Management of Paget-Schroetter Syndrome: a Systematic Review and Meta-Analysis.

OBJECTIVE: Currently, there is no consensus on the optimal management of Paget-Schroetter syndrome (PSS). The objective was to summarise the current evidence for management of PSS with explicit attention to the clinical outcomes of different management strategies. DATA SOURCES: The Cochrane, PubMed, and Embase databases were searched for reports published between January 1990 and December 2021. REVIEW METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. The primary endpoint was the proportion of symptom free patients at last follow up. Secondary outcomes were success of initial treatment, recurrence of thrombosis or persistent occlusion, and patency at last follow up. Meta-analyses of the primary endpoint were performed for non-comparative and comparative reports. The quality of evidence was assessed using the GRADE approach. RESULTS: Sixty reports were included (2 653 patients), with overall moderate quality. The proportions of symptom free patients in non-comparative analysis were: anticoagulation (AC), 0.54; catheter directed thrombolysis (CDT) + AC, 0.71; AC + first rib resection (FRR), 0.80; and CDT + FRR, 0.96. Pooled analysis of comparative reports confirmed the superiority of CDT + FRR compared with AC (OR 13.89, 95% CI 1.08 - 179.04; p = .040, I2 87%, very low certainty of evidence), AC + FRR (OR 2.29, 95% CI 1.21 - 4.35; p = .010, I2 0%, very low certainty of evidence), and CDT + AC (OR 8.44, 95% CI 1.12 - 59.53; p = .030, I2 63%, very low certainty of evidence). Secondary endpoints were in favour of CDT + FRR. CONCLUSION: Non-operative management of PSS with AC alone results in persistent symptoms in 46% of patients, while 96% of patients managed with CDT + FFR were symptom free at end of follow up. Superiority of CDT + FRR compared with AC, CDT + AC, and AC + FRR was confirmed by meta-analysis. The overall quality of included reports was moderate, and the level of certainty was very low.

Feasibility of Microbubble-Accelerated Low-Dose Thrombolysis of Peripheral Arterial Occlusions Using an Ultrasound Catheter.

PURPOSE: Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models. MATERIALS AND METHODS: SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length. RESULTS: US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07-7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09-2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02-1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%-79%), and a median thrombus weight and length of 1.02 (0.96-1.43) g and 2.25 (1.5-4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model. CONCLUSION: SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions. CLINICAL IMPACT: Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models.

Editor's Choice - Post-operative Surveillance and Long Term Outcome after Endovascular Aortic Aneurysm Repair in Patients with an Initial Post-operative Computed Tomography Angiogram Without Abnormalities: the Multicentre Retrospective ODYSSEUS Study.

OBJECTIVE: Lifelong imaging surveillance is recommended following endovascular aneurysm repair (EVAR). This study aimed to examine the association between adherence to post-operative surveillance and survival and secondary interventions in patients with an initial post-operative computed tomography angiogram (CTA) without abnormalities. METHODS: All consecutive patients undergoing EVAR for intact abdominal aortic aneurysm (AAA) in 16 hospitals between 2007 and 2012 were identified retrospectively, with follow up until December 2018. Patients were included if the initial post-operative CTA showed no types I - III endoleak, kinking, infection, or limb occlusion. Discontinued follow up was defined as at least one 16 month period in which no imaging surveillance was performed. Primary outcomes were aneurysm related mortality and secondary interventions, and secondary outcome all cause mortality. Kaplan-Meier analysis was used to estimate survival, and Cox regression analyses to identify the association between independent variables and outcome. Sensitivity analyses were performed by varying the definition of continued yearly follow up. The study protocol was published (bmjopen-2019-033584). RESULTS: 1 596 patients (552 continued, 1 044 discontinued follow up) were included with a median (interquartile range) follow up of 89.1 months (52.6). Cumulative aneurysm related, overall, and intervention free survival was 99.4/94.8/96.1%, 98.5/72.9/85.9%, and 96.3/45.4/71.1% at 1, 5, and 10 years, respectively. American Society of Anesthesiologists (ASA) classification (ASA IV hazard ratio [HR] 3.810, 95% confidence interval [CI] 1.296 - 11.198), increase in AAA diameter (HR 3.299, 95% CI 1.408 - 7.729), and continued follow up (HR 3.611, 95% CI 1.780 - 7.323) were independently associated with aneurysm related mortality. The same variables and age (HR 1.063 per year, 95% CI 1.052 - 1.074) were significantly associated with all cause mortality. No difference in secondary interventions was observed between patients with continued vs. discontinued follow up (89/552; 16% vs. 136/1044; 13%; p = .091). Sensitivity analyses showed worse aneurysm related and overall survival in patients with continued follow up. CONCLUSION: Discontinued follow up is not associated with poor outcomes. Future prospective studies are indicated to determine in which patients imaging follow up can be safely reduced.

A systematic review and meta-analysis of treatment modalities for anterior accessory saphenous vein insufficiency.

OBJECTIVE: To investigate and compare the outcomes of the available treatment modalities for anterior accessory saphenous vein (AASV) incompetence. METHODS: A systematic literature search was performed in MEDLINE, Embase, and the Cochrane Library. Studies reporting the outcomes of patients who were treated for primary AASV incompetence were included. The methodologic quality of the articles was assessed using the Methodological Index for Non-Randomized Studies (MINORS). A random-effects model was used to estimate anatomic success, defined as AASV occlusion. The secondary outcomes were pain during and after treatment, venous clinical severity score, quality of life, esthetic result, time to return to daily activities, and complications. RESULTS: The search identified 860 articles, of which 16 met the inclusion criteria. A total of 609 AASVs were reported. The included studies were of poor or moderate quality according to MINORS score. The pooled anatomic success rates were 91.8% after endovenous laser ablation and radiofrequency ablation (EVLA, RFA, 11 studies), 93.6% after cyanoacrylate closure (3 studies), and 79.8% after sclerotherapy (2 studies). The non-pooled anatomic success rate was 97.9% after phlebectomy and 82% after CHIVA. Paresthesia was seen after EVLA in 0.7% of patients (6 studies). Phlebitis was seen in 2.6% of patients after RFA (2 studies), 27% after sclerotherapy (1 study), and 12% after the phlebectomy (1 study). Deep venous thrombosis and skin burn did not occur. CONCLUSION: Treatment of AASV incompetence is safe and effective. Despite limited evidence, occlusion of the AASV can be achieved with endovenous thermal ablation and cyanoacrylate. There does not appear to be a benefit of EVLA compared to RFA regarding treatment efficacy. Phlebectomy shows promising results if the saphenofemoral junction is competent. Lower results are seen after sclerotherapy and CHIVA. However, studies with sufficient sample sizes of solely treatment of AASV incompetence are needed to draw firm conclusions.

A systematic review and meta-analysis of mechanochemical endovenous ablation using Flebogrif for varicose veins.

OBJECTIVE: In the present study, we reviewed and analyzed the currently available data on the Flebogrif device (Balton, Warsaw, Poland) to define its role in the global varicose vein treatment devices market. METHODS: A systematic literature search was performed in MEDLINE, Embase, and the Cochrane Library. Studies were eligible if they had included patients treated using the Flebogrif for saphenous vein incompetence, had been reported in English, and had the full text available. The methodologic quality of the studies was assessed using the methodologic index for nonrandomized studies (MINORS) score. A random effects model was used to estimate the primary outcome of anatomic success, defined as the occlusion rate of the treated vein. The estimates are reported with the 95% confidence intervals (CIs). The secondary outcomes were clinical success, complication rate, pain during and after the procedure, and time to return to work. RESULTS: Five articles met the inclusion criteria, reporting 348 procedures in 392 patients. Four studies reported the 3-month anatomic success, and three studies reported the 12-month anatomic success. The pooled 3-month anatomic success rate was 95.6% (95% CI, 93.2%-98.0%). The 12-month anatomic success rate was 93.2% (95% CI, 90.3%-96.1%). The only major complication reported within 3 months was deep vein thrombosis, which developed in 0.3% of the patients. The minor complications of thrombophlebitis and hyperpigmentation had occurred in 13.3% to 14.5% and 3.3% to 10.0% of patients, respectively, within 3 months. The methodologic quality of the included studies was moderate. CONCLUSIONS: Mechanochemical ablation using the Flebogrif device is a safe and well-tolerated procedure for the treatment of saphenous vein insufficiency. However, well-designed studies of sufficient sample size and follow-up are required to compare the effectiveness with other endovenous treatment modalities and define the definitive role of the Flebogrif device.

Survival and Living Situation After Ruptured Abdominal Aneurysm Repair in Octogenarians.

OBJECTIVE: To determine the 30 day and one year mortality and post-operative living situation in octogenarians treated for ruptured abdominal aortic aneurysm (rAAA). METHODS: A retrospective study was performed at four centres in the Netherlands. All consecutive patients aged ≥80 years, presenting with a rAAA between January 2013 and October 2018, were included. The primary outcomes were post-operative living situation and one year mortality. RESULTS: In total, 157 patients were included. Forty-seven received palliative care and 110 patients had surgery. After endovascular or open repair, the one year mortality rate was 50.0%. The 30 day mortality rate was 40.8% (95% confidence interval [CI] 27-55) and 31.7% (95% CI 20-44), for endovascular and open repair, respectively (p = .32). Sixty-five per cent of survivors were discharged home, while 34.8% went to a nursing home for rehabilitation. Of the surviving patients, 82.6% went back to living in their pre-rupture home situation. Of the investigated variables, only a high body mass index proved a significant predictor of death at 30 days and one year. Compared with operated patients, patients turned down for surgery were older (mean age 87.5 ± 3.8 vs. 84.0 ± 3.5; p < .001), lived significantly more often in a nursing home (odds ratio 1.02, 95% CI 1.00-1.03; p < .001), were more often dependent (odds ratio 3.69, 95% CI 2.31-5.88; p < .001) and had a lower Glasgow Coma Scale score on arrival (odds ratio 0.42, 95% CI 0.25-0.69; p = .002). All palliative patients died within three days. CONCLUSION: Overall treatment outcomes showed that octogenarians should not be denied surgery based on age alone, as half of the octogenarians that undergo surgical treatment are still alive one year after rAAA repair. In addition, > 80% returned to their own home after rehabilitation.

Image Fusion During Standard and Complex Endovascular Aortic Repair, to Fuse or Not to Fuse? A Meta-analysis and Additional Data From a Single-Center Retrospective Cohort.

PURPOSE: To determine if image fusion will reduce contrast volume, radiation dose, and fluoroscopy and procedure times in standard and complex (fenestrated/branched) endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: A search of the PubMed, Embase, and Cochrane databases was performed in December 2019 to identify articles describing results of standard and complex EVAR procedures using image fusion compared with a control group. Study selection, data extraction, and assessment of the methodological quality of the included publications were performed by 2 reviewers working independently. Primary outcomes of the pooled analysis were contrast volume, fluoroscopy time, radiation dose, and procedure time. Eleven articles were identified comprising 1547 patients. Data on 140 patients satisfying the study inclusion criteria were added from the authors' center. Mean differences (MDs) are presented with the 95% confidence interval (CI). RESULTS: For standard EVAR, contrast volume and procedure time showed a significant reduction with an MD of -29 mL (95% CI -40.5 to -18.5, p<0.001) and -11 minutes (95% CI -21.0 to -1.8, p<0.01), respectively. For complex EVAR, significant reductions in favor of image fusion were found for contrast volume (MD -79 mL, 95% CI -105.7 to -52.4, p<0.001), fluoroscopy time (MD -14 minutes, 95% CI -24.2 to -3.5, p<0.001), and procedure time (MD -52 minutes, 95% CI -75.7 to -27.9, p<0.001). CONCLUSION: The results of this meta-analysis confirm that image fusion significantly reduces contrast volume, fluoroscopy time, and procedure time in complex EVAR but only contrast volume and procedure time for standard EVAR. Though a reduction was suggested, the radiation dose was not significantly affected by the use of fusion imaging in either standard or complex EVAR.

Secondary Interventions and Long-term Follow-up after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Early morbidity and mortality are low after endovascular abdominal aneurysm repair (EVAR), but secondary interventions and late complications are common. The aim of the present multicenter cohort study is to detail the frequency and indication for interventions after EVAR and the impact on long-term survival. METHODS: A retrospective multicenter cohort study of secondary interventions after elective EVAR for an infrarenal abdominal aortic aneurysm was conducted. Consecutive patients (n = 349) undergoing EVAR between January 2007 and January 2012 were analyzed, with long-term follow-up until December 2018. Those requiring intervention were classified in accordance with the indications and specific nature of the intervention and treatment. The primary study end point was overall survival classified for patients with and without intervention. Kaplan-Meier analysis was used to estimate overall survival for those who did and who did not undergo secondary interventions. Univariable and multivariable Cox regression were performed to identify independent variables associated with mortality. RESULTS: Some 56 patients (16%) underwent 72 secondary interventions after EVAR during a median (interquartile range) follow-up period of 53.2 months (60.1). Some 45 patients (80.4%) underwent one intervention. Indications for intervention included mainly endograft kinking/outflow obstruction and type II endoleak. An endovascular technique was used in 40.3% of interventions. Median time to secondary intervention was 24.1 months. In 93 patients with abnormalities on imaging, no intervention was performed mainly because the abnormality had disappeared on follow-up imaging (43%). Kaplan-Meier curves showed no difference in survival for patients with and without secondary interventions (P = 0.153). Age (hazard ratio [HR]: 1.089, 95% confidence interval [CI]: 1.063-1.116), ASA classification (ASA III, IV HR: 1.517, 95% CI: 1.056-2.178) were significantly related to mortality. CONCLUSIONS: Secondary intervention rates are still considerable after EVAR. Endograft kinking/outflow obstruction and endoleak type II are the most common indications for a secondary intervention. Secondary interventions did not adversely affect long-term overall survival after EVAR.

Anatomic Suitability for Branched Thoracic Endovascular Repair in Patients with Aortic Arch Pathological Features.

Background Endovascular repair has become a viable alternative for aortic pathological features, including those located within the aortic arch. We investigated the anatomic suitability for branched thoracic endovascular repair in patients previously treated with conventional open surgery for aortic arch pathological features. Methods and Results Patients who underwent open surgery for aortic arch pathological features at our institution between 2000 and 2018 were included. Anatomic suitability was determined by strict compliance with the anatomic criteria within manufacturers' instructions for use for each of the following branched thoracic stent grafts: Relay Plus Double-Branched (Terumo-Aortic), TAG Thoracic Branch Endoprosthesis (W.L. Gore & Associates), Zenith Arch Branched Device (Cook-Medical), and Nexus Stent Graft System (Endospan Ltd/Jotec GmbH). Computed tomography angiography images were analyzed with outer luminal line measurements. A total of 377 patients (mean age, 64±14 years; 64% men) were identified, 153 of whom had suitable computed tomography angiography images for measurements. In total, 59 patients (15.6% of the total cohort and 38.6% of the measured cohort) were eligible for endovascular repair using at least one of the devices. Device suitability was 30.9% for thoracic aneurysms, 4.6% for type A dissections, 62.5% for type B dissections, and 28.6% for other pathological features. Conclusions The anatomic suitability for endovascular repair of all aortic arch pathological features was modest. The highest suitability rates were observed for thoracic aneurysms and for type B dissections, of which repair included part of the aortic arch. We suggest endovascular repair of arch pathological features should be reserved for high-volume centers with experience in endovascular arch repair.

Outcome of Ruptured Abdominal Aortic Aneurysm Repair in Octogenarians: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis sought to identify the mortality and ambulatory state 30 days and one year post-operatively in octogenarians treated for ruptured abdominal aortic aneurysm (rAAA) by endovascular aneurysm repair (EVAR) or open repair (OR). rAAA is a life threatening emergency occurring increasingly in octogenarians. Surgical treatment, open or endovascular, offers the only chance of survival albeit with significant mortality and morbidity rates and a high burden to society. In order to make an informed decision on management, contemporary treatment outcomes should be known. The aim of this study was to perform a systematic review and meta-analysis on rAAA repair in octogenarians. METHODS: The Pubmed, Embase and Cochrane databases were searched for articles published between 2013 and October 2018 on octogenarians treated for a rAAA. Meta-analysis was performed using the random effects model to calculate the 30 day and one year mortality. RESULTS: The search resulted in a total of 1569 articles, of which eight retrospective studies could be included, reporting on 7526 patients. All studies reported 30 day mortality in octogenarians, and the one year mortality was addressed in four studies. Ambulatory state was not reported. Meta-analysis showed a 30 day mortality of 43% (95% confidence interval (CI) 33-53) and a one year mortality of 47% (95% CI 32-62). Patients after EVAR had a significant lower mortality at 30 days (risk ratio (RR) 0.50, 95% CI 0.38-0.67) and at one year (RR 0.65, 95% CI 0.44-0.96). CONCLUSION: The 30 day and one year mortality rates for rAAA repair in octogenarians are similar to the outcome at all ages, with a significant survival advantage of EVAR over OR. Patients should therefore not be denied treatment of a rAAA based on age alone.

Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats.

OBJECTIVES: Juxtarenal aortic surgery induces renal ischaemia reperfusion, which contributes to systemic inflammatory tissue injury and remote organ damage. Renal cooling during suprarenal cross clamping has been shown to reduce renal damage. It is hypothesised that renal cooling during suprarenal cross clamping also has systemic effects and could decrease damage to other organs, like the sigmoid colon. METHODS: Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45 min, followed by 20 min of infrarenal aortic clamping. Four groups were created: sham, no, warm (37 °C saline), and cold (4 °C saline) renal perfusion during suprarenal cross clamping. Primary outcomes were renal damage and sigmoid damage. To assess renal damage, procedure completion serum creatinine rises were measured. Peri-operative microcirculatory flow ratios were determined in the sigmoid using laser Doppler flux. Semi-quantitative immunofluorescence microscopy was used to measure alterations in systemic inflammation parameters, including reactive oxygen species (ROS) production in circulating leukocytes and leukocyte infiltration in the sigmoid. Sigmoid damage was assessed using digestive enzyme (intestinal fatty acid binding protein - I-FABP) leakage, a marker of intestinal integrity. RESULTS: Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45 mg/dL without renal perfusion, 0.33 mg/dL, and 0.14 mg/dL (p = .009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p = .002) and cold renal perfusion (p = .002). A smaller increase of ROS production (p = .034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p = .006) and cold perfusion (p = .018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p = .007) and cold renal perfusion (1.2AU; p = .002). CONCLUSIONS: Renal ischaemia/reperfusion injury after suprarenal cross clamping decreased microcirculatory flow, increased systemic ROS production, leukocyte infiltration, and I-FABP leakage in the sigmoid colon. Cold renal perfusion was superior to warm perfusion and reduced renal damage and had beneficial systemic effects, reducing sigmoid damage in this experimental study.

Design and protocol of a comprehensive multicentre biobank for abdominal aortic aneurysms.

INTRODUCTION: The pathophysiology and natural course of abdominal aortic aneurysms (AAAs) are insufficiently understood. In order to improve our understanding, it is imperative to carry out longitudinal research that combines biomarkers with clinical and imaging data measured over multiple time points. Therefore, a multicentre biobank, databank and imagebank has been established in the Netherlands: the 'Pearl Abdominal Aortic Aneurysm' (AAA bank). METHODS AND ANALYSIS: The AAA bank is a prospective multicentre observational biobank, databank and imagebank of patients with an AAA. It is embedded within the framework of the Parelsnoer Institute, which facilitates uniform biobanking in all university medical centres (UMCs) in the Netherlands. The AAA bank has been initiated by the two UMCs of Amsterdam UMC and by Leiden University Medical Center. Participants will be followed during AAA follow-up. Clinical data are collected every patient contact. Three types of biomaterials are collected at baseline and during follow-up: blood (including DNA and RNA), urine and AAA tissue if open surgical repair is performed. Imaging data that are obtained as part of clinical care are stored in the imagebank. All data and biomaterials are processed and stored in a standardised manner. AAA growth will be based on multiple measurements and will be analysed with a repeated measures analysis. Potential associations between AAA growth and risk factors that are also measured on multiple time points can be assessed with multivariable mixed-effects models, while potential associations between AAA rupture and risk factors can be tested with a conditional dynamic prediction model with landmarking or with joint models in which linear mixed-effects models are combined with Cox regression. ETHICS AND DISSEMINATION: The AAA bank is approved by the Medical Ethics Board of the Amsterdam UMC (University of Amsterdam). TRIAL REGISTRATION NUMBER: NCT03320408.

Catheter Directed Thrombolysis Protocols for Peripheral Arterial Occlusions: a Systematic Review.

OBJECTIVE: Catheter directed thrombolysis (CDT) for peripheral arterial occlusions is a well established alternative to thrombo-embolectomy in patients with (sub)acute limb ischaemia. However, protocols are heterogeneous and need optimisation to improve results and lower bleeding risks. The objective was to review the results and outcomes of different CDT protocols for patients with peripheral arterial occlusions. DATA SOURCES: Electronic information sources (MEDLINE, Embase, Cochrane) and reference lists were searched to identify studies reporting results of CDT of peripheral arterial occlusions. METHODS: Two independent observers performed study selection, quality assessment and data extraction. Primary outcomes were treatment duration, success rates, and bleeding complications. Secondary outcomes were mortality and amputation rates. RESULTS: One hundred and six studies were included: 19 randomised controlled trials (RCTs), 38 prospective studies, 48 retrospective studies, and one mixed cohort study. The studies comprised a total number of 10,643 cases of which 9877 received CDT for lower extremity arterial occlusion, with a mean treatment duration of 21.4 h (95% confidence interval [CI] 21.0-21.8), an angiographic patency of 75% (95% CI 74.6-75.1), and freedom from amputation rate of 91% (95% CI 90.3-90.7). Pooled results showed a thrombolysis duration with high dose protocols of 21.9 h (95% CI 21.4-22.5) and 32.7 h with low dose protocols, with bleeding rates of 16.7% (95% CI 16.3-17.1) and 13.4% (95% CI 12.8-14.0), respectively. Weighted mean results for all RCTs and prospective cohorts of >100 cases analysed separately, showed comparable results to all observational cohorts pooled. Bleeding complications occurred in 18% (95% CI 17.8-18.3) of patients and remain an important risk of CDT. CONCLUSION: CDT is an effective treatment for peripheral arterial occlusions, the main concern is bleeding complications. Although no formal meta-analysis could be performed, the pooled results suggest that lower doses of fibrinolytics lead to similar success rates at a cost of longer treatment duration but with less bleeding. There is large variation in treatment protocols and the available literature suffers from absence of reporting standards and high heterogeneity.

The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms.

BACKGROUND: In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. METHODS: In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. RESULTS: NGAL (in µg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively). CONCLUSIONS: This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.

The Value of Sigmoidoscopy to Detect Colonic Ischaemia After Ruptured Abdominal Aortic Aneurysm Repair.

OBJECTIVES: Diagnosing colonic ischaemia (CI) after ruptured abdominal aortic aneurysm (RAAA) repair is challenging. This study determined the diagnostic value of sigmoidoscopy in patients suspected of CI after RAAA repair. METHODS: This was a retrospective multicentre cohort study. Patients who underwent RAAA repair in three hospitals in Amsterdam, the Netherlands, between 2004 and 2011 (AJAX cohort) were included. Sigmoidoscopies were carried out based on clinical judgment. Endoscopy results were classified as "no ischaemia," "mild CI," or "moderate to severe CI." The surgical diagnosis was classified as "transmural" or "no transmural" CI. The value of sigmoidoscopy was assessed with calculation of positive and negative predictive values (PPV, NPV) with 95% CI for transmural CI. Logistic regression analysis was used to express the association of risk factors with CI as adjusted OR. RESULTS: Transmural CI was diagnosed in 23 of 351 patients (6.6%). Thirteen of sixteen patients (81%) who underwent direct laparotomy for high suspicion of CI indeed had transmural CI. Forty-six patients (13%) underwent sigmoidoscopy. The prevalence of transmural CI was 22% (10/46; 95% CI 12-36%) in these patients. The PPV for transmural CI of "moderate to severe CI" on sigmoidoscopy was 73% (8/11; 95% CI 43-90%). The PPV of "mild CI" on sigmoidoscopy was 11% (2/19; 95% CI 2.9-31%). The NPV of "no ischaemia" on sigmoidoscopy was 100% (95% CI 78-100%). Cardiac comorbidity (OR 3.1, 95% CI 1.19-7.97), low first haemoglobin (OR 0.6, 95% CI 0.47-0.87), and high vasopressor administration (OR 9.4, 95% CI 1.99-44.46) were independently associated with CI. CONCLUSIONS: Sigmoidoscopy increases the likelihood of correctly identifying the presence or absence of transmural CI, especially in patients with a moderate clinical suspicion for CI after RAAA repair.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. METHODS: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. RESULTS: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (ß = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (ß = 0.566, 0.200, p = .005). CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.

Efficacy versus Complications in Arterial Thrombolysis.

BACKGROUND: Acute peripheral arterial occlusions threaten life and limb. Thrombolysis is an established, minimally invasive alternative treatment for surgical thromboembolectomy. Yet, there is no consensus regarding an optimal thrombolysis protocol, and current knowledge is largely based on studies from the 1990s. This study reviews a contemporary cohort of patients treated with thrombolysis and aims to evaluate the treatment results and to identify possible predictors for outcome and (bleeding) complications. METHODS: The electronic health record data of all consecutive patients who underwent thrombolysis for acute limb ischemia due to thromboembolic lower extremity arterial occlusions between April 2006 and June 2012 were analyzed. End points were change in clinical stage of ischemia, incidence of bleeding complications, duration of thrombolysis, predictors of outcome and complications, and mortality and amputation-free rates after 30-day and 6-months follow-up. RESULTS: In total, 109 cases were included. Clinical improvement was observed in 79%. Amputation-free rates at 30 days and 6 months were 94% and 90%, respectively. The incidence of major bleeding complications was 13%. Median duration of thrombolysis was 27 (4-68) hr. Mortality rates at 30 days and 6 months were 7% and 16%, respectively; none bleeding related. In addition to age, popliteal artery occlusions and a progressed chronic vascular stage are predictive for a worse outcome. Age, female sex, and cardiac history were risk factors for bleeding. CONCLUSIONS: Treatment of peripheral arterial occlusions with high-dose thrombolysis on an intensive-care unit yields high clinical success rates, but major bleeding complications are often observed. Strict clinical observation remains essential since intensive monitoring of hemostatic parameters during thrombolysis does not predict bleeding complications.

Long-term survival after acute kidney injury following ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Acute kidney injury (AKI) is a major complication of ruptured abdominal aortic aneurysm (RAAA). Severe AKI is associated with high morbidity and mortality in the short term. The objective of this study was to determine the association between AKI after RAAA repair and long-term survival. METHODS: We conducted a retrospective cohort study of all patients undergoing RAAA repair in three hospitals between 2004 and 2011. Outcomes were long-term survival after RAAA repair, incidence of postoperative AKI, and chronic dialysis rates. Survival rates were compared between different AKI groups (no AKI, Risk, Injury, Failure) with Kaplan-Meier survival analyses and log-rank tests. Univariable and multivariable Cox regression analyses were carried out to assess the association of survival with AKI, preoperative shock, postoperative shock, and sex. The main analysis focused on the group of patients surviving initial hospital stay. RESULTS: Our study encompassed 362 patients with RAAA. AKI occurred in 267 of 362 patients (74%). At discharge, 267 patients were alive (74%). Median survival in this group was 7.2 years. Survival was not significantly different between the four AKI groups (P = .07). However, the univariable Cox regression analysis demonstrated a significant association between Failure and reduced long-term survival compared with having no AKI (hazard ratio, 1.85; 95% confidence interval, 1.15-2.97). This association did not remain significant after multivariable adjustment. Four patients were discharged with chronic dialysis, and four other patients needed chronic dialysis later after discharge. CONCLUSIONS: This study demonstrates no significant independent association between AKI after RAAA repair and long-term survival. Only a small proportion of patients developed end-stage renal disease at a later stage in life.

Intravenous Targeted Microbubbles Carrying Urokinase versus Urokinase Alone in Acute Peripheral Arterial Thrombosis in a Porcine Model.

BACKGROUND: Standard therapy in acute peripheral arterial occlusion consists of intra-arterial catheter-guided thrombolysis. As microbubbles may be used as a carrier for fibrinolytic agents and targeted to adhere to the thrombus, we can theoretically deliver the thrombolytic medication locally following simple intravenous injection. In this intervention-controlled feasibility study, we compared intravenously administered targeted microbubbles incorporating urokinase and locally applied ultrasound, with intravenous urokinase and ultrasound alone. METHODS: In 9 pigs, a thrombus was created in the left external iliac artery, after which animals were assigned to either receive targeted microbubbles and urokinase (UK + tMB group) or urokinase alone (UK group). In both groups, ultrasound was applied at the site of the occlusion. Blood flow through the iliac artery and microcirculation of the affected limb were monitored and the animals were euthanized 1 hr after treatment. Autopsy was performed to determine the weight of the thrombus and to check for adverse effects. RESULTS: In the UK + tMB group (n = 5), median improvement in arterial blood flow was 5 mL/min (range 0-216). Improvement was seen in 3 of these 5 pigs at conclusion of the experiment. In the UK group (n = 4), median improvement in arterial blood flow was 0 mL/min (-10 to 18), with slight improvement in 1 of 4 pigs. Thrombus weight was significantly lower in the UK + tMB group (median 0.9383 g, range 0.885-1.2809) versus 1.5399 g (1.337-1.7628; P = 0.017). No adverse effects were seen. CONCLUSIONS: Based on this experiment, minimally invasive thrombolysis using intravenously administered targeted microbubbles carrying urokinase combined with local application of ultrasound is feasible and might accelerate thrombolysis compared with treatment with urokinase and ultrasound alone.