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
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This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.Aims
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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
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The rationale for exacting restoration of skeletal anatomy after unstable ankle fracture is to improve outcomes by reducing complications from malunion; however, current definitions of malunion lack confirmatory clinical evidence. Radiological (absolute radiological measurements aided by computer software) and clinical (clinical interpretation of radiographs) definitions of malunion were compared within the Ankle Injury Management (AIM) trial cohort, including people aged ≥ 60 years with an unstable ankle fracture. Linear regressions were used to explore the relationship between radiological malunion (RM) at six months and changes in function at three years. Function was assessed with the Olerud-Molander Ankle Score (OMAS), with a minimal clinically important difference set as six points, as per the AIM trial. Piecewise linear models were used to investigate new radiological thresholds which better explain symptom impact on ankle function.Aims
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The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months.Aims
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Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN). Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received.Aims
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Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were
The aim of this study was to longitudinally compare the clinical and radiological outcomes of anatomical total shoulder arthroplasty (aTSA) up to long-term follow-up, when using cemented keel, cemented peg, and hybrid cage peg glenoid components and the same humeral system. We retrospectively analyzed a multicentre, international clinical database of a single platform shoulder system to compare the short-, mid-, and long-term clinical outcomes associated with three designs of aTSA glenoid components: 294 cemented keel, 527 cemented peg, and 981 hybrid cage glenoids. Outcomes were evaluated at 4,746 postoperative timepoints for 1,802 primary aTSA, with a mean follow-up of 65 months (24 to 217).Aims
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Aims. The aim of this study was to examine the recent trend in delivery of arthroscopic subacromial decompression (ASD) in Scotland and to determine if this varies by geographical location. Methods. Scottish Morbidity Records were reviewed retrospectively between March 2014 and April 2018 to identify records for every admission to each NHS hospital. The Office of Population Censuses and Surveys (OPCS-4) surgical codes were used to identify patients undergoing primary ASD. Patients who underwent acromioclavicular joint excision (ACJE) and rotator cuff repair (RCR) were identified and grouped separately. Procedure rates were age and sex standardized against the European standard population. Results. During the study period the number of ASDs fell by 649 cases (29%) from 2,217 in the first year to 1,568 in the final year. The standardized annual procedure rate fell from 41.6 (95% confidence interval (CI) 39.9 to 43.4) to 28.9 (95% CI 27.4 to 30.3) per 100,000. The greatest reduction occurred between 2017 and 2018. The number of ACJEs rose from 41 to 188 (a 3.59-fold increase). The number of RCRs fell from 655 to 560 (-15%). In the year 2017 to 2018 there were four (28.6%) Scottish NHS board areas where the ASD rate was greater than 3 standard deviations (SDs) from the national average, and two (14.3%) NHS boards where the rate was less than 3 SDs from the national average. Conclusion. There has been a clear decline in the rate of ASD in Scotland since 2014. Over the same period there has been an increase in the rate of ACJE. The greatest decline occurred between 2017 and 2018, corresponding to the publication of epidemiological studies demonstrating a rise in ASD, and awareness of studies which questioned the benefit of ASD. This paper demonstrates the potential impact of information from epidemiological studies, referral guidelines, and well-designed large multicentre
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Aims. To establish whether there was a consensus among the members of the Hip Society (HS) on the role of direct anterior approach (DAA) contemporary primary total hip arthroplasty (THA). Methods. An online survey was sent to all 112 active and senior members of the HS, to which 71 members responded. The survey was constructed to determine whether they believed that evidence-based medicine proves, in modern clinical practice, that the DAA has significant benefits compared to risks when contrasted with other approaches. In addition, they were asked if they currently used the DAA. Results. While only 16.9% (12/71) of respondents had been trained in a generic anterior approach during residency, 49.3% (35/71) had used the DAA in their clinical practice in the past or were using it at the present time. Unexpectedly, 42.9% (15/35) of respondents who had used the DAA in the past had abandoned it by the time of this survey. Only 22.5% (16/71) of all respondents believed that evidence-based medicine proves that the DAA has significant benefits compared to risks in contrast to other approaches. Conclusion. A comprehensive literature review found only three prospective
The Cochrane Collaboration has produced three new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner. These are relevant to a wide range of musculoskeletal specialists, and include reviews in lateral elbow pain, osteoarthritis of the big toe joint, and cervical spine injury in paediatric trauma patients.