Next-generation transcarotid artery revascularization: TransCarotid flOw Reversal Cerebral Protection And CGUARD MicroNET-Covered Embolic Prevention Stent System To Reduce Strokes - TOPGUARD Study.

BACKGROUND: Stent-assisted carotid artery revascularization employing surgical cutdown for transcervical access and dynamic flow reversal (TCAR) is gaining popularity. TCAR, despite maximized intra-procedural cerebral protection, shows a marked excess of 30-day neurologic complications in symptomatic vs. asymptomatic stenoses. The TCAR conventional single-layer stent (free-cell area 5.89mm2) inability to seal embologenic lesions may be particularly relevant after the flow reversal neuroprotection is terminated. METHODS: We evaluated peri-procedural and 30-day major adverse cerebral and cardiac events (MACCE) of TCAR (ENROUTE, SilkRoad Medical) paired with MicroNET-covered neuroprotective stent (CGuard, InspireMD) in consecutive patients at elevated risk of complications with transfemoral/transradial filter-protected stenting (increased lesion-related and/or access-related risk). CGuard (MicroNET free cell area ≈0.02-0.03 mm2) has level-1 evidence for reducing intra- and abolishing post-procedural lesion-related cerebral embolism. RESULTS: One hundred and six increased-risk patients (age 72 [61-76] years, median [Q1-Q3]; 60.4% symptomatic, 49.1% diabetic, 36.8% women, 61.3% left-sided index lesion) were enrolled in three vascular surgery centers. Angiographic stenosis severity was 81 (75-91)%, lesion length 21 (15-26)mm, increased-risk lesional characteristics 87.7%. Study stent use was 100% (no other stent types). 74.5% lesions were predilated; post-dilatation rate was 90.6%. Flow reversal duration was 8 (5-11)min. One stroke (0.9%) occurred in an asymptomatic patient prior to establishing neuroprotection (index lesion disruption with the sheath insertion wire); there were no other peri-procedural MACCE. No further adverse events occurred by 30-days. 30-day stent patency was 100% with normal velocities and absence of any in-stent material by Duplex Doppler. CONCLUSIONS: Despite a high proportion of increased-risk lesions and clinically symptomatic patients in this study, TCAR employing the MicroNET-covered anti-embolic stent showed 30-day MACCE rate <1%. This suggests a clinical role for combining maximized intra-procedural prevention of cerebral embolism by dynamic flow reversal with anti-embolic stent prevention of peri- and post-procedural cerebral embolism (TOPGUARD NCT04547387).

Carotid artery stenting with flow inversion cerebral protection and MicroNet-covered stent.

BACKGROUND: The study aims to evaluate the association of proximal flow-inversion cerebral protection and MicroNet-covered CGuard stents in reducing early and late embolic events in carotid artery stenting procedures. METHODS: From 2018 to 2023, we performed 204 procedures in 180 patients with flow inversion cerebral protection and CGuard stents at the Vascular Surgery Unit of Sant'Eugenio Hospital in Rome. Cerebral protection was achieved with a Flow-Gate2 catheter connected to a peripheral vein. The tip balloon is inflated in the CCA to obtain an effective endoclamping, the pressure difference between the carotid bifurcation and the venous compartment ensures a constant back flow with wash-out in the venous compartment. Inclusion criteria were: life expectancy of >12 months, target lesions indicating treatment according to ESVS Guidelines, increased surgical risk due to comorbidities or anatomic issues. ECD follow-up was performed immediately postoperatively, at 30 days, 6 and 12 months, and subsequently annually. RESULTS: The treatment protocol was successfully implemented in 99% of cases. No major strokes occurred, while one minor stroke (0.5%) occurred within 8 hours of the procedure, regressing in the following months. One perioperative death (0.5%) due to cerebral hemorrhage occurred three hours after the procedure. All patients remained asymptomatic, with no short or medium-term neurological score deterioration. One hemodynamically significant restenosis (0.5%) was detected at the 6-month follow-up. All patients completed the 6 months follow-up, though 6 (3%) were lost at the 12-month appointment. CONCLUSIONS: Our prospective monocentric study has demonstrated the effectiveness and safety of the FlowGate2 flow inversion cerebral protection system in association with MicroNet covered CGuard stent.

High-frequency repetitive transcranial magnetic stimulation ameliorates memory impairment by inhibiting neuroinflammation in the chronic cerebral hypoperfusion mice.

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH). AIM: To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice. MATERIALS AND METHODS: Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1ß, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group. RESULTS: Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). CONCLUSIONS: HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

Outcome of CAS under flow reversal and analysis for the intraprocedural flow of internal carotid artery.

OBJECTIVE: Carotid artery stenting (CAS) under flow reversal with dual protection using a proximal balloon and distal filter has been an established procedure for internal carotid artery (ICA) stenosis. This study investigates the effect of external carotid artery (ECA) occlusion on outcomes of CAS and ICA flow under flow reversal. METHODS: We reviewed 231 cases of CAS under flow reversal with ECA occlusion and 32 without. In the last 14 of 32 cases, the flow in the ICA under flow reversal was analyzed by ultrasound. The collateral index, which was defined as the total value of the maximum diameters of the ipsilateral anterior cerebral artery at the A1 segment and the anterior communicating artery, as well as those of the ipsilateral posterior cerebral artery at the P1 segment and the ipsilateral posterior communicating artery, and the maximum diameter of the ipsilateral ECA were correlated with the flow direction in the ICA. RESULTS: There was no significant difference in the outcome of CAS between the groups with or without ECA occlusion. Among the 14 cases without ECA occlusion, antegrade flow in the ICA was observed in 6 cases (42.9 %). The group with the antegrade flow in the ICA exhibited a significantly lower collateral index (5.08±0.33 vs 6.71±0.28, p=0.01) and a significantly larger ECA diameter (4.66±0.51 mm vs 3.21±1.24 mm, p=0.01) than the group with the stagnant or retrograde flow in the ICA. CONCLUSIONS: The outcomes of CAS under flow reversal were acceptable even without ECA occlusion. The ECA occlusion may not be necessary for CAS under dual protection; however, distal filter protection should be used even under flow reversal.

Fabrication, characterization and numerical validation of a novel thin-wall hydrogel vessel model for cardiovascular research based on a patient-specific stenotic carotid artery bifurcation.

In vitro vascular models, primarily made of silicone, have been utilized for decades for studying hemodynamics and supporting the development of implants for catheter-based treatments of diseases such as stenoses and aneurysms. Hydrogels have emerged as prominent materials in tissue-engineering applications, offering distinct advantages over silicone models for fabricating vascular models owing to their viscoelasticity, low friction, and tunable mechanical properties. Our study evaluated the feasibility of fabricating thin-wall, anatomical vessel models made of polyvinyl alcohol hydrogel (PVA-H) based on a patient-specific carotid artery bifurcation using a combination of 3D printing and molding technologies. The model's geometry, elastic modulus, volumetric compliance, and diameter distensibility were characterized experimentally and numerically simulated. Moreover, a comparison with silicone models with the same anatomy was performed. A PVA-H vessel model was integrated into a mock circulatory loop for a preliminary ultrasound-based assessment of fluid dynamics. The vascular model's geometry was successfully replicated, and the elastic moduli amounted to 0.31 ± 0.007 MPa and 0.29 ± 0.007 MPa for PVA-H and silicone, respectively. Both materials exhibited nearly identical volumetric compliance (0.346 and 0.342% mmHg-1), which was higher compared to numerical simulation (0.248 and 0.290% mmHg-1). The diameter distensibility ranged from 0.09 to 0.20% mmHg-1 in the experiments and between 0.10 and 0.18% mmHg-1 in the numerical model at different positions along the vessel model, highlighting the influence of vessel geometry on local deformation. In conclusion, our study presents a method and provides insights into the manufacturing and mechanical characterization of hydrogel-based thin-wall vessel models, potentially allowing for a combination of fluid dynamics and tissue engineering studies in future cardio- and neurovascular research.

Quantitative evaluation using carotid ultrasonography-based high-frame-rate vector flow imaging in patients with low carotid stenosis.

OBJECTIVE: To explore the role of quantitative evaluation using carotid ultrasonography (US)-based high-frame-rate vector flow (V Flow) imaging in patients with low carotid stenosis. METHODS: This single-centre cross-sectional study consecutively recruited volunteers without carotid plaque and patients with low carotid stenosis from August 2022 to May 2023. Patients were divided into symptomatic and asymptomatic groups according to their head CT or MRI results within 8 weeks. All V Flow imaging examinations were performed using a Mindray Resona R9 US system. The wall shear stress (WSS) values, oscillatory shear index (OSI) values, and turbulence (Tur) indexes in the normal common carotid artery (CCA), normal carotid bifurcation (CB), and on the upstream and downstream surface of carotid plaque were measured. Pearson Chi-square test and Fisher exact test were used for counting data according to their type. For measurement data, independent sample t test and non-parametric rank sum test were used. RESULTS: The results proved that patients have higher WSS values and Tur indexes of CB than volunteers, and higher WSS values were detected on the surface of the plaques in symptomatic patients. What's more, the downstream side of the plaque was more vulnerable to plaque rupture than the upstream side due to more dynamic blood flow. CONCLUSION: Therefore, carotid US-based high-frame-rate V Flow imaging provides reliable mechanical biomarkers for assessing the haemodynamic change in patients with low stenosis. Our study may provide a new imaging tool for monitoring the progression of atherosclerosis and aiding the management of early atherosclerotic patients. ADVANCES IN KNOWLEDGE: Our study firstly investigated the difference of V Flow parameters on the surface of carotid plaques between symptomatic and asymptomatic patients with low carotid stenosis, which is expected to provide haemodynamic information and the mechanical basis for plaque rupture.

Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI.

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

Color Duplex Ultrasonography for the Evaluation of Innominate, Subclavian, and Common Carotid Artery Stenosis.

OBJECTIVE: This study aimed to validate the efficiency of Doppler ultrasonography for predicting the innominate, subclavian, and common carotid artery stenosis. METHODS: This retrospective multicenter study between 2013 and 2022 enrolled 636 patients who underwent carotid Doppler ultrasonography and subsequent digital subtraction angiography. And 58 innominate artery stenosis, 147 common carotid artery stenosis, and 154 subclavian artery stenosis were included. The peak systolic velocity at innominate, subclavian, and common carotid artery, and velocity ratios of innominate artery to common carotid artery, innominate artery to subclavian artery, and common carotid artery to internal carotid artery were measured or calculated. The threshold values were determined using receiver operating characteristic analysis. RESULTS: The threshold values of innominate artery stenosis were peak systolic velocity >206 cm/s (sensitivity: 82.8%; specificity: 91.4%) to predict ≥50% stenosis and >285 cm/s (sensitivity: 89.2%; specificity: 94.9%) to predict ≥70% stenosis. The threshold values of common carotid artery stenosis were peak systolic velocity >175 cm/s (sensitivity: 78.2%; specificity: 91.9%) to predict ≥50% stenosis and >255 cm/s (sensitivity: 87.1%; specificity: 87.2%) to predict ≥70% stenosis. The threshold values of subclavian artery stenosis were peak systolic velocity >200 cm/s (sensitivity: 68.2%; specificity: 84.4%) to predict ≥50% stenosis and >305 cm/s (sensitivity: 57.9%; specificity: 91.4%) to predict ≥70% stenosis. CONCLUSIONS: Symptomatic patients with ultrasonic parameters of velocity at innominate artery ≥206 cm/s, velocity at common carotid artery ≥175 cm/s, or velocity at subclavian artery ≥200 cm/s need to be considered for further verification and whether revascularization is necessary.

Territory-Related Functional Connectivity Changes Associated with Verbal Memory Decline in Patients with Unilateral Asymptomatic Internal Carotid Stenosis.

BACKGROUND AND PURPOSE: Verbal memory decline is a common complaint of patients with severe asymptomatic stenosis of the internal carotid artery (aICS). Previous publications explored the associations between verbal memory decline and altered functional connectivity (FC) after aICS. Patients with severe aICS may show reduced perfusion in the ipsilateral territory and redistribution of cerebral blood flow to compensate for the deficient regions, including expansion of the posterior and contralateral ICA territories via the circle of Willis. However, aICS-related FC changes in anterior and posterior territories and the impact of the sides of stenosis were less explored. This study aims to investigate the altered FC in anterior and posterior circulation territories of patients with left or right unilateral aICS and its association with verbal memory decline. MATERIALS AND METHODS: We enrolled 15 healthy controls (HCs), 22 patients with left aICS (aICSL), and 33 patients with right aICS (aICSR) to receive fMRI, Mini-Mental State Examination (MMSE), the Digit Span Test (DST), and the 12-item Chinese version of Verbal Learning Tests. We selected brain regions associated with verbal memory within anterior and posterior circulation territories. Territory-related FC alterations and verbal memory decline were identified by comparing the aICSL and aICSR groups with HC groups (P < .05, corrected for multiple comparisons), respectively. Furthermore, the association between altered FC and verbal memory decline was tested with the Pearson correlation analysis. RESULTS: Compared with HCs, patients with aICSL or aICSR had significant impairment in delayed recall of verbal memory. Decline in delayed recall of verbal memory was significantly associated with altered FC between the right cerebellum and right middle temporal pole in the posterior circulation territory (r = 0.40, P = .03) in the aICSR group and was significantly associated with altered FC between the right superior medial frontal gyrus and left lingual gyrus in the anterior circulation territory (r = 0.56, P = .01) in the aICSL group. CONCLUSIONS: Patients with aICSL and aICSR showed different patterns of FC alterations in both anterior and posterior circulation territories, which suggests that the side of aICS influences the compensatory mechanism for decline in delayed recall of verbal memory.

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice.

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.

[Dynamic functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Dinamicheskaya funktsional'naya otsenka patologicheskikh izvitostei vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom. Klinicheskii sluchai.

A personalized approach with attention to anamnesis and specific symptoms is necessary in patients with internal carotid artery tortuosity. Neuroimaging (especially before elective surgery) or functional stress tests following ultrasound of supra-aortic vessels may be necessary depending on medical history and complaints. In addition to standard Doppler ultrasound, these patients should undergo rotational and orthostatic transformation tests. We analyze changes in shape and hemodynamic parameters within the tortuosity area in various body positions. This is especially valuable for patients with concomitant carotid artery stenosis. The article presents a clinical case illustrating the importance of such approach.

[Functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Vazhnost' dinamicheskoi funktsional'noi otsenki patologicheskoi izvitosti vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom.

The review is devoted to diagnosis and treatment of internal carotid artery tortuosity. The authors consider modern classification, epidemiology and diagnostic options using neuroimaging or ultrasound-assisted functional stress tests depending on medical history and complaints. In addition to standard Doppler ultrasound, rotational and orthostatic tests are advisable due to possible changes of local shape and hemodynamic parameters following body position changes, especially in patients with concomitant atherosclerotic stenosis. Thus, a personalized approach is especially important for treatment and diagnostics of internal carotid artery tortuosity.

A patient-specific circle of Willis blood flow model in predicting outcomes of balloon test occlusion.

BACKGROUND AND PURPOSE: Balloon test occlusion (BTO) evaluates cerebral ischemic tolerance before internal carotid artery (ICA) sacrifice but carries risks like dissection and thrombosis. This study introduces a new approach using a patient-specific circle of Willis (COW) blood flow model, based on non-invasive quantitative MR angiography (qMRA) measurements, to predict the outcomes of BTO. METHODS: We developed individualized COW blood flow models for 43 patients undergoing BTO. These models simulated blood flow and pressure under normal conditions and with the ICA occlusion. We then compared the model's predictions of blood flow changes due to the simulated ICA occlusion to actual qMRA measurements before the BTO. RESULTS: For all 31 BTO failures, the ipsilateral hemisphere showed an average flow decrease of 15 ± 10% (mean ± standard deviation), compared to 3 ± 2% in the contralateral hemisphere. In all 12 BTO passes, these figures were 6 ± 3% and 1 ± 0.8%, respectively. Notably, all BTO passes had less than a 10% reduction in the ipsilateral hemisphere. In contrast, 65% of BTO failures and 67% single-photon emission computed tomography (SPECT) failures exhibited a decrease of 10% or more in the same region. CONCLUSION: Blood flow reduction exceeding 10% in the ipsilateral hemisphere during BTO is a strong predictor of failure in both BTO and SPECT. Our patient-specific COW blood flow models, incorporating detailed flow and arterial geometry data, offered valuable insights for predicting BTO outcomes. These models are especially beneficial for situations where conducting BTO or SPECT is clinically impractical.

Risk Factors for and Intraoperative Management of Intolerance to Flow Reversal in TCAR.

BACKGROUND: In patients deemed high risk for carotid endarterectomy (CEA) who are indicated for treatment of carotid artery stenosis (CAS), transcarotid artery revascularization (TCAR) has been demonstrated as a safe and effective alternative to trans-femoral carotid artery stenting (TF-CAS). Compared to CEA, where approx. 12% of patients undergoing awake intervention do not tolerate internal carotid artery (ICA) clamping, only 1-2% of patients were observed to have intolerance to flow reversal during TCAR based on data from the ROADSTER1/2 trials. This study reviewed awake interventions from those trials to assess factors associated with intolerance to flow reversal and review how those cases were managed. METHODS: This is a retrospective review of prospectively collected data from Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial along with the subsequent post-approval (ROADSTER-2) trial. The subset of patients from both trials undergoing awake TCAR was analyzed to compare demographics, procedural details, and anatomic factors between patients who did and did not experience intolerance to reversal of flow to assess for predisposing factors. Patients were deemed intolerant to flow reversal at the discretion of the operator, often related to changes in completion of neurologic tasks, hemodynamic stability, or patient reported symptoms. RESULTS: A total of 103 patients from ROADSTER and 194 patients from ROADSTER-2 underwent TCAR under local/regional anesthesia. Of these, 8 patients had intolerance to flow reversal, though all cases were successfully completed. While intraoperative hemodynamic data was only available for 5 of the 8 intolerant patients, none experienced hypotension. 4 cases were completed under low flow reversal, 3 cases were successfully weaned from low to high flow over several minutes, and 1 case required general anesthesia. No significant association was found between intolerance to flow reversal and comorbidities including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), congestive heart failure (CHF), prior MI or angina, pre-op CAS-related symptoms, prior stroke, prior CAS or CEA, prior neck radiation, tandem stenosis, high cervical stenosis, or hostile neck. A trend towards significance was seen with chronic obstructive pulmonary disease (COPD) and contralateral carotid artery occlusion (P = 0.086 and 0.139, respectively). CONCLUSIONS: Despite intolerance to flow reversal, TCAR cases were successfully completed by adjusting reversal-of-flow rate and do not typically require conversion to GETA. While factors contributing to intolerance of flow reversal during TCAR remain poorly understood, this study identified a trend towards significance with an association of preexisting COPD and contralateral carotid artery occlusion. Given the low number of patients who experienced this issue, a larger sample size is required to better elucidate these trends.

Modifications in Near Infrared Spectroscopy for Cerebral Monitoring During Carotid Endarterectomy in Asymptomatic and Symptomatic Patients.

BACKGROUND: To evaluate trends and differences in Near Infrared Spectroscopy (NIRS) monitoring during carotid endarterectomy (CEA) in patients affected by asymptomatic and symptomatic carotid artery stenosis, to predict postoperative neurological complications (PNCs). METHODS: NIRS data of CEAs performed in a University Hospital were retrospectively reviewed. All the interventions were performed under general anesthesia and patients with intraoperative complications were excluded. Mean regional Oxygen Saturation Index (rSO2), pre-clamp values (mean baseline value, MBv and Single Mark Baseline value, SMBv) were collected and compared to the lowest rSO2 values during carotid cross-clamp (LSO2v) calculated within 3 min (percentage drop, PD). ROC curve analysis with Youden's Test was performed to determine the best threshold value of PD, in order to identify PNCs in both asymptomatic and symptomatic groups. RESULTS: Between 2007 and 2015, a total of 399 CEAs were consecutively performed with NIRS monitoring. Three-hundred-seventy-two CEAs in 355 patients were reviewed. Asymptomatic stenoses were 291 (81.9%), eleven (2.9%) PNC were registered (5 in asymptomatic and 6 in symptomatic group). Asymptomatic and symptomatic diseases had different MBv (69.5 ± 7.5 vs. 71.8 ± 6.9, respectively; P = 0.011) and similar rSO2 value during carotid clamping (63.7 ± 8.0 vs. 63.7 ± 6.7, respectively: P = 0.958). Asymptomatic patients experiencing PNCs had a greater PD than non-PNCs group (20.5 ± 10.2% vs. 12.5 ± 7.6%, respectively using MBv as baseline value; P = 0.002), in contrast, in symptomatic patients, in which a low PD was associated with PNCs, it does not reach statistical significance (using MBv, 12.6 ± 5.4% vs. 14.8 ± 6.7%, respectively; P= 0.476). In order to detect PNCs, ROC analysis revealed an optimal PD cut-off value of -17% in asymptomatic CEAs. (Sensibility (Se) 0.80, Specificity (Sp) 0.76, PPV 0.05, NPV 0.99, Youden's index 0.56; P = 0.020) In symptomatic a threshold value of -9% was found, without reaching statistical significance. CONCLUSIONS: NIRS as cerebral monitoring during CEA can predict PNCs in asymptomatic stenosis. Asymptomatic and symptomatic groups differ in baseline and intraprocedural cut-off values to detect an augmented PNCs risk.

Hemodynamic Impact of Stenting on Carotid Bifurcation: A Potential Role of the Stented Segment and External Carotid Artery.

Carotid stenting near the bifurcation carina is associated with adverse events, especially in-stent restenosis, thrombosis, and side branch occlusion in clinical data. This study is aimed at determining the potential biomechanical mechanisms for these adverse events after carotid stenting. The patient-specific carotid models were constructed with different stenting scenarios to study the flow distribution and hemodynamic parameters, such as wall shear stress (WSS), flow velocity, relative residence time (RRT), and oscillating shear index (OSI) in the carotid bifurcation. The results suggested that the existing stents surely reduced blood flow to the external carotid artery (ECA) but enhanced local flow disturbance both in ECA and stented internal carotid artery (ICA), and the inner posterior wall of the stented ICA and the outer posterior wall of ECA might endure a relatively low level of WSS and remarkably elevated OSI and RRT. In addition, the implanted stent leads to more ECA adverse flow than ICA after stenting. While disturbed flow near the strut increased as stent length increased, blood flow and areas of local flow disturbance in ECA slightly decreased as stent length increased. In conclusion, the results revealed that ECA might be in relatively high levels of abnormal local hemodynamics after stenting, followed by stented ICA, leading to potential adverse events after intervention.

Different causes and diverse outcomes of extremely rare septic cavernous sinus thrombosis complicated with internal carotid artery stenosis.

BACKGROUND: Cases of acute sphenoid sinusitis complicated by septic cavernous sinus (CS) thrombosis and internal carotid artery (ICA) stenosis are rarely reported. Different causative pathogens have been reported for this condition. We present two extremely rare and special cases with diverse clinical presentations and outcomes. Case 1 involved a female patient with less extensive sinusitis, but critical ICA occlusion. Case 2 involved a male patient with extensive pansinusitis, meningitis, cerebritis, and vasculitis due to fungal infection, but less stenosis of the ICA lumen. Both patients underwent surgical debridement and received broad-spectrum antibiotics. Additional anti-fungal medication was also administered in Case 2. However, outcomes differed considerably between cases. DISCUSSION: Case 1 recovered with minimal neurological deficits and had Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) scores of 5 and 2, respectively; however, the Case 2 had GOS and mRS scores of 3 and 4, respectively. Although rare, septic CS thrombosis with ICA stenosis can lead to unexpected and severe neurological sequelae. Fungal infection can result in catastrophic complications and poorer prognosis. CONCLUSION: In addition to early detection, aggressive surgical debridement and adequate antimicrobial treatment are crucial to satisfactory outcomes in patients with septic CS thrombosis complicated with ICA stenosis.

MicroRNA-375-3p is implicated in carotid artery stenosis by promoting the cell proliferation and migration of vascular smooth muscle cells.

BACKGROUND: Atherosclerosis is the main cause of carotid artery stenosis (CAS) which mostly occurs in the elderly. In this paper, the expression level of miR-375-3p in asymptomatic CAS patients and its diagnostic value for asymptomatic CAS were investigated, and the effects of miR-375-3p on the cell proliferation and migration of vascular smooth muscle cells (VSMCs) was further explored. METHODS: 98 healthy subjects and 101 asymptomatic CAS patients were participated in this study. qRT-PCR was used to measure the expression level of serum miR-375-3p, and the ROC curve was established to evaluate the predictive value of miR-375-3p for asymptomatic CAS. After transfection with miR-375-3p mimic or inhibitor in vitro, cell proliferation and migration were detected by CCK-8 assay, colony formation assay, and Transwell assay, respectively. The levels of TNF-α, IL-1ß, IL-6 were detected by ELISA. Western blot was used to detect the protein expression of XIAP. Finally, luciferase reporter gene assay was applied to assess the interaction of miR-375-3p with target genes. RESULTS: The expression level of serum miR-375-3p in asymptomatic CAS patients was significantly higher than that in healthy controls, and the AUC value of ROC curve was 0.888. The sensitivity and specificity were 80.2 and 86.7%, respectively, indicating that miR-375-3p had high diagnostic value for asymptomatic CAS. In vitro cell experiments showed that up-regulation of miR-375-3p significantly promoted the proliferation and migration of VSMCs, and also promoted the generation of inflammatory factors and phenotypic transformation of VSMCs. Luciferase reporter gene assay confirmed that XIAP was a target gene of miR-375-3p and was negatively regulated by miR-375-3p. CONCLUSIONS: In this study, miR-375-3p may have a clinical diagnostic value for asymptomatic CAS patients which need further validation. Increased miR-375-3p levels in CAS may be associated with increased proliferation and migration of VSMCs via downregulation of the apoptosis inducing gene XIAP.

Association of Lower Extremity Vascular Disease, Coronary Artery, and Carotid Artery Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

The motive of this article is to present the case study of patients to investigate the association between the ultrasonographic findings of lower extremity vascular disease (LEAD) and plaque formation. Secondly, to examine the association between the formation of coronary artery and carotid artery atherosclerosis in patients with type 2 diabetes mellitus. 124 patients with type 2 diabetes (64 males and 60 females with the age group 25-78 years) are considered for the research studies who have registered themselves in the Department of Endocrinology and Metabolism from April 2017 to February 2019. All participants have reported their clinical information regarding diabetes, alcohol consumption, smoking status, and medication. The blood samples from subjects are collected for measurement of HbA1c, total cholesterol, triglycerides, HDL-c, and LDL-c levels. Two-dimensional ultrasound has been used to measure the inner diameter, peak flow velocity, blood flow, and spectral width of the femoral artery, pop artery, anterior iliac artery, posterior tibial artery, and dorsal artery and to calculate the artery stenosis degree. Independent factors of atherosclerosis are determined by multivariate logistic regression analysis. The results are evaluated within the control group and it is found that there is no significant impact of gender, age, and body mass index (P > 0.05) on the lower extremity vascular diseases. Those with smoking, alcohol consumption, hypertension, and dyslipidemia have higher positive rate (P < 0.05). The type 2 diabetes mellitus group has higher diastolic blood pressure and lower triglyceride (P < 0.05). Diastolic blood pressure, HbA1C, total cholesterol, HDL-c, and LDL-C are not remarkably dissimilar between the type 2 diabetes mellitus group and the control group (P > 0.05). Compared with the control group, the type 2 diabetes mellitus group has higher frequency of lower extremity vascular diseases in the dorsal artery than in the pop artery (P < 0.05). The blood flow of type 2 diabetes mellitus group is found to be lower than that of the control group, especially in the dorsal artery (P < 0.05). The blood flow velocity of the dorsal artery is accelerated (P < 0.01). Among 117 patients of type 2 diabetes mellitus (94.35%) with a certain degree of injury, there are 72 cases of type I carotid stenosis (58.06%), 30 cases of type II carotid stenosis (24.19%), and 15 cases of type III carotid stenosis (12.10%). Out of 108 subjects in the control group, there are 84 cases of type 0 carotid stenosis (77.78%), 19 cases of type I carotid stenosis (17.59%), 5 cases of type II carotid stenosis (4.63%), and 0 case of type III carotid stenosis (0.00%). Compared with the control group, carotid stenosis is more common in patients with type 2 diabetes mellitus (P < 0.05). Age, smoking, duration of diseases, systolic blood pressure, and degree of carotid stenosis are found to be associated with atherosclerosis. The findings suggest that the color Doppler ultrasonography can give early warning when applied in patients with carotid and lower extremity vascular diseases to delay the incidence of diabetic macroangiopathy and to control the development of cerebral infarction, thus providing an important basis for clinical diagnosis and treatment.

Surgery for near occlusion of the internal carotid arteries. A single center experience.

Several experiences have shown the benefits of carotid endarterectomy (CEA) to treat symptomatic acute occlusion of common and internal carotid arteries. Instead, surgery for carotid near occlusion remains controversial. We report successful surgical treatment in three patients with near occluded carotid artery. Doppler ultrasound scan was performed and showed common or internal carotid artery (ICA) near occlusion with controlateral carotid stenosis <50% (NASCET) with distal recanalization supported by collateral arteries of the external carotid artery (ECA) documented by preoperative CT-scan or selected angiography. Cases were treated by CEA of bifurcation and common-internal carotid bypass, using a PTFE graft or with longitudinal CEA and direct reconstruction. Perioperative and three months follow-up were free from new neurological events. In conclusion surgery for carotid near occlusion can be safely and successfully performed in selected cases with distal recanalization.