Hepatic lipase: a pro- or anti-atherogenic protein?

Hepatic lipase (HL) plays a role in the metabolism of pro- and anti-atherogenic lipoproteins affecting their plasma level and composition. However, there is controversy regarding whether HL accelerates or retards atherosclerosis. Its effects on different lipoprotein classes show that, potentially, HL may promote as well as decrease atherogenesis. Studies in animals with genetically modulated HL expression show that it depends on the model used whether HL acts pro- or anti-atherogenic. In humans, HL activity seems to correlate inversely with atherosclerosis in (familial) hypercholesterolemia, and positively in hypertriglyceridemia. In normolipidemia, HL activity is weakly associated with coronary artery disease (CAD). Genetically low or absent HL activity is usually associated with increased CAD risk, especially if plasma lipid transport is impaired due to other factors. Since HL promotes the uptake of lipoproteins and lipoprotein-associated lipids, HL may affect intracellular lipid content. We hypothesize that the prime role of HL is to maintain, in concert with other factors (e.g., lipoprotein receptors), intracellular lipid homeostasis. This, and the uncertainties about its impact on human atherosclerosis, makes it difficult to predict whether HL is a suitable target for intervention to lower CAD risk. First, the physiological meaning of changes in HL activity under different conditions should be clarified

Richting een geautomatiseerde continuïteitsanalyse

Het beoordelen van de continuïteitsanalyse in het controleproces berust op het professionele oordeel van de controlerend accountant. Om het individuele en persoonlijk oordeel (professional judgement) van de accountant te ondersteunen en willekeur zoveel mogelijk te vermijden, zou een directere bron van informatie, in de vorm van een geautomatiseerde continuïteitsanalyse, ondersteuning kunnen bieden. Met behulp van een combinatie van zestien forecasting algoritmes is een methode ontwikkeld om de continuïteitsanalyse te automatiseren. Ten behoeve van het valideren van de forecasting algoritmes zijn 225 administraties verdeeld in een train- en testset. De resultaten tonen een betrouwbaarheidspercentage van 96,49% voor het Extra Trees Regressor model op basis van de conditie ‘lopende verplichtingen’ voor één van de administraties

An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation

There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery)

Clinical characteristics and outcomes of patients with hepatic angiomyolipoma:A literature review

First reported in 1976, hepatic angiomyolipoma (HAML) is a rare mesenchymal liver tumor occurring mostly in middle-aged women. Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms. Nearly 10% of HAMLs are associated with tuberous sclerosis complex. HAML contains variable proportions of blood vessels, smooth muscle cells and adipose tissue, which renders radiological diagnosis hazardous. Cells express positivity for HMB-45 and actin, thus these tumors are integrated into the group of perivascular epithelioid cell tumors. Typically, a HAML appears on magnetic resonance imaging (or computed tomography scan) as a hypervascular solid tumor with fatty areas and with washout, and can easily be misdiagnosed as other liver tumors, particularly hepatocellular carcinoma. The therapeutic strategy is not clearly defined, but surgical resection is indicated for symptomatic patients, for tumors showing an aggressive pattern (i.e., changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy), for large (> 5 cm) biopsy-proven HAML, and if doubts remain on imaging or histology. Conservative management may be justified in other conditions, since most cases follow a benign clinical course. In summary, the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings

Endovascular treatment of popliteal artery aneurysms: Results of a prospective cohort study

ObjectivePopliteal artery aneurysms can be treated endovascularly with less perioperative morbidity compared with open repair. To evaluate suitability of the endovascular technique and the clinical results of this treatment, we analyzed a prospective cohort of consecutive popliteal aneurysms referred to a tertiary university vascular center.MethodsAll popliteal artery aneurysms between June 1998 and June 2004 that measured >20 mm in diameter were analyzed for endovascular repair. Anatomic suitability was based largely on quality of the proximal and distal landing zone as determined by angiography. Endovascular treatment was performed by using a nitinol-supported expanded polytetrafluoroethylene lined stent graft introduced through the common femoral artery.ResultsWe analyzed 67 aneurysms in 57 patients. Ten aneurysms (15%) were excluded from endovascular repair, or from any repair at all, for various reasons. The remaining 57 (85%) were treated endovascularly, of which 5 were treated emergently for acute ischemia. During a mean 24-month follow-up, 12 stent grafts (21%) occluded. Primary and secondary patency rates were 80% and 90% at 1 year, and 77% and 87% at 2 years of follow-up. Postoperative treatment with clopidogrel proved to be the only significant predictor for success.ConclusionsEndovascular repair of a popliteal artery aneurysm is feasible. Changes in the material used and the addition of clopidogrel may improve patency rates

Visceral stent patency in fenestrated stent grafting for abdominal aortic aneurysm repair

ObjectiveFenestrated endovascular abdominal aortic aneurysm repair (F-EVAR) has been introduced for treatment of aneurysms in which visceral arteries are incorporated. Patency of target vessels has been reported to be excellent. Results of the use of stent grafts to accommodate visceral arteries in F-EVAR are presented in this study, including an overview of factors that affect outcome.MethodsAll patients treated with fenestrated stent grafts in a single center between November 2001 and October 2011 were reviewed. Patients treated for suprarenal, juxtarenal, and infrarenal short-necked aortic aneurysms were included. Patients with thoraco-abdominal aneurysms or aneurysms treated with grafts with fixed side branches were excluded. Polytetrafluoroethylene covered stents were used routinely since June 2005. Target vessels and stents were examined using computed tomography angiography reconstructions. Primary end points were primary patency, defined as the absence of occlusion, and loss of renal function. Secondary end points were technical success, stenosis (defined as a ≥50% angiographic diameter reduction), stent fracture, and mortality.ResultsA total of 138 patients with a median age of 73 years (range, 50-91 years) met the inclusion criteria. Median computed tomography angiography follow-up was 13 months (range, 1-97 months). In total, 392 target vessels were provided with 140 scallops and 252 fenestrations. Visceral stents (−grafts) were placed in 254 target vessels. Technical success was obtained in 249 arteries (98.0%). Overall stent patency of target vessels was 95.7% at 1 year and 88.6% at 4 years. Renal artery stent patency was 97.4% at 1 year and 91.2% at 4 years (96.8% and 89.1% for uncovered stents; 97.3% and 92.4% for covered stents, respectively). There was no significant difference in patency between covered and uncovered stents in renal arteries (P = .71). Renal artery stenosis occurred in 26 stented arteries (11.3%) and occlusion in seven arteries. Renal artery stent stenosis occurred significantly more in uncovered than in covered stents (P = .04). Stent fractures occurred more in uncovered than in covered stents (P = .01) and was associated with a significantly lower visceral stent patency rate (P < .01). During follow-up, 13 patients developed permanent renal function impairment (9.4%), of which two required permanent dialysis (1.4%). Renal dysfunction was significantly associated with renal stent occlusion or stenosis (P < .01).ConclusionsPatency rates of visceral artery stent (–grafts) in F-EVAR were 95.7% at 1 year and 88.6% at 4 years. Patency rates were affected by stent fractures, which occurred more in uncovered compared with covered stents. Renal artery stent stenosis occurred more in uncovered compared with covered stents. Renal dysfunction was significantly associated with renal stent occlusion or stenosis

Is emergency endovascular aneurysm repair associated with higher secondary intervention risk at mid-term follow-up?

ObjectiveThe study assessed mid-term outcome of emergency endovascular repair for acute infrarenal abdominal aortic aneurysms, with special attention to secondary interventions.MethodsBetween May 1998 and August 2005, 56 patients underwent emergent endovascular repair for a ruptured abdominal aortic aneurysm (n = 34) or an acute nonruptured abdominal aortic aneurysm (n = 22). During the same period, 322 consecutive patients underwent elective endovascular aneurysm repair and were used as control group. Five types of stent grafts were used: Vanguard, Talent, Excluder, Zenith, and Quantum. Follow-up included abdominal radiograph, duplex ultrasound scanning, and computed tomographic angiography. Outcome measures included all-cause and aneurysm-related mortality, complications, and secondary interventions.ResultsMortality at 30 days was 18%, 5%, and 1% in the ruptured, acute nonruptured, and elective aneurysm groups, respectively. Overall mean follow-up was 38 ± 26 months. In the ruptured aneurysm group, survival was 67.8% ± 8.6% at 1 year and 62.1% ± 9.5% at 2 and 3 years. Seven secondary interventions (4 early and 3 late) were required in five patients (15%), with a cumulative risk of 9.2% ± 5.1% at 1 year and 16.2% ± 8.2% at 2 and 3 years. In the acute nonruptured aneurysm group, survival was 90.9% ± 6.1% at 1 year, 84.8% ± 8.2% at 2 years, and 76.4% ± 10.9% at 3 years. Four secondary interventions (1 early and 3 late) were required in four patients (18%), with a cumulative risk of 9.6% ± 6.5% at 1 and 2 years and 20.9% ± 12.0% at 3 years. In the elective aneurysm (control) group, survival was 95.2% ± 1.2% at 1 year, 89.9% ± 1.8% at 2 years, and 86.2% ± 2.1% at 3 years. A total of 51 secondary interventions (4 early, 47 late) were required in 38 patients (12%), with a cumulative risk of 4.2% ± 1.1% at 1 year, 7.6% ± 1.6% at 2 years, and 12.9% ± 2.2% at 3 years.ConclusionsTo our surprise, emergency endovascular aneurysm repair did not present with higher secondary intervention rate at mid-term follow-up

HLA-DR expression on monocytes and systemic inflammation in patients with ruptured abdominal aortic aneurysms

INTRODUCTION: Mortality from ruptured abdominal aortic aneurysms (RAAA) remains high. Severe systemic inflammation, leading to multi-organ failure, often occurs in these patients. In this study we describe the level of HLA-DR expression in a consecutive group of patients following surgery for RAAA and compare results between survivors and non-survivors. A similar comparison is made for IL-6 and IL-10 levels and Sequential Organ Failure Assessment (SOFA) scores. METHODS: This is a prospective observational study. Patients with RAAA were prospectively analysed. Blood samples were collected on days 1, 3, 5, 7, 10 and 14. The fraction of CD-14 positive monocytes expressing HLA-DR was measured by flow-cytometry. IL-6 and IL-10 levels were measured by ELISA. RESULTS: The study included 30 patients with a median age of 70 years, of which 27 (90%) were men. Six patients died from multiple organ failure, all other patients survived. The SOFA scores were significantly higher in non-survivors on days 1 through 14. HLA-DR expression on monocytes was significantly lower on days 3, 5, 7, 10 and 14 in non-survivors. IL-6 and IL-10 levels were significantly higher in non-survivors on day 1 and days 1 and 3, respectively. CONCLUSION: HLA-DR expression on monocytes was decreased, especially in non-survivors. All patients with RAAA displayed a severe inflammatory and anti-inflammatory response with an increased production of IL-6 and IL-10. Poor outcome is associated with high levels of IL-6 and IL-10 and a high SOFA score in the first three days after surgery, while low levels of HLA-DR expression are observed from day three after RAAA repair