MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. . Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment. Cite this article: Bone Joint J 2015; 97-B:1144–51

Injuries to growth plates may initiate the formation of reversible or irreversible bone-bridges, which may lead to partial or full closure of the growth plate resulting in bone length discrepancy, axis deviation or joint deformity. Blood vessels and vascular invasion are essential for the formation of new bone tissue. The aim of our study was to investigate the spatial and temporal expression VEGF and its receptors R1 and R2 as well as the ingrowth of vessels in the formation of bone bridges in a rat physeal injury model. Quantitative Real Time - Polymerase Chain Reaction (qRT-PCR) was performed for Vascular Endothelial Growth Factor (VEGF) and its R1 and R2 receptors. Samples from the proximal epiphysis, physis and metaphysis of the tibial bone were prepared for immunohistochemical analysis to demonstrate the spatial expression of VEGF and its R1 and R2 receptors as well as laminin. Kinetic expression of VEGF and VEGF-R1 mRNA documented a tendency towards an expression increase on day 7. Histological analysis showed a haematoma containing bone fragments on day 1which was replaced by a bony bridge by day 14. This remodelled and consolidated by day 82. These trabeculae were accompanied by vessel formation. Expression of VEGF was observed on the bone fragments and the haematoma from day 1 through to day 82. Although VEGF-R1 was expressed at all time points the expression of VEGF-R2 was noted until the 14th day. Physeal bone bridge formation is a combination of both enchondral and intramembranous ossification. This is in part triggered by the bony debris observed within the lesion in the first few days. By washing this debris out the likelihood of bone bridge formation may be reduced. We recommend this practice when operating on the physis in order to avoid iatrogenic physeal bar formation

INTRODUCTION. There is increasing evidence for a multi-stage model of rotator cuff (RC) tendon tears, wherein healing is affected by tear size. The underlying pathophysiology however is not fully understood. Changes in the production and remodeling of the RC extracellular matrix (ECM) are likely to be important determinants of RC tendinopathy as they affect healing and the ability to bear loads. This study aimed to gain greater insight into size related tear pathogenesis by analyzing gene expression profiles from normal, small and massive RC tears. METHODS. The genetic profiles of 28 human RC tendons were analyzed using microarrays representing the entire genome. 11 massive and 5 small torn RC tendon specimens were obtained from tear edges intraoperatively, and compared to 12 age matched normal controls. Semiquantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemistry were performed for validation. RESULTS. Numerous insightful gene changes were detected. Key changes included upregulation of aggrecan in massive tendon tears compared to normal controls, but not in small tears (p < 0.05 and > 2-fold change). Matrix metallopeptidases (MMP)-3,-10,-12,-13,-15,-21,-25 and a disintegrin and metallopeptidase (ADAMs)-12,-15,-22 were significantly upregulated in tears. Aggrecan was upregulated in massive tendon tears but not in small tears. Amyloid was downregulated in the small and massive tear groups when compared to normals. BMP-5 was upregulated in small tears only when compared to normals. As part of the chemotaxis pathway, IL-3,-10,-13,-15,-18 were upregulated in tears, whereas downregulation of IL-1,-8,-11,-27, was seen. RT-PCR and immunohistochemistry confirmed altered gene expression. CONCLUSION. The gene profiles of normal, small and massive RC tear groups suggested they are biologically distinct groups. In addition to confirming altered gene expression in pathways reported in previous studies, this study has identified a number of novel pathways which are affected between the different tendon tear and normal groups. This study identified that RC tear pathogenesis is contributed to by ECM remodeling genes, chemotaxis genes, aggrecan and amyloid. Further investigation is required to determine whether some of these genes may potentially have a role as biomarkers of failure. Modulating these ECM pathways may be a useful treatment strategy for improving clinical outcomes

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This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

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Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era.

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Within the UK, around 70,000 patients suffer neck of femur (NOF) fractures annually. Patients presenting with this injury are often frail, leading to increased morbidity and a 30-day mortality rate of 6.1%. COVID-19 infection has a broad spectrum of clinical presentations with the elderly, and those with pre-existing comorbidities are at a higher risk of severe respiratory compromise and death. Further increased risk has been observed in the postoperative period. The aim of this study was to assess the impact of COVID-19 infection on the complication and mortality rates of NOF fracture patients.

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The primary aim was to assess the independent influence of coronavirus disease (COVID-19) on 30-day mortality for patients with a hip fracture. The secondary aims were to determine whether: 1) there were clinical predictors of COVID-19 status; and 2) whether social lockdown influenced the incidence and epidemiology of hip fractures.

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To determine whether there is any difference in infection rate at 90 days between trauma operations performed in laminar flow and plenum ventilation, and whether infection risk is altered following the installation of laminar flow (LF).