Explore the vast range of titles available.

Objective To assess the three year clinical outcomes and cost effectiveness of a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair for patients with suspected ruptured abdominal aortic aneurysm.Design Randomised controlled trial.Setting 30 vascular centres (29 in UK, one in Canada), 2009-16.Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm, of whom 502 underwent emergency repair for rupture.Interventions 316 patients were randomised to an endovascular strategy (275 with confirmed rupture) and 297 to open repair (261 with confirmed rupture).Main outcome measures Mortality, with reinterventions after aneurysm repair, quality of life, and hospital costs to three years as secondary measures.Results The maximum follow-up for mortality was 7.1 years, with two patients in each group lost to follow-up by three years. After similar mortality by 90 days, in the mid-term (three months to three years) there were fewer deaths in the endovascular than the open repair group (hazard ratio 0.57, 95% confidence interval 0.36 to 0.90), leading to lower mortality at three years (48% v 56%), but by seven years mortality was about 60% in each group (hazard ratio 0.92, 0.75 to 1.13). Results for the 502 patients with repaired ruptures were more pronounced: three year mortality was lower in the endovascular strategy group (42% v 54%; odds ratio 0.62, 0.43 to 0.88), but after seven years there was no clear difference between the groups (hazard ratio 0.86, 0.68 to 1.08). Reintervention rates up to three years were not significantly different between the randomised groups (hazard ratio 1.02, 0.79 to 1.32); the initial rapid rate of reinterventions was followed by a much slower mid-term reintervention rate in both groups. The early higher average quality of life in the endovascular strategy versus open repair group, coupled with the lower mortality at three years, led to a gain in average quality adjusted life years (QALYs) at three years of 0.17 (95% confidence interval 0.00 to 0.33). The endovascular strategy group spent fewer days in hospital and had lower average costs of −£2605 (95% confidence interval −£5966 to £702) (about €2813; $3439). The probability that the endovascular strategy is cost effective was >90% at all levels of willingness to pay for a QALY gain.Conclusions At three years, compared with open repair, an endovascular strategy for suspected ruptured abdominal aortic aneurysm was associated with a survival advantage, a gain in QALYs, similar levels of reintervention, and reduced costs, and this strategy was cost effective. These findings support the increasing use of an endovascular strategy, with wider availability of emergency endovascular repair.Trial registration Current Controlled Trials ISRCTN48334791; ClinicalTrials NCT00746122.

Abdominal aortic aneurysm is the only cardiovascular disease targeted by population screening. In this study, we test the effect of screening and subsequent intervention for abdominal aortic aneurysm, peripheral arterial disease, and hypertension combined. In this randomised controlled trial, we randomly allocated (1:1) all men aged 65–74 years living in the Central Denmark Region to screening for abdominal aortic aneurysm, peripheral arterial disease, and hypertension, or to no screening. We based allocation on computer-generated random numbers from 1 to 100 in blocks of 1067 to 4392, stratified by 19 municipalities. Only the non-screening group and the investigator assessing outcomes were masked. We invited participants who were found to have abdominal aortic aneurysm or peripheral arterial disease back for confirmation and eventual initiation of relevant pharmacological therapy. We further offered participants with abdominal aortic aneurysm annual control or surgical repair. We referred participants with suspected hypertension to their general practitioner. The primary outcome was all-cause mortality, assessed 5 years after randomisation, analysed in all randomly allocated participants except for those who had incorrect person identification numbers. This trial is registered at ClinicalTrials.gov, number NCT00662480. Between Oct 8, 2008, and Jan 11, 2011, we randomly allocated 50 156 participants, with 25 078 (50%) each in the screening and non-screening groups. Four (<1%) participants in the screening group were lost to follow-up. After a median follow-up of 4·4 years (IQR 3·9–4·8), 2566 (10·2%) of 25 074 participants in the screening group and 2715 (10·8%) of 25 078 in the non-screening group had died. This finding resulted in a significant hazard ratio of 0·93 (95% CI 0·88–0·98; p=0·01), an absolute risk reduction of 0·006 (0·001–0·011), and a number needed to invite of 169 (89–1811). Incidences of diabetes (3995 per 100 000 person-years in the screening group vs 4129 per 100 000 person-years in the non-screening group), intracerebral haemorrhage (146 vs 140), renal failure (612 vs 649), cancer (3578 vs 3719), or 30 day mortality after cardiovascular surgery (44·57 vs 39·33) did not differ between groups. The observed reduction of mortality risk from abdominal aortic aneurysm, peripheral arterial disease, and hypertension has never been seen before in the population screening literature and can be linked primarily to initiation of pharmacological therapy. Health policy makers should consider implementing combined screening whether no screening or isolated abdominal aortic aneurysm screening is currently offered. The 7th European Framework Programme, Central Denmark Region, Viborg Hospital, and the Danish Council for Independent Research.

Repair of Abdominal Aortic Aneurysm This clinical trial compared endovascular with open repair of unruptured abdominal aortic aneurysm. An early survival advantage with endovascular repair was not sustained after 3 years. Aneurysm rupture remains a concern with this type of repair. Each year, 40,000 patients in the United States undergo elective procedures to repair abdominal aortic aneurysms. 1 These procedures result in about 1250 perioperative deaths — more than for any other general or vascular surgical procedure, with the exception of colectomy. 2 Endovascular repair was introduced in the 1990s as a less invasive method than traditional open repair. Randomized trials have shown that endovascular repair reduces perioperative mortality, 3 – 5 but in the United Kingdom Endovascular Aneurysm Repair 1 (EVAR 1) trial 3 and the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial, 4 this advantage was lost within 2 years owing to excess late deaths . . .

A new appraisal of the management of acute aortic dissection is timely because of recent developments in diagnostic strategies (including biomarkers and imaging), endograft design, and surgical treatment, which have led to a better understanding of the epidemiology, risk factors, and molecular nature of aortic dissection. Although open surgery is the main treatment for proximal aortic repair, use of endovascular management is now established for complicated distal dissection and distal arch repair, and has recently been discussed as a pre-emptive measure to avoid late complications by inducing aortic remodelling.

A randomized, multicenter trial that compared endovascular repair with open repair of abdominal aortic aneurysm showed no significant difference between these approaches in overall survival after 8 years.

Background Although an association between elevated blood pressure and risk of aortic aneurysm is established, few studies have investigated the association with aortic aneurysm subtypes. We investigated the association between systolic and diastolic blood pressure and hypertension status with the risk of aortic aneurysm in the UK Biobank. Methods The analysis included 495,542 men and women aged 37–73 years at recruitment between 2006 and 2010. Aortic aneurysm cases were identified by linkage to hospitalization and mortality records. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between blood pressure and hypertension and risk of aortic aneurysm overall and for subtypes. Results During a mean follow-up of 12.3 years, 3,346 incident aortic aneurysm cases were identified. Hypertension vs. no hypertension was associated with increased risk (HR, 95% CI) of aortic aneurysm (1.17, 1.08–1.27), and for thoracic (1.23, 1.04–1.46), abdominal (1.16, 1.04–1.30), and non-ruptured (1.18, 1.08–1.28) aortic aneurysm, and suggestively with unspecified site aortic aneurysm (1.18, 0.96–1.46) and aortic aneurysm mortality (1.26, 0.87–1.82), but not ruptured aortic aneurysm (1.02, 0.67–1.58). Systolic blood pressure was not associated with risk of aortic aneurysm overall or for any subtype. Diastolic blood pressure was positively associated with aortic aneurysm (1.74, 1.26–2.41, p trend <0.0001) for ≥ 110 vs. <80 mmHg, abdominal aortic aneurysm (1.95, 1.28–2.96, p trend <0.0001), unspecified site aortic aneurysm (2.02, 0.94–4.33, p trend =0.005), non-ruptured aortic aneurysm (1.79, 1.29–2.47), and aortic aneurysm mortality (2.32, 0.56–9.58, p trend <0.0001), and with ruptured aortic aneurysm (2.48, 1.22–5.03, p trend <0.0001 for 100–109 vs. <80 mmHg), while the association with thoracic aortic aneurysm was less clear (1.30, 0.64–2.63). These associations were strengthened and positive associations emerged for systolic blood pressure and abdominal and non-ruptured aortic aneurysm in sensitivity analyses when excluding participants with prevalent ischemic heart disease, stroke, those using hypertension medications and the first 3 years of follow-up. Conclusion We found that hypertension status and higher diastolic blood pressure were associated with increased risk of aortic aneurysm overall and most aortic aneurysm subtypes. No association was observed for systolic blood pressure. Although further studies are needed on aortic aneurysm subtypes, these findings provide strong support that controlling blood pressure is important for reducing the risk of aortic aneurysm.

Purpose To evaluate the performance of periscope and/or chimney grafts (CPGs) in the endovascular treatment of pararenal or thoracoabdominal aneurysms using off-the-shelf devices. Methods Between February 2002 and August 2012, 77 consecutive patients (62 men; mean age 73±9 years) suffering from pararenal aortic (n=55), thoracoabdominal (n=16), or arch to visceral artery aneurysms (n=6) were treated with aortic stent-graft implantation requiring chimney and/or periscope grafts to maintain side branch perfusion. CPGs were planned in advance and were not used as bailout. A standardized follow-up protocol including computed tomographic angiography, laboratory testing, and clinical examination was performed at 6 weeks; 3, 6, and 12 months; and annually thereafter. Results Technical success was achieved in 76 (99%) patients; 1 branch stent-graft became dislocated from a renal artery, which could not be re-accessed. Overall, 169 target vessels (121 renal arteries, 30 superior mesenteric arteries, 17 celiac trunks, and 1 inferior mesenteric artery) were addressed with the chimney graft configuration in 111 and the periscope graft configuration in 58. In total, 228 devices were used for the CPGs: 213 Viabahn stent-grafts and 15 bare metal stents. Over a mean 25±16 months (range 1–121), 9 patients died of unrelated causes. Nearly all (95%) of the patients demonstrated a decreased or stable aneurysm size on imaging; there was a mean 13% shrinkage in aneurysm diameter. Twenty patients had primary type I/III endoleaks at discharge; in follow-up, only 3 of these were still present (no secondary or recurrent endoleaks were noted). Additional endovascular maneuvers were required for CPG-related complications in 13 patients from intervention throughout follow-up. Overall, 4 CPGs occluded (98% target vessel patency); no stent-graft migration was observed. Renal function remained stable in all patients. Conclusion In this series, the use of CPGs has proven to be a feasible, safe, and effective way to treat thoracoabdominal and pararenal aneurysms with maintenance of blood flow to the renovisceral arteries. Nearly all of the aneurysms showed no increase in diameter over a >2-year mean follow-up, which supports the midterm adequacy of the CPG technique as a method to effectively revascularize branch vessels with few endoleaks or branch occlusions.

Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10 μg) or matching placebo for 6 days after surgery. Major exclusion criteria included fatal hemorrhagic shock, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 min. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline except more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI 0.21–8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the IFN beta-1a arm vs. 9.1% in the placebo arm). Patients with high level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta-1a neutralizing antibodies associated with a poor CD73 response and survival. The initial aim of the trial, if postoperative INF beta-1a treatment results on better RAAA survival, could not be demonstrated. Nonetheless the anticipated target mechanism up-regulation of CD73 was associated with 100% survival. According to present results the INF beta-1a induced up-regulation of serum CD73 was blocked with both use of glucocorticoids and serum IFN beta-1a neutralizing antibodies. The study was pre-maturely stopped due to interim analysis after a study concerning the use if IV IFN beta-1a in ARDS suggested that the concomitant use of glucocorticoids and IFN beta-1a block the CD73 induction. Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered).

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.

Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.