Publications
867 results found
Colgan FE, Bungay PM, Burfitt N, et al., 2018, Operative and 1-Year Outcomes of the Custom-Made Fenestrated Anaconda Aortic Stent Graft-A UK Multicenter Study, ANNALS OF VASCULAR SURGERY, Vol: 46, Pages: 257-264, ISSN: 0890-5096
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- Citations: 12
Toghill BJ, Saratzis A, Freeman PJ, et al., 2018, SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells., Clin Epigenetics, Vol: 10
BACKGROUND: Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. RESULTS: We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter (P < 0.0001, R2 = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R, 2 CpGs were hyper-methylated (P = 0.0145); in ERG, 13 CpGs were hyper-methylated (P = 0.0005); in SERPINB9, 6 CpGs were hypo-methylated (P = 0.0037) and 1 CpG was hyper-methylated (P = 0.0098); and in SMYD2, 4 CpGs were hypo-methylated (P = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression (P = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. CONCLUSIONS: This study is the first to assess DNA methylation in VSMCs from individuals with AAA us
Coupland AP, Bootun R, Davies AH, 2017, Should re-intervention be the definitive outcome measure for varicose vein intervention?, Phlebology, Pages: 268355517749113-268355517749113
Cohen A, Lim CS, Davies AH, 2017, Venous Thromboembolism in Gynecological Malignancy, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 27, Pages: 1970-1978, ISSN: 1048-891X
Clark S, Westley S, Coupland A, et al., 2017, Buttock wounds: beware what lies beneath, BMJ Case Reports, Vol: 2017, ISSN: 1757-790X
A 25-year-old man presented to a major trauma centre with multiple stab wounds, most significantly to the right buttock. Triple-phase CT revealed no acute bleeding and his wounds were closed. In the month following injury, he re-presented seven times to the emergency department (ED) complaining of bleeding and wound breakdown. After his seventh ED attendance, he was examined under general anaesthesia. Intraoperatively, profuse arterial bleeding was encountered and the local major haemorrhage protocol was activated. The on-call consultant vascular surgeon attended and definitive control was achieved. A large haematoma had acted to tamponade ongoing arterial bleeding and an underlying pseudoaneurysm: a finding not reported, but present, on the initial CT angiogram. Following 24 hours in the intensive care unit, he was transferred to the surgical ward and discharged 4 days later. Regular review in the outpatient department over the following 9 weeks monitored successful wound healing.
Abbott AL, Silvestrini M, Topakian R, et al., 2017, Optimizing the Definitions of Stroke, Transient Ischemic Attack, and Infarction for Research and Application in Clinical Practice, Frontiers in Neurology, Vol: 8, ISSN: 1664-2295
Background and purpose: Until now, stroke and transient ischemic attack (TIA) havebeen clinically based terms which describe the presence and duration of characteristicneurological deficits attributable to intrinsic disorders of particular arteries supplying thebrain, retina, or (sometimes) the spinal cord. Further, infarction has been pathologicallydefined as death of neural tissue due to reduced blood supply. Recently, it has beenproposed we shift to definitions of stroke and TIA determined by neuroimaging resultsalone and that neuroimaging findings be equated with infarction.Methods: We examined the scientific validity and clinical implications of these proposalsusing the existing published literature and our own experience in research and clinicalpractice.results: We found that the proposals to change to imaging-dominant definitions, aspublished, are ambiguous and inconsistent. Therefore, they cannot provide the standardizationrequired in research or its application in clinical practice. Further, we foundthat the proposals are scientifically incorrect because neuroimaging findings do notalways correlate with the clinical status or the presence of infarction. In addition, wefound that attempts to use the proposals are disrupting research, are otherwise clinicallyunhelpful and do not solve the problems they were proposed to solve. Conclusion: We advise that the proposals must not be accepted. In particular, weexplain why the clinical focus of the definitions of stroke and TIA should be retainedwith continued sub-classification of these syndromes depending neuroimaging results(with or without other information) and that infarction should remain a pathologicalterm. We outline ways the established clinically based definitions of stroke and TIA,and use of them, may be improved to encourage better patient outcomes in themodern era.
Thapar A, davies AH, 2017, Re: Endovascular Stroke Treatment of Acute Tandem Occlusion: A Single-Center Experience., JVIR: Journal of Vascular and Interventional Radiology, Vol: 28, Pages: 1288-1289, ISSN: 1051-0443
Milinis K, Thapar A, O'Neill K, et al., 2017, History of Aneurysmal Spontaneous Subarachnoid Hemorrhage, STROKE, Vol: 48, Pages: E280-E283, ISSN: 0039-2499
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- Citations: 4
Kafeza M, Shalhoub J, Salooja N, et al., 2017, Systematic Review of Clinical Prediction Scores for Deep Vein Thrombosis, Phlebology, Vol: 32, Pages: 516-531, ISSN: 0268-3555
Objective:Diagnosis of Deep Vein Thrombosis (DVT) remains a challenging problem. Various clinical prediction rules have been developed in order to improve diagnosis and decision-making in relation to DVT. The purpose of this review is to summarise the available clinical scores and describe their applicability and limitations.Methods:A systematic search of PubMed, MEDLINE and EMBASE databases was conducted in accordance with PRISMA guidance using the keywords: clinical score, clinical prediction rule, risk assessment, clinical probability, pretest probability, diagnostic score and MeSH terms: “Venous Thromboembolism/diagnosis” OR “Venous Thrombosis/diagnosis”. Both development and validation studies were eligible for inclusion.Results:The search strategy returned a total of 2036 articles, of which 102 articles met a priori criteria for inclusion. Eight different diagnostic scores were identified. The development of these scores differs in respect of the population included (hospital inpatients, hospital outpatients or primary care patients), the exclusion criteria, the inclusion of distal DVT and the use of D-dimer. The reliability and applicability of the scores in the context of specific subgroups (inpatients, cancer patients, elderly patients, and those with recurrent DVT) remains controversial.Conclusion:Detailed knowledge of the development of the various clinical prediction scores for DVT is essential in understanding the power, generalisability and limitations of these clinical tools.
Lane TRA, Varatharajan L, Fiorentino F, et al., 2017, Truncal varicose vein diameter and patient-reported outcome measures, British Journal of Surgery, Vol: 104, Pages: 1648-1655, ISSN: 1365-2168
BackgroundVaricose veins and chronic venous disease are common, and some funding bodies ration treatment based on a minimum diameter of the incompetent truncal vein. This study assessed the effect of maximum vein diameter on clinical status and patient symptoms.MethodsA prospective observational cohort study of patients presenting with symptomatic varicose veins to a tertiary referral public hospital vascular clinic between January 2011 and July 2012. Patients underwent standardized assessment with venous duplex ultrasonography, and completed questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated. Regression analysis was used to investigate the relationship between QoL, symptoms and vein diameter.ResultsSome 330 patients were assessed before surgery. The median maximum vein diameter was 7·0 (i.q.r. 5·3–9·2) mm overall, 7·9 (6·0–9·8) mm for great saphenous vein and 6·0 (5·2–8·9) mm for small saphenous vein. In linear regression analysis, vein diameter was shown to have a significant association with VCSS (P = 0·041). For every 1-mm increase in vein diameter, there was a 2·75-fold increase in risk of being in CEAP class C4 compared with C2. No other QoL or symptom measures were related to vein diameter.ConclusionIncompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures.
Lim C, Shalhoub J, Davies AH, 2017, Deep venous procedures performed in the National Health Service in England between 2005 and 2015, European Journal of Vascular and Endovascular Surgery, Vol: 54, Pages: 487-494, ISSN: 1532-2165
ObjectivesRecent advances in imaging technology and endovenous interventions have revolutionised the management of specific groups of patients with deep venous pathology. This study aimed to examine data published by Hospital Episode Statistics (HES) to assess trends in the number of endovascular and open surgical deep venous procedures performed in National Health Service (NHS) hospitals in England between 2005 and 2015.Materials and methodsThe main diagnosis of deep venous thrombosis (DVT), and total number of primary open and percutaneous procedures for deep venous pathology for patients admitted to the NHS hospitals in England from 2005 to 2015 were retrieved from the HES database and analysed.ResultsAn overall declining trend in the annual number of admissions for a primary diagnosis of DVT was observed (linear regression r2 = 0.9, p < .0001). The number of open surgical procedures for removal of thrombus remained largely unchanged (range 26–70); the frequency of percutaneous procedures increased steadily over the study period (range 0–311). The number of open surgical procedures relating to the vena cava fell between 2005 and 2009, and remained around 50 per year thereafter. Annual numbers of cases of deep venous bypass (range 17–33) and venous valve surgery (range 8–47) remained similar in trend over this period. The number of vena cava stent (range 0–405), other venous stent (range 0–316), and percutaneous venoplasty (range 0–972) procedures increased over the first 5 years of the study period.ConclusionsThere is an increasing trend in relation to endovenous procedures but not open surgery, being carried out for deep venous pathology in the last decade in NHS hospitals in England. Despite a number of limitations with HES, the increase in the number of endovenous procedures shown is likely to have significant implications for the provision of care and healthcare resources for patients with deep venous pathology.
Kosasih S, moore H, Lane TRA, et al., 2017, Deep Venous Reconstruction: A Case Series, Cureus, Vol: 9, ISSN: 2168-8184
ObjectivesThis study aims to review a case series of deep venous reconstruction procedures performed at one centre by a single consultant.MethodsA retrospective review of deep venous reconstruction procedures performed by a single consultant from 1994 to 2013 was carried out and all notes were reviewed for outcomes. A 58-month cumulative patency rate was calculated using Kaplan-Meier survival analysis.ResultsNineteen patients underwent deep venous reconstruction procedures including the Palma bypass, May-Husni bypass, femoral vein transposition and axillary vein transplant techniques from 1994 to 2013. Eleven patients were male and eight were female with a mean average age of 45.2 years (range 29-63). Clinical severity of disease ranged from C3 to C6, and 16 patients had a confirmed history of deep vein thrombosis. Cumulative primary patency rate for all reconstructions at 58 months was 89.5%, with two patients occluding and 17 remaining patent at last follow-up.ConclusionDeep venous reconstructions, particularly the Palma and May-Husni procedures, are feasible and can have good outcomes in patients failed by endovascular techniques and other more conservative therapies.
Cheung WK, Williams KJ, Christensen-Jeffries K, et al., 2017, A temporal and spatial analysis approach to automated segmentation of microbubble signals in contrast-enhanced ultrasound images: application to quantification of active vascular density in human lower limbs, Ultrasound in Medicine and Biology, Vol: 43, Pages: 2221-2234, ISSN: 0301-5629
Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has shown great promise in visualising and quantifying active vascular density. Most existing approaches for vascular density quantification using CEUS are calculated based on image intensity and are susceptible to confounding factors and imaging artefact. Poor reproducibility is a key challenge to clinical translation. In this study, a new automated temporal and spatial signal analysis approach is developed for reproducible microbubble segmentation and quantification of contrast enhancement in human lower limbs. The approach is evaluated in vitro on phantoms and in vivo in lower limbs of healthy volunteers before and after physical exercise. In this approach, vascular density is quantified based on the relative areas microbubbles occupy instead of their image intensity. Temporal features of the CEUS image sequences are used to identify pixels that contain microbubble signals. A microbubble track density (MTD) measure, the ratio of the segmented microbubble area to the whole tissue area, is calculated as a surrogate for active capillary density. In vitro results reveal a good correlation (r(2) = 0.89) between the calculated MTD measure and the known bubble concentration. For in vivo results, a significant increase (129% in average) in the MTD measure is found in lower limbs of healthy volunteers after exercise, with excellent repeatability over a series of days (intra-class correlation coefficient = 0.96). This compares to the existing state-of-the-art approach of destruction and replenishment analysis on the same patients (intra-class correlation coefficient ≤0.78). The proposed new approach shows great potential as an accurate and highly reproducible clinical tool for quantification of active vascular density.
Albazde O, Shalhoub J, Davies A, 2017, The effect of supervised exercise on biomarker levels in individuals with peripheral arterial disease - a systematic review, International Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland, Publisher: WILEY, Pages: 82-82, ISSN: 0007-1323
Anwar MA, Adesina-Georgiadis KN, Spagou K, et al., 2017, A comprehensive characterisation of the metabolic profile of varicose veins; implications in elaborating plausible cellular pathways for disease pathogenesis, Scientific Reports, Vol: 7, ISSN: 2045-2322
Metabolic phenotypes reflect both the genetic and environmental factors which contribute to the development of varicose veins (VV). This study utilises analytical techniques to provide a comprehensive metabolic picture of VV disease, with the aim of identifying putative cellular pathways of disease pathogenesis. VV (n = 80) and non-VV (n = 35) aqueous and lipid metabolite extracts were analysed using 600 MHz 1H Nuclear Magnetic Resonance spectroscopy and Ultra-Performance Liquid Chromatography Mass Spectrometry. A subset of tissue samples (8 subjects and 8 controls) were analysed for microRNA expression and the data analysed with mirBase (www.mirbase.org). Using Multivariate statistical analysis, Ingenuity pathway analysis software, DIANALAB database and published literature, the association of significant metabolites with relevant cellular pathways were understood. Higher concentrations of glutamate, taurine, myo-inositol, creatine and inosine were present in aqueous extracts and phosphatidylcholine, phosphatidylethanolamine and sphingomyelin in lipid extracts in the VV group compared with non-VV group. Out of 7 differentially expressed miRNAs, spearman correlation testing highlighted correlation of hsa-miR-642a-3p, hsa-miR-4459 and hsa-miR-135a-3p expression with inosine in the vein tissue, while miR-216a-5p, conversely, was correlated with phosphatidylcholine and phosphatidylethanolamine. Pathway analysis revealed an association of phosphatidylcholine and sphingomyelin with inflammation and myo-inositol with cellular proliferation.
Onida S, Karia M, Bootun R, et al., 2017, VTE Risk Assessment Scoring in Day Surgery Patients: US and UK Perspectives on Risk Stratification, Vascular Annual Meeting of the Society-for-Vascular-Surgery, Publisher: MOSBY-ELSEVIER, Pages: 129S-129S, ISSN: 0741-5214
Masood M, Thapar A, Qureshi M, et al., 2017, Temporal Trends in Perioperative Safety of Carotid Endovascular Treatment in Average-Risk Symptomatic Patients: Systematic Review, Vascular Annual Meeting of the Society-for-Vascular-Surgery, Publisher: MOSBY-ELSEVIER, Pages: 83S-84S, ISSN: 0741-5214
Onida S, Clark S, Davies AH, 2017, Travel-Related Deep Venous Thrombosis in the Context of Endovenous Ablation: What Is the Evidence?, Vascular Annual Meeting of the Society-for-Vascular-Surgery, Publisher: MOSBY-ELSEVIER, Pages: 129S-130S, ISSN: 0741-5214
Bootun R, Epstein D, Onida S, et al., 2017, Cost-Effectiveness of Current and Emerging Treatments of Varicose Veins, 2017 Vascular Annual Meeting, Publisher: ELSEVIER, Pages: 128S-128S, ISSN: 0741-5214
Shalhoub J, Norrie J, Baker C, et al., 2017, Graduated compression stockings as an adjunct to low dose low molecular weight heparin in venous thromboembolism prevention in surgery– a multi-centre randomised controlled trial, European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 880-885, ISSN: 1532-2165
Background:The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying Graduated Compression Stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million each year in England alone.Objective:To determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE.Methods:A randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial [ISRCTN 13911492] will randomise adult elective surgical patients identified as being at moderate and high risk for VTE to receive either the current ‘standard’ combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH-related complications (including bleeding).Recruitment commenced in April 2016 with the seven UK centres coming ‘on-line’ in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK [14/140/61].
Sinha Y, Busuttil A, Onida S, et al., 2017, A systematic review into quality of life following endovenous interventions for varicose veins, BRITISH JOURNAL OF SURGERY, Vol: 104, Pages: 56-56, ISSN: 0007-1323
Mursia FM, Busuttil A, Onida S, et al., 2017, A systematic review on anticoagulation following deep venous stenting, BRITISH JOURNAL OF SURGERY, Vol: 104, Pages: 48-48, ISSN: 0007-1323
TAHA, BUSUTTIL, Bootun R, et al., 2017, The use of deep venous stenting for acute venous thrombosis of the lower limb, Society for Academic and Research Surgery (SARS), Publisher: Wiley, Pages: 11-11, ISSN: 1365-2168
Introduction: Venous stenting following successful acute DVT thrombolysisis thought to reduce recurrence rates and the rates of post thrombotic syndrome (PTS).The aim of this review is to evaluate venous stent patency and the impact on the development of PTS, recurrence, quality of life(QOL) and optimal post-procedural anticoagulation regimen in acute iliofemoral DVT treatment.Method: EMBASE and Medline databases were interrogated to identify studies in which patients with acuteDVT where stented. The inclusion criteria were; RCTs for acute venous stenting, case serieswithmore than 5 patients, and studies published in English or Arabic.Result: 760 articles were identified and following title, abstract and full textscreening, 27 articles were included. This included 542 patients stented following thrombolysis. Primary, assisted primary and secondary patency rates 12 months after stent placement ranged from 74-95%,90-95% and 84-100% respectively. Recurrence rates from 3 RCTs(n=213) showed a statistically significant difference in short-term follow-up favouring stenting, with lower recurrence rates of DVT mean numbers(P=0.002). PTS was assessed in most studies with an overall observed rate of 14.6% The incidence of stent re-thrombosis (n=542) was 7.9%. In 26% of studies, patients received additional antiplatelet therapy. QOL questionnaires were only employed in 11.1% of studies demonstrating an improvement in CIVIQ (22.67±3.01 vs 39.34±6.66) between test and control groups.Conclusion: Venous stenting appears to be an effective adjunct to earlythrombus removal, lowering recurrence and PTS rates. Further studies areneeded to identify optimal anticoagulant regimen and to look at the effect ofinterventional therapy on longterm QOL. Take-home message: Venous stenting appears to be an effective procedure in the context of acute lower limb DVT management, as well as lowering recurrence and PTS rates.
Bootun R, Epstein D, onida, et al., 2017, Effectiveness of treatments of varicose veins: systematic review and evidence synthesis, Society for Academic and Research Surgery, Publisher: Wiley, Pages: 28-28, ISSN: 1365-2168
BackgroundNovel methods of varicose vein treatment have been introduced in the past few years with the expectation that they might be more advantageous than conventional procedures. A systematic review and network meta-analysis was conducted comparing the effectiveness of current treatment (conservative care, surgery, ultrasound guided foam sclerotherapy (UGFS), endovenous laser ablation (EVLA), and radiofrequency ablation (RFA)) to emerging technologies (mechanochemical ablation (MOCA) and cyanoacrylate glue occlusion (CAE)).MethodsA systematic review of the literature was undertaken with evidence from randomised controlled trials (RCTs) collected for current technologies. However, because of a paucity of randomised studies, evidence for the newer endovenous ablation procedures was obtained from non-randomised studies in a secondary analysis. Outcomes measured were re-intervention on the truncal vein and re-treatment for residual varicosities.ResultsThirty-three RCTs and a further ten non-randomised studies evaluating MOCA or CAE were analysed. Thirteen RCTs and three non-randomised studies reported on re-interventions and re-treatments. The rate of re-interventions was found to be similar between EVLA, RFA and surgery. The rate of re-intervention after MOCA appears lower than UGFS (incidence rate ratio MOCA v UGFS 0.395) and greater than surgery (incidence rate ratio MOCA v surgery 1.378). ConclusionThis is the first systematic review that has conducted a meta-analysis of re-intervention and retreatment. The high attrition rate is the main risk of bias identified in the RCTs. Further, high quality studies comparing MOCA and CAE to other modalities are needed to establish truncal re-intervention rates and rate of re-treatment of residual varicosities.
Bootun R, Onida S, Lane, et al., 2017, Pilot study of the use of cyanoacrylate in the treatment of varicose veins, Society for Academic and Research Surgery (SARS), Publisher: Wiley, Pages: 46-47, ISSN: 1365-2168
BackgroundThe treatment of varicose vein disease has changed significantly over the past decade. Endovenous ablation, especially using thermal methods, has become the new norm. However, it is often associated with patient discomfort during tumescent infiltration and the ablative procedure. The non-thermal, non-tumescent (NTNT) techniques are believed to be more advantageous as they eliminate these potential adverse events. In this study, the use of a new cyanoacrylate compound (Variclose vein sealing system, Biolas®, Ankara, Turkey) is assessed.MethodPatients with symptomatic varicose veins were invited to have their truncal saphenous incompetence treated using the new cyanoacrylate glue. Intraoperatively, their level of discomfort was assessed. Patients also had their clinical status and quality of life assessed at baseline and at 1 month post-operatively. ResultsSeventeen patients (20 limbs) were recruited. The mean age was 54 years. Eighty-five percent of limbs were reviewed at the 30-day follow-up. The mean baseline VCSS was 3.6 (±2.5), which improved to 2.4 (±3) at the 30-day point. Improvements were also noted in both the generic and specific quality of life scores. The median maximum pain score using a VAS was 34mm and 33mm for average pain. The complete/proximal occlusion rate at 30 days was 88%.ConclusionsThese preliminary results suggest that endovenous ablation using cyanoacrylate is safe and results in quality of life improvements similar to that seen in studies evaluating thermal techniques along with a low degree of intra-operative pain. Larger comparative studies are, however, required to confirm its effectiveness.
Donnely E, Busuttil A, Davies AH, 2017, Do Not Forget Popliteal Venous Entrapment, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 53, Pages: 613-614, ISSN: 1078-5884
Langley SR, Willeit K, Didangelos A, et al., 2017, Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques, Journal of Clinical Investigation, Vol: 127, Pages: 1546-1560, ISSN: 0021-9738
BACKGROUND: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms. METHODS: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies. RESULTS: Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study. CONCLUSION: The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery. FUNDING: UK: British Heart Foundation (BHF); King's BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy's and St Th
Bootun R, Epstein D, Onida S, et al., 2017, Effectiveness of treatments of varicose veins: systematic review and evidence synthesis, Publisher: WILEY, Pages: 28-28, ISSN: 0007-1323
Taha M, Busuttil A, Bootun R, et al., 2017, The use of deep venous stenting for acute venous thrombosis of the lower limb, Publisher: WILEY, Pages: 11-11, ISSN: 0007-1323
Bootun R, Onida S, Lane TRA, et al., 2017, Pilot study of the use of cyanoacrylate in the treatment of varicose veins, Annual Meeting of the Society-of-Academic-and-Research-Surgery (SARS), Publisher: Wiley, Pages: 46-47, ISSN: 1365-2168
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