Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: Protocol for a phase II single-arm trial

Introduction Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated. Methods and analysis A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life. Ethics and dissemination Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal. Trial registration numbers Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results

Intragraft Obstructive Thrombus Two Years After Endovascular Repair of Traumatic Aortic Injury: A Case Report and Review of the Literature

Introduction: Thoracic endovascular aortic repair (TEVAR) is the treatment of choice for blunt thoracic aortic injury (BTAI) and has proven to be a good alternative to open surgery. TEVAR requires less operation time, has fewer complications, can be used for relatively unstable patients, and is associated with a significantly lower mortality rate. Moreover, long term follow up data demonstrate low re-intervention rates and stentgraft failure. Report: The case of a 21 year old man who sustained severe trauma, including a traumatic pseudoaneurysm of the descending thoracic aorta distal to the left subclavian artery in 2016, is presented. The patient was treated by TEVAR. Two years later, he presented with progressive paraplegia due to stentgraft occlusion occurring four days after a new high velocity motor vehicle accident. An axillofemoral bypass was performed to assure blood flow to the lower body. Two days later the stentgraft was removed via left thoracotomy and replaced by a Dacron graft. Gross examination showed severe thrombus formation at the proximal edge, and a thrombotic occlusion in the middle and distal third of the stent. After three months of hospitalisation the patient was discharged to a rehabilitation clinic with partial recovery of his paraplegia. As of June 2020, the patient was able to walk without assistance and his paraplegia improved with only loss of sensation of his lower legs. Conclusion: A serious thrombotic complication two years after TEVAR is described. Although TEVAR is the currently preferred treatment for BTAI, more research is needed to examine the mechanisms behind this thrombotic complication and to elucidate whether TEVAR is definitive treatment or a “bridge to further surgery”. Smaller diameter stentgrafts, anticoagulation, regular (lifelong) follow up imaging, and prophylactic surgical conversion in (selected) patients might help to prevent this serious complication

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

Therapeutic Use of Microbubbles and Ultrasound in Acute Peripheral Arterial Thrombosis: A Systematic Review

Catheter-directed thrombolysis (CDT) for acute peripheral arterial occlusion is time consuming and carries a risk of major hemorrhage. Contrast-enhanced sonothrombolysis (CEST) might enhance outcomes compared with standard CDT. In the study described here, we systematically reviewed all in vivo studies on contrast-enhanced sonothrombolysis in a setting of arterial thrombosis. A systematic search of the PubMed, Embase, Cochrane Library and Web of Science databases was conducted. Two reviewers independently performed the study selection, quality assessment and data extraction. Primary outcomes were recanalization rate and thrombus weight. Secondary outcome was any possible adverse event. The 35 studies included in this review were conducted in four different (pre)clinical settings: ischemic stroke, myocardial infarction, (peripheral) arterial thrombosis and arteriovenous graft occlusion. Because of the high heterogeneity among the studies, it was not possible to conduct a meta-analysis. In almost all studies, recanalization rates were higher in the group that underwent a form of CEST. One study was terminated early because of a higher incidence of intracranial hemorrhage. Studies on CEST suggest that adding microbubbles and ultrasound to standard intra-arterial CDT is safe and might improve outcomes in acute peripheral arterial thrombosis. Further research is needed before CEST can be implemented in daily practice

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

Feasibility study for performing uterus transplantation in the Netherlands

STUDY QUESTION: Is it feasible to perform uterus transplantations (UTx) in a tertiary centre in the Netherlands? SUMMARY ANSWER: Considering all ethical principles, surgical risks and financial aspects, we have concluded that at this time, it is not feasible to establish the UTx procedure at our hospital. WHAT IS KNOWN ALREADY: UTx is a promising treatment for absolute uterine factor infertility. It is currently being investigated within several clinical trials worldwide and has resulted in the live birth of 19 children so far. Most UTx procedures are performed in women with the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a congenital disorder characterized by absence of the uterus. In the Netherlands, the only possible option for these women for having children is adoption or surrogacy. STUDY DESIGN SIZE DURATION: We performed a feasibility study to search for ethical, medical and financial support for performing UTx at the Amsterdam UMC, location VUmc. PARTICIPANTS/MATERIALS SETTING METHODS: For this feasibility study, we created a special interest group, including gynaecologists, transplant surgeons, researchers and a financial advisor. Also, in collaboration with the patients' association for women with MRKH, a questionnaire study was performed to research the decision-making in possible recipients. In this paper, we present an overview of current practices and literature on UTx and discuss the results of our feasibility study. MAIN RESULTS AND THE ROLE OF CHANCE: A high level of interest from the possible recipients became apparent from our questionnaire amongst women with MRKH. The majority (64.8%) positively considered UTx with a live donor, with 69.6% having a potential donor available. However, this 'non-life-saving transplantation' requires careful balancing of risks and benefits. The UTx procedure includes two complex surgeries and unknown consequences for the unborn child. The costs for one UTx are calculated to be around €100 000 and will not be compensated by medical insurance. The Clinical Ethics Committee places great emphasis on the principle of non-maleficence and the 'fair distribution of health services'. LIMITATIONS REASONS FOR CAUTION: In the Netherlands, alternatives for having children are available and future collaboration with experienced foreign clinics that offer the procedure is a possibility not yet investigated. WIDER IMPLICATIONS OF THE FINDINGS: The final assessment of this feasibility study is that that there are not enough grounds to support this procedure at our hospital at this point in time. We will closely follow the developments and will re-evaluate the feasibility in the future. STUDY FUNDING/COMPETING INTERESTS: This feasibility study was funded by the VU Medical Center (Innovation grant 2017). No conflicts of interest have been reported relevant to the subject of all authors. TRIAL REGISTRATION NUMBER: n.a

Value of risk scores in the decision to palliate patients with ruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48-h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C-statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48-h mortality in the IMPROVE data was reasonable (C-statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C-statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life-saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non-intervention rates, while respecting the wishes of the patient and family