Dynamic cell culture modulates colon cancer cell migration in a novel 3D cell culture system.

The progression of cancer cell migration, invasion and subsequent metastasis is the main cause of mortality in cancer patients. Through creating more accurate cancer models, we can achieve more precise results, which will lead to a better understanding of the invasion process. This holds promise for more effective prevention and treatment strategies. Although numerous 2D and 3D cell culture systems have been developed, they poorly reflect the in vivo situation and many questions have remained unanswered. This work describes a novel dynamic 3D cell culture system aimed at advancing our comprehension of cancer cell migration. With the newly designed cultivation chamber, 3D tumor spheroids were cultivated within a collagen I matrix in the presence of fluid flow to study the migration of cancer cells from spheroids in the matrix. Using light sheet microscopy and histology, we demonstrated that the morphology of spheroids is influenced by dynamic culture and that, in contrast to static culture, spheroids in dynamic culture are characterized by the absence of a large necrotic core. Additionally, this influence extends to an increase in the size of migration area, coupled with an increase in expression of some genes related to epithelial-mesenchymal transition (EMT). The results here highlight the importance of dynamic culture in cancer research. Although the dynamic 3D cell culture system in this study was used to investigate migration of one cell type into a matrix, it has the potential to be further developed and used for more complex models consisting of different cell types or to analyze other steps of metastasis development such as transendothelial migration or extravasation.

Significant variation in histopathological assessment of endoscopic resections for Barrett's neoplasia suggests need for consensus reporting: propositions for improvement.

Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett's esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.

Plexus anesthesia versus general anesthesia for carotid endarterectomy: A systematic review with meta-analyses.

INTRODUCTION: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of plexus anesthesia or general anesthesia in traditional carotid endarterectomy is, to date, not unequivocally proven to be superior to one other. A systematic review was needed for evaluation of benefits and harms to determine which technique, plexus anesthesia or general anesthesia is more effective for traditional carotid endarterectomy in patients with symptomatic carotid stenosis. METHODS: The review was conducted according to our protocol following the recommendations of Cochrane and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Searches were updated on the October 1, 2020. We did not find any randomized clinical trial comparing plexus anesthesia and general anesthesia in carotid endarterectomy with patch angioplasty matching our protocol criteria in patients with a symptomatic and significant (≥50%) carotid stenosis. CONCLUSIONS: Based on the current, high risk of bias evidence, we concluded there is a need for new randomized clinical trials with overall low risk of bias comparing plexus anesthesia with general anesthesia in carotid endarterectomy with patch closure of the arterial wall in patients with a symptomatic and significant (≥50%) stenosis of the internal carotid artery.Protocol unique identification number (UIN): CRD42019139913, (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139913).

Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15-20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. METHODS: This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009-2015) and cohort B (period 2015-2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. RESULTS: Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). CONCLUSION: Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

Plexus anesthesia versus general anesthesia in patients for carotid endarterectomy with patch angioplasty: Protocol for a systematic review with meta-analyses and Trial Sequential Analysis of randomized clinical trials.

INTRODUCTION: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of plexus anesthesia or general anesthesia in traditional carotid endarterectomy is, to date, not unequivocally proven to be superior to one other. A systematic review is needed for evaluation of benefits and harms to determine which technique, plexus anesthesia or general anesthesia is more effective for traditional carotid endarterectomy in patients with symptomatic carotid stenosis. METHODS AND OUTCOMES: The review will be conducted according to this protocol following the recommendations of the 'Cochrane Handbook for Systematic Reviews' and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Randomized Clinical Trials comparing plexus anesthesia versus general anesthesia in traditional carotid endarterectomy will be included. Primary outcomes will be postoperative death and/ or stroke (<30 days) and serious adverse events. Secondary outcomes will be non-serious adverse events.We will primarily base our conclusions on meta-analyses of trials with overall low risk of bias. We will use Trial Sequential Analysis to assist the evaluation of imprecision in Grading of Recommendations Assessment, Development and Evaluation. However, if pooled point-estimates of all trials are similar to pooled point-estimates of trials with overall low risk of bias and there is lack of a statistical significant interaction between estimates from trials with overall high risk of bias and trials with overall low risk of bias we will consider the Trial Sequential Analysis adjusted confidence interval precision of the estimate achieved in all trials as the result of our meta-analyses. ETHICS AND DISSEMINATION: The proposed systematic review will collect and analyze secondary data from already performed studies therefore ethical approval is not required. The results of the systematic review will be disseminated by publication in a peer-review journal and submitted for presentation at relevant conferences.

Cardiovascular and all-cause mortality in patients with intermittent claudication and critical limb ischaemia.

BACKGROUND: The aim of this study was to evaluate absolute mortality risks and to determine whether changes in mortality risk occurred in patients with intermittent claudication (IC) or critical limb ischaemia (CLI) in the Netherlands between 1998 and 2010. METHODS: Data for patients treated between 1998 and 2010 were obtained from Dutch nationwide registers: the Hospital Discharge Register, Population Register and Cause of Death Register. The registers were used to obtain information regarding IC and CLI hospitalizations, co-morbidities, demographic factors, and date and cause of death. The cohort was split into two time intervals for comparison: 1998-2004 (period 1) and 2005-2010 (period 2). Thirty-day mortality was excluded to eliminate per-admission complications. One- and 5-year cardiovascular and all-cause mortality rates were compared with those of a representative sample of the general Dutch population (28 494 persons) by Cox proportional hazards models. RESULTS: Some 47 548 patients were included, 34 078 with IC and 13 470 with CLI. In patients with IC, the age-adjusted 5-year mortality risk for cardiovascular disease decreased significantly in period 2 (14·1 per cent) compared with that in period 1 (16·1 per cent) in men only (5-year adjusted hazard ratio (HR) 0·76, 95 per cent c.i. 0·69 to 0·83; P < 0·001). In patients with CLI, the cardiovascular mortality risk decreased significantly only in women, with the 5-year risk reducing from 31·2 per cent in period 1 to 29·2 per cent in period 2 (adjusted HR 0·84, 0·74 to 0·94; P = 0·004). Compared with the general population, the mortality risk in patients with IC was increased between 1·70 (1·58 to 1·83) and 3·20 (2·69 to 3·81) times, and in those with CLI the risk was increased between 2·24 (2·09 to 2·40) and 5·19 (4·30 to 6·26) times. CONCLUSION: The risk of premature death in patients with IC and CLI declined significantly in the Netherlands, in a sex-specific manner, over the period from 1998 to 2010. The absolute risk of cardiovascular mortality remains high in these patients.

Time-dependent trends in cardiovascular adverse events during follow-up after carotid or iliofemoral endarterectomy.

BACKGROUND: Recent observations have suggested a decline in vulnerable carotid artery and iliofemoral atherosclerotic plaque characteristics over the past decade. The aim of this study was to determine whether, in the presence of clinically manifest carotid or peripheral artery disease, secondary adverse cardiovascular events decreased over this period. METHODS: Patients included in the Athero-Express biobank between 2003 and 2012 were analysed. During 3-year follow-up, composite cardiovascular endpoints were documented yearly, including: myocardial infarction, coronary interventions, stroke, peripheral interventions and cardiovascular death. The major cardiovascular endpoint consisted of myocardial infarction, stroke and cardiovascular death. RESULTS: Some 1684 patients who underwent carotid endarterectomy (CEA) and another 530 who had iliofemoral endarterectomy (IFE) were analysed. In total, 405 (25·2 per cent) and 236 (45·9 per cent) patients had a composite cardiovascular endpoint within 3 years after CEA and IFE respectively. Corrected for possible confounders, the percentage of patients with a secondary cardiovascular event after CEA did not change over time (hazard ratio (HR) 0·91, 95 per cent c.i. 0·65 to 1·28; P = 0·590, for 2011-2012 versus 2003-2004). In patients who had IFE, the incidence of secondary cardiovascular events significantly decreased only in the last 2 years (HR 0·62, 0·41 to 0·94; P = 0·024), owing to a decrease in peripheral (re)interventions in 2011-2012 (HR 0·59, 0·37 to 0·94; P = 0·028). No decrease in major cardiovascular events was observed in either group. CONCLUSION: In patients who had undergone either CEA or IFE there was no evidence of a decrease in all secondary cardiovascular events. There were no differences in major cardiovascular events.

Upper Extremity Blood Pressure Difference in Patients Undergoing Carotid Revascularisation.

INTRODUCTION: Blood pressure (BP) regulation is important in patients with carotid artery atherosclerotic disease. Concomitant subclavian artery stenosis (SAS) might lead to an underestimation of the true systemic BP in the monitoring of these patients. This study aimed to assess the prevalence of the inter-arm BP difference in patients undergoing carotid intervention and its association with ipsilateral significant subclavian stenosis and clinical outcome. METHODS: Bilateral BP measurements and vascular imaging (CTA and MRA) of both subclavian arteries and the innominate artery were assessed in 182 symptomatic patients with carotid artery stenosis undergoing revascularisation in the International Carotid Stenting Study (ICSS). Data were separately analysed according to previously described cutoff values for systolic BP (SBP) differences of ≥10 and <15 mmHg, ≥15 and <20 mmHg, or ≥20 mmHg. Significant SAS was defined as a >50% diameter reduction. RESULTS: Of the 182 patients, 39 (21%) showed an inter-arm difference in SBP >15 mmHg. The mean inter-arm SBP difference associated with ipsilateral SAS was 14 mmHg. SAS was present in 21/182 (12%) patients. Only two patients (1%) had bilateral stenotic disease. An inter-arm SBP difference of ≥20 mmHg was associated with unilateral SAS (RR 11.8; 95% CI 3.2-43.1) with a sensitivity of 23% and a specificity of 98%. Patients were followed up for a median of 4.0 years (IQR 3.0-6.0; maximum 7.5). Risk of stroke or death during follow-up was 20.0% (95% CI 11.1-28.9) in patients with, and 15.1% (95% CI 12.3-17.9) in patients without SAS (p = .561). The hospital stay was longer in patients with significant SAS (5.0 days, SD 4.9 vs. 2.7 days, SD 4.3, p = .035). CONCLUSION: The present study is the first to affirm the clinical need for the measurement of inter-arm BP differences in patients undergoing carotid revascularisation, especially in the post-operative phase in the prevention of cerebral hyperperfusion.

Extensibility and Distensibility of the Thoracic Aorta in Patients with Aneurysm.

OBJECTIVES: Reference values of aortic deformation during the cardiac cycle can be valuable for the pre-operative planning of thoracic endovascular aortic repair (TEVAR) and for facilitating computational fluid dynamics. This study aimed to quantify normal aortic extensibility (longitudinal extension) and distensibility (radial expansion), as well as pulsatile strain, in a group of 10 (>60 years) individuals with abdominal or thoracic aortic aneurysms. METHODS: ECG gated CT images of the thoracic aorta were reconstructed into virtual 3D models of aortic geometry. The centre lumen line length of the thoracic aorta and three longitudinal segments, and the aortic diameter and luminal areas of four radial intersections were extracted with a dedicated software script to calculate extensibility, longitudinal strain, distensibility, and circumferential area strain. RESULTS: Mean extensibility and longitudinal strain of the entire thoracic aorta were 3.5 [1.3-6.8] × 10-3 N-1, and 2.7 [1.0-4.5]%, respectively. Extensibility and longitudinal strain were most pronounced in the ascending aorta (20.6 [5.7-36.2] × 10-3 N-1 and 15.9 [6.6-31.9]%) and smallest in the descending aorta (4.4 [1.6-12.3] × 10-3 N-1 and 2.2 [0.7-4.7]%). Mean distensibility and circumferential area strain were most pronounced at the sinotubular junction (1.7 [0.5-2.9] × 10-3 mmHg-1 and 11.3 [3.3-18.5]%, respectively). Distensibility varied between 0.9 [0.3-2.5] × 10-3 mmHg-1 and 1.2 [0.3-3.3] × 10-3 mmHg-1 at the intersections in the aortic arch and descending aorta. CONCLUSIONS: Pulsatile deformations in both longitudinal and circumferential directions are considerable throughout the thoracic aorta. These findings may have implications for pre-operative TEVAR planning and highlight the need for devices that can mimic the significant aortic longitudinal and circumferential strains.

[Memory in disciplinary cultures and "sites" of memory in medicine : Maximilian Nitze (1848-1906) and the establishment of urology]. / Fachkulturelles Gedächtnis und Erinnerungsorte in den medizinischen Wissenschaften : Maximilian Nitze (1848-1906) und die Etablierung der Urologie.

The canon of material and immaterial references of the urological heritage must always be recognized as a part of a continous process of negotiation. Within German Urology the culture of remembrance on Maximilian Nitze reveals one of such processes.

Lack of Evidence for Dual Antiplatelet Therapy after Endovascular Arterial Procedures: A Meta-analysis.

INTRODUCTION: Dual antiplatelet therapy (DAPT) has mainly replaced mono antiplatelet therapy (MAPT) and is recommended after arterial endovascular revascularization. The aim of this meta-analysis was to summarize the available evidence for DAPT after endovascular revascularization throughout the arterial system. METHODS: A systematic search was performed in Medline, Embase, and the Cochrane Register. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration risk of bias assessment tool. Included in the search were randomized controlled trials (RCTs) comparing DAPT with MAPT after endovascular procedures for the treatment of coronary, carotid, or peripheral artery disease, reporting at least one clinical outcome. Articles were excluded if patients received anticoagulation in addition to antiplatelet therapy in the post-procedural phase. The primary outcome was restenosis or stent thrombosis, and secondary outcomes were major adverse cardiac events (MACE), target lesion revascularization, cerebrovascular accident or transient ischemic attack, bleeding, and death. Meta-analyses of binary outcomes were performed using the random effects model and described as risk ratios (RRs) and 95% confidence intervals (95% CIs). Chi-square tests were used to test for heterogeneity. RESULTS: Nine articles were included in this study, involving lower limb peripheral arteries (1), carotid arteries (2), and coronary arteries (6). The pooled results of coronary trials showed a RR for restenosis with DAPT of 0.60 (95% CI 0.28-1.31) and for myocardial infarction 0.49 (95% CI 0.12-2.03). In the carotid artery trials the RR for restenosis was 0.22 (95% CI 0.04-1.20) and for peripheral arteries 1.02 (95% CI 0.56-1.82). A meta-analysis of bleeding risk of all the included trials showed a RR of 1.06 (95% CI 0.32-3.52) with DAPT. CONCLUSION: The available evidence comparing DAPT with MAPT after endovascular arterial revascularization is limited and the majority of trials were conducted in the cardiology field. No significant evidence for superiority of DAPT compared with MAPT was found, but there was also no evidence of an increased bleeding risk with DAPT over MAPT.

High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values.

OBJECTIVE: Restenosis and stent thrombosis after endovascular intervention in patients with peripheral arterial disease (PAD) can potentially be tackled by more intensive antiplatelet therapy, such as dual antiplatelet therapy (DAPT) consisting of aspirin and P2Y12 inhibitor. Despite clopidogrel treatment, some patients still display high platelet reactivity (HCPR). Tailored antiplatelet therapy, based on platelet reactivity testing, might overcome HCPR. However, more data are warranted regarding the proportion of patients with HCPR in the PAD population, different platelet reactivity tests, their correlation, and the optimal timing for these tests as a stepping stone for a future trial investigating the potential benefit of tailored antiplatelet therapy in PAD patients. METHODS: Thirty patients on DAPT after percutaneous transluminal angioplasty underwent platelet reactivity testing by VerifyNow, vasodilator-stimulated phosphoprotein (VASP) and platelet activation assay, and CYP2C19-polymorphism testing. RESULTS: The proportion of patients with HCPR measured by VerifyNow varied between 43.3% and 83.3%, depending on the cut off values used. Testing within 24 hours of initiation of DAPT gave a higher proportion of HCPR than testing after more than 24 hours. According to DNA testing, 14.8% were CYP2C19*2 homozygote, 22.2% heterozygote, and 63% CYP2C19*2 negative. VASP assay revealed 24% HCPR. The highest HCPR rate was found with a VerifyNow cut off of less than 40% inhibition, whereas the lowest HCPR rate was found with the VASP assay. There was a low correlation between the tests. CONCLUSION: HCPR is present in PAD patients and research on HCPR is needed in this population; timing of tests is relevant and standardisation of tests is needed. The optimal conditions for platelet function testing should be determined.

Treatment of aortic graft infection by in situ reconstruction with Omniflow II biosynthetic prosthesis.

Currently available conduits for in situ reconstruction after excision of infected aortic grafts have significant limitations. The Omniflow II vascular prosthesis is a biosynthetic graft associated with a low incidence of infection that has succesfully been used in the treatment of infected infrainguinal bypass. We report on the first use of the Omniflow II prosthesis for in situ reconstruction after aortic graft infection.A bifurcated biosynthetic bypass was created by spatulating and anastomosing two 8-mm tubular Omniflow II grafts. This bypass was used for in situ reconstruction after excision of infected aortic grafts in three cases. After a mean follow-up of 2.2 years, no occlusion, degeneration, or rupture of the Omniflow II grafts was observed. Although one patient suffered from graft reinfection, the bypass retained structural integrity and no anastomotic dehiscence was observed.Treatment of aortic graft infection by in situ reconstruction with the Omniflow II vascular prosthesis is feasible. Its resistance to infection and off-the-shelf availability make this graft a promising conduit for aortoiliac reconstruction.

Quality of Life After Treatment with Autologous Bone Marrow Derived Cells in No Option Severe Limb Ischemia.

OBJECTIVE: Quality of life (QoL) is an important outcome in evaluating treatment effect in severe limb ischemia. The randomized, double blind, placebo controlled JUVENTAS trial, investigating the effect of bone marrow derived mononuclear cell (BMMNC) administration in no option severe limb ischemia, showed an improved QoL at 6 months compared with baseline in both the treatment and placebo groups. The aim of the present study was to evaluate whether the improved QoL persisted beyond 6 months' follow up, whether this differed in both trial arms, and if major amputation influenced QoL. METHODS: Short form 36 (SF-36) and EuroQol 5D (EQ5D), including the EQ Visual Analogue Scale (EQ-VAS), questionnaires were sent to JUVENTAS trial participants. In the JUVENTAS trial, a norm based scoring method was applied to report the results of the SF-36. The results of the long-term follow up were compared with baseline and 6 month follow up and the results of both trial arms were compared, as were the results of patients with and without amputation. RESULTS: One hundred and nine patients (86.5% of surviving patients) responded to the questionnaires. Median follow up after inclusion was 33 months (interquartile range [IQR] 21.2-50.6) for the BMMNC and 36 months (IQR 21.4-50.9) for the placebo group. The improvement in QoL at 6 months persisted in both arms at a median follow up of 35 months. The long-term QoL did not differ between the BMMNC and placebo group in any of the SF-36 or EQ5D domains. Patients with and without a major amputation had similar QoL scores. CONCLUSIONS: The increased QoL in patients with no option severe limb ischemia persisted until 3 years after inclusion, but did not differ between the BMMNC and placebo arms or between patients with and without a major amputation.

Bone Marrow derived Cell Therapy in Critical Limb Ischemia: A Meta-analysis of Randomized Placebo Controlled Trials.

OBJECTIVE/BACKGROUND: Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. METHODS: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. RESULTS: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group. CONCLUSIONS: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.

Common variants associated with blood lipid levels do not affect carotid plaque composition.

INTRODUCTION: Although plasma lipid levels are known to influence the risk of cardiovascular disease (CVD), little is known about their effect on atherosclerotic plaque composition. To date, large-scale genome-wide association studies have identified 157 common single-nucleotide polymorphisms (SNPs) that influence plasma lipid levels, providing a powerful tool to investigate the effect of plasma lipid levels on atherosclerotic plaque composition. METHODS: In this study, we included 1443 carotid endarterectomy patients from the Athero-Express Biobank Study with genotype data. Plasma concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) were determined at the time of endarterectomy. Atherosclerotic plaques, obtained during surgery, were histologically examined. For all patients, we calculated weighted genetic burden scores (GBS) for all lipid traits on the basis of the available genotype data. Plasma lipid levels and GBS were tested for association with 7 histological features using linear and logistic regression models. RESULTS: All GBS were associated with their respective plasma lipid concentrations (pHDL-C = 2.4 × 10(-14), pLDL-C = 0.003, pTC = 2.1 × 10(-6), pTG = 3.4 × 10(-8)). Neither the measured plasma lipids, nor the GBS, were associated with histological features of atherosclerotic plaque composition. In addition, neither the plasma lipids nor the GBS were associated with clinical endpoints within 3 years of follow-up, with the notable exception of a negative association between HDL-C and composite cardiovascular endpoints. CONCLUSION: This study found no evidence that plasma lipid levels or their genetic determinants influence carotid plaque composition.

Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals.

BACKGROUND: The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin fibrous cap, a large lipid core, high macrophage count, and intraplaque haemorrhage have all been identified as markers of the so-called "vulnerable" plaque being related to a higher stroke risk. There is a need to assess the accuracy of in vivo imaging to identify vulnerable plaque characteristics, thereby enabling in vivo risk stratification to guide clinical decision-making. METHODS: The aim of this topical review is to assess the roles of currently available imaging modalities that are applied in clinical practice and those experimental techniques that are close to clinical translation in defining carotid plaque characteristics and in informing clinical practice. RESULTS: Ultrasound is a low cost and ready available low-risk tool, but it lacks the accuracy to reliably detect individual plaque components and characteristics. Computed tomography is considered to be the best imaging technique to identify calcification in the carotid plaque. Magnetic resonance imaging (MRI) can identify most described plaque characteristics with moderate to good agreement. Positron emission tomography allows assessment of specific metabolic functions with tracers labelled with positron emitting radio-isotopes, but limited spatial resolution makes anatomic precision imprecise. CONCLUSION: MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke.

Differential FDG-PET Uptake Patterns in Uninfected and Infected Central Prosthetic Vascular Grafts.

OBJECTIVE: (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been suggested as a means to detect vascular graft infections. However, little is known about the typical FDG uptake patterns associated with synthetic vascular graft implantation. The aim of the present study was to compare uninfected and infected central vascular grafts in terms of various parameters used to interpret PET images. METHODS: From 2007 through 2013, patients in whom a FDG-PET scan was performed for any indication after open or endovascular central arterial prosthetic reconstruction were identified. Graft infection was defined as the presence of clinical or biochemical signs of graft infection with positive cultures or based on a combination of clinical, biochemical, and imaging parameters (other than PET scan data). All other grafts were deemed uninfected. PET images were analyzed using maximum systemic uptake value (SUVmax), tissue to background ratio (TBR), visual grading scale (VGS), and focality of FDG uptake (focal or homogenous). RESULTS: Twenty-seven uninfected and 32 infected grafts were identified. Median SUVmax was 3.3 (interquartile range [IQR] 2.0-4.2) for the uninfected grafts and 5.7 for the infected grafts (IQR 2.2-7.8). Mean TBR was 2.0 (IQR 1.4-2.5) and 3.2 (IQR 1.5-3.5), respectively. On VGS, 44% of the uninfected and 72% of the infected grafts were judged as a high probability for infection. Homogenous FDG uptake was noted in 74% of the uninfected and 31% of the infected grafts. Uptake patterns of uninfected and infected grafts showed a large overlap for all parameters. CONCLUSION: The patterns of FDG uptake for uninfected vascular grafts largely overlap with those of infected vascular grafts. This questions the value of these individual FDG-PET-CT parameters in identifying infected grafts.