Introduction

recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”.

Purpose: Glucocorticoids (GCs) are widely prescribed drugs in a large variety of diseases. Their use are strongly influenced by their associated negative side effects. Bone-related effects are mainly osteoporosis and osteonecrosis (ON). Despite the strong link between GCs and ON, the pathogenic mechanisms by which GCs cause ON are still unclear. Cumulative evidence shows that dysfunction or activation of endothelial cells (ECs) play an important role in ON.

Method: In this study, we investigated the influence of dexamethasone (Dex) on the Tumor Necrosis Factor-alpha [TNF-alpha] or Lipopolysaccharide [LPS] or Thrombin [IIa] -stimulated Human Umbilical Vein Endothelial Cells (HUVEC). We examined the molecular expression of 9 candidate genes (E-selectin [E-Sel], Intracellular adhesion molecule-1 [ICAM-1], Plasminogen activator inhibitor-1 [PAI-1], Tissue Factor [TF], Tissue plasminogen activator [t-PA], Urokinase plasminogen activator [u-PA], Vascular adhesion molecule-1 [VCAM-1], Von Willebrand Factor [vWF] and Thrombomodulin [THBD]) by real-time PCR. Live cell number of HUVEC under exposure to Dex was also assayed by viability test. All experiments were performed in triplicates and Standard error of the mean (SEM) was obtained.

Results: We showed that Dex alone significantly induced the expression of E-Sel, ICAM-1, TF, VCAM-1 and VWF while downregulating THBD and U-PA expression. Our results also showed a significant priming effect of Dex on E-Sel and TF inflammatory-mediated induction by TNF-alpha and LPS respectively. Comparable results were obtained from Northern Blot analysis; results from FACS analysis and Functional assays will be presented at the meeting.

Conclusion: Our observations suggest a procoagulant activity of Dex on HUVEC. We also observed a priming activity of Dex on E-Sel and TF inflammatory-mediated induction. These results suggest a potential endothelial cell activation mechanism and subsequent microvascular thrombosis in glucocorticoid-induced ON.

Objective

Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery.

Summary Statement. The incidence of osteonecrosis was significantly lower in the anti-vasospasm agent group (32%) than that in the control group (75%). Vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis. Introduction. A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. It has recently been reported that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) is considered to be involved in the possible pathogenesis of various cardiovascular disorders as well as cerebral vasospasm. We examined the effects of fasudil (Rho-kinase inhibitor), an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits. Materials & Methods. One group of rabbits received 15 mg/kg of fasudil intravenously, which were then injected once intramuscularly with 20 mg/kg of methylprednisolone (n = 33, MF group), and one received methylprednisolone alone as a control (n = 28, M group). Eight rabbits from each group were sacrificed 24 hour after the methylprednisolone injection to analyze them by immunohistochemical staining, a Western blotting analysis. Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the incidence of osteonecrosis. Results. The incidence of osteonecrosis was significantly lower in the MF group (32%) than that in the M group (75%) (P < 0.01). Immunohistochemically, endothelin. A. -receptor (ET. A. Rc) expressions levels were decreased in the smooth muscle of the bone marrow in the MF group in comparison to that in the M group. In the M group, the average relative phospho-myosin light chain (p-MLC) expression level in the bone marrow tissue was significantly higher than that observed in the MF group (P < 0.01). In the MF group, the average relative total-eNOS expression level as well as the average relative phospho-eNOS (p-eNOS) expression level was almost 1.5 times higher than that observed in the M group (P < 0.05). The eNOS expressions levels in both serum and bone marrow in the MF group were significantly higher than those in the M group (P < 0.05). Discussion/Conclusion. The potential mechanisms resulting in vasospasm include the increased release of vasoconstrictors or increased sensitivity to these vasoconstrictors. ET-1 has been demonstrated to cause vascular smooth muscle cell constriction via ET. A. Rc stimulation. The expression of ET. A. Rc in rabbits treated with methylprednisolone plus fasudil (MF group) decreased in comparison with that in rabbits treated with the methylprednisolone alone (M group). In this study, both the eNOS and p-eNOS expressions levels in the M group were decreased in comparison to those observed in the MF group. A previous study suggested that high-dose steroid administration causes the overproduction of reactive oxygen species, and thereby perturbs nitric oxide (NO) availability in the vascular endothelium, leading to vascular endothelial dysfunction in patients receiving high-dose steroid therapy. Considering the pathogenesis of the development of osteonecrosis, we speculate that endothelial dysfunction may thus be a preliminary condition leading to the vasospasm. In conclusion, this study indicates that vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis and that the anti-vasospasm agents seem to decrease the incidence of steroid-induced osteonecrosis

The aim of this study was to examine the effects of cement in total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. A total of 36 patients were recruited, with 18 in each of the cemented and uncemented groups. Both groups were matched for age, sex and body mass index. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF□?, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. The only variable to demonstrate a significant difference between the two groups was the CD1442a count. There was a significant difference in the first 24 hours (p=0.00) and from day 1 to day 7 (p=0.02). Our study suggests that the use of bone cement causes a significant rise in CD1442a count which has been linked to atherothrombosis and acute coronary syndromes. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively. However more research required in this field to delineate the exact pathways involved

Background. Despite the suggestion by Virchow in 1856 that thrombosis was the result of venous stasis, endothelial dysfunction and hypercoagulability there are some fundamental questions which remain to be answered. The published studies fail to provide specific details such as cast type and anatomical location of the thrombosis, but instead focus on the incidence of VTE and which chemical thromboprophylaxis is most effective. Previous studies of VTE in trauma patients have involved small numbers of patients and have not look at the risk medium to long term risk. Most importantly they have not looked at the site of the VTE. This makes interpretation of the link between cast and VTE even more complex. Methodology. We analysed 1479 consecutive trauma cast applications and the incidence of symptomatic VTE in the six months following the injury. The diagonosis, cast type and site of the VTE was recorded. Results. The overall incidence of DVT was 2.5% (2.2% distal and 0.3% proximal), 50% occured inthe first 3 weeks, the rest were between 6–13 weeks. The incidence of PE was 0.7%, there was 1 death due to PE. Achilles tendon injury was a statistically significant risk factor, there were no other conditions with a specific risk. There was no difference between above and below knee cast immobilisation. However all symptomatic DVTs occured in the casted leg. Discussion. This is the first study to look at long term VTE risk and the site of thrombosis, these findings have implications for VTE prophylaxis. It would appear that the risk of developing symptomatic VTE extends beyound the currently advised treatment period. It also suggests that venous stasis and endothelial damage are more important that hypercoagulability in the development of VTE after cast treatment for trauma. We recommend a programme of exercises within the cast to reduce this risk

Aim. To examine the effects of total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. Methods. All patients undergoing an elective uncemented total knee arthroplasty at a district general hospital were approached at the pre-assessment clinic. The study was explained and the patients were enrolled into the study following written consent. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF??, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. Results. Significant rises were seen with vWF, tPA and sCD40L levels up to day 7 (p= 0.01, 0.00. 0.00 respectively). IL6, e-selectin and TNF? levels were also significantly raised up to day 7 (p= 0.017, 0.031, 0.00). Analysis of the flow cytometry data revealed significant rises in the expression of CD40 (p= 0.006) and CD14/CD42a (P= 0.013) on monocytes over the same time period. Conclusion. Our study strongly suggests that patients undergoing an uncemented total knee arthroplasty provokes the release of vasoactive substances within the vasculature. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively as well as a potential increased risk of arterial thrombosis and sequelae from atherosclerotic plaque rupture

The beneficial effects of insulin in the maintenance of normoglycaemia in non-diabetic myocardial infarct and intensive care patients have recently been reported. Hyperglycaemia and neutrophilia have been shown to be independent prognostic indicators of poor outcome in the traumatised patient. The role of insulin and the maintenance of normoglycaemia in the trauma patient have as yet not been explored. We hypothesised that through the already described anti-inflammatory effects of insulin and the maintenance of normoglycaemia, that neutrophil activation and endothelial dysfunction would be attenuated, in the injured patient. This might result in less adult respiratory distress syndrome (ARDS) and multi-organ dysfunction and therefore less morbidity and mortality for the trauma patient. Materials and Methods: To study this we used a previously validated rodent trauma model. There were 2 groups, both groups underwent bilateral femur fracture and 15% blood loss via cannulation and aspiration of the external jugular vein. The treatment group immediately receive subcutaneous insulin according to a recently identified sliding scale, and thereafter subcutaneous boluses, dependent on half hourly blood sugar estimations. The control group received the same volume of normal saline half hourly, subcutaneously. The animals were maintained under anaesthetic for 4 hours from injury via inhaled halothane and oxygen. Core temperature and 0. 2. saturations were recorded throughout. At 4 hours, each animal underwent midline laparotomy and cannulation of the IVC for blood sampling for full blood counts, lactate levels and for flow cytometry to estimate neutrophil activation via respiratory burst and CD11b upregulation. Bronchoalveolar lavage (BAL) was performed for neutrophil content and total protein estimation. The left lower lobe was harvested for wet-dry lung weight ratios. Results: While 0. 2. saturations were equal throughout in both groups, respiratory rates were persistently elevated in the controls. Wet:Dry lung ratios and lactate levels were reduced in the insulin treated animals compared to controls. There were similarly fewer neutrophils in the BAL specimens of the insulin treated animals (p< 0.05). Conclusions: Insulin reduces leukocyte lung sequestration in the injured animal model. This work confirms that insulin may have a role in reducing ARDS in the trauma patient, be that as an anti-inflammatory agent or anti-hyperglycaemic agent, or both, indicating that outcomes might be improved by treating hyperglycaemic trauma patients with insulin. Further work needs to be done to elucidate its exact mechanism of action and role in the injured patient

Aims

This study aimed to investigate the risk of postoperative complications in COVID-19-positive patients undergoing common orthopaedic procedures.

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Aims

As the first wave of the COVID-19 pandemic began to dip, restarting elective orthopaedics became a challenge. Protocols including surgery at ‘green’ sites, self-isolation for 14 days, and COVID-19 testing were developed to minimize the risk of transmission. In this study, we look at risk effects of 14-day self-isolation on the incidence of venous thromboembolism (VTE) in our green site hospital among patients undergoing total joint replacement (TJR).

Aims

The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes.

Objectives

Using a simple classification method, we aimed to estimate the collapse rate due to osteonecrosis of the femoral head (ONFH) in order to develop treatment guidelines for joint-preserving surgeries.

Aims

The aim of this study was to utilize a national paediatric inpatient database to determine whether obesity influences the operative management and inpatient outcomes of paediatric limb fractures.

Aims

Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA.

Objectives

The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models.