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Introduction: 30-day mortality is routinely used to assess proximal femoral fracture care, though patients might remain at risk for poor outcome for longer. This work has examined the survivorship out to one year of a consecutive series of patients admitted for proximal femoral fracture to a single institution. We wished to quantify the temporal impact of fracture upon mortality, and also the influence of patient age, gender, surgical delay and length of stay on mortality from both cardiorespiratory and non-cardiorespiratory causes., Patients and Methods: Data were analysed for 561 consecutive patients with 565 fragility type proximal femoral fractures treated surgically at our trauma unit. Dates and causes of death were obtained from death certificates and also linked to data from the Office of National Statistics. Mortality rates and causes were collated for two time periods: day 0-30, and day 31-365., Results: Cumulative incidence analysis showed that mortality due to cardiorespiratory causes (pneumonia, myocardial infarction, cardiac failure) rose steeply to around 100 days after surgery and then flattened reaching approximately 12% by 1 year. Mortality from non-cardiorespiratory causes (kidney failure, stroke, sepsis etc.) was more progressive, but with a rate half of that of cardiorespiratory causes. Progressive modelling of mortality risks revealed that cardiorespiratory deaths were associated with advancing age and male gender (p<0.001 for both), but the effect of age declined after 100 days. Non-cardiorespiratory deaths were not time-dependent., Conclusion: We believe this analysis extends our understanding of the temporal impact of proximal femoral fracture and its surgical management upon outcome beyond the previously accepted standard (30 days) and supports the use of a new, more relevant timescale for this high risk group of patients. It also highlights the need for planning and continuing physiotherapy, respiratory exercises and other chest-protective measures from 31 to 100 days., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Cerebral emboli have been detected during intramedullary orthopaedic procedures. The quantity of emboli produced and their clinical effects are currently not known. This study aimed to quantify the intra-operative cerebral embolic load using transcranial Doppler ultrasound during the intramedullary stabilisation of femoral and tibial diaphyseal fractures. Clinical cognitive function was also assessed after surgery and any relationship to the cerebral embolic load determined., Patients and Methods: Prospective cohort study of 20 patients with femoral or tibial diaphyseal fractures treated with reamed intramedullary nailing. The intra-operative cerebral embolic load was measured using transcranial Doppler ultrasound of the middle meningeal artery. Cognitive function was assessed 3 days after surgery using a range of validated neuropsychological tests. The cognitive results were compared to predicted scores matched for age and intelligence quotient as is the standard method of cognitive assessment after trauma., Results: Four patients had detectable cerebral emboli with counts of only 2, 3, 3, and 9 respectively. A significantly poorer than predicted cognitive score occurred in immediate and delayed memory recall tests. However there was no significant difference in any cognitive function score between those patients who had detectable cerebral emboli and those who did not., Discussion: Small numbers of cerebral emboli were detected during intramedullary stabilisation of lower limb long bone fractures but with no apparent cognitive effect. This poor correlation is similar to recent studies performed on arthroplasty patients and also conforms to the extensive cardiac surgery literature which would indicate that such low levels of systemic embolisation are unlikely to consistently produce cerebral clinical effects.

Introduction: The outcome of displaced intra-articular fractures of the calcaneus is affected by many factors such as fracture type and age. The restoration and maintenance of the posterior facet is a priority and has a strong correlation with improved outcome. The fracture occasionally extends anteriorly to the calcaneocuboid joint (CCJ). Currently there is little literature discussing pain, functional or radiographic information about calcaneal fractures, which involve the CCJ or those that do not. The aim of this study was to compare pain and functional outcome measurements in a cohort of calcaneal fractures treated operatively and non-operatively to determine whether CCJ involvement was important., Patients and Methods: A prospective database of calcaneal fractures managed by a single surgeon was reviewed. CT images allowed us to assess the degree of CCJ involvement before and after surgery. Final outcome was determined by pain (validated visual analogue score) and functional outcomes (SF-36) taken 2 years after injury with further CT imaging used to determine the presence of arthritic change at the CCJ. 59 patients with 64 intra-articular calcaneal fractures were identified who also had 35 fractures that extended to the CCJ. Pre-operative CT imaging identified 3 levels of CCJ involvement: Undisplaced fracture line (n=27); fractures that involved <50% of the CCJ (n=4) and fractures that involved >50% of the CCJ with joint subluxation (n=4)., Results: Pain and functional scores were comparable between fractures that involved the CCJ and those that did not. All fractures that involved >50% of the CCJ demonstrated arthritic change 2-years after injury., Discussion: Displaced intra-articular fractures of the calcaneus will often have a fracture line extending into the CCJ. This is commonly undisplaced and does not appear to predict continued pain, dysfunction on radiographic appearance using generalised outcome measurements.

The opioid receptors, mu, delta and kappa, conduct the major pharmacological effects of opioid drugs, and exhibit intriguing functional relationships and interactions in the CNS. Previously established hypotheses regarding the mechanisms underlying these phenomena specify theoretical patterns of relative cellular localisation for the different receptor types. In this study, we have used double-label immunohistochemistry to compare the cellular distributions of delta and kappa receptors with those of mu receptors in the rat CNS. Regions of established significance in opioid addiction were examined. Extensive mu/delta co-localisation was observed in neuron-like cells in several regions. mu and kappa receptors were also often co-localised in neuron-like cell bodies in several regions. However, intense kappa immunoreactivity (ir) also appeared in a separate, morphologically distinct population of cells that did not express mu receptors. These small, ovoid cells were often closely apposed against the larger, mu-ir cell bodies. Such cellular appositions were seen in several regions, but were particularly common in the medial thalamus, the periaqueductal grey and brainstem regions. These findings support proposals that functional similarities, synergy and cooperativity between mu and delta receptors arise from widespread co-expression by cells and intracellular molecular interactions. Although co-expression of mu and kappa receptors was also detected, the appearance of a separate population of kappa-expressing cells supports proposals that the contrasting and functionally antagonistic properties of mu and kappa receptors are due to expression in physiologically distinct cell types. Greater understanding of opioid receptor interaction mechanisms may provide possibilities for therapeutic intervention in opioid addiction and other conditions.

We have previously shown that antisense oligonucleotides effectively reduced insulin-like growth factor I receptor expression in human psoriatic skin grafted on to nude mice when injected intradermally. We therefore investigated the penetration of C-5 propyne modified antisense oligonucleotides into human normal and psoriatic skin after topical administration. Oligonucleotide (37.5 microg; 250 microM) was applied in aqueous solution or 5% methylcellulose gel for 24 h, prior to live confocal microscopy and fluorescence microscopy of fixed sections. We found that oligonucleotide could penetrate through the stratum corneum of psoriatic but not normal human skin over large regions of the epidermis. The oligonucleotide was localized to the nucleus of large parakeratotic cells in the psoriatic skin as well as smaller basal and suprabasal keratinocytes. In normal human skin, oligonucleotide was confined to the stratum corneum, with little or no oligonucleotide apparent in the viable epidermis. Electrophoresis of oligonucleotide recovered from treated psoriatic and normal skin revealed that the oligonucleotide remained intact over the 24 h period. In summary, we found that C-5 propyne modified antisense oligonucleotides could reach the target cells (in this case basal keratinocytes) after topical administration to psoriatic but not normal skin.