AbstractObjectiveAn endovascular-first approach is usually recommended in femoropopliteal occlusive disease. However, despite high technical success, plain old balloon angioplasty (POBA) is burdened ...with high restenosis rates. To reduce this phenomenon, local delivery of drugs has been proposed by way of drug-coated balloons (DCBs). Our goal was to review the evidence for the use of DCBs in the management of femoropopliteal disease and to determine whether it is associated with improved outcomes compared with POBA. MethodsElectronic searches of PubMed (MEDLINE), Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and proceedings of international conferences were performed to identify randomized controlled trials (RCTs) and observational registries evaluating the use of DCBs for femoropopliteal arterial occlusive disease. ResultsThis meta-analysis included 13 RCTs, 6 global registries, and 3 global registries focusing on long lesions. They all used paclitaxel in the DCB arm. There was heterogeneity between trials, and the frequency of stent deployment and duration of dual antiplatelet therapy differed. At 2 years, there were significantly better outcomes for DCBs in terms of target lesion revascularization (odds ratio OR, 0.29; 95% confidence interval CI, 0.20-0.40), primary patency (OR, 0.38; 95% CI, 0.27-0.54), late lumen loss (mean diameter, −0.80 mm; 95% CI, −1.44 to −0.16), and Rutherford category (OR, 0.82; 95% CI, 0.57-1.19). There was no significant difference between DCBs and POBA in amputation or change in ankle-brachial index. A subgroup analysis revealed that male patients treated with DCBs performed significantly better than female patients and that diabetics, heavily calcified lesions, and popliteal lesions performed significantly worse than nondiabetics, noncalcified and mild to moderately calcified lesions, and exclusive superficial femoral artery lesions, respectively. Secondarily stented and nonpredilated lesions did not perform significantly worse, but standard-dose (3 μg/mm 2) DCBs were significantly more effective than low-dose (2 μg/mm 2) DCBs in reducing binary restenosis. In addition, in a low-dose DCB, the polyethylene glycol excipient performed significantly better than polysorbate and sorbitol, whereas binary restenosis was significantly less frequent with the urea excipient, associated with a standard-dose DCB, compared with the polysorbate and sorbitol excipient, associated with a low-dose DCB. ConclusionsDCB angioplasty is an effective treatment associated with high procedural success. In a meta-analysis of industry-sponsored trials, it consistently reduced late lumen loss, binary restenosis, and target lesion revascularization compared with POBA alone in the treatment of femoropopliteal disease. Further independent, non-industry-sponsored RCTs are necessary to better delineate the role of DCBs in the treatment of infrainguinal occlusive disease.
Lower-extremity arterial disease (LEAD) is a major endemic disease with an alarming increased prevalence worldwide. It is a common and severe condition with excess risk of major cardiovascular events ...and death. It also leads to a high rate of lower-limb adverse events and non-traumatic amputation. The American Diabetes Association recommends a widespread medical history and clinical examination to screen for LEAD. The ankle brachial index (ABI) is the first non-invasive tool recommended to diagnose LEAD although its variable performance in patients with diabetes. The performance of ABI is particularly affected by the presence of peripheral neuropathy, medial arterial calcification, and incompressible arteries. There is no strong evidence today to support an alternative test for LEAD diagnosis in these conditions. The management of LEAD requires a strict control of cardiovascular risk factors including diabetes, hypertension, and dyslipidaemia. The benefit of intensive versus standard glucose control on the risk of LEAD has not been clearly established. Antihypertensive, lipid-lowering, and antiplatelet agents are obviously worthfull to reduce major cardiovascular adverse events, but few randomised controlled trials (RCTs) have evaluated the benefits of these treatments in terms of LEAD and its related adverse events. Smoking cessation, physical activity, supervised walking rehabilitation and healthy diet are also crucial in LEAD management. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in LEAD management. The revascularization strategy should take into account several factors including anatomical localizations of lesions, medical history of each patients and operator experience. Further studies, especially RCTs, are needed to evaluate the interest of different therapeutic strategies on the occurrence and progression of LEAD and its related adverse events in patients with diabetes.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
RATIONALE:Klf (kruppel-like factor) 2 is critical to establish and maintain endothelial integrity.
OBJECTIVE:Therefore, determining upstream and downstream mediators of Klf2 would lead to alternative ...therapeutic targets in cardiovascular disease management.
METHODS AND RESULTS:Here we identify Dhh (desert hedgehog) as a downstream effector of Klf2, whose expression in endothelial cells (ECs) is upregulated by shear stress and decreased by inflammatory cytokines. Consequently, we show that Dhh knockdown in ECs promotes endothelial permeability and EC activation and that Dhh agonist prevents TNF-α (tumor necrosis factor alpha) or glucose-induced EC dysfunction. Moreover, we demonstrate that human critical limb ischemia, a pathological condition linked to diabetes mellitus and inflammation, is associated to major EC dysfunction. By recreating a complex model of critical limb ischemia in diabetic mice, we found that Dhh-signaling agonist significantly improved EC function without promoting angiogenesis, which subsequently improved muscle perfusion.
CONCLUSION:Restoring EC function leads to significant critical limb ischemia recovery. Dhh appears to be a promising target, downstream of Klf2, to prevent the endothelial dysfunction involved in ischemic vascular diseases.
Purpose To evaluate the feasibility of endovascular exclusion of popliteal artery aneurysm (PAA) using stent grafts. Methods The clinical data of all patients who underwent endovascular exclusion of ...PAA at three French vascular departments between December 1999 and December 2007 were retrospectively analyzed. Outcome measures included graft patency and endoleak. The Kaplan-Meier method was used to calculate the primary and secondary patency curves. Results A total of 57 PAA in 50 patients (48 men; mean age, 72 ± 11 years; range, 57-96 years) were treated. The type of stent graft used was Hemobahn/Viabahn in 42 (73.7%) cases, Wallgraft in 14 (24.5%) and Passager in one. The mean duration of hospitalization was 5 ± 1.8 days (range, 3-11 days). No patients were lost from follow up (mean, 36 ± 19.4 months; range, 6-96 months). Nine (16%) occlusions and six (10.5%) endoleaks occurred. The global limb salvage rate was 96.5% (55 of 57 PAA). Kaplan-Meier estimates for primary and secondary patency were 85.8% and 87.5% at one year and 82.3% and 87.5% at three years. Conclusions Endovascular treatment of PAA is feasible in selected patients. The main determinants of success are suitable aneurysm anatomy and dual antiplatelet postoperative therapy. Further studies are warranted to determine long-term outcomes of endovascular repair for PAA.
This paper describes how a modal approach in the time-domain can be suitable for calculating the elastodynamic field in a layered plate. This elastodynamic field is generated by impulsive sources ...located in a small region of a composite plate consisting of anisotropic layers stuck together. The aim is to calculate the transient response of the elastic plate around the location of the sources, generally emitting n-cycle pulses. First, we apply a 2D Fourier transform to the wave equation with respect to the coordinates in the plate plane, and then, in the 2D spectrum domain, for any given wave-vector in the plate plane, solving a vibration problem with respect to time and position in the direction perpendicular to the plate. The solution is expressed as the sum of mode responses, each mode having a resonance frequency and a shape which depend on the wave-vector in the plate plane.
These calculations are different from those obtained by the usual method in the harmonic domain, where the modes are searched for a fixed frequency, such as Lamb waves, i.e. guided waves that propagate along the plate. In our case, the solution is given as a summation of plate resonances, i.e. a decomposition on the real eigenfrequencies, associated to Lamb waves with the same fixed wave-vector. This difference is of importance since only Lamb modes with real frequencies and real-valued wavenumbers in the plate plane are involved here, contrary to the usual harmonic methods, where these modes can be evanescent. This is of great interest as it can simplify the calculation of the generated field near the source.
Finally, we obtain a solution in the physical domain by performing an inverse 2D Fourier transform. After a detailed description of the method, results are shown for two typical plates. It is emphasized that the method is accurate for observation points located both above or below the source and reasonably far from it along the plate.
•Response of a layered anisotropic plate to an ultrasonic source calculated in the time-domain.•Independent one-dimensional vibration problems to solve.•Eigenfrequency and shape of a Lamb mode calculated with respect to its wave-vector.
Background Atherosclerosis is a complex pathology in which dysfunctional endothelium, activated leucocytes, macrophages, and lipid-laden foam cells are implicated, and in which plaque disruption is ...driven by many putative actors. This study aimed to identify accurate targetable biomarkers using new in vivo approaches to propose tools for improved diagnosis and treatment. Methods and Results Human scFv (single-chain fragment variable) selected by in vivo phage display in a rabbit model of atherosclerosis was reformatted as scFv fused to the scFv-Fc (single-chain fragment variable fused to the crystallizable fragment of immunoglobulin G format) antibodies. Their reactivity was tested using flow cytometry and immunoassays, and aorta sections from animal models and human carotid and coronary artery specimens. A pool of atherosclerotic proteins from human endarterectomies was co-immunoprecipitated with the selected scFv-Fc followed by mass spectrometry for target identification. Near-infrared fluorescence imaging was performed in
mice after injection of an Alexa Fluor 647-labeled scFv-Fc-2c antibody produced in a baculovirus system with 2 additional cysteine residues (ie, 2c) for future coupling to nano-objects for theranostic applications. One scFv-Fc clone (P3) displayed the highest cross-reactivity against atherosclerotic lesion sections (rabbit, mouse, and human) and was chosen for translational development. Mass spectrometry identified galectin-3, a β-galactoside-binding lectin, as the leader target. ELISA and immunofluorescence assays with a commercial anti-galectin-3 antibody confirmed this specificity. P3 scFv-Fc-2c specifically targeted atherosclerotic plaques in the
mouse model. Conclusions These results provide evidence that the P3 antibody holds great promise for molecular imaging of atherosclerosis and other inflammatory pathologies involving macrophages. Recently, galectin-3 was proposed as a high-value biomarker for the assessment of coronary and carotid atherosclerosis.
Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for in situ bladder carcinomas; however, extravesical BCG infection may occur in remote organs in patients with underlying ...primary immunodeficiency and is a potentially serious complication in 3–5% of cases. It includes granulomatous pneumonia, hepatitis as well as specific dermatological, ophthalmic, and haematopoietic manifestations. Diagnosis is difficult and often based on high clinical suspicion as in many cases Mycobacterium bovis is not isolated. This report presents a rare case of BCGaortitis treated in a tertiary care centre.
A 74 year old man, with a history of bladder cancer treated with BCG therapy over a year ago, presented with malaise, abdominal pain, anorexia, and significant weight loss for several months associated with acute on chronic renal failure and a tender aneurysm. He was diagnosed with hepatic BCGitis and pararenal BCGaortitis. He was considered too high risk for open surgery after a multidisciplinary team meeting and was treated with a four vessel physician modified endograft (PMEG) and antituberculous therapy. At seven month follow up, he was clinically well and control computed tomography showed a patent endograft with complete exclusion of the aortic aneurysm.
Infectious BCG complications after intravesical BCG administration for in situ bladder carcinomas can lead to severe early and late complications. In the present case, the patient presented with both liver and aortic BCG infection. The lack of positive microbiological data should not discourage clinicians from considering BCG infection even if several months have passed since the last BCG instillation.
•Aortic BCGitis should be considered in patients with a history of BCG therapy presenting with fever, fatigue, pain and aortic aneurysm.•Other synchronous localizations should be searched for on PET/CT.•Mycobacteria research should be mandatory in surgical samples.•Histology showing granulomas is often crucial for a definitive diagnosis.•Management often implies surgical treatment and antituberculous therapy for at least a 9-month course.
Objective The primary end points of this study were safety and efficacy of early cannulation of the Flixene graft (Maquet-Atrium Medical, Hudson, NH). Secondary end points were complications and ...patency. Methods This is a prospective single-center nonrandomized study. Study data included patient characteristics; history of vascular access; operative technique; interval between implantation and initial cannulation; complications; and patency at 1 month, 3 months, and every 6 months. Patency rates were estimated by the Kaplan-Meier method. Results Between January 2011 and September 2013, a total of 46 Flixene grafts were implanted in 44 patients (27 men) with a mean age of 63 years. The implantation site was the upper arm in 67% of cases, the forearm in 11%, and the thigh in 22%. Seven grafts were never cannulated during the study period. Of the remaining 39 grafts, 32 (82%) were successfully cannulated within the first week after implantation, including 16 (41%) on the first day. The median interval from implantation to initial cannulation was 2 days (interquartile range, 1-3 days). The median follow-up was 223.5 days (interquartile range, 97-600 days). Five hematomas occurred, but only one required surgical revision. Primary assisted and secondary patency rates were 65% and 86%, respectively, at 6 months and 56% and 86%, respectively, at 1 year. Conclusions This study suggests that cannulation of the Flixene graft within 1 week after implantation is safe and effective. Early cannulation avoids or shortens the need for a temporary catheter. One-year patency rates appeared to be comparable to those achieved with conventional grafts, but long-term follow-up and randomized controlled studies will be needed to confirm this finding.
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