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Stroke intervention and pharmacotherapy guidelines Knowledge-to-practice translation gaps among the emergency resident physicians in Riyadh, Saudi Arabia.

Translating the updated medical guidelines into routine clinical practice is an important initiative to improve the populations health and decrease disease outcomes. A cross-sectional survey-based study was conducted in Riyadh City, Saudi Arabia, to evaluate the knowledge and degree of application (practice) of the stroke management guidelines among emergency resident physicians. An interview-based self-administered questionnaire was used to survey the emergency resident doctors in Riyadh hospitals from May 2019 to January 2020. Of 129 participants, 78 valid, complete responses were obtained (60.5% response rate). Descriptive statistics, principle component, and correlation analyses were used. Most resident doctors were men(69.4%) with a mean age of 28.4±3.37 years. More than 60% of the residents were satisfied with their knowledge of the stroke guidelines meanwhile, 46.2% were satisfied with their application of the guidelines. Both Knowledge and practice compliance components were significantly and positively correlated. Also, both components were significantly correlated with being updated, aware of, and strictly following these guidelines. The mini-test challenge showed a negative result with a mean knowledge score of 1.03±0.88. Even though the majority of participants utilized different tools of education and were aware of the American Stroke Association Guidelines. It was concluded that a considerable gap in the residents knowledge regarding the current stroke management guidelines was present in Saudi hospitals. Also, it was reflected on their actual implementation and application into clinical practice. Continuous medical education, training, and follow-up of the emergency resident doctors, administered as a part of the government health programs, are crucial to improve the health care delivery for acute stroke patients.

Identification microenvironment immune features and key genes in elderly stroke patients.

The purpose of this study was to identify the signaling pathways and immune microenvironments related to elderly stroke patients. We downloaded the public transcriptome data (GSE37587) from the gene expression omnibus and divided the patients into young and old groups and identified differentially expressed genes (DEGs). Gene ontology function analysis, Kyoto encyclopedia of genes and genomes pathway analysis, and gene set enrichment analysis (GSEA) were performed. A protein-protein interaction network was constructed and hub genes were identified. Gene-miRNA, gene-TF, and gene-drug networks were constructed using the network analyst database. The immune infiltration score was evaluated using single-sample gene set enrichment analysis GSEA, its correlation with age was computed and visualized using R software. We identified 240 DEGs, including 222 upregulated and 18 downregulated DEGs. Gene ontology enrichment was significantly enriched in response to the virus, type I interferon signaling pathway, cytological component, focal adhesion, cell-substrate adherents junction, and the cytosolic ribosome. GSEA identified the following mechanisms heme metabolism, interferon gamma response, and interferon alpha response. Ten hub genes included interferon alpha-inducible protein 27, human leucocyte antigen-G, interferon-induced protein with tetratricopeptide repeats 2, 2-5-oligoadenylate synthetase 2, interferon alpha-inducible protein 6, interferon alpha-inducible protein 44-like, interferon-induced protein with tetratricopeptide repeats 3, interferon regulatory factor 5, myxovirus resistant 1, and interferon-induced protein with tetratricopeptide repeats 1. Quantitative analysis of immune infiltration showed that increased age was significantly positively correlated with myeloid-derived suppressor cells and natural killer T cells, and negatively correlated with immature dendritic cells. The present research could help us better understand the molecular mechanisms and immune microenvironment of elderly patients with stroke.

Acupuncture for thalamic pain after stroke A systematic review and meta-analysis.

To evaluate the efficacy and safety of acupuncture on thalamic pain after stroke. The self-established database was searched from 8 Chinese and English databases to June 2022, and the randomized controlled trials articles on the comparative treatment of thalamic pain after stroke with acupuncture were included. That visual analog scale, present pain intensity score, pain rating index, the total efficiency, and adverse reactions were mainly used to evaluate the outcomes. A total of 11 papers were included. Meta-analysis showed that acupuncture appeared to be more effective than drugs for treatment of thalamic pain, as assessed by the visual analog scale mean difference (MD) -1.06, 95% confidence interval (CI) (-1.20, -0.91), P < .00001, the present pain intensity score MD -0.27, 95% CI (-0.43, -0.11), P .001, the pain rating index MD -1.02, 95% CI (-1.41, -0.63), P < .00001, and the total efficiency risk ratio 1.31, 95% CI (1.22,1.41), P < .00001. Meta-analysis results show that there is no significant difference in safety between acupuncture and drug therapy risk ratio 0.50, 95% CI (0.30,0.84), P .009. Studies have shown that acupuncture in the treatment of thalamic pain is effective, and it does not prove to have a higher safety than drug treatment, therefore a large-scale multicenter randomized controlled trials study is needed to further prove.

Edaravone combined with Shuxuening versus edaravone alone in the treatment of acute cerebral infarction A systematic review and meta-analysis.

Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction. PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Seventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio 3.94 95% CI 2.85, 5.44 I2 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD -1.39 95% CI -1.73, -1.05 I2 71%, P < .00001), lower neural function defect score (SMD -0.75 95% CI -1.06,-0.43 I2 67%, P < .00001), and lower level of neuron-specific enolase (SMD -2.10 95% CI -2.85, -1.35 I2 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD -0.87 95% CI -1.17, -0.57 I2 0%, P < .00001), and whole blood low shear viscosity (SMD -1.50 95% CI -1.65, -1.36 I2 0%, P < .00001) compared to ERI alone. ERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.

Phase I cardiac rehabilitation with 5-phase music after emergency percutaneous coronary intervention for acute myocardial infarction A prospective randomized study.

Five-phase music therapy was reported to be effective in the treatment and rehabilitation of several diseases. This study explored the effect of phase I cardiac rehabilitation combined with 5-phase music in acute myocardial infarction (AMI) patients after emergency percutaneous coronary intervention. This prospective pilot study enrolled AMI patients who received percutaneous coronary intervention from the Traditional Chinese Medicine Hospital from July 2018 to December 2019. The participants were randomized in a 111 ratio to the control, cardiac rehabilitation, and rehabilitation-music groups. The primary endpoint was the hospital anxiety and depression scale. The secondary endpoints were the myocardial infarction dimensional assessment scale, self-rating sleep status, 6-minute walk test, and left ventricular ejection fraction. The study included 150 AMI patients (n 50group). Hospital anxiety and depression scale showed significant time effects for both anxiety and depression (both P < .05), a treatment effect for depression (P .02), and an interaction effect for anxiety (P .02). A time effect was also observed for diet, sleep disorders, 6-minute walk test, and left ventricular ejection fraction (all P < .001). A difference among groups was observed for emotional reaction (P .001). Interactions effects were observed for diet (P .01) and sleep disorders (P .03). Phase I cardiac rehabilitation combined with 5-phase music could alleviate anxiety and depression and improve sleep quality.

Regulatory mechanism of immune-related genes in patients with hypertension.

Hypertension (HT) is among the most common cardiovascular diseases in the world and is an important risk factor for stroke, myocardial infarction, heart failure, and kidney failure. Recent studies have demonstrated that activation of the immune system plays an important role in the occurrence and maintenance of HT. Thus, this research aimed to determine the immune-related biomarkers in HT. In this study, RNA sequencing data of the gene expression profiling datasets (GSE74144) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes between HT and normal samples were identified using the software limma. The immune-related genes associated with HT were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the program clusterProfiler of the R package. The protein-protein interaction network of these differentially expressed immune-related genes (DEIRGs) was constructed based on the information from the STRING database. Finally, the TF-hub and miRNA-hub gene regulatory networks were predicted and constructed using the miRNet software. Fifty-nine DEIRGs were observed in HT. The Gene Ontology analysis indicated that DEIRGs were mainly enriched in the positive regulation of cytosolic calcium ions, peptide hormones, protein kinase B signaling, and lymphocyte differentiation. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these DEIRGs were significantly involved in the intestinal immune network for IgA production, autoimmune thyroid disease, JAK-STAT signaling pathway, hepatocellular carcinoma, and Kaposi sarcoma-associated herpesvirus infection, among others. From the protein-protein interaction network, 5 hub genes (insulin-like growth factor 2, cytokine-inducible Src homology 2-containing protein, suppressor of cytokine signaling 1, cyclin-dependent kinase inhibitor 2A, and epidermal growth factor receptor) were identified. The receiver operating characteristic curve analysis was performed in GSE74144, and all genes with an area under the curve of > 0.7 were identified as the diagnostic genes. Moreover, miRNA-mRNA and TF-mRNA regulatory networks were constructed. Our study identified 5 immune-related hub genes in patients with HT and demonstrated that they were potential diagnostic biomarkers for HT.

Efficacy and safety of Guipi Decoction in the treatment of chronic heart failure A systematic review and meta-analysis of randomized controlled trials.

Chronic heart failure (CHF) is the ultimate destination of most cardiovascular diseases and one of the leading causes of death for the elderly. Despite significant advances in the therapy of heart failure, the mortality and rehospitalization rates remain high. Guipi Decoction (GPD) has been reported to be significantly effective on patients with CHF, but it still lacks evidence-based medicine support. Two investigators systematically searched a total of 8 databases including PubMed, Embase, The Cochrane Library, Web of Science, Wanfang, China National Knowledge Infrastructure (CNKI), VIP, and CBM from construction to Nov 2022. Randomized controlled trials that compared GPD or in combination with conventional western medicine versus western medicine alone in the treatment of CHF were eligible for selection. The quality of included studies were evaluated and assigned data were extracted according to the method provided by Cochrane. All analyses used Review Manager 5.3 software. The search identified 17 studies with a sample size of 1806 patients. Meta-analysis showed that GPD intervention was associated with an improvement in total clinical effective rate with a relative risk of 1.19 (95% confidence interval CI 1.15, 1.24), P < .00001. In terms of cardiac function and ventricular remodeling, GPT could improve left ventricular ejection fraction (mean difference MD 6.41, 95% CI 4.32, 8.50, P < .00001), reduce left ventricular end diastolic diameter (MD -6.22, 95% CI -7.17, -5.28, P < .00001) and left ventricular end systolic diameter (MD -4.92, 95% CI -5.93, -3.90, P < .00001). In terms of hematological indices, GPD could decrease the levels of N-terminal pro-brain natriuretic peptide (standardized MD -2.31, 95% CI -3.05, -1.58, P < .00001) and C-reactive protein (MD -3.51, 95% CI -4.10, -2.92, P < .00001). And the analysis of safety revealed no significant differences in adverse effects between the 2 groups with a relative risk of 0.56 (95% CI 0.20, 0.89, P .55). GPD can improve cardiac function and inhibit ventricular remodeling with few adverse effects. However, more rigorous and high-quality randomized controlled trials are needed to verify the conclusion.

The impact of SARS-CoV-2 infection on the outcome of acute ischemic stroke-A retrospective cohort study.

Acute ischemic stroke (AIS) is a common complication of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection (COVID-19), but the prognosis of these patients is poorly understood. To explore the impact of COVID-19 on neurological outcomes in AIS patients. A comparative retrospective cohort study was conducted in 32 consecutive AIS patients with and 51 without COVID-19 between the 1st of March 2020 and 1st of May 2021. The evaluation was based on a detailed chart review for demographic data, medical history, stroke severity, cranial and vessel imaging results, laboratory parameters, COVID-19 severity, hospitalization time, in-hospital mortality, and functional deficits at discharge (modified Rankin Scale, mRS). COVID-19 AIS patients showed tendency to worse initial neurological deficit (NIHSS 9 (3-13) vs. 4 (2-10) p 0.06), higher rate of large vessel occlusion (LVO 1332 vs. 1451 p 0.21), had prolonged hospitalization (19.4 ± 17.7 vs. 9.7 ± 7 days p 0.003), had lower chance of functional independence (mRS≤2) (1232 vs. 3251 p 0.02) and showed higher in-hospital mortality (1032 vs. 651 p 0.02). In COVID-19 AIS patients, LVO was more common with COVID-19 pneumonia than without (55.6% vs. 23.1% p 0.139). COVID-19-related AIS carries a worse prognosis. COVID-19 with pneumonia seems to be associated with a higher rate of LVO.

Predictors of post-stroke cognitive impairment at three-month following first episode of stroke among patients attended at tertiary hospitals in Dodoma, central Tanzania A protocol of a prospective longitudinal observational study metadata.

Neurocognitive deficits after stroke are a common manifestation and pose a significant impact on the quality of life for patients and families however, little attention is given to the burden and associated impact of cognitive impairment following stroke. The study aims to determine the prevalence and predictors of post-stroke cognitive impairment (PSCI) among adult stroke patients admitted to tertiary hospitals in Dodoma, Tanzania. A prospective longitudinal study is conducted at tertiary hospitals in the Dodoma region, central Tanzania. Participants with the first stroke confirmed by CTMRI brain aged ≥ 18 years who meet the inclusion criteria are enrolled and followed up. Baseline socio-demographic and clinical factors are identified during admission, while other clinical variables are determined during the three-month follow-up period. Descriptive statistics are used to summarize data continuous data will be reported as Mean (SD) or Median (IQR), and categorical data will be summarized using proportions and frequencies. Univariate and multivariate logistic regression analysis will be used to determine predictors of PSCI.

Investigation of in-phase bilateral exercise effects on corticospinal plasticity in relapsing remitting multiple sclerosis A registered report single-case concurrent multiple baseline design across five subjects.

Relapsing-remitting Multiple Sclerosis is the most common demyelinating neurodegenerative disease and is characterized by periods of relapses and generation of various motor symptoms. These symptoms are associated with the corticospinal tract integrity, which is quantified by means of corticospinal plasticity which can be probed via transcranial magnetic stimulation and assessed with corticospinal excitability measures. Several factors, such as exercise and interlimb coordination, can influence corticospinal plasticity. Previous work in healthy and in chronic stroke survivors showed that the greatest improvement in corticospinal plasticity occurred during in-phase bilateral exercises of the upper limbs. During in-phase bilateral movement, both upper limbs are moving simultaneously, activating the same muscle groups and triggering the same brain region respectively. Altered corticospinal plasticity due to bilateral cortical lesions is common in MS, yet, the impact of these type of exercises in this cohort is unclear. The aim of this concurrent multiple baseline design study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures using transcranial magnetic stimulation and standardized clinical assessment in five people with relapsing-remitting MS. The intervention protocol will last for 12 consecutive weeks (30-60 minutes session x 3 sessionsweek) and include in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training. To define functional relation between the intervention and the results on corticospinal plasticity (central motor conduction time, resting motor threshold, motor evoked potential amplitude and latency) and on clinical measures (balance, gait, bilateral hand dexterity and strength, cognitive function), we will perform a visual analysis and if there is a potential sizeable effect, we will perform statistical analysis. A possible effect from our study, will introduce a proof-of-concept for this type of exercise that will be effective during disease progression. Trial registration ClinicalTrials.gov NCT05367947.

Impact of gender on mid-term prognosis of patients undergoing coronary artery bypass grafting.

We evaluated the impact of sex on mid-term prognosis in patients who underwent coronary artery bypass grafting (CABG). Data on gender differences in current management or clinical outcomes after CABG are controversial, and there have been limited data focusing on them. This was a retrospective and prospective, single-center, observational study. Between January 2001 and December 2017, 6613 patients who underwent CABG were enrolled from an institutional registry of Samsung Medical Center, Seoul, Korea (Clinicaltrials.gov, NCT03870815) and divided into two groups according to sex (female group, n 1679 vs. male group, n 4934). The primary outcome was cardiovascular death or myocardial infarction (MI) at 5 years. Propensity score matching analysis was performed to reduce confounding factors. During a mean follow-up duration of 54 months, a total of 252 cardiovascular death or MIs occurred (female, 78 7.5% vs. male, 174 5.7%). Multivariate analysis revealed no significant difference in the incidence of cardiovascular death or MI at 5 years between female and male groups (hazard ratio HR 1.05 95% confidence interval CI 0.78 to 1.41 p 0.735). After propensity score matching, the incidence of cardiovascular death or MI was still similar between the two groups (HR 1.08 95% CI 0.76 to 1.54 p 0.666). The similarity of long-term outcomes between the two groups was consistent across various subgroups. There was also no significant difference in the risk of 5-year cardiovascular death or MI between males and females according to age (pre- and postmenopausal status) (p for interaction 0.437). After adjusting for baseline differences, sex does not appear to influence long-term risk of cardiovascular death or MI in patients undergoing CABG. NCT03870815.

Assessment of Frailty Index at 66 Years of Age and Association With Age-Related Diseases, Disability, and Death Over 10 Years in Korea.

A frailty index has been proposed as a measure of aging among older individuals. However, few studies have examined whether a frailty index measured at the same chronologic age at younger ages could forecast the development of new age-related conditions. To examine the association of the frailty index at 66 years of age with incident age-related diseases, disability, and death over 10 years. This retrospective nationwide cohort study used the Korean National Health Insurance database to identify 968 885 Korean individuals who attended the National Screening Program for Transitional Ages at 66 years of age between January 1, 2007, and December 31, 2017. Data were analyzed from October 1, 2020, to January 2022. Frailty was defined using a 39-item frailty index ranging from 0 to 1.00 as robust (<0.15), prefrail (0.15-0.24), mildly frail (0.25-0.34), and moderately to severely frail (≥0.35). The primary outcome was all-cause death. Secondary outcomes were 8 age-related chronic diseases (congestive heart failure, coronary artery disease, stroke, type 2 diabetes, cancer, dementia, fall, and fracture) and disability qualifying for long-term care services. Cox proportional hazards regression and cause-specific and subdistribution hazards regression were used to examine hazard ratios (HRs) and 95% CIs for the outcomes until the earliest of date of death, the occurrence of relevant age-related conditions, 10 years from the screening examination, or December 31, 2019. Among the 968 885 participants included in the analysis (517 052 women 53.4%), the majority were classified as robust (65.2%) or prefrail (28.2%) only a small fraction were classified as mildly frail (5.7%) or moderately to severely frail (1.0%). The mean frailty index was 0.13 (SD, 0.07), and 64 415 (6.6%) were frail. Compared with the robust group, those in the moderately to severely frail group were more likely to be women (47.8% vs 61.7%), receiving medical aid insurance for low income (2.1% vs 18.9%), and less active (median, 657 IQR, 219-1133 vs 319 IQR, 0-693 metabolic equivalent task minwk). After adjusting for sociodemographic and lifestyle characteristics, moderate to severe frailty was associated with increased rates of death (HR, 4.43 95% CI, 4.24-4.64) and new diagnosis of all chronic diseases, including congestive heart failure (adjusted cause-specific HR, 2.90 95% CI, 2.67-3.15), coronary artery disease (adjusted cause-specific HR, 1.98 95% CI, 1.85-2.12), stroke (adjusted cause-specific HR, 2.22 95% CI, 2.10-2.34), diabetes (adjusted cause-specific HR, 2.34 95% CI, 2.21-2.47), cancer (adjusted cause-specific HR, 1.10 95% CI, 1.03-1.18), dementia (adjusted cause-specific HR, 3.59 95% CI, 3.42-3.77), fall (adjusted cause-specific HR, 2.76 95% CI, 2.29-3.32), fracture (adjusted cause-specific HR, 1.54 95% CI, 1.48-1.62), and disability (adjusted cause-specific HR, 10.85 95% CI, 10.00-11.70). Frailty was associated with increased 10-year incidence of all the outcomes, except for cancer (moderate to severe frailty adjusted subdistribution HR, 0.99 95% CI, 0.92-1.06). Frailty at 66 years of age was associated with greater acquisition of age-related conditions (mean SD conditions per year for the robust group, 0.14 0.32 for the moderately to severely frail group, 0.45 0.87) in the next 10 years. The findings of this cohort study suggest that a frailty index measured at 66 years of age was associated with accelerated acquisition of age-related conditions, disability, and death over the next 10 years. Measuring frailty at this age may offer opportunities to prevent age-related health decline.

Estimated Burden of Stroke in China in 2020.

Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. The study included 676 394 Chinese adults (395 122 58.4% females mean SD age, 59.7 11.0 years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% 95% CI, 2.6%-2.7% vs 2.5% 95% CI, 2.5%-2.6% P .02), but the incidence rate (485.5 95% CI, 462.8-508.3 vs 520.8 95% CI, 496.3-545.2 per 100 000 person-years P < .001) and mortality rate (309.9 95% CI, 291.7-328.1 vs 369.7 95% CI, 349.1-390.3 per 100 000 person-years P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 95% CI, 3.09-3.32). In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

Validation of the

Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an We examined the concordance of Among 1357 patients, 395 (29.1%) had an When present,

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.

Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation A Structured Narrative Review.

Older adults, the fastest growing population, represent almost 50% of all users of direct oral anticoagulants (DOACs). Unfortunately, we have very little relevant pharmacological and clinical data on DOACs, especially in older adults with geriatric profiles. This is highly relevant as pharmacokinetics and pharmacodynamics (PKPD) often differ substantially in this population. Hence, we need to obtain a better understanding of the PKPD of DOACs in older adults, to ensure appropriate treatment. This review summarises the current insights into PKPD of DOACs in older adults. A search was undertaken up to October 2022 to identify PKPD studies of apixaban, dabigatran, edoxaban, and rivaroxaban, that included older adults aged ≥ 75 years. This review identified 44 articles. Older age alone did not influence exposure of edoxaban, rivaroxaban and dabigatran, while apixaban peak concentrations were 40% higher in older adults than in young volunteers. Nevertheless, high interindividual variability in DOAC exposure in older adults was noted, which can be explained by distinctive older patient characteristics, such as kidney function, changes in body composition (especially reduced muscle mass), and co-medication with P-gp inhibitors, which is in line with the current dosing reduction criteria of apixaban, edoxaban, and rivaroxaban. Dabigatran had the largest interindividual variability among all DOACs since its dose adjustment criterion is only age, and thus it is not a preferable option. Additionally, DOAC exposure, which fell outside of on-therapy ranges, was significantly related to stroke and bleeding events. No definite thresholds linked to these outcomes in older adults have been established.

Phosphodiesterase 4 D (PDE4D) gene polymorphisms and risk of ischemic stroke A systematic review and meta-analysis.

Studies on the relationship between Phosphodiesterase 4 D (PDE4D) gene polymorphism with the risk of ischemic stroke (IS) have shown discordant results. The present meta-analysis was aimed to clarify the relationship between PDE4D gene polymorphism with the risk of IS by estimating pooled analysis of published epidemiological studies. A comprehensive literature search for all the published articles was performed in various electronic databases, including PubMed, EMbase, Cochrane Library, Trip Database, Worldwide Science, CINAHL, and Google Scholar up to 22 In our meta-analysis, we identified a total of 47 case-control studies with 20,644 ischemic stroke (IS) cases and 23,201 control subjects, including 17 studies of Caucasian descent and 30 studies of Asian descent. Our findings suggest that there was a significant relationship between SNP45 gene polymorphism and risk of IS (Recessive model OR 2.06, 95% CI 1.31-3.23), SNP83 overall (allelic model OR 1.22, 95% CI 1.04-1.42), Asian (allelic model OR 1.20, 95% CI 1.05-1.37), and SNP89 Asian (Dominant model OR 1.43, 95% CI 1.29-1.59, recessive model OR 1.42, 95% CI 1.28-1.58) respectively. However, no significant relationship was found between SNP32, SNP41, SNP26, SNP56, and SNP87 gene polymorphisms and risk of IS. Findings of this meta-analysis conclude that SNP45, SNP83, and SNP89 polymorphism could be capable of increasing stroke susceptibility in Asians but not in the Caucasian population. Genotyping of SNP 45, 83, 89 polymorphisms may be used as a predictor for the occurrence of IS.

Computed Tomography of the Head A Systematic Review on Acquisition and Reconstruction Techniques to Reduce Radiation Dose.

In 1971, the first computed tomography (CT) scan was performed on a patients brain. Clinical CT systems were introduced in 1974 and dedicated to head imaging only. New technological developments, broader availability, and the clinical success of CT led to a steady growth in examination numbers. Most frequent indications for non-contrast CT (NCCT) of the head include the assessment of ischemia and stroke, intracranial hemorrhage and trauma, while CT angiography (CTA) has become the standard for first-line cerebrovascular evaluation however, resulting improvements in patient management and clinical outcomes come at the cost of radiation exposure, increasing the risk for secondary morbidity. Therefore, radiation dose optimization should always be part of technical advancements in CT imaging but how can the dose be optimized What dose reduction can be achieved without compromising diagnostic value, and what is the potential of the upcoming technologies artificial intelligence and photon counting CT In this article, we look for answers to these questions by reviewing dose reduction techniques with respect to the major clinical indications of NCCT and CTA of the head, including a brief perspective on what to expect from current and future developments in CT technology with respect to radiation dose optimization.

Dual-Energy Computed Tomography in Stroke Imaging Value of a New Image Acquisition Technique for Ischemia Detection after Mechanical Thrombectomy.

To assess if a new dual-energy computed tomography (DECT) technique enables an improved visualization of ischemic brain tissue after mechanical thrombectomy in acute stroke patients. The DECT head scans with a new sequential technique (TwinSpiral DECT) were performed in 41 patients with ischemic stroke after endovascular thrombectomy and were retrospectively included. Standard mixed and virtual non-contrast (VNC) images were reconstructed. Infarct visibility and image noise were assessed qualitatively by two readers using a 4-point Likert scale. Quantitative Hounsfield units (HU) were used to assess density differences of ischemic brain tissue versus healthy tissue on the non-affected contralateral hemisphere. Infarct visibility was significantly better in VNC compared to mixed images for both readers R1 (VNC median 1 (range 1-3), mixed median 2 (range 1-4), p < 0.05) and R2 (VNC median 2 (range 1-3), mixed 2 (range 1-4), p < 0.05). Qualitative image noise was significantly higher in VNC compared to mixed images for both readers R1 (VNC median 3, mixed 2) and R2 (VNC median 2, mixed 1, p < 0.05, each). Mean HU were significantly different between the infarcted tissue and the reference healthy brain tissue on the contralateral hemisphere in VNC (infarct 24 ± 3) and mixed images (infarct 33 ± 5, p < 0.05, each). The mean HU difference between ischemia and reference in VNC images (mean 8 ± 3) was significantly higher (p < 0.05) compared to the mean HU difference in mixed images (mean 5 ± 4). TwinSpiral DECT allows an improved qualitative and quantitative visualization of ischemic brain tissue in ischemic stroke patients after endovascular treatment.

Endovascular treatment achieves better outcomes than best medical management in patients with M2 occlusion and high stroke severity a meta-analysis.

The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for patients with M2 occlusion. This study aims to compare the efficacy and safety of endovascular treatment (EVT) with best medical management (BMM) in patients with M2 occlusion, and to investigate whether the optimal treatment varies according to stroke severity. Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT and BMM. According to stroke severity, the study population were classified into those with moderate-severe stroke and those with mild stroke. National Institute of Health Stroke Scale (NIHSS) scores ≥ 6 was defined as moderate-severe stroke, and NIHSS scores 0-5 as mild stroke. Random-effects meta-analyses were performed to measure the symptomatic intracranial hemorrhage (sICH) within 72 h, and the modified Rankin Scale (mRS) scores 0-2 and the mortality at 90 days. Totally, 20 studies were identified, including 4358 patients. In the moderate-severe stroke population, the EVT had 82% higher odds for mRS scores 0-2 (OR 1.82, 95% CI 1.34-2.49) and a 43% lower odds for mortality (OR 0.57, 95% CI 0.39-0.82) compared with the BMM. However, no difference was found in the sICH rate (OR 0.88, 95% CI 0.44-1.77). In the mild stroke population, no differences were observed in the mRS scores 0-2 (OR 0.81, 95% CI 0.59-1.10) or mortality (OR 1.23, 95% CI 0.72-2.10) between EVT and BMM, whereas EVT was associated with higher sICH rate (OR 4.21, 95% CI 1.86-9.49). EVT may be only beneficial for patients with M2 occlusion and high stroke severity, but not for those with NIHSS scores 0-5.

Coronavirus disease 2019 infection and cerebrovascular diseases an update on the pathophysiology and management.

COVID-19 is an ongoing global pandemic since it was first discovered in 2020. Cerebral vascular disease and stroke are among the most common and devastating neurological manifestations of COVID-19. This review offers an up-to-date information on the possible underlying mechanism of COVID-19-related stroke, its diagnosis, and management. The thromboembolism associated with COVID-19 infection is likely related to the cytokine storm with innate immune activation, pulmonary disease leading to hypoxia-induced ischemia, thrombotic microangiopathy, endothelial damage and multifactorial activation of the coagulation cascade. Currently, there is no clear guidelines on the use of antithrombotics for the prevention and treatment of this phenomenon. COVID-19 infection can directly cause a stroke or facilitate the formation of thromboembolism in the presence of other medical conditions. Physicians treating patients with COVID-19 should stay vigilant about the signs and symptoms of stroke, detect and treat early.

A Comparison of Outcomes Between Transfemoral Versus Transradial Access for Carotid Stenting.

The transradial (TR) approach has emerged as an alternative to the transfemoral (TF) approach in carotid artery stenting (CAS) because of its perceived benefits in access site complications and overall patient experience. To assess outcomes of TF vs TR approach for CAS. This is a retrospective single-center review of patients receiving CAS through the TR or TF route between 2017 and 2022. All patients with symptomatic and asymptomatic carotid disease who underwent attempted CAS were included in our study. A total of 342 patients were included in this study 232 underwent CAS through TF approach vs 110 through the TR route. On univariate analysis, the rate of overall complications was more than double for the TF vs TR cohort however, this did not achieve statistical significance (6.5% vs 2.7%, odds ratio OR 0.59 P .36). The rate of cross-over from TR to TF was significantly higher on univariate analysis (14.6 % vs 2.6%, OR 4.77, P .005) and on inverse probability treatment weighting analysis (OR 6.11, P < .001). The rate of in-stent stenosis (TR 3.6% vs TF 2.2%, OR 1.71, P .43) and strokes at follow-up (TF 2.2% vs TR 1.8%, OR 0.84, P .84) was not significantly different. Finally, median length of stay was comparable between both cohorts. The TR approach is safe, feasible, and provides similar rates of complications and high rates of successful stent deployment compared with the TF route. Neurointerventionalists adopting the radial first approach should carefully assess the preprocedural computed tomography angiography to identify patients amenable to TR approach for carotid stenting.

The entorhinal-DGCA3 pathway in the medial temporal lobe retains visual working memory of a simple surface feature.

Classic models consider working memory (WM) and long-term memory as distinct mental faculties that are supported by different neural mechanisms. Yet, there are significant parallels in the computation that both types of memory require. For instance, the representation of precise item-specific memory requires the separation of overlapping neural representations of similar information. This computation has been referred to as pattern separation, which can be mediated by the entorhinal-DGCA3 pathway of the medial temporal lobe (MTL) in service of long-term episodic memory. However, although recent evidence has suggested that the MTL is involved in WM, the extent to which the entorhinal-DGCA3 pathway supports precise item-specific WM has remained elusive. Here, we combine an established orientation WM task with high-resolution fMRI to test the hypothesis that the entorhinal-DGCA3 pathway retains visual WM of a simple surface feature. Participants were retrospectively cued to retain one of the two studied orientation gratings during a brief delay period and then tried to reproduce the cued orientation as precisely as possible. By modeling the delay-period activity to reconstruct the retained WM content, we found that the anterior-lateral entorhinal cortex (aLEC) and the hippocampal DGCA3 subfield both contain item-specific WM information that is associated with subsequent recall fidelity. Together, these results highlight the contribution of MTL circuitry to item-specific WM representation.

Structural Insight on GPR119 Agonist as Potential Therapy for Type II Diabetes A Comprehensive Review.

Diabetes Mellitus DM is a long-term metabolic condition that is characterized by excessive blood glucose. DM is the third most death-causing disease, leading to retinopathy, nephropathy, loss of vision, stroke, and cardiac arrest. Around 90% of the total cases of diabetic patients have Type II Diabetes MellitusT2DM. Among various approaches for the treatment of T2DM. G protein-coupled receptors GPCRs 119 have been identified as a new pharmacological target. GPR119 is distributed preferentially in the pancreas β-cells and gastrointestinal tract enteroendocrine cells in humans. GPR119 receptor activation elevates the release of incretin hormones such as Glucagon-Like Peptide GLP1 and Glucose Dependent Insulinotropic Polypeptide GIP from intestinal K and L cells. GPR119 receptor agonists stimulate intracellular cAMP production via Gαs coupling to adenylate cyclase. GPR119 has been linked to the control of insulin release by pancreatic β-cells, as well as the generation of GLP-1 by enteroendocrine cells in the gut, as per In vitro assays. The dual role of the GPR119 receptor agonist in the treatment of T2DM leads to the development of a novel prospective anti-diabetic drug and is thought to have decreased the probability of inducing hypoglycemia. GPR119 receptor agonists exert their effects in one of two ways either by promoting glucose absorption by β-cells, or by inhibiting α-cells ability to produce glucose. In this review, we summarized potential targets for the treatment of T2DM with special reference to GPR119 along with its pharmacological effects, several endogenous as well as exogenous agonists, and its pyrimidine nucleus containing synthetic ligands.

Outcome of COVID-19-Associated Acute Stroke A Study from South India.

Coronavirus 2019 (COVID-19) infection is prevalent worldwide. COVID-19 infection can lead to various neurological disorders including acute stroke. We investigated the functional outcome and its determinants among our patients with acute stroke associated with COVID-19 infection in the present setup. This study is a prospective study in which we recruited acute stroke patients with COVID-19 positivity. Data on duration of COVID-19 symptoms and type of acute stroke were recorded. All patients underwent stroke subtype workup and measurement of D-dimer, C-reactive protein (CRP), lactate-dehydrogenase (LDH), procalcitonin, interleukin-6, and ferritin levels. Poor functional outcome was defined by modified Rankin score (mRS) ≥3 at 90 days. During the study period, 610 patients were admitted for acute stroke, of whom 110 (18%) tested positive for COVID-19 infection. Majority (72.7%) were men with a mean age of 56.5 years and mean duration of COVID-19 symptoms for 6.9 days. Acute ischemic and hemorrhagic strokes were observed in 85.5% and 14.5% patients, respectively. Poor outcome was observed in 52.7%, including in-hospital mortality in 24.5% patients. COVID-19 symptoms ≤5 days (odds ratio OR 1.41, 95% confidence interval CI 1.20-2.99), CRP positivity (OR 1.97, 95% CI 1.41-4.87), elevated levels of D-dimer (OR 2.11, 95% CI 1.51-5.61), interleukin-6 (OR 1.92, 95% CI 1.04-4.74), and serum ferritin (OR 2.4, 95% CI 1.02-6.07), and cycle threshold (Ct) value ≤25 (OR 8.8, 95% CI 6.52-12.21) were independent predictors of poor outcome. Poor outcomes were relatively higher among acute stroke patients with concomitant COVID-19 infection. In the present study, we established the independent predictors of poor outcome to be onset of COVID-19 symptoms (<5 days) and elevated levels of CRP, D-dimer, interleukin-6, ferritin, and Ct value ≤25 in acute stroke.

Stroke Prevention and Treatment in People With Type 2 Diabetes Is There a Role for GLP-1 (Glucagon-Like Peptide-1) Analogues

Stroke is a leading cause of disability and death, and people with type 2 diabetes (T2D) have a greater risk of stroke and death or disability from stroke. The underlying pathophysiology associating stroke and T2D is complicated by the association of risk factors for stroke frequently seen in people with T2D. Treatments to reduce the excess risk of new-onset stroke or to improve outcomes in people with T2D following stroke would be of major clinical interest. In practice, the focus of care in people with T2D remains treating risk factors for stroke, such as lifestyle and pharmacological interventions for hypertension, dyslipidemia, obesity, and glycemic control. More recently, cardiovascular outcome trials primarily designed to assess the cardiovascular safety of GLP-1RAs (glucagon-like peptide-1 receptor analogues) have consistently observed a reduced stroke risk in people with T2D. This is supported by several meta-analyses of cardiovascular outcome trials observing clinically important risk reductions in stroke. Moreover, phase II trials have described reductions in poststroke hyperglycemia in people with acute ischemic stroke suggestive of improved outcomes following admission to hospital with acute stroke. In this review, we discuss the increased risk of stroke in people with T2D and outline the key associated mechanisms responsible. We discuss the evidence from cardiovascular outcome trials exploring GLP-1RA use and highlight areas of potential interest for future work in this rapidly developing area of clinical research.

Drug-drug interactions with direct oral anticoagulants for the prevention of ischemic stroke and embolism in atrial fibrillation a narrative review of adverse events.

In randomized trials, direct oral anticoagulants (DOAC) were non-inferior to the vitamin-K-antagonist (VKA) warfarin in preventing strokeembolism in patients with atrial fibrillation (AF). DOAC are substrates for P-glycoprotein (P-gp), CYP3A4 and CYP2C9. The activity of these enzymes is modulated by several drugs which might induce pharmacokinetic drug-drug interactions (DDI). Drugs affecting platelet function have the potential for pharmacodynamic DDI of DOAC. The literature was searched for dabigatran, rivaroxaban, edoxaban, or apixaban and drugs affecting platelet function, CYP3A4-, CYP2C9- or P-gp-activity. Reports about bleeding and embolic events attributed to DDI with DOAC in AF-patients were found for 43 of 171 drugs with interacting potential (25%), most frequently with antiplatelet and nonsteroidal anti-inflammatory drugs. Whereas a co-medication of platelet-affecting drugs is invariably reported to increase the bleeding risk, the findings regarding P-gp-, CYP3A4- and CYP2C9- activity-affecting drugs are ambiguous. Tests for plasma DOAC-levels and information about DDI of DOAC should be widely available and user-friendly. If advantages and disadvantages of DOAC and VKA can be investigated exhaustively, individualized anticoagulant therapy can be offered to patients, considering co-medication, comorbidities, genetic and geographic factors and the health care system.

Neurologic outcome following liver transplantation for methylmalonic aciduria.

Liver and liverkidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF. Differently, biomarkers of mitochondrial dysfunction (lactate, alanine and related ratios) significantly decreased in CSF. Neurocognitive evaluation documented significant higher post transplant developmental cognitive scores and maturation of executive functions corresponding to improvement of brain atrophy, cortical thickness and white matter maturation indexes at MRI. Three patients presented post transplantation reversible neurological events, which were differentiated, by means of biochemical and neuroradiological evaluations, into calcineurin inhibitor induced neurotoxicity and in metabolic stroke-like episode. Our study show that transplantation has a beneficial impact on neurological outcome in methylmalonic aciduria. Early transplantation is recommended due to the high risk of long-term complications, high disease burden and low quality of life. This article is protected by copyright. All rights reserved.

Health literacy correlates with abbreviated full-scale IQ in adolescent and young adults with sickle cell disease.

Sickle cell disease (SCD) is a chronic condition with progressive neurocognitive deficits. Health literacy (HL) is essential during adolescence and young adulthood, as the transition to adult care requires healthcare decisions. HL is known to be low in SCD however, relation between general cognitive ability and HL has not been investigated. This cross-sectional study included adolescent and yound adults (AYAs) with SCD from two institutions. Logistic regression measured the association between HL, measured by the Newest Vital Sign tool, and general cognitive ability, measured with abbreviated full-scale intelligence quotient (FSIQ) on the Wechsler Abbreviated Scale of Intelligence. Our cohort contained 93 participants at two sites 47 (51%) at Memphis, TN and 46 (49%) at St. Louis, MO, ranging from ages 15-45 years (mean 21 years) and with a majority (70%) possessing a high school education or greater. Only 4093 participants (43%) had adequate HL. Lower abbreviated FSIQ (p < .0001) and younger age at assessment (p .0003) were associated with inadequate HL. For every standard score point increase in abbreviated FSIQ, the odds of having adequate HL compared to limited or possibly limited HL increase by 1.142 (95% confidence interval CI 1.019-1.322) and 1.116 (95% CI 1.045-1.209), respectively, after adjusting for age, institution, income, and educational attainment. Understanding and addressing HL is imperative in improving self-management and health outcomes. Among AYA with SCD, low HL was prevalent and influenced by abbreviated FSIQ. Routine screening for neurocognitive deficits and HL should be performed to guide development of interventions to adapt to the HL of AYA with SCD.

Comparison of Efficacy and Safety of Direct Oral Anticoagulants and Warfarin between Patients in Asian and non-Asian Regions A Systematic Review and Meta-Regression Analysis.

Direct oral anticoagulants (DOACs) have increasingly replaced warfarin for treating patients with non-valvular atrial fibrillation (NVAF). DOACs have been demonstrated to be more useful than warfarin which was highlighted at its ethnic differences in efficacy and safety however, the regional differences of DOACs remain unclear. We conducted a systematic review, meta-analysis, and meta-regression to evaluate the efficacy and safety of DOACs in patients from Asian and non-Asian regions with NVAF. We systematically searched randomized control trials published before August 2019. We defined 11 studies comprising 7,118 Asian and 53,282 non-Asian patients, totaling 60,400 NVAF patients. The risk ratios (RRs) of DOACs were calculated against warfarin. The efficacy of DOACs was significantly higher in Asian regions regarding strokesystemic embolism events (RR 0.62 and 95% confidence interval (CI) 0.49-0.78 for Asian regions RR 0.83 and 95% CI 0.75-0.92 for non-Asian regions P interaction 0.02), when compared with warfarin. The safety of DOACs was significantly higher in Asian regions regarding major bleeding (RR 0.62 and 95% CI 0.51-0.75 for Asian regions RR 0.90 and 95% CI 0.76-1.05 for non-Asian regions P interaction 0.004), compared with warfarin. In addition, we conducted meta-regression analysis to discuss the true regional differences of DOACs to warfarin. The meta-regression analysis, which adjusts the effect of individual backgrounds in each study, indicated that the regional differences were observed in the efficacy but not in drug safety. These results suggest that treatment with DOACs may be more effective than the conventional warfarin in the Asian region.

Early Versus Delayed Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The optimal timing of coronary angiography remains unclear following out-of-hospital cardiac arrest (OHCA) without ST elevation on electrocardiogram. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of early angiography versus delayed angiography following OHCA without ST elevation. The databases MEDLINE, PubMed EMBASE, and CINHAL, as well as unpublished sources from inception to March 9, 2022. A systematic search was performed for randomized controlled trials of adult patients after OHCA without ST elevation who were randomized to early as compared to delayed angiography. Reviewers screened and abstracted data independently and in duplicate. The certainty of evidence was assessed for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. The protocol was preregistered (CRD 42021292228). Six trials were included ( In OHCA patients without ST elevation, early angiography probably has no effect on mortality and may have no effect on survival with good neurologic outcome and ICU LOS. Early angiography has an uncertain effect on adverse events.

Recurrent hemichorea with different etiologies in one patient.

Hemichorea is a unilateral movement disorder caused by acute ischemic or hemorrhagic stroke of contralateral cerebral lesions. It is followed by hyperglycemia, and other systemic diseases. Several cases of recurrent hemichorea associated with the same etiology have been reported, but cases with different etiologies have rarely been reported. We report a case in which the patient experienced both strokes and post-stroke-related hyperglycemic hemichorea. Magnetic resonance imaging of the brain appeared different in these two episodes. Our case demonstrates the importance of evaluating every patient presented with recurrent hemichorea carefully, as the disorder may be caused by different conditions.

The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage.

Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearmans analysis. A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC 0.748, 95% CI 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR1.090, 95% CI 1.029-1.155). Among the four indexes, Spearmans analysis showed that the NLR was the most highly correlated with the CPIS (r0.537, 95% CI 0.395-0.654). The NLR could effectively predict ICU admission (AUC 0.732, 95% CI 0.671-0.786), and this finding remained significant in the multivariable analysis (RR1.049, 95% CI 1.009-1.089, P0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC 0.761, 95% CI 0.707-0.8147). Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

Effects of Mitral Valve Prolapse on Quantification of Mitral Regurgitation and Ejection Fraction Using Cardiac MRI.

To determine the impact of prolapsed volume on regurgitant volume (RegV), regurgitant fraction (RF), and left ventricular ejection fraction (LVEF) in patients with mitral valve prolapse (MVP) using cardiac MRI. Patients with MVP and mitral regurgitation who underwent cardiac MRI from 2005 to 2020 were identified retrospectively from the electronic record. RegV is the difference between left ventricular stroke volume (LVSV) and aortic flow. Left ventricular end-systolic volume (LVESV) and LVSV were obtained from volumetric cine images, with prolapsed volume inclusion (LVESVp, LVSVp) and exclusion (LVESVa, LVSVa) providing two estimates of RegV (RegVp, RegVa), RF (RFp, RFa), and LVEF (LVEFa, LVEFp). Interobserver agreement for LVESVp was assessed using intraclass correlation coefficient (ICC). RegV was also calculated independently using measurements from mitral inflow and aortic net flow phase-contrast imaging as the reference standard (RegVg). The study included 19 patients (mean age, 28 years ± 16 SD 10 male patients). Interobserver agreement for LVESVp was high (ICC, 0.98 95% CI 0.96, 0.99). Prolapsed volume inclusion resulted in higher LVESV (LVESVp 95.4 mL ± 34.7 vs LVESVa 82.4 mL ± 33.8 Measurements that included prolapsed volume most closely reflected mitral regurgitation severity, but inclusion of this volume resulted in a lower LVEF.

Development of a tailored intervention targeting sedentary behavior and physical activity in people with stroke and diabetes A qualitative study using a co-creation framework.

Type 2 diabetes and sedentary behavior pose serious health risks in stroke survivors. Using a co-creation framework, this study aimed to develop an intervention in collaboration with stroke survivors with type 2 diabetes, relatives, and cross-sectoral health care professionals to reduce sedentary behavior and increase physical activity. This qualitative explorative study used a co-creation framework consisting of a workshop and focus group interviews with stroke survivors with type 2 diabetes ( The developed Everyday Life is Rehabilitation (ELiR) intervention consisted of a tailored 12-week home-based behavior change intervention with two consultations of action planning, goal setting, motivational interviewing, and fatigue management including education on sedentary behavior, physical activity, and fatigue. The intervention has a minimalistic setup using a double-page paper Everyday Life is Rehabilitation (ELiR) instrument making it implementable and tangible. In this study, a theoretical framework was used to develop a tailored 12-week home-based behavior change intervention. Strategies to reduce sedentary behavior and increase physical activity through activities of daily living along with fatigue management in stroke survivors with type 2 diabetes were identified.

Homocysteine level at the acute stage of ischemic stroke as a biomarker of poststroke depression A systematic review and meta-analysis.

Studies on the association of homocysteine level with poststroke depression (PSD) have yielded conflicting results. This systematic review and meta-analysis aimed to evaluate the elevated homocysteine level at the acute stage of ischemic stroke in predicting PSD. Two authors systematically searched articles indexed in PubMed and Embase databases up to 31 January 2022. Studies evaluating the association of homocysteine level with the development of PSD in patients with acute ischemic stroke were selected. A total of 10 studies involving 2,907 patients were identified. The pooled adjusted odds ratio (OR) of PSD was 3.72 95% confidence intervals (CI) 2.03-6.81 for the top vs. bottom homocysteine level. The value of elevated homocysteine level in predicting PSD was stronger in ≥6-month follow-up (OR 4.81 95% CI 3.12-7.43) than those in ≤ 3-month follow-up subgroup (OR 3.20 95% CI 1.29-7.91). Moreover, a per unit increase in homocysteine level conferred a 7% higher risk of PSD. Elevated homocysteine level in the acute stage of ischemic stroke may be an independent predictor of PSD.

Videofluoroscopy dysphagia severity scale is predictive of subsequent remote pneumonia in dysphagia patients.

Characteristics of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.2 Subvariant in Jilin, China from March to May 2022.

In the midst of the pandemic, new coronavirus mutants continue to emerge the most relevant variant worldwide is omicron. Here, patients who recovered from the disease living in Jilin Province were analyzed to identify factors affecting the severity of omicron infection and to provide insights into its spread and early indication. In this study, 311 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were divided into two groups. Data on the patients demographic characteristics and laboratory tests, including platelet count (PLT), neutrophil count (NE), C-reactive protein (CRP), serum creatinine (SCR), and neutrophil-to-lymphocyte ratio (NLR), were collected. The biomarkers for moderate and severe coronavirus disease 2019 (COVID-19) and factors affecting the incubation period and time to subsequent negative nucleic acid amplification test (NAAT) were also investigated. Age, gender, vaccination, hypertension, stroke, chronic obstructive pulmonary disease (COPD)chronic bronchitisasthma, and some laboratory tests were statistically different between the two groups. In the receiver operating characteristic (ROC) analysis, PLT and CRP had higher area under the ROC curve values. In the multivariate analysis, age, hypertension, COPDchronic bronchitisasthma, and CRP were correlated with moderate and severe COVID-19. Moreover, age was correlated with longer incubation. In the Kaplan-Meier curve analysis, gender (male), CRP, and NLR were associated with longer time to subsequent negative NAAT. Older patients with hypertension and lung diseases were likely to have moderate or severe COVID-19, and younger patients might have a shorter incubation. A male patient with high CRP and NLR levels might take more time to turn back negative in the NAAT.

The carotid web Current research status and imaging features.

The carotid web is commonly found in the carotid bulb or the beginning of the internal carotid artery. It presents as a thin layer of proliferative intimal tissue originating from the arterial wall and extending into the vessel lumen. A large body of research has proven that the carotid web is a risk factor for ischemic stroke. This review summarizes the current research status of the carotid web and focuses on its imaging presentation.

Sedation protocols in non-traumatic SAH (SPRINT-SAH) A cross-sectional survey among German-speaking neurointensivists.

In subarachnoid hemorrhage (SAH), titrating sedation to find a balance between wakefulness with the ability to perform valid clinical examinations on the one hand, and deep sedation to minimize secondary brain damage, on the other hand, is challenging. However, data on this topic are scarce, and current guidelines do not provide recommendations for sedation protocols in SAH. We designed a web-based, cross-sectional survey for German-speaking neurointensivists to map current standards for the indication and monitoring of sedation, duration of prolonged sedation, and biomarkers for the withdrawal of sedation. Overall, 17.4% (37213) of neurointensivists answered the questionnaire. Most of the participants were neurologists (54.1%, 2037) and exhibited a long-standing experience in intensive care medicine (14.9 years, SD 8.3). Among indications for prolonged sedation in SAH, the control of intracranial pressure (ICP) (94.6%) and status epilepticus (91.9%) were most significant. With regard to further complications in the course of the disease, therapy refractory ICP (45.9%, 1737) and radiographic surrogates of elevated ICP, such as parenchymal swelling (35.1%, 1337), were the most relevant topics for experts. Regular awakening trials were performed by 62.2% of neurointensivists (2337). All participants used clinical examination for the therapeutic monitoring of sedation depth. A total of 83.8% of neurointensivists (3137) used methods based on electroencephalography. As a mean duration of sedation before attempting an awakening trial in patients with unfavorable biomarkers, neurointensivists suggested 4.5 days (SD 1.8) for good-grade SAH and 5.6 days (SD 2.8) for poor-grade SAH, respectively. Many experts performed cranial imaging before the definite withdrawal of sedation 84.6% (2226), and 63.6% (1422) of the participants required an absence of herniation, space-occupying lesions, or global cerebral edema. The values of ICP tolerated for definite withdrawal were smaller compared to that of awakening trials (17.3 mmHg vs. 22.1 mmHg), and patients were required to stay below the threshold value for several hours (21.3 h, SD 10.7). Despite the paucity of clear recommendations for sedation management in SAH in the pre-existing literature, we found some level of agreement indicating clinical efficacy for certain clinical practices. By mapping the current standard, this survey may help to identify controversial aspects in the clinical care of SAH and thereby streamline future research.

Age-to-Glasgow Coma Scale score ratio predicts gastrointestinal bleeding in patients with primary intracerebral hemorrhage.

Recent clinical studies have demonstrated that advanced age and low initial Glasgow Coma Scale (GCS) score were independent predictors of gastrointestinal bleeding (GIB) in patients with primary intracerebral hemorrhage (ICH). However, used singly, age and GCS score have their respective shortcomings in predicting the occurrence of GIB. This study aimed to investigate the association between the age-to-initial GCS score ratio (AGR) and the risk of GIB following ICH. We conducted a single-center, retrospective observational study of consecutive patients presenting with spontaneous primary ICH at our hospital from January 2017 through January 2021. Patients who fulfilled the inclusion and exclusion criteria were categorized into GIB and non-GIB groups. Univariate and multivariate logistic regression analyses were implemented to identify the independent risk factors for the occurrence of GIB, and a multicollinearity test was performed. Furthermore, one-to-one matching was conducted to balance important patient characteristics by the groups propensity score matching (PSM) analysis. A total of 786 consecutive patients fulfilled the inclusionexclusion criteria for the study, and 64 (8.14%) patients experienced GIB after primary ICH. Univariate analysis revealed that patients with GIB were significantly older 64.0 (55.0-71.75) years vs. 57.0 (51.0-66.0) years, A higher AGR was associated with an increased risk of GIB and unfunctional 90-day outcomes in patients with primary ICH.

A bibliometric analysis of the studies in high-altitude induced sleep disturbances and cognitive impairment research.

Predictors of post-stroke depression Validation of established risk factors and introduction of a dynamic perspective in two longitudinal studies.

Cerebral insults lead in many cases not only to cognitive impairment but also to disturbed emotionality. After stroke, one in three survivors develops a depression which impacts quality of life and rehabilitation. Meta-analyses have identified five main predictors of post-stroke depression (PSD) history of mental disorder, stroke severity, physical disability, cognitive impairment, and social support. However, these five established variables have never been conjointly investigated in a sample of stroke survivors. Therefore, their independent predictive values remain unclear. Moreover, predictors are most often used as time-invariant factors (status scores), neglecting the intraindividual dynamics after stroke. Our study analyses the data of two prospective longitudinal studies, investigating stroke survivors from two rehabilitation hospitals ( History of mental disorder was a risk factor for depressive symptoms after stroke at all measurement times ( History of mental disorder, physical disability, and social support are independent predictors of depressive symptoms in the first year post-stroke, also when considered conjointly. Future studies should control for these variables when investigating new predictors of PSD. In addition, intraindividual changes in known predictors after stroke play a relevant role in the pathogenesis of PSD and should be considered in clinical practice and future research.

Mesenchymal stem cell-derived extracellular vesiclesexosome A promising therapeutic strategy for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the second largest type of stroke with high mortality and morbidity. The vast majority of survivors suffer from serious neurological defects. Despite the well-established etiology and diagnose, there is still some controversy over the ideal treatment strategy. MSC-based therapy has become an attractive and promising strategy for the treatment of ICH through immune regulation and tissue regeneration. However, accumulating studies have revealed that MSC-based therapeutic effects are mainly attributed to the paracrine properties of MSC, especially small extracellular vesiclesexosome (EVsexo) which are considered to be the key mediators of the protective efficacy from MSCs. Moreover, some papers reported that MSC-EVsexo have better therapeutic effects than MSCs. Therefore, EVsexo has become a new choice for the treatment of ICH stroke in recent years. In this review, we mainly concentrate on the current research progress on the use of MSC-EVsexo in the treatment of ICH and the existing challenges in their transplation from lab to clinical practice.

Moyamoya Syndrome (MMS) in a Patient With Sickle Cell Disease (SCD) and Protein S Deficiency.

The association between Moyamoya syndrome (MMS) and sickle cell disease (SCD) has been well-established in pediatric populations however, limited literature exists documenting the characteristics and management of MMS in adult SCD patients. Studies have indicated the role of endovascular management in secondary stroke prevention for pediatric populations, with no current guidelines available for adult populations. Here, we describe a unique case of MMS in a 30-year-old patient with SCD and incidental protein S deficiency. Our unique case highlights a patient at high risk for neurosurgical intervention due to her hypercoagulable state who has benefitted from medical management. We also discuss current literature for the prevention of secondary cerebral vascular events and the role of further studies involving adult populations with MMS and SCD.

Determinants and clinical outcomes of stroke following revascularization among patients with reduced ejection fraction.

Stoke after revascularization including both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is an uncommon but devastating complication. Patients with reduced ejection fraction (EF) had an increased risk of stroke after revascularization. However, little is known about the determinants and outcomes of stroke among patients with reduced EF following revascularization. A cohort study of patients with preoperative reduced EF (≤40%) who received revascularization by either PCI or CABG between January 1, 2005 and December 31, 2014 was performed. Multivariate logistic regression was used to identify independent correlates of stroke. Logistic regression models were applied to evaluate the association of stroke with clinical outcomes. A total of 1937 patients were enrolled in this study. Of these, 111 (5.7%) patients suffered from stroke during the median 3.5-year follow-up. Older age (odds ratio OR, 1.03 95% CI, 1.01-1.05 p .009), history of hypertension (OR, 1.79 95% CI, 1.18-2.73 p .007), and history of stroke (OR, 2.00 95% CI, 1.19-3.36 p .008) were found to be independent predictors for stroke. Patients with and without stroke had similar risk of all-cause death (OR, 0.91 95% CI, 0.59-1.41 p .670). However, stroke was associated with higher odds ratio of heart failure (HF) hospitalization (OR, 2.77 95% CI, 1.74-4.40 p < .001) and composite end point (OR, 1.61 95% CI, 1.07-2.42 p .021). Further research appears warranted to minimize the complication of stroke and improve long-term outcomes among patients with reduced EF who underwent such high risk revascularization procedural.

Pupillary evidence reveals the influence of conceptual association on brightness perception.

Our visual experience often varies based on momentary thoughts and feelings. For example, when positive concepts are invoked, visual objects may appear brighter (e.g., a brighter smile). However, it remains unclear whether this phenomenological experience is driven by a genuine top-down modulation of brightness perception or by a mere response bias. To investigate this issue, we use pupillometry as a more objective measure of perceived brightness. We asked participants to judge the brightness level of an iso-luminant gray color patch after evaluating the valence of a positive or negative word. We found that the gray color patch elicited greater pupillary light reflex and more frequent brighter responses after observers had evaluated the valence of a positive word. As pupillary light reflex is unlikely driven by voluntary control, these results suggest that the conceptual association between affect and luminance can modulate brightness perception.

Transorbital sonography and MRI reliability to assess optic nerve sheath diameter in idiopathic intracranial hypertension.

The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) in measuring the optic nerve sheath diameter (ONSD) compared to the established method transorbital sonography (TOS) in patients with idiopathic intracranial hypertension (IIH). Twenty-three patients with IIH were prospectively included applying IIH diagnostic criteria. All patients received a lumbar puncture with assessment of the cerebrospinal fluid (CSF) opening pressure to assure the IIH diagnosis. Measurement of ONSD was performed 3 mm posterior to inner sclera surface in B-TOS by an expert examiner, while three independent neuroradiologists took measurements in axial T-weighted MRI examinations. The sella turcica with the pituitary gland (and potential presence of an empty sella) and the trigeminal cavity were also assessed on sagittal and transversal T1-weighted MRI images by one independent neuroradiologist. The means of ONSD between ultrasound and MRI measurements were 6.3 mm (standard deviation SD 0.6 mm) and 6.2 mm (SD 0.8 mm). The interrater reliability between three neuroradiologists showed a high interclass correlation coefficient (ICC) (confidence interval .573 < ICC < .8 p < .001). In patients with an empty sella, the ONSD evaluated by MRI was 6.6 mm, while measuring 6.1 mm in patients without empty sella. No correlation between CSF opening pressure and ONSD was found. MRI can reliably measure ONSD and yields similar results compared to TOS in patients with IIH. Moreover, patients with empty sella showed significantly larger ONSD than patients without empty sella.

Incidence and predictors of cardiovascular outcomes after acute coronary syndrome in a population-based cohort study.

There is limited data on long-term outcomes after hospitalization for ACS. We aimed to estimate the rate of recurrent cardiovascular events in the long-term, in a population-based, unselected cohort of ACS patients. We included 1379 patients with ACS hospitalized at Östersund hospital 2010-2014 and followed them from the day after discharge to 31 December 2017. The primary endpoint was the unadjusted rate of the composite of CV death, AMI and ischemic stroke. Risk factors for the primary endpoint were assessed in a multivariable Cox proportional hazards regression model. During a median follow-up of 4.7 years, the unadjusted rate of the primary endpoint was 10.3% at 1 year and 28.6% at the end of follow-up. Predictors of increased risk for subsequent events were congestive heart failure, diabetes mellitus, angina pectoris, prior revascularization with PCI or CABG and treatment with diuretics at discharge. Lipid-lowering therapy at discharge and revascularization with PCI or CABG were associated with a lower risk of recurrent events. The risk of recurrent cardiovascular was high at 1 year and continued to be so during the following almost 3 years of median follow-up. Established predictors of cardiovascular risk were confirmed.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GHCH) and preeclampsiaeclampsia (PEE), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later-life. We examined the effects of any HDP, GHCH, PEE, and nulliparity on cognition in later-life. Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical-record abstracted pregnancy information. A cognitive battery of nine tests was conducted every 15 months. Global cognitive and domain-specific z-scores (memory, executiveattention, visuospatial, language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype GHCH, PEE, or nulliparous) and cognitive decline adjusting for age and education. Additional models adjusted for Of the 2,239 women, 1,854 (82.8%) had at least one pregnancy (1,607 all normotensive, 100 GHCH, 147 PEE) 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GHCH, or PEE versus women with a history of all normotensive pregnancies women who were nulliparous had lower global and domain-specific cognition (all Women with a history of HDP, especially PEE, are at greater risk of cognitive decline in later life.

Clinical significance of obstructive sleep apnea in patients with acute coronary syndrome with or without prior stroke a prospective cohort study.

Whether obstructive sleep apnea (OSA) is associated with worse prognosis in patients with acute coronary syndrome (ACS) with or without prior stroke remains unclear. We investigated the association of OSA with cardiovascular events in ACS patients with or without prior stroke. Between June 2015 and January 2020, we prospectively recruited eligible ACS patients who underwent cardiorespiratory polygraphy during hospitalization. We defined OSA as an apnea hypopnea index (AHI) ≥ 15 eventshour. The primary composite end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1927 patients enrolled, 207 patients had prior stroke (10.7%) and 1014 had OSA (52.6%). After a mean follow-up of 2.9 years, patients with stroke had significantly higher risk of MACCEs than those without stroke (hazard ratio HR1.49 95% confidence interval CI 1.12-1.98, P 0.007). The multivariate analysis showed that patients with OSA had 2.0 times the risk of MACCEs in prior stroke group (41 events 33.9% vs 18 events 20.9% HR2.04, 95% CI1.13-3.69, P 0.018), but not in non-prior stroke group (186 events 20.8% vs 144 events 17.4 HR1.21, 95% CI 0.96-1.52, P 0.10). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P 0.17). Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted. Trial registration Clinicaltrials.gov identifier NCT03362385.

Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output.

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in sub-cortical motor pathways such as the reticulospinal tract could help to boost recovery after damage (e.g. stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20 and 30 minutes after stimulus pairing ended, TMS responses were enhanced, indicating the induction of long-term potentiation. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared to other available paradigms.

Mitochondrial diseases in Hong Kong prevalence, clinical characteristics and genetic landscape.

To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly andor enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords andor International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

A case of limb shaking transient ischaemic attack due to internal carotid artery dissection an unusual presentation of fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) has a high prevalence of associated nontraumatic carotid artery dissection, which could further result in transient ischaemic attack (TIA) or stroke. Limb shaking TIA is an unusual form of TIA that is commonly discribed in elderly patients with atherosclerotic backgrounds, while there are limited data about it in patients with FMD. Furthermore, discussions of limb shaking TIA in nonelderly patients are scarce. An Asian 47-year-old female presented with intermittent involuntary movement of the left upper limb accompanied by neck torsion. The episode stopped soon after changing to the supine position. On native source images of time-of-flight magnetic resonance angiography (TOF-MRA), the right internal carotid artery showed a dual lumen sign with an intimal flap. On contrast-enhanced magnetic resonance angiography and sagittal black-blood T1WI, an intravascular haematoma with irregular lumen stenosis was observed, which overall indicated right internal carotid artery dissection. Digital subtraction angiography showed the characteristic string-of-beads appearance in the left internal carotid artery, and the presence of this sign pointed to the diagnosis of FMD. The patient was finally diagnosed with limb shaking TIA due to internal carotid dissection with fibromuscular dysplasia. The patient was prescribed dual anti-platelet therapy. The limb shaking vanished soon after admission with no reoccurrence in the three-month follow-up. This case demonstrates that limb shaking TIA can present in patients with FMD. Limb shaking TIA in nonelderly patients can be caused by multiple diseases, and more detailed patient guidance is required in clinical practice.

Thyroid Dysfunction and Cardiovascular Events in Patients With Dysglycemia.

Subclinical thyroid disease is the most common form of thyroid dysfunction and may be associated with adverse cardiovascular outcomes in people at high risk for cardiovascular events. Our objective in this study was to assess the association of thyroid function and thyroid hormone replacement with cardiovascular outcomes in high-risk individuals with dysglycemia and additional cardiovascular risk factors. The relationship between baseline thyrotropin (TSH) level and incidence of the composite outcome of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death an expanded composite of this outcome plus revascularization or hospitalization for heart failure and mortality was assessed in 8,401 ORIGIN trial participants with a baseline measurement of TSH. The hazard of each outcome according to either baseline levothyroxine use or TSH-defined hyperthyroidism, euthyroidism, subclinical hypothyroidism and overt hypothyroidism was estimated before and after adjustment for baseline demographic and clinical characteristics and treatment allocation. Of all participants, 91.5% were euthyroid, 0.8% were hyperthyroid, 5.5% had subclinical hypothyroidism and 2.2% had overt hypothyroidism. Subclinical hypothyroidism predicted both the expanded cardiovascular outcome (hazard ratio HR1.24, 95% confidence interval CI 1.06 to 1.46) and mortality (HR1.37, 95% CI 1.12 to 1.67), whereas levothyroxine use predicted fewer deaths (HR0.72, 95% CI 0.56 to 0.94). Subclinical hypothyroidism predicts future cardiovascular events and mortality in people with dysglycemia and other cardiovascular risk factors.

Takotsubo Syndrome in Orthotopic Liver Transplant A Systematic Review and Pooled Analysis of Published Studies and Case Reports.

Takotsubo syndrome (TTS) has been reported in solid-organ transplant recipients. However, the pooled data regarding TTS after liver transplant remain limited. A systematic review was performed through February 2022 using PubMed, Embase, Scopus, and Google Scholar to review case reportsseries and original studies on liver transplant-associated TTS. Descriptive analysis was performed for case reports and pooled analysis for the prevalence using random effects models. A total of 56 case reports were included from 30 articles (51.8 % male mean age, 53 years India 56%, US 27%, and Europe 8.93%) and 10 original studies (US 88.65%, India 10.92%) revealing liver transplant-associated TTS. The pooled prevalence of TTS was 1.1% (95% Cl, 0.6%-1.7%) of all liver transplants with comparable rates in studies from India and the US (P .92). Indications for liver transplant included end-stage liver disease due to alcohol-related cirrhosis (25%), hepatitis C virus infection (17.9%), hepatocellular carcinoma (10.7%), and non-alcohol-related steatohepatitis (8.9%) the average Model for End-Stage Liver Disease score was 24.75. TTS commonly presented as hypotension (30%), dyspnea (14%), and oliguria, occurring mostly post-transplant (82%), whereas 14% were intraoperative. Common electrocardiogram findings were ST changes, ventricular tachycardia, and atrial fibrillation. Common echocardiogram findings showed left ventricular apical ballooning in 46.5% of cases and reduced ejection fraction < 20% in 41.9% of cases. Common complications were cardiogenic shock (32.1 %), acute kidney injury (12.5%), arrhythmia, stroke, cardiac arrest, and hepatic artery thrombosis. Mechanical circulatory support was required in 30.3%. Recurrence was reported in 15, and mortality in 30.4% of patients. Takotsubo syndrome prevalence after liver transplant is significantly higher than TTS prevalence in general US hospitalizations with potentially worse outcomes. Prospective registries reporting TTS in liver transplant recipients are warranted.

Pharmacology of pannexin channels.

Pannexin channels play fundamental roles in regulating inflammation and have been implicated in many diseases including hypertension, stroke, and neuropathic pain. Thus, the ability to pharmacologically block these channels is a vital component of several therapeutic approaches. Pharmacologic interrogation of model systems also provides a means to discover new roles for pannexins in cell physiology. Here, we review the state of the art for agents that can be used to block pannexin channels, with a focus on chemical pharmaceuticals and peptide mimetics that act on pannexin 1. Guidance on interpreting results obtained with pannexin pharmacologics in experimental systems is discussed, as well as strengths and caveats of different agents, including specificity and feasibility of clinical application.

Loss of a child and the risk of atrial fibrillation a Danish population-based prospective cohort study.

Several studies suggest that bereavement is associated with increased risks of ischaemic heart disease, heart failure, stroke and cardiovascular mortality. Knowledge regarding the link between bereavement and the risk of atrial fibrillation (AF) is limited. We investigated whether the death of a child, one of the most severe forms of bereavement, is associated with AF. We conducted a population-based cohort study involving parents of live-born children during 1973-2016 from the Danish Medical Birth Register (n2 804 244). Information on childrens death, parental AF and sociodemographic and other health-related characteristics was obtained by individual-level linkage between several Danish population-based registers. We analysed the association between loss of a child and AF using Poisson regression. During the up to 39 years follow-up, 64 216 (2.3%) parents lost a child and 74 705 (2.7%) had an AF. Bereaved parents had a higher risk of AF than the non-bereaved the corresponding incidence rate ratio (IRR) and 95% CI were 1.12 (1.08 to 1.17). The association was present both when the child died of cardiovascular diseases (IRR (95% CI) 1.42 (1.20 to 1.69)), and of other causes (IRR (95% CI) 1.11 (1.06 to 1.16)), tended to be U-shaped according to the deceased childs age at loss, but did not differ substantially according to the number of remaining live children at loss, the number of deceased children or the time since the loss. The death of a child was associated with a modestly increased risk of AF. Bereaved parents may benefit from increased support from family members and health professionals.

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.

Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF. This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity. The primary endpoint was similar between treatment groups (HR 1.17 95% CI 0.81-1.69 P 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR 0.42 95% CI 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR 0.72 95% CI 0.51-1.03) in the analysis population (n 537), and by 75% (HR 0.25 95% CI 0.09-0.66) and 38% (HR 0.62 95% CI 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mgL). The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.

Systemic Delivery of Extracellular Vesicles Attenuates Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) patients. To date, treatments for HFpEF-related AF have been limited to anti-arrhythmic drugs and ablation. Here we examined the effects of immortalized cardiosphere-derived extracellular vesicles (imCDCevs) in rats with HFpEF. This study sought to investigate the mechanisms of AF in HFpEF and probe the potential therapeutic efficacy of imCDCevs in HFpEF-related AF. Dahl salt-sensitive rats were fed a high-salt diet for 7 weeks to induce HFpEF and randomized to receive imCDCevs (n 18) or vehicle intravenously (n 14). Rats fed a normal-salt diet were used as control animals (n 26). A comprehensive characterization of atrial remodeling was conducted using functional and molecular techniques. HFpEF-verified animals showed significantly higher AF inducibility (84%) compared with control animals (15%). These changes were associated with prolonged action potential duration, slowed conduction velocity (connexin 43 lateralization), and fibrotic remodeling in the left atrium of HFpEF compared with control animals. ImCDCevs reversed adverse electrical remodeling (restoration of action potential duration to control levels and reorganization of connexin 43) and reduced AF inducibility (33%). In addition, fibrosis, inflammation, and oxidative stress, which are major pathological AF drivers, were markedly attenuated in imCDCevs-treated animals. Importantly, these effects occurred without changes in blood pressure and diastolic function. Thus, imCDCevs attenuated adverse remodeling, and prevented AF in a rat model of HFpEF.

5-Year Outcomes With Self-Expanding vs Balloon-Expandable Transcatheter Aortic Valve Replacement in Patients With Small Annuli.

Self-expanding transcatheter heart valves (THVs) are associated with better echocardiographic hemodynamic performance than balloon-expandable THVs and are considered preferable in patients with small annuli. This study sought to compare 5-year outcomes between self-expanding vs balloon-expandable THVs in severe aortic stenosis (AS) patients with small annuli. Consecutive severe AS patients with an aortic valve annulus area <430 mm A total of 723 patients were included, and propensity score matching resulted in 171 pairs. Technical success was achieved in over 85% of both groups with no significant difference. Self-expanding THVs were associated with a lower transvalvular gradient (8.0 ± 4.8 mm Hg vs 12.5 ± 4.5 mm Hg P < 0.001), a larger effective orifice area (1.81 ± 0.46 cm The echocardiographic hemodynamic advantage of self-expanding THVs was not associated with better clinical outcomes compared with balloon-expandable THVs up to 5 years in patients with small annuli. (Swiss TAVI Registry NCT01368250).

Vascular Access in Patients With Peripheral Arterial Disease Undergoing TAVR The Hostile Registry.

The optimal access route in patients with severe peripheral artery disease (PAD) undergoing transcatheter aortic valve replacement (TAVR) remains undetermined. This study sought to compare clinical outcomes with transfemoral access (TFA), transthoracic access (TTA), and nonthoracic transalternative access (TAA) in TAVR patients with severe PAD. Patients with PAD and hostile femoral access (TFA impossible, or possible only after percutaneous treatment) undergoing TAVR at 28 international centers were included in this registry. The primary endpoint was the propensity-adjusted risk of 30-day major adverse events (MAE) defined as the composite of all-cause mortality, stroketransient ischemic attack (TIA), or main access site-related Valve Academic Research Consortium 3 major vascular complications. Outcomes were also stratified according to the severity of PAD using a novel risk score (Hostile score). Among the 1,707 patients included in the registry, 518 (30.3%) underwent TAVR with TFA after percutaneous treatment, 642 (37.6%) with TTA, and 547 (32.0%) with TAA (mostly transaxillary). Compared with TTA, both TFA (adjusted HR 0.58 95% CI 0.45-0.75) and TAA (adjusted HR 0.60 95% CI 0.47-0.78) were associated with lower 30-day rates of MAE, driven by fewer access site-related complications. Composite risks at 1 year were also lower with TFA and TAA compared with TTA. TFA compared with TAA was associated with lower 1-year risk of strokeTIA (adjusted HR 0.49 95% CI 0.24-0.98), a finding confined to patients with low Hostile scores (P Among patients with PAD undergoing TAVR, both TFA and TAA were associated with lower 30-day and 1-year rates of MAE compared with TTA, but 1-year strokeTIA rates were higher with TAA compared with TFA.

Rapid Evaluation of Large Vessel Occlusion for Mechanical Thrombectomy Using Carotid Duplex Ultrasound.

Objectives This study clarified the usefulness of carotid duplex ultrasound (CDU) in evaluating large vessel occlusion (LVO) in patients with acute stroke planned to be treated with mechanical thrombectomy (MT). Methods This study was single-center, prospective, observational trial. If the ratio of end-diastolic velocity in the common carotid arteries was ≥1.4, or diastolic flow in the affected internal carotid artery (ICA) was absent on CDU, patients were immediately transferred to the angio-suite without additional cerebrovascular imaging. Clinical parameters, including time metrics and outcomes, were evaluated in participants. Patients We enrolled stroke patients with a National Institutes of Health Stroke Scale score ≥6 and Alberta Stroke Program Early CT score ≥6 in whom MT could be initiated within 6 hours of the stroke onset. Results Among 140 patients screened during the study period, 48 were ultimately enrolled. Twenty-seven patients were diagnosed with LVO by CDU alone. CDU offered 83% sensitivity and 82% specificity for identifying the occlusion of the ICA or M1 segment of the middle cerebral artery. Among the 29 total patients treated with MT, 20 (67%) showed a modified Rankin Scale score ≤2 at 90 days. The door-to-puncture time was significantly shorter in patients evaluated by CDU alone (34 minutes) than in those evaluated by magnetic resonance angiography after CDU (47.5 minutes, p<0.001). Conclusion CDU might reduce the time metrics for early initiation of MT with good sensitivity and specificity in identifying LVO.

Interference of New Antiseizure Agents with Hospital Transfer of Stroke Patients in Japan A Retrospective Cohort Study.

Patients in Japan often have difficulty in screening and selecting chronic-care and rehabilitation hospitals for transfer because of the high cost and unavailability of new antiseizure medications, such as perampanel and lacosamide. To investigate whether the requirement for perampanel and lacosamide interfered with patients hospital transfer by comparing the number of days required for hospital transfer. Data were obtained from patients 1) who were diagnosed with intracerebral hemorrhage or cerebral infarction, 2) who were treated with antiseizure medications for epilepsy, and 3) who were transferred to another hospital. The main outcome measures were the length of hospital stay and days from the last seizure to hospital transfer.Ninety-four eligible patients were divided into those treated with perampanel or lacosamide (n 18) and those treated with other agents (n 76). The mean length of hospital stay and days from the last seizure to hospital transfer were 52.9 and 45.4 d in the perampanel and lacosamide group, and 32.7 and 28.6 d in the other medication group (p < 0.001). The mean antiseizure medication costs and total drug costs were U.S. $4.88 and $6.85 in the perampanellacosamide group and U.S. $1.94 and $4.41 in the other medication group (p < 0.001, p 0.007), respectively. Considering antiseizure medication availability and cost in the transfer destination hospital is important when choosing medications for patients requiring hospital transfer from an acute-care hospital.

Associations of Plasma 25-Hydroxy Vitamin D and Dietary Vitamin D Intake with Insulin Resistance in Healthy Japanese Women.

We investigated the associations of plasma 25-hydroxy vitamin D (25(OH)D) concentration and the dietary intake of vitamin D with insulin resistance in Japanese women. Study participants were 406 Japanese women attended a health examination. They were not taking hormones or medications for diabetes and had no history of cancer, ischemic heart disease, or stroke. Information regarding medical history and lifestyle factors was obtained by a self-administered questionnaire, while hours of sun exposure were determined through interviews. Dietary intake of vitamin D was evaluated using a validated food frequency questionnaire. Fasting plasma glucose and insulin concentrations were measured, and insulin resistance (HOMA-IR) scores were calculated based on homeostasis model assessment. Women with vitamin D deficiency (25(OH)D<20 ngmL) had significantly higher fasting plasma insulin concentration and HOMA-IR than did the other women. Plasma 25(OH)D concentration was significantly and inversely associated with fasting plasma insulin level and HOMA-IR after controlling for age, season, menopausal status, BMI, smoking status, alcohol intake, physical exercise, and intakes of fat and calcium. Dietary vitamin D intake was not associated with HOMA-IR concentration after adjusting for these covariates and hours of sun exposure. Although significant inverse association between plasma 25(OH)D concentration and HOMA-IR was observed in women with a low BMI, low fat intake, or a high calcium intake, the interaction terms were not statistically significant. Data suggest that plasma vitamin D, but not dietary vitamin D, is inversely associated with fasting plasma insulin concentration and HOMA-IR in non-diabetic Japanese women.

Development of rapid and effective risk prediction models for stroke in the Chinese population a cross-sectional study.

The purpose of this study was to use easily obtained and directly observable clinical features to establish predictive models to identify patients at increased risk of stroke. A total of 46 240 valid records were obtained from 8 research centres and 14 communities in Jiangxi province, China, between February and September 2018. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy were calculated to test the performance of the five models (logistic regression (LR), random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost) and gradient boosting DT). The calibration curve was used to show calibration performance. The results indicated that XGBoost (AUC 0.924, accuracy 0.873, sensitivity 0.776, specificity 0.916) and RF (AUC 0.924, accuracy 0.872, sensitivity 0.778, specificity 0.913) demonstrated excellent performance in predicting stroke. Physical inactivity, hypertension, meat-based diet and high salt intake were important prediction features of stroke. The five machine learning models all had good predictive and discriminatory performance for stroke. The performance of RF and XGBoost was slightly better than that of LR, which was easier to interpret and less prone to overfitting. This work provides a rapid and accurate tool for stroke risk assessment, which can help to improve the efficiency of stroke screening medical services and the management of high-risk groups.

Association between seropositivity for toxocariasis and cognitive functioning in older adults an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES), 2011-2014.

This study sought to examine the relationship between seropositivity for toxocariasis and cognitive functioning in a nationally representative sample of US older adults. A cross-sectional study. National Health and Nutrition Examination Survey (NHANES) data collection took place in the US at participants homes and mobile examination centres with specialised equipment. The study population consisted of 3188 community-dwelling US older adults aged 60 and above from the NHANES 2011 to 2014. IgG antibody against The study population consisted of 3188 participants who represented a total of 111 896 309 civilian citizens in the USA. The mean age of the participants was 69.6 years (standard deviation 6.8). The prevalence of toxocariasis in this population was 7.3% (95% confidence interval CI 6.1% to 8.5%). The survey-weighted linear regression model showed that compared with participants who were toxocariasis seronegative, those who were seropositive had lower DSST z score (beta β -0.12, 95% CI -0.22 to -0.01) and global cognition z score (β-0.11, 95% CI -0.22 to -0.01), after controlling for age, sex, raceethnicity, education, depressive symptoms, smoking status, body mass index, prevalent coronary heart disease, prevalent stroke, and systolic blood pressure, physical activity, and total cholesterol. In our study, seropositive toxocariasis was independently and significantly associated with worse working memory, sustained attention, processing speed and global cognition in older adults. If this association is causal, public health measures to prevent human toxocariasis might help protect older adults cognitive function.

Retinal microvascular signs and recurrent vascular events in patients with TIA or minor stroke.

Retinal pathologies are an independent risk factor for ischaemic stroke, but research on the predictive value of retinal abnormalities for recurrent vascular events in patients with prior stroke is inconclusive. We investigated the association of retinal pathologies with subsequent vascular events. In a substudy of the Intensified secondary prevention intending a reduction of recurrent events in TIA and minor stroke patients (INSPiRE-TMS) trial, we enrolled patients with recent transient ischaemic attack (TIA) or minor stroke with at least one modifiable risk factor. Primary outcome was the composite of subsequent vascular events. Retinal photographs were taken at baseline and categorised into three different fundus groups by a telemedically linked ophthalmologist. 722 patients participated in the current study and 109 major vascular events occurred. After multivariable adjustments, we did not find a significant association between fundus categories and risk for subsequent vascular events (HRs for moderate vascular retinopathy and vascular retinopathy with vessel rarefaction in comparison to no vascular retinopathy 1.03 (95% CI 0.64 to 1.67), p0.905 and 1.17 (95% CI 0.62 to 2.20), p0.626). In a selective post hoc analysis in patients with diabetes mellitus and hypertension, patients with vascular retinopathy with vessel rarefaction had a higher risk for recurrent stroke (HR 24.14 (95% CI 2.74 to 212.50), p0.004). Retinal changes did not predict major subsequent vascular events in patients with recent TIA or minor stroke. Further studies are needed to examine the utility of fundus photography in assessing the risk of stroke recurrence in patients with diabetes mellitus and hypertension.

Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples.

Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment. We conducted analyses in three study samples the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case-control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type. The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger. PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring.

Acupoints compatibility rules of acupuncture for depression disease based on data mining technology.

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24 运用数据挖掘技术探析针刺治疗郁病的腧穴配伍规律。检索中国期刊全文数据库（CNKI）、万方数据知识服务平台（Wangfang）、维普资讯中文期刊服务平台（VIP）、中国生物医学文献数据库（SinoMed）、PubMed、EMbase、Web of Science、Cochrane Library建库至2022年9月2日针刺治疗郁病的随机对照试验文献，采用Python编程语言分析针刺治疗原发性抑郁症、脑卒中后抑郁、更年期综合征、神经官能症、焦虑症5种常见郁病的腧穴使用频次、归经、特定穴选用情况及穴位关联规则，应用Cytoscape软件对穴位关联及病-穴共现网络进行可视化分析。共纳入文献387篇，提取上述5种常见郁病的穴方共计319个，涉及159个腧穴，使用频次共计2 574次。高频使用腧穴依次为百会、三阴交、太冲、内关、神门、印堂、足三里、合谷、四神聪、太溪等，常涉及经脉为督脉、足太阳膀胱经、足太阴脾经、足厥阴肝经等；特定穴使用频率从高到低依次为交会穴、五输穴、原穴、背俞穴、络穴、八脉交会穴等，常与关联度最高的“百会-印堂”组合配伍使用；郁病-穴位的共现网络分析表明存在针刺治疗郁病的核心腧穴群“百会、太冲、神门、足三里、内关、三阴交”。郁病针刺治疗已逐渐形成了以特定穴配伍为主体，以“通督调神，调畅气机”为主要治则的腧穴配伍规律。.

Safety and Efficacy of Stereotaxic Surgery Combined with Urokinase in the Treatment of Ventricular Hemorrhage A Retrospective Propensity-matched Score Analysis.

Intraventricular hemorrhage (IVH) is a severe and devastating stroke. Research on existing treatment options has been controversial. Therefore, we aimed to evaluate the safety and efficacy of minimally implanted stereotactic puncture (MISPT) combined with urokinase (uPA) in the treatment of IVH. The clinical data of 122 IVH patients admitted to our department from 2018 to 2022 were retrospectively analyzed. According to the modified RanKin score (mRS) after 30 days, the patients were divided into good prognosis (mRS0-3) and poor prognosis (mRS4-6), and the factors affecting the prognosis were screened by univariate and multivariate analysis, and then the tendency Score matching and paired patient screening were performed for comparative analysis between uPA and non-uPA groups. Patients age, uPA usage, initial Glass coma Scale (GCS) and primary blood volume all could affect the mRS score of patients. 100 patients were finally included, including 50 cases in the uPA group and 50 cases in the non-uPA group. The analysis showed that at follow-up after 30 days, 46.0% of the patients in the uPA group and 28.0% in the non-uPA group had an mRS score of 0-3 however, they were not statistically significantly different. The postoperative hematoma clearance rate in the uPA group was significantly higher than that in the non-uPA group (P < 0.001), and the incidence of postoperative complications was not increased (P > 0.05). uPA treatment can improve the treatment efficiency. However, its effect in improving patient outcomes does not appear to be significant.

Sensorimotor control of object manipulation following middle cerebral artery (MCA) stroke.

Methods for assessing the loss of hand function post-stroke examine limited aspects of motor performance and are not sensitive to subtle changes that can cause deficits in everyday object manipulation tasks. Efficiently lifting an object entails a prediction of required forces based on intrinsic features of the object (sensorimotor integration), short-term updates in the forces required to lift objects that are poorly predicted (sensorimotor memory), as well as the ability to modulate distal fingertip forces, which are not measured by existing assessment tools used in clinics for both diagnostic and rehabilitative purposes. The presented research examined these three components of skilled object manipulation in 60 chronic, unilateral middle cerebral artery stroke participants. Performance was compared to age-matched control participants, and linear regressions were used to predict performance based on clinical scores. Most post-stroke participants performed below control levels in at least one of the tasks. Post-stroke participants presented with combinations of deficits in each of the tasks performed, regardless of the hemisphere damaged by the stroke. Surprisingly, the ability to modulate distal forces was impaired in those patients with damage ipsilateral (right hemisphere) to the hand being used. Sensorimotor integration was also impaired in patients with right hemisphere damage, though they performed at control levels in later lifts, whereas left-hemisphere-damaged patients did not. Lastly, during a task requiring sensorimotor memory, neither patient group performed outside of control ranges on initial lifts, with patients with right hemisphere damage showing impaired performance in later lifts suggesting they were unable to learn the mapping novel mapping of color and mass of the objects. The presented research demonstrates unilateral MCA stroke patients can have deficits in one or more components required for the successful manipulation of hand-held objects and that skillful object lifting requires intact bilateral systems. Further, this information may be used in future studies to aid efforts that target rehabilitation regimens to a stroke survivors specific pattern of deficits.

Longer time in blood pressure target range improves cardiovascular outcomes among patients with Type 2 diabetes A Secondary Analysis of a Randomized Clinical Trial.

To examine the prognostic value of time in target range (TIR) with adverse outcomes and validate it with common blood pressure (BP) metrics among patients with Type 2 diabetes mellitus. We performed a post hoc analysis of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. TIR for each subject was calculated using linear interpolation and an SBP target range of 110 to 130mmHg. Cox models were used to assess the association of TIR and other BP metrics with the rate of clinical outcomes. A higher TIR (61.9-100.0%) was associated with a 46% reduction in major adverse cardiovascular events (MACE) (hazard ratio HR0.54 95% CI 0.43, 0.67) compared with TIR 0-22.9%. Results were similar for stroke (0.19 0.10, 0.36), myocardial infarction (0.67 0.51, 0.89), heart failure (0.47 0.33, 0.66), cardiovascular death (0.63 0.42, 0.93) and all-cause mortality (0.70 0.54, 0.91). Further analyses suggested a curvilinear association of TIR with MACE, and this association was independent with baseline, final SBP, mean SBP, or visit-to-visit SBP variability. Longer TIR is associated with lower cardiovascular risk and may add value as an outcome measure for hypertension control studies among patients with diabetes.

The mediating role of systemic inflammation in the effects of fetal famine exposure on cardiovascular disease in adults a cohort study.

A few studies have reported the association between famine exposure during fetal and the risk of cardiovascular disease (CVD), but no mechanisms have been explored. The objective of this study was to examine the risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. A total of 59,416 participants of the Kailuan study without cardiovascular diseases were included. All participants were divided into three groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocyte lymphocyte) are two novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on the risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. During a median follow-up period of 12.36 (12.69, 13.16) years, a total of 3,772 cases of CVD were documented. Compared with unexposed participants, the fetal exposed group had an increased risk of CVD (HR 1.19 95% CI 1.04, 1.38) and stroke (HR 1.28 95% CI 1.09,1.51), but not myocardial infarction (MI). No association was observed in the childhood-exposed. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke, and 31.25% of MI). Fetal exposure to famine may increase the risk of cardiovascular disease in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.

Too loud to handle transportation noise and cardiovascular disease.

The WHO reports that more than 1.6 million healthy life-years are lost yearly from traffic-related noise in Western Europe. In addition, the number of studies reporting health side effects in response to traffic noise is steadily growing, mainly cardiovascular disease (CVD), such as acute and chronic ischemic heart disease, heart failure, arrhythmia, and stroke. Pathophysiologically nighttime noise has been shown to cause sleep disturbances, including too short sleep periods and frequent interruption of sleep leading to an increase in the levels of circulating stress hormones and subsequently to a significant increase in the production of reactive oxygen species (ROS oxidative stress) and inflammation in the vasculature and the brain. The consequence is arterial hypertension and vascular (endothelial) dysfunction, which may increase the risk of cardiovascular disease. With the present review, we will give an overview of the so-called non-auditory cardiovascular health effects of noise, which have been proposed to be responsible for the future development of CVD. We will present epidemiological evidence but also evidence provided by translational human and experimental noise studies. Finally, we will discuss maneuvers to mitigate noise effectively.

Minimally Invasive Mitral Valve Surgery in the Elderly.

The minimally invasive mitral valve procedure warrants minimal surgical trauma and might influence the postoperative course positively, especially in old patients. In this retrospective study, we reviewed our experience in minimally invasive mitral valve surgery (miMVS) in patients aged ≥ 75 years. In this retrospective cohort study, based on propensity score matching, we compared patients aged ≥75 years with patients aged <75 years who underwent miMVS. The primary endpoint was 30-day mortality. Secondary endpoints were myocardial infarction, stroke, and renal failure. Between January 2011 and February 2021, 761 patients underwent miMVS at our institution. After propensity score matching, a study group (≥75 years, miMVS results in satisfactory early postoperative outcomes in elderly patients.

Endometriosis-associated chronic pelvic pain.

Endometriosis is a heterogeneous disease where neurogenic sensitization can lead to chronic pain within and beyond the pelvis. Coincident pain and comorbidities merit specific attention. We discuss the causes, comorbidities, and management of endometriosis-associated chronic pelvic pain, advocating for a multidisciplinary approach to develop more effective treatments.

Multimorbidity and functional disability among older adults - the role of inflammation and glycemic status An Observational Longitudinal Study.

Specific multimorbidity combinations, in particular those including arthritis, stroke, and cognitive impairment, have been associated with high burden of ADL-IADL disability in older adults. The biologic underpinnings of these associations are still unclear. Observational longitudinal study using data from the Health Retirement Study (N8,618, mean age74 years, 58% female, 25% non-White) and negative binomial regression models stratified by sex to evaluate the role of inflammatory and glycemic biomarkers (high-sensitivity C-reactive protein (hs-CRP) and HbA1c) in the association between specific multimorbidity combinations (grouped around one of eight index diseases arthritis, cancer, cognitive impairment, diabetes, heart disease, hypertension, lung disease, and stroke assessed between 2006-2014) and prospective ADL-IADL disability (2 years later, 2008-2016). Results were adjusted for sociodemographic characteristics, body-mass index, number of coexisting diseases, and baseline ADL-IADL score. Multimorbidity combinations indexed by arthritis (IRR1.1, 95%CI1.01-1.20), diabetes (IRR1.19, 95%CI1.09-1.30), and cognitive impairment (IRR1.11, 95%CI1.01-1.23) among men, and diabetes-indexed multimorbidity combinations (IRR1.07, 95%CI1.01-1.14) among women were associated with higher ADL-IADL scores at increasing levels of HbA1c. Across higher levels of hs-CRP, multimorbidity combinations indexed by arthritis (IRR1.06, 95%CI1.02-1.11), hypertension (IRR1.06, 95%CI1.02-1.11), heart disease (IRR1.06, 95%CI1.01-1.12), and lung disease (IRR1.14, 95%CI1.07-1.23) were associated with higher ADL-IADL scores among women, while there were no significant associations among men. The findings suggest potential for anti-inflammatory management among older women and optimal glycemic control among older men with these particular multimorbidity combinations as focus for therapeuticpreventive options for maintaining functional health.

Implication of a novel measure of obstructive sleep apnea severity for cardiovascular morbidity.

To evaluate the association between cardiovascular morbidity and obstructive sleep apnea (OSA) severity quantified using the sleep breathing impairment index (SBII), a novel measure that captures both respiratory events and event-associated hypoxia. This retrospective follow-up study included 737 participants with OSA who were diagnosed based on an apnea-hypopnea index of >5h in polysomnography from January 1, 2012 to December 31, 2015. Data on baseline clinical characteristics and polysomnography parameters were collected. SBII was determined as the sum of products of respiratory events and event-related desaturation areas, and was categorized based on its quintiles. The outcomes were any hospital admission for cardiovascular diseases, including coronary heart disease, stroke, peripheral vascular disease, or heart failure after the diagnosis of OSA. Logistic regression models were constructed to estimate the potential association between SBII and cardiovascular morbidity after adjusting for confounders. A total of 60 cardiovascular events were recorded. Compared with the first quintile of SBII, the odds ratio (95% confidence interval CI) of cardiovascular morbidity for the second, third, and fourth quintiles were 4.01 (95% CI, 1.22-13.24), 3.91 (95% CI, 1.05-14.53), and 7.57 (95% CI, 1.70-33.68) after adjusting for covariables, including anthropometric variables, medical conditions, and sleep parameters. In patients with OSA, higher SBII was associated with an increased cardiovascular risk. These findings suggest that a more comprehensive measure, such as SBII incorporating the respiratory event and related hypoxia during sleep, may better capture the disease burden and reflect the OSA-associated adverse outcomes.

Development and validation of echocardiography-based machine-learning models to predict mortality.

Echocardiography (echo) based machine learning (ML) models may be useful in identifying patients at high-risk of all-cause mortality. We developed ML models (ResNet deep learning using echo videos and CatBoost gradient boosting using echo measurements) to predict 1-year, 3-year, and 5-year mortality. Models were trained on the Mackay dataset, Taiwan (6083 echos, 3626 patients) and validated in the Alberta HEART dataset, Canada (997 echos, 595 patients). We examined the performance of the models overall, and in subgroups (healthy controls, at risk of heart failure (HF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)). We compared the models performance to the MAGGIC risk score, and examined the correlation between the models predicted probability of death and baseline quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Mortality rates at 1-, 3- and 5-years were 14.9%, 28.6%, and 42.5% in the Mackay cohort, and 3.0%, 10.3%, and 18.7%, in the Alberta HEART cohort. The ResNet and CatBoost models achieved area under the receiver-operating curve (AUROC) between 85% and 92% in internal validation. In external validation, the AUROCs for the ResNet (82%, 82%, and 78%) were significantly better than CatBoost (78%, 73%, and 75%), for 1-, 3- and 5-year mortality prediction respectively, with better or comparable performance to the MAGGIC score. ResNet models predicted higher probability of death in the HFpEF and HFrEF (30%-50%) subgroups than in controls and at risk patients (5%-20%). The predicted probabilities of death correlated with KCCQ scores (all p < 0.05). Echo-based ML models to predict mortality had good internal and external validity, were generalizable, correlated with patients quality of life, and are comparable to an established HF risk score. These models can be leveraged for automated risk stratification at point-of-care. Funding for Alberta HEART was provided by an Alberta Innovates - Health Solutions Interdisciplinary Team Grant no. AHFMRITG 200801018. P.K. holds a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair and a Heart Stroke Foundation Chair in Cardiovascular Research. A.V. and V.S. received funding from the Mitacs Globalink Research Internship.

Prediction of epilepsy surgery outcome using foramen ovale EEG - A machine learning approach.

Patients with drug-resistant focal epilepsy may benefit from ablative or resective surgery. In presurgical work-up, intracranial EEG markers have been shown to be useful in identification of the seizure onset zone and prediction of post-surgical seizure freedom. However, in most cases, implantation of depth or subdural electrodes is performed, exposing patients to increased risks of complications. We analysed EEG data recorded from a minimally invasive approach utilizing foramen ovale (FO) and epidural peg electrodes using a supervised machine learning approach to predict post-surgical seizure freedom. Power-spectral EEG features were incorporated in a logistic regression model predicting one-year post-surgical seizure freedom. The prediction model was validated using repeated 5-fold cross-validation and compared to outcome prediction based on clinical and scalp EEG variables. Forty-seven patients (26 patients with post-surgical 1-year seizure freedom) were included in the study, with 31 having FO and 27 patients having peg onset seizures. The area under the receiver-operating curve for post-surgical seizure freedom (Engel 1A) prediction in patients with FO onset seizures was 0.74 ± 0.23 using electrophysiology features, compared to 0.66 ± 0.22 for predictions based on clinical and scalp EEG variables (p < 0.001). The most important features for prediction were spectral power in the gamma and high gamma ranges. EEG data from peg electrodes was not informative in predicting post-surgical outcomes. In this hypothesis-generating study, a data-driven approach based on EEG features derived from FO electrodes recordings outperformed the predictive ability based solely on clinical and scalp EEG variables. Pending validation in future studies, this method may provide valuable post-surgical prognostic information while minimizing risks of more invasive diagnostic approaches.

Deferoxamine in intracerebral hemorrhage Systematic review and meta-analysis.

Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.

Comparison of Clinical and Molecular Features Between Patients With Essential Thrombocythemia and EarlyPrefibrotic Primary Myelofibrosis Presenting With Thrombocytosis in Taiwan.

The clinical presentations of essential thrombocythemia (ET) may be quite similar to earlyprefibrotic primary myelofibrosis (pre-PMF), especially in pre-PMF presenting with thrombocytosis (pre-PMF-T), but may be associated with a different outcome. It is very important to distinguish these two entities. The aim of this study was to address the clinical and prognostic relevance of distinguishing pre-PMF-T from ET. All patients, including 258 with ET and 105 with pre-PMF-T, received JAK2V617F, MPL (exon 10), and CALR (exon 9) mutation analysis and allele burden measurement for JAK2V617F and CALR mutants. Patients with pre-PMF-T had an older age and higher leukocyte and platelet counts but lower hemoglobin levels than patients with ET. Patients with pre-PMF-T had a shorter overall, leukemia-free, and thrombosis-free survival compared with patients with ET. Patients with ET had a higher rate of cerebral ischemic stroke, whereas patients with pre-PMF-T tended to have splanchnic vein thrombosis. The frequencies of JAK2V617F, CALR, and MPL mutations and CALR allele burden were no different, but JAK2V617F allele burden was significantly higher in pre-PMF-T. Patients with pre-PMF-T with the JAK2V617F mutation had an inferior overall survival and thrombosis-free survival, whereas the status of driver gene mutations did not influence the outcomes of patients with ET. ET and pre-PMF-T were two distinct disease entities and exhibited different clinical phenotype, genotype, and outcomes.

Left atrial appendage closure device outcomes among cirrhosis patients with atrial fibrillation a United States National Cohort Study.

Literature regarding outcomes associated with atrial fibrillation among cirrhosis patients who had left atrial appendage occlusion (LAAO) device procedure is limited. We aim to evaluate the in-hospital clinical outcomes and 30-day readmissions among LAAO with and without cirrhosis. We performed a retrospective study of all hospitalizations associated with the LAAO procedure, using the Nationwide Readmissions Database for the years 2016-19. Primary outcomes were in-hospital clinical outcomes and 30-day readmissions. A total of 54 897 index hospitalizations for LAAO (female 41.8%) were reported. Of these, 905(1.65%) had cirrhosis. Gastrointestinal (GI) bleeding was reported in 44 (4.9%) vs. 1606 (2.97%) and coagulopathy in 21 (2.3%) vs. 521 (0.96%) in cirrhosis and without-cirrhosis groups, respectively. A total of 872 (1.59%) patients needed blood transfusion, 24 (2.7%) vs. 848(1.57%) in cirrhosis vs. without-cirrhosis groups (P 0.047). Fresh frozen plasma (FFP) transfusion was reported among 888 (1.62%), with cirrhosis 26 (3%) vs. without cirrhosis 862 (1.6%) (P 0.05). On adjusted multivariate logistic regression analysis, acute kidney injury, coagulopathy, FFP transfusion, and blood transfusion were strongly associated with cirrhosis, and GI bleeding, ischaemic stroke, and intracranial haemorrhage were not associated with cirrhosis. Readmissions in 30 days were 5028 (9.18%), 167 (18.5%) in the cirrhosis group and 4861 (9%) without-cirrhosis group (P 0.01). On multivariate Cox regression, CHA2DS2-Vasc score of six was significantly associated with 30-day readmission compared with other scores hazard ratio 2.24 95% confidence interval (1.58-3.16) P < 0.001. Left atrial appendage occlusion procedure in patients with cirrhosis had relatively similar GI bleeding and stroke rates, however, had higher rates of 30-day readmission. A higher CHA2DS2-Vasc score was more likely to be associated with 30-day readmissions and hence would help in discharge planning. The long-term safety and efficacy of LAAO in the cirrhosis population need to be demonstrated.

Prognostic impact of hypercoagulability and impaired fibrinolysis in acute myocardial infarction.

Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n 2705) were grouped according to disease acuity acute myocardial infarction (AMI) vs. non-AMI. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength maximal amplitude (MA) 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001 and lower fibrinolytic activity clot lysis at 30 min (LY30) 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001. Index AMI presentation was associated with MA per one-mm increase odds ratio (OR) 1.024 95% confidence interval (CI) 1.013-1.036 P < 0.001 and LY30 (per one% increase OR 0.934 95% CI 0.893-0.978 P 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of MA ≥ 68 mm and LY30 < 0.2% was a major predictor of post-PCI MACE in the AMI group adjusted hazard ratio (HR) 1.744 95% CI 1.135-2.679 P 0.011, but not in the non-AMI group (adjusted HR 1.031 95% CI 0.499-2.129 P 0.935). AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529.

Mechanisms of antigen-induced reversal of CNS inflammation in experimental demyelinating disease.

Autoimmune central nervous system (CNS) demyelinating diseases are a major public health burden and poorly controlled by current immunosuppressants. More precise immunotherapies with higher efficacy and fewer side effects are sought. We investigated the effectiveness and mechanism of an injectable myelin-based antigenic polyprotein MMPt (myelin oligodendrocyte glycoprotein, myelin basic protein and proteolipid protein, truncated). We find that it suppresses mouse experimental autoimmune encephalomyelitis without major side effects. MMPt induces rapid apoptosis of the encephalitogenic T cells and suppresses inflammation in the affected CNS. Intravital microscopy shows that MMPt is taken up by perivascular F480

Stroke An electromyographic approach to the masseter and temporal muscles, orofacial soft tissue pressure, and occlusal force.

Stroke is a cerebrovascular disease that triggers changes in the central and peripheral nervous systems, and can compromise human body function. This cross-sectional observational study aimed to analyze the electromyographic (EMG) activity of the masseter and temporal muscles, orofacial soft tissue pressure, and strength of occlusal contacts in patients who had suffered a stroke. Twenty-four patients were divided into two groups stroke (n 12) and control (n 12). The EMG of the masseter and temporal muscles was evaluated during mandibular rest, protrusion, right laterality, left laterality, and maximal voluntary contraction. The Iowa Oral Pressure Instrument (IOPI) was used to measure pressure from the tongue, lips, and buccinator muscles. A computerized system for occlusal analysis (T-Scan III) was used to measure the occlusal contact points of the right and left hemiarches (upper and lower) and the upper and lower first molars. Data were subjected to Students t-test (p < 0.05). The stroke group had lower normalized electromyographic activity, with a significant difference in the left temporal muscle during rest (p 0.03) when compared to the control group. There was a significant difference between the groups in tongue pressure (p 0.004) with a lower mean value in the stroke group. There was a significant difference between the groups in the evaluation of the occlusal contact points of the first permanent molars, with a lower mean percentage in the stroke group. The results indicate that stroke negatively affects functional performance of the stomatognathic system.

Causes of death of patients with non-valvular atrial fibrillation in Asians.

The aim of this study was to determine the causes of death among Asian non-valvular atrial fibrillation (AF) patients who were registered in a nationwide AF registry, and to investigate the differences in the causes of death in AF patients compared between those who were taking and not taking oral anticoagulant (OAC). The COhort of antithrombotic use and Optimal INR Level in patients with non-valvular Atrial Fibrillation in Thailand (COOL-AF) study enrolled non-valvular AF patients from 27 centers in Thailand during 2014-2017 to create the COOL-AF Thailand registry. Cause of death was classified as cardiovascular (CV) death, non-CV death, or undetermined cause of death. All events were evaluated and verified by an independent adjudication committee. There was a total of 3,405 patients (mean age 67.8 years, 41.8% female), and the mean follow-up duration was 31.8±8.7 months. Three hundred and eighty patients (11.2%) died during follow-up. CV death, non-CV death, and undetermined cause accounted for 121 (31.8%), 189 (49.7%), and 70 (18.4%) patients, respectively. Of those with a known cause of death, heart failure (10%), intracranial hemorrhage (ICH 10%), sudden cardiac death (6.8%), and ischemic stroke (5.8%) were the most often observed causes of death. Concerning non-CV death, infectionsepsis (27.7%), cancer (5.5%), respiratory (5.2%), and major bleeding (4.5%) were the most prevalent causes of death. The use and type of OAC were found to be major determinants of ICH and major bleeding incidence. Death due to ischemic stroke was responsible for only 4.7% of all deaths in Asian AF patients. Non-CV death, such as infectionsepsis or malignancy, was more far more prevalent than CV death in Asian AF patients. An improved integrated care approach is needed to reduce the prevalence of non-CV death in Asian AF patients.

Clinical utility of the 4S-AF scheme in predicting progression of atrial fibrillation data from the RACE V study.

The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF. We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 interquartile range (IQR) 58-71 years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA2DS2-VASc (the CHA2DS2-VASc score assesses thromboembolic risk. C, congestive heart failureleft ventricular dysfunction H, hypertension A2, age ≥ 75 years D, diabetes mellitus S2, stroketransient ischaemic attacksystemic embolism V, vascular disease A, age 65-74 years Sc, sex category (female sex)) score was 2 (IQR 2-3), and median follow-up was 2.1 (1.5-2.6) years. The average score of the 4S-AF scheme was 4.6 ± 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression odds ratio (OR) 1.1 95% CI 0.88-1.41, C-statistic 0.53. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severity, only including stroke risk, severity of AF burden and substrate of AF) scheme, predicted the risk of progression (OR 1.59 95% CI 1.15-2.27, C-statistic 0.62) even after adjusting for sex and age. In self-terminating AF patients, the 4S-AF scheme does not predict AF progression. The 3S-AF scheme, excluding the symptom domain, may be a more appropriate score to predict AF progression. Clinicaltrials.gov NCT02726698 for RACE V.

Characterizing acute and chronic complications among patients with diabetes mellitus in community health centers.

Context Diabetes mellitus affects about 10% of the worlds population and can lead to serious complications, which reduce life quality and expectancy. People with low income have higher risk of diabetes complications than those with high income, but data on the trends of diabetes complications in underserved populations are scarce. Community health centers (CHCs) serve millions of patients in the United States regardless of their health insurance status and are an ideal setting for assessing the rate of diabetes complications in underserved populations. Objectives To describe diabetes-related acute and chronic complications among patients served by CHCs. Study Design Retrospective cohort study of electronic health record data from the ADVANCE clinical research network. Population studied Patients with diabetes between ages 19 and 64 (excluding pregnant women) and ≥1 primary care ambulatory CHC visit in 2017 (N85,442). Outcome Measures Rates and type of diabetes-related acute and chronic complications recorded in 2017. Results The incidence of acute complications among patients with diabetes in 2017 was 14%. Patients experiencing acute diabetes-related complications had on average 1.8 complications (range 1-33). The most common acute complications were infections (58.3%), abnormal blood glucose or related metabolic abnormalities (20.5%), and strokes or transient neurological deficits (6.8%). Patients with acute complications were proportionally more likely to be female, non-Hispanic white, have Medicaid insurance, out-of-control diabetes, a prescription for insulin, a diagnosis of substance use disorder, and co-occurring physical or mental conditions. For chronic complications, the prevalence in 2017 was 77% among patients with diabetes. Patients experiencing chronic diabetes-related complications had on average 2.3 complications (range 1-19). The most common chronic complications were cardiovascular disease (33.9%), endocrinemetabolic symptoms (22.8%), and neurological symptoms (13.0%). Patients with chronic complications were proportionally more likely to be male, non-Hispanic black, have health insurance, obesity, substance use disorder, longer period with diabetes diagnosis, and co-occurring conditions. Conclusions The vast majority of patients with diabetes receiving care in CHCs had chronic complications. These findings are concerning, as diabetes-related complications are associated with greater healthcare utilization and patient morbidity.

Operative Outcomes of Women Undergoing Coronary Artery Bypass Surgery in the US, 2011 to 2020.

It has been reported that women undergoing coronary artery bypass have higher mortality and morbidity compared with men but it is unclear if the difference has decreased over the last decade. To evaluate trends in outcomes of women undergoing coronary artery bypass in the US from 2011 to 2020. This retrospective cohort study at hospitals contributing to the Adult Cardiac Surgery Database of the Society of Thoracic Surgeons included 1 297 204 patients who underwent primary isolated coronary artery bypass from 2011 to 2020. Coronary artery bypass. The primary outcome was operative mortality. The secondary outcome was the composite of operative mortality and morbidity (including operative mortality, stroke, kidney failure, reoperation, deep sternal wound infection, prolonged mechanical ventilation, and prolonged hospital stay). The attributable risk (the association of female sex with coronary artery bypass grafting outcomes) for the primary and secondary outcomes was calculated. Between 2011 and 2020, 1 297 204 patients underwent primary isolated coronary artery bypass grafting with a mean age of 66.0 years, 317 716 of which were women (24.5%). Women had a higher unadjusted operative mortality (2.8% 95% CI, 2.8-2.9 vs 1.7% 95% CI, 1.7-1.7 P < .001) and overall unadjusted incidence of the composite of operative mortality and morbidity compared with men (22.9% 95% CI, 22.7-23.0 vs 16.7% 95% CI, 16.6-16.8 P < .001). The attributable risk of female sex for operative mortality varied from 1.28 in 2011 to 1.41 in 2020, with no significant change over the study period (P for trend 0.38). The attributable risk for the composite of operative mortality and morbidity was 1.08 in both 2011 and 2020 with no significant change over the study period (P for trend 0.71). Women remain at significantly higher risk for adverse outcomes following coronary artery bypass grafting and no significant improvement has been seen over the course of the last decade. Further investigation into the determinants of operative outcomes in women is urgently needed.

Functional and Safety Outcomes of Carotid Artery Stenting and Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke With Tandem Lesions.

Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs however, optimal management and procedural strategy of the cervical lesion remain unclear. To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs. This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Patients with TLs were divided into CAS vs nonstenting groups. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days. Of 685 patients, 623 (mean SD age, 67 12.2 years 406 65.2% male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 10.6% vs 49 19.2%, P .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99% 107 32.2% vs 42 20.5%, P < .001) and atherosclerotic disease (296 82.0% vs 194 74.6%, P .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 10-19 vs 17 13-21, P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio aOR, 1.67 95% CI, 1.20-2.40 P .007), favorable shift in mRS scores (aOR, 1.46 95% CI, 1.02-2.10 P .04), and successful reperfusion (aOR, 1.70 95% CI, 1.02-3.60 P .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90 95% CI, 0.46-2.40 P .87) and 90-day mortality (aOR, 0.78 95% CI, 0.50-1.20 P .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups. In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers Post Hoc Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean SD age, 67.7 8.0 years 200 men 56.3%) received intensive BP treatment and 315 participants (mean SD age, 67.0 8.4 years 199 men 63.2%) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 95% CI, 16.0-44.5 mm3 standard treatment, 80.5 mm3 95% CI, 53.8-107.2 mm3), left tapetum (intensive treatment, 11.8 mm3 95% CI, 4.4-19.2 mm3 standard treatment, 27.2 mm3 95% CI, 19.4-35.0 mm3), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 95% CI, 0.7-5.8 mm3 standard treatment, 9.4 mm3 95% CI, 5.5-13.4 mm3), left posterior corona radiata (intensive treatment, 26.0 mm3 95% CI, 12.9-39.1 mm3 standard treatment, 52.3 mm3 95% CI, 34.8-69.8 mm3), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 95% CI, 25.1-65.7 mm3 standard treatment, 83.0 mm3 95% CI, 58.7-107.2 mm3), left posterior thalamic radiation (intensive treatment, 53.0 mm3 95% CI, 29.8-76.2 mm3 standard treatment, 106.9 mm3 95% CI, 73.4-140.3 mm3), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 95% CI, 24.3-74.7 mm3 standard treatment, 102.6 mm3 95% CI, 71.0-134.2 mm3). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier NCT01206062.

Association of Cardiac Biomarkers With Major Adverse Cardiovascular Events in High-risk Patients With Diabetes A Secondary Analysis of the DECLARE-TIMI 58 Trial.

Dapagliflozin reduces the risk of hospitalizations for heart failure and the progression of chronic kidney disease in patients with and without type 2 diabetes (T2D), whereas the effects on reducing atherosclerotic events appear less clear. To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) levels can identify a subset of patients with T2D at higher risk and who might benefit more from dapagliflozin with regard to atherosclerotic events. This was a secondary analysis of the DECLARE-TIMI 58 trial, a randomized clinical trial of dapagliflozin in patients with T2D and either multiple risk factors for atherosclerotic cardiovascular disease (ASCVD approximately 60%) or established ASCVD (approximately 40%). All patients with available blood samples at randomization were included in these analyses. Data were collected from May 2013 to September 2018, and data were analyzed from May 2019 to June 2022. Dapagliflozin vs placebo. Major adverse cardiovascular events (MACE), the composite of myocardial infarction, ischemic stroke, or cardiovascular death, which was one of dual primary outcomes of the main trial. Of 14 565 included patients, 9143 (62.8%) were male, and the mean (SD) age was 63.9 (6.8) years. When tested individually in a multivariable model for MACE risk, NT-proBNP and hsTnT were each significantly associated with the risk of MACE (adjusted hazard ratio aHR per 1 SD in log-transformed biomarker NT-proBNP, 1.62 95% CI, 1.49-1.76 hsTnT 1.59 95% CI, 1.46-1.74). The magnitude of the association was similar in patients with ASCVD (NT-proBNP aHR, 1.60 95% CI, 1.45-1.77 hsTnT aHR, 1.62 95% CI, 1.45-1.81) and multiple risk factors for ASCVD (NT-proBNP aHR, 1.62 95% CI, 1.40-1.88 hsTnT aHR, 1.51 95% CI, 1.29-1.77). Moreover, both biomarkers remained independently associated with MACE when both were included in the multivariable model (NT-proBNP aHR, 1.46 95% CI, 1.34-1.60 hsTnT aHR, 1.39 95% CI, 1.26-1.53). Modeled as a continuous variable, baseline biomarker levels did not modify the relative treatment effect of dapagliflozin vs placebo with MACE. However, the relative risk reduction numerically grew with higher biomarker levels, as did the baseline risk. Thus, MACE event rates were nominally lower in dapagliflozin-treated vs placebo-treated patients with biomarker concentrations in the top quartile (NT-proBNP HR, 0.83 95% CI, 0.71-0.97 absolute risk reduction ARR, 2.4% hsTnT HR, 0.85 95% CI, 0.72-0.99 ARR, 2.7%), whereas there was no significant treatment effect in patients with biomarkers levels in quartiles 1 to 3 (NT-proBNP HR, 1.02 95% CI, 0.88-1.18 ARR, 0% hsTnT HR, 0.97 95% CI, 0.84-1.13 ARR, 0.2%). In this study, NT-proBNP and hsTnT levels were associated with the risk for future cardiovascular events in both primary and secondary prevention patients with T2D. Both cardiac biomarkers were helpful to identify patients at very high risk for atherosclerotic events that may derive reduction in risk of MACE with dapagliflozin. ClinicalTrials.gov Identifier NCT01730534.

Percutaneous left atrial appendage occlusion in patients with a cardiac implantable electronic device.

Left atrial appendage occlusion (LAAO) may be a viable option for stroke prevention in patients with non-valvular atrial fibrillation and a contraindication for oral anticoagulation. No evidence evaluating the safety of this procedure in patients with a cardiac implantable electronic device (CIED) exists. The aim of this study was to evaluate whether CIED function is affected by LAAO and to explore LAAO procedural characteristics and complications in patients with a CIED. This single-center cohort study included consecutive patients scheduled for percutaneous LAAO. Patients with a CIED prior to LAAO were selected and compared to the patients without CIED, concerning procedural characteristics and peri-procedural complications. In the group of patients with CIEDs, essential pacemaker integrity parameters were compared before and after the procedure to detect possible micro and macro lead displacements. Thirty-one patients with CIED were scheduled for LAAO (age 73.7 ± 5.4 years, 65% males, CHA This study supports the feasibility and safety of LAAO in patients with a CIED.

Role of oncostatin-M in ECM remodeling and plaque vulnerability.

Atherosclerosis is a multifactorial inflammatory disease characterized by the development of plaque formation leading to occlusion of the vessel and hypoxia of the tissue supplied by the vessel. Chronic inflammation and altered collagen expression render stable plaque to unstable and increase plaque vulnerability. Thinned and weakened fibrous cap results in plaque rupture and formation of thrombosis and emboli formation leading to acute ischemic events such as stroke and myocardial infarction. Inflammatory mediators including TREM-1, TLRs, MMPs, and immune cells play a critical role in plaque vulnerability. Among the other inflammatory mediators, oncostatin-M (OSM), a pro-inflammatory cytokine, play an important role in the development and progression of atherosclerosis, however, the role of OSM in plaque vulnerability and extracellular matrix remodeling (ECM) is not well understood and studied. Since ECM remodeling plays an important role in atherosclerosis and plaque vulnerability, a detailed investigation on the role of OSM in ECM remodeling and plaque vulnerability is critical. This is important because the role of OSM has been discussed in the context of proliferation of vascular smooth muscle cells and regulation of cytokine expression but the role of OSM is scarcely discussed in relation to ECM remodeling and plaque vulnerability. This review focuses on critically discussing the role of OSM in ECM remodeling and plaque vulnerability.

Neuroplasticity Following Stroke from a Functional Laterality Perspective A fNIRS Study.

To explore alterations of resting-state functional connectivity (rsFC) in sensorimotor cortex following strokes with left or right hemiplegia considering the lateralization and neuroplasticity. Seventy-three resting-state functional near-infrared spectroscopy (fNIRS) files were selected, including 26 from left hemiplegia (LH), 21 from right hemiplegia (RH) and 26 from normal controls (NC) group. Whole-brain analyses matching the Pearson correlation were used for rsFC calculations. For right-handed normal controls, rsFC of motor components (M1 and M2) in the left hemisphere displayed a prominent intensity in comparison with the right hemisphere (p < 0.05), while for stroke groups, this asymmetry has disappeared. Additionally, RH rather than LH showed stronger rsFC between left S1 and left M1 in contrast to normal controls (p < 0.05), which correlated inversely with motor function (r - 0.53, p < 0.05). Regarding M1, rsFC within ipsi-lesioned M1 has a negative correlation with motor function of the affected limb (r - 0.60 for the RH group and - 0.43 for the LH group, p < 0.05). The rsFC within contra-lesioned M1 that innervates the normal side was weakened compared with that of normal controls (p < 0.05). Stronger rsFC of motor components in left hemisphere was confirmed by rs-fNIRS as the secret of dominance for the first time, while post-stroke hemiplegia broke this cortical asymmetry. Meanwhile, a statistically strengthened rsFC between left S1 and M1 only in right-hemiplegia group may act as a compensation for the impairment of the dominant side. This research has implications for brain-computer interfaces synchronizing sensory feedback with motor performance and transcranial magnetic regulation for cortical excitability to induce cortical plasticity.

Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes.

Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles association with SVD. This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 74-83, 75 70-80, and 75 72-81 mmHg, p 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1% 46.8% 37.1% versus 15.4% 41.9% 42.7% (p 0.758). Minor allele frequencies were 39.5% versus 36.3% (p 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p 0.790 microbleeds 25.0% vs 21.9%, p 0.904 lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.

Prospective cohort study on potato intake and mortality from cardiovascular diseases the Japan Collaborative Cohort Study (JACC study).

The association between potato intake and risk of cardiovascular diseases is unknown. This study aimed to examine the association between potatoes intake and mortality from stroke and coronary heart disease among Japanese. The study included 74,750 participants of the Japan Collaborative Cohort Study, aged 40-79, who were initially free of cardiovascular diseases or cancer at baseline (1988-1990) and provided information on their potato intake. Hazard ratios and 95% confidence intervals were estimated by fitting a Cox proportional hazards model according to the frequency of potatoes intake (0, 0.4, 1.5, 3.5 and 7 servings per week) adjusting for geographic location, age, body mass index, drinking status, smoking status, perceived mental stress, education level, walking time, dietary intakes of total energy, meat, fish, vegetables, fruit, dairy products, cakes, and salt. Over a median of 19.2 years of follow-up, 4908 deaths from cardiovascular diseases were identified 1019 from coronary heart diseases and 2153 from strokes (738 ischemic strokes and 495 hemorrhagic strokes). After adjustment for potential confounding factors, the hazard ratio of mortality from cardiovascular diseases for daily potato intake compared with no potato intake was 0.82 (95% confidence interval 0.70, 0.95) among women, and 1.01 (0.88, 1.16) among men. Among women, the multivariable hazard ratios were 0.67 (0.48, 0.96) for coronary heart disease, 0.83 (0.66-1.05) for total stroke, 0.70 (0.43-1.15) for hemorrhagic stroke, and 0.75 (0.49-1.13) for ischemic stroke. We found an inverse association of potato intake with mortality from total cardiovascular diseases, especially that from coronary heart disease, among Japanese women. To our knowledge, this is the first report to show an inverse association between potato intake and total cardiovascular diseases.

SGLT2 inhibitors Effect on myocardial infarction and stroke in type 2 diabetes.

SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) have recently been recommended as preferred agents for management of hyperglycemia in type 2 diabetes, primarily based on their ability to reduce a composite of major cardiovascular adverse events (3P MACE), predominantly by reducing cardiovascular death. However reduction of the individual components, myocardial infarction (MI) or stroke (fatal and non-fatal) events have not been well explored. In this meta-analysis, we included data available from cardiovascular outcome trials only (CVOTs), which were event-driven, randomized, and placebo-controlled. Pooled efficacy outcomes included Mantel Haenszel (MH) risk ratio using fixed model (with 95% CI) for fatal and nonfatal MI, stroke and total MI and stroke. Data from four eligible trials included 42568 subjects. Total MACE, MI and stroke were reported in4176, 2157 and 1288 subjects respectively. SGLT2i (SGLT2 inhibitors) did not significantly reduce either MI or stroke individually or in totality. The MH risk ratio (95% CI) for fatal and nonfatal MI and stroke with differentSGLT2i was found to be 0.93 (95% CI 0.85, 1.01) and 1.00 (95% CI 0.89, 1.11), respectively. For total ASCVD events, MH risk ratio (95% CI) was 0.95 (95% CI 0.89, 1.02). For all nonfatal ASCVD (combined nonfatal MI and nonfatal stroke)MH risk ratio (95% CI) was 0.94 (95% CI 0.88, 1.02). SGLT2i reduce MACE without any discernable significant reduction of in the incidence of MI or Stroke (fatal and non-fatal), probably implicating mechanisms unrelated to anti-atherogenic effects.