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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Performance indicators are increasingly used to evaluate the quality of healthcare provided to patients with a hip fracture. The aim of this review was to map the variety of performance indicators used around the world and how they are defined. We present a mixed methods systematic review of literature on the use of performance indicators in hip fracture care. Evidence was searched through 12 electronic databases and other sources. A Mixed Methods Appraisal Tool was used to assess methodological quality of studies meeting the inclusion criteria. A protocol for a suite of related systematic reviews was registered at PROSPERO (CRD42023417515).Aims
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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:
Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing muscle regeneration, disrupting the normal structure of skeletal muscle extracellular matrix, and contributing to neuromuscular junction lesion and vascular disorders. This article reviews studies focused on the pathogenic role of AGEs in sarcopenia and the potential mechanisms of the detrimental effects, aiming to provide new insights into the pathogenesis of sarcopenia and develop novel methods for the prevention and therapy of sarcopenia. Cite this article:
Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments. Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed.Aims
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The T1 pelvic angle (T1PA) provides a consistent global measure of sagittal alignment independent of compensatory mechanisms and positional changes. However, it may not explicitly reflect alignment goals that correlate with a lower risk of complications. This study assessed the value of T1PA in achieving sagittal alignment goals in patients with an adult spinal deformity (ASD). Patients aged ≥ 18 years who had undergone surgery for ASD and had complete baseline data and at least two-year postoperative, radiological, and health-related quality of life follow-up were included. A total of 596 patients met the inclusion criteria (mean age 61.5 years (SD 13.4); 78.8% females; mean BMI 27.8 kg/m2 (SD 5.9); mean Charlson Comorbidity Index 1.9 (SD 1.8)). The primary outcome was development of mechanical complications. Cohorts were based on postoperative T1PA (T1PA < 10° or > 30° = unfavourable vs T1PA 10° to 30° = favourable). Adjustments for confounders with separate analyses were done using multivariable logistic regression analysis.Aims
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The use of patient-reported outcome measures (PROMs) to assess the outcome after total knee (TKA) and total hip arthroplasty (THA) is increasing, with associated regulatory mandates. However, the robustness and clinical relevance of long-term data are often questionable. It is important to determine whether using long-term PROMs data justify the resources, costs, and difficulties associated with their collection. The aim of this study was to assess studies involving TKA and THA to determine which PROMs are most commonly reported, how complete PROMs data are at ≥ five years postoperatively, and the extent to which the scores change between early and long-term follow-up. We conducted a systematic review of the literature. Randomized controlled trials (RCTs) with sufficient reporting of PROMs were included. The mean difference in scores from the preoperative condition to early follow-up times (between one and two years), and from early to final follow-up, were calculated. The mean rates of change in the scores were calculated from representative studies. Meta-analyses were also performed on the most frequently reported PROMs.Aims
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Aims. Adult spinal deformity (ASD) surgery can reduce pain and
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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The use of arthroscopy of the hand and wrist has recently increased sharply in the elective setting and this, not surprisingly, has been followed by an increasing use in the trauma setting. Advocates for the use of arthroscopy in these patients cite the improved assessment of the displacement and reduction of fractures and the early diagnosis of associated injuries, while others temper this with concerns about increased operating time and possible complications. The data relating to patient-reported benefits and costs are limited. The aim of this review was to discuss the current available literature for the use of arthroscopy in the management of injuries of the hand and wrist. Cite this article:
One of the most common patient-reported complaints following intramedullary nailing (IMN) of tibial shaft fractures is anterior knee pain reported by 10% to 80% of patients. The present study aimed to compare the 12-month Knee injury and Osteoarthritis Outcome Score (KOOS) sport and recreation activities subscale (sport/rec) scores after IMN with external ring fixation (RF) to adult patients with tibial shaft fractures. This study was a pragmatic multicentre randomized, non-blinded trial, with two-group parallel design. Included were adult patients (aged ≥ 18 years) presenting with an acute tibial shaft fracture deemed operable with an intramedullary nail. The primary outcome was the KOOS sport/rec, ranging from 0 (worst score) to 100 (best score) at 12-month follow-up. Secondary outcomes included the Foot and Ankle Outcome Score (FAOS), health-related quality of life assessed by EuroQol five-dimension five-level health questionnaire, and pain scores.Aim
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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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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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The February 2025 Foot & Ankle Roundup360 looks at:Percutaneous Zadek osteotomy for insertional Achilles tendinopathy; Association of extraosseous arterial diameter with talar dome osteochondral lesions; Autologous chondrocyte implantation for osteochondral lesions of the talus; Symptomatic thromboembolism and mortality in foot and ankle surgery in the UK; Corticosteroid or hyaluronic acid in Morton’s neuroma?
The February 2025 Wrist & Hand Roundup360 looks at: Delayed fixation of distal radial fractures beyond three weeks increases the odds of reoperation; A systematic review of management options for symptomatic scaphometacarpal impingement after trapeziectomy; Diagnosing occult scaphoid fractures: an art or science?; Dual-mobility trapeziometacarpal arthroplasty shows promising outcomes but lacks long-term evidence; 3D-printed titanium scaphoid implant offers a promising alternative for unreconstructable scaphoid nonunion; Lidocaine co-injection reduces pain intensity during corticosteroid injections in hand and wrist conditions; Long-term outcomes of PyroDisk arthroplasty for trapeziometacarpal osteoarthritis; Evaluating the impact of COVID-19 on hand surgery practices: adaptations and missed opportunities.
