Editor's Choice - Infra-Renal Aortic Diameter and Cardiovascular Risk: Making Better Use of Abdominal Aortic Aneurysm Screening Outcomes.

OBJECTIVE: Aortic diameter (AD), used traditionally for abdominal aortic aneurysm (AAA) screening may have a role in assessing cardiovascular risk. Unfortunately, AD estimates for those without AAA are underutilised, whilst cardiovascular risk is sub-optimally managed in those with AAA. Our objective was to examine the association between AD measurements and future cardiovascular risk. METHODS: Retrospective analysis of three databases of male participants screened for aortic aneurysm disease. Imaging and clinical data were obtained from three independent sources: 1) the Multi-centre Aneurysm Screening Study (MASS) trial (n = 26 882 men); 2) the 2013/14 cohort of the English NHS AAA Screening Programme (NAAASP) (n = 237 441 men) linked with NHS hospital admission and death registry data; and 3) the Framingham Heart Study (FHS) offspring cohort (n = 649). Associations between maximal aortic diameter, as measured on ultrasound or computed tomography, and cardiovascular outcomes were examined. RESULTS: Cardiovascular mortality in the MASS trial, was higher in men with AAA at 13 years of follow up, compared to those without (Hazard Ratio [HR] 2.22, 95% CI 1.97-2.50, p < .001). Contemporary risk of major adverse cardiovascular events in the NAAASP was highest in those with an AAA (HR 2.91, 95% CI 2.00-4.25), whilst, extremes of aortic diameter were associated with increased risk for cardiovascular events. Aortic diameter was an independent risk factor for cardiovascular events in the FHS dataset. CONCLUSION: Irrespective of the diagnosis of AAA, men attending for AAA screening who are found to have an abnormal aortic diameter are at high risk of future cardiovascular events. This currently unutilised data from AAA screening programmes has the potential to improve preventative management of cardiovascular risk.

Effects of Left Renal Vein Ligation During Open Abdominal Aortic Aneurysm Repair on Renal Function.

OBJECTIVE: Left renal vein (LRV) ligation is performed during open abdominal aortic aneurysm (AAA) repair to facilitate proximal anastomosis. Its impact on short, medium, and long term renal function has not been investigated in detail using appropriately validated endpoints. METHODS: This was a nested case control study using data from a prospectively maintained AAA institutional dataset (tertiary centre). A total of 76 patients who underwent elective open AAA repair and had LRV ligation (1 January 2012 to 1 January 2018) were individually case matched based on age (within two years), sex, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologist (ASA) score, chronic kidney disease (CKD) stage, and history of diabetes with 76 patients who had open AAA repair without LRV ligation. Renal outcomes were compared between groups, including proportion of patients developing acute kidney injury (AKI) using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, proportion developing major adverse kidney events (MAKE90) at 90 days (comprising mortality and/or decrease in eGFR >25%), and absolute decrease in eGFR at latest follow up. RESULTS: A higher proportion of patients developed AKI and MAKE90 in the LRV ligation group (AKI: 11 patients [14.8%] vs. 2 [2.6%], p = .009; MAKE90: 6 [7.9%] vs. 1 [1.3%] p = .053, in the LRV ligation and the non-LRV ligation groups, respectively) - even though the difference in the MAKE90 endpoint was not statistically significant. Changes in eGFR were not statistically different in the LRV ligation group at 90 days (4.0 ± 1.1 mL/min/1.73 m2vs. 4.4 ± 2.1, p = .64) or by the time of latest follow up (median: 28 months; 3.7 ± 1.6 vs. 2.6 ± 2.0, p = .55). CONCLUSION: Ligation of the LRV is associated with increased levels of AKI and renal deterioration in the early post-operative phase using validated reporting criteria; however, long term renal function does not seem to be affected.

Editor's Choice - The Impact of Endovascular Aneurysm Repair on Long Term Renal Function Based on Hard Renal Outcomes.

INTRODUCTION: Over the short term endovascular aneurysm repair (EVAR) is associated with superior outcomes compared with open repair; however, the progression of renal function after EVAR remains unknown because of the use of inconsistent reporting measures. The aim was to define long term renal decline following elective EVAR using estimated glomerular filtration rate (eGFR). METHODS: The prospectively maintained in house database was used to identify consecutive patients having elective EVAR who had been followed up for more than five years. Overall, 275 patients (23 females, 8%; mean age, 75 years) who were not previously on renal replacement therapy (RRT) were included (January 2000 to July 2010). Pre-operative, post-operative, and most recent eGFR values were evaluated using the chronic kidney disease epidemiology collaboration equation. The primary outcome was change in eGFR at latest follow up. RESULTS: Patients were followed up over a median of 9 years (range 5-17 years). Their mean eGFR dropped from a pre-operative value of 67 mL/min/1.73 m2 (standard deviation [SD]: 9.4) to 52 mL/min/1.73 m2 (SD 7.7), which amounts to a yearly loss of 1.7 units; six patients (2%) required RRT (dialysis) during late follow up. Patients requiring RRT and those with an eGFR loss exceeding 20% at latest follow up compared with baseline were more likely to die during late follow up (odds ratio 2.4 and 3.3 respectively, p < .001). CONCLUSION: This analysis, with some of the longest available follow up to date, suggests that patients undergoing EVAR may experience a significant long term decrease in renal function. This needs to be taken into account when offering EVAR in younger patients; renal follow up and preservation should be optimised in this patient group.

Mortality from thoracic aortic diseases and associations with cardiovascular risk factors.

BACKGROUND: Temporal trends in mortality from thoracic aortic disease are unclear. This study examined trends in mortality from thoracic aortic aneurysm (TAA) and aortic dissection (AD) with the aim of identifying associations with trends in established cardiovascular risk factors. METHODS AND RESULTS: TAA and AD mortality (1994-2010) using International Classification of Diseases codes was extracted from the World Health Organization mortality database and age standardized. World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Eighteen World Health Organization member states were included (Europe=13, Australasia=2, North America=2, Asia=1). Ecological regression was performed of temporal trends in cardiovascular risk factors (1946-2010) and independent correlations to mortality trends. TAA and AD mortality trends show substantial heterogeneity but are generally declining. TAA mortality has increased in Hungary, Romania, Japan, and Denmark, and AD mortality has increased in Romania and Japan; therefore, the mortality decline is not universal. A linear relationship exists between trends in systolic blood pressure, cholesterol, and body mass index and mortality from TAA. Body mass index demonstrated a negative linear association with female AD mortality, whereas trends in systolic blood pressure demonstrated a positive linear relationship with male AD mortality. Trends in smoking prevalence were not associated with TAA or AD mortality trends. CONCLUSIONS: This population-level ecological regression provides evidence that mortality secondary to TAA and mortality secondary to AD are both in decline. Differences between countries could be explained by population-level changes in common cardiovascular risk factors. Public health measures could further reduce mortality from TAA and AD.

Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality.

BACKGROUND: Contemporary data from Western populations suggest steep declines in abdominal aortic aneurysm (AAA) mortality; however, international trends are unclear. This study aimed to investigate global AAA mortality trends and to analyze any association with common cardiovascular risk factors. METHODS AND RESULTS: AAA mortality (1994-2010) using International Classification of Diseases codes were extracted from the World Health Organization mortality database and age standardized. The World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Nineteen World Health Organization member states were included (Europe, 14; Australasia, 2; North America, 2; Asia, 1). Regression analysis of temporal trends in cardiovascular risk factors (1946-2010) was done independently for correlations to AAA mortality trends. Global AAA mortality trends show substantial heterogeneity, with the United States and United Kingdom recording the greatest national decline, whereas internationally, male individuals and those <75 years of age demonstrated the greatest reductions. AAA mortality has increased in Hungary, Romania, Austria, and Denmark; therefore, the mortality decline is not universal. A positive linear relationship exists between global trends in systolic blood pressure (P≤0.03), cholesterol (P≤0.03), and smoking prevalence (P≤0.02) in males and females. Body mass index demonstrated a negative linear association with AAA mortality (P≤0.007), whereas fasting blood glucose showed no association. CONCLUSIONS: AAA mortality has not declined globally, and this study reveals that differences between nations can be explained by variations in traditional cardiovascular risk factors. Declines in smoking prevalence correlate most closely with declines in AAA mortality, and a novel obesity paradox has been identified that requires further investigation. Public health measures could therefore further reduce global AAA mortality, with greatest benefits in the younger age group.

A systematic review and meta-analysis of the association between markers of hemostasis and abdominal aortic aneurysm presence and size.

OBJECTIVE: The purpose of this study was to summarize the current evidence of the association between markers of hemostasis and both the presence and size of abdominal aortic aneurysms (AAAs). METHODS: A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines by use of the search terms "aneurysm AND abdominal AND aortic AND coagulation" NOT "thoracic." Outcome data including concentration of hemostatic marker, number of patients, and significance level were recorded. RESULTS: A total of 22 nonrandomized studies were included in the analysis, with a total of 9862 patients. Fibrinogen mean difference (MD) (0.43 g/L; 95% confidence interval [CI], 0.28-0.58 g/L; P ≤ .00001), D-dimer MD (325.82 ng/mL; 95% CI, 199.74-451.89 ng/mL; P ≤ .00001), and thrombin-antithrombin III complex MD (5.58 g/L; 95% CI, 3.34-7.83 g/L; P ≤ .0001) were significantly elevated in the presence of AAAs. Tissue plasminogen activator, prothrombin fragments F1+F2, and platelet count were not shown to be significantly different between patients with and those without AAAs. Meta-regression of studies reporting plasma D-dimer concentration and aneurysm diameter suggests a strong and significant association (r(2) = 0.94; P ≤ .0001). CONCLUSIONS: This study suggests that the presence of AAAs is associated with increased fibrin turnover, fibrinolysis, and thrombin generation, as shown by increased levels of fibrinogen, D-dimer, and thrombin-antithrombin III complex. This is clinically relevant because markers of hemostasis are independent risk factors for cardiovascular events, highlighting the necessity of addressing all modifiable cardiovascular risk factors in patients with AAAs. Furthermore, the finding that plasma D-dimer concentration appears to have a linear relationship with aneurysm diameter may be useful as a future biomarker of AAAs.

Type II endoleaks: challenges and solutions.

Type II endoleaks are the most common endovascular complications of endovascular abdominal aortic aneurysm repair (EVAR); however, there has been a divided opinion regarding their significance in EVAR. Some advocate a conservative approach unless there is clear evidence of sac expansion, while others maintain early intervention is best to prevent adverse late outcomes such as rupture. There is a lack of level-one evidence in this challenging group of patients, and due to a low event rate of complications, large numbers of patients would be required in well-designed trials to fully understand the natural history of type II endoleak. This review will discuss the imaging, management, and outcome of patients with isolated type II endoleaks following infra-renal EVAR.

Impact of hospital volume on outcomes following treatment of thoracic aortic aneurysms and type-B dissections.

Previous research suggests an association between hospital volume and outcomes in high-risk surgical pathologies. The association between hospital volume and outcomes in patients with isolated descending thoracic aortic aneurysms (DTAAs) and type-B thoracic aortic dissections (TBADs) is conflicting. We aimed to investigate this in a literature review and meta-analysis. A systematic review of the literature was performed to identify studies reporting mortality and morbidity following repair (elective or emergency) of DTAA and/or TBAD using the Medline and Embase Databases (2000-2015). Hospital volume was assessed based on the number of patients treated per institution: low volume (1-5 cases per year), medium volume (6-10) and high volume (>10). The primary outcome of interest was all-cause mortality during inpatient stay and at 30 days. Eighty-four series of non-dissecting DTAA or TBAD were included in data synthesis (4219 patients; mean age: 62 years; males: 73.5%). For all patients (emergency and elective) undergoing DTAA repair, in-hospital mortality was 8% [95% confidence interval (CI): 6-8%]. Results were not superior in high-volume centres (8 vs 6 vs 11% for high-, medium- and low-volume, respectively). Sub-analyses for emergency and elective repairs showed no significant differences. For TBAD repairs, in the combined population (emergency and elective), results reached borderline significance (P = 0.0475), favouring high-volume centres (6 vs 11 vs 14%), but this association disappeared when emergency and elective repairs were analysed separately. Nine series reported outcomes at 1 year and 5 series followed DTAA and 18 TBAD treatment. No meaningful long-term comparisons were possible due to the lack of data. No significant associations were detected between hospital volume and subsequent mortality following DTAA or TBAD treatment. Data were heterogeneous and long-term results were scarcely reported. A well-designed longitudinal study of sufficient size is required to inform future strategies in this area.

A comparison of infections and complications in central venous catheters in adults with solid tumours.

AIM: The aim of this study is to compare the complication rates of three vascular access devices in patients with solid tumours having infusion chemotherapy. MATERIALS AND METHODS: An observational study of 58 central venous catheter (CVC) lines inserted in 55 patients with solid tumours requiring infusional chemotherapy was performed. The study was conducted between January 2011 and August 2013, looking at complication and infection rates as primary outcomes. Data were recorded from patients with 19 tunnelled cuffed silicone catheters, nine with peripherally inserted central catheters (PICCs) and 30 central venous ports. RESULTS: The two CVC groups (ports and non-ports) matched equally in terms of tumour site; all patients with solid tumours were included, haematology patients were excluded and chemotherapy regimens were comparable. Thirteen out of 28 non- ports had complications compared with one out of 30 central venous ports. Ten out of 19 tunnelled catheters had complications including three displacements and seven were removed due to infection. There were no reports of line-related sepsis in the PICC or ports. Three out of nine PICC lines had complications including two displacements and one PICC blocked permanently requiring removal. In addition, one port out of 30 was removed due to erosion through the skin. There were no episodes of thrombosis or fibrin sheath formation related to any of the devices. CONCLUSIONS: In our study, we demonstrated that central venous ports and PICC lines in patients undergoing infusional chemotherapy had lower line infection rates than tunnelled catheters, and only ports have been shown to be almost complication-free. In addition, we found infection rates higher in CVCs s cared for by patient/carers rather than hospital only care, and higher in colorectal patients with stomas. Therefore, we recommend that central venous ports are a safe, acceptable CVC option for infusional chemotherapy for adults with solid tumours.

Outcomes Following Limb Crossing in Endovascular Aneurysm Repairs.

BACKGROUND: Crossing the limbs of the stent during endovascular aneurysm repair (EVAR) is often used to aid cannulation of the contralateral limb. This study assessed outcomes following the use of this technique. METHODS: Retrospective review of crossed (n = 43) and uncrossed (n = 269) EVARs was performed at a tertiary vascular center over 5 years. Primary end points were graft limb occlusion (GLO), endoleak, and sac expansion rates. Indications for limb crossing were also assessed. RESULTS: Two-year GLO (P = .34) and type 1 endoleak (P = .413) rates were similar between groups. Patients undergoing crossed EVAR experienced more type 2 endoleaks (P = .002) at 24 months but no increase in sac expansion rates was observed (P = .275). Thirty-day (P = .57) and late (P = .268) mortalities were similar between groups. The main indication for limb crossing was distal aortic angulation (48.8%). CONCLUSIONS: Crossed EVAR does not increase the risk of GLOs or clinically significant endoleaks. Further studies are needed to determine the effect on type 2 endoleak rates.

Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals.

Polyunsaturated fatty acids (PUFA) of the omega-3 series and omega-6 series modulate neurite outgrowth in immature neurones. However, it has not been determined if their neurotrophic effects persist in adult and aged tissue. We prepared cultures of primary sensory neurones from male and female rat dorsal root ganglia (DRG), isolated at different ages: post-natal day 3 (P3) and day 9 (P9), adult (2-4 months) and aged (18-20 months). Cultures were incubated with the omega-6 PUFA arachidonic acid (AA) and the omega-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), at 0.8, 4, 8 and 40muM. PUFA increased neurite outgrowth throughout the developmental stages studied. The effects of omega-3 PUFA, in particular DHA, were still prominent in aged tissue. The amplitude of the effects was comparable to that of nerve growth factor (NGF; 50ng/ml) and all-trans-retinoic acid (ATRA; 0.1muM). The effects of PUFA were similar in cells positive or negative for the N52 neurofilament marker. Our results show that omega-3 PUFA have a marked neurite-promoting potential in neurones from adult and aged animals.