Human synovium harbours macrophages and T-cells that secrete inflammatory cytokines, stimulating chondrocytes to release proteinases like aggrecanases and matrix metalloproteinases (MMPs) during the development of Osteoarthritis (OA). Inflammation of the synovium is a key feature of OA, linked to several clinical symptoms and the disease progression. As a prelude to testing in an OA mouse model, we have used the tetracycline system (Tet) to modify mouse mesenchymal stem cells (mMSCs) to over-express viral interleukin 10 (vIL10), an anti-inflammatory cytokine, to modulate the osteoarthritic environment and prevent disease development. MSCs isolated from the marrow of C57BL/6J mice expressed CD90.2, SCA-1, CD105, CD140a, and were negative for CD34, CD45 and CD11b by flow cytometry. Adenoviral transduction of MSCs carrying CMVIL10 and TetON as test, and untransduced, AdNull and TetOFF as negative controls was successful and tightly controlled vIL10 production was demonstrated by CMVIL10 and TetON MSCs using a vIL10 ELISA kit. Co-incubation of vIL10MSC CM with lipopolysaccharide activated bone-marrow derived murine macrophages (BMDMs) resulted in reduction of TNF-α, IL-6 levels and elevated production of IL-10 by ELISA and high iNOS release by Griess assay. Co-culture of active macrophages with TetON MSCs, resulted in polarisation of macrophage cell population from M1 to M2 phase, with decrease in pro-inflammatory MHC-II (M1 marker) and increase in regulatory CD206 (M2 marker) expression over time. The PCR profiler array on MSC CM treated BMDMs, also showed changes in gene expression of critical pro-inflammatory cytokines and receptors involved in the TLR4 pathway. The biscistronic TetON transduced MSCs proved to be most immuno-suppressive and therefore feasible as efficient anti-inflammatory therapy that can utilised in vivo.

Familial osteochondritis dissecans (FOCD) is an inherited defect of cartilage and bone characterized by development of large cartilage lesions in multiple joints, short stature and early onset osteoarthritis. We have studied a family from Northern Sweden with FOCD over five generations. All affected family members have a heterozygous missense mutation on exon 17 of the aggrecan gene, resulting in a Val-Met amino acid replacement in the G3 aggrecan C-type lectin domain (CLD). Aggrecan, a major proteoglycan of articular cartilage produced by chondrocytes, has a large protein core richly substituted with sulfated glycosaminoglycan chains. The unique structure, its high concentration within the cartilage extracellular matrix and its ability to form a supermolecular complex with hyaluronan and bind to other matrix proteins all profoundly influence the biomechanical properties of the tissue. Deletion of CLD in a chick aggrecan construct was found to influence its secretion from chondrocytes and human aggrecan constructs carrying the V2303M mutation showed diminished interactions with the ECM proteins tenascin-R, fibulin-1 and fibulin-2. To investigate the pathogenesis of FOCD, we studied chondrogenic differentiation of patient bone marrow mesenchymal stem cells and induced pluripotent stem cells. We demonstrated that the mutation results in accumulation of unfolded or misfolded aggrecan within the lumen of the chondrocyte endoplasmic reticulum. Associated with this is the failure to assemble a normal extracellular matrix. This explains the susceptibility of these patients to cartilage injury and the degenerative changes that lead to early onset osteoarthritis.

Synovitis has been shown to play a role in pathophysiology of OA promoting cartilage destruction and pain. Synovium is mainly composed of synovial fibroblast (SF) and macrophage (SM) that guide synovial inflammation. Adipose stromal cells (ASC) promising candidate for cell therapy in OA are able to counteract inflammation. Two different subsets of macrophages have been described showing a pro-inflammatory (M1) and an anti-inflammatory (M2) phenotype. Macrophage markers: CD68, CD80 (M1-like) and CD206 (M2-like) were evaluated in osteoarthritic synovial tissue. GMP-clinical grade ASC were isolated from subcutaneous adipose tissue and M1-macrophages were differentiated from CD14+ obtained from peripheral blood of healthy donors. ASC were co-cultured in direct and indirect contact with activated (GM-CSF+IFNγ)-M1 macrophages for 48h. At the end of this co-culture we analyzed IL1β, TNFα, IL6, MIP1α/CCL3, S100A8, S100A9, IL10, CD163 and CD206 by qRT-PCR or immunoassay. PGE2 blocking experiments were performed. In moderate grade OA synovium we found similar percentages of CD80 and CD206. M1-activated macrophage factors IL1β, TNFα, IL6, MIP1α/CCL3, S100A8 and S100A9 were down-modulated both co-culture conditions. Moreover, ASC induced the typical M2 macrophage markers IL10, CD163 and CD206. Blocking experiments showed that TNFα, IL6, IL10, CD163 and CD206 were significantly modulated by PGE2. We confirmed the involvement of PGE2/COX2 also in CD14+ OA synovial macrophages. In conclusion we demonstrated that ASC are responsible for the switching of activated-M1-like to a M2-like anti-inflammatory phenotype, mainly through PGE2. This suggested a specific role of ASC as important determinants in therapeutic dampening of synovial inflammation in OA.

Osteoarthritis (OA) is a degenerative disease with a strong inflammatory component. Intra-articular (IA) injections of mesenchymal stem cells (MSCs) modulate local inflammation, although the lack of engraftment suggests that they undergo apoptosis. The aim of this study is to investigate the fate of IA-delivered MSCs in an animal model of OA and to assess the role of apoptosis in vitro. Collagenase-induced OA (CIOA) was performed on C57BL/6 mice and 2×10∧5 GFP+ MSCs were IA-injected in the animals. 3 days later, knee joints were digested into a single-cell suspension and MSCs retrieved by cell sorting. Conditioned medium (CM) of retrieved cells was tested on murine macrophages and cytokine secretion was measured. Apoptosis of MSCs was induced in vitro with staurosporine (STS) and evaluated by Annexin V/Sytox Blue staining; activation of caspases was measured by FLICA assays. Murine lymphocytes were cocultured with apoptotic MSCs and their proliferation measured by quantification of Cell Trace Violet. 1.63% of injected cells were retrieved and proliferated in culture. Their CM significantly modulated activation of macrophages, with greater effects from OA-induced MSCs. STS induced apoptosis with activation of Caspase 3/7. Apoptotic MSCs significantly prevented the proliferation of murine lymphocytes. MSCs can be administered and retrieved from murine knees. Retrieval yield is low, consistent with previous studies. MSCs were licensed from the OA joint to produce an immunosuppressive milieu that modulated macrophages ex vivo. In vitro, apoptosis increased the immunomodulatory potential of MSCs. This suggests that apoptosis may contribute to the therapeutic effects of MSCs in OA.

Human mesenchymal stem cells are considered the golden standard for clinical application in regenerative medicine for their multilineage differentiation potential, best candidates to treat diseases such as osteoarthritis and osteogenesis imperfecta. In the past few years several molecules have been described to induce the hMSCs differentiation into osteo cell progenitors, mainly discovered by screening of single metabolites bioactivity. However, hMSCs osteogenic differentiation potential is still poor, and the discovery of differentiation inducers with high efficiency is needed. Thanks to automated processes, High Throughput Screening (HTS) strategies shorten the metabolites bioactivity investigation timeline, allowing testing of many molecules simultaneously. In this work, reliable assays for natural products bioactivity investigation detection were developed using HTS methodologies and validated by testing 15 purified compounds derived by marine fungi and sponges. The HTS cytotoxicity investigation using HepG2 cells allowed to test in a single experiment, 15 metabolites in 4 concentrations ranging from 1 to 20µM. Low cytotoxicity was detected for metabolites concentrations from 1 to 10µM and so set as treatment concentrations to be tested in further assays. Anti-inflammatory bioactivity was tested on THP1 cells triggered by LPS. Five out of 15 metabolites showed to prevent the LPS induced THP1 inflammatory activation by lowering the TNF-α production. The metabolites pro-osteogenic potential was investigated using hMSCs: their differentiation was evaluated by calcium mineralization after 10 days differentiation. Pro-osteogenic molecules were not detected in this screening, but the method validation represents a powerful tool for future natural product and synthetic molecules libraries screenings.

Inflammation has been associated with early degradative changes in articular cartilage and immune responses are key factor influencing normal tissue regeneration and repair. With synovitis a prominent feature in osteoarthritis (OA) and associated with the progressive degradation of articular cartilage, immune factors need to be factored into efforts to achieve efficient cartilage repair/regeneration. Recent efforts have focused on the use of autologous or allogeneic mesenchymal stem/stromal cells (MSCs) to modulate the inflammatory environment in the injured or osteoarthritic joint. Intraarticular injection of MSCS has modulated cartilage degradation in a variety of pre-clinical OA models. Results from early clinical trials have also shown effects on pain and function-associated outcome measures. Other cell types may also have some capacity for use as a therapy for OA. For example, primary allogeneic chondrocytes also seem to have some immune-privilege in the synovial joint and are immunomodulatory in a rat model. Although MSCs isolated from bone marrow that are induced to undergo chondrogenic differentiation do not retain these properties, MSCs isolated from the synovium or chondroprogenitors generated from cartilage itself may represent the future of cell therapy for OA.

Osteoarthritis (OA) is a debilitating joint disease that severely affects elderly populations. At present there are no effective treatments for OA and mechanisms of disease progression are poorly understood. Previous work has identified that neuronal-Interleukin-16 (nIL-16) was significantly up-regulated in cartilage during the later stages of OA. Preliminary investigations identified co-localisation of nIL-16 with the Transient Receptor Potential cation ion-channel sub-Family-V-member-4 (TRPV4) in the primary cilium and the pericellular matrix of human OA chondrocytes. Perturbation of both TRPV4 and cilia are strongly associated with OA. We hypothesised that nIL-16 and TRPV4 work in tandem in a pathway that leads to chondrocyte hypertrophy and calcification that is seen in late OA and contributes to the loss of joint integrity. This makes it a promising target for development of a gene therapy to combat the disease. With the aim of elucidating the mechanism involved, nIl-16 knock-out cell lines generated using the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system will be used to knock out nIl-16 PDZ domains to investigate whether this is the mechanism in which nIL-16 functions to anchor TRPV4 to the membrane of chondrocytes at the primary cilium. This work will be carried out using an immortalized hTERT mesenchymal stromal cell (MSC) cell line and effects on terminal MSC chondrogenesis, where hypertrophy mimics the process of calcification seen in OA, will be used to define functional effects of the knockout. Cell lines will be made using the RALA peptide (Phion Therapeutics), a bioinspired nanoparticle, for delivery the CRISPR/Cas9 system.

Background and purpose

To identify methods used to measure free living sedentary behaviour in people with back pain and review the validity and reliability of identified measures.

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.

Epidemiological studies have shown that accumulated mechanical stress is a risk factor for the development of osteoarthritis (OA). This debilitating progressive clinical condition affects a broad spectrum of patients and will ultimately lead to definitive arthroplasty surgery as the endpoint treatment option in many cases. The aim of this study is to establish a graded murine model of OA by medial meniscotibial destabilisation of the knee joint and in phase two, to investigate the migration and engraftment of radioisotope labeled mesenchymal stem cells (MSCs) at varying points of disease progression. The first phase of the study was to establish the murine model, an Irish first. All procedures were performed aseptically under general anaesthesia via a midline medial parapatellar approach on a murine fracture table. Microsurgical dissection was performed through necropsy analysed layers to the joint space and the meniscotibial ligament identified and transected. Validated histopathological analysis was performed at two, four, eight and twelve weeks postoperatively. The results showed a gradation of OA changes from mild unicondylar changes at two weeks, moderate unicompartmental change at four, severe unicompartmental change at eight and severe bicompartmental change at twelve weeks post-operatively. In vivo Bazooka-Single Photon Emission Computed Tomography (SPECT) (Phase 2) imaging studies are currently ongoing following the model establishment.

Background

70% of Breast Cancer patients develop metastatic bone deposits, predominantly spinal metasases. Adult Mesenchymal Stem Cells (MSCs) are multiprogenitor stem cells found within the bone marow which have the ability to self renew and differentiate into multiple cell types. MSCs home specifically to tumour sites, highlighting their potential as delivery vehicles for therapeutic agents. However studies show they may also increase tumour metastatic potential.

Introduction

Tibial patho-morphology has been described as a factor that predisposes to medial compartment osteoarthritis of the knee in 2D analysis. The aim of this study was to investigate whether the morphology of normal and pre-OA medial compartments are really different in 3 dimensions.

We analysed the morbidity, mortality and outcome of cervical spine injuries in patients over the age of 65 years in a retrospective review of 107 elderly patients admitted to our tertiary referral spinal injuries unit with cervical spine injuries between 1994 and 2002. The data were acquired by analysis of the national spinal unit database, hospital inpatient enquiry (HIPE) system, chart and radiographic review. Mean age was 74 years (range 66-93yrs). The male to female ratio was 2.1: 1(M=72, F=35). The mean follow-up was 4.4 years (1-9 years) and mean in-hospital stay was 10 days. The mechanism of injury was a fall in 75 and a road traffic accident (RTA) in the remaining 32 patients. The overall complication rate was 18.6% with an associated in-hospital mortality of 11.2%. Outcome was assessed using the Cervical Spine Outcomes Questionnaire (CSOQ) from Johns Hopkins School of Medicine.

Functional outcome scores approached pre-morbid level in almost all patients. Functional disability was more marked in the patients with neurological deficit at the time of injury. Outcome of the injury is related to the increasing age, co-morbidity and the severity of the neurological deficit. Injuries of the cervical spine are a not infrequent occurrence in the elderly and occur with relatively minor trauma.

Neck pain in the elderly patient should be thoroughly evaluated to exclude C2 injuries. Most patients can be managed in an orthosis but unstable injuries require rigid external immobilisation.

When navigating patellofemoral/unicompartmental knee surgery, the surgeon makes assumptions based upon algorithms developed for total knee arthroplasty. In this study we set out to show how variable the normal knee is. Minor anatomical variations in the shape of our knee may make a big difference in terms of orientation and joint wear patterns. Tibial patho-morphology has been described as a factor that predisposes to medial compartment osteoarthritis of the knee (anteromedial-OA), yet this is limited to 2D analysis. We aimed to describe the 3D morphology of both the tibial and femoral components of the medial compartment of the knee. We hypothesized that morphological differences do exist between normal knees and those predisposed to osteoarthritis.

A total of 20 normal (group A) and 20 pre-OA knees (group B) were included. Group A consisted of contra lateral knees of young patients (< 55 years) awaiting hip surgery and group B of asymptomatic contra lateral knees of patients awaiting unicompartmental knee arthroplasty (UKA). Using 3D reconstructions from CT scans, we analyzed the tibiofemoral joint, which consists of the femoral condyles and the tibial plateau. The femur was aligned to the transcondylar and anatomical axes. The medial femoral extension facet (MFEF) was modeled as a segment of a sphere. The offsets between the MFEF centre and the medial femoral flexion facet centre were measured. The MFEF radius and the MFEF 2D arc angle in the sagittal plane were also measured. The tibias were aligned for flexion-extension and varus-valgus to a flat portion of the flexion facet (flexion facet plane), which lie’s roughly perpendicular to the tibial mechanical axis. To control for axial rotation, the anatomical tibial axis was used. A model of analysis was developed by rotating several increments towards and away from the midline to obtain several sagittal section images. For each sagittal section the medial tibial extension facet (MTEF) slope angle, its length, and the medial tibial submeniscal plane (MTSP) angle and length were analyzed. The relative length proportions of the MTEF, medial tibial flexion facet and MTSP were also measured.

The MFEF was larger and more offset in pre-OA knees. Pre-OA knees also had a significantly larger MFEF arc angle than normals (p< 0.05). The MTEF appeared similar between normal and pre-OA knees. The submeniscal plane was highly variable between subjects but on average horizontally inclined (median 0o, range −15–14o) and formed a crescent shape anteriorly. There was no significant difference in tibial measured parameters between normal and pre-OA tibias (p> 0.05). The method showed good reproducibility using intraclass correlation coefficient (ICC value> 0.9) and Bland-Altman plot analysis.

This study gives the CAOS surgeon some interesting insights into the anatomical variation of the normal knee. We have found evidence of a predisposing patho-morphology to medial-OA in the femoral condyle, but not the tibia. There is evidence of an enlarged flatter extension facet on the medial femoral condyle in the pre-OA knees, with no significant difference in the geometry of the medial tibial plateau, which is now reliably defined based upon a flexion plateau frame of reference.

Background: 70% of Breast Cancer patients develop metastatic bone deposits, predominantly spinal metasases. Adult Mesenchymal Stem Cells (MSCs) are multiprogenitor stem cells found within the bone marow which have the ability to self renew and differentiate into multiple cell types. MSCs home specifically to tumour sites, highlighting their potential as delivery vehicles for therapeutic agents. However studies show they may also increase tumour metastatic potential.

Aims: The aim of this study was to investigate interactions between MSCs and breast cancer cells to further elucidate their role in the tumour microenvironment and hence understand factors involved in stimulating the formation of bone metastases.

Methods: MSCs harvested from the iliac crest of healthy volunteers were grown for collection of conditioned medium (CM), containing all factors secreted by the cells. Breast cancer cell lines (T47D, SK-BR3) were then cultured in MSC CM +/− antibodies to TGFβ, VEGF, MCP-1 and CCL5 for 72hrs. Cell proliferation was assessed using an Apoglow^® assay and RNA harvested for analysis of changes in Epithelial Mesenchymal Transition specific gene expression: N-Cadherin, E-Cadherin, Vimentin, Twist, Snail.

Results: A significant down regulation of breast cancer cell proliferation in the presence of MSC secreted factors was observed (p< 0.05). There was a dramatic increase in expression of EMT specific genes in both cell lines following exposure to MSC-secreted factors. Inclusion of antibodies to TGF, VEGF, MCP-1 and CCL5 inhibited the effect seen, suggesting these paracrine factors played a role in the elevated expression levels.

Conclusion: MSCs clearly have a distinct paracrine effect on breast cancer epithelial cells, mediated at least in part through secretion of growth factors and chemokines. These factors play an important role in the metastatic cascade and may represent potential therapeutic targets to inhibit MSC-breast cancer interactions, helping to prevent the formation of bone metastases in cancer.

Introduction: K wiring is a popular technique to help maintain anatomic reduction of distal radial fractures. It has the advantage of being a semi-closed procedure, which is simple to perform. Complications related to K wires include infection, migration and damage to tendons and nerves.

We aimed to perform a randomized prospective study to determine the outcome of Buried versus Exposed K wire placement.

Methods: We prospectively recruited 60 consecutive patients with displaced distal radius fractures requiring K wiring to our study. They were randomized to Buried versus Exposed K wire groups.

Patient details were collected and follow up was performed at 2 and 6 weeks post op.

Infection at pin sites was measured on a 0 to 6 point scale. Superficial radial nerve was assessed with light touch and 2 point discrimination. EPL tendon was also assessed for damage.

Results: 60 consecutive patients were recruited to the study and randomized to buried or exposed k wires. There were 30 patients in each group.

No damage to EPL tendon was recorded in either group at 6/52 follow up.

There was a slight increased rate of superficial infection at exposed pin sites noted at 2/52 follow up however this was not seen at the 6/52 follow up. Superficial radial nerve damage was noted in one case only. This was in the buried k wire group and occurred following removal of the radial wire.

Conclusion: There appears to be slight increased risk of superficial pin site infection in the exposed k wire group at 2/52 but this is not seen at 6/52 follow up. Buried k wires require a second procedure to remove the wires and this runs the risk of superficial radial nerve damage.

Introduction: The increasing numbers and costs of lower limb arthroplasty procedures has lead to medical and administrative pressures to reduce lengths of stay (LOS) and the hospital costs associated with these procedures. We compared a prospective application of an arthroplasty care pathway in a tertiary referral unit in the United States (US) to a retrospective review of standard practice in an Irish unit to assess reasons for delayed discharge.

Methods: We performed the study in 2 orthopaedic units, one in the US and one in Ireland. In the US an arthroplasty perioperative care pathway was implemented, which among other elements involved a coordinated undertaking by therapists, surgeons and social workers to achieve discharge on the 3rd postoperative day. A consecutive series of primary total knee and hip arthroplasty patients were entered into that limb of the study and had demographic, clinical and LOS data collected. We then collected the same data from a randomly selected consecutive series of primary total knee and hip arthroplasty patients in the Irish unit.

Results: In the US orthopaedic unit 43 patients were included, 24 women and 19 men, of average age 60.5 years (range, 36–82). The average LOS was 3.6 days (range, 2–10), with 27 patients going to a rehabilitation facility and 16 directly home.

In the Irish orthopaedic unit 42 consecutive hip and knee arthroplasty patients from a single consultant were included. There were 26 women and 16 men with average age of 63.9 years (range 36 to 88 years). The average LOS was 6.5 days (range, 3 to 10 days), with 24 patients going to a rehabilitation facility and 18 directly home.

There was no correlation found between LOS and either comorbidities, social factors or complications, in both groups although one patient had a delayed discharge due to haematoma and wound drainage in the US. Prolonged LOS in both groups was correlated with delays in rehabilitation bed and transportation availability, reported short staffing in hospital and weekend stays.

Both groups were well matched for comparison. The average shorter LOS noted in the US unit appears to be almost entirely attributable to an implemented perioperative care pathway and a more proactive coordinated approach to discharge planning.

Discussion and Conclusion: This study demonstrates the effectiveness of multidisciplinary clinical pathways in achieving desired LOS objectives but that substantial impediments still exist from an administrative and logistical viewpoint. Such information is important for clinicians in negotiating and establishing appropriate management of their arthroplasty patients in the current care provision climate.

Introduction: K wiring is a popular technique to help maintain anatomic reduction of distal radial fractures. It has the advantage of being a semi-closed procedure, which is simple to perform. Complications related to K wires include infection, migration and damage to tendons and nerves.

We aimed to perform a randomized prospective study to determine the outcome of Buried versus Exposed K wire placement.

Methods: We prospectively recruited 60 consecutive patients with displaced distal radius fractures requiring K wiring to our study. They were randomized to Buried versus Exposed K wire groups.

Patient details were collected and follow up was performed at 2 and 6 weeks post op.

Infection at pin sites was measured on a 0 to 6 point scale. Superficial radial nerve was assessed with light touch and 2 point discrimination. EPL tendon was also assessed for damage.

Results: 60 consecutive patients were recruited to the study and randomized to buried or exposed k wires. There were 30 patients in each group.

No damage to EPL tendon was recorded in either group at 6/52 follow up.

There was a slight increased rate of superficial infection at exposed pin sites noted at 2/52 follow up however this was not seen at the 6/52 follow up. Superficial radial nerve damage was noted in one case only. This was in the buried k wire group and occurred following removal of the radial wire.

Conclusion: There appears to be slight increased risk of superficial pin site infection in the exposed k wire group at 2/52 but this is not seen at 6/52 follow up. Buried k wires require a second procedure to remove the wires and this runs the risk of superficial radial nerve damage.

Thus it would appear that leaving k wires exposed is the safer and more convenient method of K wiring the displaced distal radius fracture.

Introduction: Fasting overnight NPO (Nulla per os) has been routine before surgery for the past century. The practice was previously designed to reduce the risk of pulmonary aspiration on induction. However this practice has been challenged over the recent years and is changing anaesthetic practices are now more liberal. There are many new concepts aimed at improving patient outcome by regulating metabolic, endocrine, inflammatory and immune responses. This combined with better patient satisfaction and lower anxiety has led to research in this area.

Overnight fasting can induce post operative insulin resistance. Insulin resistance is related to infectious morbidity and increased hospital length of stay (HLOS). Previously this concept was only important in diabetic patients. Surgery places the body under metabolic stress and even a short period of fasting will change the metabolic state of the patient. Indeed physical trauma can cause a triad known as the “diabetes of injury”: insulin resistance, hyperglycaemia and glucose intolerance. Preparation for surgery by maintaining a fasted state and catabolic metabolism may have deleterious consequences for the patient.

Previous studies on elective patients has shown that pre operative carbohydrate loading can reduce insulin resistance and mitigate the inflammatory response by immunomodulation. It has not previously been shown to have an effect in the hip fracture population. This particular group of patients are often elderly and require medical and anaesthetic work up. This delay can mean that the patient is kept fasting for prolonged periods and often overnight.

Methods: With full ethical approval at Connolly Hospital we prospectively randomised all femoral and hip fractures for surgery. We excluded diabetics and pregnant women from the study. A high carbohydrate drink called Nutritia Pre Op was selected. Random serum glucose was taken on admission. Patients were randomised and selected for the trial by hidden ballot. Anaesthetic approval was sought for each case. We compared our standard treatment for hip and femoral fractures of strict NPO prior to surgery versus giving patients the Pre Op drink. Each carton was 200ml and up to 4 were given the night before surgery. In the morning the patients were given another 2 drinks. There was a strict minimum 2 hour NPO period before leaving the ward. Glucose levels were then taken at 1 and 12 hours post operatively to assess whether hyperglycaemia was present. As per laboratory values a normoglycaemia was considered as 4–6mmol/l. Gender, age, type of operation, HLOS, complications and re-admissions were noted.

Results: In total 17 patients were enrolled in the study. Group A had 9 patients and were kept NPO as the control group. Group B had 8 patients enlisted in the Pre Op Drink group. In group A, 6 of 9 (67%) patients had a post operative hyperglycaemia. Average age in group A was 79.6 years with an average HLOS of 15.8 days. 4 patients between them required 8 readmissions over a 3 month post operative period. Group B showed 2 out of 8 (25%) patients had a hyperglycaemia. They had an average age of 69 years with an average HLOS of 11.75 days. 4 patients required 4 readmissions.

Conclusions: Pre Op high carbohydrate drinks significantly decrease post operative hyperglycaemia as per the laboratory ranges. This in turn supports that it decrease insulin resistance by preparing the body for surgery in a fed state. In the same way that one would not prepare for a marathon by fasting 24 hours before hand so the body recognizes that the surgical stress is not best dealt with when in a fasted state. The control group had twice as many readmissions and a longer HLOS. Previous studies show that there is decreased anxiety, thirst and hunger both pre and post operatively. We have shown that this is a safe drink to give and that post operative hyperglycaemia was better controlled.

Many pedicle screw instrumentation systems are currently available to the spine surgeon. Each system has its unique characteristics. It is important for the surgeon to understand the differences in these pedicle screw systems¹

Following the introduction of a new spinal instrumentation set to our clinical practice we encountered two cases of pedicle screw breakage. We thus decided to investigate the mechanism of this screw failure (screw A) in these particular cases and to compare the biomechanical properties, through independent analysis, of a variety of pedicle screws from different manufacturers.

Samples of the broken pedicle screws were retrieved at surgery. Surface analysis of the fracture area using the electron microscope, demonstrated features consistent with fatigue fracture.

Pedicle screws of comparable size from a variety of manufacturers were gathered for independent analysis. Shadowgraph analysis was performed of each screw allowing multiple measurements to be taken of the screw’s geometry. Using this data stress concentration factors were determined demonstrating screw A to have larger values than all the other screws ranging from 2 – 3.6 times the nominal stress. The smaller teeth of screw A, spaced further apart than in the other screws, means that the large proportion of the load which would be carried by the threads is distributed over a smaller area resulting in higher stresses in the threads. The sharp corner at the root of the thread, acting as a stress concentrator, would become the focal point of these high stresses, and magnify them by 2 to 3.6 times.

These increased stresses most likely account for an increased susceptibility to fatigue fracture seen in screw A.

In conclusion it is important to be careful with the introduction and use of new pedicle screw materials and designs, that all the standard biomechanical testing has been performed to a satisfactory standard.

Knowing the physical characteristics of the available pedicle screw instrumentation systems may allow the choice of pedicle screw best suited for a given clinical situation.