CAEP 2015 Academic Symposium: Leadership within the emergency medicine academic community and beyond

OBJECTIVES: A panel of emergency medicine (EM) leaders endeavoured to define the key elements of leadership and its models, as well as to formulate consensus recommendations to build and strengthen academic leadership in the Canadian EM community in the areas of mentorship, education, and resources

Characterisation of paediatric brain tumours by their MRS metabolite profiles

1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Osbourn Trough: Structure, geochemistry and implications of a mid-Cretaceous paleospreading ridge in the South Pacific

Osbourn Trough is a key piece in an outstanding problem: do the Ontong Java, Manihiki and Hikurangi large igneous provinces represent a single ~100 million km3 magmatic pulse? Bathymetric mapping of a 145-km-wide swath across the ∼900-km-long Osbourn Trough revealed three segments offset by 23–35-km-long basins that strike perpendicular to the trough axis. Each segment comprises a 10–15-km-wide axial valley bounded by 300–500-m-high ridge mountains, has inside corner highs at its NW and SE margins that rise 1000–1200 m above the axial valley, and has a flanking set of subparallel abyssal hills. Dredging on steep escarpments successfully penetrated thick sediments and recovered Fe–Mn oxyhydroxide-encrusted volcaniclastic breccias. Lava clasts within the breccias have undergone variable degrees of marine weathering, leading to strong enrichment in most alkali elements and the light REE (except Ce). Nevertheless, their immobile element concentrations are consistently MORB-like and they plot within the MORB fields of tectonic discrimination diagrams. Isotope analyses indicate an affinity with Pacific MORB-source mantle. Both the morphology of Osbourn Trough and geochemistry of its lavas establish that it represents an extinct spreading ridge system. The trough is nearly equidistant (1750 km vs. 1550 km) from the Manihiki and Hikurangi Plateaus, which we interpret as remnants of a formerly contiguous Ontong Java–Manihiki–Hikurangi large igneous province. Inception of the Osbourn spreading ridge was coincident with reorganization of the former Pacific–Phoenix–Farallon spreading system and mega-plateau fragmentation at ∼118 Ma. Spreading across Osbourn Trough ceased when the Hikurangi Plateau collided with and blocked a southward-dipping subduction system developed along the Chatham Rise (eastern New Zealand) sector of the Gondwana margin at ∼86 Ma

Total gastric necrosis due to aberrant arterial anatomy and retrograde blood flow in the gastroduodenal artery: a complication following pancreaticoduodenectomy

Patients with coeliac artery occlusion often remain asymptomatic due to the rich collateral blood supply (pancreaticoduodenal arcades) from the superior mesenteric artery. However, division of the gastroduodenal artery (GDA) during pancreaticoduodenectomy may result in compromised blood supply to the liver, stomach and spleen. Postoperative complications associated with this condition are rarely reported in the literature. We report two cases of coeliac artery occlusion encountered during pancreaticoduodenectomy, one of which was complicated by hepatic ischaemia and total gastric infarction postoperatively. Based on our experience and review of the literature, a management algorithm for coeliac artery stenosis encountered during pancreaticoduodenectomy is propose