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It has been suggested that covered stents (CS) may lower restenosis rates compared with bare metal stents (BMS) after endovascular treatment of the common iliac artery. This trial aimed to provide additional evidence on the efficacy of CS vs. BMS in the common iliac artery. This multicentre, randomised, single blind controlled superiority trial compared balloon expandable CS and balloon expandable BMS for advanced atherosclerotic lesions in the common iliac artery; this was defined as a stenosis > 3 cm in length or occlusion. The primary end point was freedom from binary restenosis after two years of follow up. The study was conducted according to the principles of the Declaration of Helsinki (version: October 2008) and registered with the Dutch Trial register (NTR3381). One hundred and seventy-four limbs were included between 2012 and 2019 with 87 limbs in each group. Six patients crossed over from the BMS group to the CS group but were analysed according to an intention to treat principle. Freedom from binary restenosis after two years of follow up was 84.7% (95% CI 76.7 – 92.7%) in the BMS group and 89.1% (95% CI 82.4 – 95.8%) in the CS group (p =.40). Freedom from occlusion was 95.0% (95% CI 90.3 – 95.7%) in the BMS group and 96.4% (95% CI 92.5 – 100%) in the CS group (p =.66). Freedom from target lesion revascularisation was 91.1% (95% CI 84.8 – 97.3%) and 95.2% (95% CI 90.7 –99.7%), respectively (p =.31). Technical success, complications, haemodynamic success, and clinical success were also comparable between both groups. Per-protocol analysis did not affect the outcomes of the study. No difference was found between balloon expandable CS and BMS for treating advanced atherosclerotic lesions of the common iliac artery. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of thoracic endovascular aortic repair (TEVAR) in the treatment of patients with complicated type B aortic intramural haematoma (IMH). A retrospective observational study of patients treated between January 2002 and December 2017 was performed. Complicated type B IMH was defined as persistent pain, rapid dilatation, presence of ulcer-like projections (ULPs), haemothorax, and other signs of (impending) rupture. Thirty day results and long term follow up outcomes were reported. Thirty-nine patients were included for analysis (mean age 68 ± 8 years, 36% male). The thirty day mortality rate was 5%, stroke rate 10%, and re-intervention rate 3%. The median follow up duration was 49 months (25th – 75th percentile: 2 – 96 months). At 10 years, estimated freedom from all cause mortality was 66 ± 9%. During follow up, nine re-interventions were performed, leading to a 10 year estimated freedom from re-intervention rate of 72 ± 8%. Estimated freedom from aortic growth at 10 years was 85 ± 9%. Complicated type B IMH can be treated effectively by TEVAR, thus preventing death from aortic rupture. However, severe early post-operative complications, most importantly stroke, are of concern. Long term outcomes are excellent, although re-interventions are not uncommon, either for progression of proximal or distal aortic disease or due to stent graft related complications. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe single-center intraoperative details and early outcome of the new GORE TAG conformable stent graft with ACTIVE CONTROL (C-TAG ACTIVE CONTROL; W. L. Gore & Associates, Flagstaff, Ariz). Between September 2017 and June 2018, a consecutive 30 patients underwent thoracic endovascular aortic repair with C-TAG ACTIVE CONTROL. This new system provides an intermediate deployment step at 50% and optional angulation control of the proximal part of the stent graft. Indications for thoracic endovascular aortic repair varied widely, including chronic postdissection and degenerative aneurysms, complicated acute dissections, and intramural hematomas, among others, in an elective (63.3%), urgent (13.3%), or emergent (23.3%) setting. The proximal landing zone (LZ) was LZ 2 in 23.3%, LZ 3 in 43.3%, and LZ 4 in 33.3%. Data were collected retrospectively and analyzed for technical and clinical success. In all patients, the stent graft was successfully introduced and deployed at the intended position, with complete exclusion of aortic disease and without intraoperative mortality (primary technical success, 100%). One emergent patient died at 2 days of ongoing septic shock (clinical success at 30 days, 96.6%). Median follow-up was 107 days (range, 33-271 days); late mortality was 3.4% (one patient died of stent graft infection at 40 days). Freedom from type I and type III endoleak at the early follow-up was 100%. No patients required other surgical or endovascular procedures for the primary treated aortic disease. Our reported initial experience in 30 patients with the C-TAG ACTIVE CONTROL showed excellent early results, with high deployment accuracy and conformability. The additional features of staged deployment and angulation control may be of great help in challenging aortic arch diseases, allowing precise positioning and preventing bird-beak effect. [ABSTRACT FROM AUTHOR]

Goal: Insufficient data is available about safety and efficacy of endovascular treatment (EVT) in patients with minor stroke symptoms because these patients were excluded from most randomized trials. We aimed to compare characteristics, functional outcome, and complications in patients with minor ischemic stroke National Institutes of Health Stroke Scale score ≤5 (NIHSS score ≤5) and moderate to severe ischemic stroke (NIHSS score ≥6) due to intracranial proximal artery occlusion of the anterior circulation who underwent EVT.Materials and Methods: We report patients with an anterior circulation occlusion who were included between March 2014 and June 2016 in the multicenter randomized clinical trial of EVT of acute ischemic stroke in the Netherlands Registry, a prospective, multicenter, observational study for stroke centers that perform EVT in the Netherlands. Minor ischemic stroke was defined as baseline NIHSS score of 5 or less. Primary outcome is the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes include symptomatic intracranial hemorrhage (sICH) and mortality.Findings: Seventy-one (5.5%) patients had a NIHSS score of 5 or less. Functional independence (mRS 0-2 at 90 days) was reached in 75% of these patients, compared to 40% of patients with NIHSS score of 6 or more. sICH occurred in 4% of patients, of which 1% occurred peri-interventionally. Death occurred in 6% of patients.Conclusions: Patients with minor ischemic stroke with an intracranial proximal arterial occlusion of the anterior circulation who underwent EVT have a high chance of favorable outcome and appear to have low occurrence of treatment-related sICH. Therefore, our results encourage the use of EVT for minor ischemic stroke in the absence of effect estimates from controlled studies. [ABSTRACT FROM AUTHOR]

Introduction: The Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) trial showed efficacy of intra-arterial (IA) treatment in acute ischemic stroke (AIS). We studied the evolution of IA treatment for AIS and its effects on clinical outcome and recanalization in The Netherlands in the pre-MR CLEAN era.Methods: Data on 517 patients with AIS treated with IA therapy were collected retrospectively from all intervention centers in The Netherlands from 2002 to the start of participation in the MR CLEAN trial. Clinical outcome was measured by means of the modified Rankin Scale score and recanalization with the Thrombolysis in Cerebral Infarction Scale.Results: IA therapy was first used in patients with basilar artery occlusion. Over the years, there was a gradual increase in the number of anterior circulation strokes treated. There was a shift in applied therapies from primary IA therapy to combined intravenous and IA therapy and from IA thrombolysis to mechanical thrombectomy. Time from symptom onset to treatment decreased. Recanalization rates gradually increased. At the same time, there was a trend toward more favorable outcomes after 3 months and fewer deceased patients both at discharge and after 3 months. However, none of these changes reached statistical significance.Conclusion: The treatment approach used in the MR CLEAN trial was the result of an evolution of practise in the preceding years, with gradual improvement in technical and clinical outcomes. [ABSTRACT FROM AUTHOR]

Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of cholesterol synthesis and plasma cholesterol levels is incomplete. One way of addressing the remaining questions is by making use of computational models. Here, we critically evaluate existing computational models of cholesterol metabolism making use of ordinary differential equations and addressed whether they used assumptions and make predictions in line with current knowledge on cholesterol homeostasis. Having studied the results described by the authors, we have also tested their models. This was done primarily by testing the effect of statin treatment in each model. Ten out of eleven models tested have made assumptions in line with current knowledge of cholesterol metabolism. Three out of the ten remaining models made correct predictions, i.e. predicting a decrease in plasma total and LDL cholesterol or increased uptake of LDL upon treatment upon the use of statins. In conclusion, few models on cholesterol metabolism are able to pass a functional test. Apparently most models have not undergone the critical iterative systems biology cycle of validation. We expect modeling of cholesterol metabolism to go through many more model topologies and iterative cycles and welcome the increased understanding of cholesterol metabolism these are likely to bring. [ABSTRACT FROM AUTHOR]

Independent Environmental Impact Assessment (EIA) follow-up verifiers such as monitoring agencies, checkers, supervisors and control officers are active on various construction sites across the world. There are, however, differing views on the value that these verifiers add and very limited learning in EIA has been drawn from independent verifiers. This paper aims to appraise how and to what extent independent EIA follow-up verifiers add value in major construction projects in the developing country context of South Africa. A framework for appraising the role of independent verifiers was established and four South African case studies were examined through a mixture of site visits, project document analysis, and interviews. Appraisal results were documented in the performance areas of: planning, doing, checking, acting, public participating and integration with other programs. The results indicate that independent verifiers add most value to major construction projects when involved with screening EIA requirements of new projects, allocation of financial and human resources, checking legal compliance, influencing implementation, reporting conformance results, community and stakeholder engagement, integration with self-responsibility programs such as environmental management systems (EMS), and controlling records. It was apparent that verifiers could be more creatively utilized in pre-construction preparation, providing feedback of knowledge into assessment of new projects, giving input to the planning and design phase of projects, and performance evaluation. The study confirms the benefits of proponent and regulator follow-up, specifically in having independent verifiers that disclose information, facilitate discussion among stakeholders, are adaptable and proactive, aid in the integration of EIA with other programs, and instill trust in EIA enforcement by conformance evaluation. Overall, the study provides insight on how to harness the learning opportunities arising from EIA follow-up through the appointment of independent verifiers. [ABSTRACT FROM AUTHOR]

GALNT2 , encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. Experimental data were obtained through studies in Galnt2 −/− mice and wild-type littermates on both control and high-fat diet. First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2 −/− mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor. [ABSTRACT FROM AUTHOR]

Little is known regarding the long-term patency rates of surgical left subclavian artery (LSA) revascularization, especially when performed concomitant to thoracic endovascular aortic repair and without arterial occlusive disease. Our aim is to contribute to the existing evidence by reporting the patency rates at mid- and long-term follow-up after surgical LSA revascularization. This observational, retrospective, single-center cohort study included 90 eligible patients who underwent a left common carotid artery to LSA bypass (72%) or transposition (28%) from December 31, 2017 to January 1, 2000. Data regarding demographics, medical history, intraoperative characteristics, and outcomes regarding bypass graft or transposition patency, severe stenosis, or occlusion were assessed at discharge, 3 months, 1 year, and maximum follow-up using consecutive follow-up computed tomography scans. In our predominantly male (74%) cohort with a mean age of 66 years (standard deviation, ±12 years), LSA revascularization was mostly performed concomitant to or adjacent to thoracic endovascular aneurysm repair procedures (98%) with the primary indication for surgery being degenerative or saccular aneurysmatic aortic disease (50%), subacute or acute type B aortic dissection (17%), post-dissection aortic aneurysm (16%), type B intramural hematoma (6%), and other indications (11%). Ninety-seven percent of our left common carotid artery to LSA bypasses were performed using a central, supraclavicular approach, and the other 3% were performed using an infraclavicular approach to the LSA. Median diameter of the bypass was 6 mm (range, 6-12 mm). We found two occlusions at 7.7 and 12.9 months follow-up and four severe stenoses at 21.2, 35.4, 38.3, and 46.7 months follow-up, respectively. Estimated freedom from occlusion was 97% ± 2% and freedom from severe stenosis was 90% ± 4% at both midterm (5 years) and long-term (10 years) follow-up, with a median follow-up duration of 42.2 months for occlusion (25th-75th percentile, 15.4-67.4 months) and 41.9 months (25th-75th percentile, 15.4-67.4 months) for severe stenosis. Open surgical LSA revascularization may be considered the gold standard to preserve antegrade LSA flow in the context of debranching for thoracic endovascular aneurysm repair or open surgical aortic arch repair, with excellent patency rates at mid-term and long-term follow-up. [ABSTRACT FROM AUTHOR]

Mining of the genome for lipid genes has since the early 1970s helped to shape our understanding of how triglycerides are packaged (in chylomicrons), repackaged (in very low density lipoproteins; VLDL), and hydrolyzed, and also how remnant and low-density lipoproteins (LDL) are cleared from the circulation. Gene discoveries have also provided insights into high-density lipoprotein (HDL) biogenesis and remodeling. Interestingly, at least half of these key molecular genetic studies were initiated with the benefit of prior knowledge of relevant proteins. In addition, multiple important findings originated from studies in mouse, and from other types of non-genetic approaches. Although it appears by now that the main lipid pathways have been uncovered, and that only modulators or adaptor proteins such as those encoded by LDLRAP1 , APOA5 , ANGPLT3/4 , and PCSK9 are currently being discovered, genome wide association studies (GWAS) in particular have implicated many new loci based on statistical analyses; these may prove to have equally large impacts on lipoprotein traits as gene products that are already known. On the other hand, since 2004 – and particularly since 2010 when massively parallel sequencing has become de rigeur – no major new insights into genes governing lipid metabolism have been reported. This is probably because the etiologies of true Mendelian lipid disorders with overt clinical complications have been largely resolved. In the meantime, it has become clear that proving the importance of new candidate genes is challenging. This could be due to very low frequencies of large impact variants in the population. It must further be emphasized that functional genetic studies, while necessary, are often difficult to accomplish, making it hazardous to upgrade a variant that is simply associated to being definitively causative. Also, it is clear that applying a monogenic approach to dissect complex lipid traits that are mostly of polygenic origin is the wrong way to proceed. The hope is that large-scale data acquisition combined with sophisticated computerized analyses will help to prioritize and select the most promising candidate genes for future research. We suggest that at this point in time, investment in sequence technology driven candidate gene discovery could be recalibrated by refocusing efforts on direct functional analysis of the genes that have already been discovered. This article is part of a Special Issue entitled: From Genome to Function. [ABSTRACT FROM AUTHOR]

Objective The durability of an infrainguinal bypass may be hampered by development of stenosis at the anastomoses. We describe the patency of percutaneous transluminal angioplasty (PTA) of these anastomotic stenoses. Methods Any venous or prosthetic infrainguinal bypass with a hemodynamically significant anastomotic stenosis, symptomatic or asymptomatic, was considered a bypass at risk (BAR) for occlusion. All BARs undergoing PTA in two large vascular referral centers between January 2005 and December 2010 were retrospectively reviewed. Procedural success was defined as <30% residual stenosis. Primary end points were primary, assisted primary, and secondary patency rates. Results Included were 43 patients with 43 BARs (31 venous, 11 prosthetic, and 1 unknown conduit; 19 supragenicular and 24 infragenicular). Mean follow-up was 17 months (range, 0-57 months). Procedures constituted 48 interventions for proximal (n = 13), distal (n = 25), or combined (n = 5) anastomotic stenoses. Procedural success was 96%. The primary, assisted primary, and secondary patency rates were 58%, 85%, and 88%, respectively, at 2 years. Conclusions PTA for infrainguinal BAR due to anastomotic stenosis is technically feasible with acceptable durability. PTA for these anastomotic stenoses may be considered a safe option as the first-line treatment. [ABSTRACT FROM AUTHOR]

Objective: The Endurant endograft (Medtronic Inc, Minneapolis, Minn) is a new-generation device specifically developed to perform well in complex abdominal aortic aneurysm anatomy. Previous reports on the 1- and 2-year results of endovascular aneurysm repair (EVAR) with the Endurant endograft showed excellent outcome, including prevention of migration and type I endoleaks, but occurrence and outcome of post-EVAR occlusion have not been determined in a large multicenter patient cohort with midterm follow-up, which is the objective of this study. Methods: Data of consecutive patients treated with the Endurant from December 2007 to April 2012 in three Dutch tertiary vascular referral hospitals were prospectively gathered and retrospectively analyzed. Follow-up consisted of regular office visits, computed tomography angiography at 1 and 12 months after EVAR, and subsequently, duplex ultrasound imaging or computed tomography angiography at regular intervals. Patients with ruptured aneurysms or with earlier abdominal aortic surgery were excluded. The incidence and clinical outcome of endograft occlusions were analyzed. An expert review board assessed all cases in the search for possible causes of occlusion. Results: Included were 496 patients (87.7% male), who were a median age of 74 years (range, 68-78 years). Median follow-up was 1.7 years (range, 0-4.6 years). Twenty graft occlusions (4.0%) occurred during follow-up. Median time between primary EVAR and detection of the occlusion was 1 month, with 55% occurring ≤60 postoperative days and 90% ≤1 year. No association was found between occlusion and sex (P = .28), age (P = .96), or use of an aortouniiliac device (P = .66). Technical error was the considered cause of the occlusion in 12 patients (60%). The estimated freedom from occlusion was 98.4% at 30 days, 95.7% at 1 year, and 95.3% at 3 years. Presenting symptoms of occlusion were acute limb ischemia in 50%. Treatment was surgical (75%) or percutaneous (25%). Successful revascularization was achieved in 17 of 20 patients, but reocclusions occurred in five, resulting in a transfemoral amputation in one patient. Occlusion-related mortality was 0.6% (3 of 496). Conclusions: At a median follow-up of 1.7 years, Endurant endograft occlusion occurred in 4.0% of 496 patients. Most occlusions occurred ≤2 months after EVAR, and rarely after 1 year. A technical justification for occlusion could be found for 60% of patients. A more liberal intraoperative and early postoperative (re)intervention strategy may reduce the occlusion rates and improve outcome. [Copyright &y& Elsevier]

Background: Since the introduction of endovascular aneurysm repair (EVAR), long-term follow-up studies reporting single-device results are scarce. In this study, we focus on EVAR repair with the Talent stent graft (Medtronic, Santa Rosa, Calif). Methods: Between July 2000 and December 2007, 365 patients underwent elective EVAR with a Talent device. Patient data were gathered prospectively and evaluated retrospectively. By American Society of Anesthesiologists category, 74% were categories III and IV. Postoperative computed tomography (CT) scanning was performed before discharge, at 3, 12 months, and yearly thereafter. Data are presented according to reporting standards for EVAR. Results: The mean proximal aortic neck diameter was 27 mm (range, 16-36 mm), with a neck length <15 mm in 31% (data available for 193 patients). Deployment of endografts was successful in 361 of 365 patients (99%). Initially, conversion to laparotomy was necessary in four patients. Primary technical success determined by results from computed tomography (CT) scans before discharge was achieved in 333 patients (91%). Proximal type I endoleaks were present in 28 patients (8%) during follow-up, and 14 of these patients needed additional treatment for type I endoleak. The 30-day mortality for the whole Talent group was 1.1% (4 of 365). Follow-up to 84 months is reported for 24 patients. During follow-up, 122 (33%) patients died; in nine, death was abdominal aortic aneurysm (AAA)-related (including 30-day mortality). Kaplan-Meier estimates revealed primary clinical success rates of 98% at 1 year, 93% at 2 years, 88% at 3 years, 79% at 4 years, 64% at 5 years, 51% at 6 years, and 48% at 7 years. Secondary interventions were performed in 73 of 365 patients (20%). Ten conversions for failed endografts were performed. Life-table yearly risk for AAA-related reintervention was 6%, yearly risk for conversion to open repair was 1.1%, yearly risk for total mortality was 8.9%, and yearly risk for AAA-related mortality was 0.8%. Conclusion: Initially, technical success of endovascular aneurysm repair (EVAR) using the Talent endograft is high, with acceptable yearly risk for AAA-related mortality and conversion. However, a substantial amount of mainly endovascular reinterventions is necessary during long-term follow-up to achieve these results. [Copyright &y& Elsevier]

Background: Carotid angioplasty and stenting (CAS) for recurrent stenosis after carotid endarterectomy (CEA) has been proposed as an alternative to redo CEA. Although early results are encouraging, the extended durability remains unknown. We present the long-term surveillance results of CAS for post-CEA restenosis. Methods: Between 1998 and 2004, 57 CAS procedures were performed in 55 patients (36 men) with a mean age of 70 years. The mean interval between CEA and CAS was 83 months (range, 6 to 245). Nine patients (16%) were symptomatic. Results: CAS was performed successfully in all patients. No deaths or strokes occurred. A periprocedural transient ischemic attack (TIA) occurred in two patients. During a mean follow-up of 36 months (range, 12 to 72 months), two patients exhibited ipsilateral cerebral symptoms (1 TIA, 1 minor stroke). In 11 patients (19%), in-stent restenosis (≥50%) was detected post-CAS at month 3 (n = 3), 12 (n = 3), 24 (n = 2), 36 (n = 1), 48 (n = 1), and 60 (n = 1). The cumulative rates of in-stent restenosis-free survival at 1, 2, 3, and 4 years were 93%, 85%, 82%, and 76%, respectively. Redo procedures were performed in six patients, three each received repeat angioplasty and repeat CEA with stent removal. The cumulative rates of freedom from reintervention at 1, 2, 3, and 4 years were 96%, 94%, 90%, and 84%, respectively. Conclusion: Carotid angioplasty and stenting for recurrent stenosis after CEA can be performed with a low incidence of periprocedural complications with durable protection from stroke. The rate of in-stent recurrent stenosis is high, however, and does not only occur early after CAS but is an ongoing process. [Copyright &y& Elsevier]

Background: Elective endovascular repair of the thoracic aorta has shown reduced morbidity and mortality when compared with open surgery. The number of studies describing the use of thoracic endovascular stent grafts for acute pathology is limited, however. The purpose of this study was to describe our increasing experience with stent grafting for acute thoracic aortic pathology. Methods: Since January 2002, 28 patients underwent endovascular stent graft treatment for various types of acute thoracic aorta diseases, including complicated Stanford type B dissection (n = 12), ruptured descending aorta aneurysms (n = 7), intramural hematoma (n = 4), traumatic rupture of the thoracic aorta (n = 2), aortopulmonary fistula (n = 2), and penetrating aortic ulcer (n = 1). These acute thoracic aortic syndromes were predominantly localized in the proximal descending thoracic aorta (75%). Talent stent grafts were used in 26 patients and Excluder stent grafts in 2 patients. Results: Stent graft deployment at the intended position was successful in all patients. There was 1 intraoperative death (3.6%), due to acute myocardial infarction, after successful exclusion of the lesion with a stent graft. Hospital mortality was 21.4% (n = 6). Four of 6 hospital deaths, however, were directly related to the severely compromised clinical status preoperatively, including extensive bowel ischemia and irreversible cerebral damage after resuscitation. New neurologic symptoms were seen in 4 patients. The majority of the neurologic symptoms improved and faded away during hospital stay. Mean follow-up was 11 months (range, 1 to 31), and all the hospital survivors (n = 22) were alive. There was 1 nonrelated stroke 4 months postoperatively. During follow-up, 2 patients required transposition of the left subclavian artery for malperfusion, and 2 patients required a second stent graft procedure for endoleak. Additionally, 2 patients with early type II endoleaks were treated conservatively, and 1 of them sealed spontaneously at 6 months. Conclusions: Thoracic stent grafting for acute aortic pathology is feasible in critically ill patients. Postoperative morbidity and mortality is predominantly related to the compromised preoperative clinical status, illustrating its use as salvage strategy. [Copyright &y& Elsevier]

The use of femoral artery closure devices to obtain hemostasis after percutaneous catheterization has become widespread because of their proven feasibility in combination with patient-related advantages. Since 2002 more than 6,500 patients have undergone either diagnostic angiography or therapeutic intervention via the femoral route with an Angioseal closure device in our hospital. We were faced with six cases of limb-threatening complications, which are described here. Most (5/6) complications were of obstructive origin due to traumatic dissection or occlusion of the artery mainly caused by malpositioning of the device. Recommendations are made in order to prevent or successfully overcome this certainly increasing problem in the vascular field. [ABSTRACT FROM AUTHOR]

Abstract: The frequent lipoprotein lipase S447X variant (LPLS447X) is firmly associated with a lower incidence of cardiovascular disease, the mechanisms for which remain to be established. To further unravel these beneficial effects, we studied the consequences of LPLS447X heterozygosity on LPL mass and activity, as well as on the postprandial lipoprotein profile. Fifteen male heterozygous LPLS447X carriers and 15 matched control subjects received an oral fat load (30 g/m2). Lipid parameters were evaluated at baseline and 2, 3, 4, and 6 hours after fat loading. LPL concentration and activity were analyzed, and endothelial function was evaluated noninvasively as flow-mediated dilation of the brachial artery. Although baseline apoprotein B-48 (apoB48) levels were similar, the rise in apoB48 was attenuated in LPLS447X carriers with 25% lower peak values compared with controls (P = .04). In conjunction, LPLS447X carriers were characterized by a 2.4-fold increase in preheparin LPL mass (P < .0001). The decrease in postprandial flow-mediated dilation was comparable in both groups. LPLS447X carriers exhibit enhanced apoB48 clearance with concomitant increase in preheparin LPL mass, without changes in LPL activity. This combination might suggest a role for increased ligand action of LPL in LPLS447X carriers contributing to the cardiovascular protection in carriers of this mutation. [Copyright &y& Elsevier]

The inhibition of cholesteryl ester transfer protein (CETP) has recently been shown to effectively increase high-density lipoprotein (HDL) cholesterol. This study examined the use of the CETP inhibitor JTT-705 combined with pravastatin. In a randomized, double-blind, placebo-controlled trial, 155 patients with type II dyslipidemia using pravastatin 40 mg were treated with placebo or JTT-705 300 or 600 mg. Four weeks of treatment with JTT-705 600 mg led to a 30% decrease in CETP activity (p &#60;0.001), a 28% increase in HDL cholesterol (p &#60;0.001), and a 5% decrease in low-density lipoprotein cholesterol (p &#60;0.03). Combination therapy using JTT-705 and pravastatin effectively increases HDL cholesterol levels and is safe and well tolerated up to 4 weeks of administration. [Copyright &y& Elsevier]

Purpose: To assess the long-term technical success of repeated endovascular intervention in stenosed renal artery stents.Materials and Methods: Fifteen patients with stenoses >or=50% in a renal stent placed because of an ostial atherosclerotic renal artery stenosis were included in this study. In the presence of increased blood pressure or decreased renal function, the in-stent restenosis was treated with percutaneous transluminal angioplasty (PTA) in the stent or placement of a second stent if the stenosis was located too distally in the stent. The results of these repeat interventions were evaluated by angiography.Results: The 15 patients had a total of 20 stenosed stents. Eighteen of these in-stent stenoses were treated with PTA and two were treated with placement of a second stent. Angiographic follow-up was available in 16 arteries, showing in-stent restenosis in four (25%; mean follow-up, 11 mo). The cumulative patency rates after repeat endoluminal intervention were 93% (95% CI: 80%-106%) and 76% (95% CI: 52%-101%) after 6 and 12 months, respectively. Renal function remained stable or improved in most patients (80%) after repeated intervention in the stent, and hypertension was classified as improved or cured in 47% of patients after 1 year.Conclusion: Patients with stenosed renal artery stents can be treated successfully with PTA in a majority of cases, with a long-term success rate of 75% and stable renal function 1 year after repeated intervention. [ABSTRACT FROM AUTHOR]

An 86-year-old lady presented after waking up with left sided paresis and neglect. Right hemispheral stroke was suspected, but initial MRI with Diffusion Weighted Imaging (DWI) was negative and there was no large vessel occlusion. We accordingly withheld intravenous thrombolysis. She did not improve clinically and follow-up MRI after three days showed a marked lesion compatible with acute ischemic stroke in the right middle cerebral artery territory. This case shows that even with a disabling stroke in the anterior circulation initial DWI may be negative. Former studies established that thrombolysis can be safe in these cases when there is no doubt about the clinical diagnosis of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

An 86-year-old lady presented after waking up with left sided paresis and neglect. Right hemispheral stroke was suspected, but initial MRI with Diffusion Weighted Imaging (DWI) was negative and there was no large vessel occlusion. We accordingly withheld intravenous thrombolysis. She did not improve clinically and follow-up MRI after three days showed a marked lesion compatible with acute ischemic stroke in the right middle cerebral artery territory. This case shows that even with a disabling stroke in the anterior circulation initial DWI may be negative. Former studies established that thrombolysis can be safe in these cases when there is no doubt about the clinical diagnosis of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Distal migration of aortic abdominal endografts may lead to endoleaks and must be overcome. Revision surgery has been related to substantial morbidity and mortality. In this case report, a new endovascular technique has been described to secure migrated primary endografts and proximal extender cuffs during revision surgery after failed endovascular aneurysm repair with the use of endostaples. At 6-month follow-up, no complications were noticed in both treated patients. [Copyright &y& Elsevier]

The Percutaneous transluminal Angioplasty and Drug eluting stents for Infrapopliteal lesions in critical limb ischemia (PADI) trial is a prospective, multicenter, randomized, controlled, double-arm study investigating the safety and efficacy of primary paclitaxel-eluting stent implantation vs primary percutaneous transluminal angioplasty (PTA) in infrapopliteal lesions in critical limb ischemia (CLI). PTA with provisional “bailout” stent implantation is currently an accepted treatment for arterial obstructions in CLI, including those in below-the-knee arteries. A drawback compared to open bypass surgery is the relatively high restenosis rate. One proposed method to reduce restenosis is the use of drug-eluting stents (DES), as these have shown good results in the coronary bed. Primary DES implantation for focal obstructions in infrapopliteal arteries in CLI potentially reduces restenosis compared to PTA alone and may subsequently prolong effect of treatment, allowing for better wound healing, and preventing recurrence of symptoms. In this article, we report on rationale, design, and progress of the PADI trial, which investigates the safety and efficacy of a paclitaxel-eluting stent system compared to PTA with provisional bare metal stent implantation (Clinicaltrials.gov number NCT00471289). [Copyright &y& Elsevier]

We report the case of a 71-year-old man with acute back and left flank pain caused by a large pseudoaneurysm of the left renal artery. The pseudoaneurysm resulted from a complete fracture of a stent that had been placed at the origin of this vessel 10 months earlier. Because the left kidney had no residual function, the patient was treated by percutaneous occlusion of the left renal artery with a vascular plug. The symptoms rapidly subsided, and he remained symptom free at the 6-month follow-up. Stent fractures, their complications, and management are discussed. [Copyright &y& Elsevier]

Purpose: To compare outcomes after endovascular treatment (EVT) for acute ischemic stroke with and without the use of a balloon guide catheter (BGC) in clinical practice.Materials and Methods: Data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry were used, in which all patients who underwent EVT for anterior-circulation stroke in The Netherlands between 2014 and 2016 were enrolled. Primary outcome was modified Rankin scale (mRS) score at 90 days. Secondary outcomes included reperfusion grade (extended Thrombolysis In Cerebral Infarction [eTICI] score) and National Institutes of Health Stroke Scale (NIHSS) score 24-48 hours after intervention. The association between the use of a BGC and outcomes was estimated with logistic regression adjusted for age, sex, prestroke mRS score, NIHSS score, collateral grade, and time from onset to EVT.Results: A total of 887 patients were included. Thrombectomy was performed with the use of a BGC in 528 patients (60%) and without in 359 patients (40%). There was no significant association between use of a BGC and a shift on the mRS toward better outcome (adjusted common odds ratio, 1.17; 95% confidence interval [CI], 0.91-1.52). Use of a BGC was associated with higher eTICI score (adjusted common OR, 1.33; 95% CI, 1.04-1.70) and improvement of ≥ 4 points on the NIHSS (adjusted OR, 1.40; 95% CI, 1.04-1.88).Conclusions: In clinical practice, use of a BGC was associated with higher reperfusion grade and early improvement of neurologic deficits, but had no positive effect on long-term functional outcome. [ABSTRACT FROM AUTHOR]

Environmental impact assessment (EIA) and responsible tourism both aspire to contribute to sustainable development. EIA is the process of identifying, assessing and managing the potential impacts of new developments and is legally mandated in most countries of the world. Tourism developments are subject to EIA under South African legislation, which requires consideration of the full range of sustainable development objectives. This paper highlights the parallels found in the discourses of EIA and responsible tourism, identified through a focused literature review, and develops a framework comprising five characteristics that EIA should embody to maximize its contribution to responsible tourism. It tests the framework by evaluating three EIAs conducted in the Kruger National Park since 2011, when South African National Parks (SANParks) formally committed to responsible tourism. The evaluation process confirmed the utility of the framework and highlighted areas in which responsible tourism principles could be more explicitly reflected in SANParks EIAs. • EIA and responsible tourism literature is reviewed and commonalities identified. • EIA has considerable potential to contribute to responsible tourism developments. • EIAs of proposed tourism developments in the Kruger National Park are evaluated. • More could be done to better align EIAs with principles of responsible tourism. [ABSTRACT FROM AUTHOR]

• Computational Chemistry can be used to identify alternative catalysts materials. • The NiCo 3 alloy is electronically similar to pure Co. • Co-Ni alloy catalysts for Fischer-Tropsch synthesis were made and characterized. • Co-Ni alloy catalysts perform similar to Co up to 25% Ni content. The low temperature Fischer-Tropsch (FT) synthesis reaction is commercially performed on either Fe- or Co-based systems, while Ni-based systems are not considered due to a poor selectivity profile. This study focuses on alternative bimetallic catalytic materials for FT in which both Co and Ni are present. Co-Ni based alloys have been identified as a possible FT synthesis catalyst through a separate, DFT based computational chemistry screening approach of various bimetallic alloys based on the similarity of their underlying calculated electronic structures to that of Co. Based on this screening result and a cost filtering, several supported catalysts have been prepared with varying Co:Ni ratios. These catalysts have been characterised with various techniques (TPR, EDS, EELS, Magnetic measurements) to assess whether these catalysts indeed show Co-Ni alloy formation. These materials were also tested for FT synthesis activity, showing that the selectivities of the Co-Ni alloys are similar to that of pure Co up to a nickel content of 25%. It was also concluded that the computational screening approach can be used to execute predictive metal screening. [ABSTRACT FROM AUTHOR]

Objectives: This study compared transcranial Doppler (TCD) imaging and outcomes of carotid angioplasty and stenting (CAS) in stenosis after carotid endarterectomy (CEA) vs primary atherosclerotic stenoses. Methods: A prospectively accumulated database of 812 CAS procedures was analyzed retrospectively. Two groups were created. Group 1 had 72 restenoses at a mean of 71 months (range, 5-245 months) after initial CEA. Group 2 had 740 primary stenoses. Clinical end points were cerebral ischemic events and death. TCD end points were numbers of isolated microemboli and microembolic showers during five procedural phases. Results: Groups 1 and 2 were evenly matched for demographic data: median age, 70 vs 71 years; 44 (61%) vs 525 men (71%); 14 (19%) vs 147 symptomatic (20%). Seven (0.9%) deaths and 10 major (1.2%) and 21 minor (2.6%) strokes occurred in group 2 (P = .049). Mean (standard deviation) numbers of isolated microemboli for groups 1 vs 2 were wiring, 37.0 (31.1) vs 50.4 (52.6); predilation, 14.8 (18.7) vs 21.7 (21.8); stent placement, 58.6 (31.1) vs 64.7 (38.8); postdilation, 20.4 (16.5) vs 27.2 (34.9), cerebral protection device (CPD) use, 44.2 (30.2) vs 37.5 (36.8); total, 134.8 (68.7) vs 175.3 (113.8). Microembolic showers: wiring, 1.7 (4.5) vs 2.2 (6.4); predilation, 2.1 (4.1) vs 3.3 (5.8); stent placement, 21.5 (22.0) vs 26.9 (25.1); postdilation, 5.3 (15.7) vs 5.0 (8.1); CPD use, 5.8 (6.9) vs 6.2 (8.9); total, 30.4 (36.0) vs 39.6 (35.0). TCD data for CPD use vs without for isolated emboli: wiring, 53.2 (45.1) vs 44.3 (51.7); predilation, 24.7 (20.2) vs 18.2 (22.5); stent placement, 77.5 (34.8) vs 53.5 (37.3); postdilation, 33.6 (36.6) vs 20.7 (21.8); CPD use, 38.3 (36.6) vs 0; total, 222.5 (113.8) vs 132.3 (89.1). Showers: wiring, 2.4 (6.6) vs 1.9 (5.8); predilation, 4.2 (6.4) vs 2.4 (5.0); stent placement, 38.9 (25.8) vs 16.2 (18.7); post-dilation, 7.0 (11.2) vs 3.4 (6.4); CPD use, 6.3 (8.9) vs 0; total, 58.4 (37.7) vs 23.3 (23.1). P = .01 for showers during wiring and P < .001 for all other variables. After correction for the difference in CPD use between groups 1 and 2 (17 out of 72 [24%] vs 369 out of 740 [50%]), no statistically significant differences remained in numbers of isolated emboli and embolic showers in the procedural phases or for the entire procedure. No statistically significant differences were found when TCD-detected microembolic load for early (<3 years between CEA and CAS) and late (>5 years) restenoses were compared. Conclusions: CAS for restenosis after CEA has a complication rate lower than primary CAS. The time interval between CEA and CAS did not influence micro embolic load. [Copyright &y& Elsevier]

Abstract: Rationale: Lipoprotein lipase (LPL) X447 homozygotes are characterized by enhanced conversion of TRL apoB100. Here, we set out to investigate whether this LPL variant is also associated with enhanced apoB48 clearance. Therefore, we evaluated apoB48 kinetics in X447 homozygotes in the fed state by infusion of isotope l-[1-13C]-valine and subsequent compartmental modeling. Methods and results: ApoB48 metabolism was assessed in five X447 homozygotes (X/X genotype) and five S447 homozygotes (S/S genotype). Subjects were continuously fed and received infusion of stable isotope l-[1-13C]-valine. Results were analyzed by SAAM II modeling. Fasting (2.4-fold, p =0.02) as well as non-fasting (1.6-fold, p =0.09) apoB48 concentration was increased in the X447 homozygotes compared to S447 homozygotes. In addition, the X447 homozygotes exhibited a 1.7-fold higher apoB48 poolsize (p =0.04). Interestingly, apoB48 fractional catabolic rate (FCR) was 1.9-fold higher (p =0.007) and apoB48 synthesis was more than two-fold higher (p =0.006) in the X447 homozygotes compared to S447 homozygotes. Conclusion: In the present study, we show that X447 homozygotes exhibit enhanced apoB48 clearance. Previously, these homozygotes were shown to present with enhanced apoB100 TRL conversion. Combined, this LPLS447X gain of function variant affects apoB48 as well as apoB100 TRL metabolism. [Copyright &y& Elsevier]

• Mechanisms of cardiovascular disease are complex and multifactorial, driven by genetic variants. • Attractive drug targets require a substantial body of mechanistic and clinical evidence. • Drug target discovery in CVD is only possible through multidisciplinary collaboration. • To maximise impact, collaboration between independent research consortia is advised. Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for cardiovascular disease treatment. Each consortium followed a unique and independent research strategy. However, as coordinators of these consortia we envisioned we could increase impact, outcomes and efficiency by intensifying our interaction. At an agreed stage during our projects we chose to share our knowledge, vision and ideas. In this paper we present what we learned, in the hope that future consortia will see the benefits of this approach. [ABSTRACT FROM AUTHOR]

Background Intra-arterial treatment in acute ischemic stroke is safe and effective as recently shown in several randomized clinical trials. The level of experience of the interventionist performing the IAT procedure has not been studied. The present study investigates effects of interventionists' experience on technical aspects of the procedure and clinical outcome of the patient. Methods In this study of 313 patients with a proximal intracranial arterial anterior circulation occlusion, treated in the Netherlands from 2002 until participation in the Multicenter Randomized Clinical trial of Endovascular treatment for acute ischemic stroke (MR CLEAN), data were collected retrospectively. The association of the senior interventionists' experience with duration of the procedure, adverse events, recanalization, neurological outcome, and functional outcome at discharge was analyzed. Multiple regression models adjusted for age, sex, stroke severity, carotid terminus occlusion, use of a retrievable stent and onset to door time were used. Results No association between interventionists' experience and recanalization, neurological outcome, or functional outcome was observed in a strict selection of patients. This strict selection include a start of intra-arterial treatment within 6 h, no coagulation disturbances, systolic blood pressure < 185 mmHg and diastolic blood pressure < 110 mmHg), blood glucose level between 2.7 and 22.2 mmol/L and the existence of a proximal intracranial occlusion. However, significant shorter procedure times were found with more experienced interventionists' [adjusted beta coefficient − 0.67, 95% CI: − 1.24 to − 0.11], when using less strict inclusion criteria. Conclusion No significant relation between the level of experience and either serious neurologic adverse events or poor outcomes was observed in this study of treatments by interventionists with experience of < 50 previous procedures. We need further research to explore the relation of much higher levels of interventionists' and team experience with procedure times, results and patient outcomes. [ABSTRACT FROM AUTHOR]

Background and aims Among subjects with high-density-lipoprotein cholesterol (HDL-C) below the 1st percentile in the general population, we identified a heterozygous variant OSBPL1A p . C39X encoding a short truncated protein fragment that co-segregated with low plasma HDL-C. Methods We investigated the composition and function of HDL from the carriers and non-carriers and studied the properties of the mutant protein in cultured hepatocytes. Results Plasma HDL-C and apolipoprotein (apo) A-I were lower in carriers versus non-carriers, whereas the other analyzed plasma components or HDL parameters did not differ. Sera of the carriers displayed a reduced capacity to act as cholesterol efflux acceptors ( p < 0.01), whereas the cholesterol acceptor capacity of their isolated HDL was normal. Fibroblasts from a p . C39X carrier showed reduced cholesterol efflux to lipid-free apoA-I but not to mature HDL particles, suggesting a specific defect in ABCA1-mediated efflux pathway. In hepatic cells, GFP-OSBPL1A partially co-localized in endosomes containing fluorescent apoA-I, suggesting that OSBPL1A may regulate the intracellular handling of apoA-I. The GFP-OSBPL1A-39X mutant protein remained in the cytosol and failed to interact with Rab7, which normally recruits OSBPL1A to late endosomes/lysosomes, suggesting that this mutation represents a loss-of-function. Conclusions The present work represents the first characterization of a human OSBPL1A mutation. Our observations provide evidence that a familial loss-of-function mutation in OSBPL1A affects the first step of the reverse cholesterol transport process and associates with a low HDL-C phenotype. This suggests that rare mutations in OSBPL genes may contribute to dyslipidemias. [ABSTRACT FROM AUTHOR]

The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1 P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1 P297S heterozygotes. Lipoproteins from six SR-B1 P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed. Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I. The SR-B1 P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1. [ABSTRACT FROM AUTHOR]

Summary Background Patients with a recent vertebrobasilar transient ischaemic attack or ischaemic stroke and vertebral artery stenosis of at least 50% have a high risk of future vertebrobasilar stroke. Stenting of vertebral artery stenosis is promising, but of uncertain benefit. We investigated the safety and feasibility of stenting of symptomatic vertebral artery stenosis of at least 50%, and assessed the rate of vascular events in the vertebrobasilar supply territory to inform the design of a phase 3 trial. Methods Between Jan 22, 2008, and April 8, 2013, patients with a recent transient ischaemic attack or minor stroke associated with an intracranial or extracranial vertebral artery stenosis of at least 50% were enrolled from seven hospitals in the Netherlands in a phase 2 open-label trial with masked assessment of outcome. Patients were randomly allocated in a 1:1 ratio to stenting plus best medical treatment or best medical treatment alone by the local investigators using a web-based randomisation system. The primary outcome was the composite of vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment. The secondary outcomes were stroke in the supply territory of the symptomatic vertebral artery during follow-up, the composite outcome during follow-up, and the degree of stenosis in the symptomatic vertebral artery at 12 months. The trial is registered, number ISRCTN29597900. Findings The trial was stopped after inclusion of 115 patients because of new regulatory requirements, including the use of a few prespecified stent types and external monitoring, for which no funding was available. 57 patients were assigned to stenting and 58 to medical treatment alone. Three patients in the stenting group had vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment (5%, 95% CI 0–11) versus one patient in the medical treatment group (2%, 0–5). During a median follow-up of 3 years (IQR 1·3–4·1), seven (12%, 95% CI 6–24) patients in the stenting group and four (7%, 2–17) in the medical treatment group had a stroke in the territory of the symptomatic vertebral artery; 11 (19%) patients in the stenting group and ten (17%) in the medical treatment group had vascular death, myocardial infarction, or any stroke. The small size of the vertebral artery and stent artifacts did not allow exact grading of restenosis on CT angiography. During the complete period of follow-up, there were 60 serious adverse events (eight strokes) in the stenting group and 56 (seven strokes) in the medical treatment alone group. Interpretation Stenting of symptomatic vertebral artery stenosis is associated with a major periprocedural vascular complication in about one in 20 patients. In the population we studied, the risk of recurrent vertebrobasilar stroke under best medical treatment alone was low, questioning the need for and feasibility of a phase 3 trial. Funding Dutch Heart Foundation. [ABSTRACT FROM AUTHOR]