients aged > 60 years with a hip fracture, involving 77 hospitals in England, Wales, and Northern Ireland, between January 2015 and 2022. The primary outcomes of interest were mortality and surgery-specific and general complications, at 120 days postoperatively.Aims
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To assess whether chronic knee pain (CKP) influenced health-related quality of life (HRQoL), knee-specific health, wellbeing, and use of opioid analgesia, and identify variables associated with CKP in patients awaiting knee arthroplasty. This study included 217 patients (mean age 69.7 years (SD 8.7), 116 female (53%)) who completed questionnaires that included the EuroQol five-dimension questionnaire (EQ-5D) and EuroQol-visual analogue scale (EQ-VAS), Oxford Knee Score (OKS), and wellbeing assessments at six and 12 months after being listed for surgery. Analgesia use at 12 months was also recorded. CKP was defined using the OKS pain score (PS) of ≤ 14 points at 12 months.Aims
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Aims. A large number of surgical operations are available to treat osteochondral defects of the knee. However, the knee
Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex. Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed.Aims
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Osseous invasion exhibited in soft-tissue sarcoma (STS) is recognized as a prognostic risk factor. Achieving a wide margin is the default surgical approach for local control. However, for STSs where the tumour is in contact with the adjacent cortex but without clear evidence of osseous invasion, such as medullary invasion, the question of whether bone resection can provide better local control or survival than more conservative sub-periosteal excision remains controversial. The aim of this study was to assess whether bone resection for thigh STS with cortical contact of the adjacent bone results in better local control and survival compared to sub-periosteal dissection, and to investigate the prognostic factors for clinical outcomes in STS. A retrospective cohort study was conducted on 142 patients with thigh STS exhibiting cortical contact but without medullary invasion, from May 2000 to May 2020. Patients underwent either composite bone resection or sub-periosteal excision. Demographics, clinical outcomes, and functional outcomes were compared between the two groups. Additionally, Cox regression analysis was used to analyze risk factors for local recurrence.Aims
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Revision hip arthroplasty for femoral stem loosening remains challenging due to significant bone loss and deformities requiring specialized revision stems. The aim of this study was to evaluate the clinical and radiological outcomes, and survival, of a consecutive series of femoral revisions performed using a primary cementless stem with tapered geometry and rectangular cross-section at medium-term follow-up. We retrospectively evaluated 113 patients (115 hips) with intraoperative Paprosky type I (n = 86) or II (n = 29) defects, who underwent femoral revision with Alloclassic Zweymüller SL stem for one-stage aseptic revision or two-stage septic revision from January 2011 to December 2020. The mean follow-up was 77.9 months (SD 33.8). Nine patients were lost to follow-up (deceased or not available), leaving 104 patients (106 hips) for the clinical and radiological analysis. Clinical assessment was performed with Harris Hip Score (HHS) and visual analogue scale (VAS) before surgery and at final follow-up.Aims
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Valgus subsidence of uncemented tibial components following medial unicompartmental knee arthroplasty (UKA) poses a challenge in the early postoperative phase, necessitating a comprehensive understanding of its prevalence, risk factors, and impact on patient outcomes. This prospective multicentre study analyzed 97 knees from 90 patients undergoing UKA across four participating hospitals. A standardized surgical technique was employed uniformly by all participating surgeons. Postoperative evaluations were conducted preoperatively, and one day, four weeks, three months, and one year postoperative, encompassing weightbearing radiographs, bone mineral density assessments, and clinical outcome reports using the Forgotten Joint Score and Oxford Knee Score. Statistical analyses, including non-parametric correlation analysis using the Kendall correlation coefficient and Mann-Whitney U test, were performed to explore associations between subsidence and various patient-related or radiological parameters.Aims
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Unicompartmental knee arthroplasty (UKA) is associated with an accelerated recovery, improved functional outcomes, and retention of anatomical knee kinematics when compared to manual total knee arthroplasty (mTKA). UKA is not universally employed by all surgeons as there is a higher revision risk when compared to mTKA. Robotic arm-assisted (ra) UKA enables the surgeon to position the prosthesis more accurately when compared to manual UKA, and is associated with improved functional outcomes and a lower early revision risk. Non-randomized data suggests that, when compared to mTKA, raUKA has a clinically meaningful greater functional benefit. This protocol describes a randomized controlled trial that aims to evaluate the clinical and cost-effectiveness of raUKA compared to mTKA for individuals with isolated medial compartment osteoarthritis (OA). The total versus robotic-assisted unicompartmental knee arthroplasty (TRAKER) trial is a patient- and assessor-blinded, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary knee arthroplasty for primary medial compartment OA at a single NHS hospital (ClinicalTrials.gov NCT05290818). Participants will be randomly allocated on a 1:2 basis to either raUKA or mTKA, respectively. The primary analysis will compare the Oxford Knee Score (OKS) six months after surgery. Secondary outcomes measured at three, six, and 12 months include the OKS, Forgotten Joint Score, patient expectations, EuroQol five-dimension questionnaire (EQ-5D), and EQ-visual analogue scale (EQ-VAS), patient satisfaction, range of motion, postoperative complications, need for further surgery, resource use, and financial costs. Cost-effectiveness will be measured over a ten-year time span. A total of 159 patients will be randomized (n = 53 raUKA vs n = 106 mTKA) to obtain 80% power to detect a five-point difference in OKS between the groups six months after surgery.Aims
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Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system. PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials.Aims
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Over time, the locking mechanism of Modular Universal Tumour and Revision System (MUTARS) knee arthroplasties changed from polyethylene (PE) to polyether-ether-ketone Optima (PEEK) and metal-on-metal (MoM) in an attempt to reduce the risk of mechanical failure. In this study, we aimed to assess the cumulative incidence of locking mechanism revision for symptomatic instability by type of material, and assess potential associated risk factors. The MUTARS Orthopaedic Registry Europe was used for a retrospective review of 316 patients (54% male (n = 170), median age 44 years (IQR 23 to 61)) who underwent a MUTARS knee arthroplasty for oncological indications between December 1995 and January 2023. The minimum follow-up was 12 months, and the median follow-up was 7.9 years (IQR 3.3 to 13.0). A competing risk model was used to estimate the cumulative incidence of first locking mechanism revision with death and revision for any other reason as competing events. Possible risk factors were assessed employing a univariate cause-specific hazards regression model.Aims
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While cementless fixation offers potential advantages over cemented fixation, such as a shorter operating time, concerns linger over its higher cost and increased risk of periprosthetic fractures. If the risk of fracture can be forecasted, it would aid the shared decision-making process related to cementless stems. Our study aimed to develop and validate predictive models of periprosthetic femoral fracture (PPFF) necessitating revision and reoperation after elective total hip arthroplasty (THA). We included 154,519 primary elective THAs from the Swedish Arthroplasty Register (SAR), encompassing 21 patient-, surgical-, and implant-specific features, for model derivation and validation in predicting 30-day, 60-day, 90-day, and one-year revision and reoperation due to PPFF. Model performance was tested using the area under the curve (AUC), and feature importance was identified in the best-performing algorithm.Aims
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