ARTICLE | doi:10.20944/preprints201609.0002.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: fractal dimension; carotid plaque characterization; three dimensional ultrasound; an evaluation of the vulnerability of the plaques
Online: 1 September 2016 (10:48:18 CEST)
Carotid atherosclerotic lesions are a major cause of cerebrovascular disease (CVD). Identification and quantification of carotid plaques are important for categorizing the vulnerability of plaques for rupture and assessing the impact of treatments. The irregularity of plaque surface is associated with previous plaque rupture and plays an important role in the risk of stroke. Thus, the aim of this study is to develop and validate novel vulnerability biomarkers from three-dimensional ultrasound (3DUS) images by analyzing the surface morphological characterization of carotid plaque using fractal geometry features. 3D box-counting and 3D blanket are the two types of 3D fractal dimension that were employed to describe the smoothness of plaques. This fractal dimension analysis tool was used to evaluate the effect of atorvastatin using 3DUS carotid images, which were acquired from 6 patients treated with atorvastatin with 80 mg daily and 5 patients with placebo. The Student's T Test results showed that those two fractal features were effective for detecting the statin-related changes in carotid atherosclerosis with p<0.0068 and p<0.015 respectively, suggesting that 3D fractal dimension measurements can be used effectively to analyze the surface characteristics of carotid plaques, especially for evaluating the impact of the treatment.
ARTICLE | doi:10.20944/preprints202102.0577.v1
Subject: Medicine & Pharmacology, Allergology Keywords: carotid atherosclerosis; pre-diabetes mellitus; microRNAs; inflammation; metformin therapy
Online: 25 February 2021 (11:43:02 CET)
BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.
ARTICLE | doi:10.20944/preprints201910.0230.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: carotid intraplaque hemorrhage; carotid atherosclerosis; semi-automatic quantification; MPRAGE
Online: 20 October 2019 (01:39:19 CEST)
Purpose: Carotid intraplaque hemorrhage (IPH) increases risk of territorial cerebral ischemic events, but different sequences or criteria have been used to diagnose or quantify carotid IPH. The purpose of this study was to compare manual segmentation and semi-automatic segmentation for quantification of carotid IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) sequences. Methods: Forty patients with 16–79% carotid stenosis and IPH on MPRAGE sequences were reviewed by two trained radiologists with more than five years of specialized experience in carotid plaque characterization with carotid plaque MRI. Initially, the radiologists manually viewed the IPH based on the MPRAGE sequence. IPH volume was then measured by three different semi-automatic methods, with high signal intensity 150%, 175%, and 200%, respectively, above that of adjacent muscle on the MPRAGE sequence. Agreement on measurements between manual segmentation and semi-automatic segmentation was assessed using the intraclass correlation coefficient (ICC). Results: There was near-perfect agreement between manual segmentation and the 150% and 175% criteria for semi-automatic segmentation in quantification of IPH volume. The ICC of each semi-automatic segmentation were as follows: 150% criteria: 0.861, 175% criteria: 0.809, 200% criteria: 0.491. The ICC value of manual vs. 150% criteria and manual vs. 175% criteria were significantly better than the manual vs. 200% criteria (p < 0.001). Conclusions: The ICC of 150% and 175% criteria for semi-automatic segmentation are more reliable for quantification of IPH volume. Semi-automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.
ARTICLE | doi:10.20944/preprints201611.0004.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: thin film nitinol; carotid artery; micro mesh stent; micropatterning
Online: 1 November 2016 (06:54:40 CET)
Stenting is an alternative to endarterectomy for the treatment of carotid artery stenosis. However, stenting is associated with a higher risk of procedural stroke secondary to distal thromboembolism. Hybrid stents with a micromesh layer have been proposed to address this complication. We developed a micropatterned thin film nitinol (M-TFN) covered stent designed to prevent thromboembolism during carotid intervention. This innovation may obviate the need or work synergistically with embolic protection devices. The proposed double layered stent is low-profile, thromboresistant, and covered with a M-TFN that can be fabricated with fenestrations of varying geometries and sizes. The M-TFN was created in multiple geometries, dimensions, and porosities by sputter deposition. The efficiency of various M-TFN to capture embolic particles was evaluated in different atherosclerotic carotid stenotic conditions through in vitro tests. The covered stent prevented emboli dislodgement in the range of 70-96% during 30min duration tests. In vitro vascular cell growth study results showed that endothelial cell elongation, alignment and growth behaviour silhouettes significantly enhance specifically on the diamond-shape M-TFN with the dimensions of 145µm×20µm and a porosity of 32%. Future studies will require in-vivo testing. Our results demonstrate that M-TFN has a promising potential for carotid artery stenting.
CASE REPORT | doi:10.20944/preprints202205.0005.v1
Subject: Medicine & Pharmacology, Other Keywords: skull base; high-flow bypass; sustentacular cell; endoscopic sinus surgery; internal carotid artery
Online: 4 May 2022 (12:22:23 CEST)
In the diagnosis of olfactory neuroblastoma (ONB), the presence of S-100–positive sustentacular cells surrounding the tumor is important; however, these are also present in normal nasal sinus epithelium. Although ONB often has a different final diagnosis, complete resection of the tumor has a good prognosis and minimally affects the patient's treatment plan. When the tumor extends around the internal carotid artery (ICA), complete resection is difficult due to the high risk of vascular injury; revascularization using a high-flow bypass can avoid this complication. In the present case, the tumor was located in the left sphenoid sinus and extended around the ICA. Preoperative biopsy tissue was positive for neuroendocrine markers and slightly positive for S-100 protein, leading to a diagnosis of ectopic ONB. High-flow bypass revascularization with trapping of the ICA allowed complete tumor resection. The postoperative histopathological diagnosis was neuroendocrine carcinoma, showing no S-100 protein–positive cells. There was no sign of recurrence two and a half years after surgery without additional treatment. This case demonstrates that the presence of S-100 protein–positive cells in ONB may be misleading. Although misdiagnosis of ectopic ONB should be anticipated, a complete resection of the tumor is an effective treatment strategy.
ARTICLE | doi:10.20944/preprints202206.0230.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; carotid stenosis; abdominal aortic aneurysm; chronic limb-threatening ischemia; amputation; deep venous thrombosis
Online: 16 June 2022 (04:40:54 CEST)
Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study conducted through cross-sectional survey. Each received a 13-point questionnaire, investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs 2019 (9161 patients): post-EVAR surveillance, treatment for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased [1484 (16.2%) vs 1014 (14.3%), p=0.0009; 1401 (15.29%) vs 959 (13.52%), p=0.0006; and 1558 (17.01%) vs 934 (13.17%), p<0.0001, respectively]; while revascularization or major amputations for chronic limb-threatening ischemia, and urgent revascularization for symptomatic carotid stenosis significantly increased [1204 (16.98%) vs 1245 (13.59%), p<0.0001; 355 (5.01%) vs 358 (3.91%), p=0.0007; and 153 (2.16%) vs 140 (1.53%), p=0.0009, respectively]. Conclusions: The suspension of elective activities during the COVID-19 pandemic caused a significant reduction in asymptomatic carotid stenosis revascularization, treatment for Rutherford 3 peripheral arterial disease, post-EVAR surveillance. Contestually, we observed a significant increase in urgent revascularization for symptomatic carotid stenosis, and revascularization or major amputations for chronic limb-threatening ischemia.
ARTICLE | doi:10.20944/preprints201802.0165.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuco encephalopathy (CADASIL); Carotid Endarterectomy (CEA); Modified Rankin Scale (MRS); Computed Tomography(CT); Tissue plasminogen activator (tPA); Diffusion weighted Imaging (DWI); Recognition of Stroke in the Emergency Room (ROSIER) scale; Magnetic resonance Imaging (MRI); Internal Carotid Artery (ICA)
Online: 26 February 2018 (11:46:47 CET)
In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.
ARTICLE | doi:10.20944/preprints202210.0314.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Aortic surgery; Aortic arch; Three-way cannulation approach; Carotid artery perfusion; Pressure-volume loop; Lumped parameter model; Software simulation; Cardiovascular modelling.; CARDIOSIM
Online: 20 October 2022 (14:19:25 CEST)
Aortic disease has a significant impact on quality of life. Involvement of the aortic arch requires preservation of blood supply to the brain during surgery. Deep hypothermic circulatory arrest is an established technique for this purpose although neurological injury remains high. Additional techniques have been used to reduce the risk although controversy still remains. A three-way cannulation approach, including both carotid arteries and the femoral artery or the ascending aorta, has been used successfully for aortic arch replacement and redo procedures. We have de-veloped circuits of the circulation to simulate blood flow during this type of cannulation set up. The aim is to analyse using CARDIOSIM© cardiovascular simulation platform, how the haemodynamic and energetic parameters are affected and the benefit derived with particular reference to the cerebral circulation.
ARTICLE | doi:10.20944/preprints201808.0491.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: type 2 diabetes mellitus; carotid intima-media thickness; glucagon-like peptide-1; dipeptidyl peptidase-4; clusterin; amylin; secreted Frizzled-related protein-4
Online: 29 August 2018 (09:38:37 CEST)
Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.
ARTICLE | doi:10.20944/preprints202205.0400.v1
Subject: Biology, Physiology Keywords: Internal carotid artery sidewall aneurysm (ICASA); hemodynamic behaviors; computational fluid dynamics (CFD); pulsatile flow rate (PFR); bifurcated shunt ratio; wall shear stress (WSS); oscillatory shear index (OSI); time-averaged pressure (TAP)
Online: 30 May 2022 (11:38:31 CEST)
The pulsatile flow rate (PFR) in the cerebral artery system and shunt ratios in bifurcated arteries are two patient-specific parameters which may affect the hemodynamic characteristics on the pathobiology of cerebral aneurysms (CAs). Accordingly, a systematic study was employed to investigate the effects of the two parameters on hemodynamic characteristics in two internal carotid artery sidewall aneurysms (i.e., ICASA-1 and ICASA-2) models. Numerical results indicate larger PFRs can cause higher WSS in some local regions of the aneurysmal dome that may increase the probability of small/secondary aneurysms generation than under smaller PFRs. The low WSS and relatively high oscillatory shear index (OSI) could appear under a smaller PFR, which has the potential to cause aneurysmal sac growth and rupture. However, the variances in PFRs and bifurcated shunt ratios have rare impacts on the time-average pressure distributions on the aneurysmal sac, although a higher PFR can contribute more to the pressure increase in ICASA-1 dome due to the relatively stronger impingement by the redirected blood stream than in ICASA-2. Simulation results also present the variances of shunt ratios have rare impacts on the hemodynamic characteristics in sacs, mainly because the bifurcated location is not close enough to the sac in present models. Furthermore, it has been found that the vortex location plays a major role in the temporal and spatial distribution of the WSS on the luminal wall, varying significantly with the cardiac period.