Plasma levels of ß2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study.

Objective The objective of this paper is to examine the association between plasma levels of ß2-microglobulin (ß2MG), a protein previously associated with atherosclerosis, and the presence of carotid plaque (CP) or coronary artery calcium (CAC) in a cross-sectional cohort study of patients with systemic lupus erythematosus (SLE). Methods Patients with SLE were enrolled between June 2013 and May 2014. The presence of CP and CAC was assessed with ultrasonography and computed tomography scan, respectively. The presence of CP or CAC in the SLE patients was analyzed with respect to plasma levels of ß2MG and renal function expressed as the estimated glomerular filtration rate (eGFR). Results The study cohort consisted of 147 patients, 89% women and 95% Caucasians. The median age was 46 (range: 21-75) years with a median disease duration of 14 years. CP and CAC was observed in 29 (20%) and 57 (39%) of patients, respectively. CP or CAC was seen in 62 (42%) patients and was associated with the highest quartile of plasma ß2MG in patients with eGFR ≥ 90 ml/min/1.73 m2; OR = 18 (95% CI: 1.7-181). ß2MG adjusted for eGFR was also associated with presence of CP or CAC in the total cohort. The exclusion of 25 patients with a prior history of cardiovascular disease did not change the observed associations. Conclusion In this study, we found significant associations between imaging markers of atherosclerosis and high plasma levels of plasma ß2MG. These data suggest that ß2MG is a candidate for further study as a biomarker for atherosclerosis in SLE.

Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study.

BACKGROUND: In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES: This trial investigated the effect of platelets administered before transport to surgery. METHODS: In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS: Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0·32). Post-operative thrombotic events (14 vs 15; P = 0·69), renal failure (11 vs 10; P = 0·15) and pulmonary insufficiency (34 vs 39; P = 0·15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS: For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.

Three-year follow-up of implementation of evidence-based transfusion practice in a tertiary hospital.

BACKGROUND AND OBJECTIVES: Traditionally, Denmark has had a high rate of allogeneic red blood cell transfusion caused by a liberal transfusion practice despite the existence of restrictive guidelines. We established a Patient Blood Management programme in a tertiary hospital and report the results of the implementation of evidence-based transfusion practice. MATERIALS AND METHODS: Red blood cell transfusion quality indicators were compared with the evidence-based guideline at hospital and department level. Based on this evaluation, wards were selected for interventions targeting doctors and nurses. The implementation process was monitored by transfusion quality and utilization data over a 3-year period with totally 166 341 admissions in 98 960 mixed, adult medical and surgical patients. RESULTS: At the hospital level, transfusion above the upper guideline limit decreased from 23 to 10% (P < 0·001), and transfusion at or below the restrictive haemoglobin trigger of 7·3 g/dl increased from 7 to 19% (P < 0·001). The percentage of single-unit transfusions increased from 72 to 78% (P < 0·001), and the majority of transfusion rates and volumes decreased significantly. Red cell use decreased with 41% in surgical procedures and 28% in admissions (P < 0·001). CONCLUSION: The intervention was associated with a significant and sustained overall increase in compliance with national guidelines for red blood cell transfusion for non-bleeding patients, and led to significantly fewer patients being exposed to transfusion.

Follow-up on Small Abdominal Aortic Aneurysms Using Three Dimensional Ultrasound: Volume Versus Diameter.

OBJECTIVES: Rupture risk in abdominal aortic aneurysms (AAAs) is assessed using AAA diameter; yet 10% of ruptures occur in a small aneurysm. This underlines the inadequacy of diameter as a standalone parameter. In this prospective follow-up study, ultrasound determined aneurysm diameter was compared with aneurysm volume determined by three dimensional ultrasound (3D-US) in a group of 179 AAAs. DESIGN: This was a prospective cohort study with repeated diameter and volume measurements by 3D-US. MATERIAL AND METHODS: In total, 179 patients with small infrarenal AAAs (diameter 30-55 mm) were enrolled consecutively. At enrolment and at 12 month follow-up, maximum diameter, using dual plane technique, and three dimensional volume were measured. Based on a previous accuracy study, significant change in diameter and volume were defined as an increase exceeding the known range of variability (ROV) of each US technique; ±3.7 mm and ±8.8 mL, respectively. Post-hoc Kaplan-Meier analysis was performed to estimate time to conversion to treatment after the conclusion of the follow-up period between two groups. RESULTS: In total, 125 patients (70%) had an unchanged diameter during follow-up. In this group, 50 patients (40%) had an increasing aortic volume. Forty-five (83%) of the 54 patients with an increasing aortic diameter showed a corresponding volume increase. During a median follow-up of 367 days (364-380 days), a mean increase in diameter of 2.7 mm (±2.6 mm) and a mean increase in volume of 11.6 mL (±9.9 mL) were recorded. In post-hoc analysis, it was found that more AAAs with a stable diameter and a growing volume than AAAs with a stable diameter and volume were undergoing aortic repair during follow-up, based on the maximum diameter. CONCLUSION: In this cohort of small AAAs, 40% of patients with a stable diameter had an increasing volume at 12 month follow-up. From this perspective, 3D-US could have a future supplemental role in AAA surveillance programmes.

Three-dimensional Ultrasound in the Management of Abdominal Aortic Aneurysms: A Topical Review.

Three-dimensional (3D) ultrasound is an evolving modality that may have numerous applications in the management of abdominal aortic aneurysms. Many vascular specialists will not be familiar with the different ways in which 3D vascular ultrasound data can be acquired nor how potential applications are being explored by researchers. Most of the current literature consists of small series and single-centre experience, although clinical themes such as measurement of abdominal aortic aneurysm volume and surveillance following endovascular repair are emerging. The aim of this topical review is to introduce clinicians to the current concepts of 3D ultrasound, review the current literature, and highlight avenues for further research in this new and exciting field of vascular imaging.

Contrast Enhanced Ultrasound can Replace Computed Tomography Angiography for Surveillance After Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: Surveillance after endovascular aortic aneurysm repair (EVAR) is mandatory and computed tomography angiography (CTA) is considered the standard imaging modality, although patients are exposed to ionizing radiation and nephrotoxic contrast medium. The primary aim of this study was to determine the diagnostic efficacy of duplex ultrasound (DUS) and contrast enhanced ultrasound (CEUS) using CTA as the gold standard. The secondary aim was to determine the clinical consequences of endoleaks missed by DUS and CEUS, or CTA. METHODS: All patients with EVAR for an aorto-iliac aneurysm between 1 August 2011 and 31 October 2014 were prospectively and consecutively enrolled. CEUS was added to the existing surveillance protocol, which included DUS, plain abdominal X-ray, and CTA at 3 and 12 months after stent implantation. RESULTS: In 278 patients, endoleaks were detected in 68, 69, and 46 cases by CTA, CEUS, and DUS, respectively. The sensitivity and specificity of DUS and CEUS were 46% and 93%, and 85% and 95%, respectively. CEUS and CTA were diagnostically equivalent, as opposed to DUS and CTA (p = .002). Endoleaks detected by CTA led to re-intervention in 11 (4%) patients. These endoleaks were also detected by CEUS; however, three out of 11 patients were missed by DUS and underwent re-intervention: limb extension, re-cuff, and attempt to coil lumbar leaks. Endoleaks missed by CEUS or CTA were type II endoleaks without sac expansion. CONCLUSION: In surveillance programs after EVAR a diagnostic CEUS examination may replace CTA.

Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is thought to develop as a result of inflammatory processes in the aortic wall. In particular, mast cells are believed to play a central role. The AORTA trial was undertaken to investigate whether the mast cell inhibitor, pemirolast, could retard the growth of medium-sized AAAs. In preclinical and clinical trials, pemirolast has been shown to inhibit antigen-induced allergic reactions. METHODS: Inclusion criteria for the trial were patients with an AAA of 39-49 mm in diameter on ultrasound imaging. Among exclusion criteria were previous aortic surgery, diabetes mellitus, and severe concomitant disease with a life expectancy of less than 2 years. Included patients were treated with 10, 25 or 40 mg pemirolast, or matching placebo for 52 weeks. The primary endpoint was change in aortic diameter as measured from leading edge adventitia at the anterior wall to leading edge adventitia at the posterior wall in systole. All ultrasound scans were read in a central imaging laboratory. RESULTS: Some 326 patients (mean age 70·8 years; 88·0 per cent men) were included in the trial. The overall mean growth rate was 2·42 mm during the 12-month study. There was no statistically significant difference in growth between patients receiving placebo and those in the three dose groups of pemirolast. Similarly, there were no differences in adverse events. CONCLUSION: Treatment with pemirolast did not retard the growth of medium-sized AAAs. REGISTRATION NUMBER: NCT01354184 (https://www.clinicaltrials.gov).

Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.

OBJECTIVE: The aim of this review was to identify clinical and/or imaging parameters that are associated with an increased (decreased) risk of early/late stroke in patients with symptomatic carotid disease. IN THE FIRST 14 DAYS: Natural history studies suggest that 8-15% of patients with 50-99% stenoses will suffer a stroke within 72 hours of their index symptom. Currently, there are insufficient validated data to identify highest-risk patients for emergency carotid endarterectomy (CEA), but an increased risk of stroke appears to be predicted by (i) an ABCD(2) score of 4-7; (ii) the presence of acute cerebral injury on CT/MRI; (iii) Gray Scale Median (GSM) <15, (iv) spontaneous embolisation on Transcranial Doppler (TCD); and (v) increased fluorodeoxyglucose (FDG) uptake in the carotid plaque on positron emission tomography (PET). A future goal must be to develop predictive algorithms (based on accessible imaging strategies) for identifying acutely symptomatic patients with highly unstable plaques for emergency CEA. MEDIUM TO LONG TERM: In the randomised trials, about 70% of patients with symptomatic 70-99% stenoses were stroke-free on "best medical therapy" at 5 years. Clinical predictors of increased stroke risk include (i) male gender; (ii) age >75; (iii) hemispheric symptoms; and (iv) increasing comorbidity. Imaging features associated with increased stroke risk include (i) irregular stenoses; (ii) contralateral occlusion; (iii) increasing stenosis severity, but not subocclusion; (iv) tandem intracranial disease; (v) a failure to recruit intracranial collaterals; (vi) low GSM; (vii) MR diagnosis of intra-plaque haemorrhage; (vii) spontaneous embolisation on TCD; and (viii) increased FDG uptake in the carotid plaque on PET. Clinical/imaging parameters associated with a lower risk of stroke include (i) female gender, especially those with 50-99% stenoses; (ii) ocular symptoms/lacunar stroke; (iii) smooth stenoses; and (iv) chronic subocclusion.

Three-dimensional ultrasound evaluation of small asymptomatic abdominal aortic aneurysms.

OBJECTIVE: Non-invasive and reproducible size measurements that correlate well with computed tomography (CT) are desirable in the management of small abdominal aortic aneurysms (AAA). Three dimensional ultrasound (3D-US) technology may reduce inaccuracy because of variations in orientation of the image planes and axis. This study aimed to determine any differences in paired size estimation associated with three 3D-US derived methods using 3D-CT as the gold standard. When CTA was not available, the patients were enrolled anyway to assess 3D-US reproducibility in terms of agreement between two physicians. METHODS: In the period from 1 March 2013 to 27 February 2014, consecutive patients with a small AAA, <5.5 cm for men and <5.2 cm for women, underwent 3D-US examination and three AAA size measures were obtained: dual plane diameter, diameter perpendicular to the residual sac's centreline and a partial volume. RESULT: In all, 122 consecutive US examinations were performed. Patients were excluded because of inadequate AAA size (n = 11) and for technical reasons (n = 11). Thus, 100 patients (F/M; 20/80) with a median maximum AAA diameter of 46 (range 31-55) mm were analysed. The mean US dual plane diameter and the 3D-US centreline diameter were 2.6 mm and 1.8 mm smaller than the mean 3D-CT centreline diameter, respectively (p = .003). The inter-observer reproducibility coefficient was 3.7 mm for the US dual plane diameter and 3.2 mm for the 3D-US centreline diameter (p = 0.222). For the partial volume, the reproducibility was 8-12%, corresponding to a diameter variability of ±3 mm. The median time used for post-processing of the 3D-US acquisition was 72 (range 46-108) seconds per examination. CONCLUSION: 3D-US demonstrated an acceptable reproducibility and a good agreement with 3D-CT, and has the potential to improve future AAA management through more reliable ultrasound guided size estimates.

Clinical and imaging features associated with an increased risk of late stroke in patients with asymptomatic carotid disease.

BACKGROUND: The 2011 American Heart Association Guidelines on the management of asymptomatic carotid disease recommends that carotid endarterectomy (CEA) (with carotid artery stenting (CAS) as an alternative) may be considered in highly selected patients with 70-99% stenoses. However, no guidance was provided as to what "highly selected" meant. This caveat is, however, important as up to 95% of asymptomatic individuals undergoing prophylactic CEA or CAS will ultimately undergo an unnecessary procedure. Even if the procedural risk following CEA or CAS could be reduced to 0%; 93% of patients would still undergo an unnecessary intervention. This, coupled with growing awareness that the risk of stroke in medically treated patients appears to be diminishing, has led to a renewed drive towards identifying patients with the highest risk of suffering a stroke whilst on medical therapy in whom to target CEA/CAS. METHODS: Review of clinical and/or imaging based scoring systems, predictive algorithms and imaging parameters that may be associated with an increased (or decreased) risk of stroke in patients with asymptomatic carotid disease. RESULTS: Parameters associated with an increased risk of late stroke include: (a) silent infarction on CT/MRI; (b) stenosis progression; (c) hypoechoic plaques or GSM <15; (d) irregular plaques; (e) evidence of spontaneous embolization on TCD; (f) AHA plaque types IV-V, VI; (g) MR diagnosed IPH; (h) plaque area >80 mm(2); (i) juxta-luminal black area >10 mm(2); and (j) tandem intracranial disease. CONCLUSIONS: A number of imaging parameters have been shown to be predictive of an increased risk of late stroke in previously asymptomatic patients. None have been independently validated, but many could easily be evaluated in natural history studies or randomized trials in order to identify a "high risk for stroke" cohort in whom CEA/CAS could be prioritized.

Reproducibility of ECG-gated ultrasound diameter assessment of small abdominal aortic aneurysms.

OBJECTIVE: No standardised ultrasound procedure to obtain reliable growth estimates for abdominal aortic aneurysms (AAA) is currently available. We investigated the feasibility and reproducibility of a novel approach controlling for a combination of vessel wall delineation and cardiac cycle variation. DESIGN: Prospective comparative study. METHODS: Consecutive patients (N = 27) with an AAA, attending their 6-month control as part of a medical treatment trial, were scanned twice by two ultrasound operators. Then, all ultrasound recordings were transferred to a core facility and analysed by a third person. The AAA diameter was determined in four different ways: from the leading edge of adventitia on the anterior wall to either the leading edge of the adventitia (method A) or leading edge of the intima (method B) on the posterior wall, with both measurements performed in systole and diastole. RESULT: Inter-operator reproducibility was ± 3 mm for all methods applied. There was no difference in outcome between methods A and B; likewise, end-diastolic measurement did not improve reproducibility in preference to peak-systolic measurement. CONCLUSION: The use of a standardised ultrasound protocol including ECG-gating and subsequent off-line reading with minute calliper placement reduces variability. This may be of use in developing protocols to better detect even small AAA growth rates during clinical trials.

Volume estimation of the aortic sac after EVAR using 3-D ultrasound - a novel, accurate and promising technique.

OBJECTIVES: Volume estimation is more sensitive than diameter measurement for detection of aneurysm growth after endovascular aneurysm repair (EVAR), but this has only been confirmed on three-dimensional, reconstructed computer tomography (3-D CT). The potential of 3-D ultrasound (3-D US) for volume estimation in EVAR surveillance is unknown. DESIGN: Prospective validation study comparing 3-D US with 3-D CT, using 3-D CT as the gold standard. MATERIALS AND METHODS: From August 2011 to March 2012, 93 consecutive EVAR patients were enrolled and examined with both 3-D US and CT angiography (CTA). Image data were analysed in a mutual blinded setup using a 3-D interactive segmentation technique. RESULTS: The technical success rate of 3D-US was 98% (91/93). In 91 EVAR patients (F/M; 10/81) eligible for further analysis, the mean maximum volume (SD) was 126 (58) ml using 3-D US and 128 (58) ml using 3-D CT. The mean difference was 1 ml (0.4%) and the limits of agreement were -14 to 16 ml (-11; 12%). CONCLUSION: Volume estimation of the aortic sac after EVAR using 3-D US is a feasible and accurate method using 3-D CT as the gold standard.

Three-dimensional ultrasound improves the accuracy of diameter measurement of the residual sac in EVAR patients.

OBJECTIVES: Discrepancy between maximum diameters obtained with two-dimensional ultrasound and computed tomography (CT) after endovascular aneurysm repair (EVAR) is well known. The maximal diameter is ideally measured perpendicular to the centerline, a methodology so far only feasible with three-dimensional (3D) CT and magnetic resonance angiography (MRA). We aimed to investigate the agreement between 3D ultrasound and 3D CT and to determine reproducibility measures. METHODS: Prospective study comparing 3D ultrasound with 3D CT in 124 consecutive patients seen 3 or 12 month after EVAR. RESULTS: Replacing 2D with 3D ultrasound, the mean difference was improved from 6.0 mm to -1.3 mm (p < .001), and the range of variability was reduced from 9.4 mm to 6.6 mm (p = .009) using 3D CT as the gold standard. The mean difference between 3D ultrasound and 3D CT maximum diameter of the residual sac was -1.3 mm with upper and lower limits of agreement of 5.2 mm and -7.9 mm, respectively. Reproducibility measures of 3D ultrasound were ± 4 mm. CONCLUSION: 3D ultrasound correlate significantly better to 3D CT than the currently used 2D ultrasound method when assessing maximum diameter of the residual sac after EVAR, and reproducibility measures were within clinical acceptable values.

Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis.

OBJECTIVES: The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology. METHODS: We investigated cervical and cerebral veins in 24 patients with relapsing-remitting MS (RRMS) and 15 healthy controls, using extracranial high-resolution ultrasound colour Doppler (US-CD) and transcranial colour Doppler sonography (TCDS), as well as magnetic resonance imaging (MRI) and phase-contrast MR blood flow measurements (PC-MR) of the cervical veins. RESULTS: US-CD could not identify the left internal jugular vein (IJV) in one MS patient, other ultrasound examinations were normal in patients with MS. There was no difference in mean cross-sectional area of the IJV in MS patients compared with controls. Only one patient with MS and two healthy controls fulfilled one CCSVI criterion, and none fulfilled more than one CCSVI criterion. MR venography showed insignificant IJV stenosis (1-49%) in two patients with MS, whereas 50-69% IJV stenosis was detected in two healthy controls. There was no difference in PC-MR measurements of mean IJV blood flow between patients with MS and controls. CONCLUSION: Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

Observer agreement of lower limb venous reflux assessed by duplex ultrasound scanning using manual and pneumatic cuff compression in patients with chronic venous disease and controls.

OBJECTIVES: The study aimed to evaluate observer agreement between two experienced ultrasound operators examining deep venous reflux assessed by duplex ultrasound (DU) using either manual or pneumatic cuff compression. In addition, the two methods were compared with each other with regard to immediate "eyeballing" and direct measurements of reflux time from Doppler flow curves. DESIGN: This was a case control study. MATERIAL AND METHODS: Cases were found among patients admitted to our department with deep venous thrombosis of the iliac, femoral or popliteal veins during the period 1999-2006. Controls were departmental staff. DU was used to assess valve function in the common femoral, femoral and popliteal veins in the standing position using manual and pneumatic cuff compression. The investigators were blinded to the other's observations. Observer agreement was assessed using the Rasch model for binary items. RESULTS: Twenty patients and 20 controls participated in the study and were analysed by the Rasch model. Quantitative measurement was found to be more reliable than "eyeballing", and cuff compression was more reproducible in identifying reflux than manual compression. We found that assessment by manual measurement by one investigator functioned at a lower level of expertise than for the other investigator. CONCLUSIONS: Cuff measurements were more accurate in diagnosing deep venous reflux than manual measurements, and measurement was more accurate than "eyeballing". The fact that assessment by manual compression by one investigator functioned at a lower level of expertise suggests that cuff measurement might be the optimal assessment method, especially in the difficult cases.

World Federation of Vascular Societies: presidential address.

The presidential address describes briefly the history of the World Federation for Vascular Societies (WFVS) and its objectives. Vascular Surgery today includes interventional procedures (open surgical and endovascular) in addition to risk factor reduction and medical treatment. It is equally important to train in clinical investigative methods, non-surgical treatment, decision making as is training in technical aspects of interventions. Similarly, it is vital, that the vascular specialist always recommends the treatment which is best to the individual patient, not only what he can do or what is best for other reasons, i.e. financial. Due to the increasing complex procedures - endovascular evolution and what is then "left" for open surgery - specialisation into "mainly open vascular surgeon" and "mainly endovascular surgeon" preceded by a common basic training into both, seems unavoidable. Similar, in order to be able to train with relevant case mix and numbers, and in order always to have both complex open and endovascular skills on call 24 hours per day, 365 days a year, centralisation into larger units is necessary. The WFVS is important simply looking at the huge demographic differences throughout the world. In addition, for introduction of new treatments, training issues and dissemination of science a global organisation like the WFVS is needed.

Comparison of ankle-brachial index measured by an automated oscillometric apparatus with that by standard Doppler technique in vascular patients.

OBJECTIVES: To evaluate the determination of ankle-brachial indices (ABIs) using a simple automated ankle pressure measurement device in comparison with the Doppler technique. DESIGN: ABI was measured in 61 patients (122 legs) admitted to the department of vascular surgery, Rigshospitalet. ABI was calculated twice using both the methods on both legs. MATERIALS AND METHODS: We tested the automated oscillometric blood pressure device, CASMED 740, for measuring ankle and arm blood pressure and compared it with the current gold standard, the hand-held Doppler technique, by the Bland-Altman analysis. RESULTS: Using the Doppler-derived ABI as the gold standard, the sensitivity and specificity of the oscillometric method for determining an ABI