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Predictors of externalizing behavior outcomes following pediatric stroke.

Children who experience pediatric stroke are at higher risk for future behavioral problems in childhood. We examined the prevalence of parent reported externalizing behaviors and executive function problems in children following stroke and neurological predictors. This study included 210 children with pediatric ischemic stroke (mean age 9.18 years (SD 3.95)). The parent form of the Behavioral Assessment System for Children-Second Edition (BASC-2) and Behavior Rating Inventory of Executive Function (BRIEF) were used to evaluate externalizing behavior and executive function. No externalizing behavior or executive function differences were found between perinatal (

High plasma complement C4 levels as a novel predictor of clinical outcome in intracerebral hemorrhage.

The complement cascade is activated and contributes to the brain injury after intracerebral hemorrhage (ICH). Complement component 4 (C4), an important component of complement cascade, has been associated with severity of neurological impairment that occurs during ICH. However, the correlation of plasma complement C4 levels with hemorrhagic severity and clinical outcome in ICH patients has not been reported. This study is a monocentric, real-world, cohort study. In this study, we measured the plasma complement C4 levels of 83 ICH patients and 78 healthy controls. The hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, the Glasgow Coma Scale (GCS) score, and the permeability surface (PS) were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma complement C4 levels to hemorrhagic severity and clinical outcomes. The contribution of complement C4 to secondary brain injury (SBI) was assessed by changes in plasma C4 levels between admission and at day 7 after ICH. There was a significant elevation of plasma complement C4 levels in ICH patients than in healthy controls (40.48 ± 1.07 vs. 35.25 ± 0.60, Plasma complement C4 levels are significantly elevated in ICH patients and positively correlated with the illness severity. Thus, these findings highlight the importance of complement C4 in brain injury after ICH and provide a novel predictor of clinical outcome for this disease.

Prevalence of selected bleeding and thrombotic events in persons with hemophilia versus the general population A scoping review.

Life expectancy for persons with hemophilia has increased over recent decades due to advances in treatment practice and patient care. Those with hemophilia are now more likely to be affected by conditions associated with aging, such as myocardial infarction, hemorrhagicischemic stroke, deep vein thrombosis, pulmonary embolism, and intracranial hemorrhage. Here, we describe the results of a literature search designed to summarize current data on the prevalence of the above selected bleeding and thrombotic events in persons with hemophilia vs the general population. A total of 912 articles published between 2005 and 2022 were identified in a search of BIOSIS Previews, Embase, and MEDLINE databases conducted in July 2022. Case studies, conference abstracts, review articles, studies focusing on hemophilia treatments or surgical outcomes, and studies examining patients with inhibitors only were excluded. After screening, 83 relevant publications were identified. The prevalence of bleeding events was consistently higher in hemophilia populations vs reference populations (hemorrhagic stroke, 1.4%-5.31% vs 0.2%-0.97% intracranial hemorrhage, 1.1%-10.8% vs 0.04%-0.4%). Serious bleeding events showed a high rate of mortality with standardized mortality ratios for intracranial hemorrhage ranging from 3.5 to 14.88. Although 9 studies reported lower prevalence of arterial thrombosis (myocardial infarctionstroke) in hemophilia vs general populations, 5 studies reported higher or comparable prevalence in hemophilia. Prospective studies are therefore needed to understand the prevalence of bleeding and thrombotic events in hemophilia populations, particularly with the observed increases in life expectancy and availability of novel treatments.

Risk factors of hemorrhagic transformation in acute ischaemic stroke A systematic review and meta-analysis.

Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT). Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR 2.605, 95% CI 1.212-5.599, Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. httpswww.crd.york.ac.ukprosperodisplayrecord.phpRecordID268927, identifier CRD42021268927.

Neurological scoring and gait kinematics to assess functional outcome in an ovine model of ischaemic stroke.

Assessment of functional impairment following ischaemic stroke is essential to determine outcome and efficacy of intervention in both clinical patients and pre-clinical models. Although paradigms are well described for rodents, comparable methods for large animals, such as sheep, remain limited. This study aimed to develop methods to assess function in an ovine model of ischaemic stroke using composite neurological scoring and gait kinematics from motion capture. Merino sheep ( Neurological scoring was moderately repeatable across baseline trials (ICC > 0.50) and detected marked impairment post-stroke ( This study developed repeatable methods to assess function in sheep using composite scoring and gait kinematics, allowing for the evaluation of deficit 3 days post-stroke. Despite utility of each method independently, there was poor association observed between gait kinematics, composite scoring, and infarct volume on PCA. This suggests that each of these measures has discreet utility for the assessment of stroke deficit, and that multimodal approaches are necessary to comprehensively characterise functional impairment.

Selection of patients with acute vertebrobasilar artery occlusion for endovascular treatment by magnetic resonance imaging.

The best method for selecting patients with acute vertebrobasilar artery occlusion (VBAO) who would benefit from endovascular treatment (EVT) is still the key question. This study aimed to assess the efficacy of magnetic resonance imaging (MRI) for selecting patients with acute VBAO for EVT. A total of 14 patients with suspected acute VBAO on MR angiography (MRA) in the EVT database (from April 2016 to August 2019) were enrolled. Acute Stroke Prognosis Early Computed Tomography Score (ASPECTS) and pons-midbrain index were assessed on diffusion-weighted imaging (DWI). EVT included a stent retriever and a rescue treatment (angioplasty andor stenting). The proportion of successful reperfusion and favorable functional outcomes (modified Rankin Scale ≤ 3) at 90 days was documented. A total of 11 patients were included in the final analysis. The median DWI-ASPECTS and pons-midbrain index were 7 and 2, respectively. Underlying stenosis was detected in 10 of 11 (90.9%) patients. Balloon angioplasty andor stenting were used as rescue therapy for five patients and two patients, respectively. A total of nine patients (81.8%) achieved successful reperfusion (mTICI, 2b, or 3). The 90-day mRS score of 0-3 was achieved in six (54.5%) patients. The mortality rate within 90 days was 18.2% (two of 11 patients). DWI plus MRA could help select the patients with acute VBAO for EVT by assessing ASPECTS and the pons-midbrain index. Patients could achieve good reperfusion and favorable functional outcomes.

Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies. One of the main issues related to CIRI treatment is the presence of the blood-brain barrier (BBB), which affects the intracerebral delivery of drugs. Ginkgolide B (GB), a major bioactive component in commercially available products of

Early Discontinuation of Phenobarbital After Acute Symptomatic Neonatal Seizures in the Term Newborn.

Acute symptomatic seizures in the term newborn are often seen after perinatal brain injury. Common etiologies include hypoxic-ischemic encephalopathy, ischemic stroke, intracranial hemorrhage, metabolic derangements, and intracranial infections. Neonatal seizures are often treated with phenobarbital, which may cause sedation and may have significant long-term effects on brain development. Recent literature has suggested that phenobarbital may be safely discontinued in some patients before discharge from the neonatal intensive care unit. Optimizing a strategy for selective early phenobarbital discontinuation would be of great value. In this study, we present a unified framework for phenobarbital discontinuation after resolution of acute symptomatic seizures in the setting of brain injury of the newborn.

Preliminary findings on left atrial appendage occlusion simulations applying different endocardial devices.

Atrial fibrillation (AF) is one of the most investigated arrhythmias since it is associated with a five-fold increase in the risk of strokes. Left atrium dilation and unbalanced and irregular contraction caused by AF favour blood stasis and, consequently, stroke risk. The left atrial appendage (LAA) is the site of the highest clots formation, increasing the incidence of stroke in AF population. For many years oral anticoagulation therapy has been the most used AF treatment option available to decrease stroke risk. Unfortunately, several contraindications including bleeding risk increase, interference with other drugs and with multiorgan functioning, might outweigh its remarkable benefits on thromboembolic events. For these reasons, in recent years, other approaches have been designed, including LAA percutaneous closure. Unfortunately, nowadays, LAA occlusion (LAAO) is restricted to small subgroups of patients and require a certain level of expertise and training to successfully complete the procedure without complications. The most critical clinical problems associated with LAAO are represented by peri-device leaks and device related thrombus (DRT). The anatomical variability of the LAA plays a key role in the choice of the correct LAA occlusion device and in its correct positioning with respect to the LAA ostium during the implant. In this scenario, computational fluid dynamics (CFD) simulations could have a crucial role in improving LAAO intervention. The aim of this study was to simulate the fluid dynamics effects of LAAO in AF patients to predict hemodynamic changes due to the occlusion. LAAO was simulated by applying two different types of closure devices based on the plug and the pacifier principles on 3D LA anatomical models derived from real clinical data in five AF patients. CFD simulations were performed on the left atrium model before and after the LAAO intervention with each device. Blood velocity, particle washout and endothelial damage were computed to quantify flow pattern changes after the occlusion in relation to the thrombogenic risk. Our preliminary results confirmed an improved blood washout after the simulated implants and the capability of foreseeing thrombogenic risk based on endothelial damage and maximum blood velocities in different scenarios. This tool may help to identify effective device configurations in limiting stroke risk for patient-specific LA morphologies.

Remote Patient Monitoring for Patients with Heart Failure Sex- and Race-based Disparities and Opportunities.

Remote patient monitoring (RPM), within the larger context of telehealth expansion, has been established as an effective and safe means of care for patients with heart failure (HF) during the recent pandemic. Of the demographic groups, female patients and black patients are underenrolled relative to disease distribution in clinical trials and are under-referred for RPM, including remote haemodynamic monitoring, cardiac implantable electronic devices (CIEDs), wearables and telehealth interventions. The sex- and race-based disparities are multifactorial stringent clinical trial inclusion criteria, distrust of the medical establishment, poor access to healthcare, socioeconomic inequities, and lack of diversity in clinical trial leadership. Notwithstanding addressing the above factors, RPM has the unique potential to reduce disparities through a combination of implicit bias mitigation and earlier detection and intervention for HF disease progression in disadvantaged groups. This review describes the uptake of remote haemodynamic monitoring, CIEDs and telehealth in female patients and black patients with HF, and discusses aetiologies that may contribute to inequities and strategies to promote health equity.

Magnetic resonance imaging in the evaluation of the pathologies affecting large intracranial arteries.

Our aim is to describe the utility of magnetic resonance imaging (MRI) in the evaluation of pathologies affecting large intracranial arteries. We performed a prospective and observational study from 2018 to 2020 using 1.5 T MRI. Our study included 75 patients who were referred for MRI brain with clinical features of stroke or having tumorsinfection involving large intracranial arteries (vertebral, basilar, and internal carotid arteries) on initial MRI. Correlation of MRI diagnosis was done with final diagnosis. Atherothrombosis was the most common pathology involving all the intracranial large arteries and was most commonly seen in elderly male patients. The second most common pathology involving the internal carotid, vertebral, and basilar arteries was tumors, dissection, and aneurysms, respectively. The most common artery involved by atherothrombosis, tumor, and infectioninflammation was internal carotid artery, whereas it was basilar artery and vertebral artery in cases of aneurysm and dissection, respectively. MRI is an extremely useful modality to study large intracranial arteries. It is useful to demonstrate the site of abnormality, vessel lumen and caliber, vessel wall changes, and perivascular areas. This can help in arriving at correct diagnosis and thereby guide appropriate timely management.

Ankle dorsiflexion assist using a single sensor-based FES Results from clinical study on patients with stroke.

Ankle foot orthosis (AFO) commonly prescribed to manage foot-drop following stroke restricts ankle mobility. Commercially available functional electrical stimulation (FES) is an expensive alternative to achieve desired dorsiflexion during swing phase of the gait cycle. An in-house cost-effective innovative solution was designed and developed to address this problem.The aim of the study was to compare spatiotemporal gait characteristics of patients with foot-drop following stroke using commercially available FES against in-house developed versatile single sensor-based FES. Ten patients with cerebrovascular accident of at least 3 months duration and ambulant withwithout AFO were recruited prospectively. They were trained with Device-1 (Commercial Device) and Device-2 (In-house developed, Re-Lift) for 7 h over 3 consecutive days with each device. Outcome measures included timed-up-and-go-test (TUG), six-minute-walk-test (6MWT), ten-meter-walk-test (10MWT), physiological cost index (PCI), instrumented gait analysis derived spatiotemporal parameters, and patient satisfaction feedback questionnaire. We calculated intraclass correlation between devices and median interquartile range. Statistical analysis included Wilcoxon-signed-rank-test and F-test ( Intraclass correlation coefficient for 6MWT (0.96), 10MWT (0.97), TUG test (0.99), and PCI (0.88) reflected high agreement between the two devices. Scatter plot and Bland Altman plots for the outcome parameters showed good correlation between two FES devices. Patient satisfaction scores were equal for both Device-1 and Device-2. There was statistically significant change in swing phase ankle dorsiflexion. The study demonstrated good correlation between commercial FES and Re-Lift suggestive of the utility of low-cost FES device in clinical setting.

Asymptomatic Hyperuricemia as an Independent Risk Factor for Myocardial Infarction in Adult Population A Four-Year Follow-Up Study.

Introduction A condition in which uric acid levels are elevated but there are no accompanying symptoms is known as asymptomatic hyperuricemia. As a result of the disparity in opinions and findings between the studies, the guidelines regarding whether or not asymptomatic hyperuricemia should be treated are unclear. Material and methods Between the months of January 2017 and June 2022, this research was carried out in the community in collaboration with the internal medicine unit and the public health unit of Liaquat University of Medical and Health Sciences. After obtaining informed consent from each participant, the researchers enrolled 1,500 patients in the study who had uric acid levels that were greater than 7.0 mgdL. These patients ranged in age from 40 to 70 years old and were of either gender. As a control group, 1,500 patients were recruited who did not have abnormally high levels of uric acid. Patients were monitored for a total of 48 months or until the occurrence of a major cardiovascular event (MACCE) or death from all causes, whichever occurred first. Death, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke were the four categories that made up the primary outcome, also known as MACCEs. Results In the hyperuricemic group, the incidence of myocardial infarction that did not result in death was significantly higher than in the non-hyperuricemic group (1.6% vs. 0.7% p-value, 0.04). However, the result was not significant for deaths from all causes, deaths from cardiovascular disease, or strokes that did not result in death. Conclusion Asymptomatic hyperuricemia is a potential threat to ones health that can lead to cardiovascular diseases and may go undiagnosed in some cases. It is important to remember that hyperuricemia can lead to delirious complications, so efforts should be made to perform routine monitoring and management of the condition.

The Use of Caffeine Citrate for Respiratory Stimulation in Acquired Central Hypoventilation Syndrome A Case Series.

Caffeine is commonly used as a respiratory stimulant for the treatment of apnea of prematurity in neonates. However, there are no reports to date of caffeine used to improve respiratory drive in adult patients with acquired central hypoventilation syndrome (ACHS). We report two cases of ACHS who were successfully liberated from mechanical ventilation after caffeine use, without side effects. The first case was a 41-year-old ethnic Chinese male, diagnosed with high-grade astrocytoma in the right hemi-pons, intubated and admitted to the intensive care unit (ICU) in view of central hypercapnia with intermittent apneic episodes. Oral caffeine citrate (1600mg loading followed by 800mg once daily) was initiated. His ventilator support was weaned successfully after 12 days. The second case was a 65-year-old ethnic Indian female, diagnosed with posterior circulation stroke. She underwent posterior fossa decompressive craniectomy and insertion of an extra-ventricular drain. Post-operatively, she was admitted to the ICU and absence of spontaneous breath was observed for 24 hours. Oral caffeine citrate (300mg twice daily) was initiated and she regained spontaneous breath after 2 days of treatment. She was extubated and discharged from the ICU. Oral caffeine was an effective respiratory stimulant in the above patients with ACHS. Larger randomized controlled studies are needed to determine its efficacy in the treatment of ACHS in adult patients.

Mortality among over 6 million internal and international migrants in Brazil a study using the 100 Million Brazilian Cohort.

To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR 0.99, 95% CI 0.98-0.99), marginally higher mortality for ischaemic heart diseases (aHR 1.04, 95% CI 1.03-1.05) and higher for stroke (aHR 1.11, 95% CI 1.09-1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR 0.82, 95% CI 0.80-0.84), with up to 50% lower mortality from interpersonal violence among men (aHR 0.50, 95% CI 0.40-0.64), but higher mortality from avoidable causes related to maternal health (aHR 2.17, 95% CI 1.17-4.05). Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. The Wellcome Trust.

INVICTUS Vitamin K antagonists remain the standard of care for rheumatic heart disease-associated atrial fibrillation.

Rheumatic heart disease (RHD) remains a major healthcare problem. Atrial fibrillation (AF) is the commonest sustained arrhythmia in RHD, leading to major complications and morbidity in a young population. Currently, anticoagulation with vitamin K antagonists (VKA) is the mainstay of therapy for the prevention of thromboembolic adverse events. However, effective use of VKA remains challenging, especially in developing countries, showing a need for alternatives. Novel oral anticoagulants (NOACs), including rivaroxaban, could form a safe and effective alternative to fulfil a major unmet need in RHD patients with AF. However, until recently, no data was available for the use rivaroxaban in patients with rheumatic heart disease associated AF. Study and Results The INVICTUS trial was conducted to assess efficacy and safety of once-daily rivaroxaban compared with a dose-adjusted VKA for the prevention of cardiovascular events in patients with RHD-associated AF. A total of 4531 patients (age 50.5 ± 14.6 years) were followed for 3.1 ± 1.2 years in which 5602292 patients in the rivaroxaban group and 4462273 in the VKA group had a primary-outcome adverse event. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the VKA group (difference, -76 days 95% confidence interval CI, -121 to -31 P <0.001). A higher incidence of death occurred in the rivaroxaban group than in the VKA group (restricted mean survival time, 1608 days vs. 1680 days difference, -72 days 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. The INVICTUS trial shows that Rivaroxaban is inferior to Vitamin K-antagonists in patients with RHD associated AF as VKA therapy led to a lower rate of ischemic and lower mortality due to vascular causes, without significantly increasing the rate of major bleeding. The results support current guidelines, which recommend vitamin K antagonist therapy for the prevention of stroke in patients with RHD associated AF.

Effects of High- or Moderate-intensity Rosuvastatin on 1-year Major Adverse Cardiovascular Events Post-percutaneous Coronary Intervention.

Oxymatrine and insulin resistance Focusing on mechanistic intricacies involve in diabetes associated cardiomyopathy via SIRT1AMPK and TGF-β signaling pathway.

Cardiomyopathy (CDM) and related morbidity and mortality are increasing at an alarming rate, in large part because of the increase in the number of diabetes mellitus cases. The clinical consequence associated with CDM is heart failure (HF) and is considerably worse for patients with diabetes mellitus, as compared to nondiabetics. Diabetic cardiomyopathy (DCM) is characterized by structural and functional malfunctioning of the heart, which includes diastolic dysfunction followed by systolic dysfunction, myocyte hypertrophy, cardiac dysfunctional remodeling, and myocardial fibrosis. Indeed, many reports in the literature indicate that various signaling pathways, such as the AMP-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), PI3KAkt, and TGF-βsmad pathways, are involved in diabetes-related cardiomyopathy, which increases the risk of functional and structural abnormalities of the heart. Therefore, targeting these pathways augments the prevention as well as treatment of patients with DCM. Alternative pharmacotherapy, such as that using natural compounds, has been shown to have promising therapeutic effects. Thus, this article reviews the potential role of the quinazoline alkaloid, oxymatrine obtained from the Sophora flavescensin CDM associated with diabetes mellitus. Numerous studies have given a therapeutic glimpse of the role of oxymatrine in the multiple secondary complications related to diabetes, such as retinopathy, nephropathy, stroke, and cardiovascular complications via reductions in oxidative stress, inflammation, and metabolic dysregulation, which might be due to targeting signaling pathways, such as AMPK, SIRT1, PI3KAkt, and TGF-β pathways. Thus, these pathways are considered central regulators of diabetes and its secondary complications, and targeting these pathways with oxymatrine might provide a therapeutic tool for the diagnosis and treatment of diabetes-associated cardiomyopathy.

Retrospective Analysis of Direct-Acting Oral Anticoagulants (DOACs) Initiation Timing and Outcomes After Thrombolysis in High- and Intermediate-Risk Pulmonary Embolism.

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n 53) had shorter hospital LOS compared to those in warfarin (n 39) and enoxaparin (n 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively

Multidisciplinary coordinated care of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare disorder with a case prevalence as high as one in 5000, causing arteriovenous malformations in multiple organ systems. HHT is familial with autosomal dominant inheritance, with genetic testing allowing confirmation of the diagnosis in asymptomatic kindreds. Common clinical manifestations are epistaxis and intestinal lesions causing anemia and requiring transfusions. Pulmonary vascular malformations predispose to ischemic stroke and brain abscess and may cause dyspnea and cardiac failure. Brain vascular malformations can cause hemorrhagic stroke and seizures. Rarely, liver arteriovenous malformations can cause hepatic failure. A form of HHT can cause juvenile polyposis syndrome and colon cancer. Specialists in multiple fields may be called to care for one or more aspects of HHT, but few are familiar with evidence-based guidelines for HHT management or see a sufficient number of patients to gain experience with the unique characteristics of the disease. Primary care physicians and specialists are often unaware of the important manifestations of HHT in multiple systems and the thresholds for their screening and appropriate management. To improve familiarity, experience, and coordinated multisystem care for patients with HHT, the Cure HHT Foundation, which advocates for patients and families with this disease, has accredited 29 centers in North America with designated specialists for the evaluation and care of patients with HHT. Team assembly and current screening and management protocols are described as a model for evidence-based, multidisciplinary care in this disease.

Impact of the COVID-19 pandemic on acute stroke care An analysis of the 24-month data from a comprehensive stroke center in Shanghai, China.

Whether the coronavirus disease-2019 (COVID-19) pandemic is associated with a long-term negative impact on acute stroke care remains uncertain. This study aims to compare the timing of key aspects of stroke codes between patients before and after the COVID-19 pandemic. This retrospective cohort study was conducted at an academic hospital in Shanghai, China and included all adult patients with acute ischemic stroke hospitalized via the emergency department (ED) stroke pathway during the 24 months since the COVID-19 outbreak (COVID-19 January 1, 2020-December 31, 2021). The comparison cohort included patients with ED stroke pathway visits and hospitalizations during the same period (pre-COVID-19 January 1, 2018-December 31, 2019). We compared critical time points of prehospital and intrahospital acute stroke care between patients during the COVID-19 era and patients during the pre-COVID-19 era using t test, χ A total of 1194 acute ischemic stroke cases were enrolled, including 606 patients in COVID-19 and 588 patients in pre-COVID-19. During the COVID-19 pandemic, the median onset-to-hospital time was about 108 min longer compared with the same period of pre-COVID-19 (300 vs 192 min, p 0.01). Accordingly, the median onset-to-needle time was 169 min in COVID-19 and 113 min in pre-COVID-19 (p 0.0001), and the proportion of patients with onset-to-hospital time within 4.5 h was lower (292606 48.2% vs 328558 58.8%, p 0.0003) during the pandemic period. Furthermore, the median door-to-inpatient admission and door-to-inpatient rehabilitation times increased from 28 to 37 h and from 3 to 4 days (p 0.014 and 0.0001). During the 24 months of COVID-19, a prolongation of stroke onset to hospital arrival and to intravenous rt-PA administration times were noted. Meanwhile, acute stroke patients needed to stay in the ED for a longer time before hospitalization. Educational system support and process optimization should be pursued in order to acquire timely delivery of stroke care during the pandemic.

Validation of diagnosis codes in healthcare databases in Taiwan, a literature review.

To compile validation findings of diagnosis codes and related algorithms for health outcomes of interest from National Health Insurance (NHI) or electronic medical records in Taiwan. We carried out a literature review of English articles in PubMed® and Embase from 2000 through July 2022 with appropriate search terms. Potentially relevant articles were identified through review of article titles and abstracts, full text search of methodology terms validation, positive predictive value, and algorithm in Subjects Methods (or Methods) and Results sections of articles, followed by full text review of potentially eligible articles. We identified 50 published reports with validation findings of diagnosis codes and related algorithms for a wide range of health outcomes of interest in Taiwan, including cardiovascular diseases, stroke, renal impairment, malignancy, diabetes, mental health diseases, respiratory diseases, viral (B and C) hepatitis, and tuberculosis. Most of the reported PPVs were in the 80% 99% range. Assessment of algorithms based on ICD-10 systems were reported in 8 articles, all published in 2020 or later. Investigators have published validation reports that may serve as empirical evidence to evaluate the utility of secondary health data environment in Taiwan for research and regulatory purpose. This article is protected by copyright. All rights reserved.

Free sugar intake from snacks and beverages in Canadian preschool- and toddler-aged children a cross-sectional study.

Excess consumption of free sugar (FS) increases the risk of dental caries and unhealthy weight gain. However, the contribution of snacks and beverages to young childrens FS intake is not well understood. The purpose of this study was to determine FS intake from snacks and beverages among preschool-aged Canadian children. This cross-sectional study examined baseline data from 267 children 1.5 to 5 y enrolled in the Guelph Family Health Study. Dietary assessment was completed over a 24-h period using ASA24-Canada-2016 to, 1) estimate the proportion of children whose FS intake from snacks and beverages consumed exceeded 5% total energy intake (TE) and 10% TE, and 2) identify the top snack and beverage sources of FS. FS contributed 10.6 ± 6.9% TE (mean ± SD). 30 and 8% of children consumed ≥ 5% TE and ≥ 10% TE from snack FS, respectively. Furthermore, 17 and 7% of children consumed ≥ 5% TE and ≥ 10% TE from beverages FS, respectively. Snacks and beverages accounted for 49 ± 30.9% of FS energy. Top snack sources of FS (% children, childrens %TE from FS) were bakery products (55%, 2.4%), candy and sweet condiments (21%, 3.0%), and sugar-containing beverages (20%, 4.1%). Top sugar-containing beverage sources of FS (48%, 5.3%) were 100% fruit juice (22%, 4.6%) and flavored milk (11%, 3.1%). Snacks and beverages contributed nearly half of FS intake among a sample of young children in Canada. Thus, long-term monitoring of snacking behavior and consumption of FS is warranted. These findings may help inform nutritional strategies and public policies to improve diet quality and FS intake in preschool-aged children. The Clinical Trial Registry number is NCT02939261 from clinicaltrials.gov. Date of Registration October 20, 2016.

Dual-task versus single-task gait rehabilitation after stroke the protocol of the cognitive-motor synergy multicenter, randomized, controlled superiority trial (SYNCOMOT).

Gait disorders and cognitive impairments are prime causes of disability and institutionalization after stroke. We hypothesized that relative to single-task gait rehabilitation (ST GR), cognitive-motor dual-task (DT) GR initiated at the subacute stage would be associated with greater improvements in ST and DT gait, balance, and cognitive performance, personal autonomy, disability, and quality of life in the short, medium and long terms after stroke. This multicenter (n12), two-arm, parallel-group, randomized (11), controlled clinical study is a superiority trial. With p<0.05, a power of 80%, and an expected loss to follow-up rate of 10%, the inclusion of 300 patients will be required to evidence a 0.1-m.s The main study limitation is the open design. The trial will focus on a new GR program applicable at various stages after stroke and during neurological disease. NCT03009773 . Registered on January 4, 2017.

Microgliamacrophages require vitamin D signaling to restrain neuroinflammation and brain injury in a murine ischemic stroke model.

Vitamin D deficiency is associated with worse clinical outcomes after ischemic stroke nevertheless, the pathophysiological mechanisms remain largely unexplored. In this study, we characterized the molecular mechanisms of how vitamin D signaling modulated stroke progression in male mouse ischemia-reperfusion stroke models. We found that vitamin D receptor (VDR) exhibited a predominant upregulation in peri-infarct microgliamacrophages following cerebral ischemia. Conditional Vdr inactivation in microgliamacrophages markedly augmented infarct volumes and neurological deficits. VDR-deficient microgliamacrophages exhibited a more primed proinflammatory phenotype with substantial secretion of TNF-α and IFN-γ. These inflammatory cytokines further enhanced CXCL10 release from endothelial cells and blood-brain barrier disruption, and ultimately infiltration of peripheral T lymphocytes. Notably, blocking TNF-α and IFN-γ significantly ameliorated stroke phenotypes in Vdr conditional knockout mice. Collectively, VDR signaling in microgliamacrophages plays a crucial role in restraining ischemia-elicited neuroinflammation and stroke progression. Our findings delineate a novel mechanism underlying the association between vitamin D deficiency and poor stroke outcomes, and underline the significance of maintaining a functional vitamin D signaling in the management of acute ischemic stroke.

Evaluation of early arterial wall lesions by elastography parameters in spontaneously hypertensive rats.

Arterialsclerosis caused by hypertension can lead to many complications, such as heart attack, stroke and so on. Early diagnosis and treatment of arterialsclerosis can prevent cardiovascular and cerebrovascular diseases and improve the prognosis. The present study aimed to explore the value of ultrasonography in evaluating the early lesion of the local arterial wall in hypertensive rats and identify useful elastography parameters. A total of 24 spontaneously hypertensive rats (SHR), 10-, 20-, 30-, and 40-weeks-old, were used in this study, with 6 rats in each group. Blood pressure was recorded using the Animal Noninvasive Blood Pressure Measurement System (Kent company, model CODA, USA), and the local elasticity of the abdominal aorta of rats was measured using a ultrasound diagnostic instrument (VINNO, Suzhou city, China). According to the histopathological results, SHR were divided into two groups the normal arterial elasticity and the early arterial wall lesions. Mann-Whitney U test was used to compare the differences in elastic parameters and influencing factors between the above two groups, and receiver operating characteristic curve (ROC) was used to analyze and judge the value of each elastic parameter in evaluating early arterial lesions. A total of 22 cases were divided into two groups 14 in the normal arterial elasticity and 8 in the early arterial wall lesions. The differences in age, blood pressure, pulse wave velocity (PWV), compliance coefficient (CC), distensibility coefficient (DC), and elasticity parameter (EP) between the two groups were compared. The differences in PWV, CC, DC and EP were statistically significant. Subsequently, the ROC curve analysis was performed for the above four evaluation indexes of arterial elasticity the results were as follows the area under the curve of PWV, CC, DC, and EP was 0.946, 0.781, 0.946, and 0.911, respectively. Early arterial wall lesions can be evaluated by ultrasound measurement of local PWV. PWV and DC can accurately evaluate the early arterial wall lesions in SHR, and the combined application of the two can improve the sensitivity and specificity of the approach.

Left ventricular ejection fraction using a simplified wall motion score based on mid-parasternal short axis and apical four-chamber views for non-cardiologists.

There is a need for a convenient, yet reliable method to assess left ventricular ejection fraction (LVEF) with point-of-care ultrasound study (POCUS). We aim to validate a novel and simplified wall motion score LVEF based on the analysis of a simplified combination of echocardiographic views. In this retrospective study, transthoracic echocardiograms of randomly selected patients were analysed by the standard 16-segments wall motion score index (WMSI) to derive the reference semi-quantitative LVEF. To develop our semi-quantitative simplified-views method, a limited combination of imaging views and only 4 segments per view were tested (1) A combination of the three parasternal short-axis views (PSAX BASE, MID-, APEX) (2) A combination of the three apical views (apical 2-chamber, 3-chamber and 4-chamber) and (3) A more limited combination of PSAX-MID and apical 4-chamber is called the MID-4CH. Global LVEF is obtained by averaging segmental EF based on contractility (normal 60%, hypokinesia 40%, and akinesia 10%). Accuracy of the novel semi-quantitative simplified-views WMS method compared to the reference WMSI was evaluated using Bland-Altman analysis and correlation was assessed in both emergency physicians and cardiologists. In the 46 patients using the 16 segments WMSI method, the mean LVEF was 34 ± 10%. Among the three combinations of the two or three imaging views analysed, the MID-4CH had the best correlation with the reference method (r Cardiac POCUS by emergency physicians and other non-cardiologists is a decisive therapeutic and prognostic tool. A simplified semi-quantitative WMS method to assess LVEF using the easiest technically achievable combination of mid-parasternal and apical four-chamber views provides a good approximative estimate for both non-cardiologist emergency physicians and cardiologists.

Automatic Segmentation of the Left Atrium from Computed Tomography Angiography Images.

The left atrial appendage (LAA) causes 91% of thrombi in atrial fibrillation patients, a potential harbinger of stroke. Leveraging computed tomography angiography (CTA) images, radiologists interpret the left atrium (LA) and LAA geometries to stratify stroke risk. Nevertheless, accurate LA segmentation remains a time-consuming task with high inter-observer variability. Binary masks of the LA and their corresponding CTA images were used to train and test a 3D U-Net to automate LA segmentation. One model was trained using the entire unified-image-volume while a second model was trained on regional patch-volumes which were run for inference and then assimilated back into the full volume. The unified-image-volume U-Net achieved median DSCs of 0.92 and 0.88 for the train and test sets, respectively the patch-volume U-Net achieved median DSCs of 0.90 and 0.89 for the train and test sets, respectively. This indicates that the unified-image-volume and patch-volume U-Net models captured up to 88 and 89% of the LALAA boundarys regional complexity, respectively. Additionally, the results indicate that the LALAA were fully captured in most of the predicted segmentations. By automating the segmentation process, our deep learning model can expedite LALAA shape, informing stratification of stroke risk.

Impact of diabetic status and contribution of office and home blood pressure across diabetic status for cardiovascular disease the J-HOP study.

Few studies have investigated whether the prognostic power of home blood pressure (BP) for cardiovascular disease (CVD) events differs across subjects with different diabetic status. We used the dataset of the J-HOP (Japan Morning Surge-Home Blood Pressure) study, which enrolled patients having cardiovascular risks to investigate relationships between home BP and CVD events. We classified the patients as having diabetes mellitus (DM), prediabetes or normal glucose metabolism (NGM) as follows for DM, a self-reported history of physician-diagnosed DM andor use of DM medication, a fasting plasma glucose ≥126 mgdL, a casual plasma glucose level ≥200 mgdL or hemoglobin A1c (HbA1c) ≥6.5% (n 1034) for prediabetes, HbA1c of 5.7-6.4% (n 1167), and for NGM, those who remained (n 2024). CVD outcome was defined as coronary artery disease, stroke or heart failure. During a median 6.2 ± 3.8 years of follow-up, 259 CVD events occurred. Analysis found both prediabetes (Unadjusted Hazard ratio uHR, 1.43 95% confidence interval CI, 1.05-1.95), and DM (uHR, 2.13 95% CI, 1.59-2.85) as risks of CVD compared to NGM. In DM, patients with a 10-mmHg elevation of office systolic BP (SBP) and morning home SBP had 16% and 14% higher risks for CVD events. In the prediabetes group, only an elevated morning home SBP conferred a risk of CVD events (uHR, 1.15 95% CI, 1.00-1.31), but this association did not hold for the adjusted model. Like DM, prediabetes should be recognized as a risk for CVD events, albeit weakly. Elevated home BP contributes to increased CVD risk in diabetes. Our study demonstrated the impact of prediabetes and diabetes on CVD and the impact of office and home BP on CVD events in each group.

Left Atrial Appendage Occlusion in the Elderly Insights From PROTECT-AF, PREVAIL, and Continuous Access Registries.

Data on the safety and efficacy of left atrial appendage occlusion (LAAO) in elderly patients are limited. We aimed to compare the outcomes of LAAO between patients ≥80 and <80 years of age. We included patients enrolled in randomized trials and nonrandomized registries of the Watchman 2.5 device. The primary efficacy endpoint was a composite of cardiovascularunknown death, stroke, or systemic embolism at 5 years. Secondary endpoints included cardiovascularunknown death, stroke, systemic embolism, and major and nonprocedural bleeding. Survival analyses were performed using the Kaplan-Meier, Cox proportional hazards, and competing risk analysis methods. Interaction terms were used to compare the 2 age groups. We also estimated the average treatment effect of the device with the use of inverse probability weighting. We studied 2,258 patients, of whom 570 (25.2%) were ≥80 years old, and 1,688 (74.8%) were <80 years old. Procedural complications at 7 days were similar in both age groups. The primary endpoint occurred in 12.0% in the device group vs 13.8% in the control group (HR 0.9 95% CI 0.6-1.4) among patients <80 years of age and in 25.3% vs 21.7%, respectively (HR 1.2 95% CI 0.7-2.0) among patients ≥80 (interaction P value 0.48). There was no interaction between age and treatment effect for any of the secondary outcomes. The average treatment effects of LAAO (compared with warfarin) were similar in the elderly population (compared with younger patients). Despite the higher event rates, octogenarians derive similar benefits from LAAO as their younger counterparts. Age alone should not preclude LAAO in otherwise suitable candidates.

Impact of amiodarone on plasma concentration of direct oral anticoagulant in patients with atrial fibrillation.

Amiodarone increases exposure of direct oral anticoagulants (DOACs). We aimed to analyze the effects of concurrent amiodarone use on DOAC concentrations and clinical outcomes. Patients who were ≥20 years of age, had atrial fibrillation, and took DOAC were enrolled to provide trough and peak samples for DOAC concentration measurements using ultra-high-performance liquid chromatography-tandem mass spectrometry. The results were compared with concentrations reported in clinical trials to define above, within, or under the expected range. The outcomes of interest were major bleeding and any gastrointestinal bleeding. Multivariate logistic regression and Cox proportional hazards model were used to determine the impact of amiodarone on above-range concentration and clinical outcomes, respectively. A total of 722 participants (420 men, 58.2%) were enrolled to provide 691 trough samples and 689 peak samples. Among them, 21.3% concurrently used amiodarone. The proportion of patients with above-range trough and peak concentrations was 16.4% and 30.2%, respectively, for amiodarone users, in contrast to 9.4% and 19.8% for amiodarone non-users. The use of amiodarone was associated with above-range trough and peak concentrations (odds ratio OR 2.00 1.16, 3.47 and 1.82 1.19, 2.79, respectively). However, amiodarone was not a significant predictor of major bleeding or any gastrointestinal bleeding. Concurrent amiodarone use led to increased DOAC concentration but was not associated with a higher risk of major bleeding or any gastrointestinal bleeding. Therapeutic monitoring of DOAC users concurrently taking amiodarone may be recommended for patients with an additional risk of increased DOAC exposure.

Temporal relationship between hyperuricemia and hypertension and its impact on future risk of cardiovascular disease.

Although hyperuricemia and hypertension are significantly correlated, their temporal relationship and whether this relationship is associated with risk of cardiovascular disease (CVD) are largely unknown. This study aimed to examine temporal relationship between hyperuricemia and hypertension, and its association with future risk of CVD. This study included 60,285 participants from the Kailuan study. Measurement of serum uric acid (SUA), systolic and diastolic blood pressure (SBP and DBP) were obtained twice at 2006 (baseline) and 2010. Cross-lagged and mediation analysis were used to examine the temporal relationship between hyperuricemia and hypertension, and the association of this temporal relationship with CVD events risk after 2010. After adjusting for covariates, the cross-lagged path coefficients (β Increased SUA levels probably precede elevated BP, and BP partially mediates the pathway from SUA to incident CVD.

Depressive Symptoms and Risk of Acute Stroke INTERSTROKE Case-Control Study.

and ObjectivesDepression has been reported to be a risk factor for acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke typeMethodsINTERSTROKE is an international case-control study of risk factors for first acute stroke, conducted in 32 countries. Cases were patients with CT or MRI confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of pre-stroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of pre-stroke depressive symptoms with post-stroke functional outcome, measured with the modified-Rankin scale at 1-month after stroke.ResultsOf 26,877 participants, 40.4% were women, the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared to controls (18.3%vs.14.1%,

Hospitalisations for cardiovascular and respiratory disease among older adults living near unconventional natural gas development a difference-in-differences analysis.

During 2008-15, the Marcellus shale region of the US state of Pennsylvania experienced a boom in unconventional natural gas development (UNGD) or fracking. However, despite much public debate, little is known about the effects of UNGD on population health in local communities. Among other mechanisms, air pollution from UNGD might affect individuals living nearby through cardiovascular or respiratory disease, and older adults could be particularly susceptible. To study the health impacts of Pennsylvanias fracking boom, we exploited the ban on UNGD in neighbouring New York state. Using 2002-15 Medicare claims, we conducted difference-in-differences analyses over multiple timepoints to estimate the risk of living near UNGD for hospitalisation with acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD) and bronchiectasis, heart failure, ischaemic heart disease, and stroke among older adults (aged ≥65 years). Pennsylvania ZIP codes that started UNGD in 2008-10 were associated with more hospitalisations for cardiovascular diseases in 2012-15 than would be expected in the absence of UNGD. Specifically, in 2015, we estimated an additional 11·8, 21·6, and 20·4 hospitalisations for AMI, heart failure, and ischaemic heart disease, respectively, per 1000 Medicare beneficiaries. Hospitalisations increased even as UNGD growth slowed. Results were robust in sensitivity analyses. Older adults living near UNGD could be at high risk of poor cardiovascular outcomes. Mitigation policies for existing UNGD might be needed to address current and future health risks. Future consideration of UNGD should prioritise local population health. University of Chicago and Argonne National Laboratories.

Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality A Meta-Analysis.

Left ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent. The aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post-TAVR-related morbidity and mortality. The authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking-derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events MACE) post-TAVR outcomes. Of the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (-13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR 2.01 95% CI 1.59-2.55) and MACE (pooled odds ratio OR 1.26 95% CI 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR 1.06 95% CI 1.04-1.08) and MACE risk (OR 1.08 95% CI 1.01-1.15). Preprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation a meta-analysis CRD42021289626).

Prevalence of spontaneous recanalisation of complete internal carotid occlusion protocol for a systematic scoping review.

Although previously thought to be a rare occurrence, spontaneous recanalisation is not uncommon, with a growing number of reports describing this phenomenon. However, the frequency, time course and mechanism of spontaneous recanalisation remain unknown. A better characterisation of these events is essential to ensuring adequate identification and proper future trial design for treatment. To describe the current body of literature around spontaneous recanalisation following internal carotid occlusion. With the assistance of an information specialist, we will search MEDLINE, Embase, Cochrane Central Register for Controlled Trials and Web of Science for studies of adults with spontaneous recanalisation or transient occlusion of the internal carotid artery. Two reviewers will independently collect data on included studies pertaining to publication data, study population information, timepoints of initial presentation, recanalisation and subsequent follow-up. Primary data will not be collected therefore, formal ethics is not required. The findings of this study will be disseminated through peer-reviewed publications and presentations at academic conferences.

Lipid management in ischaemic stroke or transient ischaemic attack in China result from China National Stroke Registry III.

The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA). Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III). We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China. 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018. The primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmolL and LDL-C<1.4mmolL, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months. Among the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmolL and 1.4mmolL was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR0.69, 95% CI 0.48-0.99, p0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmolL had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months. The LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmolL might be a safe standard for this population.

Positive airway pressure therapy for post-stroke sleep disordered breathing a systematic review, meta-analysis and meta-regression.

Sleep disordered breathing (SDB) is an under-recognised independent risk factor and a potential consequence of stroke. We systematically reviewed and meta-analysed the effectiveness of positive airway pressure (PAP) therapy in improving post-stroke outcomes. We searched CENTRAL, Embase, PubMed, CINAHL, PsycINFO, Scopus, ProQuest, Web of Science and CNKI (China National Knowledge Infrastructure) for randomised controlled trials comparing PAP therapy against a control or placebo group. We evaluated the pooled effects of PAP therapy on recurrent vascular events, neurological deficit, cognition, functional independence, daytime sleepiness and depression using random effects meta-analyses. We identified 24 studies. Our meta-analyses showed that PAP therapy reduced recurrent vascular events (risk ratio 0.47, 95% CI 0.28-0.78), and showed significant beneficial effects on neurological deficit (Hedges g -0.79, 95% CI -1.19- -0.39), cognition (g0.85, 95% CI 0.04-1.65), functional independence (g0.45, 95% CI 0.01-0.88) and daytime sleepiness (g -0.96, 95% CI -1.56- -0.37). However, there was insignificant reduction in depression (g -0.56, 95% CI -2.15-1.02). No publication bias was detected. Post-stroke patients with SDB benefited from PAP therapy. Prospective trials are needed to determine the ideal initiation period and the minimum effective therapeutic dose.

Three cases of mechanical thrombectomy in patients over 100 years old.

While several cases involving mechanical thrombectomy in patients >90 years old have been reported, only 1 case involving a patient >100 years old has been described. We herein report 3 cases of mechanical thrombectomy performed in patients >100 years old, along with a review of the literature.Case 1 A 102-year-old woman with a National Institute of Health Stroke Scale (NIHSS) score of 20 and diffusion weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 8 points showed M1 occlusion. She was treated with tissue plasminogen activator followed by mechanical thrombectomy. Recanalization of thrombosis in cerebral infarction (TICI)-3 was obtained at 1 pass. After 90 days, her modified Rankin Scale (mRS) was 2, and she returned to living independently.Case 2 A 104-year-old woman with a NIHSS score of 13 and DWI-ASPECTS of 9 points showed M1 occlusion, so mechanical thrombectomy was performed. Recanalization of TICI-3 was obtained. She was admitted with an mRS of 5.Case 3 A 101-year-old woman with an NIHSS score of 8 and DWI-ASPECTS of 10 points showed right internal carotid artery occlusion, so mechanical thrombectomy was performed. Direct puncture of the right common carotid artery was performed due to access difficulties. Recanalization of TICI-3 was obtained. She was admitted with an mRS of 5. In all cases, occlusion access using techniques such as direct carotid puncture was possible, but two of the three patients had an mRS of 5, resulting in a poor prognosis. The indication for treatment in patients >100 years old should be carefully considered.

Efficacy of Treatment with and without Initial Clopidogrel Loading in Branch Atheromatous Disease.

Objectives Despite aggressive therapeutic interventions during the acute phase of branch atheromatous disease (BAD)-type cerebral infarction, many patients, even those with a mild condition at the onset, experience neurological deterioration after hospitalization and develop serious deficits. We compared the therapeutic efficacy of multiple antithrombotic therapies for BAD between patients who received a clopidogrel loading dose (loading group LG) and those without loading (non-loading group NLG). Patients Between January 2019 and May 2022, patients with BAD-type cerebral infarction in the lenticulostriate artery admitted within 24 h of the onset were recruited. This study included 95 consecutive patients who received combination argatroban and dual antiplatelet therapy (aspirin and clopidogrel). Methods Patients were classified into the LG and NLG according to whether or not a loading dose of clopidogrel (300 mg) had been administered on admission. Changes in neurological severity National Institutes of Health Stroke Scale (NIHSS) score during the acute phase were retrospectively evaluated. Results There were 34 (38%) and 61 (62%) patients in the LG and NLG, respectively. On admission, the median NIHSS score was similar between the groups LG 2.5 (2-4) vs. NLG 3 (2-4), p0.771. At 48 h following admission, the median NIHSS scores were 1 (0.25-4), and 2 (1-5) in the LG and NLG, respectively (p0.045). Early neurological deterioration (END defined as worsening of the NIHSS score by ≥4 points at 48 h after admission) occurred in 3% of LG and 20% of NLG patients (p0.028). Conclusions Administration of a clopidogrel loading dose with combination antithrombotic therapy for BAD reduced END.

Anticoagulation Strategies in Non-Critically Ill Patients Hospitalized with COVID-19 A Randomized Clinical Trial.

Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in non-critically ill patients with COVID-19. Patients hospitalized with COVID-19 not requiring intensive care unit (ICU) treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for ICU level-of-care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. Between August 26, 2020, and September 19, 2022, 3398 non-critically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n1141), therapeutic-dose enoxaparin (n1136) or therapeutic-dose apixaban (n1121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR 0.85 95% CI 0.69 to 1.04 p0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR 0.70 95% CI 0.52 to 0.93 p0.01), and intubation was required in 8.4% vs. 6.4% of patients respectively (HR 0.75 95% CI 0.58 to 0.98 p0.03). Results were similar in the two therapeutic-dose groups, and major bleeding in all three groups was infrequent. Among non-critically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation or died.

Regulatory T cell expansion promotes white matter repair after stroke.

Recent research highlights the function of regulatory T cells (Tregs) in white matter integrity in CNS diseases. Approaches that expand the number of Tregs have been utilized to improve stroke recovery. However, it remains unclear if Treg augmentation preserves white matter integrity early after stroke or promotes white matter repair. This study evaluates the effect of Treg augmentation on white matter injury and repair after stroke. Adult male C57BL6 mice randomly received Treg or splenocyte (2 million, iv) transfer 2 h after transient (60 min) middle cerebral artery occlusion (tMCAO). Immunostaining showed improved white matter recovery after tMCAO in Treg-treated mice compared to mice received splenocytes. In another group of mice, IL-2IL-2 antibody complexes (IL-2IL-2Ab) or isotype IgG were administered (i.p) for 3 consecutive days starting 6 h after tMCAO, and repeated on day 10, 20 and 30. The IL-2IL-2Ab treatment boosted the number of Tregs in blood and spleen and increased Treg infiltration into the ischemic brain. Longitudinal in vivo and ex vivo diffusion tensor imaging analysis revealed an increase in fractional anisotropy 28d and 35d, but not 14d, after stroke in IL-2IL-2Ab-treated mice compared to isotype-treated mice, suggesting a delayed improvement in white matter integrity. IL-2IL-2Ab also improved sensorimotor functions (rotarod test and adhesive removal test) 35d after stroke. There were correlations between white matter integrity and behavior performance. Immunostaining confirmed the beneficial effects of IL-2IL-2Ab on white matter structures 35d after tMCAO. IL-2IL-2Ab treatment starting as late as 5d after stroke still improved white matter integrity 21d after tMCAO, suggesting long-term salutary effects of Tregs on the late-stage tissue repair. We also found that IL-2IL-2Ab treatment reduced the number of deaddying OPCs and oligodendrocytes in the brain 3d after tMCAO. To confirm the direct effect of Tregs on remyelination, Tregs were cocultured with lysophosphatidyl choline (LPC)-treated organotypic cerebella. LPC exposure for 17 h induced demyelination in organotypic cultures, followed by gradual spontaneous remyelination upon removal of LPC. Co-culture with Tregs accelerated remyelination in organotypic cultures 7d after LPC. In conclusion, Boosting the number of Tregs protects oligodendrocyte lineage cells early after stroke and promotes long-term white matter repair and functional recovery. IL-2IL-2Ab represents a feasible approach of Treg expansion for stroke treatment.

A Cannabinoid Type 2 (CB2) Receptor Agonist Augments NOS-Dependent Responses of Cerebral Arterioles During Type 1 Diabetes.

While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D). The goal was to test the hypothesis that administration of a CB2 agonist (JWH-133) would improve impaired endothelial (eNOS)- and neuronal (nNOS)- dependent dilation of cerebral arterioles during T1D. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to an eNOS-dependent agonist (adenosine 5-diphosphate ADP), an nNOS-dependent agonist (N-methyl-Daspartate NMDA), and an NOS-independent agonist (nitroglycerin) before and 1 hour following JWH-133 (1 mgkg IP). In a second series of experiments, to determine the role of CB2 receptors, rats were injected with AM-630 (3 mgkg IP). AM-630 has been shown to be a specific antagonist to CB2 receptors. After 30 minutes, the nondiabetic and T1D rats were treated with JWH-133 (1 mgkg IP). One hour after the injection of JWH-133, responses of arterioles to the agonists were again examined. In a third series of experiments, a potential time-dependency in reactivity of cerebral arterioles to the agonists was examined. Initially responses of arterioles to ADP, NMDA and nitroglycerin were examined. Then, one hour after injection of vehicle (ethanol) for JWH-133 and AM-630 responses of arterioles to the agonists were again examined. Baseline diameter of cerebral arterioles was similar in nondiabetic and T1D rats across all groups of rats. In addition, treatment of the rats with JWH-133, JWH-133 and AM-630 or vehicle (ethanol) did not produce a change in baseline diameter in either nondiabetic or T1D rats. Dilation of cerebral arterioles to ADP and NMDA was greater in nondiabetic than in diabetic rats. Treatment with JWH-133 increased responses of cerebral arterioles to ADP and NMDA in both nondiabetic and diabetic rats. Responses of cerebral arterioles to nitroglycerin were similar between nondiabetic and diabetic rats, and JWH-133 did not influence responses to nitroglycerin in either group. The restoration in responses to the agonists by JWH-133 could be inhibited by treatment with a specific inhibitor of CB2 receptors. This study showed that acute treatment with a specific activator of CB2 receptors could potentiate dilation of cerebral resistance arterioles to eNOS- and nNOS-dependent agonists in both nondiabetic and T1D rats. In addition, the influence of activation of CB2 receptors on cerebral vascular function could be attenuated by treatment with a specific antagonist of CB2 receptors (AM-630). Based on these findings, one could speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular disease that can contribute to the pathogenesis of stroke.

To engage or not engage Early incentive motivation prevents symptoms of chronic post-stroke depression - A longitudinal study.

Although post-stroke depression (PSD) is known to disrupt motor rehabilitation after stroke, PSD is often undertreated and its relationship with motor impairment remains poorly understood. In a longitudinal study design we investigated, which factors at the early post-acute stage may increase the risk for PSD symptoms. We were especially interested in whether interindividual differences in the motivational drive to engage in physically demanding tasks indicate PSD development in patients suffering from motor impairments. Accordingly, we used a monetary incentive grip force task where participants were asked to hold their grip force for high and low rewards at stake to maximize their monetary outcome. Individual grip force was normalized according to the maximal force prior to the experiment. Experimental data, depression, and motor impairment were assessed from 20 stroke patients (12 male 7.7 ± 6.78 days post-stroke) with mild-to-moderate hand motor impairment and 24 age-matched healthy participants (12 male). Both groups showed incentive motivation as indicated by stronger grip force for high versus low reward trials and the overall monetary outcome in the task. In stroke patients, severely impaired patients showed stronger incentive motivation, whereas early PSD symptoms were associated with reduced incentive motivation in the task. Larger lesions in corticostriatal tracts correlated with reduced incentive motivation. Importantly, chronic motivational deficits were preceded by initially reduced incentive motivation and larger corticostriatal lesions in the early stage post-stroke. More severe motor impairment motivates reward-dependent motor engagement, whereas PSD and corticostriatal lesions potentially disturb incentive motivational behavior, thereby increasing the risk of chronic motivational PSD symptoms. Acute interventions should address motivational aspects of behavior to improve motor rehabilitation post-stroke.

Post-stroke sleep disturbance and recurrent cardiovascular and cerebrovascular events A systematic review and meta-analysis.

Despite improvements in survival rates, risk of recurrent events following stroke remains high. Identifying intervention targets to reduce secondary cardiovascular risk in stroke survivors is a priority. The relationship between sleep and stroke is complex sleep disturbances are likely both a contributor to, and consequence of, stroke. The current aim was to examine the association between sleep disturbance and recurrent major acute coronary events or all-cause mortality in the post-stroke population. Thirty-two studies were identified, including 22 observational studies and 10 randomized clinical trials (RCTs). Identified studies included the following as predictors of post-stroke recurrent events obstructive sleep apnea (OSA, n 15 studies), treatment of OSA with positive airway pressure (PAP, n 13 studies), sleep quality andor insomnia (n 3 studies), sleep duration (n 1 study), polysomnographic sleepsleep architecture metrics (n 1 study), and restless legs syndrome (n 1 study). A positive relationship of OSA andor OSA severity with recurrent eventsmortality was seen. Findings on PAP treatment for OSA were mixed. Positive findings indicating a benefit of PAP for post-stroke risk came largely from observational studies (pooled RR 95% CI for association between PAP and recurrent cardiovascular event 0.37 0.17-0.79, I

Myocardial injury and cardiovascular complications in COVID-19 a cohort study in severe and critical patients.

To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit. This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury. Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p 0.01). Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients. Caracterizar a lesão miocárdica e as complicações cardiovasculares e seus preditores em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. Este foi um estudo de coorte observacional em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. A lesão miocárdica foi definida como níveis sanguíneos de troponina cardíaca acima do limite de referência superior ao percentil 99. Os eventos cardiovasculares considerados foram combinação de trombose venosa profunda, embolia pulmonar, acidente vascular cerebral, infarto do miocárdio, isquemia aguda de membros, isquemia mesentérica, insuficiência cardíaca e arritmia cardíaca. Regressão logística univariada e multivariada ou modelos de risco proporcional de Cox foram utilizados para determinar os preditores de lesão miocárdica. Foram admitidos à unidade de terapia intensiva 567 pacientes graves e críticos com COVID-19, dos quais 273 (48,1%) apresentavam lesão miocárdica. Dos 374 pacientes críticos com COVID-19, 86,1% tinham lesão miocárdica, além de apresentarem mais disfunção orgânica e maior mortalidade aos 28 dias (56,6% versus 27,1% p < 0,001). Foram preditores de lesão miocárdica idade avançada, hipertensão arterial e uso de imunomoduladores. Complicações cardiovasculares ocorreram em 19,9% dos pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva, e a maioria dos eventos deu-se em pacientes com lesão miocárdica (28,2% versus 12,2% p < 0,001). A ocorrência de evento cardiovascular precoce durante internação em unidade de terapia intensiva estava associada à maior mortalidade aos 28 dias em comparação com eventos tardios ou inexistentes (57,1% versus 34,0% versus 41,8% p 0,01). Pacientes com formas graves e críticas de COVID-19 admitidos à unidade de terapia intensiva foram comumente diagnosticados com lesão miocárdica e complicações cardiovasculares, e ambas estavam associadas à maior mortalidade nesses pacientes.

Complex Left Atrial Appendage Occlusion Using the Novel Amplatzer Steerable Delivery Sheath.

Left atrial appendage (LAA) occlusion has emerged as an al- ternative to oral anticoagulation in non-valvular atrial fibril- lation. The success rate is high, but we are still facing some challenging LAA anatomies that may increase the risk of sub- optimal results. These images show that the Amplatzer steer- able sheath is useful for LAA occlusion, especially in cases with challenging anatomies. Small variations of the distal end angle can improve the success rate and reduce complications.

The effect of robot-assisted walking in different modalities on cardiorespiratory responses and energy consumption in patients with subacute stroke.

The aim of our study was to evaluate the effect of robot-assisted walking in different modalities on cardiorespiratory responses and energy consumption in subacute stroke patients. Our study consisted of 16 individuals between the ages of 18-65 years. Individuals diagnosed with hemiplegia after unilateral ischemic or haemorrhagic stroke constitute the stroke group. Eight subacute stroke individuals were included in the experimental group, and eight healthy individuals were included in the control group. Each participant tested on the Lokomat in three consecutive days in random sequence, with three tests the first test 100% guiding strength (GF)and 100% body weight support (BWS) the second test 80% GF, 50% BWS the third test 60% GF, 30% BWS was achieved. Gas analyzer (Cosmed, Quark CPET, Italy) measurements were made with the help of a mask to evaluate the cardiorespiratory responses of the participants during all tests. In the comparison of the three test results of the two groups separately, the stroke groups oxygen consumption (VO2), carbon dioxide production (VCO2), tidal volume (VT), pulse reserve (HRR), calories burned per hour (EEh), Borg dyspnea values, control groups VO2, VCO2, VE, HR, HRR, and EEh, Borg values were statistically significantly different ( By decreasing GF and BWS values during robot-assisted walking, adequate cardio-metabolic and energy response in both subacute stroke patients and healthy individuals could be achieved. These results show us that it is important to consider the cardiorespiratory function of the patient when choosing training protocols.

Association of Posttraumatic Headache With Symptom Burden After Concussion in Children.

Headache is the most common symptom after pediatric concussion. To examine whether posttraumatic headache phenotype is associated with symptom burden and quality of life 3 months after concussion. This was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study, conducted September 2016 to July 2019 at 5 Pediatric Emergency Research Canada (PERC) network emergency departments. Children aged 8.0-16.99 years presenting with acute (<48 hours) concussion or orthopedic injury (OI) were included. Data were analyzed from April to December 2022. Posttraumatic headache was classified as migraine or nonmigraine headache, or no headache, using modified International Classification of Headache Disorders, 3rd edition, diagnostic criteria based on self-reported symptoms collected within 10 days of injury. Self-reported postconcussion symptoms and quality-of-life were measured at 3 months after concussion using the validated Health and Behavior Inventory (HBI) and Pediatric Quality of Life Inventory-Version 4.0 (PedsQL-4.0). An initial multiple imputation approach was used to minimize potential biases due to missing data. Multivariable linear regression evaluated the association between headache phenotype and outcomes compared with the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score and other covariates and confounders. Reliable change analyses examined clinical significance of findings. Of 967 enrolled children, 928 (median IQR age, 12.2 10.5 to 14.3 years 383 41.3% female) were included in analyses. HBI total score (adjusted) was significantly higher for children with migraine than children without headache (estimated mean difference EMD, 3.36 95% CI, 1.13 to 5.60) and children with OI (EMD, 3.10 95% CI, 0.75 to 6.62), but not children with nonmigraine headache (EMD, 1.93 95% CI, -0.33 to 4.19). Children with migraine were more likely to report reliable increases in total symptoms (odds ratio OR, 2.13 95% CI, 1.02 to 4.45) and somatic symptoms (OR, 2.70 95% CI, 1.29 to 5.68) than those without headache. PedsQL-4.0 subscale scores were significantly lower for children with migraine than those without headache only for physical functioning (EMD, -4.67 95% CI, -7.86 to -1.48). In this cohort study of children with concussion or OI, those with posttraumatic migraine symptoms after concussion had higher symptom burden and lower quality of life 3 months after injury than those with nonmigraine headache. Children without posttraumatic headache reported the lowest symptom burden and highest quality of life, comparable with children with OI. Further research is warranted to determine effective treatment strategies that consider headache phenotype.

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease.

Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events. To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE). This prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021. Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories. The main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria. Of 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mLmin per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio HR, 2.61 95% CI, 1.30-5.22 P .002), diabetic nephropathy (HR, 3.56 95% CI, 1.62-7.83 P .002), and kidney vascular diseases (HR, 2.86 95% CI, 1.51-5.41 P .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98 95% CI, 1.08-8.30 P .04) and arteriolar sclerosis (HR, 1.68 95% CI, 1.03-2.72 P .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe HR, 2.50 95% CI, 1.06-5.87 P .04 moderate HR, 1.66 95% CI, 0.74-3.75 P .22 mild HR, 2.22 95% CI, 1.01-4.89 P .047) in fully adjusted models. In this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat How Does the Brain Breathe

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasmmitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His

Paraneoplastic neurological syndromes of the central nervous system a single institution 7-year case series.

Paraneoplastic neurological syndromes (PNSs) are nonmetastatic complications of malignancy, defined by the presence of onconeural antibodies (ONAs). ONAs may be found in 60% of patients with central nervous system (CNS) involvement, and they are directed against intraneuronal antigens or channels, receptors or associated proteins located at the synaptic or extra-synaptic neuronal cell membrane. Given its rare incidence, there are few epidemiological case series on CNS-PNS. We aim to discuss the variability of CNS-PNSs etiology, clinical features, management and outcome, highlighting the importance of early recognition and appropriate treatment, leading to significant reduction of mortality and morbidity. We retrospectively reviewed our 7-years single-center experience, and specifically discussed the underlying etiology, parenchymal CNS involvement, and the acute treatment response. Only cases fulfilling PNS Euronetwork criteria for definitive PNS were included. A total of 26 probable PNSs cases involving CNS were identified. We reported medical records of eleven (42.3%) illustrative cases, meeting the criteria of definite PNS and presenting variable clinical spectrum and different radiological appearances. Our series has a relative paucity of the most common syndromes and larger portion of clinical diagnosis with ONAs. Well-characterized ONAs had been detected in CSF of six patients. Our case series supports the utmost importance of early recognition of CNS-PNSs. Screening for occult malignancies should not be limited to patients with classical CNS syndrome. Empiric immunomodulatory therapy may be considered before the diagnostic evaluation is completed, in order to prevent unfavorable outcome. Late presentations should not discourage initiation of treatment.

Cerebrovascular involvement in systemic childhood vasculitides.

Pediatric vasculitides sometimes involve central nervous system (CNS). The manifestations are diverse, ranging from headache, seizures, vertigo, ataxia, behavioral changes, neuropsychiatric symptoms, consciousness disorders, and even cerebrovascular (CV) accidents that may lead to irreversible impairment and even death. Stroke, on the other hand despite the great progress in prevention and treatment, is still one of the leading causes of morbidity and mortality in the general population. The aim of this article was to summarize CNS manifestations and CV issues observed in primary pediatric vasculitides and the current knowledge of etiology and CV risk factors, preventive strategies, and therapeutic options in this target patient population. Pathophysiological links reveal similar immunological mechanisms involved in both pediatric vasculitides and CV events with endothelial injury and damage being the central point. From the clinical point of view, CV events in pediatric vasculitides were associated with increased morbidity and poor prognosis. If damage has already occurred, the therapeutic approach consists of good management of the vasculitis itself, antiplatelet and anticoagulation therapy, and early rehabilitation. Risk factors for acquiring cerebrovascular disease (CVD) and stroke, particularly hypertension and early atherosclerotic changes, already begin in childhood, with vessel wall inflammation contributing itself, once more emphasizing that appropriate preventive measures are certainly necessary in pediatric vasculitis population to improve their long-term outcome.

Association between computed tomography perfusion and the effect of intravenous alteplase prior to endovascular treatment in acute ischemic stroke.

Intravenous alteplase (IVT) prior to endovascular treatment (EVT) is neither superior nor noninferior to EVT alone in acute ischemic stroke patients. We aim to assess whether the effect of IVT prior to EVT differs according to CT perfusion (CTP)-based imaging parameters. In this retrospective post hoc analysis, we included patients from the MR CLEAN-NO IV with available CTP data. CTP data were processed using syngo.via (version VB40). We performed multivariable logistic regression to obtain the effect size estimates (adjusted common odds ratio acOR) on 90-day functional outcome (modified Rankin Scale mRS) and functional independence (mRS 0-2) for CTP parameters with two-way multiplicative interaction terms between IVT administration and the studied parameters. In 227 patients, median CTP-estimated core volume was 13 (IQR 5-35) mL. The treatment effect of IVT prior to EVT on outcome was not altered by CTP-estimated ischemic core volume, penumbral volume, mismatch ratio, and presence of a target mismatch profile. None of the CTP parameters was significantly associated with functional outcome after adjusting for confounders. In directly admitted patients with limited CTP-estimated ischemic core volumes who presented within 4.5 h after symptom onset, CTP parameters did not statistically significantly alter the treatment effect of IVT prior to EVT. Further studies are needed to confirm these results in patients with larger core volumes and more unfavorable baseline perfusion profiles on CTP imaging.

The DZHK research platform maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

Early blood pressure management in hemorrhagic stroke a meta-analysis.

The aim of the present meta-analysis was to evaluate the outcomes and effects of different systolic blood pressure (SBP) lowering in patients with hemorrhagic stroke using data from randomized controlled trials. A total of 2592 records were identified for this meta-analysis. We finally included 8 studies (6119 patients mean age 62.8 ± 13.0, 62.7% men). No evidence of heterogeneity between estimates (I

A rare adult case of asymptomatic double aortic arch accompanied by the right vertebral artery directly originating from the aortic arch.

A double aortic arch (DAA) is a rare congenital vascular anomaly. No case of DAA with a direct aortic origin of the right vertebral artery (VA) has been reported in adults. Here, we report a rare case of an asymptomatic DAA accompanied by the right VA directly originating from the right aortic arch in an adult. A DAA and right VA directly originating from the right aortic arch were identified in a 63-year-old man using digital subtraction angiography and computed tomography angiography. The patient underwent digital subtraction angiography for evaluation of an unruptured cerebral aneurysm. Intraprocedural selection of vessels branching from the aorta with the catheter was difficult. To confirm the bifurcation of the aorta, aortography was performed, which revealed a DAA. Following digital subtraction angiography, computed tomography angiography was performed, which showed that the right VA originated directly from the right aortic arch. The trachea and esophagus were located in the vascular ring of the DAA however, they were not compressed by the aorta. This was consistent with the lack of symptoms related to the DAA. This is the first adult case of an asymptomatic DAA with an unusual origin of the VA. A rare asymptomatic vascular anomaly, such as a DAA, can be incidentally identified using angiography.

Fatty Liver Disease, Heart Rate, and Cardiac Remodelling Evidence from the UK Biobank.

Growing evidence supports an association between fatty liver disease (FLD) and cardiac dysfunction and remodelling, leading to cardiovascular disease and heart failure. Herein, we investigated the independent contribution of FLD to cardiac dysfunction and remodelling in participants from the UK Biobank with cardiac magnetic resonance (CMR) data available. A total of 18,848 Europeans without chronic viral hepatitis and valvular heart diseases, with liver magnetic resonance imaging and CMR data were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures. Multivariable regression models were used to test the association between FLD and CMR endpoints, after adjusting for several cardiometabolic risk factors. Linear regression models with regularization (Least Absolute Shrinkage and Selection Operator LASSO, Ridge, and Elastic Net) were used to generate predictive models for heart-related endpoints. FLD was independently associated with higher average heart rate, higher cardiac remodelling (higher eccentricity ratio and lower remodelling index), lower left and right ventricular volumes (end-systolic, end-diastolic, and stroke volumes) as well as with lower left and right atrial maximal volumes (P<0.001). FLD was the strongest positive predictor for average heart rate, followed by age, hypertension, and type 2 diabetes. Male sex was the strongest positive predictor for eccentricity ratio followed by FLD, age, hypertension, and BMI. For LV volumes, FLD was the strongest negative predictor along with age. FLD is an independent predictor of higher heart rate and early cardiac remodelling associated with reduced ventricular volumes.

Heterosynaptic long-term potentiation of non-nociceptive synapses requires endocannabinoids, NMDARs, CamKII, and PKCζ.

Noxious stimuli or injury can trigger long-lasting sensitization to non-nociceptive stimuli (referred to as allodynia in mammals). Long-term potentiation (LTP) of nociceptive synapses has been shown to contribute to nociceptive sensitization (hyperalgesia) and there is even evidence of heterosynaptic spread of LTP contributing to this type of sensitization. However, it is not clear whether activation of nociceptors elicits heterosynaptic LTP (hetLTP) in non-nociceptive synapses. Previous studies in the medicinal leech (Hirudo verbana) have demonstrated that high frequency stimulation (HFS) of nociceptors produce both homosynaptic LTP as well as hetLTP in non-nociceptive afferent synapses. This hetLTP involves endocannabinoid-mediated disinhibition of non-nociceptive synapses at the presynaptic level, but it is not clear if there are additional processes contributing to this synaptic potentiation. In this study, we found evidence for the involvement of postsynaptic level change and observed that postsynaptic NMDA receptors (NMDAR) were found to be required for this potentiation. Next Hirudo orthologues for known LTP signaling proteins, CamKII and PKCζ, were identified based on sequences from humans, mice, and the marine mollusk Aplysia. In electrophysiological experiments, inhibitors of CamKII (AIP) and PKCζ (ZIP) were found to interfere with hetLTP. Interestingly, CamKII was found to be necessary for both induction and maintenance of hetLTP, while PKCζ was only necessary for maintenance. These findings show activation of nociceptors can elicit a potentiation of non-nociceptive synapses through a process that involves both endocannabinoid-mediated disinhibition and NMDAR-initiated signaling pathways.

Oscillation analysis as a supporting element toward safe and reliable lumbar catheter intracranial pressure monitoring.

Lumbar drainage of cerebrospinal fluid for treatment of refractory increased intracranial pressure (ICP) is associated with the risk of infratentorial herniation, but real-time biomarkers for signaling herniation at bedside are lacking. Here, the authors tested whether an alteration of pulsatile waveform conduction across the level of the foramen magnum could serve as an indicator of insufficient hydrostatic communication and impending herniation. This prospective observational cohort study included patients with severe acute brain injury who underwent continuous external ventricular drain monitoring of ICP and lumbar drain pressure monitoring. Continuous recordings of ICP, lumbar pressure (LP), and arterial blood pressure (ABP) were screened throughout a recording period of 4-10 days. Pressure differences between ICP and LP > 5 mm Hg for 5 minutes were defined as a Δ-event, implicating nonsufficient hydrostatic communication. During this period, oscillation analysis of the ICP, LP, and ABP waveforms was performed by determining the eigenfrequencies (EFs) and their amplitudes (AEF) via Fourier transformation scripted in Python. Of 142 patients, 14 exhibited a Δ-event, with a median (range) ICP of 12.2 (10.7-18.8) mm Hg and LP of 5.6 (3.3-9.8) mm Hg during 2993 hours of recording time. The AEF ratio between ICP and LP (p < 0.01) and between ABP and LP (p 0.032) increased significantly during Δ-events compared with the baseline values determined 3 hours prior to the event. The ratio between ICP and ABP remained unaffected. Oscillation behavior analysis of LP and ABP waveforms during controlled lumbar drainage may serve as a personalized, simple, and effective biomarker to signal impending infratentorial herniation in real time without the need for simultaneous ICP monitoring.

Clinical and prognostic associations of autoantibodies recognizing adrenergicmuscarinic receptors in patients with heart failure.

The importance of autoantibodies (AABs) against adrenergicmuscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinicalprognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF. Serum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analyzed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF-rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (p0.045). Seropositivity occurred more frequently only for anti-M2 AABs (p0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, atrial fibrillation), and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome hazard ratio (95% confidence interval) 1.37 (1.04-1.81), p0.024 and HF-rehospitalization 1.57 (1.13-2.19), p0.010 in univariable analyses, but remained associated only with HF-rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model 1.47 (1.05-2.07), p0.030. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function. AAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF-rehospitalization. The exact clinical value of AABs remains to be elucidated.

Predictive value of liver fibrosis scores in cardiovascular diseases among hypertensive population.

To explore the predictive value of liver fibrosis scores fibrosis-4, ASTplatelet ratio index, BAAT score (BMI Age ALT TG), and BARD score (BMI ASTALT Ratio Diabetes) for the risk of cardiovascular disease (CVD) in a hypertensive population. A total of 4164 hypertensive participants without history of CVD were enrolled in the follow-up. Four liver fibrosis scores (LFSs) were used, including the fibrosis-4 (FIB-4), APRI, BAAT score, and BARD score. The endpoint was CVD incidence which was defined as stroke or coronary heart disease (CHD) during the follow-up period. Cox regression analyses were used to calculate hazard ratios between LFSs and CVD. Kaplan-Meier curve was used to show the probability of CVD in different levels of LFSs. Restricted cubic spline further explored whether the relationship between LFSs and CVD was linear. Finally, we assessed the discriminatory ability of each LFS for CVD was assessed using C-statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI). During a median follow-up time of 4.66 years, 282 hypertensive participants had CVD. Kaplan-Meier curve showed that four LFSs were associated with CVD and high levels of LFSs significantly increase the probability of CVD in hypertensive population. In the multivariate Cox regression analysis, the adjusted hazard ratios for four LFSs were 3.13 in FIB-4, 1.66 in APRI, 1.47 in BAAT score, and 1.36 in BARD score. Moreover, after adding LFSs to original risk prediction model, we find that all four new models have higher C-statistics of CVD than the traditional model. Furthermore, the results of both NRI and IDI were positive, indicating that LFSs enhanced the effect on the prediction of CVD. Our study showed that LFSs were associated with CVD in hypertensive populations in northeastern China. Furthermore, it suggested that LFSs could be a new tool for identifying patients at high risk of primary CVD in a hypertensive population.

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS) A Mission Thrombectomy (MT-2020 Plus) Study.

Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Our survey was conducted in 75 countries through the Mission Thrombectomy 2020 global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as (current MT operators×50current annual number of estimated thrombectomy-eligible LVOs×100 MT operator availability) and (current MT centers×150current annual number of estimated thrombectomy-eligible LVOs×100 MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high odds ratio, 0.08 95% CI, 0.04-0.12), MT operator availability (odds ratio, 3.35 95% CI, 2.07-5.42), MT center availability (odds ratio, 2.86 95% CI, 1.84-4.48), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 95% CI, 1.70-9.42) were significantly associated with increased odds of MTA. Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the countrys per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Impact of atrial fibrillation on the accuracy of oscillometric blood pressure monitoring in ICU patients from a large real-world database.

Oscillometric blood pressure (BP) measurement in atrial fibrillation patients is controversial due to stroke volume variation. Here, we performed a cross-sectional study to investigate the impact of atrial fibrillation on the accuracy of oscillometric BP in the ICU setting. Adult patients with atrial fibrillation or sinus rhythm records were enrolled from Medical Information Mart for Intensive Care-III database. Concurrently recorded noninvasive oscillometric BPs (NIBPs) and intra-arterial BPs (IBPs) were classified as atrial fibrillation or sinus rhythm group according to heart rhythm. Bland-Altmann plots assessed bias and limits of agreement of NIBP to IBP. Pairwise comparison was performed on NIBPIBP bias between atrial fibrillation and sinus rhythm. Linear mixed-effect model was used to assess the impact of heart rhythm on NIBPIBP bias after adjusting confounders. Two thousand, three hundred and thirty-five patients (71.95 ± 11.23 years old, 60.90% were men) were included. Systolic, diastolic, and mean NIBPIBP biases were not clinically different between atrial fibrillation and sinus rhythm circumstances (SBP bias 0.66 vs. 1.21 mmHg, P 0.002 DBP -5.29 vs. -5.17, P 0.1 mean BP -4.45 vs. -4.19, P 0.01). After adjusting for age, sex, heart rate, arterial BP, and vasopressor usage, the effect of heart rhythm on NIBPIBP bias was within ±5 mmHg for SBP and DBP effect on SBP bias 3.32 mmHg (95% confidence interval (CI) 2.89-3.74), P < 0.001 DBP -0.89 (-1.17 to -0.60), P < 0.001, while the effect on mean BP bias was not significant 0.18 mmHg (-0.10 to 0.46), P 0.2. Atrial fibrillation would not influence the agreement of oscillometric BP to IBP in ICU patients compared with sinus rhythm.

Incident Atrial Fibrillation and Risk of Dementia in a Diverse, Community-Based Population.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 11 match of incident AF no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio sHR, 1.13 95% CI, 1.09-1.16). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 95% CI, 1.07-1.15). Associations were stronger for age <65 (sHR, 1.65 95% CI, 1.29-2.12) versus ≥65 (sHR, 1.07 95% CI, 1.03-1.10) years (interaction

Gut microbiota-associated metabolites and risk of ischemic stroke in REGARDS.

Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke. Metabolites (n 162) were measured in a case-control cohort nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 1,075 ischemic stroke cases and 968 random cohort participants. Cox models were adjusted for age, gender, race, and age-race interaction (base model) and further adjusted for the Framingham stroke risk factors (fully adjusted model). EFA identified fifteen metabolite factors, each representing a well-defined metabolic pathway. Of these, factor 3, a gut microbiome metabolism factor, was associated with an increased risk of stroke in the base (hazard ratio per one-unit standard deviation, HR 1.23 95%CI 1.15-1.31 P 1.98 × 10

A brief overview of a mouse model of cerebral hypoperfusion by bilateral carotid artery stenosis.

Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder related to cerebrovascular diseases, including vascular mild cognitive impairment, post-stroke dementia, multi-infarct dementia, subcortical ischemic vascular dementia (SIVD), and mixed dementia. Among the causes of VCI, more attention has been paid to SIVD because the causative cerebral small vessel pathologies are frequently observed in elderly people and because the gradual progression of cognitive decline often mimics Alzheimers disease. In most cases, small vessel diseases are accompanied by cerebral hypoperfusion. In mice, prolonged cerebral hypoperfusion is induced by bilateral carotid artery stenosis (BCAS) with surgically implanted metal micro-coils. This cerebral hypoperfusion BCAS model was proposed as a SIVD mouse model in 2004, and the spreading use of this mouse SIVD model has provided novel data regarding cognitive dysfunction and histologicalgenetic changes by cerebral hypoperfusion. Oxidative stress, microvascular injury, excitotoxicity, blood-brain barrier dysfunction, and secondary inflammation may be the main mechanisms of brain damage due to prolonged cerebral hypoperfusion, and some potential therapeutic targets for SIVD have been proposed by using transgenic mice or clinically used drugs in BCAS studies. This review article overviews findings from the studies that used this hypoperfused-SIVD mouse model, which were published between 2004 and 2021.

Noise and transient ischaemic attacks - A challenge

Consistency in medical decision-making is ideally expected. This includes consistency between different clinicians so that the same patient will receive the same diagnosis regardless of the assessing clinician. It also encompasses reliability as an individual clinician meaning at any given time or context, we apply the same process and principles to ensure the decisions we make do not deviate significantly from our peers or indeed our own past decisions. However, consistency in decision-making can be challenged when working within a busy healthcare system. We discuss the concept of noise and explore how it affects decision-making in acute presentations of transient neurology where doctors can differ in terms of their diagnostic decisions.

Traumatic posterior cerebral artery dissection and dissecting aneurysms A systematic review with an illustrative case report.

Traumatic posterior cerebral artery (tPCA) dissection and dissecting aneurysms are rare and constitute a challenging clinical entity. We analyze existing literature on tPCA dissection and present our institutional experience. We retrospectively queried our database for tPCA isolated dissection or dissecting aneurysms from 2008 until now and conducted a systematic literature review of published cases. We analyzed the clinical and radiographic characteristics and treatment outcomes of tPCA dissection. Including our case, a total of 11 cases with either isolated dissection ( tPCA dissection is diagnosed late and commonly affects the young population. The clinical outcome for this condition is typically favorable. Current endovascular techniques showed considerable efficacy and safety.

Staged endovascular recanalization for symptomatic atherosclerotic non-acutely occluded internal carotid artery.

Symptomatic non-acutely occluded internal carotid artery (NAOICA) results in stroke, cognitive impairment, and hemicerebral atrophy through cerebral hypoperfusion and artery-to-artery embolism. Atherosclerosis is the main cause of NAOICA. Conventional one-stage endovascular recanalization showed effectiveness but was plagued by many challenges. This retrospective analysis reports the technical feasibility and outcomes of the staged endovascular recanalization in patients with NAOICA. Eight consecutive patients with atherosclerotic NAOICA and ipsilateral ischemic stroke within 3 months between January 2019 and March 2022 were retrospectively reviewed. The patients (all males, with a mean age of 64.6 years) underwent staged endovascular recanalization 13 to 56 days after documented occlusion by imaging techniques (mean 28.8 days) the mean follow-up period was 20 months (range 6-28). The approach of the staged intervention was as follows. In the first stage, the occluded ICA was successfully recanalized using the simple small balloon dilation technique. In the second stage, angioplasty with a stent implant was performed with >50% residual stenosis in the initial segment or ≥70% residual stenosis in the C2-C5 segment. The technical success rate, the incidence of clinical adverse events (any stroke, death, cerebral hyperperfusion), and long-term in-stent stenosis (ISR) and reocclusion rates were evaluated. Technical success was achieved in seven patients, with early reocclusion occurring in one patient after the first-stage intervention. There were no adverse events observed within 30 days (0%), and long-term reocclusion and long-term ISR rates were both 14% (17). However, all patients developed iatrogenic arterial dissections during the first stage, indicating the challenge of reaching the true lumen through the occlusion site without damaging the intima. Based on the National Heart, Lung and Blood Institute (NHLBI) classification, there were two type A, four type B, three type C, and two type D dissections. The mean time interval between the two stages was 46.1 days (21-152 days). All type A and B dissections resolved spontaneously after ≥3 weeks of dual antiplatelet therapy, whereas most type C and all type D dissections did not heal spontaneously before the second stage. Also, one type C dissection led to reocclusion. This observation suggested that occlusions without flow limit and persistent vessel staining or extravasation could be clinically observed, while severe dissections (characterized as type C or greater) required prompt stenting rather than conservative treatment. Performing high-resolution MRI preoperatively to exclude fresh thrombus in the occluded vessel segment is indispensable in selecting appropriate candidates for endovascular recanalization. This could avoid downstream embolism during the interventional procedure. This retrospective study found that staged endovascular recanalization for symptomatic atherosclerotic NAOICA may be feasible with an acceptable technical success rate and a low complication rate in the selected candidates.

Investigating the in vivo effect of Tribulus terrestris extract in MCAO rats by using LC-MS-based metabolomics combined with the molecular docking.

Tribulus terrestris L. fruit (TT) is a traditional Chinese herbal medicine and has been used to treat ischemic stroke (IS). This study aimed to investigate the protective effect of TT extract, named TT15, on middle cerebral artery occlusion (MCAO) rats by metabolomics and molecular docking, and find the targets of action and the material basis of TT15 against IS. The results of the infarct volume and neurological defect scores confirmed the efficacy of TT15. The serum metabolomics analysis using LC-MS revealed that Model group animals experienced a variety of metabolic disturbances when compared to the Sham group. TT15 can restore the MCAO-induced serum metabolite changes by modulating multiple metabolic pathways. Six enzymes were highlighted by the metabolite-reaction-enzyme-gene (M-R-E-G) network analysis, which might be the possible targets for the TT15 against IS. Molecular docking analysis was applied to show binding affinities between active compounds and these enzymes. The representative docking mode with the lowest binding energy between three compounds and phospholipase A 2 (PLA2) and peroxidase (POD), respectively, were displayed by the ribbon binding map. This study profiles the metabolic changes of MCAO-induced IS and investigates the efficacy and the corresponding mechanism of TT15 in the treatment of IS.

Physicomechanical properties and in vitro release behaviors of electrospun ibuprofen-loaded blend PEOEC fibers.

Electrospinning is a fiber manufacturing technique with the possibility of encapsulating high levels of small molecule drugs while providing controlled release rates. In this study, electrospun blend fibers were produced from polyethylene oxide (PEO) and ethyl cellulose (EC) at various compositions to encapsulate a poorly water-soluble drug of ibuprofen (IBP) at 30% loading. Microscopic evaluation showed smooth and defect-free fiber morphologies for blank and IBP-loaded PEOEC fibers. The average fiber diameters and fiber yields suggested a potential optimization on the blend fiber composition for the electrospun drug-eluting PEOEC fibers, where the highest average fiber diameter and fiber yield occurred at 50PEO50EC fiber composition. Surface wettability studies demonstrated the effects on surface hydrophobicity from blend fibers of water-soluble PEO and hydrophobic EC as well as the incorporation of IBP. In addition, blend fibers containing more PEO promoted the water absorption rates through dissolution of the polymer matrix. Furthermore, results from mechanical testing of the blend fibers showed the highest fiber elastic modulus and tensile strength at fiber compositions in between 75PEO25EC and 50PEO50EC, corresponding to the average fiber diameter measurements. The in vitro IBP release rates demonstrated a dependence on the EC compositions supported by the surface wettability and water absorption rate studies. In general, our work demonstrated the ability to electrospin blank and IBP-loaded PEOEC fibers with the scientific understandings of EC compositions on modulations of fiber physicomechanical properties and in vitro drug release rates. The findings from the work indicated the potential engineering and pharmaceutical applications of electrospun drug-eluting fibers for topical drug delivery.

Superior stroke prevention with angiotensin receptor blockers compared with other antihypertensive drugs.

Stroke is a major cause of death and disability and its incidence is linearly increased with the elevation of blood pressure (BP) and the advancement of age in both men and women, with its incidence being higher in older subjects, the blacks and women. The annual worldwide incidence of stroke is 7.6 million for subjects ≥ 20 years of age with the average direct and indirect annual costs of stroke care, is expected to be $94.3 billion between 2014 and 2015. With respect to the cause of stroke, this is multifactorial, due to atherosclerotic heart disease, inflammation, atrial fibrillation, and hypertension with the latter being the most important cause. Therefore, control of BP is the major factor for its prevention. In order to get a better perspective on the current management of stroke, a Medline search of the English literature was conducted between 2014 and 2022 and 26 pertinent papers were selected. Review of data from the selected papers demonstrated that control of SSBP < 130 mmHg was better in stroke prevention than SBP 130-140 mmHg for primary and secondary strokes. Among the drugs used, angiotensin receptor blockers provided superior stroke prevention compared to angiotensin converting enzyme inhibitors and other antihypertensive drugs.

Basic psychological needs satisfaction of stroke patients a qualitative study.

Previous studies have shown that the satisfaction of basic psychological needs is related to psychological well-being. Improving satisfaction will increase personal well-being, promote positive health outcomes, and improve disease recovery. However, no research has focused on the basic psychological needs of stroke patients. Therefore, this study aims to determine the basic psychological needs experience, satisfaction, and its influencing factors of stroke patients. 12 males and 6 females in the non-acute phase with stroke were recruited in the Department of Neurology, Nanfang Hospital. The individual, semi-structured interviews were conducted in a separate room. The data were imported to Nvivo 12 and analyzed using the directed content analysis approach. Three main themes consisting of 9 sub-themes were derived from the analysis. These three main themes focused on the needs for autonomy, competence, and relatedness of stroke patients. Participants have different degrees of satisfaction of their basic psychological needs, which may be related to their family environment, work environment, stroke symptoms, or other factors. Stroke symptoms can significantly reduce the patients needs for autonomy and competence. However, the stroke seems to increase the patients satisfaction of the need for relatedness.

Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivationreoxygenation-mediated neuronal injury.

The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemiareperfusion injury (CIRI). Since the effect of miR-181d on CIRI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain IR injury. To replicate in vivo and in vitro CIRI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiencyreoxygenation (OGDR) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGDR-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGDR injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181dDOCK4 axis might be a novel therapeutic target for IS.

Automatic comprehensive aspects reports in clinical acute stroke MRIs.

The Alberta Stroke Program Early CT Score (ASPECTS) is a simple visual system to assess the extent and location of ischemic stroke core. The capability of ASPECTS for selecting patients treatment, however, is affected by the variability in human evaluation. In this study, we developed a fully automatic system to calculate ASPECTS comparable with consensus expert readings. Our system was trained in 400 clinical diffusion weighted images of patients with acute infarcts and evaluated with an external testing set of 100 cases. The models are interpretable, and the results are comprehensive, evidencing the features that lead to the classification. This system adds to our automated pipeline for acute stroke detection, segmentation, and quantification in MRIs (ADS), which outputs digital infarct masks and the proportion of diverse brain regions injured, in addition to the predicted ASPECTS, the prediction probability and the explanatory features. ADS is public, free, accessible to non-experts, has very few computational requirements, and run in real time in local CPUs with a single command line, fulfilling the conditions to perform large-scale, reproducible clinical and translational research.

Race, ethnicity, sex, and socioeconomic disparities in anticoagulation for atrial fibrillation A narrative review of contemporary literature.

Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and is responsible for 1 in 7 ischemic strokes. While anticoagulation is effective at preventing strokes, prior work has highlighted significant disparities in anticoagulation prescribing. Furthermore, racial, ethnic, sex, and socioeconomic disparities in AF outcomes have been described. As such, we aimed to review recent data on disparities with respect to anticoagulation for AF published between January 2018 and February 2021. The search string consisted of 7 phrases that combined AF, anticoagulation, and disparities involving sex, race, ethnicity, income, socioeconomic status (SES), and access to care and identified 13 relevant articles. The aggregate data demonstrated that Black patients were less likely to be prescribed anticoagulation than patients of other racialethnic groups. Additionally, Black patients were more likely to be prescribed warfarin instead of direct oral anticoagulants (DOACs) despite evidence that DOACs are safer and better tolerated. Lower-income patients and patients with less education were also less likely to receive DOACs. Some studies found that women were less likely to be anticoagulated than men even when their estimated stroke risk was higher, although other studies did not show sex-based differences. Building upon prior work, our study demonstrates that racial and ethnic disparities have persisted in the management of AF. Additionally, we our work highlights that there are significant disparities in anticoagulation management for AF associated with sex, income, and education. More work is needed to identify mechanisms for these disparities and identify potential solutions to achieve pharmacoequity.

Managing painful shoulder after neurological injury.

Shoulder pain is common after neurological injury and can be disabling, lead to poor functional outcomes and increase care costs. Its cause is multifactoral and several pathologies contribute to the presentation. Astute diagnostic skills and a multidisciplinary approach are required to recognise what is clinically relevant and to implement appropriate stepwise management. In the absence of large clinical trial data, we aim to provide a comprehensive, practical and pragmatic overview of shoulder pain in patients with neurological conditions. We use available evidence to produce a management guideline, taking into account specialty opinions from neurology, rehabilitation medicine, orthopaedics and physiotherapy.

Characterization of length of stay after minimally invasive endoscopic intracerebral hemorrhage evacuation.

Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P0.007), concurrent intraventricular hemorrhage (OR2.46 (1.25 to 4.86), P0.02), and deep origin (ORper point 2.42 (1.21 to 4.83), P0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.

Mechanical thrombectomy for in-hospital stroke data from the Italian Registry of Endovascular Treatment in Acute Stroke.

The benefit, safety, and time intervals of mechanical thrombectomy (MT) in patients with in-hospital stroke (IHS) are unclear. We sought to evaluate the outcomes and treatment times for IHS patients compared with out-of-hospital stroke (OHS) patients receiving MT. We analyzed data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) between 2015 and 2019. We compared the functional outcomes (modified Rankin Scale (mRS) scores) at 3 months, recanalization rates, and symptomatic intracranial hemorrhage (sICH) after MT. Time intervals from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were recorded for both groups, as were door-to-imaging and door-to-groin for OHS. A multivariate analysis was performed. Of 5619 patients, 406 (7.2%) had IHS. At 3 months, IHS patients had a lower rate of mRS 0-2 (39% vs 48%, P<0.001) and higher mortality (30.1% vs 19.6%, P<0.001). Recanalization rates and sICH were similar. Time intervals (min, median (IQR)) from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were favorable for IHS (60 (34-106) vs 123 (89-188.5) 150 (105-220) vs 220 (168-294) 227 (164-303) vs 293 (230-370) all P<0.001), whereas OHS had lower door-to-imaging and door-to-groin times compared with stroke onset-to-imaging and onset-to-groin for IHS (29 (20-44) vs 60 (34-106), P<0.001 113 (84-151) vs 150 (105-220) P<0.001). After adjustment, IHS was associated with higher mortality (aOR 1.77, 95% CI 1.33 to 2.35, P<0.001) and a shift towards worse functional outcomes in the ordinal analysis (aOR 1.32, 95% CI 1.06 to 1.66, P0.015). Despite favorable time intervals for MT, IHS patients had worse functional outcomes than OHS patients. Delays in IHS management were detected.

Effects of integrated action and sensory observation therapy based on mirror neuron and embodied cognition theory on upper limb sensorimotor function in chronic stroke a study protocol for a randomised controlled trial.

This study protocol aims to explore the effectiveness and neural mechanism of the integration of action observation therapy (AOT) and sensory observation therapy (SOT) for post-stroke patients on upper limb sensorimotor function. This is a single-centre, single-blind, randomised controlled trial. A total of 69 patients with upper extremity hemiparesis after stroke will be recruited and randomly divided into an AOT group, a combined action observation and somatosensory stimulation therapy (AOTSST) group, and a combined AOT and SOT (AOTSOT) group in a 111 ratio. Each group will receive 30 min of daily treatment, five times weekly for 4 weeks. The primary clinical outcome will be the Fugl-Meyer Assessment for Upper Extremity. Secondary clinical outcomes will include the Box and Blocks Test, modified Barthel Index and sensory assessment. All clinical assessments and resting-state functional MRI and diffusion tensor imaging data will be obtained at pre-intervention (T1), post-intervention (T2) and 8 weeks of follow-up (T3). The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2020-178). The results will be submitted to a peer-review journal or at a conference. ChiCTR2000040568.

Transcranial direct current stimulation combined with bodyweight support-tai chi footwork for motor function of stroke survivors a study protocol of randomised controlled trial.

Our previous studies have proposed the bodyweight support-tai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors. This study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 111 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. Ethics approval was obtained from the ethics committee of the Shanghai Seventh Peoples Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. ChiCTR2200059329.

Effect of socioeconomic status on patients undergoing elective abdominal aortic aneurysm repair in a publicly funded health care system.

The association between socioeconomic status (SES) and outcomes after abdominal aortic aneurysm (AAA) repair in publicly funded health care systems is poorly described. The purpose of this study was to determine the effect of SES on postoperative outcomes in patients who underwent AAA repair in Nova Scotia, Canada. We performed a retrospective analysis of all elective AAA repairs in Nova Scotia between November 2005 and March 2015 using administrative data sources. We compared postoperative 30-day outcomes and long-term survival across socio-economic quintiles, defined as the Pampalon Material Deprivation Index (MDI) and Social Deprivation Index (SDI). We also compared the relation between baseline characteristics, MDI quintile, SDI quintile and 30-day mortality. We used multivariable logistic regression and survival analysis to calculate adjusted 30-day mortality and long-term survival, respectively. A total of 1913 patients underwent AAA repair during the study period. The overall 30-day mortality rate was 2.6% (50 patients). Thirty-day outcomes including death ( Socioeconomic status does not appear to affect short- or long-term mortality after AAA repair in a publicly funded health care system. Further research is needed to address any existing gaps in screening and referral before repair. Le lien entre le statut socioéconomique (SSÉ) et les issues suivant la réparation d’un anévrisme aortique abdominal (AAA) réalisée dans un système de santé public est mal défini. Cette étude avait pour but de déterminer l’effet du SSÉ sur les issues postopératoires chez les patients ayant subi la réparation d’un AAA en Nouvelle-Écosse, au Canada. Nous avons mené une analyse rétrospective de toutes les réparations électives d’un AAA réalisées entre novembre 2005 et mars 2015 en Nouvelle-Écosse à partir de bases de données administratives. Nous avons comparé les issues postopératoires sur 30 jours et la survie à long terme pour tous les quintiles socioéconomiques, établis selon l’indice de défavorisation matérielle et sociale de Pampalon (IDMS) et l’indice de défavorisation sociale (IDS). Nous avons aussi comparé les relations entre les caractéristiques de base, les quintiles d’IDMS et d’IDS et la mortalité dans les 30 jours. Nous nous sommes servis d’une régression logistique multivariée et d’analyses de survie pour calculer respectivement la mortalité ajustée dans les 30 jours et la survie à long terme. Au total, 1913 patients ont subi une réparation d’un AAA pendant la période de l’étude. Le taux de mortalité global dans les 30 jours était de 2,6 % (50 patients). Les issues sur 30 jours, soit les décès ( Le SSÉ ne semble pas influencer la mortalité à court ni à long terme suivant la réparation d’un AAA réalisée dans un système de santé public. D’autres études seront cependant nécessaires pour examiner la présence de lacunes dans le dépistage et l’orientation du patient avant la réparation.

Long-term functional outcomes improved with deep brain stimulation in patients with disorders of consciousness.

Deep brain stimulation (DBS) has been preliminarily applied to treat patients with disorders of consciousness (DoCs). The study aimed to determine whether DBS was effective for treating patients with DoC and identify factors related to patients outcomes. Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively analysed. Multivariate regression and subgroup analysis were performed to adjust for potential confounders. The primary outcome was improvement in consciousness at 1 year. An overall improvement in consciousness at 1 year was achieved in 32.4% (1237) of the DBS group compared with 4.3% (14328) of the conservative group. After full adjustment, DBS significantly improved consciousness at 1 year (adjusted OR 11.90, 95% CI 3.65-38.46, p<0.001). There was a significant treatment×follow up interaction (H14.99, p<0.001). DBS had significantly better effects in patients with minimally conscious state (MCS) compared with patients with vegetative stateunresponsive wakefulness syndrome (p for interaction <0.001). A nomogram based on age, state of consciousness, pathogeny and duration of DoCs indicated excellent predictive performance (c-index0.882). DBS was associated with better outcomes in patients with DoC, and the effect was likely to be significantly greater in patients with MCS. DBS should be cautiously evaluated by nomogram preoperatively, and randomised controlled trials are still needed.

Three-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients with Aortic Stenosis.

Randomized data comparing outcomes of transcatheter aortic valve replacement (TAVR) to surgery in low surgical risk patients at time points beyond 2 years is limited. This presents an unknown for physicians striving to educate patients as part of a shared decision-making process. We evaluated 3-year clinical and echocardiographic outcomes from the Evolut Low Risk trial. Low-risk patients were randomized to TAVR with a self-expanding, supra-annular valve or surgery. The primary endpoint of all-cause mortality or disabling stroke and several secondary endpoints were assessed at 3 years. There were 1414 attempted implants (730 TAVR 684 surgery). Patients had a mean age of 74 years and 35% were women. At 3 years, the primary endpoint occurred in 7.4% of TAVR patients and 10.4% of surgery patients (HR, 0.70 95% CI, 0.49-1.00 p0.051). The difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time -1.8% at year 1 -2.0% at year 2 -2.9% at year 3. The incidence of mild paravalvular regurgitation (20.3% TAVR vs. 2.5% surgery) and pacemaker placement (23.2% TAVR vs. 9.1% surgery p<0.001) were lower in the surgery group. Rates of moderate or greater paravalvular regurgitation for both groups were <1% and not significantly different. Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1mmHg TAVR vs. 12.1mmHg surgery p<0.001) at 3 years. Within the Evolut Low Risk study, TAVR at 3 years showed durable benefits compared to surgery with respect to all-cause mortality or disabling stroke.

A Systematic Review and Meta-Analysis of the Association between Residual Shunts after Patent Foramen Ovale Closure and Long-Term Cerebrovascular Events.

The association between a patent foramen ovale (PFO) and cryptogenic stroke (CS) is well established, and the benefits of PFO closure are clearly recognized. This study aimed to investigate the presence of a residual shunt in patients who have experienced cryptogenic cerebrovascular events following a PFO closure. Two researchers systematically searched the PubMed and Embase online database for pertinent clinical studies published between January 2000 and July 2021 concerning the recurrence of cerebrovascular events after PFO closures. Upon screening an initial list of 2,342 articles, six studies were identified, involving 2,083 patients. Overall, the analysis indicated a marked difference in the recurrence of cerebrovascular events in 8.89% of residual shunt (RS) cases compared to only 2.90% of non-RS cases. The summary odds ratio was 3.484 (95% confidence interval, 2.169-5.596), which suggested that RS may be a risk factor for recurrent cerebrovascular events in patients that experienced PFO-related cerebrovascular events within 6 months after PFO closure surgery. The presence of RS significantly increases the risk of recurrent cerebrovascular events in patients with clinical PFO closure.

Outcomes and predictors of periprocedural stroke after transcatheter aortic valve implantation.

Risk factors for stroke after transcatheter aortic valve implantation (TAVI) are currently incompletely understood. To identify possible predictors of early post-TAVI stroke and explore its short-term outcomes. Retrospective analysis of consecutive patients (pts) submitted to TAVI between 2009 and 2020 in a tertiary center. Baseline characteristics, procedural information and stroke in first 30 days after TAVI were collected. In-hospital and 12 months outcomes were analyzed. A total of 512pts (56,1% female, mean age of 82 ± 6years.) were included. In the first 30 days after TAVI 19pts (3,7%) had a stroke. In univariate analysis stroke was associated with higher body mass index (29 vs 27kgm Periprocedural and 30-day stroke is a relatively uncommon but potentially devastating complication after TAVI. In this cohort, 30-day stroke rate after TAVI was 3.7%. Hypertriglyceridemia and post-dilatation were found to be the only independent risk predictors. Outcomes after stroke, including 30-day mortality, were significantly worse.

Outcomes of percutaneous left atrial appendage occlusion device implantation in atrial fibrillation patients based on underlying stroke risk.

To determine outcomes in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion (LAAO) based on the underlying stroke risk (defined by the CHA2DS2-VASc score). Data were extracted from the National Inpatient Sample for calendar years 2016-20. Left atrial appendage occlusion implantations were identified on the basis of the International Classification of Diseases, 10th Revision, Clinical Modification code of 02L73DK. The study sample was stratified on the basis of the CHA2DS2-VASc score into three groups (scores of 3, 4, and ≥5). The outcomes assessed in our study included complications and resource utilization. A total of 73 795 LAAO device implantations were studied. Approximately 63% of LAAO device implantations occurred in patients with CHA2DS2-VASc scores of 4 and ≥5. The crude prevalence of pericardial effusion requiring intervention was higher with increased CHA2DS2-VASc score (1.4% in patients with a score of ≥5 vs. 1.1% in patients with a score of 4 vs. 0.8% in patients with a score of 3, P < 0.01). In the multivariable model adjusted for potential confounders, CHA2DS2-VASc scores of 4 and ≥5 were found to be independently associated with overall complications adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI) 1.18-1.35, and aOR 1.88, 95% CI 1.73-2.04, respectively and prolonged length of stay (aOR 1.18, 95% CI 1.11-1.25, and aOR 1.54, 95% CI 1.44-1.66, respectively). A higher CHA2DS2-VASc score was associated with an increased risk of peri-procedural complications and resource utilization after LAAO. These findings highlight the importance of patient selection for the LAAO procedure and need validation in future studies.

Effects of exercise and bryostatin-1 on functional recovery and posttranslational modification in the perilesional cortex after cerebral infarction.

Strokes can cause a variety of sequelae, such as paralysis, particularly in the early stages after stroke onset. Rehabilitation therapy atthis time often provides some degree of paralysis recovery. Neuroplasticity in the peri-infarcted cerebral cortex induced by exercise training may contribute to recovery of paralysis after cerebral infarction. However, the molecular mechanism of this process remains unclear. This study focused on brain protein kinase C (PKC), which is speculated to be involved in neuroplasticity. We evaluated the functional recovery of cerebral infarction model rats, by using rotarod test after running wheel training and withwithout administration of bryostatin, a PKC activator. In addition, the expression of phosphorylated and unphosphorylated PKC subtypes, glycogen synthase kinase 3β (GSK3β), and collapsin response-mediator proteins 2 (CRMP2) were analyzed by Western blotting. In the rotarod test, bryostatin administration alone had no effect on gait duration, but the combination of training and this drug significantly prolonged gait duration compared with training alone. In protein expression analysis, the combination of training and bryostatin significantly increased phosphorylation of PKCα and PKCε isoforms, increased phosphorylation of GSK3β, which acts downstream of PKC, and decreased phosphorylation of CRMP2. The effect of bryostatin in combination with training appears to be mediated via PKC phosphorylation, with effects on functional recovery occurring through the downstream regulation of GSK3β and CRMP2 phosphorylation.

Cephalic electroacupuncture restores learning and memory in rats with induced ischemic stroke via inhibition of NF-κB nuclear translocation.

Inflammatory responses in the brain contribute to cognitive deficits. Nuclear factor-κB (NF-κB), a critical transcription factor in inflammatory responses, is activated in post-stroke cognitive deficit. Baihui (DU20) and Shenting (DU24) acupoints, the main acupoints of Du Meridian, are widely used to improve cognitive deficits in Chinese patients with stroke. It has been reported that post-stroke cognitive deficits can be treated by electroacupuncture (EA) but the underlying mechanisms of these effects are unclear. Using the rat middle cerebral artery occlusion cerebral ischemia-reperfusion injury model, we found that EA at these 2 acupoints improved neurological function, decreased cerebral infarct lesion volumes, and ameliorated the inflammatory response in the hippocampal CA1 region. The treatment also ameliorated memory and learning deficits by inhibiting the NF-κB signaling pathway in the ischemic hippocampal CA 1 region. This coincided with downregulation of interleukin-1β, interleukin-6, CD45, and tumor necrosis factor-α. We conclude that EA at these 2 acupoints ameliorates memory and learning deficits following experimental cerebral infarction by inhibiting NF-κB-mediated inflammatory injury in the hippocampal CA1 region.

Circulating ketone bodies and cardiovascular outcomes the MESA study.

Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) hazard ratio, HR (95% confidence interval, CI) 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively. Participants also experienced an 87% (95% CI 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB 1.68 (1.07-2.65), per 10-fold increase in total KB. The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

Joint modeling of longitudinal change in pulse rate and survival time of heart failure patients treated at Arbaminch General Hospital, Southern Ethiopia.

Heart failure is a chronic progressive disease in which the heart muscle is unable to pump enough blood to meet the bodys need. It is a severe health problem around the world with high re-hospitalization and death rates. The main aim of this study was to identify the factors associated with longitudinal change of pulse rate and survival time to death of congestive heart failure patients treated at Arba Minch General Hospital. A retrospective study design was undertaken on congestive heart failure patients admitted to the Arba Minch General Hospital from January 2017 to December 2020. Data was collected from a total of 199 patients. After evaluating the longitudinal data with a linear mixed model and the survival time to death data with cox proportional model, Bayesian joint model of both sub models was fitted in R software using JMbayes2 package. Findings from Bayesian joint model revealed that the estimated value for the association parameter was positive and statistically significant. This indicates that there is significant evidence of an association between the mean longitudinal change of pulse rate and the risk of death. Weight of patients at baseline, gender, chronic kidney disease, left ventricular ejection fraction, New York Heart Association classification, diabetes, tuberculosis, pneumonia and family history were statistically significant factors associated with mean evolution of pulse rate of congestive heart failure patients. Left ventricular ejection fraction, etiology of congestive heart failure, type of congestive heart failure, chronic kidney disease, smoking, family history, alcohol and diabetes were found to be statistically significant factors associated with survival time to death. To reduce the risk level, health professionals should give attention to congestive heart failure patients with high pulse rate, co-morbidities of chronic kidney disease, tuberculosis, diabetic, smoking status, family history, and pneumonia in the study area.

Stellate Ganglion Blocks for Refractory Central Poststroke Pain A Case Series.

Central poststroke pain (CPSP) is a neuropathic pain secondary to cerebrovascular accidents. This is characterized by pain and other sensory abnormalities, which correspond with the area of the injured brain. Despite advancements in therapeutic options, this clinical entity is still challenging to treat. We present 5 patients with CPSP, who were refractory to pharmacotherapy and were successfully managed with stellate ganglion blocks. A significant decrease in pain scores and improvement in functional disabilities were noted in all patients following the intervention.

NIH stroke scale and unfavourable outcomes in acute ischaemic stroke retrospective study.

To evaluate the determining factors of severe functional impairment (SFI) outcome at discharge and in-hospital mortality in patients who had an acute ischaemic stroke and thus favouring early implementation of primary palliative care (PC). A retrospective descriptive study by the analysis of 515 patients who had an acute ischaemic stroke admitted at stroke unit, aged≥18 years, from January 2017 to December 2018. Previous clinical and functional status data, National Institute of Health Stroke Scale (NIHSS) on admission, and data related to the evolution during hospitalisation were evaluated, relating them to the SFI outcome at discharge and death. The significance level was set at 5%. Of 515 patients included, 15% (77) died, 23.3%(120) had an SFI outcome and 9.1% (47) were evaluated by the PC team. It was observed that NIHSS Score≥16 is responsible for a 15.5-fold increase in the occurrence of death outcome. The presence of atrial fibrillation was responsible for a 3.5-fold increase in the risk of this outcome. NIHSS Score is an independent predictor of in-hospital death and SFI outcomes at discharge. Knowledge about the prognosis and risk of developing unfavourable outcomes is important for planning the care of patients affected by a potentially fatal and limiting acute vascular insult.

Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography Implications for Cardiovascular Risk Prediction.

Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented. This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care. The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value. External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio OR per SD increase in EAT volume 1.13 95% CI 1.04-1.30 P 0.01), and atrial fibrillation (OR 1.25 95% CI1.08-1.40 P 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD 1.28 95% CI 1.10-1.37 P 0.02), myocardial infarction (HR 1.26 95% CI1.09-1.38 P 0.001), and stroke (HR 1.20 95% CI 1.09-1.38 P 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR 2.67 95% CI 1.26-3.73 P ≤ 0.01) and long-term post-cardiac surgery atrial fibrillation (7-year follow-up HR 2.14 95% CI 1.19-2.97 P ≤ 0.01). Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.

Too Little of a Good Thing Strong Associations Between Cardiac Size and Fitness Among Women.

Cardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear. This study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors. A total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake Vo Vo A small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.

Association of Stress With Cognitive Function Among Older Black and White US Adults.

Perceived stress can have long-term physiological and psychological consequences and has shown to be a modifiable risk factor for Alzheimer disease and related dementias. To investigate the association between perceived stress and cognitive impairment in a large cohort study of Black and White participants aged 45 years or older. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national population-based cohort of 30 239 Black and White participants aged 45 years or older, sampled from the US population. Participants were recruited from 2003 to 2007, with ongoing annual follow-up. Data were collected by telephone, self-administered questionnaires, and an in-home examination. Statistical analysis was performed from May 2021 to March 2022. Perceived stress was measured using the 4-item version of the Cohen Perceived Stress Scale. It was assessed at the baseline visit and during 1 follow-up visit. Cognitive function was assessed with the Six-Item Screener (SIS) participants with a score below 5 were considered to have cognitive impairment. Incident cognitive impairment was defined as a shift from intact cognition (SIS score >4) at the first assessment to impaired cognition (SIS score ≤4) at the latest available assessment. The final analytical sample included 24 448 participants (14 646 women 59.9% median age, 64 years range, 45-98 years 10 177 Black participants 41.6% and 14 271 White participants 58.4%). A total of 5589 participants (22.9%) reported elevated levels of stress. Elevated levels of perceived stress (dichotomized as low stress vs elevated stress) were associated with 1.37 times higher odds of poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio AOR, 1.37 95% CI, 1.22-1.53). The association of the change in the Perceived Stress Scale score with incident cognitive impairment was significant in both the unadjusted model (OR, 1.62 95% CI, 1.46-1.80) and after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (AOR, 1.39 95% CI, 1.22-1.58). There was no interaction with age, race, and sex. This study suggests that there is an independent association between perceived stress and both prevalent and incident cognitive impairment. The findings suggest the need for regular screening and targeted interventions for stress among older adults.

Protective effect of basic helix-loop-helix family member e40 on cerebral ischemiareperfusion injury Inhibition of apoptosis via repressing the transcription of pleckstrin homology-like domain family A, member 1.

During ischemic stroke treatment, cerebral ischemiareperfusion (IR) injury results in neuronal cell death and neurological dysfunctions in brain. Previous studies indicate that basic helix-loop-helix family member e40 (BHLHE40) exerts protective effects on the pathology of neurogenic diseases. However, the protective function of BHLHE40 in IR is unclear. This study aimed to explore the expression, role and potential mechanism of BHLHE40 after ischemia. We established models of IR injury in rats and of oxygen-glucose deprivationreoxygenation (OGDR) in primary hippocampal neurons. Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to detect neuronal injury and apoptosis. Immunofluorescence was used to detect BHLHE40 expression. Cell viability and cell damage measurements were conducted using Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) assay. The regulation of BHLHE40 to pleckstrin homology-like domain family A, member 1 (PHLDA1) was assessed using the dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. Cerebral IR rats exhibited severe neuronal loss and apoptosis in hippocampal cornu Ammonis 1 (CA1) region, accompanied by downregulated BHLHE40 expression at both mRNA and protein levels, indicating that BHLHE40 may regulate the apoptosis of hippocampal neurons. The function of BHLHE40 in neuronal apoptosis during cerebral IR was further explored by establishing an OGDR model in vitro. Low expression of BHLHE40 was also observed in neurons treated with OGDR. The OGDR administration inhibited cell viability and enhanced cell apoptosis in hippocampal neurons, whereas BHLHE40 overexpression reversed those changes. Mechanistically, we demonstrated that BHLHE40 could repress PHLDA1 transcription by binding to PHLDA1 promoter. The PHLDA1 is a facilitator of neuronal damage in brain IR injury and its upregulation reversed the effects caused by BHLHE40 overexpression in vitro. The transcription factor BHLHE40 may protect against brain IR injury through repressing cell damage via regulating PHLDA1 transcription. Thus, BHLHE40 may be a candidate gene for further study of molecular or therapeutic targets for IR.

Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts.

The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Grays models were used for hazard ratios (HRs), their 95% confidence intervals (CIs), and the lifetime risk according to PRS and clinical risk categories. A total of 41,006 individuals aged 30-75 years with a mean follow-up of 9.0 years were included. Comparing the top versus bottom 5% of the PRS, the HR was 3.01 (95%CI 2.03-4.45) in the total population, and similar findings were observed within clinical risk strata. Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories. Notably, among individuals with intermediate clinical risk, the 10-year risk for those in the top 5% of the PRS (7.3%, 95%CI 7.1%-7.5%) reached the threshold of high clinical risk (⩾7.0%) for initiating preventive treatment, and this effect of the PRS on refining risk stratification was evident for ischemic stroke. Even among those in the top 10% and 20% of the PRS, the 10-year risk would also exceed this level when aged ⩾50 and ⩾60 years, respectively. Overall, the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.

Baroreflex-sympathoneural without baroreflex-cardiovagal failure in neurogenic orthostatic hypotension.

We describe a patient with neurogenic orthostatic hypotension (nOH) after brainstem neurosurgery in whom baroreflex-cardiovagal function was normal despite baroreflex-sympathoneural failure. We also cite other conditions entailing differential alterations in the two efferent limbs of the baroreflex. Any condition involving nOH from selective loss of sympathetic noradrenergic innervation, interference with sympathetic pre-ganglionic transmission in the thoracolumbar spinal cord, sympathectomies, or attenuated intra-neuronal synthesis, storage, or release of norepinephrine would be expected to manifest with selective baroreflex-sympathoneural dysfunction. We advise caution in relying on indices of baroreflex-cardiovagal function for diagnosing nOH, since normal values for these indices do not exclude nOH.