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.

Focus on the Most Common Paucisymptomatic Vasculopathic Population, from Diagnosis to Secondary Prevention of Complications.

Middle-aged adults can start to be affected by some arterial diseases (ADs), such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid, or renal artery or subclavian artery stenosis. These vasculopathies are often asymptomatic or paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of ADs is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, ADs carry a high correlation with silent coronary artery disease (CAD). This study focuses on the most common ADs, in the attempt to summarize some key points which should selectively drive screening. Since the human and economic possibilities to instrumentally screen wide populations is not evident, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physicians. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspicion of ADs after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.

Focus on the Prevention of Acute Limb Ischemia: Centrality of the General Practitioner from the Point of View of the Internist.

The thrombotic mechanism, being common to peripheral arterial disease (PAD), acute myocardial infarction (AMI), and stroke, is responsible for the highest number of deaths in the western world. However, while much has been done for the prevention, early diagnosis, therapy of AMI and stroke, the same cannot be said for PAD, which is a negative prognostic indicator for cardiovascular death. Acute limb ischemia (ALI) and chronic limb ischemia (CLI) are the most severe manifestations of PAD. They both are defined by the presence of PAD, rest pain, gangrene, or ulceration and we consider ALI if symptoms last less than 2 weeks and CLI if they last more than 2 weeks. The most frequent causes are certainly atherosclerotic and embolic mechanisms and, to a lesser extent, traumatic or surgical mechanisms. From a pathophysiological point of view, atherosclerotic, thromboembolic, inflammatory mechanisms are implicated. ALI is a medical emergency that puts both limb and the patient's life at risk. In patients over age 80 undergoing surgery, mortality remains high reaching approximately 40% as well as amputation approximately 11%. The purpose of this paper is to summarize the scientific evidence on the possibilities of primary and secondary prevention of ALI and to raise awareness among doctors involved in the management of ALI, in particular by describing the central role of the general practitioner.

In-vivo evaluation of silk fibroin small-diameter vascular grafts: state of art of preclinical studies and animal models.

Autologous vein and artery remains the first choice for vascular grafting procedures in small-diameter vessels such as coronary and lower limb districts. Unfortunately, these vessels are often found to be unsuitable in atherosclerotic patients due to the presence of calcifications or to insufficient size. Synthetic grafts composed of materials such as expanded polytetrafluoroethylene (ePTFE) are frequently employed as second choice, because of their widespread availability and success in the reconstruction of larger arteries. However, ePTFE grafts with small diameter are plagued by poor patency rates due to surface thrombogenicity and intimal hyperplasia, caused by the bioinertness of the synthetic material and aggravated by low flow conditions. Several bioresorbable and biodegradable polymers have been developed and tested to exploit such issues for their potential stimulation to endothelialization and cell infiltration. Among these, silk fibroin (SF) has shown promising pre-clinical results as material for small-diameter vascular grafts (SDVGs) because of its favorable mechanical and biological properties. A putative advantage in graft infection in comparison with synthetic materials is plausible, although it remains to be demonstrated. Our literature review will focus on the performance of SF-SDVGs in vivo, as evaluated by studies performing vascular anastomosis and interposition procedures, within small and large animal models and different arterial districts. Efficiency under conditions that more accurately mime the human body will provide encouraging evidence towards future clinical applications.

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.

Results of New Dual-Drug Coated Balloon Angioplasty versus POBA for Femoropopliteal Lesions.

BACKGROUND: The study aimed to assess the 24-month safety and effectiveness of a new generation drug-coated balloon (DCB) (Elutax; AR Baltic Medical, Vilnius Lithuania-also marketed as Emperor in some European countries; Aachen Resonance, Germany, and AB Medica, Italy) for the treatment of patients with femoropopliteal lesions. METHODS: From January 2019 to January 2020, DCB angioplasties using Elutax were performed on 53 consecutive patients (53 limbs) with femoropopliteal lesions (group A) and compared with a noncontemporary control group (group B) consisting of 71 patients (71 limbs) treated with plain old balloon angioplasty (POBA) between January 2017 and January 2018. Before performing the angioplasty, both groups underwent clinical examination, ultrasound evaluation, and computed tomography angiography to delineate subject clinical and baseline lesion characteristics. Primary end point was primary patency rate at 24 months. Secondary end points included clinically driven target lesion revascularization (CD-TLR), overall survival and limb salvage rates. RESULTS: In both groups technical success rate was 100% with bailout stenting performed in 16.9% (9/53) of lesions in group A, while stenting was necessary in 22.5% of lesions (16/71) in group B. Patients treated with Elutax exhibited lower 24-month restenosis/reocclusion rate and improved primary patency compared to those treated with POBA (restenosis/reocclusion rate: 9.4% vs. 25.3%, CI 95% 0.01-0.30, P = 0.034; primary patency: 88.2% vs. 71.5%, log rank P = 0.03). Twenty-four-month CD-TLR rate was 7.5% for DCB versus 18.3% for POBA. No device or procedure-related deaths occurred, and no 30-day mortality was observed in either group. During the follow-up period, the limb salvage rate was 94.9% for A group and 92.1% for B group. All minor amputations occurred in limbs presented with chronic limb threatening ischemia (CLTI). Overall survival was 91.7% for group A and 89.4% for group B. CONCLUSIONS: Paclitaxel + Dextran DCB angioplasty proved safe and effective in managing chronic lesions of femoropopliteal arteries. Our experience has shown superior primary patency rate for Elutax when compared to POBA.

How the First Year of the COVID-19 Pandemic Impacted Patients' Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula.

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.

COVID-19-Associated Endothelial Dysfunction and Microvascular Injury: From Pathophysiology to Clinical Manifestations.

Coronavirus-19 disease (COVID-19) affects more people than previous coronavirus infections and has a higher mortality. Higher incidence and mortality can probably be explained by COVID-19 causative agent's greater affinity (about 10-20 times) for angiotensin-converting enzyme 2 (ACE2) receptor compared with other coronaviruses. Here, the authors first summarize clinical manifestations, then present symptoms of COVID-19 and the pathophysiological mechanisms underlying specific organ/system disease. The worse clinical outcome observed in COVID-19 patients with diabetes may be in part related to the increased ADAM17 activity and its unbalanced interplay with ACE2. Therefore, strategies aimed to inhibit ADAM17 activity may be explored to develop new effective therapeutic approaches.

Is Mini-Invasive Surgery an Alternative for the Treatment of Juxtarenal Aortic Aneurysms?

INTRODUCTION: Aim of our study is to evaluate the outcomes of mini-laparotomy, suprarenal cross-clamping, and enhanced recovery after elective open surgical repair for juxta-renal abdominal aortic aneurysms (JAAA) in a tertiary referral center. METHODS: Data of all consecutive patients with abdominal aortic aneurysms (AAA) electively treated with left sub-costal mini-laparotomy requiring infrarenal or suprarenal cross-clamping between 2013 and 2018 were retrospectively collected. Patients were divided into two groups: infra-renal cross-clamping (group A) and JAAA requiring supra-renal cross-clamping (group B). Early and mid-term mortality, postoperative renal dysfunction according to RIFLE criteria and factors affecting postoperative outcome were analysed. RESULTS: Four hundred one patients, 356 (88.8%) men, mean age 70.8 yrs, underwent open surgical repair (OSR), 343 (85.5%) AAA in group A, 58 (14.5%) JAAA in group B. Mean diameter of the aneurysms was 54 ± 11.4 mm vs. 52 ± 9 mm and mean time of intervention 154.9 ± 56.3 min vs. 180.1 ± 65.7 min respectively. Total clamp time was 72.27 ± 31.4 vs. 75 ± 33.1 and suprarenal clamp time in group B 27.82 ± 14.1 min. Mean hospital length of stay was 5.1 ± 2.8 vs. 5.37 ± 3.4 days respectively. At 30 days, 3 (0.9%) patients died in group A and no one in group B; at 24 months 7 (2%) deaths in group A and 4 (6.9%) in group B. Preoperative, postoperative and discharge serum creatinine mean value, in group B, were 1.07 ± 0.32, 1.31 ± 0.36 and 1.83 ± 1.24 respectively. Based on RIFLE criteria for renal function, we observed Risk in 14.2% and Injury in 12.7% of patients after suprarenal cross clamping. CONCLUSIONS: Our results show that mini-invasive open repair for JAAA with a suprarenal cross-clamping can be performed with acceptable morbidity and mortality rates similar to traditional surgical approach without significant modifications of renal functions.

High Sensitivity C-Reactive Protein Increases the Risk of Carotid Plaque Instability in Male Dyslipidemic Patients.

BACKGROUND: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. METHODS: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. RESULTS: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73-7.48) and in aged female patients 2713 (95% CI 0.14-53.27). DISCUSSION: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease.

Monocentric case-series of mesenteric vascular disease occurred in the first month of the COVID-19 pandemic.

Objectives: we describe Coronavirus Disease (COVID-19) patients also manifesting gastro-intestinal symptoms. Methods: five women, between the ages of 32 and 82 years old, were admitted for acute abdomen, and received a nasopharyngeal swab for COVID-19 screening, lab test analysis, and contrast thoraco-abdominal CT-scan. All presented leukocytosis, different localizations of visceral vessels thrombosis and ischemia, and COVID-19. Results: emergency laparotomy was accepted by all but 1, who died after 5 days. Postoperatively, 1 died of multi-organ failure, 3 were discharged home after 14, 8 and 10 days respectively, under anti-platelet and anticoagulation treatment. Conclusions: in COVID-19 patients with acute abdomen, abdominal contrast CT-scans should be systematically extended to the thorax to detect visceral COVID-19 initial pulmonary signs. Emergency laparotomy and visceral arteries thrombectomy could be necessary.

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy.

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

Carotid intimal medial thickness in rotating night shift is related to IL1ß/IL6 axis.

BACKGROUND AND AIMS: Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors. METHODS AND RESULTS: We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1ß levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016). CONCLUSIONS: Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1ß/IL6 citokine axis connected to sleep disturbances.

Clinical and anatomical variables associated in the literature to limb graft occlusion after endovascular aneurysm repair compared to the experience of a tertiary referral center.

INTRODUCTION: Limb graft occlusion (LGO) is the third reason for hospital readmission after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm. We reviewed the clinical features, incidence, anatomical and devices related predictive factors for LGO after EVAR, and compared them with our experience. EVIDENCE ACQUISITION: EVAR between 2010-2017 were included. Patients with LGO (LGO group) were matched for age and type of endograft with the rest of the entire cohort without LGO (control group). Clinical, anatomical, operative, outcome, and follow-up data were collected. EVIDENCE SYNTHESIS: Two hundred seventy-six EVAR, (30 aorto-uniliac), 276 patients. The incidence of LGO was 2.5% (seven limbs, seven patients) at 27±24.6 days. Symptomatic patients were successfully treated. No mortality, limb loss, critical limb ischemia or residual claudication due to LGO was observed. Fifty patients resulted from the matching. Among the predictive factors of LGO between the two groups, significant differences were observed in graft limb oversizing ≥15% (57.1% vs. 8%, P=0.005), or kinking (42.9% vs. 2%, P=0.01), and diameter of the aortic bifurcation <20 mm (71.4% vs. 20%, P=0.01). Logistic regression analysis showed that these three variables increased the risk of LGO (P=0.003, P=0.006, and P=0.01, respectively). CONCLUSIONS: The strongest predictive factors of LGO issued from our review were: extension in the external iliac artery, or small diameter; tortuous, angled, and calcific iliac axis; excessive oversizing of the limb graft, or kinking; use of old generation devices; EVAR performed outside the instructions for use. Limb graft oversizing >15%, or kinking, and aortic bifurcation <20 mm appear to be independent predictive factors of LGO.

Renal artery side branches patency protection during endovascular exclusion of giant renal artery aneurysm with covered stent: Well done is better than well said.

RATIONALE: Endovascular treatment of renal artery aneurysms has offered a viable alternative with a high success rate and low procedure-related morbidity and mortality. PATIENT CONCERNS: A 60-year-old man, having a right renal artery aneurysm involving the main vessel with two arteries (supplying the inferior and superior lobes of the kidney) originating from the aneurysm sac as well. INTERVENTIONS: A 6 × 28 mm covered stent was inflated in vitro and a side hole was made with a femoral needle in the polytetrafluoroethylene (PTFE) layer, through which a wire was placed in an outside/inside direction in to be inserted in the inferior pole branch. The other wire was inserted inside the main lumen of the stent (to be inserted in the main artery) and the latter, carefully re-crimped on the balloon. This way, the authors guaranteed continuous access to both arteries during aneurysm exclusion and if needed, a second stent could be advanced at the level of the bifurcation to preserve side branch patency. CONCLUSION: Perforating the PTFE of the stent before its introduction into the vessel and keeping a wire into the side branch could be a good strategy to protect any vessel arising from aneurysmal sac that needs to be excluded..

Merits of and Technical Tips for Supra-Mesenteric Aortic Cross Clamping.

Supra-celiac aortic cross clamping is often utilized during aortic reconstruction for aneurysmal/occlusive disease involving the pararenal aorta. However, this may be accompanied a myriad of complications related to hemodynamic disturbances, cardiopulmonary compromise and hepatic ischemia. Supra-mesenteric aortic cross clamping may be an excellent option in selected patients with suitable anatomy to minimize or avoid these complications. Herein, the merits of and technical tips for supra-mesenteric aortic cross clamping are discussed.