Chronic Cerebrovascular Disease Research Articles

Aging related changes in cardiovascular system in healthy female population: photoplethysmography method and DFA analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science Technological Development and Innovation Background The cardiovascular system undergoes dynamic changes during the biological aging in humans, leading to chronic cardiovascular and cerebrovascular diseases. Purpose Developing the novel method for non-invasive monitoring of age induced changes in arterial vessels. Methodology The pilot study was performed on 58 women, in good health, non-smokers, between the ages of 20 and 70, divided into three age groups. All subjects underwent arterial blood pressure measurement using a photoplethysmography sensor. Recordings were performed in left carotid artery and the left index finger area. Arterial blood flow waveform was then analyzed using DFA analysis, calculating the values of the scalar coefficients α1 and α2. Based on the waveform time interval shift between the standing and supine positions, the pulse wave velocity (PWV) ratio was determined. Results Systolic and diastolic arterial pressure showed a slight linear increase with the age, but without significant difference between the three age categories (p > 0.5). Also, the PWV ratio between the supine and standing positions did not show a statistically significant increase between the age groups. Only scalar coefficients ratio α1/α2 demonstrated a significant difference in value between all age categories. Conclusion In subjects included in this pilot study, only the scalar coefficients ratio varied significantly with the age, indicating the occurrence of structural changes in the cardiovascular system caused by biological aging.

#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?

Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS). Method We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score. Results A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22). Conclusion Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.

Alzheimer's disease: diagnosis and treatment, errors in patient management

Alzheimer's disease (AD) is the most common degenerative disease of the brain leading to dementia. AD is the most common cause of disability among age-related diseases. The diagnosis of AD is based on clinical findings and is confirmed by the presence of positive biological markers of the disease, which reflect the pathological formation of beta-amyloid and tau protein in the brain. Magnetic resonance imaging of the brain shows brain atrophy in AD and helps to rule out other diseases. Psychosocial and behavioral approaches form the basis for the treatment of patients with AD; cognitive training in combination with regular physical exercise is recommended. Acetylcholinesterase inhibitors and the glutamate receptor blocker memantine are used as drugs that improve the cognitive functions of patients with AD. Dispersible forms of memantine are used to treat dysphagia in patients with AD. The efficacy and safety of pathogenetic therapy aimed at eliminating cerebral beta-amyloid by passive immunization is under discussion. Unfortunately, AD is rarely diagnosed in our country; doctors are not sufficiently informed about the diagnosis and modern treatment methods of AD. Many AD patients are observed with the misdiagnosis of chronic cerebrovascular disease and do not receive effective therapy. A clinical observation of a patient with early-onset AD is presented, reflecting typical errors in patient management. Issues for optimizing the management of AD patients are discussed.

Risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly patients infected with the Omicron variant of SARS-CoV-2: a retrospective study at Shanghai Fourth People's Hospital, School of Medicine, Tongji University.

In elderly patients infected with the Omicron variant, disease progression to severe infection can result in poor outcomes. This study aimed to identify risk and protective factors associated with disease progression to severe infection and viral clearance time in elderly Omicron-infected patients. Shanghai Fourth People's Hospital, School of Medicine, Tongji University, was officially designated to provide treatment to patients with COVID-19. This study was conducted on confirmed Omicron cases admitted to the hospital between 10 April 2022 and 21 June 2022. In total, 1,568 patients aged 65 years or older were included. We conducted a retrospective, observational study using logistic regression to analyze risk and protective factors for the development of severe disease and Cox proportional hazards regression models to analyze factors influencing viral clearance time. Aged over 80 years, having 2 or more comorbidities, combined cerebrovascular disease, chronic neurological disease, and mental disorders were associated with the development of severe disease, and full vaccination was a protective factor. Furthermore, aged over 80 years, combined chronic respiratory disease, chronic renal disease, cerebrovascular disease, mental disorders, and high viral load were associated with prolonged viral clearance time, and full vaccination was a protective factor. This study analyzed risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly Omicron-infected patients. Aged patients with comorbidities had a higher risk of developing severe infection and had longer viral clearance, while vaccination protected them against the Omicron infection.

Red Blood Cell Distribution Width as a Risk Factor for 30/90-Day Mortality in Patients with Gastrointestinal Bleeding: Analysis of the MIMIC-IV Database.

The purpose of this research was to assess the relationship between red blood cell distribution width (RDW) and mortality in patients with gastrointestinal (GIB) bleeding in the intensive care unit (ICU). The information of the participantswas obtained from the Medical Information Mart for Intensive Care IV database. The main outcome of this research was 30/90-day mortality, with ICU mortality and in-hospital mortality as secondary outcomes. This research included 2924 patients with gastrointestinal bleeding in total. Patients with higher RDW had considerably higher 30/90-day and in-hospital mortality rates,as well as longer hospital stays and ICUstays. According to the Kaplan-Meier analysis, the 30/90-day mortality rate was remarkably higher among participants in the higher RDW group (P < 0.0001). In the adjusted multivariate Cox regression analysis, for 30-day mortality, the HR (95% CI) was 1.75 (1.37, 2.24) in comparison to Q1 in the reference group (P < 0.001). Analyses of 90-day mortality and in-hospital mortality both showed the same results. In the subgroup analysis, gender, myocardial infarction, chronic pulmonary disease, cerebrovascular disease and renal disease had no significant effect on the correlation between RDW values and mortality (all P > 0.05). The area under the ROC curve for RDW was 0.599 (95% CI 0.581-0.617) and 0.606 (95% CI 0.588-0.624) in 30/90-day ICU mortality. The current research showed that RDW could be utilized as an independent indicator of short-term mortality in critically ill GIB patients at 30 and 90days of hospital admission.

Clinical and neuroimaging correlations in patients with chronic cerebrovascular disease and type 2 diabetes mellitus

A comprehensive examination was made in 81 patients with chronic cerebrovascular disease (CVD) concurrent with type 2 diabetes mellitus. The patients were divided into 3 groups: 1) patients with mild cognitive impairment (CI) (Study Group 1); 2) patients with moderate CI (Study Group 2); 3) patients without CI (a comparison group). The investigators studied the neuroimaging structure of the brain substance (BS) and the state of the brachiocephalic vessels. The study showed that the morphofunctional changes in the brain were most pronounced in moderate CI Group 2, which confirmed the association between the severity of clinical manifestations of CVD and atherosclerotic lesions of the cerebral vessels and degenerative changes in the BS. Analysis of MMSE and MoCA scores indicated statistically significant differences between the indicators of the comparison group and the study groups, as well as between those of Groups 1 and 2. There were statistically significant differences in the incidence of postischemic subcortical cysts in the brain between Group 2 and the comparison group, as well as between Groups 1 and 2.

Travel distance and outcomes after surgical aortic valve among veterans.

To investigate the association between travel distance and postoperative length of stay (LOS) and discharge disposition among veterans undergoing surgical aortic valve replacement (SAVR). We performed a retrospective cohort study of patients undergoing SAVR, with or without coronary artery bypass grafting (CABG) at VA Boston Healthcare (January 1, 2005-December 31, 2015). Postoperative LOS and discharge disposition were compared for SAVR patients based on travel distance to the facility: <100 miles or ≥100 miles. Multivariable regression was performed to ascertain factors associated with LOS and home discharge. Data were collected via chart review. All patients undergoing SAVR at our institution who primarily resided within the defined region were included. Of 597 patients studied, 327 patients underwent isolated SAVR; 270 patients underwent SAVR/CABG. Overall median (IQR) distance between the patient's residence and the hospital was 49.95 miles (27.41-129.94 miles); 190 patients (32%) resided further than 100 miles away. There were no differences in the proportion of patients with diabetes, hypertension, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, atrial fibrillation, or prior myocardial infarction between groups. Overall LOS (IQR) was 9 (7-13) days and did not differ between groups (p = 0.18). The proportion of patients discharged home was higher among patients who resided more than 100 miles from the hospital (71% vs. 58%, p = 0.01). On multivariable analysis, residing further than 100 miles from the hospital was independently associated with home discharge (OR = 1.64, 95% CI: 1.09-2.48). Travel distance was not associated with LOS. Based on our institutional experience, potential concerns of longer hospital stay or discharge to other inpatient facilities for geographically distanced patients undergoing SAVR do not appear supported. Continued examination of the drivers underlying the marked shift of veterans to the private sector appears warranted.

Identification of diagnostic markers for moyamoya disease by combining bulk RNA-sequencing analysis and machine learning

Moyamoya disease (MMD) remains a chronic progressive cerebrovascular disease with unknown etiology. A growing number of reports describe the development of MMD relevant to infection or autoimmune diseases. Identifying biomarkers of MMD is to understand the pathogenesis and development of novel targeted therapy and may be the key to improving the patient’s outcome. Here, we analyzed gene expression from two GEO databases. To identify the MMD biomarkers, the weighted gene co-expression network analysis (WGCNA) and the differential expression analyses were conducted to identify 266 key genes. The KEGG and GO analyses were then performed to construct the protein interaction (PPI) network. The three machine-learning algorithms of support vector machine-recursive feature elimination (SVM-RFE), random forest and least absolute shrinkage and selection operator (LASSO) were used to analyze the key genes and take intersection to construct MMD diagnosis based on the four core genes found (ACAN, FREM1, TOP2A and UCHL1), with highly accurate AUCs of 0.805, 0.903, 0.815, 0.826. Gene enrichment analysis illustrated that the MMD samples revealed quite a few differences in pathways like one carbon pool by folate, aminoacyl-tRNA biosynthesis, fat digestion and absorption and fructose and mannose metabolism. In addition, the immune infiltration profile demonstrated that ACAN expression was associated with mast cells resting, FREM1 expression was associated with T cells CD4 naive, TOP2A expression was associated with B cells memory, UCHL1 expression was associated with mast cells activated. Ultimately, the four key genes were verified by qPCR. Taken together, our study analyzed the diagnostic biomarkers and immune infiltration characteristics of MMD, which may shed light on the potential intervention targets of moyamoya disease patients

Associations between air pollution and the risk of first admission and multiple readmissions for cardiovascular diseases

ObjectivesWe aimed to investigate the associations between air pollutants and the risk of admission and multiple readmission events for cardiovascular disease (CVD).MethodsA total of 285 009 participants free of CVD...

The effects of anastomoses between anterior and posterior circulation on postoperative prognosis of patients with moyamoya disease

BackgroundMoyamoya disease (MMD) is a chronic ischemic cerebrovascular disease. Collateral circulation in MMD has emerged as a research focus. Our aims were to assess the impact of anastomoses between the anterior and posterior circulations on the prognosis of MMD patients.MethodsWe reviewed the preoperative digital subtraction angiography images of patients with MMD who underwent revascularization surgery at our hospital between March 2014 and May 2020 and divided the patients into two groups: those with anastomoses (PtoA group) and those without anastomoses (non-PtoA group). The differences in follow-up (more than 6 months) collateral vessel establishment (Matsushima grade) and the modified Rankin Scale (mRS) were compared between the two groups as well as between the patients with different degrees of anastomoses. The early complications following revascularization were also compared between the two groups.ResultsThis study included 104 patients with MMD, of which 38 were non-PtoA and 66 were PtoA. There were no significant differences in Matsushima score (P = 0.252) and mRS score (P = 0.066) between the two groups. In addition, Matsushima score (P = 0.243) and mRS score (P = 0.360) did not differ significantly between patients with different degrees of anastomoses. However, the non-PtoA group had a significantly higher rate of cerebral hyperperfusion syndrome (CHS) than the PtoA group (34.2% vs 16.7%, P = 0.041).ConclusionMMD patients without anastomoses between anterior and posterior circulations preoperatively should be vigilant of the occurrence of CHS in the early stages after revascularization.

Clinical characteristics of elderly hip fracture patients with chronic cerebrovascular disease and construction of a clinical predictive model for perioperative pneumonia

IntroductionThe recovery of cerebrovascular disease (CVD) will increase the incidence of perioperative pneumonia (POP). However, there is limited research on POP in elderly patients with hip fractures complicated by CVD. Therefore, our research focuses on the following two issues: (1) What are the clinical features of elderly patients with hip fractures combined with CVD? (2) What are the predictive factors for the occurrence of POP in such patients? HypothesisMale, femoral neck fracture and hypoalbuminemia can be predictive factors for the development of POP after hip fracture in CVD patients. Material and methodsThis is a nested case-control study that included patients aged 65 to 105 years with CVD who had a hip fracture between January 2021 and January 2023. According to the occurrence of POP, they were divided into case group and control group. Collecting data includes demographic information, clinical data, and surgical information. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses were used to select variables. The constructed predictive model was transformed into a nomogram. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). ResultsWe ultimately included 714 patients, 69.3% female, with a median age of 80 years. Asymptomatic cerebral infarction (ACI) is the most common CVD (55.7%). More patients developed intertrochanteric fractures than femoral neck fractures (57.1 vs. 42.9%). In total, 606 patients (84.9%) underwent surgery. The most common perioperative complications were anemia (76.9%) and hypoalbuminemia (71.8%). POP (20.0%) was more common preoperatively (89.5%). Factors such as fracture type, surgical wait time, implant used for surgery, and anesthesia type did not differ between the presence or absence of postoperative pneumonia. 143 patients with POP served as the case group. Five hundred and seventy one patients did not develop POP and served as the control group. The predictors of POP were male (OR 1.699,95%CI 1.150–2.511, p<0.05), femoral neck fracture (OR 2.182,95%CI 1.491–3.192, p<0.05), and hypoalbuminemia (OR 3.062, 95%CI 1.833–5.116, p<0.05). This model has good discrimination, calibration, and clinical practicality. DiscussionIn this study, we constructed a clinical prediction model for the occurrence of POP in CVD combined with hip fracture in the elderly, with risk factors including gender, fracture type and perioperative hypoproteinemia. Therefore, we can take effective preventive measures against the occurrence of POP in patients with these factors in our clinical work. Level of proofIV; nested case-control study.

Impairment of attention and executive functions in chronic cerebrovascular disease and Alzheimer's disease

To establish specific features of executive functions (EF) impairment and attention in vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Eighty people (over the age of 50) diagnosed with cerebrovascular disease (CVD) and AD, as well as 29 healthy volunteers (control group), were examined. The following neuropsychological methods were used to study the quantitative and qualitative characteristics of cognitive impairments: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), EXIT-25, Frontal Assessment Battery (FAB), Clock Drawing Test, «12 Words» test, verbal associations (literal and categorical) method, Trail Making Test A and B, Symbol-Digit Modalities Test (SDMT), Stroop Test, and Benton Visual Retention Test. Mandatory inclusion criteria in the study included having a completed magnetic resonance imaging (MRI) of the brain (in T1, T2, FLAIR, DWI, SWI modes) within 1 year before enrollment in one of the groups. No significant differences in age, sex, and level of education were found between the groups. Groups AD and CVD were also comparable in the severity of cognitive impairment overall. Attention and working memory deficits were observed in both CVD and AD, with slightly more pronounced deficits in the AD group. Qualitative analysis of individual components of working memory revealed that both CVD and AD groups had comparable cognitive control impairment compared to the control group, while AD was characterized by a more significant decrease in intellectual flexibility compared to CVD. Sustained attention was equally impaired among patients in the CVD and AD groups, with a significant difference from the control group (p<0.05). In terms of memory, it was found that auditory-verbal memory and semantic memory were significantly more affected in AD, while visual memory was impaired in both conditions. Attention and EF impairments are not specific to the «subcortical» type of cognitive disorders. Already in the early stages, AD is characterized by a significant impairment of attention and EF, and such a component of EF as intellectual flexibility suffers at the onset of AD to a greater extent than in VCI. Memory impairments are not specific to AD; already at the onset of VCI, visual memory impairment comparable to AD is noted. The obtained data can be used for early neuropsychological diagnosis and differential diagnosis of dementing cerebral diseases.

Clinical value of retinol binding protein, C-reactive protein and urine microalbumin in patients with chronic renal disease and ischemic cerebrovascular disease.

To explore the diagnostic value of retinol binding protein (RBP), C-reactive protein (CRP) and urine microalbumin (UMA) for ischemic cerebrovascular disease (ICD) in patients with chronic kidney disease (CKD). In this study, a total of 118 patients with CKD were selected and grouped into two groups: a group of patients who were complicated with ICD (CKD+ICD group, n=58), and a group of patients with CKD only (CKD group, n=60). Then, the patients in the CKD+ICD group were further classified into a good prognosis group and a bad prognosis group according their modified Rankin scale score at sixth months after discharge. Serum RBP, CRP and urine UMA levels were compared between the CKD group and CKD+ICD group. The diagnostic efficiency of serum RBP, CRP and urine UMA levels for ICD in patients with CKD was analyzed. The receiver operating characteristic (ROC) curve was used to assess their prognostic performance. Logistic regression analysis was used to evaluate the risk factors for poor prognosis of patients with CKD and ICD. The levels of RBP, CRP, and UMA in the CKD+ICD group were significantly higher than those in the CKD group (all P<0.05). RBP demonstrated the highest diagnostic accuracy and sensitivity for ICD in CKD patients, while CRP and UMA exhibited equivalent specificity, surpassing that of RBP. ROC curves showed that the areas under the curve (AUCs) of RBP and CRP were significantly greater than that of UMA (P<0.05) and there was no significant difference for AUCs between RBP and CRP. In addition, the levels of RBP, CRP and UMA in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). Logistic regression analysis showed that RBP, CRP and UMA were independent risk factors for the poor prognosis of patients with CKD and ICD (Odds ratios =2.507, 3.677 and 1.919, respectively; all P<0.05). The assessment of RBP, CRP and UMA is recommended for diagnosis of ICD in CKD patients. RBP, CRP and UMA are independent risk factors for poor prognosis of CKD patients with ICD.

Ethoxyquin, a Lipid Peroxidation Inhibitor, Has Protective Effects against White Matter Lesions in a Mouse Model of Chronic Cerebral Hypoperfusion.

White matter lesions induced by chronic cerebral hypoperfusion can cause vascular dementia; however, no appropriate treatments are currently available for these diseases. In this study, we investigated lipid peroxidation, which has recently been pointed out to be associated with cerebrovascular disease and vascular dementia, as a therapeutic target for chronic cerebral hypoperfusion. We used ethoxyquin, a lipid-soluble antioxidant, in a neuronal cell line and mouse model of the disease. The cytoprotective effect of ethoxyquin on glutamate-stimulated HT-22 cells, a mouse hippocampal cell line, was comparable to that of a ferroptosis inhibitor. In addition, the administration of ethoxyquin to bilateral common carotid artery stenosis model mice suppressed white matter lesions, blood-brain barrier disruption, and glial cell activation. Taken together, we propose that the inhibition of lipid peroxidation may be a useful therapeutic approach for chronic cerebrovascular disease and the resulting white matter lesions.

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels. Immune inflammation is associated with the occurrence and development of MMD. However, the mechanisms underlying the formation of the abnormal vascular network remain unclear. Twenty-eight patients with MMD, 26 ischemic stroke patients, and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were higher in MMD patients than in healthy controls (P <0.01), and GM-CSF was mainly from Th1 and Th17 cells in MMD. We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis, inflammation, and chemotaxis. In summary, our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

Health and job-related factors associated with work ability in older working populations of Korea.

Knowledge about determinants of workability is crucial for designing interventions to increase the participation of older employees in the workforce and maintain or increase their productivity levels at work. This study explored the impact of health conditions and job characteristics on poor work ability. This study used data from the Korean Longitudinal Study of Aging (KLoSA) from 2014 to 2020, which is a nationally representative population-based panel study of Korean citizens aged ≥45 years. The KLoSA survey assessed subjective work ability using work ability score. The participants were asked if they had been diagnosed with any underlying diseases by a physician. The job characteristics were assessed in terms of working conditions and satisfaction. Generalized estimating equations were used to calculate the odds ratios (ORs) and 95% confidence intervals for workers' health-related variables and job characteristics associated with poor work ability. The results showed that workers' health-related factors were associated with poor work ability; poor vision (OR = 1.52) and bad hearing ability (OR = 2.37); low gripping strength (OR = 2.29); poor self-rated health (OR = 3.77) and various diseases such as hypertension, diabetes, cancer, chronic lung disease, liver disease, heart disease, cerebrovascular disease, mental illness, arthritis, prostate disease, gastrointestinal disease and disc disease. Additionally, high physical work demands (OR = 1.51) and low job satisfaction (OR = 4.23) were highly correlated with poor work ability. The findings addressing poor work abilities caused by individuals' health- and job-related factors can help prioritize worker health management and the development of more effective human capital investment strategies at the workplace.

Assessment of plasma soluble Tie-2 level to distinguish moyamoya disease from atherosclerotic cerebrovascular disease and predict postoperative neovascularization.

Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease and features the formation of hazy collateral vessels at the base of the brain. Angiopoietin (Ang)-1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) that regulate angiogenesis might be important in MMD pathophysiology and postoperative collateral formation. The goal of this study was to determine whether levels of these angiogenic factors could predict collateralization in patients with MMD. A total of 196 patients with MMD and 57 with atherosclerotic cerebrovascular disease serving as controls were enrolled. Ang-1, Ang-2, Tie-2, and VEGF mRNA levels were analyzed in middle cerebral artery (MCA) arterial wall specimens by using real-time quantitative polymerase chain reaction. MCA and peripheral plasma concentrations of Ang-1, Ang-2, soluble Tie-2 (sTie-2), and VEGF were examined by enzyme-linked immunosorbent assay. Cerebral arteriography was performed 6 months after bypass surgery to assess the postoperative collateralization. In MCA specimens, patients with MMD exhibited higher expression levels of Ang-1 and Ang-2 but lowered VEGF expression. The patients with MMD had significantly higher concentrations of Ang-1 and Ang-2 but lower levels of VEGF in MCA plasma. Peripheral plasma concentrations of these growth factors were not changed. MCA and peripheral plasma sTie-2 levels were both reduced in patients with MMD. The 6-month follow-up showed that patients with good collateral formation had lower sTie-2 levels in both MCA and peripheral plasma. Furthermore, the Suzuki stage and peripheral plasma sTie-2 level were significantly correlated with good postoperative collateral formation on multivariate analysis. Ang-1, Ang-2, Tie-2, and VEGF are involved in MMD pathogenesis. The peripheral plasma level of sTie-2 can differentiate MMD from atherosclerotic cerebrovascular disease and serve as a novel biomarker to predict postoperative collateral formation.

Exosomal miRNAs as Biomarkers of Ischemic Stroke.

Exosomes are small lipid bilayer membrane particles released from all living cells into the extracellular environment. They carry several molecules and have a critical role in cell-cell communication under physiological and pathological conditions. In recent decades, exosomes, and especially their cargo, have emerged as a promising tool for several clinical conditions. However, the literature has become increasingly unambiguous in defining the role of exosomes in chronic cerebrovascular diseases. Because they can pass through the blood-brain barrier, they have great potential to reflect intracerebral changes. They can, thus, provide valuable insight into the mechanisms of central nervous system diseases. The purpose of this review is to describe the literature on the role of exosomal miRNA, which represents the most widely investigated exosomal biomarker, in strokes. First, we provide an overview of exosomes, from biology to isolation and characterization. Then, we describe the relationship between exosomes and stroke pathogenesis. Finally, we summarize the human studies evaluating exosomal miRNA biomarkers of stroke. Although the collective literature supports the potential use of exosomal miRNA as biomarkers of ischemic stroke, there are still several limitations hampering their introduction into clinical practice.

Clinical observation of patient with moya-moya syndrome complicated by transient ischemic attack followed by development of hemorrhagic stroke. Features of diagnosis and treatment

Moya-moya syndrome is a chronic cerebrovascular disease associated with narrowing of the arteries of the brain, manifested by headache, epileptic seizures, transient ischemic attack, leading to the development of ischemic or hemorrhagic stroke. To date, the main pathogenetic mechanisms of moya-moya syndrome have not yet been fully identified, but some studies have shown that an important component of the development of moya-moya is a genetic factor. However, if the issue of diagnosis of this syndrome can be considered solved – it is the use of neuroimaging methods (MRI, CT) with contrast of cerebral vessels, then the issue of treatment remains relevant. The article presents a clinical case of a patient with moya-moya syndrome with the transformation of an ischemic stroke into a hemorrhagic type.

Mortality Risk and Burden From a Spectrum of Causes in Relation to Size-Fractionated Particulate Matters: Time Series Analysis.

There is limited evidence regarding the adverse impact of particulate matters (PMs) on multiple body systems from both epidemiological and mechanistic studies. The association between size-fractionated PMs and mortality risk, as well as the burden of a whole spectrum of causes of death, remains poorly characterized. We aimed to examine the wide range of susceptible diseases affected by different sizes of PMs. We also assessed the association between PMs with an aerodynamic diameter less than 1 µm (PM1), 2.5 µm (PM2.5), and 10 µm (PM10) and deaths from 36 causes in Guangzhou, China. Daily data were obtained on cause-specific mortality, PMs, and meteorology from 2014 to 2016. A time-stratified case-crossover approach was applied to estimate the risk and burden of cause-specific mortality attributable to PMs after adjusting for potential confounding variables, such as long-term trend and seasonality, relative humidity, temperature, air pressure, and public holidays. Stratification analyses were further conducted to explore the potential modification effects of season and demographic characteristics (eg, gender and age). We also assessed the reduction in mortality achieved by meeting the new air quality guidelines set by the World Health Organization (WHO). Positive and monotonic associations were generally observed between PMs and mortality. For every 10 μg/m3 increase in 4-day moving average concentrations of PM1, PM2.5, and PM10, the risk of all-cause mortality increased by 2.00% (95% CI 1.08%-2.92%), 1.54% (95% CI 0.93%-2.16%), and 1.38% (95% CI 0.95%-1.82%), respectively. Significant effects of size-fractionated PMs were observed for deaths attributed to nonaccidental causes, cardiovascular disease, respiratory disease, neoplasms, chronic rheumatic heart diseases, hypertensive diseases, cerebrovascular diseases, stroke, influenza, and pneumonia. If daily concentrations of PM1, PM2.5, and PM10 reached the WHO target levels of 10, 15, and 45 μg/m3, 7921 (95% empirical CI [eCI] 4454-11,206), 8303 (95% eCI 5063-11,248), and 8326 (95% eCI 5980-10690) deaths could be prevented, respectively. The effect estimates of PMs were relatively higher during hot months, among female individuals, and among those aged 85 years and older, although the differences between subgroups were not statistically significant. We observed positive and monotonical exposure-response curves between PMs and deaths from several diseases. The effect of PM1 was stronger on mortality than that of PM2.5 and PM10. A substantial number of premature deaths could be preventable by adhering to the WHO's new guidelines for PMs. Our findings highlight the importance of a size-based strategy in controlling PMs and managing their health impact.