Long-Term Stroke Risk in Patients With New Ischemic Brain Lesions on MRI After Carotid Revascularization.

BACKGROUND: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. METHODS: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). RESULTS: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. CONCLUSIONS: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ISRCTN 25337470.

Editor's Choice - Interventions to Achieve Functionality in Newly Created Arteriovenous Fistulas in the Shunt Simulation Study Cohort.

OBJECTIVE: Although observational cohort studies report that interventions to achieve functionality are clinically successful in 85% of patients, the proportion of newly created autologous arteriovenous fistulas that result in functional vascular access typically is only 70 - 80%. To address this discrepancy, the selection and outcomes of interventions to achieve functionality in a multicentre prospective cohort study were analysed. METHODS: The Shunt Simulation Study enrolled 222 patients who needed a first arteriovenous fistula in nine dialysis units in The Netherlands from 2015 to 2018 and followed these patients until one year after access creation. In this observational study, the technical and clinical success rates of interventions to achieve functionality based on lesion and intervention characteristics were analysed and the clinical outcomes of arteriovenous fistulas with assisted and unassisted functionality were compared. RESULTS: For patients who were on dialysis treatment at the end of the study, unassisted fistula functionality was 54% and overall fistula functionality was 78%. Thirty-four per cent of arteriovenous fistulas required an intervention to achieve functionality, 68% of which eventually became functional. Seventy-five per cent of these interventions were percutaneous balloon angioplasties of vascular access stenoses. Patients with clinically successful interventions to achieve functionality had larger pre-operative vein diameters (2.8 ± 1.0 mm vs. 2.3 ± 0.6 mm, p = .036) and less often presented with thrombosed fistulas than patients with unsuccessful interventions (7% vs. 43%, p = .006). Arteriovenous fistulas with assisted functionality had similar secondary patency as fistulas with unassisted functionality (100% and 98% at six months, p = .44), although they required more interventions to maintain function (2.6 vs. 1.7 per year; rate ratio 1.52, 95% CI 1.04 - 2.18, p = .032). CONCLUSION: Interventions to achieve functionality were needed in about a third of newly created arteriovenous fistulas. Most thrombosed fistulas were abandoned, and when selected for thrombectomy rarely reached clinical success. On the other hand, interventions to achieve functionality of patent fistulas had high clinical success rates and therefore can be done repeatedly until the fistula has become functional.

Editor's Choice - Risk of Bleeding Complications With Different Peri-Operative Antithrombotic Regimens During Carotid Endarterectomy: a National Registry Analysis.

OBJECTIVE: Antithrombotic therapy is one of the cornerstones of the prevention of (recurrent) ocular or cerebral ischaemic events in patients with carotid artery stenosis. Randomised controlled trials on antithrombotic therapy for patients with minor ischaemic stroke and transient ischaemic attack (TIA) have recommended dual antiplatelet therapy (DAPT) in the three weeks following the index event. However, these trials excluded patients undergoing carotid revascularisation. To date, the optimal antithrombotic therapy during the peri-operative period of carotid endarterectomy (CEA) remains unclear. METHODS: Symptomatic and asymptomatic patients with carotid artery stenosis undergoing primary CEA from the Dutch Audit for Carotid Interventions registry between June 2013 and December 2020 were eligible for inclusion. The primary outcome was defined as post-operative cervical bleeding needing re-intervention or intracranial haemorrhage during the first 30 days following CEA. The secondary outcomes were ischaemic stroke or TIA or all cause mortality during the first 30 days following CEA. Descriptive statistics and multiple logistic regressions analyses were applied, with acetylsalicylic acid (ASA) as the reference value. RESULTS: A total of 12 317 patients were included. In the peri-operative phase, 31.0% of patients were treated with ASA, 32.4% with clopidogrel, 11.1% with ASA plus clopidogrel, 10.4% with ASA plus dipyridamole, 10.3% with vitamin K antagonist, and 4.8% with direct acting oral anticoagulants therapy. After multiple logistic regression analysis, no association was seen with the primary outcome in ASA plus clopidogrel (odds ratio [OR] 0.81; confidence interval [CI] 0.58 - 1.13; p = .23), and ASA plus dipyridamole (OR 0.69; CI 0.47 - 1.00; p = .059). Both the DAPT therapies were not associated with the secondary outcome. CONCLUSION: The effectiveness and safety of DAPT did not differ from single antiplatelet therapy (SAPT) in patients undergoing CEA and further evaluation is needed in prospective studies. Considering additional data from the literature and guideline recommendations, DAPT should be started immediately after stroke until 30 days after CEA followed by SAPT, due to a possible reduction in the risk of recurrence.

Long-term Outcome of Axillo-axillary Bypass in Patients with Subclavian or Innominate Artery Stenosis.

BACKGROUND: Subclavian or innominate artery stenosis (SAS) may cause upper extremity and cerebral ischemia. In patients with symptomatic subclavian or innominate artery stenosis, percutaneous transluminal angioplasty is the treatment of first choice. When percutaneous transluminal angioplasty is technically restricted or unsuccessful, an extrathoracic bypass grafting, such as an axillo-axillary bypass can be considered. The patency rate of axillo-axillary bypass is often questioned. The aim of this study was to assess long-term outcomes of patients undergoing axillo-axillary bypass for subclavian or innominate artery stenosis (SAS) and to provide a literature overview. METHODS: In this single-center study, data from patients who underwent axillo-axillary bypass for symptomatic SAS between 2002 and 2018 were retrospectively analyzed. Bypass material was Dacron® (54%) or polytetrafluoroethylene (PTFE) (46%). Primary outcome was graft patency and secondary outcome was the occurrence of mortality and stroke. In addition, a systematic literature search was performed in MEDLINE and EMBASE databases including all studies describing patency of axillo-axillary bypass. RESULTS: In total, 28 axillo-axillary bypasses had been performed. Cumulative primary, primary-assisted, and secondary patency rates at one year were 89%, 93%, and 96%, respectively. Cumulative primary, primary-assisted, and secondary patency rates at five years were 76%, 84%, and 87%, respectively. The primary-assisted patency rates at five years for Dacron® and PTFE were 93% and 73%, respectively. A total of four primary axillo-axillary bypass occlusions occurred (14%), with a mean of 12 months (range, 0.4-25) after operation. The 30-day mortality was 7%; one patient died after a stroke and one died of a myocardial infarction. At the first postoperative follow-up control, 22 of the 26 remaining patients (85%) had relief of symptoms. The literature search included 7 studies and described a one-year primary patency range of 93-100% (n = 137) and early postoperative adverse events included death (range, 0-13%) and stroke (range, 0-5%). CONCLUSIONS: Patency rates of axillo-axillary bypasses for patients with a symptomatic SAS are good. However, the procedural complication rate in this series is high and attention should be paid to intervention indication.

Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

BACKGROUND: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted. METHODS: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres. RESULTS: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr). CONCLUSIONS: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.

Pre-operative Patient Specific Flow Predictions to Improve Haemodialysis Arteriovenous Fistula Maturation (Shunt Simulation Study): A Randomised Controlled Trial.

OBJECTIVE: An arteriovenous fistula (AVF) needs to mature before it becomes suitable to cannulate for haemodialysis treatment. Maturation importantly depends on the post-operative flow increase. Unfortunately, 20-40% of AVFs fail to mature (FTM). A patient specific computational model that predicts immediate post-operative flow was developed, and it was hypothesised that providing information from this model for planning of fistula creation might reduce FTM rates. METHODS: A multicentre, randomised controlled trial in nine Dutch hospitals was conducted in which patients with renal failure who were referred for AVF creation, were recruited. Patients were randomly assigned (1:1) to the control or computer simulation group. Both groups underwent a work up, with physical and duplex ultrasonography (DUS) examination. In the simulation group the data from the DUS examination were used for model simulations, and based on the immediate post-operative flow prediction, the ideal AVF configuration was recommended. The primary endpoint was AVF maturation defined as an AVF flow ≥500 mL/min and a vein inner diameter of ≥4 mm six weeks post-operatively. The secondary endpoint was model performance (i.e. comparisons between measured and predicted flows, and (multivariable) regression analysis for maturation probability with accompanying area under the receiver operator characteristic curve [AUC]). RESULTS: A total of 236 patients were randomly assigned (116 in the control and 120 in the simulation group), of whom 205 (100 and 105 respectively) were analysed for the primary endpoint. There was no difference in FTM rates between the groups (29% and 32% respectively). Immediate post-operative flow prediction had an OR of 1.15 (1.06-1.26; p < .001) per 100 mL/min for maturation, and the accompanying AUC was 0.67 (0.59-0.75). CONCLUSION: Providing pre-operative patient specific flow simulations during surgical planning does not result in improved maturation rates. Further study is needed to improve the predictive power of these simulations in order to render the computational model an adjunct to surgical planning.

Short-Term Double Layer Mesh Stent Patency for Emergent or Elective Carotid Artery Stenting.

Background and Purpose- Novel double layer micromesh stents have recently been introduced for treatment of patients with significant carotid stenosis. Strict evaluation of safety and patency of such novel devices is required both in elective and in emergency interventions. We report a single center experience with double layer mesh stents for carotid artery revascularization. Methods- Consecutive patients who underwent carotid artery stenting with a double layer mesh stent between June 2015 and September 2018 in our tertiary vascular referral center were included. Treatment indications were emergent carotid artery stenting for intracranial or extracranial carotid stenosis in patients undergoing intraarterial thrombectomy for acute ischemic stroke in the anterior circulation, or elective carotid artery stenting for significant symptomatic or asymptomatic stenosis. End points were postprocedural thrombotic stent occlusion and procedural stroke or death. Results- Fifty-four patients were included; 27 were treated for acute stroke with intracranial and extracranial (tandem) lesions and 27 for elective stenting. Follow-up imaging was available for 9/27 (33%) patients with acute stroke, and 19/27 (70%) electively treated patients. Five stent occlusions occurred, of which 2 were symptomatic with clinical deterioration within one day. Another patient deteriorated on postprocedural day one, but imaging of the carotids was not performed, and the stent turned out occluded on the 30-day duplex. All stent occlusions occurred in patients treated for acute stroke. Conclusions- This study suggests that occlusion of novel double layer mesh stents occurs in a considerable proportion of carotid artery stenting procedures performed in the emergency setting for acute stroke, with occlusion-related symptoms in half the cases. Future prospective studies should clarify the role of double layer mesh stents in this high-risk patient population.

Long-Term Outcome of Symptomatic Patients Undergoing Hybrid Revascularisation for Extracranial Carotid Artery Tandem Stenosis.

OBJECTIVES: Carotid tandem lesions are a multilevel significant (>50%) atherosclerotic disease involving both the internal carotid artery (ICA) and either the ipsilateral common carotid artery (CCA) or the innominate artery (IA). These lesions may be challenging to treat. Current guidelines offer no definitive recommendation on the optimal treatment algorithm. The aim of this analysis was to assess the long-term outcome of patients undergoing surgical revascularisation for tandem lesions. METHODS: In two centres, consecutive patients who underwent carotid endarterectomy (CEA) for a symptomatic carotid artery stenosis between 2003 and 2017 were screened retrospectively for the presence of a carotid artery tandem lesion. All eligible patients were treated by a hybrid approach, consisting of retrograde stenting of the proximal CCA or IA followed by CEA. All patients had a yearly clinical check up including duplex ultrasound. The primary outcome was occurrence of any stroke, death, myocardial infarction (MI), or transient ischaemic attack (TIA) within 30 days. Secondary outcomes were any stroke, death, MI, or TIA and occurrence of restenosis ≥50% during follow up. RESULTS: Sixteen of 2368 symptomatic patients were included. Besides a high grade ICA stenosis, patients had a significant ipsilateral stenosis of the CCA (n = 13) or IA (n = 3). Within 30 days there were no deaths, strokes, or TIAs. Two patients had a clinical MI. During a median follow up of 73 (interquartile range 22-85) months, three patients died. One patient developed a symptomatic restenosis of the ICA (ipsilateral TIA). Two patients (without restenosis) developed an ipsilateral stroke and a MI. CONCLUSIONS: In this small case series, hybrid revascularisation of carotid tandem lesions in symptomatic patients seems feasible and safe. Long-term data show a relatively high number of any adverse events. These surgical outcomes need to be offset against the natural course in patients with a symptomatic carotid tandem lesion.

Transcranial Doppler 24 Hours after Carotid Endarterectomy Accurately Identifies Patients Not at Risk of Cerebral Hyperperfusion Syndrome.

OBJECTIVES: Intra-operative transcranial Doppler (TCD) is the gold standard for prediction of cerebral hyperperfusion syndrome (CHS) in patients after carotid endarterectomy (CEA) under general anaesthesia. However, post-operative cerebral perfusion patterns may result in a shift in risk assessment for CHS. This is a study of the predictive value of additional post-operative TCD measurements for prediction of CHS after CEA. METHODS: This was a retrospective analysis of prospectively collected data in patients undergoing CEA with available intra- and post-operative TCD measurements between 2011 and 2016. The mean blood flow velocity in the middle cerebral artery (MCAVmean) was measured pre-operatively, intra-operatively, and post-operatively at two and 24 h. Intra-operative MCAVmean increase was compared with MCAVmean increase two and 24 h post-operatively in relation to CHS. Cerebral hyperperfusion (CH) was defined as MCAVmean increase ≥ 100%, and CHS as CH with the presence of headache or neurological symptoms. Positive (PPV) and negative predictive values (NPV) of TCD measurements were calculated to predict CHS. RESULTS: Of 257 CEA patients, 25 (9.7%) had CH intra-operatively, 45 (17.5%) 2 h post-operatively, and 34 (13.2%) 24 h post-operatively. Of nine patients (3.5%) who developed CHS, intra-operative CH was diagnosed in two and post-operative CH in eight (after 2 h [n = 5] or after 24 h [n = 6]). This resulted in a PPV of 8%, 11%, and 18%, and a NPV of 97%, 98%, and 99% for intra-operative, 2 h and 24 h post-operative TCD, respectively. CONCLUSIONS: TCD measurement of the MCAVmean 24 h after CEA under general anaesthesia is most accurate to identify patients who are not at risk of CHS.

Posterior transverse plication of the internal carotid artery to correct for kinking.

BACKGROUND: The occasional need for shortening of the internal carotid artery (ICA) following carotid endarterectomy (CEA) to correct for kinking is still controversial. Although several technical options have been suggested, the impact on perioperative outcome remains unclear, and long-term clinical follow-up is lacking. Shortening by resection has a theoretical risk for a twisted anastomosis and subsequent ICA thrombosis. Posterior transverse plication (PTP) offers an alternative shortening technique without the need for a new anastomosis. We aimed to assess the safety and patency of CEA with concomitant PTP. Secondly, we aimed to provide an overview of different technical modalities for shortening of the carotid artery in current literature. METHODS: Within the time frame of 2000 through 2011, 29 patients (mean age, 73.4 years) undergoing CEA with additional PTP of the ICA and standardized patchplasty were retrospectively identified. Patient characteristics, surgical procedural details, and both short- (<30 days) and long- (>30 days) term clinical and duplex ultrasound follow-up were retrieved. Restenosis was defined as ≥50% stenosis on duplex ultrasound. In addition, a literature search was performed on different techniques for ICA shortening. RESULTS: Thirty-day outcome revealed no deaths or strokes. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. During follow-up (mean, 34.3 months; range, 3-125 months), one patient (4%) died of a noncardiovascular cause. Three patients (11%) developed ipsilateral neurological symptoms (1 stroke, 2 transient ischemic attacks) after 5, 19, and 66 months follow-up, respectively. Of these, two patients (7%) had restenosis at the site of PTP. Asymptomatic restenosis occurred in one other patient (4%) after 16 months. CONCLUSIONS: Although the indications for additional shortening procedures following CEA need to be defined, in this small series, PTP as an additional shortening procedure of the ICA following CEA seems feasible and safe with no additional periprocedural risk for narrowing at the plicature or thrombosis of the endarterectomy plane. However, restenosis at the plicature may hamper the long term benefit of carotid reconstruction.

Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Guideline recommendations on minimal blood vessel diameters and arteriovenous fistula outcomes.

OBJECTIVE: Clinical guidelines provide recommendations on the minimal blood vessel diameters required for arteriovenous fistula creation but the evidence for these recommendations is limited. We compared vascular access outcomes of fistulas created in agreement with the ESVS Clinical Practice Guidelines (i.e. arteries and veins >2 mm for forearm fistulas and >3 mm for upper arm fistulas) with fistulas created outside these recommendations. METHODS: The multicenter Shunt Simulation Study cohort contains 211 hemodialysis patients who received a first radiocephalic, brachiocephalic, or brachiobasilic fistula before publication of the ESVS Clinical Practice Guidelines. All patients had preoperative duplex ultrasound measurements according to a standardized protocol. Outcomes included duplex ultrasound findings at 6 weeks after surgery, vascular access function, and intervention rates until 1 year after surgery. RESULTS: In 55% of patients, fistulas were created in agreement with the ESVS Clinical Practice Guidelines recommendations on minimal blood vessel diameters. Concordance with the guideline recommendations was more frequent for forearm fistulas than for upper arm fistulas (65% vs 46%, p = 0.01). In the entire cohort, agreement with the guideline recommendations was not associated with an increased proportion of functional vascular accesses (70% vs 66% for fistulas created within and outside guideline recommendations, respectively; p = 0.61) or with decreased access-related intervention rates (1.45 vs 1.68 per patient-year, p = 0.20). In forearm fistulas, however, only 52% of arteriovenous fistulas created outside these recommendations developed into a timely functional vascular access. CONCLUSIONS: Whereas upper arm arteriovenous fistulas with preoperative blood vessel diameters <3 mm had similar vascular access function as fistulas created with larger blood vessels, forearm arteriovenous fistulas with preoperative blood vessel diameters <2 mm had poor clinical outcomes. These results support that clinical decision-making should be guided by an individual approach.

Living Kidney Donor Knowledge of Provided Information and Informed Consent: The PRINCE Study.

BACKGROUND: Informed consent for living kidney donation is paramount, as donors are healthy individuals undergoing surgery for the benefit of others. The informed consent process for living kidney donors is heterogenous, and the question concerns how well they are actually informed. Knowledge assessments, before and after donor education, can form the basis for a standardized informed consent procedure for live kidney donation. METHODS: In this prospective, a multicenter national cohort study conducted in all eight kidney transplant centers in The Netherlands, we assessed the current status of the informed consent practice for live donor nephrectomy. All of the potential living kidney donors in the participating centers were invited to participate. They completed a pop quiz during their first outpatient appointment (Cohort A). Living kidney donors completed the same pop quiz upon admission for donor nephrectomy (Cohort B). RESULTS: In total, 656 pop quizzes were completed (417 in Cohort A, and 239 in Cohort B). The average donor knowledge score was 7.0/25.0 (±3.9, range 0-18) in Cohort A, and 10.5/25.0 (±2.8, range 0-17.5) in Cohort B. Cohort B scored significantly higher on overall knowledge, preparedness, and the individual item scores (p < 0.0001), except for the long-term complications (p = 0.91). CONCLUSIONS: Donor knowledge generally improves during the live donor workup, but it is still quite disappointing. Long-term complications, especially, deserve more attention during living kidney donor education.

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease.

OBJECTIVE: In this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization. BACKGROUND: Carotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure. METHODS: A literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk. CONCLUSIONS: The applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.

(In)comparability of Carotid Artery Stent Characteristics: A Systematic Review on Assessment and Comparison with Manufacturer Data.

PURPOSE: Carotid stent (CS) characteristics, such as radial force, scaffolding and flexibility, are continuously modified by stent manufacturers aiming to improve stent performance. Since manufacturers' definitions and assessment methods are not disclosed, it is unknown how characteristics of different CSs relate to each other or to published literature. We examined in vitro methodological techniques used to measure CS characteristics and assessed comparability between published papers and outcomes as provided by the manufacturers. METHODS: A systematic review was conducted in MEDLINE, Embase, Cochrane, and Scopus databases. Studies reporting on in vitro investigations of predefined characteristics of CS used in current everyday clinical practice were included. The predefined characteristics were radial force, scaffolding, flexibility, foreshortening, side-branch preservation and visibility. Eight manufacturers of 10 currently used CS were contacted and data on the predefined device characteristics was requested. RESULTS: 12 published articles were included and six stent manufacturers provided data on six stents (two refused to share data). Used methodologies to measure stent characteristics in published literature and manufacturer data varied greatly for all included characteristics except foreshortening. The number of different units of measurement to express outcomes ranged from two for foreshortening to six for radial force. CONCLUSION: A variety of methodologies and outcome measures is used to quantify CS characteristics, which hampers comparisons between published studies and manufacturer data. Future studies are encouraged to synchronize methodologies and outcome measures. Manufacturers are encouraged up to increase transparency of applied testing methodologies and outcomes.

Anatomy of the carotid sinus nerve and surgical implications in carotid sinus syndrome.

BACKGROUND: The carotid sinus syndrome (CSS) is characterized by syncope and hypotension due to a hypersensitive carotid sinus located in the carotid bifurcation. Some patients ultimately require surgical sinus denervation, possibly by transection of its afferent nerve (carotid sinus nerve [CSN]). The aim of this study was to investigate the anatomy of the CSN and its branches. METHODS: Twelve human carotid bifurcations were microdissected. Acetylcholinesterase (ACHE) staining was used to identify location, side branches, and connections of the CSN. RESULTS: A distinct CSN originating from the glossopharyngeal (IX) nerve was identified in all specimens. A duplicate CSN was incidentally present (2/12). Mean CSN length measured from the hypoglossal (XII) nerve to the carotid sinus was 29 +/- 4 mm (range, 15-50 mm). The CSN was frequently located on anterior portions of the internal carotid artery, either laterally (5/12) or medially (6/12). Separate connections to pharyngeal branches of the vagus (X) nerve (6/12), vagus nerve itself (3/12), sympathetic trunk (2/12), as well as the superior cervical ganglion (2/12) were commonly observed. The CSN always ended in a network of small separate branches innervating both carotid sinus and carotid body. CONCLUSION: Anatomical position of the CSN and its side branches and communications is diverse. From a microanatomical standpoint, CSN transection as a single treatment option for patients with CSS is suboptimal. Surgical denervation at the carotid sinus level is probably more effective in CSS. CLINICAL RELEVANCE: Some patients suffering from CSS ultimately require surgical carotid sinus denervation, possibly by transection of its afferent nerve (CSN). This study was performed to investigate the anatomy of the CSN using a nerve-specific ACHE staining technique. Microdissection demonstrated a great variability of the CSN and its branches. Simple high transection of the CSN may lead to an incomplete sinus denervation in patients with CSS. Surgical denervation at the level of the carotid sinus itself may be more effective in CSS.

The Small RNA Repertoire of Small Extracellular Vesicles Isolated From Donor Kidney Preservation Fluid Provides a Source for Biomarker Discovery for Organ Quality and Posttransplantation Graft Function.

Delayed graft function (DGF) after kidney transplantation is negatively associated with long-term graft function and survival. Kidney function after transplantation depends on multiple factors, both donor- and recipient-associated. Prediction of posttransplantation graft function would allow timely intervention to optimize patient care and survival. Currently, graft-based predictions can be made based on histological and molecular analyses of 0-hour biopsy samples. However, such analyses are currently not implemented, as biopsy samples represent only a very small portion of the entire graft and are not routinely analyzed in all transplantation centers. Alternatives are thus required. METHODS: We analyzed whether donor organ preservation fluid contain small extracellular vesicles (sEV) and whether the RNA content of these vesicles could be used as a source for potential biomarkers for posttransplantation kidney function. RESULTS: We provide proof of principle that sEVs are present in preservation fluid, which contain RNAs associated with donor origin. Furthermore, sEV micro RNA profiles could be associated with graft function during the first 7 days posttransplantation, but no significant correlation with DGF could be established based on the current dataset. CONCLUSIONS: Overall, the predictive potential of sEV RNA biomarkers together with relatively easy and noninvasive sample collection and analysis methods could pave the way towards universal screening of donor kidney-associated risk for DGF, optimized patient treatment, and subsequently improved short- and long-term graft function and survival.

Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease.

BACKGROUND: Cell-based therapies are being developed to meet the need for curative therapy in chronic kidney disease (CKD). Bone marrow- (BM-) derived mesenchymal stromal cells (MSCs) enhance tissue repair and induce neoangiogenesis through paracrine action of secreted proteins and extracellular vesicles (EVs). Administration of allogeneic BM MSCs is less desirable in a patient population likely to require a kidney transplant, but potency of autologous MSCs should be confirmed, given previous indications that CKD-induced dysfunction is present. While the immunomodulatory capacity of CKD BM MSCs has been established, it is unknown whether CKD affects wound healing and angiogenic potential of MSC-derived CM and EVs. METHODS: MSCs were cultured from BM obtained from kidney transplant recipients (N = 15) or kidney donors (N = 17). Passage 3 BM MSCs and BM MSC-conditioned medium (CM) were used for experiments. EVs were isolated from CM by differential ultracentrifugation. BM MSC differentiation capacity, proliferation, and senescence-associated ß-galactosidase activity was assessed. In vitro promigratory and proangiogenic capacity of BM MSC-derived CM and EVs was assessed using an in vitro scratch wound assay and Matrigel angiogenesis assay. RESULTS: Healthy and CKD BM MSCs exhibited similar differentiation capacity, proliferation, and senescence-associated ß-galactosidase activity. Scratch wound migration was not significantly different between healthy and CKD MSCs (P = 0.18). Healthy and CKD BM MSC-derived CM induced similar tubule formation (P = 0.21). There was also no difference in paracrine regenerative function of EVs (scratch wound: P = 0.6; tubulogenesis: P = 0.46). CONCLUSIONS: Our results indicate that MSCs have an intrinsic capacity to produce proangiogenic paracrine factors, including EVs, which is not affected by donor health status regarding CKD. This suggests that autologous MSC-based therapy is a viable option in CKD.