[Drug-coated balloons in the treatment of peripheral artery disease (PAD). History and current level of evidence]. / Medikamentenbeschichtete Ballonkatheter in der PAVK­Behandlung. Entwicklung der Methode und aktuelle Studienlage.

BACKGROUND: Despite initially encouraging technical success after femoropopliteal PTA, restenosis remains the major challenge in patients with peripheral artery disease (PAD). The main cause of restenosis is neointimal hyperplasia which can be suppressed by antiproliferative drugs. Drug-coated balloons (DCB) or drug-eluting stents (DES) are used for the inhibition of restenosis. OBJECTIVES: The present article gives an overview of DCB development, actual DCB systems for femoro- and infrapopliteal use, displays the outcomes of randomized clinical trials and the discusses the evidence for the DCB treatment in PAD. METHODS: A systematic literature search was performed in i) medical journals (i. e. MEDLINE), ii) in international registers for clinical studies (i. e. www.clinicaltrials.gov ) and in iii) scientific session abstracts. RESULTS: The clinical evidence of the PTX-DCB of the first and following generation has been shown in several controlled randomized trials. CONCLUSIONS: Major advantages of the DCBs lie in leaving no stent scaffold behind, the immediate release of high drug concentrations with a single dosage, their efficacy in areas, where stents have been contra-indicated until now and its use for secondary interventions. As their effect seems to be limited in severely calcified lesions, prior plaque preconditioning or removal could be advantageous. First positive results data supporting this hypothesis do exist.

Early experience with the EntrustTM delivery system for stent treatment of the lower extremities' arteries via transbrachial approach.

AIM: The femoral artery remains the access of choice in the majority of peripheral vascular interventions. However, specific conditions indicate catheterization of the brachial artery. Contrary to balloon catheters, the majority of stent delivery systems are too short to facilitate transbrachial implantation of self-expandable stents (SES) in the superficial femoral artery (SFA). We report our experience with a new 150 cm working length SES-delivery system for transbrachial lower extremity interventions. METHODS: All patients treated with the Entrust(TM) delivery system (EDS) for lower extremity peripheral arterial disease (PAD) via a transbrachial access between December 2012 and February 2014 were included into this study. All data were prospectively collected and analyzed. Primary endpoints were the feasibility and safety of the EDS in the transbrachial setting. Secondary endpoints consisted of stent length accuracy after deployment, early clinical outcome and perioperative complications. RESULTS: Thirty-seven EverFlex(TM) stents with Entrust(TM) delivery system were implanted transbrachially in twenty-eight (N.=28) patients. The transbrachial implantation of a SES using the EDS was feasible in all patients. Stent compression or elongation >10%, premature jumping or movements of the implanted stents were not observed in any patient. Although no stent fractures were observed, a single stent occlusion was noticed. Early clinical success was achieved in all but one patient, with one patient requiring a surgical revision of the puncture site due to pseudoaneurysm. CONCLUSION: The early experience with the new SES-delivery system suggests that EDS enables the safe and effective treatment of the lower extremities PAD via a transbrachial approach. However, further evaluation is needed to define whether the use of the new long shaft stent delivery system influences the performance of the EverFlex(TM) stent in the long run.

Midterm results of the transarterial use of Onyx in the treatment of persisting type II endoleaks after EVAR.

AIM: Type II endoleaks with growing aneurysm sac >5 mm in diameter after EVAR require treatment. Different treatment options have been reported. The aim of this study was to evaluate the use of an ethylene-vinyl alcohol copolymer (Onyx) in an endovascular approach. METHODS: Between January 2010 and December 2011, 10 consecutive patients with persistent type II endoleaks leading to aneurysm growth >5 mm were treated in our center by transarterial Onyx embolization by super selective cannulation of the endoleak with microcatheters. Technical success was defined as transarterial Onyx deployment directly into the aneurysm sac. Clinical success was defined as stable or shrinking axial aneurysmal diameter during follow- up using an angiographic computed tomography. RESULTS: Ten patients with 13 persistent type II endoleaks leading to aneurysm sac growth of >5 mm were identified in the time period. Technical success was 92% (12/13 patients). Two patients underwent a staged procedure because several, unconnected type II endoleaks were present. In one patient a cannulation of the inflow vessel responsible for the endoleak was not possible, continued efforts led to a rupture of the hypogastric artery which was treated by covered stent implantation. In one patient an extravasation of onyx out of the aneurysm sac into the inferior vena cava during the embolization process made a transvenous goose snare maneuver necessary to retrieve the dislocated copolymer. No further complications were observed during the mean follow-up of 19.8 months (range, 3-31 months). In all patients with successful embolization the aneurysm sac remained stable or was decreased within the follow-up period. CONCLUSION: Use of Onyx in the endovascular treatment of type II endoleaks after EVAR is feasible, safe when accurately deployed and efficient. Further studies are necessary to evaluate the value of the different treatment modalities (translumbar vs. transarterial).

Successful percutaneous endovascular treatment of symptomatic infrarenal aortic stenosis caused by soft-plaque with the Endurant stent-graft.

Focal stenosis or occlusion of the infrarenal aorta is a relatively rare entity. In particular, soft-plaque of atherothrombotic origin in the aortic segment is linked to high-risk for peripheral embolisation. To our knowledge, the present case report describes for first time in the literature successful percutaneous treatment of a symptomatic soft-plaque infrarenal aortic stenosis with severe calcification of the iliac vessels by stent-graft, in particular by the new Endurant. Endovascular exclusion of the thrombotic lesion by endoprosthesis covers the atherosclerotic wall treating the potential underlying cause of the thrombus formation. The radial force of the endoprosthesis seems to be sufficient achieving complete expansion. However, long-term results are warranted.

Endovascular treatment of profunda femoris artery obstructive disease: nonsense or useful tool in selected cases?

BACKGROUND: To evaluate the therapeutic value of endovascular techniques for the treatment of profunda femoris artery obstructive disease (PFAOD) in critical limb ischaemia (CLI) patients, with technically demanding open profunda repair. DESIGN: Retrospective study of prospectively collected data of 15 consecutive CLI patients with technically demanding surgical treatment of PFAOD, that were treated by endovascular means in two European Centers of Vascular Surgery. MATERIALS: All patients had critical limb ischaemia with a history of at least two previous vascular reconstructions in the ipsilateral groin and severe co-morbid conditions. All patients had good common femoral artery flow, long occlusion of the superficial femoral and popliteal arteries and impairment of crural arteries. METHODS: Twelve patients underwent balloon angioplasty alone and, in the other three cases, an additional stent placement was necessary, due to flow-limiting dissection. The follow-up (mean 29.2+/-10 months) included a surveillance protocol with the best medical treatment and duplex scanning at 1, 3, 6, 12 months and yearly thereafter. RESULTS: The endovascular approach was technically successful in all cases and the procedure-related morbidity and mortality rates were 0% for the entire follow-up period. The 3-year primary and secondary patency rates of the treated segment were 80% and 86.7%, respectively. The limb salvage rate was 93.3%. CONCLUSIONS: The outcome of our series underscores the therapeutic value of balloon angioplasty in cases of severe PFAOD, as bailout treatment in critical limb ischaemia patients with technically demanding open profunda repair. This procedure can be repeated easily if significant restenosis occurs and provides a useful tool in selected cases.

Below-knee bare nitinol stent placement in high-risk patients with critical limb ischaemia and unlimited supragenicular inflow as treatment of choice.

PURPOSE: To evaluate the effectiveness of nitinol stent placement in long infrapopliteal lesions in patients with critical limb ischaemia. MATERIALS AND METHODS: Between January 2005 and January 2008, 34 high-risk patients (18 female; mean age: 73.8+/-6.1 years) with critical limb ischaemia underwent infragenicular stenting. They had serious cardiovascular co-morbidities (>3, such as chronic obstructive pulmonary disease (COPD), congestive heart failure and coronary artery occlusive disease), American Society of Anaesthesiologists score of 3 or more, previous myocardial infarction, coronary stent or bypass. The mean stenosis length was 6.5+/-0.9 cm (range: 2.2-8 cm), and the mean occlusion length was 7.5+/-2.9 cm (range: 3-9.6 cm). Primary stent implantation was performed for long stenosis or occlusion based on the TransAtlantic InterSociety Consensus (TASC) C and D classification, secondary stenting for flow-limiting dissections or elastic recoil after balloon dilatation. All patients who returned to the outpatient clinic were assessed for claudication by clinical examination, ankle-brachial index (ABI) measurements, colour flow and duplex Doppler ultrasound (US). Digital subtraction angiography was performed if restenosis or re-occlusion was identified by Doppler US or transcutaneous measurement of partial oxygen pressure (TcpO(2)) measurements, when appropriate. RESULTS: The technical success rate was 97.1% (33 of 34 cases). The crude rate of primary patency rate was 91.1% during a follow-up period of 10.4+/-7.3 months. The mean ankle-brachial index increased significantly following intervention (0.45+/-0.25-0.92+/-0.13, p<0.001). Two patients underwent successful redo angioplasty after tibioperoneal interventions due to in-stent restenosis (>70%) with relevant limitation of pain-free walking distance. In another patient, bypass surgery to the anterior tibial artery 6 months after primary intervention was necessary due to rest pain. Two patients required surgical revision of the femoral artery after antegrade access. No procedure-related death was recorded in the entire follow-up period. CONCLUSIONS: The mid-term outcome underscores infrapopliteal stent placement as a reliable treatment option in patients with critical limb ischaemia. In patients at high risk for crural bypass, with no flow-limiting supragenicular lesions, below-knee stent-supported angioplasty should be considered as a first choice of treatment.

Gene expression in the liver of rainbow trout, Oncorhynchus mykiss, during the stress response.

To better appreciate the mechanisms underlying the physiology of the stress response, an oligonucleotide microarray and real-time RT-PCR (QRT-PCR) were used to study gene expression in the livers of rainbow trout (Oncorhynchus mykiss). For increased confidence in the discovery of candidate genes responding to stress, we conducted two separate experiments using fish from different year classes. In both experiments, fish exposed to a 3 h stressor were compared to control (unstressed) fish. In the second experiment some additional fish were exposed to only 0.5 h of stress and others were sampled 21 h after experiencing a 3 h stressor. This 21 h post-stress treatment was a means to study gene expression during recovery from stress. The genes we report as differentially expressed are those that responded similarly in both experiments, suggesting that they are robust indicators of stress. Those genes are a major histocompatibility complex class 1 molecule (MHC1), JunB, glucose 6-phosphatase (G6Pase), and nuclear protein 1 (Nupr1). Interestingly, Nupr1 gene expression was still elevated 21 h after stress, which indicates that recovery was incomplete at that time.

Motor system abnormalities in hereditary spastic paraparesis type 4 (SPG4) depend on the type of mutation in the spastin gene.

BACKGROUND: Hereditary spastic paraparesis (HSP) denotes a group of inherited neurological disorders with progressive lower limb spasticity as their clinical hallmark; a large proportion of autosomal dominant HSP belongs to HSP type 4, which has been linked to the SPG4 locus on chromosome 2. A variety of mutations have been identified within the SPG4 gene product, spastin. OBJECTIVE: Correlation of genotype and electrophysiological phenotype. MATERIAL: Two large families with HSP linked to the SPG4 locus with a very similar disease with respect to age of onset, progression, and severity of symptoms. METHODS: Mutation analysis was performed by PCR from genomic DNA and cDNA, and direct sequencing. The motor system was evaluated using transcranial magnetic stimulation. RESULTS: Patients differ in several categories depending on the type of mutation present. CONCLUSIONS: For the first time in hereditary spastic paraparesis, a phenotypic correlate of a given genetic change in the spastin gene has been shown.