Extracranial cerebrovascular disease has been the subject of intense research throughout the world, and is of paramount importance for vascular surgeons. This guideline, written by the Brazilian Society of Angiology and Vascular Surgery (SBACV), supersedes the 2015 guideline. Non-atherosclerotic carotid artery diseases were not included in this document. The purpose of this guideline is to bring together the most robust evidence in this area in order to help specialists in the treatment decision-making process. The AGREE II methodology and the European Society of Cardiology system were used for recommendations and levels of evidence. The recommendations were graded from I to III, and levels of evidence were classified as A, B, or C. This guideline is divided into 11 chapters dealing with the various aspects of extracranial cerebrovascular disease: diagnosis, treatments and complications, based on up-to-date knowledge and the recommendations proposed by SBACV.

UNASSIGNED: The intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.
UNASSIGNED: IH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro, CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo, all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.
UNASSIGNED: TF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.

BACKGROUND: Iatrogenic pseudoaneurysms arising from the internal carotid artery subsequent to carotid endarterectomy are exceptionally infrequent. Herein, we present a case detailing an internal carotid artery pseudoaneurysm that manifested subsequent to a hybrid carotid endarterectomy and endovascular therapy intervention. Our approach to managing this condition involved a novel technique wherein thrombin was directly injected into the luminal cavity of the pseudoaneurysm under the guidance of a C-arm.
METHODS: A 66-year-old male patient of Chinese ethnicity exhibited a 4-month history of headache and a 20-day history of gait disturbance. Digital subtraction angiography revealed occlusion in the cervical region of the left carotid artery. Following a hybrid surgical procedure, the patient reported mild pain and bruising surrounding the incision site of the left internal carotid artery endarterectomy. Subsequent angiography identified the presence of a carotid artery pseudoaneurysm. Utilizing C-arm guidance, thrombin was then directly injected into the luminal cavity of the pseudoaneurysm, resulting in complete healing during follow-up.
CONCLUSIONS: For the management of pseudoaneurysms arising post carotid endarterectomy, the direct injection of thrombin into the aneurysm cavity under the guidance of a C-arm is deemed both safe and efficacious.

BACKGROUND: Extracranial carotid artery (CA) pseudoaneurysms are uncommon and can cause embolic stroke, compressive symptoms, or (rarely) can rupture. It is of paramount importance to treat this entity to avoid life-threatening complications. In this study, the authors described a cohort of patients that required open surgical repair.
METHODS: This article reported the authors\' experience with open surgical repair of extracranial CA pseudoaneurysms by presenting a retrospective review of data at their institution from 2016 to 2022.
RESULTS: Of 8 patients that underwent open repair, 6 were male and 8 were female. The most common etiology was traumatic (penetrating trauma in 4 patients, iatrogenic injury in 2, and blunt trauma in 1) and 1 was infective. All patients presented with a neck mass, and 5 had compressive symptoms. Primary repair was performed in 4 patients, interposition graft using an autologous vein in 2, and patch repair in 2. None of the patients experienced perioperative mortality or stroke; nor did they develop any complications over a median follow-up period of 30 months.
CONCLUSIONS: This report demonstrated that large-size extracranial pseudoaneurysms, whether traumatic or infective etiology, can be safely repaired using an open surgical approach.

OBJECTIVE: Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation.
RESULTS: Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFβ1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries.
CONCLUSIONS: We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.

BACKGROUND: Vertebral artery injury is a rare condition in trauma settings. In the advanced stages, it causes death.
METHODS: A 31-year-old Sundanese woman with cerebral edema, C2-C3 anterolisthesis, and Le Fort III fracture after a motorcycle accident was admitted to the emergency room. On the fifth day, she underwent arch bar maxillomandibular application and debridement in general anesthesia with a hyperextended neck position. Unfortunately, her rigid neck collar was removed in the high care unit before surgery. Her condition deteriorated 72 hours after surgery. Digital subtraction angiography revealed a grade 5 bilateral vertebral artery injury due to cervical spine displacement and a grade 4 left internal carotid artery injury with a carotid cavernous fistula (CCF). The patient was declared brain death as not improved cerebral perfusion after CCF coiling.
CONCLUSIONS: Brain death due to cerebral hypoperfusion following cerebrovascular injury in this patient could be prevented by early endovascular intervention and cervical immobilisation.

Background and Objectives: Traumatic vascular injuries of the head and neck pose significant treatment challenges due to the complex anatomy, diverse clinical presentation, and mostly emergent nature. Endovascular treatment increasingly complements traditional surgical approaches. This study aimed to report our 10-year experience in treating traumatic vascular injuries of the head and neck with endovascular therapy and to determine the effectiveness of endovascular treatment. Materials and Methods: A retrospective analysis of 21 patients treated for head and neck vascular injuries between May 2011 and April 2021 was performed. Patients\' medical histories, clinical presentations, imaging findings, treatment materials, and clinical outcomes were reviewed. Treatments included stenting, coil embolization, and other endovascular techniques focused on hemostasis and preservation of the parent vessel. Results: The most common injuries involved the internal maxillary artery branches (n = 11), followed by the common or internal carotid artery (n = 6), vertebral artery (n = 3), and others. Endovascular treatment achieved successful hemostasis in all but one case. In five of six carotid artery injuries and two of three vertebral artery injuries, we achieved successful hemostasis while preserving the parent vessel using covered and bare stents, respectively. Conclusions: Endovascular therapy might be a useful treatment modality for traumatic vascular injuries in the head and neck region, offering efficacy, safety, and a minimally invasive approach.

The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague-Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway.

Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.

Ruptured cerebral aneurysms that occur in the anterior wall of the internal carotid artery (ICA) are known as blood blister-like aneurysms (BBAs); they have been reported to account for 0.3% to 1% of all ruptured ICA aneurysms. In this report, we describe the treatment of an unusual traumatic BBA (tBBA) with high-flow bypass using a radial artery graft, which resulted in a favorable outcome. A 59-year-old female suffered from an acute epidural hematoma, traumatic subarachnoid hemorrhage, and traumatic carotid-cavernous sinus fistula (tCCF) after being involved in a motor vehicle accident. Her angiography results showed tCCF and a tBBA on the anterior wall of the right ICA. On the fourth day after injury, we found rebleeding from the tBBA and performed an emergency high-flow bypass using a radial artery graft with lesion trapping as a curative procedure for the tCCF and tBBA. Postoperatively, right abducens nerve palsy appeared, but no other neurological symptoms were noted; the patient was thereafter transferred to a rehabilitation hospital 49 days after injury. Traumatic ICA aneurysms commonly occur close to the anterior clinoid process, form within 1 to 2 weeks of injury, and often rupture around 2 weeks after trauma. This case was considered rare as the ICA was likely injured and bleeding at the time of injury, resulting in a form of tBBA; this allowed early detection and appropriate treatment that resulted in a good outcome.