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Funding Information: On behalf of the Public and Community Oversight Group (PCOG) of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards: Ian Wright; John Phipps; Colette Kelly; Robert Goundry; Eve Smyth; Andrew Wood; Paul Dale (also of the Scottish Environment Protection Agency). On behalf of the Society and College of Radiographers Patient Advisory Group: Lynda Johnson; Philip Plant; Michelle Carmichael – Specialist Senior Staff Nurse Guy's and St Thomas’ NHS Foundation trust.

Plasma extracellular vesicles (EV) are an emerging source of biomarkers for diagnosis and prognosis of cardiovascular disease (CVD). Risk stratification for common adverse events such as major adverse limb events (MALE) and major adverse cardiovascular events (MACE) by an EV blood sample could improve healthcare management by individualising drug therapy or improving informed decision making regarding revascularisations in patients with peripheral artery disease (PAD). As such, this study investigated the associations between plasma EV proteins and prospectively registered MALE and MACE in consecutive patients undergoing femoral endarterectomy.Using the Athero-Express biobank study, four EV proteins (Cystatin C, CD14, Serpin C1, and Serpin G1) were measured in the high density lipoprotein subfraction isolated from plasma of 317 PAD patients undergoing arterial revascularisation. Multivariable Cox proportional hazard regression was used to investigate the association between plasma EV protein levels and MACE and MALE in the three year post-operative period.Most patients were treated for claudication (Fontaine II, 52.8%), although rest pain (Fontaine III, 30.1%) and ischaemic wounds (Fontaine IV, 17.1%) were common in this cohort. Within three years 51 patients died, amongst whom 25 deaths were due to CVD, 39 patients experienced a MACE, and 125 patients experienced a MALE. Multivariable regression models, based on statistically proven covariables and literature, showed a significant association of Serpin G1 (HR 1.49; 95% CI 1.08 - 2.06; p = .016) and CD14 (HR 1.40; 1.03 - 1.90; p = .029) with MACE, and of Serpin G1 (HR 1.29; 1.07 - 1.57; p = .009) with MALE.Serpin G1 and CD14 plasma EV protein levels are associated with future MACE and MALE in patients with severe PAD.

Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4+ T cells, and these clonally expanded T cells expressed genes such as CD69, FOS and FOSB, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4+ T cells with foam cells. Finally, we integrated a published scTCR-seq dataset of the autoimmune disease psoriatic arthritis, and we report various commonalities between the two diseases. In conclusion, our data suggest that atherosclerosis has an autoimmune compondent driven by autoreactive CD4+ T cells.

Contains fulltext : 282329.pdf (Publisher’s version ) (Open Access) BACKGROUND: High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD. METHODS: A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group. RESULTS: Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking. CONCLUSION: Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.

Peri-operative antiplatelet therapy (APT) aims to prevent thrombotic events such as stroke. High platelet reactivity ,despite the use use of APT, increases the risk of thrombotic events. Transcranial Doppler imaging (TCD) is used to detect peri-operative microembolic signals (MES) during carotid endarterectomy (CEA). Peri-operative MES are associated with an increased risk of procedural stroke and new silent lesions on diffusion weighted magnetic resonance imaging following surgery. The main components of TCD detected MES are platelet aggregates, and therefore patients displaying multiple MES during surgery could have benefited from more stringent APT. This study investigated whether the use of flow cytometry based platelet reactivity measurements were correlated with the incidence of pre-operative MES and thereby in the future suitable to predict patients at increased risk of peri-operative thrombotic events.Bilateral TCD with MES detection was performed in 197 patients undergoing CEA. Platelet reactivity was assessed with a flow cytometry based platelet reactivity assay measuring platelet response in whole blood. High on treatment platelet reactivity status was assessed for all patients. The secondary outcome was major adverse cardiovascular events (MACE) within one year.In total, 197 patients were included, 49 had peri-operative MES. The platelet response to adenosine diphosphate (ADP) correlated with MES (p = .021), and high on treatment platelet reactivity after adenosine diphosphate stimulation was associated with MACE (OR 2.34, 95% confidence interval 1.126 - 4.890, p = .023).Pre-operative platelet reactivity determined by flow cytometry after ADP stimulation correlated with the occurrence of intra-operative MES and post-operative MACE. Clopidogrel treatment showed the most substantial effect on reducing MES frequency and platelet reactivity measured by flow cytometry.

INTRODUCTION: Carotid plaque intraplaque haemorrhage (IPH) is associated with future cardiovascular events. It was hypothesised that plasma proteins associated with carotid plaque IPH are also likely to be associated with major adverse cardiovascular events (MACE) after carotid endarterectomy (CEA). METHODS: In pre-operative blood samples from patients undergoing CEA within the Athero-Express biobank, proteins involved in cardiovascular disease were measured using three OLINK proteomics immunoassays. The association between proteins and IPH was analysed using logistic regression analyses. Subsequently, the association between the IPH associated plasma proteins and the three year post-operative risk of MACE (including stroke, myocardial infarction, or cardiovascular death) was analysed. RESULTS: Within the three year follow up, 130 patients (18.9%) of 688 symptomatic and asymptomatic patients undergoing CEA developed MACE. Six of 276 plasma proteins were found to be significantly associated with IPH, from which only lipoprotein lipase (LPL) was associated with the post-operative risk of MACE undergoing CEA. Within the 30 day peri-operative period, high plasma LPL was independently associated with an increased risk of MACE (adjusted hazard ratio [HR] per standard deviation [SD] 1.60, 1.10 - 2.30), p = .014). From 30 days to three years, however, high LPL was associated with a lower risk of MACE (adjusted HR per SD 0.80, 0.65 - 0.99, p= .036). CONCLUSION: High LPL concentrations were found to be associated with a higher risk of MACE in the first 30 post-operative days but with a lower risk MACE between 30 days and three years, meaning that LPL has different hazards at different time points. ispartof: EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY vol:65 issue:5 pages:700-709 ispartof: location:England status: published

Background and aim: Sex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data. Methods: XCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models. Results: XCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06 - 1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09 – 1.97]; P = 0.007). Conclusions: XCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy.

BackgroundTissue segmentation of histology whole-slide images (WSI) remains a critical task in automated digital pathology workflows for both accurate disease diagnosis and deep phenotyping for research purposes. This is especially challenging when the tissue structure of biospecimens is relatively porous and heterogeneous, such as for atherosclerotic plaques.MethodsIn this study, we developed a unique approach called EntropyMasker based on image entropy to tackle the fore- and background segmentation (masking) task in histology WSI. We evaluated our method on 97 high-resolution WSI of human carotid atherosclerotic plaques in the Athero-Express Biobank Study, constituting hematoxylin and eosin (H&E) and 8 other staining types.Results and ConclusionUsing multiple benchmarking metrics, we compared our method with four widely used segmentation methods: Otsu’s method, Adaptive mean, Adaptive Gaussian and slideMask and observed that our method had the highest sensitivity and Jaccard similarity index. We envision EntropyMasker to fill an important gap in WSI preprocessing and deep learning image analysis pipelines and enable disease phenotyping beyond the field of atherosclerosis.

Purpose: The aim of this paper was to report our experience with arterial and venous endovascular stent placement in the thoracic outlet (TO) and review available literature. Methods: All patients that underwent arterial or venous stent placement in the TO between 2013 and 2020 in 5 Dutch vascular teaching-hospitals were retrospectively identified. Primary endpoint was symptomatic stent failure due to stenosis, chronic or posture dependent compression, fracture, or occlusion of the stent. Secondary endpoints were symptoms at last follow-up and re-interventions. For the literature review, we searched studies reporting on stenting in the TO. Results: Twenty-six patients were included with 11 arterial and 15 venous stents implanted to treat angioplasty resistant stenosis in arterial or venous TO syndrome, iatrogenic or traumatic vascular injury, radiotherapy fibrosis, or arterial dissection. Median follow-up was 19 and 14 months in the arterial and venous-group, respectively. Eight (73%) patients in the arterial, and 9 (60%) in the venous-group suffered symptomatic stent failure. Seven (64%) patients in the arterial, and 9 (60%) in the venous-group required at least 1 re-intervention. When comparing all patients with stent placement after TO decompression (TOD) to patients without, there were substantially more symptomatic stent failures and re-interventions required in the patients without TOD. Six patients (54%) in the arterial-group and 11 (73%) in the venous-group were symptom-free at last follow-up. Five articles describing 51 patients with arterial and 6 articles describing 81 patients with venous stents were included in the literature review. In the arterial-group, no TOD prior to stent placement was performed, while in the venous-group all but 1 article performed TOD prior to stent placement. Results showed comparable rates of symptomatic stent failure (24% vs 30%), and patients requiring re-interventions (29% vs 21%) between groups. Conclusion: Based on our multicenter series and review, stents in the TO have a considerable risk of failure, both in the venous and the arterial territory. Especially in patients without TOD: the need for re-interventions is high and half the patients eventually undergo TOD. Based on the currently available data, stenting in the TO should be applied cautiously while TOD should be considered.

Background and Purpose: The net benefit of carotid endarterectomy (CEA) is determined partly by the risk of procedural stroke or death. Current guidelines recommend CEA if 30-day risks are Methods: We conducted a systematic search in MEDLINE and EMBASE for prediction models of procedural outcomes after CEA. We validated these models with data from patients who underwent CEA in the American College of Surgeons National Surgical Quality Improvement Program (2011–2017). We assessed discrimination using C statistics and calibration graphically. We determined the number of patients with predicted risks that exceeded recommended thresholds of procedural risks to perform CEA. Results: After screening 788 reports, 15 studies describing 17 prediction models were included. Nine were developed in populations including both asymptomatic and symptomatic patients, 2 in symptomatic and 5 in asymptomatic populations. In the external validation cohort of 26 293 patients who underwent CEA, 702 (2.7%) developed a stroke or died within 30-days. C statistics varied between 0.52 and 0.64 using all patients, between 0.51 and 0.59 using symptomatic patients, and between 0.49 to 0.58 using asymptomatic patients. The Ontario Carotid Endarterectomy Registry model that included symptomatic status, diabetes, heart failure, and contralateral occlusion as predictors, had C statistic of 0.64 and the best concordance between predicted and observed risks. This model identified 4.5% of symptomatic and 2.1% of asymptomatic patients with procedural risks that exceeded recommended thresholds. Conclusions: Of the 17 externally validated prediction models, the Ontario Carotid Endarterectomy Registry risk model had most reliable predictions of procedural stroke or death after CEA and can inform patients about procedural hazards and help focus CEA toward patients who would benefit most from it.

This review aimed to analyse the timing of carotid endarterectomy (CEA) and carotid artery stenting (CAS) after the index event as well as 30 day outcomes at varying time periods within 14 days of symptom onset.A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-analysis statement, comprising an online search of the Medline and Cochrane databases. Methodical quality assessment of the included studies was performed. Endpoints included procedural stroke and/or death stratified by delay from the index event and surgical technique (CEA/CAS).Seventy-one studies with 232 952 symptomatic patients were included. Overall, 34 retrospective analyses of prospective databases, nine prospective, three RCT, three case control, and 22 retrospective studies were included. Compared with CEA, CAS was associated with higher 30 day stroke (OR 0.70; 95% CI 0.58 - 0.85) and mortality rates (OR 0.41; 95% CI 0.31 - 0.53) when performed ≤ 2 days of symptom onset. Patients undergoing CEA/CAS were analysed in different time frames (≤ 2 vs. 3 - 14 and ≤ 7 vs. 8 - 14 days). Expedited CEA (vs. 3 - 14 days) presented a sampled 30 day stroke rate of 1.4%; 95% CI 0.9 - 1.8 vs. 1.8%; 95% CI 1.8 - 2.0, with no statistically significant difference. Expedited CAS (vs. 3 - 14 days) was associated with no difference in stroke rate but statistically significantly higher mortality rate (OR 2.76; 95% CI 1.39 - 5.50).At present, CEA is safer than transfemoral CAS within 2/7 days of symptom onset. Also, considering absolute rates, expedited CEA complies with the accepted thresholds in international guidelines. The ideal timing for performing CAS (when indicated against CEA) is not yet defined. Additional granular data and standard reporting of timing of intervention will facilitate future monitoring.

Epigenetic age estimators (clocks) are known to be predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques can be used for predicting secondary events. Here we estimated an age adjusted measure of epigenetic age, epigenetic age acceleration (EAA), using DNA methylation of human atherosclerotic plaques and of blood. EAA of plaque, but not blood, independently predicted secondary events in a 3-year follow-up (HR=1.3, p= 0.018). Plaque EAA concurred with a high metabolic epigenetic and transcriptional state in plaques. Patients with diabetes and a high body mass index had a higher plaque EAA. EAA was lower in female plaques compared to male plaques by approximately 2 years. Single-cell RNA-seq revealed mesenchymal smooth muscle cells and endothelial cells as main drivers of EAA. Plaque-specific ageing may help identify processes that explain poor health outcomes.

Plaque smooth muscle cells are critical players in the initiation and advancement of atherosclerotic disease. They produce extracellular matrix (ECM) components, which play a role in lesion progression and stabilization. Despite clear phenotypic differences between plaque smooth muscle cells and vascular smooth muscle cells (VSMCs), VSMCs are still widely used as a model system in atherosclerotic research.Here we present a conditioned outgrowth method to isolate plaque smooth muscle cells. We obtained plaque cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that these cells keep their proliferative capacity for eight passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, DCN) and smooth muscle cell markers (ACTA2, MYH11, CNN1).Single-cell transcriptomics of plaque tissue and cultured cells reveals that cultured plaque cells closely resemble the myofibroblast fraction of plaque smooth muscle cells. Chromatin immunoprecipitation sequencing (ChIP-seq) shows the presence of histone H3 lysine 4 dimethylation (H3K4me2) at theMYH11promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque cells can be efficiently transduced (>97%) and are capable to take up oxidized LDL (oxLDL) and undergo calcification.In conclusion, we present a method to isolate and culture primary human plaque cells that retain plaque myofibroblast-like cells’ phenotypical and functional capabilities - making them a suitablein vitromodel for studying selected mechanisms of atherosclerosis.

Women presenting with coronary artery disease (CAD) more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.

Extracellular vesicles (EV) are a novel biomarker source for diagnosis and prognosis of cardiovascular disease. A protein comparison of plasma EVs in relation to blood plasma and atherosclerotic plaque has not been performed but would provide insight into the origin and content of biomarker sources and their association with atherosclerotic progression. Using samples of 88 carotid endarterectomy patients in the Athero-Express, 92 proteins (Olink Cardiovascular III panel) were measured in citrate plasma, plasma derived LDL-EVs and atherosclerotic plaque. Proteins were correlated between sources and were related to pre-operative stroke and 3-year major adverse cardiovascular events (MACE). Plasma and EV proteins correlated moderately on average, but with substantial variability. Both showed little correlation with plaque, suggesting that these circulating biomarkers may not originate from the latter. Plaque (n = 17) contained most differentially-expressed proteins in patients with stroke, opposed to EVs (n = 6) and plasma (n = 5). In contrast, EVs contained most differentially-expressed proteins for MACE (n = 21) compared to plasma (n = 9) and plaque (n = 1). EVs appear to provide additional information about severity and progression of systemic atherosclerosis than can be obtained from plasma or atherosclerotic plaque.

info:eu-repo/semantics/publishedVersion

Contains fulltext : 291124.pdf (Publisher’s version ) (Open Access) BACKGROUND: In upper extremity thrombosis research, the occurrence of upper extremity postthrombotic syndrome (UE-PTS) is commonly used as the main outcome parameter. However, there is currently no reporting standard or a validated method to assess UE-PTS presence and severity. In a recent Delphi study, consensus was reached on a preliminary UE-PTS score, combining 5 symptoms, 3 signs, and the inclusion of a functional disability score. However, no consensus was reached on which functional disability score to be included. OBJECTIVES: The aim of the current Delphi consensus study was to determine the specific type of functional disability score to finalize UE-PTS score. METHODS: This Delphi project was designed as a three-round study using open text questions, statements with 7-point Likert scales, and multiple-choice questions. The CREDES recommendations for Delphi studies were applied. In this context, a systematic review was conducted before the start of the Delphi rounds to identify the available functional disability scores as available in the literature and present these to the expert panel. RESULTS: Thirty-five of 47 initially invited international experts from multiple disciplines completed all the Delphi rounds. In the second round, consensus was reached on the incorporation of the quick disabilities of the arm, shoulder, and hand (QuickDASH) in the UE-PTS score, rendering the third round obsolete. CONCLUSION: Consensus was reached that the QuickDASH should be incorporated in the UE-PTS score. The UE-PTS score will need to be validated in a large cohort of patients with upper extremity thrombosis before it can be used in clinical practice and future research. 01 januari 2023

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry metaanalysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) R01HL127564 R01HL142711, Wellcome Trust 201543/B/16/Z 202802/Z/16/Z, European Commission HEALTH-F2-2013-601456 608765 786833, TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation NNF15CC0018486, American Diabetes Association 1-19-ICTS-068, Academy of Finland 312062 Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Finnish innovation fund Sitra (EW) Finska Lakaresallskapet, American Heart Association 15POST24470131 17POST33650016, University of Bristol NIHR Biomedical Research Centre BRC-1215-2001, MRC & WT 217065/Z/19/Z, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MC_UU_00011, CRUK Integrative Cancer Epidemiology Programme C18281/A19169, Medical Research Council UK (MRC) MC_UU_00011/1, UK National Institute for Health Research Academic Clinical Fellowship, American Heart Association 18CDA34110116, Miguel Servet contract from the ISCIII Spanish Health Institute CP17/00142, European Social Fund (ESF), Westlake Education Foundation, British Heart Foundation FS/14/66/3129 Z01HG200362 R01HL142302 R01HL105756

Dissection of the carotid artery (CaAD) may result in aneurysm formation. The present study was undertaken to evaluate the time of onset of post-dissection extracranial carotid artery aneurysms (ECAA) following CaAD, and to analyse independent risk factors for the development of these aneurysms.From four European stroke centres, 360 patients with extracranial CaAD were included. The time between the estimated dissection onset and aneurysm formation was analysed, and the clinical risk factors increasing the probability of aneurysm were assessed.The median duration of follow up was 5.2 months (range 0 - 24 months). A total of 75 post-dissection ECAAs were identified in 70 patients (19.4%, 95% confidence interval [CI] 15.7 - 23.8). In 52 of 70 (74%) patients, the ECAA was diagnosed at the initial clinical work up of CaAD diagnosis, with the median estimated time of dissection onset to ECAA diagnosis being six days (interquartile range [IQR] 0 - 25). In the remaining 18 (26%) patients who had normal carotid arteries at the initial imaging, the aneurysm diagnosis was made a median of 6.2 months (189 days) from the original imaging (IQR 128 - 198). A Cox proportional hazards model showed that both multiple artery dissections (hazard ratio [HR] 2.58, 95% CI 1.54 - 4.33) and arterial tortuosity (HR 1.79, 95% CI 1.08 - 2.95) were associated with presence of ipsilateral ECAA.This post hoc cohort analysis showed substantially delayed development of ipsilateral ECAA in patients with CaAD, months after baseline. Multiple dissections and arterial tortuosity are associated with the presence of ECAA and can be used in future prediction models of ECAA development in patients with CaAD.

Purpose Photo-optical TCpO2 (pTCpO2) has been proposed as a new method to determine the partial oxygen pressure of the lower extremity in patients with peripheral arterial disease. It is aimed to determine the level of agreement between pTCpO2 and the traditional electro-chemical transcutaneous oxygen tension measurement (eTCpO2). Methods Eighteen patients with intermittent claudication underwent simultaneous ankle-brachial index measurement, toe-pressure, pTCpO2 and eTCpO2 tests. Oxygen tension levels were measured on anterior chest and calf prior in rest (T0), during induced ischemia (T1) and after blood flow restoration (T2). TCpO2 agreement was assessed according to the principles of Bland and Altman. Results Absolute average TCpO2 values differed between eTCpO2 and pTCpO2 for calf in T2 (38,1 mmHg (σ 14,4) vs. 49,8 (σ 22.3) with P = 0.35). The Bland-Altman plots demonstrated eTCpO2 and pTCpO2 bias of 3,7 mmHg (σ 18,8), 11,6 mmHg (σ 17,6) and 6,7 mmHg (σ 23,5) for T0, T1 and T2 for the calf. Conclusion pTCpO2 is in agreement with eTCpO2 in measuring pO2 levels of the lower extremity in rest and during induced ischemia in patients with vascular claudication. The large variability between eTCpO2 and pTCpO2 should be accounted for, while pTCpO2 values have a tendency to demonstrate higher values in comparison to eTCpO2.

Objective Closure of the artery during carotid endarterectomy (CEA) can be done with or without a patch, or performed with the eversion technique, while the use of intra-operative shunts is optional. The influence of these techniques on subsequent restenosis is uncertain. Long term carotid restenosis rates and risk of future ipsilateral stroke with these techniques were compared. Methods Patients who underwent CEA in the International Carotid Stenting Study were divided into patch angioplasty, primary closure, or eversion endarterectomy. Intra-operative shunt use was reported. Carotid duplex ultrasound was performed at each follow up. Primary outcomes were restenosis of ≥ 50% and ≥ 70%, and ipsilateral stroke after the procedure to the end of follow up. Results In total, 790 CEA patients had restenosis data at one and five years. Altogether, 511 (64.7%) had patch angioplasty, 232 (29.4%) primary closure, and 47 (5.9%) eversion endarterectomy. The cumulative incidence of ≥ 50% restenosis at one year was 18.9%, 26.1%, and 17.7%, respectively, and at five years it was 25.9%, 37.2%, and 30.0%, respectively. There was no difference in risk between the eversion and patch angioplasty group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.45 – 1.81; p = .77). Primary closure had a higher risk of restenosis than patch angioplasty (HR 1.45, 95% CI 1.06 – 1.98; p = .019). The cumulative incidence of ≥ 70% restenosis did not differ between primary closure and patch angioplasty (12.1% vs. 7.1%, HR 1.59, 95% CI 0.88 – 2.89; p = .12) or between patch angioplasty and eversion endarterectomy (4.7%, HR 0.45, 95% CI 0.06 – 3.35; p = .44). There was no effect of shunt use on the cumulative incidence of restenosis. Post-procedural ipsilateral stroke was not more common in either of the surgical techniques or shunt use. Conclusion Restenosis was more common after primary closure than conventionally with a patch closure. Shunt use had no effect on restenosis. Patch closure is the treatment of choice to avoid restenosis.

Objective: Previous studies on carotid endarterectomy and transfemoral carotid artery stenting demonstrated that perioperative outcomes differed according to preoperative neurologic injury severity, but this has not been assessed in transcarotid artery revascularization (TCAR). In this study, we examined contemporary perioperative outcomes in patients who underwent TCAR stratified by specific preprocedural symptom status. Methods: Patients who underwent TCAR between 2016 and 2021 in the Vascular Quality Initiative were included. We stratified patients into the following groups based on preprocedural symptoms: asymptomatic, recent (symptoms occurring 180 days before TCAR). First, we used trend tests to assess outcomes in asymptomatic patients versus those with an increasing severity of recent neurologic injury (recent ocular TIA vs recent hemispheric TIA vs recent stroke). Then, we compared outcomes between asymptomatic and formerly symptomatic patients. Our primary outcome was in-hospital stroke/death rates. Multivariable logistic regression was used to adjust for demographics and comorbidities across groups. Results: We identified 18,477 patients undergoing TCAR, of whom 62.0% were asymptomatic, 3.2% had a recent ocular TIA, 7.6a % had recent hemispheric TIA, 18.0% had a recent stroke, and 9.2% were formerly symptomatic. In patients with recent symptoms, we observed higher rates of stroke/death with increasing neurologic injury severity: asymptomatic 1.1% versus recent ocular TIA 0.8% versus recent hemispheric TIA 2.1% versus recent stroke 3.1% (Ptrend < .01). In formerly symptomatic patients, the rate of stroke/death was higher compared with asymptomatic patients, but this difference was not statistically significant (1.7% vs 1.1%; P = .06). After risk adjustment, compared with asymptomatic patients, there was a higher odds of stroke/death in patients with a recent stroke (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.1-3.7; P < .01), a recent hemispheric TIA (OR, 2.0; 95% CI, 1.3-3.0; P < .01), and former symptoms (OR, 1.6; 95% CI, 1.1-2.5; P = .02), but there was no difference in stroke/death rates in patients with a recent ocular TIA (OR, 0.9; 95% CI, 0.4-2.2; P = .78). Conclusions: After TCAR, compared with asymptomatic status, a recent stroke and a recent hemispheric TIA were associated with higher stroke/death rates, whereas a recent ocular TIA was associated with similar stroke/death rates. In addition, a formerly symptomatic status was associated with higher stroke/death rates compared with an asymptomatic status. Overall, our findings suggest that classifying patients undergoing TCAR as symptomatic versus asymptomatic may be an oversimplification and that patients’ specific preoperative neurologic symptoms should instead be used in risk assessment and outcome reporting for TCAR.