An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression.

BACKGROUND: IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). METHODS: Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. RESULTS: There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (ß=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. CONCLUSIONS: Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

Vascular handlebar syndrome with blunt injury of common femoral artery.

Vascular handlebar syndrome with blunt injury of the common femoral artery is a rare vascular trauma mechanism, with high possibility of being missed or delayed. We present two cases of vascular handlebar syndrome treated in our hospital and a systematic review of the literature using MEDLINE and SCOPUS databases. Literature review identified 20 similar cases. The median age of patients was 18 years, and in vast majority males in gender. In most cases, the common femoral artery injury was an intimal flap and lumen occlusion with intramural thrombosis followed by transection and intimal injury without occlusion or thrombosis. The median time between injury and diagnosis/treatment was half an hour. Clinical presentation ranged from asymptomatic to acute limb ischemia. The grade of acute ischemia was mostly Rutherford class I (n=14), while acute IIa (n=4), chronic ischemia (n=3), and no ischemia (n=1) were also noticed. The correct diagnosis was revealed by clinical examination only (n=1), or by the combination of clinical and imaging techniques including computed tomography angiography (n=7) and duplex ultrasonography (n=4) or both (n=10). Management of the handlebar trauma syndrome injuries was surgical in most cases. Outcome was favorable in all patients. Vascular handlebar syndrome is extremely rare and high suspicion is required for early diagnosis and definitive treatment, as the early management is effective and crucial for averting the devastating consequences. An individualized approach to the vascular trauma patient is to be applied with considerations taken to the age of the patient, the mechanism of the injury, the anatomy of the lesion, and symptomatology of the case.

A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.

OBJECTIVE: Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease. METHODS: A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. RESULTS: There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes. CONCLUSION: ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.

Antithrombotic Therapy for Aortic Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVES: The role of antithrombotic therapy in the management of aortic and peripheral aneurysms is unclear. This systematic review and meta-analysis aimed to assess the impact of antithrombotics on clinical outcomes for aortic and peripheral aneurysms. METHODS: Medline, Embase, and CENTRAL databases were searched. Randomised controlled trials and observational studies investigating the effect of antithrombotic therapy on clinical outcomes for patients with any aortic or peripheral artery aneurysm were included. RESULTS: Fifty-nine studies (28 with antiplatelet agents, 12 anticoagulants, two intra-operative heparin, and 16 any antithrombotic agent) involving 122 102 patients were included. Abdominal aortic aneurysm (AAA) growth rate was not significantly associated with the use of antiplatelet therapy (SMD -0.36 mm/year; 95% CI -0.75 - 0.02; p = .060; GRADE certainty: very low). Antithrombotics were associated with increased 30 day mortality for patients with AAAs undergoing intervention (OR 2.30; 95% CI 1.51 - 3.51; p < .001; GRADE certainty: low). Following intervention, antiplatelet therapy was associated with reduced long term all cause mortality (HR 0.84; 95% CI 0.76 - 0.92; p < .001; GRADE certainty: moderate), whilst anticoagulants were associated with increased all cause mortality (HR 1.64; 95% CI 1.14 - 2.37; p = .008; GRADE certainty: very low), endoleak within three years (OR 1.99; 95% CI 1.10 - 3.60; p = .020; I2 = 60%; GRADE certainty: very low), and an increased re-intervention rate at one year (OR 3.25; 95% CI 1.82 - 5.82; p < .001; I2 = 35%; GRADE certainty: moderate). Five studies examined antithrombotic therapy for popliteal aneurysms. Meta-analysis was not possible due to heterogeneity. CONCLUSIONS: There was a lack of high quality data examining antithrombotic therapy for patients with aneurysms. Antiplatelet therapy was associated with a reduction in post-intervention all cause mortality for AAA, whilst anticoagulants were associated with an increased risk of all cause mortality, endoleak, and re-intervention. Large, well designed trials are still required to determine the therapeutic benefits of antithrombotic agents in this setting.

Editor's Choice - European Society for Vascular Surgery Clinical Practice Guideline Development Scheme: An Overview of Evidence Quality Assessment Methods, Evidence to Decision Frameworks, and Reporting Standards in Guideline Development.

OBJECTIVE: A structured and transparent approach is instrumental in translating research evidence to health recommendations and evidence informed clinical decisions. The aim was to conduct an overview and analysis of principles and methodologies for health guideline development. METHODS: A literature review on methodologies, strategies, and fundamental steps in the process of guideline development was performed. The clinical practice guideline development process and methodology adopted by the European Society for Vascular Surgery are also presented. RESULTS: Sophisticated methodologies for health guideline development are being applied increasingly by national and international organisations. Their overarching principle is a systematic, structured, transparent, and iterative process that is aimed at making well informed healthcare choices. Critical steps in guideline development include the assessment of the certainty of the body of evidence; evidence to decision frameworks; and guideline reporting. The goal of strength of evidence assessments is to provide well reasoned judgements about the guideline developers' confidence in study findings, and several evidence hierarchy schemes and evidence rating systems have been described for this purpose. Evidence to decision frameworks help guideline developers and users conceptualise and interpret the construct of the quality of the body of evidence. The most widely used evidence to decision frameworks are those developed by the GRADE Working Group and the WHO-INTEGRATE, and are structured into three distinct components: background; assessment; and conclusions. Health guideline reporting tools are employed to ensure methodological rigour and transparency in guideline development. Such reporting instruments include the AGREE II and RIGHT, with the former being used for guideline development and appraisal, as well as reporting. CONCLUSION: This guide will help guideline developers/expert panels enhance their methodology, and patients/clinicians/policymakers interpret guideline recommendations and put them in context. This document may be a useful methodological summary for health guideline development by other societies and organisations.

Superficialization Methods of Arteriovenous Fistula in Obese Patients: A Review of the Literature.

BACKGROUND: The creation of an arteriovenous fistula in obese patients with end-stage-renal-disease, might not lead to a successful hemodialysis session, partly due to excess adipose tissue overlapping the enlarged vein. This review summarizes the available evidence on superficialization methods in studies dealing with obese patients. METHODS: An English-language literature search was undertaken in the MEDLINE/SCOPUS databases looking for publications that described procedures of salvaging autologous arteriovenous access in upper extremities of obese patients. Perioperative outcomes including technical and clinical success, mean vein depth reduction, wound complications and patency rates were compared within all identified techniques. RESULTS: We identified 12 prospective and 8 retrospective studies. A total of 1149 patients with a mean age 57.2 (range: 49-68) years and a mean BMI 35.8 (range: 28.2-40.8) kg/m2 underwent mainly radial-cephalic and brachial-cephalic arteriovenous fistula superficialization procedures [transposition, 54%; elevation, 11.1%; lipectomy, 26.1%; liposuction, 2.4%; implantation of a venous window needle guide device, 6.4%]. Technical success was similar between all methods (≥96%). However, successful cannulation was lower after liposuction and elevation (81.5% and 78.1% respectively). Transposition achieved lower mean vein depth reduction and clinical success when compared with lipectomy (4.9 mm vs. 8.8 mm and 90% vs. 92.7% respectively). Transposition and liposuction had the lowest and highest complication rate respectively (1.6% vs. 40.8%). Primary and secondary patency rates were lower with liposuction (51.8% and 76.6% respectively), while lipectomy and elevation achieved the highest primary patency rates (68.3% and 71.6% respectively) at 12 months. CONCLUSIONS: In obese patients, all superficialisation techniques report high technical success rates. Although limited by the design of individual published studies and lack of a standard for reporting outcomes, these results lead to satisfactory postoperative and early outcomes. In aggregate, lipectomy and transposition are more clinically effective and more durable procedures.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas.

OBJECTIVE: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. METHODS: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. RESULTS: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. CONCLUSIONS: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population.

A Systematic Review and Meta-analysis of Peri-Procedural Outcomes in Patients Undergoing Carotid Interventions Following Thrombolysis.

OBJECTIVE: To evaluate the safety of carotid artery stenting (CAS) and carotid endarterectomy (CEA) after thrombolytic therapy (TT). DATA SOURCES: Medline, Scopus, and Cochrane databases. REVIEW METHODS: Systematic review and meta-analysis of studies involving patients who underwent CEA/CAS after TT. RESULTS: In 25 studies (n = 147 810 patients), 2 557 underwent CEA (n = 2 076) or CAS (n = 481) following TT. After CEA, the pooled peri-procedural stroke/death rate was 5.2% (95% confidence interval [CI] 3.3 - 7.5) and intracranial haemorrhage (ICH) was 3.4% (95% CI 1.7 - 5.6). After CAS, the pooled peri-procedural stroke/death rate was 14.9% (95% CI 11.9 - 18.2) and ICH was 5.5% (95% CI 3.7 - 7.7). In case control studies comparing CEA outcomes in patients receiving TT vs. no TT, peri-procedural death/stroke was non-significantly higher after TT (4.3% vs. 1.5%; odds ratio [OR] 2.34, 95% CI 0.74 - 7.47), but ICH was significantly higher after TT (2.2% vs. 0.12%; OR 7.82, 95% CI 4.07 - 15.02), as was local haematoma formation (3.6% vs. 2.26%; OR 1.17, 95% CI 1.17 - 2.33). In case control studies comparing CAS outcomes in patients receiving TT vs. no TT, peri-procedural stroke/death was significantly higher after TT (5.2% vs. 1.5%; OR 8.49, 95% CI 2.12 - 33.95) as was ICH (5.4% vs. 0.7%; OR 7.48, 95% CI 4.69 - 11.92). Meta-regression analysis demonstrated an inverse association between the time interval from intravenous (IV) TT to undergoing CEA and the risk of peri-procedural stroke/death (p = .032). Peri-operative stroke/death was 13.0% when CEA was performed three days after TT and 10.6% when performed four days after TT, with the risk reducing to within the currently accepted 6% threshold after six-seven days had elapsed. CONCLUSION: Peri-procedural ICH and local haematoma were significantly more frequent in patients undergoing CEA after TT (vs. no TT), although there were no randomised comparisons. Peri-procedural hazards were also significantly higher for CAS after TT. The inverse relationship between timing to CEA and peri-procedural stroke/death mandates careful patient selection and suggests that it may be safer to defer CEA for six-seven days after TT.

Outcome Predictors in Civilian and Iatrogenic Arterial Trauma.

BACKGROUND: Our aim was to identify predictors of mortality and limb loss in iatrogenic and civilian arterial trauma. METHODS: Cases were identified by searching prospectively maintained registries. Multivariable logistic regression was used to identify independent outcome predictors. RESULTS: During the study period, 285 patients with arterial trauma were managed with endovascular (n = 20) or open (n = 265) repair. Iatrogenic injuries increased in frequency during the course of the study, from 23.9% during the first decade to 35.9 and 55.7% during the second and third decade, respectively (p < 0.001). Endovascular management increased in frequency during the course of the study, from 0% during the first decade to 5.1 and 11.1% during the second and third decade, respectively (p = 0.005). Mortality was 9.8%, and limb loss (in cases with injury of the aorta or limb arteries, n = 259) was 6.2%. Independent predictors of mortality included increased age (odds ratio, 95% confidence interval [OR, 95% CI] 1.05 (1.02-1.07), p < 0.001), blunt trauma (OR [95% CI] 4.8 (1.9-12.2), p = 0.001) and the number of RBC units transfused intraoperatively (OR [95% CI] 1.25 (1.1-1.4), p = 0.001). Independent predictors of limb loss included the first half of the study period (OR [95% CI] 3.9 (1.1-14.1), p = 0.04), lower extremity arterial trauma (vs upper extremity, aortic, common or external iliac artery trauma, OR [95% CI] 8.3 (1.9-35.7), p = 0.004), bone fracture (OR [95% CI] 16.9 (4.7-62.5), p < 0.001) and the number of RBC units transfused intraoperatively (OR [95% CI] 1.16 (1.02-1.33), p = 0.024). CONCLUSION: Increasingly iatrogenic in cause and managed by endovascular methods, arterial trauma remains a problem associated with significant mortality and limb loss. Identification of unfavourable outcome predictors may help clinicians involved with arterial trauma to escalate the level of care.

Predictors of Operative Mortality of 928 Intact Aortoiliac Aneurysms.

BACKGROUND: The aim of this study is to identify preoperative and intraoperative factors associated with in-hospital mortality of intact abdominal aortoiliac aneurysm repair. METHODS: In this observational study, prospectively collected information included demographics, risk factors, comorbidities, aneurysm characteristics (including special aneurysm presentation, i.e., inflammatory, mycotic/infected, aortocaval fistula), investigations, and operative variables. Receiver operating characteristic) curve analysis of the Glasgow aneurysm score (GAS) and the Vascular Study Group of New England (VSGNE) score was performed in the subgroup of bland aneurysms undergoing isolated elective repair. RESULTS: A total of 928 cases with intact aortoiliac aneurysms had an elective (n = 882) or urgent (n = 46) repair, associated with an in-hospital mortality of 1.7% and 8.7%, respectively (P = 0.01). Open repair (n = 514) was a predictor of higher mortality (3.3% vs. 0.5% for endovascular aneurysm repair [EVAR], n = 414, odds ratio [OR] 7.1, P = 0.003), and so was the pre-EVAR era (4.8% vs. 1.3% in the EVAR era, OR 4.0, P = 0.004). Other significant predictors included the presence of abdominal/back pain (7.5% vs. 1.3%, OR = 6.0, P = 0.001), preoperative angiography (7% vs. 1.6%, OR = 4.5, P = 0.01), special aneurysm presentation (10.9% vs. 1.5%, OR = 8.1, P < 0.001), concomitant major procedures (19% vs. 1.7%, OR = 14.0, P < 0.001), serious intraoperative complications (9.1% vs. 1.5%, OR = 6.6, P = 0.001), median number of transfused units of blood intraoperatively (2 and 0 for cases with and without mortality, respectively, P < 0.001), and procedure duration (270 and 150 min for cases with and without mortality, respectively, P < 0.001). Open repair (OR = 4.5, P = 0.05), special aneurysm presentation (OR = 6.58, P = 0.001), and concomitant major procedures (OR = 14.3, P < 0.001) were independent predictors of higher mortality. ROC curve analysis for the GAS (P = 0.87) and VSGNE score (P = 0.10) failed to demonstrate statistical significance in the subgroup of bland aneurysms undergoing isolated elective repair. CONCLUSIONS: Our study has demonstrated independent risk factors for mortality, which should be considered when contemplating aortoiliac aneurysm repair. We failed to externally validate the GAS and VSGNE score.

Validation of the 3D SYM VEIN Symptom Assessment Tool.

OBJECTIVE: The aim was to validate the SYM VEIN consensus 3D scoring tool in chronic venous disease (CVD). METHODS: This was a prospective cohort study with a total of 35 consecutive patients with CVD. Patients with CVD undergoing saphenectomy were assessed with the revised Venous Clinical Severity Score (r-VCSS), the CIVIQ-20 quality of life score questionnaire, and the SYM VEIN consensus statement 3D system, pre-operatively and four weeks post-operatively. The total 3D score was tested for reliability, construct validity, and responsiveness. RESULTS: The total 3D score demonstrated good reliability and internal consistency (Cronbach's alpha 0.85). Principal component analysis identified three groups of symptoms (paraesthesia, burning pain, and pruritus, vs. heaviness, sensation of swelling and aching/pain, vs. restless leg and throbbing pain) demonstrating a high intragroup correlation and likely to share similar pathophysiology, indicative of adequate construct validity. The total 3D score showed a significant correlation with r-VCSS and CIVIQ-20 score (rho .46, p = .005 and rho .65, p < .001, respectively) indicative of adequate convergent validity. After saphenectomy, significant reductions (p < .001) of the total 3D, and 3D scores for all but two individual venous symptoms were observed, indicative of excellent responsiveness. Median total 3D score was reduced from 31 to 6 (83.8% decrease, p < .001), median r-VCSS was reduced from 6 to 0 (100% decrease, p < .001), and median CIVIQ-20 score was reduced from 24 to 14 (40% decrease, p < .001). The difference of median percentage change between r-VCSS and CIVIQ-20 score vs. total 3D score was significant (p = .005 and p < .001, respectively). CONCLUSION: The total SYM VEIN 3D score has good reliability, construct validity and excellent responsiveness, although less prone to change after saphenectomy compared with r-VCSS.

Treatment of distal deep vein thrombosis.

BACKGROUND: The treatment of distal (below the knee) deep vein thrombosis (DVT) is not clearly established. Distal DVT can either be treated with anticoagulation, or monitored with close follow-up to detect progression to the proximal veins (above the knee), which requires anticoagulation. Proponents of this monitoring strategy base their decision to withhold anticoagulation on the fact that progression is rare and most people can be spared from potential bleeding and other adverse effects of anticoagulation. OBJECTIVES: To assess the effects of different treatment interventions for people with distal (below the knee) deep vein thrombosis (DVT). SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 12 February 2019. We also undertook reference checking to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) for the treatment of distal DVT. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. We resolved disagreements by discussion. Primary outcomes of interest were recurrence of venous thromboembolism (VTE), DVT and major bleeding and follow up ranged from three months to two years. We performed fixed-effect model meta-analyses with risk ratio (RRs) and 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified eight RCTs reporting on 1239 participants. Five trials randomised participants to anticoagulation for up to three months versus no anticoagulation. Three trials compared anticoagulation treatment for different time periods. Anticoagulant compared to no intervention or placebo for distal DVT treatment Anticoagulation with a vitamin K antagonist (VKA) reduced the risk of recurrent VTE during follow-up compared with participants receiving no anticoagulation (RR 0.34, 95% CI 0.15 to 0.77; 5 studies, 496 participants; I2 = 3%; high-certainty evidence), and reduced the risk of recurrence of DVT (RR 0.25, 95% CI 0.10 to 0.67; 5 studies, 496 participants; I2 = 0%; high-certainty evidence). There was no clear effect on risk of pulmonary embolism (PE) (RR 0.81, 95% CI 0.18 to 3.59; 4 studies, 480 participants; I2 = 0%; low-certainty evidence). There was little to no difference in major bleeding with anticoagulation compared to placebo (RR 0.76, 95% CI 0.13 to 4.62; 4 studies, 480 participants; I2 = 26%; low-certainty evidence). There was an increase in clinically relevant non-major bleeding events in the group treated with anticoagulants (RR 3.34, 95% CI 1.07 to 10.46; 2 studies, 322 participants; I2 = 0%; high-certainty evidence). There was one death, not related to PE or major bleeding, in the anticoagulation group. Anticoagulation for three months or more compared to anticoagulation for six weeks for distal DVT treatment Three RCTs of 736 participants compared three or more months of anticoagulation with six weeks of anticoagulation. Anticoagulation with a VKA for three months or more reduced the incidence of recurrent VTE to 5.8% compared with 13.9% in participants treated for six weeks (RR 0.42, 95% CI 0.26 to 0.68; 3 studies, 736 participants; I2 = 50%; high-certainty evidence). The risk for recurrence of DVT was also reduced (RR 0.32, 95% CI 0.16 to 0.64; 2 studies, 389 participants; I2 = 48%; high-certainty evidence), but there was probably little or no difference in PE (RR 1.05, 95% CI 0.19 to 5.88; 2 studies, 389 participants; I2 = 0%; low-certainty evidence). There was no clear difference in major bleeding events (RR 3.42, 95% CI 0.36 to 32.35; 2 studies, 389 participants; I2 = 0%; low-certainty evidence) or clinically relevant non-major bleeding events (RR 1.76, 95% CI 0.90 to 3.42; 2 studies, 389 participants; I2 = 1%; low-certainty evidence) between three months or more of treatment and six weeks of treatment. There were no reports for overall mortality or PE and major bleeding-related deaths. AUTHORS' CONCLUSIONS: Our review found a benefit for people with distal DVT treated with anticoagulation therapy using VKA with little or no difference in major bleeding events although there was an increase in clinically relevant non-major bleeding when compared to no intervention or placebo. The small number of participants in this meta-analysis and strength of evidence prompts a call for more research regarding the treatment of distal DVT. RCTs comparing different treatments and different treatment periods with placebo or compression therapy, are required.

Improved effectiveness of the repositionable GORE EXCLUDER AAA endoprosthesis featuring the C3 delivery system compared with the original GORE EXCLUDER AAA endoprosthesis for within the instructions for use treatment of aortoiliac aneurysms.

OBJECTIVE: To compare two endograft types, the original GORE EXCLUDER AAA endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz) with the repositionable GORE EXCLUDER featuring the C3 delivery system, which allows repositioning of the proximal part of the graft to achieve accurate placement in relation to the renal arteries, in unselected patients with aortoiliac aneurysms. In a second nested, substudy we investigated the relative effect of the standard Gore and Gore Dryseal introducer sheaths on intraoperative transfusion needs. METHODS: We retrospectively analyzed prospectively collected information. The primary composite outcome measure was the intraoperative misdeployment or migration of the endograft's main body, proximally or distally to the renals (leading to technical failure or requiring either placement of aortic cuff extenders or conversion to open repair). Secondary outcome measures included the composite long-term event of rupture and/or type I/III endoleak. RESULTS: A total of 313 consecutive patients (303 males; median age, 73 years) had either an original GORE EXCLUDER device (n = 174) or the new device (n = 139) placed between 2004 and 2011 and 2011 and 2017, respectively, to treat an infrarenal aortoiliac aneurysm or an isolated common iliac artery aneurysm. The primary composite outcome measure occurred more often in patients who had the original GORE EXCLUDER device placed (10.9% vs 3.6% for the new device; odds ratio, 0.30; 95% confidence interval, 0.11-0.84; P = .016), confirmed by multivariate logistic regression analysis. This difference between the two groups was exclusively driven by distal misdeployment or migration of the endograft (10.3% vs 2.9% for the new device; P = .01), mostly requiring aortic extender placement. Intraoperative blood transfusion rates were lower in patients who had the GORE Dryseal introducer sheath used (1.1% vs 18.9% for the original GORE introducer sheath; OR, 0.05; 95% confidence interval, 0.006-0.35; P < .001). At a mean follow-up of 1.7 years (maximum, 13 years), 11 patients developed the composite event. On univariate Cox analysis, significant predictors included female gender (P = .003), absence of dyslipidemia (P = .023), the primary outcome measure (P = .006), and failure to cannulate (P = .009), but not device type or other variables. On multivariate Cox regression, female gender (hazard ratio, 37; P < .001), chronic obstructive pulmonary disease (hazard ratio, 3.99; P = .045), the primary outcome measure of the study (hazard ratio, 8.9; P = .002), and failure to cannulate (hazard ratio, 43; P = .003) were all independent predictors. CONCLUSIONS: Our study has demonstrated that the repositionable GORE EXCLUDER has important safety characteristics compared with the original device and equivalent long-term effectiveness. Additional benefit was obtained with the use of the Gore Dryseal introducer sheath.

Editor's Choice - A Systematic Review and Meta-Analysis of the Efficacy and Safety of Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer.

OBJECTIVE/BACKGROUND: The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. METHODS: A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method. RESULTS: Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high. CONCLUSION: Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.