Cerebrovascular Research Articles

Clinical Predictors of Postmortem Amyloid and Nonamyloid Cerebral Small Vessel Disease in Middle-Aged to Older Adults.

Sporadic cerebral small vessel disease (CSVD) is a class of important pathologic processes known to affect the aging brain and to contribute to cognitive impairment. We aimed to identify clinical risk factors associated with postmortem CSVD in middle-aged to older adults. We developed and tested risk models for their predictive accuracy of a pathologic diagnosis of nonamyloid CSVD and cerebral amyloid angiopathy (CAA) in a retrospective sample of 160 autopsied cases from the Edinburgh Brain Bank. Individuals aged 40 years and older covering the spectrum of healthy aging and common forms of dementia (i.e., highly-prevalent etiologies such as Alzheimer disease (AD), vascular cognitive impairment (VCI), and mixed dementia) were included. We performed binomial logistic regression models using sample splitting and cross-validation methods. Demographics, lifestyle habits, traditional vascular risk factors, chronic medical conditions, APOE4, and cognitive status were assessed as potential predictors. Forty percent of our sample had a clinical diagnosis of dementia (AD = 33, VCI = 26 and mixed = 5) while others were cognitively healthy (n = 96). The mean age at death was 73.8 (SD 14.1) years, and 40% were female. The presence of none-to-mild vs moderate-to-severe nonamyloid CSVD was predicted by our model with good accuracy (area under the curve [AUC] = 0.84, sensitivity [SEN] = 72%, specificity [SPE] = 95%), with the most significant clinical predictors being age, history of cerebrovascular events, and cognitive impairment. The presence of CAA pathology was also predicted with high accuracy (AUC = 0.86, SEN = 93%, SPE = 79%). Significant predictors included alcohol intake, history of cerebrovascular events, and cognitive impairment. In a subset of atypical dementias (n = 24), our models provided poor predictive performance for both nonamyloid CSVD (AUC = 0.50) and CAA (AUC = 0.43). CSVD pathology can be predicted with high accuracy based on clinical factors in patients within the spectrum of AD, VCI, and normal aging. Whether this prediction can be enhanced by the addition of fluid and neuroimaging biomarkers warrants additional study. Improving our understanding of clinical determinants of vascular brain health may lead to novel strategies in the prevention and treatment of vascular etiologies contributing to cognitive decline. This study provides Class II evidence that selected clinical factors accurately distinguish between middle-aged to older adults with and without cerebrovascular small vessel disease (amyloid and nonamyloid) pathology.

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study.

Studies on incidence and prevalence of vestibular disorders tend to focus on small pockets of patients recruited from specialized clinics and often exclude measures of vestibular function. The objectives of the study were to characterize patients with common vestibular disorders, estimate the prevalence of common vestibular disorders, and ascertain whether patients with vestibular disorders experience increased risks of falls and morbidity. This retrospective cohort study includes both inpatient and outpatient routine clinical care data culled from a nationally representative, population-based sample. Patients were included if their record in the TriNetX Diamond Cohort comprised at least one vestibular function test or vestibular diagnosis. The main outcome measures were diagnosis with a vestibular disorder, a fall, or a common medical comorbidity (e.g., diabetes, cerebrovascular disease). The cohort includes n = 4,575,724 patients, of which 55% (n = 2,497,136) had a minimum of one vestibular diagnosis. Patients with vestibular diagnoses were 61.3 ± 16.6 years old (mean ± standard deviation), 67% women, 28% White race (69% unknown race), and 30% of non-Hispanic or Latino ethnicity (66% unknown ethnicity). The prevalence of vestibular disorders was estimated at 2.98% (95% confidence interval [CI]: 2.98-2.98%). Patients with vestibular diagnoses experienced a significantly greater odds of falls (odds ratio [OR] = 1.04; 95% CI: 1.02-1.05), cerebrovascular disease (OR = 1.42; 95% CI: 1.40-1.43), ischemic heart disease (OR = 1.17; 95% CI: 1.16-1.19), and diabetes (OR = 1.14; 95% CI: 1.13-1.15), among others. Vestibular disorders affect an estimated 3% of the U.S. population, after weighting. Patients with these disorders are at greater risk for many common, consequential medical conditions.

Neuroimaging Features of Cytokine-related Diseases.

Cytokines are small secreted proteins that have specific effects on cellular interactions and are crucial for functioning of the immune system. Cytokines are involved in almost all diseases, but as microscopic chemical compounds they cannot be visualized at imaging for obvious reasons. Several imaging manifestations have been well recognized owing to the development of cytokine therapies such as those with bevacizumab (antibody against vascular endothelial growth factor) and chimeric antigen receptor (CAR) T cells and the establishment of new disease concepts such as interferonopathy and cytokine release syndrome. For example, immune effector cell-associated neurotoxicity is the second most common form of toxicity after CAR T-cell therapy toxicity, and imaging is recommended to evaluate the severity. The emergence of COVID-19, which causes a cytokine storm, has profoundly impacted neuroimaging. The central nervous system is one of the systems that is most susceptible to cytokine storms, which are induced by the positive feedback of inflammatory cytokines. Cytokine storms cause several neurologic complications, including acute infarction, acute leukoencephalopathy, and catastrophic hemorrhage, leading to devastating neurologic outcomes. Imaging can be used to detect these abnormalities and describe their severity, and it may help distinguish mimics such as metabolic encephalopathy and cerebrovascular disease. Familiarity with the neuroimaging abnormalities caused by cytokine storms is beneficial for diagnosing such diseases and subsequently planning and initiating early treatment strategies. The authors outline the neuroimaging features of cytokine-related diseases, focusing on cytokine storms, neuroinflammatory and neurodegenerative diseases, cytokine-related tumors, and cytokine-related therapies, and describe an approach to diagnosing cytokine-related disease processes and their differentials. ©RSNA, 2024 Supplemental material is available for this article.

Detection of miR-203 expression using a nanofluorescent probe to study the neuroprotective effect of sevoflurane in a neuroinflammatory injury rat model

Ischemic cerebrovascular disease has high disability and mortality rates that can result in related sequelae if not treated promptly and properly. Nanofluorescent probes are useful in the early diagnosis of the disease due to their high sensitivity and specificity, thus facilitating early therapeutic measures and observation of disease progression. Here, a novel nanostructure probe was designed to detect the expression of miR-203 in a cerebral ischemia-reperfusion injury (CIRI) model after sevoflurane treatment, and the effects of sevoflurane and neuroinflammatory injury were discussed. A CIRI rat model was established to study miR-203 expression, nerve injury, oxidative stress, and inflammatory factors in the brain tissue of rats treated with sevoflurane. The nanofluorescent probe showed high specificity and sensitivity for miR-203 detection. miR-203 was over-expressed in CIRI rats, which was decreased by sevoflurane treatment. In addition, sevoflurane treatment significantly improved neurological function, learning, and memory in CIRI rats; decreased malondialdehyde, lactate dehydrogenase, and superoxide dismutase levels; and inhibited the expression of tumor necrosis factor α and interleukins 1 and 6. Moreover, an inverse correlation was determined between miR-203 expression and the degree of neuroinflammation. This study demonstrated that miR-203 may be a useful diagnostic and prognostic index for neuroinflammatory injury.

Impact of prognostic nutritional index on the occurrence of post-operative delirium after total knee arthroplasty

PurposeDelirium has been reported to cause delayed functional recovery, prolonged hospitalization, future institutionalization, increased mortality, and increased healthcare costs. However, there are no reports on how prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index (GNRI) are related to delirium after total knee arthroplasty (TKA). This study aimed to identify risk factors for post-operative delirium after TKA using various pre-operative nutritional assessments (PNI, CONUT score, and GNRI). MethodsIn total, 289 patients who underwent primary TKA between September 2011 and April 2022 in our institute (Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan) were enrolled. Patients were divided into two groups: those who developed post-operative delirium (Group D), and those who did not (Group ND). Pre-operative risk factors, including nutritional indices, for post-operative delirium were evaluated. ResultsGroup D comprised 16 participants, while Group ND comprised 273 participants. Comparisons between the two groups revealed significant differences in age, PNI, CONUT score, GNRI, and history of cerebrovascular disease. Multiple logistic regression analysis revealed that significant risk factors for delirium after TKA were age, PNI, and history of cerebrovascular disease. A receiver operating characteristic curve indicated that the cutoff values for delirium were 47.4 for PNI (sensitivity, 0.810; specificity, 0.875) and 78.5 years for age (sensitivity, 0.813; specificity, 0.722). ConclusionsRisk factors for post-operative delirium after TKA were PNI <47.4, age >78.5 years, and history of cerebrovascular disease. Patients exceeding these pre-operative cutoff values or with a history of cerebrovascular disease should receive counseling about delirium before surgery.

Does Carotid Endarterectomy Provide Benefits in Cognitive Functions in Patients With Severe Extracranial Cerebrovascular Disease?

Does Carotid Endarterectomy Provide Benefits in Cognitive Functions in Patients With Severe Extracranial Cerebrovascular Disease?

Association of NOTCH3 Variant Risk Category With 2-Year Clinical and Radiologic Small Vessel Disease Progression in Patients With CADASIL.

Pathogenic variants in NOTCH3 are the main cause of hereditary cerebral small vessel disease (SVD). SVD-associated NOTCH3 variants have recently been categorized into high risk (HR), moderate risk (MR), or low risk (LR) for developing early-onset severe SVD. The most severe NOTCH3-associated SVD phenotype is also known as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to investigate whether NOTCH3 variant risk category is associated with 2-year progression rate of SVD clinical and neuroimaging outcomes in CADASIL. A single-center prospective 2-year follow-up study was performed of patients with CADASIL. Clinical outcomes were incident stroke, disability (modified Rankin Scale), and executive function (Trail Making Test B given A t-scores). Neuroimaging outcomes were mean skeletonized mean diffusivity (MSMD), normalized white matter hyperintensity volume (nWMHv), normalized lacune volume (nLV), and brain parenchymal fraction (BPF). Cox regression and mixed-effect models, adjusted for age, sex, and cardiovascular risk factors, were used to study 2-year changes in outcomes and differences in disease progression between patients with HR-NOTCH3 and MR-NOTCH3 variants. One hundred sixty-two patients with HR (n = 90), MR (n = 67), and LR (n = 5) NOTCH3 variants were included. For the entire cohort, there was 2-year mean progression for MSMD (β = 0.20, 95% CI 0.17-0.23, p = 7.0 × 10-24), nLV (β = 0.13, 95% CI 0.080-0.19, p = 2.1 × 10-6), nWMHv (β = 0.092, 95% CI 0.075-0.11, p = 8.8 × 10-20), and BPF (β = -0.22, 95% CI -0.26 to -0.19, p = 3.2 × 10-22), as well as an increase in disability (p = 0.002) and decline of executive function (β = -0.15, 95% CI -0.30 to -3.4 × 10-5, p = 0.05). The HR-NOTCH3 group had a higher probability of 2-year incident stroke (hazard ratio 4.3, 95% CI 1.4-13.5, p = 0.011), and a higher increase in MSMD (β = 0.074, 95% CI 0.013-0.14, p = 0.017) and nLV (β = 0.14, 95% CI 0.034-0.24, p = 0.0089) than the MR-NOTCH3 group. Subgroup analyses showed significant 2-year progression of MSMD in young (n = 17, β = 0.014, 95% CI 0.0093-0.019, p = 1.4 × 10-5) and premanifest (n = 24, β = 0.012, 95% CI 0.0082-0.016, p = 1.1 × 10-6) individuals. In a trial-sensitive time span of 2 years, we found that patients with HR-NOTCH3 variants have a significantly faster progression of major clinical and neuroimaging outcomes, compared with patients with MR-NOTCH3 variants. This has important implications for clinical trial design and disease prediction and monitoring in the clinic. Moreover, we show that MSMD is a promising outcome measure for trials enrolling premanifest individuals.

Novel inflammatory and insulin resistance indices provide a clue in cerebral amyloid angiopathy

This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07–1.30, P < 0.001), and triglyceride–glucose index (TyG, OR = 0.56, 95% CI 0.36–0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764–0.865) in the training set and 0.830 (95% CI 0.718–0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.

Precise Modulation of Pericyte Dysfunction by a Multifunctional Nanoprodrug to Ameliorate Alzheimer's Disease.

Pericyte dysfunction severely undermines cerebrovascular integrity and exacerbates neurodegeneration in Alzheimer's disease (AD). However, pericyte-targeted therapy is a yet-untapped frontier for AD. Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Importantly, VLC@Cur-NPs effectively homed to pericyte lesions via VLC and released their contents upon ROS stimulation to maximize their regulatory effects. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases.

Complications and survival following percutaneous endoscopic gastrostomy tube placement.

Percutaneous endoscopic gastrostomy (PEG) is considered a safe and effective method for nutritional support in patients with malnutrition and swallowing impairment with an estimated survival of over two months. Some indications, such as advanced cognitive decline, contraindicate the technique. All patients who underwent PEG placement between January 2001 and May 2019 were included. Clinical data, indication, complications, and mortality were retrospectively analyzed. A total of 648 patients (46.5% male, mean age 70±18.5 years) were included. The most common indications for PEG were advanced cognitive decline (31.5%) and cerebrovascular disease (18.8%). The mean follow-up was 12.07 months (IQR 3.27-34.73). 39.5% of patients experienced complications (systemic 17.9%, local 28.5%). The most frequent were bronchoaspiration (9.7%) and rupture/dysfunction (13.9%), respectively. The presence of early complications (HR 1.63 [1.20-2.21]) and age (HR 1.02 [1.01-1.02]) were associated with shorter survival time, while female sex was a protective factor (HR 0.78 [0.66-0.94]). PEG is not without complications, with 39.5% of patients experiencing them. Patients with advanced dementia, male sex, older age, and systemic complications have lower survival following PEG placement.

Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia

BackgroundThe gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine – have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain.MethodsIn the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function.ResultsOverall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses.ConclusionsPlasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.

Human Plasma‐Derived Extracellular Vesicles Protect Against Cerebral Ischemia‐Reperfusion Injury via HSP27 Phosphorylation

AbstractIschemic stroke (IS) has become a serious public health problem, with patients undergoing endovascular treatment experiencing ischemia‐reperfusion (I/R) injury, which exacerbates cerebrovascular diseases. Circulating extracellular vesicles (EVs) have shown potential for treating cerebral I/R injury. In this study, the therapeutic effect of human plasma‐derived EVs and protective mechanisms in cerebral I/R injury is explored. An oxygen‐glucose deprivation/reperfusion (OGD/R) model is used to treat SH‐SY5Y cells in vitro, and an I/R injury model is constructed by transient middle cerebral artery occlusion (tMCAO) in mice. Human plasma‐derived EVs are extracted by size exclusion chromatography. Western blot, Immunofluorescence Staining, and 2,3,5‐Triphenyltetrazolium Chloride (TTC) Staining are employed to observe the effects of EVs on the neuroinflammatory response and infarct volumes in tMCAO mice, while TUNEL Staining, Flow Cytometry, and Western Blot are employed to assess cell apoptosis. Human plasma‐derived EVs alleviated apoptosis in SH‐SY5Y cells under OGD/R stress and exerted a protective effect against brain I/R injury in tMCAO mice. Mechanistically, EVs protected against cerebral I/R injury via HSP27 phosphorylation, and the HSP27 phosphorylation inhibitor KRIBB3 attenuated the anti‐apoptotic effects of EVs. Human plasma‐derived EVs activated the phosphorylation of HSP27, thereby inhibiting cell apoptosis and protecting against cerebral I/R injury.

Cross-sectional association of continuous glucose monitoring-derived metrics with cerebral small vessel disease in older adults with type 2 diabetes.

To examine cross-sectional associations between continuous glucose monitoring (CGM)-derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes. In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70-180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0-4). Ordinal logistic regression analyses were performed to examine the association of CGM-derived metrics with the total SVD score. The median SVD score was 1 (interquartile range 0-2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56-0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores. The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes.

DIABETES TYPE 2 AND OBESITY

Diabetes mellitus type 2 is a socially significant disease, which etiologically and pathogenetically is to the greatest extent influenced by body weight. Obesity has become a pandemic of our time. It is most often caused by the imbalance between energy intake and energy expenditure. Excess calories accumulate as fat. In patients with DM type 2, obesity further increases the risk of atherosclerosis, ischemic heart disease, cerebrovascular disease, arterial hypertension, hepatic steatosis, chronic kidney disease, increased mortality. The aim of the present analysis is to determine the frequency of patients with type 2 DM 170 patients with DM type-2 were studied. Of them, 77 with a relative share of 45.% are men, 93 are women, who make up 54.7%. The method of calculating the body mass index, which serves to assess the physical condition of the patients, was applied. After processing the data, it was found that 4.4% of the patients had a normal body weight, 26.5% were overweight, 1st degree obesity - 34.7%, 2nd degree obesity - 20.3% and with obesity of the 3rd degree are 14.1% of the studied patients. Obesity is a serious metabolic disorder that harbors multiple health risk factors that may reduce quality and life expectancy among patients with type-2 DM.

A nomogram-based prediction model for dysphagia in patients with chronic obstructive pulmonary disease: A cross-sectional study.

To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. A cross-sectional design. From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. No patient or public contribution.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study

AimsWe aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region.Material and methodsWe used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD.ResultsThe study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75.ConclusionsIn individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

Imaging and blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease

ObjectiveTo explore the imaging and transcranial Doppler cerebral blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease.MethodsA retrospective analysis was conducted on the imaging data of 194 patients with cerebrovascular fenestration malformation who visited the Heyuan People’s Hospital from July 2021 to July 2023. The location and morphology of the fenestration malformation blood vessels as well as the presence of other cerebrovascular diseases were analyzed. Transcranial Doppler cerebral blood flow detection data of patients with cerebral infarction and those with basilar artery fenestration malformation were also analyzed.ResultsA total of 194 patients with cerebral vascular fenestration malformation were found. Among the artery fenestration malformation, basilar artery fenestration was the most common, accounting for 46.08% (94/194). 61 patients (31.44%) had other vascular malformations, 97 patients (50%) had cerebral infarction, of which 30 were cerebral infarction in the fenestrated artery supply area. 28 patients with cerebral infarction in the fenestrated artery supply area received standardized antiplatelet, lipid-lowering and plaque-stabilizing medication treatment. During the follow-up period, these patients did not experience any symptoms of cerebral infarction or transient ischemic attack again. There were no differences in peak systolic flow velocity and end diastolic flow velocity, pulsatility index and resistance index between the ischemic stroke group and the no ischemic stroke group in patients with basal artery fenestration malformation (P > 0.05).ConclusionCerebrovascular fenestration malformation is most common in the basilar artery. Cerebrovascular fenestration malformation may also be associated with other cerebrovascular malformations. Standardized antiplatelet and statin lipid-lowering and plaque-stabilizing drugs are suitable for patients with cerebral infarction complicated with fenestration malformation. The relationship between cerebral blood flow changes in basilar artery fenestration malformation and the occurrence of ischemic stroke may not be significant.

Deregulated miR-146a-3p alleviates disease progression in atherosclerosis through inactivating NF-κB: An experimental study.

Atherosclerosis (AS), as a complex chronic inflammatory disease, is 1 of the main causes of cardiovascular and cerebrovascular diseases. This study aimed to confirm the direct interaction between miR-146a-3p and NF-κB, and explore the role of miR-146a-3p/NF-κB in the regulation of inflammation in AS. Bioinformatic prediction and dual-luciferase reporter assay were used to confirm the interaction between miR-146a-3p and NF-κB. Lipopolysaccharides stimulation was performed to establish AS inflammatory cell model, and the levels of pro-inflammatory cytokines were estimated using an enzyme-linked immunosorbent assay. miR-146a-3p and NF-κB expression were evaluated using reverse transcription quantitative PCR, and their clinical value was examined using a receiver operating characteristic curve. Inflammatory cell model showed increased IL-1β, IL-6, and TNF-α. NF-κB was a target gene of miR-146a-3p, and mediated the inhibitory effects of miR-146a-3p on inflammatory responses in the cell model. In patients with AS, miR-146a-3p/NF-κB was associated with patients' clinical data and inflammatory cytokine levels, and aberrant miR-146a-3p and NF-κB showed diagnostic accuracy to distinguish AS patients from healthy populations. miR-146a-3p might inhibit inflammation by targeting NF-κB in AS progression, and miR-146a-3p/ NF-κB might provide novel biomarkers and therapeutic targets for the prevention of AS and related vascular events.

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

IMPACT OF POLYVASCULAR DISEASE ON LONG–TERM PROGNOSIS IN PATIENTS WITH ACUTE CORONARY SYNDROME. A PROSPECTIVE COHORT STUDY IN ITALY

Abstract Background Atherothrombosis should be considered a systemic disease that may involve one or more than one vascular beds. Data on the impact of polyvascular disease on long–term prognosis in patients with acute coronary syndrome (ACS) are still scarce. Aim To assess the prevalence of symptomatic polyvascular disease in a cohort of patients with ACS and to investigate the impact on long–term outcomes of single versus multiple vascular beds involvement. Methods We analyzed a nationwide, comprehensive, and universal administrative database of consecutive patients older than 40 years admitted for a new episode of ACS in 2013–14 in Italy. Patients with ACS were stratified according to the presence of Peripheral Arterial Disease (PAD) only, Cerebrovascular Disease (CeVD) only, PAD and CeVD (PAD+CeVD) or neither (noPAD/noCeVD). A Cox proportional hazard multivariate model was used to evaluate the impact of PAD only, CeVD only and PAD+CeVD on 5–year MACCE. Results 331320 new episode of ACS were identified. Among them, 24491 (7.4%) were patients with PAD only, 16269 (4.9%) with CeVD only and 4710 (1.4%) with PAD+CeVD. The 5 years MACCE was 42.6%, 64.7%, 66.1 and 72.2 (p&amp;lt;0.001) for noPAD/noCeVD, PAD only, CeVD only and PAD+CeVD, respectivelly. After adjustment for age, sex, and comorbidities, the hazard ratio (HR) for 5–year MACCE was 1.30 (p&amp;lt;0.0001), 1.39 (p&amp;lt;0.0001), and 1.46 (p&amp;lt;0.0001) in patients with PAD only, CeVD only, and PAD+CeVD, respectively, as compared with patients without PAD and CeVD. Conclusion Polyvascular disease represents a major risk factor in patients with ACS. The simultaneous involvement of three vascular beds further increases the risk of long–term outcomes. Greater effort should be directed toward identification of subclinical/clinical atherosclerosis of beds different from coronary for a better risk stratification.