Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

An association between chronic obstructive pulmonary disease and abdominal aortic aneurysm beyond smoking: results from a case-control study.

OBJECTIVES: It is currently unclear whether the parallels between abdominal aortic aneurysms (AAAs) and chronic obstructive pulmonary disease (COPD) are explained by common risk factors alone, such as cigarette smoking, or by a predetermined cause. Given the persistent controversy with regard to the association between AAA and COPD, we studied this association in depth. METHODS: We conducted a case-control study comparing patients with a small AAA (maximum infrarenal diameter 35-50 mm, n = 221) with controls diagnosed with peripheral artery disease (PAD, n = 87). The controls were matched to the cases for lifetime cigarette smoking. Pulmonary function was measured by spirometry, and all subjects completed a questionnaire on medical history and smoking habits (current, former and never smokers). RESULTS: Aneurysm patients were similar to controls with respect to gender (p = 0.71), lifetime cigarette smoking (39 vs. 34 pack years, p = 0.23) and history of cardiovascular disease (45% vs. 55%, p = 0.12). Aneurysm patients had more airway obstruction (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (0.69 ± 0.12 vs. 0.78 ± 0.11, p < 0.001)), which was most pronounced in never smokers (0.73 ± 0.07 vs. 0.86 ± 0.07, p < 0.001). COPD was more prevalent in aneurysm patients (44%; 98/221) than in controls (20%; 17/87) (adjusted odds ratio (OR) 3.0; 95% confidence interval (95%CI) 1.6-5.5, p < 0.001). In particular, a major proportion of AAA patients was newly diagnosed with COPD; only 40 of 98 patients (41%) with COPD (mild, moderate or severe/very severe) were known before with obstructive pulmonary defects and received treatment. CONCLUSIONS: This study confirms an association between AAA and COPD and shows that this association is independent from smoking. Findings also demonstrate that COPD is under-diagnosed in AAA patients.

A comparison of the Doppler-derived maximal systolic acceleration versus the ankle-brachial pressure index or detecting and quantifying peripheral arterial occlusive disease in diabetic patients.

AIM: The aim of this study was to assess the diagnostic accuracy of the Doppler derived maximal systolic acceleration (ACCmax) as a novel technique for evaluating peripheral arterial occlusive disease (PAOD) in patients with diabetes mellitus, who are known for a falsely elevated ankle-brachial index (ABI). METHODS: In this retrospective analysis ACCmax was measured at ankle level in a series of 163 consecutive patients referred to the vascular laboratory for initial assessment of PAOD. Patients were classified according to the presence or absence of diabetes. In the non-diabetic patients PAOD was defined as ABI < or =0.90. This group was used to establish the association between ACCmax and ABI in a linear regression model. The result was then used to predict the presence or absence of PAOD in the diabetic patients. RESULTS: The authors examined 301 lower limbs. The study group consisted of 166 limbs of patients without diabetes and 135 limbs of patients with diabetes. PAOD was present in 52% of limbs in the nondiabetic group versus 59% of limbs in the diabetic group (ABI < or =0.90, or in case of non-compliant vessels toe-brachial index (TBI) < or =0.70). An ACCmax cut-off value of >10 m/s2 was found to be highly predictive for the exclusion of PAOD (negative predictive value 95%). In addition, the ACCmax cut-off value of <6.5 m/s2 was highly predictive for the detection of PAOD (positive predictive value 99%). A strong quadratic association was found between ACCmax and ABI in the non-diabetic group (R2=0.85). In the diabetic patients R2 values were 0.81 and 0.79 after ABI and TBI measurement respectively. CONCLUSION: DUS-derived ACCmax is an accurate marker that could offer significant benefits for the diagnosis of PAOD, especially in diabetic patients.

Effectiveness of a hospital-based vascular screening programme (SMART) for risk factor management in patients with established vascular disease or type 2 diabetes: a parallel-group comparative study.

AIMS: Modification of vascular risk factors is effective in reducing mortality and morbidity in patients with symptomatic atherosclerosis; however, it is difficult to achieve and maintain. The aim of the Risk management in Utrecht and Leiden Evaluation (RULE) study was to assess risk factor status after referral in patients with established vascular disease or type 2 diabetes who took part in the multidisciplinary hospital-based vascular screening programme, Second Manifestations of ARTerial disease, compared with a group who did not participate in such a programme. METHODS AND RESULTS: Patients with type 2 diabetes, coronary artery disease, cerebrovascular disease or peripheral arterial disease referred by general practitioners to the medical specialist at the University Medical Center (UMC) Utrecht (a setting with a vascular screening programme of systematic screening of risk factors followed by treatment advice) and the Leiden UMC (a setting without such a screening programme), were enrolled in the study. Blood pressure, levels of lipids, glucose and creatinine, weight, waist circumference and smoking status were measured in patients 12-18 months after referral to the two hospitals. A total of 604 patients were treated in the setting with a vascular screening programme and 566 in the setting without such a programme; 70% of all patients were male, with a mean age of 61 +/- 10 years. Amongst screened patients, systolic blood pressure [2.5 mmHg, 95% confidence interval (CI) 0.3-4.6] and the level of LDL cholesterol (0.3 mmol L(-1), 95% CI 0.2-0.4) were lower compared with the group that received usual care, after a median of 16 months from referral. CONCLUSION: Systematic screening of risk factors, followed by evidence-based, tailored treatment advice contributed to slightly better risk factor reduction in patients with established vascular disease or type 2 diabetes. However, a large proportion of patients did not reach the treatment goals according to (inter)national guidelines. Systematic screening of vascular risk factors alone is not enough for adequate risk factor management in high-risk patients.

Vascular training and endovascular practice in Europe.

OBJECTIVE: To evaluate the influence of the status of vascular surgery (VS) training paradigms on the actual practice of endovascular therapy among the European countries. METHODS: An email-based survey concerning vascular surgery training models and endovascular practices of different clinical specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. RESULTS: Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1. Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted specifically to VS (3.9 vs 2.7 years, p=0.008). Among countries with independent certification an average of 76% of aortic and 50% of peripheral endovascular procedures are performed by vascular surgeons, while the corresponding values, for countries with a non-independent certification, are 69% and 36% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral endovascular procedures, though, have similar growth rates in both country groups (VS independent 62% vs VS non-independent 60%). CONCLUSIONS: In European countries with VS as an independent specialty, vascular surgeons have a shorter total training period but spend more time in VS training, although they may not undertake a greater proportion of the endovascular procedures their countries appear to have adopted endovascular technologies more rapidly compared to the ones with non-independent VS curricula. Whether such differences influence patient outcomes requires investigation in future studies.

Vascular growth in ischemic limbs: a review of mechanisms and possible therapeutic stimulation.

Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into mechanisms of vascular growth in the adult, in particular the role of angiogenic factors, the immune system, and bone marrow, were reviewed, together with modes of its therapeutic stimulation and results from recent clinical trials. Three concepts of vascular growth have been described to date-angiogenesis, vasculogenesis, and arteriogenesis (collateral artery growth)-which represent different aspects of an integrated process. Stimulation of arteriogenesis seems clinically most relevant and has most recently been attempted using autologous bone marrow transplantation with some beneficial results, although the mechanism of action is not completely understood. Better understanding of the highly complex molecular and cellular mechanisms of vascular growth may yet lead to meaningful clinical applications.

Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia.

AIM: Recent evidence indicates that bone marrow mononuclear cells (BMC) promote collateral vessel formation in patients with severe peripheral arterial disease (PAD). However, aspects concerning optimal administration mode, durability and long-term safety require consideration. Combined intra-arterial (IA) plus intramuscular (IM) BMC delivery may be more effective than exclusive intramuscular injections. The aim of this study was to evaluate feasibility, safety and effect of exclusive IM versus combined IM+IA delivery of autologous BMC in patients who were not candidates for surgical or endovascular treatment. METHODS: Twenty-seven patients were treated with either combined IA+IM (N=12) or sole IM (N=15) administration of autologous BMC. Efficacy was assessed after 1, 6 and 12 months. Limb salvage, pain-free walking distance, ankle-brachial pressure index (ABI) and pain scores were evaluated. RESULTS: There were no adverse reactions related to injection of the cells. Three patients died within the first year of follow-up due to non-procedure related causes. Two patients in the IA+IM group required limb amputation because of ongoing critical ischemia versus 7 patients in the IM group (P=0.17). BMC treatment in the remaining patients resulted in a significant and sustained (>12 months) improvement. Pain-free walking distance improved from 81+/-56 meters at baseline to 257+/-126 meters at t=6 months (P=0.0002). Mean ABI increased 23% after 6 months (P=0.01) and pain score reduced for up to 50% as shown by Brief Pain Inventory (P=0.001). CONCLUSION: Both IM and combined IM/IA delivery of autologous BMC are safe, and result in relevant and sustained improvement in a considerable proportion of patients with severe PAD who are not amenable for conventional treatment.

European continuing medical education in vascular surgery: 5-year results of congresses approved by the Union Européenne des Médecins Spécialistes Section of Vascular Surgery.

AIM: Continuing medical education (CME) can be defined as ''educational activities that serve to maintain, develop, or increase the knowledge, skills and professional performance of a physician to provide services for patients, the public, or the profession''. CME is a major professional responsibility. The European Board of Vascular Surgery of the Union Européenne des Médecins Spécialistes (UEMS) Section of Vascular Surgery has, through its European Vascular CME (EVCME) Committee, accredited 74 congresses during the 5-year period from 2000-2004. METHODS: Official evaluation forms were completed by the congress participants for a personal appraisal of the quality of the activities. The data in this manuscript focused on questions that were the most relevant and of the greatest interest to the participants. A statistical analysis of the results was performed utilizing ANOVA and Robust tests of equality of means as well as a posthoc analysis for further investigation, and non parametric Wilcoxon signed ranks test. RESULTS: The educational needs of participants regarding new diagnostic and therapeutic modes were stated as ''important'' and ''extremely important'' in the responses at over 80% in total. Over 75% of the participants answered ''extremely important'' and ''important'' to the question ''how important is evidence-based practice to your practice''. CONCLUSION: This survey indicates that the EVCME approved congresses had a positive impact for the vascular surgeon by updating overall knowledge on vascular surgery; the majority of comments by the participants also indicates that EVCME is fulfilling its aim to bring as much evidence-based practice as possible into the daily work schedule of the surgeon by turning knowledge acquired by CME into performance of the participants.

Assessment of three-dimensional stent-graft dynamics by using fluoroscopic roentgenographic stereophotogrammetric analysis.

OBJECTIVE: To validate the use of fluoroscopic roentgenographic stereophotogrammetric analysis (FRSA) for its feasibility and accuracy for measuring the three-dimensional dynamic motion of stent grafts. METHODS: A digital biplane fluoroscopy setup was calibrated (Siemens Axiom Artis dBc). Stereo images were acquired of a static aortic model with a stent graft in different axial positions, imposed by a micromanipulator. The three-dimensional measurement error of FRSA was determined by comparing FRSA measurements with the micromanipulator. An aortic model with a stent graft was constructed and connected to an artificial circulation with a physiological flow and pressure profile. Markers were added to the spine (tantalum spherical markers; diameter 1 mm) and stent (welding tin; diameter 1 mm). The three-dimensional measurement precision was determined by measuring the position of a single (stable) spine marker during two pulsatile cycles. Finally, three-dimensional stent marker motion was analyzed with a frame rate of 30 images per second, including three-dimensional marker position (change), diameter change, and center of circle position change. RESULTS: The mean error of FRSA measurement of displacement was 0.003 mm (SD, 0.019 mm; maximum error, 0.058 mm). A very high precision of position measurement was found (SD, 0.009-0.015 mm). During pulsatile motion, the position (changes) of the markers could be assessed in the x, y, and z directions, as well as the stent diameter change and center of circle position change. CONCLUSIONS: FRSA has proven to be a method with very high accuracy and temporal resolution to measure three-dimensional stent-graft motion in a pulsatile environment. This technique has the potential to contribute significantly to the knowledge of stent-graft behavior after endovascular aneurysm repair and improvements in stent-graft design. The technique is ready for clinical testing.

Natural killer cells and CD4+ T-cells modulate collateral artery development.

OBJECTIVE: The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS: Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell-deficient transgenic mice. Arteriogenesis was, however, unaffected in J alpha281-knockout mice that lack NK1.1+ Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4+ T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II-deficient mice that more selectively lack mature peripheral CD4+ T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II-deficient mice that lack both NK- and CD4+ T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. CONCLUSIONS: These data show that both NK-cells and CD4+ T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease.

Aneurysm sac pressure after EVAR: the role of endoleak.

OBJECTIVE: The relation between endoleak and aneurysm sac pressure is not completely clear. This review evaluates the effect of endoleaks on aneurysm sac pressure and summarizes the present knowledge regarding aneurysm sac pressure after EVAR. METHODS: A systematic search of literature was carried out using MEDLINE, EMBASE and Web of Science. Studies were included if aneurysm sac pressure measurements as well as systemic pressure measurements were performed during or after EVAR. Mean pressure indices (MPI), ratio mean aneurysm sac pressure to mean systemic pressure), in the absence of endoleaks and in the presence of different type of endoleaks were compared. RESULTS: Stent-graft deployment does not seem to result in immediate reduction of aneurysm sac in the absence of an endoleak. Aneurysm sac pressure is elevated in the presence of an endoleak. However, the MPIs differ widely between studies both in the absence and presence of an endoleak. CONCLUSION: MPI is not specific to the type of endoleak. This implies that the same type of endoleak does not necessarily pose the same MPI and by this the same hazard of aneurysm rupture, because the aneurysm sac pressure is directly related to the aneurysm wall stress.

Human visceral adipose tissue and the plasminogen activator inhibitor type 1.

OBJECTIVE: The objective of this study was to systematically evaluate the molecular basis of the association between visceral fat mass and plasma plasminogen activator inhibitor-1 (PAI-1) levels in man. DESIGN: A comprehensive approach comprising observational, in vitro, and human intervention studies. MEASUREMENTS AND RESULTS: We confirmed an exclusive relationship between visceral fat and plasma PAI-1 levels (r=0.79, P<0.001) and corroborated preferential PAI-1 release from adipose tissue explants. Yet, messenger RNA analysis and in vivo measurement of PAI-1 release from visceral fat (AV-differences over the omentum) not only excluded visceral adipose tissue as a relevant source of circulating PAI-1, but also excluded visceral fat as a significant source of proinflammatory mediators such as tumor necrosis factor-alpha, IL-1 or transforming growth factor-beta that could induce PAI-1 expression in tissues other than visceral fat. Short-term interventions with acipimox and growth hormone (GH) as well as statistical evaluation excluded free fatty acids and GH as metabolic links. Further analysis of the metabolic data in a stepwise regression model indicated that plasma PAI-1 levels and visceral fat rather are co-correlates that both relate to impaired lipid handling. CONCLUSION: Our PAI-1 studies show that visceral fat mass and plasma PAI-1 levels are co-correlated rather than causatively related, with lipid load as common denominator.

Development of fibrinous thrombus analogue for in-vitro abdominal aortic aneurysm studies.

PURPOSE: To develop different thrombus analogues, with mechanical properties similar to those of human fibrinous thrombus, for in-vitro aneurysm sac pressure studies. METHODS: Using dynamic mechanical analysis we determined the E-modulus (/E(*)/) at 0.8, 1.0, 1.5 and 3.9 Hz of ten different human fibrinous thrombus samples. We also determined loss and storage modulus to quantify the visco-elastic properties. For comparison, we measured the E-modulus (|E(*)|), loss and storage modulus of gelatin, Novalyse ST8, ST14 and ST20 with and without contrast agent. RESULTS: Mean E-modulus of the thrombus samples (SD) at 0.8, 1.0, 1.5 and 3.9 Hz was 39 (16), 37 (15), 37 (15) and 38 (14)kPa, respectively. Median (SD) storage and loss modulus were 35 (12) and 8 (4)kPa, respectively. Median (SD) tandelta was 0.25 (0.06). The E-modulus of gelatin, Novalyse ST8, ST14 and ST20 was 4, 27, 48 and 60 kPa, respectively. The E-modulus of Novalyse ST8, ST14 and ST20 mixed with contrast agent was 18, 23 and 33 kPa, respectively. Median (SD) storage, loss modulus and tan delta of the six Novalyse samples were 30 (15), 3 (1) and 0.087 (0.04), respectively. CONCLUSION: All the thrombus analogues, except gelatin, had an E-modulus in the range of human fibrinous thrombi. Novalyse samples are validated thrombus analogues for in-vitro aneurysm sac pressure studies. Gelatin is not appropriate to simulate fibrinous thrombus.

Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice.

BACKGROUND: Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated atherosclerosis of vein grafts has not yet been explored, however. METHODS AND RESULTS: To assess the role of complement in the development of vein graft atherosclerosis, a mouse model, in which a venous interposition was placed in the common carotid artery, was used. In this model, vein graft thickening appeared within 4 weeks. The expression of complement components was studied with the use of immunohistochemistry on sections of the thickened vein graft. C1q, C3, C9, and the regulatory proteins CD59 and complement receptor-related gene y could be detected in the lesions 4 weeks after surgery. Quantitative mRNA analysis for C1q, C3, CD59, and complement receptor-related gene y revealed expression of these molecules in the thickened vein graft, whereas C9 did not show local mRNA expression. Furthermore, interference with C3 activation with complement receptor-related gene y-Ig was associated with reduced vein graft thickening, reduced C3 and C9 deposition, and reduced inflammation as assessed by analysis of influx of inflammatory cells, such as leukocytes, T cells, and monocytes. In addition, changes in apoptosis and proliferation were observed. When C3 was inhibited by cobra venom factor, a similar reduction in vein graft thickening was observed. CONCLUSIONS: The complement cascade is involved in vein graft thickening and may be a target for therapy in vein graft failure disease.

Anti-MCP-1 gene therapy inhibits vascular smooth muscle cells proliferation and attenuates vein graft thickening both in vitro and in vivo.

OBJECTIVE: Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease. METHODS AND RESULTS: MCP-1 expression is demonstrated in various stages of vein graft disease in a murine model in which venous interpositions are placed in the carotid arteries of hypercholesterolemic ApoE3Leiden mice and in cultured human saphenous vein (HSV) segments in which IH occurs. The functional involvement of MCP-1 in vein graft remodeling is demonstrated by blocking the MCP-1 receptor CCR-2 using 7ND-MCP-1. 7ND-MCP1 gene transfer resulted in 51% reduction in IH in the mouse model, when compared with controls. In HSV cultures neointima formation was inhibited by 53%. In addition, we demonstrate a direct inhibitory effect of 7ND-MCP-1 on the proliferation of smooth muscle cell (SMC) in HSV cultures and in SMC cell cultures. CONCLUSIONS: These data, for the first time, prove that MCP-1 has a pivotal role in vein graft thickening due to intimal hyperplasia and accelerated atherosclerosis.

Aneurysm sac pressure monitoring: effect of technique on interpretation of measurements.

OBJECTIVES: The purpose of this study is to determine the accuracy of measuring pressure with a fluid filled pressure device (needle) and a non-fluid filled pressure device (catheter) inside a thrombosed aneurysmal sac after exclusion from circulation by endovascular grafting. METHODS: In a static environment, consisting of a syringe to which a pressure monitoring kit was connected, experiments were performed to study the influence of the type of device (either needle or catheter) and the effect of the characteristics of the medium on the accuracy and reproducibility of pressure measurements. The pressures obtained with the needle in the different kinds of media were compared with those obtained in blood. Similar experiments were performed using a pressure catheter. Subsequently, pressure measurements were performed in a dynamic and physiological environment. This environment consisted of an artificial circulation in which an aneurysm, constructed of porcine aorta and filled with human aortic thrombus, was mounted. The pressures were compared and analyzed by Bland-Altman plots. RESULTS: Under static conditions, the pressure levels obtained by a needle in blood, starch solution and thrombus were similar. Under identical conditions, pressures obtained by a catheter in starch solution were significant lower than the pressures measured in blood (P<0.05). Under dynamic pressure conditions the reproducibility of pressures obtained with the needle inserted in the human thrombus was very poor. CONCLUSION: A needle pressure measuring device, inserted into media like human fibrin thrombus, does not yield accurate and reproducible results. A catheter with a tip-sensor rather than a needle is superior to study the pressure in the aneurysm sac after EVAR.

Inhibition of intimal hyperplasia by the tetracycline derived mmp inhibitor doxycycline in vein graft disease in vitro and in vivo.

AIMS: Intimal hyperplasia, characterised by smooth muscle cell migration and proliferation, requires extracellular matrix degradation which is mediated by matrix metalloproteinases (MMPs). In this study, the effect of tetracycline derived doxycycline, a specific MMP inhibitor of both activity and synthesis, on intimal hyperplasia in vitro and in vivo was assessed. METHODS AND RESULTS: Segments of human saphenous veins were cultured for 4 weeks in absence or presence of doxycycline (10microg/ml) (n=6). A 81% inhibition in intimal hyperplasia was observed in the doxycycline treated segments compared to controls. To assess the effect of doxycycline on intimal hyperplasia in vivo, perivascular cuffs were placed around femoral arteries in mice with or without doxycycline in the drinking water (3 mg/ml). In this in vivo model for intimal hyperplasia doxycycline significantly reduced (68%, n=6) intimal hyperplasia when compared to controls. In addition the effect of doxycycline on vein graft thickening was assessed in a murine venous interposition model. In this in vivo model vein graft thickening was reduced by 35 % in the doxycycline treated mice (3 mg/ml in drinking water). Furthermore, a reduction in vascular MMP expression was observed in these mice. CONCLUSION: Treatment with tetracycline derived doxycycline results in significant inhibition of intimal hyperplasia in vitro and in vivo and may be an effective strategy to prevent post interventional restenosis and vein graft disease.

Optimal follow-up strategies after aorto-iliac prosthetic reconstruction: a decision analysis and cost-effectiveness analysis.

OBJECTIVE: The primary aim of ultrasound follow-up after aorto-iliac prosthetic reconstruction is to correct false aneurysms before rupture occurs. We investigated whether follow-up improves the life expectancy of patients and sought to identify the most cost-effective follow-up strategy. DESIGN OF THE STUDY: A Monte Carlo Markov decision model was constructed. The occurrence of false aneurysms was modelled as a time-dependent process for each anastomotic site, based on published series. Using this model, the impact of various follow-up strategies was investigated for three types of prostheses, aorto-distal tube, aorto-bi-iliac, and aorto-bi-femoral prostheses. Main outcome measures were discounted quality adjusted life years (dQALYs), discounted costs, and (discounted) cost-effectiveness (CE) ratios. RESULTS: Follow-up of patients with aorto-distal tube and aorto-bifemoral prostheses did not result in an improvement life expectancy and was not cost-effective, QALYs 7.53 and 7.62 years, respectively. The results for aorto-distal tube and aorto-bifemoral prostheses were not sensitive to any variation in the model parameters. In the base case analysis, the life expectancy of patients with aorto-bi-iliac prostheses was 7.50 QALYs (95% confidence interval 7.46-7.54) whether or not they underwent routine follow-up. However, patients aged 54 years or younger gained 0.11 QALYs with annual follow-up (p<0.05). The most cost-effective strategy was annual follow-up that starts 10 years after the initial operation, and continues up to 30 years after surgery (4600 Euro; CE ratio 21,000 Euro per QALY). When perioperative mortality of elective reconstruction of false aneurysms is 2% or lower (e.g. when endovascular treatment is used), a small improvement is observed (7.56 vs. 7.50 QALYs; p<0.05; CE ratio 35,000 Euro per QALY). CONCLUSIONS: Annual follow-up of aorto-bi-iliac prostheses should be restricted to patients aged 54 or younger and not start before 10 years after surgery. The same strategy can only be considered for older patients if mortality for secondary intervention is lower than 2%. Since patients with aorto-distal tube and aorto-bi-femoral prostheses do not benefit from follow-up for the detection of false aneurysms, this practice should be discouraged in these patient groups.

Ideals of patient autonomy in clinical decision making: a study on the development of a scale to assess patients' and physicians' views.

OBJECTIVES: Evidence based patient choice seems based on a strong liberal individualist interpretation of patient autonomy; however, not all patients are in favour of such an interpretation. The authors wished to assess whether ideals of autonomy in clinical practice are more in accordance with alternative concepts of autonomy from the ethics literature. This paper describes the development of a questionnaire to assess such concepts of autonomy. METHODS: A questionnaire, based on six moral concepts from the ethics literature, was sent to aneurysm patients and their surgeons. The structure of the questionnaire was assessed by factor analysis, and item reduction was based on reliability. RESULTS: Ninety six patients and 58 surgeons participated. The questionnaire consisted of four scales. Two of the scales reflected the paternalistic and consumerist poles of the liberal individualist model, one scale reflected concepts of Socratic autonomy and of procedural independence, and the fourth scale reflected ideals of risk disclosure. DISCUSSION: The Ideal Patient Autonomy Scale is a 14 item normative instrument. It is clearly distinct from the generally used psychological preference questionnaires that assess preferences for physician-patient roles.