Factors Associated with High-Risk Plaque Characteristics Among Patients with Medium to Severe Carotid Artery Stenosis.

BACKGROUND: There has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis. This study aims to identify potential risk factors associated with high-risk carotid plaques. METHODS: This is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, North American Symptomatic Carotid Endarterectomy Trial criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. RESULTS: A total of 62 patients (mean age: 68.7 ± 9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81% ± 13.53%. In multivariate regression analysis, C-reactive protein > 2 mg/l was strongly associated with symptomatic stenosis (odds ratio [OR] = 9.92 [1.12-88.178]; P = 0.039), and low high-density lipoprotein levels (<1200 mmol/l) were associated with lipidic/necrotic plaque core (OR = 16.88 [1.10-259.30]; P = 0.043). Low high-density lipoprotein levels (OR = 7.22 [1.00-51.95], P = 0.049) and HbA1c >7% (OR = 0.08 [0.01-0.93], P = 0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR = 14.26 [1.21-168.34], P = 0.035) was associated with type V plaques. CONCLUSIONS: This preliminary study has revealed some potential risk factors associated with unstable carotid plaques. These data could help the future development of prognostic models for early detection patients that could benefit from further intervention.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition.

Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Using a novel three-dimensional holographic technology to perform open vascular surgery procedures.

Augmented reality technology has been introduced during recent years into everyday clinical practice. Several surgical specialties have begun using such technology for preoperative planning as well as intraoperatively. Regarding vascular surgery, a limited number of reports have described the benefits, mainly for endovascular procedures. We aim to present a novel three-dimensional holographic system we used to perform an open vascular procedure.

Extra-anatomic bypass procedures for severe aortoiliac occlusive disease-A cohort study.

OBJECTIVES: Extra-anatomic bypass (ExAB) grafting has been questioned due its inferior durability compared to anatomic bypass for aortoiliac occlusive disease (AIOD). This study aims to present early and late outcomes of patients treated with ExAB as well as to evaluate potential prognostic factors. METHODS: This is a retrospective cohort study presenting a series of patients treated with ExAB for AIOD. All patients were treated between 2005 and 2022 within the Vascular Surgery Unit of a University Surgery Clinic. Both early (30-day) and late outcomes were evaluated. Univariate and multivariate analyses were conducted for potential predictors. Kaplan-Meier curve was produced for long-term patency. RESULTS: A total of 41 patients were treated (85.3% males; mean age: 76.3 ± 4.2 years). Indication for treatment included severe claudication or critical limb ischemia (Rutherford stages III-VI). The following procedures were recorded: Femorofemoral bypass (FFB; n = 21) and axillofemoral bypass (AxFB; n = 20). All procedures were conducted using synthetic grafts with external rings. Early outcomes included no death, no myocardial infarction, no major bleeding, no graft infection, and no major amputation. Regarding late outcomes, 14.6% patients were lost after the first month. For the rest of patients (n = 35), five-year primary patency was 88.6%, primary-assisted patency was 94.3%, and secondary patency was also 94.3%. Limb salvage was 100% within follow-up. Endarterectomy at the distal anastomosis was the only independent predictor associated with worse patency in the long-term (OR = 5.356; 95% CI (1.012-185.562); p = .041). CONCLUSIONS: FFB and AxFB is a safe and durable strategy for treating patients with severe AIOD where no other option is feasible. Regarding predictors, only endarterectomy at the distal anastomosis site was associated with an increased risk for graft failure.

The effect of cilostazol on late outcomes after endovascular treatment for occlusive femoropopliteal disease.

OBJECTIVE: Restenosis and late occlusion remain a significant problem for endovascular treatment of peripheral artery disease. This meta-analysis aims to evaluate the effect of cilostazol on late outcomes after endovascular repair of occlusive femoropopliteal disease. METHODS: A systematic literature review was conducted conforming to established criteria to identify articles published up to September 2023 evaluating late outcomes after endovascular treatment for atherosclerotic femoropopliteal disease. Eligible studies should compare outcomes between patients treated with cilostazol and patients not treated with cilostazol. Both prospective and retrospective studies were eligible. Late outcomes included primary patency (PP), restenosis, target lesion revascularization (TLR), and major amputation during follow-up. RESULTS: Overall, 10 clinical studies were identified for analysis including 4721 patients (1831 with cilostazol vs 2890 without cilostazol) that were treated for 5703 lesions (2235 with cilostazol vs 3468 without cilostazol). All studies were performed in Japan. Mean follow-up was 24.1 ± 12.5 months. Cilostazol was associated with a lower risk for restenosis (pooled odds ratio [OR], 0.503; 95% confidence interval [CI], 0.383-0.660; P < .0001). However, no association was found between cilostazol and TLR (pooled OR, 0.918; 95% CI, 0.300-2.812; P = .881) as well as major amputation (pooled OR, 1.512; 95% CI, 0.734-3.116; P = .263). Regarding primary patency, cilostazol was associated with a higher 12-month PP (OR, 3.047; 95% CI, 1.168-7.946; P = .023), and a higher 36-month PP (OR, 1.616; 95% CI, 1.412-1.850; P < .0001). No association was found between cilostazol and mortality during follow-up (pooled OR, .755; 95% CI, 0.293-1.946; P = .561). CONCLUSIONS: Cilostazol seems to have a positive effect on 1- to 3-year PP and restenosis rates among patients treated endovascularly for atherosclerotic femoropopliteal disease. A positive effect on TLR and amputation risk was not verified in this review.

Enhancing risk prediction capabilities in patients with carotid artery disease using a 2-level computational approach.

One of the main causes of death worldwide is carotid artery disease, which causes increasing arterial stenosis and may induce a stroke. To address this problem, the scientific community aims to improve our understanding of the underlying atherosclerotic mechanisms, as well as to make it possible to forecast the progression of atherosclerosis. Additionally, over the past several years, developments in the field of cardiovascular modeling have made it possible to create precise three-dimensional models of patient-specific main carotid arteries. The aforementioned 3D models are then implemented by computational models to forecast either the progression of atherosclerotic plaque or several flow-related metrics which are correlated to risk evaluation. A precise representation of both the blood flow and the fundamental atherosclerotic process within the arterial wall is made possible by computational models, therefore, allowing for the prediction of future lumen stenoses, plaque areas and risk prediction. This work presents an attempt to integrate the outcomes of a novel plaque growth model with advanced blood flow dynamics where the deformed luminal shape derived from the plaque growth model is compared to the actual patient-specific luminal model in terms of several hemodynamic metrics, to identify the prediction accuracy of the aforementioned model. Pressure drop ratios had a mean difference of <3%, whereas OSI-derived metrics were identical in 2/3 cases.Clinical Relevance-This establishes the accuracy of our plaque growth model in predicting the arterial geometry after the desired timeline.

A Machine Learning Model for the prediction of the progression of carotid arterial stenoses.

Atherosclerotic carotid plaque development results in a steady narrowing of the artery lumen, which may eventually trigger catastrophic plaque rupture leading to thromboembolism and stroke. The primary cause of ischemic stroke in the EU is carotid artery disease, which increases the demand for tools for risk stratification and patient management in carotid artery disease. Additionally, advancements in cardiovascular modeling over the past few years have made it possible to build accurate three-dimensional models of patient-specific primary carotid arteries. Computational models then incorporate the aforementioned 3D models to estimate either the development of atherosclerotic plaque or a number of flow-related parameters that are linked to risk assessment. This work presents an attempt to provide a carotid artery stenosis prognostic model, utilizing non-imaging and imaging data, as well as simulated hemodynamic data. The overall methodology was trained and tested on a dataset of 41 cases with 23 carotid arteries with stable stenosis and 18 carotids with increasing stenosis degree. The highest accuracy of 71% was achieved using a neural network classifier. The novel aspect of our work is the definition of the problem that is solved, as well as the amount of simulated data that are used as input for the prognostic model.Clinical Relevance-A prognostic model for the prediction of the trajectory of carotid artery atherosclerosis is proposed, which can support physicians in critical treatment decisions.

Postcarotid Endarterectomy Hematoma Induced Arrhythmia: Report of a Rare Case.

Postcarotid endarterectomy (CEA) hematomas are common although they are rarely threatening and necessitate reoperation. We aim to report a rare case of an expanding hematoma that caused a cardiac arrhythmia (bigeminy) which was reversed after hematoma evacuation.

Life-threatening urosepsis because of ureteral entrapment within a large inguinal hernia.

Ureteral hernias are an uncommon entity that are usually incidentally discovered during inguinal hernia repair. However, when symptomatic, they could cause severe symptoms from the urinary system and even affect renal function. We aim to report a rare case of a 91-year-old male patient with urosepsis because of ureteral entrapment within an inguinal hernia, and further discuss proper management of such cases.

Direct oral anticoagulants for deep vein thrombosis among patients with hereditary thrombophilia-A cohort study.

OBJECTIVES: to evaluate direct oral anticoagulants (DOACs) in patients with hereditary thrombophilia and deep venous thrombosis (DVT). METHODS: This is a retrospective observational study. RESULTS: In total, 45 patients were treated between 01/2012 and 12/2022 (mean follow-up: 1.5 +/- 0.3 years). The most frequent thrombophilias were heterozygous V Leiden (20%), heterozygous MTHFR C677T (37.8%), heterozygous MTHFR A1298C (24.4%), and hyperhomocysteinemia (26.7%). The patients received rivaroxaban (n = 19), apixaban (n = 15), and dabigatran (n = 11). Three cases presented symptoms' recurrence without evidence of thrombosis' recurrence (two under rivaroxaban and one under apixaban; p > .05). These patients improved under parenteral anticoagulation and were further treated with dabigatran. No other event or major bleeding occurred during the follow-up. The presence of more than two factors was associated with acute recurrence of symptoms (OR = 25.9; 95% CI [1.454-461.262]; p = .026). CONCLUSIONS: DOACs seem to be safe and efficient for patients with hereditary thrombophilia and DVT. The presence of more than two thrombophilia factors is associated with a higher risk for symptom recurrence. Although statistically non-significant, symptoms' recurrence was also observed more frequently among patients under anti-Xa inhibitors than antithrombin inhibitors. This should be verified in larger comparative studies.

Acute limb ischemia.

Acute limb ischemia (ALI) is an emergency situation requiring rapid diagnosis and treatment. Although the traditional treating strategy for ALI includes open surgery, novel endovascular techniques have been introduced during the last decade. Additionally, many new cases of ALI have been reported due to infection by the SARS-CoV-2 virus. The aim of this study was to present an updated overview of characteristics, diagnosis, and current treating strategies of patients with ALI.

A systematic review and meta-analysis of early and late outcomes after endovascular angioplasty among patients with thromboangiitis obliterans and chronic limb ischemia.

BACKGROUND: No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients. METHODS: We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis. RESULTS: Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months. CONCLUSIONS: Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable.

New paradigms in minimally-invasive vascular surgery.

INTRODUCTION: Vascular surgery has been greatly evolved during the last decades and novel minimally invasive techniques have been introduced. Aim of this review is to briefly present all these advances and compare them with traditional repairs. AREAS COVERED: The authors have extensively searched literature through the Pubmed and Embase databases. All articles published up to December 2021 referring to minimally invasive techniques used for treatment of peripheral artery disease, carotid disease, aortic aneurysms, and venous disease were evaluated. Minimally invasive techniques under investigation included endovascular and hybrid techniques, robot-assisted and laparoscopic approaches. EXPERT OPINION: Several minimally invasive techniques such as endovascular and hybrid approaches have been extensively used during the last two decades to treat vascular surgery patients offering them lower mortality and morbidity risks. Novel robot-assisted techniques have shown promising results in preclinical studies although further clinical evaluation is needed.

Acute limb ischemia among patients with COVID-19 infection.

OBJECTIVE/BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with thrombotic complications such as deep vein thrombosis or stroke. Recently, numerous cases of acute limb ischemia (ALI) have been reported although pooled data are lacking. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane Library for studies published online up to January 2021 that reported cases with SARS-CoV-2 infection and ALI. Eligible studies should have reported early outcomes including mortality. Primary endpoints included also pooled amputation, clinical improvement, and reoperation rates. RESULTS: In total, 34 studies (19 case reports and 15 case series/cohort studies) including a total of 540 patients (199 patients were eligible for analysis) were evaluated. All studies were published in 2020. Mean age of patients was 61.6 years (range, 39-84 years; data from 32 studies) and 78.4% of patients were of male gender (data from 32 studies). There was a low incidence of comorbidities: arterial hypertension, 49% (29 studies); diabetes mellitus, 29.6% (29 studies); dyslipidemia, 20.5% (27 studies); chronic obstructive pulmonary disease, 8.5% (26 studies); coronary disease, 8.3% (26 studies); and chronic renal disease, 7.6% (28 studies). Medical treatment was selected as first-line treatment for 41.8% of cases. Pooled mortality rate among 34 studies reached 31.4% (95% confidence interval [CI], 25.4%%-37.7%). Pooled amputation rate among 34 studies reached 23.2% (95% CI, 17.3%-29.7%). Pooled clinical improvement rate among 28 studies reached 66.6% (95% CI, 55.4%%-76.9%). Pooled reoperation rate among 29 studies reached 10.5% (95% CI, 5.7%%-16.7%). Medical treatment was associated with a higher death risk compared with any intervention (odds ratio, 4.04; 95% CI, 1.075-15.197; P = .045) although amputation risk was not different between the two strategies (odds ratio, 0.977; 95% CI, 0.070-13.600; P = .986) (data from 31 studies). CONCLUSIONS: SARS-CoV-2 infection is associated with a high risk for thrombotic complications, including ALI. COVID-associated ALI presents in patients with a low incidence of comorbidities, and it is associated with a high mortality and amputation risk. Conservative treatment seems to have a higher mortality risk compared with any intervention, although amputation risk is similar.

A systematic review of therapies for aortobronchial fistulae.

OBJECTIVE: The aim of the study was to summarize epidemiologic data about aortobronchial fistulae and compare outcomes (mortality, recurrence, reoperation) of open, staged, and endovascular repair of aortobronchial fistula. METHODS: A systematic literature review was conducted to identify eligible studies published between January 1999 and December 2019. The Cochrane Library, PubMed, and Scopus databases were used as search engines. Eligible studies included articles reporting postoperative outcomes (death/follow-up). Literature review revealed only case reports and small case series, and thus, only descriptive data with data heterogeneity were available. The corresponding authors were contacted to provide additional information or outcome updates (recurrence/reoperation/death). RESULTS: Overall, 214 patients (90 studies) underwent 271 procedures (including redo procedures and staged procedures). Most of the patients were treated by endovascular means (72.42%). Open surgical repair was performed in 21.96% and staged procedures in 5.6%. Aortobronchial fistulae were located most often in the descending thoracic aorta (zone 3 or 4) (64.6%) and in zone 2 (23.8%). Fourteen percent of aortobronchial fistulae developed after thoracic endovascular aneurysm repair. Recurrence or infection occurred in 20% (43) patients. Recurrences were, to some extent, associated with the presence of endoleak. Long-term antibiotic administration (>1 month) was instituted in 63 patients (29.4%), whereas 90 patients (42%) did not receive antibiotics beyond hospitalization. From the remaining 61 patients, 3 received lifelong antibiotics and for 58 patients data were not available. Considering outcomes, the mean follow-up was 25.1 months (0-188 months) and not significantly different among treatments. LIMITATIONS: Literature review has revealed only case reports and small case series, and thus, only descriptive data were available. Randomized controlled trials are not available due to the rarity of the disease, which significantly decreases the power of the present study. Also, this study reflects significant data heterogeneity due to the nature of the analyzed manuscripts and would benefit from large patient cohort studies that have not been conducted till today. CONCLUSIONS: Aortobronchial fistula is a complex disease. Endoleaks may be involved in the development and the recurrence process, and they should not be disregarded. Considering major outcomes (length of follow-up), the available treating strategies are equal, and thus, surgeons should feel confident to apply the treatment of their choice, keeping in mind their experience, patient's age, and clinical condition.

Computational modeling of atherosclerotic plaque progression in carotid lesions with moderate degree of stenosis.

Carotid atherosclerotic plaque growth leads to the progressive luminal stenosis of the vessel, which may erode or rupture causing thromboembolism and cerebral infarction, manifested as stroke. Carotid atherosclerosis is considered the major cause of ischemic stroke in Europe and thus new imaging-based computational tools that can improve risk stratification and management of carotid artery disease patients are needed. In this work, we present a new computational approach for modeling atherosclerotic plaque progression in real patient-carotid lesions, with moderate to severe degree of stenosis (>50%). The model incorporates for the first time, the baseline 3D geometry of the plaque tissue components (e.g. Lipid Core) identified by MR imaging, in which the major biological processes of atherosclerosis are simulated in time. The simulated plaque tissue production results in the inward remodeling of the vessel wall promoting luminal stenosis which in turn predicts the region of the actual stenosis progression observed at the follow-up visit. The model aims to support clinical decision making, by identifying regions prone to plaque formation, predict carotid stenosis and plaque burden progression, and provide advice on the optimal time for patient follow-up screening.

Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo- double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.