Aims. To identify the minimum set of outcomes that should be collected in clinical practice and reported in research related to the care of children with idiopathic congenital talipes equinovarus (CTEV). Methods. A list of outcome measurement tools (OMTs) was obtained from the literature through a systematic review. Further outcomes were collected from patients and families through a questionnaire and interview process. The combined list, as well as the appropriate follow-up timepoint, was rated for importance in a two-round Delphi process that included an international group of orthopaedic surgeons, physiotherapists, nurse practitioners, patients, and families. Outcomes that reached no consensus during the Delphi process were further discussed and scored for inclusion/exclusion in a final consensus meeting involving international stakeholder representatives of practitioners, families, and patient charities. Results. In total, 39 OMTs were included from the systematic review. Two additional OMTs were identified from the interviews and questionnaires, and four were added after round one Delphi. Overall, 22 OMTs reached ‘consensus in’ during the Delphi and two reached ‘consensus out’; 21 OMTs reached ‘no consensus’ and were included in the final consensus meeting. In all, 21 participants attended the consensus meeting, including a wide diversity of clubfoot practitioners, parent/patient representative, and an independent chair. A total of 21 outcomes were discussed and voted upon; six were voted ‘in’ and 15 were voted ‘out’. The final COS document includes nine OMTs and two existing outcome scores with a total of 31 outcome parameters to be collected after a minimum follow-up of five years. It incorporates static and dynamic clinical findings, patient-reported outcome measures, and a definition of CTEV
Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or
Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre. A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes.Aims
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Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the For the haematogenous infection, Aims
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The aim of this study was to gain an agreement on the management of idiopathic congenital talipes equinovarus (CTEV) up to walking age in order to provide a benchmark for practitioners and guide consistent, high-quality care for children with CTEV. The consensus process followed an established Delphi approach with a predetermined degree of agreement. The process included the following steps: establishing a steering group; steering group meetings, generating statements, and checking them against the literature; a two-round Delphi survey; and final consensus meeting. The steering group members and Delphi survey participants were all British Society of Children’s Orthopaedic Surgery (BSCOS) members. Descriptive statistics were used for analysis of the Delphi survey results. The Appraisal of Guidelines for Research & Evaluation checklist was followed for reporting of the results.Aims
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Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set. A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.Aims
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The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital.Aims
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Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach. Cite this article:
CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.Aims
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Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis.Aims
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Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.Aims
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To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective. We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded.Aims
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To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity. Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation.Aims
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To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms. Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay.Aims
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Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
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Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).Aims
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To analyze outcomes reported in studies of Ponseti correction of idiopathic clubfoot. A systematic review of the literature was performed to identify a list of outcomes and outcome tools reported in the literature. A total of 865 studies were screened following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 124 trials were included in the analysis. Data extraction was completed by two researchers for each trial. Each outcome tool was assigned to one of the five core areas defined by the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT). Bias assessment was not deemed necessary for the purpose of this paper.Aims
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To determine if the results of treatment of adolescents with coccydynia are similar to those found in adults. Adult patients with coccydynia may benefit from injection therapy or operative treatment. There is little data evaluating treatment results in adolescents. We have treated adolescent patients similarly to adults and compared the outcomes. Overall, 32 adolescents with coccydynia were treated at our institution during a seven-year period; 28 responded to final follow-up questionnaires after a minimum of one year, 14 had been treated with only injection therapy, and 14 had been operated with coccygectomy. We collected data with regards to pain while sitting, leaning forward, rising from a sitting position, during defecation, while walking or jogging, and while travelling in trains, planes, or automobiles. Pain at follow-up was registered on a numeric pain scale. Each adolescent was then matched to adult patients, and results compared in a case control fashion. The treatment was considered successful if respondents were either completely well or much better at final follow-up after one to seven years.Aims
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This study aims to define a set of core outcomes (COS) to allow consistent reporting in order to compare results and assist in treatment decisions for idiopathic clubfoot. A list of outcomes will be obtained in a three-stage process from the literature and from key stakeholders (patients, parents, surgeons, and healthcare professionals). Important outcomes for patients and parents will be collected from a group of children with idiopathic clubfoot and their parents through questionnaires and interviews. The outcomes identified during this process will be combined with the list of outcomes previously obtained from a systematic review, with each outcome assigned to one of the five core areas defined by the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT). This stage will be followed by a two round Delphi survey aimed at key stakeholders in the management of idiopathic clubfoot. The final outcomes list obtained will then be discussed in a consensus meeting of representative key stakeholders.Aims
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Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
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