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Adjustment for Social Risk Factors in a Measure of Clinician Quality Assessing Acute Admissions for Patients With Multiple Chronic Conditions.

Adjusting quality measures used in pay-for-performance programs for social risk factors remains controversial. To illustrate a structured, transparent approach to decision-making about adjustment for social risk factors for a measure of clinician quality that assesses acute admissions for patients with multiple chronic conditions (MCCs). This retrospective cohort study used 2017 and 2018 Medicare administrative claims and enrollment data, 2013 to 2017 American Community Survey data, and 2018 and 2019 Area Health Resource Files. Patients were Medicare fee-for-service beneficiaries 65 years or older with at least 2 of 9 chronic conditions (acute myocardial infarction, Alzheimer diseasedementia, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or asthma, depression, diabetes, heart failure, and stroketransient ischemic attack). Patients were attributed to clinicians in the Merit-Based Incentive Payment System (MIPS primary health care professionals or specialists) using a visit-based attribution algorithm. Analyses were conducted between September 30, 2017, and August 30, 2020. Social risk factors included low Agency for Healthcare Research and Quality Socioeconomic Status Index, low physician-specialist density, and Medicare-Medicaid dual eligibility. Number of acute unplanned hospital admissions per 100 person-years at risk for admission. Measure scores were calculated for MIPS clinicians with at least 18 patients with MCCs assigned to them. There were 4 659 922 patients with MCCs (mean SD age, 79.0 8.0 years 42.5% male) assigned to 58 435 MIPS clinicians. The median (IQR) risk-standardized measure score was 38.9 (34.9-43.6) per 100 person-years. Social risk factors of low Agency for Healthcare Research and Quality Socioeconomic Status Index, low physician-specialist density, and Medicare-Medicaid dual eligibility were significantly associated with the risk of hospitalization in the univariate models (relative risk RR, 1.14 95% CI, 1.13-1.14, RR, 1.05 95% CI, 1.04-1.06, and RR, 1.44 95% CI, 1.43-1.45, respectively), but the association was attenuated in adjusted models (RR, 1.11 95% CI 1.11-1.12 for dual eligibility). Across MIPS clinicians caring for variable proportions of dual-eligible patients with MCCs (quartile 1, 0%-3.1% quartile 2, >3.1%-9.5% quartile 3, >9.5%-24.5%, and quartile 4, >24.5%-100%), median measure scores per quartile were 37.4, 38.6, 40.0, and 39.8 per 100 person-years, respectively. Balancing conceptual considerations, empirical findings, programmatic structure, and stakeholder input, the Centers for Medicare Medicaid Services decided to adjust the final model for the 2 area-level social risk factors but not dual Medicare-Medicaid eligibility. This cohort study demonstrated that adjustment for social risk factors in outcome measures requires weighing high-stake, competing concerns. A structured approach that includes evaluation of conceptual and contextual factors, as well as empirical findings, with active engagement of stakeholders can be used to make decisions about social risk factor adjustment.

Cerebral Hemodynamics Underlying Artery-to-Artery Embolism in Symptomatic Intracranial Atherosclerotic Disease.

Artery-to-artery embolism (AAE) is a common stroke mechanism in intracranial atherosclerotic disease (ICAD), associated with a considerable risk of recurrent stroke. We aimed to investigate cerebral hemodynamic features associated with AAE in symptomatic ICAD. Patients with anterior-circulation, symptomatic ICAD confirmed in CT angiography (CTA) were recruited. We classified probable stroke mechanisms as isolated parent artery atherosclerosis occluding penetrating artery, AAE, hypoperfusion, and mixed mechanisms, largely based on infarct topography. CTA-based computational fluid dynamics (CFD) models were built to simulate blood flow across culprit ICAD lesions. Translesional pressure ratio (PR Pressure

Residual risks and evolving atherosclerotic plaques.

Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity. The chronic occlusive diseases have changed the epidemiological landscape of health problems both in developed and the developing countries. Despite the enormous benefit of advanced revascularization techniques, use of statins, and successful attempts of targeting modifiable risk factors, like smoking and exercise in the last four decades, there is still a definite residual risk in the population, as evidenced by many prevalent and new cases every year. Here, we highlight the burden of the atherosclerotic diseases and provide substantial clinical evidence of the residual risks in these diseases despite advanced management settings, with emphasis on strokes and cardiovascular risks. We critically discussed the concepts and potential underlying mechanisms of the evolving atherosclerotic plaques in the coronary and carotid arteries. This has changed our understanding of the plaque biology, the progression of unstable vs stable plaques, and the evolution of plaque prior to the occurrence of a major adverse atherothrombotic event. This has been facilitated using intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the clinical settings to achieve surrogate end points. These techniques are now providing exquisite information on plaque size, composition, lipid volume, fibrous cap thickness and other features that were previously not possible with conventional angiography.

Is the robotic rehabilitation that is added to intensive body rehabilitation effective for maximization of upper extremity motor recovery following a stroke A randomized controlled study.

Trunk stabilization, which is a factor that directly affects the performance of affected upper-limb movements in stroke patients, is of critical importance in the performance of selective motor control. This study aimed to investigate the effects on upper-limb motor function of the addition of robotic rehabilitation (RR) and conventional rehabilitation (CR) to intensive trunk rehabilitation (ITR). A total of 41 subacute stroke patients were randomly allocated to two groups RR and CR. Both groups received the same ITR procedure. Following ITR, a robot-assisted rehabilitation program of 60 min, 5 days a week, for 6 weeks, was applied to the RR group, and an individualized upper-limb rehabilitation to the CR group. Assessments were made at baseline and after 6 weeks using the Trunk Impairment Scale (TIS), Fugl-Meyer Upper Extremity Motor Evaluation Scale (FMA-UE), and Wolf Motor Function Test (WMFT). Improvements were obtained in the TIS, FMA-UE, and WMFT scores for both groups (p < 0.001), with no superiority detected between the groups (p > 0.05). The RR group scores were relatively high, but not to a statistically significant. When added to intensive trunk rehabilitation, the robot-assisted systems, which are recommended as a stand-alone therapy method, produced similar results to conventional therapies. This technology can be used as an alternative to conventional methods under appropriate conditions of clinical opportunity, access, time management, and staff limitations. However, when RR is combined with traditional interventions such as intensive trunk rehabilitation, it is essential to investigate if the real effect is due to the robotic rehabilitation or the accumulation of positive effects of excessive movement or force spread associated with trained muscles. This trial was retrospectively registered in the ClinicalTrials.gov with NCT05559385 registration number (25092022).

Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors A retrospective, observational study based on healthcare claims and national death index data.

Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED). The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality. A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 14 on baseline risk variables. The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling. Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n 23 816) to PDE-5is (hazard ratio HR 0.87 95% CI 0.79-0.95 P .001) vs nonexposure (n 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85 95% CI 0.73-0.98 P .029), heart failure (HR 0.83 95% CI 0.72-0.97 P .016), unstable angina (HR 0.78 95% CI 0.64-0.96 P .021), and CV death (HR 0.61 95% CI 0.41-0.90 P .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor-exposed men had a 25% lower incidence of overall mortality (HR 0.75 95% CI 0.65-0.87 P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45 95% CI 0.37-0.54 P < .001) and overall mortality (HR 0.51 95% CI 0.37-0.71 P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79 95% CI 0.64-0.97 P .022). PDE-5is may have cardioprotective effects. Strengths are the large numbers of participants and consistency of the data limitations include the retrospective nature of the study and unknown confounders. In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.

Risk factors variability and cardiovascular risk among patients with diabetes a nationwide observational study.

Cardiovascular risk factors control is fluctuating, tends to change over time, and is potentially impacted by multifactorial interactions. Currently, the existence of risk factors, rather than their variability or interplay with one another, is used to define the population at risk. The association between variability of risk factors and cardiovascular morbidity and mortality risk among patients with T2DM remains debatable. Using registry-derived data, we identified 29,471 people with T2D, without CVD at baseline, and with at least five measurements of risk factors. Variability for each variable was expressed as quartiles of the standard deviation during three years (exposure). The incidence of myocardial infarction, stroke, and all-cause mortality was assessed during 4.80 (2.40-6.70) years following the exposure phase. The association between measures of variability and the risk of developing the outcome was investigated through multivariable Cox proportional-hazards regression analysis with stepwise variable selection. Then, the recursive partitioning and amalgamation (RECPAM) algorithm was used to explore the interaction among the variability of risk factors associated with the outcome. An association between the variability of HbA1c, body weight, systolic blood pressure, and total cholesterol with the outcome considered was found. Among the 6 classes of risk identified by RECPAM, patients with a high variability of both body weight and blood pressure had the highest risk (Class 6, HR 1.81 95% CI 1.61-2.05) compared with patients with low variability of both body weight and total cholesterol (Class 1, reference), despite a progressive reduction in the mean level of risk factors during successive visits. Individuals with high weight variability but low-moderate systolic blood pressure variability (Class 5, HR 1.57 95% CI 1.28-1.68), patients with moderatehigh weight variability associated with highvery high HbA1c variability (Class 4, HR 1.33 95%CI 1.20-1.49), subjects with moderatehigh weight variability and with lowmoderate HbA1c variability (Class 3, HR 1.12 95%CI 1.00-1.25), as well as those with low weight variability associated with highvery high total cholesterol variability (Class 2, HR 1.14 95%CI 1.00-1.30) also showed a significant increase in the risk of event. Combined high variability of two risk factors, particularly body weight and blood pressure, is associated with cardiovascular risk among patients with T2DM. These findings highlight the importance of continuous balancing of multiple risk factors. The variability of multiple risk factors is associated with an increased risk of cardiovascular events and mortality in patients with type 2 diabetes. These variabilities interact one another to identify classes of patients with increased risk of having an event.Patients with a high variability of both body weight and systolic blood pressure had the greatest risk of cardiovascular diseases or mortality despite a progressive reduction in the mean level of risk factorsIndividuals with high weight variability but low systolic blood pressure variability, patients with moderatehigh weight variability associated with high HbA1c variability, subjects with moderatehigh weight variability and with lowmoderate HbA1c variability, as well as those with low weight variability but high total cholesterol variability also showed a significant increase in the risk of event.

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion Results of the BArONIS Study.

To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT (mean age 66.7 years, median NIHSS score 22). On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46 p 0.004, but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94 p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89 p < 0.001), but not with sICH. This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. This article is protected by copyright. All rights reserved.

Association between comorbidities and longitudinal changes in total testosterone among men from the Baltimore Longitudinal Study of Aging.

Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men, without consideration of acquired comorbidities in aging males. We evaluated the longitudinal association between age and testosterone levels as well as the impact of several comorbidities on this relationship using multivariate panel regression analysis. Participants were selected from the Baltimore Longitudinal Study of Aging. Data were obtained on the presence of several comorbidities and total testosterone level during each follow-up visit. A multivariate panel regression analysis was performed to determine the impact of age on testosterone level while controlling for individual comorbidities. The primary outcomes were strength of association between age and various comorbidities, and testosterone level. A total of 625 men were included in this study, with a mean age of 65 years and a mean testosterone level of 463 ngdL. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. This study indicates that a decline in testosterone levels over time may be due to the presence of various comorbidities, which affects the medical management of hypogonadism in aging men. The strengths of this study include the standardized acquisition of testosterone tests and uniform collection of variables, while limitations include the lack of follow-up data from 205 patients and the limited racialethnic diversity in the cohort. In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level. With the overall increase in life expectancy and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities.

Mecp2 deletion results in profound alterations of developmental and adult functional connectivity.

As a regressive neurodevelopmental disorder with a well-established genetic cause, Rett syndrome and its Mecp2 loss-of-function mouse model provide an excellent opportunity to define potentially translatable functional signatures of disease progression, as well as offer insight into the role of Mecp2 in functional circuit development. Thus, we applied widefield optical fluorescence imaging to assess mesoscale calcium functional connectivity (FC) in the Mecp2 cortex both at postnatal day (P)35 in development and during the disease-related decline. We found that FC between numerous cortical regions was disrupted in Mecp2 mutant males both in juvenile development and early adulthood. Female Mecp2 mice displayed an increase in homotopic contralateral FC in the motor cortex at P35 but not in adulthood, where instead more posterior parietal regions were implicated. An increase in the amplitude of connection strength, both with more positive correlations and more negative anticorrelations, was observed across the male cortex in numerous functional regions. Widespread rescue of MeCP2 protein in GABAergic neurons rescued none of these functional deficits, nor, surprisingly, the expected male lifespan. Altogether, the female results identify early signs of disease progression, while the results in males indicate MeCP2 protein is required for typical FC in the brain.

Systematic Review and Meta-Analysis of Ex-Situ and In-Situ Fenestrated Stent-Grafts for Endovascular Repair of Aortic Arch Pathologies.

To gain insight into safety and efficacy of in situ and ex-situ fenestration techniques for total endovascular arch repair. The term ex-situ fenestration is referring to physician-modified stent-graft technique where fenestration is performed on a back table. Electronic search was conducted according to PRISMA (Preferred Reporting Items for Systematic review and Meta-analyses) guidelines from 2000 to 2020. The main outcomes measured were 30-day mortality, stroke, aortic-related mortality, and reintervention rates. Fifteen studies were eligible 7 ex-situ fenestration (189 patients) and 8 in-situ fenestration (149 patients). In ex-situ group, dissection was the main pathology treated and proximal sealing zones were Z0 or 1 in 53.5% of patients. In in-situ group, dissection and aneurysm were equally represented in around 40% of cases and proximal sealing zones were Z0 or 1 in 46.5% of patients. Cumulative 30-day all-cause mortality was similar in both groups 3.8% (95% confidence interval CI 1.7%-8.2%) and 3.8% (95% CI 1.6%-8.9%), respectively, in ex-situ and in-situ groups and stroke rate of 2.8% (95% CI 1.1%-7%) and 5.3% (95% CI 2.6%-10.5%). After a 11.1 ± 2.6 months mean follow-up for ex-situ and 16.7 ± 2.3 months for in-situ group, there were 5.2 and 1.4 reinterventions per 100 patients-years, respectively, for ex-situ and in situ groups. Aortic-related mortality rates of, respectively, 3.2% (95% CI 1.3%-7.4%) and 2.6% (95% CI 0.9%-7.3%) were noted in ex-situ and in situ groups. The reported data show favorable short-term results of both ex-situ and in-situ fenestration techniques with low mortality and strokes rates. However, durability is still questionable given the lack of long-term data. Both options may have their place in arch repair beyond the spectrum of emergent and urgent cases, on condition that results stand the test of time. In situ and ex-situ fenestration techniques have been initially developed to overcome emergency or as a bail out techniques however giving the promessing favorable short term results indications of these techniques may be extended to elective patients ineligible to customized stent-grafts and possibly in the futur to more elective cases as an option for total endovascular arch repair.

Non-homogeneous continuous-time Markov chain with covariates Applications to ambulatory hypertension monitoring.

Hypertension significantly increases the risk for many health conditions including heart disease and stroke. Hypertensive patients often have continuous measurements of their blood pressure to better understand how it fluctuates over the day. The continuous-time Markov chain (CTMC) is commonly used to study repeated measurements with categorical outcomes. However, the standard CTMC may be restrictive, because the rates of transitions between states are assumed to be constant through time, while the transition rates for describing the dynamics of hypertension are likely to be changing over time. In addition, the applications of CTMC rarely account for the effects of other covariates on state transitions. In this article, we considered a non-homogeneous continuous-time Markov chain with two states to analyze changes in hypertension while accounting for multiple covariates. The explicit formulas for the transition probability matrix as well as the corresponding likelihood function were derived. In addition, we proposed a maximum likelihood estimation algorithm for estimating the parameters in the time-dependent rate function. Lastly, the model performance was demonstrated through both a simulation study and application to ambulatory blood pressure data.

Long-term outcomes in heart failure with preserved ejection fraction Predictors of cardiac and non-cardiac mortality.

Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non-CV events, but long-term risk is poorly studied. We assessed incidence and predictors of the long-term CV and non-CV events. Patients presenting with acute HF, EF ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ngL were enrolled in the Karolinska-Rennes study in 2007-11 and were reassessed after 4-8 weeks in a stable state. Long-term follow-up was conducted in 2018. The Fine-Gray sub-distribution hazard regression was used to detect predictors of CV and non-CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4-8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled median age 78 (interquartile range 72-84) years 52% female, 397 patients were available for the long-term follow-up. Over a median follow-up time from acute presentation of 5.4 (2.1-7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non-CV causes. Incidence rates per 1000 patient-years were 62 95% confidence interval (CI) 52-74 for CV and 58 (95% CI 48-69) for non-CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non-CV death. From the stable 4-8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 ms) were independent predictors of CV death, and higher age of non-CV death. In patients with acute decompensated HFpEF, over 5 years of follow-up, nearly of patients died, half from CV and the other half from non-CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non-CV death. Anaemia and higher age were associated with both outcomes.

Prognostic implications of stress hyperglycemia ratio in patients with myocardial infarction with nonobstructive coronary arteries.

The role of stress hyperglycemia in acute myocardial infarction (AMI) has long been emphasized. Recently, the stress hyperglycemia ratio (SHR), a novel index reflecting an acute glycemia rise, has shown a good predictive value in AMI. However, its prognostic power in myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. In a prospective cohort of 1179 patients with MINOCA, relationships between SHR levels and outcomes were analyzed. SHR was defined as acute-to-chronic glycemic ratio using admission blood glucose (ABG) and glycated hemoglobin. The primary endpoint was defined as major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Survival analyses and receiver-operating characteristic (ROC) curve analyses were performed. Over the median follow-up of 3.5 years, the incidence of MACE markedly increased with higher SHR tertile levels (8.1%, 14.0%, 20.5% The SHR independently confers the cardiovascular risk after MINOCA, and may serve as a better predictor than glycemia at admission alone, particularly in those with diabetes.KEY MESSAGESStress hyperglycemia ratio (SHR) is independently associated with the prognosis in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA).SHR is a better predictor of prognosis than admission glycemia alone, especially in diabetic patients with MINOCA.SHR may serve as a prognostic marker for risk stratification as well as a potential target for tailored glucose-lowering treatment in MINOCA.

Left atrial appendage filling defect in exclusive early-phase scanning of dual-phase cardiac computed tomography an indicator for elevated thromboembolic risk.

Dual-phase cardiac computed tomography (CCT) has been applied to detect left atrial appendage (LAA) thrombosis, which is characterized as the presence of left atrial appendage filling defects (LAADF) in both early- and delayed-phase scanning. However, the clinical implication of LAAFD in exclusive early-phase scanning (LAAFD-EEpS) of CCT in patients with atrial fibrillation (AF) is unclear. The baseline clinical data and dual-phase CCT findings in 1183 AF patients (62.1 ± 11.6 years, 59.9% male) was collected and analyzed. A further analysis of CCT and transesophageal echocardiography (TEE) data (within 5 days) in a subgroup of 687 patients was performed. LAAFD-EEpS was defined as LAAFD present in early-phase and absent in delayed-phase scanning of dual-phase CCT. A total of 133 (11.2%) patients were detected with LAAFD-EEpS. Patients with LAAFD-EEpS had a higher prevalence of ischemic stroke or transient ischemic attack (TIA) (p < 0.001) and a higher predefined thromboembolic risk (p < 0.001). In multivariate analysis, a history of ischemic stroke or TIA was independently associated with LAAFD-EEpS (odds ratio OR 11.412, 95% confidence interval CI 6.561-19.851, p < 0.001). When spontaneous echo contrast in TEE was used as the reference standard, the sensitivity, specificity, positive predictive value, and negative predictive value of LAAFD-EEpS was 77.0% (95% CI 66.5-87.6%), 89.0% (95% CI 86.5-91.4%), 40.5% (95% CI 31.6-49.5%), 97.5% (96.3-98.8%), respectively. In AF patients, LAAFD-EEpS is not an uncommon finding in dual-phase CCT scanning, and is associated with elevated thromboembolic risk.

Preclinical Common Data Elements for General Pharmacological Studies (Pharmacokinetic Sample Collection, Tolerability, and Drug Administration). A Report of the TASK3-WG1A General Pharmacology Working Group of the ILAEAES Joint Translational Task Force.

Growing concerns over rigor and reproducibility of preclinical studies, including consistency across laboratories and translation to clinical populations, have triggered efforts to harmonize methodologies. This includes the first set of preclinical common data elements (CDEs) for epilepsy research studies, as well as Case Report Forms (CRFs) for widespread use in epilepsy research. The General Pharmacology Working Group of the ILAEAES Task Force (TASK3-WG1A) has continued in this effort by adapting and refining CDEsCRFs to address specific study design areas as they relate to preclinical drug screening general pharmacology, pharmacokinetics (PK) and pharmacodynamics (PD), and tolerability. This work has expanded general pharmacology studies to include dose records, PKPD, tolerability, and elements of rigor and reproducibility. Tolerability testing CRFs included rotarod and IrwinFunctional Observation Battery assays. The material provided in the form of CRFs can be delivered for widespread use within the epilepsy research community.

The Impact of Complete Revascularization in Symptomatic Severe Left Ventricular Dysfunction between Coronary Artery Bypass Graft and Percutaneous Coronary Intervention.

The study aimed to compare the clinical outcomes between the patients receiving coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the patients with symptomatic severe left ventricular (LV) dysfunction and coronary artery disease (CAD). Between February 2007 and February 2020, a total of 745 patients who received coronary artery angiography for reduced LV ejection fraction (LVEF) < 40% and symptomatic New York Heart Association (NYHA) functional class ≥ 3 were recruited. The patients ( There was no significant difference in the incidence values of in-hospital course and those of in-hospital mortality, acute kidney injury, and postprocedural hemodialysis. There was no significant difference in the 1-yearfollow-up of recurrent MI, revascularization, or stroke between the groups. The 1-year heart failure (HF) hospitalization rate was significantly lower in the CABG group than in all patients of the PCI group (13.2% vs. 33.3% In patients with symptomatic (NYHA class ≥ 3) severe LV dysfunction and CAD, CABG brought less HF admission when compared to patients in the PCI group, but this did not differ when compared to the complete revascularization subgroup. Therefore, an extensive revascularization, achieved by CABG or PCI, is associated with a lower HF hospitalization rate during the 3-yearfollow-up period in such populations.

Pictorial Essay of Cervical Duplex Ultrasonography.

Indian Society of Critical Care Medicine Consensus Statement for Prevention of Venous Thromboembolism in the Critical Care Unit.

Deep vein thrombosis (DVT) is a preventable complication of critical illness, and this guideline aims to convey a pragmatic approach to the problem. Guidelines have multiplied over the last decade, and their utility has become increasingly conflicted as the reader interprets all suggestions or recommendations as something that must be followed. The nuances of grade of recommendation vs level of evidence are often ignored, and the difference between a we suggest vs a we recommend is overlooked. There is a general unease among clinicians that failure to follow the guidelines translates to poor medical practice and legal culpability. We attempt to overcome these limitations by highlighting ambiguity when it occurs and refraining from dogmatic recommendations in the absence of robust evidence. Readers and practitioners may find the lack of specific recommendations unsatisfactory, but we believe that true ambiguity is better than inaccurate certainty. We have attempted to comply with the guidelines on how to create guidelines. Jagiasi BG, Chhallani AA, Dixit SB, Kumar R, Pandit RA, Govil D,

Depression, anxiety, insomnia, stress, and the way of coping emotions as risk factors for ischemic stroke and their influence on stroke severity A case-control study in Lebanon.

Stroke is a leading cause of disability and death worldwide. There are numerous debates regarding the relationship between depression, anxiety, insomnia, perceived stress, and ischemic stroke. Moreover, no research on the efficacy of emotion regulation, which is critical for various components of healthy affective and social adaptability, is being conducted. To the best of our knowledge, this is the first study in the MENA region to shed light on the relationship between these conditions and stroke risk, aiming to determine whether depression, anxiety, insomnia, stress, and the way of coping with emotions may be risk factors for ischemic stroke occurrence and to further investigate the ability of two specific types of emotion regulation (cognitive reappraisal and expressive suppression) as possible moderators of the relationship between these psychological diseases and ischemic stroke risk. As a secondary objective, we sought to determine how these pre-existing conditions affect stroke severity levels. This is a case-control survey study involving 113 Lebanese inpatients with a clinical diagnosis of ischemic stroke admitted in hospitals and rehabilitation centers in Beirut and Mount Lebanon, and 451 gender-matched volunteers without clinical signs of stroke as controls recruited from the same hospitals as the cases or attending outpatient clinics for illnesses or treatments unconnected to stroke or transient ischemic attack, as well as visitors or relatives of inpatients (April 2020-April 2021). Data was collected by filling out an anonymous paper-based questionnaire. According to the outcomes of the regression model, depression (aOR 1.232, 95%CI 1.008-1.506), perceived stress (aOR 1.690, 95%CI 1.413-2.022), a lower educational level (aOR 0.335, 95%CI 0.011-10.579), and being married (aOR 3.862, 95%CI 1.509-9.888) were associated with an increased risk of ischemic stroke. The moderation analysis revealed that expressive suppression had a significant moderating effect on the relationship between depression, anxiety, perceived stress, insomnia, and ischemic stroke risk, resulting in an increased risk of stroke incidence. In contrast, cognitive reappraisal significantly reduced the risk of ischemic stroke by moderating the association between ischemic stroke risk and the following independent variables perceived stress and insomnia. On the other hand, our multinomial regression model revealed that the odds of moderate to severesevere stroke were significantly higher in people with pre-stroke depression (aOR 1.088, 95% CI 0.747-1.586) and perceived stress (aOR 2.564, 95% CI 1.604-4.100) compared to people who had never had a stroke. Despite several limitations, the findings of our study suggest that people who are depressed or stressed are more likely to have an ischemic stroke. Consequently, additional research into the causes and effects of depression and perceived stress may provide new directions for preventive strategies that can help reduce the risk of stroke. Since pre-stroke depression and perceived stress were also found to be strongly correlated with stroke severity, future studies should evaluate the association between pre-stroke depression, perceived stress, and stroke severity to gain a deeper understanding of the complex interaction between these variables. Lastly, the study shed new light on the role of emotion regulation in the relationship between depression, anxiety, perceived stress, insomnia, and ischemic stroke.

Standardized tools for assessing balance and mobility in stroke clinical practice guidelines worldwide A scoping review.

Use of standardized tools to assess balance and mobility limitations is a recommended practice in stroke rehabilitation. The extent to which clinical practice guidelines (CPGs) for stroke rehabilitation recommend specific tools and provide resources to support their implementation is unknown. To identify and describe standardized, performance-based tools for assessing balance andor mobility and describe postural control components challenged, the approach used to select tools, and resources provided for clinical implementation, in CPGs for stroke. A scoping review was conducted. We included CPGs with recommendations on the delivery of stroke rehabilitation to address balance and mobility limitations. We searched seven electronic databases and grey literature. Pairs of reviewers reviewed abstracts and full texts in duplicate. We abstracted data about CPGs, standardized assessment tools, the approach for tool selection, and resources. Experts identified postural control components challenged by each tool. Of the 19 CPGs included in the review, 7 (37%) and 12 (63%) were from middle- and high-income countries, respectively. Ten CPGs (53%) recommended or suggested 27 unique tools. Across 10 CPGs, the most commonly cited tools were the Berg Balance Scale (BBS) (90%), 6-Minute Walk Test (6MWT) (80%), Timed Up and Go Test (80%) and 10-Meter Walk Test (70%). The tool most frequently cited in middle- and high-income countries was the BBS (33 CPGs), and 6MWT (77 CPGs), respectively. Across 27 tools, the three components of postural control most frequently challenged were underlying motor systems (100%), anticipatory postural control (96%), and dynamic stability (85%). Five CPGs provided information in varying detail on how tools were selected only 1 CPG provided a level of recommendation. Seven CPGs provided resources to support clinical implementation one CPG from a middle-income country included a resource available in a CPG from a high-income country. CPGs for stroke rehabilitation do not consistently provide recommendations for standardized tools to assess balance and mobility or resources to facilitate clinical application. Reporting of processes for tool selection and recommendation is inadequate. Review findings can be used to inform global efforts to develop and translate recommendations and resources for using standardized tools to assess balance and mobility post-stroke. httpsosf.io, identifier 10.17605OSF.IO6RBDV.

Glucagon-Like Peptide 1 Receptor Agonists Versus Sodium-Glucose Cotransporter 2 Inhibitors for Atherosclerotic Cardiovascular Disease in Patients With Type 2 Diabetes.

Beyond improving hemoglobin A1c (HbA1c) in adults with type 2 diabetes, glucagon-like peptide 1 receptor agonists (GLP-1RA) have been approved for reducing risk of major adverse cardiovascular events (MACE) with established cardiovascular disease (CVD) or multiple CV risk factors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also reduced the risk for the primary composite CV outcome in patients with type 2 diabetes at high risk for CV events. In the American Diabetes Association (ADA) and European Association of Study in Diabetes (EASD) consensus report 2022, there is the description In people with established atherosclerotic CVD (ASCVD) or with a high risk for ASCVD, GLP-1RA were prioritized over SGLT2i however, the evidence supporting such statement is limited. Therefore, we studied the superiority of GLP-1RA over SGLT2i for prevention of ASCVD from various viewpoints. We could not find a meaningful difference in the risk reduction in three-point MACE (3P-MACE), mortality due to any cause, mortality due to CV cause and nonfatal myocardial infarction between GLP-1RA and SGLT2i trials. The risk of nonfatal stroke decreased in all five GLP-1RA trials however, two of three SGLT2i trials showed an increase in risk of nonfatal stroke. The risk of hospitalization for heart failure (HHF) decreased in all three SGLT2i trials, and one GLP-1RA trial showed an increase in risk of HHF. The risk reduction of HHF in SGLT2i trials was greater than that in GLP-1RA trials. These findings were consistent with current systematic reviews and meta-analyses. The risk reduction of 3P-MACE was significantly and negatively correlated with changes in HbA1c (R -0.861, P 0.006) and body weight (R -0.895, P 0.003) in GLP-1RA and SGLT2i trials. The studies using SGLT2i failed to reduce carotid intima media thickness (cIMT), the surrogate marker for atherosclerosis however, several studies using GLP-1RA successfully reduced cIMT in patients with type 2 diabetes. Compared with SGLT2i, GLP-1RA had a higher probability of decreasing serum triglyceride. GLP-1RA have multiple vascular biological anti-atherogenic properties.

The Complexity of Peripheral Arterial Disease and Coronary Artery Disease in Diabetic Patients An Observational Study.

Atherosclerosis is a systemic disease that causes luminal narrowing. Patients with peripheral arterial disease (PAD) also exhibit an increased risk of death from cardiovascular complications. This risk is the same for symptomatic or asymptomatic patients. Over a 5-year period, patients with PAD have a 20% chance of suffering from a stroke or myocardial infarction. Additionally, their mortality rate is 30%. This study aimed to assess the relationship between coronary artery disease (CAD) complexity using SYNTAX score and PAD complexity using Trans-Atlantic Inter-Society Consensus II (TASC II) score. The study was designed as single-center cross-sectional observational and included 50 diabetic patients referred for elective coronary angiography and peripheral angiography was done. Most of the patients were males (80%) and smokers (80%) with mean age of 62 years. The mean SYNTAX score was 19.88. There was a significant negative correlation between SYNTAX score and ankle brachial index (ABI) (r -0.48, P 0.001) and a significant positive correlation with glycated hemoglobin (HbA1c) level (R Diabetic patients with more complex CAD had more complex PAD. In diabetic patients with CAD, those with worse glycemic control had higher SYNTAX scores and the higher the SYNTAX score, the lower the ABI.

Stroke and the risk of gastrointestinal disorders A Mendelian randomization study.

The issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). We applied two-sample Mendelian randomization to investigate relationships with gastrointestinal disorders. We obtained genome-wide association study (GWAS) summary data of any stroke, ischemic stroke, and its subtypes from the MEGASTROKE consortium. From the International Stroke Genetics Consortium (ISGC) meta-analysis, we acquired GWAS summary information on intracerebral hemorrhage (ICH), including all ICH, deep ICH, and lobar ICH. Several sensitivity studies were performed to identify heterogeneity and pleiotropy, while inverse-variance weighted (IVW) was utilized as the most dominant estimate. No evidence for an effect of genetic predisposition to ischemic stroke and its subtypes on gastrointestinal disorders were found in IVW. The complications of deep ICH are a higher risk for PUD and GERD. Meanwhile, lobar ICH has a higher risk of complications for PUD. This study provides proof of the presence of a brain-gut axis. Among the complications of ICH, PUD and GERD were more common and associated with the site of hemorrhage.

Peripheral eosinophil trends and clinical outcomes after non-traumatic subarachnoid hemorrhage.

Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH. This retrospective observational study included patients with SAH admitted from January 2009 to July 2016. Variables included demographics, modified Fisher scale (mFS), Hunt-Hess Scale (HHS), global cerebral edema (GCE), and the presence of any infection. Peripheral eosinophil counts were examined as part of routine clinical care on admission and daily for 10 days after aneurysmal rupture. Outcome measures included dichotomized discharge mortality, modified Ranked Scale (mRS) score, delayed cerebral ischemia (DCI), vasospasm, and need for ventriculoperitoneal shunt (VPS). Statistical tests included the chi-square test, Students A total of 451 patients were included. The median age was 54 (IQR 45, 63) years, and 295 (65.4%) were female patients. On admission, 95 patients (21.1%) had a high HHS (>4), and 54 (12.0%) had GCE. A total of 110 (24.4%) patients had angiographic vasospasm, 88 (19.5%) developed DCI, 126 (27.9%) had an infection during hospitalization, and 56 (12.4%) required VPS. Eosinophil counts increased and peaked on days 8-10. Higher eosinophil counts on days 3-5 and day 8 were seen in patients with GCE ( This study demonstrated that a delayed increase in eosinophils after SAH occurs and may contribute to functional outcomes. The mechanism of this effect and the relationship with SAH pathophysiology merit further investigation.

A deep learning approach to predict collateral flow in stroke patients using radiomic features from perfusion images.

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for bias and inconsistency in the final grade assigned to a patient depending on the experience level of the clinician. We present a multi-stage deep learning approach to predict collateral flow grading in stroke patients based on radiomic features extracted from MR perfusion data. First, we formulate a region of interest detection task as a reinforcement learning problem and train a deep learning network to automatically detect the occluded region within the 3D MR perfusion volumes. Second, we extract radiomic features from the obtained region of interest through local image descriptors and denoising auto-encoders. Finally, we apply a convolutional neural network and other machine learning classifiers to the extracted radiomic features to automatically predict the collateral flow grading of the given patient volume as one of three severity classes - no flow (0), moderate flow (1), and good flow (2). Results from our experiments show an overall accuracy of 72% in the three-class prediction task. With an inter-observer agreement of 16% and a maximum intra-observer agreement of 74% in a similar experiment, our automated deep learning approach demonstrates a performance comparable to expert grading, is faster than visual inspection, and eliminates the problem of grading bias.

Machine learning-based prediction of clinical outcomes after first-ever ischemic stroke.

Accurate prediction of clinical outcomes in individual patients following acute stroke is vital for healthcare providers to optimize treatment strategies and plan further patient care. Here, we use advanced machine learning (ML) techniques to systematically compare the prediction of functional recovery, cognitive function, depression, and mortality of first-ever ischemic stroke patients and to identify the leading prognostic factors. We predicted clinical outcomes for 307 patients (151 females, 156 males 68 ± 14 years) from the PROSpective Cohort with Incident Stroke Berlin study using 43 baseline features. Outcomes included modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Examination (MMSE), Modified Telephone Interview for Cognitive Status (TICS-M), Center for Epidemiologic Studies Depression Scale (CES-D) and survival. The ML models included a Support Vector Machine with a linear kernel and a radial basis function kernel as well as a Gradient Boosting Classifier based on repeated 5-fold nested cross-validation. The leading prognostic features were identified using Shapley additive explanations. The ML models achieved significant prediction performance for mRS at patient discharge and after 1 year, BI and MMSE at patient discharge, TICS-M after 1 and 3 years and CES-D after 1 year. Additionally, we showed that National Institutes of Health Stroke Scale (NIHSS) was the top predictor for most functional recovery outcomes as well as education for cognitive function and depression. Our machine learning analysis successfully demonstrated the ability to predict clinical outcomes after first-ever ischemic stroke and identified the leading prognostic factors that contribute to this prediction.

Low-dose vs. standard-dose alteplase for Chinese patients with acute ischemic stroke A propensity score analysis.

Previous studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry. We analyzed data from the Shanghai Stroke Service System. Patients receiving alteplase intravenous thrombolysis within 4.5 hours were included. These patients were divided into the low-dose alteplase group (0.55-0.65 mgkg) and the standard-dose alteplase group (0.85-0.95 mgkg). Baseline imbalances were adjusted by using the propensity score matching. The primary outcome was mortality or disability, which was defined as the modified Rankin scale (mRS) score ranging from 2 to 6 at discharge. The secondary outcomes were in-hospital mortality, symptomatic intracranial hemorrhage (sICH) and functional independence (mRS score 0-2). From January 2019 to December 2020, a total of 1,334 patients were enrolled and 368 (27.6%) were treated with low-dose alteplase. The median age of the patients was 71 years, and 38.8% were female. Our study showed that the low-dose group had significantly higher rates of death or disability (adjusted odds ratio (aOR) 1.49, 95% confidence interval (CI) 1.12, 1.98) and less functional independence (aOR 0.71, 95%CI 0.52, 0.97) than the standard-dose group. There was no significant difference in sICH or in-hospital mortality between the standard-dose and low-dose alteplase groups. Low-dose alteplase was related to a poor functional outcome without lowering the risk of sICH, compared with standard-dose alteplase for AIS patients in China.

Bilateral vertebral artery dissection extending to the left posterior cerebral artery A case report.

Intracranial artery dissection accounts for a small percentage (1%-2%) of all ischemic strokes. Vertebral artery dissection sometimes extends to the basilar artery but very rarely to the posterior cerebral artery. We report a case of bilateral vertebral artery dissection extending to the left posterior cerebral artery with the characteristic distribution of intramural hematoma. A 51-year-old woman presented with right hemiparesis and dysarthria 3 days after sudden neck pain. Magnetic resonance imaging on admission revealed infarcts in the left thalamus and temporo-occipital lobe and findings suggestive of bilateral vertebral artery dissection. No infarct was detected in the brainstem. The patient was treated conservatively. Initially, we suspected that infarction in the left posterior cerebral artery territory had been caused by artery-to-artery embolism from the dissected vertebral arteries. However, T1-weighted imaging on day 15 of admission revealed intramural hematoma extending from the left vertebral artery to the left posterior cerebral artery. Therefore, we diagnosed bilateral vertebral artery dissection extending to the basilar artery and the left posterior cerebral artery. The patients symptoms subsequently improved with conservative treatment, and she was discharged with a modified Rankin Scale score of 1 on day 62 of admission. In this case, intramural hematoma of the basilar artery was found in the anterior vessel wall. Brainstem infarction is less likely when intramural hematoma is located in the anterior vessel wall of the basilar artery in vertebrobasilar artery dissection. T1-weighted imaging is useful for the diagnosis of this rare condition and can predict potentially impaired branches and possible symptoms.

Pregnancy loss and risk of incident CVD within 5 years Findings from the Womens Health Initiative.

Previous studies have demonstrated an increased risk of cardiovascular disease (CVD) in women with a history of pregnancy loss. Less is known about whether pregnancy loss is associated with age at the onset of CVD, but this is a question of interest, as a demonstrated association of pregnancy loss with early-onset CVD may provide clues to the biological basis of the association, as well as having implications for clinical care. We conducted an age-stratified analysis of pregnancy loss history and incident CVD in a large cohort of postmenopausal women aged 50-79 years old. Associations between a history of pregnancy loss and incident CVD were examined among participants in the Womens Health Initiative Observational Study. Exposures were any history of pregnancy loss (miscarriage andor stillbirth), recurrent (2) loss, and a history of stillbirth. Logistic regression analyses were used to examine associations between pregnancy loss and incident CVD within 5 years of study entry in three age strata (50-59, 69-69, and 70-79). Outcomes of interest were total CVD, coronary heart disease (CHD), congestive heart failure, and stroke. To assess the risk of early onset CVD, Cox proportional hazard regression was used to examine incident CVD before the age of 60 in a subset of subjects aged 50-59 at study entry. After adjustment for cardiovascular risk factors, a history of stillbirth was associated with an elevated risk of all cardiovascular outcomes in the study cohort within 5 years of study entry. Interactions between age and pregnancy loss exposures were not significant for any cardiovascular outcome however, age-stratified analyses demonstrated an association between a history of stillbirth and risk of incident CVD within 5 years in all age groups, with the highest point estimate seen in women aged 50-59 (OR 1.99 95% CI, 1.16-3.43). Additionally, stillbirth was associated with incident CHD among women aged 50-59 (OR 3.12 95% CI, 1.33-7.29) and 60-69 (OR 2.06 95% CI, 1.24-3.43) and with incident heart failure and stroke among women aged 70-79. Among women aged 50-59 with a history of stillbirth, a non-significantly elevated hazard ratio was observed for heart failure before the age of 60 (HR 2.93, 95% CI, 0.96-6.64). History of stillbirth was strongly associated with a risk of cardiovascular outcomes within 5 years of baseline in a cohort of postmenopausal women aged 50-79. History of pregnancy loss, and of stillbirth in particular, might be a clinically useful marker of cardiovascular disease risk in women.

Risk Factors and Functional Outcomes with Early Neurological Deterioration after Mechanical Thrombectomy for Acute Large Vessel Occlusion Stroke.

Early neurological deterioration (END) is associated with a poor survival after mechanical thrombectomy (MT) in acute ischemic stroke (AIS). To assess risk factors and functional outcomes of END after MT in patients, we analyzed data from 79 patients who received MT with large-vessel occlusion. END after MT in patients is defined as an increase of two points or more in the National Institute of Health Stroke Scale (NIHSS) score, compared with the best neurological status within 7 days. The mechanism of END can be classified into AIS progression, sICH, and encephaledema. A total of 32 AIS patients (40.5%) had END after MT. Risk factors for END after MT included history of oral antiplatelet andor anticoagulation drugs before MT (OR 9.56,95% CI 1.02-89.57), higher NIHSS score when admitted to hospital (OR 1.24, 95% CI 1.04-1.48), under the subtype of atherosclerotic stroke (OR 17.36, 95% CI 1.51-199.56), ASITNSIR< 2 (OR 15.78, 95% CI 1.65-151.26), and prolonged period from AIS onset to the first revascularization (OR 1.01, 95% CI 1.00-1.02). AIS patients who had END at early stages were more likely to experience poor outcomes (Modified Rankin Scale mRS >2) at 90 days after MT (OR 6.829, 95% CI 1.573-29.655). Thus, AIS patients who had experienced END at early stages were more likely to have poor outcomes (mRS >2) at 90 days after MT, and the risk factors of END were connected to the mechanism of END.

A Comparison of Outcomes Using Combined Intra- and Extradural versus Extradural-Only Repair of Tegmen Defects.

Creative Art Therapy for Improving Depression, Anxiety, and Stress in Patients with Stroke A Quasi-Interventional Study.

Creative art therapy is a psychotherapeutic approach used to enhance the mental health status of patients. This study aimed to evaluate the effect of creative art therapy on the levels of depression, anxiety, and stress in Jordanian patients following stroke. One-group pretest-posttest design was used it included four sessions of creative art therapy which were conducted as two sessions for two weeks. This study recruited 85 participants who were within three months poststroke diagnosis. The Depression, Anxiety, and Stress Scale was used to assess the levels of psychological reactions pre and post creative art therapy intervention. The data showed that there was a statistically significant improvement in the levels of depression ( The findings of this study suggest that creative art therapy is a valuable method to complement other types of treatments among patients with stroke, resulting in positive patient mental health outcomes. Creative art therapy could be used as a psychotherapeutic approach to manage mental health complexities among patients with stroke. Health policymakers are invited to use the findings of this study to establish tailored counselor services using this new psychotherapeutic approach.

Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy.

Classical homocystinuria is a hereditary defect of the enzyme cystathionine beta synthase, which is produced in the liver. If this enzyme fails, the synthesis pathway of cysteine from methionine is interrupted, leading to the accumulation of homocysteine in the blood plasma and homocysteine in the urine. After birth, the children are unremarkable except for the characteristic laboratory findings. Symptoms rarely appear before the second year of life. The most common symptom is a prolapse of the crystalline lens. This finding is seen in 70% of untreated 10-year-old affected individuals. As the earliest symptom, psychomotor retardation occurs in the majority of patients already during the first two years of life. Limiting factors in terms of life expectancy are thromboembolism, peripheral arterial disease, myocardial infarction, and stroke. These symptoms are due to the damage to the vessels caused by the elevated amino acid levels. About 30% suffer a thromboembolic event by the age of 20, about half by the age of 30. This review focus on present and new therapeutical approaches like the role of enzyme replacement with presentation of different novel targets in research like pegtibatinase, pegtarviliase, CDX-6512, erymethionase, chaperones, proteasome inhibitors and probiotic treatment with SYNB 1353. Furthermore, we analyze the role of liver-directed therapy with three dimensional (3D) bioprinting, liver bioengineering of liver organoids

Mean Platelet Volume to Platelet Count Ratio Predicts Left Atrial Stasis in Patients with Non-Valvular Atrial Fibrillation.

The mean platelet volume to platelet count ratio (MPVPC) has been investigated in the diagnosis, prognosis and risk stratification in several diseases. However, the predictive role of MPVPC in left atrial stasis (LAS) of non-valvular atrial fibrillation (NVAF) patients remains unknown. A total of 217 consecutive NVAF patients undergoing transesophageal echocardiogram (TEE) evaluation were retrospectively enrolled. The demographic, clinical, admission laboratory and TEE data were extracted and analyzed. Patients were categorized into those with or without LAS. The associations between the MPVPC ratio and LAS were assessed by multivariate logistic regression analysis. There were 24.9% (n 54) patients with LAS according to TEE. Compared with patients without LAS, the MPVPC ratio was significantly higher in those with LAS (5.6±1.6 vs 4.8±1.0, P < 0.001). After multivariable adjustment, higher MPVPC ratio levels (OR 1.747, 95% CI 1.193-2.559, P 0.004) were positively associated with LAS, with the optimal cut-point for LAS prediction of 5.36 (area under the curve, AUC 0.683, sensitivity 48%, specificity 73%, 95% CI 0.589-0.777, P < 0.001). The stratification analysis showed that a significant positive correlation between MPVPC ratio ≥5.36 and LAS in patients of male, younger (<65 years), paroxysmal AF, without history of strokeTIA, CHA Increasing MPVPC ratio was associated with an increased risk of LAS, which was mainly reflected in the subgroups of male, younger (<65 years), paroxysmal AF, without history of strokeTIA, CHA

Dementia prevention in memory clinics recommendations from the European task force for brain health services.

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.

Is the excellent air quality a protective factor of health problems for Taitung County in eastern Taiwan Perspectives from visual analytics.

Taitung, an agricultural country in Eastern Taiwan, was famous for its fresh air with less industrial and petrochemical pollution. Air pollution may induce cardiovascular disease, chronic obstructive pulmonary disease (COPD), asthma, and stroke, poor air quality also resulted in a higher depression rate and less feeling of happiness therefore, our study aims to use visualization tools to demonstrate the association between air quality index (AQI) and the among negative factors and try to find that whether Taitung got the benefit of good air quality on health issues. We retrieved data from the government of Taiwan and other open sources in the year 2019, then visual maps and generalized association plots with clusters demonstrated the relationship between each factor and each countycity. Taitung had the lowest AQI and asthma attack rate, but AQI had a negative relationship to air pollution-caused death (R -0.379), happiness index (R -0.358), and income (R -0.251). The GAP analysis revealed that smoke and overweight were the nearest to air pollution causing death, also counties and cities were divided into two major clusters initially based on the air pollution-related variables. In conclusion, the World Health Organization (WHO) definition and the weight of each air pollution cause death may not be suitable for Taiwan due to too many confounding factors.

Experience and lessons learned from blunt cerebrovascular injuries A case report.

Blunt cerebrovascular injuries are rare and serious complications of trauma that can lead to cerebral vascular dissection or aneurysm. Improving awareness of blunt cerebrovascular injuries and using computed tomography angiography to pre-screen patients at high risk is recommended by current guidelines to prevent the occurrence of ischemic stroke complications. A 32-year-old male patient was admitted to the hospital following neck trauma accompanied by stroke symptoms. Imaging revealed intimal injury of the right common carotid artery and acute cerebral infarction. After an endarterectomy and repair, the vascular lumen obstruction resolved, blood flow was restored, and the patients condition stabilized. Blunt cerebrovascular injury has been seriously neglected in clinical practice. Delayed or under-diagnosis of blunt cerebrovascular injury can result large strokes. Standardized treatment protocols, which include the screening and grading of blunt cerebrovascular injury, may reduce the risk of permanent neurological dysfunction, and even death, in patients.

Unexpected paradoxical embolization following catheter-directed thrombectomy with the FlowTriever™ system in a patient with pulmonary embolism a case report.

The optimal therapy for patients suffering from acute pulmonary embolism (PE) classified as intermediate-high risk still needs to be identified. Catheter-directed thrombectomy (CDTE) is a safe procedure to reduce thrombus burden immediately. The lack of randomized trials is one reason catheter-directed thrombolysis (CDT) has not yet received a clear recommendation in our guidelines. Herein, we report an unexpected event in the course of a patient with PE treated with CDTE using the FlowTriever™ system, the only FDA-approved catheter system for percutaneous mechanical thrombectomy regarding this indication. A 57-year-old male presented with dyspnoea at the emergency department of our university hospital. The computed tomography (CT) scan showed bilateral PE, and ultrasound of the left lower limb revealed deep venous thrombosis. According to the current ESC guidelines, he was classified intermediate-high risk. We performed bilateral CDTE. On the first and third day post-intervention, our patient presented neurological deficits. Whereas the first CT scan of the cerebrum remained normal, the CT scan at Day 3 showed demarcated embolic stroke. Further imaging diagnostic gave evidence to an ischemic lesion in the left kidney. Transesophageal echocardiography revealed a patent foramen ovale (PFO) as the origin of paradoxical embolism and thus mechanism of both ischemic lesions. Compliant to the current recommendations, percutaneous PFO closure was performed. Our patient recovered properly without any sequelae. Whether the deep venous thrombosis is the source of embolization or the catheter-directed retrieval of clots may have transported clot material to the right atrium which further on embolized systemically will remain unclear. Yet, we have to consider it as a potential complication in catheter-directed treatment of PE in patients with a PFO.

From Molecule to Patient Rehabilitation The Impact of Transcranial Direct Current Stimulation and Magnetic Stimulation on Stroke-A Narrative Review.

Stroke is a major health problem worldwide, with numerous health, social, and economic implications for survivors and their families. One simple answer to this problem would be to ensure the best rehabilitation with full social reintegration. As such, a plethora of rehabilitation programs was developed and used by healthcare professionals. Among them, modern techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are being used and seem to bring improvements to poststroke rehabilitation. This success is attributed to their capacity to enhance cellular neuromodulation. This modulation includes the reduction of the inflammatory response, autophagy suppression, antiapoptotic effects, angiogenesis enhancement, alterations in the blood-brain barrier permeability, attenuation of oxidative stress, influence on neurotransmitter metabolism, neurogenesis, and enhanced structural neuroplasticity. The favorable effects have been demonstrated at the cellular level in animal models and are supported by clinical studies. Thus, these methods proved to reduce infarct volumes and to improve motor performance, deglutition, functional independence, and high-order cerebral functions (i.e., aphasia and heminegligence). However, as with every therapeutic method, these techniques can also have limitations. Their regimen of administration, the phase of the stroke at which they are applied, and the patients characteristics (i.e., genotype and corticospinal integrity) seem to influence the outcome. Thus, no response or even worsening effects were obtained under certain circumstances both in animal stroke model studies and in clinical trials. Overall, weighing up risks and benefits, the new transcranial electrical and magnetic stimulation techniques can represent effective tools with which to improve the patients recovery after stroke, with minimal to no adverse effects. Here, we discuss their effects and the molecular and cellular events underlying their effects as well as their clinical implications.

Controversies and challenges of coil embolization for intracranial aneurysm in a continuous-flow LVAD implanted patient A case report.

Continuous-flow left ventricular assist device (CF-LVAD) technology has rapidly developed to support the failing heart refractory to standard medical treatments. Although the expected prognosis has improved dramatically, ischemic and hemorrhagic strokes are possible complications and the leading causes of death in the CF-LVAD population. We encountered a case of an unruptured large internal carotid aneurysm in a patient with a CF-LVAD. Following a detailed discussion of his expected prognosis, the risk of aneurysm rupture, and the inherited risk of aneurysm treatment, coil embolization was performed without adverse events. The patient remained recurrence-free for 2-year postoperatively. This report illustrates the feasibility of coil embolization in a CF-LVAD recipient and emphasizes the necessity of vigilant consideration of whether to intervene in an intracranial aneurysm after CF-LVAD implantation. We confronted several challenges during the treatment optimal endovascular technique, management of antithrombotic drugs, safe arterial access, desirable perioperative imaging modalities, and prevention of ischemic complications. This study aimed to share this experience.

Traumatic dissection of the anterior cerebral artery secondary to a rugby related impact A case report with emphasis on the usefulness of T1-VISTA.

Cerebrovascular injuries (CVIs) are not usually considered in the differential diagnosis of sport-related head injuries (SRHIs). We encountered a rugby player with traumatic dissection of the anterior cerebral artery (ACA) after impact on the forehead. Head magnetic resonance imaging (MRI) with T1-volume isotropic turbo spin-echo acquisition (VISTA) was used to diagnose the patient. The patient was a 21-year-old man. During a rugby tackle, his forehead collided with the forehead of an opponent. He did not have a headache or disturbance of consciousness immediately after the SRHI. On the 2 Accurate detection of morphological changes in cerebral arteries is important for the diagnosis of intracranial vascular injuries. When paralysis or sensory deficits occur after SRHIs, it is difficult to differentiate between concussion from CVI. Athletes with red-flag symptoms after SRHIs should not merely be suspected to have concussion they should be considered for imaging studies.

Herpes simplex virus encephalitis mimicking acute ischemic stroke.

Infections of the central nervous system might present in an acute form such as to be similar with the clinical characteristics of a stroke. This situation will hamper a correct diagnosis and a prompt treatment that can otherwise be successful. We present the case of a herpes virus encephalitis that came up in the emergency department with an admission diagnosis of ischemic cerebral accident. Being the symptomatology unclear, the findings of magnetic resonance of the brain oriented versus an infectious disorder. The lumbar tap confirmed the presence of herpes simplex virus (HSV) 1 virus and an antiviral therapy was administered, leading to resolution of the condition within the 3 weeks of hospitalization. HSV infections may mimic stroke and therefore should be included in the differential diagnosis of atypical acute nervous conditions. In neurological events of acute nature, especially in febrile patients whose brain imaging is suspicious or inconclusive, the eventuality of a herpetic encephalitis should be kept in mind. This will lead to a prompt antiviral therapy and to a favorable outcome.

Thirty-day and one-year outcomes of the Navitor transcatheter heart valve in patients with aortic stenosis the prospective, multicentre, global PORTICO NG Study.

The Navitor transcatheter heart valve (THV) is a self-expanding valve, with an intra-annular leaflet position and an outer cuff intended to reduce paravalvular leak (PVL). The aim of the PORTICO NG Study is to assess the safety and performance of the Navitor THV in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. PORTICO NG is a prospective, multicentre, global, single-arm, investigational study with follow-up at 30 days, 1 year, and annually up to 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. A total of 120 high- or extreme-risk subjects (age 83.5±5.4 years 58.3% female Society of Thoracic Surgeons score 4.0±2.0%) were enrolled in the European conformity (CE) mark cohort. Procedural success was high at 97.5%. At 30 days, the rate of all-cause mortality was 0%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 0.8%, life-threatening bleeding was 2.5%, stage 3 acute kidney injury 0%, major vascular complications 0.8%, and new pacemaker implantation 15.0%. At 1 year, the rates of all-cause mortality and disabling stroke were 4.2% and 0.8%, respectively. The rate of moderate PVL was 1.0% at 1 year. Haemodynamic performance with a mean gradient of 7.5±3.2 mmHg and effective orifice area of 1.9±0.4 cm The PORTICO NG Study demonstrates low rates of adverse events and PVL up to 1 year in patients at high or extreme surgical risk, confirming the safety and efficacy of the Navitor THV system.

Outflow cannula alignment in continuous flow left ventricular devices is associated with stroke.

We sought to evaluate whether differences in left ventricular assist device (LVAD) canula alignment are associated with stroke. There is a paucity of clinical data on contribution of LVAD canulae alignment to strokes. We conducted a retrospective analysis of patients who underwent LVAD implantation at Houston Methodist hospital from 2011 to 2016 and included those who had undergone cardiac computed tomography (CT) with contrast. LVAD graft alignment using X-ray, echocardiography, and cardiac CT was evaluated. The primary outcome was stroke within 1 year of LVAD implantation. Of the 101 patients that underwent LVAD Implantation and cardiac CT scan during the study period, 78 met inclusion criteria. The primary outcome occurred in 12 (15.4%) patients with a median time to stroke of 77 days (interquartile range 42-132 days). Of these, 10 patients had an ischemic and two had hemorrhagic strokes. The predominant device type was Heart Mate II (94.8%). Patients with LVAD outflow cannula to aortic angle lesser than 37.5° and those with outflow graft diameter of anastomosis less than 1.5 cm (assessed by cardiac CT) had significantly higher stroke risk (

Coexistence of large meningioma and arteriovenous malformationA case report and literature review.

The simultaneous presence of a giant intracranial meningioma and an arteriovenous malformation(AVM)in the same cerebral hemisphere is extremely rare. The treatment should be individualized depending on the case. A 49-year-old man presented with hemiparesis. Preoperative neuroimaging revealed a giant lesion and an AVM on the left hemisphere of the brain. Craniotomy and tumour resection were performed. The AVM was not treated and needed to be followed up. The histological diagnosis was meningioma (World Health Organization grade I). The patient was in good neurological condition postoperatively. This case adds to the growing literature suggesting that the association between the two lesions is complex. Besides, treatment depends on the risk of neurologic function damage and hemorrhagic stroke of meningiomas and AVMs.

Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimers disease within a cognitive reserve framework.

We constructed a polygenic risk score (PRS) for β-amyloid (PRSAβ42) to proxy AD pathology and investigated its association with incident Alzheimers disease (AD)amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSAβ42 and ADaMCI risk. A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAβ42 and CR with ADaMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAβ42 and CR and the CR effect across participants with different PRSAβ42 levels. Higher PRSAβ42 and CR were associated with a 33.9% higher risk and 8.3% less risk for ADaMCI, respectively. An additive interaction between PRSAβ42 and CR was observed. High CR was associated with 62.6% less risk of ADaMCI incidence only in the high-PRSAβ42 group. A super-additive effect of PRSAβ42 and CR on ADaMCI risk was observed. CR influence was evident in participants with high PRSAβ42.

Development and feasibility testing of action observation training videos in acute stroke survivors Preliminary findings.

A 14-year-old boy with multiple trauma and bilateral basal ganglia hemorrhage due to coronavirus disease 2019 a case report.

In December 2019, coronavirus disease 2019 spread worldwide, causing acute respiratory distress syndrome. Coronavirus disease 2019 presents from an asymptomatic infection to severe disease causing multiorgan failure. Neurological manifestations were observed in some patients, including intracerebral hemorrhage. Bilateral basal ganglia hemorrhage is rare due to trauma. Our patient was a 14-year-old Iranian boy with multiple trauma and loss of consciousness who tested positive for coronavirus disease 2019. The brain computed tomography scan reported bilateral basal ganglia hemorrhage. Bilateral ground glass opacity was reported through a chest computed tomography scan. In this study, we reported a 14-year-old boy referred to the emergency room due to multiple trauma. Through the medical interventions, bilateral basal ganglia hemorrhage was discovered incidentally. Coronavirus disease 2019 was detected in this patient on the basis of findings in chest computed tomography scan and positive real reverse transcription polymerase chain reaction test. Several clinical reports and series exploring the relationship between coronavirus disease 2019 and ischemic strokes have been published. Coronavirus disease 2019, like other acute respiratory syndromes, can invade the central nervous system through hematogenous and neuronal dissemination or it can be an immune response to the cytokine storm. In conclusion, it is vital to know the pathophysiology of the neurological manifestations of coronavirus disease 2019 and prevent the mild neurological manifestations leading to severe conditions.

GAS6-AS1, a long noncoding RNA, functions as a key candidate gene in atrial fibrillation related stroke determined by ceRNA network analysis and WGCNA.

Stroke attributable to atrial fibrillation (AF related stroke, AFST) accounts for 13 26% of ischemic stroke. It has been found that AFST patients have a higher risk of disability and mortality than those without AF. Additionally, its still a great challenge to treat AFST patients because its exact mechanism at the molecular level remains unclear. Thus, its vital to investigate the mechanism of AFST and search for molecular targets of treatment. Long non-coding RNAs (lncRNAs) are related to the pathogenesis of various diseases. However, the role of lncRNAs in AFST remains unclear. In this study, AFST-related lncRNAs are explored using competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA). GSE66724 and GSE58294 datasets were downloaded from GEO database. After data preprocessing and probe reannotation, differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) between AFST and AF samples were explored. Then, functional enrichment analysis and protein-protein interaction (PPI) network analysis of the DEMs were performed. At the meantime, ceRNA network analysis and WGCNA were performed to identify hub lncRNAs. The hub lncRNAs identified both by ceRNA network analysis and WGCNA were further validated by Comparative Toxicogenomics Database (CTD). In all, 19 DELs and 317 DEMs were identified between the AFST and AF samples. Functional enrichment analysis suggested that the DEMs associated with AFST were mainly enriched in the activation of the immune response. Two lncRNAs which overlapped between the three lncRNAs identified by the ceRNA network analysis and the 28 lncRNAs identified by the WGCNA were screened as hub lncRNAs for further validation. Finally, lncRNA GAS6-AS1 turned out to be associated with AFST by CTD validation. These findings suggested that low expression of GAS6-AS1 might exert an essential role in AFST through downregulating its downstream target mRNAs GOLGA8A and BACH2, and GAS6-AS1 might be a potential target for AFST therapy.

Spectrum of Complications and Complication Rates After Diagnostic Catheter Angiography in Neuroradiology.

To retrospectively evaluate the total complication rates and type of complications after diagnostic cerebral and spinal catheter angiography. Data from 2340 patients undergoing diagnostic angiography over a period of 10 years in a neuroradiologic center were retrospectively evaluated. Local, systemic, neurological, and technical complications were analyzed. A total of 75 clinically noted complications occurred. The risk for clinical complications was increased when the angiography was performed under emergency conditions (p 0.009). The most common complication was groin hematoma (1.32%). Neurological complications occurred in 0.68% of patients, of which 0.13% were stroke with permanent disability. Technical complications without noticeable clinical symptoms of the patients occurred in 2.35% of the angiographic procedures. Deaths caused by angiography did not occur. There is a definite risk for complications after diagnostic angiography. Although a very broad spectrum of complications was considered, complications in the individual subgroups showed a low incidence.

Association between exercise habit changes and incident dementia after ischemic stroke.

We aimed to investigate the effects of exercise habit changes on the risk of incident dementia after ischemic stroke using the Korean National Health Insurance Services Database. This study included 223,426 patients with a new diagnosis of ischemic stroke between 2010 and 2016 who underwent two serial ambulatory health checkups. The participants were divided into four categories according to their habit change or regular exercise persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was new diagnosis of dementia. Multivariate Cox proportional models were used to assess the effects of changes in exercise habits on the risk of incident dementia. After a median of 4.02 years of follow-up, 22,554 (10.09%) dementia cases were observed. After adjusting for covariates, exercise dropouts, new exercisers, and exercise maintainers were significantly associated with a lower risk of incident dementia than persistent non-exercisers (adjusted hazard ratio aHR 0.937 95% confidence interval CI 0.905-0.970, aHR 0.876 95% CI 0.843-0.909, aHR 0.705 95% CI 0.677-0.734, respectively). The impact of changes in exercise habit was more prominent in the 40-65 years age group. An energy expenditure ≥ 1000 metabolic equivalents of task-minwk post-stroke, regardless of pre-stroke physical activity status, was mostly associated with a lower risk of each outcome. In this retrospective cohort study, initiating or continuing moderate-to-vigorous exercise after ischemic stroke was associated with a lower risk of dementia development. Further, pre-stroke regular physical activity also reduced the risk of incident dementia. The promotion of exercise in ambulatory stroke patients may reduce their future risk of incident dementia.

Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.

The underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box-binding protein-1 (Xbp1s), a key effector of UPR signaling, in forebrain excitatory neurons, rapidly develop neurologic deficits, most notably recurrent spontaneous seizures. This seizure phenotype begins around 8 days after Xbp1s transgene expression is induced in XBP1s-TG mice, and by approximately 14 days post induction, the seizures evolve into status epilepticus with nearly continuous seizure activity followed by sudden death. Animal death is likely due to severe seizures because the anticonvulsant valproic acid could significantly prolong the lives of XBP1s-TG mice. Mechanistically, our gene profiling analysis indicates that compared to control mice, XBP1s-TG mice exhibit 591 differentially regulated genes (mostly upregulated) in the brain, including several GABA

Rationale and design of a randomized controlled pilot trial to assess stent retriever thrombectomy for thrombus burden reduction in patients with acute myocardial infarction The RETRIEVE-AMI study.

ST-elevation myocardial infarction (STEMI) is typically caused by thrombotic occlusion of a coronary artery with subsequent hypoperfusion and myocardial necrosis. In approximately half of patients with STEMI, despite successful restoration of epicardial coronary patency, downstream myocardium perfusion remains impeded. Coronary microvascular injury is one of the key mechanisms behind suboptimal myocardial perfusion and it is primarily, yet not exclusively, related to distal embolization of atherothrombotic material following recanalization of the culprit artery. Routine manual thrombus-aspiration has failed to show clinical efficacy in this scenario. This could be related with limitations in technology adopted as well as patients selection. To this end, we set out to explore the efficacy and safety of stent retriever-assisted thrombectomy based on clot-removal device routinely used in stroke intervention. The stent RETRIEVEr thrombectomy for thrombus burden reduction in patients with Acute Myocardial Infarction (RETRIEVE-AMI) study has been designed to establish whether stent retriever-based thrombectomy is safe and more efficacious in thrombus modification than the current standard of care manual thrombus aspiration or stenting. The RETRIEVE-AMI trial will enrol 81 participants admitted for primary PCI for inferior STEMI. Participants will be 111 randomised to receive either standalone PCI, thrombus aspiration and PCI, or retriever-based thrombectomy and PCI. Change in thrombus burden will be assessed via optical coherence tomography imaging. A telephone follow-up at 6 months will be arranged. It is anticipated by the investigators that stent retriever thrombectomy will more effectively reduce the thrombotic burden compared to current standard of care whilst being clinically safe.

Early and long-term outcomes of bioprosthetic versus mechanical tricuspid valve replacement A nationwide population-based study.

We compared early and long-term clinical outcomes of bioprosthetic versus mechanical tricuspid valve replacement in a nationwide study based on the database from the National Health Insurance Service. Of 1425 patients who underwent tricuspid valve replacement from 2003 to 2018, 1241 patients were enrolled after excluding retricuspid valve replacement, complex congenital heart disease, Ebstein anomaly, and age less than 18 years at operation. Bioprostheses (group B) and mechanical prostheses (group M) were used in 562 patients (45.3%) and 679 patients (54.7%), respectively. The median follow-up duration was 5.6 years. Propensity score matching was performed. Subgroup analysis was performed in patients aged 50 to 65 years. There was no difference in operative mortality or postoperative complications between the groups. All-cause mortality was higher in group B (7.8 vs 4.6 per 100 patient-years, hazard ratio, 1.75, 95% confidence interval, 1.33-2.30, P < .001). The cumulative incidence of stroke was higher in group M (hazard ratio, 0.65, 95% confidence interval, 0.43-0.99, P .043), whereas the cumulative incidence of reoperation was higher in group B (hazard ratio, 4.20, 95% confidence interval, 1.53-11.54, P .005). In terms of the age-dependent hazard of all-cause mortality, group B demonstrated a higher hazard than group M below the age of 75 years, and it was statistically significant between 54 and 65 years of age. In the subgroup analysis, all-cause mortality was also higher in group B. Mechanical tricuspid valve replacement demonstrated higher long-term survival than bioprosthetic tricuspid valve replacement. In particular, mechanical tricuspid valve replacement showed significantly higher overall survival between 54 and 65 years of age.

Does left atrial appendage morphology and dimension differ amongst etiological stroke subtypes in patients without known Atrial Fibrillation Results from the Left Atrial Appendage morphology and dimension assessment by TEE in patients with stroke without known Atrial Fibrillation (LAMDA-STROKE) Study..

Complex left atrial appendage (LAA) morphology is increasingly associated with cryptogenic ischemic stroke as compared to cardioembolic stroke due to atrial fibrillation (AF). However, data on such an association in patients with other etiological stroke subtypes in the absence of AF is limited. The study aimed to assess the LAA morphology, dimension and other echocardiographic parameters by transesophageal echocardiography (TEE) in patients with embolic stroke of undetermined source (ESUS) and compare it with other etiological stroke subtypes without known AF. This was a single-Centre, observational study involving comparison of echocardiographic parameters including LAA morphology and dimension in ESUS patients (group A n30) with other etiological stroke subtypes i.e., TOAST (Trial of Org 10172 in Acute Stroke Treatment) class I-IV without AF (group B n30). Complex LAA morphology was predominant in group A (18 patients in group A versus 5 patients in group B, p-Value 0.001). Mean LAA orifice diameter (15.33.5mm in group A versus 172.0 mm in group B, p-Value0.027) and LAA depth were significantly lower in group A (28.46.6mm in group A versus 31.74.3mm in group B, p-Value0.026). Out of these three parameters only complex LAA morphology was found to be independently associated with ESUS OR6.003, 95% CI 1.225-29.417, p0.027. Complex LAA morphology is a predominant feature in ischemic stroke patients with ESUS and may contribute to an increased risk of stroke in these patients.

Long-term exposure to fine particulate matter and cardiovascular disease The mitigation role of environmental concerns.

Although it is widely acknowledged that environmental concerns can reduce PM

Identification and characterization of new candidates for abdominal aortic aneurysm screening in patients outside of current accepted guidelines.

Previous studies have identified groups of patients with abdominal aortic aneurysm (AAA) that fall outside of currently accepted screening guidelines. Population-based studies have found AAA screening would be cost-effective at a prevalence of 0.5-1%. The goal of this study was to determine the prevalence of AAA in patients that fall outside of the current screening guidelines. In addition, we analyzed outcomes of the groups with a prevalence of greater than 1%. Using the TriNetX Analytics Network, several patient cohorts were abstracted with a diagnosis of ruptured or unruptured AAA based on previously identified groups with potential high risk for AAA that fall outside of currently accepted screening guidelines. Groups were also stratified by sex. For groups found to have a prevalence of greater than 1%, the unruptured patients were further analyzed for long term rates of rupture and included male ever-smokers aged 45-65, male never-smokers aged 65-75, male never-smokers aged >75, and female ever-smokers aged 65 or greater. Long-term mortality, stroke, and myocardial infarction rates were compared in patients with treated and untreated AAA after propensity score matching. 148,279 patients were identified across the four groups with prevalence of AAA greater than 1% with female ever smokers aged 65 or older being the most prevalent (2.73%). In each of the four groups, the rate of AAA rupture increased every five years and all had rupture rates greater than 1% at 10 years. Meanwhile, controls for each of these four subgroups without a previous AAA diagnosis had rupture rates between 0.09% and 0.013% at 10 years. Those who underwent repair of their AAA had decreased incidence of mortality, stroke, and MI. Specifically, male ever-smokers 45-64 had a significant difference in incidence of mortality and MI at 5-years and stroke at 1- and 5-years. Our analysis suggests male ever-smokers aged 45-65, male never-smokers aged 65-75, male never-smokers aged >75, and female ever-smokers aged 65 or greater have a >1% prevalence of AAA, and therefore may benefit from screening. Outcomes were significantly worse compared to well-matched controls in these groups.

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.

Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. We analyzed claims and medical data for 34,569 patients who initiated a non-vitamin K antagonist oral anticoagulant (NOAC apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08012010 and 11292017 from the OptumLabs® Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14916 (43.1%), and 25051 (72.5%) respectively. During a mean follow up of 8.3 (SD, 9.0) months, 2110 (6.1%) of patients experienced the composite outcome, of whom 1675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran 2 subgroups favoring apixaban over rivaroxaban 1 subgroup favoring dabigatran over rivaroxaban and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

Stroke-induced hexokinase 2 in circulating monocytes exacerbates vascular inflammation and atheroprogression.

Stroke accelerates inflammatory monocyte recruitment to the endothelium and consequent atheroprogression via high-mobility group box 1-receptor for advanced glycation end products (Hmgb1-RAGE) signaling. Notably, Hmgb1 interacts with multiple Toll-like receptors (TLRs) and promotes TLR4-mediated pro-inflammatory myeloid cell activation. Therefore, TLR-associated mechanism(s) within monocytes may play a role in Hmgb1-driven post-stroke atheroprogression. We aimed to elucidate the TLR-associated mechanism(s) within monocytes that contribute to stroke-induced exacerbation of atherosclerotic disease. A weighted gene co-expression network analysis (WGCNA) on whole blood transcriptomes of stroke model mice identified hexokinase 2 (HK2) as a key gene associated with TLR signaling in ischemic stroke. We conducted a cross-sectional analysis of monocyte hexokinase 2 (HK2) levels in ischemic stroke patients. We performed in vitro and in vivo studies using high-cholesterol diet (HCD)-fed myeloid-specific Hk2-null ApoE We found markedly higher monocyte HK2 levels in ischemic stroke patients during the acute and subacute phases post-stroke. Similarly, stroke model mice displayed a profound increase in monocyte Hk2 levels. Using aortas and aortic valve samples collected from HCD-fed ApoE Stroke-induced monocyte Hk2 upregulation is a key mechanism underlying post-stroke vascular inflammation and atheroprogression.

Not Available.

Acute pulmonary embolism (PE) is a major cause of morbidity and mortality in Portugal. It is the third most common cause of cardiovascular death after stroke and myocardial infarction. However, the management of acute PE remains poorly standardized, and there is a lack of access to mechanical reperfusion when indicated. This working group analyzed the current clinical guidelines for the use of percutaneous catheter-directed treatment in this setting and proposed a standardized approach for severe forms of acute PE. This document also proposes a methodology for the coordination of regional resources in order to create an effective PE response network, based on the hub-and-spoke organization design. This model can be applied at the regional level, but it is desirable to extend it to the national level.

An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and stroke patient-derived MMP-9 activity.

Rapid upregulation of matrix metalloproteinase 9 (MMP-9) leads to blood-brain barrier (BBB) breakdown following stroke, but no MMP-9 inhibitors have been approved in clinic largely due to their low specificities and side effects. Here, we explored the therapeutic potential of a human IgG monoclonal antibody (mAb), L13, which was recently developed with exclusive neutralizing specificity to MMP-9, nanomolar potency, and biological function, using mouse stroke models and stroke patient samples. We found that L13 treatment at the onset of reperfusion following cerebral ischemia or after intracranial hemorrhage (ICH) significantly reduced brain tissue injury and improved the neurological outcomes of mice. Compared to control IgG, L13 substantially attenuated BBB breakdown in both types of stroke model by inhibiting MMP-9 activity-mediated degradations of basement membrane and endothelial tight junction proteins. Importantly, these BBB-protective and neuroprotective effects of L13 in wild-type mice were comparable to Mmp9 genetic deletion and fully abolished in Mmp9 knockout mice, highlighting the in vivo target specificity of L13. Meanwhile, ex vivo co-incubation with L13 significantly neutralized the enzymatic activities of human MMP-9 in the sera of ischemic and hemorrhagic stroke patients, or in the peri-hematoma brain tissues from hemorrhagic stroke patients. Overall, we demonstrated that MMP-9 exclusive neutralizing mAbs constitute a potential feasible therapeutic approach for both ischemic and hemorrhagic stroke.

Ozone pollution and hospital admissions for cardiovascular events.

The available literature on morbidity risk of cardiovascular diseases associated with ambient ozone pollution is still limited. This study examined the potential acute effects of exposure to ambient ozone pollution on hospital admissions of cardiovascular events in China. A two-stage multi-city time-series study approach was used to explore the associations of exposure to ambient ozone with daily hospital admissions (n 6 444 441) for cardiovascular events in 70 Chinese cities of prefecture-level or above during 2015-17. A 10 μgm3 increment in 2-day average daily 8 h maximum ozone concentrations was associated with admission risk increases of 0.46% 95% confidence interval (CI) 0.28%, 0.64% in coronary heart disease, 0.45% (95% CI 0.13%, 0.77%) in angina pectoris, 0.75% (95% CI 0.38%, 1.13%) in acute myocardial infarction (AMI), 0.70% (95% CI 0.41%, 1.00%) in acute coronary syndrome, 0.50% (95% CI 0.24%, 0.77%) in heart failure, 0.40% (95% CI 0.23%, 0.58%) in stroke and 0.41% (95% CI 0.22%, 0.60%) in ischemic stroke, respectively. The excess admission risks for these cardiovascular events associated with high ozone pollution days (with 2-day average 8-h maximum concentrations ≥100 µgm3 vs. < 70 µgm3) ranged from 3.38% (95% CI 1.73%, 5.06%) for stroke to 6.52% (95% CI 2.92%, 10.24%) for AMI. Ambient ozone was associated with increased hospital admission risk for cardiovascular events. Greater admission risks for cardiovascular events were observed under high ozone pollution days. These results provide evidence for the harmful cardiovascular effects of ambient ozone and call for special attention on the control of high ozone pollution.

Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus.

Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF K

Increased Two-Hour Post-Load Plasma Glucose Fluctuation Corresponds with Worse Clinical Prognoses among Acute Ischemic Stroke Patients without a History of Diabetes Mellitus.

This study aimed to evaluate the relationship between 2-h post-load minus fasting plasma glucose (2hPG-FPG) and 1-year clinical outcomes, such as death, stroke recurrence, and modified Rankin Scale (mRS) ≥2-3 among acute ischemic stroke (AIS) patients without diabetes mellitus (DM) history. 1,214 AIS patients without DM history, obtained from ACROSS-China, were divided into 4 quartiles, based on 2hPG-FPG measurements obtained 14 days post-admission. Four models were constructed using multivariate Cox and logistic regression analyses, based on the inclusion of age, gender, trial of ORG 10172 in acute stroke treatment, NIH Stroke Scale scores (model 1), plus 10 other clinical parameters (model 2), plus newly diagnosed DM (NDDM) post-admission (model 3), plus 2hPG and FPG (model 4). Associations found from those 4 models between 2hPG-FPG and 1-year clinical outcomes were confirmed via stratification, multiplicative interaction, sensitivity, and restricted cubic spline analyses. The highest quartile of 2hPG-FPG, after adjusting for variables, such as stroke severity (model 2), was independently associated with death, stroke recurrence, and mRS ≥2-3 (odds ratio OR 3.95, 2.96, 4.15, and 4.83, respectively, all p < 0.0001). Increased 2hPG-FPG remained independently associated with mRS ≥2-3 in models 3-4, as well as increased mRS ≥2 under stratification analyses among both non-NDDM and NDDM patients. 2hPG-FPG is a relatively specific indicator of poorer 1-year clinical prognoses among AIS patients, independent of NDDM, 2hPG, and FPG post-hospital admission. Therefore, the oral glucose tolerance test could be a useful approach for detecting a higher likelihood for developing poorer prognoses among patients without DM history.

Segmentation of acute stroke infarct core using image-level labels on CT-angiography.

Acute ischemic stroke is a leading cause of death and disability in the world. Treatment decisions, especially around emergent revascularization procedures, rely heavily on size and location of the infarct core. Currently, accurate assessment of this measure is challenging. While MRI-DWI is considered the gold standard, its availability is limited for most patients suffering from stroke. Another well-studied imaging modality is CT-Perfusion (CTP) which is much more common than MRI-DWI in acute stroke care, but not as precise as MRI-DWI, and it is still unavailable in many stroke hospitals. A method to determine infarct core using CT-Angiography (CTA), a much more available imaging modality albeit with significantly less contrast in stroke core area than CTP or MRI-DWI, would enable significantly better treatment decisions for stroke patients throughout the world. Existing deep-learning-based approaches for stroke core estimation have to face the trade-off between voxel-level segmentation image-level labels and the difficulty of obtaining large enough samples of high-quality DWI images. The former occurs when algorithms can either output voxel-level labeling which is more informative but requires a significant effort by annotators, or image-level labels that allow for much simpler labeling of the images but results in less informative and interpretable output the latter is a common issue that forces training either on small training sets using DWI as the target or larger, but noisier, dataset using CT-Perfusion (CTP) as the target. In this work, we present a deep learning approach including a new weighted gradient-based approach to obtain stroke core segmentation with image-level labeling, specifically the size of the acute stroke core volume. Additionally, this strategy allows us to train using labels derived from CTP estimations. We find that the proposed approach outperforms segmentation approaches trained on voxel-level data and the CTP estimation themselves.

Mechanical thrombectomy for acute large vessel occlusion stroke beyond 24 h.

Multiple trials have shown that mechanical thrombectomy (MT) is superior to medical therapy. However, no robust evidence is available regarding MT beyond 24 h. In this study, we aimed to determine the safety and efficacy of endovascular stroke therapy in this late window. We conducted a retrospective study of prospectively collected data of patients who met extended window trial criteria, but underwent MT beyond 24 h. Safety and efficacy outcomes included symptomatic intracerebral hemorrhage (sICH), procedural complications, number of passes, successful recanalization (mTICI 2b - 3), delta (Δ) NIHSS (baseline-discharge), and favorable outcomes (mRS 0-2 at 90 days). A total of 39 patients were included with a median age of 69 years (IQR 61.5, 73.5) 54% were females. Hypertension was present in 76% of patients 23% were smokers. Half of the patients had M1 occlusion (48.7%). Median preprocedural NIHSS was 11 (IQR 7.0, 19.5). Successful revascularization was achieved in 87% median number of passes was 2 (IQR 1.0, 3.0). Median ΔNIHSS was 3.0 (IQR -1.5, 8.0). Favorable outcome was achieved in 49% (95% CI 34%-64%), and 95% were free of complications. A total of 3 patients (7.7%) had sICH. In an exploratory analysis, posterior circulation occlusion was associated with higher mRS at 90 days (OR 14.7, p 0.016). Favorable discharge facility was associated with lower mRS at 90 days (OR 0.11, p 0.004). Our study showed comparable clinical outcomes of MT beyond 24 h compared to MT trials within 24 h in patients with favorable imaging profile, especially in anterior circulation occlusions.

Interhemispheric Asymmetries in Intracortical Facilitation Correlate With Fatigue Severity in Individuals With Poststroke Fatigue.

Poststroke fatigue (PSF) contributes to increased mortality and reduces participation in rehabilitative therapy. Although PSFs negative influences are well known, there are currently no effective evidence-based treatments for PSF. The lack of treatments is in part because of a dearth of PSF pathophysiological knowledge. Increasing our understanding of PSFs causes may facilitate and aid the development of effective therapies. Twenty individuals, >6 months post stroke, participated in this cross-sectional study. Fourteen participants had clinically relevant pathological PSF, based on fatigue severity scale (FSS) scores (total score ≥36). Single-pulse and paired-pulse transcranial magnetic stimulation were used to measure hemispheric asymmetries in resting motor threshold, motor evoked potential amplitude, and intracortical facilitation (ICF). Asymmetry scores were calculated as the ratios between lesioned and nonlesioned hemispheres. The asymmetries were then correlated (Spearman rho) to FSS scores. In individuals with pathological PSF (N 14, range of total FSS scores 39-63), a strong positive correlation (rs 0.77, P 0.001) between FSS scores and ICF asymmetries was calculated. As the ratio of ICF between the lesioned and nonlesioned hemispheres increased so did self-reported fatigue severity in individuals with clinically relevant pathological PSF. This finding may implicate adaptivemaladaptive plasticity of the glutamatergic systemtone as a contributor to PSF. This finding also suggests that future PSF studies should incorporate measuring facilitatory activity and behavior in addition to the more commonly studied inhibitory mechanisms. Further investigations are required to replicate this finding and identify the causes of ICF asymmetries.

Outpatient EEG in Routine Clinical Care of Patients With Stroke-Related Acute Symptomatic Seizure Concerns.

Acute symptomatic seizures (ASyS) after stroke contribute the highest risk to poststroke epilepsy (PSE) development. We investigated the use of outpatient EEG (oEEG) among stroke patients with ASyS concerns. Adults with acute stroke, ASyS concerns (underwent cEEG), and outpatient clinical follow-up were included (study population). Patients with oEEG (oEEG cohort) were analyzed for electrographic findings. Univariable and multivariable analyses helped identify predictors of oEEG use in routine clinical care. Among 507 patients, 83 (16.4%) underwent oEEG. The independent predictors of oEEG utilization included age (OR 1.03 1.01 to 1.05, P 0.01), electrographic ASyS on cEEG (OR 3.9 1.77 to 8.9, P < 0.001), ASMs at discharge (OR 3.6 1.9 to 6.6, P < 0.001), PSE development (OR 6.6 3.5 to 12.6, P < 0.001), and follow-up duration (OR 1.01 1.002 to 1.02, P 0.016). Almost 40% of oEEG cohort developed PSE, but only 12% had epileptiform abnormalities. Close to a quarter (23%) of oEEGs were within normal limits. One in six patients with ASyS concern after stroke undergoes oEEG. Electrographic ASyS, PSE development, and ASM at discharge are primary drivers of oEEG use. While PSE drives oEEG use, we need systematic, prospective investigation of outpatient EEGs role as prognostic tool for PSE development.

Clinical criteria to exclude acute vascular pathology on CT angiogram in patients with dizziness.

Patients presenting to the emergency department (ED) with dizziness may be imaged via CTA head and neck to detect acute vascular pathology including large vessel occlusion. We identify commonly documented clinical variables which could delineate dizzy patients with near zero risk of acute vascular abnormality on CTA. We performed a cross-sectional analysis of adult ED encounters with chief complaint of dizziness and CTA head and neck imaging at three EDs between 112014-12312017. A decision rule was derived to exclude acute vascular pathology tested on a separate validation cohort sensitivity analysis was performed using dizzy stroke code presentations. Testing, validation, and sensitivity analysis cohorts were composed of 1072, 357, and 81 cases with 41, 6, and 12 instances of acute vascular pathology respectively. The decision rule had the following features no past medical history of stroke, arterial dissection, or transient ischemic attack (including unexplained aphasia, incoordination, or ataxia) no history of coronary artery disease, diabetes, migraines, currentlong-term smoker, and currentlong-term anti-coagulation or anti-platelet medication use. In the derivation phase, the rule had a sensitivity of 100% (95% CI 0.91-1.00), specificity of 59% (95% CI 0.56-0.62), and negative predictive value of 100% (95% CI 0.99-1.00). In the validation phase, the rule had a sensitivity of 100% (95% CI 0.61-1.00), specificity of 53% (95% CI 0.48-0.58), and negative predictive value of 100% (95% CI 0.98-1.00). The rule performed similarly on dizzy stroke codes and was more sensitivepredictive than all NIHSS cut-offs. CTAs for dizziness might be avoidable in 52% (95% CI 0.47-0.57) of cases. A collection of clinical factors may be able to exclude acute vascular pathology in up to half of patients imaged by CTA for dizziness. These findings require further development and prospective validation, though could improve the evaluation of dizzy patients in the ED.

In-hospital stress and patient outcomes A systematic review and meta-analysis.

Hospital inpatients are exposed to high levels of stress during hospitalisation that may increase susceptibility to major adverse health events post-hospitalisation (known as post-hospital syndrome). However, the existing evidence base has not been reviewed and the magnitude of this relationship remains unknown. Therefore, the aim of the current systematic review and meta-analysis was to 1) synthesise existing evidence and to determine the strength of the relationship between in-hospital stress and patient outcomes, and 2) determine if this relationship differs between (i) in-hospital vs post-hospital outcomes, and (ii) subjective vs objective outcome measures. A systematic search of MEDLINE, EMBASE, PsychINFO, CINAHL, and Web of Science from inception to February 2023 was conducted. Included studies reported a measure of perceived and appraised stress while in hospital, and at least one patient outcome. A random-effects model was generated to pool correlations (Pearsons r), followed by sub-group and sensitivity analyses. The study protocol was preregistered on PROSPERO (CRD42021237017). A total of 10 studies, comprising 16 effects and 1,832 patients, satisfied the eligibility criteria and were included. A small-to-medium association was found as in-hospital stress increased, patient outcomes deteriorated (r 0.19 95% CI 0.12-0.26 I2 63.6 p < 0.001). This association was significantly stronger for (i) in-hospital versus post-hospital outcomes, and (ii) subjective versus objective outcome measures. Sensitivity analyses indicated that our findings were robust. Higher levels of psychological stress experienced by hospital inpatients are associated with poorer patient outcomes. However, more high-quality, larger scale studies are required to better understand the association between in-hospital stressors and adverse outcomes.

The impact of visuospatial and executive function on activity performance and outcome after robotic or conventional gait training, long-term after stroke-as part of a randomized controlled trial.

Visuospatial and executive impairments have been associated with poor activity performance sub-acute after stroke. Potential associations long-term and in relation to outcome of rehabilitation interventions need further exploration. To explore associations between visuospatial and executive function and 1) activity performance (mobility, self-care and domestic life) and 2) outcome after 6 weeks of conventional gait training andor robotic gait training, long term (1-10 years) after stroke. Participants (n 45), living with stroke affecting walking ability and who could perform the items assessing visuospatialexecutive function included in the Montreal Cognitive Assessment (MoCA VisEx) were included as part of a randomized controlled trial. Executive function was evaluated using ratings by significant others according to the Dysexecutive Questionnaire (DEX) activity performance using 6-minute walk test (6MWT), 10-meter walk test (10MWT), Berg balance scale, Functional Ambulation Categories, Barthel Index and Stroke Impact Scale. MoCA VisEx was significantly associated with baseline activity performance, long-term after stroke (r .34-.69, p < .05). In the conventional gait training group, MoCA VisEx explained 34% of the variance in 6MWT after the six-week intervention (p 0.017) and 31% (p 0.032) at the 6 month follow up, which indicate that a higher MoCA VisEx score enhanced the improvement. The robotic gait training group presented no significant associations between MoCA VisEx and 6MWT indicating that visuospatialexecutive function did not affect outcome. Rated executive function (DEX) presented no significant associations to activity performance or outcome after gait training. Visuospatialexecutive function may significantly affect activity performance and the outcome of rehabilitation interventions for impaired mobility long-term after stroke and should be considered in the planning of such interventions. Patients with severely impaired visuospatialexecutive function may benefit from robotic gait training since improvement was seen irrespective of visuospatialexecutive function. These results may guide future larger studies on interventions targeting long-term walking ability and activity performance. clinicaltrials.gov (NCT02545088) August 24, 2015.

Elevated levels of total homocysteine after ischemic stroke a potential marker for in-hospital outcomes.

Our goal was to determine the risk conferred by elevated total homocysteine (tHcy) levels on recurrent stroke and cardiovascular disease (CVD) events after an ischemic stroke (IS), using data from the Chinese Stroke Center Alliance (CSCA). The study consisted of 746,854 total participants with IS. Subjects were split into groups as well as quartiles according to tHcy level. Groups included a hyperhomocysteinemia (HHcy) group with tHcy ≥15 μmoll and a normohomocysteinemia group (nHcy) with tHcy <15 μmoll. The determined groups and quartiles underwent multiple logistic regression models with nHcy or quartile 1 as reference groups, respectively. The information from these analyses was adjusted for potential covariates and used to investigate the association between blood tHcy and in-hospital outcomes. Information collected at discharge included in-hospital stroke recurrence and CVD events. The mean SD age of participants was 66.2 12.0 and 37.4% (n 279,571) were female. The median hospital duration was 11.0 days (interquartile range, 8.0-14.0 days) and 343,346 (46.0%) patients were identified as HHcy cases (tHcy ≥15 μmol). According to the tHcy quartile, the cumulative rates of stroke recurrence (from lowest quartile to highest) were 5.2%, 5.6%, 6.1%, and 6.6% (P < 0.0001). Similarly, those of CVD events were 5.8%, 6.1%, 6.7%, and 7.2% (P < 0.0001). Compared with the nHcy group, the HHcy group was associated with increased risks of in-hospital stroke recurrence (21912 6.4% vs. 22048 5.5%, with the adjusted odds ratio (OR) 1.08, 95% CI 1.05 to 1.10) as well as CVD events (24001 7.0% vs. 24236 6.0%, with the adjusted OR 1.08, 95% CI 1.06 to 1.10) among patients with IS in the fully adjusted model. HHcy was associated with increased in-hospital stroke recurrence and CVD events among patients with IS. In low-folate regions, tHcy levels may potentially predict in-hospital outcomes after IS.

Deep isoflurane anesthesia is associated with alterations in ion homeostasis and specific NaK-ATPase impairment in the rat brain.

Maintenance of ion homeostasis is essential for normal brain function. Inhalational anesthetics are known to act on various receptors but their effects on ion homeostatic systems, such as the NaK-ATPase, remain largely unexplored. Based on reports demonstrating global network activity and wakefulness modulation by interstitial ions, we hypothesized that deep isoflurane anesthesia affects ion homeostasis and the key mechanism for clearing extracellular K, the NaK-ATPase. Using ion-selective microelectrodes, we assessed isoflurane-induced extracellular ion dynamics in cortical slices of male and female Wistar rats in the absence of synaptic activity, the presence of two-pore-domain K channel antagonists, during seizures, and spreading depolarizations. We measured specific isoflurane effects on NaK-ATPase function using a coupled enzyme assay and studied the relevance of our findings in vivo and in silico. Isoflurane concentrations clinically relevant for burst suppression anesthesia increased baseline Ko (mean±SD 3.0 ± 0.0 versus 3.9 ± 0.5mM, p<0.001, n39) and lowered Nao (153.4 ± 0.8 versus 145.2 ± 6.0mM, p<0.001, n28). Similar changes in Ko, Nao, and a substantial drop in Ca2o (1.5 ± 0.0 versus 1.2 ± 0.1mM, p0.001, n16) during inhibition of synaptic activity and two-pore-domain K suggested a different underlying mechanism. Following seizure-like events and spreading depolarization, isoflurane greatly slowed Ko clearance (63.4 ± 18.2 versus 196.2 ± 82.4s, p<0.001, n14). NaK-ATPase activity was markedly reduced after isoflurane exposure (>25%), affecting specifically the α23 activity fraction. In vivo, isoflurane-induced burst suppression resulted in impaired Ko clearance and interstitial K accumulation. A computational biophysical model reproduced the observed effects on Ko and displayed intensified bursting when NaK-ATPase activity was reduced by 35%. Finally, NaK-ATPase inhibition with ouabain induced burst-like activity during light anesthesia in vivo. Our results demonstrate cortical ion homeostasis perturbation and specific NaK-ATPase impairment during deep isoflurane anesthesia. Slowed K clearance and extracellular accumulation might modulate cortical excitability during burst suppression generation while prolonged NaK-ATPase impairment could contribute to neuronal dysfunction after deep anesthesia.

Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke.

Synaptotagmin III (Syt3) is a Ca

Interprofessional Education Through a Monthly Stroke Support Group.

Interprofessional education (IPE) is an accreditation requirement in many health professional programs. A semester-long community-based stroke support group was designed with participation from faculty and health professional students in the occupational therapy, physical therapy, speech and language pathology, and therapeutic recreation programs. Objectives centered on measuring student perception of stroke and interprofessional collaboration. A mixed-methodology using a concurrent triangulation design included a faculty developed pretest-posttest survey and focus group. The Student Perceptions of Interprofessional Clinical Education Revised (SPICE-R2) was given in the final two semesters. 45 students were involved in the program from 2016 to 2019. Findings were significant for all items on the pretest- posttest survey indicating students improved on their perception of stroke, the roles of other professions, and the value of interprofessional teamwork and team-based practice. Thematic analysis revealed that students identified the differences in stroke impact among participants and the importance of using a team approach in meeting participants goals. Faculty and student participation in IPE delivery models coupled with perceived community benefit may positively impact program sustainability and improve student perceptions of interprofessional collaboration.

MiR-17-5p Mediates the Effects of ACE2-Enriched Endothelial Progenitor Cell-Derived Exosomes on Ameliorating Cerebral Ischemic Injury in Aged Mice.

Aging is one of the key mechanisms of vascular dysfunction and contributes to the initiation and progression of ischemic stroke (IS). Our previous study demonstrated that ACE2 priming enhanced the protective effects of exosomes derived from endothelial progenitor cells (EPC-EXs) on hypoxia-induced injury in aging endothelial cells (ECs). Here, we aimed to investigate whether ACE2-enriched EPC-EXs (ACE2-EPC-EXs) could attenuate brain ischemic injury by inhibiting cerebral EC damage through their carried miR-17-5p and the underlying molecular mechanisms. The enriched miRs in ACE2-EPC-EXs were screened using the miR sequencing method. EPC-EXs, ACE2-EPC-EXs, and ACE2-EPC-EXs with miR-17-5p deficiency (ACE2-EPC-EXs

Nootropic Activity of Prospekta in a Blind Placebo-Controlled Study in a Model of Focal Cerebral Ischemia in Rats.

Analysis of the pharmacological activity of the original drug Prospekta in a rat model of focal cerebral ischemia revealed its nootropic effect course treatment in the post-ischemic period led to recovery of the neurological status of animals at the peak of neurological deficit. Evaluation of the therapeutic potential of the drug in morphological and functional CNS disorders allowed us to conclude that it is advisable to carry out further studies of its biological activity at the preclinical stage (the results obtained in animals were successfully confirmed in a clinical trial of drug efficacy in the treatment of moderate cognitive disorders in the early recovery period after ischemic stroke). Studies of the nootropic activity in other pathologies of the nervous system are also promising.

Lower-extremity constraint-induced movement therapy improved motor function, mobility, and walking after stroke.

To regain the ability to walk is one of the most commonly stated goals for people who have had a stroke due to its importance in everyday life. Walking ability affects patients mobility, self-care, and social lives. Constraint-induced movement therapy (CIMT) is known to be effective in improving upper extremity outcomes post-stroke. However, there is insufficient evidence regarding its efficacy in improving lower extremity outcomes. To investigate whether a highly intensive CIMT for lower extremity (LE-CIMT) function post-stroke can improve motor function, functional mobility, and walking ability. Furthermore, it also aimed to investigate whether age, gender, stroke type, more-affected side, or time after stroke onset affect the efficacy of LE-CIMT on walking ability outcomes. Longitudinal cohort study. Outpatient clinic in Stockholm, Sweden. A total of 147 patients mean age 51 years (68% males 57% right-sided hemiparesis), at the sub-acute or chronic phases post-stroke who had not previously undergone LE-CIMT. All patients received LE-CIMT for 6 hours per day over 2 weeks. The Fugl-Meyer Assessment (FMA) of the lower extremity, Timed Up and Go (TUG) test, Ten-Meter Walk Test (10MWT), and six-Minute Walk Test (6MWT) were used to assess functional outcomes before and directly after the 2-week treatment was complete as well at 3-month post-intervention. Compared to baseline values, FMA (P<0.001), TUG (P<0.001), 10MWT (P<0.001) and 6MWT (P<0.001) scores were statistically significantly improved directly after the LE-CIMT intervention. These improvements persisted at the 3-month post-intervention follow-up. Those who completed the intervention 1-6 months after stroke onset had statistically significant larger improvements in 10MWT compared to those who received the intervention later than 6 months after stroke onset. Age, gender, stroke type, and more-affected side did not impact 10MWT results. In an outpatient clinic setting, high-intensity LE-CIMT statistically significant improved motor function, functional mobility, and walking ability in middle-aged patients in the sub-acute and chronic post-stroke phases. However, studies with more robust designs need to be conducted to deepen the understanding of the efficacy of LE-CIMT. High-intensity LE-CIMT may be a feasible and useful treatment option in outpatient clinics to improve post-stroke walking ability.

Risk-related clinical outcomes after minimally invasive mitral valve surgery insights from the mini-mitral international registry (MMIR).

With the popularization of catheter-based mitral valve procedures, evaluating risk-specific differentiated clinical outcomes after contemporary mitral valve surgery is crucial. In this study, we assessed the operative results of minimally invasive mitral valve operations across different patient risk profiles and evaluated the value of EuroSCORE II predicted risk of mortality model for risk prediction, in the large cohort of Mini-Mitral International Registry (MMIR). The MMIR database was used to analyze mini-mitral operations between 2015 and 2021. Patients were categorized as low- (<4%), intermediate- (4% to < 8%), high- (8% to < 12%) and extreme risk (≥12%) according to EuroSCORE II. The observed to expected (O E) mortality ratio was calculated for each risk group. A total of 6541 patients were included in the analysis. Of those, 5546 (84.8%) were classified as low risk, 615 (9.4%) as intermediate risk, 191 (2.9%) as high risk and 189 (2.9%) as extreme risk. Overall operative mortality and stroke rates were 1.7% and 1.4%, respectively, and were significantly associated with patients risk. The observed mortality was significantly lower than expected -according to the EuroSCORE II- in all risk categories (O E ratio < 1). The present study provides an international contemporary benchmark for operative outcomes after minimally invasive mitral surgery. Operative results were excellent in low-, intermediate- and high risk patients, but were less satisfactory in extreme risk. The EuroSCORE II model overestimated the in-hospital mortality. We believe findings from the MMIR may assist surgeons and cardiologists in clinical decision-making and treatment allocation for patients with mitral valve disease.

Left Atrial Appendage Amputation concomitant to Cardiac Surgery in Patients with Sinus Rhythm.

Since recent data demonstrated the benefit of left atrial appendage (LAA) amputation in patients with atrial fibrillation, the long-term impact of LAA amputation on stroke rate and mortality in patients with no history of atrial fibrillation is still unknown. Patients with no history of atrial fibrillation who underwent coronary artery bypass grafting by off-pump technique between 2014 and 2016 were retrospectively examined. Cohorts were divided by the concomitant execution of LAA amputation and propensity score matching was applied by baseline characteristics. The stroke rate in a five-year follow-up served as the primary end-point. Secondary end-points were the mortality rate and rehospitalization in the same time span. A total of 1,522 patients were enrolled, of whom 1,267 and 255 were included in the control and the LAA amputation group, respectively. These were matched to 243 patients in each group. In total, patients with LAA amputation showed a significantly lower rate of stroke in a five-year follow-up (7.0% vs 2.9%, HR 0.41 95% CI 0.17 0.98, p 0.045). However, there was no difference in all-cause mortality (p 0.23) or rehospitalization (p 0.68). Subgroup analysis revealed LAA amputation in patients with a CHA2DS2VASc-Score of ≥ 3 to be associated with a reduction of stroke (9.4% vs 3.1%, HR 0.33 95% CI 0.12 0.92, p 0.034). LAA amputation concomitant to cardiac surgery reduces the stroke rate in patients with no history of atrial fibrillation and a high CHA2DS2VASc-Score (≥3) in a five-year follow-up.

Characteristics of stroke-like lesions on cerebral imaging.

<p><strong>Objective<strong> ndash Stroke-like lesions (SLLs) are pathognomonic for mitochondrial enceshyphashylopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome but occur in other mitochondrial and non-mitochondrial disorders as well. This mini-review aims at summarising and discussing recent findings to open up future perspectives how to manage this fleeting phenomenon.<br><strong>Results <strong>ndash<strong> <strong>Typically, SLLs are dynamic lesions, which increase in size and intensity to regress after a nadir. SLLs are incongruent with a vascular territory, originate frequently from the cortex to spread subcortically, can be monofocal or multifocal, run through an acute (attack) and chronic (remission) stage, and may either completely disappear or end up as laminar cortical necrosis, white matter lesion, subcortical atrophy, cyst, or the toenail sign. On cerebral CT, SLLs are hypodense. SLLs can be best visualized on multimodal MRI showing up as hyperintensity on T2, FLAIR, DWI, and PWI, and as hypointensity on OEF-MRI. On MR-spectroscopy, SLLs typically present with a decreased N-acetyl-aspartate peak and an increased lactate peak. DTI in acute SLLs reveals reduced connectivity, increased global efficiency, and reduced focal efficiency. Tc-HMPAO SPECT of SLLs indicates hyperperfusion and L-iomazenil SPECT reduced tracer uptake. FDG-PET typically shows hypometabolism within a SLL.<br><strong>Conclusion<strong> ndash SLLs present with typical findings on various imaging modalities but the combination of cerebral CT, multimodal MRI, MRS, and PET clearly delineate a SLL from other acute or chronic cerebral lesions.nbsp<p>. <p><strong>Ceacutelkitűzeacutes<strong> - A stroke-szerű laesioacutek (stroke-like lesion, SLL) a mitochondrialis encephalopathia, a tejsavas acidoacutezis eacutes a stroke-szerű epizoacuted szindroacutema (stroke-like episodes syndrome, MELAS) jellegzetesseacutegei, de egyeacuteb mitochondrialis eacutes nem mitochondrialis betegseacutegekben is előfordulnak. Roumlvid aacutettekinteacutesem az SLL-ekkel kapcsolatos leguacutejabb eredmeacutenyek taacutergyalja eacutes foglalja oumlssze abboacutel a ceacutelboacutel, hogy bemutassa, a joumlvőben hogyan lehet majd menedzselni ezt a vaacuteltozatos jelenseacuteget.<br><strong>Eredmeacutenyek<strong> - Az SLL-ek tipikus formaacutejukban dinamikus laesioacutek, amiknek előszoumlr nő a meacuteretuumlk eacutes az intenzitaacutesuk, majd egy maximum eleacutereacutese utaacuten regrediaacutelnak. Kialakulaacutesuk nem mutat szoros oumlsszefuumlggeacutest az erek ellaacutetaacutesi teruumlleteacutevel, gyakran keacutergi eredetűek eacutes subcorticalisan terjednek, mono- eacutes multifokaacutelisak egyaraacutent lehetnek, akut eacutes kroacutenikus faacutezisuk is van (roham, majd remisszioacute), lehetseacuteges, hogy teljesen felsziacutevoacutednak, de olyan is van, ami laminaris corticalis necrosissal, feheacuteraacutellomaacuteny-laesioacuteval, subcorticalis atroacutefiaacuteval, cystakialakulaacutessal vagy toenail-jel kialakulaacutesaacuteval veacutegződik. Az agyi CT-felveacutetelen az SLL-ek hypodensitaskeacutent aacutebraacutezoloacutednak. Legjobban multimodaacutelis MR-felveacutetelen vizualizaacutelhatoacutek, T2-, FLAIR-, DWI- eacutes PWI-hiperintenzitaacuteskeacutent, valamint OEF-MR-hipointenzitaacuteskeacutent. MR-spektoszkoacutepos felveacutetelen az SLL tipikusan csoumlkkent N-acetil-aszpartaacutet-csuacuteccsal eacutes megnoumlvekedett laktaacutetcsuacuteccsal jelentkezik. A DTI akut SLL eseteacuten csoumlkkent konnektivitaacutest, megnoumlvekedett globaacutelis effektivitaacutest eacutes csoumlkkent fokaacutelis effektivitaacutest mutat. Az SLL Tc-HMPAO SPECT-vizsgaacutelata hiperperfuacutezioacutet jelez, miacuteg az L-iomazenil SPECT-vizsgaacutelat csoumlkkent tracer-felveacutetelt. Az FDG-PET-vizsgaacutelat aacuteltalaacuteban az SLL-en beluumlli hipometabolizmust mutatja.<br><strong>Koumlvetkezteteacutes <strong>-<strong> <strong>Az SLL a kuumlloumlnboumlző keacutepalkotoacute modalitaacutesokra tipikus jellegzetesseacutegekkel aacutebraacutezoloacutedik, de az agyi CT, a multimodaacutelis MR, az MR-spektroszkoacutepia eacutes a PET kombinaacutecioacuteja reacuteveacuten pontosan elkuumlloumlniacutethető a toumlbbi akut vagy kroacutenikus cerebralis laesioacutetoacutel.<p>.

The effects of mindfulness-based interventions in post-stroke rehabilitation.

<p>Stroke is nowadays one of the most prevalent diseases worldwide causing devastating impairments and negative consequences for survivors. It is a main cause of adult onset disability and it can have a negative impact on psychological health, cognitive function and quality of life. Post-stroke rehabilitation may reduce long-term disability, and in recent years several innovations have emerged to improve recovery. Decades of research suggest that mindfulness-based interventions support a greater capacity to live with chronic medical conditions and contribute to lowering stress levels. Previous works report positive results amoung stroke survivors, improvements in mood, mental fatigue and in some degree in cognitive and physical functioning, plus represent a promising option in seconshydary prevention. Since the early 2000s, numerous clinical studies have investigated the efficacy of mindfulness-based interventions in post-stroke rehabilitation. In this paper the main results of the relevant international research is reviewed and also, the main modalities of the mindfulness-based interventions are presented. Our primary goal is to evaluate the results in order to draw attention to the importance of rehabilitation of patients with stroke and hopefully the theoretical and practical knowledge of the review will contribute to development effective and secure protocols in future research. Mindfulness-based techniques can become clinically valuable complementary therapeutic interventions in post-stroke rehabilitation. More research in this area is warranted to evaluate these specific practices and their suitability using randomized, controlled, follow up designs, rigorous methods, and different treatment settings expanding outcomes to include physiological, health care use, and health-related outcomes exploring mediating factors and discerning dose effects and optimal frequency and length of practice.nbsp<p>. <p>A stroke napjainkban az egyik leggyakoribb, suacutelyos foshygyateacutekossaacutegot okozoacute betegseacuteg vilaacutegszerte, ami a mozshygaacutesshyszervi kaacuterosodaacuteson tuacutelmenően olyan hangulati eacutes kognitiacutev vaacuteltozaacutesokkal jaacuterhat, amelyek jelentősen kihatnak a beteg eacuteletminőseacutegeacutere. A folyamatosan zajloacute kutataacutesoknak koumlshyszoumlnhetően egyre toumlbb teraacutepiaacutes eszkoumlz eacutes lehetőseacuteg segiacuteti a kaacuterosodott funkcioacutek helyreaacutelliacutetaacutesaacutet. A tudatos jelenleacutet alapuacute technikaacutek szaacutemos koacuterkeacutepben bizonyiacutetottan csoumlkkentik a stressz-szintet, eacutes segiacutetik a kroacutenikus betegseacutegekkel valoacute megkuumlzdeacutest. Az eddigi kutataacutesi eredmeacutenyek alapjaacuten a tudatos jelenleacutet alapuacute beavatkozaacutesok pozitiacutev vaacuteltozaacutesoshykat ideacuteznek elő a stroke-kal egyuumltt jaacuteroacute hangulatzavarok, mentaacutelis faacuteradtsaacuteg, valamint egyes kognitiacutev eacutes fizikai funkcshyioacutek tereacuten, mikoumlzben fokozzaacutek a joacutelleacutetet, eacutes iacutegeacuteretes lehetőseacuteget jelentenek a szekunder prevencioacuteban is. A 2000-es eacutevek elejeacutetől szaacutemos kutataacutest veacutegeztek a tushydashytos jelenleacutet alapuacute beavatkozaacutesok hateacutekonysaacutegaacutenak felshymeacuteshyreacuteseacutere a stroke utaacuteni rehabilitaacutecioacuteban, folyamatosan fejshylődő kezeleacutesi protokollokkal. A jelen tanulmaacutenyban oumlsszefoglaloacutet kiacutevaacutenunk nyuacutejtani e nemzetkoumlzi kutataacutesok fonshytoshysabb eredmeacutenyeiről, eacutes bemutatjuk a tudatos jelenleacutet alapuacute technikaacutek moacutedszertanaacutet. Elsődleges ceacutelunk, hogy az eredmeacutenyeket eacuterteacutekelve felhiacutevjuk a figyelmet a teacutema fontossaacutegaacutera remeacutenyeink szerint az elmeacuteleti eacutes gyakorlati ismereteket tartalmazoacute oumlsszefoglaloacutenk hozzaacutejaacuterul a kutashytaacutesokban hataacutesosan eacutes biztonsaacutegosan alkalmazhatoacute protokollok kifejleszteacuteseacutehez. A tudatos jelenleacutet alapuacute progshyrashymok klinikailag relevaacutens, kiegeacutesziacutető teraacutepiaacutes eljaacuteraacutessaacute vaacutelhatnak a stroke utaacuteni rehabilitaacutecioacuteban, azonban alkalshymazshyhatoacutesaacuteguk eacutes hateacutekonysaacuteguk pontosiacutetaacutesaacutera nagy volumenű randomizaacutelt, kontrollaacutelt, utaacutenkoumlveteacuteses vizsgaacutelatok szuumlkseacutegesek, egyeacuteb eacutelettani parameacuteterekre kifejtett hataacutesaik felmeacutereacuteseacutevel, a hataacutesmechanizmusban szereplő koumlztes teacutenyezők felteacuterkeacutepezeacuteseacutevel eacutes a kuumlloumlnboumlző kezeleacutesi helyzetekre kidolgozott egyseacuteges eacutes optimalizaacutelt treacuteningprotokollok alkalmazaacutesaacuteval.<p>.

Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis.

Adult hippocampal neurogenesis is important for preserving learning and memory-related cognitive functions. Physical exercise, especially voluntary running, is one of the strongest stimuli to promote neurogenesis and has beneficial effects on cognitive functions. Voluntary running promotes exit of neural stem cells (NSCs) from the quiescent stage, proliferation of NSCs and progenitors, survival of newborn cells, morphological development of immature neuron, and integration of new neurons into the hippocampal circuitry. However, the detailed mechanisms driving these changes remain unclear. In this review, we will summarize current knowledge with respect to molecular mechanisms underlying voluntary running-induced neurogenesis, highlighting recent genome-wide gene expression analyses. In addition, we will discuss new approaches and future directions for dissecting the complex cellular mechanisms driving change in adult-born new neurons in response to physical exercise.

Choice and Timing of Antithrombotic After Ischemic Stroke, Intracerebral Hemorrhage or Cerebral Venous Thrombosis.

Stroke is a multifactorial vascular disease and remains a leading cause of disability in the United States. Strokes can be ischemic or hemorrhagic in nature and secondary to arterial or venous disease, making determining the etiology and secondary prevention strategy important for preservation of the injured brain, prevention of recurrent strokes, and in the maintenance of good functional outcomes for patients impacted by stroke. In this narrative review, we provide a synopsis of the available medical evidence surround selection, timing, and choice of therapy, including utilization of left atrial appendage closure, in patients with ischemic, hemorrhagic or venous stroke. .

Variability in Nonvitamin K Oral Anticoagulant Dose Eligibility and Adjustment According to Renal Formulae and Clinical Outcomes in Patients With Atrial Fibrillation With and Without Chronic Kidney Disease Insights From ORBIT-AF II.

Background Nonvitamin K oral anticoagulants require dose adjustment based on kidney function.The most common estimate of kidney function employed in clinical practice is estimated glomerular filtration rate (eGFR) however, product monographs recommend the use of the Cockcroft-Gault estimated creatinine clearance (eCrCl) for dose adjustment. Methods and Results The authors included patients enrolled in the ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation AF II) trial. Dosing was considered inappropriate when use of eGFR resulted in a lower (undertreatment) or higher (overtreatment) dose than that recommended by the eCrCl. The primary outcome of major adverse cardiovascular and neurological events was a composite of cardiovascular death, stroke or systemic embolism, new-onset heart failure, and myocardial infarction. Among 8727 in the overall cohort, agreement between eCrCl and eGFR was observed in 93.5% to 93.8% of patients. Among 2184 patients with chronic kidney disease (CKD), the agreement between eCrCl and eGFR was 79.9% to 80.7%. Dosing misclassification was more frequent in the CKD population (41.9% of rivaroxaban users, 5.7% of dabigatran users, and 4.6% apixaban users). At 1 year, undertreated patients in the CKD group had significantly greater major adverse cardiovascular and neurological events (adjusted hazard ratio, 2.93 95% CI, 1.08-7.92) compared with the group with appropriate nonvitamin K oral anticoagulants dosing (

Role of Polymorphonuclear Myeloid-Derived Suppressor Cells and Neutrophils in Ischemic Stroke.

Background Immune cells play a vital role in the pathology of ischemic stroke. Neutrophils and polymorphonuclear myeloid-derived suppressor cells share a similar phenotype and have attracted increasing attention in immune regulation research, yet their dynamics in ischemic stroke remain elusive. Methods and Results Mice were randomly divided into 2 groups and intraperitoneally treated with anti-Ly6G (lymphocyte antigen 6 complex locus G) monoclonal antibody or saline. Distal middle cerebral artery occlusion and transient middle cerebral artery occlusion were applied to induce experimental stroke, and mice mortality was recorded until 28 days after stroke. Green fluorescent nissl staining was used to measure infarct volume. Cylinder and foot fault tests were used to evaluate neurological deficits. Immunofluorescence staining was conducted to confirm Ly6G neutralization and detect activated neutrophils and CD11b

The effect of statins on the differentiation and function of central nervous system cells.

Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation, and oxidative stress. The effect of statins on the central nervous system (CNS), particularly on cognition and neurological disorders such as cerebral ischemic stroke, multiple sclerosis (MS), and Alzheimers disease (AD), has received increasing attention in recent years, both within the scientific community and in the media. This review aims to provide an updated discussion on the effects of statins on the differentiation and function of various nervous system cells, including neurons and glial cells. Additionally, the mechanisms of action and how different types of statins enter the CNS will be discussed.

Neutrophil Extracellular Traps in Cerebral IschemiaReperfusion Injury Friend and Foe.

Cerebral ischemic injury, one of the leading causes of morbidity and mortality worldwide, triggers various central nervous system (CNS) diseases, including acute ischemic stroke (AIS) and chronic ischemia-induced Alzheimers disease (AD). Currently, targeted therapies are urgently needed to address neurological disorders caused by cerebral ischemiareperfusion injury (CIRI), and the emergence of Neutrophil extracellular traps (NETs) may be able to relieve the pressure. Neutrophils are precursors to brain injury following ischemic stroke and exert complicated functions. NETs extracellularly release reticular complexes of neutrophils, i.e., double-stranded DNA (dsDNA), histones, and granulins. Paradoxically, NETs play a dual role, friend and foe, under different conditions, for example, physiological circumstances, infection, neurodegeneration, and ischemiareperfusion. Increasing evidence indicates that NETs exert anti-inflammatory effects by degrading cytokines and chemokines through protease at a relatively stable and moderate level under physiological conditions, while excessive amounts of NETs release (NETosis) irritated by CIRI exacerbate the inflammatory response and aggravate thrombosis, disrupt the blood-brain barrier (BBB), and initiates sequential neuron injury and tissue damage. This review provides a comprehensive overview of the machinery of NETs formation and the role of an abnormal cascade of NETs in CIRI, as well as other ischemia-induced neurological diseases. Herein, we highlight the potential of NETs as a therapeutic target against ischemic stroke that may inspire translational research and innovative clinical approaches.

What is resistant arterial hypertension

The current review is to describe the definition and prevalence of resistant arterial hypertension (RAH), the difference between refractory hypertension, patient characteristics and major risk factors for RAH, how RAH is diagnosed, prognosis and outcomes for patients. According to the WHO, approximately 1.28 billion adults aged 30-79 worldwide have arterial hypertension, and over 80% of them do not have blood pressure (BP) under control. RAH is defined as above-goal elevated BP despite the concurrent use of 3 or more classes of antihypertensive drugs, commonly including a long-acting calcium channel blocker, an inhibitor of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a thiazide diuretic administered at maximum or maximally tolerated doses and at appropriate dosing frequency. RAH occurs in nearly 1 of 6 hypertensive patients. It often remains unrecognised mainly because patients are not prescribed ≥3 drugs at maximal doses despite uncontrolled BP. RAH distinctly increases the risk of developing coronary artery disease, heart failure, stroke and chronic kidney disease and confers higher rates of major adverse cardiovascular events as well as increased all-cause mortality. Timely diagnosis and treatment of RAH may mitigate the associated risks and improve short and long-term prognosis. Resistant arterial hypertension is a serious condition that leads to severe cardiovascular complications, such as heart attack, stroke and death.It is defined as above-goal elevated blood pressure despite the concurrent use of 3 or more classes of antihypertensive medications administered at maximum or maximally tolerated doses and at appropriate dosing frequency.Non-adherence to antihypertensive medications must be excluded before resistant arterial hypertension is diagnosed.Blood pressure should be measured appropriately. A person should sit in a comfortable chair with back supported, both feet flat on the ground, and legs uncrossed for at least 5 min before blood pressure measurement. A cuff length is supposed to be at least 80% and a width of at least 40% of the arm circumference. Placing the cuff directly on the skin of the upper arm at the level of the heart. Obtaining 3 readings 1 min apart. Discarding the first reading and taking the mean of the second and third readingsResistant arterial hypertension should be distinguished from refractory hypertension, when blood pressure remains uncontrolled on maximal or near-maximal therapy of 5 or more antihypertensive agents of different classes.

Frequency and Size of In Situ Thrombus Within Patent Foramen Ovale.

High-resolution optical coherence tomography can detect in situ thrombi within patent foramen ovale (PFO), which can become a dangerous embolic source. This study aimed to investigate the frequency and size of in situ thrombus within PFO using optical coherence tomography. The cross-sectional study was conducted at Fuwai Hospital (Beijing, China) between 2020 and 2021. From 528 consecutive patients with PFO, 117 (age, 34.33 SD, 11.30 years) without known vascular risk factors were included according to PFO-related symptoms, they were divided into the stroke (n43, including 5 patients with transient ischemic attack), migraine (n49) and asymptomatic (n25) groups. Optical coherence tomography was used to evaluate in situ thrombi and abnormal endocardium within PFO. Univariable analysis and a logistic model were used to evaluate the association between stroke and in situ thrombus age, sex, body mass index, and antithrombotic therapy were included as covariates. Antithrombotic therapy was used more frequently in the stroke group than in the migraine group (76.7% versus 12.2% The frequency of in situ thrombus was extremely high in stroke and migraine groups, while none of the asymptomatic individuals presented with an in situ thrombus. In situ thrombus formation may play a role in patients with PFO-associated stroke or migraines and have therapeutic implications. URL httpswww. gov Unique identifier NCT04686253.

Genetically Proxied CRP (C-Reactive Protein) Levels and Lobar Intracerebral Hemorrhage Risk.

Recent evidence suggests that higher CRP (C-reactive protein) levels are associated with lower risk of Alzheimer disease, speculating that CRP might be involved in Aβ clearance mechanisms. Testing this hypothesis, we explored whether genetically proxied CRP levels are also associated with lobar intracerebral hemorrhage (ICH), commonly caused by cerebral amyloid angiopathy. We used 4 genetic variants within the Higher genetically proxied CRP levels were associated with lower odds of lobar ICH (odds ratio per SD increment in CRP, 0.45 95% CI, 0.25-0.73) but not deep ICH (odds ratio, 0.72 95% CI, 0.45-1.14). There was evidence of colocalization (posterior probability of association, 72.4%) in the signals for CRP and lobar ICH. Our results provide supportive evidence that high CRP levels may have a protective role in amyloid-related pathology.

Ablation of Ventricular Preexcitation to Cure Preexcitation-Induced Dilated Cardiomyopathy in Infants Diagnosis and Outcome.

To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients. This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA. All 10 patients underwent RFCA. All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed. Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.

Impaired gating of γ- and ε-AChR respectively causes Escobar syndrome and fast-channel myasthenia.

To dissect the kinetic defects of acetylcholine receptor (AChR) γ subunit variant in an incomplete form of the Escobar syndrome without pterygium and compare it with those of a variant of corresponding residue in the AChR ε subunit in a congenital myasthenic syndrome (CMS). Whole exome sequencing, α-bungarotoxin binding assay, single channel patch-clamp recordings, and maximum likelihood analysis of channel kinetics. We identified compound heterozygous variants in AChR γ and ε subunits in three Escobar syndrome (1-3) and three CMS patients (4-6), respectively. Each Escobar syndrome patient carries γP121R along with γV221Afs44 in patients 1 and 2, and γY63 in patient 3. Three CMS patients share εP121T along with εR20W, εG-8R, and εY15H in patients 4, 5, and 6, respectively. Surface expressions of γP121R- and εP121T-AChR were 80% and 138% of the corresponding wild-type AChR, whereas εR20W, εG-8R, and εY15H reduced receptor expression to 27%, 35%, and 30% of wild-type εAChR, respectively. γV221Afs44 and γY63 are null variants. Thus, γP121R and εP121T determine the phenotype. γP121R and εP121T shorten channel opening burst duration to 28% and 18% of corresponding wild-type AChR by reducing the channel gating equilibrium constant 44- and 63-fold, respectively. Similar impairment of channel gating efficiency of a corresponding P121 residue in the acetylcholine-binding site of the AChR γ and ε subunits causes Escobar syndrome without pterygium and fast-channel CMS, respectively, suggesting that therapy for the fast-channel CMS will benefit Escobar syndrome.

Knockdown of A20 attenuates microglial susceptibility to OGDR-induced ferroptosis and upregulates inflammatory responses.

The A20 protein is considered to have a potent anti-inflammatory effect, but its mechanism of action in the regulation of ferroptosis and inflammation after stroke is still unknown. In this study, the A20-knockdown BV2 cell line (sh-A20 BV2) was constructed at first, and the oxygen-glucose deprivationre-oxygenation (OGDR) cell model was constructed. Both the BV2 and sh-A20 BV2 cells were treated with the ferroptosis inducer erastin for 48 h, the ferroptosis-related indicators were detected by western blot. The mechanism of ferroptosis was explored by western blot and immunofluorescence. Under OGDR pressure, the oxidative stress level of sh-A20 BV2 cells was inhibited, but the secretion of the inflammatory factors TNF-α, IL-1β, and IL-6 was significantly upregulated. And sh-A20 BV2 cells had higher expression levels of GPX4 and NLRP3 proteins under OGDR induction. Western blot further confirmed that sh-A20 BV2 cells inhibited OGDR-induced ferroptosis. Under the effect of erastin of the ferroptosis inducer (0-1000 nM), sh-A20 BV2 cells had higher cell viability than wild-type BV2 cells and significantly inhibited the accumulation of ROS and the level of oxidative stress damage. It was confirmed that A20 could promote the activation of the IκBαNFκBiNOS pathway. It was confirmed by an iNOS inhibitor that iNOS inhibition could reverse the resistance effect of BV2 cells to OGDR-induced ferroptosis after A20 knockdown. In conclusion, this study demonstrated that inhibition of A20 mediates a stronger inflammatory response while enhancing microglial resistance by knocking down A20 in BV2 cells.

Systematic Review and Meta-Analysis of the Outcome of Different Treatments for Innominate Artery Stenosis or Occlusion.

The present study reported the outcomes of different treatments for innominate artery (IA) atherosclerotic stenosis or occlusion. We performed a systematic review of the literature (4 database searched last search February 2022), including articles with ≥5 patients. We performed meta-analyses of proportions for different postoperative outcomes. Fourteen studies were included (656 patients 396 underwent surgery, 260 endovascular procedures). IA lesions were asymptomatic in 9.6% (95% CI 4.6-14.6). Overall estimated technical success (TS) rate was 91.7% (95% CI 86.9-96.4) weighted TS rate was 86.8% (95% CI 75-98.6) in the surgical group (SG), 97.1% (95% CI 94.6-99.7) in the endovascular group (EG). Postoperative stroke in SG was 2.5% (95% CI 1-4.1) and 2.1% in EG (95% CI .3-3.8). Overall, 30-day occlusion was estimated .9% (95% CI 0-1.8) in SG and .7% (95% CI 0-1.7) in EG. Thirty-day mortality was 3.4% (95% CI .9-5.8) in SG and .7% (95% CI 0-1.7) in EG. Estimated mean follow-up after intervention was 65.5 months (95% CI 45.5-85.5) in SG and 22.4 months (95% CI 14.72-30.16) in EG. During follow-up, restenosis in SG were 2.8% (95% CI .5-5.1) and 16.6% (95% CI 5- 28.1) in EG. In conclusion, the endovascular approach seems to offer good short to mid-term outcomes, but with a higher rate of restenosis during follow-up.

Causal association of cardiovascular disease with erectile dysfunction A two-sample bidirectional Mendelian randomization analysis.

The association between cardiovascular diseases (CVD), including ischemic stroke (IS), heart failure (HF), myocardial infarction (MI), and coronary heart disease (CHD), and erectile dysfunction (ED) remains unclear from observational studies. We explored the potential bidirectional association between CVD and ED by Mendelian randomization (MR). Data from genome-wide association studies for CVD in individuals with European ancestry were obtained from several databases, with 1,711,875-977,323 participants, while that for ED included 223,805 participants. We conducted univariate MR (UVMR), inverse variance-weighting (IVW), weighted median, MR-Egger, and multivariate MR (MVMR) analyses to explore the bidirectional causal effects between CVD and ED. UVMR indicated that IS (odds ratios OR 1.34, 95% confidence interval CI 1.08-1.21, P 0.007), HF (OR 1.36, 95% CI 1.07-1.74, P 0.013), and CHD (OR 1.15, 95% CI 1.09-1.18, P 0.022) were associated with ED. By MVMR, IS estimates remained significant after accounting for combining single nucleotide polymorphisms from CVDs (OR 1.42, 95%CI 1.13-1.79, P 0.002). Moreover, the effect of a genetic susceptibility to IS on ED was not mediated by type 2 diabetes or triglycerides that of HF was not mediated by type 2 diabetes, and that of CHD was not mediated by body mass index. Bidirectional analyses showed that genetic susceptibility to ED did not confer any increased CVD risk. Our results, based on MR, indicated that genetic susceptibility to IS, HF, and CHD was causally associated with ED. These findings can inform prevention and intervention strategies for ED in IS, HF, and CHD patients. This article is protected by copyright. All rights reserved.

Meta-analysis and meta-regression of the total endovascular aortic repair in aortic arch.

Favorable Remodeling After TEVAR in Uncomplicated Acute and Subacute Type B Aortic Dissection in Comparison to Conservative Treatment A Midterm Analysis.

The purpose of the study was to evaluate the midterm and long-term outcomes of patients who underwent thoracic endovascular aortic repair (TEVAR) procedure to treat an uncomplicated acute and subacute type B aortic dissection (uATBAD) with high risk for subsequent aortic complications compared with the group of patients who received a conservative treatment protocol during the same period. Between 2008 and 2019, 35 patients who had TEVAR due to uATBAD and those with conservative procedure (n18) were included in a retrospective analysis and follow-up study. The primary endpoints were false lumen thrombosisperfusion, true lumen diameter, and aortic dilatation. The aortic-related mortality, reintervention, and long-term survival were the secondary endpoints. In the study period, 53 patients (22 females) with a mean age of 61.1±13 years were included. No 30-day and in-hospital mortality was recorded. Permanent neurological deficits occurred in 2 patients (5.7%). In the TEVAR group (n35) and in a median follow-up period of 34 months, a significant reduction of maximum aortic and false lumen diameter as well as a significant increase of true lumen diameter were detected (p<0.001 each). Complete false lumen thrombosis increased from 6% preoperatively to 60% at follow-up. The median difference in aortic, false lumen, and true lumen diameter was -5 mm (interquartile range IQR-28 to 8 mm), -11 mm (IQR-53 to 10 mm), and 7 mm (IQR-13 to 17 mm), respectively. In 3 patients (8.6%), a reintervention was needed. Two patients (1 aortic-related) died during follow-up. The estimated survival according to Kaplan-Meyer analysis was 94.1% after 3 years and 87.5% after 5 years. Similar to the TEVAR group, no 30-day or in-hospital mortality was recorded in the conservative group. During follow-up, 2 patients died and 5 patients underwent conversion-TEVAR (28%). In a median follow-up period of 26 months (range150), a significant increase of maximum aortic diameter (p0.006) and a tendency to augmentation of the false lumen (p0.06) were noted. No significant reduction of the true lumen was seen. Thoracic endovascular aortic repair in patients at high risk of subsequent aortic complications in uncomplicated acute and subacute type B aortic dissection is safe and is associated with favorable midterm outcomes regarding aortic remodeling. In a retrospective, single center analysis of prospectively collected data with follow-up, we compared 35 patients with high-risk features who recieved TEVAR in acute and sub-acute uncomplicated type B aortic dissection to a control-group (n18). The TEVAR group showed a significant positive remoduling (reduction of max. aortic and false lumen diameter and increase of true lumen diameter (p<0.001 each)) during follow-up with an estimated survival of 94.1% after 3 years and 87.5% after 5 years.

KARER intervention on care ability and burden for caregiving relatives of disabled patients with cardiocerebrovascular diseases EMICARE mixed randomized clinical protocol.

Determine efficacy of KARER educational intervention on caring ability and burden of caregiving relatives of disabled patients with stroke and cardiovascular diseases. Clinical, randomized, controlled and double blinded trial with a mixed approach. Study population will be made up of 96 caregiving relatives of patients of home-hospitalized care programs in the cities of Bogotá and Bucaramanga, (Colombia), between March 2021 and March 2022. Participants will be randomly assigned into two groups, either intervention (n 48) or control (n 48). The intervention is interdisciplinary and multi-component B-Learning modality and clinical simulation. Follow-up of participants will last 8 weeks from intervention period start-out, and measurements will be taken and analysed in masked form. The main results will be the mean score changes of care ability and caregiver burden. Caregiving relatives will show better adaptation to their role through effective use of caring abilities as they look after disabled persons with chronic diseases.