Periprosthetic Femoral Fractures around Primary Total Hip Replacements

Post-operative periprosthetic femoral fractures (POPFF) increase morbidity and mortality, and premature failure of hip replacements. POPFF is most likely after cementless femoral stem implantation and are caused by intraoperative and post-operative injury. Prevention of POPFF may be possible by modifying implant selection, design and use. Propensity matched survival analysis of 4831 intraoperative periprosthetic femoral fractures (IOPFF) from the National Joint Registry of England, Wales and the Isle of Man (NJR) identified increased risk of POPFF revision and mortality when compared to propensity matched controls. IOPFF risk-factor modelling using 793977 primary total hip replacements identified that cementless femoral implants doubled the risk of any IOPFF, but particularly calcar and shaft fractures. A novel design-linked analysis of 349161 cementless hip replacements from the NJR identified stem features which were associated with increased risk of POPFF within 90-days, including: collarless design, mineralised and porous coatings, and triple-tapered stem bodies. A novel manual segmentation method to analyse POPFF fracture patterns was developed and used to analyse a series of 125 cases from four large UK centres. This analysis demonstrated that POPFF within 90 days occurred almost exclusively around the femoral stem, probably as a result of rotational and axial forces. Experimental simulation of early POPFF in paired cadaveric femurs established that the force required to fracture was increased when a calcar collar was present. Further testing revealed that the increased fracture resistance during simulation was dependent on calcar-collar contact and was most likely when the initial separation was 1 mm or less. A strong relationship between femoral implant design and risk of subsequent POPFF exists. The ability to associate specific design features with clinical outcomes and ratify the findings with experimental methods will help to develop this field further and improve implant use and design for future generations of patients with hip replacement

Image Based Fracture Prediction Diagnostic Tool for Avascular Necrosis of the Femoral Head

Current methods to diagnose bone diseases like avascular necrosis (AVN) are subjective and a reliable assessment of the fracture risk is not available. A diagnostic fracture prediction tool would aid clinical diagnosis, anticipate disease progression and help with the planning of subsequent interventions. The strength of bones, including the femur, can be calculated using structural mechanics with a view to ascertaining fracture risk. The aim of this thesis was to develop and validate a fracture prediction method based tomographic imaging and beam theory. In-vitro disease models were created from additive manufacturing, explanted porcine and human femoral heads. The disease models contained a simulated lesion that was either lateral or medial to the fovea to analyse the effects of different lesion positions and to verify the ability of the developed fracture prediction tool. Current classification methods rely on the identification of the lesion volume and location to quantify the fracture risk, an approach that is purely based on geometrical information. The fracture prediction method based on structural stiffness also considered material properties which potentially added predictive capability. The tool was subsequently validated by predicting the fracture risk of femoral heads from AVN patients to demonstrate the ability to identify necrotic lesions that were likely to progress to fracture. The predicted fracture risk was compared to the current diagnostic gold standard to diagnose AVN. The beam tool was also compared against another novel fracture prediction tool based on FEA to identify possible advantages of beam theory. The verification tests confirmed that samples with a lesion in the weight bearing area were statistically more likely to fracture at a low load. A low fracture load meant a high fracture risk. However the experimental fracture load of porcine and human femoral heads, even among samples with similar lesions, showed variations indicating that lesion volume and location were not good predictors of fracture risk alone. There was a good correlation between the predicted fracture risk and in-vitro fracture loads of the human femoral head disease model indicating that the developed tool was able to objectively predict the fracture risk. The beam tool had similar good predictive capabilities as current diagnostic methods and fracture prediction methods based on FEA. An objective in-vivo analysis of the mechanical fracture risk helps identifying patients whose disease is at risk of progressing, as well as stratifying surgical interventions

Regeneration of new bone in revision hip replacements using a tissue engineering technique.

Impaction allografting is used to fill osteolytic defects during revision total hip replacements (rTHR). However clinical results are inconsistent as bone fracture and excessive implant migration are a major complication. Most importantly allograft does not adequately enhance new bone formation. As a consequence the results of rTHR are often inferior to primary THR due to lack of bone stock. Other studies indicate that tissue engineering (TE) using Mesenchymal Stromal Cells (MSCs) seeded onto a resorbable scaffold can regenerate new bone. The overall aim of my thesis was to test the hypothesis that TE of autologous MSCs and MSC derived osteoblast cells incorporated with impaction allografting will significantly enhance new bone formation in revision THRs. The study is divided into in vitro and in vivo phases. In the in vitro phase the technique of osteogenic differentiation and seeding of the autologous ovine MSCs onto allograft was optimised. Previously determined normal impaction forces of 3, 6 and 9kN were used to study the viability of these impacted MSCs and osteogenically seeded cells on the allograft. The results showed that both MSCs and osteoblast cells are affected by the impaction forces. However the MSCs can survive normal impaction forces of 3-6kN while osteoblast cells can only survive impaction forces under 3kN. The in vivo phase was an ovine model used to compare new bone formation between MSCs, osteoblasts and a control group in an orthotopic, ectopic and revision hip. The results show that overall MSCs enhance new bone formation in all the scaffolds compared with the osteoblast and control group. However osteoblast cells do not contribute to new bone formation. The conclusion from the study was that MSCs in conjunction with the impaction allografting technique enhance new bone formation. The tissue engineering technique can be developed into a clinical application in revision THRs where large bone defects have become problematic

Pain Management

Pain Management - Current Issues and Opinions is written by international experts who cover a number of topics about current pain management problems, and gives the reader a glimpse into the future of pain treatment. Several chapters report original research, while others summarize clinical information with specific treatment options. The international mix of authors reflects the "casting of a broad net" to recruit authors on the cutting edge of their area of interest. Pain Management - Current Issues and Opinions is a must read for the up-to-date pain clinician

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

Cinnamtannin B1: a small compound having antidiabetes properties

Type 2 diabetes mellitus is a chronic metabolic disease that results from defects in insulin secretion and insulin receptor kinase. Investigation of novel small active molecule that can potentiate insulin action or having a similar action as insulin is important in the treatment of diabetes. World ethnobotanical information on medicinal plants reports almost 800 plants used in the treatment of diabetes mellitus. However, only a small number of them have been studied thoroughly. Recent study conducted on Cinnamomum reported that it has a great activity in activating insulin receptor kinase and inhibiting insulin receptor phosphatase leading to increased insulin sensitivity and function as a mimetic for insulin. Our study was designed to investigate insulin-mimetic activity of cinnamtannin B1 isolated from Cinnamomum zeylanicum on adipocyte cells. The insulin-mimetic activity of cinnamtannin B1 was evaluated by monitoring preadipocytes differentiation, glucose uptake and phosphorylation of insulin receptor β-subunit in 3T3-L1 adipocytes. To determine whether cinnamtannin B1 able to promote differentiation of preadipocytes, we cultured 3T3-L1 preadipocytes in the presence of cinnamtannin B1, or combination of cinnamtannin B1 and insulin, and then cell proliferation was measured at several points during the course of growth. Investigation of role of cinnamtannin B1 on tyrosine posphorylation of insulin receptor of 3T3-L1 cells was done by immunoprecipitation of cells lysate with anti-insulin receptor β-subunit antibody and the immunocomplex samples were subjected to SDS-PAGE, transferred to nitrocelluose membranes, and immunoblotted with monoclonal anti-phosphotyrosine antibody. Evaluation of glucose uptake by adipocyte cells after treatment with cinnamtannin B1 was carried out by analyzing of radioactive glucose uptake with liquid scintillation counter. Based on these experiments, it was found that, a mixture cinnamtannin B1 with differentiation cocktail was able to induce differentiation of preadipocytes cells. Cinnamtannin B1 was found to active to stimulate phosphorylation of insulin receptor β-subunit by positively exhibited phosphorylation at 170-kDa. The mixture of cinnamtannin B1 was also able to stimulate glucose uptake from a basal value. The results demonstrated that activity of cinnamtannin B1 on adipocyte cells was found to mimicking insulin action. It acted directly on insulin receptor β-subunit by activation of PI3-kinase that stimulates glucose transporter-4 (GLUT-4) translocation. Stimulation of GLUT4 translocation therefore stimulates glucose uptake lead to glucose disposal process in adipocytes. Based on the work that has been carried out, it was suggested that cinnamtannin B1 could be one of the Annals of Medicine & Healthcare Research Page 452 potential lead drug compound in the treatment of type 2 diabetes