Impact of Frailty and Sarcopenia on Thirty-Day and Long-Term Mortality in Patients Undergoing Elective Endovascular Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis.

Background: The aim of this study was to assess the prognostic role of frailty and sarcopenia on the survival of patients with AAA undergoing elective endovascular repair (EVAR). Methods: A systematic review of the literature was conducted in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE). The association of frailty or sarcopenia with 30-day mortality and late survival was expressed as odds ratios (ORs) or hazard ratios (HRs) with a 95% confidence interval (CI). Meta-analysis random effects models were applied. The five-factor modified frailty index (mFI-5) was used as a frailty metric and sarcopenia was determined using computed tomography angiography (CTA) with measurements of the total psoas muscle area. Frailty was defined as patients with mFI-5 ≥ 0.6 and sarcopenia was defined as the total psoas muscle area (TPA) within the lowest tertile. Results: Thirteen observational cohorts reporting a total of 56,756 patient records were eligible for analysis. Patients with frailty (mFI-5 ≥ 0.6) had significantly increased 30-day mortality than those without frailty (random effects method: OR, 4.84, 95% CI 3.34-7.00, p < 0.001). Patients with sarcopenia (lowest TPA tertile) had significantly increased 30-day mortality according to the fixed effects method (OR, 3.30, 95% CI 2.17-5.02, p < 0.001), but not the random effects method (OR, 2.64, 95% CI 0.83-8.39, p = 0.098). Patients with sarcopenia or frailty had a significantly increased hazard ratio (HR) for late mortality than those without frailty or sarcopenia according to the random effects method (HR, 2.39, 95% CI 1.66-3.43, p < 0.001). The heterogeneity of the studies was low (I2: 0.00%, p = 0.86). The relation of frailty to age extracted from four studies demonstrates that the risk of frailty increases with age according to the random effects method (standard mean differences, SMD, 0.52, 95% CI 0.44-0.61, p < 0.001). The heterogeneity of the studies was low (I2: 0.00%, p = 0.64). Conclusions: Patients with sarcopenia or frailty have a significantly increased risk of mortality following elective EVAR. Prospective studies validating the use of frailty and sarcopenia for risk prediction after EVAR are needed before these tools can be used to support decision making.

European Expert Opinion on Infrarenal Sealing Zone Definition and Management in Endovascular Aortic Repair Patients: A Delphi Consensus.

PURPOSE: The purpose of the study was to provide a consensus definition of the infrarenal sealing zone and develop an algorithm to determine when and if adjunctive procedure(s) or reintervention should be considered in managing patients undergoing endovascular aortic repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). METHODS: A European Advisory Board (AB), made up of 11 vascular surgeons with expertise in EVAR for AAA, was assembled to share their opinion regarding the definition of preoperative and postoperative infrarenal sealing zone. Information on their current clinical practice and level of agreement on proposed reintervention paths was used to develop an algorithm. The process included 2 virtual meetings and 2 rounds of online surveys completed by the AB (Delphi method). Consensus was defined as reached when ≥ 8 of 11 (73%) respondents agreed or were neutral. RESULTS: The AB reached complete consensus on definitions and measurement of the pre-EVAR target anticipated sealing zone (TASZ) and the post-EVAR real achieved sealing zone (RASZ), namely, the shortest length between the proximal and distal reference points as defined by the AB, in case of patients with challenging anatomies. Also, agreement was achieved on a list of 4 anatomic parameters and 3 prosthesis-/procedure-related parameters, considered to have the most significant impact on preoperative and postoperative sealing zones. Furthermore, the agreement was reached that in the presence of visible neck-related complications, both adjunctive procedure(s) and reintervention should be contemplated (100% consensus). In addition, adjunctive procedure(s) or reintervention can be considered in the following cases (% consensus): insufficient sealing zone on completion imaging (91%) or on the first postoperative computed tomography (CT) scan (91%), suboptimal sealing zone on completion imaging (73%) or postoperative CT scan (82%), and negative evolution of the actual sealing zone over time (91%), even in the absence of visible complications. CONCLUSIONS: AB members agreed on definitions of the pre- and post-EVAR infrarenal sealing zone, as well as factors of influence. Furthermore, a clinical decision algorithm was proposed to determine the timing and necessity of adjunctive procedure(s) and reinterventions.

Bioadhesive Perivascular Microparticle-Gel Drug Delivery System for Intimal Hyperplasia Prevention: In Vitro Evaluation and Preliminary Biocompatibility Assessment.

Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft failure. Topically applied atorvastatin (ATV) has been shown to slow down this process. To be effective, the drug delivery system should remain at the perivascular site for 5-8 weeks, corresponding to the progression of IH, and be capable of releasing an initial dose of the drug followed by a sustained release. Ideally, bioadhesion would anchor the gel to the application site. To meet these needs, we encapsulated ATV in a 2-component system: a hyaluronic acid-dopamine bioadhesive gel for rapid release and biodegradable microparticles for sustained release. The system was characterized by scanning electron microscopy, rheology, bioadhesion on porcine arteries, and a release profile. The rheological properties were adequate for perivascular application, and we demonstrated superior bioadhesion and cohesion compared to the control HA formulations. The release profile showed a burst, generated by free ATV, followed by sustained release over 8 weeks. A preliminary evaluation of subcutaneous biocompatibility in rats showed good tolerance of the gel. These results offer new perspectives on the perivascular application towards an effective solution for the prevention of IH.

Predictors and Consequences of Sac Shrinkage after Endovascular Infrarenal Aortic Aneurysm Repair.

Background: Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). We evaluated the impact of sac shrinkage on secondary interventions, on survival and its association with endoleaks, and on compliance with instructions for use (IFU). Methods: This observational retrospective study was conducted on all consecutive patients receiving EVAR for an infrarenal abdominal aortic aneurysm (AAA) using exclusively Endurant II/IIs endograft from 2014 to 2018. Sixty patients were entered in the study. Aneurysm sac shrinkage was defined as decrease ≥5 mm of the maximum aortic diameter. Univariate methods and Kaplan-Meier plots assessed the potential impact of shrinkage. Results: Twenty-six patients (43.3%) experienced shrinkage at one year, and thirty-four (56.7%) had no shrinkage. Shrinkage was not significantly associated with any demographics or morbidity, except hypertension (p = 0.01). No aneurysm characteristics were associated with shrinkage. Non-compliance with instructions for use (IFU) in 13 patients (21.6%) was not associated with shrinkage. Three years after EVAR, freedom from secondary intervention was 85 ± 2% for the entire series, 92.3 ± 5.0% for the shrinkage group and 83.3 ± 9% for the no-shrinkage group (Logrank: p = 0.49). Survival at 3 years was not significantly different between the two groups (85.9 ± 7.0% vs. 79.0 ± 9.0%, Logrank; p = 0.59). Strict compliance with IFU was associated with less reinterventions at 3 years (92.1 ± 5.9% vs. 73.8 ± 15%, Logrank: p = 0.03). Similarly, survival at 3 years did not significantly differ between strict compliance with IFU and non-compliance (81.8 ± 7.0% vs. 78.6 ± 13.0%, Logrank; p = 0.32). Conclusion: This study suggests that shrinkage ≥5 mm at 1-year is not significantly associated with a better survival rate or a lower risk of secondary intervention than no-shrinkage. In this series, the risk of secondary intervention regardless of shrinkage seems to be linked more to non-compliance with IFU. Considering the small number of patients, these results must be confirmed by extensive prospective studies.

Pharmacological prevention of intimal hyperplasia: A state-of-the-art review.

Intimal hyperplasia (IH) occurs in a considerable number of cases of blood vessel reconstruction by stenting or balloon angioplasty, venous bypass grafting, and arteriovenous dialysis accesses. It is triggered by endothelial injury during the vascular intervention and leads to vessel restenosis with life-threatening consequences for patients. To date, the drugs used for IH prevention in clinics-paclitaxel and rapalog drugs-have been focusing primarily on the vascular smooth muscle cell (VSMC) proliferation pathway of IH development. Limitations, such as endothelial toxicity and inappropriate drug administration timing, have spurred the search for new and efficient pharmacological approaches to control IH. In this state-of-the-art review, we present the pathways of IH development, focusing on the key events and actors involved in IH. Subsequently, we discuss different drugs and drug combinations interfering with these pathways based on their effect on peripheral circulation IH models in animal studies, or on clinical reports. The reports were obtained through an extensive search of peer-reviewed publications in Pubmed, Embase, and Google Scholar, with search equations composed based on five concepts around IH and their various combinations. To improve vascular intervention outcomes, rethinking of conventional therapeutic approaches to IH prevention is needed. Exploring local application of drugs and drug combinations acting on different pathophysiological pathways of IH development has the potential to provide effective and safe restenosis prevention.

Stapled Porcine Pericardium Displays Lower Infectivity In Vitro Than Native and Sutured Porcine Pericardium.

BACKGROUND: Biological xenografts using tubulized porcine pericardium are an alternative to replace infected prosthetic graft. We recently reported an innovative technique using a stapled porcine pericardial bioconduit for immediate vascular reconstruction in emergency. The objective of this study is to compare the growth and adherence to grafts of bacteria and yeast incubated with stapled porcine pericardium, sutured or naked pericardium. MATERIAL AND METHODS: One square centimeter of porcine pericardial patches, with or without staples or sutures, was incubated with 105 colony forming units of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans for 1, 6, and 24 h. The medium was collected to quantify planktonic microorganisms, while grafts were sonicated to quantify adherent microorganisms. Dacron and Dacron Silver were analyzed in parallel as synthetic reference prostheses. RESULTS: Stapled porcine pericardium reduced the growth and the adherence of E coli (2- to 30-fold; P < 0.0005), S aureus (11- to 1000-fold; P < 0.0006), S epidermidis (>500-fold; P < 0.0001), and C albicans (12- to 50-fold; P < 0.0001) when compared to medium alone (growth) and pericardium or Dacron (adherence). Native and sutured porcine pericardium interfered with the growth and the adherence of E coli and C albicans, and Dacron with that of S epidermidis. As expected, Dacron Silver was robustly bactericidal. CONCLUSIONS: Stapled porcine pericardium exhibited a lower susceptibility to infection by bacteria and yeasts in vitro when compared to the native and sutured porcine pericardium. Stapled porcine pericardium might be a good option for rapid vascular grafting without increasing infectivity.

The role of Doppler ultrasonography in vascular access surveillance-controversies continue.

Chronic hemodialysis therapy required regular entry into the patient's blood stream with adequate flow. The use of arteriovenous fistulas and grafts is linked with lower morbidity and mortality than the use of catheters. However, these types of accesses are frequently affected by stenoses, which decrease the flow and lead to both inadequate dialysis and access thrombosis. The idea of duplex Doppler ultrasound surveillance is based on the presumption that in-time diagnosis of an asymptomatic significant stenosis and its treatment prolongs access patency. Details of performed trials are conflicting, and current guidelines do not support ultrasound surveillance. This review article summarizes the trials performed and focuses on the reasons of conflicting results. We stress the need of precise standardized criteria of significant access stenosis and the weakness of the metaanalyses performed.

Vessel Preparation Is Essential to Optimize Endovascular Therapy of Infrainguinal Lesions.

Symptomatic peripheral arterial disease management involves medical treatment and interventional procedures. Intermittent claudication and critical limb threatened ischemia (CLTI) should be individually considered with specific outcomes and procedures. When intervention is required, an endovascular approach is usually the first-line option. Plain balloon angioplasty was previously used to dilate clinically significant femoropopliteal lesions with variable results. However, over recent years, the use of self-expanding nitinol stents has enabled treatment of long lesions, yielding significantly improved clinical results. Drug-eluting technology has also exhibited a capacity to limit in-stent restenosis and to drive target revascularization. Nevertheless, calcifications and elastic recoil of the arterial wall remain risk factors for early restenosis and failure. Therefore, vessel preparation using specific devices is required to modify vessel compliance and debulk obstructive calcification. In this short review, we provide an overview of the options for gaining lumen before stenting or dilation using drug-coated balloons.

Ten Year Experience of Using Cryopreserved Arterial Allografts for Distal Bypass in Critical Limb Ischaemia.

OBJECTIVE/BACKGROUND: In critical limb ischaemia (CLI), current guidelines recommend revascularisation whenever possible, preferentially through endovascular means. However, in the case of long occlusions or failed endovascular attempts, distal bypasses still have a place. Single segment great saphenous vein (GSV), which provides the best conduit, is often not available and currently there is no consensus about the best alternative graft. METHODS: From January 2006 to December 2015, 42 cryopreserved arterial allografts were used for a distal bypass. Autologous GSVs or alternative autologous conduits were unavailable for all patients. The patients were observed for survival, limb salvage, and allograft patency. The results were analysed with Kaplan-Meier graphs. RESULTS: Estimates of secondary patency at one, two and five years were 81%, 73%, and 57%, respectively. Estimates of primary patency rates at one, two and five years were 60%, 56%, and 26%, respectively. Estimates of limb salvage rates at one, two and five years were 89%, 89%, and 82%, respectively. Estimates of survival rates at one, two and five years were 92%, 76% and 34%, respectively. At 30 days, major amputations and major adverse cardiac events were one and zero, respectively. Six major amputations occurred during the long-term follow up. CONCLUSION: Despite a low primary patency rate at two years, the secondary patency of arterial allografts is acceptable for distal bypasses. This suggests that cryopreserved arterial allografts are a suitable alternative for limb saving distal bypasses in the absence of venous conduits, improving limb salvage rates and, possibly, quality of life.

Percutaneous intentional intra-luminal-assisted recanalization (PILAR technique) of challenging chronic total occlusions using a high-frequency vibration device.

OBJECTIVES: Recanalization of peripheral chronic total occlusions (CTO) is technically challenging especially in cases of in-stent and/or pre-stent and heavily calcified lesions. A high-frequency vibrational device (HFVD) was first used as a secondary-intention device in CTO recanalizations when they were refractory to a guidewire. The aim of this study was to assess the safety and efficacy of the HFVD as a first-line treatment for challenging CTOs and thus to define the percutaneous intentional intraluminal-assisted recanalization (PILAR) technique. METHODS: Fifty-two patients were treated with the HFVD. Only challenging CTOs were included: 7 pre-stent, 7 in-stent, and 38 highly calcified CTOs. Technical success was defined as the ability to cross the CTO using the HFVD. Secondary outcome was defined as successful intraluminal crossing. Safety endpoints were procedure-related thromboembolism or perforation. Patients were followed up at 3 months and 1 year. RESULTS: The technical success rate for recanalization was 90%, of which 83% were intraluminal. The mean recanalized length was 91 ± 44 mm. One thromboembolic complication occurred, which was subsequently treated with thromboaspiration. Three-month and 1-year primary patency rates were 92% and 79%, respectively. CONCLUSIONS: HFVD-based PILAR is a safe and effective technique for in-stent or pre-stent CTO recanalization of long and calcified lesions. KEY POINTS: • Intraluminal recanalization is the preferred procedure in heavily calcified or pre-/in-stent CTO. • First-line use of assisted intraluminal recanalization for CTO defines the PILAR technique. • HFVD-based PILAR is safe and provides a high success rate for challenging CTO recanalization.

Evaluating intimal hyperplasia under clinical conditions.

OBJECTIVES: Open arterial revascularization using venous segments is frequently associated with the development of intimal hyperplasia (IH), leading to severe restenosis and graft failure. The lack of treatment to prevent this pathology is a major problem. Therefore, we generated a new porcine model, which closely mimics the clinical development of human IH, to test the therapeutic potential of candidate drugs. METHODS: A patch of jugular vein was sutured to the right common carotid artery of pigs, to expose the vein to haemodynamic conditions of the arterial bed. Four weeks after surgery, the operated vessels which received no further treatment (the control group) were compared with (i) contralateral, non-operated vessels (the healthy group); (ii) vessels of pigs that received a perivascular application of a drug-free microparticle gel (the placebo group) and (iii) vessels of pigs that perioperatively received the same gel loaded with 10-mg atorvastatin (the atorvastatin group). RESULTS: When compared with non-operated vessels, all operated segments displayed a sizable IH which was thicker in the venous patch than in the host artery. These alterations were associated with a thickening of the intima layer of both vessels in the absence of inflammation. The intima/media ratio has been significantly increased by 2000-fold in the vein patches. Perivascular application of atorvastatin did not prevent IH formation. However, the drug increased the adventitial neovascularization in the operated vessels. CONCLUSIONS: The novel porcine model allows for monitoring IH formation under haemodynamic conditions which mimic clinical situations. It should facilitate the screening of innovative treatments to prevent restenosis.

Who Should Be Operated When Presenting with a Ruptured Abdominal Aortic Aneurysm? A Monocentric Study in a Tertiary Hospital.

BACKGROUND: Mortality with ruptured abdominal aortic aneurysms (rAAAs) is 80% overall, 50% when operated, and 100% when not operated. Distinguishing in emergency patients who should be operated versus being offered palliative treatment is difficult. We sought to identify key factors to consider in this decision-making. METHODS: Between 2001 and 2014, we selected all consecutive patients with rAAA treated by open or endovascular procedures in a tertiary hospital for inclusion in this retrospective, single-center study. Symptomatic aneurysms and isolated ruptured iliac aneurysms were excluded. The primary outcome was in-hospital mortality, and secondary outcomes were institutionalization rate and long-term mortality. Associations between predictive factors and in-hospital mortality were evaluated using univariate logistic regression. The local ethics committee approved this study. RESULTS: The mean age (±standard deviation) of the 72 included patients was 73 years (±9.0) and 88% were men. Among the 65 open (90%) and 7 endovascular procedures (10%), overall in-hospital mortality was 21%, 1- and 2-year mortalities were both 26%, and the institutionalization rate was 5%. Mean follow-up was 43 months (Kaplan-Meier estimate). Univariate analysis identified age as associated with a 20% per year increased risk of in-hospital mortality (correlation, P < 0.0001). Female sex was the other main preoperative risk factor correlated with in-hospital mortality (P = 0.006). Significant perioperative risk factors were suprarenal clamping (P = 0.038), amount of fresh frozen plasma transfused (P = 0.018), and number of blood transfusions (P < 0.0001). CONCLUSIONS: The most significant preoperative mortality-related factors were age and female sex. Our study also showed that institutionalization and long-term mortality are not factors to consider in the decision-making process.

[Rare vascular diseases, building dedicated multidisciplinary specialized center]. / Maladies vasculaires rares, mise en place d'un centre multidisciplinaire spécialisé au CHUV.

Rare Vascular Diseases (RVD) encompass different types of vessel involvement. Some cause a dilation, others a weakening or tortuosity of the arterial wall, others an obstruction or excessive calcification of arterial walls. Clinical pathway of patients with RVD to diagnosis is often long and complex. Thus, in order to allow early diagnosis and coordinated multidisciplinary management and follow-up, a specialized RVD centre has been set-up at the CHUV, following the framework of the national concept of rare diseases.

Les maladies vasculaires rares (MVR) englobent différents types d'atteintes des vaisseaux. Certaines engendrent une dilatation ou une tortuosité de la paroi artérielle, d'autres une fragilisation de la paroi, d'autres encore entraînent une obstruction du vaisseau, une calcification excessive des parois, ou des malformations vasculaires. Comme pour toutes les maladies rares, le parcours des patients vers un diagnostic est souvent long et complexe. Afin de permettre un diagnostic le plus précoce possible, ainsi qu'un suivi coordonné et une prise en charge multidisciplinaire médicale et sociale, un centre des MVR a été mis en place au CHUV, dans le cadre du concept national des maladies rares.

Perivascular medical devices and drug delivery systems: Making the right choices.

Perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery. These systems provide mechanical support and/or pharmacological activity for the prevention of intimal hyperplasia following vessel injury. Despite abundant reports in the literature and numerous clinical trials, no efficient perivascular treatment is available. In this review, the existing perivascular medical devices and perivascular drug delivery systems, such as polymeric gels, meshes, sheaths, wraps, matrices, and metal meshes, are jointly evaluated. The key criteria for the design of an ideal perivascular system are identified. Perivascular treatments should have mechanical specifications that ensure system localization, prolonged retention and adequate vascular constriction. From the data gathered, it appears that a drug is necessary to increase the efficacy of these systems. As such, the release kinetics of pharmacological agents should match the development of the pathology. A successful perivascular system must combine these optimized pharmacological and mechanical properties to be efficient.

Zenith Bifurcated Iliac Side Branch Device: Mid-term Results and Assessment of Risk Factors for Intraoperative Thrombosis.

BACKGROUND: The aim of this study is to evaluate the short- and mid-term results of the Zenith bifurcated iliac side branch device (ZBIS) in the treatment of common iliac artery (CIA) aneurysms, and to assess risk factors for intraoperative internal iliac artery (IIA) thrombosis. METHODS: All patients who underwent endovascular treatment of either an isolated CIA aneurysm or an aortoiliac aneurysm using the ZBIS device in the departments of vascular surgery of Strasbourg (France) and Lausanne (Switzerland) between January 2010 and December 2014 were retrospectively collected. RESULTS: Thirty-one implantations were performed: 30 patients underwent 31 endovascular CIA aneurysm treatments with the ZBIS device. Mean operative time was 188 min. Technical success was obtained in 26 implantations (84%). In 5 implantations (16%), the final angiogram revealed an IIA thrombosis. Thirty-day mortality was 3.2%. Thirty-day morbidity was 13.3%. Mean follow-up was 15 months. Overall survival was 96% at 1 year and 89% at 2 years. In intention-to-treat analysis, primary patency of the internal iliac side branch was 84% at 1 year and 76% at 2 years (5 peroperative IIA occlusions and 1 late occlusion). Freedom from reintervention was 89% at 1 and 2 years. One case of type III endoleak and 2 cases of type II endoleaks were identified. Only type III endoleak required an additional intervention with a covered stent. Aneurysm diameter decreased in 15 implantations (48%) and remained stable in 16 implantations (52%). Clinical, radiological, and peroperative parameters were analyzed to identify risk factor for intraoperative thrombosis of the internal iliac side branch. Notion of intraoperative difficulties (any additional procedure that was not initially planned and increasing the operating time) appeared as a risk factor in multivariate analysis (P < 0.01, standard deviation 1.27, odds ratio 30.6). CONCLUSIONS: The main findings of our study is that the procedure can be difficult to perform in particular conditions and can lead to peroperative failure in these cases, highlighting the need for adequate patients screening. When technical success is obtained, outcomes can be considered as satisfactory.

Surgical and endovascular hybrid approach in peripheral arterial disease of the lower limbs.

BACKGROUND: Multilevel peripheral arterial disease is frequently observed in patients with intermittent claudication or critical limb ischemia. This report evaluates the efficacy of one-stage hybrid revascularization in patients with multilevel arterial peripheral disease. PATIENTS AND METHODS: A retrospective analysis of a prospective database included all consecutive patients treated by a hybrid approach for a multilevel arterial peripheral disease. The primary outcome was the patency rate at 6 months and 1 year. Secondary outcomes were early and midterm complication rate, limb salvage and mortality rate. Statistical analysis, including a Kaplan-Meier estimate and univariate and multivariate Cox regression analyses were carried out with the primary, primary assisted and secondary patency, comparing the impact of various risk factors in pre- and post-operative treatments. RESULTS: 64 patients were included in the study, with a mean follow-up time of 428 days (range: 4 - 1140). The technical success rate was 100 %. The primary, primary assisted and secondary patency rates at 1 year were 39 %, 66 % and 81 %, respectively. The limb-salvage rate was 94 %. The early mortality rate was 3.1 %. Early and midterm complication rates were 15.4 % and 6.4 %, respectively. The early mortality rate was 3.1 %. CONCLUSIONS: The hybrid approach is a major alternative in the treatment of peripheral arterial disease in multilevel disease and comorbid patients, with low complication and mortality rates and a high limb-salvage rate.

Perivascular sustained release of atorvastatin from a hydrogel-microparticle delivery system decreases intimal hyperplasia.

Intimal hyperplasia (IH) is the major cause of grafted vessel occlusion and occurs frequently after bypass intervention. No pharmaceutical formulation is currently available to prevent this pathology. Local perivascular delivery of an appropriate active compound released in a time-dependent manner (from day one up to 4weeks) is necessary for an efficient single-administration preventive therapy. To this aim, we propose the combination of gel and microparticles delivery system containing atorvastatin (ATV). The incorporation of ATV in a cross-linked hyaluronic acid gel, provided in vitro a fast release over 3days, while ATV-loaded poly-lactic-co-glycolic acid (PLGA) microparticles dispersed in the gel gave a sustained release over 4weeks. In vivo, ATV formulations were applied perivascularly in mice undergoing carotid artery ligation. IH was significantly reduced (-68%) in presence of ATV incorporated in hyaluronic acid gel and encapsulated in microparticles compared to control. No significant IH alteration was observed when ATV was incorporated only in the gel (fast release) or only in the microparticles (slow release) demonstrating that a biphasic release of ATV is essential to interfere with the development of IH. ATV was detected in adjacent tissues 28days after the intervention, showing the sustained presence of the drug in vivo. After four weeks ATV was not detected in remote tissues, except at a very low concentration (0.044ng/mg) in the liver, suggesting a very low risk of systemic toxicity of locally delivered ATV. Additionally, the ex vivo data showed that ATV in solution permeates through isolated human saphenous veins and thus is a good candidate for perivascular delivery. Our data demonstrate that a local biphasic ATV release on the mice ligated carotid efficiently prevents the development of IH without apparent toxicity.

Early cannulation of the Flixene™ arteriovenous graft.

PURPOSE: The aim of this review was to search for evidence of the efficiency of early cannulation of the Flixene™ (Maquet-Atrium Medical, Hudson, NH, USA) arteriovenous graft (AVG) in the current literature and to assess its patency and complication rates. METHODS: Searches in Pubmed, Medline, Embase and the Cochrane Library were performed using the following specific search terms: early cannulation AVG and/or Flixene™ graft. The primary outcomes were mean time to first cannulation and patency rates at 12 months. Secondary outcomes were complications. RESULTS: Six studies reporting outcomes in a total of 260 procedures were included in this review. The median delay from intervention to first cannulation was documented in four studies and was less than 3 days. Primary assisted patency at 12 months ranged from 45% to 53% in the four documented series. In five studies, documented secondary patency at 12 months ranged from 63% to 92%. Two studies compared outcomes between traditional and Flixene™ grafts: one study reported significantly (p<0.01) improved one-year patency using the Flixene™ graft, the two studies did not report significant differences in complication rates between both groups. The rate of infection and pseudo-aneurysm formation ranged from 0 to 11% and 0 to 6%, respectively. CONCLUSIONS: This review shows that early cannulation of the Flixene™ graft within 3 days following its implantation is feasible with one-year patency and complication rates equivalent to those of conventional grafts which can be cannulated only after 2 weeks.