Limb Salvage and Survival in Chronic Limb-Threatening Ischemia: The Need for a Fast-Track Team-Based Approach.

Chronic limb-threatening ischemia (CLTI) represents the end-stage form of peripheral arterial disease (PAD) and is associated with a very poor prognosis and high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease, reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage, and mortality, with a focus on the need of a fast-track team-based management that is a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and to promote the standardisation of care and communication between specialist and non-specialist healthcare professionals.

Sex-Related Differences and Factors Associated with Peri-Procedural and 1 Year Mortality in Chronic Limb-Threatening Ischemia Patients from the CLIMATE Italian Registry.

BACKGROUND: Identifying sex-related differences/variables associated with 30 day/1 year mortality in patients with chronic limb-threatening ischemia (CLTI). METHODS: Multicenter/retrospective/observational study. A database was sent to all the Italian vascular surgeries to collect all the patients operated on for CLTI in 2019. Acute lower-limb ischemia and neuropathic-diabetic foot are not included. FOLLOW-UP: One year. Data on demographics/comorbidities, treatments/outcomes, and 30 day/1 year mortality were investigated. RESULTS: Information on 2399 cases (69.8% men) from 36/143 (25.2%) centers. Median (IQR) age: 73 (66-80) and 79 (71-85) years for men/women, respectively (p < 0.0001). Women were more likely to be over 75 (63.2% vs. 40.1%, p = 0.0001). More men smokers (73.7% vs. 42.2%, p < 0.0001), are on hemodialysis (10.1% vs. 6.7%, p = 0.006), affected by diabetes (61.9% vs. 52.8%, p < 0.0001), dyslipidemia (69.3% vs. 61.3%, p < 0.0001), hypertension (91.8% vs. 88.5%, p = 0.011), coronaropathy (43.9% vs. 29.4%, p < 0.0001), bronchopneumopathy (37.1% vs. 25.6%, p < 0.0001), underwent more open/hybrid surgeries (37.9% vs. 28.8%, p < 0.0001), and minor amputations (22% vs. 13.7%, p < 0.0001). More women underwent endovascular revascularizations (61.6% vs. 55.2%, p = 0.004), major amputations (9.6% vs. 6.9%, p = 0.024), and obtained limb-salvage if with limited gangrene (50.8% vs. 44.9%, p = 0.017). Age > 75 (HR = 3.63, p = 0.003) is associated with 30 day mortality. Age > 75 (HR = 2.14, p < 0.0001), nephropathy (HR = 1.54, p < 0.0001), coronaropathy (HR = 1.26, p = 0.036), and infection/necrosis of the foot (dry, HR = 1.42, p = 0.040; wet, HR = 2.04, p < 0.0001) are associated with 1 year mortality. No sex-linked difference in mortality statistics. CONCLUSION: Women exhibit fewer comorbidities but are struck by CLTI when over 75, a factor associated with short- and mid-term mortality, explaining why mortality does not statistically differ between the sexes.

Device selection for carotid stenting: reviewing the evidence.

INTRODUCTION: Carotid artery stenting (CAS) has recently changed the status in the treatment of the extracranial carotid atheromasic disease. In recent years, evolution in both stents and protection devices as well as in carotid stenting techniques, has resulted in an important reduction in the rate of stroke in patients undergoing CAS procedures. Areas covered: The purpose of this article is reviewing the literature and summarizing the current evidence of the new available materials to underline the importance of the correct choice of the devices during the procedure. Expert commentary: Certainly a key issue in order to limit the periprocedural events to the lowest possible, is to select the appropriate device for the appropriate patient anatomy and clinical syndrome, the so called 'tailored approach'.

Endovascular correction in acute bleeding after femoro-popliteal bypass: a single-center experience.

BACKGROUND: The endovascular correction (EC) has emerged in recent years as a possible alternative to surgical revision (SR) in case of bleeding complications after peripheral bypass (PB). The purpose of this study is to evaluate the efficacy and safety of EC compared to SR in case of bleeding complications of PB. METHODS: From January 2004 to December 2014, we have submitted 32 patients to surgery for acute bleeding in previous PB (25 venous bypass, in situ or reversed, 6 PTFE bypass and 1 composite bypass). The cause of the bleeding was the dehiscence of proximal anastomosis in 14 patients, the dehiscence of distal anastomosis in 11 patients and the rupture of the graft in 7 patients. All patients postoperatively underwent anticoagulation or antiplatelet therapy, antibiotic therapy and close ultrasound follow-up. Patency rate, limb salvage rate and survival rate in the short term were assessed by Kaplan-Meier curves. RESULTS: Of the 32 patients treated for acute bleeding in previous PB, 11 underwent endovascular correction with a technical success of 100% (no need for reintervention), while in 21 patients a surgical revision was performed. Among the latter, in 4 cases (19.1%) an early bleeding occurred, and endovascular correction was promptly performed solving the bleeding in the absence of sequelae (then a total of 15 patients were treated by endovascular correction). The 12-month patency, limb salvage and survival rates were respectively 71.4%, 88.2% and 88.2% in the SR group and 80%, 93.3% and 100% in the EC. CONCLUSIONS: This topic underlines that endovascular correction after peripheral bypass bleeding is an attractive alternative to surgery, but there are still a few data to change the gold standard treatment. Randomized clinical trials comparing the two treatment options are warranted.

Carotid artery stenting renaissance: is it safe and effective using new materials?

Data from randomized controlled trials (RCTs) demonstrated significant differences between carotid artery stenting (CAS) and carotid endarterectomy (CEA) in terms of early neurological outcomes (from 0 to 30 days), although mid- and long-term neurological results are indistinguishable. CAS in symptomatic standard risk patients is coupled with a higher risk of any stroke, and death or any stroke at 30 days, while the rates of disabling or major stroke do not vary remarkably between treatments. Since the micro-embolization through the stent struts is the primary suspected cause of suspected early postoperative neurological complications (i.e., non-disabling stroke), surgical technology has focused on the production of a new generation of stents with a double layer of mesh to reduce the "free area" of the cells, and on new cerebral protection devices. Another major determinant of early negative outcomes is believed to be the intraluminal manipulation occurring during carotid engagement from the aortic arch, the crossing maneuvers at the level of the culprit lesion and vessel trauma during angioplasty. To address these subject matters, new embolic protection devices and innovative strategies have been developed, consequently. This review is designed to furnish the current status of CAS results, to update the ongoing RCTs comparing CAS vs. CEA outcomes, and to recapitulate the features and clinical outcomes for a new carotid stent design, the so called "mesh-stents", and new embolic protection tools.

Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of body weight loss in subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES).

OBJECTIVE: Physical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes. Here, we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study. RESEARCH DESIGN AND METHODS: Sedentary patients with type 2 diabetes (n = 606) were enrolled in 22 outpatient diabetes clinics and randomized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months. Baseline to end-of-study changes in cardiorespiratory fitness, strength, and flexibility, as assessed by Vo(2max) estimation, a 5-8 maximal repetition test, and a hip/trunk flexibility test, respectively, were calculated in the whole cohort, and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors. RESULTS: Changes in Vo(2max), upper and lower body strength, and flexibility were significantly associated with the variation in the volume of physical activity, HbA(1c), BMI, waist circumference, high-sensitivity C-reactive protein (hs-CRP), coronary heart disease (CHD) risk score, and inversely, HDL cholesterol. Changes in fitness predicted improvements in HbA(1c), waist circumference, HDL cholesterol, hs-CRP, and CHD risk score, independent of study arm, BMI, and in case of strength, also waist circumference. CONCLUSIONS: Physical activity/exercise-induced increases in fitness, particularly muscular, predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss, thus indicating the need for targeting fitness in these individuals, particularly in subjects who struggle to lose weight.

Advanced lipoxidation end-products mediate lipid-induced glomerular injury: role of receptor-mediated mechanisms.

Atherosclerosis and renal disease are related conditions, sharing several risk factors. This includes hyperlipidaemia, which may result in enhanced lipoprotein accumulation and chemical modification, particularly oxidation, with formation of advanced lipoxidation endproducts (ALEs). We investigated whether increased lipid peroxidation plays a major role in the pathogenesis of lipid-induced renal disease, via receptor-mediated mechanisms involving the scavenger and advanced glycation endproduct (AGE) receptors. Mice knocked out for galectin-3 (Gal3(-/-)), an AGE receptor previously shown to protect from AGE-induced renal injury, and the corresponding wild-type (Gal3(+/+)) animals, were fed an atherogenic high-fat diet (HFD; 15% fat, 1.25% cholesterol and 0.5% sodium cholate); mice fed a normal-fat diet (NFD; 4% fat) served as controls. Gal3(+/+) mice fed a HFD developed glomerular disease, as indicated by proteinuria, mesangial expansion and glomerular hypertrophy and sclerosis. Glomerular injury was associated with increased glomerular matrix protein expression, ALE and oxidized LDL content, oxidative stress, AGE and scavenger receptor expression and macrophage infiltration, with only modest renal/glomerular fat accumulation and changes in lipid metabolism. Fibrotic and inflammatory changes, together with accumulation of ALEs, such as 4-hydroxy-2-nonenal adducts and N(epsilon)-carboxymethyllysine, oxidative stress and expression of the receptor of AGEs (RAGE), were significantly more marked in Gal3(-/-) animals, whereas fat deposition and abnormalities in lipid metabolism remained modest. Thus, lipid-induced renal damage is mainly dependent on lipid peroxidation with formation of carbonyl reactive species and ALEs, which accumulate within the kidney tissue, thus triggering receptor-mediated pro-inflammatory signalling pathways, as in atherogenesis. Moreover, galectin-3 exerts a significant role in the uptake and effective removal of modified lipoproteins, with diversion of these products from RAGE-dependent pro-inflammatory pathways associated with downregulation of RAGE expression.