Use of the Nellix EVAS system to treat post-EVAR complications and to treat challenging infrarenal necks.

AIM: Current commercially available modular stentgrafts are associated with relevant reintervention rates during follow-up. The Nellix Endovascular Aneurysm Sealing (EVAS) System is a potential device to overcome these limitations of EVAR. Device implantations outside of manufacturer instructions for use due to challenging neck anatomies are very common. This article presents very early experience in the treatment of patients with post EVAR complications and challenging neck anatomies. METHODS: EVAS with the Nellix System consists of bilateral PTFE-covered stentgrafts surrounded by endobags which are filled with biostable polymer which cures after 3-5 minutes. The device and concept is designed to seal the entire aneurysm lumen, to withstand lateral displacement forces and effectively seal lumbar or inferior mesenteric arteries. Potentially, device migration, type II endoleak, and subsequent reinterventions will be reduced in the longterm. Single case experience in four European vascular centers is reported using Nellix off-IFU (instructions for use), addressing technical aspects as well as patient selection criterias. RESULTS: Recent preliminary clinical experience using Nellix outide of the IFU in challenging neck anatomies prooves early feasibility and efficacy in patients being excluded for open repair (OR) and also for EVAR and FEVAR within OR. Short-term results are promising. Migration, renal artery occlusions or type II endoleaks were not observed. One type Ia endoleak was observed but was temporary and resolved. We also found that the chimney technique is feasible with Nellix, where secondary target vessel loss nor gutters were observed. The EVAS concept is a potential tool to treat post EVAR complications such as secondary type I endoleak or type IV material fatigue. Feasibility has been proven in single cases. CONCLUSION: EVAS is an innovative, intriguing concept in the treatment of abdominal aortic aneurysm (AAA). Short-term outcomes of the Nellix system is promising. Early experience of Nellix out of IFU when treating patients with challenging proximal infraenal necks, with post EVAR complications, short necks and chimney techniques show technical feasibility and promising short-term results. Mid- and long-term data are needed to validate device and procedure durability.

Acute and multiple-dose studies to determine the safety, tolerability, and pharmacokinetic profile of advantame in healthy volunteers.

Advantame, a new, high-intensity sweetener that is thought not to be absorbed from the human gastrointestinal tract in appreciable quantities, was evaluated for safety and tolerability in a total of 48 healthy adult volunteers in 2 studies. In the first study 24 subjects were randomized to receive escalating single doses of 0.1, 0.25, or 0.5mg/kg of body weight, and pharmacokinetic and safety parameters were assessed subsequently for 8 days. In the second study, 24 subjects were randomized to receive over 4 weeks either 30 mg advantame/day (split into 3 doses per day), or placebo. All subjects completed both studies and no significant treatment-related adverse effects were observed in any subjects in either study. There were no clinically relevant changes in laboratory parameters, vital signs, electrocardiogram, or physical examination findings. Plasma concentrations of advantame were mostly below the limit of quantification in all samples taken after a single dose or prior to the dose in the repeat-dose study. The concentrations of the hydrolysis product, advantame-acid, were also below the limit of quantification at 12, 36, and 48 h after a single dose of 0.1, 0.25, and 0.5mg/kg body weight, respectively. These studies demonstrate the safety and tolerability of advantame in healthy subjects at doses far exceeding those likely to be encountered in food and beverage use.

Randomized phase II clinical trial of avotermin versus placebo for scar improvement.

BACKGROUND: Scarring is a major problem following skin injury. In early clinical trials, transforming growth factor ß3 (avotermin) improved scar appearance. The aim of this study was to determine whether an injection of avotermin at the time of wound closure is effective in improving scar appearance. METHODS: Study RN1001-0042, a double-blind, randomized, within-patient, placebo-controlled trial, investigated the efficacy and safety of four doses of avotermin given once. Patients undergoing bilateral surgery to remove varicose leg veins by saphenofemoral ligation and long saphenous vein stripping were enrolled at 20 European centres. A total of 156 patients were randomized to receive one of four doses of avotermin (5, 50, 200 or 500 ng per 100 µl, at 100 µl per linear cm of wound margin), administered by intradermal injection to the groin and distal wound margins of one leg; placebo was administered to the other leg. Scar appearance was evaluated by an independent panel of lay people (lay panel), investigators and patients. The primary efficacy variable was lay panel Total Scar Score (ToScar), derived from visual analogue scale scores for groin scars between 6 weeks and 7 months. RESULTS: Avotermin 500 ng significantly improved groin scar appearance compared with placebo (mean lay panel ToScar difference 16·49 mm; P = 0·036). CONCLUSION: Avotermin 500 ng per 100 µl per linear cm of wound margin given once is well tolerated and significantly improves scar appearance.

EVAR using the Nellix Sac-anchoring endoprosthesis: treatment of favourable and adverse anatomy.

OBJECTIVE: The study aimed to review the results of endovascular aneurysm repair (EVAR) using a novel sac-anchoring endoprosthesis in patients with favourable and adverse anatomy. DESIGN: This is a prospective, multicentre, clinical trial. MATERIALS: The Nellix endoprosthesis consists of dual, balloon-expandable endoframes, surrounded by polymer-filled endobags, which obliterate the aneurysm sac and maintain endograft position. METHODS: The study reviewed worldwide clinical experience and Core Lab evaluation of computed tomography (CT) scans. RESULTS: From 2008 to 2010, 34 patients (age 71 ± 8 years, abdominal aortic aneurysm (AAA) diameter 5.8 ± 0.8 cm) were treated at four clinical sites. Seventeen patients (50%) met the inclusion criteria for Food and Drug Administration (FDA)-approved endografts (favourable anatomy); 17 (50%) had one or more adverse anatomic feature: neck length <10 mm (24%), neck angle >60° (9%) and iliac diameter >23 mm (38%). Device deployment was successful in all patients; iliac aneurysm treatment preserved hypogastric patency. Perioperative mortality was 1/34 (2.9%); one patient died at 10 months of congestive heart failure (CHF); one patient had a secondary procedure at 15 months. During 15 ± 6 months follow-up, there were no differences in outcome between favourable and adverse anatomy patients. Follow-up CT extending up to 2 years revealed no change in aneurysm size or endograft position and no new endoleaks. CONCLUSIONS: Favourable and adverse anatomy patients can be successfully treated using the Nellix sac-anchoring endoprosthesis. Early results are promising but longer-term studies are needed.

Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections.

Iclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin for S. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused by S. aureus, including MRSA.

The incidence of arterial stent fractures with exclusion of coronary, aortic, and non-arterial settings.

BACKGROUND: This study aimed to review the literature regarding fracture of arterial stents, especially its relation to location of placement, clinical relevance, and type of stents. MATERIAL AND METHODS: We searched published articles in PubMed up to February 2008 by using the terms: stent fracture or stent breakage. RESULTS: Thirty-one articles met our inclusion and exclusion criteria. Most of the studies reported fractures in stents placed in the superficial femoral artery or popliteal arteries. The cumulative incidence of stent fractures ranged from 2% to 65%, i.e. 0.6 to 60 per 1000 person-months. Stent fractures occur more frequently in the superficial femoral artery and are common when multiple stents are deployed and overlap. Stent fractures are associated with a higher risk of in-stent restenosis and re-occlusion. CONCLUSION: The incidence of stent fracture, its location of placement, and type of stent used were diverse across studies. Stent fracture may cause clinical deterioration especially in the femoropopliteal segment, and it should be detected before clinical manifestation appears. Further studies with larger study population involving new type of stents for a longer follow up period are warranted.

Prevention of spinal cord ischemia in an ovine model of abdominal aortic aneurysm treated with a self-expanding stent-graft.

PURPOSE: To present novel techniques to prevent spinal ischemia during aneurysm creation and chronic bifurcated stent-graft implantation in an ovine model of abdominal aortic aneurysm (AAA). METHOD: Experimental AAAs were created in 38 sheep. To prevent spinal ischemia, an internal aortic shunt was used during aneurysm creation. In the animals designated to receive bifurcated stent-grafts, a left external iliac-to-internal iliac bypass was performed to revascularize the caudal artery and prevent postdeployment spinal cord ischemia. Specimens were harvested at 1 week, 1, 3, and 6 months, and 1 year. RESULTS: Aneurysms were successfully created without paralysis in 35 animals. Two died due to aspiration pneumonia. Of the 33 animals implanted with endografts, 16 (94%) of 17 with straight devices and 15 (94%) of 16 with bifurcated stent-grafts survived with well-functioning, patent stent-grafts. Paralysis developed in 2 animals after endografting due to technical failures. CONCLUSIONS: The use of an internal shunt during aneurysm creation and internal iliac-to-external iliac transposition prior to bifurcated stent-graft deployment prevented spinal ischemia in an ovine AAA model. Chronically deployed stent-grafts were well tolerated.