Adjunctive techniques in endovascular repair of postcarotid endarterectomy pseudoaneurysm: Case report and literature review.

Pseudoaneurysm (PA) following carotid endarterectomy (CEA) is a rare and dangerous complication. In recent years endovascular approach has been preferred to open surgery as it is less invasive and reduces complications in an already operated neck, especially cranial nerve injuries. We report a case of large post-CEA PA causing dysphagia, successfully treated by deployment of two balloon-expandable covered stents and coil embolization of the external carotid artery. A literature review dealing with all cases of post-CEA PAs since 2000 treated by endovascular means is also reported. The research was conducted on Pubmed database using keywords "carotid pseudoaneurysm after carotid endarterectomy," "false aneurysm after carotid endarterectomy," "postcarotid endarterectomy pseudoaneurysm," and "carotid pseudoaneurysm."

Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study.

BACKGROUND: Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. METHODS: An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. RESULTS: Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. CONCLUSION: Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level IV.

Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

BACKGROUND: CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. METHODS: IDO-1 expression in mice and human vessels was examined. IDO-1-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. RESULTS: Both global IDO-1-/- CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. CONCLUSION: Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.

A multi-registry analysis of military and civilian penetrating cervical carotid artery injury.

INTRODUCTION: Penetrating cervical carotid artery injury is an uncommon but high-stake scenario associated with stroke and death. The objective of this study was to characterize and compare penetrating carotid injury in the military and civilian setting, as well as provide considerations for management. METHODS: Cohorts with penetrating cervical carotid artery injury from the Department of Defense Trauma Registry (2002-2015) and the American Association for the Surgery of Trauma Prospective Observation Vascular Injury Treatment Registry (2012-2018) were analyzed. A least absolute shrinkage and selection operator multivariate analysis using random forest-based imputation was performed to identify risk factors affecting stroke and mortality. RESULTS: There were a total of 157 patients included in the study, of which 56 (35.7%) were military and 101 (64.3%) were civilian. The military cohort was more likely to have been managed with open surgery (87.5% vs. 44.6%, p < 0.001) and to have had any procedure to restore or maintain flow to the brain (71.4% vs. 35.6%, p < 0.001), while the civilian cohort was more likely to undergo nonoperative management (45.5% vs. 12.5%, p < 0.001). Stroke rate was higher within the military cohort (41.1% vs. 13.9%, p < 0.001); however, mortality did not differ between the groups (12.5% vs. 17.8%, p = 0.52). On multivariate analysis, predictors for stroke were presence of a battle injury (log odds, 2.1; p < 0.001) and internal or common carotid artery ligation (log odds 1.5, p = 0.009). For mortality outcome, protective factors included a high Glasgow Coma Scale on admission (log odds, -0.21 per point; p < 0.001). Increased admission Injury Severity Score was a predictor of mortality (log odds, 0.05 per point; p = 0.005). CONCLUSION: The stroke rate was higher in the military cohort, possibly reflecting complexity of injury; however, there was no difference in mortality between military and civilian patients. For significant injuries, concerted efforts should be made at carotid reconstruction to reduce the occurrence of stroke. LEVEL OF EVIDENCE: Retrospective cohort analysis, level III.

Hybrid Repair of a Common Carotid Pseudoaneurysm and Concomitant Internal Carotid Stenosis With Retrograde Stenting and Carotid Endarterectomy.

This report aims to present a rare case of a common carotid artery (CCA) pseudoaneurysm with a concomitant internal carotid artery (ICA) stenosis that were treated with a hybrid technique. This strategy included the retrograde placement of a CCA covered stent under ICA clamping followed by standardized carotid endarterectomy. The technique will be discussed and compared with other possible treatments.

Caso clínico: Fístula carótido-yugular: complicación inusual de cateterismo venoso central / Case report: Carotid jugular fistula: an uncommon complication of central venous access

Resumen La fístula carótido yugular es una complicación inusual del proceder de colocación del catéter venoso central en la vena yugular interna. Esto puede tener serias consecuencias, tales como infecciones, embolismo y fallo cardíaco por sobrecarga de volumen, que requieren corrección. Reportamos el caso relativo a una paciente con fístula carótido yugular de 40 años de evolución secundaria a la realización de un cateterismo en la vena yugular interna durante la infancia, con evolución natural sin complicaciones relativas a la fístula post cateterismo.

Abstract Carotid-jugular fistula is one of the uncommon complications of jugular vein catheterization. It can have serious complications such as infection, embolization, and high output cardiac failure and requires invasive repair. We describe a case of uncommon carotid artery jugular vein artiovenous fistula following the insertion of a catheter for cardiac study during childhood, with 40 years of evolution without complications in relationship with post catheterism fistula.

MicroRNA-302a promotes neointimal formation following carotid artery injury in mice by targeting PHLPP2 thus increasing Akt signaling.

The excessive proliferation and migration of smooth muscle cells (SMCs) play an important role in restenosis following percutaneous coronary interventions. MicroRNAs are able to target various genes and involved in the regulation of diverse cellular processes including cell growth and proliferation. In this study we investigated whether and how MicroRNAs regulated vascular SMC proliferation and vascular remodeling following carotid artery injury in mice. We showed that carotid artery injury-induced neointimal formation was remarkably ameliorated in microRNA (miR)-302 heterozygous mice and SMC-specific miR-302 knockout mice. In contrast, delivery of miR-302a adenovirus to the injured carotid artery enhanced neointimal formation. Upregulation of miR-302a enhanced the proliferation and migration of mouse aorta SMC (MASMC) in vitro by promoting cell cycle transition, whereas miR-302a inhibition caused the opposite results. Moreover, miR-302a promoted Akt activation by corporately decreasing Akt expression and increasing Akt phosphorylation in MASMCs. Application of the Akt inhibitor GSK690693 (5 µmol/L) counteracted the functions of miR-302a in promoting MASMC proliferation and migration. We further revealed that miR-302a directly targeted at the 3' untranslated region of PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2) and negatively regulated PHLPP2 expression. Restoration of PHLPP2 abrogated the effects of miR-302a on Akt activation and MASMC motility. Furthermore, knockdown of PHLPP2 largely abolished the inhibition of neointimal formation that was observed in miR-302 heterozygous mice. Our data demonstrate that miR-302a exacerbates SMC proliferation and restenosis through increasing Akt signaling by targeting PHLPP2.

Down-regulation of Suv39h1 attenuates neointima formation after carotid artery injury in diabetic rats.

Patients with diabetes have an increased risk of vascular complications. Suv39h1, a histone methyltransferase, plays a protective role against myocardial injury in diabetes. Herein, we intend to explore whether Suv39h1 could affect neointimal formation after vascular injury in diabetic rats and reveal the underlying mechanism. In this study, we generated adenovirus expressing Suv39h1 as well as lentivirus expressing Suv39h1-targeting shRNA and evaluated the significance of Suv39h1 in vascular smooth muscle cells (VSMCs) under diabetic conditions. In vitro, we examined proliferative and migratory behaviours as well as the underlying signalling mechanisms in VSMCs in response to high glucose treatment. In vivo, we induced diabetes in SD rats with streptozocin and established the common carotid artery balloon injury model. Suv39h1 was found to be both necessary and sufficient to promote VSMC proliferation and migration under high glucose conditions. We observed corresponding changes in intracellular signalling molecules including complement C3 and phosphor-ERK1/2. However, either up-regulating or down-regulating Suv39h1, phosphor-p38 level was not significantly affected. Consistently, Suv39h1 overexpression led to accelerated neointima formation, while knocking down Suv39h1 reduced it following carotid artery injury in diabetic rats. Using microarray analyses, we showed that altering the Suv39h1 level in vivo dramatically altered the expression of myriad genes mediating different biological processes and molecular function. This study reveals the novel role of Suv39h1 in VSMCs of diabetes and suggests its potential role as a therapeutic target in diabetic vascular injury.

LncRNA GAS5 regulates vascular smooth muscle cell cycle arrest and apoptosis via p53 pathway.

Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA growth arrest specific 5 (GAS5) serves as a negative regulator for VSMC survival in vascular remodeling. By manipulating GAS5 expression via adenoviral overexpression or short hairpin RNA knockdown, we found that GAS5 suppresses VSMC proliferation while promoting cell cycle arrest and inducing cell apoptosis. Mechanistically, GAS5 directly binds to p53 and p300, stabilizes p53-p300 interaction, and thus regulates VSMC cell survival via induction of p53-downstream target genes. Importantly, local delivery of GAS5 via adenoviral vector suppresses balloon injury-induced neointima formation along with an increased expression of p53 and apoptosis in neointimal SMCs. Our study demonstrated for the first time that GAS5 negatively impacts VSMC survival via activation the p53 pathway during vascular remodeling.

Time to stroke: A Western Trauma Association multicenter study of blunt cerebrovascular injuries.

BACKGROUND: Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury. METHODS: Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed. RESULTS: During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred. CONCLUSIONS: The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level III.

Upregulated 14­3­3ß aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids.

Mono­unsaturated free fatty acids (FFAs) can serve as a predictive indicator of vascular restenosis following interventional therapy, particularly in individuals with high­fat diet­induced type 2 diabetes. However, the pathogenic mechanism remains to be fully elucidated. In the present study, the levels of tyrosine 3­monooxygenase/tryptophan 5­monooxygenase activation protein ß (YWHAB; also known as 14­3­3ß), in vascular smooth muscle cells (VSMCs) treated with different concentrations of oleic acid (OA) were examined by reverse transcription­quantitative polymerase chain reaction and western blot analyses. The migration of VSMCs was examined using wound­healing and Transwell migration assays. The protein distribution of B­cell lymphoma 2 (BCL­2)­associated death promoter (BAD) in VSMCs treated with OA was examined by immunofluorescence and western blot analyses. In in vivo experiments, the carotid artery morphology of rats in different groups was assessed at 14 days post­injury by non-invasive ultrasonographic imaging and confirmed by histological staining. The expression of YWHAB was upregulated by OA in a concentration­dependent manner in VSMCs. In the in vivo experiments, carotid stenosis was more serious among high­FFA diabetic rats. However, silencing of YWHAB significantly alleviated carotid neointimal hyperplasia among the diabetic rats with elevated FFA levels. In addition, YWHAB silencing alleviated the migration of OA­treated VSMCs and increased translocation of the BAD protein from the cytoplasm to the mitochondria. In conclusion, the results showed that FFA­induced upregulation of YWHAB was involved in neointimal hyperplasia by enhancing the migration of VSMCs following carotid artery injury. The inhibition of YWHAB may serve as a novel potential pharmacological target for preventing vascular restenosis following interventional therapy in diabetic individuals with high FFA levels.

Delayed extrusion of embolic coils into the airway after embolization of an external carotid artery pseudoaneurysm.

Carotid blowout syndrome (CBS) is a known devastating complication of head and neck surgery. The risk of developing CBS increases in the setting of radiation therapy, wound breakdown, or tumor recurrence. Traditionally, the treatment of choice for CBS is surgical ligation of the bleeding artery; however, recently, endovascular occlusion has become a more common option. If a pseudoaneurysm is present, treatment consists of trapping with endovascular coils or occlusion with a liquid embolic agent. Delayed migration of embolization coils into the airway causing acute respiratory distress is a rare occurrence. This report presents a case of a 57-year-old woman who presented to her otolaryngologist after experiencing an episode of acute respiratory distress which resolved when she expectorated embolization coil material from her tracheostomy tube. Three months prior to the episode she underwent coil embolization of an external carotid artery pseudoaneurysm for life-threatening hemorrhage.

Exogenous SERP1 attenuates restenosis by restoring GLP-1 receptor activity in diabetic rats following vascular injury.

The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing restenosis following vascular injury; however, the mechanism of dysfunctional GLP-1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces in diabetic patients are poorly understood. In the present study, we investigated the N-glycosylation level and role of stress-associated endoplasmic reticulum protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic rats. Our results showed that N-glycosylation levels in both rat aortic endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased gradually following glucose treatment in a concentration dependant manner. Furthermore, co-immunoprecipitation (Co-IP) analyses indicated that SERP1 could interact with GLP-1R in RAOECs and VSMCs. Moreover, SERP1 enhanced GLP-1R N-glycosylation and increased the production of phosphorylated endothelial nitric oxide synthase (eNOS) as well as proliferation of RAOECs. SERP1 also increased phosphorylated adenosine monophosphate activated protein kinase (AMPK) and decreased the migration of VSMCs. Importantly, intima media thickness (IMT) and neointimal hyperplasia were alleviated in the carotid artery of diabetic rats injected with SERP1 following balloon injury. We also found an increase in re-endothelialization and a decrease in VSMC proliferation in the carotid artery of diabetic rats injected with SERP1. In summary, the remarkable effects of SERP1 on reducing restenosis following vascular injury may contribute to future advancements in the treatment of diabetic vascular complications.

Blunt Cerebrovascular Artery Injury and Stroke in Severely Injured Patients: An International Multicenter Analysis.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) is considered to be a rare entity in patients with high-energy trauma and is a potentially preventable cause of secondary brain damage. If it occurs, it may be fatal or associated with poor outcomes related to devastating complications. We hypothesized that analyses of epidemiology and concomitant injuries may predict the development of BCVI and associated complications. METHODS: The TraumaRegister DGU® (TR-DGU), a prospectively maintained database, was used for retrospective data analysis (01/2009-12/2015). INCLUSION CRITERIA: adult trauma patients (≥16 years) with severe injuries (ISS ≥ 16 points) with and without BCVI. Subgroups: carotid artery injury (CAI) and vertebral artery injury (VAI). The degree of vascular injury was classified according to the Abbreviated Injury Scale values. Demographic, injury, therapy and outcome characteristic data (length of stay, stroke, multiple organ failure and mortality) were collected and analyzed for each patient with SPSS statistics (Version 23, IBM Inc., Armonk, NY). RESULTS: Out of 76,480 individuals, a total of 786 patients with BCVI (1%) were identified. The 435 CAI patients included 263 dissections, 78 pseudoaneurysms and 94 bilateral injuries. The 383 VAI patients presented with 198 dissections, 43 pseudoaneurysms, 122 thrombotic occlusions and 20 bilateral injuries. The risk for stroke was excessive in BCVI patients versus controls (11.5 vs. 1.1%, p < 0.001) and increased with vascular injury severity, up to 24.1% in CAI patients and 30.0% in VAI patients. We confirmed that cervical spine injuries were a major BCVI predictor (OR 6.46, p < 0.001, 95% CI 5.34-7.81); furthermore, high-energy mechanisms (OR 1.79), facial fractures (OR 1.56) and general injury severity (OR 1.05) were identified as independent predictors. Basilar skull fractures (BSF) were found with comparable frequency (p = 0.63) in both groups, and the predictive value was found to be insignificant (OR 1.1, p = 0.36, 95% CI 0.89-1.37). Age ≥ 60 years was associated with a decreased risk for BCVI (OR 0.54, p < 0.001, 95% CI 0.45-0.65); however, in BCVI patients over 60 years of age, mortality was excessive (OR 4.33, p < 0.001, 95% CI 2.40-7.80). Even after adjusting for head injuries, BCVI-associated stroke remained a significant risk factor for mortality (OR 2.52, p < 0.001, 95% CI 1.13-5.62). CONCLUSION: Our data validated cervical spine injuries as a major predictor, but the predictive value of BSF must be scrutinized. Patient age appears to play a contradictory role in BCVI risk and BCVI-associated mortality. Predicting which patients will develop BCVI remains an ongoing challenge, especially since many patients do not present with concomitant injuries of the head or spine and therefore might not be captured by standard screening criteria.

Bilateral Traumatic Caroticocavernous Fistulas: A Case Report and Review of the Literature.

A traumatic caroticocavernous fistula (CCF) is an acquired, abnormal communication between the internal carotid artery and the cavernous sinus, secondary to trauma. This rare condition can initially be misdiagnosed, because its presentation shares features common to those of facial trauma, which can result in serious complications. We describe a case of bilateral CCF in an adult patient after a road traffic accident.

Loss of Spry1 attenuates vascular smooth muscle proliferation by impairing mitogen-mediated changes in cell cycle regulatory circuits.

Signals from growth factors or mechanical stimuli converge to promote vascular smooth muscle cell (VSMC) migration and proliferation, key events in the pathogenesis of intimal hyperplasia upon vascular injury. Spry1, a regulator of receptor tyrosine kinases (RTK), plays a role in maintaining the contractile phenotype of VSMC. The aim of the current study was to determine the role of Spry1 in VSMC proliferation in vitro and injury induced neointimal hyperplasia in vivo. VSMC proliferation and neointima formation were evaluated in cultured human aortic SMC (hAoSMC) and ligation-induced injury of mouse carotid arteries from Spry1 gene targeted mice, and their corresponding wild type littermates. Human Spry1 or non-targeting control lentiviral shRNAs were used to knock down Spry1 in hAoSMC. Time course cell cycle analysis showed a reduced fraction of S-phase cells at 12 and 24 h after growth medium stimulation in Spry1 shRNA transduced hAoSMC. Consistent with reduced S-phase entry, the induction of cyclinD1 and the levels of pRbS807/S811, pH3Ser10, and pCdc2 were also reduced, while the cell cycle inhibitor p27Kip1 was maintained in Spry1 knockdown hAoSMC. In vivo, loss of Spry1 attenuated carotid artery ligation-induced neointima formation in mice, and this effect was accompanied by a decrease in cell proliferation similar to the in vitro results. Our findings demonstrate that loss of Spry1 attenuates mitogen-induced VSMC proliferation, and thus injury-induced neointimal hyperplasia likely via insufficient activation of Akt signaling causing decreased cyclinD1 and increased p27Kip1 and a subsequent decrease in Rb and cdc2 phosphorylation.

[Post-traumatic carotido-jugular fistula: Case report and review of the literature]. / Fistule carotido-jugulaire post-traumatique : à propos d'un cas opéré.

The neck, being not protected by skeleton, is vulnerable to external trauma and injury which can involve blood vessels, muscles, nerves, and trachea. Carotid injuries can be potentially life-threatening by hemorrhage and stroke. We present a case of a 26-year-old manual worker who presented a neck injury caused by a metallic projectile. The injury involved the right common carotid artery with an internal jugular vein fistula, and tracheal damage. The patient was managed with surgical repair of the tracheal lesion, reconstruction of the carotid section using a PTFE graft bypass, and ligation of the internal jugular vein. In the immediate postoperative period, the patient presented with no neurological deficits, but he did develop a pulmonary infection that resolved with antibiotic therapy. The follow-up is now 3months. The patient is doing well without any neurological disorder.