Datasets:

Gaborandi

/

Stroke_pubmed_abstracts

like 0

Risks of Right Heart Catheterization and Right Ventricular Biopsy A 12-year, Single-Center Experience.

To study the incidence of complications when undergoing right heart catheterization (RHC) and right ventricular biopsy (RVB). Complications following RHC and RVB are not well reported. We studied the incidence of death, myocardial infarction, stroke, unplanned bypass, pneumothorax, hemorrhage, hemoptysis, heart valve repairreplacement, pulmonary artery perforation, ventricular arrhythmias, pericardiocentesis, complete heart block, and deep vein thrombosis (primary endpoint) following these procedures. We also adjudicated the severity of tricuspid regurgitation and causes of in-hospital death following RHC. Diagnostic RHC procedures, RVB, multiple right heart procedures alone or combined with left heart catheterization, and complications from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system and electronic records at Mayo Clinic, Rochester, Minnesota. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All clinical events and echocardiograms for worsening tricuspid regurgitation were reviewed and adjudicated. A total of 17,696 procedures were identified. Procedures were categorized into those undergoing RHC (n5556), RVB (n3846), multiple right heart catheterization (n776), and combined right and left heart catheterization procedures (n7518). Primary endpoint was seen in 21.6 and 20.8 of 10,000 procedures for RHC and RVB, respectively. There were 190 (1.1%) deaths during hospital admission and none was related to the procedure. Complications following diagnostic RHC and RVB are seen in 21.6 and 20.8 procedures, respectively, of 10,000 procedures and all deaths were secondary to acute illness.

Antidepressant Advisor (ADeSS) a decision support system for antidepressant treatment for depression in UK primary care - a feasibility study.

To develop and probe the first computerised decision-support tool to provide antidepressant treatment guidance to general practitioners (GPs) in UK primary care. A parallel group, cluster-randomised controlled feasibility trial, where individual participants were blind to treatment allocation. South London NHS GP practices. Ten practices and eighteen patients with treatment-resistant current major depressive disorder. Practices were randomised to two treatment arms (a) treatment-as-usual, (b) computerised decision support tool. Ten GP practices participated in the trial, which was within our target range (8-20). However, practice and patient recruitment were slower than anticipated and only 18 of 86 intended patients were recruited. This was due to fewer than expected patients being eligible for the study, as well as disruption resulting from the COVID-19 pandemic. Only one patient was lost to follow-up. There were no serious or medically important adverse events during the trial. GPs in the decision tool arm indicated moderate support for the tool. A minority of patients fully engaged with the mobile app-based tracking of symptoms, medication adherence and side effects. Overall, feasibility was not shown in the current study and the following modifications would be needed to attempt to overcome the limitations found (a) inclusion of patients who have only tried one Selective Serotonin Reuptake Inhibitor, rather than two, to improve recruitment and pragmatic relevance of the study (b) approaching community pharmacists to implement tool recommendations rather than GPs (c) further funding to directly interface between the decision support tool and self-reported symptom app (d) increasing the geographic reach by not requiring detailed diagnostic assessments and replacing this with supported remote self-report. NCT03628027.

Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most common causes of fatal stroke, yet has no specific drug therapies. Many attempts at passive intravenous (IV) delivery in ICH have failed to deliver drugs to the salvageable area around the hemorrhage. The passive delivery method assumes vascular leak through the ruptured blood-brain barrier will allow drug accumulation in the brain. Here we tested this assumption using intrastriatal injection of collagenase, a well-established experimental model of ICH. Fitting with hematoma expansion in clinical ICH, we showed that collagenase-induced blood leak drops significantly by 4 h after ICH onset and is gone by 24 h. We observed passive-leak brain accumulation also declines rapidly over ∼4 h for 3 model IV therapeutics (non-targeted IgG a protein therapeutic PEGylated nanoparticles). We compared these passive leak results with targeted brain delivery by IV monoclonal antibodies (mAbs) that actively bind vascular endothelium (anti-VCAM, anti-PECAM, anti-ICAM). Even at early time points after ICH induction, where there is high vascular leak, brain accumulation via passive leak is dwarfed by brain accumulation of endothelial-targeted agents At 4 h after injury, anti-PECAM mAbs accumulate at 8-fold higher levels in the brain vs. non-immune IgG anti-VCAM nanoparticles (NPs) deliver a protein therapeutic (superoxide dismutase, SOD) at 4.5-fold higher levels than the carrier-free therapeutic at 24 h after injury. These data suggest that relying on passive vascular leak provides inefficient delivery of therapeutics even at early time points after ICH, and that a better strategy might be targeted delivery to the brain endothelium, which serves as the gateway for the immune attack on the peri-hemorrhage inflamed brain region.

Efficacy of robot-assisted training on rehabilitation of upper limb function in stroke patients A Systematic Review and Meta-Analysis.

To systematically evaluate the effect of robot-assisted training (RAT) on upper limb function recovery in stroke patients, providing the evidence-based medical basis for the clinical application of RAT. We searched online electronic databases up to June 2022, including PubMed, The Cochrane Library, Scopus, Web of Science, EMBASE, WanFang Data, CNKI, and VIP full-text databases. Randomized controlled trials (RCTs) of the effect of RAT on upper extremity functional recovery in stroke patients. The Cochrane Collaboration Tool for Assessing the Risk of Bias was used to assess study quality and risk of bias. Fourteen RCTs involving 1275 patients were included for review. Compared with the control group, RAT significantly improved upper limb motor function and daily living ability. The differences have statistical significance in overall differences, FMA-UE SMD0.69, 95%CI (0.34, 1.05), P0.0001, MBI SMD0.95, 95%CI (0.75, 1.15), P< 0.00001 while the differences in MAS, FIM and WMFT scores were not statistically significant. Subgroup analysis Compared with the control group, the differences between FMA-UE and MBI at 4 and 12 weeks of RAT, there were statistically significant for both FMA-UE and MAS in stroke patients in the acute and chronic phases. The present study showed that RAT can significantly enhance the upper limb motor function and activities of daily life in stroke patients undergoing upper limb rehabilitation.

Comparative Effectiveness of Treatment Modalities for Complex Aortic Aneurysms A Network Meta-Analysis of Observational Studies.

To conduct a network meta-analysis comparing multiple treatments for complex aortic aneurysms (CAAs). Medical databases were searched on November 11, 2022. Twenty-five studies (5149 patients) and 4 treatments (open surgery OS, chimneysnorkel endovascular aneurysm repair CEVAR, fenestrated endovascular aneurysm repair FEVAR and branched endovascular aneurysm repair BEVAR) were selected. Outcomes were branch vessel patency, mortality and reintervention at short- and long-term follow-up and perioperative complications. Regarding branch vessel patency, OS was the most effective treatment and had higher 24-month branch vessel patency rates than CEVAR (odds ratio OR, 10.77 95% confidence interval CI, 2.08-55.79). FEVAR (OR, 0.52 95% CI, 0.27-1.00) and OS (OR, 0.39 95% CI, 0.17-0.93) were better than CEVAR regarding 30-day mortality and 24-month mortality, respectively. Regarding 24-month reintervention, OS was better than CEVAR (OR, 3.07 95% CI, 1.15-8.18) and FEVAR (OR, 2.48 95% CI, 1.08-5.73). Regarding perioperative complications, FEVAR had lower acute renal failure rates than OS (OR, 0.42 95% CI, 0.27-0.66) and CEVAR (OR, 0.47 95% CI, 0.25-0.92) and lower myocardial infarction rates than OS (OR, 0.49 95% CI, 0.25-0.97) and was the most effective treatment in preventing acute renal failure, myocardial infarction, bowel ischemia, and stroke, and OS was the most effective treatment in preventing spinal cord ischemia (SCI). OS might have advantages regarding branch vessel patency, 24-month mortality and reintervention and is similar to FEVAR regarding 30-day mortality. Regarding perioperative complications, FEVAR might confer advantages in preventing acute renal failure, myocardial infarction, bowel ischemia, and stroke, and OS in preventing SCI.

Computed diffusion-weighted imaging in patients with transient neurovascular symptoms with and without ischemic infarction.

Detection of ischemic lesions in patients with transient neurovascular symptoms is relevant for the estimation of the risk of a subsequent stroke and etiological classification. To improve detection rates, different technical approaches have been used, such as diffusion-weighted imaging (DWI) with high b-values or higher magnetic field strength. Here, we sought to investigate the value of computed DWI (cDWI) with high b-values in these patients. From an MRI report database we identified patients with transient neurovascular symptoms who underwent repeated MRI including DWI. cDWI was calculated with a monoexponential model with high b-values (2000, 3000, and 4000 smm Overall 33 patients with transient neurovascular symptoms (71 IQR 57-83.5 years 21 63.6% male) were included. On DWI, acute ischemic lesions were observed in 22 (78.6%). Acute ischemic lesions were observed in 17 (51.5%) patients on initial DWI, and in 26 (78.8%) patients on follow-up DWI. Lesion detectability was rated significantly better on cDWI at 2000 smm cDWI might be a valuable addition to routinely acquired standard DWI in patients with transient neurovascular symptoms since its use might result in improved ischemic lesion detection. A b-value of 2000 smm

Comparison of Sex Based In-Hospital Procedural Outcomes and Hospital Readmission Frequency After Patent Foramen Ovale Occluder Device Placement A Propensity Matched National Cohort.

PFO occluder device has been shown to reduce the chance of recurrent stroke in clinically indication per guidelines, stroke is higher in females but procedural efficacy and complications based on sex difference is not well studied in literature. The Nationwide Readmission Database (NRD) was used to create sex cohorts using ICD-10 Procedural code for elective PFO occluder device placement performed during the years 2016-2019. The two groups were compared using propensity score matching (PSM) and multivariate regression models that matched for confounders to report multivariate odds ratio (mOR) for primary and secondary cardiovascular outcomes. Outcomes included in-hospital mortality, acute kidney injury (AKI), acute ischemic stroke, post-procedure bleeding, and cardiac tamponade. Statistical analysis was performed using STATA v. 17. A total of 5,818 patients who underwent PFO occluder device placement were identified, of which 3,144 (54.0%) were females, and 2,673 (46.0%) were males. There was no difference in periprocedural in-hospital mortality, new onset acute ischemic stroke, post-procedural bleeding, or cardiac tamponade between both sexes undergoing occluder device placement. AKI onset was higher in males as compared to females after matching for CKD (mOR 0.66 95% CI 0.48-0.92 p0.016) this can be procedural or can be secondary to volume status or nephrotoxins. Males also had a higher length of stay (LOS) at their index hospitalization (2 days vs 1 day) which led to slightly higher total hospitalization cost ($26,585 vs $24,265). Our data did not show a statistically significant difference in the readmission LOS trends between the two groups at 30, 90, and 180 days. PFO occluder is equally efficacious in both sex and no significant difference in sex-based complications noticed on national cohort analysis. AKI occurrence was high in males that can be limited due to unavailability of data about hydration status and nephrotoxic medications.

The Impact of MOMENTUM 3 Trial Eligibility on Left Ventricular Assist Device Outcomes A Real-World Experience.

Although the landmark MOMENTUM 3 trial was associated with excellent short-term left ventricular assist device (LVAD) outcomes, many end-stage heart failure patients would not have met the trial eligibility criteria. Moreover, the outcomes of trial ineligible patients are poorly characterized. Therefore, we undertook this study to compare MOMENTUM 3 eligible and ineligible patients. We conducted a retrospective review of all primary LVAD implants from 2017 to 2022. Primary stratification was according to MOMENTUM 3 inclusion and exclusion criteria. Primary outcome was survival. Secondary outcomes included complications and length of stay. Multivariable Cox proportional hazards regression models were constructed to further characterize outcomes. From 2017 to 2022, 96 patients underwent primary LVAD implantation. Thirty-seven (38.54%) patients were trial eligible while 59 (61.46%) were ineligible. When stratified by trial eligibility, patients who were trial eligible had higher 1-year (80.15% versus 94.52%, P 0.04) and 2-year survival (70.17% versus 94.52%, P 0.02). Multivariable analysis showed that trial eligibility was protective of mortality at both 1 y (HR 0.19 0.04-0.99, P 0.049) and 2 y (HR 0.17 0.03-0.81, P 0.03). Although the groups had similar rates of bleeding, stroke, and right ventricular failure, trial ineligibility was associated with a longer periprocedural length of stay. In conclusion, the majority of contemporary LVAD patients would not have been eligible for the MOMENTUM 3 trial. Ineligible patients have decreased but acceptable short-term survival. Our findings suggest that a simply reductionist approach to short-term mortality may improve outcomes but fail to capture the majority of patients who could benefit from therapy.

The impact of chronic obstructive pulmonary disease on the prognosis outcomes of patients with percutaneous coronary intervention or coronary artery bypass grafting A meta-analysis.

Coronary artery disease (CAD) is one of the main types of cardiovascular disease and is characterized by myocardial ischemia as a result of narrowing of the coronary arteries. To evaluate the impact of chronic obstructive pulmonary disease (COPD) on outcomes in patients with CAD treated by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). We searched PubMed, Embase, Web of Science, and Cochrane Library for observational studies and post-hoc analyses of randomized controlled trials published before Jan 20, 2022, in English. Adjusted odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for short-term outcomes (in-hospital and 30-day all-cause mortality) and long-term outcomes (all-cause mortality, cardiac death, major adverse cardiac events) were extracted or transformed. Nineteen studies were included. The risk of short-term all-cause mortality was significantly higher in patients with COPD than in those without COPD (RR 1.42, 95% CI 1.05-1.93), as were the risks of long-term all-cause mortality (RR 1.68, 95% CI 1.50-1.88) and long-term cardiac mortality (HR 1.84, 95% CI 1.41-2.41). There was no significant between-group difference in the long-term revascularization rate (HR 1.01, 95% CI 0.99-1.04) or in short-term and long-term stroke rates (OR 0.89, 95% CI 0.58-1.37 and HR 1.38, 95% CI 0.97-1.95). Operation significantly affected heterogeneity and combined results for long-term mortality (CABG, HR 1.32, 95% CI 1.04-1.66 PCI, HR 1.84, 95% CI 1.58-2.13). COPD was independently associated with poor outcomes after PCI or CABG after adjustment for confounders.

Targeting cerebral small vessel disease to promote healthy aging Preserving physical and cognitive functions in the elderly.

Cerebral small vessel disease (SVD), which is highly age-related, is the most common neuroimaging finding in community-dwelling elderly individuals. In addition to increasing the risk of dementia and stroke, SVD is associated with cognitive and physical (particularly gait speed) functional impairments in the elderly. Here, we provide evidence suggesting covert SVD, e.g. without clinically evident stroke or dementia, as a critical target to preserve the functional ability that enables well-being in older age. First, we discuss the relationship between covert SVD and geriatric syndrome. SVD lesions found in non-demented, stroke-free elderly are actually not silent but are associated with accelerated age-related functional decline. We also review the brain structural and functional abnormalities associated with covert SVD and the possible mechanisms underlying their contributions to SVD-related cognitive and physical functional impairments. Finally, we reveal current data, though limited, on the management of elderly patients with covert SVD to prevent SVD lesion progression and functional decline. Although it is important in aging health, covert SVD is still under-recognized or misjudged by physicians in both neurological and geriatric professions. Improving the acknowledgment, detection, interpretation, and understanding of SVD would be a multidisciplinary priority to maintain cognitive and physical functions in the elderly. The dilemmas and future directions of clinical practice and research for the elderly with covert SVD are also included in the present review.

Effects of Tai Chi Yunshou on upper-limb function and balance in stroke survivors A systematic review and meta-analysis.

Physical rehabilitation plays an important role in the recovery of motor function after a stroke. This study aimed to evaluate the effects of Tai Chi Yunshou (TCY), a form of physical therapy, on upper-limb function and balance in stroke survivors. MEDLINE, Embase, CENTRAL and five Chinese databases were retrieved from inception to July 1, 2020 (updated on March 31, 2022). Randomized controlled trials of TCY versus no-treatment for stroke were included. The RoB-2 was used to evaluate the quality of included studies. Upper-limb motor impairment, balance, and activities of daily living (ADLs) were measured by Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Berg Balance Scale (BBS), and Barthel Index (BI), respectively. Data synthesis was performed using RevMan (v5.3), and expressed as mean difference (MD) with 95% confidence intervals (CI). Seven studies with 529 participants were included. Compared with no-treatment, TCY improved FMA-UE (MD 7.31, 95% CI 5.86-8.77, minimal clinically important difference MCID 9-10), BBS (MD 4.68, 95% CI 0.28-9.07, MCID 4), and BI (MD 4.12, 95% CI 3.28-4.96, MCID 1.85) in stroke survivors. TCY may benefit balance and ADLs in rehabilitation after a stroke, but it may not improve upper-limb function clinically.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19 An International COVID-19 Critical Care Consortium Study.

To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. Prospective, observational study. Two hundred twenty-nine ICUs across 32 countries. Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. None. HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12 p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio HR 1.01 95% CI 0.92-1.12 p 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13 95% CI 1.02-1.25 p 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26 95% CI 1.09-1.45 p 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88 95% CI 0.79-0.99, p 0.03). HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Spatial and temporal correlations in human cortex are inherently linked and predicted by functional hierarchy, vigilance state as well as antiepileptic drug load.

The ability of neural circuits to integrate information over time and across different cortical areas is believed an essential ingredient for information processing in the brain. Temporal and spatial correlations in cortex dynamics have independently been shown to capture these integration properties in task-dependent ways. A fundamental question remains if temporal and spatial integration properties are linked and what internal and external factors shape these correlations. Previous research on spatio-temporal correlations has been limited in duration and coverage, thus providing only an incomplete picture of their interdependence and variability. Here, we use long-term invasive EEG data to comprehensively map temporal and spatial correlations according to cortical topography, vigilance state and drug dependence over extended periods of time. We show that temporal and spatial correlations in cortical networks are intimately linked, decline under antiepileptic drug action, and break down during slow-wave sleep. Further, we report temporal correlations in human electrophysiology signals to increase with the functional hierarchy in cortex. Systematic investigation of a neural network model suggests that these dynamical features may arise when dynamics are poised near a critical point. Our results provide mechanistic and functional links between specific measurable changes in the network dynamics relevant for characterizing the brains changing information processing capabilities.

The Interplay Between Walking Speed, Economy, and Stability After Stroke.

Energy minimization is thought to underlie the naturally selected, preferred walking speed however, people post-stroke walk slower than their most economical speed, presumably to optimize other objectives, such as stability. The purpose of this study was to examine the interplay between walking speed, economy, and stability. Seven individuals with chronic hemiparesis walked on a treadmill at 1 of 3 randomized speeds slow, preferred, and fast. Concurrent measurements of speed-induced changes in walking economy (ie, the energy needed to move 1 kg of bodyweight 1 ml O2kgm) and stability were made. Stability was quantified as the regularity and divergence of the mediolateral motion of the pelvic center of mass (pCoM) during walking, as well as pCoM motion relative to the base of support. Slower walking speeds were more stable (ie, pCoM motion was 10% ± 5% more regular and 26% ± 16% less divergent) but 12% ± 5% less economical. Conversely, faster walking speeds were 9% ± 8% more economical, but also less stable (ie, pCoM motion was 17% ± 5% more irregular). Individuals with slower walking speeds had an enhanced energetic benefit when walking faster (rs 0.96, P < 0.001). Individuals with greater neuromotor impairment had an enhanced stability benefit when walking slower (rs 0.86, P 0.01). People post-stroke appear to prefer walking speeds that are faster than their most stable speed but slower than their most economical speed. The preferred walking speed after stroke appears to balance stability and economy. To encourage faster and more economical walking, deficits in the stable control of the mediolateral motion of the pCoM may need to be addressed.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, httplinks.lww.comJNPTA416).

Multi-finger receptive field properties in primary somatosensory cortex A revised account of the spatiotemporal integration functions of area 3b.

The leading view in the somatosensory system indicates that area 3b serves as a cortical relay site that primarily encodes (cutaneous) tactile features limited to individual digits. Our recent work argues against this model by showing that area 3b cells can integrate both cutaneous and proprioceptive information from the hand. Here, we further test the validity of this model by studying multi-digit (MD) integration properties in area 3b. In contrast to the prevailing view, we show that most cells in area 3b have a receptive field (RF) that extends to multiple digits, with the size of the RF (i.e., the number of responsive digits) increasing across time. Further, we show that MD cells orientation angle preference is highly correlated across digits. Taken together, these data show that area 3b plays a larger role in generating neural representations of tactile objects, as opposed to just being a feature detector relay site.

The results of thrombectomy from the arteries of the lower extremities in patients infected with SARS-CoV-2 Omicron variant with different severity of respiratory failure.

Analysis of the results of thrombectomy from the arteries of the lower extremities in patients with COVID-19 against the background of different severity of respiratory failure. This retrospective, cohort, comparative study for the period from 05012022 to 20072022 included 305 patients with acute thrombosis of the arteries of the lower extremities against the background of the course of COVID-19 (SARS-CoV-2 Omicron variant). Depending on the type of oxygen support, 3 groups of patients were formed group 1 ( Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1 5.3%, In patients infected with COVID-19 and on artificial lung ventilation, a more aggressive course of the disease is noted, expressed in an increase in laboratory parameters (C-reactive protein, ferritin, interleukin-6, and D-dimer) of the degree of pneumonia (CT-4 in overwhelming number) and localization of thrombosis of the arteries of the lower extremities, mainly in the tibial arteries.

One-Year Adverse Outcomes Among US Adults With Post-COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database.

Many individuals experience ongoing symptoms following the onset of COVID-19, characterized as postacute sequelae of SARS-CoV-2 or post-COVID-19 condition (PCC). Less is known about the long-term outcomes for these individuals. To quantify 1-year outcomes among individuals meeting a PCC definition compared with a control group of individuals without COVID-19. This case-control study with a propensity score-matched control group included members of commercial health plans and used national insurance claims data enhanced with laboratory results and mortality data from the Social Security Administrations Death Master File and Datavant Flatiron data. The study sample consisted of adults meeting a claims-based definition for PCC with a 21 matched control cohort of individuals with no evidence of COVID-19 during the time period of April 1, 2020, to July 31, 2021. Individuals experiencing postacute sequelae of SARS-CoV-2 using a Centers for Disease Control and Prevention-based definition. Adverse outcomes, including cardiovascular and respiratory outcomes and mortality, for individuals with PCC and controls assessed over a 12-month period. The study population included 13 435 individuals with PCC and 26 870 individuals with no evidence of COVID-19 (mean SD age, 51 15.1 years 58.4% female). During follow-up, the PCC cohort experienced increased health care utilization for a wide range of adverse outcomes cardiac arrhythmias (relative risk RR, 2.35 95% CI, 2.26-2.45), pulmonary embolism (RR, 3.64 95% CI, 3.23-3.92), ischemic stroke (RR, 2.17 95% CI, 1.98-2.52), coronary artery disease (RR, 1.78 95% CI, 1.70-1.88), heart failure (RR, 1.97 95% CI, 1.84-2.10), chronic obstructive pulmonary disease (RR, 1.94 95% CI, 1.88-2.00), and asthma (RR, 1.95 95% CI, 1.86-2.03). The PCC cohort also experienced increased mortality, as 2.8% of individuals with PCC vs 1.2% of controls died, implying an excess death rate of 16.4 per 1000 individuals. This case-control study leveraged a large commercial insurance database and found increased rates of adverse outcomes over a 1-year period for a PCC cohort surviving the acute phase of illness. The results indicate a need for continued monitoring for at-risk individuals, particularly in the area of cardiovascular and pulmonary management.

Carotid stenting Does stent design matter

Carotid artery stenting (CAS) is considered an important tool in carotid revascularization. Carotid artery stenting is usually performed by using self-expandable stent with different designs. The stent design influences many physical characteristics. Also, it may affect the complication rate with special relevance to perioperative stroke, hemodynamic instability, and late restenosis. This study comprised all consecutive patients who underwent carotid artery stenting for atherosclerotic carotid stenosis from March 2014 to May 2021. Both symptomatic patient and asymptomatic patients were included. Patients with a symptomatic carotid stenosis of ≥50% or asymptomatic carotid stenosis of ≥60% were selected for carotid artery stenting . Patients with fibromuscular dysplasia and acute or unstable plaque were not included. Variables of clinical relevance were tested in multivariable analysis using binary logistic regression model. A total of 728 patients were enrolled. The majority of this cohort was asymptomatic (578728, 79.4%), while 150728 (20.6%) were symptomatic. The mean degree of carotid stenosis was 77.82 ± 4.73%, with a mean plaque length of 1.76 ± 0.55 cm. A total of 277 (38%) patients were treated with Xact® Carotid Stent System. Successful carotid artery stenting was achieved in 698 (96%) of patients. Of these patients, stroke rate in symptomatic patients was nine (5.8%), while in asymptomatic patients was 20 (3.4%). In a multivariable analysis, the open-cell carotid stent was not associated with a differential risk for combined acute and sub-acute neurologic complications as compared with closed-cell stents. Patients treated with open cell stents had a significantly lower rate of procedural hypotension ( Carotid artery stenting is considered a safe alternative to CEA that can be used in selected average surgical risk patient. Different stent designs can affect the rate of major adverse events in carotid artery stenting patients, but further studies are necessary with avoiding different bias to study the effect of different stent designs.

Prophylactic Efficacy and Safety of Antithrombotic Regimens in Patients with Stable Atherosclerotic Cardiovascular Disease (S-ASCVD) A Bayesian Network Meta-Regression Analysis.

The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD). A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size. Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio HR 0.53, 95% confidence interval CI 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin. Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.

Cardiovascular Risks in Testicular Cancer Assessment, Prevention, and Treatment.

Testicular cancer (TC) is the leading cancer in men between 18 and 39 years of age. Current treatment involves tumor resection followed by surveillance andor one or more lines of cisplatin-based chemotherapy (CBCT) andor bone marrow transplant (BMT). Ten years after treatment, CBCT has been associated with significant atherosclerotic cardiovascular disease (CVD) including myocardial infarction (MI), stroke, and heightened rates of hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome (MetS). Additionally, low testosterone levels and hypogonadism contribute to MetS and may further drive CVD. CVD in TCS has been associated with worse physical functioning accompanied by role limitations, decreased energy, and decreased overall health. Exercise may play a role in ameliorating these effects. Systematic CVD screening practices are needed at TC diagnosis and in survivorship. We encourage a multidisciplinary partnership between primary care physicians, cardiologists, cardio-oncologists, medical oncologists, and survivorship providers to address these needs.

A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber.

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n14), a catheter (inner diameter, 0.42 mm outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range IQR, 3-8 min). Mean infarct volume was 388 mm

Re-Exploring the Inflammation-Related Core Genes and Modules in Cerebral Ischemia.

The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed gene (DEG) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological process analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO) and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). (1) We identified 58 upregulated DEGs with more than 2-fold increase, and adj. p < 0.05 in mouse datasets. Among them, Atf3, Timp1, Cd14, Lgals3, Hmox1, Ccl2, Emp1, Ch25h, Hspb1, Adamts1, Cd44, Icam1, Anxa2, Rgs1, and Vim showed significant increases in both mouse and rat datasets. (2) Ischemic treatment and reperfusion time were the main confounding factors in gene profile changes, while sampling site and ischemic time were not. (3) WGCNA identified a reperfusion-time irrelevant and inflammation-related module and a reperfusion-time relevant and thrombo-inflammation related module. Astrocytes and microglia were the main contributors of the gene changes in these two modules. (4) Forty-four module core hub genes were identified. We validated the expression of unreported stroke-associated core hubs or human stroke-associated core hubs. Zfp36 mRNA was upregulated in permanent MCAO Rhoj, Nfkbiz, Ms4a6d, Serpina3n, Adamts-1, Lgals3, and Spp1 mRNAs were upregulated in both transient MCAO and permanent MCAO and NFKBIZ, ZFP3636, and MAFF proteins, unreported core hubs implicated in negative regulation of inflammation, were upregulated in permanent MCAO, but not in transient MCAO. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.

Serum neurofilament light chain, brain infarcts, and the risk of stroke a prospective population-based cohort study.

Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.

Patterns of Visual Task-based Functional MRI Activation in Chronic Posterior Cerebral Artery Stroke Patients.

Stroke is a principal cause of disability worldwide. In motor stroke, the tools for stratification and prognostication are plentiful. Conversely, in stroke causing mainly visual and cognitive problems, there is still no gold standard modality to use. The purpose of this study was to explore the fMRI recruitment pattern in chronic posterior cerebral artery (PCA) stroke patients and to investigate fMRI as a biomarker of disability in these patients. The study included 10 chronic PCA stroke patients and another 10 age-matched volunteer controls. The clinical presentation, cognitive state, and performance in visual perceptual skills battery (TVPS-3) were determined for both patients and control groups. Task-based fMRI scans were acquired while performing a passive visual task. Individual and group analyses of the fMRI scans as well as correlation analysis with the clinical and behavioral data were done. At the level of behavioral assessment there was non-selective global impairment in all visual skills subtests. On visual task-based fMRI, patients recruited more brain areas than controls. These activations were present in the ipsilesional side distributed in the ipsilesional cerebellum, dorsolateral prefrontal cortex mainly Brodmann area (BA) 9, superior parietal lobule (somatosensory associative cortex, BA 7), superior temporal gyrus (BA 22), supramarginal gyrus (BA 40), and contralesional associative visual cortex (BA 19). Spearmans rank correlation was computed to assess the relationship between the TVPS scores and the numbers of fMRI neuronal clusters in each patient above the main control activations, there was a negative correlation between the two variables, r(10) -0.85, p ≤ 0.001. In chronic PCA stroke patients with residual visual impairments, the brain attempts to recruit more neighboring and distant functional areas for executing the impaired visual skill. This intense recruitment pattern in poorly recovering patients appears to be a sign of failed compensation. Consequently, fMRI has the potential for clinically relevant prognostic assessment in patients surviving PCA stroke however, as this study included no longitudinal data, this potential should be further investigated in longitudinal imaging studies, with a larger cohort, and multiple time points.

Regional brain glucose metabolism is differentially affected by ketogenic diet a human semiquantitative positron emission tomography.

Ketogenic diet (KD) is recommended to avoid intense Subjects who underwent KD prior to whole-body and brain A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Students t-test, p 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them. KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.

Association between renin-angiotensin-aldosterone system blockade and clinical outcomes in patients with hypertension real-world observation from a nationwide hypertension cohort.

We investigated the association between the use of ACEi, ARB, or non-renin-angiotensin-aldosterone system inhibitors (non-RASi) and incident cardiovascular events in an unselected nationwide hypertension cohort. The information regarding 2,025,849 patients who underwent general health checkup between 2010 and 2011 and were on antihypertensive medication was collected. Patients were allocated into ACEi, ARB, and non-RASi groups and followed until 2019. The outcomes of interest were myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause deaths. Patients on ACEi and ARB showed unfavorable baseline characteristics compared to those on non-RASi. After adjusting for covariates, the ACEi group showed lower risks of MI, AF, and all-cause deaths (HR (95% CI) 0.94 (0.89-0.99), 0.96 (0.92-1.00), and 0.93 (0.90-0.96), respectively), but similar risks of IS and HF (0.97 (0.92-1.01) and 1.03 (1.00-1.06), respectively), compared to the non-RASi group. Likewise, the ARB group showed decreased risks of MI, IS, AF, HF, and all-cause deaths (HR (95% CI) 0.93 (0.91-0.95), 0.88 (0.86-0.90), 0.86 (0.85-0.88), 0.94 (0.93-0.96), and 0.84 (0.83-0.85)), compared to the non-RASi group. Sensitivity analysis of patients taking a single antihypertensive medication showed similar results. In the propensity score matching (PSM) cohort, the ARB group showed similar risks of MI and decreased risks of IS, AF, HF, and all-cause deaths compared to the ACEi group. ACEi and ARB users were associated with decreased risks of MI, IS, AF, HF, and all-cause deaths, compared to non-RASi users.

Comparison of acute stroke care pathways-A qualitative multicenter study in three referring hospitals of a stroke network.

In stroke networks, hospitals that do not provide thrombectomy (referring hospitals) refer patients to specialized hospitals (receiving hospitals) for this specific intervention. In order to improve the access and management of thrombectomy, the focus of research needs to be not only on the receiving hospitals but also on the prior stroke care pathways in referring hospitals. The purpose of this study was to investigate the stroke care pathways in different referring hospitals as well as the advantages and disadvantages associated with these pathways. A qualitative multicenter study was carried out in three referring hospitals of a stroke network. Stroke care was assessed and analyzed by using non-participant observations and 15 semi-structured interviews with employees in various health professions. The following aspects were reported as advantageous within the stroke care pathways (1) a structured and personal prenotification of the patient by the emergency medical service (EMS) members (2) a more efficiently organized teleneurology workflow (3) the provision of the secondary referral to thrombectomy by the same EMS members of the primary referral and (4) the integration of external neurologists into in-house structures. The study provides insights into different stroke care pathways of three different referring hospitals of a stroke network. The results can be used to derive potentials for improvement of other referring hospitals however, this study is too small to provide reliable information about their potential effectiveness. Future studies should investigate whether implementation of these recommendations actually leads to improvements and under which conditions they are successful. To ensure patient-centeredness, the perspectives of patients and relatives should also be included. HINTERGRUND In Schlaganfallnetzwerken verlegen Kliniken, die selbst keine endovaskuläre Thrombektomie (EVT) durchführen (hier Primärkliniken), Patientinnen für diese Therapie in spezialisierte Schlaganfallzentren. Zur Verbesserung des Zugangs und des Managements der EVT muss der Fokus der Forschung nicht nur auf den spezialisierten Zentren, sondern auch auf den vorangehenden Prozessen in den Primärkliniken liegen. Wie stellen sich die Schlaganfallbehandlungspfade in verschiedenen Primärkliniken dar und was wird in diesen Pfaden als Vor- und Nachteil gesehen Im Rahmen einer qualitativen multizentrischen Studie in drei Primärkliniken eines Schlaganfallnetzwerkes wurde die Versorgung von Schlaganfallpatientinnen mithilfe von nichtteilnehmenden Beobachtungen und 15 leitfadengestützten Interviews mit Beschäftigten unterschiedlicher Professionen erfasst und analysiert. Innerhalb der Schlaganfallbehandlungspfade wurden folgende Aspekte als vorteilhaft berichtet (1) eine strukturierte und persönliche Ankündigung von Schlaganfallpatientinnen in der Primärklinik durch den Rettungsdienst, (2) ein effizienter Ablauf des Telekonsils, (3) die Notfallverlegung zur EVT durch die gleichen Rettungsdienstmitarbeitenden der Primärzuweisung und (4) die Integration von externen Neurologinnen in klinikinterne Strukturen. Die Studie liefert einen Einblick in die z. T. unterschiedlichen Schlaganfallbehandlungspfade drei verschiedener Primärkliniken eines Schlaganfallnetzwerkes. Aus den Ergebnissen lassen sich Verbesserungspotenziale auch für andere Kliniken ableiten. Allerdings ist diese Studie zu klein, um verlässliche Aussagen über deren Wirksamkeit zu geben. Zukünftige Studien sollten daher untersuchen, ob Implementierungen der hier erarbeiteten Empfehlungen tatsächlich zu Verbesserungen führen bzw. unter welchen Bedingungen diese erfolgreich sind. Zur Sicherstellung der Patientenzentrierung sollte dabei auch die Perspektive von Betroffenen und Angehörigen miteinbezogen werden.

Validity, Intra-Rater Reliability and Normative Data of the Neuroflexor™ Device to Measure Spasticity of the Ankle Plantar Flexors after Stroke.

Quantification of lower limb spasticity after stroke and the differentiation of neural from passive muscle resistance remain key clinical challenges. The aim of this study was to validate the novel NeuroFlexor foot module, to assess the intrarater reliability of measurements and to identify normative cut-off values. Fifteen patients with chronic stroke with clinical history of spasticity and 18 healthy subjects were examined with the NeuroFlexor foot module at controlled velocities. Elastic, viscous and neural components of passive dorsiflexion resistance were quantified (in Newton, N). The neural component, reflecting stretch reflex mediated resistance, was validated against electromyography activity. A test-retest design with a 2-way random effects model permitted study of intra-rater reliability. Finally, data from 73 healthy subjects were used to establish cutoff values according to mean 3 standard deviations and receiver operating characteristic curve analysis. The neural component was higher in stroke patients, increased with stretch velocity and correlated with electromyography amplitude. Reliability was high for the neural component (intraclass correlation coefficient model 2.1 (ICC2,1) ≥ 0.903) and good for the elastic component (ICC2,1 ≥ 0.898). Cutoff values were identified, and all patients with neural component above the limit presented pathological electromyography amplitude (area under the curve (AUC) 1.00, sensitivity 100%, specificity 100%). The NeuroFlexor may offer a clinically feasible and non-invasive way to objectively quantify lower limb spasticity.

Short-term and long-term predictors of balance function in stroke patients a 6-month follow-up study.

We aimed to determine early predictors of balance function (Berg Balance Scale, BBS) at 3 and 6 months after stroke using clinical, neurophysiological, and neuroimaging variables. Seventy-nine patients with hemiparesis after a stroke were included. Demographics, stroke characteristics, and clinical variables Mini-Mental State Examination, BBS, strength in the hemiparetic hip, knee, and ankle muscles, and Fugl-Meyer Assessment Lower Extremity (FMA-LE) were evaluated 2 weeks post-stroke, on average. Somatosensory-evoked potentials (SEP) from both tibial nerves and diffusion tensor imaging data were collected respectively within 3 weeks and 4 weeks post-onset to calculate the SEP amplitude ratio and the laterality index of fractional anisotropy of the corticospinal tract. In multiple linear regression analysis, younger age, higher FMA-LE score, and stronger hemiparetic hip extensors were independent predictors of higher BBS at 3 months post-stroke (adjusted R2 0.563, P < 0.001). At 6 months post-stroke, significant predictors of higher BBS were younger age, higher FMA-LE, stronger hemiparetic hip extensors, and larger SEP amplitude ratio (adjusted R2 0.552, P < 0.001), although the incremental contribution of the latter was rather small (R2 0.019). We conclude that age and the initial motor impairment of the affected lower limb can inform the state of balance function at 3 and 6 months after stroke.

Methods to assess the effectiveness and acceptance of information and communication technology-based assistive technology for older adults a scoping review.

An aging society is a growing challenge for families, social and rehabilitation service providers, and economies. Information and communication technology-based assistive technology can bolster the independence of older adults (65 years and above) and reduce their burden on caregivers. Currently, there is no unified methodology to assess the effectiveness and acceptance of these technologies. The present study undertakes a scoping review to (1) identify and characterize the methods for assessing the acceptability and usability of information and communication technology-based assistive technologies, (2) explore the advantages and disadvantages of the assessment methods, (3) determine the possibilities of combining the assessment methods and (4) define the most commonly used assessment method and set of outcome measures. The literature was searched in MEDLINE, Scopus, IEEE Cochrane and Web of Science bibliographic databases using the keywords defined by reviewers for articles in English published between 2011 and 2021. Of the 1696 matches, 31 met the inclusion criteria. It was found that a combination of different assessment methods was common in outcome measurements. Of the 31 studies, assessment methods were combined in 21 studies and multiple questionnaires were used in 11 studies. The most common technique of outcome measurement was the use of questionnaires (81%), conducting interviews (48%) and recording usability-performance measures (39%). The advantages and disadvantages of the assessment methods could not be determined in the selected studies in this scoping review.

Analysis of pacing and kinematics in 3000 m freestyle in elite level swimmers.

This study aimed to determine elite swimmers pacing strategy in the 3000 m event and to analyse the associated performance variability and pacing factors. Forty-seven races were performed by 17 male and 13 female elite swimmers in a 25 m pool (20.7 ± 2.9 years 807 ± 54 FINA points). Lap performance, clean swim velocity (CSV), water break time (WBT), water break distance (WBD), stroke rate (SR), stroke length (SL) and stroke index (SI) were analysed including and excluding the first (0-50 m) and last lap (2950-3000 m). The most common pacing strategy adopted was parabolic. Lap performance and CSV were faster in the first half of the race compared to the second half (

Apolipoprotein E mimetic peptide COG1410 alleviates blood‑brain barrier injury in a rat model of ischemic stroke.

Blood‑brain barrier (BBB) damage is one of the main causes of poor outcomes and increased mortality rates following cerebral ischemia‑reperfusion injury. Apolipoprotein E (ApoE) and its mimetic peptide have been previously reported to exhibit potent neuroprotective properties in various central nervous system disease models. Therefore, the present study aimed to investigate the possible role of the ApoE mimetic peptide COG1410 in cerebral ischemia‑reperfusion injury and its potential underlying mechanism. Male SD rats were subjected to 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Evans blue leakage and IgG extravasation assays results revealed that COG1410 treatment significantly reduced BBB permeability. In addition,

Health-related outcomes 6 months after integrated care of older people with stroke in 2 different primary care settings.

Integrated care has been proven to be effective among stroke survivors. However, in China, these services mainly focus on connecting the healthcare system (acute, primary medical, and skilled) at the individual level. Closer health and social care integration is a new concept. This study aimed to compare health-related outcomes 6 months after the implementation of the 2 integrated care models. It was a 6-month follow-up of an open, prospectively study comparing the outcomes of a model of integrated health and social care (IHSC) versus a usual integrated healthcare (IHC) model. Outcomes were measured by Short-Form Health Survey-36 (SF-36), Modified Barthel Index (MBI), and Caregiver Strain Index (CSI) at 3 and 6 months, respectively. There were no statistically significant differences in MBI scores between patients in the 2 models either after 3 months or at the end of intervention. The same trend was not seen in Physical Components Summary, an integral component of SF-36. Patients in IHSC model scored statistically significant higher points in Mental Components Summary, another integral part of SF-36 than patients in IHC model after 6 months. Average scores of CSI were statistically significant lower for IHSC model than for IHC model after 6 months. The findings suggest the need to improve the scales of integration and recognize the vital role played by social care services when designing or improving an integrated care for older people with stroke.

Remote Diffusion-Weighted Imaging Lesions and Intracerebral Hemorrhage A Systematic Review and Meta-Analysis.

Remote diffusion-weighted imaging lesions (RDWILs) in the context of spontaneous intracerebral hemorrhage (ICH) are associated with an increased risk of recurrent stroke, worse functional outcome, and death. To update current knowledge on RDWILs, we conducted a systematic review and meta-analysis of the prevalence, associated factors and presumed causes of RDWILs. We searched Pubmed, Embase, and Cochrane up to June 2022 for studies reporting RDWILs in adults with symptomatic ICH of no-identified-cause, assessed by magnetic resonance imaging, and analyzed associations between baseline variables and RDWILs in random-effects meta-analyses. Eighteen observational studies (7 prospective), reporting 5211 patients were included, of whom 1386 had ≥1 RDWIL (pooled prevalence 23.5% 19.0-28.6). RDWIL presence was associated with neuroimaging features of microangiopathy, atrial fibrillation (odds ratio, 3.67 1.80-7.49), clinical severity (mean difference in National Institutes of Health Stroke Scale score, 1.58 points 0.50-2.66), elevated blood pressure (mean difference, 14.02 mmHg 9.44-18.60), ICH volume (mean difference, 2.78 mL 0.97-4.60), and subarachnoid (odds ratio, 1.80 1.00-3.24) or intraventricular (odds ratio, 1.53 1.28-1.83) hemorrhage. RDWIL presence was associated with poor 3-month functional outcome (odds ratio, 1.95 1.48-2.57). RDWILs are detected in approximately 1-in-4 patients with acute ICH. Our results suggest that most RDWILs result from disruption of cerebral small vessel disease by ICH-related precipitating factors such as elevated intracranial pressure and cerebral autoregulation impairment. Their presence is associated with worse initial presentation and outcome. However, given the mostly cross-sectional designs and heterogeneity in study quality, further studies are needed to investigate whether specific ICH treatment strategies may reduce the incidence of RDWILs and in turn improve outcome and reduce stroke recurrence.

Cerebral Venous Reflux and Cerebral Amyloid Angiopathy An Magnetic Resonance ImagingPositron Emission Tomography Study.

Cerebral venous outflow alterations contribute to central nervous system pathology in aging and neurodegenerative disorders and are potentially linked to underlying cerebral microangiopathy. We investigated whether cerebral venous reflux (CVR) is more closely associated with cerebral amyloid angiopathy (CAA) than hypertensive microangiopathy in intracerebral hemorrhage (ICH) survivors. This cross-sectional study included 122 patients of spontaneous ICH with magnetic resonance and positron emission tomography imaging studies (2014-2022) in Taiwan. The presence of CVR was defined as abnormal signal intensity in the dural venous sinus or internal jugular vein on magnetic resonance angiography. Cerebral amyloid load was measured using the Pittsburgh compound B standardized uptake value ratio. Clinical and imaging characteristics associated with CVR were evaluated in univariable and multivariable analyses. In the subset of patients with CAA, we applied univariable and multivariable linear regression analyses to evaluate the association between CVR and cerebral amyloid retention. Compared with patients without CVR (n84, 64.5±12.1 years), patients with CVR (n38, 69.4±11.5 years) were significantly more likely to have CAA-ICH (53.7% versus 19.8% In spontaneous ICH, CVR is associated with CAA and a higher amyloid burden. Our results suggest venous drainage dysfunction potentially plays a role in CAA and cerebral amyloid deposition.

Early Brain Injury After Subarachnoid Hemorrhage Incidence and Mechanisms.

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

Prehospital Stroke Care Part 2 On-Scene Evaluation and Management by Emergency Medical Services Practitioners.

The prehospital phase is a critical component of delivering high-quality acute stroke care. This topical review discusses the current state of prehospital acute stroke screening and transport, as well as new and emerging advances in prehospital diagnosis and treatment of acute stroke. Topics include prehospital stroke screening, stroke severity screening, emerging technologies to aid in the identification and diagnosis of acute stroke in the prehospital setting, prenotification of receiving emergency departments, decision support for destination determination, and the capabilities and opportunities for prehospital stroke treatment in mobile stroke units. Further evidence-based guideline development and implementation of new technologies are critical for ongoing improvements in prehospital stroke care.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking. Using LAAO was associated with low rates of early stroke (0.63%), early mortality (0.53%), and procedural complications (2.59%). Among patients who had readmissions with strokes after LAAO, the median time from implant to readmission was 35 days (interquartile range, 9-57 days) 67% of readmissions with strokes occurred <45 days postimplant. Between 2016 and 2019, the rates of early stroke after LAAO significantly decreased (0.64% versus 0.46% In this contemporary real-world analysis, the early stroke rate after LAAO was low, with the majority occurring within 45 days of device implantation. Despite an increase in LAAO procedures between 2016 and 2019, there with a significant decline in early strokes after LAAO during that period.

Cost-Effectiveness of Smoking Cessation Interventions in Patients With Ischemic Stroke and Transient Ischemic Attack.

Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries The SAFE-AAA Study.

Concerns have been raised about the long-term performance of aortic stent grafts for the treatment of abdominal aortic aneurysms, in particular, unibody stent grafts (eg, Endologix AFX AAA stent grafts). Only limited data sets are available to evaluate the long-term risks related to these devices. The SAFE-AAA Study was designed with the Food and Drug Administration to provide a longitudinal assessment of the safety of unibody aortic stent grafts among Medicare beneficiaries. The SAFE-AAA Study was a prespecified, retrospective cohort study evaluating whether unibody aortic stent grafts are noninferior to non-unibody stent grafts with respect to the composite primary outcome of aortic reintervention, rupture, and mortality. Procedures were evaluated from August 1, 2011, through December 31, 2017. The primary end point was evaluated through December 31, 2019. Inverse probability weighting was used to account for imbalances in observed characteristics. Sensitivity analyses were used to evaluate the effect of unmeasured confounding, including the falsification end points of heart failure, stroke, and pneumonia. A prespecified subgroup includes patients treated from February 22, 2016, through December 31, 2017, corresponding to the market release of the most contemporary unibody endograft (Endologix AFX2 AAA stent graft). Of 87 163 patients who underwent aortic stent grafting at 2146 US hospitals, 11 903 (13.7%) received a unibody device. The average age was 77.0±6.7 years, 21.1% were female, 93.5% were White, 90.8% had hypertension, and 35.8% used tobacco. The primary end point occurred in 73.4% of unibody device-treated patients versus 65.0% of non-unibody device-treated patients (hazard ratio, 1.19 95% CI, 1.15-1.22 noninferior In the SAFE-AAA Study, unibody endografts failed to meet noninferiority compared with non-unibody endografts with respect to aortic reintervention, rupture, and mortality. These data support the urgency of instituting a prospective longitudinal surveillance program for monitoring safety events related to aortic stent grafts.

Ischemic stroke and cranial radiotherapy may induce brain inflammatory response, oxidative stress, apoptosis and neuronal loss, and impairment of neurogenesis.

Apparent Treatment Resistant Hypertension Associated Lifetime Cardiovascular Risk in a Longitudinal National Registry.

Apparent treatment resistant hypertension (aRH), wherein blood pressure elevation requires treatment with multiple medications, is associated with adverse cardiovascular events over the short-term. We sought to evaluate the degree of excess risk associated with aRH across the lifespan. We identified all individuals with hypertension who were prescribed at least 1 anti-hypertensive medication from the FinnGen Study, a cohort of randomly selected individuals across Finland. We then identified the maximum number of concurrently prescribed anti-hypertensive medication classes prior to age 55 and classified those co-prescribed ≥4 anti-hypertensive medication classes as apparent treatment resistant hypertensives. Using multivariable adjusted Cox proportional hazards models, we assessed the association of aRH well as the number of co-prescribed anti-hypertensive classes with cardiorenal outcomes across the lifespan. Among 48,721 hypertensive individuals, 5,715 (11.7%) met aRH criteria. Compared to those prescribed only 1 anti-hypertensive medication class, the lifetime risk of renal failure increased with the addition of each additional medication class, beginning with the second, while the risk of heart failure and ischemic stroke increased after addition of the third drug class. Similarly, those with aRH suffered increased risk of renal failure (Hazard Ratio 2.30, 95% CI 2.00-2.65), intracranial hemorrhage (1.50, 1.08-2.05), heart failure (1.40, 1.24-1.63) cardiac death (1.79, 1.45-2.21), and all-cause death (1.76, 1.52-2.04). Among individuals with hypertension, aRH that develops prior to mid-life is associated with substantially elevated cardiorenal disease risk across the lifespan. Examination of medical records from over 48,000 Finnish individuals found that the risk of future adverse medical events increased with a need for greater number of blood pressure medications in middle-age. Using the number of blood pressure medications simultaneously prescribed before age 55, the risk of kidney problems increased with the addition of each antihypertensive medication, starting after the first, while the risk of heart failure and stroke increased with the addition of 2 more blood pressure medications. Individuals with very difficult to treat high blood pressure (needing at least 4 medications) had greater risk of nearly all assessed clinical outcomes, including death. These findings indicate that needing more medications to treat blood pressure in midlife is associated with worse clinical outcomes. The most important goal for such patients should be to improve their blood pressure control early in life.

Adjusting to life after pediatric stroke A qualitative study.

To examine adjustment after stroke in adolescence from the perspective of affected young people. Fourteen participants (10 female) aged 13 to 25 years with a history of ischemic or hemorrhagic stroke in adolescence participated in one-on-one semi-structured interviews at the Hospital for Sick Children, Toronto, Canada. Interviews were audio-recorded and transcribed verbatim. Two independent coders conducted a reflexive thematic analysis. Five themes were identified as representative of adjustment after stroke (1) Processing the story (2) Loss and challenges (3) Ive changed (4) Keys to recovery and (5) Adjustment and acceptance. This qualitative study provides medical professionals with a personal, patient-driven lens through which to better understand the challenges of adjusting to life after pediatric stroke. Findings highlight the need to provide mental health support to patients to assist them in processing their stroke and adapting to long-lasting sequelae.

Experimental animal models and evaluation techniques in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal type of cerebral stroke without effective therapy. Although clinical trials with various surgeries have been conducted, none have improved clinical outcomes compared to the current medical management for ICH. Several ICH animal models, including autologous blood injection, collagenase injection, thrombin injection, and microballoon inflation methods, have been developed to elucidate the underlying mechanisms of ICH-induced brain injury. These models could also be used for discovering new therapy for ICH preclinically. We summarize the existing ICH animal models and the evaluation parameters used to measure the disease outcomes. We conclude that these models, resembling the different aspects of ICH pathogenesis, have their advantages and disadvantages. None of the current models closely represent the severity of ICH seen in clinical settings. More appropriate models are needed to streamline ICHs clinical outcomes and be used for validating newly developed treatment protocols.

Association between bilirubin levels with incidence and prognosis of stroke A meta-analysis.

Bilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted. Studies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17. A total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference -1.33 μmolL, 95% CI -2.12 to -0.53, While our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number CRD42022374893).

Quadriceps Weakness is Associated with Neuroplastic Changes Within Specific Corticospinal Pathways and Brain Areas After Anterior Cruciate Ligament Reconstruction Theoretical Utility of Motor Imagery-Based Brain-Computer Interface Technology for Rehabilitation.

Persistent quadriceps weakness is a problematic sequela of anterior cruciate ligament reconstruction (ACLR). The purposes of this review are to summarize neuroplastic changes after ACL reconstruction provide an overview of a promising interventions, motor imagery (MI), and its utility in muscle activation and propose a framework using a brain-computer interface (BCI) to augment quadriceps activation. A literature review of neuroplastic changes, MI training, and BCI-MI technology in postoperative neuromuscular rehabilitation was conducted in PubMed, Embase, and Scopus. Combinations of the following search terms were used to identify articles quadriceps muscle, neurofeedback, biofeedback, muscle activation, motor learning, anterior cruciate ligament, and cortical plasticity. We found that ACLR disrupts sensory input from the quadriceps, which results in reduced sensitivity to electrochemical neuronal signals, an increase in central inhibition of neurons regulating quadriceps control and dampening of reflexive motor activity. MI training consists of visualizing an action, without physically engaging in muscle activity. Imagined motor output during MI training increases the sensitivity and conductivity of corticospinal tracts emerging from the primary motor cortex, which helps exercise the connections between the brain and target muscle tissues. Motor rehabilitation studies using BCI-MI technology have demonstrated increased excitability of the motor cortex, corticospinal tract, spinal motor neurons, and disinhibition of inhibitory interneurons. This technology has been validated and successfully applied in the recovery of atrophied neuromuscular pathways in stroke patients but has yet to be investigated in peripheral neuromuscular insults, such as ACL injury and reconstruction. Well-designed clinical studies may assess the impact of BCI on clinical outcomes and recovery time. Quadriceps weakness is associated with neuroplastic changes within specific corticospinal pathways and brain areas. BCI-MI shows strong potential for facilitating recovery of atrophied neuromuscular pathways after ACLR and may offer an innovative, multidisciplinary approach to orthopaedic care. V, expert opinion.

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A domino effect is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Repetitive Transcranial Magnetic Stimulation and Rehabilitation Therapy for Upper Limb Hemiparesis in Stroke Patients A Narrative Review.

Recent technological advances in non-invasive brain stimulation (NIBS) have led to the development of therapies for post-stroke upper extremity paralysis. Repetitive transcranial magnetic stimulation (rTMS), a NIBS technique, controls regional activity by non-invasively stimulating selected areas of the cerebral cortex. The therapeutic principle by which rTMS is thought to work is the correction of interhemispheric inhibition imbalances. The guidelines for rTMS for post-stroke upper limb paralysis have graded it as a highly effective treatment, and, based on functional brain imaging and neurophysiological testing, it has been shown to result in progress toward normalization. Our research group has published many reports showing improvement in upper limb function after administration of the NovEl Intervention Using Repetitive TMS and intensive one-to-one therapy (NEURO), demonstrating its safety and efficacy. Based on the findings to date, rTMS should be considered as a treatment strategy based on a functional assessment of the severity of upper extremity paralysis (Fugl-Meyer Assessment), and NEURO should be combined with pharmacotherapy, botulinum treatment, and extracorporeal shockwave therapy to maximize therapeutic effects. In the future, it will be important to establish tailormade treatments in which stimulation frequency and sites are adjusted according to the pathological conditions of interhemispheric imbalance, as revealed by functional brain imaging.

Flavonoid intake is associated with lower all-cause and disease-specific mortality The National Health and Nutrition Examination Survey 2007-2010 and 2017-2018.

Adequate intake of flavonoids may influence mortality, particularly of heart and cerebrovascular diseases. However, the importance of each flavonoid and its subclasses in preventing all-cause and disease-specific mortalities remain unclear. In addition, it is unknown which population groups would benefit from high flavonoid intake. Therefore, personalized mortality risk based on flavonoid intake needs to be estimated. The association between flavonoid intake and mortality among 14,029 participants in the National Health and Nutrition Examination Survey was examined using Cox proportional hazards analysis. A prognostic risk score and nomogram linking flavonoid intake and mortality were constructed. During a median follow-up of 117 months (9.75 years), 1,603 incident deaths were confirmed. Total flavonol intake was associated with a significantly reduced all-cause mortality multivariable adjusted hazard ratio HR (95% confidence interval CI), 0.87 (0.81, 0.94),

Predictive discriminative accuracy of walking abilities at discharge for community ambulation levels at 6 months post-discharge among inpatients with subacute stroke.

Purpose This study aimed to compare the predictive accuracy of walking ability at discharge among subacute stroke inpatients at 6 months post-discharge in terms of community ambulation level and establish optimal cut-off values. Participants and Methods This prospective observational study included 78 patients who completed follow-up assessments. Patients were classified into three groups based on the Modified Functional Walking Category (householdmost limited community walkers, least limited community walkers, and unlimited community walkers) obtained by telephone survey at 6 months post-discharge. Predictive accuracy and cut-off values for discriminating among groups were calculated from 6-minute walking distance and comfortable walking speed measured at the time of discharge using receiver operating characteristic curves. Results Between householdmost limited and least limited community walkers, 6-minute walking distance and comfortable walking speed offered similar predictive accuracy (area under the curve, 0.6-0.7), with cut-off values of 195 m and 0.56 ms, respectively. Between least limited and unlimited community walkers, the areas under the curve were 0.896 for 6-minute walking distance and 0.844 for comfortable walking speed, with cut-off values of 299 m and 0.94 ms, respectively. Conclusion Walking endurance and walking speed among inpatients with subacute stroke provided superior predictive accuracy for unlimited community walkers at 6 months post-discharge.

Brain regions associated with Brunnstrom and functional independence measure scores in patients after a stroke a tract-based spatial statistics study.

Purpose We aimed to assess diffusion tensor fractional anisotropy to outline the brain regions associated with the long-term motor and cognitive functional outcomes of patients with stroke. Participants and Methods Eighty patients from our previous study were enrolled. Fractional anisotropy maps were acquired on days 14-21 after stroke onset, and tract-based spatial statistics were applied. Outcomes were scored using the Brunnstrom recovery stage and Functional Independence Measure motor and cognition components. Fractional anisotropy images were assessed in relation to outcome scores using the general linear model. Results For both the right (n37) and left (n43) hemisphere lesion groups, the corticospinal tract and the anterior thalamic radiation were most strongly associated with the Brunnstrom recovery stage. In contrast, the cognition component involved large regions encompassing the anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, cingulum bundle, forceps major, and forceps minor. The results for the motor component were intermediate between those for the Brunnstrom recovery stage and those for the cognition component. Conclusion Motor-related outcomes were associated with fractional anisotropy decreases in the corticospinal tract, whereas cognitive outcomes were related to broad regions of association and commissural fibers. This knowledge will help scheduling appropriate rehabilitative treatments.

Predictive factors for walking in acute stroke patients a multicenter study using classification and regression tree analysis.

Purpose Walking ability should be predicted as early as possible in acute stroke patients. The purpose is to construct a prediction model for independent walking from bedside assessments using classification and regression tree analysis. Participants and Methods We conducted a multicenter case-control study with 240 stroke patients. Survey items included age, gender, injured hemisphere, the National Institute of Health Stroke Scale, the Brunnstrom Recovery Stage for lower extremities, and turn over from a supine position from the Ability for Basic Movement Scale. The National Institute of Health Stroke Scale items, such as language, extinction, and inattention, were grouped under higher brain dysfunction. We used the Functional Ambulation Categories to classify patients into independent (four or more the Functional Ambulation Categories n120) and dependent (three or fewer the Functional Ambulation Categories n120) walking groups. A classification and regression tree analysis was used to create a model to predict independent walking. Results The Brunnstrom Recovery Stage for lower extremities, turn over from a supine position from the Ability for Basic Movement Scale, and higher brain dysfunction were the splitting criteria for classifying patients into four categories Category 1 (0%), severe motor paresis Category 2 (10.0%), mild motor paresis and could not turn over Category 3 (52.5%), with mild motor paresis, could turn over, and had higher brain dysfunction and Category 4 (82.5%), with mild motor paresis, could turn over, and no higher brain dysfunction. Conclusion We constructed a useful prediction model for independent walking based on the three criteria.

Musician Conserved Absolute Pitch Ability Despite a Right Parietal Subcortical Hemorrhage.

Absolute pitch (AP) can identify and designate the pitch chroma of a particular tone without using any external references. Unknown neurological mechanisms underlie it. We report the case of a 53-year-old AP musician who developed a right parietal hemorrhage but conserved AP ability. Our case had a lesion in the right parietal lobe that did not affect her AP ability. Our case further supports the hypothesis that the left cerebral hemisphere is important for AP ability.

Recurrent Transient Ischemic Attacks and Stroke Due to Carotid Dissection During Air Travel A Case Report.

Carotid artery dissection causes 2.5% of ischemic acute strokes and is more common in younger rather than older patients. Extracranial lesions often manifest as transient and reversible neurological deficits until a stroke occurs. In this case, we describe a 60-year-old male patient with no known cardiovascular risk factors who experienced three transient ischemic attacks (TIAs) in four days while traveling in Portugal. At the emergency department, he was treated for an occipital headache associated with nausea and two episodes of decreased left upper-limb muscle strength lasting two to three minutes with spontaneous recovery. He requested discharge against medical advice so that he could travel home. During the return flight, he had a severe right parietal headache followed by decreased muscle strength in the left arm. After an emergency landing in Lisbon, he was referred to the local emergency department, where his neurological examination revealed preferential gaze to the right exceeding the midline, left homonymous hemianopsia, minor left central facial paresis, and spastic left brachial paresis. On the National Institutes of Health Stroke Scale, he scored 7. A head CT was performed, showing no acute vascular lesions (i.e., Alberta Stroke Program Early CT Score of 10). However, an image compatible with dissection was identified on CT angiography of the head and neck and confirmed by digital subtraction angiography. The patient underwent balloon angioplasty and placement of three stents in the right internal carotid artery with vascular permeabilization. This case highlights how prolonged and incorrect cervical posture and microtrauma secondary to aircraft turbulence may be associated with carotid artery dissection in predisposed individuals. The Aerospace Medical Association guidelines advocate that patients with a recent acute neurological event should avoid air travel until clinical stability is assured. As TIA is considered a harbinger of stroke, patients should be properly evaluated and avoid air travel for at least two days after the event.

Corrigendum Network pharmacology and experimental study of phenolic acids in salvia miltiorrhiza bung in preventing ischemic stroke.

This corrects the article DOI 10.3389fphar.2023.1108518..

Effect and Mechanism of Traditional Chinese Medicine Exercise Therapy on Stroke Recovery.

Stroke is currently the second largest contributor to disability-adjusted life years (DALYs) in developing countries, and it is the third largest contributor to DALYs in developed countries. It requires a large number of resources from the health care system every year, which places a great burden on society, families, and individuals. The treatment of traditional Chinese medicine exercise therapy (TCMET) during stroke recovery has become a hot topic of current research due to its few adverse events and high efficiency. This article sorts out the latest progress of TCMET on the recovery of stroke through the review method and explores its role and mechanism based on existing clinical and experimental studies. TCMET treatment of stroke recovery mainly includes Tai Chi, Baduanjin, Daoyin, Yi Jin Jing, five-fowl play, and six-character tips, which can effectively improve motor function, balance and coordination ability, cognitive dysfunction, nerve function, depression or emotional state, daily living ability, and so on after stroke. The mechanisms of stroke treated by TCMET are discussed, and deficiencies in the literature are discussed and analyzed. It is hoped that some guiding suggestions will be provided for future clinical treatment and experimental studies.

Neurological consequences of SARS-CoV-2 infections in the pediatric population.

COVID-19 in the pediatric population is mostly asymptomatic. However, 1 out of 5 children presents non-specific neurologic symptoms such as headache, weakness, or myalgia. Furthermore, rarer forms of neurological diseases are increasingly being described in association to a SARS-CoV-2 infection. Encephalitis, stroke, cranial nerves impairment, Guillain-Barré syndrome or acute transverse myelitis have been reported and account for around 1% of pediatric COVID-19 cases. Some of these pathologies may occur during or after the SARS-CoV-2 infection. The pathophysiological mechanisms range from direct invasion of the central nervous system (CNS) by SARS-CoV-2 itself to postinfectious immune-mediated CNS inflammation. In most cases, patients presenting neurological pathologies related to SARS-CoV-2 infection are at greater risk of life-threatening complications and should be closely monitored. Further studies are needed to acknowledge the potential long-term neurodevelopmental consequences of the infection.

CPAP for secondary cardiovascular prevention in obstructive sleep apnoea patients not only one moon, but many stars.

While continuous positive airway pressure (CPAP) therapy has a strong evidence base for the treatment of obstructive sleep apnoea (OSA), its impact on cardiovascular comorbidity remains unclear. This journal club reviews three recent randomised controlled trials aimed to evaluate the impact of CPAP therapy in secondary prevention of cerebrovascular and coronary heart disease (SAVE trial), comorbid coronary heart disease (RICCADSA trial) and in patients admitted with acute coronary syndrome (ISAACC trial). All three trials included patients with moderate-to-severe OSA and excluded patients with severe daytime sleepiness. When CPAP was compared with usual care, they all reported no difference in a similar primary composite end-point including death from cardiovascular disease, cardiac events, and strokes. These trials faced the same methodological challenges, including a low primary end-point incidence, the exclusion of sleepy patients, and a low CPAP adherence. Therefore, caution must be taken when broadening their results to the wider OSA population. Although randomised controlled trials provide a high level of evidence, they may not be sufficient to capture the diversity of OSA. Large-scale, real-world data may be able to provide a more rounded and generalisable picture of the effects of routine clinical use of CPAP on cardiovascular morbimortality.

Pediatric Moyamoya Syndrome Secondary to Tuberculous Meningitis A Case Report.

Tuberculosis is uncommon in the United States and a rare cause of meningitis in children with severe neurologic consequences. Tuberculous meningitis (TBM) is an even rarer cause of moyamoya syndrome with only a handful of cases previously reported. We report the case of a female patient who initially presented at 6 years of age with TBM and developed moyamoya syndrome requiring revascularization surgery. She was found to have basilar meningeal enhancement and right basal ganglia infarcts. She was treated with 12 months of antituberculosis therapy and 12 months of enoxaparin and maintained on daily aspirin indefinitely. However, she developed recurrent headaches and transient ischemic attacks and was found to have progressive bilateral moyamoya arteriopathy. At age 11 years, she underwent bilateral pial synangiosis for the treatment of her moyamoya syndrome. Moyamoya syndrome is a rare but serious sequalae of TBM and may be more common in pediatric patients. The risk of stroke may be mitigated by pial synangiosis or other revascularization surgeries in carefully selected patients.

Carotid Intimal Sarcoma Presenting as Large Vessel Occlusion and Diagnosed by Embolus Histopathology Case Report.

The objective of this study was to present the clinical, histopathologic, and radiographic findings of a unique case of intimal sarcoma (IS) embolus presenting as a large vessel occlusion causing an ischemic stroke without a detectable primary tumor site. Extensive examinations, multimodal imaging, laboratory testing, and histopathologic analysis were used in evaluation. We report the case of a patient who presented with acute embolic ischemic stroke and was found to have IS based on a histopathologic evaluation of his embolectomy specimen. Subsequent comprehensive imaging studies failed to detect a primary tumor site. Multidisciplinary interventions including a course of radiotherapy were performed. The patient died of recurrent multifocal strokes 92 days after diagnosis. Meticulous histopathologic analysis should be conducted on cerebral embolectomy specimens. Histopathology may be useful in diagnosing IS.

Sequential Gaze-Shifting Approach to Reconstruct Self-portrait and Daily Activities in Hemispatial Neglect After Stroke A Case Report.

The aim of this study was to demonstrate the use of a sequential gaze-shifting approach to complete a self-portrait in a patient with hemispatial neglect after stroke as a means of rehabilitation to restore skills to perform activities of daily living (ADL). This case report describes a 71-year-old amateur painter who presented with severe left hemispatial neglect after stroke. Initially, he drew self-portraits omitting the left side. Six months poststroke, the patient was able to complete well-composed self-portraits by sequentially shifting his gaze and intentionally directing his visual attention from the right non-neglected space to the left neglected space. Then the patient was instructed to repeatedly practice a serial movement of each ADL using this sequential gaze-shifting technique. Seven months poststroke, the patient achieved independence in ADL such as dressing the upper body, grooming, eating, and toileting although moderate hemispatial neglect and hemiparesis were still present. The effects of existing rehabilitation approaches can be difficult to generalize and apply to the performance of each individual ADL in patients with hemispatial neglect after stroke. Sequential gaze shifting may be a viable compensation strategy in directing attention to the neglected space and restoring the ability to perform each ADL.

Practice Current Variability in Smoking Cessation Intervention Practice Patterns After Ischemic Stroke and Transient Ischemic Attack.

People who continue to smoke after ischemic stroke and transient ischemic attack (TIA) are at increased risk for subsequent stroke and cardiovascular events. Although effective smoking cessation strategies exist, smoking rates after stroke remain high. Through case-based discussions with 3 international vascular neurology panelists, this article seeks to explore practice patterns and barriers to smoking cessation for patients with strokeTIA. We sought to answer these questions What are the barriers to using smoking cessation interventions for patients with strokeTIA Which interventions are most used for hospitalized patients with strokeTIA Which interventions are most used for patients who continue smoking during follow-up Our synthesis of panelists commentaries is complemented by the preliminary results of an online survey posed to global readership. Together, the interviews and survey results identify practice variability and barriers to smoking cessation after strokeTIA, suggesting that there is substantial need for research and standardization.

Enrollment of Participants From Marginalized Racial and Ethnic Groups A Comparative Assessment of the STEADY-PD III and SURE-PD3 Trials.

Representation of persons from marginalized racial and ethnic groups in Parkinson disease (PD) trials has been low, limiting the generalizability of therapeutic options for individuals with PD. Two large phase 3 randomized clinical trials sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), STEADY-PD III and SURE-PD3, screened participants from overlapping Parkinson Study Group clinical sites under similar eligibility criteria but differed in participation by underrepresented minorities. The goal of this research is to compare recruitment strategies of PD participants belonging to marginalized racial and ethnic groups. A total of 998 participants with identified race and ethnicity consented to STEADY-PD III and SURE-PD3 from 86 clinical sites. Demographics, clinical trial characteristics, and recruitment strategies were compared. NINDS imposed a minority recruitment mandate on STEADY-PD III but not SURE-PD3. Ten percent of participants who consented to STEADY-PD III self-identified as belonging to marginalized racial and ethnic groups compared to 6.5% in SURE-PD3 (difference 3.9%, 95% confidence interval CI 0.4%-7.5%, Although both trials targeted similar participants, STEADY-PD III was able to consent and recruit a higher percentage of patients from racial and ethnic marginalized groups. Possible reasons include differential incentives for achieving minority recruitment goals. This study used data from The Safety, Tolerability, and Efficacy Assessment of Isradipine for Parkinson Disease (STEADY-PD III NCT02168842) and the Study of Urate Elevation in Parkinsons Disease (SURE-PD3 NCT02642393).

Exploring Stroke Risk Factors and Outcomes in Sexual and Gender Minority People.

Cerebrovascular disease in sexual and gender minority (SGM) people remains poorly understood. Our primary objective was to describe the epidemiology and outcomes in a sample of SGM people with stroke. As a secondary objective, we compared this group with non-SGM people with stroke to assess for significant differences in risk factors or outcomes. This was a retrospective chart review study of SGM people admitted to an urban stroke center with primary diagnosis of stroke (ischemic or hemorrhagic). We evaluated stroke epidemiology and outcomes, summarizing with descriptive statistics. We then matched 1 SGM person to 3 non-SGM people by year of birth and year of diagnosis to compare demographics, risk factors, inpatient stroke metrics, and outcomes. A total of 26 SGM people were included in the analysis 20 (77%) had ischemic strokes, 5 (19%) intracerebral hemorrhages, and 1 (4%) subarachnoid hemorrhage. Compared with non-SGM people (n 78), stroke subtypes showed a similar distribution (64 (82%) ischemic strokes, 12 (15%) intracerebral hemorrhages, 1 (1%) subarachnoid hemorrhage, and 1 nontraumatic subdural hematoma, SGM people may have different risk factors, different mechanisms of stroke, and higher risk of recurrent stroke compared with non-SGM people. Standardized collection of sexual orientation and gender identity would enable larger studies to further understand disparities, leading to secondary prevention strategies.

If Time is Neuron, What Are We Waiting for

Stroke Thrombolysis Beating the Clock.

Recombinant tissue plasminogen activator (rtPA) has revolutionized the management of acute ischemic stroke. Shorter door-to-imaging and door-to-needle (DTN) times are crucial for improving the outcomes in thrombolysed patients. Our observational study evaluated the door-to-imaging time (DIT) and DTN times for all thrombolysed patients. The study was a cross-sectional observational study over a period of 18 months at a tertiary care teaching hospital and included 252 acute ischemic stroke patients of which 52 underwent thrombolysis with rtPA. The time intervals between arrival to neuroimaging and initiation of thrombolysis were noted. Of the total patients thrombolysed, only 10 patients underwent neuroimaging non-contrast computed tomography (NCCT) head with MRI brain screen within 30 minutes of their arrival in the hospital, 38 patients within 30-60 minutes and 2 each within the 61-90 and 91-120 minute time frames. The DTN time was 30-60 minutes for 3 patients, while 31 patients were thrombolysed within 61-90 minutes, 7 patients within 91-120 minutes, while 5 each took 121-150 and 151-180 minutes for the same. One patient had a DTN between 181 and 210 minutes. Most patients included in the study underwent neuroimaging within 60 minutes and subsequent thrombolysis within 60-90 minutes of their arrival in the hospital. But the time frames did not meet the recommended ideal intervals, and further streamlining of stroke management is needed even at tertiary care centers in India. Shah A, Diwan A. Stroke Thrombolysis Beating the Clock. Indian J Crit Care Med 202327(2)107-110.

Incidence of Parkinsons disease and modifiable risk factors in Korean population A longitudinal follow-up study of a nationwide cohort.

We aimed to investigate the incidence of Parkinsons disease (PD) by age and year for each sex as well as the modifiable risk factors for PD. Using data from the Korean National Health Insurance Service, 938,635 PD and dementia-free participants aged ≥40 years who underwent general health examinations were followed to December 2019. We analyzed the PD incidence rates according to age, year and sex. To investigate the modifiable risk factors for PD, we used the Cox regression model. Additionally, we calculated the population-attributable fraction to measure the impact of the risk factors on PD. During follow-up, 9,924 of the 938,635 (1.1%) participants developed PD. The incidence of PD increased continuously from 2007 to 2018, reaching 1.34 per 1,000 person-years in 2018. The incidence of PD also increases with age, up to 80 y. Presence of hypertension (SHR 1.09, 95% CI 1.05 to 1.14), diabetes (SHR 1.24, 95% CI 1.17 to 1.31), dyslipidemia (SHR 1.12, 95% CI 1.07 to 1.18), ischemic stroke (SHR 1.26, 95% CI 1.17 to 1.36), hemorrhagic stroke (SHR 1.26, 95% CI 1.08 to 1.47), ischemic heart disease (SHR 1.09, 95% CI 1.02 to 1.17), depression (SHR 1.61, 95% CI 1.53 to 1.69), osteoporosis (SHR 1.24, 95% CI 1.18 to 1.30), and obesity (SHR 1.06, 95% CI 1.01 to 1.10) were independently associated with a higher risk for PD. Our results highlight the effect of modifiable risk factors for PD in the Korean population, which will help establish health care policies to prevent the development of PD.

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery.

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively.

Intensive Systolic Blood Pressure Treatment Remodels Brain Perivascular Spaces A Secondary Analysis of SPRINT.

Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. This is a secondary analysis of the Systolic PRessure INTervention (SPRINT) Trial MRI Substudy a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs. < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). For 610 participants with sufficient quality MRI at baseline (mean age 67±8, 40% female, 32% black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median 3.9 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient -0.029 -0.055 to -0.0029 p0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB) and diuretics. Intensive SBP lowering partially reverses PVS enlargement. The effects of CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. Clincaltrials.gov NCT01206062.

Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke.

Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations. Assess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT. The HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD. Net gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations. To increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.

Genetic variation supports a causal role for valproate in prevention of ischemic stroke.

Valproate is a candidate for ischemic stroke prevention due to its anti-atherosclerotic effects in vivo. Although valproate use is associated with decreased ischemic stroke risk in observational studies, confounding by indication precludes causal conclusions. To overcome this limitation, we applied Mendelian randomization to determine whether genetic variants that influence seizure response among valproate users associate with ischemic stroke risk in the UK Biobank (UKB). Using independent genome-wide association data of seizure response after valproate intake from the EpiPGX consortium, a genetic score for valproate response was derived. Valproate users were identified from UKB baseline and primary care data, and the association of the genetic score with incident and recurrent ischemic stroke was tested in Cox proportional hazard models. Among 2,150 valproate users (mean 56 years, 54% females), 82 ischemic strokes occurred over a mean 12-year follow-up. A higher genetic score was associated with an increased effect of valproate dose on serum valproate levels (0.48 µgml per 100mgday per one SD, 95%CI0.28, 0.68). After adjusting for age and sex, a higher genetic score was associated with lower ischemic stroke risk (HR per one SD 0.73, 0.58, 0.91) with a halving of absolute risk in the highest compared to the lowest score tertile (4.8% vs 2.5%, p-trend0.027). In the 194 valproate users with prevalent stroke at baseline, a higher genetic score was associated with lower recurrent ischemic stroke risk (HR per one SD 0.53, 0.32, 0.86) with reduced absolute risk in the highest compared to the lowest score tertile (351, 5.9% vs. 1371, 18.3%, p-trend0.026). The genetic score was not associated with ischemic stroke among the 427,997 valproate non-users (p0.61), suggesting minimal contribution of pleiotropic effects from included genetic variants. Among valproate users, genetically predicted favorable seizure response to valproate was associated with higher serum valproate levels and reduced ischemic stroke risk, providing causal support for valproate utility in ischemic stroke prevention. The strongest effect was found for recurrent ischemic stroke, suggesting potential dual-use benefits of valproate for post-stroke epilepsy. Clinical trials are warranted to identify populations that may benefit most from valproate for stroke prevention.

Stroke in hemodialysis patients and its association with CHA

In the general population, the CHA This is a retrospective study including all HD patients treated between January 2010 and December 2019 in two Lebanese dialysis facilities. Exclusion criteria are patients younger than 18 years old and patients with a dialysis vintage less than 6 months. A total of 256 patients were included (66.8% men mean age 69.3 ± 13.9 years). The CHA In HD patients, CHA

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST) a multicentre, double-blinded, randomised, placebo-controlled trial.

People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference -0.17, 95% CI -0.52 to 0.17, p 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. The British Heart Foundation and the UK Stroke Association.

SCORE2 cardiovascular risk prediction models in an ethnic and socioeconomic diverse population in the Netherlands an external validation study.

Socioeconomic status and ethnicity are not explicitly incorporated as risk factors in the four SCORE2 cardiovascular disease (CVD) risk models developed for country-wide implementation across Europe (low, moderate, high and very-high model). The aim of this study was to evaluate the performance of the four SCORE2 CVD risk prediction models in an ethnic and socioeconomic diverse population in the Netherlands. The SCORE2 CVD risk models were externally validated in socioeconomic and ethnic (by country of origin) subgroups, from a population-based cohort in the Netherlands, with GP, hospital and registry data. In total 155,000 individuals, between 40 and 70 years old in the study period from 2007 to 2020 and without previous CVD or diabetes were included. Variables (age, sex, smoking status, blood pressure, cholesterol) and outcome first CVD event (stroke, myocardial infarction, CVD death) were consistent with SCORE2. 6966 CVD events were observed, versus 5495 events predicted by the CVD low-risk model (intended for use in the Netherlands). Relative underprediction was similar in men and women (observedpredicted (OE-ratio), 1.3 and 1.2 in men and women, respectively). Underprediction was larger in low socioeconomic subgroups of the overall study population (OE-ratio 1.5 and 1.6 in men and women, respectively), and comparable in Dutch and the combined other ethnicities low socioeconomic subgroups. Underprediction in the Surinamese subgroup was largest (OE-ratio 1.9, in men and women), particularly in the low socioeconomic Surinamese subgroups (OE-ratio 2.5 and 2.1 in men and women). In the subgroups with underprediction in the low-risk model, the intermediate or high-risk SCORE2 models showed improved OE-ratios. Discrimination showed moderate performance in all subgroups and the four SCORE2 models, with C-statistics between 0.65 and 0.72, similar to the SCORE2 model development study. The SCORE 2 CVD risk model for low-risk countries (as the Netherlands are) was found to underpredict CVD risk, particularly in low socioeconomic and Surinamese ethnic subgroups. Including socioeconomic status and ethnicity as predictors in CVD risk models and implementing CVD risk adjustment within countries is desirable for adequate CVD risk prediction and counselling. Leiden University Medical Centre and Leiden University.

Stroke risk prediction by color Doppler ultrasound of carotid artery-based deep learning using Inception V3 and VGG-16.

This study aims to automatically classify color Doppler images into two categories for stroke risk prediction based on the carotid plaque. The first category is high-risk carotid vulnerable plaque, and the second is stable carotid plaque. In this research study, we used a deep learning framework based on transfer learning to classify color Doppler images into two categories one is high-risk carotid vulnerable plaque, and the other is stable carotid plaque. The data were collected from the Second Affiliated Hospital of Fujian Medical University, including stable and vulnerable cases. A total of 87 patients with risk factors for atherosclerosis in our hospital were selected. We used 230 color Doppler ultrasound images for each category and further divided those into the training set and test set in a ratio of 70 and 30%, respectively. We have implemented Inception V3 and VGG-16 pre-trained models for this classification task. Using the proposed framework, we implemented two transfer deep learning models Inception V3 and VGG-16. We achieved the highest accuracy of 93.81% by using fine-tuned and adjusted hyperparameters according to our classification problem. In this research, we classified color Doppler ultrasound images into high-risk carotid vulnerable and stable carotid plaques. We fine-tuned pre-trained deep learning models to classify color Doppler ultrasound images according to our dataset. Our suggested framework helps prevent incorrect diagnoses caused by low image quality and individual experience, among other factors.

Telestroke networks for area-wide access to endovascular stroke treatment.

Endovascular therapy (EVT) offers a highly effective therapy for patients with acute ischemic stroke due to large vessel occlusion. Comprehensive stroke centers (CSC) are required to provide permanent accessibility to EVT. However, when affected patients are not located in the immediate catchment area of a CSC, i.e. in rural or structurally weaker areas, access to EVT is not always ensured. Telestroke networks play a crucial role in closing this healthcare coverage gap and thereby support specialized stroke treatment. The aim of this narrative review is to elaborate the concepts for the indication and transfer of EVT candidates via telestroke networks in acute stroke care. The targeted readership includes both comprehensive stroke centers and peripheral hospitals. The review is intended to identify ways to design care beyond those areas with narrow access to stroke unit care to provide the indicated highly effective acute therapies on a region-wide basis. Here, the two different models of care mothership and drip-and-ship concerning rates of EVT and its complications as well as outcomes are compared. Decisively, forward-looking new model approaches such as a third model the flyingdriving interentionalists are introduced and discussed, as far as few clinical trials have investigated these approaches. Diagnostic criteria used by the telestroke networks to enable appropriate patient selection for secondary intrahospital emergency transfers are displayed, which need to meet the criteria in terms of speed, quality and safety. The few findings from the studies with telestroke networks are neutral for comparison in the drip-and-ship and mothership models. Supporting spoke centres through telestroke networks currently seems to be the best option for offering EVT to a population in structurally weaker regions without direct access to a CSC. Here, it is essential to map the individual reality of care depending on the regional circumstances.

Construct of qualitative diagnostic biomarkers specific for glioma by pairing serum microRNAs.

Serum microRNAs (miRNAs) are promising non-invasive biomarkers for diagnosing glioma. However, most reported predictive models are constructed without a large enough sample size, and quantitative expression levels of their constituent serum miRNAs are susceptible to batch effects, decreasing their clinical applicability. We propose a general method for detecting qualitative serum predictive biomarkers using a large cohort of miRNA-profiled serum samples (n 15,460) based on the within-sample relative expression orderings of miRNAs. Two panels of miRNA pairs (miRPairs) were developed. The first was composed of five serum miRPairs (5-miRPairs), reaching 100% diagnostic accuracy in three validation sets for distinguishing glioma and non-cancer controls (n 436 glioma 236, non-cancers 200). An additional validation set without glioma samples (non-cancers 2611) showed a predictive accuracy of 95.9%. The second panel included 32 serum miRPairs (32-miRPairs), reaching 100% diagnostic performance in training set on specifically discriminating glioma from other cancer types (sensitivity 100%, specificity 100%, accuracy 100%), which was reproducible in five validation datasets (n 3387 glioma 236, non-glioma cancers 3151, sensitivity> 97.9%, specificity> 99.5%, accuracy> 95.7%). In other brain diseases, the 5-miRPairs classified all non-neoplastic samples as non-cancer, including stroke (n 165), Alzheimers disease (n 973), and healthy samples (n 1820), and all neoplastic samples as cancer, including meningioma (n 16), and primary central nervous system lymphoma samples (n 39). The 32-miRPairs predicted 82.2 and 92.3% of the two kinds of neoplastic samples as positive, respectively. Based on the Human miRNA tissue atlas database, the glioma-specific 32-miRPairs were significantly enriched in the spinal cord (p 0.013) and brain (p 0.015). The identified 5-miRPairs and 32-miRPairs provide potential population screening and cancer-specific biomarkers for glioma clinical practice.

Development and validation of a clinical nomogram for differentiating hemorrhagic and ischemic stroke prehospital.

The early detection and identification of stroke are essential to the prognosis of patients with suspected stroke symptoms out-of-hospital. We aimed to develop a risk prediction model based on the FAST score to identify the different types of strokes early for emergency medical services (EMS). This retrospective observational study enrolled 394 stroke patients at a single center from January 2020 to December 2021. Demographic data, clinical characteristics, and stroke risk factors with patients were collected from the EMS record database. Univariate and multivariate logistic regression analysis was used to identify the independent risk predictors. The nomogram was developed based on the independent predictors, in which the discriminative value and calibration of the nomogram were verified by the receiver operator characteristic (ROC) curve and calibration plots. A total of 31.90% (88276) of patients were diagnosed with hemorrhagic stroke in the training set, while 36.40% (43118) in the validation set. The nomogram was developed based on the multivariate analysis, including age, systolic blood pressure, hypertension, vomiting, arm weakness, and slurred speech. The area under the curve (AUC) of the ROC with nomogram was 0.796 (95% CI 0.740-0.852, P < 0.001) and 0.808 (95% CI0.728-0.887, P < 0.001) in the training set and validation set, respectively. In addition, the AUC with the nomogram was superior to the FAST score in both two sets. The calibration curve showed a good agreement with the nomogram and the decision curves analysis also demonstrated that the nomogram had a wider range of threshold probabilities than the FAST score in the prediction risk of hemorrhagic stroke. This novel noninvasive clinical nomogram shows a good performance in differentiating hemorrhagic and ischemic stroke for EMS staff prehospital. Moreover, all of the variables of nomogram are acquired in clinical practice easily and inexpensively out-of-hospital.

Clustering of serum biomarkers involved in post-aneurysmal subarachnoid hemorrhage (aSAH) complications.

Post-aSAH sequela is characterized by the onset of life-threatening complications along with the upregulated underlying inflammation. Cerebral vasospasm (CVS) is one of the most frequent complication after aSAH, which contributes majorly to delayed cerebral ischemia and poor clinical outcome. The objective of this study was to identify the clusters of serum biomarkers that are associated with cerebral vasospasm (CVS) after suffering from aneurysmal subarachnoid hemorrhage (aSAH). In this single-center study, serum concentrations of 10 potential biomarkers, together with clinical and demographic parameters, for 66 aSAH patients were recorded within 24 h after aSAH. The dataset was split into a training set (43 patients) and a validation set. Correlation heatmaps for both datasets were computed. Variables with inconsistent correlations on the two subsets were excluded. Clusters of relevant biomarkers were identified on the complete set, separately for patients who developed post-aSAH CVS and those who did not. Two clusters were found to be specific for patients who suffered from CVS mitochondrial gene fragments (cytochrome B (Cyt-B), cytochrome C oxidase subunit-1 (Cox-1), displacement loop (D-loop), and IL-23, and the other one, containing IL-6, IL-10, age, and Hunt and Hess score. Clusters of serum biomarkers, analyzed within 24 h of the onset of aSAH, days before the CVS development, are expressed differently in patients suffering from post-aSAH CVS, compared to patients without CVS. This suggests that these biomarkers may be involved in the pathophysiological processes leading to CVS and may be used as its early predictors. These interesting findings are potentially highly relevant for the management of CVS and call for validation on a larger sample of patients.

P-selectin-targeted nanocarriers induce active crossing of the blood-brain barrier via caveolin-1-dependent transcytosis.

Medulloblastoma is the most common malignant paediatric brain tumour, with 30% mediated by Sonic hedgehog signalling. Vismodegib-mediated inhibition of the Sonic hedgehog effector Smoothened inhibits tumour growth but causes growth plate fusion at effective doses. Here, we report a nanotherapeutic approach targeting endothelial tumour vasculature to enhance blood-brain barrier crossing. We use fucoidan-based nanocarriers targeting endothelial P-selectin to induce caveolin-1-dependent transcytosis and thus nanocarrier transport into the brain tumour microenvironment in a selective and active manner, the efficiency of which is increased by radiation treatment. In a Sonic hedgehog medulloblastoma animal model, fucoidan-based nanoparticles encapsulating vismodegib exhibit a striking efficacy and marked reduced bone toxicity and drug exposure to healthy brain tissue. Overall, these findings demonstrate a potent strategy for targeted intracranial pharmacodelivery that overcomes the restrictive blood-brain barrier to achieve enhanced tumour-selective penetration and has therapeutic implications for diseases within the central nervous system.

Relationship between health literacy and physical function of patients participating in phase I cardiac rehabilitation a multicenter clinical study.

Health literacy (HL) is an important decision factor for health. Both low HL and low physical function cause adverse events in cardiovascular disease patients, but their relationship is not well documented. To clarify the relationship between HL and physical function of patients participating in cardiac rehabilitation and calculate the cutoff value of the 14-item HL scale (HLS) for low handgrip strength, this multicenter clinical study named the Kobe-Cardiac Rehabilitation project for people around the World (K-CREW) was conducted among four affiliated hospitals with patients who underwent cardiac rehabilitation. We used the 14-item HLS to assess HL, and the main outcomes were handgrip strength and Short Physical Performance Battery (SPPB) score. The study included 167 cardiac rehabilitation patients with a mean age of 70.5 ± 12.8 years, and the ratio of males was 74%. Among them, 90 patients (53.9%) had low HL and scored significantly lower in both handgrip strength and SPPB. Multiple linear regression analysis revealed that HL was a determinant factor (β 0.118, p 0.04) for handgrip strength. Receiver operating characteristic analysis revealed the cutoff value of the 14-item HLS for screening for low handgrip strength was 47.0 points, and the area under the curve was 0.73. This study showed that HL was significantly associated with handgrip strength and SPPB in cardiac rehabilitation patients and suggests the possibility of early screening for low HL to improve physical function in cardiac rehabilitation patients with low HL.

The medial temporal lobe supports the quality of visual short-term memory representation.

The quality of short-term memory (STM) underlies our ability to recall the exact details of a recent event, yet how the human brain enables this core cognitive function remains poorly understood. Here we use multiple experimental approaches to test the hypothesis that the quality of STM, such as its precision or fidelity, relies on the medial temporal lobe (MTL), a region commonly associated with the ability to distinguish similar information remembered in long-term memory. First, with intracranial recordings, we find that delay-period MTL activity retains item-specific STM content that is predictive of subsequent recall precision. Second, STM recall precision is associated with an increase in the strength of intrinsic MTL-to-neocortical functional connections during a brief retention interval. Finally, perturbing the MTL through electrical stimulation or surgical removal can selectively reduce STM precision. Collectively, these findings provide converging evidence that the MTL is critically involved in the quality of STM representation.

Prognosis after discontinuing renin angiotensin aldosterone system inhibitor for heart failure with restored ejection fraction after acute myocardial infarction.

Prognostic effect of discontinuing renin-angiotensin-aldosterone-system-inhibitor (RAASi) for patients with heart failure (HF) after acute myocardial infarction (AMI) whose left ventricular (LV) systolic function was restored during follow-up is unknown. To investigate the outcome after discontinuing RAASi in post-AMI HF patients with restored LV ejection fraction (EF). Of 13,104 consecutive patients from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry, HF patients with baseline LVEF < 50% that was restored to ≥ 50% at 12-month follow-up were selected. Primary outcome was a composite of all-cause death, spontaneous MI, or rehospitalization for HF at 36-month after index procedure. Of 726 post-AMI HF patients with restored LVEF, 544 maintained RAASi (Maintain-RAASi) beyond 12-month, 108 stopped RAASi (Stop-RAASi), and 74 did not use RAASi (RAASi-Not-Used) at baseline and follow-up. Systemic hemodynamics and cardiac workloads were similar among groups at baseline and during follow-up. Stop-RAASi group showed elevated NT-proBNP than Maintain-RAASi group at 36-month. Stop-RAASi group showed significantly higher risk of primary outcome than Maintain-RAASi group (11.4% vs. 5.4% adjusted hazard ratio HR

Glycolysis-enhancing α

Terazosin is an α

Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism.

Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.

Trunk training following stroke.

Previous systematic reviews and randomised controlled trials have investigated the effect of post-stroke trunk training. Findings suggest that trunk training improves trunk function and activity or the execution of a task or action by an individual. But it is unclear what effect trunk training has on daily life activities, quality of life, and other outcomes. To assess the effectiveness of trunk training after stroke on activities of daily living (ADL), trunk function, arm-hand function or activity, standing balance, leg function, walking ability, and quality of life when comparing with both dose-matched as non-dose-matched control groups. We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, and five other databases to 25 October 2021. We searched trial registries to identify additional relevant published, unpublished, and ongoing trials. We hand searched the bibliographies of included studies. We selected randomised controlled trials comparing trunk training versus non-dose-matched or dose-matched control therapy including adults (18 years or older) with either ischaemic or haemorrhagic stroke. Outcome measures of trials included ADL, trunk function, arm-hand function or activity, standing balance, leg function, walking ability, and quality of life. We used standard methodological procedures expected by Cochrane. Two main analyses were carried out. The first analysis included trials where the therapy duration of control intervention was non-dose-matched with the therapy duration of the experimental group and the second analysis where there was comparison with a dose-matched control intervention (equal therapy duration in both the control as in the experimental group). MAIN RESULTS We included 68 trials with a total of 2585 participants. In the analysis of the non-dose-matched groups (pooling of all trials with different training duration in the experimental as in the control intervention), we could see that trunk training had a positive effect on ADL (standardised mean difference (SMD) 0.96 95% confidence interval (CI) 0.69 to 1.24 P < 0.001 5 trials 283 participants very low-certainty evidence), trunk function (SMD 1.49, 95% CI 1.26 to 1.71 P < 0.001 14 trials, 466 participants very low-certainty evidence), arm-hand function (SMD 0.67, 95% CI 0.19 to 1.15 P 0.006 2 trials, 74 participants low-certainty evidence), arm-hand activity (SMD 0.84, 95% CI 0.009 to 1.59 P 0.03 1 trial, 30 participants very low-certainty evidence), standing balance (SMD 0.57, 95% CI 0.35 to 0.79 P < 0.001 11 trials, 410 participants very low-certainty evidence), leg function (SMD 1.10, 95% CI 0.57 to 1.63 P < 0.001 1 trial, 64 participants very low-certainty evidence), walking ability (SMD 0.73, 95% CI 0.52 to 0.94 P < 0.001 11 trials, 383 participants low-certainty evidence) and quality of life (SMD 0.50, 95% CI 0.11 to 0.89 P 0.01 2 trials, 108 participants low-certainty evidence). Non-dose-matched trunk training led to no difference for the outcome serious adverse events (odds ratio 7.94, 95% CI 0.16 to 400.89 6 trials, 201 participants very low-certainty evidence). In the analysis of the dose-matched groups (pooling of all trials with equal training duration in the experimental as in the control intervention), we saw that trunk training had a positive effect on trunk function (SMD 1.03, 95% CI 0.91 to 1.16 P < 0.001 36 trials, 1217 participants very low-certainty evidence), standing balance (SMD 1.00, 95% CI 0.86 to 1.15 P < 0.001 22 trials, 917 participants very low-certainty evidence), leg function (SMD 1.57, 95% CI 1.28 to 1.87 P < 0.001 4 trials, 254 participants very low-certainty evidence), walking ability (SMD 0.69, 95% CI 0.51 to 0.87 P < 0.001 19 trials, 535 participants low-certainty evidence) and quality of life (SMD 0.70, 95% CI 0.29 to 1.11 P < 0.001 2 trials, 111 participants low-certainty evidence), but not for ADL (SMD 0.10 95% confidence interval (CI) -0.17 to 0.37 P 0.48 9 trials 229 participants very low-certainty evidence), arm-hand function (SMD 0.76, 95% CI -0.18 to 1.70 P 0.11 1 trial, 19 participants low-certainty evidence), arm-hand activity (SMD 0.17, 95% CI -0.21 to 0.56 P 0.38 3 trials, 112 participants very low-certainty evidence). Trunk training also led to no difference for the outcome serious adverse events (odds ratio (OR) 7.39, 95% CI 0.15 to 372.38 10 trials, 381 participants very low-certainty evidence). Time post stroke led to a significant subgroup difference for standing balance (P < 0.001) in non-dose-matched therapy. In non-dose-matched therapy, different trunk therapy approaches had a significant effect on ADL (< 0.001), trunk function (P < 0.001) and standing balance (< 0.001). When participants received dose-matched therapy, analysis of subgroup differences showed that the trunk therapy approach had a significant effect on ADL (P 0.001), trunk function (P < 0.001), arm-hand activity (P < 0.001), standing balance (P 0.002), and leg function (P 0.002). Also for dose-matched therapy, subgroup analysis for time post stroke resulted in a significant difference for the outcomes standing balance (P < 0.001), walking ability (P 0.003) and leg function (P < 0.001), time post stroke significantly modified the effect of intervention. Core-stability trunk (15 trials), selective-trunk (14 trials) and unstable-trunk (16 trials) training approaches were mostly applied in the included trials. There is evidence to suggest that trunk training as part of rehabilitation improves ADL, trunk function, standing balance, walking ability, upper and lower limb function, and quality of life in people after stroke. Core-stability, selective-, and unstable-trunk training were the trunk training approaches mostly applied in the included trials. When considering only trials with a low risk of bias, results were mostly confirmed, with very low to moderate certainty, depending on the outcome.

Posterior spinal artery infarct.

Posterior spinal artery syndrome has a variable presentation and often poses a clinical challenge. We describe an acute posterior spinal artery syndrome in a man in his 60s with vascular risk factors, who presented with altered sensation in the left arm and left side of his torso but with normal tone, strength and deep tendon reflexes. MR imaging showed a left paracentral T2 hyperintense area affecting the posterior spinal cord at the level of C1. Diffusion-weighted MRI (DWI) showed high signal intensity in the same location. He was medically managed as having ischaemic stroke and made a good recovery. Three-month MRI follow-up showed a persisting T2 lesion but the DWI changes had resolved, consistent with the time course for infarction. Posterior spinal artery stroke has a variable presentation and is probably under-recognised clinically, requiring careful attention to MR imaging for its diagnosis.

COVID-19 vaccination willingness and uptake among rural BlackAfrican American, Latino, and White adults.

The purpose of this study was to assess differences in COVID-19 vaccine willingness and uptake between rural and nonrural adults, and within rural racial-ethnic groups. We utilized data from the COVID-19s Unequal Racial Burden online survey, which included 1,500 BlackAfrican American, Latino, and White rural adults (n 500 each). Baseline (122020-22021) and 6-month follow-up (82021-92021) surveys were administered. A cohort of nonrural BlackAfrican American, Latino, and White adults (n 2,277) was created to compare differences between rural and nonrural communities. Multinomial logistic regression was used to assess associations between rurality, race-ethnicity, and vaccine willingness and uptake. At baseline, only 24.9% of rural adults were extremely willing to be vaccinated and 28.4% were not at all willing. Rural White adults were least willing to be vaccinated, compared to nonrural White adults (extremely willing aOR 0.44, 95% CI 0.30-0.64). At follow-up, 69.3% of rural adults were vaccinated however, only 25.3% of rural adults who reported being unwilling to vaccinate were vaccinated at follow-up, compared to 95.6% of adults who were extremely willing to be vaccinated and 76.3% who were unsure. Among those unwilling to vaccinate at follow-up, almost half reported distrust in the government (52.3%) and drug companies (46.2%) 80% reported that nothing would change their minds regarding vaccination. By August 2021, almost 70% of rural adults were vaccinated. However, distrust and misinformation were prevalent among those unwilling to vaccinate at follow-up. To continue to effectively combat COVID-19 in rural communities, we need to address misinformation to increase COVID-19 vaccination rates.

Extracardiac Prothrombotic Effects of COVID-19.

COVID-19 infection triggers a heightened inflammatory response which in turn, increases thrombosis and thromboembolism. Microvascular thrombosis has been detected in various tissue beds which may account for some of the multi-system organ dysfunction associated with COVID-19. Additional research is needed to understand which prophylactic and therapeutic drug regimens are best for the prevention and treatment of thrombotic complications of COVID-19.

Cistanche tubulosa alleviates ischemic stroke-induced blood-brain barrier damage by modulating microglia-mediated neuroinflammation.

Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. This study aimed to identify CTs curative effect on IS and explore its underlying mechanism. IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mgkgday was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.

Neuroprotection by the cannabidiol aminoquinone VCE-004.8 in experimental ischemic stroke in mice.

Synthetic cannabidiol (CBD) derivative VCE-004.8 is a peroxisome proliferator-activated receptor gamma (PPARγ) and cannabinoid receptor type 2 (CB

Retrospective analysis of carotid body tumor surgical management roles of preoperative image investigation and preoperative embolization.

To analyze the management of carotid body tumors (CBTs), particularly the use of preoperative embolization (EMB) and image features in minimizing surgical complications. CBT surgery is a challenging procedure, and the role of EMB in CBT surgery has remained unclear. A total of 200 CBTs were identified among 184 medical records involving CBT surgery. Regression analysis was used to explore the prognostic predictors of cranial nerve deficit (CND), including image features. In addition, blood loss, operation times, and complication rates were compared between patients who had surgery only versus patients who had surgery along with preoperative EMB. Overall, 96 males and 88 females were identified for inclusion in the study, with a median age of 37.0 years. Computed tomography angiography (CTA) showed the presence of a tiny gap adjacent to the encasement of carotid vessels, which could help minimize carotid arterial injury. High-lying tumors that encased the cranial nerve were usually managed with synchronous cranial nerve resection. Regression analysis revealed that the incidence of CND was positively associated with Shamblin Ⅲ, high-lying, and a maximal CBT diameter of ≥ 5cm. Among 146 EMB cases, two cases of intracranial arterial embolization occurred. No statistical difference was found between the EBM and Non-EBM groups in terms of bleeding volume, operation time, blood loss, blood transfusion requirement, stroke, and permanent CND. Subgroup analysis revealed that EMB decreased CND in Shamblin III and low-lying tumors. CBT surgery should be performed with preoperative CTA to identify favorable factors for minimizing surgical complications. Shamblin Ⅲ or high-lying tumors, as well as CBT diameter, are predictors of permanent CND. EBM does not reduce blood loss or shorten operation time.

Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern.

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, BacteroidalesS24-7group, Prevotella9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.

Patients with inflammatory bowel disease are at increased risk of atherothrombotic disease A systematic review with meta-analysis.

Patients with inflammatory bowel disease (IBD) are known to be at increased risk for venous thrombosis, while their risk for arterial ischemic events is debated. The purpose of this study was to conduct a systematic review of the published literature on the risk of myocardial infarction (MI) in IBD patients and to identify any potential risk factors. The present study was performed according to PRISMA, with a systematic search on PubMed, Cochrane, and Google Scholar. Risk of MI was the primary end point, while all causes of death and stroke were secondary endpoints. Both univariate and multivariate pooled analysis were performed. An overall population of 515,455 controls and 77,140 persons with IBD (26,852, 34.8% Crohns disease, CD and 50,288, 65.2% ulcerative colitis, UC) was included. Mean age was similar across controls and IBD. Persons with CD and UC had lower rates of hypertension (14.5% vs. 14.6% vs. 25%), diabetes (2.9% vs. 5.2% vs. 9.2%) and dyslipidaemia (3.3% vs. 6.5% vs. 16.1%) compared to controls. Smoking did not significantly differ (17% vs. 17.5% vs. 10.6%). Pooled results of multivariate adjustment showed that, after a 5 years-follow-up, both CD and UC were at increased risk of MI (respectively HR 1.36 1.12-1.64 and HR 1.24 1.05-1.46), of death (HR 1.55 1.27-1.90 and HR 1.29 1.01-1.64), and of other CV disease as stroke (HR 1.22 1.01-1.49 and HR 1.09 1.03-1.15, all 95% CI). Persons with IBD are at increased risk of MI, despite a lower prevalence of the classic risk factors for MI (hypertension, diabetes, dyslipidemia).

Expression analysis and targets prediction of microRNAs in OGDR treated astrocyte-derived exosomes by smallRNA sequencing.

Astrocytes activate and crosstalk with neurons influencing inflammatory responses following ischemic stroke. The distribution, abundance, and activity of microRNAs in astrocytes-derived exosomes after ischemic stroke remains largely unknown. In this study, exosomes were extracted from primary cultured mouse astrocytes via ultracentrifugation, and exposed to oxygen glucose deprivationre‑oxygenation injury to mimic experimental ischemic stroke. SmallRNAs from astrocyte-derived exosomes were sequenced, and differentially expressed microRNAs were randomly selected and verified by stem-loop real time quantitative polymerase chain reaction. We found that 176 microRNAs, including 148 known and 28 novel microRNAs, were differentially expressed in astrocyte-derived exosomes following oxygen glucose deprivationre‑oxygenation injury. In gene ontology enrichment, Kyoto encyclopedia of genes and genomes pathway analyses, and microRNA target gene prediction analyses, these alteration in microRNAs were associated to a broad spectrum of physiological functions including signaling transduction, neuroprotection and stress responses. Our findings warrant further investigating of these differentially expressed microRNAs in human diseases particularly ischemic stroke.

Protocol for a Systematic Review and Individual Participant Data Meta-Analysis of Randomized Trials of Screening for Atrial Fibrillation to Prevent Stroke.

Atrial fibrillation (AF) is a common cause of stroke. Timely diagnosis of AF and treatment with oral anticoagulation (OAC) can prevent up to two-thirds of AF-related strokes. Ambulatory electrocardiographic (ECG) monitoring can identify undiagnosed AF in at-risk individuals, but the impact of population-based ECG screening on stroke is uncertain, as ongoing and published randomized controlled trials (RCTs) have generally been underpowered for stroke. The AF-SCREEN Collaboration, with support from AFFECT-EU, have begun a systematic review and individual participant data meta-analysis of RCTs evaluating ECG screening for AF. The primary outcome is stroke. Secondary outcomes include AF detection, OAC prescription, hospitalization, mortality, and bleeding.After developing a common data dictionary, anonymized data will be collated from individual trials into a central database. We will assess risk of bias using the Cochrane Collaboration tool, and overall quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach.We will pool data using random effects models. Prespecified subgroup and multilevel meta-regression analyses will explore heterogeneity. We will perform prespecified trial sequential meta-analyses of published trials to determine when the optimal information size has been reached, and account for unpublished trials using the SAMURAI approach. Individual participant data meta-analysis will generate adequate power to assess the risks and benefits of AF screening. Meta-regression will permit exploration of the specific patient, screening methodology, and health system factors that influence outcomes. PROSPERO CRD42022310308.

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study.

The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0-1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p ≤ 0.001), and less often large-vessel occlusion on initial MRI (793 12.1% versus 40291 29.9%, p 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval CI 0.954-1.100), lower baseline stroke volume (OR 0.965, 95% CI 0.932-0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI 0.989-0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p ≤ 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9-96%) of the treatment effect. Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h.

Microglia as drivers of neurodegeneration The role of innate-adaptive immune signaling.

Microglia contribute to neurodegeneration through numerous mechanisms. In this issue of Neuron, Shi et al.

Dietary diversity and risk of late-life disabling dementia in middle-aged and older adults.

A balanced diet integrating several foods and nutrients may promote the maintenance of brain function. Previous studies have substantiated the above hypothesis in the regional population in Japan. This study aimed to investigate the potential effect of dietary diversity on the risk of disabling dementia in a nationwide large-scale cohort of the Japanese population. A total of 38,797 participants (17,708 men and 21,089 women) aged 45-74 years were followed up for a median of 11.0 years. The daily frequencies of the consumption of each of the 133 food and beverage items listed on a food frequency questionnaire (excluding five alcoholic beverages) were measured. The dietary diversity score was calculated as the number of food items consumed per day. Multivariable adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of the dietary diversity score quintile groups. We documented 4302 participants with disabling dementia (11.1%) during the follow-up period. Among women, the dietary diversity score was inversely associated with disabling dementia (highest quintile HR with the lowest quintile as the reference 0.67 95% CI 0.56-0.78 Q1-Q5 p for trend <0.001), but this was not true among men (highest quintile HR 1.06 95% CI 0.87-1.29 Q1-Q5 p for trend 0.415). These results did not change substantially when using disabling dementia with stroke as the outcome the association remained significant among women but was absent among men. Our findings indicate that eating a variety of foods may prevent disabling dementia only among women. Thus, the habit of consuming a variety of food items has important public health implications for women.

Prevalence, electroclinical spectrum and effect on the outcome of non-convulsive status epilepticus in critically ill patients the utility of routine electroencephalogram.

To highlight the importance of routine electroencephalogram (rEEG) in detecting non-convulsive status epilepticus (NCSE), describing the electroclinical spectrum and effect on outcome in critically ill patients with altered mental status (CIPAMS). This retrospective study was conducted at King Fahd University Hospital. Clinical data and EEG recordings of CIPAMS to rule out NCSE were reviewed. All patients had at least 30 minutes of EEG recording. The Salzburg Consensus criteria (SCC) were applied to diagnose NCSE. The data analysis was performed using SPSS version 22.0. The chi-squared test was used to compare categorical variables such as etiologies, EEG findings, and functional outcomes. Multivariable analysis was performed to identify the predictors of unfavorable outcomes. A total of 323 CIPAMS referred to rule out NCSE were enrolled (mean age 57.8 ± 20 years). Nonconvulsive status epilepticus was diagnosed in 54 (16.7%) patients. A significant association was found between subtle clinical features and NCSE (P < 0.01). Acute ischemic stroke (18.5%), sepsis (18.5%), and hypoxic brain injury (22.2%) were the main etiologies. The previous history of epilepsy was significantly associated with NCSE (P 0.01). Acute stroke, cardiac arrest, mechanical ventilation, and NCSE were statistically associated with unfavorable outcomes. Nonconvulsive status epilepticus was an independent predictor of unfavorable outcomes (P 0.02, OR 2.75, CI 1.16-6.48) during multivariable analysis. Sepsis was associated with higher mortality (P < 0.01, OR 2.4, CI 1.4-4.0). Our study findings suggest that the utility of rEEG in detecting NCSE in CIPAMS should not be underestimated. Important observations further indicate that repeating rEEG is advisable, as this would increase the likelihood of identifying NCSE. Thus, physicians should consider and repeat rEEG when evaluating CIPAMS in order to detect NCSE, which is an independent predictor of unfavorable outcomes. Nonetheless, further studies comparing rEEG and cEEG yields are required to augment the current understanding of the electroclinical spectrum and better describe NCSE in CIPAMS.