We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.
Tibial plateau fractures classically present in a bimodal distribution associated with high energy mechanisms in the younger population and fragility fractures in the elderly populations as a result they are well suited for looking at the effect major trauma centre status. Military trauma surgeons in training should be exposed to as much young high-energy trauma as possible to equip them for operations. Retrospective review of all tibial plateaus presenting to RVI 20 months before MTC status and 20 months following this. 61 patients pre, 66 post. Schatzker grade 1–4 were similar pre and post change. Post change there was an increase in Schatzker 5 (62%) and 6 (27%). High energy injuries were most common in younger males, cause was falls followed by RTAs. MTC status has meant an increase in high energy tibial plateaus (Schatzker 5–6) These were predominantly seen in younger males with high-energy mechanisms. As this is likely to be replicated across all injuries, we would recommend military trauma surgeons have a significant period of time training in major trauma centres to ensure adequate exposure to young high energy trauma.
Epidemiological data about tibial plateau and associated intra-articular proximal tibial fractures provides clinicians with an understanding of the range, variety, and patterns of injury. There are relatively few studies examining this injury group as a whole. We prospectively recorded all tibial plateau and intra-articular proximal tibial fractures occurring in our regional population of 545,000 adults (aged 15 years or older) in 2007–2008. We then compared our results with previous research from our institution in 2000. There were 173 fractures around the knee, 65 of these involved the tibial plateau. Median age was 59 years (IQR, 36.5–77.5 yrs). Tibial plateau fractures were more common in women (58.5%vs 41.5%). The median age of men was 37 years (IQr, 29–52 yrs) compared to women, 73 years (IQR, 57–82 yrs). Tibial plateau fractures accounted for 0.9% overall and 2.5% of lower limb fractures. Incidence was 1.2/10,000/yr (95% CI, 0.9–1.5). We have prospectively identified and described the epidemiological characteristics of tibial plateau fractures in adults from our region. We have identified a change to the epidemiology of these fractures over a relatively short time frame as the patients at risk age.
There were 70000 people admitted to hospital with fractured hips in 2007 and the incidence is rising by 2% each year. Hip fractures represent significant morbidity and mortality to patients and cost the NHS £1.8 billion annually. In 2008 the British Orthopaedic Association Standards for Trauma (BOAST) issued a 14-point guideline to be followed for the management of hip fractures. The aim was to improve secondary prevention of osteoporosis, reduce the falls risk and further fractures. This aimed to provide better care to improve the outcomes for patients and reduce the burden of hip fractures on society. The aim of the audit was to see if the BOAST guidelines are met before and after the transition to a level 1 MTC (Major Trauma Centre) and to measure any impact the change had. Methods: Prospective data was collected for three months in 2010, 2011 and 2012. 94 case notes were reviewed and compared to the outcomes laid out in the BOAST guidelines to see if standards were met. Overall adherence to the guideline's recommendations was high throughout the 3 sample months. For each of the 3 sample months 100% adherence was seen in all of the following criteria: further imaging if x-rays unclear, appropriate analgesia, pre-op assessment, seniority of surgeon, orthogeriatrician involvement, seniority of surgeons and submission to the National Hip Fracture Database. The main common area where adherence was less than 100% was with A and E breaches (i.e. greater than 4 hours referral to the ward). Despite relocation and transition to a level 1 MTC, the management of fractured neck of femur patients compared to the BOAST guidelines remained of a high standard. Further improvements have also been made since moving to the new hospital site where shortcomings in management have been identified. Improvements from year one to three include prophylactic antibiotics and warfarin reversal; there is now a new trust protocol in place for warfarin reversal in the case of hip fractures. Elsewhere adherence to the guidelines remains high across the sample months. Confirming that despite moving to a level 1 status the trauma team continues to be performing well and managing this group appropriately. In January 2012 BOAST published a second version of the hip fracture guidelines: A and E breaches were removed from the guidelines. There have also been several new additions to the guidelines, which prompt a further re-audit in the future.
