Transmembrane Protein TMEM230, Regulator of Glial Cell Vascular Mimicry and Endothelial Cell Angiogenesis in High-Grade Heterogeneous Infiltrating Gliomas and Glioblastoma.

High-grade gliomas (HGGs) and glioblastoma multiforme (GBM) are characterized by a heterogeneous and aggressive population of tissue-infiltrating cells that promote both destructive tissue remodeling and aberrant vascularization of the brain. The formation of defective and permeable blood vessels and microchannels and destructive tissue remodeling prevent efficient vascular delivery of pharmacological agents to tumor cells and are the significant reason why therapeutic chemotherapy and immunotherapy intervention are primarily ineffective. Vessel-forming endothelial cells and microchannel-forming glial cells that recapitulate vascular mimicry have both infiltration and destructive remodeling tissue capacities. The transmembrane protein TMEM230 (C20orf30) is a master regulator of infiltration, sprouting of endothelial cells, and microchannel formation of glial and phagocytic cells. A high level of TMEM230 expression was identified in patients with HGG, GBM, and U87-MG cells. In this study, we identified candidate genes and molecular pathways that support that aberrantly elevated levels of TMEM230 play an important role in regulating genes associated with the initial stages of cell infiltration and blood vessel and microchannel (also referred to as tumor microtubule) formation in the progression from low-grade to high-grade gliomas. As TMEM230 regulates infiltration, vascularization, and tissue destruction capacities of diverse cell types in the brain, TMEM230 is a promising cancer target for heterogeneous HGG tumors.

Empty vein ablation (EVA) technique: an in-vivo animal model to assess the effects of sclerosing agent concentration and wall contact time on intima and media tunicae structure.

BACKGROUND: Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact time between sclerosant agent and vein wall [ctSA/VW]) to maximize outcomes remain an unsolved problem and a source of debate. An innovative three-balloon catheter has been developed to allow sclerotherapy in empty vein conditions (Empty Vein Ablation technique, EVA), revolutionizing the definition of SLAC and ctSA/VW. Aim of this experimental study is to analyze EVA effects on intima and media vessel tunicae using different SLAC and ctSA/VW in an in-vivo animal model. METHODS: Two adult sheep were treated by EVA using jugular and common iliac vein axes (eight vein segments). Different SLAC (polidocanol 0.5% or 1%) and different ctSA/VW (3 or 5 minutes) were combined for testing residual circumferential intima percentage and media thickness after EVA. RESULTS: Intact circumferential residual intima after the treatment was 21.3±4.9%, 18.2±7.4%, 15.7±2.4% and 8.9±2.0% using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.945; control sample: 97.6%). Media thickness after the treatment was 121.6±35.3 µm, 110.9±7.8 µm, 96.1±30.4 µm and 79.1±34.1 µm using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.990; control sample 125.7 µm). No significant modifications were detected analyzing the adventitia in all samples. CONCLUSIONS: EVA proved to be effective in venous wall destruction even with a very low SLAC and ctSA/VW (0.5% in 3 minutes), in quite large caliber veins. Direct comparisons with foam/liquid sclerotherapy should be done to confirm therapeutic effectiveness of these results, despite EVA has provided a maximized and controlled SA/VW contact time and ratio.

3D patient-specific modeling and structural finite element analysis of atherosclerotic carotid artery based on computed tomography angiography.

The assessment of carotid plaque vulnerability is a relevant clinical information that can help prevent adverse cerebrovascular events. To this aim, in this study, we propose a patient-specific computational workflow to quantify the stress distribution in an atherosclerotic carotid artery, by means of geometric modeling and structural simulation of the plaque and vessel wall. Ten patients were involved in our study. Starting with segmentation of the lumen, calcific and lipid plaque components from computed tomography angiography images, the fibrous component and the vessel wall were semi-automatically reconstructed with an ad-hoc procedure. Finite element analyses were performed using local pressure values derived from ultrasound imaging. Simulation outputs were analyzed to assess how mechanical factors influence the stresses within the atherosclerotic wall. The developed reconstruction method was first evaluated by comparing the results obtained using the automatically generated fibrous component model and the one derived from image segmentation. The high-stress regions in the carotid artery wall around plaques suggest areas of possible rupture. In mostly lipidic and heterogeneous plaques, the highest stresses are localized at the interface between the lipidic components and the lumen, in the fibrous cap.

Low profile endografts for the endovascular treatment of abdominal aortic aneurysms.

INTRODUCTION: Favorable midterm outcomes have been reported with the use of low-profile endografts (LPE), but long-term data is still needed. Furthermore, it is unclear if each of these LPE may have advantages over the other, which may, in turn, affect the outcomes. We systematically reviewed the literature about complications and reintervention rates of patients submitted to endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA) using LPE. MATHERIALS AND METHODS: A literature search was conducted including articles that reported 30-days and follow-up mortality, complications, and reintervention rates of patients treated with EVAR using Incraft (Cordis), Zenith LP/Alpha (Cook Medical Inc) and Ovation (Endologix) endografts. RESULTS: 36 papers were evaluated, reporting results of 582 patients treated with Zenith device, 1211 with Incraft and 3449 with Ovation. During follow up, similar survival and freedom from reintervention rates were reported among the various types of endograft both at 1 and 3 years. The incidence of limb stenosis/kinking was significantly higher in patients treated with Zenith LP/Alpha (2.1%, P = 0.008), while the Incraft device had a significantly lower proportion of type III endoleaks (P < 0.001). CONCLUSIONS: Long-term survival and freedom from reintervention rates were comparable among the three LPEs. The Cook Zenith device had the highest rates of limb stenosis/kinking, while the Incraft device had the lowest occurrence of type III endoleak. PROSPERO: Registration number: CRD42022315875.

Current Opinions in Open and Endovascular Treatment of Major Arterial Injuries in Pediatric Patient.

Pediatric major arterial vascular injuries may belong to the same principal categories as adults, but have been poorly documented, with an estimated overall incidence of <2% of all vascular traumas. Open surgery has been the mainstay of treatment, but no clear guidelines have been developed to recommend the best practice patterns in terms of strategy or repair as well as postoperative pharmacological regimen. Herein, we report three cases and a narrative review of the available literature regarding the main aspects when dealing with pediatric arterial injuries based on the predominant series available from the most recent published literature.

Solving Intraoperative Complications During Endovascular Repair of Late Contained Ruptured Aortic Pseudoaneurysm After Surgical De-coarctation: Case Report and Systematic Review of Literature.

AIM: We present a case of successful endovascular repair of late ruptured aortic anastomotic pseudoaneurysm following previous left subclavian artery-descending thoracic aorta bypass and concomitant emergency thoracic endovascular aortic repair (TEVAR) of complicated endovascular aortic de-coarctation never previously described is also presented. A review of the intraoperative, 30-day, and follow-up morbidity, mortality, and complications of TEVAR as endovascular treatment of late aneurysm/pseudoaneurysms after surgical aortic de-coarctation was also performed. METHODS: The systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and following PICO model. A literature search was conducted on MEDLINE, PubMed, EMBASE, Cochrane Library, Google Scholar, Science Direct, and Web of Science using the words "tevar of late complication of aortic coarctation surgical repair" and "endovascular repair of anastomotic pseudoaneurysm in coarctation" up to June 17, 2022. Data were extracted from study documents about study design, patient's demographics and comorbidities, details about primary surgical repair, type of late complication, time between open surgery and occurrence of complications, details of the secondary endovascular procedure with technical success, early, and follow-up mortality and morbidity. RESULTS: A total of 18 papers were included with 78 patients (48 men, 69.5%). The most frequent type of primary open surgical repair was patch aortoplasty (46, 58.9%). Focusing on aneurysm and pseudoaneurysm as late complications, most of the patients were asymptomatic (45, 57.7%). All patients underwent TEVAR, 14 of them (17.9%) in urgent/emergent setting. The technical success was 98.7%, with 1 intraoperative death due to rupture of the aorta. In total, 31 patients out of 78 (39.7%) showed different complications in the immediate postoperative time, with type II endoleak being the most observed (8/31, 25.8%). The mean follow-up time was about 2 years (26.5 months, range 3-92). Overall, 30-day mortality was 2.6%. Complications occurred in 30 patients (39.4%), 23 of them resolved during the follow-up period. CONCLUSIONS: With the limit of low-quality data, TEVAR can be considered a safe and effective option for the treatment of late complications after open surgery for aortic coarctation, even in urgent settings. CLINICAL IMPACT: Different specialists have to face the technical complexities and risks related to treatment of late complications after surgical de-coartaction, which can be either surgical or endovascular, and depend on patient's ages. Although covered stents appear to have some protection from the development of stent fractures, doesn't provide complete protection from late aneurysm formation. In this setting, TEVAR may represent a valuable option, combining the advantages of the covered stent with those of a device that can cover a wider range of aortic length, especially in adult patients. This study shows thoracic endovascular repair can be considered a safe and effective option in clincal practice for the treatment of late complications after open surgery for AC, even in urgent settings.

Four-Dimensional Flow MRI for the Evaluation of Aortic Endovascular Graft: A Pilot Study.

We aimed to explore the feasibility of 4D flow magnetic resonance imaging (MRI) for patients undergoing thoracic aorta endovascular repair (TEVAR). We retrospectively evaluated ten patients (two female), with a mean (±standard deviation) age of 61 ± 20 years, undergoing MRI for a follow-up after TEVAR. All 4D flow examinations were performed using a 1.5-T system (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany). In addition to the standard examination protocol, a 4D flow-sensitive 3D spatial-encoding, time-resolved, phase-contrast prototype sequence was acquired. Among our cases, flow evaluation was feasible in all patients, although we observed some artifacts in 3 out of 10 patients. Three individuals displayed a reduced signal within the vessel lumen where the endograft was placed, while others presented with turbulent or increased flow. An aortic endograft did not necessarily hinder the visualization of blood flow through 4D flow sequences, although the graft could generate flow artifacts in some cases. A 4D Flow MRI may represent the ideal tool to follow up on both healthy subjects deemed to be at an increased risk based on their anatomical characteristics or patients submitted to TEVAR for whom a surveillance protocol with computed tomography angiography would be cumbersome and unjustified.

Penetrating Vascular Injuries of the Lower Limbs after Stab Wounds: Predictive Factors of Limb Loss and Mortality.

BACKGROUND: Penetrating vascular injuries (PVIs) of the lower limbs due to stab wounds are associated with high mortality and limb loss rates. We analyzed the outcomes of a series of patients who underwent surgical treatment of these lesions, assessing the presence of any factor associated with limb loss and mortality; (2) Methods: Data of patients admitted from 01/2008 to 12/2018 were retrospectively analyzed. Primary outcomes were the limb loss and the mortality rate at 30 days postoperatively. Univariate and multivariate analyses were performed as appropriate. p values < 0.05 were considered significant; (3) Results: Data of 67 male patients were analyzed. Two died (3%) and three (4.5%) had a lower limb amputation after failed revascularization. In the univariate analysis, the clinical presentation significantly affected the risk of postoperative mortality and limb loss. The location of the lesion at the superficial femoral artery (OR 4.32, p = 0.001) or at the popliteal artery (OR 4.89, p = 0.0015) also increased the risk. In the multivariate analysis, the need for a vein graft bypass was the only significant predictor of limb loss and mortality (OR 4.58, p < 0.0001); (4) Conclusions: PVIs of lower limbs due to stab wounds were lethal in 3% of cases and lead to a secondary major amputation in 4.5% more cases. The need for a vein bypass grafting was the strongest predictor of postoperative limb loss and mortality.

Blunt Thoracic Aortic Injury.

Blunt thoracic aortic injury (BTAI) is a potentially fatal condition that needs prompt recognition and expedited management. Clinical manifestations of BTAI are not straight forwarding and may be misdiagnosed. The grade of aortic injury is an important determinant of perioperative mortality and morbidity, as well as the indication of treatment, along with the presence of concomitant lesions of other involved organs. The mainstay of treatment nowadays for hemodynamically stable patients who survive the trauma scene is represented by delayed endovascular repair whenever anatomically and clinically feasible. Endovascular repair, in fact, is burdened by lower perioperative mortality and morbidity rates if compared to open surgical repair, but concerns remain about the need for long-term surveillance and radiation exposure in patients who are at a younger age than patients treated for the aneurysmal disease. The aim of the paper is to provide an update on the diagnostic modalities and strategies of treatment for patients affected by BTAI.

Partial Eversion Carotid Endarterectomy versus Conventional Techniques for Significant Carotid Stenosis.

BACKGROUND: To compare the outcomes of patients who were submitted to partial carotid endarterectomy (P-CEA) to those of patients who underwent standard conventional CEA with patch closure (C-CEA) and eversion CEA (E-CEA) for a significant carotid stenosis. METHODS: Data of patients who consecutively underwent CEA from January 2014 to December 2018 for a significant carotid stenosis were retrospectively collected. Primary outcomes included mortality and the occurrence of neurologic and cardiologic complications, both at 30 days and during follow-up. Secondary outcomes included the occurrence of perioperative local complications (i.e. cranial nerve injuries, hematomas) and restenosis during follow-up. P values < 0.5 were considered statistically significant. RESULTS: Three-hundred twenty-seven patients (241 males, 74%) underwent CEA for carotid stenosis (28.6% symptomatic). P-CEA was performed in 202 patients (61.8%), while C-CEA and E-CEA were performed in 103 and 22 cases respectively. At 30 days, neurologic complications were not significantly different among the 3 groups (2.8% in the group of C-CEA, 2.4% after P-CEA and 0% in E-CEA patients, P = 0.81), neither during follow-up. Perioperative local complications also were not significantly different among the 3 groups (P = 0.16). CONCLUSIONS: P-CEA had similar outcomes if compared to C-CEA and to E-CEA in terms of perioperative mortality, occurrence of neurologic and cardiologic complications, and occurrence of local complications. Also, in the long-term, P-CEA, C-CEA, and E-CEA were burdened by similar rates of mortality, neurologic, and cardiologic complications and restenosis.

Role of Preoperative Ultrasound Shear-Wave Elastography and Radiofrequency-Based Arterial Wall Tracking in Assessing the Vulnerability of Carotid Plaques: Preliminary Results.

We aimed at evaluating the ability of point shear-wave elastography (pSWE) and of a radiofrequency (RF) echo-tracking-based method in preoperatively assessing the vulnerability of the carotid plaque in patients undergoing carotid endarterectomy (CEA) for significant asymptomatic stenosis. All patients who underwent CEA from 03/2021 to 03/2022 performed a preoperative pSWE and an RF echo-based wall evaluation of arterial stiffness using an Esaote MyLab ultrasound system (EsaoteTM, Genova, Italy) with dedicated software. The data derived from these evaluations (Young's modulus (YM), augmentation index (AIx), pulse-wave velocity (PWV)) were correlated with the outcome of the analysis of the plaque removed during the surgery. Data were analyzed on 63 patients (33 vulnerable and 30 stable plaques). In stable plaques, YM was significantly higher than in vulnerable plaques (49.6 + 8.1 kPa vs. 24.6 + 4.3 kPa, p = 0.009). AIx also tended to be slightly higher in stable plaques, even if it was not statistically significant (10.4 + 0.9% vs. 7.7 + 0.9%, p = 0.16). The PWV was similar (12.2 + 0.9 m/s for stable plaques vs. 10.6 + 0.5 m/s for vulnerable plaques, p = 0.16). For YM, values >34 kPa had a sensitivity of 50% and a specificity of 73.3% in predicting plaque nonvulnerability (area under the curve = 0.66). Preoperative measurement of YM by means of pSWE could be a noninvasive and easily applicable tool for assessing the preoperative risk of plaque vulnerability in asymptomatic patients who are candidates for CEA.

Factors associated with perioperative mortality after late open conversion for failed endovascular aortic repair.

INTRODUCTION: The aim of this study was to perform a systematic review about the clinical and technical aspects of late open conversion for failed endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA), and to investigate if the need for suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture were associated with an increase of 30-days (perioperative) mortality. EVIDENCE ACQUISITION: A literature search was conducted on PubMed using the words "open conversion endovascular" on December 29th, 2021. Studies included randomized controlled trials, cohort studies, and case series of patients submitted to open conversion that were performed at least 1 month after the initial EVAR for AAA, reporting about 30-days mortality after surgery. A meta-analysis was performed to explore the association of suprarenal aortic cross clamping, graft infection, urgent procedures, endoleaks and aortic rupture with 30-days postoperative mortality using log odds ratios (ORs), with STATA/MP 17.0 (Stata Corp. 2021, LLC). Two-sided P values less than 0.05 were considered statistically significant. EVIDENCE SYNTHESIS: The search retrieved 985 results on PubMed from 1994 to 2021. Among them, 40 papers were included in the study for the systematic review, and 5 of them for the meta-analysis. A total of 2297 patients from 1992 to 2020 were submitted to open conversion after a median of 40.4 months from the initial EVAR. Endoleak was the most frequent cause of open conversion (76.3%). Perioperative mortality was 23.5% for urgent and 5.3% for elective conversions. At meta-analysis, urgent procedures and aortic rupture were both associated with higher perioperative mortality (OR 5.27, 95% CI 2.90-9.57 and OR 5.61, 95% CI 3.09-10.19 respectively). Similarly, patients with infections and who needed suprarenal aortic clamping were at higher risk of 30-days postoperative death (OR 3.74, 95% CI 1.96-7.13) and OR 2.23, 95% CI 1.24-4.02), while the presence of a preoperative endoleaks was not associated with a higher 30-days mortality. CONCLUSIONS: Late open conversion after EVAR of AAA is burdened by a perioperative mortality rate of 23.5% for urgent and 5.3% for elective cases. Urgent treatment, presence of aortic rupture or infection, and the need for suprarenal aortic cross clamping were associated with increased perioperative mortality, while the presence of an endoleak did not affect perioperative mortality.

Fast Approximate Quantification of Endovascular Stent Graft Displacement Forces in the Bovine Aortic Arch Variant.

PURPOSE: Displacement forces (DFs) identify hostile landing zones for stent graft deployment in thoracic endovascular aortic repair (TEVAR). However, their use in TEVAR planning is hampered by the need for time-expensive computational fluid dynamics (CFD). We propose a novel fast-approximate computation of DFs merely exploiting aortic arch anatomy, as derived from the computed tomography (CT) and a measure of central aortic pressure. MATERIALS AND METHODS: We tested the fast-approximate approach against CFD gold-standard in 34 subjects with the "bovine" aortic arch variant. For each dataset, a 3-dimensional (3D) model of the aortic arch lumen was reconstructed from computed tomography angiography and CFD then employed to compute DFs within the aortic proximal landing zones. To quantify fast-approximate DFs, the wall shear stress contribution to the DF was neglected and blood pressure space-distribution was averaged on the entire aortic wall to reliably approximate the patient-specific central blood pressure. Also, DF values were normalized on the corresponding proximal landing zone area to obtain the equivalent surface traction (EST). RESULTS: Fast-approximate approach consistently reflected (r2=0.99, p<0.0001) the DF pattern obtained by CFD, with a -1.1% and 0.7° bias in DFs magnitude and orientation, respectively. The normalized EST progressively increased (p<0.0001) from zone 0 to zone 3 regardless of the type of arch, with proximal landing zone 3 showing significantly greater forces than zone 2 (p<0.0001). Upon DF normalization to the corresponding aortic surface, fast-approximate EST was decoupled in blood pressure and a dimensionless shape vector (S) reflecting aortic arch morphology. S showed a zone-specific pattern of orientation and proved a valid biomechanical blueprint of DF impact on the thoracic aortic wall. CONCLUSION: Requiring only a few seconds and quantifying clinically relevant biomechanical parameters of proximal landing zones for arch TEVAR, our method suits the real preoperative decision-making process. It paves the way toward analyzing large population of patients and hence to define threshold values for a future patient-specific preoperative TEVAR planning.

Clopidogrel Resistance and Ticagrelor Replacement in Dual Antiplatelet Therapy for Carotid Artery Stenting.

BACKGROUNDS: Resistance to the pharmacological effect of clopidogrel in patients undergoing dual antiplatelet therapy for carotid stenting may increase the risk of periprocedural neurological events. The purpose of the study was to describe the phenomenon of clopidogrel resistance in a series of patients undergoing carotid stenting. METHODS: Data of patients who consecutively underwent carotid stenting from November 2016 to December 2020 for a significant stenosis and who underwent a dual antiplatelet therapy using acetyl-salicylic acid and clopidogrel were prospectively collected. Patients who were already taking a different thienopyridine were excluded. The effectiveness of antiplatelet drugs was assessed by the impedance aggregometry test. Primary endpoint was to evaluate the incidence of clopidogrel resistance and the effectiveness of ticagrelor as alternative therapy. P values < 0.05 were considered statistically significant. RESULTS: Two-hundred patients (80 females, 40%) underwent stenting for carotid stenosis (94% asymptomatic). The phenomenon of clopidogrel resistance was observed in 38 patients (19%), in whom clopidogrel was replaced by ticagrelor (90 mg/bis in die) with 100% effectiveness at aggregometry test. Platelet counts was associated to clopidogrel resistance (P = 0.001). There was no stent thrombosis at 30 days, neither major hemorrhagic events; a total of 12/200 major adverse cardiovascular events occurred (6%), including 1 in the group of patients who took ticagrelor and 11 in group of patients under clopidogrel (2.6% versus 6.7%, P = 0.55). CONCLUSIONS: Clopidogrel was ineffective in 19% of patients undergoing carotid stenting. Platelet count seemed to affect this phenomenon. In these patients, clopidogrel was effectively replaced by ticagrelor.

Endovascular Treatment of Abdominal Aorta Floating Thrombus in a Patient with Recurrent Peripheral Embolization and COVID-19.

PURPOSE: To present stent-graft treatment of floating thrombus in the abdominal aorta. A review of the literature about aortic floating thrombus (AFT) was also performed. CASE REPORT: A 56-year-old female with no risk factors for vascular disease but with history of a mild COVID-19 infection in the previous month, for which she had started anticoagulant therapy at a prophylactic dosage, developed an acute ischemia of the lower limbs and was diagnosed with floating thrombosis of the abdominal aorta. The thrombus was excluded from the aortic blood flow by deployment of a stent-graft in the abdominal aorta. At 12 months, the patient was well, and the thrombus in the abdominal aorta appears to be completely excluded by the stent-graft. A review of the available literature from 1980 to 2022 showed 74 cases of AFT located in the aortic arch, in the descending thoracic and in the abdominal aorta. In most cases the AFT involved the aortic arch (38/74, 51.3%) and/or the descending thoracic aorta (30/74, 40.5%), while the abdominal aorta was involved in 6 cases. In 2 of these 6 cases, the patients had a COVID-19 infection. The AFT was mostly approached either medically with anticoagulation/systemic thrombolysis (32/74, 43.2%) or with surgical removal (31/74, 41.9%), while endovascular coverage of the thrombus with an endograft was performed in 6 cases of AFT located in the aortic arch and in the descending thoracic aorta (3 cases each). CONCLUSION: There is no consensus about the optimal treatment of AFT. In selected cases, abdominal stent-grafts may be used for stabilization and exclusion of symptomatic abdominal aorta floating thrombosis to prevent progression and recurrent embolization.

CircANKRD12 Is Induced in Endothelial Cell Response to Oxidative Stress.

Redox imbalance of the endothelial cells (ECs) plays a causative role in a variety of cardiovascular diseases. In order to better understand the molecular mechanisms of the endothelial response to oxidative stress, the involvement of circular RNAs (circRNAs) was investigated. CircRNAs are RNA species generated by a "back-splicing" event, which is the covalent linking of the 3'- and 5'-ends of exons. Bioinformatics analysis of the transcriptomic landscape of human ECs exposed to H2O2 allowed us to identify a subset of highly expressed circRNAs compared to their linear RNA counterparts, suggesting a potential biological relevance. Specifically, circular Ankyrin Repeat Domain 12 (circANKRD12), derived from the junction of exon 2 and exon 8 of the ANKRD12 gene (hsa_circ_0000826), was significantly induced in H2O2-treated ECs. Conversely, the linear RNA isoform of ANKRD12 was not modulated. An increased circular-to-linear ratio of ANKRD12 was also observed in cultured ECs exposed to hypoxia and in skeletal muscle biopsies of patients affected by critical limb ischemia (CLI), two conditions associated with redox imbalance and oxidative stress. The functional relevance of circANKRD12 was shown by the inhibition of EC formation of capillary-like structures upon silencing of the circular but not of the linear isoform of ANKRD12. Bioinformatics analysis of the circANKRD12-miRNA-mRNA regulatory network in H2O2-treated ECs identified the enrichment of the p53 and Foxo signaling pathways, both crucial in the cellular response to redox imbalance. In keeping with the antiproliferative action of the p53 pathway, circANKRD12 silencing inhibited EC proliferation. In conclusion, this study indicates circANKRD12 as an important player in ECs exposed to oxidative stress.

Endovascular therapy for steno-occlusive subclavian artery disease early and long-term outcomes in a multicentric Tunisian study.

AIM: To evaluate the outcomes of endovascular therapy in patients with subclavian steno-occlusive disease over the short and long term in a Tunisian population. MATERIALS AND METHODS: Patients who underwent endovascular treatment of subclavian artery (SCA) steno-occlusive disease between 2013 and 2019 in three Tunisian centers were evaluated retrospectively. After treatment, patients were follow-up was scheduled at 1, 3, 6, 12 months postoperatively and annually afterwards by Doppler ultrasound and clinical findings. Primary outcomes included technical, clinical procedural success rates and limb salvage rate. Secondary outcomes included the occurrence of periprocedural complications and primary patency rates. RESULTS: 56 patients (33 males, 58.9%) were evaluated. Patients' mean age was 61.5 + years. Technical success rate was 94.6 %, being 100% in case of stenosis and 78.5% in case of occlusion. The technical success rate was 94.6%. The clinical success rate was 100% and the upper limb salvage rate was 100%. Minor amputations were performed on 5 patients. Perioperative mortality and morbidity rates were 0% and 8.9% respectively. Mean follow-up was 26.7±16.4 months (range 12-86 months). Two in-stent restenosis occurred (at 12 and 15 months) and one case of thrombosis at the 16th month. The primary patency rates were 88.7%+4.3% at the end of the first year and 78.7%+6.1% at 3 years. CONCLUSION: Endovascular treatment can be considered as a safe and effective treatment of SCA steno-occlusive disease, with low perioperative complication rates and a good patency rates over long term. KEY WORDS: Subclavian artery stenosis, Subclavian artery occlusion, endovascular, subclavian revascularization.

Guideline on carotid surgery for stroke prevention: updates from the Italian Society of Vascular and Endovascular Surgery. A trend towards personalized medicine.

BACKGROUND: This guideline (GL) on carotid surgery as updating of "Stroke: Italian guidelines for Prevention and Treatment" of the ISO-SPREAD Italian Stroke Organization-Group, has recently been published in the National Guideline System and shared with the Italian Society of Vascular and Endovascular Surgery (SICVE) and other Scientific Societies and Patient's Association. METHODS: GRADE-SIGN version, AGREE quality of reporting checklist. Clinical questions formulated according to the PICO model. Recommendations developed based on clinical questions by a multidisciplinary experts' panel and patients' representatives. Systematic reviews performed for each PICO question. Considered judgements filled by assessing the evidence level, direction, and strength of the recommendations. RESULTS: The panel provided indications and recommendations for appropriate, comprehensive, and individualized management of patients with carotid stenosis. Diagnostic and therapeutic processes of the best medical therapy, carotid endarterectomy (CEA), carotid stenting (CAS) according to the evidences and the judged opinions were included. Symptomatic carotid stenosis in elective and emergency, asymptomatic carotid stenosis, association with ischemic heart disease, preoperative diagnostics, types of anesthesia, monitoring in case of CEA, CEA techniques, comparison between CEA and CAS, post-surgical carotid restenosis, and medical therapy are the main topics, even with analysis of uncertainty areas for risk-benefit assessments in the individual patient (personalized medicine [PM]). CONCLUSIONS: This GL updates on the main recommendations for the most appropriate diagnostic and medical-surgical management of patients with atherosclerotic carotid artery stenosis to prevent ischemic stroke. This GL also provides useful elements for the application of PM in good clinical practice.