Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks.

PURPOSE: The aim of this study was to assess the initial experience, technical success, and clinical benefit of AneuFix (TripleMed, Geleen, the Netherlands), a novel biocompatible and non-inflammatory elastomer that is directly injected into the aneurysm sac by a translumbar puncture in patients with a type II endoleak and a growing aneurysm. MATERIALS AND METHODS: A multicenter, prospective, pivotal study was conducted (ClinicalTrials.gov:NCT02487290). Patients with a type II endoleak and aneurysm growth (>5 mm) were included. Patients with a patent inferior mesenteric artery connected to the endoleak were excluded for initial safety reasons. The endoleak cavity was translumbar punctured with cone-beam computed tomography (CT) and software guidance. Angiography of the endoleak was performed, all lumbar arteries connected to the endoleak were visualized, and AneuFix elastomer was injected into the endoleak cavity and short segment of the lumbar arteries. The primary endpoint was technical success, defined as successful filling of the endoleak cavity with computed tomography angiography (CTA) assessment within 24 hours. Secondary endpoints were clinical success defined as the absence of abdominal aortic aneurysm (AAA) growth at 6 months on CTA, serious adverse events, re-interventions, and neurological abnormalities. Computed tomography angiography follow-up was performed at 1 day and at 3, 6, and 12 months. This analysis reports the initial experience of the first 10 patients treated with AneuFix. RESULTS: Seven men and 3 women with a median age of 78 years (interquartile range (IQR), 74-84) were treated. Median aneurysm growth after endovascular aneurysm repair (EVAR) was 19 mm (IQR, 8-23 mm). Technical success was 100%; it was possible to puncture the endoleak cavity of all treated patients and to inject AneuFix. Clinical success at 6 months was 90%. One patient showed 5 mm growth with persisting endoleak, probably due to insufficient endoleak filling. No serious adverse events related to the procedure or AneuFix material were reported. No neurological disorders were reported. CONCLUSION: The first results of type II endoleak treatment with AneuFix injectable elastomer in a small number of patients with a growing aneurysm show that it is technically feasible, safe, and clinically effective at 6 months. CLINICAL IMPACT: Effective and durable embolization of type II endoleaks causing abdominal aortic aneurysms (AAA) growth after EVAR is challenging. A novel injectable elastic polymer (elastomer) was developed, specifically designed to treat type II endoleaks (AneuFix, TripleMed, Geleen, the Netherlands). Embolization of the type II endoleak was performed by translumbar puncture. The viscosity changes from paste-like during injection, into an elastic implant after curing. The initial experience of this multicentre prospective pivotal trial demonstrated that the procedure is feasible and safe with a technical success of 100%. Absence of AAA growth was observed in 9 out of 10 treated patients at 6 months.

Automated image fusion during endovascular aneurysm repair: a feasibility and accuracy study.

PURPOSE: Image fusion merges preoperative computed tomography angiography (CTA) with live fluoroscopy during endovascular procedures to function as an overlay 3D roadmap. However, in most current systems, the registration between imaging modalities is performed manually by vertebral column matching which can be subjective, inaccurate and time consuming depending on experience. Our objective was to evaluate feasibility and accuracy of image-based automated 2D-3D image fusion between preoperative CTA and intraoperative fluoroscopy based on vertebral column matching. METHODS: A single-center study with offline procedure data was conducted in 10 consecutive patients which had endovascular aortic repair in which we evaluated unreleased automated fusion software provided by Philips (Best, the Netherlands). Fluoroscopy and digital subtraction angiography images were collected after the procedures and the vertebral column was fused fully automatically. Primary endpoints were feasibility and accuracy of bone alignment (mm). Secondary endpoint was vascular alignment (mm) between the lowest renal artery orifices. Clinical non-inferiority was defined at a mismatch of < 1 mm. RESULTS: In total, 87 automated measurements and 40 manual measurements were performed on vertebrae T12-L5 in all 10 patients. Manual correction was needed in 3 of the 10 patients due to incomplete visibility of the vertebral edges in the fluoroscopy image. Median difference between automated fusion and manual fusion was 0.1 mm for bone alignment (p = 0.94). The vascular alignment was 4.9 mm (0.7-17.5 mm) for manual and 5.5 mm (1.0-14.0 mm) for automated fusion. This did not improve, due to the presence of stiff wires and stent graft. CONCLUSION: Automated image fusion was feasible when all vertebral edges were visible. Accuracy was non-inferior to manual image fusion regarding bone alignment. Future developments should focus on intraoperative image-based correction of vascular alignment.

Catheter Directed Thrombolysis for Not Immediately Threatening Acute Limb Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis reports the outcomes of catheter directed thrombolysis (CDT) in patients with not immediately threatening (Rutherford I) acute lower limb ischaemia (ALI). DATA SOURCES: PubMed, Embase, and the Cochrane Library. REVIEW METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify observational studies and trials published between 1990 and 2022 reporting on the results of CDT in patients with Rutherford I ALI. A meta-analysis was performed using a random effects model with 95% confidence intervals (CIs). The outcomes of interests were treatment duration, angiographic success, bleeding complications, amputation and mortality rates, primary and secondary patency, and functional outcome expressed as pain free walking distance. RESULTS: Thirty-nine studies were included, comprising 1 861 patients who received CDT for not immediately threatening ALI. Funnel plots showed an indication of publication bias, and heterogeneity was substantial. Data from 5 to 13 studies were included in the meta-analysis. The pooled treatment duration was 2 days (95% CI 1 - 2), with an angiographic success rate of 80% (95% CI 73 - 86) and a 30 day freedom of amputation rate of 98% (95% CI 92 - 100). The major bleeding rate was 5% (95% CI 2 - 14), with a 30 day mortality rate of 3% (95% CI 1 - 5). The amputation free survival rate was 71% (95% CI 62 - 80) at the one year and 63% (95% CI 51 - 73) at the three year follow up. Long term patency rates were retrieved from four studies: 48% at one year (95% CI 27 - 70). No data could be retrieved on patient walking distance. CONCLUSION: Although CDT in the treatment of not immediately threatening ALI showed high angiographic success, the long term outcomes were relatively poor, with low patency and a substantial risk of major amputation. Further research is required to interpret the outcome of CDT in the context of potential confounders such as age and comorbidities.

Deep Learning-Based Intraoperative Stent Graft Segmentation on Completion Digital Subtraction Angiography During Endovascular Aneurysm Repair.

PURPOSE: Modern endovascular hybrid operating rooms generate large amounts of medical images during a procedure, which are currently mostly assessed by eye. In this paper, we present fully automatic segmentation of the stent graft on the completion digital subtraction angiography during endovascular aneurysm repair, utilizing a deep learning network. TECHNIQUE: Completion digital subtraction angiographies (cDSAs) of 47 patients treated for an infrarenal aortic aneurysm using EVAR were collected retrospectively. A two-dimensional convolutional neural network (CNN) with a U-Net architecture was trained for segmentation of the stent graft from the completion angiographies. The cross-validation resulted in an average Dice similarity score of 0.957 ± 0.041 and median of 0.968 (IQR: 0.950 - 0.976). The mean and median of the average surface distance are 1.266 ± 1.506 mm and 0.870 mm (IQR: 0.490 - 1.430), respectively. CONCLUSION: We developed a fully automatic stent graft segmentation method based on the completion digital subtraction angiography during EVAR, utilizing a deep learning network. This can provide the platform for the development of intraoperative analytical applications in the endovascular hybrid operating room such as stent graft deployment accuracy, endoleak visualization, and image fusion correction.

Major Bleeding During Thrombolytic Therapy for Acute Lower Limb Ischaemia: Value of Laboratory Tests for Clinical Decision Making, 17 Years of Experience.

OBJECTIVE: Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. METHODS: All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. RESULTS: Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. CONCLUSION: High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.

Endovascular Treatment of Aortic Stump Rupture After Extra-anatomic Aortoduodenal Fistula Repair is not a Definitive Treatment: A Case Report and Literature Review.

Introduction: Endovascular treatment of an aortic stump rupture is technically feasible. Whether this is a definitive treatment or a bridge to further surgery is unknown. Report: Previously a Case of an aortic stump rupture following extra-anatomic repair of a recurrent aortoduodenal fistula (ADF), which was successfully treated endovascularly by placement of an Amplatzer® Vascular Plug was described. The patient survived this acute procedure, but four years later was admitted with fever and back pain. Imaging revealed progressive enlargement of the aortic stump. A re-exploration was performed with removal of the infected aortic stump including the Amplatzer plug. A new aortic stump was created together with resection of an adherent part of the duodenum. The patient was discharged after five months and was able to survive for two more years without any recurring vascular complications. Discussion: This Case demonstrates that after four years, endovascular treatment was not a definitive treatment for aortic stump rupture. Endovascular treatment should be followed by definitive treatment when the patient is fit for surgery, especially in cases of ADF. If the patient is unfit for surgery, conservative treatment with culture based antibiotics is a reasonable alternative. Positive obstinacy lengthened the survival of this patient with eight years of reasonably good quality life.

Living Kidney Donor Knowledge of Provided Information and Informed Consent: The PRINCE Study.

BACKGROUND: Informed consent for living kidney donation is paramount, as donors are healthy individuals undergoing surgery for the benefit of others. The informed consent process for living kidney donors is heterogenous, and the question concerns how well they are actually informed. Knowledge assessments, before and after donor education, can form the basis for a standardized informed consent procedure for live kidney donation. METHODS: In this prospective, a multicenter national cohort study conducted in all eight kidney transplant centers in The Netherlands, we assessed the current status of the informed consent practice for live donor nephrectomy. All of the potential living kidney donors in the participating centers were invited to participate. They completed a pop quiz during their first outpatient appointment (Cohort A). Living kidney donors completed the same pop quiz upon admission for donor nephrectomy (Cohort B). RESULTS: In total, 656 pop quizzes were completed (417 in Cohort A, and 239 in Cohort B). The average donor knowledge score was 7.0/25.0 (±3.9, range 0-18) in Cohort A, and 10.5/25.0 (±2.8, range 0-17.5) in Cohort B. Cohort B scored significantly higher on overall knowledge, preparedness, and the individual item scores (p < 0.0001), except for the long-term complications (p = 0.91). CONCLUSIONS: Donor knowledge generally improves during the live donor workup, but it is still quite disappointing. Long-term complications, especially, deserve more attention during living kidney donor education.

Microbubbles and Ultrasound Accelerated Thrombolysis for Peripheral Arterial Occlusions: The Outcomes of a Single Arm Phase II Trial.

OBJECTIVE: Acute peripheral arterial occlusions can be treated by catheter directed thrombolysis (CDT). However, CDT is time consuming and accompanied by the risk of bleeding complications. The addition of contrast enhanced ultrasound and microbubbles could improve thrombus susceptibility to thrombolytic agents and potentially shorten treatment time with a lowered risk of bleeding complications. This article reports the outcomes of the safety and feasibility of this novel technique. METHODS: In this single arm phase II trial, 20 patients with acute lower limb ischaemia received CDT combined with an intravenous infusion of microbubbles and locally applied ultrasound during the first hour of standard intra-arterial thrombolytic therapy. The primary endpoint was safety, i.e., occurrence of serious adverse events (haemorrhagic complications and/or amputation) and death within one year. Secondary endpoints included angiographic and clinical success, thrombolysis duration, additional interventions, conversion, and quality of life. RESULTS: The study included 20 patients (16 men; median age 68.0 years; range, 50.0 - 83.0; and 40% native artery and 60% bypass graft). In all patients, the use of microbubble contrast enhanced sonothrombolysis could be applied successfully. There were no serious adverse events related to the experimental treatment. Duplex examination showed flow distal from the occlusion after 23.1 hours (range 3.1 - 46.5) with a median thrombolysis time of 47.5 hours (range 6.0 - 81.0). The short term ABI and pain scores significantly improved; however, no changes were observed before or after thrombolysis in the microcirculation. Overall mortality and amputation rates were both 2% within one year. The one year patency rate was 55%. CONCLUSION: Treatment of patients with acute peripheral arterial occlusions with contrast enhanced sonothrombolysis is feasible and safe to perform in patients. Further research is necessary to investigate the superiority of this new treatment over standard treatment.

Systematic review of embolization of type I endoleaks using liquid embolic agents.

OBJECTIVE: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. METHODS: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. RESULTS: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. CONCLUSIONS: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.

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.

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.

Repeat Rupture of a Giant Abdominal Aortic Aneurysm after EVAR.

INTRODUCTION: Ruptured abdominal aortic aneurysms (AAAs) are known to be associated with high fatal outcomes. Giant AAAs are often defined as having a maximum diameter over 13 cm. Large AAAs over 8 cm have demonstrated a yearly rupture rate of 30-50%, which explains the rarity of giant AAAs. Endovascular repair of ruptured AAAs (rAAAs) is increasingly advocated because of the shorter hospital stay and fewer post-operative complications. Nonetheless, outcomes regarding mortality and cost-effectiveness show a large variability and long-term outcomes are lacking. Few data have been published on treatment of giant AAAs and rAAAs; however, open surgery is generally the preferred option. REPORT: An 83 year old presented to the Emergency Department with a history of ruptured abdominal aortic aneurysm treated with an aorto-uni-iliac endograft and a femorofemoral crossover bypass. During follow up, this was complicated by a symptomatic type III endoleak, which was treated by endovascular repair. During the current admission, he presented with a re-rupture of his former aneurysm, which now was 18 cm diameter because of a type IA endoleak. Open surgical repair was performed and the post-operative course was without complications. DISCUSSION: The current case underlines the value of vascular surgeons being able to perform both open and endovascular surgery in rAAA.

Secondary Fill Minimizes Gutter Size in Chimney EVAS Configurations In Vitro.

PURPOSE: To investigate in an in vitro model if secondary endobag filling can reduce gutter size during chimney endovascular aneurysm sealing (chEVAS). MATERIALS AND METHODS: Nellix EVAS systems were deployed in 2 silicone juxtarenal aneurysm models with suprarenal aortic diameters of 19 and 24 mm. Four configurations were tested: EVAS with 6-mm balloon-expandable (BE) or self-expanding (SE) chimney grafts (CGs) in the renal branches of both models. Balloons were inflated simultaneously in the CGs and main endografts during primary and secondary endobag filling and polymer curing. Computed tomography (CT) was performed immediately after the primary and secondary fills. Cross-sectional lumen areas were measured on the CT images to calculate gutter volumes and percent change. CG compression was calculated as the reduction in lumen surface area measured perpendicular to the central lumen line. The largest gutter volume and highest compression were presented per CG configuration per model. RESULTS: Secondary endobag filling reduced the largest gutter volumes from 99.4 to 73.1 mm3 (13.2% change) and 84.2 to 72.0 mm3 (27.6% change) in the BECG configurations and from 67.2 to 44.0 mm3 (34.5% change) and 92.7 to 82.3 mm3 (11.2% change) in the SECG configurations in the 19- and 24-mm models, respectively. Secondary endobag filling increased CG compression in 6 of 8 configurations. BECG compression changed by -0.2% and 5.4% and by -1.0% and 0.4% in the 19- and 24-mm models, respectively. SECG compression changed by 10.2% and 16.0% and by 7.2% and 7.3% in the 19- and 24-mm models, respectively. CONCLUSION: Secondary endobag filling reduced paragraft gutters; however, this technique did not obliterate them. Increased CG compression and prolonged renal ischemia time should be considered if secondary endobag filling is used.

An in vitro method to keep human aortic tissue sections functionally and structurally intact.

The pathophysiology of aortic aneurysms (AA) is far from being understood. One reason for this lack of understanding is basic research being constrained to fixated cells or isolated cell cultures, by which cell-to-cell and cell-to-matrix communications are missed. We present a new, in vitro method for extended preservation of aortic wall sections to study pathophysiological processes. Intraoperatively harvested, live aortic specimens were cut into 150 µm sections and cultured. Viability was quantified up to 92 days using immunofluorescence. Cell types were characterized using immunostaining. After 14 days, individual cells of enzymatically digested tissues were examined for cell type and viability. Analysis of AA sections (N = 8) showed a viability of 40% at 7 days and smooth muscle cells, leukocytes, and macrophages were observed. Protocol optimization (N = 4) showed higher stable viability at day 62 and proliferation of new cells at day 92. Digested tissues showed different cell types and a viability up to 75% at day 14. Aortic tissue viability can be preserved until at least 62 days after harvesting. Cultured tissues can be digested into viable single cells for additional techniques. Present protocol provides an appropriate ex vivo setting to discover and study pathways and mechanisms in cultured human aneurysmal aortic tissue.

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.

Minimally Invasive, Laparoscopic, and Robotic-assisted Techniques Versus Open Techniques for Kidney Transplant Recipients: A Systematic Review.

CONTEXT: Literature on conventional and minimally invasive operative techniques has not been systematically reviewed for kidney transplant recipients. OBJECTIVE: To systematically evaluate, summarize, and review evidence supporting operating technique and postoperative outcome for kidney transplant recipients. EVIDENCE ACQUISITION: A systematic review was conducted in PubMed-Medline, Embase, and Cochrane Library between 1966 up to September 1, 2016, according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Articles were included and scored by two independent reviewers using Group Reading Assessment and Diagnostic Evaluation (GRADE), Newcastle-Ottawa Quality Assessment Scale (NOS), and Oxford guidelines for level of evidence. Main outcomes were graft survival, surgical site infection, incisional hernia, and cosmetic result. In total, 18 out of 1954 identified publications were included in this analysis. EVIDENCE SYNTHESIS: Included reports described conventional open, minimally invasive open, laparoscopic, and robotic-assisted techniques. General level of evidence of included studies was low (GRADE: 1-3; NOS: 0-4; and Oxford level of evidence: 4-2). No differences in graft or patient survival were found. For open techniques, Gibson incision showed better results than the hockey-stick incision for incisional hernia (4% vs 16%), abdominal wall relaxation (8% vs 24%), and cosmesis. Minimally invasive operative recipient techniques showed lowest surgical site infection (range 0-8%) and incisional hernia rates (range 0-6%) with improved cosmetic result and postoperative recovery. Disadvantages included prolonged cold ischemia time, warm ischemia time, and total operation time. CONCLUSIONS: Although the level of evidence was generally low, minimally invasive techniques showed promising results with regard to complications and recovery, and could be considered for use. For open surgery, the smallest possible Gibson incision appeared to yield favorable results. PATIENT SUMMARY: In this paper, the available evidence for minimally invasive operation techniques for kidney transplantation was reviewed. The quality of the reviewed research was generally low but suggested possible advantages for minimally invasive, laparoscopic, and robot-assisted techniques.

The Importance of Early Diagnosis and Treatment of Patients with Aortoenteric Fistulas Presenting with Herald Bleeds.

BACKGROUND: Massive bleeding in patients with aortoenteric fistula (AEF) may be preceded by minor, intermittent gastrointestinal (GI) blood loss, termed the "herald bleed." The aims of this retrospective study were to: (i) analyze the interval between the herald bleed and onset of major GI hemorrhage and/or diagnosis of AEF and (ii) to evaluate the diagnostic roles of endoscopy and computed tomography imaging. METHODS: Analysis of all patients diagnosed with AEF or iliac-enteric fistulas between 1994 and 2013 in a single institution. RESULTS: In 31 of a total of 34 fistula cases, GI bleeding was the presenting symptom. Of these, 17 of 31 presented with herald bleed while 14 of 31 presented with massive GI bleeding. In patients with a herald bleed, median time from first bleeding to diagnosis was 14 (2-137) days. In 5/17 patients, herald bleeding preceded major hemorrhage with a median of 6 (4-92) days before a diagnosis of AEF was made or intervention could be initiated. CT angiography (CTA) showed abnormalities associated with a fistula in 27 (79%) cases, of which in 12 (35%) cases a fistula was actually identified. Esophagogastroduodenoscopy (EGD) demonstrated a fistula in 8 (25%) patients, while 50% of EGDs were completely normal. CONCLUSIONS: Any patient with history of aortic surgery and GI bleeding should be considered to have an AEF until proven otherwise. The sensitivity of CTA for detecting AEF is substantially greater than that of EGD. The time interval between herald bleed and subsequent massive hemorrhage associated with AEF is unpredictable but may be as short as 4 days.

Towards a standardised informed consent procedure for live donor nephrectomy: the PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study.

INTRODUCTION: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. METHODS AND ANALYSIS: The PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof. ETHICS AND DISSEMINATION: Approval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought. RESULTS: Outcome will be published in a scientific journal. TRIAL REGISTRATION NUMBER: NTR5374; Pre-results.