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Physicians may receive diagnostic information in different orders, and there is a lack of empirical evidence that the order of presentation may influence clinical reasoning. We investigated whether diagnostic accuracy of chest pain cases is influenced by the order of presentation of the history and electrocardiogram (EKG) to cardiology residents. We conducted an experimental study during a resident training in 2019. Twelve clinical cases were presented in 2 diagnostic rounds. Residents were randomly allocated to seeing the EKG first (EKGF) or the history first (HF). The mean diagnostic accuracy scores (range 0-1) and confidence level (0-100) in each diagnostic round and time needed to make the diagnosis were evaluated. The final diagnostic accuracy was higher than the initial in both groups. After the first round, diagnostic accuracy was higher in HF (n=24) than in EKGF (n=28). Time taken to judge the history was comparable in both groups. Time taken to judge the EKG was shorter in HF (40±11 vs 64±13 seconds; P<.01). Time invested in the second round was significantly correlated with changing the initial diagnosis. A significant difference was observed in confidence ratings after the initial diagnosis, with EKGF reporting less confidence relative to HF. The order in which history and EKG are presented influences the clinical reasoning process. [ABSTRACT FROM AUTHOR]

Teaching and learning practices often fail to incorporate new concepts in the ever-evolving field of medical education. Although medical education research provides new insights into curricular development, learners' engagement, assessment methods, professional development, interprofessional education, and so forth, faculty members often struggle to modernize their teaching practices. Communities of practice (CoP) for faculty development offer an effective and sustainable approach for knowledge management and implementation of best practices. A successful CoP creates and shares knowledge in the context of a specific practice toward the development of expertise. CoPs' collaborative nature, based on the co-creation of practical solutions to daily problems, aligns well with the goals of applying best practices in health professions education and training new faculty members. In our article, we share 12 tips for implementing a community of practice for faculty development. The tips were based on a comprehensive literature review and the authors' experiences. [ABSTRACT FROM AUTHOR]

Background:Self-regulated learning is an important determinant of academic performance. Previous research has shown that cumulative assessment encourages students to work harder and improve their results. However, not all students seem to respond as intended. We investigated the influence of students’ behavioral traits on their responsiveness to a cumulative assessment strategy. Method:The cumulative test results of a third-year integrated ten-week course unit were analyzed. The test was divided into three parts delivered at 4, 8 and 10 weeks. Low starters (below median) with low or high improvement (below or above the median) were identified and compared regarding their behavioral traits (assessed with the Temperament and Character Inventory questionnaire). Results:A total of 295 students filled out the questionnaire. A percentage of 70% of the students below the median on the first two test parts improved during the final part. Students who were less responsive to improve their test results, scored low only on the TCI scale “self directedness” (t = 2.49;p = 0.011). Conclusion:Behavioral traits appear to influence student reactions to feedback on test results, with students with low self-directedness scores being particularly at risk. They can thus be identified and should receive special attention from student counselors. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the feasibility of intracoronary application of endothelial progenitor cells and the subsequent distribution within the heart. Methods: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty-four hours before cell transplantation, EPCs were labeled with 5-bromo-2′-deoxyuridine (BrdU). Cells (5×105 in 250-μl medium) were injected into healthy rats, either as intracoronary application (n=11) or as intramyocardial injection (n=6). At 15 min or 3 days posttransplantation, hearts as well as other organs (lung, liver, kidney, and spleen) were collected and processed for subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per tissue area was counted. Results: Compared to intramyocardial injection, intracoronary administration resulted in more than twice as much positive cells in the heart (P<.05), with no local differences within the heart. Whereas after 15 min, EPCs were equally distributed in all examined organs (except for the spleen), cells that were still present after 3 days, approximately 10%, were selectively restricted to the heart. Conclusions: Our data indicate that the intracoronary application provides a promising technique for EPC transplantation in the rat heart. [Copyright &y& Elsevier]

BACKGROUND: Circulating vascular endothelial growth factor (VEGF) was studied as a substitute endpoint for treatment response after VEGF plasmid therapy. The effect of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) on systemic VEGF levels are however largely unknown, therefore, we studied the effect of this procedure to measure VEGF levels after surgery alone. METHODS: Fourteen patients requiring CABG were included. VEGF165 levels, ischemic markers, and hematology were measured before, directly after six days after surgery. RESULTS: VEGF165 in serum and whole blood levels were increased up to six days after CABG, respectively 249.6±50.4 to 451.7±56.4 (day 6) and 581.9±105.1 to 783.4±97.7 (day six). There was a close correlation of circulating VEGF165 with leukocyte counts and platelets and not with ischemic markers. CONCLUSION: Following surgery and in case of activated leukocyte and platelet counts care must be taken in the interpretation of systemic VEGF165 levels. [ABSTRACT FROM AUTHOR]

Cardiovascular gene therapy is a promising new approach for a variety of diseases. As far as gene therapy aimed at the myocardium is concerned a new transcutaneous delivery method may be into the pericardial sac. Objective: To evaluate the safety and applicability of the percutaneous pericardial delivery route for drug- or gene-therapy. Methods: A percutaneous pericardial access device called a perducer® was used to deliver either Indian ink or methylene blue to the pericardium of male yorkshire pigs under hemodynamic surveillance. Animals were sacrificed after either 3 h or 3 days. Post mortem distribution of the injectate was evaluated macroscopically and microscopically. Results: With the perducer®, the pericardial cavity was punctured in 10 pigs without hemodynamic complications. Although traces of dye could be seen in the pleural cavity in pigs sacrificed after 3 h, no evidence for dissemination was found in myocardial, lung, mediastinal lymph node and liver tissue in pigs sacrificed after 3 days. In two additional pigs the pericardium was punctured with the same perducer® technique under simultaneous thoracoscopic monitoring. Visualization of the surface of the pericardium facilitated the procedure because pericardial fat could be avoided. Conclusion: Obtaining access to the pericardium with the perducer® technique is safe and feasible. In addition thoracoscopic guidance may improve success rate and offers the possibility of on line surveillance. [Copyright &y& Elsevier]

Experimental data have shown that rIL2 has negative inotropic properties. This has not been investigated in humans with normal left ventricular function. Seventeen consecutive renal cell carcinoma patients who received rIL2 therapy because of dissemination were analyzed before and after treatment with a low dose of rIL2 subcutaneously. Left ventricular ejection fraction (echocardiography), heart rate variability parameters (24 h electrocardiography), and TNFα, IL1β and nitric oxide metabolites (NOx) were measured. LVEF decreased from 54 ± 7 to 50 ± 6% (mean ± S.D.; P = 0.012), with a concomitant increase in heart rate from 87 ± 13 to 94 ± 13 beats/min (P = 0.031). All frequency domain HRV parameters decreased: the total power from 18.0 ± 7.9 to 14.0 ± 5.0 ms (P = 0.001), the low frequency from 10.3 ± 5.4 to 8.3 ± 3.4 ms (P = 0.001), and the high frequency from 6.3 ± 2.6 to 4.5 ± 1.1 ms (P = 0.001). There was no measurable effect on TNFα, IL1β concentrations. Plasma levels of nitrate (NOx) increased from 22.8 ± 14.4 to 41.8±26.6 μmol/l (P = 0.007).Conclusions:: A low dose of rIL2 has a negative inotropic effect that may be mediated by increased NO concentrations. It also reduces sympathetic activity as reflected in HRV parameters. [ABSTRACT FROM PUBLISHER]

Background: Assessment is an essential part of the educational system. Usually, assessment is used to measure students’ knowledge, but it can also be used to drive students’ learning and behaviors. Assessment programs should be constructed in a well-balanced way allowing not only measuring students’ knowledge but also changing students’ behavior. Objectives: In this paper, we will discuss different strategies that can be used to change students’ behaviors which may improve their learning. Main findings: Assessment as well as the learning material should be congruent with the objectives. Based on the literature, we summarize findings that would address key points to allow assessment for learning instead of learning. Conclusions: When constructing an assessment program, choices have to be made that depend on aspects like logistics, financial, organizational, managerial, educational culture, and cooperation of individual and key faculty members. It is important to realize that whatever decisions you make, students will always adapt their behavior to the way you construct your assessment program. [ABSTRACT FROM AUTHOR]

Purpose: In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.Procedures: Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.Results: There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.Conclusion: MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography. Background: CHD occurs in patients with serotonin producing NET. The diagnostic method of choice remains echocardiography. The precise prevalence of cardiac metastases is unknown given the limitations of standard technologies. Nuclear medicine modalities have the potential to visualize metastases of NET. Methods: All patients who underwent 18F-FDOPA PET/CT because of serotonin producing NET between November 2009 and May 2012 were retrospectively analyzed. The presence of cardiac metastasis was defined as myocardial tracer accumulation higher than the surrounding physiological myocardial uptake. Laboratory tests and transthoracic echocardiography (TTE) results were digitally collected. Results: 116 patients (62 male) underwent 18F-FDOPA PET/CT, mean age was 61±13 years. TTE was performed in 79 patients. Cardiac metastases were present in 15 patients, of which 10 patients also underwent TTE. One patient had both cardiac metastasis (only on 18F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no differences in echocardiographic parameters for CHD between patients with and without cardiac metastases. TTE in none of the 79 patients showed cardiac metastases. Conclusion: The prevalence of cardiac metastases detected with 18F-FDOPA PET/CT in this study is 13%. 18F-FDOPA PET/CT can visualize cardiac metastases in serotonin producing NET patients. There appears to be no relationship between the presence of cardiac metastases and TTE parameters of CHD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and prospectively determined the association of new major adverse cardiovascular events (MACE) with this metric of HDL function. Methods: A prospective study was carried out in 93 patients referred for acute chest pain (65 patients with acute MI). The HDL anti-inflammatory capacity was determined as the ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 mRNA expression in endothelial cells in vitro. Results: Acute MI at admission was associated with impaired HDL anti-inflammatory capacity (p =0.001), even after adjustment for HDL cholesterol and apolipoprotein A-I (p =0.003). Twenty nine MACE were ascertained during a median follow-up of 1210 (910–1679) days. New MACE was associated with impaired HDL anti-inflammatory capacity (hazard ratio: 1.80 (1.17–2.77) per SD change, p =0.007) in age, sex, HDL cholesterol and apolipoprotein-AI adjusted analysis. Conclusions: The ability of HDL to attenuate endothelial inflammation is impaired in acute MI, and this metric of HDL function may serve as a predictor of new MACE, even independent of HDL cholesterol and apolipoprotein A-I. [Copyright &y& Elsevier]

Abstract: Introduction: Myocardial perfusion gating techniques offer the possibility of measurement of left ventricular end-systolic (ESV) and end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) in clinical and preclinical trials. The aim of this study was to evaluate left ventricular volumes (LVV) and LVEF with 13N-NH3 in comparison with the reference 18F-FDG in different rat models. Methods: In this study, 18 male Wistar rats, 12 control rats and 6 rats with myocardial infarction (MI) were imaged with micro-PET. The ratswere scanned with gated 13N-NH3 and 18F-FDG sequentially for the assessment of LVV and LVEF. A validated three-dimensional segmentation algorithm was used to calculate LVV and LVEF. Results: Mean LVEF measured with 13N-NH3 was 45.6±8.9 and 75.3±9.4%, mean ESV was 0.40±0.12 and 0.14±0.11 ml, and mean EDVwas 0.53±16 and 0.75±0.18 ml for MI and control rats, respectively. Moderate to good correlations were observed between values of 13N-NH3 and 18F-FDG for calculation of ESV [r=0.80, P<.0001, standard error of estimate (SEE)=0.10], EDV (r=0.63, P=.005, SEE=0.14) and LVEF (r=0.84, P<.0001, SEE=9.5). LVEF measured with 13N-NH3 was significantly lower in MI rats in comparison to measurement with 18F-FDG (45.6±8.9 vs 54.9±9.3 %; P=.04). Conclusion: Correlations were moderate to good for the assessment of ESV, EDV and LVEF between gated 13N-NH3 and 18F-FDG. LVEF was underestimated with gated 13N-NH3 in rats with myocardial infarction. In healthy rats, LV volumes and LVEF can be measured reproducibly with either approach. [Copyright &y& Elsevier]

The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology as well as in atherosclerotic plaques has not been well investigated. Hence, we determined the status of HH pathway activity both in healthy vessels and atherosclerotic plaques. A series of 10 healthy organ donor-derived human vessels, 17 coronary atherosclerotic plaques and 24 atherosclerotic carotid plaques were investigated for HH pathway activity. We show that a healthy vessel is characterized by a high level of HH pathway activity but that atherosclerotic plaques are devoid of HH signaling despite the presence of HH ligand in these pathological structures. Thus, a dichotomy between healthy vessels and atherosclerotic plaques with respect to the activation status of the HH pathway exists, and it is tempting to suggest that downregulation of HH signaling contributes to long-term plaque stability. [ABSTRACT FROM AUTHOR]

Abstract: Treatment of carotid artery stenosis by endarterectomy or stenting can significantly reduce stroke risk, but is also associated with surgery related mortality and morbidity. At present it is neither possible to assess whether a carotid plaque will become symptomatic or not, nor to define the time when symptoms will occur. Identification of carotid plaques which confer excess risk of neurologic events is fundamental in the selection of patients for vascular intervention. Molecular processes such as inflammation, lipid accumulation, apoptosis, proteolysis, thrombosis and angiogenesis have shown to be highly related with plaque vulnerability. Serum biomarkers reflecting these processes may distinguish unstable from stable carotid artery stenosis and thus be a powerful tool in the selection of patients for carotid surgery. Until now, no serum biomarker has qualified for regular clinical use in carotid artery disease. However, several biomarkers, especially markers of inflammatory or proteolytic activity seem to be promising in the identification of vulnerable carotid plaques. Therefore, it is anticipated that non-invasive risk assessment in carotid artery disease by determination of serum biomarker levels may play an important future role in clinical practice improving better selection criteria for vascular intervention. [Copyright &y& Elsevier]

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients with metabolic syndrome is rapidly increasing, and these patients often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis in patients undergoing percutaneous coronary intervention (PCI).Research Design and Methods: To assess the role of metabolic syndrome in the development of restenosis, we performed an analysis in a population of patients from the GENetic DEterminants of Restenosis (GENDER) study. The GENDER project, a multicenter prospective study, included consecutive patients after successful PCI and was designed to study the predictive value of various genetic and other risk factors for subsequent clinical restenosis, defined as target vessel revascularization (TVR) or combined end point of death, myocardial infarction, and TVR. This subpopulation of GENDER consisted of 901 patients, 448 of whom (49.7%) had metabolic syndrome.Results: On multivariable Cox regression analysis, controlling for age, sex, previous myocardial infarction, stent length, current smoking, and statin therapy, there was no association between increased risk of TVR (hazard ratio 1.03 [95% CI 0.68-1.57]) or the combined end point (1.05 [0.71-1.55]) and the presence of metabolic syndrome.Conclusions: This study demonstrates that metabolic syndrome is not associated with TVR or the combined end point after PCI. Furthermore, accumulating characteristics of metabolic syndrome were neither associated with increased risk of TVR nor with the combined end point. Therefore, PCI has equal beneficial results in patients with or without metabolic syndrome. This is important information in light of the pandemic proportion of metabolic syndrome that the medical community will face. [ABSTRACT FROM AUTHOR]

Background: A high throughput animal model may enhance pathophysiological studies to mechanisms of in-stent restenosis (ISR). More and appropriate antibodies and transgenic and knockout strains are available in rats. Consequently, a model for ISR in the rat would be convenient for pathobiological studies. Here we present the full characteristics of a rat ISR model suitable for high throughput stent research. Methods: The abdominal aorta of rats was separated from surrounding tissue and a BeStent™ 2 or a Cypher™ sirolimus-eluting stent was locally inserted. After 1, 3, 7, 28 and 56 days, the aortas were harvested, fixed, embedded and cut. Morphometric analysis was performed and inflammation scored. Results: The neointimal area increased to a maximum after 28 days (0.55 ± 0.08 mm2). Subsequently, the neointimal area slightly decreased. The injury score and the neointimal area were linearly correlated (r = 0.85, p < 0.01). Thrombus formation was present after 1 day. Leukocyte adherence was evident after 1 day, maximal after 3 days (93 ± 21 cells/section) and decreased thereafter. The inflammation score increased after 3 days to a maximum after 7 days (1.37 ± 0.06) and declined thereafter. After 28 days the Cypher sirolimus-eluting stent decreased the stenosis in comparison to the BeStent 2 (10.2 ± 0.85 vs. 18.0 ± 2.0%, respectively, p < 0.01). Conclusions: Stent deployment in the rat abdominal aorta results in thrombus formation, inflammation and neointimal formation. Moreover, there is a linear correlation between the injury score and the neointimal area. These responses resemble ISR events as seen in other animal models. Moreover, a known anti-restenotic stent also reduces neointimal formation in this model. Rat abdominal aorta stenting is a promising animal model for ISR, it is suitable for testing commercially manufactured stents and studying the pathophysiology of ISR. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Many medical skills are complex due to their requirements for integration of declarative (biomedical) knowledge with perceptual–motor and perceptual–cognitive proficiency. While feedback generally helps learners guide their actions, it is unclear how feedback supports the integration of declarative knowledge with skills. Thus, we investigated the effect of expert and augmented feedback on acquisition and retention of a complex medical skill (acquiring a transthoracic echocardiogram) in a simulation study. We randomly assigned 36 medical undergraduate students to one of three feedback sources: Expert (EF), Augmented visual (HS), and Expert plus Help Screen (EF + HS). Participants practiced until reaching proficiency. Outcome measures (knowledge test and practical skill ratings on a 5-point scale), were gathered at initial acquisition and at retention after 11 days, the time needed to obtain the images and the quality of images obtained. We divided the knowledge test into three topics: names of the images, manipulation of the probe, and anatomy of the heart. At acquisition, immediately after training, EF group participants were faster at obtaining images than participants in the two other groups. On the retention test, there were no group differences for speed of obtaining images, but the EF + HS group scored significantly higher than the other two groups on image quality. Thus, expert feedback best assisted initial acquisition and combined augmented and expert feedback best assisted retention of this complex medical task. Expert assistance reduced learners' cognitive load during initial practice, helping learners integrate declarative knowledge with physical skills. [ABSTRACT FROM AUTHOR]

The article presents a double-blind study on chronic heart failure (CHF) patients to determine the effects of carvedilol on plasma vascular endothelial growth factor (VEGF). It states that carvedilol or placebo were given randomly to patients, who were treated based on an uptitration schedule. Results show the benefits of beta-blockers in ischemic heart disease (IHD) and CHF. It concludes that CHF patients using carvedilol had increased VEGF.

Purpose: Assessment in different languages should measure the same construct. However, item characteristics, such as item flaws and content, may favor one test-taker group over another. This is known as item bias. Although some studies have focused on item bias, little is known about item bias and its association with items characteristics. Therefore, this study investigated the association between item characteristics and bias. Methods: The University of Groningen offers both an international and a national bachelor's program in medicine. Students in both programs take the same progress test, but the international progress test is literally translated into English from the Dutch version. Differential item functioning was calculated to analyze item bias in four subsequent progress tests. Items were also classified by their categories, number of alternatives, item flaw, item length, and whether it was a case-based question. Results: The proportion of items with bias ranged from 34% to 36% for the various tests. The number of items and the size of their bias was very similar in both programmes. We have identified that the more complex items with more alternatives favored the national students, whereas shorter items and fewer alternatives favored the international students. Conclusion: Although nearly 35% of all items contain bias, the distribution and the size of the bias were similar for both groups. The findings of this paper may be used to improve the writing process of the items, by avoiding some characteristics that may benefit one group whilst being a disadvantage for others. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with research which investigated the attitudes medical students in the Middle East and Gulf Region had about medical research and the factors which lead a medical student to pursue a research career.

Background:Beside acquiring knowledge, medical students should also develop the ability to apply and reflect on it, requiring higher-order cognitive processing. Ideally, students should have reached higher-order cognitive processing when they enter the clinical program. Whether this is the case, is unknown. We investigated students’ cognitive processing, and awareness of their knowledge during medical school. Methods:Data were gathered from 347 first-year preclinical and 196 first-year clinical students concerning the 2008 and 2011 Dutch progress tests. Questions were classified based upon Bloom’s taxonomy: “simple questions” requiring lower and “vignette questions” requiring higher-order cognitive processing. Subsequently, we compared students’ performance and awareness of their knowledge in 2008 to that in 2011 for each question type. Results:Students’ performance on each type of question increased as students progressed. Preclinical and first-year clinical students performed better on simple questions than on vignette questions. Third-year clinical students performed better on vignette questions than on simple questions. The accuracy of students’ judgment of knowledge decreased over time. Conclusions:The progress test is a useful tool to assess students’ cognitive processing and awareness of their knowledge. At the end of medical school, students achieved higher-order cognitive processing but their awareness of their knowledge had decreased. [ABSTRACT FROM PUBLISHER]

Introduction: The use of group work assessment in medical education is becoming increasingly important to assess the competency of collaborator. However, debate continues on whether this does justice to individual development and assessment. This paper focuses on assessing the individual component within group work. Method: An integrative literature review was conducted and complemented with a survey among representatives of all medical schools in the Netherlands to investigate current practices. Results: The 14 studies included in our review show that an individual component is mainly assessed by peer assessment of individual contributions. Process and product of group work were seldom used separately as criteria. The individual grade is most often based on a group grade and an algorithm to incorporate peer grades. The survey provides an overview of best practices and recommendations for implementing group work assessment. Discussion: The main pitfall when using peer assessment for group work assessment lies in differentiating between the group work process and the resulting product of the group work. Hence, clear criteria are needed to avoid measuring only effort. Decisions about how to weigh assessment of the product and peer assessment of individual contribution should be carefully made and based on predetermined learning goals. [ABSTRACT FROM AUTHOR]

Context Students tend to postpone preparation for a test until the test is imminent, which raises various risks associated with 'cramming' behaviours, including that for suboptimal learning. Cumulative assessment utilises spaced testing to stimulate students to study more frequently and to prevent procrastination. This randomised controlled study investigated how cumulative assessment affects time spent on self-study and test performance compared with end-of-course assessment. Methods A total of 78 undergraduate medical students in a Year 2 pre-clinical course were randomly assigned to either of two conditions. Students in the cumulative assessment condition were assessed in weeks 4, 8 and 10. Students in the end-of-course assessment condition were assessed in week 10 only. Each week, students reported the number of hours they spent on self-study. Results Students in the cumulative assessment condition ( n = 25) spent significantly more time on self-study than students in the end-of-course assessment condition ( n = 37) in all weeks of the course except weeks 5, 9 and 10. Overall, the cumulative assessment group spent 69 hours more on self-study during the course than did the control group, although the control group spent 7 hours more in studying during the final week of the course than did the cumulative assessment group. Students in the cumulative assessment condition scored slightly higher on questions concerning the content of the last part of the course. Conclusions Cumulative assessment encourages students to distribute their learning activities over a course, which leaves them more opportunity to study the content of the last part of the course prior to the final examination. There was no evidence for a short-term effect of cumulative assessment on overall knowledge gain. We hypothesise that larger positive effects might be found if retention were to be measured in the long term. [ABSTRACT FROM AUTHOR]

Objectives: This study reports the long-term follow-up of the randomised controlled HEBE trial. The HEBE study is a multicentre trial that randomised 200 patients with large first acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention to either intracoronary infusion of bone marrow mononuclear cells (BMMCs) (n=69), peripheral blood mononuclear cells (PBMCs) (n=66) or standard therapy (n=65). Methods: In addition to 3-5 days, and 4 months after AMI, all patients underwent cardiac MRI after 2 years. A follow-up for 5 years after AMI was performed to assess clinical adverse events, including death, myocardial reinfarction and hospitalisation for heart failure Results: Of the 200 patients enrolled, 9 patients died and 12 patients were lost to follow-up at 5 years after AMI. BMMC group showed less increase in LV end-diastolic volume (LVEDV) (3.5±16.9 mL/m²) compared with (11.2±19.8 mL/m², p=0.03) in the control group, with no difference between the PBMC group (9.2±20.9 mL/m²) and controls (p=0.69). Moreover, the BMMC group showed a trend for decrease in LV end systolic volume (-1.8±15.0 mL/m²) as compared with controls (3.0±16.3 mL/m², p=0.07), with again no difference between PBMC (3.3±18.8 mL/m²) and controls (p=0.66). The combined endpoint of death and hospitalisation for heart failure was non-significantly less frequent in the BMMC group compared with the control group (n=4 vs n=1, p=0.20), with no difference between PBMC and controls (n=6 vs n=4, p=0.74). The composite endpoint of death or recurrent myocardial infarction was significantly higher in the PBMC group compared with controls (14 patients vs 3 patients, p=0.008), with no difference between the BMMC group and controls (2 vs 3 patients, p=0.67). Conclusions: Long-term follow-up of the HEBE trial showed that increase in LVEDV was lower in the BMMC group. This study supports the long-term safety of intracoronary BMMC therapy. However, major clinical cardiovascular adverse events were significantly more frequent in the PBMC group. [ABSTRACT FROM AUTHOR]

Background: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass predicts future cardiovascular events in the non-acute setting. We tested the extent to which Lp-PLA2 is elevated in patients with acute coronary syndrome. Methods: A total of 231 consecutive patients referred for acute chest pain participated. Of this number, 144 were diagnosed with myocardial infarction (MI; 100 were classified as MI with ST-elevation (STEMI) and 44 as MI without ST-elevation (non-STEMI)). Eighty-seven patients had non-cardiac chest pain. Plasma Lp-PLA2 mass was measured using turbidimetric immunoassay. Results: Lp-PLA2 mass was not different between MI patients and patients with non-cardiac chest pain (231±72μg/l vs.243±88μg/l, p =0.29), and did not relate to MI in age- and sex-adjusted logistic regression analysis (odds ratio per SD increment, 0.92 (95% CI, 0.69–1.23), p =0.58). However, Lp-PLA2 mass was elevated in STEMI compared to non-STEMI patients (246±73 vs. 198±58ng/ml, p <0.001), and independently predicted STEMI (odds ratio, 2.35 (95% CI, 1.46–3.79), p <0.001). Among MI patients maximal creatine kinase was correlated positively with Lp-PLA2 (r =0.183, p =0.034). Conclusions: In the acute setting, plasma Lp-PLA2 mass is not elevated in MI patients, although Lp-PLA2 mass appears to relate to the severity of myocardial damage. [ABSTRACT FROM AUTHOR]

Purpose: Left ventricular ejection fraction (LVEF) after myocardial infarction is considered to be determined by the size of the infarction and residual function of the spared myocardium. Myocardial perfusion reserve (MPR) has been shown to be a strong prognostic factor in patients with ischaemic heart failure, even stronger than LVEF. In the present study, the interrelationship between MPR, LVEF and infarct size was investigated. Methods: In total, 102 patients with a prior history of myocardial infarction were included. All underwent rest and stress N-ammonia and gated F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) for evaluation of myocardial ischaemia and viability. FDG polar maps were used to determine the size of the infarction. The LVEF was obtained by gated F-FDG PET or another available method within 3 months of the PET scan. MPR was obtained per segment in the spared myocardium. Results: The mean age of the subjects was 68 ± 12 years. Global MPR was 1.63 ± 0.51. The mean LVEF was 36 ± 10 % and mean infarct size 23.72 ± 14.8 %. A linear regression model was applied for the analysis considering the LVEF as a dependent variable. All risk factors, mean stress flow, infarct size and MPR were entered as variables. The infarct size ( p < 0.001) and MPR ( p = 0.04) reached statistical significance. In a multivariate model MPR had a stronger correlation with LVEF than infarct size. Conclusion: In patients with a prior history of myocardial infarction, LVEF is not just related to infarct size but also to MPR in the spared myocardium. [ABSTRACT FROM AUTHOR]

Purpose: Unstable plaques may cause clinical events. Plaque destabilization results from the synergy between intraplaque angiogenesis and inflammation. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are considered to be involved in these processes. We investigated the efficacy of the anti-VEGFR mimic single-chain VEGF (scVEGF) to map intra-plaque VEGFR expression and atherosclerotic plaque instability using near-infrared fluorescence (NIRF). Procedures: Human carotid plaques were retrieved from 15 symptomatic and five asymptomatic patients. NIRF plaque imaging was performed pre-/post-incubation with scVEGF/Cy5.5. Biopsies taken from regions with high (hot spot) and low (cold spot) NIRF signals were examined for VEGF-A, VEGFR-1 and VEGFR-2 mRNA expression levels using real-time RT-PCR analysis. Immunohistochemistry for CD31 (endothelium), CD68 (macrophages) and αSMA (smooth muscle cells) was performed to evaluate plaque composition. Results: NIRF imaging of 20 plaques revealed a heterogeneous distribution of scVEGF/Cy5.5 binding. After incubation NIRF activity increased from 3.9×10 ± 5.2×10 to 3.0×10 ± 2.2×10 and 5.8×10 ± 1.9×10 to 3.1×10 ± 1.9×10 photons/s/cm/sr/illumination intensity on the intraluminal and extraluminal side, respectively (both p < 0.001). Real-time RT-PCR analysis showed a ~1.2- and ~16.4-fold increased mRNA expression of VEGFR-1 and VEGFR-2, respectively, in hot spots (vs. cold spots). Immunohistochemistry exhibited higher intraplaque capillary density in hot spots (vs. cold spots) (17.2 ± 3.7 vs. 5.4 ± 2.2 capillary/mm; p = 0.037). Hot spots contained significantly reduced numbers of α-SMA-positive cells (vs. cold spots) (2.2 ± 0.7 % vs. 6.9 ± 1.5 %; p = 0.038). Finally, a ~2-fold increase of CD68 infiltrating macrophages within hot spots (vs. cold spots) was observed (not significant, p = 0.17). Significant higher capillary density in hot spots (vs. cold spots) was observed in plaques from symptomatic patients but not in plaques from asymptomatic patients. Conclusion: Our data support that scVEGF/Cy5.5 is a suitable indicator for plaque instability and a promising diagnostic tool for risk assessment in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA) specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET) was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%lnc/g) and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111ln-lgG uptake was demonstrated by gamma counting. The mean %lnc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001). It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. Methods: 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. Results: On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B =0.02, SE=0.02, p <0.001). Routine TTE had a sensitivity of 21–24% and a specificity of 95–98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ =0.91 and κ =0.96) compared to TTE (κ =0.74 and κ =0.53). Conclusion: LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large. [Copyright &y& Elsevier]

Purpose: Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. I-MIBG can detect these innervation changes. Methods: Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Results: Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 ± 0.75, and the mean wash-out rate was 8.6 ± 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 ± 0.70 versus 2.8 ± 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (−3.3 ± 9.9 % vs. 17 ± 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 ± 0.59 vs. 2.9 ± 0.50, p = 0.007). Conclusion: MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, I-MIBG scintigraphy can detect cardiac denervation in ATTR patients before signs of amyloidosis are evident on echocardiography. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (7): 795-803 Abstract Background Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance. Materials and methods In recent years, many observational and interventional studies have shown important adverse cardiovascular effects of AAS abuse. Conclusions This review discusses established and future perspectives of novel molecular imaging techniques that may serve as potential tools for early detection of AAS-associated cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Background: Deterioration of left ventricular (LV) function after myocardial infarction (MI) is a major cause of heart failure. Myocardial perfusion performance may play an important role in deterioration or improvement in LV function after MI. The aim of this study was to evaluate the myocardial perfusion reserve (MPR) and stress perfusion in deteriorating and non-deteriorating LV segments in patients after MI by PET and MRI, respectively. Methods: Regional wall thickening of 352 segments in 22 patients was assessed at 4 and 24 months after MI by cardiac MRI. PET was performed to evaluate MPR and adenosine stress N-ammonia perfusion 24 months after MI. Segments were divided into four groups according to deterioration or improvement in wall thickening. Results: Normal functional segments at 4 months after MI that remained stable had a significantly higher mean MPR and mean stress perfusion PET value than deteriorated segments ( p < 0.001). Furthermore, dysfunctional segments that improved had a significantly higher mean stress perfusion PET value than dysfunctional segments that remained dysfunctional ( p < 0.001). Conclusion: This study demonstrated the additional value of myocardial perfusion assessment in relation to the functional integrity of the injured myocardium. Segmental functional LV improvement after MI was associated with better regional myocardial perfusion characteristics. Furthermore, the amount of wall thickening reduction was associated with regional myocardial perfusion abnormalities in patients after MI. [ABSTRACT FROM AUTHOR]

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (8): 820-827 Abstract Background A recent meta-analysis showed that both plasma lipoprotein-associated phospholipase A [ABSTRACT FROM AUTHOR]

Abstract: Background: Current key issues in ischemic stroke are related to carotid plaque vulnerability, brain viability, and timing of intervention. The treatment of ischemic stroke has evolved into urgent active interventions, as ‘time is brain’. Functional imaging such as positron emission tomography (PET)/single photon emission computed tomography (SPECT) could improve selection of patients with a vulnerable plaque and evaluation of brain viability in ischemic stroke. Objective: To describe the current applications of PET and SPECT as a diagnostic tool in relation to ischemic stroke. Methods: A literature search using PubMed identified articles. Manual cross-referencing was also performed. Results: Several papers, all observational studies, identified PET/SPECT to be used as a tool to monitor systemic atheroma modifying treatment and to select high-risk patients for surgery regardless of the degree of luminal stenosis in carotid lesions. Furthermore, PET/SPECT is able to quantify the penumbra region during ischemic stroke and in this way may identify those patients who may benefit from timely intervention. Discussion: Functional imaging modalities such as PET/SPECT may become important tools for risk-assessment and evaluation of treatment strategies in carotid plaque vulnerability and brain viability. Prospective clinical studies are needed to evaluate the diagnostic accuracy of PET/SPECT. [Copyright &y& Elsevier]

MicroRNAs (miRNAs) are tiny, endogenous nucleotides that bind to mRNA and induce translation repression within metazoan cells. Since their discovery in 1993 in Caenorhabditis elegans and the demonstration of miRNAs in Homo sapiens in 2000, research has been fruitful in deciphering the role of these nucleotides in development, tissue homeostasis, and pathologic processes. In humans, around 700 human miRNA nucleotides have been verified, which interfere with 30% of all genes. Recently, the role of miRNA in cardiovascular research gained attention and the involvement of miRNAs in several cardiovascular diseases has been identified. In this review, we focus on the role of miRNAs in atherosclerosis and in particular on the potential role of miRNAs in the development of vulnerable atherosclerotic plaques. The role of miRNA in the main characteristics of these plaques, inflammation, angiogenesis, and apoptosis will be discussed. Finally, the future perspectives and miRNA-based diagnostic and therapeutic potentials will be highlighted. [Copyright &y& Elsevier]

Although cells constantly adapt to external humoral cues, like cytokines and hormones, in practice, most cellular behavior is under locally guided control, via cell–cell interactions. The most prominent members of this group of molecules involved in this intercellular signaling are the galectins, a family of carbohydrate-binding proteins, which by binding specific receptors induce signaling. It has become clear that galectins are important in the pathogenesis of cardiovascular disease, in particular atherosclerosis, stroke, myocardial infarction, and heart failure. Modulation of galectin signaling holds great promise for the treatment of cardiovascular disease as evident from preclinical studies. [Copyright &y& Elsevier]

Patients with chronic renal failure have increased cardiac calcium loads. Previous studies have investigated the prevalence and quantitative extent of aortic valve calcium (AVC) and coronary artery calcium (CAC) in patients with various stages of chronic kidney disease (CKD). However, the impact of preexisting atherosclerosis on the calcification burden has not been clarified. Therefore, this study was conducted to examine the effect of CKD stage as well as the primary cause of renal failure (atherosclerotic vs nonatherosclerotic) on AVC and CAC. Twenty-two, 13, and 28 patients with stage 3, 4, and 5 CKD, respectively, were included, of whom 24 had atherosclerotic CKD. Patients underwent electron-beam computed tomography to assess AVC and CAC. AVC was present in 27% of patients with stage 3 CKD, in 38% of patients with stage 4 CKD, and in 43% of patients with stage 5 CKD. CAC was present in 77% of patients with stage 3 CKD, in 54% of patients with stage 4 CKD, and in 64% of patients with stage 5 CKD. There was no correlation between CKD stage and the quantitative extent of AVC and CAC. AVC was more frequent (58% vs 23%, p <0.01) and more extensive (median score 43 [range 0 to 494] vs 0 [range 0 to 8], p <0.01) in patients with CKD caused by atherosclerotic renal disease than in patients with nonatherosclerotic causes of CKD. CAC was more frequent (83% vs 56%, p <0.05) and more extensive (median score 437 [range 61 to 1,565] vs 31 [range 0 to 155], p <0.001) in patients with atherosclerotic causes of CKD than in patients with CKD caused by nonatherosclerotic renal disease. In conclusion, the prevalence as well as the severity of AVC and CAC did not vary between patients with stage 3, 4, and 5 CKD. Cardiac calcification, both AVC and CAC, were more frequent and more severe in patients with atherosclerotic causes of renal failure. These results suggest that cardiac calcium is related to atherosclerotic burden rather than to the severity of CKD. [Copyright &y& Elsevier]

Variation in the NOS3 gene has been related to the development of restenosis. The Glu298Asp polymorphism has previously been investigated for its effect on NO levels and the development of restenosis. However, the variability of findings gave rise to the hypothesis that the functional significance of this polymorphism may only become manifest under conditions of endothelial dysfunction. Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance of NOS3 polymorphisms may depend on the presence of the metabolic syndrome. We examined the impact of the -949 A/G, the -716 C/T and the Glu298Asp polymorphisms in the NOS3 gene on the risk of clinical restenosis in a previously described subpopulation of the GENDER-study, a multicenter prospective study design that enrolled consecutive patients after successful PCI. This subpopulation consisted of 901 patients of whom sufficient data were available to establish absence or presence of the metabolic syndrome. Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined as target vessel revascularization (TVR), was the primary endpoint. We demonstrated that the minor -949G, -716T and 298Asp alleles were associated with a significantly increased risk of TVR in patients with the metabolic syndrome (HR: 1.58 [95%CI: 1.04–2.40], HR: 1.95 [95%CI: 1.02–3.70] and HR: 1.67 [95%CI: 1.09–2.54], respectively). In the group without the metabolic syndrome we observed no association between the three polymorphisms and TVR. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) function assessment by dual-source computed tomography (DSCT) was compared with the reference standard method using magnetic resonance imaging (MRI). Accurate assessment of LV function is essential for the prediction of prognosis in cardiac disease. Thirty-four patients undergoing DSCT examination of the heart for various clinical indications underwent MRI after DSCT. Short-axis cine images were reconstructed from the DSCT datasets and were analyzed using a dedicated post-processing software-tool to generate global left ventricular function parameters. Five DSCT datasets were considered to be of insufficient image quality. DSCT showed a small overestimation of end-diastolic and end-systolic volumes of 11.0 ml and 3.5 ml, respectively. Myocardial mass assessed by DSCT showed an average underestimation of 0.2 g. DSCT showed a small overestimation of LV ejection fraction (LVEF) of 0.4%-point with a Bland-Altman interval of [-8.67 (0.40) 9.48]. Global LV functional parameters calculated from DSCT datasets acquired in daily clinical practice correlated well with MRI and may be considered interchangeable. However, visual assessment of the image quality of the short-axis cine slices should be performed to detect any artifacts in the DSCT data which could influence accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Carotid endarterectomy (CEA) is still considered the “gold-standard” of the treatment of patients with significant carotid stenosis and has proven its value during past decades. However, endovascular techniques have recently been evolving. Carotid artery stenting (CAS) is challenging CEA for the best treatment in patients with carotid stenosis. This review presents the development of CAS according to early reports, results of recent randomized trials, and future perspectives regarding CAS. Methods: A literature search using the PubMed and Cochrane databases identified articles focusing on the key issues of CEA and CAS. Results: Early nonrandomized reports of CAS showed variable results, and the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy trial led to United States Food and Drug Administration approval of CAS for the treatment of patients with symptomatic carotid stenosis. In contrast, recent trials, such as the Stent-Protected Angioplasty Versus Carotid Endarterectomy trial and the Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis trial, (re)fuelled the debate between CAS and CEA. In the Stent-Protected Angioplasty Versus Carotid Endarterectomy trial, the complication rate of ipsilateral stroke or death at 30 days was 6.8% for CAS versus 6.3% for CEA and showed that CAS failed the noninferiority test. Analysis of the Endarterectomy Versus Stenting in Patients With Symptomatic Severe Carotid Stenosis trial showed a significant higher risk for death or any stroke at 30 days for endovascular treatment (9.6%) compared with CEA (3.9%). Other aspects–such as evolving best medical treatment, timely intervention, interventionalists’ experience, and analysis of plaque composition–may have important influences on the future treatment of patients with carotid artery stenosis. Conclusions: CAS performed with or without embolic-protection devices can be an effective treatment for patients with carotid artery stenosis. However, presently there is no evidence that CAS provides better results in the prevention of stroke compared with CEA. [Copyright &y& Elsevier]

We determined the efficiency of a screening protocol based on coronary calcium scores (CCS) compared with exercise testing in patients with suspected coronary artery disease (CAD), a normal ECG and troponin levels. Three-hundred-and-four patients were enrolled in a screening protocol including CCS by electron beam computed tomography (Agatston score), and exercise testing. Decision-making was based on CCS. When CCS≥400, coronary angiography (CAG) was recommended. When CCS<10, patients were discharged. Exercise tests were graded as positive, negative or nondiagnostic. The combined endpoint was defined as coronary event or obstructive CAD at CAG. During 12±4 months, CCS≥400, 10–399 and <10 were found in 42, 103 and 159 patients and the combined endpoint occurred in 24 (57%), 14 (14%) and 0 patients (0%), respectively. In 22 patients (7%), myocardial perfusion scintigraphy was performed instead of exercise testing due to the inability to perform an exercise test. A positive, nondiagnostic and negative exercise test result was found in 37, 76 and 191 patients, and the combined endpoint occurred in 11 (30%), 15 (20%) and 12 patients (6%), respectively. Receiver-operator characteristics analysis showed that the area under the curve of 0.89 (95% CI: 0.85–0.93) for CCS was superior to 0.69 (95% CI: 0.61–0.78) for exercise testing ( P<0.0001). In conclusion, measurement of CCS is an appropriate initial screening test in a well-defined low-risk population with suspected CAD. [ABSTRACT FROM AUTHOR]

Abstract: Aims: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population. Methods and results: Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37±19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1–3 and >3mg/L of, respectively, 1.26 (95% CI 0.67–2.40) and 3.16 (95% CI 1.26–3.16), relative to hs-CRP <1mg/L. Conclusion: In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis. [Copyright &y& Elsevier]

Genetic factors appear to be important in the development of restenosis after percutaneous coronary intervention, as well as in the process of inflammation, a pivotal factor in restenosis. Caspase-1, interleukin-1-receptor and protein tyrosine phosphatase nonreceptor type 22 are important mediators in the inflammatory response and caspase-1 also in apoptosis. Therefore, we examined whether polymorphisms in these candidate genes are related to the risk of developing restenosis after percutaneous coronary intervention.The GENetic DEterminants of Restenosis-project is a multicenter prospective follow-up study. The 5352G/A (L235L) caspase-1-polymorphism, the 7464C/G (A124G) interleukin-1r-polymorphism and the 1858C/T (R620W) protein tyrosine phosphatase nonreceptor type 22-polymorphism were genotyped. To examine the functional effect of the caspase-1 polymorphism, mature plasma interleukin-1β levels were measured by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated whole blood from a subpopulation of patients.A total of 3104 patients, age 62.1±10.7 years, were included after successful percutaneous coronary intervention. A significant association between the 5352AA genotype of the caspase-1 gene and target vessel revascularization (relative risk 2.2, 95% confidence interval 1.32-3.76) was observed after correcting for clinical variables. Angiographic analysis of a subgroup of patients (N=478) also showed an increased risk for developing restenosis for patients having the 5352GA/AA genotype (P=0.001). The results were corroborated, although they were not statistically significant, by somewhat higher mature interleukin-1β levels in patients with the 5352AA genotype.The present study shows that patients with the 5352AA genotype in the caspase-1 gene are at increased risk of developing restenosis. If confirmed by other studies, screening patients for this genotype can lead to better risk stratification and provide indications for improving individual treatment; for instance, by providing a new target for drug-eluting stents. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems.The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region.A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism.We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation. [ABSTRACT FROM AUTHOR]

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNFα gene was performed. The role of TNFα in restenosis was also assessed in ApoE*3-Leiden mice, TNFα knockout mice, and by local delivery of a TNFα biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFα gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFα mRNA was significantly time-dependently up-regulated. Mice lacking TNFα or treated locally with thalidomide showed a reduction in reactive stenosis (P=0.01 and P=0.005, respectively). Clinical and preclinical data indicate that TNFα plays an important role in restenosis. Therefore, TNFα genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNFα may be an anti-restenotic target strategy. [ABSTRACT FROM AUTHOR]