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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Aims. This study investigates the effectiveness and adequacy of the informed
Nonoperative treatment for developmental dysplasia of the hip (DDH) typically involves numerous in-person clinic visits, which can place a significant burden on healthcare services and patients’ families. We therefore aimed to establish and validate a pilot hybrid-virtual clinic to evaluate the clinical outcomes with the delivery of a comprehensive nonoperative treatment protocol for infant DDH to streamline care and minimize in-person visits. This was a prospective, single-centre, quality improvement (QI) study of infants with DDH who underwent a comprehensive nonoperative treatment protocol in a unified multidisciplinary infant hip clinic from December 2022 to October 2023. Practice changes were made to our published nonoperative treatment protocol, where specific in-person follow-up visits were replaced with virtual appointments, and a dedicated institutional infant hip clinic email was created for caregiver inquiries.Aims
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Diagnostic wrist arthroscopy is considered the gold standard for evaluating wrist joint complaints. Although this tool is often used to diagnose and stage scapholunate ligament (SLL) lesions, reports about the possible findings and their clinical relevance are scarce. Therefore, this study describes the patient characteristics, arthroscopic findings, and treatment of patients who underwent diagnostic arthroscopy for suspected SLL injury. We conducted a retrospective cohort study of patients who underwent diagnostic wrist arthroscopy due to suspicion of a SLL lesion based on medical history, physical examination, and imaging. We systematically gathered arthroscopic findings and complications.Aims
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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. 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).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 evaluate patient-reported outcomes three months after treatment of metacarpal and phalangeal fractures or dislocations, and to identify factors that are associated with worse patient-reported outcomes. This cross-sectional, multicentre snapshot study included all adult patients with metacarpal and phalangeal fractures or dislocations during a three-month period between August and October 2020. The primary outcome was the Michigan Hand Outcomes Questionnaire (MHQ) three months after injury. The MHQ scores were compared to normative MHQ scores of 90 points of the affected hand of patients who sustained unilateral trauma derived from a previous study. Subgroup analyses were performed for the most common injury types. Multivariable linear regression was used to study associations between patient characteristics and worse MHQ scores.Aims
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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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To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.Aims
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Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients’ quality of life. A prospective study was conducted at a level 1 trauma centre between January 2020 and December 2022. In total, 56 patients participated, with quality of life assessed at five timepoints: one week preoperatively, and one, three, six, and 12 months postoperatively. Statistical analysis was performed using repeated measures analysis of variance (ANOVA) with adjusted post-hoc analysis.Aims
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To develop a multidisciplinary health research agenda (HRA) utilizing expertise from various disciplines to identify and prioritize evidence uncertainties in orthopaedics, thereby reducing research waste. We employed a novel, structured framework to develop a HRA. We started by systematically collecting all evidence uncertainties from stakeholders with an interest in orthopaedic care, categorizing them into 13 sub-themes defined by the Dutch Orthopaedic Association (NOV). Subsequently, a modified two-phased Delphi study (two rounds per phase), adhering to the Conducting and REporting DElphi Studies (CREDES) guideline, was conducted. In Phase 1, board members assessed the collected evidence uncertainties on a three-point Likert scale to confirm knowledge gaps. In Phase 2, diverse stakeholders, including orthopaedic surgeons, rated the confirmed knowledge gaps on a seven-point Likert scale. Panel members rated one self-selected sub-theme and two randomly assigned sub-themes. The results from Phase 2 were ranked based on the overall average score for each uncertainty. Finally, a focus group discussion with patient associations’ representatives identified their top-ranked uncertainty from a predefined consensus process, leading to the final HRA. An advisory board, the Federation of Medical Specialists, and the NOV research coordinator oversaw the process.Aims
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We aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis. Postmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher’s discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model.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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This study aimed to investigate whether the use of CT-based navigation enhances: 1) the accuracy of cup placement; and 2) the achievement rate of required range of motion (ROM). Additionally, we investigated the impact of using a large femoral head and dual-mobility liner on the achievement rates. This retrospective study analyzed 60 manual and 51 CT-based navigated primary total hip arthroplasties performed at a single facility. Postoperative CT scans and CT-based simulation software were employed to measure the cup orientation and to simulate the ROM. We compared the absolute errors for radiological inclination (RI) and radiological anteversion (RA) between the two groups. We also examined whether the simulated ROM met the required ROM criteria, defined as flexion > 110°, internal rotation > 30°, extension > 30°, and external rotation > 30°. Furthermore, we performed simulations with 36 mm femoral head and dual-mobility liner.Aims
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Aims. The Bracing Adolescent Idiopathic Scoliosis (BASIS) study is a randomized controlled non-inferiority pragmatic trial of ‘full-time bracing’ (FTB) compared to ‘night-time bracing’ (NTB) for the treatment of adolescent idiopathic scoliosis (AIS). We anticipated that recruiting patients to BASIS would be challenging, as it is a paediatric trial comparing two markedly different bracing pathways. No previous studies have compared the experiences of AIS patients treated with FTB to those treated with NTB. This qualitative study was embedded in BASIS to explore families’ perspectives of BASIS, to inform trial communication, and to identify strategies to support patients treated in a brace. Methods. Semi-structured interviews were conducted with parents (n = 26) and young people (n = 21) who had been invited to participate in BASIS at ten of the 22 UK paediatric spine services in hospitals recruiting to BASIS. Audio-recorded interviews were transcribed and analyzed thematically. Results. Families viewed their interactions with BASIS recruiters positively, but were often confused about core aspects of BASIS, such as the aims, expectations of bracing, and the process of randomization. Participants typically expressed a preference for NTB, but recruiters may have framed NTB more favourably. Patients and parents reported challenges wearing a brace, such as physical discomfort, feelings of self-consciousness, difficulty participating in physical activities, and strain on financial resources to support brace use. Patients in FTB reported more pronounced challenges. While families valued health professional support, they felt there was a lack of social, emotional, and school support, and relied on online resources, as well private counselling services to address this need. Conclusion. The findings informed the development of resources and strategies, including guidance for schools and the recommendations in this paper, to support patients to wear NTB and FTB as prescribed. The results indicated opportunities for recruiters to enhance trial communication in ways that could improve informed
To establish cut-off values for lateral pubofemoral distance (PFD) measurements for detecting hip dysplasia in early (four days) and standard care (six weeks) screening for developmental dysplasia of the hip (DDH). All newborns, during a one-year period (October 2021 to October 2022), were offered a PFD ultrasound (US) examination in addition to the existing screening programme for DDH. Newborns who were referred for standard care hip US, suspected for DDH, received a secondary PFD US examination in conjunction with the standard care Graf/Harcke hip US examination. Receiver operating characteristic curves and empirically optimal cut-off values were calculated with a true positive defined as a Graf type ≥ IIc hip.Aims
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In this study, we aimed to evaluate incidence trends and potential risk factors associated with Perthes’ disease in Denmark, using publicly available data. Our population-based case-control study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,924,292 infants born between 1985 and 2016. We estimated age-specific incidence rates for four birth periods of equal duration (1985 to 1992, 1993 to 2000, 2001 to 2008, and 2009 to 2016) and investigated associations with perinatal conditions, congenital malformations, coagulation defects, autism spectrum disorders (ASD), and attention deficit hyperactivity disorders (ADHD).Aims
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Sagittal lumbar pelvic alignment alters with posterior pelvic tilt (PT) following total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH). The individual value of pelvic sagittal inclination (PSI) following rebalancing of lumbar-pelvic alignment is unknown. In different populations, PT regresses in a linear relationship with pelvic incidence (PI). PSI and PT have a direct relationship to each other via a fixed individual angle ∠γ. This study aimed to investigate whether the new PI created by acetabular component positioning during THA also has a linear regression relationship with PT/PSI when lumbar-pelvic alignment rebalances postoperatively in patients with Crowe type III/IV DDH. Using SPINEPARA software, we measured the pelvic sagittal parameters including PI, PT, and PSI in 61 patients with Crowe III/IV DDH. Both PSI and PT represent the pelvic tilt state, and the difference between their values is ∠γ (PT = PSI + ∠γ). The regression equation between PI and PT at one year after THA was established. By substituting ∠γ, the relationship between PI and PSI was also established. The Bland-Altman method was used to evaluate the consistency between the PSI calculated by the linear regression equation (ePSI) and the actual PSI (aPSI) measured one year postoperatively.Aims
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