Vascular Registries Contributing to VASCUNET Collaborative Abdominal Aortic Aneurysm Outcome Projects: A Scoping Review.

OBJECTIVE: Vascular surgery registries report on procedures and outcomes to promote patient safety and drive quality improvement. International registries have significantly contributed to the VASCUNET collaborative abdominal aortic aneurysm (AAA) outcome projects. This scoping review aimed to outline the national registries in vascular surgery that currently participate in the VASCUNET collaborative AAA projects. METHODS: A scoping review of all published VASCUNET AAA studies and validation reports between 1997 and 2024 was undertaken. A survey was conducted among representatives of the international vascular registries contributing to VASCUNET collaborative AAA projects. RESULTS: Currently, vascular registries from 10 countries (Australia, Denmark, Finland, Hungary, Iceland, New Zealand, Norway, Sweden, Switzerland, and the UK) contribute to the current VASCUNET collaborative AAA project, of which eight have national coverage. In the past, three countries (Germany, Malta, and Italy) have participated in previous VASCUNET AAA projects, and a further three countries (Serbia, Greece, and Portugal) have planned participation in future projects. External validity is high for all current registries, with most reporting rates of > 90%. The majority have internal validation processes to assess data accuracy. VASCUNET mediated validation has also been performed by the consortium for five countries to date (Hungary, Sweden, Denmark, Malta, and Switzerland), for which a high degree of external and internal validity was identified. Most registries have established mechanisms for data linkage with national administrative datasets or insurance claims datasets, and contribute to quality improvement through regular reporting to participating centres. CONCLUSION: National vascular registries from nations participating in the VASCUNET collaborative AAA projects are largely comprehensive, with high case ascertainment rates and good quality data with internal quality assurance. This provides a template for new registries wishing to join the VASCUNET collaboration and a benchmark for future research.

Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a systemic, inflammatory vasculitis primarily affecting people over the age of 50 years. GCA is treated as a medical emergency due to the potential for sudden, irreversible visual loss. Temporal artery biopsy (TAB) is one of the five criteria of the American College of Rheumatology (ACR) 1990 classification, which is used to aid the diagnosis of GCA. TAB is an invasive test, and it can be slow to obtain a result due to delays in performing the procedure and the time taken for histopathologic assessment. Temporal artery ultrasonography (US) has been demonstrated to show findings in people with GCA such as the halo sign (a hypoechoic circumferential wall thickening due to oedema), stenosis or occlusion that can help to confirm a diagnosis more swiftly and less invasively, but requiring more subjective interpretation. This review will help to determine the role of these investigations in clinical practice. OBJECTIVES: To evaluate the sensitivity and specificity of the halo sign on temporal artery US, using the ACR 1990 classification as a reference standard, to investigate whether US could be used as triage for TAB. To compare the accuracy of US with TAB in the subset of paired studies that have obtained both tests on the same patients, to investigate whether it could replace TAB as one of the criteria in the ACR 1990 classification. SEARCH METHODS: We used standard Cochrane search methods for diagnostic accuracy. The date of the search was 13 September 2022. SELECTION CRITERIA: We included all participants with clinically suspected GCA who were investigated for the presence of the halo sign on temporal artery US, using the ACR 1990 criteria as a reference standard. We included studies with participants with a prior diagnosis of polymyalgia rheumatica. We excluded studies if participants had had two or more weeks of steroid treatment prior to the investigations. We also included any comparative test accuracy studies of the halo sign on temporal artery US versus TAB, with use of the 1990 ACR diagnostic criteria as a reference standard. Although we have chosen to use this classification for the purpose of the meta-analysis, we accept that it incorporates unavoidable incorporation bias, as TAB is itself one of the five criteria. This increases the specificity of TAB, making it difficult to compare with US. We excluded case-control studies, as they overestimate accuracy, as well as case series in which all participants had a prior diagnosis of GCA, as they can only address sensitivity and not specificity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion in the review. They extracted data using a standardised data collection form and employed the QUADAS-2 tool to assess methodological quality. As not enough studies reported data at our prespecified halo threshold of 0.3 mm, we fitted hierarchical summary receiver operating characteristic (ROC) models to estimate US sensitivity and also to compare US with TAB. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: Temporal artery ultrasound was investigated in 15 studies (617 participants with GCA out of 1479, 41.7%), with sample sizes ranging from 20 to 381 participants (median 69). There was wide variation in sensitivity with a median value of 0.78 (interquartile range (IQR) 0.45 to 0.83; range 0.03 to 1.00), while specificity was fair to good in most studies with a median value of 0.91 (IQR 0.78 to 1.00; range 0.40 to 1.00) and four studies with a specificity of 1.00. The hierarchical summary receiver operating characteristic (HSROC) estimate of sensitivity (95% confidence interval (CI)) at the high specificity of 0.95 was 0.51 (0.21 to 0.81), and 0.84 (0.58 to 0.95) at 0.80 specificity. We considered the evidence on sensitivity and specificity as of very low certainty due to risk of bias (-1), imprecision (-1), and inconsistency (-1). Only four studies reported data at a halo cut-off > 0.3 mm, finding the following sensitivities and specificities (95% CI): 0.80 (0.56 to 0.94) and 0.94 (0.81 to 0.99) in 55 participants; 0.10 (0.00 to 0.45) and 1.00 (0.84 to 1.00) in 31 participants; 0.73 (0.54 to 0.88) and 1.00 (0.93 to 1.00) in 82 participants; 0.83 (0.63 to 0.95) and 0.72 (0.64 to 0.79) in 182 participants. Data on a direct comparison of temporal artery US with biopsy were obtained from 11 studies (808 participants; 460 with GCA, 56.9%). The sensitivity of US ranged between 0.03 and 1.00 with a median of 0.75, while that of TAB ranged between 0.33 and 0.92 with a median of 0.73. The specificity was 1.00 in four studies for US and in seven for TAB. At high specificity (0.95), the sensitivity of US and TAB were 0.50 (95% CI 0.24 to 0.76) versus 0.80 (95% CI 0.57 to 0.93), respectively, and at low specificity (0.80) they were 0.73 (95% CI 0.49 to 0.88) versus 0.92 (95% CI 0.69 to 0.98). We considered the comparative evidence on the sensitivity of US versus TAB to be of very low certainty because specificity was overestimated for TAB since it is one of the criteria used in the reference standard (-1), together with downgrade due to risk of bias (-1), imprecision (-1), and inconsistency (-1) for both sensitivity and specificity. AUTHORS' CONCLUSIONS: There is limited published evidence on the accuracy of temporal artery US for detecting GCA. Ultrasound seems to be moderately sensitive when the specificity is good, but data were heterogeneous across studies and either did not use the same halo thickness threshold or did not report it. We can draw no conclusions from accuracy studies on whether US can replace TAB for diagnosing GCA given the very low certainty of the evidence. Future research could consider using the 2016 revision of the ACR criteria as a reference standard, which will limit incorporation bias of TAB into the reference standard.

Cost Effectiveness of Early Endovenous Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis in the United Kingdom.

OBJECTIVE: Early clot removal using endovascular intervention aims to reduce post-thrombotic syndrome (PTS) following iliofemoral deep venous thrombosis (DVT). This may reduce long term morbidity but incurs a higher initial cost. This study examined the cost effectiveness of catheter directed thrombolysis (CDT) and pharmacochemical thrombectomy (PMT) compared with oral anticoagulation (OAC) alone for treatment of acute iliofemoral DVT in the United Kingdom. METHODS: A combined decision tree (acute DVT complications) and Markov model (long term complications [PTS]) was used for decision analytic modelling with five states: no PTS, mild PTS, moderate PTS, severe PTS, and dead. All patients started with acute DVT. Patients who survived acute complications transitioned into the Markov model. Cycle time was six months. A healthcare payer perspective and lifetime horizon was used, adjusting for excess mortality due to history of thrombosis. Data for probabilities, transition probabilities, mortality, and utilities were obtained from the published literature. Cost data were obtained from UK NHS tariffs and published literature. Outcomes were mean lifetime cost, quality adjusted life years (QALYs), and cost effectiveness. RESULTS: Over a patient's lifetime, OAC was more costly (£37 206) than CDT (£32 043) and PMT (£36 288). Mean lifetime QALYs for OAC (12.9) were lower than CDT (13.5) and PMT (13.3). Therefore, in the incremental cost effectiveness analysis, both CDT and PMT were dominant: CDT was less costly (-£5 163) and more effective (+0.6 QALYs) than OAC, and PMT was also less costly (-£917) and more effective (+0.3 QALYs) than OAC. Results were robust to univariable sensitivity analyses, but probabilistic sensitivity analyses suggested considerable parameter uncertainty. CONCLUSION: Early interventional treatment of iliofemoral DVT is cost effective in the UK. Future clinical and epidemiological studies are needed to characterise parameter uncertainty. Further analysis of modern practice, alternative treatments, and optimised care models is warranted.

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

BACKGROUND: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. METHODS: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. RESULTS: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. CONCLUSIONS: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Sex-specific differences in the standard of care for infrarenal abdominal aortic aneurysm repair, and risk of major adverse cardiovascular events and death.

BACKGROUND: This study investigated whether sex-specific differences in preoperative/perioperative standard of care (SOC) account for disparity in outcomes after elective infrarenal abdominal aortic aneurysm repair. METHODS: This was a retrospective cohort study of elective infrarenal abdominal aortic aneurysm repairs (2013-2020) using depersonalized patient-level National Vascular Registry data. SOC was defined for waiting times, preoperative assessment (multidisciplinary/anaesthetic review), cardiovascular risk prevention, and perioperative medication. The primary outcome was major cardiovascular event and/or death (MACED). RESULTS: Some 21 810 patients with an infrarenal abdominal aortic aneurysm were included, 2380 women and 19 430 men. Women less often underwent aneurysm repair within SOC waiting times (51.5 versus 59.3 per cent; P < 0.001), but were equally likely to receive preoperative assessment (72.1 versus 72.5 per cent; P = 0.742). Women were less likely to receive secondary prevention for known cardiac disease (34.9 versus 39.6 per cent; P = 0.015), but more often met overall cardiovascular risk prevention standards (52.1 versus 47.3 per cent; P < 0.001). Women were at greater risk of MACED (open: 12.0 versus 8.9 per cent, P < 0.001; endovascular: 4.9 versus 2.9 per cent, P < 0.001; risk-adjusted OR 1.33, 95 per cent c.i. 1.12 to 1.59). A significant reduction in the odds of MACED was associated with preoperative assessment (OR 0.86, 0.75 to 0.98) and SOC waiting times (OR 0.78, 0.69 to 0.87). There was insufficient evidence to confirm a significant sex-specific difference in the effect of SOC preoperative assessment (women: OR 0.69, 0.50 to 0.97; men: OR 0.89, 0.77 to 1.03; interaction P = 0.170) or SOC waiting times (women: OR 0.84, 0.62 to 1.16; men: OR 0.76, 0.67 to 0.87; interaction P = 0.570) on the risk of MACED. CONCLUSION: SOC waiting times and preoperative assessment were not met for both sexes, which was associated with an increased risk of MACED. Sex-specific differences in SOC attenuated but did not fully account for the increased risk of MACED in women.

Risk factors and classification of reintervention following deep venous stenting for acute iliofemoral deep vein thrombosis.

BACKGROUND: Acute iliofemoral deep vein thrombosis (DVT) is associated with the development of post-thrombotic syndrome (PTS). Thrombolysis and deep venous stenting can restore vessel outflow and can reduce the incidence of PTS. However, for a proportion of patients, subsequent stenosis or reocclusion will necessitate further intervention. In the present study, we aimed to identify the risk factors, examine the outcomes (reintervention success and PTS), and develop a classification system for reintervention. METHODS: A retrospective single-center cohort study of patients who had undergone successful lysis for iliofemoral DVT from 2013 to 2017. The patients' records and imaging studies were examined for demographics, risk factors, extent of thrombus and vessel clearance, stenting, flow, reintervention, anticoagulation compliance, Villalta score, and secondary patency. From our findings, a system of classification for patients for whom procedures have failed was developed, constituting technical, hematologic, flow related, or multiple factors. RESULTS: Of 143 limbs (133 patients), 48 (33.6%) had required reintervention, of which 25 had presented with reocclusion (17.4%). The median time to reintervention was 45 days. The need for reintervention was associated with inferior vena cava thrombus (risk ratio [RR], 2.16; P < .01), stenting across the inguinal ligament (RR, 2.08; P < .01), and anticoagulation noncompliance (RR, 7.09; P < .01). Successful reintervention was achieved in 31 limbs (64.6%): 23 of 23 (100%) treated before occlusion vs 8 of 25 (36.4%) treated after occlusion (RR, 32.31; P < .01). A greater incidence of any PTS was observed for patients requiring reintervention (median Villalta score, 3 [interquartile range, 1-5]; vs 1 [interquartile range, 1-4]; RR, 2.28; P = .029). Cases without complete vessel occlusion (reintervention and control) had a lower rate of any PTS (14.0% vs 42.9%; RR, 3.06; P < .01) and moderate to severe PTS (3.0% vs 14.3%; RR, 4.76; P = .046) Technical issues were observed in 54.2% of reintervention cases and 6.3% of cases not requiring reintervention (P < .01). Hematologic issues were identified in 33.3% of reintervention cases and 1.1% of cases not requiring reintervention (P < .01). Flow-related issues were observed in 43.8% of the reintervention cases and no cases not requiring reintervention (P < .01). Of the reintervention cases, 27.1% were multifactorial and were associated with a lower rate of vessel salvage; however, this did not translate into a significant difference in secondary patency on survival analysis (RR, 1.70; P = .429). CONCLUSIONS: A large proportion of patients required reintervention because of potentially preventable factors. Anticoagulation compliance, thrombus burden, and poor flow are important risk factors to consider in patient selection. Reintervention increased the risk of PTS and was more often successful when achieved before vessel occlusion.

Editor's Choice - Systematic Review and Meta-Analysis of Sex Specific Differences in Adverse Events After Open and Endovascular Intact Abdominal Aortic Aneurysm Repair: Consistently Worse Outcomes for Women.

OBJECTIVE: Previously, reports have shown that women experience a higher mortality rate than men after elective open (OAR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With recent improvements in overall AAA repair outcomes, this study aimed to identify whether sex specific disparity has been ameliorated by modern practice, and to define sex specific differences in peri- and post-operative complications and pre-operative status; factors which may contribute to poor outcome. METHODS: This was a systematic review, meta-analysis, and meta-regression of sex specific differences in 30 day mortality and complications conducted according to PRISMA guidance (Prospero registration CRD42020176398). Papers with ≥ 50 women, reporting sex specific outcomes, following intact primary AAA repair, from 2000 to 2020 worldwide were included; with separate analyses for EVAR and OAR. Data sources were Medline, Embase, and CENTRAL databases 2005 - 2020 searched using ProQuest Dialog. RESULTS: Twenty-six studies (371 215 men, 65 465 women) were included. Meta-analysis and meta-regression indicated that sex specific odds ratios (ORs) for 30 day mortality were unchanged from 2000 to 2020. Mortality risk was higher in women for OAR and more so for EVAR (OR [95% CI] 1.49 [1.37 - 1.61]; 1.86 [1.59 - 2.17], respectively) and this remained following multivariable risk adjustment. Transfusion, pulmonary complications, and bowel ischaemia were more common in women after OAR and EVAR (OAR: ORs 1.81 [1.60 - 2.04], 1.40 [1.28 - 1.53], 1.54 [1.36 - 1.75]; EVAR: ORs 2.18 [2.08 - 2.29] 1.44 [1.17 - 1.77], 1.99 [1.51 - 2.62], respectively). Arterial injury, limb ischaemia, renal and cardiac complications were more common in women after EVAR (ORs 3.02 [1.62 - 5.65], 2.13 [1.48 - 3.06], 1.46 [1.22 - 1.72] and 1.19 [1.03 - 1.37], respectively); the latter was associated with greater mortality risk on meta-regression. CONCLUSION: Increased mortality risk for women following AAA repair remains. Women had a higher incidence of transfusion, pulmonary and bowel complications after EVAR and OAR. Higher mortality risk ratios for EVAR may result from cardiac complications, additional arterial injury, and embolisation, leading to renal and limb ischaemia. These findings indicate possible causes for observed outcome disparities and targets for quality improvement.

Quality of life outcomes for patients undergoing venous stenting for chronic deep venous disease.

OBJECTIVE: The objective of the study was to evaluate change in venous disease-specific quality of life (QoL) after iliac vein stenting for chronic venous outflow obstruction. METHODS: We performed a retrospective analysis of all Venous Insufficiency Epidemiological and Economic Study - Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaires completed at a single-center between 2016 and 2019 by patients treated with iliac vein stenting for chronic venous outflow obstruction. Patients were asked to complete the questionnaire at baseline (before stenting) and at subsequent follow-up appointments (after stenting), at 6, 12, 24, and 36 months. The Villalta score was recorded by a venous nurse specialist. The initial unpaired analysis compared all completed VEINES-QoL/Sym and Villalta scores at baseline to all follow-up time-points, and then compared them individually between baseline and each follow-up point. A secondary paired analysis included data only from patients who had completed the questionnaire at baseline and at least one follow-up. RESULTS: A total of 385 questionnaires from 187 patients who completed the VEINES-QoL/Sym between 2016 and 2019 were included. The median follow-up was 12 months, 127 patients (68%) were female, and 148 (79%) were treated for post-thrombotic syndrome. The median VEINES-QoL score at baseline was 35.69 (interquartile range [IQR], 20.85-46.67). Significant improvement was observed postoperatively and sustained throughout the study period (6 months, 64.81 [IQR, 38.12-83.88]; 12 months, 60.52 [IQR, 33.6-82.3]; 24 months, 60.37 [IQR, 34.31-80.65]; 36 months, 55.98 [IQR, 39.18-81.47]). The VEINES-Sym scores demonstrated similar improvement. A secondary analysis of paired baseline/follow-up data from 61 patients confirmed significant improvement from baseline for VEINES-QoL (6 months +26.45; 12 months, +25.81; 24 months, +30.09; P ≤ .0001), VEINES-Sym (6 months, +23.86; 12 months, +20.43; 24 months, +27.55; P > .001), and Villalta scores (6 months, -3.7; 12 months, -4.2; 24 months, -6.4; P < .0001). The median Villalta score was 14 (IQR, 10-16). This score improved to 9 (IQR, 5-13) at 6 months of follow-up; to 8 (IQR, 5-11) at 12 months; to 7 (IQR, 4-12) at 24 months; and to 6 (IQR, 3.75-10.25) at 36 months (P ≤ .0001). Good correlation between the Villalta and both VEINES-QoL and SYM scores was observed at follow-up (r = 0.69 and r = 0.71, respectively; P < .0001). CONCLUSIONS: Venous disease-specific QoL improves and severity of post-thrombotic syndrome is decreased after iliac vein stenting for chronic venous outflow obstruction. These improvements are sustained at 36-month follow-up.

AngioJet Pharmacomechanical Thrombectomy and Catheter Directed Thrombolysis vs. Catheter Directed Thrombolysis Alone for the Treatment of Iliofemoral Deep Vein Thrombosis: A Single Centre Retrospective Cohort Study.

OBJECTIVE: Percutaneous thrombus removal is used for the treatment of iliofemoral deep vein thrombosis (DVT), but the efficacy of different treatment modalities has not yet been determined. The aim of this study was to compare the outcomes of patients treated with additional AngioJet pharmacomechanical thrombectomy (PCDT) vs. catheter directed lysis (CDT) alone. METHODS: A retrospective review of all patients who received thrombolysis for the treatment of symptomatic acute iliofemoral DVT between 2011 and 2017 was carried out. Outcome measures included the incidence of post-thrombotic syndrome (PTS), procedural outcomes (lytic exposure), the incidence of complications, and vessel patency. All patients were followed up for a minimum of one year. RESULTS: A total of 151 limbs were treated, 70 limbs with PCDT and 81 limbs with CDT alone. Demographic data and prevalence of risk factors were comparable. Incidence of PTS (Villalta score at one year) showed no significant difference (22.2% PCDT vs. 24.7% CDT alone, p = .74). Use of PCDT resulted in a non-statistically significant trend for fewer bleeds (n = 4/63 [6.3%] vs. 13/76 [17.1%]; relative risk 0.37, 95% confidence interval [CI] 0.13-1.08; p = .07), a statistically significant reduction in lysis duration (40 h [95% CI 34-46] vs. 53 h [95% CI 49-58]; p < .001) and a reduction in lytic dose (49 mg [95% CI 42-55] vs. 57 mg [95% CI 52-61]; p = .011) compared with CDT. This reduction was accentuated in 24 cases primarily treated with AngioJet PowerPulse mode (27 h, 95% CI 20-34 [p < .001] and 42 mg, 95% CI 34-50 [p = .009]). Incidences of complications were comparable between groups, with one death due to an intracranial haemorrhage following CDT. Although the incidence of haemoglobinuria was increased following PCDT (12/63 [19.0%] vs. 3/76 [3.9%]; p = .006), no significant difference in acute kidney injury was observed (3/63 [4.8%] vs. 1/76 [1.3%]; p = .33). No significant difference in vessel patency over two years was observed (p = .73). CONCLUSION: The use of PCDT for the treatment of iliofemoral DVT was observed to provide comparable patient outcomes, comparable vessel patency, an acceptable safety profile, and reduced overall lytic dose.

Colorectal carcinogenesis: an archetype of gut microbiota-host interaction.

Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia?