Reporting Peripheral Artery Disease in Claudicants: Lessons Learned From the TASC-Ability Study.

BACKGROUND: The Trans-Atlantic Inter-Society Consensus Document (TASC II) aims to comprehensively describe the case scenarios of aortoiliac and femoropopliteal lesions to suggest an endovascular or a surgical approach. Over time, it has become a guide for describing the gravity of arterial lesions. PURPOSE: To assess the revised TASC II system for classifying arterial lesions in a large database of patients presenting with claudication. MATERIALS AND METHODS: This study was a retrospective review of the arteriograms of patients with intermittent claudication. Aortoiliac and femoropopliteal lesions were classified according to the TASC II. When no consensus was reached, the lesion was rated as unTASCable. RESULTS: In total, 1454 patients were included (male: 62.1%, 66.8±9.3 years). There were 39% aortoiliac lesions (n=960/2462) and 61% femoropopliteal lesions (n=1502/2462); 33.6% of the patients (n=489/1454) were associated with aortoiliac and femoropopliteal lesions. In addition, 20% of the lesions (n=493/2462) were unTASCable, and 26.7% of the patients (n=388/1454) had at least 1 unTASCable lesion. There were 4 categories of unTASCable lesions: (1) association with a common femoral artery lesion in 53.1% (n=262/493); (2) iliac artery lesions in 23.1% (n=114/493); (3) femoropopliteal lesions whose lengths did not fit into any category in 16.6% (n=82/493); and (4) association with an aortic lesion in 7.1% (n=35/493). The interobserver agreement was 0.97 for anatomically describing the infrarenal arterial tree and 0.85 for TASCing, with the lesions lowering to 0.69 for aortoiliac lesions. CONCLUSION: Using the revised TASC II case scenario, 26.7% of the patients had at least 1 unTASCable lesion. Reporting peripheral artery disease using a comprehensive anatomical description of the infrarenal arterial tree showed better interobserver reproducibility.

Diabetes Impaired Ischemia-Induced PDGF (Platelet-Derived Growth Factor) Signaling Actions and Vessel Formation Through the Activation of Scr Homology 2-Containing Phosphatase-1.

Objective: Critical limb ischemia is a major complication of diabetes characterized by insufficient collateral vessel development and proper growth factor signaling unresponsiveness. Although mainly deactivated by hypoxia, phosphatases are important players in the deregulation of proangiogenetic pathways. Previously, SHP-1 (Scr homology 2-containing phosphatase-1) was found to be associated with the downregulation of growth factor actions in the diabetic muscle. Thus, we aimed to gain further understanding of the impact of SHP-1 on smooth muscle cell (SMC) function under hypoxic and diabetic conditions. Approach and Results: Despite being inactivated under hypoxic conditions, high glucose level exposure sustained SHP-1 phosphatase activity in SMC and increased its interaction with PDGFR (platelet-derived growth factor receptor)-ß, thus reducing PDGF proangiogenic actions. Overexpression of an inactive form of SHP-1 fully restored PDGF-induced proliferation, migration, and signaling pathways in SMC exposed to high glucose and hypoxia. Nondiabetic and diabetic mice with deletion of SHP-1 specifically in SMC were generated. Ligation of the femoral artery was performed, and blood flow was measured for 4 weeks. Blood flow reperfusion, vascular density and maturation, and limb survival were all improved while vascular apoptosis was attenuated in diabetic SMC-specific SHP-1 null mice as compared to diabetic mice. Conclusions: Diabetes and high glucose level exposure maintained SHP-1 activity preventing hypoxia-induced PDGF actions in SMC. Specific deletion of SHP-1 in SMC partially restored blood flow reperfusion in the diabetic ischemic limb. Therefore, local modulation of SHP-1 activity in SMC could represent a potential therapeutic avenue to improve the proangiogenic properties of SMC under ischemia and diabetes.

Deletion of AT2 Receptor Prevents SHP-1-Induced VEGF Inhibition and Improves Blood Flow Reperfusion in Diabetic Ischemic Hindlimb.

OBJECTIVE: Ischemia caused by narrowing of femoral artery is a major cause of peripheral arterial disease and morbidity affecting patients with diabetes mellitus. We have previously reported that the inhibition of the angiogenic response to VEGF (vascular endothelial growth factor) in diabetic mice was associated with the increased expression of SHP-1 (SH2 domain-containing phosphatase 1), a protein that can be activated by the AT2 (angiotensin II type 2) receptor. Deletion of AT2 receptor has been shown to promote angiogenesis within the ischemic muscle. However, the relative impact of AT2 receptor in diabetic condition remains unknown. APPROACH AND RESULTS: Nondiabetic and diabetic AT2 null (Atgr2-/Y) mice underwent femoral artery ligation after 2 months of diabetes mellitus. Blood perfusion was measured every week ≤4 weeks post-surgery. Expression of the VEGF, SHP-1, and renin-angiotensin pathways was evaluated. Blood flow in the ischemic muscle of diabetic Atgr2-/Y mice recovered faster and ≤80% after 4 weeks compared with 51% recovery in diabetic control littermates. Diabetic Atgr2-/Y had reduced apoptotic endothelial cells and elevated small vessel formation compared with diabetic Atgr2+/Y mice, as well as increased SHP-1 expression and reduced VEGF receptor activity. In endothelial cells, high glucose levels and AT2 agonist treatment did not change SHP-1, VEGF, and VEGF receptor expression. However, the activity of SHP-1 and its association with the VEGF receptors were increased, causing inhibition of the VEGF action in endothelial cell proliferation and migration. CONCLUSIONS: Our results suggest that the deletion of AT2 receptor reduced SHP-1 activity and restored VEGF actions, leading to an increased blood flow reperfusion after ischemia in diabetes mellitus.

Is radiofrequency ablation of varicose veins a valuable option? A systematic review of the literature with a cost analysis.

BACKGROUND: Since the 1990s, new techniques for the treatment of varicose veins have emerged, including radiofrequency ablation (RFA) and laser treatment. We performed a study to compare the safety, efficacy and outcomes of RFA compared to those of open surgery and laser ablation for the treatment of varicose veins. We also carried out a cost analysis of RFA compared to open surgery to assess whether RFA could help free up operating room time by being performed in an outpatient context. METHODS: We conducted a systematic literature review (publication date May 2010-September 2013 for articles in English, January 1991-September 2013 for those in French). We used several checklists to measure the quality of the studies. We also collected data on costing. RESULTS: The literature search identified 924 publications, of which 38 were retained for analysis: 15 literature reviews, 1 good-practice guideline and 22 new primary studies. The overall level of evidence was low to moderate owing to the limited sample sizes, lack of information on patient characteristics and lack of standardization of the outcome measures. However, the results obtained are consistent from study to study. In the short and medium term, RFA is considered as effective as open surgery or laser treatment (moderate level of evidence) and presents fewer major and minor complications than open surgery (low level of evidence). Radiofrequency ablation can be performed on an outpatient basis. We calculated that RFA would be about $110-$220 more expensive per patient than open surgery. CONCLUSION: Radiofrequency ablation is a valuable alternative to open surgery and would free up operating room time in a context of low accessibility.

CONTEXTE: Depuis les années 1990, de nouvelles techniques pour le traitement des varices ont émergé, y compris l'ablation par radiofréquence (ARF) et le traitement au laser. Nous avons procédé à une étude afin de comparer l'innocuité, l'efficacité et les résultats de l'ARF à ceux de la chirurgie ouverte et de l'ablation par laser pour le traitement des varices. Nous avons aussi procédé à une analyse des coûts de l'ARF comparativement à la chirurgie pour vérifier si, en étant effectuée en consultation externe, l'ARF permet de libérer du temps de bloc opératoire. MÉTHODES: Nous avons réalisé une revue systématique de la documentation (articles publiés entre mai 2010 et septembre 2013 en langue anglaise, et entre janvier 1991 et septembre 2013 en langue française). Nous avons utilisé plusieurs séries de critères pour mesurer la qualité des études. Nous avons aussi recueilli des données sur l'estimation des coûts. RÉSULTATS: La recherche documentaire a permis de recenser 924 publications, dont 38 ont été retenues pour analyse : 15 examens documentaires, 1 directive de pratique optimale et 22 études principales. Le niveau de preuve global a été jugé de faible à modéré en raison de la taille limitée des échantillons, du manque d'information sur les caractéristiques des patients et de l'absence de normalisation des mesures paramétriques. Toutefois, les résultats obtenus concordent d'une étude à l'autre. À court et à moyen terme, l'ARF est considérée aussi efficace que la chirurgie ouverte ou que le traitement au laser (niveau de preuve modéré) et s'accompagne de moins de complications majeures et mineures que la chirurgie ouverte (faible niveau de preuve). L'ablation par radiofréquence peut être effectuée en consultation externe. Nous avons calculé que l'ARF couterait environ 110 à 220 $ de plus par patient comparativement à la chirurgie. CONCLUSION: L'ablation par radiofréquence est une solution de rechange valable à la chirurgie ouverte et pourrait libérer du temps de bloc opératoire dans un contexte d'accès restreint.

How mechanical deformations contribute to the effectiveness of negative-pressure wound therapy.

Negative-pressure wound therapy (NPWT) has significantly improved healing rates and patient comfort since its inception. However, a considerable number of questions have been raised regarding its mechanisms of action. Many health care workers and researchers have attempted to clarify the role of NPWT in wound healing. The purpose of this perspective article is to assemble some of the concepts that have been put forward in order to propose an integrated view of the mechanisms involved in NPWT. Particular emphasis will be placed on mechanically induced tissue deformations and their involvement in some of the key processes of wound healing, including nutrient and oxygen transport, blood vessel formation, and cellular proliferation and differentiation, mainly of myofibroblasts.

Removal of the cervical collar from alpine rescue protocols? A biomechanical non-inferiority trial in real-life mountain conditions.

BACKGROUND: Alpine skiing rescues are challenging because of the mountainous environment and risks of cervical spine motion (CSM) induced during victims' extrications (EXs) and downhill evacuations (DEs). The benefits of applying a cervical collar (CC) over manual in-line stabilization without CC (MILS) in terms of spinal motion restriction during simulated alpine rescues are undocumented. Our hypothesis was that CSM recorded using MILS alone is non-inferior to CSM recorded with a CC according to a 10 degrees margin. METHODS: A total of 32 alpine extrications and 4 downhill evacuations on different slope conditions were performed using a high fidelity mannequin designed with a motion sensors instrumented cervical spine. The primary outcome was the peak extrication 3D excursion angle (Peak 3D θEX,) of the mannequin's head. The secondary objectives were to describe the time to extrication completion (tEX) and to highlight which extrication manipulation is more likely to induce CSM. RESULTS: The median Peak 3D θEX recorded during flat terrain extrications using CC was 10.77° (95% CI 7.31°-16.45°) compared to 13.06° (95% CI 10.20°-30.36°) using MILS, and 16.09° (95% CI 9.07°-37.43°) for CC versus 16.65° (95% CI 13.80°-23.40°) using MILS on a steep slope. Peak 3D θEX with CC or using MILS during extrications were equivalent according to a 10 degrees non-inferiority hypothesis testing (p < 0.05). Time to extrication completion (tEX) was significantly reduced using MILS without CC on a flat terrain with a median duration of 237,3 s (95% CI 197.8 s, 272.2 s) compared to 358.7 s (95% CI 324.1 s, 472.4 s). During downhill evacuations, CSM with and without CC across all terrain conditions were negligible (< 5°). When CC is used; its installation manipulation induces the highest CSM. When EXs are done using MILS without CC, the logroll initiation is the manipulation inducing the highest risk of CSM. CONCLUSION: For experienced ski patrollers, the biomechanical benefits of spinal motion restriction provided by CC over MILS during alpine skiing rescues appear to be marginal and CC use negatively affects rescue time.

Endothelial deletion of PKCδ prevents VEGF inhibition and restores blood flow reperfusion in diabetic ischemic limb.

AIMS: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling. METHODS: Nondiabetic and diabetic mice, with (ec-Prkcd-/-) or without (ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs. RESULTS: Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd-/- mice. VEGF signaling pathway was restored in diabetic ec-Prkcd-/- mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity. CONCLUSIONS: Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.

Paclitaxel and mortality in patients with claudication and de novo femoropopliteal lesions: a historical cohort study.

OBJECTIVE: To compare the mortality rates of patients with claudication and de novo femoropopliteal lesions treated with and without paclitaxel coated devices (PCD). BACKGROUND: A recent meta-analysis, mostly including patients with claudication and de novo femoropopliteal lesions but also with recurrent stenoses and critical limb ischemia, has shown a significant excess mortality in patients treated with PCD. METHODS: Comparison of two historical cohorts of patients presenting with claudication and de novo femoropopliteal lesions treated with and without PCD between 2008 and 2018. RESULTS: After review of 5219 arteriograms in patients presenting with peripheral artery disease, 700 consecutive patients were included consisting in 72.6% of male (n = 508). Mean age was 68.1 ± 8.5 years. 45.7% of the patients (n = 320) had a treatment including a PCD. Mean femoropopliteal lesion length was 123 ± 91 mm including 44.6% of occlusions. Patients of the control group were censored at crossover to paclitaxel when applicable. Mortality rates at 1, 2 and 5 years were 4.6%, 7.5%, 19.4% and 1.6%, 6.2%, 16.6% in the non-PCD and PCD groups respectively. The relative risks of death when using PCD were 0.35 (p = 0.03), 0.83 (p = NS) and 0.86 (p = NS) at 1, 2 and 5 years respectively. CONCLUSION: There was no excess mortality in patients with claudication and de novo femoropopliteal lesions treated with paclitaxel coated devices at 1, 2 and 5 years of follow-up in this cohort. The current study suggests that additional prospective randomized studies properly powered to study mortality are necessary.

Novel Crossing System for the Recanalization of Complex Chronic Total Occlusions: Ex vivo Proof of Concept of the SoundBite Crossing System.

Chronic total occlusion (CTO) lesions are frequent in patients with peripheral and coronary artery disease, and associated with a higher risk of adverse events, including mortality, decreased quality of life, and increased health-care costs. Percutaneous intervention of CTO lesions has been associated with a lower procedural success rate, and current dedicated CTO devices may be of limited use for the non-CTO expert, and associated with increased intraprocedural complication rates. The SoundBite Crossing System (SoundBite Medical Solutions, Inc) is a newly developed device using shockwaves (short-duration, high-amplitude pressure pulses) to facilitate penetration of the proximal cap and crossing of the occlusion. The current report describes the first use of the SoundBite Crossing System in the recanalization of human ex vivo occluded arteries below the knee during a simulated procedure performed under fluoroscopy. Microcomputed tomography and histologic evaluation of the occluded and recanalized segment are provided to support therapeutic mechanism.