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Background: Post-thrombotic syndrome is a common complication of iliofemoral deep venous thrombosis (IFDVT). Existing evidence and National Institute for Health and Care Excellence guidelines suggest that this can be reduced by prompt thrombolytic therapy or thrombectomy. We aimed to evaluate the characteristics of IFDVT patients and to identify whether patients are being offered the recommended treatment pathway., Methods: A multicenter cross-sectional study was conducted across eight hospital sites in the North West London region, of which two were hub hospitals in their local vascular service networks. Patients with proximal DVT were identified using International Classification of Diseases, Tenth Revision coding during a 1-year period. Data on demographics, diagnostic methods used, interventions, and referrals were extracted from electronic and paper medical records., Results: During the study period, 132 patients with IFDVT were identified (mean age, 59.4 years; 55% female); 75% of these patients had an IFDVT. In this cohort, the biggest predisposing factors were previous DVT (n = 35), malignant disease (n = 35), and immobility (n = 20). In total, 104 patients were administered anticoagulation, and 88 of these patients received anticoagulation within 24 hours. The cases of 45 patients were either discussed with or promptly referred to a vascular service, after which 20 patients were treated solely with anticoagulation, whereas 20 patients received thrombolysis of varying methods., Conclusions: A significant proportion (56%) of symptomatic IFDVT patients are not being appropriately referred to or discussed with vascular services. Of these, 43% would have been eligible for consideration of early thrombus removal. Adherence to the National Institute for Health and Care Excellence guidelines could be improved by increasing awareness among emergency department colleagues., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Supervised exercise programmes for intermittent claudication have poor access and limited compliance. Neuromuscular electrical stimulation (NMES) may be an effective alternative. A proof-of-concept study and RCT were conducted., Methods: In study 1, eligible patients underwent baseline assessment; treadmill testing for initial (ICD) and maximum (MCD) claudication distance; EuroQoL Five Dimensions five-level instrument (EQ-5D-5L™) and Intermittent Claudication Questionnaire (ICQ) assessment; and measurement of ultrasound haemodynamics of the superficial femoral artery. After familiarization with the NMES device, participants underwent a 30-min session of stimulation with concomitant recording of haemodynamic measures at 15 min, and after device cessation. Measurements were repeated after 6 weeks of daily use of NMES. In study 2, consecutive patients underwent baseline assessment before online randomization to a supervised exercise programme only, or adjunctive NMES treatment for 6 weeks, followed by repeat measurements., Results: Study 1 (20 patients) showed a significant improvement in MCD (46 per cent; P < 0·001) and ICD (71 per cent; P < 0·001). The RCT (42 patients) showed a significant adjunctive benefit of NMES in ICD (46 per cent; P = 0·014). Improvements were seen in the ICQ (9 points; P = 0·009) and EQ-5D-5L™ (P = 0·007) in study 1, and there was a significant adjunctive benefit of NMES on the ICQ score in patients who did supervised exercise (11·2 points; P = 0·031). Blood volume flow and time-adjusted mean velocity increased significantly with the device on (P < 0·050). Overall, NMES compliance exceeded 95 per cent., Conclusion: Footplate NMES significantly improved walking distance in patients with intermittent claudication when used independently and also as an adjunct to supervised exercise. Registration number: trial 1, NCT02436200; trial 2, NCT02429310 (http://www.clinicaltrials.gov)., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt to damage or changes in the environment. By using stereology and expression of cell cycle markers, we found that the placenta grows under normal conditions not just by hyperplasia of trophoblast cells but also through extensive polyploidy and cell hypertrophy. In response to feeding a low protein diet to mothers prior to and during pregnancy, to mimic chronic malnutrition, we found that this normal program was altered and that it was influenced by the sex of the conceptus. Male fetuses showed intrauterine growth restriction (IUGR) by embryonic day (E) 18.5, just before term, whereas female fetuses showed IUGR as early as E16.5. This difference was correlated with differences in the size of the labyrinth layer of the placenta, the site of nutrient and gas exchange. Functional changes were implied based on up-regulation of nutrient transporter genes. The junctional zone was also affected, with a reduction in both glycogen trophoblast and spongiotrophoblast cells. These changes were associated with increased expression of Phlda2 and reduced expression of Egfr. Polyploidy, which results from endoreduplication, is a normal feature of trophoblast giant cells (TGC) but also spongiotrophoblast cells. Ploidy was increased in sinusoidal-TGCs and spongiotrophoblast cells, but not parietal-TGCs, in low protein placentas. These results indicate that the placenta undergoes a range of changes in development and function in response to poor maternal diet, many of which we interpret are aimed at mitigating the impacts on fetal and maternal health., Competing Interests: The authors have declared that no competing interests exist.

Venous thromboembolism (VTE), chronic venous disease (CVD), and venous leg ulceration (VLU) are clinical manifestations of a poorly functioning venous system. Though common, much is unknown of the pathophysiology and progression of these conditions. Metabolic phenotyping has been employed to explore mechanistic pathways involved in venous disease. A systematic literature review was performed: full text, primary research articles on the applications of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) in human participants and animals were included for qualitative synthesis. Seventeen studies applying metabolic phenotyping to venous disease were identified: six on CVD, two on VLU, and nine on VTE; both animal ( n = 6) and human ( n = 10) experimental designs were reported, with one study including both. NMR, MS, and MS imaging were employed to characterize serum, plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated in CVD included lipids, branched chain amino acids (BCAA), glutamate, taurine, lactate, and myo-inositol identified in vein tissue. Upregulated metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate, and glutamate identified in wound fluid and ulcer biopsies. VTE cases were associated with reduced carnitine levels, upregulated aromatic amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum, thrombus, and vein wall; kynurenine and tricarboxylic acid pathway dysfunction were reported. Future research should focus on targeted studies with internal and external validation.

Background: Athletes are generally young, high-functioning individuals. Pathology in this cohort is associated with a decrease in function and consequently has major implications on quality of life. Venous disorders can be attributed to a combination of vascular compression with a high burden of activity., Objective: This article promotes increased awareness of these uncommon conditions specific to the athlete by summarizing pathophysiology, clinical features, investigation, and treatment protocols for use in clinical practice. Prognostic outcomes of these management regimens are also discussed, allowing for clinicians to counsel these high-functioning individuals appropriately. With the aim of providing an overview of sport-related venous pathology, a literature review was undertaken identifying articles that were independently reviewed by the authors., Results: Lower limb venous thrombosis has been identified in young, high-functioning athletes attributed to both compression-related venous trauma, associated with repetitive movements resulting in intimal damage, and blunt trauma. The diagnosis and treatment follow the same protocols as for the general population. Of note, early ambulation is advocated, with an aim to return to premorbid (noncontact) function within 6 weeks. Athletes performing high-intensity repetitive upper limb movement, such as baseball players, are predisposed to upper limb deep venous thrombosis (DVT). Diagnosis follows the same protocols as for lower extremity DVT; however, the optimal treatment strategy remains debated. Current guidelines advocate the use of anticoagulation alone. A specific subset of primary upper limb DVT is effort thrombosis, where there is compression at the level of the thoracic outlet. Thrombolysis with first rib resection is indicated in the acute setting within 14 days. In cases of complete occlusion, surgical decompression with venous reconstruction may be required. Popliteal vein entrapment syndrome is also discussed. This entity has been identified as an overuse injury associated with popliteal vein compression. Duplex ultrasound examination is indicated as a first-line investigation, with conservative noninvasive options considered as an initial management strategy. Chronic venous insufficiency or persistent symptoms may require subsequent surgical decompression., Conclusions: Key conditions including upper extremity and lower extremity venous thrombosis, venous aneurysms, Paget-Schroetter syndrome (effort thrombosis), and popliteal vein entrapment syndrome are discussed. Further studies evaluating long-term outcomes on morbidity for current treatment regimens in upper extremity DVT, effort thrombosis, venous thoracic outlet syndrome, and popliteal venous entrapment syndrome are required., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background/objective: Sport-related vascular trauma is an important consequence of increased physical activity. Repetitive, high-intensity movements predispose athletes to vascular disease, including arterial pathology, by exerting increased pressure on neurovascular structures. This is an important source of morbidity in an otherwise young and healthy population. Arterial pathology associated with repetitive trauma is often misdiagnosed as musculoskeletal injury. This article increases awareness of sport-related arterial disease by reviewing the symptomatology, investigation, and treatment modalities of this pathology. In addition, prognostic outcomes specific to the athlete are discussed., Results: Arterial thoracic outlet syndrome and vascular quadrilateral space syndrome are associated with athletes involved in overhead throwing exercises. Sport-related arterial pathology of the lower limb include external iliac artery endofibrosis (EIAE), popliteal artery entrapment syndrome (PAES), and adductor canal syndrome. Vascular stress and kinking secondary to vessel tethering are important contributors to pathology in EIAE. Chronic exertional compartment syndrome must also be considered, presenting with clinical features similar to PAES. In addition, athletes are predisposed to blunt mechanical trauma. Hypothenar hammer syndrome is one such example, contributing to a high burden of morbidity in this population., Conclusions: In arterial thoracic outlet syndrome and vascular quadrilateral space syndrome, surgery is advocated in symptomatic individuals, with postoperative outcomes favorable for the athlete. Acute limb ischemia may occur as a result of secondary thrombosis or embolization, often without preceding claudication. PAES and adductor canal syndrome are associated with functional entrapment in the athlete, secondary to muscular hypertrophy. Surgical exploration may be indicated. Poorer outcomes are noted when this process is associated with vascular reconstruction. Surgical treatment of EIAE follows failure of conservative management, with limited data available on postoperative prognosis. Investigations for all these conditions should be targeted based on clinical suspicion. A delay in diagnosis can have severe consequences on return to competition in these high-functioning individuals., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Ambulatory phlebectomies and foam sclerotherapy are two of the most common treatments for varicose vein tributaries. Many studies have been published on these treatments, but few comparative studies have attempted to determine their relative effectiveness., Methods/design: This is a prospective single-centre randomised clinical trial. Patients with primary truncal vein incompetence and varicose vein tributaries requiring treatment will be assigned randomly to either ambulatory phlebectomies or foam sclerotherapy. The primary outcome measure is the re-intervention rate for the varicose vein tributaries during the study period. The secondary outcomes include the degree of pain during the first two post-operative weeks and the time to return to usual activities or work. Improvements in clinical scores, quality of life scores, occlusion rates and cost-effectiveness for each intervention are other secondary outcomes. The re-intervention rate will be considered from the third month., Discussion: This study compares ambulatory phlebectomies and foam sclerotherapy in the treatment of varicose vein tributaries. The re-intervention rates, safety, patient experience and the cost-effectiveness of each intervention will be assessed. This study aims to recruit 160 patients and is expected to be completed by the end of 2019., Trial Registration: ClinicalTrials.gov, NCT03416413 . Registered on 31 January 2018.

Objective/background: The aim was to summarise the evidence for the relationship between vein diameters and clinical severity, and elucidate the relationship between diameters and health related quality of life (HRQoL) METHODS: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The MEDLINE and Embase databases were searched from 1946 to 31 August 2018. Reference lists of included studies were searched for further relevant papers. Full text studies in English reporting the relationship between great and small saphenous vein diameters and clinical severity and/or HRQoL scores measured using validated instruments were included. All study designs were included. Studies that did not include relationships between these parameters, non-English studies, and studies focusing on non-truncal veins were excluded. Two reviewers independently performed the study selection, data extraction, and risk of bias assessment., Results: Eleven eligible studies were identified, reporting on 2,732 limbs (range 22-681). Four studies correlated truncal vein diameter with both clinical severity and HRQoL, while seven reported only on clinical severity measures. Multiple instruments were used to quantify HRQoL and clinical severity. Seven studies assessed the relationship with CEAP class, with the majority observing a positive correlation between vein diameter and disease severity. Four studies found weak correlations with VCSS, with one showing correlations with VCSS components. No significant relationship between diameters and HRQoL scores was reported. One study also revealed no correlation with Aberdeen Varicose Vein Questionnaire improvements post-treatment. The majority of studies failed to include C 0 and C 1 participants., Conclusions: While further studies are required to improve the level of evidence, the existing literature suggests that truncal vein diameters correlate with clinical severity. Diameters are a poor predictor of HRQoL, with no relationship to patients' perceived impact of chronic venous disease. As such, vein diameter should not be used as a measure to decide who needs venous intervention., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device to improve the absolute walking distance in patients with intermittent claudication as an adjunct to the local standard care available at the study sites compared with local standard care alone., Methods: This open, multicenter, randomized controlled trial included eight participating centers in England. Sites are equally distributed between those that provide supervised exercise therapy programs and those that do not. Patients with intermittent claudication meeting the eligibility criteria and providing consent will be randomized, depending on the center type, to either NMES and locally available standard care or standard care alone. The primary end point is change in absolute walking distance at 3 months (the end of the intervention period) by treadmill testing. Secondary outcomes include quality of life, compliance with the interventions, economic evaluation of the NMES device, and lower limb hemodynamic measures to further the understanding of underlying mechanisms. Recruitment commenced in March 2018 and will continue for a total of 15 months. The Neuromuscular Electrical Stimulation Improves the Absolute Walking Distance in Patients with Intermittent Claudication trial is funded by the UK Efficacy and Mechanism Evaluation Programme, Medical Research Council, and National Institute for Health Research partnership., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Varicose veins are a very common condition and have been the subject of a recent proliferation of treatment modalities. The advent of the endovenous treatment era has led to a confusing array of different techniques that can be daunting when making the transition from traditional surgery. All modalities offer excellent results in the right situation, and each has its own treatment profile. Thermal ablation techniques have matured and have a reassuring and reliable outcome, but the arrival of nonthermal techniques has delivered further options for both patient and surgeon. This article provides an overview of the different treatment devices and modalities available to the modern superficial vein surgeon and details the currently available evidence and summation analysis to help surgeons to make an appropriate treatment choice for their patients.

Background: Venous ulceration is a common and costly health-care issue worldwide, with poor healing rates greatly affecting patient quality of life. Compression bandaging has been shown to improve healing rates and reduce recurrence, but does not address the underlying cause, which is often superficial venous reflux. Surgical correction of the reflux reduces ulcer recurrence; however, the effect of early endovenous ablation of superficial venous reflux on ulcer healing is unclear., Objectives: To determine the clinical effectiveness and cost-effectiveness of compression therapy with early endovenous ablation of superficial venous reflux compared with compression therapy with deferred endovenous ablation in patients with venous ulceration., Design: A pragmatic, two-arm, multicentre, parallel-group, open randomised controlled trial with a health economic evaluation., Setting: Secondary care vascular centres in England., Participants: Patients aged ≥ 18 years with a venous leg ulcer of between 6 weeks' and 6 months' duration and an ankle-brachial pressure index of ≥ 0.8 who could tolerate compression and were deemed suitable for endovenous ablation of superficial venous reflux., Interventions: Participants were randomised 1 : 1 to either early ablation (compression therapy and superficial endovenous ablation within 2 weeks of randomisation) or deferred ablation (compression therapy followed by endovenous ablation once the ulcer had healed)., Main Outcome Measures: The primary outcome measure was time from randomisation to ulcer healing, confirmed by blinded assessment. Secondary outcomes included 24-week ulcer healing rates, ulcer-free time, clinical success (in addition to quality of life), costs and quality-adjusted life-years (QALYs). All analyses were performed on an intention-to-treat basis., Results: A total of 450 participants were recruited (224 to early and 226 to deferred superficial endovenous ablation). Baseline characteristics were similar between the two groups. Time to ulcer healing was shorter in participants randomised to early superficial endovenous ablation than in those randomised to deferred ablation [hazard ratio 1.38, 95% confidence interval (CI) 1.13 to 1.68; p  = 0.001]. Median time to ulcer healing was 56 (95% CI 49 to 66) days in the early ablation group and 82 (95% CI 69 to 92) days in the deferred ablation group. The ulcer healing rate at 24 weeks was 85.6% in the early ablation group, compared with 76.3% in the deferred ablation group. Median ulcer-free time was 306 [interquartile range (IQR) 240-328] days in the early ablation group and 278 (IQR 175-324) days in the deferred endovenous ablation group ( p  = 0.002). The most common complications of superficial endovenous ablation were pain and deep-vein thrombosis. Differences in repeated measures of Aberdeen Varicose Vein Questionnaire scores ( p  < 0.001), EuroQol-5 Dimensions index values ( p  = 0.03) and Short Form questionnaire-36 items body pain ( p  = 0.05) over the follow-up period were observed, in favour of early ablation. The mean difference in total costs between the early ablation and deferred ablation groups was £163 [standard error (SE) £318; p  = 0.607]; however, there was a substantial and statistically significant gain in QALY over 1 year [mean difference between groups 0.041 (SE 0.017) QALYs; p  = 0.017]. The incremental cost-effectiveness ratio of early ablation at 1 year was £3976 per QALY, with a high probability (89%) of being more cost-effective than deferred ablation at conventional UK decision-making thresholds (currently £20,000 per QALY). Sensitivity analyses using alternative statistical models give qualitatively similar results., Limitations: Only 7% of screened patients were recruited, treatment regimens varied significantly and technical success was assessed only in the early ablation group., Conclusions: Early endovenous ablation of superficial venous reflux, in addition to compression therapy and wound dressings, reduces the time to healing of venous leg ulcers, increases ulcer-free time and is highly likely to be cost-effective., Future Work: Longer-term follow-up is ongoing and will determine if early ablation will affect recurrence rates in the medium and long term., Trial Registration: Current Controlled Trials ISRCTN02335796., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 24. See the NIHR Journals Library website for further project information., Competing Interests: Manjit S Gohel has received personal fees from Medtronic pLc (Minneapolis, MN, USA) and Cook Medical LLC (Bloomington, IN, USA), plus a grant from Laboratoires Urgo S.A. (Chenôve, France). Andrew Bradbury had committee membership for the National Institute for Health Research Health Technology Assessment (HTA) Prioritisation Group and HTA Surgery Themed Call Board 2012–13, HTA Efficient Study Designs Board 2014–16, HTA Interventional Procedures Methods Group 2015–19 and HTA IP Panel 2015–19. In addition, Andrew Bradbury has received funding from STD Pharmaceutical Products Ltd (Hereford, UK) to travel to a foam sclerotherapy workshop in Tehran, Iran, in October 2016 and a grant to cover costs of undertaking a post-authorisation safety study in the UK and Europe. He also sat on the National Institute for Health and Care Excellence (NICE) committee for a clinical guideline (CG168) for the diagnosis and management of varicose veins. Nicky Cullum had committee membership on the HTA Commissioning Board from 2003 to 2008. David M Epstein has received grant funding from Vascular Insights LLC (Quincy, MA, USA) which was administered by the University of Granada. Alun H Davies has received grant funding from Medtronic, Vascular Insights, Laboratoires Urgo, Vascutek (Inchinnan, UK) and Actegy Health Ltd (Bracknell, UK), which are administered by Imperial College London. In addition, Alun H Davies has chaired the NICE clinical guideline (CG168) for the diagnosis and management of varicose veins.

Background: Treatment of superficial venous reflux in addition to compression therapy accelerates venous leg ulcer healing and reduces ulcer recurrence. The aim of this study was to evaluate the costs and cost-effectiveness of early versus delayed endovenous treatment of patients with venous leg ulcers., Methods: This was a within-trial cost-utility analysis with a 1-year time horizon using data from the EVRA (Early Venous Reflux Ablation) trial. The study compared early versus deferred endovenous ablation for superficial venous truncal reflux in patients with a venous leg ulcer. The outcome measure was the cost per quality-adjusted life-year (QALY) over 1 year. Sensitivity analyses were conducted with alternative methods of handling missing data, alternative preference weights for health-related quality of life, and per protocol., Results: After early intervention, the mean(s.e.m.) cost was higher (difference in cost per patient £163(318) (€184(358))) and early intervention was associated with more QALYs at 1 year (mean(s.e.m.) difference 0·041(0·017)). The incremental cost-effectiveness ratio (ICER) was £3976 (€4482) per QALY. There was an 89 per cent probability that early venous intervention is cost-effective at a threshold of £20 000 (€22 546)/QALY. Sensitivity analyses produced similar results, confirming that early treatment of superficial reflux is highly likely to be cost-effective., Conclusion: Early treatment of superficial reflux is highly likely to be cost-effective in patients with venous leg ulcers over 1 year. Registration number: ISRCTN02335796 (http://www.isrctn.com)., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objectives: The aim was to assess the effectiveness and safety of catheter-directed thrombolysis in children with deep venous thrombosis and to evaluate its long-term effect., Method and Results: EMBASE, Medline and Cochrane databases were searched to identify studies in which paediatric acute deep venous thrombosis patients received thrombolysis. Following title and abstract screening, seven cohort studies with a total of 183 patients were identified. Technical success was 82% and superior in regional rather than systemic thrombolysis (p < 0.00001). One cohort study identified significant difference in thrombus resolution at one year between thrombolytic and anticoagulant groups (p = 0.01). The complication rate was low, with incidence rates of major bleeding, pulmonary embolism and others at 2.8%, 1.8% and 8.4%, respectively. The overall post-thrombotic syndrome rate was 12.7%. The incidence of re-thrombosis ranged from 12.3% to 27%., Conclusion: Thrombolysis for paediatric deep venous thrombosis is an effective and relatively safe therapeutic option, lowering the incidence of post-thrombotic syndrome and deep venous thrombosis recurrence.

Surgical site infection (SSI) is associated with increased morbidity, length of stay, and cost. Cyanoacrylate glue is a low-cost, fluid-proof, antimicrobial barrier. The aim of this systematic review is to assess the use of cyanoacrylate glue after standard wound closure versus dressings in the reduction of SSI. Medline, Embase, Cochrane Library, and clinical trial registries were searched with no restrictions in accordance with PRISMA guidelines. Eligibility criteria were prospective studies comparing glue versus dressings after standardised wound closure. Two reviewers independently screened articles and utilised GRADE for quality assessment. Meta-analysis was not performed because of the heterogeneity of the data. Three articles were included in the review. Study quality was uniformly low. Incidence of SSI was low, between 0% and 4%. No significant differences were reported in the single randomised controlled trial. A single non-randomised parallel group trial reported a significant reduction in the incidence of SSI in the cyanoacrylate group. There was no consistent evidence demonstrating reduction in SSI as a result of the use of cyanoacrylate glue. Future studies should assess the use of cyanoacrylate in procedures with a higher rate of SSI, for example, lower limb bypass., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objectives: The aim is to evaluate venous stent patency, the development of post-thrombotic syndrome, recurrence, quality of life and the optimal post-procedural anticoagulation regimen in the treatment of iliofemoral deep venous thrombosis., Method and Results: EMBASE and Medline databases were interrogated to identify studies in which acute deep venous thrombosis patients were stented. Twenty-seven studies and 542 patients were identified. Primary, assisted primary and secondary patency rates 12 months after stent placement ranged from 74 to 95, 90 to 95 and 84 to 100%, respectively. The observed post-thrombotic syndrome rate was 14.6%. The incidence of stent re-thrombosis was 8%. In 26% of studies, patients received additional antiplatelet therapy. Quality of life questionnaires employed in 11% of studies, demonstrating an improvement in the chronic venous insufficiency questionnaire (22.67 ± 3.01 versus 39.34 ± 6.66)., Conclusion: Venous stenting appears to be an effective adjunct to early thrombus removal; however, further studies are needed to identify optimal anticoagulant regimen and effect on quality of life.

Chronic venous disease (CVD) is a prevalent condition that tends to worsen with age. Patients initially seek treatment to relieve symptoms of leg pain, discomfort, heaviness and swelling, all of which impact their quality of life. As the disease increases in severity to include varicose veins, skin changes, and venous ulcer, the demand for treatment increases while the quality of life further diminishes. The prevalence of CVD is highest in Western countries where it already consumes up to 2% of healthcare budgets. With the aging of the global population, the prevalences of CVD and severe CVD are projected to increase substantially, foretelling unsustainably large increases in the healthcare resources and costs needed to treat CVD patients in the coming decades. Effective venoactive drug treatments and ablation procedures are available that provide symptom relief, improve quality of life, slow disease progression, and promote ulcer healing. In addition, venoactive drug treatments may be highly cost-effective. However, there is evidence that physician awareness of CVD is suboptimal and that many patients with CVD are not being treated or referred to specialists according to established guidelines. To decrease this treatment gap and prevent unnecessary disease progression, international guidelines are available to help physicians consider CVD treatment options and refer patients when warranted. Improved disease awareness and appropriate early treatment may help reduce the coming burden of CVD.Funding: Servier.

Objective: The aim was to evaluate the quality of current venous leg ulcer (VLU) clinical practice guidelines (CPGs) to assist healthcare professionals in choosing an accessible high quality CPG to advise their practice, and to identify areas for improvement in future versions of current CPGs., Methods: A systematic review of PubMed, Embase, online CPG databases, and reference lists of included CPGs was carried out. Full text CPGs published no earlier than 1998 reporting evidence based recommendations on VLU diagnosis and management in English were included. CPGs that were only available if purchased were excluded. Two reviewers identified eligible CPGs, extracted data, and assessed the quality independently using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Significant scoring discrepancies were discussed with a third reviewer., Results: Fourteen eligible CPGs were identified (1999-2016). The majority of CPGs originated from Europe or North America. Overall, there was good inter-reviewer reliability of scores with an intraclass correlation coefficient of 0.986 (95% confidence interval 0.979-0.991). No single CPG achieved the highest score in all six domains. Significant methodological heterogeneity was observed across VLU CPGs; however, consistently, poor performance was noted in domain 5, concerning CPG applicability., Conclusion: Four CPGs were considered of adequate quality for clinical use. Consolidation of efforts to drive high quality, comprehensive VLU CPGs is necessary to reduce the number of and heterogeneity seen in currently published guidelines. Elements of methodological quality are lacking and a structured approach with use of checklists and CPG creation tools, such as AGREE II or others, may bolster rigour in future VLU CPGs., (Copyright © 2018. Published by Elsevier B.V.)

Background: Stroke occurs in 3% to 8% and silent cerebral infarction in >60% of patients undergoing thoracic endovascular aortic repair (TEVAR). We investigated the utility of a filter cerebral embolic protection device (CEPD) to reduce diffusion-weighted magnetic resonance imaging (DW-MRI) detected cerebral injury and gaseous and solid embolization during TEVAR., Methods: Patients anatomically suitable underwent TEVAR with CEPD, together with intraoperative transcranial Doppler to detect gaseous and solid high-intensity transient signals (HITSs), pre- and postoperative DW-MRI, and clinical neurologic assessment ≤6 months after the procedure., Results: Ten patients (mean age, 68 years) underwent TEVAR with a CEPD. No strokes or device-related complications developed. The CEPD added a median of 7 minutes (interquartile range [IQR], 5-16 minutes) to the procedure, increased the fluoroscopy time by 3.3 minutes (IQR, 2.4-3.9 minutes), and increased the total procedural radiation by 2.2%. The dose area product for CEPD was 1824 mGy·cm 2 (IQR, 1235-3392 mGy·cm 2 ). The average contrast volume used increased by 23 mL (IQR, 24-35 mL). New DW-MRI lesions, mostly in the hindbrain, were identified in seven of nine patients (78%). The median number was 1 (IQR, 1-3), with a median surface area of 6 mm 2 (IQR, 3-16 mm 2 ). A total of 2835 HITSs were detected in seven patients: 91% gaseous and 9% solid. The maximum number of HITSs were detected during CEPD manipulation: 142 (IQR, 59-146; 95% gaseous and 5% solid). The maximum number of HITSs during TEVAR occurred during stent deployment: 82 (IQR, 73-142; 81% gas and 11% solid). Solid HITSs were associated with an increase in surface area of new DW-MRI lesions (r s  = 0.928; P = .01). Increased gaseous HITSs were associated with new DW-MRI lesions (r s  = 0.912; P = .01), which were smaller (<3 mm; r = 0.88; P = .02). Embolic debris was captured in 95% of the filters. The median particle count was 937 (IQR, 146-1687), and the median surface area was 2.66 mm 2 (IQR, 0.08-9.18 mm 2 )., Conclusions: The use of a CEPD with TEVAR appeared to be safe and feasible in this first pilot study and could serve as a useful adjunct to reduce cerebral injury. The significance of gaseous embolization and its role in cerebral injury in TEVAR warrants further investigation., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Chronic venous disease (CVD) represents a significant healthcare burden. Thrombophilia is proposed as a risk factor, particularly for post-thrombotic CVD. A systematic review was performed to determine the relationship between thrombophilia and non-thrombotic CVD. MEDLINE ® and Embase ® databases were searched from 1946 up to March 2018. Case-control studies, cohort studies or randomised clinical trials reporting on thrombophilias in non-thrombotic lower limb CVD in adult patients were included. Non-English and post-thrombotic syndrome studies were excluded. Study selection and data extraction were performed by two reviewers. Fifteen studies were included, reporting on 916 cases and 1261 controls. Studies largely focused on venous ulceration and investigated multiple haemostatic factors. An association between thrombophilia and non-thrombotic CVD was identified, with greater prevalence and factor concentration alteration reported in patients compared to controls. Concomitant thrombophilia presence was associated with earlier CVD onset. Relationship strength varied, with commoner aetiologies showing clearer correlation than rarer ones. Thrombophilia is associated with non-thrombotic CVD but the mechanism is unclear and causation cannot be determined. Future research should focus on prospective studies with larger populations and identify adjunct therapies targeting thrombophilia., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: There is an increasing evidence base to support the use of extended pharmacologic thromboprophylaxis in selected surgical patients to prevent venous thromboembolism (VTE). The benefit of graduated compression stockings (GCS) in addition to extended pharmacologic thromboprophylaxis is unclear. The aim of this study was to systematically review the evidence relating to the effectiveness of using GCS in conjunction with extended pharmacologic thromboprophylaxis to prevent VTE in surgical patients., Methods: A literature search of MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in April 2017. The review protocol was published on PROSPERO (CRD42017062655). Randomized controlled trials (RCTs) were eligible if one of the study arms included patients receiving extended pharmacologic thromboprophylaxis alone (>21 days) or in conjunction with GCS. Data on deep venous thrombosis (DVT), pulmonary embolism (PE), and VTE-related death were compiled. Pooled proportions of the VTE rates were determined using random-effects meta-analysis., Results: The systematic search identified 1291 studies, of which 19 studies were eligible for inclusion. No RCT directly compared extended pharmacologic thromboprophylaxis alone with GCS plus extended pharmacologic thromboprophylaxis. A total of 9824 patients from 16 RCTs were treated with extended pharmacologic thromboprophylaxis, of whom 0.81% (95% confidence interval [CI], 0.5-1.20) were diagnosed with symptomatic DVT and 0.2% (95% CI, 0.12-0.36) with PE. Three trials included 337 patients who received extended pharmacologic thromboprophylaxis in conjunction with GCS. In this group, 1.61% (95% CI, 0.03-5.43) had symptomatic DVT with no reported PE. Similar VTE rates were observed when studies in orthopedic and abdominal surgery were analyzed separately., Conclusions: There is insufficient evidence to recommend GCS in conjunction with extended pharmacologic prophylaxis to prevent VTE in patients undergoing orthopedic and abdominal surgery. A clinical trial directly investigating this important subject is needed., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Thermal ablation techniques have become the first-line treatment of truncal veins in the management of chronic venous disease (CVD). Despite excellent outcomes, these methods are often associated with pain; generally due to their use of heat and the necessity of fluid infiltration around the vein. More recently, novel non-thermal techniques, such as mechanochemical ablation (MOCA) and cyanoacrylate adhesive (CAE) have been developed to overcome these unwelcome effects. So far, the novel techniques have been found to have similar efficacy to thermal methods, yet no direct comparisons between the non-thermal treatment techniques have been conducted to date, giving rise to this study., Methods/design: This is a prospective, multicentre, randomised clinical trial, recruiting patients with truncal saphenous incompetence. Patients will be randomised to undergo either MOCA or CAE truncal ablation, followed by treatment of any varicosities. All patients will be required to wear compression stockings for 4 days post intervention. The primary outcome measure is the pain score immediately following completion of truncal ablation, measured by a 100-mm Visual Analogue Scale (VAS). The secondary outcomes are entire treatment pain scores, clinical scores, quality of life scores, occlusion rates, time to return to usual activities/work at 2 weeks, 3, 6 and 12 months. Re-intervention rate will be considered from the third month. Cost-effectiveness will be assessed for each intervention at 12 months. The study is powered to detect a mean 10-mm difference in maximum pain score. Allowing for loss to follow-up, the total target recruitment is 180 patients., Discussion: The study will be the first study to compare MOCA against CAE and is designed to determine which method causes less pain. Completion of this study is expected to be the end of 2019., Trial Registration: ClinicalTrials.gov, ID: NCT03392753 . Registered on 17 November 2017.

Competing Interests: Competing interests: None declared.

Objectives: To analyze the cost-effectiveness of current technologies (conservative care [CONS], high-ligation surgery [HL/S], ultrasound-guided foam sclerotherapy [UGFS], endovenous laser ablation [EVLA], and radiofrequency ablation [RFA]) and emerging technologies (mechanochemical ablation [MOCA] and cyanoacrylate glue occlusion [CAE]) for treatment of varicose veins over 5 years., Methods: A Markov decision model was constructed. Effectiveness was measured by re-intervention on the truncal vein, re-treatment of residual varicosities, and quality-adjusted life-years (QALYs) over 5 years. Model inputs were estimated from systematic review, the UK National Health Service unit costs, and manufacturers' list prices. Univariate and probabilistic sensitivity analyses were undertaken., Results: CONS has the lowest overall cost and quality of life per person over 5 years; HL/S, EVLA, RFA, and MOCA have on average similar costs and effectiveness; and CAE has the highest overall cost but is no more effective than other therapies. The incremental cost per QALY of RFA versus CONS was £5,148/QALY. Time to return to work or normal activities was significantly longer after HL/S than after other procedures., Conclusions: At a threshold of £20,000/QALY, RFA was the treatment with highest median rank for net benefit, with MOCA second, EVLA third, HL/S fourth, CAE fifth, and CONS and UGFS sixth. Further evidence on effectiveness and health-related quality of life for MOCA and CAE is needed. At current prices, CAE is not a cost-effective option because it is costlier but has not been shown to be more effective than other options., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Aneurysms of the inferior vena cava (IVC) are rare, with only 54 cases reported in the literature. They carry a significant morbidity and mortality risk. A case of an IVC aneurysm in a patient with Klippel-Trenaunay syndrome (KTS) is reported. Open aneurysmorrhaphy of the type III aneurysm was successfully performed. The patient's leg swelling, back pain, and exercise tolerance improved. IVC aneurysms are not known to be associated with KTS. However, clinicians should have a high index of suspicion for great vessel aneurysms in these patients as they are associated with greater thromboembolic risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is a significant cause of morbidity and mortality, affecting one in 1000 adults per year. Neuromuscular electrical stimulation is the transcutaneous application of electrical impulses to elicit muscle contraction, preventing venous stasis. This review aims to investigate the evidence underlying the use of neuromuscular electrical stimulation in thromboprophylaxis. Methods The Medline and Embase databases were systematically searched, adhering to PRISMA guidelines, for articles relating to electrical stimulation and thromboprophylaxis. Articles were screened according to a priori inclusion and exclusion criteria. Results The search strategy identified 10 randomised controlled trials, which were used in three separate meta-analyses: five trials compared neuromuscular electrical stimulation to control, favouring neuromuscular electrical stimulation (odds ratio of deep vein thrombosis 0.29, 95% confidence interval 0.13-0.65; P = .003); three trials compared neuromuscular electrical stimulation to heparin, favouring heparin (odds ratio of deep vein thrombosis 2.00, 95% confidence interval 1.13-3.52; P = .02); three trials compared neuromuscular electrical stimulation as an adjunct to heparin versus heparin only, demonstrating no significant difference (odds ratio of deep vein thrombosis 0.33, 95% confidence interval 0.10-1.14; P = .08). Conclusion Neuromuscular electrical stimulation significantly reduces the risk of deep vein thrombosis compared to no prophylaxis. It is inferior to heparin in preventing deep vein thrombosis and there is no evidence for its use as an adjunct to heparin.

Background: Venous leg ulcers impair quality of life significantly, with substantial costs to health services. The aim of this study was to estimate the cost-effectiveness of interventional procedures alongside compression therapy versus compression therapy alone for the treatment of chronic venous leg ulceration., Methods: A Markov decision analytical model was developed. The main outcome measures were quality-adjusted life-years (QALYs) and lifetime costs per patient, from the perspective of the UK National Health Service at 2015 prices. Resource use included the initial procedures, compression therapy, primary care and outpatient consultations. The interventional procedures included superficial venous surgery, endothermal ablation and ultrasound-guided foam sclerotherapy (UGFS). The study population was patients with a chronic venous ulcer who were eligible for either compression therapy or an interventional procedure. Data were obtained from systematic review and meta-analysis of RCTs., Results: Surgery gained 0·112 (95 per cent c.i. -0·011 to 0·213) QALYs compared with compression therapy alone, with a difference in lifetime costs of €-1330 (-3570 to 1262). Given the expected savings in community care, the procedure would pay for itself within 4 years. There was insufficient evidence regarding endothermal ablation and UGFS to draw conclusions., Discussion: This modelling study found surgery to be more effective and less costly than compression therapy alone. Further RCT evidence is required for both endothermal ablation and UGFS.

The success of next-generation androgen receptor (AR) pathway inhibitors, such as abiraterone acetate and enzalutamide, in treating prostate cancer has been hampered by the emergence of drug resistance. This acquired drug resistance is driven, in part, by the ability of prostate cancer cells to change their phenotype to adopt AR-independent pathways for growth and survival. Around one-quarter of resistant prostate tumours comprise cells that have undergone cellular reprogramming to become AR-independent and to acquire a continuum of neuroendocrine characteristics. These highly aggressive and lethal tumours, termed neuroendocrine prostate cancer (NEPC), exhibit reactivation of developmental programmes that are associated with epithelial-mesenchymal plasticity and acquisition of stem-like cell properties. In the past few years, our understanding of the link between lineage plasticity and an emergent NEPC phenotype has considerably increased. This new knowledge can contribute to novel therapeutic modalities that are likely to improve the treatment and clinical management of aggressive prostate cancer.

Objectives: Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality. The identification of a simple and effective diagnostic biomarker of DVT remains a challenge. Metabolomics have recently emerged as a new powerful scientific tool to characterise metabolic phenotypes of complex diseases and investigate small molecules in biofluids. The aim of the study was to identify the blood and vein wall metabolomic signature of DVT in a murine experimental model., Methods: An established inferior vena cava ligation mouse model of DVT (n=10) was used and compared with sham surgery controls (n=10). Comprehensive untargeted metabolic profiling of serum and vein wall extracts was undertaken using liquid chromatography coupled mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy., Results: Multivariate and univariate statistical analysis demonstrated a differential metabolic profile when comparing DVT mice and control animals. Serum from DVT mice was characterised by differential concentrations of adenosine (decreased in DVT mice 9.6 fold), adenine (decreased 10.6 fold), and tricyclic acid cycle (TCA) intermediates, including citrate, succinate, and fumarate (1.5, 2.3, and 2.8 fold decreases, respectively). l-carnitine was found to be of greater abundance in the serum of DVT animals (67.0 fold change). A number of lipid moiety classes, including sphingomyelins, phosphatidylcholines, and triglycerides, were differentially abundant. Several metabolites were found in vein wall, including acetylcarnitine (increased in DVT mice 1.9 fold), adenosine (increased 2.2 fold), and ceramide (increased 2.7 fold). Correlation analysis illustrated the biochemical relationships between assigned metabolites, with the discriminatory molecules being highly correlated with each other, in both serum and vein wall., Conclusions: The present findings demonstrate that metabolic dysregulations in DVT centre on energy metabolism, sphingolipid, and adenosine metabolism, representing a DVT specific metabolite signature in a murine experimental model., (Copyright © 2018 European Society for Vascular Surgery. All rights reserved.)

The structure of microvasculature cannot be resolved using conventional ultrasound (US) imaging due to the fundamental diffraction limit at clinical US frequencies. It is possible to overcome this resolution limitation by localizing individual microbubbles through multiple frames and forming a superresolved image, which usually requires seconds to minutes of acquisition. Over this time interval, motion is inevitable and tissue movement is typically a combination of large- and small-scale tissue translation and deformation. Therefore, super-resolution (SR) imaging is prone to motion artifacts as other imaging modalities based on multiple acquisitions are. This paper investigates the feasibility of a two-stage motion estimation method, which is a combination of affine and nonrigid estimation, for SR US imaging. First, the motion correction accuracy of the proposed method is evaluated using simulations with increasing complexity of motion. A mean absolute error of 12.2 was achieved in simulations for the worst-case scenario. The motion correction algorithm was then applied to a clinical data set to demonstrate its potential to enable in vivo SR US imaging in the presence of patient motion. The size of the identified microvessels from the clinical SR images was measured to assess the feasibility of the two-stage motion correction method, which reduced the width of the motion-blurred microvessels to approximately 1.5-fold.

Background Although well characterised in adults, less is known about post-thrombotic syndrome in children. In this review, current knowledge regarding paediatric post-thrombotic syndrome is summarised, with particular emphasis on pathophysiology, aetiology, diagnosis and management. Methods A Medline literature review was performed using search terms 'post thrombotic syndrome', 'post phlebitic syndrome', paediatric and children. Relevant articles were identified and included for summation analysis. Results The incident of paediatric venous thromboembolism is rising. Deep vein thrombosis can cause venous hypertension through a combination of venous reflux, venous obstruction and impairment of the calf muscle pump, leading to development of post-thrombotic syndrome. In children, this is more likely to occur if deep vein thrombosis diagnosis and treatment are delayed, if a higher number of vessels are involved, and if factors such as D-dimer are elevated at diagnosis and throughout treatment. Post-thrombotic syndrome occurs in about 26% of paediatric deep vein thrombosis, though the results of individual studies vary widely. A number of tools exist to diagnose paediatric post-thrombotic syndrome, including the modified Villalta scale and Manco-Johnson instrument. Once post-thrombotic syndrome develops, the mainstay of treatment remains supportive, with little evidence of benefit from pharmacological measures. Conclusion Surgical or interventional treatment is not advised except in exceptional cirumstances, due to variable prognosis of PTS in paediatric populations with rising incidence of paediatric venous thromboembolism, it follows that the prevalence of post-thrombotic syndrome in children may also increase. Evidence-based venous thromboembolism prevention strategies need to be implemented for prevention of deep vein thrombosis, but when it does occur, deep vein thrombosis requires prompt and effective treatment to prevent post-thrombotic syndrome. Optimum treatment strategies for post-thrombotic syndrome require further investigation.

Objective/background: Deep venous stenting is increasingly used in the treatment of deep venous obstruction; however, there is currently no consensus regarding post-procedural antithrombotic therapy. The aim of the present study was to determine the most commonly used antithrombotic regimens and facilitate global consensus., Methods: An electronic survey containing three clinical scenarios on venous stenting for non-thrombotic iliac vein lesions, acute deep vein thrombosis (DVT), and post-thrombotic syndrome was distributed to five societies whose members included vascular surgeons, interventional radiologists, and haematologists. The results of the initial survey (phase 1) were used to produce seven consensus statements, which were distributed to the respondents for evaluation in the second round (phase 2), along with the results of phase 1. Consensus was defined a priori as endorsement or rejection of a statement by ≥ 67% of respondents., Results: Phase 1 was completed by 106 experts, who practiced in 78 venous stenting centres in 28 countries. Sixty-one respondents (58% response rate) completed phase 2. Five of seven statements met the consensus criteria. Anticoagulation was the preferred treatment during the first 6-12 months following venous stenting for a compressive iliac vein lesion. Low molecular weight heparin was the antithrombotic agent of choice during the first 2-6 weeks. Lifelong anticoagulation was recommended after multiple DVTs. Discontinuation of anticoagulation after 6-12 months was advised following venous stenting for a single acute DVT. No agreement was reached regarding the role of long-term antiplatelet therapy., Conclusions: Consensus existed amongst respondents regarding anticoagulant therapy following venous stenting. At present, there is no consensus regarding the role of antiplatelet agents in this context., (Copyright © 2018 European Society for Vascular Surgery. All rights reserved.)

Objectives: Compression stockings are commonly prescribed for patients with a range of venous disorders, but are difficult to don and uncomfortable to wear. This study aimed to investigate compliance and complications of compression stockings in patients with chronic venous disease (CVD) and post-thrombotic syndrome (PTS)., Methods: A literature search of the following databases was carried out: MEDLINE (via PubMed), EMBASE (via OvidSP, 1974 to present), and CINAHL (via EBSCOhost). Studies evaluating the use of compression stockings in patients with CVD (CEAP C2-C5) or for the prevention or treatment of PTS were included. After scrutinising full text articles, compliance with compression and associated complications were assessed. Compliance rates were compared based on study type and degree of compression. Good compliance was defined as patients wearing compression stockings for >50% of the time., Results: From an initial search result of 4303 articles, 58 clinical studies (37 randomised trials and 21 prospective studies) were selected. A total of 10,245 limbs were included, with compression ranging from 15 to 40 mmHg (not stated in 12 studies) and a median follow-up of 12 months (range 1-60 months). In 19 cohorts, compliance was not assessed and in a further nine, compliance was poorly specified. Overall, good compliance with compression was reported for 5371 out of 8104 (66.2%) patients. The mean compliance, weighted by study size, appeared to be greater for compression ≤25 mmHg (77%) versus > 25 mmHg (65%) and greater in the randomised studies (74%) than in prospective observational studies (64%). Complications of stockings were not mentioned in 43 out of 62 cohorts reviewed. Where complications were considered, skin irritation was a common event., Conclusions: In published trials, good compliance with compression is reported in around two thirds of patients, with inferior compliance in those given higher degrees of compression. Further studies are required to identify predictors of non-compliance, to help inform the clinical management of these patients. Complications of compression are not documented in many studies and should be given more consideration in the future., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Recently, there has been renewed interest in the development and characterization of patient-derived tumour xenograft (PDX) models. Numerous PDX models have been established for prostate cancer and, importantly, retain the principal molecular, genetic, and histological characteristics of the donor tumour. As such, these models provide significant improvements over standard cell line xenograft models for biological studies, preclinical drug development, and personalized medicine strategies. This review summarizes the current state of the art in this field, illustrating the opportunities and limitations of PDX models in translational prostate cancer research., (Copyright © 2017. Published by Elsevier B.V.)

Endovascular aneurysm repair (EVAR) has become the intervention of choice for supra-threshold aortic aneurysms due to the lower 30-day mortality of EVAR as compared with open surgery, despite no long-term longevity gains. Trials such as EVAR-1 that established the current status of endovascular aortic intervention often excluded participants over the age of 80, and specific studies of EVAR in the elderly reveal higher mortality than accepted averages. Analyses of the cost-effectiveness of EVAR have not demonstrated superiority of endovascular intervention over open repair, in particular when considering complications such as endoleak. Post-intervention surveillance and the frequent need for re-intervention following EVAR has a detrimental impact on quality of life. Taking these factors into consideration, combined with an ageing population and the likely increase in octogenarian endovascular intervention, there is a clear clinical need for appropriate risk-stratification of elderly patients with supra-threshold aneurysms to determine who will benefit from endovascular repair.

Background: Early and 1-year outcomes are presented for fenestrated endovascular aneurysm repair (FEVAR) of complex aortic aneurysmal disease with the custom-made Anaconda fenestrated stent graft in 101 patients., Methods: Retrospective site-reported data from the first 101 elective cases (2010-2014) from 4 UK centers were studied to evaluate patient demographics, aneurysm morphology, clinical success, and 1-year outcomes in patients undergoing fenestrated aneurysm repair with the custom-made Anaconda device., Results: 101 fenestrated grafts (median age 76, 85% male) were implanted with a total of 255 fenestrations (196 renal arteries, 48 superior mesenteric artery, and 11 celiac arteries) with 3% mortality, 98.4% target vessel patency (TVP) at 30 day follow-up. Although 15 type I or III endoleaks were demonstrated at completion angiography, all 10 type Ia endoleaks resolved spontaneously. Survival by Kaplan-Meier analysis was 97% and 91% at 1 month and 1 year, respectively; with 75.8% showing reduction in abdominal aortic aneurysm diameter and only 1 patient with sac expansion. Freedom from loss of TVP was 97.6%., Conclusions: Custom-made fenestrated Anaconda devices demonstrate low procedural mortality and a high rate of technical and clinical success at 30 days and 1 year., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Venous thromboembolism (VTE) is a recognized complication of gynecological malignancy and represents a leading cause of morbidity and mortality in these patients. The review aimed to discuss the incidence, risk factors, and clinical presentation of VTE before examining the literature on the diagnosis, prevention, and management in the context of uterine, cervical, ovarian, and vulval cancers., Methods/materials: A literature search was performed using Ovid Medline and Embase with the following words: "gynecological malignancy," "pelvic tumor," "venous thromboembolism," "deep vein thrombosis" and "pulmonary embolism.", Results: The incidence of VTE in patients with gynecological malignancy ranged between 3% and 25% and was affected by several patient and tumor factors. Duplex ultrasonography is currently the first-line imaging modality for deep venous thrombosis with sensitivity and specificity of up to 95% and 100%, respectively. Low-molecular-weight heparin is currently the VTE prophylaxis and treatment of choice for patients with gynecological malignancy, although warfarin and unfractionated heparin play a role in selected circumstances. The relatively new direct oral anticoagulants including factor Xa inhibitors and direct thrombin inhibitors are increasingly being used, although further evaluations are required, particularly in cancer patients. Catheter-directed thrombolysis and percutaneous mechanical and surgical thrombectomy may have a role in treating patients with severe symptomatic iliocaval or iliofemoral deep venous thrombosis. Overall, VTE is a poor prognosis marker in patients with gynecological malignancy., Conclusions: Gynecological malignancy-associated VTE is associated with significant morbidity, contributing to a large number of life years lost. Although promising new therapies are emerging, a 2-pronged approach is required to simultaneously target cancer-specific management and predict early on those who are likely to be affected. In the meantime, clinicians should continue to combine current guidelines with a multidisciplinary team approach to ensure that these complex patients receive the best evidence-based and compassionate care.

Background: Varicose 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., Methods: A 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., Results: Some 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., Conclusion: Incompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)