The burden of osteoporosis (OP), and its accompanied low energy fractures, is ever increasing. Targeted therapies are under development to stem the tide of the disease, with microRNAs identified as biomarkers and potential targets. Assessing the functional capacity of bone marrow mesenchymal stromal cells (BMSC) from patients with low energy neck of femur fractures (NOF) will identify the expected outcomes to be achieved from new, targeted osteogenic therapies.

Two patient groups were assessed; low energy NOF and osteoarthritic. Bone marrow aspirates were taken at time of arthroplasty surgery. The adherent fraction was cultured and assessed by flow cytometry, microRNA expression and differentiation functionality.

Both patient groups demonstrated characteristic extracellular markers of BMSCs. 3 key markers were significantly reduced in their expression in the NOF group (CD 90, 13, 166 P=0.0286). Reduced differentiation capacity was observed in the NOF group when cultured in osteogenic and adipogenic culture medium. 105 microRNAs were seen to be significantly dysregulated, with microRNAs known to be crucial to osteogenesis and disease process such as osteoporosis abnormally expressed.

This data demonstrates the impaired functional capacity of BMSCs and their abnormal microRNA expression in patients who suffer a low energy NOF. Future targeted therapies for OP must address this to maximise their restorative effect on diseased bone. The important role microRNAs can play as biomarkers and target sites has been further reinforced.

Control of stem cell fate and function is critical for clinical and academic work. By combining surface chemistry-driven extracellular matrix (ECM) assembly with mesenchymal stem cells (MSCs) we are developing a system which can be used to regulate the behaviour of MSCs. The conformation of the ECM glycoprotein fibronectin (Fn) is different when adsorbed onto poly methylacrylate (PMA) where it is globular, and on poly ethylacrylate (PEA) where it forms a physiologically-similar network^[1] (Fig. 1). Using these polymers to govern Fn conformation, we are developing a 3D system incorporating MSC-responsive growth factors (GFs) and bone marrow MSCs capable of regulating MSC behaviour.

Toluene-dissolved PMA and PEA were spin coated onto glass coverslips before solvent extraction in vacuo and UV sterilisation. 20 mg ml⁻¹ human plasma FN was adsorbed onto the surfaces followed by 25 ng ml⁻¹ recombinant human BMP2/VEGF. FN conformations were characterised by atomic force microscopy (AFM). A collagen hydrogel was placed above the substrate. Adult human bone marrow STRO-1+ were cultured on the substrates for 3 weeks in supplemented DMEM. Expression of MSC stemness and HSC maintenance factors were analysed by In-Cell Western assay.

To establish the best combination of polymer/FN/GF, MSC stemness markers (ALCAM, NESTIN and STRO1), osteogenic differentiation markers (OCN and OPN) and bone marrow markers (SCF and VCAM1) were measured in MSCs cultured for 3-weeks on substrates. OCN, SCF, and VCAM1 expression was enhanced across all combinations compared to glass control, while for ALCAM/STRO1/NESTIN and OPN, PEA combinations enhanced their expression. PEA + FN + VEGF appeared to be system best suited to maintaining MSC stemness and supporting expression of osteogenesis markers and bone marrow markers.

We have shown that MSCs maintain their stem cells state and express high levels of SCF and VCAM-1 when cultured on PEA with adsorbed Fn and VEGF or BMP2. Next stages of this work will use PCR to verify results and analyse expression of other MSC markers to develop a role for these synthetic polymers as biomaterials.

Purpose

To determine if clinical outcomes are correlated with center of rotation (COR) in patients implanted with a viscoelastic total disc replacement (VTDR).

Surgical management of symptomatic lumbar degenerative disc disease (DDD) currently consists of fusion or implantation of a first generation total disc replacement (TDR). This study is the first to evaluate an elastomeric one-piece TDR in a 50-patient European study.

Fifty patients with single-level, symptomatic lumbar DDD at L4-S1 who were unresponsive to at least 6-months of non-operative therapy were enrolled in a clinical trial of a viscoelastic TDR (VTDR) at three European sites. Patients were assessed clinically and radiographically at 6 weeks, 3 and 6 months, and 1 and 2 years. Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to assess clinical outcomes.

Twenty-eight males and twenty-two females were enrolled in the study. The average age of patients was 39.7 (23 to 61). The operative level was L4/L5 in 13 patients and L5/S1 in 37 patients. There were no intra-operative complications. Quantitative radiographic assessment indicates that the VTDR restores and maintains a physiologically appropriate disc height and angle, while providing range of motion and translation similar to those provided by the natural disc. Mean ODI scores decreased from 48% pre-operatively to 25% at two years follow up. Mean VAS low back pain scores decreased from 7.1 cm pre-op to 3 cm at two years. Median scores indicate that half of the patient population has ODI scores below 13% and VAS back pain scores below 0.5 cm. Clinically and radiologically, this elastomeric disc is performing satisfactorily, and the causes of clinical failures can be more readily identified.

Introduction

Many journals require outcome data at 2 years post-operative for the assessment of operative procedures in spinal surgery. This study seeks to clarify the timescale of improvement after surgery to see if a shorter period of assessment will indicate the final outcome.

Introduction

Advances in the management of open tibial fractures have reduced the incidence of long-term complications of these injuries. However, a number of patients continue to suffer from sequelae such as infection, non-union and malunion. Many orthopaedic surgeons believe a below-knee amputation with a well-fitted prosthesis is a better alternative to limb reconstruction surgery. There are few studies that evaluate the long-term functional outcomes of amputees against patients who have undergone limb salvage procedures, and their results are conflicting. The hypothesis of this study is that patients who have undergone limb salvage have as good or better outcomes than those who have had below-knee amputations.

X-ray is the standard method for monitoring fracture healing however it is not ideal; signs of healing are not normally visible on X-ray until around 6–8 weeks post fracture. Ultrasonography allows the detection of both the initial haematoma, usually formed immediately after fracture, and the small calcium deposits laid down between broken bone ends in the first stages of fracture healing. It has been reported that these early indicators of the healing process are visible as early as 1–2 weeks after fracture. We use Freehand 3D Ultrasound to monitor the early stages of fracture healing as both the bone surface and surrounding soft tissues can be imaged simultaneously.

The Freehand 3D Ultrasound system consists of a standard Ultrasound machine, a PC running STRAD-WIN (Medical Imaging Group, Cambridge University) 3D software, and an optical tracking devise (NDI Polaris) to record the position and orientation of the Ultrasound probe during scanning. Images are transferred from the Ultrasound machine to the PC using RF capture through out a scan. Calibrating the system matches up the correct image with the correct probe position to produce a 3D dataset.

We segment features of interest on the sequence of 2D images to construct a 3D model. These models are rotatable and provide views of the scanned anatomy that are not otherwise achievable using conventional Ultrasound or X-ray. The 3D data set can also be resliced through any plane to provide further views.

To conduct a 3D Ultrasound scan takes the same amount of time as a conventional 2D scan. The production of the 3D model takes between 15–60 minutes depending on the level of detail required. Distances are measurable to within ±0.4mm meaning fracture gaps of sub-millimeter width can be resolved. The system has already been evaluated on healthy volunteers and a clinical study currently underway.

Audit is an important part of surgical practice. Commissioners may use it as evidence of quality assurance. No comprehensive audit exists in spinal surgery. Usage of existing databases is disappointing. We developed an audit database which was comprehensive and gathered patient outcomes. The underlying principles were:

All patients having surgery should enter,

Demographic data, OPCS codes, length of stay and other data were downloaded directly from the hospital information systems. A monthly printout of patients enrolled was provided to the audit coordinator. She was responsible for the collection of clinical outcomes at 6 months, 12 months, and 2 years after surgery. The initial audit involved the Northwest and Mersey Regions. Data from the hospital information systems (HIS) for two years were available for comparison. Unfortunately only two centres gathered clinical outcomes. We have continued to gather data. 380 patients have been enrolled. HIS data are available for all. With varying lengths of follow up, there are 1045 potential clinical outcomes available. Only 8 patients (2%; 8 outcomes, 0.76%) have been lost to follow up. Using this data we are able to compare outcomes between surgeons, between surgical procedures, and see changes over time. As far as we know we are the only centre in the UK able to do this. It is a valuable Clinical Governance tool. We believe that the principles underlying this audit are the only means to obtain comprehensive outcome audit in surgery.

Imaging of the musculoskeletal system is vital for delivering optimum treatment particularly in the assessment of fracture healing. X-ray and CT are adequate imaging methods for bone but, soft tissue needs other modalities such as MRI and Ultrasound. We propose the use of Freehand 3D Ultrasound to study the early stages of fracture healing by imaging the bone surfaces around the fracture site and monitoring changes in the surrounding soft tissue.

Freehand 3D ultrasound is acquired by attaching a position sensor to the probe of a conventional 2D diagnostic ultrasound machine. As the probe is moved, its position and orientation are recorded along with the 2D ultrasound images. This enables slices through the body to be viewed that would be inaccessible using a normal ultrasound system. Bone surfaces around a fracture site are scanned and the data reconstructed using the Stradx and Stradwin software developed by Cambridge University, to give a 3D visualization of the area.

To assess the feasibility of this proposed method the lower limbs of healthy volunteers were scanned using a 5–10MHz ultrasound probe. The scanning resolution of the system was evaluated using a phantom to ensure millimetre detail could be detected as would be required for imaging early fracture healing. It was found that detail down to 0.8mm could easily be resolved for measurement.

The 3D system could accurately profile the different soft tissue interfaces. The visible surfaces of the tibia were reconstructed to give 3D models. Additional layers of soft tissue interfaces could easily be added to these models to provide more detail.

This imaging modality can provided detailed 3D models of bone the bone surface and surrounding soft tissue. As ultrasound is non-ionizing, rescanning can be conducted more frequently than with CT or x-ray thus offering a more accurate assessment of a patient’s response to healing.

Introduction: Disc Replacement has been described as 21st Century revolution in spinal surgery that preserves mobility and prevents adjacent segment degeneration. Numerous short-term studies are available on clinical outcome but to date there are no published long term clinical, radiological and survival data on disc replacement.

Aim: To analyse clinical, radiological & survival results of Charite III Disc Replacement.

Study Design: Ethical committee approved retrospective study.

Methodology: 160 patients (Av. Age 46yrs; Std.Dev 8.06; 62 Males & 98 Females) underwent disc replacement surgery between Jan1990 and Dec2000. An independent observer reviewed case notes, radiographs and administered a questionnaire that included Oswestry Disability Index, and Pain Score.

Results: Clinical: At an average follow up of 79 (range 31 to 161) months, mean improvement in ODI and pain score were 18.01(p< 0.001) and 1.69(p< 0.001) respectively.

Radiological: average movement at replaced disc, defined as greater than 4 degrees on flexion-extension lateral view was 1.5 degrees for L3L4, 4.01 degrees for L4L5 and 4.8 degrees for L5S1 disc replacement.

Survival: A mean survival time of 147(95% C.I. 140 to 154) months was observed with cumulative survival of 55% with implant removal as an endpoint. A mean survival time of 124(95% C.I. 116 to 133) months with cumulative survival of 35% was observed with all radiological failures as an endpoint.

Complications: were post-operative incisional hernia seen in 17(10.6%), wound infection 9(5.6%) and retrograde ejaculation in 5(3.1%) patients.

Conclusion: Charite III Disc Replacement results in clinically significant (> 15, p< 0.001) improvement in ODI, but does not result in clinical significant (> 2 points) improvement in back pain. Motion is preserved at L4L5 and L5S1 level. It has low survival rate and does not seem to prevent onset of facet arthritis. This study does not support the use of this device for management of back pain.

Study Design: Case report of four consecutive case reports of revision surgery for anterior dislocation of the Acroflex disc (DePuy Acromed, MA, USA) all of whom required vascular surgery are described.

Objective: To describe vascular complications of explanting an artificial inter-vertebral disc replacement following spontaneous anterior displacement.

Subjects: Four consecutive patients required explantation of the Acroflex disc. Two patients were male and two female with median age 44 years (range 33–51). All patients gave informed consent to enter a clinical trial, which had ethical approval.

Outcome measures: Symptom relief, vascular injury and deep vein thrombosis.

Results: All patients gained good symptomatic relief following disc replacement. Four patients suffered anterior displacement of the disc with a deterioration in symptoms during the 1^st year. Three suffered vascular damage to the iliac vessels. In two cases division and re-anastomosis of the iliac vein was required to allow disc removal. Ilio-femoral deep vein thrombosis occurred pre-operatively in one patient and post-operatively in a second, no deaths occurred.

Conclusions: Anterior intervertebral disc displacement is associated with vascular injury. Preventing anterior disc displacement must form an essential part of disc design with (i) rapid fixation to bone and (ii) a failsafe design to prevent local damage in case of failure. In the case of displacement, disc removal should be planned and performed with a vascular surgeon.

Aim: To analyse clinical, radiological & survival results of Charite III Disc Replacement.

Study Design: Ethical committee approved retrospective study.

Methodology: 160 patients (Av. Age 46yrs; Std.Dev 8.06; 62 Males & 98 Females) who underwent disc replacement surgery through transperitoneal approach using a midline incision, between Jan1990 and Dec2000 were identified from hospital records. An independent observer administered Oswestry Disability Index, Pain Score by telephone at the time of review (Aug2003) and reviewed Clinical and radiographic features that were recorded in pre designed form.

Results: Clinical: At an average follow up of 79 (range 31 to 161) months, mean improvement in ODI and pain score were 18.01(p< 0.001) and 1.69(p< 0.001) respectively. Radiological: Movement between the disc spaces, defined as greater than 4 degree on flexion-extension lateral view was preserved after surgery at L4L5 (4.01 degree) & L5S1(4.8 degree) level but not at L3L4( 1.5 degree) level. Average disc height was 19.7mm, and gross radiological loosening was observed after 04, Facet osteoarthritis after 65 and Heterotrophic ossification after 23 operations. Survival: Kaplan-Meier survival analysis showed mean survival time of 147(95% C.I. 140 to 154) months with cumulative survival of 55% at 156 months with implant removal as an endpoint. A mean survival time of 124(95% C.I. 116 to 133) months with cumulative survival of 35% was observed with all radiological failures as an endpoint. Complications: Commonest complication was post-operative incisional hernia seen in 17(10.6%) patients. Other complications were: post-operative ileus 4(2.5%), wound infection 9(5.6%) and retrograde ejaculation in 5(3.1%) patients.

Conclusion: Charite III Disc Replacement results in a clinical significant (> 15, p< 0.001) improvement in ODI, it however does not result in clinical significant (> 2 points) improvement in back pain.Preservation of motion is of questionable clinical significance and it has low survival. Prospective studies are required to confirm the efficacy of this technique

Introduction: The purpose of this study was to evaluate the design of a titanium/polyolefin artificial disc, assess its safety and measure outcome to determine if a RCT is justified.

Methods: All subjects entered this pilot study with one or two-level disc disruption at l4/l5 and/or l5/s1 and had disabling low back pain for at least 12 months. The diagnosis was confirmed by discography. Independent assessment included physical examination, VAS for pain, Low-Back Outcome Score (LBOS), Oswestry Disability Index (ODI), SF-36, lateral flexion/extension radiographs and MRI. This was carried out preoperatively, at 6 and 12 weeks, 6 months and at 1 and 2 years. Surgery was performed by an anterior retroperitoneal approach.

Results: Twenty-eight cases (14 males; average 41 years) were operated on during 1998–2000. Surgery was performed at L5/S1 in 19, L4/L5 in 5 and both levels in 4. Operating time averaged 130 minutes with 180mls average blood loss. There were no operative complications and average length of stay was 6 days. At 2 years there was 39% average improvement in vas, 15-point average improvement in ODI, 14 point average improvement in LBOS and improvement in 5 of the 8 SF-36 sub-scales. Complications included detection by plain radiographs of early partial displacement of implant in one case and late heterotopic calcification in another. Thin section helical CT, first carried out in early 2001, revealed polyolefin tears in 10 patients, four undergoing revision surgery since 2-year follow-up. CT revealed instances of osteolysis associated with polyolefin failure and hetero-topic bone formation not seen on plain radiographs.

Discussion: Although improvements in clinical outcome comparable to that reported with fusion were obtained at two years, detection of elastomer tears by thin section CT in 36% of patients indicated the prosthesis was not suitable for clinical use. This finding was unexpected given the results of prior extensive mechanical testing¹.