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Clinical outcomes in heart failure patients with and without atrial fibrillation receiving sodium-glucose cotransporter-2 inhibitor.

We report a retrospective analysis of a nationwide health database to study the association between sodium-glucose cotransporter-2 inhibitor (SGLT2I) use and the incidence of adverse clinical outcomes among heart failure (HF) patients with and without atrial fibrillation (AF) stratified by CHA2DS2-VASc score. The outcome of this study was on the development of adverse events, including acute myocardial infarction (AMI), hemorrhagic stroke, ischemic stroke, cardiovascular (CV) death, and all-cause mortality. By dividing the number of adverse events by the total person-years, the incidence rate was calculated. The hazard ratio (HR) was estimated by the Cox proportional hazard model. A total of 95% confidence interval (CI) was also presented to show the risk of adverse events for HF patients with and without AF taking SGLT2I. SGLT2I users had a lower risk of AMI (adjusted HR 0.83 95% CI 0.74, 0.94), CV death (adjusted HR 0.47 95% CI 0.42, 0.51), and all-cause death (adjusted HR 0.39 95% CI 0.37, 0.41). Considering HF patients without AF and SGLT2I as the reference group, HF patients without AF but with SGLT2I had a reduced risk of adverse outcomes of 0.48 (95% CI 0.45, 0.50), and HF patients with AF and SGLT2I had the decreased hazard ratio of 0.55 (95% CI 0.50, 0.61). The adjusted HR of adverse outcomes for HF patients with CHA2DS2-VASc score less than 2 and SGLT2I without and with AF relative to HF patients without AF nor SGLT2I were 0.53 (95% CI 0.41, 0.67) and 0.24 (95% CI 0.12, 0.47), respectively. Compared to HF patients with no history of AF and SGLT2I, if patients additionally with SGLT2I and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was reduced with adjusted HR of 0.48 (95% CI 0.45, 0.50) if patients additionally with AF and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was decreased with adjusted HR of 0.88 (95% CI 0.80, 0.97) if patients additionally with AF, SGLT2I, and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was diminished with adjusted HR of 0.52 (95% CI 0.47, 0.58). We concluded that SGLT2I has a protective effect in HF patients, and the risk reduction is greater with a score of < 2 and without AF.

Application of the 1-2-3-4-day rule to stroke severity at baseline versus at 24 h to start direct oral anticoagulant for atrial fibrillation within 7 days from symptom onset.

The aim of this study is to compare the 1-2-3-4-day rule applied to stroke severity at baseline versus at 24 h to start DOAC for AF within 7 days from symptom onset. We conducted a prospective cohort observational study based on 433 consecutive AF-related stroke patients starting DOAC within 7 days from symptom onset. Four groups were identified according to the timing of DOAC introduction 2-day, 3-day, 4-day, and 5-7-day. Three models of multivariate ordinal regression including unbalanced variables among four groups (enrolment year, dyslipidemia, known AF, thrombolysis, thrombectomy, hemorrhagic transformation, DOAC type) were used to estimate the association of neurological severity categories (reference NIHSS > 15) at baseline (Brant test 0.818), at 24 h (Brant test 0.997), and radiological severity categories (reference major infarct) at 24 h (Brant test 0.902) in the direction of earlier DOAC introduction on days (from 5-7-day to 2-day). Number of deaths was higher in early DOAC group than in late DOAC group according to the 1-2-3-4-day rule (5.4% versus 1.3%, 6.8% versus 1.1%, and 4.2% versus 1.7% when it was applied to baseline neurological severity, 24-h neurological and radiological severity, respectively), but no significant difference was found and deaths were not caused by early DOAC introduction. Rates of ischemic stroke and intracranial hemorrhage were not different between early and late DOAC groups. The application of 1-2-3-4-day rule to start DOAC for AF within 7 days from symptom onset differed when applied to baseline neurological stroke severity versus 24-h neurological and radiological severity, but safety and effecacy are similar.

Percutaneous transluminal angioplasty andor stenting for the treatment of basilar artery stenosis a systematic review and meta-analysis.

Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes after endovascular treatments. We systematically reviewed the literature on percutaneous transluminal angioplasty andor stenting (PTAS) for BAS. PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include prospectiveretrospective cohort studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses. We included 25 retrospective cohort studies comprising 1016 patients. All patients were symptomatic, presenting with transient ischemic attack or ischemic stroke. BAS frequently involved the middle basilar artery (51.4%), mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in severe (≥ 50-70%), symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) andor stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53-99%), while median post-intervention BAS was 13% (0-75%). Actuarial rates of successful intervention and good final outcome were 100% (95% CI 100-100%) and 89% (95% CI 85-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI 4-7%), differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI 0-0%), 1% (95% CI 0-1%), and 0% (95% CI 0-2%). Elective PTAS appears to be safe and effective in selected patients with medically refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions. Future randomized controlled trials are required to corroborate these findings.

Physiotherapy Efficiency in Post-stroke Upper Extremity Spasticity TENS

Post-stroke spasticity is a significant debilitating condition with negative consequences on individual functional independence and quality of life. This study aimed to identify the differences between transcutaneous electrical stimulation (TENS), ultrasound therapy and paraffin procedures on post-stroke upper extremity spasticity and dexterity. Twenty-six patients were enrolled in the study, divided into three therapy groups TENS (n9), paraffin (n10) and ultrasound therapy (n7). For 10 days, the patients received specific group therapy and conventional physical therapy exercises for upper extremities. Modified Ashworth Scale, Functional Independence Measure, Functional Coefficient, Stroke Specific Quality of Life Scale, Activities of Daily Living score and ABILHAND questionnaire were used to assess the participants before and after therapy. The results of the group comparisons by analysis of variance showed no significant difference between outcomes by the applied treatments. In contrast, one-way analysis of variance suggested significant improvements in patients in all three groups after therapy. Step-wise regression results on functional independence measure and quality-of-life scales suggested that functional range of motion values for elbow and wrist influence individual independence and quality of life. TENS, ultrasound, and paraffin therapy bring equal benefits in the management of post-stroke spasticity.

Prognostic performance of serum YKL-40 for one-year clinical outcomes in acute ischemic stroke.

Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model. Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P 0.031 IDI 0.018, P 0.001) and all-cause mortality (NRI 0.162, P 0.036). Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

Longitudinal wall shear stress evaluation using centerline projection approach in the numerical simulations of the patient-based carotid artery.

In this numerical study, areas of the carotid bifurcation and of a distal stenosis in the internal carotid artery are closely observed to evaluate the patients current risks of ischemic stroke. An indicator for the vessel wall defects is the stress exerted by blood on the vessel tissue, typically expressed by the amplitude of the wall shear stress vector (WSS) and its oscillatory shear index. To detect negative shear stresses corresponding with reversal flow, we perform orientation-based shear evaluation. We investigate the longitudinal component of the wall shear vector, where tangential vectors aligned longitudinally with the vessel are necessary. However, resulting from imaging segmentation resolution of patients computed tomography angiography scans and stenotic regions, the geometry models mesh is non-smooth on its surface areas and the automatically generated tangential vector field is discontinuous and multi-directional, making an interpretation of our orientation-based risk indicators unreliable. We improve the evaluation of longitudinal shear stress by applying the projection of the vessels centerline to the surface to construct smooth tangential field aligned longitudinally with the vessel. We validate our approach for the longitudinal WSS component and the corresponding oscillatory index by comparing them to results obtained using automatically generated tangents in both rigid and elastic vessel modeling and to amplitude-based indicators. We present the major benefit of our longitudinal WSS evaluation based on its directionality for the cardiovascular risk assessment, which is the detection of negative WSS indicating persistent reversal or transverse flow. This is impossible in the case of the amplitude-based WSS.

Modulation of bodily response to chill stimuli by impaired structural connectivity of the left insula- a functional and lesion quantification study in stroke patients.

The insula has important function in monitoring and integrating physiological responses to a personal experience of multimodal input. The experience of chills in response to auditory stimuli is an important example for a relevant arousing experience coupled with bodily response. A group study about altered chill experiences in patients with insula lesions is lacking. We investigated 28 stroke patients with predominantly insula lesions in the chronic stage and 14 age matched controls using chill stimuli of both valences (music, harsh sounds). We analyzed group differences in subjective chill reports, associated bodily responses (skin conductance response, SCR), lesion mapping, diffusion weighted imaging and functional magnetic resonance imaging (fMRI). Other neuropsychological deficits were excluded by comprehensive testing. Diffusion weighted imaging was quantified for four insula tracts using fractional anisotropy. Frequency of chill experiences was comparable between participant groups. However, bodily responses were decreased for the stroke group. Whereas there was no association of lesion location we found a positive association for the SCR during aversive sounds and the tract connecting anterior inferior insula and left temporal pole in the stroke group. Similarly, fMRI-activation in areas hypothesized to compensate for damage was increased with bodily response. We observed a decoupling of felt arousal and bodily response after insula lesion. Impaired bodily response was related to an impaired interaction of the left anterior insula and the temporal pole.

N-terminal truncated cardiac troponin I enhances Frank-Starling response by increasing myofilament sensitivity to resting tension.

Cardiac troponin I (cTnI) of higher vertebrates has evolved with an N-terminal extension, of which deletion via restrictive proteolysis occurs as a compensatory adaptation in chronic heart failure to increase ventricular relaxation and stroke volume. Here, we demonstrate in a transgenic mouse model expressing solely N-terminal truncated cTnI (cTnI-ND) in the heart with deletion of the endogenous cTnI gene. Functional studies using ex vivo working hearts showed an extended Frank-Starling response to preload with reduced left ventricular end diastolic pressure. The enhanced Frank-Starling response effectively increases systolic ventricular pressure development and stroke volume. A novel finding is that cTnI-ND increases left ventricular relaxation velocity and stroke volume without increasing the end diastolic volume. Consistently, the optimal resting sarcomere length (SL) for maximum force development in cTnI-ND cardiac muscle was not different from wild-type (WT) control. Despite the removal of the protein kinase A (PKA) phosphorylation sites in cTnI, β-adrenergic stimulation remains effective on augmenting the enhanced Frank-Starling response of cTnI-ND hearts. Force-pCa relationship studies using skinned preparations found that while cTnI-ND cardiac muscle shows a resting SL-resting tension relationship similar to WT control, cTnI-ND significantly increases myofibril Ca2 sensitivity to resting tension. The results demonstrate that restrictive N-terminal deletion of cTnI enhances Frank-Starling response by increasing myofilament sensitivity to resting tension rather than directly depending on SL. This novel function of cTnI regulation suggests a myofilament approach to utilizing Frank-Starling mechanism for the treatment of heart failure, especially diastolic failure where ventricular filling is limited.

Cardiac patterns for differentiation of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage versus acute ischemic stroke.

Neurogenic stunned myocardium (NSM) has heterogeneous presentations for acute ischemic stroke (AIS) and aneurysmal subarachnoid hemorrhage (SAH). We sought to better define NSM and differences between AIS and SAH by evaluating individual left ventricular (LV) functional patterns by speckle tracking echocardiography (STE). We evaluated consecutive patients with SAH and AIS. Via STE, LV longitudinal strain (LS) values of basal, mid, and apical segments were averaged and compared. Different multivariable logistic regression models were created by defining stroke subtype (SAH or AIS) and functional outcome as dependent variables. One hundred thirty-four patients with SAH and AIS were identified. Univariable analyses using the chi-squared test and independent samples t-test identified demographic variables and global and regional LS segments with significant differences. In multivariable logistic regression analysis, when comparing AIS to SAH, AIS was associated with older age (OR 1.07, 95% CI 1.02-1.13, p 0.01), poor clinical condition on admission (OR 7.74, 95% CI 2.33-25.71, p < 0.001), decreased likelihood of elevated admission serum troponin (OR .09, 95% CI .02-.35, p < 0.001), and worse LS basal segments (OR 1.18, 95% CI 1.02-1.37, p 0.03). In patients with neurogenic stunned myocardium, significantly impaired LV contraction by LS basal segments was found in patients with AIS but not with SAH. Individual LV segments in our combined SAH and AIS population were also not associated with clinical outcomes. Our findings suggest that strain echocardiography may identify subtle forms of NSM and help differentiate the NSM pathophysiology in SAH and AIS.

Neurological complications of critically ill COVID-19 patients.

COVID-19 and systemic critical illness are both associated with neurological complications. We provide an update on the diagnosis and critical care management of adult patients with neurological complications of COVID-19. Large prospective multicentre studies conducted in the adult population over the last 18 months improved current knowledge on severe neurological complications of COVID-19. In COVID-19 patients presenting with neurological symptoms, a multimodal diagnostic workup (including CSF analysis, brain MRI, and EEG) may identify different syndromes associated with distinct trajectories and outcomes. Acute encephalopathy, which represents the most common neurological presentation of COVID-19, is associated with hypoxemia, toxicmetabolic derangements, and systemic inflammation. Other less frequent complications include cerebrovascular events, acute inflammatory syndromes, and seizures, which may be linked to more complex pathophysiological processes. Neuroimaging findings include infarction, haemorrhagic stroke, encephalitis, microhaemorrhages and leukoencephalopathy. In the absence of structural brain injury, prolonged unconsciousness is usually fully reversible, warranting a cautious approach for prognostication. Advanced quantitative MRI may provide useful insights into the extent and pathophysiology of the consequences of COVID-19 infection including atrophy and functional imaging changes in the chronic phase. Our review highlights the importance of a multimodal approach for the accurate diagnosis and management of complications of COVID-19, both at the acute phase and in the long-term.

Transfusion medicine approaches for spontaneous intracerebral hemorrhage patients.

Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype. Acute treatments necessitate rapid hemorrhage control to minimize secondary brain injury. Here, we discuss the overlap of transfusion medicine and acute ICH care relating to diagnostic testing and therapies relevant for coagulopathy reversal and secondary brain injury prevention. Hematoma expansion (HE) is the largest contributor to poor outcomes after ICH. Conventional coagulation assays to diagnose coagulopathy after ICH does not predict HE. Given the testing limitations, empiric pragmatic hemorrhage control therapies have been trialed but have not improved ICH outcomes, with some therapies even causing harm. It is still unknown whether faster administration of these therapies will improve outcomes. Alternative coagulation tests (e.g., viscoelastic hemostatic assays, amongst others) may identify coagulopathies relevant for HE, currently not diagnosed using conventional assays. This provides opportunities for rapid, targeted therapies. In parallel, ongoing work is investigating alternative treatments using transfusion-based or transfusion-sparing pharmacotherapies that can be implemented in hemorrhage control strategies after ICH. Further work is needed to identify improved laboratory diagnostic approaches and transfusion medicine treatment strategies to prevent HE and optimize hemorrhage control in ICH patients, who appear particularly vulnerable to the impacts of transfusion medicine practices.

Ischemic stroke caused by spontaneous anterior circulation intracranial arterial dissections patient series.

Intracranial arterial dissections (IADs) are classically associated with the vertebrobasilar system, yet are a devastating cause of ischemic stroke within the anterior circulation. Current literature regarding the surgical management of anterior circulation IAD is lacking. As a result, data on 9 patients presenting with ischemic stroke due to spontaneous anterior circulation IAD between 2019 and 2021 were collected in a retrospective manner. Symptoms, diagnostic modalities, treatment, and outcomes are presented for each case. Patients who underwent endovascular procedures had 10-minute follow-up angiography performed to identify signs of reocclusion, which prompted initiation of glycoprotein IIbIIIa therapy and stent placement. Seven patients underwent emergent endovascular intervention (stenting n 5 thrombectomy alone n 2). The remaining 2 were managed medically. Two patients developed progressive flow limiting stenosis requiring further intervention, 2 developed asymptomatic progressive stenosisocclusion with robust collateral formation and the remainder have patent vasculature upon follow up imaging at 6 to 12 months. Seven patients had a modified Rankin Scale score of 1 or less at the 3-month follow-up. IAD is a devastating yet rare cause of anterior circulation ischemic stroke. The treatment algorithm proposed resulted in positive clinical and angiographic outcomes warranting future consideration and study in the emergent management of spontaneous anterior circulation IAD.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume ( Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

One-year outcomes after transcatheter aortic valve implantation with the latest-generation SAPIEN balloon-expandable valve the S3U registry.

Initial data about the performance of the new-generation SAPIEN 3 Ultra (S3U) valve are highly promising. However, evidence about the longer-term performance and safety of the S3U is scarce. We aimed to investigate the 1-year clinical and echocardiographic outcomes of transcatheter aortic valve implantation (TAVI) using the S3U compared with its predecessor, the SAPIEN 3 valve (S3). The SAPIEN 3 Ultra registry included consecutive patients who underwent transfemoral TAVI at 12 European centres with the S3U or S3 between October 2016 and December 2020. One-to-one propensity score (PS) matching was performed to account for differences in baseline characteristics. The primary outcomes of interest were all-cause death and the composite of all-cause death, disabling stroke and hospitalisation for heart failure at 1 year. The overall study cohort encompassed 1,692 patients treated with either the S3U (n519) or S3 (n1,173). The PS-matched population had a total of 992 patients (496 per group). At 1 year, the rate of death from any cause was 4.9% in the S3U group and 6.3% in the S3 group (p0.743). Similarly, there were no significant differences in the rates of the primary composite outcome (9.5% in the S3 group and 6.6% in the S3U group p0.162). The S3U was associated with lower rates of mild paravalvular leak (PVL) compared with the S3 (odds ratio 0.63, 95% confidence interval 0.44 to 0.88 p<0.01). No significant differences in transprosthetic gradients were observed between the two groups. Compared with the S3, the S3U transcatheter heart valve was associated with similar 1-year clinical outcomes but reduced rates of mild PVL.

Intravenous thrombolysis versus antiplatelet therapy in minor stroke patients with large vessel occlusion.

Our study aimed to explore the effectiveness and safety of intravenous t-PA compared with dual antiplatelet therapy (DAPT) and aspirin alone for minor stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤5 and large vessel occlusion (LVO). Patients with minor stroke harboring LVO within 4.5-h time window were included from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018 in China. Clinical outcomes including modified Rankin scale (mRS) score, recurrent stroke, and all-cause mortality at 90 days and 36-h symptomatic intracerebral hemorrhage (sICH) were collected. Multivariable logistic regression models and propensity score matching analyses were used to determine the association between treatment groups and clinical outcomes. A total of 1401 minor stroke patients with LVO were included. Overall 251 patients (17.9%) received intravenous t-PA, 722 patients (51.5%) received DAPT, and 428 patients (30.5%) received aspirin alone. The intravenous t-PA was associated with greater proportions of mRS 0-1 (aspirin versus t-PA adjusted odds ratio aOR, 0.50 95% confidence interval CI, 0.32 to 0.80 p 0.004 DAPT versus t-PA aOR, 0.76 95% CI, 0.49 to 1.19 p 0.23). Using propensity score matching analyses, the results were similar. There was no difference in 90-day recurrent stroke among the groups. The rates of all-cause mortality in intravenous t-PA, DAPT, and aspirin groups were 0%, 0.55%, 2.34%, respectively. No patient developed sICH within 36 h of intravenous t-PA. In patients with minor stroke harboring LVO within 4.5-h time window, intravenous t-PA was associated with higher odds for the excellent functional outcome, as compared with the aspirin alone. Further randomized controlled trials are warranted.

Outcomes of endovascular repair of infrarenal penetrating aortic ulcers.

Comparative assessment of the effects of dobutamine and levosimendan on right ventricular ejection fraction in patients with biventricular heart failure.

Aim The primary objective of this study was to comparatively assess the effects of levosimendan and dobutamine on RVEF, right ventricular diastolic function, and hormonal balance in patients with biventricular heart failure. The secondary objective was to investigate the relationship between the RVEF and the peak systolic velocity (Sa), an indicator of right ventricular systolic function, as measured by tissue Doppler echocardiography from the tricuspid annulus, and by the tricuspid annular plane systolic excursion (TAPSE).Material and Methods The population of this cross-sectional, single-center, prospective study was comprised of 81 patients, who between December 2019 and January 2022, applied to the study health institution with diagnosis of ADHF. The study sample included 67 biventricular heart failure patients with left ventricular ejection fraction (LVEF) lt35 % and RVEF lt50 %, as measured by the ellipsoidal shell model, and who met the other study inclusion criteria. Of these 67 patients, 34 were treated with levosimendan, and 33 were treated with dobutamine. RVEF, LVEF, Sa, peak early (Ea) and peak late (Aa) annular velocities, Ea Aa ratio, TAPSE, systolic pulmonary artery pressure (SPAP), n-terminal pro-brain natriuretic peptide (NT-pro BNP), and functional capacity (FC) were measured before treatment and at 48 hrs of treatment. The within group pre- and post-treatment differences (Δs) of these variables were compared.Results RVEF, SPAP, and BNP, and FC significantly improved in both treatment groups (plt0.05 for all). Sa (plt0.01), TAPSE (plt0.01), LVEF (plt0.01), and Ea Aa (plt0.05) improved only in the levosimendan group. The pre- and post-treatment Δs for RVEF, LVEF, SPAP, Sa, TAPSE, FC, and Ea Aa were higher in the levosimendan group than in the dobutamine group (plt0.05 for all).Conclusion Compared to dobutamine, levosimendan produced greater improvement in right ventricular systolic and diastolic function in patients with biventricular heart failure and in need of inotropic therapy support.

Cardiovascular effects of omega-3 polyunsaturated fatty acids position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts.

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA ACC HFSA guidelines) • for patients with hypertriglyceridemia (gt1.5 mmoll) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.) • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 gday is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

Risk Assessment of Adverse Outcomes in Symptomatic Patients With Arterial Hypertension and Chronic Heart Failure With Preserved Ejection Fraction Using THE HFA-PEFF Algorithm.

Aim To study the incidence of heart failure (HF) in patients with arterial hypertension (AH), symptoms of HF, and left ventricular ejection fraction (LV EF) ≥50 % using a novel, modified HFA-PEFF diagnostic algorithm and to evaluate the liver hydration status and density depending on the established HF profiles and the prognostic significance of this algorithm.Material and methods This study included 180 patients (median age, 72 years) with AH, symptoms of HF, and LV EF ≥50 %. The incidence of chronic HF with preserved ejection fraction (CHFpEF) was studied with the stepwise, modified HFA-PEFF diagnostic algorithm, and long-term outcomes were assessed at 3, 6, and 12 months of follow-up. The hydration status was determined by a bioimpedance vector analysis, and the liver density was measured by indirect fibroelastometry. The following tests were performed for all patients standard, general clinical and laboratory examination with evaluation of CH symptoms (including N-terminal pro-brain natriuretic peptide test) extended echocardiography with assessment of structural and functional parameters of the heart a KCCQ questionnaire was used for evaluation of patients condition and quality of life (QoL). Long-term outcomes were studied by phone calls at 3, 6, and 12 months following discharge from the hospitalvisit (worsened QoL, repeated hospitalization for cardiovascular causes, cardiovascular death or all-cause death).Results The following profiles were determined by the HFA-PEFF algorithm with CHFpEF, with intermediate probability of HF, and without HF (58.9, 31.1, and 10 %, respectively). The study showed that patients with CHFpEF compared to patients of the intermediate group and without HF, had higher levels of brain natriuretic peptide, more pronounced signs of congestion according to results of the bioimpedance vector analysis and a higher liver density according to results of indirect fibroelastometry of the liver, which allowed identification of a group of patients with a high probability of CHFpEF. The diagnosis of HF by HFA-PEFF had an adverse prognostic significance with respect of worsened QoL according to the KCCQ questionnaire, and of repeated admission for HF during a year.Conclusion In AH patients with symptoms of HF and LV EF ≥50 %, CHFpEF was detected with the HFA-PEFF algorithm in 58.9 % of cases. Patients with AH and verified CHFpEF had a high incidence of hyperhydration and increased liver density. A diagnosis of CHFpEF by the HFA-PEFF algorithm had an adverse prognostic significance with respect of long-term outcomes.

Efficacy of mirror therapy on lower limb motor recovery, balance and gait in subacute and chronic stroke A systematic review.

Mirror therapy (MT) has been proposed to be an effective therapeutic regimen for lower limb stroke rehabilitation. This review is the first to evaluate the efficacy of MT in subacute and chronic stroke for lower-limb motor functions, balance and gait focusing on particular stage of stroke with specific outcome measures. According to PRISMA guidelines, all relevant sources were searched from 2005 to 2020 using PIOD framework. Search methods included electronic database, hand and citation searching. Screening and quality assessment was performed by two individual reviewers. Data was extracted and synthesised from 10 studies. Thematic analysis was considered, random-effect models were used and pooled analysis was performed using forest plots. For motor recovery, MT showed statistically significant effects compared to control group using Fugl-Meyer Assessment and Brunnstorm stages as outcome measures (SMD 0.59 95% CI 0.29 to 0.88 p < 0.0001 I This review has shown that MT is effective in lower-limb motor recovery, balance and gait in subacute and chronic stroke in patients 18 years or above with no severe cognitive disorder, MMSE score ≥24 and FAC level ≥2. MT could be used for 30 minday, 5 daysweek for 4 weeks, as stand-alone for motor recovery and balance or as an adjunct with electric stimulation for gait for beneficial effects.

Sex Differences in Stress-Induced (Takotsubo) Cardiomyopathy.

Takotsubo cardiomyopathy (TC) affects predominantly women. Prior studies have suggested that men might have worse short-term outcomes, but limited data are available regarding long-term outcomes. We hypothesized that men, compared to women, with TC have worse short- and long-term outcomes. A retrospective study of patients diagnosed with TC between 2005 and 2018 in the Veteran Affairs system was performed. Primary outcomes were in-hospital death, 30-day risk of stroke, death, and long-term mortality. A total of 641 patients were included (444 men 69% 197 women 31%). Men had a higher median age (65 vs 60 years In our study with a predominantly male population, men had less-favourable short- and long-term outcomes after TC, compared to those of women. La cardiomyopathie de Takotsubo (CT) touche majoritairement les femmes. Or, des études antérieures semblent indiquer que les hommes pourraient connaître de pires résultats à court terme, mais peu de données portent sur les résultats à long terme. Nous avons formulé l’hypothèse selon laquelle les hommes atteints de CT obtiennent de moins bons résultats à court et à long terme que les femmes qui en sont atteintes. Nous avons réalisé une étude rétrospective auprès des patients qui étaient inscrits au système de soins de santé du département des Anciens Combattants des États-Unis et qui avaient reçu un diagnostic de CT entre 2005 et 2018. Les critères d’évaluations principaux étaient le taux de décès à l’hôpital, le risque d’AVC sur 30 jours, le taux de décès et le taux de mortalité à long terme. Au total, 641 patients ont été inclus dans l’étude (444 hommes 69 % 197 femmes 31 %). L’âge médian était plus élevé chez les hommes (65 c. 60 ans Dans notre étude portant sur une population à prédominance masculine, les hommes atteints de CT ont obtenu des résultats à court et à long terme moins favorables que les femmes atteintes de ce syndrome.

A Survey of Female-Specific Cardiovascular Protocols in Emergency Departments in Canada.

Cardiovascular diseases (CVD) remain the leading cause of death for women. However, systematic inequalities exist in how women experience clinical cardiovascular (CV) policies, programs, and initiatives. In collaboration with the Heart and Stroke Foundation of Canada, a question regarding female-specific CV protocols in an emergency department (ED), or an inpatient or ambulatory care area of a healthcare site was sent via e-mail to 450 healthcare sites in Canada. Contacts at these sites were established through the larger initiative-the Heart Failure Resources and Services Inventory-conducted by the foundation. Responses were received from 282 healthcare sites, with 3 sites confirming the use of a component of a female-specific CV protocol in the ED. Three sites noted using sex-specific troponin levels in the diagnosis of acute coronary syndromes 2 of the sites are participants in the hs- We have identified an absence of female-specific CVD protocols in EDs that may be associated with the identified poorer outcomes in women impacted by CVD. Female-specific CV protocols may serve to increase equity and ensure that women with CV concerns have access to the appropriate care in a timely manner, thereby helping to mitigate some of the current adverse effects experienced by women who present to Canadian EDs with CV symptoms. Les maladies cardiovasculaires (MCV) demeurent la principale cause de décès chez les femmes. Toutefois, il existe des inégalités systématiques à l’égard des femmes dans les politiques, les programmes et les initiatives cliniques cardiovasculaires (CV). En collaboration avec la Fondation des maladies du cœur et de l’AVC du Canada, une question relative à l’utilisation de protocoles de prise en charge des manifestations cardiovasculaires spécifiques aux femmes dans les services d’urgence ou les services de soins pour patients hospitalisés et ambulatoires a été envoyée par courriel à 450 établissements de santé au Canada. Les contacts ont été établis dans ces centres dans le cadre d’une initiative de plus grande envergure, l’inventaire des ressources et des services en matière d’insuffisance cardiaque, menée par la Fondation. Des réponses ont été reçues de 282 établissements de santé dont trois ont confirmé l’utilisation d’une composante spécifique aux femmes dans leurs protocoles de prise en charge des manifestations CV dans leur service des urgences. Trois centres ont déclaré utiliser un taux de troponine adapté au sexe pour le diagnostic du syndrome coronarien aigu or, deux de ces centres participent à l’essai CODE MI ( Nous avons constaté que l’absence de protocoles spécifiques aux femmes en matière de prise en charge des manifestations CV dans les services d’urgences pourrait être associée aux moins bons résultats observés chez les femmes atteintes de MCV. Des protocoles spécifiques aux femmes en matière de prise en charge des manifestations CV pourraient contribuer à accroître l’équité et à faire en sorte que les femmes souffrant de problèmes CV aient accès aux soins appropriés en temps opportun. Une telle initiative contribuerait à atténuer certains des effets indésirables dont sont victimes les femmes qui se présentent aux urgences des établissements de soins canadiens avec des symptômes CV.

Voluntary running exercise modifies astrocytic population and features in the peri-infarct cortex.

Rehabilitative exercise following a brain stroke has beneficial effects on the morphological plasticity of neurons. Particularly, voluntary running exercise after focal cerebral ischemia promotes functional recovery and ameliorates ischemia-induced dendritic spine loss in the peri-infarct motor cortex layer 5. Moreover, neuronal morphology is affected by changes in the perineuronal environment. Glial cells, whose phenotypes may be altered by exercise, are known to play a pivotal role in the formation of this perineuronal environment. Herein, we investigated the effects of voluntary running exercise on glial cells after middle cerebral artery occlusion. Voluntary running exercise increased the population of glial fibrillary acidic protein-positive astrocytes born between post-operative days (POD) 0 and 3 on POD15 in the peri-infarct cortex. After exercise, transcriptomic analysis of post-ischemic astrocytes revealed 10 upregulated and 70 downregulated genes. Furthermore, gene ontology analysis showed that the 70 downregulated genes were significantly associated with neuronal morphology. In addition, exercise reduced the number of astrocytes expressing lipocalin 2, a regulator of dendritic spine density, on POD15. Our results suggest that exercise modifies the composition of astrocytic population and their phenotype.

Correlation Between Cardiac Index, Plasma Troponin I, Myocardial Histopathology, CPB and AoX Duration in Glutamine versus No Glutamine Administered Patients with Low Ejection Fraction Undergoing Elective On-Pump CABG Surgery Secondary Analysis of an RCT.

On-pump coronary artery bypass graft (CABG) causes myocardial ischemia, through the cardiopulmonary bypass (CPB) and aortic cross-clamping (AoX). Glutamine supplementation protects cardiac cells during cardiac ischemia. This study analysed the correlation between cardiac index (CI), plasma troponin I, myocardial histopathology, CPB and AoX duration in low ejection fraction patients receiving glutamine and no glutamine undergoing elective on-pump CABG. This was a secondary analysis of a double-blind, randomised controlled trial of 60 patients, split into control and intervention (glutamine) groups. Glutamine was administered at a dose of 0.5 gkg24 hours. There were 29 patients in each respective groups after a total of two patients dropped out. A negative correlation (p 0.037) was observed between CPB duration and CI at 6 hours after CPB in the glutamine group. A positive correlation (p 0.002) was also observed between AoX duration and plasma troponin I at 6 hours after CPB in the control group. However, no correlation was observed between myocardial histopathology and plasma troponin I level at 5 minutes after CPB. Significant negative correlation between CPB duration and CI at 6 hours after CPB in the glutamine group, along with significant positive correlation between AoX duration and plasma troponin I level at 6 hours after CPB in the control group demonstrated the myocardial protection qualities of intravenous glutamine administration in patients with low ejection fraction undergoing elective on-pump CABG surgeries.

Stock volatility and hospital admissions for cardiovascular disease results from the National Insurance Claims for Epidemiological Research (NICER) study.

The association between stock volatility and cardiovascular diseases (CVD) was described during the 2008 Global Stock Market Crash however, whether the finding in an occasional stock market crash is spurious remains unclear. A time-series design was used to evaluate the association between short-term exposure to daily returns of two major indices and daily hospital admissions for CVD and its subtypes based on claims data from the National Insurance Claims for Epidemiological Research (NICER) study covering 174 major cities in China. The average percentage change in daily hospital admissions for cause-specific CVD per 1% change in daily index returns was calculated because the Chinese stock market policy limits its change by 10% of the previous days closing price. A Poisson regression in a generalised additive model was used to assess the city-specific association then, overall national estimations were pooled by random-effects meta-analysis. Totally 8,234,164 hospital admissions for CVD were recorded during 2014-2017. Points of the Shanghai closing indices ranged from 1991·3 to 5166·4. A U-shaped association was observed between daily index returns and CVD admissions. Changes of 1% in daily returns of the Shanghai index corresponded to 1·28%(95%CI 1·04%-1·53%), 1·25%(0·99%-1·51%), 1·42%(1·13%-1·72%), and 1·14%(0·39%-1·89%) increases in hospital admissions for total CVD, ischaemic heart disease, stroke, or heart failure on the same day, respectively. Similar results were observed for the Shenzhen index. Stock market volatility is associated with an increased CVD admission. Chinese Ministry of Science and Technology (2020YFC2003503) and National Natural Science Foundation of China (81973132, 81961128006).

Projections of future coronary heart disease and stroke mortality in Japan until 2040 a Bayesian age-period-cohort analysis.

We aimed to estimate the future burden of coronary heart disease (CHD) and stroke mortalities by sex and all 47 prefectures of Japan until 2040 while accounting for effects of age, period, and cohort and integrating them to be at the national level to account for regional differences among prefectures. We estimated future CHD and stroke mortality projections, developing Bayesian age-period-cohort (BAPC) models in population and the number of CHD and stroke by age, sex, and all 47 prefectures observed from 1995 to 2019 then applying these to official future population estimates until 2040. The present participants were all men and women aged over 30 years and were residents of Japan. In the BAPC models, the predicted number of national-level cardiovascular deaths from 2020 to 2040 would decrease (39,600 95% credible interval 32,200-47,900 to 36,200 21,500-58,900 CHD deaths in men, and 27,400 22,000-34,000 to 23,600 12,700-43,800 in women and 50,400 41,900-60,200 to 40,800 25,200-67,800 stroke deaths in men, and 52,200 43,100-62,800 to 47,400 26,800-87,200 in women). After adjusting these factors, future CHD and stroke deaths will decline until 2040 at the national level and in most prefectures. This research was supported by the Intramural Research Fund of Cardiovascular Diseases of the National Cerebral and Cardiovascular Center (21-1-6, 21-6-8), JSPS KAKENHI Grant Number JP22K17821, and the Ministry of Health, Labour and Welfare Comprehensive Research on Life-Style Related (Diseases Cardiovascular Diseases and Diabetes Mellitus Program), Grant Number 22FA1015.

Atherosclerotic patients with diabetes mellitus may break through the threshold of healthy TMAO levels formed by long-term statins therapy.

Cardiovascular disease (CVD) is the leading course of disease-related death in both developed and developing countries. Atherosclerosis is main pathology of CVD, and its severity is thought to be related to trimethylamine N-oxide (TMAO) level in plasma. Therefore, it is necessary to deeply understand the synergistic patterns between TMAO and other contribution variables to atherosclerosis, allowing for effective and timely monitoring or intervention. A total of 359 participants were recruited in our study, including 190 atherosclerosis patients, 82 MI or stroke patients, 68 non-atherosclerosis controls and 19 healthy controls. Information on their risk associated with atherosclerosis and plasma TMAO concentration were collected. LASSO regression, multivariate analysis and univariate analysis were then performed to confirm the correlation between TMAO level and risk factors of atherosclerosis. Compared to patients and non-atherosclerosis controls, healthy participants had a normal BMI range (lower than 24), lower triglyceride concentration, and healthy lifestyle habits (no smoking and low salt diet). However, under backgrounds of statins treatment and balanced dietary preferences, TMAO levels were not significantly different among patients, non-atherosclerosis controls and healthy controls. Using LASSO regression model, four indicators was identified to have contribution to TMAO levels, including diabetes, atherosclerosis, low-density lipoprotein and total cholesterol. Subsequent univariate analysis further confirmed that the presence or absence of diabetes had a decisive effect on patients plasma TMAO levels, even though they had been taking statin lipid-lowering drugs for a long time. Diabetics have abnormally high plasma TMAO levels even under continuous statins treatment, which may contribute to the development and progression of atherosclerosis. Therefore, it is necessary to focus on monitoring TMAO levels in diabetic patients to reduce adverse cardiovascular events in diabetic patients.

A Case of Metastatic Choriocarcinoma With Intracerebral Hemorrhage Caused by a Ruptured Pseudoaneurysm.

A rare cause of cerebral hemorrhage is the metastasis of choriocarcinoma from gynecology. Herein, we report a case of a patient with brain metastasis of choriocarcinoma with cerebral hemorrhage. A 14-year-old female who had undergone surgery for a hydatidiform molar pregnancy presented with a disturbance of consciousness due to cerebral hemorrhage. Imaging studies revealed the presence of a cerebral aneurysm and several mass lesions in the lung field, and high serum beta-human chorionic gonadotropin level was confirmed. Thus, we suspected cerebral hemorrhage caused by brain metastasis of choriocarcinoma. She went into a coma, and an emergency craniotomy was performed to remove the hematoma and aneurysm. The pathology of the aneurysm was pseudoaneurysm due to the rupture of the vascular wall caused by increasing metastatic cells from choriocarcinoma in the cerebrovascular wall. Therefore, multidrug chemotherapy was immediately initiated. The choriocarcinoma, including the metastatic lesions, is in remission. To improve the outcome of choriocarcinoma, it must be diagnosed early, and treatment should be immediately started. Moreover, neurosurgeons should be aware of such diseases and consider them as one of the differential diagnoses, particularly in females of reproductive age with cerebral hemorrhage.

Dual-sized hollow particle incorporated fibroin thermal insulating coatings on catheter for cerebral therapeutic hypothermia.

Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroinsilica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity. The infusate exit temperature is tunable by adjusting the coating thickness and infusion rate. No peeling or cracking was observed on the coatings under bending and rotational scenarios in the vascular models. Its efficiency was verified in a swine model, and the outlet temperature of coated catheter (75 μm thickness) was 1.8-2.0 °C lower than that of the uncoated one. This pioneering work on catheter thermal insulation coatings may facilitate the clinical translation of selective endovascular hypothermia for neuroprotection in patients with acute ischemic stroke.

GeneReviews

Fabry disease is the most common of the lysosomal storage disorders and results from deficient activity of the enzyme alpha-galactosidase A (α-Gal A), leading to progressive lysosomal deposition of globotriaosylceramide and its derivatives in cells throughout the body. The classic form, occurring in males with less than 1% α-Gal A enzyme activity, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities (acroparesthesia), the appearance of vascular cutaneous lesions (angiokeratomas), sweating abnormalities (anhidrosis, hypohidrosis, and rarely hyperhidrosis), characteristic corneal and lenticular opacities, and proteinuria. Gradual deterioration of renal function to end-stage renal disease (ESRD) usually occurs in men in the third to fifth decade. In middle age, most males successfully treated for ESRD develop cardiac andor cerebrovascular disease, a major cause of morbidity and mortality. Heterozygous females typically have milder symptoms at a later age of onset than males. Rarely, females may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype. In contrast, late-onset forms occur in males with greater than 1% α-Gal A activity. Clinical manifestations include cardiac disease, which usually presents in the sixth to eighth decade with left ventricular hypertrophy, cardiomyopathy, arrhythmia, and proteinuria renal failure, associated with ESRD but without the skin lesions or pain or cerebrovascular disease presenting as stroke or transient ischemic attack. Identification of deficient α-Gal A enzyme activity in plasma, isolated leukocytes, andor cultured cells is the most efficient and reliable method of diagnosing Fabry disease in males. Identification of a hemizygous Fabry disease is inherited in an X-linked manner hemizygous males are affected heterozygous females may be as severely affected as males or asymptomatic throughout a normal life span. In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. If a male is the only affected family member, his mother is likely heterozygous for the

TLR4 Enhances Cerebral IschemiaReperfusion Injury via Regulating NLRP3 Inflammasome and Autophagy.

Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemiareperfusion (CIR) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CIR injury. An in vivo CIR rat injury model and an in vitro hypoxiareoxygenation (HR) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CIR rats or in HR-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-

Cardiovascular outcomes among patients with castration-resistant prostate cancer A comparative safety study using US administrative claims data.

Cardiovascular conditions are the most prevalent comorbidity among patients with prostate cancer, regardless of treatment. Additionally, cardiovascular risk has been shown to increase following exposure to certain treatments for advanced prostate cancer. There is conflicting evidence on risk of overall and specific cardiovascular outcomes among men treated for metastatic castrate resistant prostate cancer (CRPC). We, therefore, sought to compare incidence of serious cardiovascular events among CRPC patients treated with abiraterone acetate plus predniso(lo)ne (AAP) and enzalutamide (ENZ), the two most widely used CRPC therapies. Using US administrative claims data, we selected CRPC patients newly exposed to either treatment after August 31, 2012, with prior androgen deprivation therapy (ADT). We assessed incidence of hospitalization for heart failure (HHF), ischemic stroke, and acute myocardial infarction (AMI) during the period 30-days after AAP or ENZ initiation to discontinuation, outcome occurrence, death, or disenrollment. We matched treatment groups on propensity-scores (PSs) to control for observed confounding to estimate the average treatment effect among the treated (AAP) using conditional Cox proportional hazards models. To account for residual bias, we calibrated our estimates against a distribution of effect estimates from 124 negative-control outcomes. The HHF analysis included 2322 (45.1%) AAP initiators and 2827 (54.9%) ENZ initiators. In this analysis, the median follow-up times among AAP and ENZ initiators (after PS matching) were 144 and 122 days, respectively. The empirically calibrated hazard ratio (HR) estimate for HHF was 2.56 (95% confidence interval CI 1.32, 4.94). Corresponding HRs for AMI and ischemic stroke were 1.94 (95% CI 0.90, 4.18) and 1.25 (95% CI 0.54, 2.85), respectively. Our study sought to quantify risk of HHF, AMI and ischemic stroke among CRPC patients initiating AAP relative to ENZ within a national administrative claims database. Increased risk for HHF among AAP compared to ENZ users was observed. The difference in myocardial infarction did not attain statistical significance after controlling for residual bias, and no differences were noted in ischemic stroke between the two treatments. These findings confirm labeled warnings and precautions for AAP for HHF and contribute to the comparative real-world evidence on AAP relative to ENZ.

EPO regulates neuronal differentiation of adult human neural-crest derived stem cells in a sex-specific manner.

Sexual differences in the biology of human stem cells are increasingly recognized to influence their proliferation, differentiation and maturation. Especially in neurodegenerative diseases such as Alzheimers disease (AD), Parkinsons disease (PD) or ischemic stroke, sex is a key player for disease progression and recovery of damaged tissue. Recently, the glycoprotein hormone erythropoietin (EPO) has been implicated as a regulator of neuronal differentiation and maturation in female rats. In this study, we used adult human neural crest-derived stem cells (NCSCs) as a model system for exploring potential sex specific effects of EPO on human neuronal differentiation. We started with expression validation of the specific EPO receptor (EPOR) by performing PCR analysis in the NCSCs. Next, EPO mediated activation of nuclear factor-κB (NF-κB) via Immunocytochemistry (ICC) was performed, followed by investigating the sex-specific effects of EPO on neuronal differentiation by determining morphological changes in axonal growth and neurite formation accompanied by ICC. Undifferentiated male and female NCSCs showed a ubiquitous expression of the EPO receptor (EPOR). EPO treatment resulted in a statistically profound (male p 0.0022, female p 0.0012) nuclear translocation of NF-κB RELA in undifferentiated NCSCs of both sexes. But after one week of neuronal differentiation, we could show a highly significant (p 0,0079) increase of nuclear NF-κB RELA in females only. In contrast, we observed a strong decrease (p 0,0022) of RELA activation in male neuronal progenitors. Extending the view on the role of sex during human neuronal differentiation, here we demonstrate a significant increase of axon lengths in female NCSCs-derived neurons upon EPO-treatment ( EPO 167,73 (SD 41,66) µm, wo EPO 77,68 (SD 18,31) µm) compared to their male counterparts ( EPO 68,37 (SD 11,97) µm, wo EPO 70,23 (SD 12,89) µm). Our present findings therefore show for the first time an EPO-driven sexual dimorphism in neuronal differentiation of human neural-crest derived stem cells and emphasize sex-specific variability as a crucial parameter in stem cell biology and for treating neurodegenerative diseases.

The impact of stroke on the ability to live an independent life at old age a community-based cohort study of Swedish men.

Few studies with controls from the same cohort have investigated the impact of stroke on the ability to live an independent life at old age. We aimed to analyze how great an impact being a stroke survivor would have on cognition and disability. We also analyzed the predictive value of baseline cardiovascular risk factors. We included 1147 men, free from stroke, dementia, and disability, from the Uppsala Longitudinal Study of Adult Men, between 69-74 years of age. Follow-up data were collected between the ages of 85-89 years and were available for 481 of all 509 survivors. Data on stroke diagnosis were obtained through national registries. Dementia was diagnosed through a systematic review of medical charts and in accordance with the current diagnostic criteria. The primary outcome, preserved functions, was a composite outcome comprising four criteria no dementia, independent in personal activities of daily living, ability to walk outside unassisted, and not living in an institution. Among 481 survivors with outcome data, 64 (13%) suffered a stroke during the follow-up. Only 31% of stroke cases, compared to 72% of non-stroke cases (adjusted OR 0.20 95% CI 0.11-0.37), had preserved functions. The chance of being free of dementia was 60% lower in the stroke group, OR 0.40 95% CI 0.22-0.72. No cardiovascular risk factors were independently able to predict preserved functions among stroke cases. Stroke has long lasting consequences for many aspects of disability at very high age.

Long-term outcomes and quantitative radiologic analysis of extracranial-intracranial bypass for hemodynamically compromised chronic large artery occlusive disease.

This study aimed to demonstrate the effectiveness of nonemergent extracranial-to-intracranial bypass (EIB) in symptomatic chronic large artery atherosclerotic stenosis or occlusive disease (LAA) through quantitative analysis of computed tomography perfusion (CTP) parameters using RAPID software. We retrospectively analyzed 86 patients who underwent nonemergent EIB due to symptomatic chronic LAA. CTP data obtained preoperatively, immediately postoperatively (PostOp0), and 6 months postoperatively (PostOp6M) after EIB were quantitatively analyzed through RAPID software, and their association with intraoperative bypass flow (BF) was assessed. The clinical outcomes, including neurologic state, incidence of recurrent infarction and complications, were also analyzed. The time-to-maximum (Tmax) > 8 s, > 6 s and > 4 s volumes decreased significantly at PostOp0 and up through PostOp6M (preoperative, 5, 51, and 223 ml (median), respectively PostOp0, 0, 20.25, and 143 ml, respectively PostOp6M, 0, 7.5, and 148.5 ml, respectively p < 0.001, p < 0.001, and p < 0.001, respectively). The postoperative improvement in the Tmax > 6 s and > 4 s volumes was significantly correlated with the BF at PostOp0 and PostOp6M (PostOp0, r 0.367 (p 0.001) and r 0.275 (p 0.015), respectively PostOp6M r 0.511 (p < 0.001) and r 0.391 (p 0.001), respectively). The incidence of recurrent cerebral infarction was 4.7%, and there were no major complications that produced permanent neurological impairment. Nonemergent EIB under strict operation indications can be a feasible treatment for symptomatic, hemodynamically compromised LAA patients.

Creatinine Index A retrospective cohort study in an urban Australian dialysis context.

Maintenance haemodialysis is a catabolic state associated with significant decrease in lean body mass (LBM) and protein energy wasting. LBM can be derived or estimated from creatinine kinetic modelling, specifically the creatinine index (CI). This has been demonstrated in cohort studies predict mortality. 179 patients undergoing haemodialysis in 2015 were included in this cohort. They were followed for five years with pertinent clinical data collected to calculate the CI as of December 2015. For the purposes of analysis, patients were split into a high and low CI group based upon the median (18.32 mgkgday). The primary outcome of interest was all-cause mortality and secondary outcomes included myocardial infarction, stroke and transplantation. During follow up, 69 (76.7%) patients in the low CI group and 28 (31.5%) patients in the high CI group died (p < 0.001). The relative risk (RR) of mortality within the low compared to high CI group was 2.43 (95% CI 1.75-3.38). Fully adjusted cox proportional hazards modelling demonstrated a HR 0.498 (95% CI 0.292-0.848) for survival in the high CI group. Lower CI was associated with increased risk of stroke (RR 5.43 95% CI 1.24-23.84) while transplant was more likely in the high CI group (RR 6.4 95% CI 1.96-20.88). In a single centre Australian haemodialysis cohort, the CI was strongly associated with mortality and stroke risk. The CI is an accurate and simple method to identify patients with low lean body mass, at risk of significant morbidity and mortality. This article is protected by copyright. All rights reserved.

The Validation of Cardiac Index and Stroke-Volume Variation Measured by the Pulse-Wave Transit Time-Analysis Versus Conventional Pulse-Contour Analysis After Off-Pump Coronary Artery Bypass Grafting Observational Study.

To compare the reliability of cardiac index (CI) and stroke-volume variation (SVV) measured by the pulse-wave transit-time (PWTT) method using estimated continuous cardiac output (esCCO) technique with conventional pulse-contour analysis after off-pump coronary artery bypass grafting (OPCAB). A single-center, prospective, observational study. At a 1,000-bed university hospital. A total of 21 patients were enrolled after elective OPCAB. The study authors performed a method comparison study with simultaneous measurement of CI and SVV based on the esCCO technique (CI The overall performance of CI

Recommended and observed statin use among U.S. adults - National Health and Nutrition Examination Survey, 2011-2018.

The American College of CardiologyAmerican Heart Association Blood Cholesterol Guideline was published in 2013 (2013 Cholesterol Guideline) and the Multi-society Guideline on the Management of Blood Cholesterol in 2018 (2018 Cholesterol Guideline). To compare differences in population level estimates for statin recommendations and use between guidelines. Using four 2-year cycles from the National Health and Nutrition Examination Survey (2011-2018), we analyzed data from 8,642 non-pregnant adults aged ≥20 years with complete information for blood cholesterol measurements and other cardiovascular risk factors used to define treatment recommendations in the 2013 or 2018 Cholesterol Guidelines. We compared the prevalence of statin recommendations and use between the guidelines, overall and among patient management groups. Under the 2013 Cholesterol Guideline, an estimated 77.8 million (33.6%) adults would be recommended statins, compared to 46.1 million (19.9%) recommended and 50.1 million (21.6%) considered for statins by the 2018 Cholesterol Guideline. Statin use among those recommended treatment was similar utilizing the 2018 Cholesterol Guideline (47.4%) compared to the 2013 Cholesterol Guideline (47.0%). Differences were observed across demographic and patient management groups. Compared to the 2013 Cholesterol Guideline, the prevalence of statin recommendations decreased utilizing the 2018 Cholesterol Guideline algorithm, though additional persons would be considered for treatment after risk factor assessment and patient-clinician discussion under the 2018 Cholesterol Guideline. Statin use was suboptimal (<50%) for those recommended treatment under either guideline. Optimizing patient-clinician risk discussions and shared decision making may be needed to improve treatment rates.

Neurologic Improvement in Acute Cerebral Ischemia Frequency, Magnitude, Predictors, and Clinical Outcomes.

Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period. We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale mRS score 0-1) and death by 90 days. Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2) 45% were women the median prehospital LAMS was 4 (interquartile range IQR 3-5) the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246378) vs 35.4% (302852), U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION clinicaltrials.gov. Unique identifier NCT00059332.

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke A Post-Hoc Analysis of the EXTEND-IA TNK Trials.

The safety and efficacy of tenecteplase in patients with tandem lesion stroke is unknown. We performed a comparative analysis of tenecteplase versus alteplase in patients with tandem lesions. We first compared the treatment effect of tenecteplase and alteplase in patients with tandem lesions using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day mRS with ordinal logistic and Firth regression models. Because two key outcomes, mortality and symptomatic intracranial hemorrhage, were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving tenecteplase. Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a tandem lesion. In tandem lesion patients, intracranial reperfusion was observed in 1156 (20%) of tenecteplase treated patients vs. 115 (7%) alteplase treated patients (aOR 2.19 95% CI0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common OR 1.48 95% CI 0.44-5.00). A pooled study-level proportion of alteplase associated mortality and symptomatic intracranial hemorrhage was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared to a mortality rate of 0.09 (95% CI 0.03-0.20) and a symptomatic intracranial hemorrhage rate of 0.07 (95% CI 0.02-0.17) in tenecteplase treated patients, no significant difference was observed. Functional outcomes, mortality, and symptomatic intracranial hemorrhage did not significantly differ between tenecteplase and alteplase treated tandem lesion patients. This study provides Class III evidence that tenecteplase is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and symptomatic intracranial hemorrhage compared with alteplase, in patients with acute stroke due to tandem lesions. However, the confidence intervals do not rule out clinically important differences.

Penumbra salvage in extensive stroke exploring limits for reperfusion therapy.

The effect of thrombectomy in patients presenting with extensive ischemic stroke at baseline is currently being investigated it remains uncertain to what extent brain tissue may be saved by reperfusion in such patients. Penumbra salvage volume (PSV) has been described as a tool to measure the volume of rescued penumbra. To assess whether the effect of recanalization on PSV is dependent on the extent of early ischemic changes. Observational study of patients with anterior circulation ischemic stroke triaged by multimodal-CT undergoing thrombectomy. PSV was defined as the difference between baseline penumbra volume and net infarct growth to follow-up. The effect of vessel recanalization on PSV depending on the extent of early ischemic changes (defined using Alberta Stroke Program Early CT Score (ASPECTS) and core volumes based on relative cerebral blood flow) was determined using multivariable linear regression analysis, and the association with functional outcome at day 90 was tested using multivariable logistic regression. 384 patients were included, of whom 292 (76%) achieved successful recanalization (modified Thrombolysis in Cerebral Infarction ≥2b). Successful recanalization was independently associated with 59 mL PSV (95% CI 29.8 to 88.8 mL) and was linked to increased penumbra salvage up to an ASPECTS of 3 and core volume up to 110 mL. Recanalization was associated with a higher probability of a modified Rankin Scale score of ≤2 up to a core volume of 100 mL. Recanalization was associated with significant penumbra salvage up to a lower ASPECTS margin of 3 and upper core volume margin of 110 mL. The clinical benefit of recanalization for patients with very large ischemic regions of >100 mL or ASPECTS <3 remains uncertain and requires prospective investigation.

Development of a clot-adhesive coating to improve the performance of thrombectomy devices.

The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures. Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model. Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model. Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus.

Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence () or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS() and 10 were HCAS(-). HCAS() were most significantly differentially abundant in actin cytoskeletal protein (P0.002, Z2.82), bleomycin hydrolase (P0.007, Z2.44), arachidonate 12-lipoxygenase (P0.004, Z2.60), and lysophospholipase D (P0.007, Z2.44), among other proteins HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P0.0009, Z3.11), tyrosine-protein kinase Fyn (P0.002, Z2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodelingassembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization.

Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events.

To determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association differs by sex. Our cohort study used routinely collected hospital, pharmaceutical dispensing and mortality data for residents of New South Wales, Australia. We included patients hospitalised for a major cardiovascular event or procedure 2011-2017, who were dispensed varenicline or prescription NRT patches within 90day postdischarge. Exposure was defined using an approach analogous to intention to treat. Using inverse probability of treatment weighting with propensity scores to account for confounding, we estimated adjusted HRs for major cardiovascular events (MACEs), overall and by sex. We fitted an additional model with a sex-treatment interaction term to determine if treatment effects differed between males and females. Our cohort of 844 varenicline users (72% male, 75% <65 years) and 2446 prescription NRT patch users (67% male, 65% <65 years) were followed for a median of 2.93 years and 2.34 years, respectively. After weighting, there was no difference in risk of MACE for varenicline relative to prescription NRT patches (aHR 0.99, 95% CI 0.82 to 1.19). We found no difference (interaction p0.098) between males (aHR 0.92, 95% CI 0.73 to 1.16) and females (aHR 1.30, 95% CI 0.92 to 1.84), although the effect among females deviated from the null. We found no difference between varenicline and prescription NRT patches in the risk of recurrent MACE. These results should be considered when determining the most appropriate choice of smoking cessation pharmacotherapy.

Blood pressure-related white matter microstructural disintegrity and associated cognitive function impairment in asymptomatic adults.

We aimed to investigate the white matter (WM) microstructuralcytostructural disintegrity patterns related to higher systolic blood pressure (SBP), and whether they mediate SBP effects on cognitive performance in middle-aged adults. Using the UK Biobank study of community-dwelling volunteers aged 40-69 years, we included participants without a history of stroke, dementia, demyelinating disease or traumatic brain injury. We investigated the association of SBP with MRI diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (a measure of neurite density), isotropic (free) water volume fraction (ISOVF) and orientation dispersion across WM tracts. Then, we determined whether WM diffusion metrics mediated the effects of SBP on cognitive function. We analysed 31 363 participants-mean age of 63.8 years (SD 7.7), and 16 523 (53%) females. Higher SBP was associated with lower FA and neurite density, but higher MD and ISOVF. Among different WM tracts, diffusion metrics of the internal capsule anterior limb, external capsule, superior and posterior corona radiata were most affected by higher SBP. Among seven cognitive metrics, SBP levels were only associated with fluid intelligence (adjusted p<0.001). In mediation analysis, the averaged FA of external capsule, internal capsule anterior limb and superior cerebellar peduncle mediated 13%, 9% and 13% of SBP effects on fluid intelligence, while the averaged MD of external capsule, internal capsule anterior and posterior limbs, and superior corona radiata mediated 5%, 7%, 7% and 6% of SBP effects on fluid intelligence, respectively. Among asymptomatic adults, higher SBP is associated with pervasive WM microstructure disintegrity, partially due to reduced neuronal count, which appears to mediate SBP adverse effects on fluid intelligence. Diffusion metrics of select WM tracts, which are most reflective of SBP-related parenchymal damage and cognitive impairment, may serve as imaging biomarkers to assess treatment response in antihypertensive trials.

Loss of life expectancy due to stroke and its subtypes in urban and rural areas in China, 2005-2020.

Stroke is characterised by high mortality and disability rate in China. This study aimed to explore the temporal trends in years of life lost (YLL) and loss of life expectancy due to stroke and its subtypes in urban and rural areas in China during 2005-2020. Data were obtained from China National Mortality Surveillance System. Abbreviated life and stroke-eliminated life tables were generated to calculate loss of life expectancy. The YLL and loss of life expectancy due to stroke in urban and rural areas at both national and provincial level during 2005-2020 were estimated. In China, the age-standardised YLL rate due to stroke and its subtypes were higher in rural areas than in urban areas. The YLL rate due to stroke showed a downward trend in both urban and rural residents from 2005 to 2020, decreased by 39.9% and 21.5%, respectively. Loss of life expectancy caused by stroke decreased from 1.75 years to 1.70 years from 2005 to 2020. During which, loss of life expectancy due to intracerebral haemorrhage (ICH) decreased from 0.94 years to 0.65 years, while that of ischaemic stroke (IS) increased from 0.62 years to 0.86 years. A slightly upward trend was observed in loss of life expectancy caused by subarachnoid haemorrhage (SAH), from 0.05 years to 0.06 years. Loss of life expectancy due to ICH and SAH was always higher in rural areas than in urban areas, whereas that of IS was higher in urban areas than in rural areas. Rural males suffered the greatest loss of life expectancy due to ICH and SAH, while the highest loss of life expectancy caused by IS was found in urban females. Furthermore, Heilongjiang (2.25 years), Tibet (2.17 years) and Jilin (2.16 years) were found to have the highest loss of life expectancy caused by stroke in 2020. Loss of life expectancy caused by ICH and SAH was higher in western China, while the disease burden of IS was heavier in northeast China. Stroke remains a major public health problem in China, although the age-standardised YLL rate and loss of life expectancy due to stroke decreased. Evidence-based strategies should be conducted to reduce the premature death burden caused by stroke and prolong life expectancy in Chinese population.

Intraoperative hypotension and postoperative stroke in older patients who had brain tumour resections a retrospective cohort analysis.

At some level intraoperative hypotension causes strokes. Elderly neurosurgical patients are presumably at especially high risk. We therefore tested the primary hypothesis that intraoperative hypotension is associated with postoperative stroke in older brain tumour patients. We considered patients more than 65 years old who had elective craniotomy for tumour resections. Our primary exposure was the area under the threshold of intraoperative hypotension. The primary outcome was newly diagnosed ischemic stroke within 30 days, confirmed by scheduled brain imaging. Among 724 eligible patients, 98 (13.5%) had strokes within 30 days after surgery, 86% of which were clinically silent. Curves of lowest mean arterial pressure versus stroke incidence suggested a threshold at 75 mmHg. Area under thresholds of mean arterial pressure below 75 mmHg was therefore incorporated into multivariable modelling. There was no association of area below 75 mmHg and stroke (adjusted odds ratio aOR, 1.00 95% CI, 1.00 to 1.00). The aOR for area below 75 mmHg between 1 to 148 mmHgmin, was 1.21 (95% CI, 0.23 to 6.23). When the area below 75 mmHg exceeding 1117 mmHgmin, the association remained insignificant. In contrast, malignant tumour and history of previous stroke or myocardial ischemia were associated with strokes. Postoperative strokes were common in older patients who had brain tumour resections, with about 14% having ischemic cerebrovascular events within 30 days - of which 86% were clinically silent. Malignant brain tumours and previous ischemic vascular events were associated with postoperative strokes, but area under 75mmHg was not.

Constraint-induced movement therapy alleviates motor impairment by inhibiting the accumulation of neutrophil extracellular traps in ischemic cortex.

Stroke is a major cause of mortality and morbidity and most acute strokes are ischemic. Evidence-based medicine has demonstrated the effectiveness of constraint-induced movement therapy (CIMT) in the recovery of motor function in patients after ischemic stroke, but the specific treatment mechanism remains unclear. Herein, our integrated transcriptomics and multiple enrichment analysis studies, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) studies show that CIMT conduction broadly curtails immune response, neutrophil chemotaxis, and chemokine-mediated signaling pathway, CCR chemokine receptor binding. Those suggest the potential effect of CIMT on neutrophils in ischemic mice brain parenchyma. Recent studies have found that accumulating granulocytes release extracellular web-like structures composed of DNA and proteins called neutrophil extracellular traps (NETs), which destruct neurological function primarily by disrupting the blood-brain barrier and promoting thrombosis. However, the temporal and spatial distribution of neutrophils and their released NETs in parenchyma and their damaging effects on nerve cells remain unclear. Thus, utilizing immunofluorescence and flow cytometry, our analyses uncovered that NETs erode multiple regions such as primary motor cortex (M1), striatum (Str), nucleus of the vertical limb of the diagonal band (VDB), nucleus of the horizontal limb of the diagonal band (HDB) and medial septal nucleus (MS), and persist in the brain parenchyma for at least 14 days, while CIMT can reduce the content of NETs and chemokines CCL2 and CCL5 in M1. Intriguingly, CIMT failed to further reduce neurological deficits after inhibiting the NET formation by pharmacologic inhibition of peptidylarginine deiminase 4 (PAD4). Collectively, these results demonstrate that CIMT could alleviate cerebral ischemic injury induced locomotor deficits by modulating the activation of neutrophils. These data are expected to provide direct evidence for the expression of NETs in ischemic brain parenchyma and novel insights into the mechanisms of CIMT protecting against ischemic brain injury.

Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy on 1.5T T2-Weighted Imaging.

Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2-weighted MRI and to evaluate possible underlying mechanisms. We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n 3 vs. n 1, p 0.0012), presence of supratentorial macrobleed adjacent to the TC (p 0.002), and TC hemosiderosis (p 0.005). Cerebellar SS in CAA patients can be identified on 1.5T T2-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds.

Dantrolene Significantly Improves Cerebral Blood Flow in a Rat Model of Hemorrhagic Vasospasms.

A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mgkg) and nimodipine (1 mgkg and 2 mgkg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. BFV was reduced by 37% with dantrolene alone (n 6, p ≤ 0.05) and by 27% with 2 mgkg nimodipine (n 6, p < 0.05), while it was not affected by 1 mgkg nimodipine. The combination of 1 mgkg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mgkg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mgkg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, lumen area of the left common carotid artery decreased, whereas media thickness and the wall-to-lumen ratio increased when compared to contralateral controls. The latter finding suggests that vascular remodeling was present at this stage. Altogether, our results indicate that 2.5 mgkg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP.

CANNA-TICS Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study.

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TSCTD (n 97, randomized 21 to nabiximolsplacebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (1464 (21·9%) vs. 333 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficithyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

Role of conformational dynamics in pathogenic protein aggregation.

The accumulation of pathogenic protein oligomers and aggregates is associated with several devastating amyloid diseases. As protein aggregation is a multi-step nucleation-dependent process beginning with unfolding or misfolding of the native state, it is important to understand how innate protein dynamics influence aggregation propensity. Kinetic intermediates composed of heterogeneous ensembles of oligomers are frequently formed on the aggregation pathway. Characterization of the structure and dynamics of these intermediates is critical to the understanding of amyloid diseases since oligomers appear to be the main cytotoxic agents. In this review, we highlight recent biophysical studies of the roles of protein dynamics in driving pathogenic protein aggregation, yielding new mechanistic insights that can be leveraged for design of aggregation inhibitors.

Quality assessment of stroke radiomics studies Promoting clinical application.

To evaluate the quality of radiomics studies on stroke using a radiomics quality score (RQS), Minimum Information for Medial AI reporting (MINIMAR) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to promote clinical application. PubMed MEDLINE and Embase were searched to identify radiomics studies on stroke. Of 464 articles, 52 relevant original research articles were included. The RQS, MINIMAR and TRIPOD were scored to evaluate the quality of the studies by neuroradiologists. Only four studies (7.7 %) performed external validation. The mean RQS was 3.2 of 36 (8.9 %), and the basic adherence rate was 24.9 %. The adherence rate was low for conducting phantom study (1.9 %), stating comparison to gold standard (1.9 %), offering potential clinical utility (13.5 %) and performing cost-effectiveness analysis (1.9 %). None of the studies performed a test-retest, stated biologic correlation, conducted prospective studies, or opened codes and data to the public, resulting in low RQS. The total MINIMAR adherence rate was 47.4 %. The overall adherence rate for TRIPOD was 54.6 %, with low scores for reporting the title (2.0 %), key elements of the study setting (6.1 %), and explaining the sample size (2.0 %). The overall radiomics reporting quality and reporting of published radiomics studies on stoke was suboptimal. More thorough validation and open data are needed to increase clinical applicability of radiomics studies.

SAN-Net Learning generalization to unseen sites for stroke lesion segmentation with self-adaptive normalization.

There are considerable interests in automatic stroke lesion segmentation on magnetic resonance (MR) images in the medical imaging field, as stroke is an important cerebrovascular disease. Although deep learning-based models have been proposed for this task, generalizing these models to unseen sites is difficult due to not only the large inter-site discrepancy among different scanners, imaging protocols, and populations, but also the variations in stroke lesion shape, size, and location. To tackle this issue, we introduce a self-adaptive normalization network, termed SAN-Net, to achieve adaptive generalization on unseen sites for stroke lesion segmentation. Motivated by traditional z-score normalization and dynamic network, we devise a masked adaptive instance normalization (MAIN) to minimize inter-site discrepancies, which standardizes input MR images from different sites into a site-unrelated style by dynamically learning affine parameters from the input i.e., MAIN can affinely transform the intensity values. Then, we leverage a gradient reversal layer to force the U-net encoder to learn site-invariant representation with a site classifier, which further improves the model generalization in conjunction with MAIN. Finally, inspired by the pseudosymmetry of the human brain, we introduce a simple yet effective data augmentation technique, termed symmetry-inspired data augmentation (SIDA), that can be embedded within SAN-Net to double the sample size while halving memory consumption. Experimental results on the benchmark Anatomical Tracings of Lesions After Stroke (ATLAS) v1.2 dataset, which includes MR images from 9 different sites, demonstrate that under the leave-one-site-out setting, the proposed SAN-Net outperforms recently published methods in terms of quantitative metrics and qualitative comparisons.

Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis.

Children with hemiparesis (CWH) due to stroke early in life face lifelong impairments in motor function. Transcranial direct current stimulation (tDCS) may be a safe and feasible adjuvant therapy to augment rehabilitation. Given the variability in outcomes following tDCS, tailored protocols of tDCS are required. We evaluated the safety, feasibility, and preliminary effects of a single session of targeted anodal tDCS based on individual corticospinal tract organization on corticospinal excitability. Fourteen CWH (age 13.8 ± 3.63) were stratified into two corticospinal organization subgroups based on transcranial magnetic stimulation (TMS)-confirmed motor evoked potentials (MEP) ipsilesional MEP presence (MEP

Loureirin C inhibits ferroptosis after cerebral ischemia reperfusion through regulation of the Nrf2 pathway in mice.

Ischemic stroke (IS) is considered as a serious cerebral vascular disease. Ferroptosis is a novel type of regulated cell death (RCD), that closely related to the occurrence and progress of IS. Loureirin C, a type of dihydrochalcone compound derived from the Chinese Dragons blood (CDB). The effective components extracted from CDB have shown neuroprotective effects in ischemia reperfusion models. However, the role of Loureirin C in mice after IS is not well understood. Thus, it is worth to identify the effect and mechanism of Loureirin C on IS. The present research aims to prove the existence of ferroptosis in IS and explore whether Loureirin C can inhibit ferroptosis by regulating nuclear factor E2 related factor 2 (Nrf2) pathway in mice and exert neuroprotective effects on IS models. Middle cerebral artery occlusion and reperfusion (MCAOR) model was established to evaluate the occurrence of ferroptosis and the potential Loureirin C brain-protective effect in vivo. The analysis of free iron, glutamate content, reactive oxygen species (ROS) and lipid peroxidation levels, along with transmission electron microscope (TEM) was applied to prove the existence of ferroptosis. The function of Loureirin C on Nrf2 nuclear translocation was verified by immunofluorescence staining. In vitro, primary neurons and SH-SY5Y cells were processed with Loureirin C after oxygen and glucose deprivation-reperfusion (OGDR). ELISA kits, western blotting, co-immunoprecipitation (Co-IP) analysis, immunofluorescence, and quantitative real-time PCR were devoted to proving the neuroprotective effects of Loureirin C on IS via regulating ferroptosis and Nrf2 pathways. The results showed that Loureirin C not only dramatically alleviated brain injury and inhibited neurons ferroptosis in mice after MCAOR, but also dose-dependently reduce ROS accumulation in ferroptosis after OGDR. Further, Loureirin C inhibits ferroptosis by activating Nrf2 pathway, and promoting nuclear translocation of Nrf2. Besides, Loureirin C increases heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and glutathione peroxidase 4 (GPX4) content after IS. Intriguingly, the anti-ferroptosis effect of Loureirin C is weakened by Nrf2 knockdown. Our discoveries first revealed that the inhibitory action of Loureirin C on ferroptosis may greatly depend on its adjusting effect on the Nrf2 pathway, suggesting that Loureirin C could act as a novel anti-ferroptosis candidate and play a therapeutic role in IS. These novel discoveries on the role of Loureirin C on IS models reveal an innovative method that may contribute to neuroprotection for the prevention of IS.

Regressive changes in sizes of somatosensory cuneate nucleus after sensory loss in primates.

Neurons in the early stages of processing sensory information suffer transneuronal atrophy when deprived of their activating inputs. For over 40 y, members of our laboratory have studied the reorganization of the somatosensory cortex during and after recovering from different types of sensory loss. Here, we took advantage of the preserved histological material from these studies of the cortical effects of sensory loss to evaluate the histological consequences in the cuneate nucleus of the lower brainstem and the adjoining spinal cord. The neurons in the cuneate nucleus are activated by touch on the hand and arm, and relay this activation to the contralateral thalamus, and from the thalamus to the primary somatosensory cortex. Neurons deprived of activating inputs tend to shrink and sometimes die. We considered the effects of differences in species, type and extent of sensory loss, recovery time after injury, and age at the time of injury on the histology of the cuneate nucleus. The results indicate that all injuries that deprived part or all of the cuneate nucleus of sensory activation result in some atrophy of neurons as reflected by a decrease in nucleus size. The extent of the atrophy is greater with greater sensory loss and with longer recovery times. Based on supporting research, atrophy appears to involve a reduction in neuron size and neuropil, with little or no neuron loss. Thus, the potential exists for restoring the hand to cortex pathway with brain-machine interfaces, for bionic prosthetics, or biologically with hand replacement surgery.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease A Randomized Clinical Trial.

In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment September 9, 2016, through November 27, 2019 final follow-up October 26, 2022). Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mgdL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Among 4400 patients, 4341 patients (98.7%) completed the trial (mean SD age, 65.1 9.9 years 1228 females 27.9%). In the treat-to-target group (n 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mgdL in the treat-to-target group and 68.4 (20.1) mgdL in the high-intensity statin group (n 2200) (P .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points upper boundary of the 1-sided 97.5% CI, 1.1 percentage points P < .001 for noninferiority). Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mgdL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. ClinicalTrials.gov Identifier NCT02579499.

Comparison of 3 CT Perfusion Software Packages in Estimation of Ischemic Lesions in Acute Ischemic Stroke Patients.

The aim of this study was to compare 3 computed tomography perfusion (CTP) software packages in the estimation of infarct core volumes, hypoperfusion volumes, and mismatch volumes. Forty-three patients with large vessel occlusion in the anterior circulation who underwent CTP imaging were postprocessed by 3 software packages RAPID, advantage workstation (AW), and NovoStroke Kit (NSK). Infarct core volumes and hypoperfusion volumes were generated by RAPID with default settings. The AW and NSK threshold settings were the following infarct core (cerebral blood flow CBF <8 mLmin100 g, CBF <10 mLmin100 g, CBF <12 mLmin100 g, and cerebral blood volume CBV <1 mL100 g) and hypoperfusion (Tmax >6 seconds). Mismatch volumes were then obtained for all the combinations of the settings. Bland-Altman, intraclass correlation coefficient (ICC), and Spearman ρ or Pearson correlation coefficient were applied for statistical analysis. In the estimation of infarct core volumes, good agreement was observed between AW and RAPID when CBV <1 mL100 g (ICC, 0.767 P < 0.001). For hypoperfusion volumes, good agreement (ICC, 0.811 P < 0.001) and strong correlation (r 0.856 P < 0.001) were observed between NSK and RAPID. For mismatch volumes, the setting of CBF <10 mLmin100 g combined with hypoperfusion with NSK resulted in moderate agreement (ICC, 0.699 P < 0.001) with RAPID, which was the best among all other settings. The estimation results varied among different software packages. Advantage workstation had the best agreement with RAPID in the estimation of infarct core volumes when CBV <1 mL100 g. NovoStroke Kit had better agreement and correlation with RAPID in the estimation of hypoperfusion volumes. NovoStroke Kit also had moderate agreement with RAPID in estimating mismatch volumes.

Toll-like receptors (TLR2 and TLR4) antagonist mitigates the onset of cerebral small vessel disease through PI3KAktGSK3β pathway in stroke-prone renovascular hypertensive rats.

To examine the effect and mechanism of Toll-Like Receptors (TLR2, TLR4) antagonist in CSVD. The rat model of stroke-induced renovascular hypertension (RHRSP) was constructed. TLR2 and TLR4 antagonist was administrated by Intracranial injection. Morris water maze was used to observe the behavioral changes of rat models. HE staining, TUNEL staining and Evens Blue staining were performed to evaluate the permeability of the blood-brain barrier (BBB) and examine the CSVD occurrence and neuronal apoptosis. The inflammation and oxidative stress factors were detected by ELISA. Hypoxia-glucose-deficiency (OGD) ischemia model was constructed in cultured neurons. Western blot and ELISA were used to examine the related protein expression in TLR2TLR4 signaling pathway and PI3KAktGSK3β signaling pathway. The RHRSP rat model was successfully constructed, and the blood well and BBB permeability were altered. The RHRSP rats showed cogitative impairment and excessive immune response. After TLR2TLR4 antagonist administration, the behavior of model rats were improved, cerebral white matter injury was reduced, and the expression of several key inflammatory factors including TLR4, TLR2, Myd88 and NF-kB were decreased, as well as the ICAM-1, VCAM-1, inflammation and oxidative stress factors.

Limb to Cranial Overflow Dystonia in a Patient After Stroke.

This case report describes noncontiguous overflow dystonia in a patient with diabetes, hypertension, and a history of left putaminal hemorrhage and right hemiparesis.

Real-World Racial Variation in Treatment and Outcomes Among Patients with Peripheral Artery Disease.

Prior studies have found considerable disparities in prevalence and outcomes for patients with peripheral arterial disease (PAD). This study compared rates of diagnostic testing, treatment patterns, and outcomes after diagnosis of PAD among commercially insured Black and White patients in the United States. Optums de-identified Clinformatics A total of 669,939 patients were identified, with 454,382 White patients and 96,162 Black patients. Black patients were younger on average (71.8 years vs. 74.2 years), but had higher comorbid burden, concomitant risk factors, and CV medication use at baseline. Prevalence of diagnostic testing, revascularization procedures, and medication use was numerically higher among Black patients. Black patients were also more likely than the White patients to receive medical therapy without a revascularization procedure adjusted odds ratio with 95% confidence interval (CI) 1.47 (1.44-1.49). However, Black patients with PAD had higher incidence of MALE and CV events than White patients adjusted hazard ratio for composite event (95% CI) 1.13, (1.11-1.15). Except myocardial infarction, the hazards of individual components of MALE and CV events were also significantly higher among Black patients with PAD. Results of this real-world study suggest that Black patients with PAD have higher disease severity at the time of diagnosis and are at increased risk of experiencing adverse outcomes following diagnosis.

Secondary Ischemic Stroke Prevention.

The health burden of ischemic stroke is high and will continue to increase with an aging population. Recurrent ischemic stroke is increasingly recognized as a major public health concern with potentially debilitating sequelae. Thus, it is imperative to develop and implement effective strategies for stroke prevention. When considering secondary ischemic stroke prevention, it is important to consider the mechanism of the first stroke and the related vascular risk factors. Secondary ischemic stroke prevention typically includes multiple medical and, potentially, surgical treatments, but with the shared goal of reducing the risk of recurrent ischemic stroke. Providers, health care systems, and insurers also need to consider the availability of treatments, their cost and patient burden, methods for improving adherence, and interventions that target lifestyle risk factors such as diet or activity. In this article, we discuss aspects from the 2021 AHA Guideline on Secondary Stroke Prevention as well as highlight additional information relevant to best practices for reducing recurrent stroke risk.

The Lived Experience of Serious Stroke Survival A Hermeneutic Phenomenological Case Study.

The aim of this study was to describe the lived experiences of a serious stroke survivor. This is a hermeneutic phenomenological case study. Data were collected via observations and conversations during 75 visits, 14 brief audiotaped interviews, field notes, and conversations with family members, close friends, and care providers. Seven themes emerged that form the general structure of the lived experience of surviving a serious stroke. These themes were organized around four fundamental existential themes including space, time, body, and relationships. Spend intentional time with patients beyond the initial stroke rehabilitation period to better understand the experience, individualize care, identify meaningful activities previously engaged in, and identify people who may be willing to partner with them to continue participation in the meaningful activities. Hermeneutic phenomenology allows the essence of the stroke survival experience to be revealed and contributes to better understanding of the phenomenon.

Coordinated Care to Optimize Cardiovascular Preventive Therapies in Type 2 Diabetes A Randomized Clinical Trial.

Evidence-based therapies to reduce atherosclerotic cardiovascular disease risk in adults with type 2 diabetes are underused in clinical practice. To assess the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the proportion of adults with type 2 diabetes and atherosclerotic cardiovascular disease prescribed all 3 groups of recommended, evidence-based therapies (high-intensity statins, angiotensin-converting enzyme inhibitors ACEIs or angiotensin receptor blockers ARBs, and sodium-glucose cotransporter 2 SGLT2 inhibitors andor glucagon-like peptide 1 receptor agonists GLP-1RAs). Cluster randomized clinical trial with 43 US cardiology clinics recruiting participants from July 2019 through May 2022 and follow-up through December 2022. The participants were adults with type 2 diabetes and atherosclerotic cardiovascular disease not already taking all 3 groups of evidence-based therapies. Assessing local barriers, developing care pathways, coordinating care, educating clinicians, reporting data back to the clinics, and providing tools for participants (n 459) vs usual care per practice guidelines (n 590). The primary outcome was the proportion of participants prescribed all 3 groups of recommended therapies at 6 to 12 months after enrollment. The secondary outcomes included changes in atherosclerotic cardiovascular disease risk factors and a composite outcome of all-cause death or hospitalization for myocardial infarction, stroke, decompensated heart failure, or urgent revascularization (the trial was not powered to show these differences). Of 1049 participants enrolled (459 at 20 intervention clinics and 590 at 23 usual care clinics), the median age was 70 years and there were 338 women (32.2%), 173 Black participants (16.5%), and 90 Hispanic participants (8.6%). At the last follow-up visit (12 months for 97.3% of participants), those in the intervention group were more likely to be prescribed all 3 therapies (173457 37.9%) vs the usual care group (85588 14.5%), which is a difference of 23.4% (adjusted odds ratio OR, 4.38 95% CI, 2.49 to 7.71 P < .001) and were more likely to be prescribed each of the 3 therapies (change from baseline in high-intensity statins from 66.5% to 70.7% for intervention vs from 58.2% to 56.8% for usual care adjusted OR, 1.73 95% CI, 1.06-2.83 ACEIs or ARBs from 75.1% to 81.4% for intervention vs from 69.6% to 68.4% for usual care adjusted OR, 1.82 95% CI, 1.14-2.91 SGLT2 inhibitors andor GLP-1RAs from 12.3% to 60.4% for intervention vs from 14.5% to 35.5% for usual care adjusted OR, 3.11 95% CI, 2.08-4.64). The intervention was not associated with changes in atherosclerotic cardiovascular disease risk factors. The composite secondary outcome occurred in 23 of 457 participants (5%) in the intervention group vs 40 of 588 participants (6.8%) in the usual care group (adjusted hazard ratio, 0.79 95% CI, 0.46 to 1.33). A coordinated, multifaceted intervention increased prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease. ClinicalTrials.gov Identifier NCT03936660.

Short-term risk of periprocedural stroke relative to radial vs. femoral access systematic review, meta-analysis, study sequential analysis and meta-regression of 2,188,047 real-world cardiac catheterizations.

To verify whether transradial (TRA) compared to transfemoral (TFA) cardiac catheterization reduces the risk of periprocedural stroke (PS). We reviewed (CRD42021277918) published real-world cohorts reporting the incidence of PS within 3 days following diagnostic or interventional catheterization. Meta-analyses and meta-regressions of odds ratios (OR) performed using the DerSimonian and Laird method were checked for publication bias (Egger test) and adjusted for false-positive results (study sequential analysis SSA). The pooled incidence of PS from 2,188,047 catheterizations (14 cohorts), was 193 (105 to 355) per 100,000. Meta-analyses of adjusted estimates (OR 0.66 (0.49 to 0.89) p 0.007 I Periprocedural stroke remains a rare and hard-to-predict adverse event associated with cardiac catheterization. TRA is associated with a 20% to 30% lower risk of PS in real-worldcommon practice settings. Future studies are unlikely to change our conclusion.

When is the best time to screen and evaluate for treatable genetic disorders A lifespan perspective.

This paper focuses on the question of, When is the best time to identify an individual at risk for a treatable genetic condition In this review, we describe a framework for considering the optimal timing for pursuing genetic and genomic screening for treatable genetic conditions incorporating a lifespan approach. Utilizing the concept of a carousel that represents the four broad time periods when critical decisions might be made around genetic diagnoses during a persons lifetime, we describe genetic testing during the prenatal period, the newborn period, childhood, and adulthood. For each of these periods, we describe the objectives of genetic testing, the current status of screening or testing, the near-term vision for the future of genomic testing, the advantages and disadvantages of each approach, and the feasibility and ethical considerations of testing and treating. The notion of a Genomics Passbook is one where an early genomic screening evaluation could be performed on each individual through a public health program, with that data ultimately serving as a living document that could be queried andor reanalyzed at prescribed times during the lifetime of that person, or in response to concerns about symptoms of a genetic disorder in that individual.

Expression of Tie2 (angiopoietin receptor) on the monocyte subpopulations from ischemic stroke patients Histological and flowcytometric studies.

Different subpopulations of monocytes play roles in phagocytosis, inflammation, and angiogenic processes e.g., Tie2-expressing monocytes (TEMs). The brain is flooded with macrophages that are derived from monocytes within 3-7 days after a stroke. This study aimed to determine the expression level of Tie2 (an angiopoietin receptor) on monocytes and their subpopulations in ischemic stroke patients using the histological and immunohistological study of bone marrow biopsies and blood flow cytometry examination. Ischemic stroke patients within two days were selected. Participants in the control group were healthy volunteers of matched age and gender. Sample collection was performed within 24 to 48 hours after medical consultants confirmed the stroke diagnosis. An iliac crest bone marrow biopsy was obtained and fixed for histological and immunohistological staining with antiCD14 and antiCD68. Flow cytometry was used to determine the total monocyte population, monocyte subpopulations, and TEMs after staining with monoclonal antibodies to CD45, CD14, CD16, and Tie2. Post-stroke patients bone marrow cells were hypercellular. There was an apparent increase in CD68 and CD14-positive cells. Ischemic stroke patients exhibited low percentages of nonclassical monocytes CD14lowCD16, with an increase in intermediate monocytes CD14highCD16. Moreover, ischemic stroke patients had significantly higher levels of TEMs than control group. The results of this study demonstrate dysregulation of angiogenesis in monocyte subsets in ischemic stroke patients, which could be used as an early diagnostic marker of neurovascular damage and may need angiogenic therapy or improved medications to prevent further damage of blood vessels.

Telerehabilitation Initiated Early in Post-Stroke Recovery A Feasibility Study.

Enhanced neural plasticity early after stroke suggests the potential to improve outcomes with intensive rehabilitation therapy. Most patients do not get such therapy, however, due to limited access, changing rehabilitation therapy settings, low therapy doses, and poor compliance. To examine the feasibility, safety, and potential efficacy of an established telerehabilitation (TR) program after stroke initiated during admission to an inpatient rehabilitation facility (IRF) and completed in the patients home. Participants with hemiparetic stroke admitted to an IRF received daily TR targeting arm motor function in addition to usual care. Treatment consisted of 36, 70-minute sessions (half supervised by a licensed therapist via videoconference), over a 6-week period, that included functional games, exercise videos, education, and daily assessments. Sixteen participants of 19 allocated completed the intervention (age 61.3 ± 9.4 years 6 female baseline Upper Extremity Fugl-Meyer UEFM score 35.9 ± 6.4 points, mean ± SD NIHSS score 4 (3.75, 5.25), median, IQR intervention commenced 28.3 ± 13.0 days post-stroke). Compliance was 100%, retention 84%, and patient satisfaction 93% 2 patients developed COVID-19 and continued TR. Post-intervention UEFM improvement was 18.1 ± 10.9 points ( These results support feasibility, safety, and potential efficacy of providing intense TR therapy early after stroke. clinicaltrials.gov NCT04657770.

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events its effects on cardiovascular outcomes remain uncertain. We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (statin-intolerant patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A total of 13,970 patients underwent randomization 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients 11.7% vs. 927 13.3% hazard ratio, 0.87 95% confidence interval CI, 0.79 to 0.96 P 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 8.2% vs. 663 9.5% hazard ratio, 0.85 95% CI, 0.76 to 0.96 P 0.006) fatal or nonfatal myocardial infarction (261 3.7% vs. 334 4.8% hazard ratio, 0.77 95% CI, 0.66 to 0.91 P 0.002) and coronary revascularization (435 6.2% vs. 529 7.6% hazard ratio, 0.81 95% CI, 0.72 to 0.92 P 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).

MTHFR C677T polymorphism, homocysteine, burden, and location of AMI and ACI.

We aimed to investigate the relationship between homocysteine levels and MTHFR C677T polymorphisms and acute ischemic vascular events and focused on the differential effects of the MTHFR C677T polymorphisms on the burden and location of AMI and ACI. 102 acute cerebral infarction (ACI) and acute myocardial infarction (AMI) patients who were admitted to the First Hospital of Jilin University in northeast China as the patient group, 83 healthy people who were hospitalized during the same period served as a control group. MTHFR C677T genotypes were identified via Polymerase Chain Reaction (PCR)-Fluorescent Probe Method. Patient group had higher serum homocysteine levels (p0.013), lower serum folic acid (p<0.001), and Vit B12 levels (p0.004) compared to the control group. Homocysteine levels in the patient group with the TT genotypes of the MTHFR C677T polymorphisms were higher than those with the CC and CT genotypes (p<0.05). Folic acid levels in the patients with TT genotypes were lower than those with the CC genotypes (p<0.05), but not in the control group (p>0.05). There were negative and significant associations between serum homocysteine levels and serum vitamin B12 levels in the control group (r-0.234, p0.033), but not between serum homocysteine levels and serum folic acid levels (r-0.103, p0.355). Conversely, there was a negative and significant association between serum homocysteine levels and serum folic acid levels in the patients group (r-0.257, p0.01), but not between serum homocysteine levels and serum vitamin B12 levels (r-0.185, p0.64). No statistically significant differences in MTHFR C677T genotype and CT alleles distribution were investigated between the patient and control group (p>0.05). The MTHFR C677T polymorphism did not differentially affect the burden and location of AMI and ACI. Homocysteine played a common role in atherosclerosis-related acute ischemic vascular events. These correlations were modified by MTHFR C677T polymorphisms and influenced by folic acid levels. The MTHFR C677T polymorphisms were not directly related to acute ischemic vascular events, nor did they differentially affect the burden and location of AMI and ACI.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. A correlation research between patients biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome.

Spreading depolarizations (SDs) are believed to contribute to injury progression and worsen outcomes in focal cerebral ischemia because exogenously induced SDs have been associated with enlarged infarct volumes. However, previous studies used highly invasive methods to trigger SDs that can directly cause tissue injury (eg, topical KCl) and confound the interpretation. Here, we tested whether SDs indeed enlarge infarcts when induced via a novel, noninjurious method using optogenetics. Using transgenic mice expressing channelrhodopsin-2 in neurons (Thy1-ChR2-YFP), we induced 8 optogenetic SDs to trigger SDs noninvasively at a remote cortical location in a noninjurious manner during 1-hour distal microvascular clip or proximal an endovascular filament occlusion of the middle cerebral artery. Laser speckle imaging was used to monitor cerebral blood flow. Infarct volumes were then quantified at 24 or 48 hours. Infarct volumes in the optogenetic SD arm did not differ from the control arm in either distal or proximal middle cerebral artery occlusion, despite a 6-fold and 4-fold higher number of SDs, respectively. Identical optogenetic illumination in wild-type mice did not affect the infarct volume. Full-field laser speckle imaging showed that optogenetic stimulation did not affect the perfusion in the peri-infarct cortex. Altogether, these data show that SDs induced noninvasively using optogenetics do not worsen tissue outcomes. Our findings compel a careful reexamination of the notion that SDs are causally linked to infarct expansion.

Change in Smoking Behavior and Outcome After Ischemic Stroke Post-Hoc Analysis of the SPS3 Trial.

Cigarette smoking is a known risk factor for cardiovascular disease, including ischemic stroke. The literature regarding the rate of persistent smoking after acute ischemic stroke and its effect on subsequent cardiovascular events is scarce. With this study, we aimed to report the rate of persistent smoking after ischemic stroke and the association between smoking status and major cardiovascular outcomes. This is a post-hoc analysis of the SPS3 trial (Secondary Prevention of Small Subcortical Strokes). Patients were divided into 4 groups based on smoking status at trial enrollment (1) never smokers, (2) former smokers, (3) smokers who quit at 3 months, and (4) persistent smokers. The primary outcome is a major adverse cardiovascular events composite of stroke (ischemic and hemorrhagic), myocardial infarction, and mortality. Outcomes were adjudicated after month 3 of enrollment until an outcome event or the end of study follow-up. A total of 2874 patients were included in the study. Of the total cohort, 570 patients (20%) were smokers at enrollment, of whom 408 (71.5%) patients continued to smoke and 162 (28.4%) quit smoking by 3 months. The major adverse cardiovascular events outcome occurred in 18.4%, 12.4%, 16.2%, and 14.4%, respectively, in persistent smokers, smokers who quit, prior smokers, and never smokers. In a model adjusted for age, sex, race, ethnicity, education, employment status, history of hypertension, diabetes, hyperlipidemia, myocardial infarction, and intensive blood pressure randomization arm, the risk of major adverse cardiovascular events, and death were higher in the persistent smokers compared with never smokers (HR for major adverse cardiovascular events 1.56 95% CI, 1.16-2.09 HR for death 2.0 95% CI, 2.18-3.12). The risk of stroke, and MI did not differ according to smoking status Conclusions Compared with never smoking, persistent smoking after acute ischemic stroke was associated with an increased risk of cardiovascular events and death. URL httpswww. gov Unique identifier NCT00059306.

Features of gas exchange and metabolism of the brain during revascularization of the carotid arteries.

The relevance of the stated topic of scientific research is determined by the fact that stroke is still the most important medical and social problem both in the world as a whole and in the Republic of Kazakhstan in particular due to high rates of morbidity, mortality, and disability. In addition, cerebrovascular diseases occupy one of the leading places in the structure of morbidity, disability and mortality, second only to coronary heart disease in Kazakhstan as well as around the world. The purpose of this research work is to study the features of gas exchange and brain metabolism during the revascularization of the carotid arteries. The basis of the methodological approach in this research work is a combination of methods of systematic analysis of the main features of gas exchange and brain metabolism in combination with a systematic study of the results obtained during the treatment of patients diagnosed with carotid artery stenosis at the Syzganov National Research Surgery Center in the period 2015-2020, divided into two main groups according to the applied principles of treatment. The results obtained in this research work indicate high efficiency of carotid endarterectomy and carotid stenting in finding ways to solve problems with cerebral circulation in patients suffering from carotid artery stenosis, as well as with the need for further use of these methods in clinical practice. The results obtained in the course of this scientific study, as well as the conclusions formulated on their basis, are of significant practical importance in terms of creating effective methods for treatment of patients recovering after a stroke, as well as for prevention of occurrence and development of stroke (Tab. 4, Ref. 20). Text in PDF www.elis.sk Keywords carotid artery stenting, carotid endarterectomy, ischemic stroke, atherosclerosis, heart attack.

Percutaneous atrial septal defect closure in Ebsteins anomaly.

We report a patient with Ebsteins anomaly, on chronic milrinone therapy for right ventricular failure, who underwent palliative percutaneous closure of her atrial septal defect (ASD) due to recurring strokes. Repeated evaluation of right-sided pressures was performed prior to ASD closure to determine if our patient could tolerate the intervention. Definitive ASD closure was performed under fluoroscopic and transesophageal echocardiogram guidance.

Improvement in Hypertension Control Among Adults Seen in Federally Qualified Health Center Clinics in the Stroke Belt Implementing a Program with a Dashboard and Process Metrics.

Attain 75% hypertension (HTN) control and improve racial equity in control with the American Medical Association Measure accurately, Act rapidly, Partner with patients blood pressure (AMA MAP BP™) quality improvement program, including a monthly dashboard and practice facilitation. Eight federally qualified health center clinics from the HopeHealth network in South Carolina participated. Clinic staff received monthly practice facilitation guided by a dashboard with process metrics (measure repeat BP when initial systolic ≥140 or diastolic ≥90 mmHg Act number antihypertensive medication classes prescribed at standard dose or greater to adults with uncontrolled BP Partner follow-up within 30 days of uncontrolled BP systolic BP fall after medication added) and outcome metric (BP <140<90). Electronic health record data were obtained on adults ≥18 years at baseline and monthly during MAP BP. Patients with diagnosed HTN, ≥1 encounter at baseline, and ≥2 encounters during 6 months of MAP BP were included in this evaluation. Among 45,498 adults with encounters during the 1-year baseline, 20,963 (46.1%) had diagnosed HTN 12,370 (59%) met the inclusion criteria (67% black, 29% white mean (standard deviation) age 59.5 (12.8) years 16.3% uninsured. HTN control improved (63.6% vs. 75.1%, With MAP BP, the HTN control goal was attained among adults eligible for analysis. Ongoing efforts aim to improve program access and racial equity in control.

Associations in Cigarette Smoking and Health Conditions by RaceEthnicity Among a Diverse Sample of Patients Receiving Treatment in a Federally Qualified Health Care Setting in Chicago.

To examine the association of cigarette use and smoking-related health conditions by raceethnicity among diverse and low-income patients at a federally qualified health center (FQHC). Demographics, smoking status, health conditions, death, and health service use were extracted from electronic medical data for patients seen between September 1, 2018, and August 31, 2020 ( Current and former smoking rates were 20.1% and 15.2%, respectively. Males, Black, White, non-partnered, older, and MedicaidMedicare patients were more likely to smoke. Compared with never smokers, former and heavy smokers had higher odds for all health conditions except respiratory failure, and light smokers had higher odds of asthma, chronic obstructive pulmonary disease, emphysema, and peripheral vascular disease. All smoking categories had more emergency department visits and hospitalizations than never smokers. The associations between smoking status and health conditions differed by raceethnicity. White patients who smoked had a greater increase in odds of stroke and other cardiovascular diseases compared with Hispanic and Black patients. Black patients who smoked had a greater increase in odds of emphysema and respiratory failure compared with Hispanic patients. Black and Hispanic patients who smoked had a greater increase in emergency care use compared with White patients. Smoking was associated with disease burden and emergency care and differed by raceethnicity. Resources to document smoking status and offer cessation services should be increased in FQHCs to promote health equity for lower income populations.

Race Analysis and Determination of Stroke Frequency - Stroke Length Combinations during the 50-M Freestyle Event.

The aims of this study were to (1) analyze and compare the stroke kinematics between junior and senior elite male swimmers in every section of the race during the 50-m freestyle event, and (2) identify stroke frequency (SF)-stroke length (SL) combinations on swim speed independently for junior and senior swimmers in each section of the 50-m freestyle event. Eighty-six junior swimmers (2019) and 95 seniors (2021) competing in the 50-m long course meter LEN Championships were analyzed. The t-test independent samples (p ≤ 0.05) were used to compare juniors and seniors. The SF and SL combinations on swim speed were explored using three-way ANOVAs. Senior swimmers were significantly faster in the 50-m race than juniors (p < 0.001). Speed presented the largest significant difference (p < 0.001) in section S0-15 m (start until the 15

Emerging role of miRNAs in the regulation of ferroptosis.

Ferroptosis is a kind of cell death which has distinctive features differentiating it from autophagy, necrosis and apoptosis. This iron-dependent form of cell death is described by an increase in lipid reactive oxygen species, shrinkage of mitochondria and decrease in mitochondrial cristae. Ferroptosis is involved in the initiation and progression of many diseases and is regarded as a hotspot of investigations on treatment of disorders. Recent studies have shown that microRNAs partake in the regulation of ferroptosis. The impact of microRNAs on this process has been verified in different cancers as well as intervertebral disc degeneration, acute myocardial infarction, vascular disease, intracerebral hemorrhage, preeclampsia, hemorrhagic stroke, atrial fibrillation, pulmonary fibrosis and atherosclerosis. miR-675, miR-93, miR-27a, miR-34a and miR-141 have been shown to affect iron metabolism, antioxidant metabolism and lipid metabolism, thus influencing all pivotal mechanisms in the ferroptosis process. In the current review, we summarize the role of microRNAs in ferroptosis and their involvement in the pathetiology of malignant and non-malignant disorders.

Effect of Postoperative Non-Weight-Bearing in Trochanteric Fracture of the Femur A Retrospective Cohort Study Using Propensity Score Matching.

The effects of postoperative early weight-bearing (WB) on walking ability, muscle mass, and sarcopenia have been investigated. Postoperative WB restriction is also reportedly associated with pneumonia and prolonged hospitalization however, its effect on surgical failures has not been studied. This study aimed to assess whether WB restriction after surgery for trochanteric fracture of the femur (TFF) is useful in preventing surgical failure, considering the unstable fracture type, quality of intraoperative reduction, and tip-apex distance. This retrospective analysis included 301 patients admitted to a single institution between January 2010 and December 2021, diagnosed with TFF, and who underwent femoral nail surgery. Eight patients were excluded, and finally 293 patients were included in the study. Propensity score (PS) matching yielded 123 cases 41 patients in the non-WB (NWB) group and 82 patients in the WB group were included in the final analysis. The primary outcome was surgical failure (cutout, nonunion, osteonecrosis, and implant failure). The secondary outcomes were medical complications (pneumonia, urinary tract infection, stroke, and heart failure), change in walking ability, period of hospitalization, and sliding distance of the lag screw. Five surgical complications occurred in the NWB group and two in the WB group, with significantly more surgical complications in the NWB group ( The results of this retrospective cohort study using a PS matching approach showed that WB restriction after TFF surgery could not decrease the incidence of surgical failures.

The quality of systematic reviewsmeta-analyses assessing the effects of ankle-foot orthosis on clinical outcomes in stroke patients A methodological systematic review.

Given the importance of systematic reviews (SRs) for practitioners, researchers, and policymakers, it is essential to assess them to ensure robust methodology and reliable results before applying them. The purpose of this methodological study was to assess the methodological and reporting quality of recently published SRs andor meta-analyses (MAs) evaluating the effects of ankle-foot orthoses (AFOs) on clinical outcomes in stroke survivors. PubMed, Scopus, Web of Science, Embase, ProQuest, CENTRAL, REHABDATA, and PEDro were searched. The research team applied A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) tool and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist for evaluating the reporting and methodological quality, respectively, and the ROBIS tool was used to evaluate the risk of bias (RoB) in the included reviews. The quality of the evidence was also judged using the (Grades of Recommendation, Assessment, Development and Evaluation) GRADE method. In final, 14 SRsMAs met inclusion criteria. Evaluation of methodological quality using the AMSTAR-2 tool demonstrated that the overall quality of included reviews was mostly critically low or low, except for two studies that were high. In addition, the findings showed that the mean score of the reporting quality of the included reviews based on the PRISMA criteria was 24.9, down from 42. In accordance with the overall evaluation applying the ROBIS tool, 14.3% of the review studies were evaluated as high RoB, 64.3% were evaluated as unclear RoB, and 21.4% were evaluated as low RoB. Regarding the level of evidence quality, the GRADE results indicated that the evidence quality of the included reviews was unsatisfactory. This study showed that although the reporting quality of recently published SRMAs evaluating the clinical effects of AFOs in stroke survivors was moderate, the methodological quality of almost all reviews was suboptimal. Therefore, reviewers must consider a number of criteria in designing, conducting, and reporting their studies to move toward transparent and conclusive results.

Association of a low vitamin D status with risk of post-stroke depression A meta-analysis and systematic review.

Although post-stroke depression (PSD) affects one-third of patients following an acute stroke, pooled evidence addressing the correlation between a low vitamin D status and the risk of PSD remains inconclusive. Comprehensive database search of Medline, EMBASE, Cochrane library, and Google Scholar was performed from inception to December 2022. The primary outcome was the association of PSD risk with a low vitamin D status, while the secondary outcomes included the relationship between PSD and other risk factors. Analysis of seven observational studies published between 2014 and 2022 with 1,580 patients showed pooled incidences of vitamin D deficiency (defined as 25OH D levels < 50 nmolL) and PSD of 60.1 and 26.1%, respectively. Patients with PSD had a lower circulating vitamin D concentration compared to those without mean difference (MD) -13.94 nmolL, 95% CI -21.83 to -6.05, The results suggested an association of a low circulating vitamin D level with an increased risk of PSD. Besides, female gender, hyperlipidemia, high NIHSS score were related to an increased risk or occurrence of PSD. The current study may imply the necessity of routine circulating vitamin D screening in this population. httpswww.crd.york.ac.ukprospero, identifier CRD42022381580.

The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma.

WD repeat-containing protein 1 (WDR1) regulates the cofilin 1 (CFL1) activity, promotes cytoskeleton remodeling, and thus, facilitates cell migration and invasion. A previous study reported that autoantibodies against CFL1 and β-actin were useful biomarkers for diagnosing and predicting the prognosis of patients with esophageal carcinoma. Therefore, the present study aimed to evaluate the serum levels of anti-WDR1 antibodies (s-WDR1-Abs) combined with serum levels of anti-CFL1 antibodies (s-CFL1-Abs) in patients with esophageal carcinoma. Serum samples obtained from 192 patients with esophageal carcinoma and other solid cancers. And s-WDR1-Ab and s-CFL1-Ab titers were analyzed using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Compared with those of healthy donors, the s-WDR1-Ab levels were significantly higher in the 192 patients with esophageal, whereas these were not significantly higher in the samples from patients with gastric, colorectal, lung, or breast cancer. In 91 patients treated with surgery, sex, tumor depth, lymph node metastasis, stage and C-reactive protein levels were significantly associated with overall survival, as determined using the log-rank test, whereas the squamous cell carcinoma antigen, p53 antibody and s-WDR1-Ab levels tended to be associated with a worse prognosis. Although no significant difference was observed in the survival between the positive and negative groups of s-WDR1-Abs or s-CFL1-Abs alone in the Kaplan-Meier test, the patients in the s-WDR1-Ab-positive and s-CFL1-Ab-negative groups exhibited a significantly poorer prognosis in the overall survival analysis. On the whole, the present study demonstrates that the combination of positive anti-WDR1 antibodies with negative anti-CFL1 antibodies in serum may be a poor prognostic factor for patients with esophageal carcinoma.

High ratio of C-reactive protein to albumin is associated with hemorrhagic transformation and poor functional outcomes in acute ischemic stroke patients after thrombolysis.

In patients with acute ischemic stroke, hemorrhagic transformation (HT) is a common complication after intravenous thrombolysis (IVT). In this study, we evaluated the relationship between the ratio of C-reactive protein to albumin (CAR) before thrombolysis, HT, and functional outcomes in patients with acute ischemic stroke. We retrospectively analyzed data from 354 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China between July 2014 and May 2022. CAR was measured on admission, and HT was identified by cranial computed tomography (CT) within 24-36 h after treatment. Poor outcome was defined as a score on the modified Rankin Scale (mRS) > 2 at discharge. The multivariate logistic regression model was used to investigate the association between CAR, HT, and poor outcome after thrombolysis, respectively. A total of 354 patients were analyzed, and their median CAR was 0.61 (interquartile range, 0.24-1.28). CAR was significantly higher in the 56 patients (15.8%) who experienced HT than in those who did not (0.94 vs. 0.56, High ratio of C-reactive protein to albumin in individuals with ischemic stroke is associated with an increased risk of HT and poor functional outcomes after thrombolysis.

Connectomics underlying motor functional outcomes in the acute period following stroke.

Stroke remains the number one cause of morbidity in many developing countries, and while effective neurorehabilitation strategies exist, it remains difficult to predict the individual trajectories of patients in the acute period, making personalized therapies difficult. Sophisticated and data-driven methods are necessary to identify markers of functional outcomes. Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 79 patients following stroke. Sixteen models were constructed to predict performance across six tests of motor impairment, spasticity, and activities of daily living, using either whole-brain structural or functional connectivity. Feature importance analysis was also performed to identify brain regions and networks associated with performance in each test. The area under the receiver operating characteristic curve ranged from 0.650 to 0.868. Models utilizing functional connectivity tended to have better performance than those utilizing structural connectivity. The Dorsal and Ventral Attention Networks were among the top three features in several structural and functional models, while the Language and Accessory Language Networks were most commonly implicated in structural models. Our study highlights the potential of machine learning methods combined with connectivity analysis in predicting outcomes in neurorehabilitation and disentangling the neural correlates of functional impairments, though further longitudinal studies are necessary.

Rehabilitation Training Can Significantly Increase the Serum IL-11 Levels and Improve the Prognosis in Ischemic Stroke Patients.

We aimed to explore the expression of IL-11 in ischemic stroke patients and its correlation with rehabilitation training and prognosis. The present randomized control study recruited ischemic stroke patients who were admitted during March 2014 to November 2020. All patients underwent computer tomography (CT) and magnetic resonance imaging (MRI) examination. All patients were randomly divided into two groups, including rehabilitation training (RT) group and control group. The patients in the RT group were received rehabilitation training within 2 days after the vital signs were stable while control group received routine nursing. The serum interleukin- (IL-) 11 levels were measured by enzyme-linked immunosorbent assay (ELISA) when patients were just hospitalized and 6 h, 24 h, 48 h, 72 h, and 90 h after treatment. Demographic, clinical statistics, imaging data, and the National Institutes of Health Stroke Scores (NIHSS) were recorded. The modified Rankin Scale (mRS) scores were measured after 90 days treatment to assess the prognosis of ischemic patients. The serum IL-11 levels of the RT group elevated more quickly during the study time compared with the control group. In addition, the NIHSS and mRS scores of ischemic stroke patients in the RT group were significantly lower than that in the control group. The NIHSS score, the proportion receiving rehabilitation training, and the levels of IL-11, triglyceride (TG), and high-density leptin cholesterol (HDLC) of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than that in the mRS score ≤ 2 group. However, the serum IL-11 levels of ischemic stroke patients were obviously decreased in the mRS score ≥ 3 group. IL-11 could be a potential diagnostic biomarker of poor prognosis of ischemic stroke patients. Furthermore, IL-11, NIHSS score, and rehabilitation training were the risk factors for poor prognosis of ischemic stroke patients. This study demonstrated that the ischemic stroke patients in the RT group had higher serum IL-11 levels and better prognosis. This study might provide a new approach to improve the prognosis of patients with ischemic stroke. This trial is registered with ChiCTR-PNR-16007706.

Design and implementation of informatization for unified management of stroke rehabilitation in urban multi-level hospitals.

With the aging of the population, the prevalence and incidence of stroke in China are increasing every year. China advocates the establishment of a three-level medical service system for stroke rehabilitation, but it lacks uniform information management among all levels of medical institutions. To achieve unified management of stroke patient rehabilitation in multilevel hospitals in the region through informatization construction. The need for informatization of three-level stroke rehabilitation management was analyzed. Then, network connections were established, and a common rehabilitation information management system (RIMS) was developed for all levels of hospitals to enable daily stroke rehabilitation management, inter-hospitals referral, and remote video consultation. Finally, the impact on the efficiency of daily rehabilitation work, the functioning and satisfaction of stroke patients were investigated after implementing the three-level rehabilitation network. One year after implementation, 338 two-way referrals and 56 remote consultations were completed using RIMS. The stroke RIMS improved the efficiency of doctors orders, reduced therapists time to write medical documents, simplified statistical analysis of data and made referrals and remote consultations more convenient compared to the traditional model. The curative effect of stroke patients managed by RIMS is better than that of traditional management. Patient satisfaction with rehabilitation services in the region has increased. The three-level stroke rehabilitation informatization has enabled the unified management of stroke rehabilitation in multilevel hospitals in the region. The developed RIMS improved the efficiency of daily work, improved the clinical outcomes of stroke patients, and increased patient satisfaction.

Brain activation of the PFC during dual-task walking in stroke patients A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Dual-task walking is a good paradigm to measure the walking ability of stroke patients in daily life. It allows for a better observation of brain activation under dual-task walking to assess the impact of the different tasks on the patient when combining with functional near-infrared spectroscopy (fNIRS). This review aims to summarize the cortical change of the prefrontal cortex (PFC) detected in single-task and dual-task walking in stroke patients. Six databases (Medline, Embase, PubMed, Web of Science, CINAHL, and Cochrane Library) were systematically searched for relevant studies, from inception to August 2022. Studies that measured the brain activation of single-task and dual-task walking in stroke patients were included. The main outcome of the study was PFC activity measured using fNIRS. In addition, a subgroup analysis was also performed for study characteristics based on HbO to analyze the different effects of disease duration and the type of dual task. Ten articles were included in the final review, and nine articles were included in the quantitative meta-analysis. The primary analysis showed more significant PFC activation in stroke patients performing dual-task walking than single-task walking ( Different dual-task paradigms produce different levels of dual-task interference in stroke patients with different disease durations, and it is important to choose the matching dual-task type in relation to the walking ability and cognitive ability of the patient, in order to better improve the assessment and training effects. httpswww.crd.york.ac.ukprospero, identifier CRD42022356699.

Oxidative stress in cerebrovascular disease and associated diseases.

Cellular aging is the most severe risk factor for neurodegenerative disease. Simultaneously, oxidative stress (OS) is a critical factor in the aging process, resulting from an imbalance between reactive oxygen and nitrogen species and the antioxidant defense system. Emerging evidence indicates that OS is a common cause of several age-related brain pathologies, including cerebrovascular diseases. Elevated OS disrupts endothelial functional ability by diminishing the bioavailability of nitric oxide (a vascular dilator), induces atherosclerosis, and impairs vasculature, which are all common characteristics of cerebrovascular disease. In this review, we summarize evidence supporting an active role of OS in cerebrovascular disease progression, focusing primarily on stroke pathogenesis. We briefly discuss hypertension, diabetes, heart disease, and genetic factors that are often linked to OS and are considered associated factors influencing stroke pathology. Finally, we discuss the current pharmaceuticstherapeutics available for treating several cerebrovascular diseases.

High triglyceride-glucose index is associated with poor cardiovascular outcomes in Chinese acute coronary syndrome patients without diabetes mellitus who underwent emergency percutaneous coronary intervention with drug-eluting stents.

Previous research has supported the association between the triglyceride-glucose index (TyG index) and the incidence and prognosis of cardiovascular disease. However, the association between the TyG index and the prognosis of patients with acute coronary syndrome (ACS) without diabetes mellitus (DM) who underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) has not been thoroughly investigated, and these patients may easily be neglected. Therefore, this study aimed to investigate the association between the TyG index and major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese ACS patients without DM who underwent emergency PCI with DES. The total number of ACS patients without DM who underwent emergency PCI with DES for this study was 1650. Ln fasting triglycerides (mgdL) ×fasting plasma glucose (mgdL)2 is the formula used to calculate the TyG index. According to the TyG index, we classified the patients into two groups. The frequency of the following endpoint events was calculated and compared between the two groups all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemia stroke, ischemia-driven revascularization and cardiac rehospitalization. After a median of 47 months of follow-up 47 (40, 54), 437 (26.5%) endpoint events were recorded in total. The TyG index was further demonstrated to be independent of MACCE by multivariable Cox regression analysis (hazard ratio HR, 1.493 95% confidence interval CI, 1.230-1.812 For ACS patients without DM who received emergency PCI with DES, the TyG index might be an independent predictor of MACCE.

Corrigendum Type 2 diabetes increases risk of unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery A retrospective cohort study.

This corrects the article DOI 10.3389fnagi.2021.810050..

Converging theories on dreaming Between Freud, predictive processing, and psychedelic research.

Dreams are still an enigma of human cognition, studied extensively in psychoanalysis and neuroscience. According to the Freudian dream theory and Solms modifications of the unconscious derived from it, the fundamental task of meeting our emotional needs is guided by the principle of homeostasis. Our innate value system generates conscious feelings of pleasure and unpleasure, resulting in the behavior of approaching or withdrawing from the world of objects. Based on these experiences, a hierarchical generative model of predictions (

Protocol for the FACE study frailty and comorbidity in elderly patients-a multicenter, Chinese observational cohort study.

The present protocol describes an observational cohort study that was designed to propose a therapeutic scheme and formulate an individualized treatment strategy for frail elderly patients diagnosed with multiple diseases in a Chinese, multicenter setting. Over a 3-year period, we will recruit 30,000 patients from 10 hospitals and collect baseline data including patient demographic information, comorbidity characteristic, FRAIL scale, age-adjusted Charlson comorbidity index (aCCI), relevant blood tests, the results of imaging examination, prescription of drugs, length of hospital stay, number of overall re-hospitalizations and death. Elderly patients (≥ 65 years old) with multimorbidity and receiving hospital care are eligible for this study. Data collection is being performed at baseline and 3, 6, 9 and 12 months after discharge. Our primary analysis was all-cause death, readmission rate and clinical events (including emergency visits, stroke, heart failure, myocardial infarction, tumor, acute chronic obstructive pulmonary disease, etc). The study is approved by the National Key R D Program of China (2020YFC2004800). Data will be disseminated in manuscripts submitted to medical journals and in abstracts submitted to international geriatric conferences. Clinical Trial Registration www.ClinicalTrials.gov, identifier ChiCTR2200056070.

Case report Discovery of a

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) are rare inherited syndromes resulting from biallelic pathogenic variants in Through informed consent and enrollment onto IRB-approved protocols (NCT01386437, NCT03206099) the patient underwent a comprehensive clinical evaluation at the NIH Clinical Center alongside exome sequencing, copy number variation analysis, autoantibody surveys, peripheral blood immunophenotyping, and salivary cytokine analyses. We report the presentation and evaluation of a 9-year-old boy who was referred to the NIH Clinical Center with an APECED-like clinical phenotype that included the classic APECED dyad of CMC and hypoparathyroidism. He was found to meet clinical diagnostic criteria for POIKTMP featuring poikiloderma, tendon contractures, myopathy, and pneumonitis, and exome sequencing revealed a This report expands upon the available genetic, clinical, autoantibody, immunological, and treatment response information on POIKTMP.

Durability is improved by both low and high intensity endurance training.

Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways Targeted Metabolomics Analysis.

Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between serum metabolite patterns and pulmonary vascular readiness for staged SVHD palliation. The purpose of this study was to evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy. This was a prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (175 metabolites) was performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record. Random forest analysis readily distinguished between cases and controls and preoperative and postoperative samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered postoperatively including arginine and tryptophan metabolism. We found trends toward increased preoperative methionine metabolites in patients with higher pulmonary vascular resistance and higher postoperative tryptophan metabolites in patients with greater postoperative hypoxemia. The circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed trends toward association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.

Ischemic Stroke Secondary to Myocarditis in the Setting of COVID-19.

Coronavirus disease (COVID-19) is primarily a respiratory disease that has also been shown to be associated with neurological complications such as ischemic stroke, Guillain-Barré syndrome, and encephalitis. Ischemic stroke in patients with COVID-19 has mostly been observed in the elderly, those with significant comorbidities, and the critically ill. In this report, we discuss a case of ischemic stroke in an otherwise healthy young male patient who only had a mild case of COVID-19. It is likely that the patient suffered from an ischemic stroke secondary to cardiomyopathy that resulted from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The ischemic stroke was most likely a result of thromboembolism caused by stasis of blood from acute dilated cardiomyopathy and the hypercoagulable state of COVID-19 patients. It is important to maintain a high degree of clinical suspicion for thromboembolic events in COVID-19 patients.

Stick a Needle in My Eye A Case Report of Penetrating Needlefish Injury Causing Cavernous Sinus Thrombosis and Carotid Cavernous Fistula.

While swimming in the ocean on vacation in Cuba, a previously healthy 17-year-old female was unexpectedly stabbed through her orbit and into her brain by a needlefish. This is a unique case of a penetrating injury causing orbital cellulitis, retro-orbital abscess, cerebral venous sinus thrombosis and carotid cavernous fistula. After initial management at a local emergency department, she was transferred to a tertiary care trauma centre where she was treated by a team of emergency, neurosurgery, stroke neurology, ophthalmology, neuroradiology and infectious disease physicians. The patient faced a significant risk of a thrombotic event. There was careful consideration from the multidisciplinary team about the utility of thrombolysis or an interventional neuroradiology procedure. Ultimately, the patient was treated conservatively with intravenous antibiotics, low molecular weight heparin and observation. The patient continued to show clinical improvement several months later, which supported the challenging decision to opt for conservative management. There are very few cases to guide the treatment of this type of contaminated penetrating orbital and brain injury.

Loss of His-bundle and Right Ventricular Septal Capture Following Transcatheter Aortic Valve Replacement-A Case Report.

Conduction abnormalities following transcatheter aortic valve replacement (TAVR) are common. High-grade atrioventricular block (AVB) and new-onset left bundle branch block remain the most reported. These often require the placement of a permanent pacemaker (PPM). His-bundle (HB) pacing is increasingly being utilized as the preferred mode of ventricular pacing due to its more physiologic ventricular activation. In this case report, we present a case of a patient who developed loss of HB capture and experienced an increase in the local right ventricular (RV) capture threshold after TAVR that led to unrecognized intermittent loss of ventricular capture and symptoms. An 80-year-old man with severe aortic stenosis presented with symptomatic bradycardia due to typical atrial flutter (AFL) with a high-grade AVB and an underlying right bundle branch block. He underwent placement of a dual-chamber PPM (Medtronic, Inc., Minneapolis, MN, USA) with a HB pacing lead. HB mapping demonstrated a normal H-V interval, and the lead was fixated with non-selective HB capture. The R-waves measured 2.8 mV, the pacing impedance was 544 Ω, and the non-selective HB and local RV capture threshold was 0.5 V 1 ms. He underwent AFL ablation, and his atrial leads were normal. He subsequently underwent successful TAVR with a 29-mm Sapien 3 valve (Edwards Lifesciences, Irvine, CA, USA). Post-TAVR, PPM interrogation showed a loss of HB capture with a left bundle paced QRS morphology. Following discharge, he presented with stroke-like symptoms and was noted to have intermittent loss of RV capture with complete heart block (CHB) and a slow ventricular escape rhythm. PPM interrogation revealed an elevated pacing threshold, and his RV output was gradually increased to a maximum output of 7.5 V 1.5 ms. He also developed a fever and was found to have enterococcal bacteremia. Transesophageal echocardiography demonstrated vegetations on his prosthetic valve and pacemaker lead, without a perivalvular abscess. He underwent explantation of the pacemaker system and insertion of a temporary PPM. After intravenous antibiotic therapy with negative blood cultures, he underwent re-implantation of a new right-sided dual-chamber PPM, and an RV pacing lead was placed into the RV outflow tract. HB pacing is becoming the preferred mode of physiologic ventricular pacing. This case illustrates the potential risks of the TAVR procedure in patients with existing HB pacing leads. We observed a loss of HB capture and the development of CHB due to traumatic injury to the HB distal to the HB pacing lead after TAVR placement together with an increase in the local RV capture threshold. The depth of TAVR placement is an important aspect of the TAVR procedure that determines the risk of developing CHB and may also affect the HB and local RV pacing thresholds post-procedure.