Background

Low back pain can lead to neuroplastic changes in the central nervous system, known as nociplastic pain. As nociplastic pain may be provoked by premorbid sensory profiles, such profiles may be prognostic in the development of nociplastic pain over time.

Abstract

Introduction

Sensory profiles classified in Low Registration, Sensory Sensitive, Sensation Avoiding and Sensation Seeking may be used in patients with non-specific chronic low back pain (CLBP) to develop a more personalized treatment program. Although psychometric properties have not been studied up till now the Adult Adolescent Sensory Profile (AASP) can be used to measure sensory profiles in CLBP patients.

Purpose:

The reverse total shoulder arthroplasty (RTSA) was approved for use by the United States FDA in 2004. Since its introduction, its popularity for treating a number of shoulder conditions has grown considerably. However, many patients inquire about the potential to return to playing recreational golf, and at present there are no published data about how the RTSA prosthesis affects the golf swing. The purpose of this study is to evaluate the biomechanics of the golf swing in patients with RTSA, as well as the postoperative changes in handicap, driving distance, and holes played/week.

Chondrosarcoma responds poorly to adjuvant therapy and therefore, new targeted therapy is required. Animal models have been utilised to test therapeutic candidates, however clinically relevant, orthotopic models are lacking. The aim of this study was to develop such a model.

In vitro: two human chondrosarcoma cell lines, JJ012 and FS090, were compared with respect to proliferation, colony formation, invasion, MMP-2 and MMP-9 secretion, osteoclastogenesis, endothelial tube stimulation, and expression of the angiogenic factor VEGF, and the anti-angiogenic factor RECK on western blotting. In vivo: 20,000 cells (JJ012 or FS090) were injected either into the intramedullary canal of the mouse tibia (n=5 for each cell line), or into the tibial periosteum (n=5 for each cell line). Animals were measured, and x-rayed weekly. Once euthanised, tibias and lungs were preserved, embedded and sectioned to determine the presence of tumour and lung metastases.

In vitro: compared with FS090, JJ012 demonstrated significantly higher proliferative capacity at both day two and day four (p=0.017, and p=0.01). JJ012 had a significantly greater ability to invade Matrigel with an average number of 812.5 invading cells, versus 140.8 FS090 cells (p=0.0005). JJ012 readily formed colonies in collagen I, while FS090 formed none. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium. In vivo: tumours formed in the intratibial and periosteal groups injected with JJ012, whilst no mice injected with FS090 cells developed discernable tumours on physical inspection, caliper measurement or histological section. Periosteal tumours grew to three times the non-injected limb size by seven weeks, whereas intratibial injected limbs required 10 weeks to achieve the same extent of tumour growth. All JJ012 periosteal tumours resulted in lung micrometastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Lung metastases stained positive with Von Kossa and alizarin red stains, indicating a tendency for calcification, which is similar to metastases in the human disease. Sectioned tumour tissue demonstrated features of grade II-III chondrosarcoma. Similarities with the human disease were also noted on the X-ray, including endosteal scalloping, and cortical thickening.

Both intratibial and periosteal JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

Introduction and aims

After internal hemipelvectomy for malignant pelvic tumors, pelvic reconstruction is necessary for eventual weight bearing and ambulation. Non-vascularised, fibular grafts (NVFG) offer fast, and stable reconstruction, post- modified Enneking's type I and I/IV resection. This study aimed to evaluate the success of graft union and patient function after NVFG reconstruction.

Aims: RECK protein is involved in angiogenesis and matrix-metalloproteinase interaction. In common cancers RECK may exert tumour control, while in sarcomas, there is insufficient research to confirm this. Our study aims to investigate the role of RECK in osteo-sarcoma (OS) and chondrosarcoma (CS) angiogenesis, using clinical data and an in vitro angiogenesis assay.

Methods: Seven OS biopsy samples, 11 OS metastases and 24 samples of CS were stained for the RECK protein using immunohistochemistry. RECK expression in vessels supplying sarcoma tissue was semi-quantified using ImageProPlus software to determine staining density. RECK density in tumour vessels was compared with density in vessels of 18 normal tissues. The human endothelial cell line, HMEC-1, was cultured and then transfected with a plasmid containing the RECK gene. HMEC-1 cells over-expressing RECK were then distributed into wells containing 100% Matrigel. Formation of vessel-like structures was observed and photographed at 8 hours. Comparison was made with a non-transfected HMEC-1 group, and an empty vector transfected HMEC-1 group. Results: RECK is predominantly expressed in vessels supplying both sarcomas and less frequently in the tumour cells. RECK density in OS and CS primary tumour vessels was no different to normal vessels (p> 0.05). However there was a significantly higher RECK density in the vessels of OS metastasis tissue (0.76 ODU-optical density units), compared with primary OS vessels (0.57 ODU, p< 0.05), and normal vessels (0.56 ODU, p< 0.05).

The average number of tube formations in the RECK transfected HMEC-1 cells was 67.8, compared with 42 in the empty vector group (p=0.03) and 54.1 in the control group (p=0.03). The average maximal wall thickness of tube formations was 100.7um versus 77.4um in the empty vector group (p=0.04) and 83.0um in the control group (p=0.09).

Conclusions: RECK is upregulated in vessels supplying OS metastases compared to vessels in primary sarcoma and normal tissue, suggesting an active role in angiogenesis. Replication of these conditions in vitro using the HMEC-1 tube formation assay demonstrates the ability of RECK to increase vessel formation within a matrix while maintaining vessel wall thickness. In sarcoma RECK may have pro-angiogenic properties and could be an important part of the metastatic cascade.

The c-jun oncogene is upregulated in a variety of cancers. c-jun has also been implicated in liposar-coma (LS) progression. A DNAzyme degrading c-jun mRNA was tested for effects on LS progression in vitro. A novel orthotopic model for LS was established in mice enabling in vivo evaluation of c-jun downregulation.

The human LS cell line (SW872) was transfected with Dz13, (DNAzyme degrading c-jun mRNA). A scrambled DNAzyme group and a non-transfected group were used as controls. Apoptosis of SW872 was evaluated with TUNEL, caspase inhibitor and Fas/FasL assays. The orthotopic mouse model involved injecting the SW872 cell line intramuscularly within the hind limb of nude mice, and calculating tumour volume on a weekly basis for 13 weeks. The effects of Dz13 transfection were then tested in this clinically relevant model.

In LS cells, caspase-10, but not Fas/FasL, was found to be responsible for apoptosis in Dz13-mediated c-jun knockdown. In the mouse model, tumour take in vivo was 100%, with growths resembling high grade aggressive LS, palpable at 8 weeks. SW872 cells grew within the muscle resembling the undifferentiated high grade malignant component of LS growth. The c-jun DNA-zyme inhibited the growth of LS in this model with at least 60% reduction of tumour weight or 70% reduction of tumour volume in the Dz13 cohort of animals at the end of the experiment. Tumour volumes were different between Dz13 and the control groups of animals by eleven days following injection (P< 0.05).

DNAzyme-mediated c-jun knockdown induces apoptosis in LS cells via caspase-10. This corresponds with reduced tumour growth in vivo. Clinically, downregulation of c-jun may proffer an improved treatment outcome for LS. The new model for LS described here will enable better testing of agents with therapeutic potential against LS.

The human RECK protein is often downregulated in cancer, which is thought to contribute to tumour progression. The role of RECK is not yet characterised in bone sarcomas. This study aims to determine the effects of increased human RECK protein expression in osteo-sarcoma and chondrosarcoma using cell invasion assays and tumour size on MRI.

The human osteosarcoma and chondrosarcoma cell lines (SaOS-2 and OUMS27 respectively) were cultured then transfected with either a plasmid containing the RECK gene, an empty vector, or not at all (control). Cells were incubated at 37 degrees within invasion chambers containing 75% matrigel. Cells invading the matrigel were counted after 3 days. Fifteen chondrosar-coma samples were stained using immunohistochemistry for the human RECK protein. RECK expression was determined to be positive or negative. MRI scans corresponding to tumour samples were viewed and the maximal tumour diameter out of all planes was manually determined with computer imaging software.

The SaOS-2 invasion assay demonstrated increased cell invasion in the RECK transfected group with an average of 502.3 invading cells, compared with 129.0 for the empty vector group (p=0.004) and 100.6 for the control group (p=0.001).

The OUMS-27 invasion assay also demonstrated increased cell invasion in RECK transfected cells with an average of 86.3 invading cells compared with 22.8 in the empty vector group (p=0.067) and 67.8 in the control group (p=0.17).

For MRI data, there were two distinct groups with roughly equal distributions of tumour grades. Group 1 had maximal tumour diameters of less than 70 mm, compared to group 2, being greater than 70mm (p=0.0006). In group 1 only 1/8 demonstrated RECK expression, while in group 2, 5/7 were RECK positive (p=0.041 Fisher exact test).

RECK overexpression in osteosarcoma and chondro-sarcoma cell lines appears to increase invasive capacity, and stands in contrast to RECK data in carcinomas. Furthermore, RECK expression in patient chondrosar-coma samples is associated with larger tumours. RECK may therefore function differently in sarcoma.

Aim: To present the features and management of Pyogenic myositis in children.

Method: Two boys of four and six years old presented to our hospital within 6 months. The initial presentation suggested septic arthritis of the hip with pain, pyrexia and limited hip movements. Serum inflammatory markers were significantly raised. Hip rotation, however, was not severely reduced when examined carefully. Neither case demonstrated an effusion on ultrasound of the hip joint. The diagnosis was made on magnetic resonance imaging which produced striking images. Staphylococcus aureus was isolated from blood cultures in each case.

Results: Both children settled with antibiotic treatment alone. The bacterial strain in the second case was of a type requiring combination antibiotic therapy for effective treatment.

Conclusions: Pyogenic myositis is not a common diagnosis in previously healthy children presenting with hip pain. It is a condition that has been reported more frequently recently and which should have a higher profile since it is probably under-diagnosed. Urgent magnetic resonance imaging is recommended for atypical cases of musculoskeletal infection in children. Care must be taken to prescribe antibiotic therapy appropriate to the particular bacterial strain.