Brain vessel status is a promising biomarker for better prevention and treatment in cerebrovascular disease. However, classic rule-based vessel segmentation algorithms need to be hand-crafted and are ...insufficiently validated. A specialized deep learning method-the U-net-is a promising alternative. Using labeled data from 66 patients with cerebrovascular disease, the U-net framework was optimized and evaluated with three metrics: Dice coefficient, 95% Hausdorff distance (95HD) and average Hausdorff distance (AVD). The model performance was compared with the traditional segmentation method of graph-cuts. Training and reconstruction was performed using 2D patches. A full and a reduced architecture with less parameters were trained. We performed both quantitative and qualitative analyses. The U-net models yielded high performance for both the full and the reduced architecture: A Dice value of ~0.88, a 95HD of ~47 voxels and an AVD of ~0.4 voxels. The visual analysis revealed excellent performance in large vessels and sufficient performance in small vessels. Pathologies like cortical laminar necrosis and a rete mirabile led to limited segmentation performance in few patients. The U-net outperfomed the traditional graph-cuts method (Dice ~0.76, 95HD ~59, AVD ~1.97). Our work highly encourages the development of clinically applicable segmentation tools based on deep learning. Future works should focus on improved segmentation of small vessels and methodologies to deal with specific pathologies.
AimStroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%–80% of all strokes. It is of considerable significance to carry out multidimensional ...management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases.MethodsWe had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years.ResultsThis evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management.ConclusionsThis updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.
Abstract
In an international comparison of recent mortality statistics among G7 countries, Japan had the longest average life expectancy, primarily due to remarkably low mortality rates from ischemic ...heart disease and cancer (particularly breast and prostate). As recently as the 1960s, life expectancy in Japan was the shortest among the G7 countries, owing to relatively high mortality from cerebrovascular disease—particularly intracerebral hemorrhage—and stomach cancer. Mortality rates for these diseases subsequently decreased significantly while the already low rates for ischemic heart disease and cancer also decreased, resulting in Japanese life expectancy becoming the longest. The low mortality rates from ischemic heart disease and cancer are thought to reflect the low prevalence of obesity in Japan; low intake of red meat, specifically saturated fatty acids; and high intakes of fish, specifically n-3 polyunsaturated fatty acids, plant foods such as soybeans, and nonsugar-sweetened beverages such as green tea. The decreasing mortality rates from cerebrovascular disease are thought to reflect the increases in animal foods, milk, and dairy products and consequently in saturated fatty acids and calcium, together with a decrease in salt intake which may have led to a decrease in blood pressure. This decrease in salt and highly salted foods also seems to account for the decrease in stomach cancer. The typical Japanese diet as characterized by plant food and fish as well as modest Westernized diet such as meat, milk and dairy products might be associated with longevity in Japan.
Objectives
Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the ...major neurological complications in a large cohort of COVID-19 patients.
Methods
Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories.
Results
Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease 53 pts (38.7%) including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases 31 (22.6%) including 17 Guillain–Barrè syndromes; (c) altered mental status 49 (35.8%) including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2;
χ
2
= 14.306;
p
< 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%;
χ
2
= 7.055;
p
< 0.01).
Conclusion
This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.
Aim
To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants.
Materials and methods
In SOUL, the effects of oral ...semaglutide, the first oral glucagon‐like peptide‐1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double‐blind, parallel‐group, placebo‐controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease CAD, cerebrovascular disease, symptomatic peripheral arterial disease PAD) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event‐driven trial will continue until 1225 first adjudication‐confirmed MACEs have occurred. Enrolment has been completed.
Results
Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m2, glycated haemoglobin 63.5 mmol/mol 8.0%). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium‐glucose cotransporter‐2 inhibitors (26.7%) and dipeptidyl peptidase‐4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants.
Conclusion
SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD.
Reduced middle cerebral artery blood velocity (MCAv) and flow pulsatility are contributors to age-related cerebrovascular disease pathogenesis. It is unknown whether the rate of changes in MCAv and ...flow pulsatility support the hypothesis of sex-specific trajectories with aging. Therefore, we sought to characterize the rate of changes in MCAv and flow pulsatility across the adult lifespan in females and males as well as within specified age ranges. Participant characteristics, mean arterial pressure, end-tidal carbon dioxide, unilateral MCAv, and flow pulsatility index (PI) were determined from study records compiled from three institutional sites. A total of 524 participants 18-90 yr; females 57 (17) yr,
= 319; males 50 (21) yr,
= 205 were included in the analysis. MCAv was significantly higher in females within the second (
< 0.001), fifth (
= 0.01), and sixth (
< 0.01) decades of life. Flow PI was significantly lower in females within the second decade of life (
< 0.01). Rate of MCAv decline was significantly greater in females than males (-0.39 vs. -0.26 cm s
·yr,
= 0.04). Rate of flow PI rise was significantly greater in females than males (0.006 vs. 0.003 flow PI,
= 0.01). Rate of MCAv change was significantly greater in females than males in the sixth decade of life (-1.44 vs. 0.13 cm s
·yr,
= 0.04). These findings indicate that sex significantly contributes to age-related differences in both MCAv and flow PI. Therefore, further investigation into cerebrovascular function within and between sexes is warranted to improve our understanding of the reported sex differences in cerebrovascular disease prevalence.
We present the largest dataset (
= 524) pooled from three institutions to study how age and sex affect middle cerebral artery blood velocity (MCAv) and flow pulsatility index (PI) across the adult lifespan. We report the rate of MCAv decline and flow PI rise is significantly greater in females compared with in males. These data suggest that sex-specific trajectories with aging and therapeutic interventions to promote healthy brain aging should consider these findings.
Background and Purpose: Although it is well established that diabetic retinopathy (DR) and diabetic macular edema (DME) are risk factors for incident cerebrovascular disease (CVD), whether the CVD ...history could be a predictor of severe DR or DME remains unknown among people with type 2 diabetes. Also, the effects of aging or systolic blood pressure on incident severe DR or DME in individuals with a history of CVD remains unknown.
Methods: Severe DR and DME were defined as vision-threatening treatment-required diabetic eye diseases (TRDED). Enrolled were 31,638 Japanese patients with type 2 diabetes. We longitudinally explored the existence of such an association not only overall but also according to various factors.
Results: The main outcome of TRDED was observed in 854 (2.7%) patients during a mean follow-up of 5.3 years (5.1/1,000 person-years). Prior CVD was present in 694 of 31,638 (2.2%) patients at baseline. In a multivariate adjusted Cox regression model, prior CVD was positively associated with incident TRDED in analysis of the study population (hazard ratio, 1.63 95% confidence interval, 1.11-2.37 overall; 1.47 0.54, 3.99 for age ≤49 y; 1.69 1.12, 2.55 for age ≥50 y; 1.46 0.89, 2.39 for SBP ≤139 mmHg; 1.97 1.09, 3.58 for SBP ≥140 mmHg). All results, including several stratified analyses, correlated with visual inspection of the corresponding Kaplan-Meier analysis with log-rank tests indicating gaps between curves for those with and without prior CVD.
Conclusions: These results indicate that CVD is a predictor of vision-threatening severe retinopathy, and suggested that they shared a common background pathophysiology. It also contributed to preventing severe visual impairment and further deterioration of the quality of life after stroke.
Disclosure
M.Yamamoto: None. M.Iwanaga: None. T.Yamada: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. H.Hasebe: None. H.Shiozaki: None. R.Kodera: None. T.Sato: None. Y.Yaguchi: None. T.Osawa: None. Y.Matsubayashi: None.
Funding
Japan Society for the Promotion of Science (JP21K11569, JP22K16212)
Background
Pre‐eclampsia is a pregnancy‐associated condition with complex disease mechanisms and a risk factor for various long‐term health outcomes for the mother and infant.
Objective
To summarise ...evidence on the association of pre‐eclampsia with long‐term health outcomes arising in women and/or infants.
Search strategy
PubMed, EMBASE, Scopus and ISI Web of Science were searched from inception to July 2020.
Selection criteria
Systematic reviews and meta‐analyses examining associations between pre‐eclampsia and long‐term health outcomes in women and their infants.
Data collection and analysis
Data were extracted by two independent reviewers. We re‐estimated the summary effect size by random‐effects and fixed‐effects models, the 95% confidence interval, the 95% prediction interval, the between‐study heterogeneity, any evidence of small‐study effects and excess significance bias.
Results
Twenty‐one articles were included (90 associations). Seventy‐nine associations had nominally statistically significant findings (P < 0.05). Sixty‐five associations had large or very large heterogeneity. Evidence for small‐study effects and excess significance bias was found in seven and two associations, respectively. Nine associations: cerebrovascular disease (cohort studies), cerebrovascular disease (overall), cardiac disease (cohort studies), dyslipidaemia (all studies), risk of death (late‐onset pre‐eclampsia), fatal and non‐fatal ischaemic heart disease, cardiovascular mortality (cohort studies), any diabetes or use of diabetic medication (unadjusted), and attention deficit/hyperactivity disorder (ADHD) (adjusted) were supported with robust evidence.
Conclusion
Many of the meta‐analyses in this research field have caveats casting doubts on their validity. Current evidence suggests an increased risk for women to develop cardiovascular‐related diseases, diabetes and dyslipidaemia after pre‐eclampsia, while offspring exposed to pre‐eclampsia are at higher risk for ADHD.
Tweetable
Cardiovascular and cerebrovascular diseases were supported with convincing evidence for long‐term health outcomes after pre‐eclampsia.
Tweetable
Cardiovascular and cerebrovascular diseases were supported with convincing evidence for long‐term health outcomes after pre‐eclampsia.
People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse.
To assess whether the ...risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England.
A population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12 251 patients with MS were matched with up to 6 people without MS (n = 72 572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date.
Multiple sclerosis status. Analyses were also stratified by sex.
Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease-specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates.
A total of 12 251 people with MS (66.9% women; mean SD age, 44.9 13.3 years) were matched with 72 572 people without MS (69.8% women; mean SD age, 44.9 13.3 years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio HR, 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI, 1.27-1.71). Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS.
This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed.
Investigations of apolipoprotein E (APOE) gene, the major genetic risk modifier for Alzheimer's disease (AD), have yielded significant insights into the pathogenic mechanism. Among the three common ...coding variants, APOE*ε4 increases, whereas APOE*ε2 decreases the risk of late-onset AD compared with APOE*ε3. Despite increased understanding of the detrimental effect of APOE*ε4, it remains unclear how APOE*ε2 confers protection against AD. Accumulating evidence suggests that APOE*ε2 protects against AD through both amyloid-β (Aβ)-dependent and independent mechanisms. In addition, APOE*ε2 has been identified as a longevity gene, suggesting a systemic effect of APOE*ε2 on the aging process. However, APOE*ε2 is not entirely benign; APOE*ε2 carriers exhibit increased risk of certain cerebrovascular diseases and neurological disorders. Here, we review evidence from both human and animal studies demonstrating the protective effect of APOE*ε2 against AD and propose a working model depicting potential underlying mechanisms. Finally, we discuss potential therapeutic strategies designed to leverage the protective effect of APOE2 to treat AD.
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