Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial.

OBJECTIVE: To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. DESIGN: Randomised controlled trial. SETTING: 30 vascular centres (29 UK, 1 Canadian), 2009-13. PARTICIPANTS: 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. INTERVENTIONS: 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). MAIN OUTCOME MEASURES: 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. RESULTS: 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval -£625 to £2997). CONCLUSIONS: A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48334791

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

Crop Updates 2004 - Cereals

This session covers twenty eight papers from different authors: PLENARY 1. Declining profitability in continuous cropping systems. Is more wheat the answer on Duplex soil? Dr Wal Anderson, Department of Agriculture 2. Disease implications of extending the wheat phase in low-medium rainfall areas, Dr Vivian Vanstone and Dr Robert Loughman, Department of Agriculture 3. Prolonged wheat phase on duplex soils – where do weeds set the boundary? Vanessa Stewart, Department of Agriculture WHEAT AGRONOMY 4. Management of small grain screenings in wheat, Dr Wal Anderson and Dr Darshan Sharma, Department of Agriculture 5. Agronomic responses of new wheat varieties, Christine Zaicou-Kunesch, Dr Darshan Sharma, Brenda Shackley, Dr Mohammad Amjad, Dr Wal Anderson and Steve Penny,Department of Agriculture 6. Managing wheat yield reduction from wide rows, Dr Mohammad Amjad and Dr Wal Anderson, Department of Agriculture 7. Row spacing and stubble effect on wheat yield and ryegrass seed set, Glen Riethmuller, Department of Agriculture 8. Grain protein management – lessons learnt on the south coast, Jeremy Lemon, Department of Agriculture 9. Unravelling the mysteries of optimum seed rates, Dr Wal Anderson, Dr Darshan Sharma, Brenda Shackley and Mario D’Antuono, Department of Agriculture 10. Agronomic features for growing better wheat – south east agricultural region 2003, Dr Mohammad Amjad, Veronika Reck and Ben Curtis, Department of Agriculture 11. Agronomic responses of new wheat varieties – great southern agricultural region 2003, Brenda Shackley and Judith Devenish, Department of Agriculture 12. Variety specific responses of new wheat varieties – central agricultural region 2003, Dr Darshan Sharma and Dr Wal Anderson, Department of Agriculture 13. Agronomic responses of new wheat varieties – northern agricultural region 2003, Christine Zaicou-Kunesch, Melaine Kupsch and Anne Smith, Department of Agriculture BARLEY AND OAT AGRONOMY 14. Gairdner for high rainfall – where does Baudin fit in? Blakely Paynter, Roslyn Jettnerand Leanne Schulz, Department of Agriculture 15. Oaten hay – varieties and agronomy, Blakely Paynter, Jocelyn Ball and Tom Sweeny, Department of Agriculture NUTRITION 16. In-furrow fungicide applications in liquid fertiliser, Dr Stephen Loss, CSBP Ltd 17. Elemental sulphur as a fertiliser source in Western Australia, Ashleigh Brooks1A, Justin Fuery2, Geoff Anderson3 and Prof Zed Rengel1,1UWA, 2Summit FertilizerFertilisers and 3Department of Agriculture 18. Genetic variation in potassium efficiency of barley, Paul Damon and Prof. Zed Rengel, Faculty of Natural and Agricultural Sciences, UWA 19. Managing protein through strategic N applications, Eddy Pol and Dr Stephen Loss, CSBP Ltd 20. Nitrogen management for wheat in high rainfall cropping areas, Narelle Hill1, Ray Tugwell1, Dr Wal Anderson1, Ron McTaggart1and Nathan Moyes2, 1Department of Agriculture and 2Landmark 21. Flag smut resistance in current WA wheat varieties, John Majewski and Dr Manisha Shankar, Department of Agriculture 22. Rust resistance update for wheat varieties in WA, Dr Manisha Shankar, John Majewski and Jamie Piotrowski, Department of Agriculture PESTS AND DISEASES 23. Stripe rust in WA – where was it and what can we learn from 2003? Dr Robert Loughman and Ciara Beard, Department of Agriculture 24. Foliar disease management – a key factor in the adoption of Baudin and Hamlin barley, Dr Kithsiri Jayasena, Dr Rob Loughman, Kazue Tanaka and Grey Poulish, Department of Agriculture 25. Validating aphid and virus risk forecasts for cereals, Dr Debbie Thackray, Rohan Prince and Dr Roger Jones, Department of Agriculture and Centre for Legumes in Mediterranean Agriculture HARVESTING 26. Swathing Gairdner barley at 30% moisture, Peter Nelson¹ and Nigel Metz², ¹Cooperative Bulk Handling and ² Fitzgerald Biosphere Group MODELLING 27. Development of a web based grower decision aid application for cereal growers, Dr Leisa Armstrong1, Yee Leong (Alex) Yung1and Dr Moin Salam2 1School of Computer and Information Science, Edith Cowan University; and 2Department of Agriculture 28. Wheat varieties updated in ‘Flowering Calculator’ – a model predicting flowering time, Brenda Shackley, Dr David Tennant, Dr Darshan Sharma and Christine Zaicou‑Kunesch, Department of Agricultur

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

Aims To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. Methods and results The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Conclusion Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. Clinical trial registration: ISRCTN 48334791

Nursing students’ experiences on blogging in the classroom: Linking between ethics and pedagogy

This paper reports students’ perspectives on using blogging in an undergraduate nursing classroom. Blogging refers to a series of entries with limited word count. Several anecdotal reports focus on the potential advantages (e.g., increasing students' writing, reflecting, collaborating, participation and critical thinking skills) of blogging in education. Yet limited reports discuss its challenges. We argue that in order to better understand the use of blogging in the classroom we need to look more closely at students’ values, beliefs and expectations. Thus, to better understand teaching and learning and evaluate blogging we used Gesler’s theory of therapeutic landscape. Students’ retrospective accounts revealed two overarching themes: students’ experiences and students’ responses to blogging. Despite the fact that students experienced and valued blogging in their everyday lives, their responses to in-class blogging were not always positive

Single-Center Experience Following the Introduction of a Percutaneous Endovascular Aneurysm Repair First Approach

We evaluated our experience following the introduction of a percutaneous endovascular aneurysm repair (pEVAR) first approach using Perclose Proglide assessing efficacy, complications, and identification of factors that could predict failure. A retrospective cohort study on patients over a 2-year period following the introduction of a pEVAR first approach was performed. The primary end point was defined as successful deployment and access site hemostasis. Percutaneous EVAR was technically successful in 41 (77.4%) of 53 patients and 83 (86.5%) of 96 access sites. Factors associated with failure were smaller common femoral artery (CFA) diameter ( P = .045) and CFA circumferential calcification of greater than 50% ( P = .0001). The incidence of access site infection was significantly higher in the failure group ( P = .008) as was procedure duration ( P = .026). Percutaneous EVAR first approach must be introduced with caution. Percutaneous EVAR failure occurs more often in patients with unfavorable access site anatomy. Success rate can be improved with careful patient selection. </jats:p

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2 , yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using wholeexome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies