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. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
Methods
The aim of this study is to report the long-term outcomes of instrumented femoral revisions with impaction allograft bone grafting (IBG) using the X-change femoral revision system at 30 years after introduction of the technique. We updated the outcomes of our previous study, based on 208 consecutive revisions using IBG and the X-change femoral revision system in combination with a cemented polished stem, performed in our tertiary care institute between 1991 and 2007. Kaplan-Meier survival analyses were used to determine the survival rate of the revisions with endpoint revision for any reason and aseptic loosening. Secondary outcomes were radiological loosening and patient-reported outcome measures.Aims
Methods
Global literature suggests that female surgical trainees have lower rates of independent operating (operative autonomy) than their male counterparts. The objective of this study was to identify any association between gender and lead/independent operating in speciality orthopaedic trainees within the UK national training programme. This was a retrospective case-control study using electronic surgical logbook data from 2009 to 2021 for 274 UK orthopaedic trainees. Total operative numbers and level of supervision were compared between male and female trainees, with correction for less than full-time training (LTFT), prior experience, and time out during training (OOP). The primary outcome was the percentage of cases undertaken as lead surgeon (supervised and unsupervised) by UK orthopaedic trainees by gender.Aims
Methods
cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.Aims
Methods
The Open-Fracture Patient Evaluation Nationwide (OPEN) study was performed to provide clarity in open fracture management previously skewed by small, specialist centre studies and large, unfocused registry investigations. We report the current management metrics of open fractures across the UK. Patients admitted to hospital with an open fracture (excluding phalanges or isolated hand injuries) between 1 June 2021 and 30 September 2021 were included. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture software. All domains of the British Orthopaedic Association Standard for Open Fracture Management were recorded.Aims
Method
Loosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening. A systematic search was undertaken using the Cochrane methodology in three online databases: MEDLINE, Embase, and CINAHL. Studies were screened against predetermined criteria, and data were extracted. Available National Joint Registries in the Network of Orthopaedic Registries of Europe were also screened. A random effects model meta-analysis was undertaken.Aims
Methods
Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.Aims
Methods
Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.Aims
Methods
Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.Aims
Methods
Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps. Cite this article:
The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion. From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective.Aims
Methods
To explore individuals’ experience of a scaphoid waist fracture and its subsequent treatment. A purposive sample was created, consisting of 49 participants in the Scaphoid Waist Internal Fixation for Fractures Trial of initial surgery compared with plaster cast treatment for fractures of the scaphoid waist. The majority of participants were male (35/49) and more younger participants (28/49 aged under 30 years) were included. Participants were interviewed six weeks or 52 weeks post-recruitment to the trial, or at both timepoints. Interviews were semistructured and analyzed inductively to generate cross-cutting themes that typify experience of the injury and views upon the treatment options.Aims
Methods
The aim of this study was to compare the cost-effectiveness of cemented hemiarthroplasty (HA) versus hydroxyapatite-coated uncemented HA for the treatment of displaced intracapsular hip fractures in older adults. A within-trial economic evaluation was conducted based on data collected from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized controlled trial in the UK. Resource use was measured over 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from the NHS and personal social service perspective. Methodological uncertainty was addressed using sensitivity analysis, while decision uncertainty was represented graphically using confidence ellipses and cost-effectiveness acceptability curves.Aims
Methods
Aims. To evaluate safety outcomes and patient satisfaction of the re-introduction of elective orthopaedic surgery on ‘green’ (non-COVID-19) sites during the COVID-19 pandemic. Methods. A strategy consisting of phased relaxation of clinical comorbidity criteria was developed. Patients from the orthopaedic waiting list were selected according to these criteria and observed recommended preoperative isolation protocols. Surgery was performed at green sites (two local private hospitals) under the COVID-19 NHS contract. The first 100 consecutive patients that met the Phase 1 criteria and underwent surgery were included. In hospital and postoperative complications with specific enquiry as to development of COVID-19 symptoms or need and outcome for COVID-19 testing at 14 days and six weeks was recorded. Patient satisfaction was surveyed at 14 days postoperatively. Results. There were 54 females and 46 males (mean age 44 years, mean body mass index (BMI) 25.6 kg/m. 2. ). In all, 56 patients underwent major orthopaedic procedures. There were no exclusions. One patient had a postoperative positive SARS-CoV-2 RT-PCR test but had no typical symptoms of COVID-19 infection and no clinical sequelae. 99% of patients were satisfied with the process and 98% would recommend undergoing elective orthopaedic surgery in the study period. Conclusion. In an environment with appropriate infrastructure, patient selection, isolation, screening, and testing, elective orthopaedic surgery is safe during the COVID-19 pandemic, and associated with high patient satisfaction. Further follow-up is required to establish that safety is maintained as the clinical restrictions are eased with the phased
Aims. Our objective is to describe our early and mid-term results with the use of a new simple primary knee prosthesis as an articulating spacer in planned two-stage management for infected knee arthroplasty. As a second objective, we compared outcomes between the group with a retained first stage and those with a complete two-stage revision. Methods. We included 47 patients (48 knees) with positive criteria for infection, with a minimum two-year follow-up, in which a two-stage
Cite this article:
