A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Hepatocyte growth factor as indicator for subclinical atherosclerosis.

Background: Hepatocyte growth factor (HGF) is a pleiotropic cytokine mainly produced by mesenchymal cells. After endothelial damage by oxidized low-density lipoprotein (LDL), HGF is produced and released into the circulation in response. Due to this mechanism HGF has been proposed as possible clinical biomarker for clinical as well as subclinical atherosclerosis. Patients and methods: The conducted study is an observational, single centre, cohort study, including 171 patients with at least one cardiovascular risk factor or already established cardiovascular disease (CVD). Each patient underwent 3D plaque volumetry of the carotid and femoral arteries as well as physical examination and record of the medical history. Additionally, plasma HGF and further laboratory parameters like high sensitivity C-reactive protein and LDL-cholesterol were determined. Results: 169 patients were available for statistical analysis. In bivariate correlation, HGF showed a highly significant correlation with total plaque volume (TPV, r=0.48; p<0.001). In receiver operating characteristic (ROC) analysis for high TPV, HGF showed an area under the curve (AUC) of 0.68 (CI 95%: 0.59-0.77, p<0.001) with a sensitivity of 78% and a specificity of 52% to predict high TPV at a cut-off of 959 ng/ml. In the ROC-analysis for the presence of CVD, HGF demonstrated an AUC of 0.65 (95% CI 0.55-0.73; p=0.01) with a sensitivity of 77% and a specificity of 52%. Conclusions: Higher plasma levels of HGF are associated with higher atherosclerotic plaque volume as measured by 3D-ultrasound.

Increasing Soluble P-Selectin Levels Predict Higher Peripheral Atherosclerotic Plaque Progression.

BACKGROUND AND AIMS: The adhesion molecule P-selectin is expressed by endothelial cells and platelets. It is involved in platelet activation and leukocyte adhesion, both important processes in the pathogenesis of atherosclerosis. Our study was designed to assess the predictive value of soluble P-selectin (sP-selectin) on the progression of peripheral atherosclerosis. METHODS: This is an observational, single-center, cohort study that included 443 patients with established cardiovascular disease (CVD) or at least one cardiovascular risk factor. Over a period of 4 years, each patient underwent three-dimensional (3D) ultrasound to assess the plaque volume of the carotid and femoral arteries once per year. In addition, plasma sP-selectin levels were measured at each visit. The association between changes in sP-selectin and peripheral atherosclerotic plaque progression was assessed using growth curve models. RESULTS: 338 patients were available for statistical analysis. Each standard deviation increase in sP-selectin was significantly (p < 0.001) associated with a 46.09 mm3 higher plaque volume. In ROC-analysis, changes in sP-selectin over time showed an optimal cut-off value around Δ 0.0 µg/mL sP-selectin and significantly improved the predictive value of the ESC-SCORE (AUC for the combination of both parameters was 0.75 (95% CI 0.68-0.81, p < 0.001). Patients with increasing sP-selectin showed a significantly higher plaque progression compared to patients with decreasing or stable sP-selectin levels (202 mm3 vs. 110 mm3, p < 0.001). CONCLUSIONS: Increasing sP-selectin levels can predict higher atherosclerotic plaque progression as measured by 3D ultrasound. We suggest serial measurements of sP-selectin as an easily measurable biomarker for peripheral atherosclerotic plaque progression.

Inverse Correlation of Cholesterol Efflux Capacity with Peripheral Plaque Volume Measured by 3D Ultrasound.

INTRODUCTION: Cardiovascular disease (CVD) is a systemic multifocal illness called atherosclerosis that causes artery constriction and blockage. By causing cholesterol to build up in the artery wall, hypercholesterolemia is a major factor in the pathophysiology of atherosclerotic plaque development. Reverse cholesterol transport is the process of transporting cholesterol from the periphery back to the liver through cholesterol efflux mediated by high-density lipoprotein (HDL). It was suggested that the cholesterol efflux capacity (CEC), which is inversely linked with cardiovascular risk, can serve as a stand-in measure for reverse cholesterol transport. In this work, we sought to investigate a potential link between the peripheral plaque volume (PV) and CEC. METHODS: Since lipid-lowering therapy interferes with CEC, we performed a cross-sectional study of 176 patients (48.9% females) with one cardiovascular risk factor or known CVD that did not currently take lipid-lowering medication. CEC was determined using cAMP-treated 3H-cholesterol-labeled J774 cells. Cholesterol ester transfer protein (CETP)-mediated cholesterol ester transfer was measured by quantifying the transfer of cholesterol ester from radiolabeled exogenous HDL cholesterol to Apolipoprotein B-containing lipoproteins. PV in the carotid and the femoral artery, defined as the total PV, was measured using a 3D ultrasound system equipped with semi-automatic software. RESULTS: In our patients, we discovered an inverse relationship between high total PV and CEC (p = 0.027). However, there was no connection between total PV and low-density lipoprotein cholesterol, lipoprotein (a), or CETP-mediated cholesterol ester transfer. CONCLUSION: In patients not receiving lipid-lowering treatment, CEC inversely correlates with peripheral atherosclerosis, supporting its role in the pathophysiology of atherosclerosis.

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.

The Post-thrombotic Syndrome-Prevention and Treatment: VAS-European Independent Foundation in Angiology/Vascular Medicine Position Paper.

Importance: The post-thrombotic syndrome (PTS) is the most common long-term complication of deep vein thrombosis (DVT), occurring in up to 40-50% of cases. There are limited evidence-based approaches for PTS clinical management. Objective: To provide an expert consensus for PTS diagnosis, prevention, and treatment. Evidence-Review: MEDLINE, Cochrane Database review, and GOOGLE SCHOLAR were searched with the terms "post-thrombotic syndrome" and "post-phlebitic syndrome" used in titles and abstracts up to September 2020. Filters Were: English, Controlled Clinical Trial / Systematic Review / Meta-Analysis / Guideline. The relevant literature regarding PTS diagnosis, prevention and treatment was reviewed and summarized by the evidence synthesis team. On the basis of this review, a panel of 15 practicing angiology/vascular medicine specialists assessed the appropriateness of several items regarding PTS management on a Likert-9 point scale, according to the RAND/UCLA method, with a two-round modified Delphi method. Findings: The panelists rated the following as appropriate for diagnosis: 1-the Villalta scale; 2- pre-existing venous insufficiency evaluation; 3-assessment 3-6 months after diagnosis of iliofemoral or femoro-popliteal DVT, and afterwards periodically, according to a personalized schedule depending on the presence or absence of clinically relevant PTS. The items rated as appropriate for symptom relief and prevention were: 1- graduated compression stockings (GCS) or elastic bandages for symptomatic relief in acute DVT, either iliofemoral, popliteal or calf; 2-thigh-length GCS (30-40 mmHg at the ankle) after ilio-femoral DVT; 3- knee-length GCS (30-40 mmHg at the ankle) after popliteal DVT; 4-GCS for different length of times according to the severity of periodically assessed PTS; 5-catheter-directed thrombolysis, with or without mechanical thrombectomy, in patients with iliofemoral obstruction, severe symptoms, and low risk of bleeding. The items rated as appropriate for treatment were: 1- thigh-length GCS (30-40 mmHg at the ankle) after iliofemoral DVT; 2-compression therapy for ulcer treatment; 3- exercise training. The role of endovascular treatment (angioplasty and/or stenting) was rated as uncertain, but it could be considered for severe PTS only in case of stenosis or occlusion above the inguinal ligament, followed by oral anticoagulation. Conclusions and Relevance: This position paper can help practicing clinicians in PTS management.

Evaluation of the in vitro stability of direct oral anticoagulants in blood samples under different storage conditions.

In this study, we evaluated the in vitro stability of direct oral anticoagulants (DOACs) in blood samples of 57 patients under different storage conditions using functional coagulation assays. We determined the analyte concentrations (1) immediately after blood collection (baseline); (2) after storage of citrated whole blood (agitated) at room temperature and citrated plasma at room temperature and at 4 °C for 4, 8, and 24 h, respectively; and (3) after storage of citrated plasma at -20 °C for 30, 60, and 90 days. According to the concept of acceptable change limits (ACL), analytes were considered stable if the mean relative analyte recovery at a given time was >78%. The mean baseline values (range) of dabigatran, rivaroxaban, apixaban, and edoxaban were 115 ng/mL (62-217), 129 ng/mL (31-215), 156 ng/mL (49-362), and 101 ng/mL (33-283), respectively. After applying the analyte stability limit, all four DOACs were stable for 24 h at room temperature and at 4 °C. The mean recovery after 24 h was 102-111% for dabigatran, 88-97% for rivaroxaban, 95-98% for apixaban, and 90-96% for edoxaban. When plasma samples were stored at -20 °C, the mean percentage deviation after 90 days for all four DOACs was ≤10%, even after three freeze-thaw cycles. Thus, for the correct determination of DOAC plasma concentrations, blood samples do not have to be analyzed immediately and can be stored at room temperature for up to 24 h before analysis. In clinical practice, blood sample transport and storage for DOAC measurements appear to be unproblematic.

Effect of chronic kidney disease and sex on carotid and femoral plaque volume as measured by three-dimensional ultrasound.

INTRODUCTION: Previously, we reported the association between cardiovascular risk factors (CVRFs) and the presence of cardiovascular disease with peripheral atherosclerosis. In this paper, we specifically aimed to investigate the association of chronic kidney disease (CKD) and sex with carotid and femoral plaque volume. MATERIALS AND METHODS: 404 patients (median age 64; 57% men) with at least 1 CVRF or established cardiovascular disease where included into the study. 3D ultrasonography evaluated with an automated software was used to measure peripheral plaque volume. Statistical analyses were performed using SPSS Statistic. RESULTS: CKD was diagnosed in 56 patients (13.9%), with most patients in stage 3a. Total atherosclerotic plaque volume was significantly higher in patients with CKD (p < 0.001) compared to those without CKD and in men compared to women in all vascular territories (p < 0.001). CONCLUSION: Our data show that we need to be even more vigilant about the presence of atherosclerotic plaques and cardiovascular disease in these patients. Already in patients with CKD stage 3a, efficient CVRF reduction and intensive treatment is warranted.

High baseline fetuin-A levels are associated with lower atherosclerotic plaque progression as measured by 3D ultrasound.

Background and aims: The glycoprotein fetuin-A has anti-inflammatory effects, increases insulin resistance and plays an important role in calcium metabolism. The aim of our study was to assess the predictive value of fetuin-A on atherosclerotic plaque progression in comparison to the established cardiovascular biomarker high sensitivity C-reactive protein (hsCRP). Methods: In this prospective, single center-, cohort study, we included 194 patients with at least one cardiovascular risk factor or established cardiovascular disease (CVD). Over a period of 4 years, each patient underwent 3D plaque volumetry of the carotid and femoral arteries on a yearly basis. To evaluate the predictive value of biomarkers in terms of plaque progression, the baseline values of fetuin-A and hsCRP were correlated with the plaque progression from baseline to the last follow up visit. Results: 171 patients were included in the final analysis. Baseline fetuin-A levels showed a significant negative correlation with plaque progression (r = -0.244; p = 0.001). In contrast, baseline hsCRP levels showed no correlation with plaque progression (r = 0.096, p = 0.20). In the ROC-analysis, fetuin-A had a significantly better predictive value than hsCRP (fetuin-A AUC 0.67; p = 0.001 vs hsCRP AUC 0.49; p = 0.88) with an optimal cut-off value at 712 µg/ml. In patients with high fetuin A levels (>712 µg/ml), a significantly lower plaque progression was observed compared to the group with low fetuin-A levels <712 µg/ml (high fetuin-A 197 mm3 vs. low fetuin-A 279 mm3; p = 0.01). Conclusions: Higher fetuin-A levels appear to predict lower atherosclerotic plaque progression in patients with or at risk of cardiovascular disease.

Association of Food and Alcohol Consumption with Peripheral Atherosclerotic Plaque Volume as Measured by 3D-Ultrasound.

BACKGROUND: Food patterns and alcohol consumption influence the risk for cardiovascular diseases (CVD) and a healthy nutrition is essential for the prevention of CVD. The aim of this study was to determine the influence of nutrition and alcohol consumption on peripheral atherosclerotic plaque volume (PV) using an innovative 3D ultrasound approach. METHODS: In this prospective, single centre study we included 342 patients with at least one cardiovascular risk factor or established CVD. PV in the carotid and femoral artery was measured using a semi-automatic software. Information on food and alcohol consumption of the participants was collected using an internationally acknowledged standardized questionnaire (DEGS1). RESULTS: Patients with low total PV consumed significantly more vegetables (p = 0.004) and vegetable juice (p = 0.019) per week compared to patients with high total PV. In contrast, patients with high total PV reported a higher alcohol consumption compared to patients with low total PV (p = 0.026). Patients without vascular disease, in particular cerebrovascular disease (p = 0.001) and peripheral arterial disease (p = 0.012), reported a significantly higher fish consumption per week. In the multivariate model, we found a significant negative association for vegetable consumption (p = 0.034) and female gender (p = 0.018) but a significant positive association for alcohol (p = 0.001), age (p < 0.001) the presence of vascular disease (p < 0.001) and cardiovascular risk factors (p < 0.001) with total PV. CONCLUSION: In this study we were able to show an association of food and alcohol consumption with peripheral atherosclerotic PV measured by 3D-ultrasonography. Following a healthy nutritional lifestyle (vegetable consumption, no excessive alcohol consumption) and regular fish consumption appears to be associated with less peripheral atherosclerosis and decreased prevalence of vascular diseases, respectively.

NGAL Correlates with Femoral and Carotid Plaque Volume Assessed by Sonographic 3D Plaque Volumetry.

BACKGROUND/OBJECTIVES: Inflammation represents a cornerstone in the development of atherosclerosis and early detection is essential to avoid cardiovascular events. Biomarkers like interleukin-1 beta, interleukin-6, or high sensitivity CRP (hs-CRP) have been investigated intensively in this field. Since they have several limitations, additional biomarkers are needed for cardiovascular risk stratification. The acute phase protein, neutrophil gelatinase-associated lipocalin (NGAL), modulates inflammation and is elevated in cardiovascular disease (CVD). Moreover, it contributes to plaque destabilization. METHODS: In this prospective, single-center study, we included 323 asymptomatic patients with at least one cardiovascular risk factor or established CVD. NGAL levels were measured in plasma samples using a commercially available ELISA. Carotid, femoral, and total atherosclerotic plaque volumes (PV) were measured using a 3D ultrasound system (Philips iU22). Patients were separated into a low (n = 243) and high (n = 80) total PV group. RESULTS: NGAL was significantly higher in patients with high total PV versus patients with low total PV. The NGAL amplitude for the prediction of high total PV was significantly higher when compared with hs-CRP. A high predictive value could also be observed for patients without established CVD. CONCLUSION: NGAL seems to be a promising biomarker for the identification of asymptomatic patients with atherosclerotic disease.

Early onset of menopause is associated with increased peripheral atherosclerotic plaque volume and progression.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of death in western countries. One risk factor unique to women is the menopausal status. The aim of this study was to analyse the influence of the onset of menopause (MP) on the extent and progression of atherosclerotic plaque volume (PV). METHODS: Postmenopausal women with at least one cardiovascular risk factor (CVRF) but without established CVD were included. Quantification of PV was performed in peripheral arteries using a three - dimensional (3D) ultrasound (US) technique. Follow-up examination to assess PV progression was performed after 19 (±8) months. RESULTS: 110 consecutive postmenopausal women (mean age 65.5) were included. Females with an earlier onset of MP (<45 years) had a significantly higher PV than those with an intermediate (45-52 years) or later onset of menopause (>52 years), irrespective of other CVRF (244 mm³ vs. 193 mm³ vs. 73 mm³, respectively, p = 0.023). In addition, women with an earlier onset of MP had a higher PV progression compared to women with an intermediate or late onset (40 mm³ vs. 35 mm³ vs. 8.5 mm³; p = 0.002, respectively). Moreover, these results were confirmed in multivariate regression, where only onset of MP (OR 0.88; 95%CI 0.81-0.96; p = 0.004) and age (OR 1.06; 95%CI 1.08-1.13; p = 0.025) were significant predictors for a higher atherosclerotic progression. CONCLUSIONS: An earlier onset of MP was associated with an increase in atherosclerotic PV and accelerated progression, independent of other CVRF.

[Austrian Consensus on High Blood Pressure 2019]. / Österreichischer Blutdruckkonsens 2019.

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.

Dabigatran Added to Dual Antiplatelet Therapy to Treat a Left Ventricular Thrombus in an 87 Year Old Patient With Myocardial Infarction and Very High Bleeding Risk.

Background: A left ventricular (LV) thrombus is detected in approximately 5-10% of patients after myocardial infarction (MI). If left untreated, these LV thrombi carry a significant risk of complications including embolic stroke. According to current guidelines, anticoagulation with vitamin K antagonists (VKA) is recommended to treat a LV thrombus. Case presentation: An 87 year old patient was referred to our department with non ST-elevation MI. Five months before, he had been diagnosed with a subacute ST elevation MI, which had been treated conservatively. Recently, a rectal neoplasia had been diagnosed, but not operated yet. The patient underwent coronary angiography with implantation of two drug eluting stents (Cre8) requiring dual antiplatelet therapy. During ventriculography an apical LV thrombus of 16 mm diameter was detected. Due to the high bleeding risk in this patient, VKA therapy with potentially fluctuating international normalized ratio (INR) values was considered unsuitable. Therefore, dabigatran at a dose of 110 mg bid was chosen as anticoagulation therapy. After 4 weeks, cardiac computed tomography was performed, which failed to detect the LV thrombus described previously. Notably, triple therapy with dabigatran, clopidogrel, and aspirin was well tolerated without evidence for bleeding. The surgical resection of the rectal neoplasm was performed 2 months later without bleeding complications. Discussion: Anticoagulation is effective in patients with MI and a LV thrombus in reducing the risk of embolization and in dissolving the thrombus. Our case is complex due to the required triple therapy, very old age and significant bleeding risk of our patient due to the rectal neoplasia. Although only few reports are available for the use of non VKA oral anticoagulants (NOAC) in this indication, we chose dabigatran at a dose of 110 mg bid added to dual antiplatelet therapy for our patient. Besides the advantage of a predictable pharmacokinetic profile of NOAC in contrast to VKA, the effect of dabigatran can rapidly be reversed by idaruzicumab in the case of severe bleeding. Conclusion remarks: Physicians should carefully weigh the risk of thromboembolic events versus the risk of bleeding when combining antiplatelet with anticoagulation therapy.

Femoral access site closure without prior femoral angiography : A retrospective analysis.

AIMS AND BACKGROUND: Although guideline recommendations have shifted towards a transradial route, femoral puncture is still an established vascular access, especially for complex coronary interventions. The FemoSeal™ vascular closure device (FVCD) helps to reduce femoral compression time and access site complications after removal of the catheter sheath. To ensure safe use, an angiography of the femoral artery prior to FVCD deployment is recommended by the manufacturer. We postulate that omitting this angiography does not relevantly increase the risk for vascular complications. METHODS AND RESULTS: In this retrospective analysis of an all-comers population (n = 1923) including patients receiving a percutaneous coronary intervention (PCI), we could show that combined vascular complication rates without femoral angiography were low (primary endpoint 4.6%) and comparable to a randomized clinical trial that did perform angiography of the vascular access site in a cohort of patients receiving diagnostic coronary angiography only. In addition to this analysis, we could demonstrate that patients with an acute coronary syndrome, receiving periprocedural anticoagulation or anti-platelet therapy had an increased risk for the formation of arterial pseudoaneurysms; however, we did not observe any ischemic vascular event after FVCD deployment. CONCLUSION: Closure of the femoral access site after coronary angiography using the FVCD can be safely performed without femoral angiography; however, due to an increased risk for the formation of pseudoaneurysms we recommend the transradial access in situations with increased bleeding risk.

Influence of Traditional Cardiovascular Risk Factors on Carotid and Femoral Atherosclerotic Plaque Volume as Measured by Three-Dimensional Ultrasound.

BACKGROUND: Atherosclerosis is a systemic multifocal disease with a preference for the branching points of the arteries. In this study, we quantitatively measured carotid and femoral plaque volume in subjects with cardiovascular risk factors (CVRF) and/or established atherosclerotic disease using a 3D ultrasound technique. METHODS: In this prospective, single-centre study, we included 404 patients (median age 64; 56.9% men) with at least one CVRF or established cardiovascular disease. Plaque volume was measured using 3D ultrasound equipped with an automated software. RESULTS: We found a strong correlation of plaque volume with CVRF and the number of vascular beds involved. The strongest associations with total and femoral plaque volume were noted for smoking, hypertension, age, as well as for the presence of peripheral arterial occlusive disease (p < 0.05). Carotid plaque volume was best predicted by hyperlipidaemia, hypertension, age, as well as the presence of cerebrovascular disease and coronary artery disease (p < 0.05). CONCLUSION: We conclude that smoking appears to be associated with total and femoral plaque volume, whereas hyperlipidaemia seems to be associated with carotid plaque volume. Measurement of 3D plaque volume is a practical and reproducible technique with the potential to become an additional screening tool in cardiovascular risk stratification.

Incidental finding of an absent left common carotid artery.

We describe a case of a young woman evaluated for Raynaud's phenomenon in whom an extremely rare variation, the absence of the left common carotid artery, was incidentally detected as an isolated finding. The detection of vascular anomalies may be important for future endovascular or surgical interventions.

Expression of a recombinant full-length LRP1B receptor in human non-small cell lung cancer cells confirms the postulated growth-suppressing function of this large LDL receptor family member.

Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B), a member of the LDL receptor family, is frequently inactivated in multiple malignancies including lung cancer. LRP1B is therefore considered as a putative tumor suppressor. Due to its large size (4599 amino acids), until now only minireceptors or receptor fragments have been successfully cloned. To assess the effect of LRP1B on the proliferation of non-small cell lung cancer cells, we constructed and expressed a transfection vector containing the 13.800 bp full-length murine Lrp1b cDNA using a PCR-based cloning strategy. Expression of LRP1B was analyzed by quantitative RT-PCR (qRT-PCR) using primers specific for human LRP1B or mouse Lrp1b. Effective expression of the full length receptor was demonstrated by the appearance of a single 600 kDa band on Western Blots of HEK 293 cells. Overexpression of Lrp1b in non-small cell lung cancer cells with low or absent endogenous LRP1B expression significantly reduced cellular proliferation compared to empty vector-transfected control cells. Conversely, in Calu-1 cells, which express higher endogenous levels of the receptor, siRNA-mediated LRP1B knockdown significantly enhanced cellular proliferation. Taken together, these findings demonstrate that, consistent with the postulated tumor suppressor function, overexpression of full-length Lrp1b leads to impaired cellular proliferation, while LRP1B knockdown has the opposite effect. The recombinant Lrp1b construct represents a valuable tool to unravel the largely unknown physiological role of LRP1B and its potential functions in cancer pathogenesis.