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Purpose: To evaluate the roles of small artery disease (SAD) and medial arterial calcification (MAC) in patients with chronic limb-threatening ischemia (CLTI) and to identify any correlation between these factors and peripheral artery disease (PAD) or outcomes after treatment., Materials and Methods: A retrospective review was conducted of 259 limbs with tissue loss among 223 CLTI patients (mean age 72.2±11.4 years; 194 men) having an angiographic foot vessel study, foot radiography, and at least 6 months of follow-up after intervention. SAD and MAC were quantified using a 3-level score (0=absent, 1=moderate, 2=severe) based on angiography for SAD and foot radiographs for MAC. The MAC score was validated and compared with the SAD score, evaluating their associations with PAD distribution and clinical outcomes., Results: Based on the MAC score, the 259 limbs were classified as 55 group 0 (21.2%), 89 group 1 (34.4%), and 115 group 2 (44.4%). The SAD score stratified the 259 limbs as 67 group 0 (25.9%), 76 group 1 (29.3%), and 116 group 2 (44.8%). Interobserver reproducibility of the MAC score was high (correlation coefficient 0.96). Sensitivity and specificity of the MAC score in detecting SAD was 100% and 98.1%, respectively, in SAD groups 0 and 2 vs 99.1% and 92.7%, respectively, for SAD group 1. PAD was more proximal in MAC and SAD groups 0 and more distal in groups 1 and 2. Both MAC and SAD scores were able to predict clinical endpoints. Multivariable analysis demonstrated that the MAC score represents an independent risk factor for adverse limb events., Conclusion: SAD and MAC must be considered expressions of the same obstructing disease, able to adversely impact the fate of CLTI patients. SAD and MAC scores are powerful prognostic indicators of major adverse limb events in CLTI patients.

Medial arterial calcification (MAC) is a known risk factor for cardiovascular morbidity. The association between vascular calcifications and poor outcome in several vascular districts suggest that infrapopliteal MAC could be a risk factor for lower-limb amputation (LLA). This study's objective is to review the available literature focusing on the association between infrapopliteal MAC and LLA in high-risk patients. The PubMed and Embase databases were systematically searched. We selected original studies reporting the association between infrapopliteal MAC and LLAs in patients with diabetes and/or peripheral artery disease (PAD). Estimates were pooled using either a fixed-effects or a random-effects model meta-analysis. Heterogeneity was evaluated using the Q and I 2 statistics. Publication bias was investigated with a funnel plot and Egger test. The trim-and-fill method was designed to estimate the possibly missing studies. Influence analysis was conducted to search studies influencing the final result. Test of moderators was used to compare estimates in good versus non-good-quality studies. Fifteen articles satisfied the selection criteria ( n = 6489; median follow-up: 36 months). MAC was significantly associated with LLAs (pooled adjusted risk ratio (RR): 2.27; 95% CI: 1.89-2.74; I 2 = 25.3%, Q -test: p = 0.17). This association was kept in the subgroup of patients with diabetes (RR: 2.37; 95% CI: 1.76-3.20) and patients with PAD (RR: 2.48; 95% CI: 1.72-3.58). The association was maintained if considering as outcome only major amputations (RR: 2.11; 95% CI: 1.46-3.06). Our results show that infrapopliteal MAC is associated with LLAs, thus suggesting MAC as a possible new marker of the at-risk limb.

Purpose: To describe a preliminary experience in treating no-option critical limb ischemia (CLI) patients with a hybrid foot vein arterialization (HFVA) technique combining open plus endovascular approaches., Materials and Methods: Between May 2016 and January 2018, 35 consecutive patients (mean age 68±12 years; 28 men) with 36 no-option CLI limbs underwent HFVA in our center. All limbs had grade 3 WIfI (Wound, Ischemia, and foot Infection) ischemia, and the wound classification was grade 1 in 4 (11%) limbs, grade 2 in 4 (11%), and grade 3 in 28 (78%). Surgical bypass was done on the medial marginal vein or a posterior tibial vein, followed by endovascular removal of foot vein valves and embolization of foot vein collaterals. A "tension-free" surgical approach was used to treat foot lesions., Results: At a mean follow-up of 10.8±2 months, limb salvage was achieved in 25 (69%) limbs and wound healing in 16 (44%); 9 patients presented an unhealed wound. Eleven (31%) patients underwent a major amputation (2 below the knee and 9 thigh). One patient with an unhealed wound and open bypass died of myocardial infarction., Conclusion: HFVA is a promising technique able to achieve acceptable rates of limb salvage and wound healing in no-option patients generally considered candidates for an impending major amputation. Further studies are needed to standardize the technique and better identify patients who can benefit from this approach.

Background: Most of the studies on peripheral artery disease (PAD) focused on above-the-ankle artery disease, while less is known about foot artery disease. We hypothesize a scenario were two different diseases can be present in PAD patients, big artery disease (BAD) and small artery disease (SAD), overlapping at the foot level; the aim of this study is to evaluate their prevalence and their correlation with risk factors and critical limb ischemia (CLI) in a large cohort of patients with symptomatic PAD., Methods: We retrospectively reviewed 1915 limbs of 1613 patients (502 females, mean age 72.4±10.8 years) who underwent angiography between September 2009 and November 2013. Age, sex, diabetes, smoke history, high blood pressure, dialysis and BMI were considered as risk factors. Logistic regression was performed to test the association of arterial lesions patterns and CLI, and to evaluate the association between risk factors and lesion localization., Results: SAD was present in 414 patients (25.2%). Patients with disease of any of plantar, dorsalis pedis arteries and SAD faced higher risk of CLI (OR=13.25, 95% CI: 1.69-104.16). SAD was associated with diabetes and dialysis (both: OR=4.85; dialysis only: OR=3.60; diabetes only: OR=1.70; none: reference OR; P<0.01), weight (underweight: OR=1.10; normal: reference OR; overweight: OR=0.81; obese: OR=0.60; P=0.03), while women and tobacco smokers were less likely to have SAD (women: OR=0.68; P<0.01; tobacco use: OR=0.54; P<0.01)., Conclusions: SAD was strongly and independently associated with CLI, diabetes and dialysis. Thus, SAD should be regarded as a leading actor in CLI.

The diabetic foot represents one of the most dangerous complications of diabetic disease, and it is characterized by the presence of infection, ulceration, or necrosis of the foot tissues associated with various degrees of neuropathy or ischemia. If not correctly and promptly treated, it leads to high rates of major amputations. Although in Italy diabetics are about 5% of the population, more than 50% of major amputations are performed in diabetic patients. Compared to non-diabetic patients, diabetic peripheral artery disease localizes more distally, mostly in the below-the-knee vessels, is typically bilateral with multi-level involvement, and presents earlier onset and more aggressive course. The primary target of revascularization, either surgical or percutaneous, is the reconstitution of a direct flow line up to the suffering tissues, essential condition for healing. Revascularization alone, however, is not sufficient, it must be integrated in a multidisciplinary context, where the internal, infectious, surgical and orthopedic aspects of treatment can drive the patient on a personalized route towards limb salvage and recovery of walking.

Recently, great attention is paid to cardiovascular impact of non-insulin glucose-lowering drugs, particularly in terms of major cardiovascular events and risk of heart failure. In this regard, a surprising diversity among different molecules within the same pharmacological class has been noticed, yielding to an intra-class discrepancy which has no analogous in other cardiovascular fields. The aim of this paper is to review the literature, giving an insight of the heterogeneous effects among groups and within group shown by oral antidiabetic drugs, with a special concern to fragile patients, such as those with or at risk of heart failure.