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BACKGROUND: The primary treatment for lower-extremity peripheral arterial occlusive disease (PAOD) is angioplasty stenting. Its main complication is in-stent restenosis. Poor selection of stent dimensions has been identified as a factor contributing to early in-stent restenosis. The aim of this study is to determine whether the implantation of stents, selected based on arterial morphological reconstruction using a sizing software program, reduces the occurrence of in-stent restenosis. The study also aims to evaluate the potential benefits of routine preoperative sizing. METHODS: Between January 2016 and December 2020, all patients treated for PAOD through scheduled angioplasty stenting in our department were included in the study. Using systematic preoperative computed tomography angiography, precise reconstruction and sizing were performed to select the ideal length and diameter of stents, resulting in the selection of a so-called IDEAL stent. During the procedure, the surgeon implanted either the IDEAL stent or a different one, named the ACTUAL stent, based on intraoperative data and/or availability. We compared the in-stent restenosis rate between IDEAL and ACTUAL stents. RESULTS: There were no significant differences in the overall characteristics between the IDEAL and ACTUAL stent groups. The in-stent restenosis rate at 1 year was 13% (N = 28/212, P = 0.994) in the IDEAL group and 17% (N = 25/149, P = 0.994) in the ACTUAL group. Among the ACTUAL stents, a total of 19.6% of stents with a diameter mismatch when chosen based on arteriography showed a significantly higher restenosis rate during the first year of follow-up (P = 0.02). CONCLUSIONS: Our study did not demonstrate a significant difference in 1-year restenosis rate between the IDEAL and the ACTUAL stent groups. It specifically revealed the significant impact of diameter selection on the intrastent restenosis rate during the first year of follow-up. Stents chosen based on arteriographic criteria, which exhibited diameter discordance, compared to the IDEAL stents group selected using sizing reconstructions, could be either oversized or undersized. This led to a significantly higher restenosis rate at 1 year postoperatively.
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Angiografia por Tomografia Computadorizada , Doença Arterial Periférica , Desenho de Prótese , Recidiva , Stents , Grau de Desobstrução Vascular , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Doença Arterial Periférica/fisiopatologia , Idoso , Feminino , Masculino , Resultado do Tratamento , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Tempo , Fatores de Risco , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Angioplastia/efeitos adversos , Angioplastia/instrumentaçãoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. METHODS: The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. RESULTS: In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1ß, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. CONCLUSION: Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. TRIAL REGISTRATION: The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).
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Aterosclerose , Doenças das Artérias Carótidas , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Idoso , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Proteína C-Reativa , Ácido Araquidônico , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Inflamação/diagnósticoRESUMO
INTRODUCTION: Unlike paclitaxel-coated balloons, pre-clinical data comparing different paclitaxel-coated stents (PCSs) are weak. The study objective was to compare the features of the 2 main PCSs: Eluvia® (Boston Scientific, Marlborough, MA) versus ZilverPTX® (Cook Medical, Bloomington, IN). METHOD: Analysis was carried out on 12 pigs divided into 2 groups: Eluvia® (n=6) and ZilverPTX® (n=6). The pigs received the PCS corresponding to their group in each external iliac artery and were paired one by one, to examine 6 different post-implantation timepoints: after 30 minutes, 6 hours, 24 hours, 3 days, 7 days, and 14 days. The paclitaxel concentration measurements and the histological analysis were carried out under blind testing on the plasma, arterial, lymph node, and muscle samples. A linear regression model and Wilcoxon Mann-Whitney test were used to study the variables. RESULTS: The plasma paclitaxel rate decrease over 24 hours after PCS implantation was significantly different between the two groups, expressed by the correlation coefficient 0.19 (0.14-0.23; p<0.001) with an undetectable concentration at the 10th hour for Eluvia® versus 3 days for ZilverPTX®. Significantly higher paclitaxel concentrations with ZilverPTX® PCS were observed in muscle samples at each timepoint: extensor digitorum brevis 3.2 (1.17-5.23; p=0.005), biceps femoris 4.27 (2.27-6.26; p<0.001), semi-tendinosus 3.79 (1.85-5.73; p=0.001), tibialis anterior 3.0 (1.37-4.64; p=0.001), and in the femoral nodes 2.27±1.74 ng/g versus 0.14±0.13 ng/g (p<0.001). Histological analysis revealed a trend for more marked intimal inflammation in the arteries stented with ZilverPTX® (p=0.063), especially after the 7th and 14th days. CONCLUSION: Such a difference in the concentration of paclitaxel in the plasma, muscles, and lymph nodes between the two stents was higher than expected based on differences in device design. The clinical consequences of these results remain to be elucidated, particularly regarding the concerning presence of paclitaxel in muscles and adjacent lymph nodes. CLINICAL IMPACT: This experimental study compares 2 paclitaxel-coated stents. It demonstrates that differences in stent designs and drug features (coatings and concentrations) translate into differences in terms of concentrations of paclitaxel in the plasma, muscles, and lymph nodes. Our results favor the Eluvia® stent over the ZilverPTX® stent, although more studies are required to confirm this conclusion.
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BACKGROUND: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS). METHODS: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity. RESULTS: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages. CONCLUSION: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.
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Disfunção Cognitiva , Demência , AVC Isquêmico , Leucoaraiose , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , AVC Isquêmico/patologia , Leucoaraiose/patologia , Disfunção Cognitiva/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Demência/diagnóstico por imagem , Demência/complicações , Demência/patologia , Atrofia/patologiaRESUMO
BACKGROUND AND AIMS: Diabetes is associated with an accelerated development of atherosclerosis. Specific mechanisms related to diabetes and hyperglycemia may play a role in this process. In particular, alterations of arachidonic acid (AA) metabolism have been reported. Our main goal was to investigate for differences in the concentration of LTB4 and RvD1 as well as selected cyclooxygenase-derived mediators in carotid plaques from diabetic and non-diabetic patients. We also aimed to analyze the relationship between omega 6 and omega 3 Poly-Unsaturated Fatty acids (PUFAs) content in the plaques and the concentrations of these lipid mediators. METHODS: 29 type 2 diabetic patients and 30 control patients admitted for surgical treatment of carotid stenosis were enrolled in the present study. Carotid plaques were harvested for in-depth lipidomic profiling. RESULTS: No differences for LTB4 or other lipid mediators were observed between diabetic and non-diabetic patients. RvD1 levels were below the threshold of quantification in most of the samples. A significant correlation was found between LTB4 and 5(S)-HETE levels. Omega 3 enrichment was not significantly different between control and diabetic plaques. There was a negative correlation between DHA/AA ratio and the level of 5(S)-HETE while there was a positive association with TXB2 and PGD2 concentrations. CONCLUSION-PERSPECTIVES: Our results does not support the hypothesis of a specific involvement of LTB4 or COX-derived mediators in diabetic atherosclerosis. The relationship between DHA enrichment and the concentrations of specific inflammatory mediators within the plaque is of interest and will need to be confirmed in larger studies.
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Aterosclerose , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Diabetes Mellitus Tipo 2/complicações , Eicosanoides/metabolismo , Humanos , Ácidos Hidroxieicosatetraenoicos , Leucotrieno B4RESUMO
PURPOSE: Carotid artery stenting (CAS) appears as a promising alternative treatment to carotid endarterectomy for radiation therapy (RT)-induced carotid stenosis. However, this is based on a poor level of evidence studies (small sample size, primarily single institution reports, few long-term data). The purpose of this study was to report the long-term outcomes of a multicentric series of CAS for RT-induced stenosis. METHODS: All CAS for RT-induced stenosis performed in 11 French academic institutions from 2005 to 2017 were collected in this retrospective study. Patient demographics, clinical risk factors, elapsed time from RT, clinical presentation and imaging parameters of carotid stenosis were preoperatively gathered. Long-term outcomes were determined by clinical follow-up and duplex ultrasound. The primary endpoint was the occurrence of cerebrovascular events during follow-up. Secondary endpoints included perioperative morbidity and mortality rate, long-term mortality rate, primary patency, and target lesion revascularization. RESULTS: One hundred and twenty-one CAS procedures were performed in 112 patients. The mean interval between irradiation and CAS was 15 ± 12 years. In 31.4% of cases, the lesion was symptomatic. Mean follow-up was 42.5 ± 32.6 months (range 1-141 months). The mortality rate at 5 years was 23%. The neurologic event-free survival and the in-stent restenosis rates at 5 years were 87.8% and 38.9%, respectively. Diabetes mellitus (p=0.02) and single postoperative antiplatelet therapy (p=0.001) were found to be significant predictors of in-stent restenosis. Freedom from target lesion revascularization was 91.9% at 5 years. CONCLUSION: This study showed that CAS is an effective option for RT-induced stenosis in patients not favorable to carotid endarterectomy. The CAS was associated with a low rate of neurological events and reinterventions at long-term follow-up.
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Estenose das Carótidas , Reestenose Coronária , Endarterectomia das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Stents/efeitos adversos , Estudos Retrospectivos , Constrição Patológica , Reestenose Coronária/complicações , Resultado do Tratamento , Recidiva , Fatores de Tempo , Endarterectomia das Carótidas/efeitos adversos , Fatores de Risco , Artérias CarótidasRESUMO
OBJECTIVE: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the trends of carotid revascularization (endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS]) for symptomatic and asymptomatic carotid stenosis before, during, and after the end of the first lockdown in 2020 in France. METHODS: Nationwide data were provided by the French National Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). We retrospectively analyzed patients admitted for CEA or TFCAS in all French public and private hospitals during a 9-month period (January-September) in 2017, 2018, 2019, and 2020. Procedures were identified using the French Common Classification of Medical Procedures. Stenoses were considered symptomatic in the presence of stroke and/or transient ischemic attack codes (according to the International Classification of Diseases-Tenth Revision) during the stay, and asymptomatic in the absence of these codes. Hospitalization rates in 2020 were compared with the rates in the same period in the 3 previous years. RESULTS: Between January and September 2020, 12,546 patients were hospitalized for carotid artery surgery (CEA and TFCAS) in France. Compared with the 3 previous years, there was a decrease in hospitalization rates for asymptomatic (-68.9%) and symptomatic (-12.6%) CEA procedures in April, starting at the pandemic peak concomitant with the first national lockdown. This decrease was significant for asymptomatic CEA (P < .001). After the lockdown, while CEA for asymptomatic stenosis returned to usual activity, CEA for symptomatic stenosis presented a significant rebound, up 18.52% in August compared with previous years. Lockdown also had consequences on TFCAS procedures, with fewer interventions for both asymptomatic (-60.53%) and symptomatic stenosis (-16.67%) in April. CONCLUSIONS: This study demonstrates a severe decrease for all interventions during the first peak of the COVID-19 pandemic in France. However, the trends in the postlockdown period were different for the various procedures. These data can be used to anticipate future decisions and organization for cardiovascular care.
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COVID-19 , Estenose das Carótidas , Endarterectomia das Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , COVID-19/epidemiologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/terapia , Controle de Doenças Transmissíveis , Constrição Patológica/complicações , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/métodos , Procedimentos Endovasculares/métodos , Humanos , Pandemias , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: There are still gaps regarding the impact of the nationwide lockdown on non-COVID-19 emergency hospitalizations. This study aims to describe the trends in hospitalizations for cardiovascular surgical emergencies in France, before, during and after the first lockdown. MATERIALS AND METHODS: All adults admitted for mechanical complications of myocardial infarction (MI), aortic dissection, aortic aneurysm rupture, acute and critical limb ischemia, circulatory assistance, heart transplantation and major amputation were included. This retrospective cohort study used the French National Hospital Discharge database. The numbers of hospitalizations per month in 2020 were compared to the previous three years. RESULTS: From January to September 2020, 94,408 cases of the studied conditions were reported versus 103,126 in the same period in 2019 (-8.5%). There was a deep drop in most conditions during the lockdown, except for circulatory assistance, which increased. After the lockdown, mechanical complications of MI and aortic aneurysm rupture increased, and cardiac transplantations declined compared with previous years. CONCLUSION: We confirmed a deep drop in most cardiovascular surgical emergencies during the lockdown. The post-lockdown period was characterized by a small over-recovery for mechanical complications of MI and aortic aneurysm rupture, suggesting that many patients were able to access surgery after the lockdown.
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Atherosclerotic carotid artery stenosis causes about 10-20% of all ischemic strokes through two main mechanisms: hemodynamic impairment in case of significant stenosis and thromboembolism from an atherosclerotic plaque regardless of the degree of stenosis. The latter is the most frequent mechanism and appear to result from embolization from a vulnerable atherosclerotic plaque or acute occlusion of the carotid artery and propagation of thrombus distally. Downstream infarcts may occur in a territory of major cerebral artery or at the most distal areas between two territories of major cerebral arteries, the so-called watershed (WS), or border zone area. Although WS infarcts, especially deep WS infarct, were historically thought to be due to hemodynamic compromise, the role of microembolism has also been documented, both mechanisms may act synergistically to promote WS infarcts. Routine and more advanced imaging techniques may provide information on the underlying mechanism involved in ipsilateral ischemic stroke. A better understanding of ischemic stroke pathogenesis in carotid stenosis may limit the use of routine non-selective shunt, whose benefit-risk balance is debated, to patients with hemodynamic impairment. After reviewing existing evidence underpinning the contribution of the two mechanisms in downstream ischemic stroke and the various imaging techniques available to investigate them, we will focus on the pathogenesis of WS infarcts that remains debated.
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INTRODUCTION: Strategy for the acute management of minor ischemic stroke (IS) with large vessel occlusion (LVO) is under debate, especially the benefits of mechanical thrombectomy. The frequency of minor IS with LVO among overall patients is not well established. This study aimed to assess the proportion of minor IS and to depict characteristics of patients according to the presence of LVO in a comprehensive population-based setting. METHODS: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Minor stroke was defined as that with a National Institutes of Health Stroke Scale (NIHSS) score of <6. Proportion of patients with LVO was estimated in the minor IS population. The clinical presentation of patients was compared according to the presence of an LVO. RESULTS: Nine hundred seventy-one patients were registered, including 582 (59.9%) patients with a minor IS. Of these patients, 23 (4.0%) had a LVO. Patients with minor IS and LVO had more severe presentation [median 3 (IQR 2-5) vs. 2 (IQR 1-3), p = 0.001] with decreased consciousness (13.0 vs. 1.6%, p<0.001) and cortical signs (56.5 vs. 30.8%, p = 0.009), especially aphasia (34.8 vs. 15.4%, p = 0.013) and altered item level of consciousness (LOC) questions (26.1 vs. 11.6%, p = 0.037). In multivariable analyses, only NIHSS score (OR = 1.45 per point; 95% CI: 1.11-1.91, p = 0.007) was associated with proximal LVO in patients with minor IS. CONCLUSION: Large vessel occlusion (LVO) in minor stroke is non-exceptional, and our findings highlight the need for emergency arterial imaging in any patients suspected of acute stroke, including those with minor symptoms because of the absence of obvious predictors of proximal LVO.
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BACKGROUND AND PURPOSE: Subset of macrophages within the atheroma plaque displays a high glucose uptake activity. Nevertheless, the molecular mechanisms and the pathophysiological significance of this high glucose need remain unclear. While the role for hypoxia and hypoxia inducible factor 1α has been demonstrated, the contribution of lipid micro-environment and more specifically oxysterols is yet to be explored. EXPERIMENTAL APPROACH: Human macrophages were conditioned in the presence of homogenates from human carotid plaques, and expression of genes involved in glucose metabolism was quantified. Correlative analyses between gene expression and the oxysterol composition of plaques were performed. KEY RESULTS: Conditioning of human macrophages by plaque homogenates induces expression of several genes involved in glucose uptake and glycolysis including glucose transporter 1 (SLC2A1) and hexokinases 2 and 3 (HK2 and HK3). This activation is significantly correlated to the oxysterol content of the plaque samples and is associated with a significant increase in the glycolytic activity of the cells. Pharmacological inverse agonist of the oxysterol receptor liver X receptor (LXR) partially reverses the induction of glycolysis genes without affecting macrophage glycolytic activity. Chromatin immunoprecipitation analysis confirms the implication of LXR in the regulation of SLC2A1 and HK2 genes. CONCLUSION AND IMPLICATIONS: While our work supports the role of oxysterols and the LXR in the modulation of macrophage metabolism in atheroma plaques, it also highlights some LXR-independent effects of plaques samples. Finally, this study identifies hexokinase 3 as a promising target in the context of atherosclerosis. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
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Aterosclerose , Oxisteróis , Aterosclerose/genética , Glicólise , Humanos , Receptores X do Fígado/metabolismo , Macrófagos/metabolismoRESUMO
BACKGROUND AND PURPOSE: Because of several methodological limitations, previous studies focusing on the prevalence of large vessel occlusion in ischemic stroke (IS) patients provided conflicting results. We evaluated the incidence of IS with a visible arterial occlusion using a comprehensive population-based registry. METHODS: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Annual incidence rates of IS (first-ever and recurrent events) and IS with a visible occlusion were calculated. RESULTS: One thousand sixty cases of IS were recorded (mean age: 76.0±15.8 years, 53.9% women). Information about arterial imaging was available in 971 (91.6%) of them, and only preexisting dementia was independently associated with having missing information (odds ratio=0.34 [95% CI, 0.18-0.65], P=0.001). Among these patients, 284 (29.2%) had a visible arterial occlusion. Occlusion site was the anterior circulation in 226 patients (23.3% of overall patients with available data) and the posterior circulation in 58 patients (6.0%). A proximal occlusion of the anterior circulation was observed in 167 patients (17.2%). The crude annual incidence rate of total IS per 100 000 was 138 (95% CI, 129-146). Corresponding standardized rates were 66 (95% CI, 50-82) to the World Health Organization and 141 (95% CI, 118-164) to the 2013 European populations. The crude annual incidence rate of IS with a visible arterial occlusion per 100 000 was 37 (95% CI, 33-41) and that of IS with a proximal occlusion of the anterior circulation was 22 (95% CI, 18-25). Corresponding standardized rates were 18 (95% CI, 10-26) and 10 (95% CI, 8-13) to the World Health Organization population, and 38 (95% CI, 26-50) and 23 (95% CI, 19-26) to the 2013 European population, respectively. CONCLUSIONS: These results will be helpful to plan the need for thrombectomy-capable stroke center resources.
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Arteriopatias Oclusivas/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Acidente Vascular Cerebral/etiologiaRESUMO
Low-grade inflammation is constitutive of atherosclerosis, and anti-inflammatory therapy inhibiting interleukin-1ß (IL-1ß) reduces the rate of cardiovascular events. While cholesterol accumulation in atheroma plaque and macrophages is a major driver of the inflammatory process, the role of the LXR cholesterol sensors remains to be clarified. Murine and human macrophages were treated with LXR agonists for 48 h before Toll-like receptor (TLR) stimulation. Unexpectedly, we observe that, among other cytokines, LXR agonists selectively increase IL1B mRNA levels independently of TLR activation. This effect, restricted to human macrophages, is mediated by activation of HIF-1α through LXR. Accordingly, LXR agonists also potentiate other HIF-1α-dependent pathways, such as glycolysis. Treatment of human macrophages with carotid plaque homogenates also leads to induction of IL1B in an LXR-dependent manner. Thus, our work discloses a mechanism by which cholesterol and oxysterols trigger inflammation in atherosclerosis. This suggests perspectives to target IL-1ß production in atherosclerotic patients.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-1beta/biossíntese , Receptores X do Fígado/metabolismo , Macrófagos/metabolismo , Animais , Aterosclerose/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Receptores X do Fígado/agonistas , Receptores X do Fígado/antagonistas & inibidores , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Background and Purpose- The ongoing ageing population is associated with an increasing number of patients with stroke who have preexisting cognitive impairment. This study aimed to evaluate clinical severity in patients with ischemic stroke according to prestroke cognitive status. Methods- Patients with ischemic stroke were prospectively identified among residents of Dijon, France using a population-based registry (2013-2017). Prestroke cognitive status (no impairment, mild cognitive impairment [MCI], or dementia) was recorded, and severity at stroke onset was measured using the National Institutes of Health Stroke Scale (NIHSS) score. Association between prestroke cognitive status and severity was evaluated using ordinal regression analysis models in which the NIHSS score was considered as a categorical variable. Results- Among the 1048 patients (mean age, 76.3±15.2 years; 54.0% women), a greater severity was observed in those with MCI (n=132; median NIHSS: 6; interquartile range, 2-15), and those with dementia (n=164; median NIHSS: 7; interquartile range, 3-16), than in patients without cognitive impairment (n=752; median NIHSS: 3; interquartile range, 1-9). MCI (odds ratio [OR], 1.70 [95% CI, 1.21-2.38]; P=0.002) and dementia (OR, 2.24 [95% CI, 1.65-3.04]; P<0.001) were both associated with a greater severity at onset. The association was still observed after adjustment for clinical variables and proximal arterial occlusion (OR, 1.52 [95% CI, 1.02-2.28]; P=0.04 for MCI; OR, 2.16 [95% CI, 1.45-3.22]; P<0.001 dementia). Further adjustment for prestroke handicap slightly reduced the magnitude of the association (OR, 1.49 [95% CI, 0.98-2.25]; P=0.06 for MCI, and OR, 1.98 [95% CI, 1.26-3.12]; P=0.02 for dementia). The greater severity in patients with prestroke cognitive impairment was not specifically driven by a more severe impairment of either motor or language function. Conclusions- Patients with preexisting cognitive impairment suffered more severe ischemic stroke. This result could reflect a lower brain tolerance of acute ischemia. Further studies are needed to explore the underlying mechanisms that could be targeted from therapeutic perspectives focusing on neuroprotection.
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Sistema de Registros , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Feminino , França/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
BACKGROUND: Beyond the age of 80 years, the preventive treatment of an asymptomatic abdominal aortic aneurysm (AAA) has to be decided in light of the life expectancy which it is difficult to evaluate, but it is important to determine who in this population will benefit from it. The objective of our study was to determine the factors influencing short-term mortality and long-term survival in patients aged 80 years and older after the endovascular treatment of AAAs (EVAR). MATERIAL AND METHODS: We present a retrospective analysis of the prospective databases of 4 French academic departments of vascular surgery, bringing together the data of all the patients presenting an AAA who were treated by EVAR between 1998 and 2011. Logistic regression and multivariate analysis with a Cox survival model were used to determine the factors influencing perioperative and long-term mortality. The cumulative rate of events for the measurement of survival was calculated with the technique of Kaplan-Meier. RESULTS: We treated 345 octogenarians and 339 younger patients. The average follow-up was 40 months. Average survival was 75% at 36 months and 49% at 60 months. There was no evidence of any risk factor influencing mortality at 30 days in the octogenarians. However, chronic kidney disease (odds ratio [OR] = 3.95, P <0.001) and chronic respiratory failure (OR = 2.62, P <0.001) proved to be independent factors of a poor long-term prognosis. CONCLUSIONS: The treatment by stent graft in octogenarians is effective in the long term. The presence of an impaired renal function or respiratory failure in this population could put into question the operative indication.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Fatores Etários , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Doenças Assintomáticas , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , França , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The prevalence of obesity is increasing, and its impact on the outcome of open and endovascular abdominal aortic aneurysm (AAA) repair remains unclear, particularly in the European population. We herein assessed the impact of obesity on the postoperative course for both techniques. METHODS: From a database that consecutively collects all patients undergoing AAA repair; we selected all patients undergoing elective surgery for open or endovascular AAA repair, between January 2003 and December 2011. We considered obese patients (body mass index >30 kg/m(2)), overweight (25.1-30 kg/m(2)), and normal-weight patients (18.7-25 kg/m(2)), and compared mortality and/or severe complications at 30 days between obese and nonobese patients (overweight and normal weight) separately for each type of surgery by logistic regression analysis. We analyzed wound complications in the 2 groups. RESULTS: We included 748 patients, 174 obese, and 574 nonobese patients. Obese patients were younger (P < 0.001) and were less likely to have renal failure (P < 0.001) in both techniques. Obese patients in the open repair (OR) group showed a trend toward lower mortality and/or complication rates than in nonobese patients (4.8% vs. 7.5%, P = 0.34). In contrast, in the endovascular aortic aneurysm repair (EVAR) group, obese patients showed a trend toward higher mortality and/or complication rates than nonobese patients (7.1% vs. 3.2%, P = 0.17). In multivariate analysis, obesity was not an independent predictor of outcomes in OR (P = 0.18) or in EVAR (P = 0.20). Wound complications were not higher in obese patients in OR and in EVAR. CONCLUSIONS: Obesity should not be considered an independent risk factor of death and severe complications at 30 days in either open or endovascular AAA repair. Therefore, obesity should not systematically lead to the decision to use EVAR.