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Lactate-to-albumin ratio is associated with in-hospital mortality in patients with spontaneous subarachnoid hemorrhage and a nomogram model construction.

Subarachnoid hemorrhage (SAH) is a severe hemorrhagic stroke with high mortality. However, there is a lack of clinical tools for predicting in-hospital mortality in clinical practice. LAR is a novel clinical marker that has demonstrated prognostic significance in a variety of diseases. Critically ill patients diagnosed and SAH with their data in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD) were included in our study. Multivariate logistic regression was utilized to establish the nomogram. A total of 244 patients with spontaneous SAH in the MIMIC-IV database were eligible for the study as a training set, and 83 patients in eICU-CRD were included for external validation. Data on clinical characteristics, laboratory parameters and outcomes were collected. Univariate and multivariate logistic regression analysis identified age (OR 1.042, LAR is closely associated with increased in-hospital mortality of patients with spontaneous SAH, which could serve as a novel clinical marker. The nomogram model combined with LAR, APSIII, age, and anion gap presents good predictive performance and clinical practicability.

A practical guide to botulinum neurotoxin treatment of shoulder spasticity 1 Anatomy, physiology, and goal setting.

Botulinum neurotoxin type A (BoNT-A) is a first-line treatment option for post-stroke spasticity, reducing pain and involuntary movements and helping to restore function. BoNT-A is frequently injected into the arm, wrist, hand andor finger muscles, but less often into the shoulder muscles, despite clinical trials demonstrating improvements in pain and function after shoulder BoNT-A injection. In part 1 of this two-part practical guide, we present an experts consensus on the use of BoNT-A injections in the multi-pattern treatment of shoulder spasticity to increase awareness of shoulder muscle injection with BoNT-A, alongside the more commonly injected upper limb muscles. Expert consensus was obtained from five European experts with a cumulative experience of more than 100 years of BoNT-A use in post-stroke spasticity. A patient-centered approach was proposed by the expert consensus to identify which activities are limited by the spastic shoulder and consider treating the muscles that are involved in hindering those activities. Two patterns of shoulder spasticity were identified for Pattern A (adduction, elevation, flexion and internal rotation of the shoulder), the expert panel recommended injecting the pectoralis major, teres major and subscapularis muscles in most cases injecting only the pectoralis major and the teres major is sufficient for the first injection cycle for Pattern B (abduction or adduction, extension and internal rotation of the shoulder), the panel recommended injecting the posterior part of the deltoid, the teres major and the latissimus dorsi in most cases. It is important to consider the local guidelines and product labels, as well as discussions within the multidisciplinary, multiprofessional team when deciding to inject shoulder muscles with BoNT-A. The choice of shoulder muscles for BoNT-A injection can be based on spastic pattern, but ideally should also firstly consider the functional limitation and patient expectations in order to establish better patient-centered treatment goals. These recommendations will be of benefit for clinicians who may not be experienced in evaluating and treating spastic shoulders.

Comparison of Efficacy and Safety of Anticoagulant Monotherapy and Combined Therapy of Anticoagulant and Antiplatelets in Patients With Stable Coronary Artery Disease and Atrial Fibrillation A Meta-Analysis.

It is still uncertain whether patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) who require long-term oral anticoagulation (OAC) should also receive antiplatelet treatment (APT). This meta-analysis aims to compare the efficacy and safety of OAC alone with OAC plus APT in individuals with AF and stable CAD. The current meta-analysis was conducted as per the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We performed electronic searches using PubMed, EMBASE, and Cochrane Library. The efficacy outcomes assessed in this meta-analysis included cardiovascular death, myocardial infarction, stroke (ischemic and hemorrhagic), and all-cause mortality. The safety outcome included major bleeding events. A total of five studies were included in the current meta-analysis enrolling 9199 patients with stable CAD and AF. Out of these five studies, three were observational and two were randomized controlled trials (RCTs). Our study showed no significant difference between two groups in the incidence of cardiovascular mortality (Hazard ratio HR 0.86, 95% confidence interval CI 0.59-1.25, I-square 44%), myocardial infarction (HR 1.21, 95% CI 0.73-2.01, I-square 0%), all-cause mortality (HR 0.95, 95% CI 0.76-1.19, I-square 68%) and stroke (HR 0.83, 95% CI 0.61-1.12, I-square 45%). However, lower incidence of major bleeding events in patients who received OAC alone as compared to patients who received a combination of OAC and anti-platelet (HR 1.37, 95% CI 1.18-1.580, I-square 78%) were found. The current meta-analysis showed that OAC monotherapy is associated with a lower incidence of major bleeding events in patients with stable CAD and AF. It is also not associated with an increased risk of all-cause mortality, cardiovascular death, stroke, and myocardial infarction.

Thyrotoxic Periodic Paralysis Case Presentation With Tetraparesis and Cardiac Dysrhythmia.

Thyrotoxic hypokalaemic periodic paralysis (THPP) is a rare complication of hyperthyroidism that is potentially life-threatening if not treated promptly. It is more common in Asian and Polynesian populations and very few cases have been reported to date in people of White ethnicity. We present a case report of a young male patient of White ethnicity, who was initially brought in as a stroke alert with tetraparesis which was ruled out on initial assessment, but then had a syncopal episode and was noted to be initially bradycardic and subsequently tachycardic. Blood tests showed hypokalaemia and hypophosphataemia and he was treated as a hypokalaemic periodic paralysis patient. Intravenous potassium replacement was commenced. Symptoms and ECG changes resolved with correction of potassium levels. Thyroid function tests requested later were suggestive of hyperthyroidism and the diagnosis of thyrotoxic hypokalaemic periodic paralysis was made. This is an interesting case given its rarity, and this case report highlights the importance of early diagnosis and prompt treatment.

Implications of COVID-19 to Stroke Medicine An Epidemiological and Pathophysiological Perspective.

The neurological complications of Coronavirus 2019 (COVID-19) including stroke have been documented in the recent literature. COVID-19-related inflammation is suggested to contribute to both a hypercoagulable state and haemorrhagic transformation, including in younger individuals. COVID-19 is associated with a heightened risk of ischaemic stroke. Haemorrhagic stroke in COVID-19 patients is associated with increased morbidity and mortality. Cerebral venous sinus thrombosis (CVST) accounts for <1% of stroke cases in the general population but has come to heightened public attention due to the increased risk associated with adenoviral COVID-19 vaccines. However, recent evidence suggests the prevalence of stroke is less in vaccinated individuals than in unvaccinated COVID-19 patients. This review evaluates the current evidence of COVID-19-related ischaemic and haemorrhagic stroke, with a focus on current epidemiology and inflammatory-linked pathophysiology in the field of vascular neurology and stroke medicine.

Remnant cholesterol and the risk of cardiovascular disease in type 2 diabetes a nationwide longitudinal cohort study.

Elevated remnant cholesterol (remnant-C) is considered a risk factor for cardiovascular disease (CVD) however, whether this notion applies to the East Asian population with type 2 diabetes (T2D) has not been established. This study investigated the association between remnant-C concentrations and the risk of CVD in Korean patients with T2D. By using the Korean National Health Insurance Service database, 1,956,452 patients with T2D and without atherosclerotic CVD who underwent regular health checks between 2009 and 2012 were included. Cox regression analyses were conducted to assess the association between remnant-C concentrations and incident CVD comprising myocardial infarction (MI) and ischemic stroke. In total, 50,120 (2.56%) cases of MI and 73,231 (3.74%) cases of ischemic strokes occurred during a median follow-up of 8.1 years. The adjusted hazard ratios for MI and stroke in the highest remnant-C quartile were 1.281 (95% confidence interval CIs, 1.249-1.314) for MI and 1.22 (1.195-1.247) for ischemic stroke, compared to those in the lowest quartiles. The results were similar, based on stratified analysis by age, sex, use of statin or fibrate, and levels of other cholesterol. The increased risk of CVD in the highest remnant-C quartile was profound in patients who had a longer T2D duration. A remnant-C concentration ≥ 30 mgdL differentiated patients who were at a higher risk of CVD, compared to patients with a lower concentrations, regardless of whether LDL-C levels were or were not on target at ≤ 100 mgdL. In Korean patients with T2D, remnant-C was associated with CVD, independent of the LDL-C level or other conventional CVD risk factors. Our finding confirmed evidence of the causal role of remnant-C on CVD, as a residual risk of CVD, in East Asian patients with T2D.

Distinct implications of body mass index in different subgroups of nonobese patients with heart failure with preserved ejection fraction a latent class analysis of data from the TOPCAT trial.

Obesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous. Latent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared. Two subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio HR 0.53, 95% confidence interval CI 0.40-0.70, P<0.001) and a trend of decreased all-cause mortality risk (HR 0.75, 95% CI 0.55-1.01, P0.06), while patients with pathological non-obesity had a 59% increase (HR 1.59, 95% CI 1.24-2.02, P<0.001) in all-cause mortality risk. Two subgroups of nonobese patients with HFpEF with distinct clinical profiles and prognostic implications were identified. The low BMI was likely physiological in one group but pathological in the other group. Using a data-driven approach, our study provided an alternative explanation for the obesity paradox that the poor prognosis of nonobese patients with HFpEF was driven by a pathological subgroup.

Developing an implementation fidelity checklist for a vocational rehabilitation intervention.

Despite growing numbers of studies reporting the efficacy of complex interventions and their implementation, many studies fail to report information on implementation fidelity or describe how fidelity measures used within the study were developed. This study aimed to develop a fidelity checklist for measuring the implementation fidelity of an early, stroke-specialist vocational rehabilitation intervention (ESSVR) in the RETAKE trial. To develop the fidelity measure, previous checklists were reviewed to inform the assessment structure, and core intervention components were extracted from intervention descriptions into a checklist, which was ratified by eight experts in fidelity measurement and complex interventions. Guidance notes were generated to assist with checklist completion. To test the measure, two researchers independently applied the checklist to fifteen stroke survivor intervention case notes using retrospective observational case review. The scoring was assessed for interrater reliability. A fidelity checklist containing 21 core components and 6 desirable components across 4 stages of intervention delivery was developed with corresponding guidance notes. Interrater reliability of each checklist item ranged from moderate to perfect (Cohens kappa 0.69-1). The resulting checklist to assess implementation fidelity is fit for assessing the delivery of vocational rehabilitation for stroke survivors using retrospective observational case review. The checklist proved its utility as a measure of fidelity and may be used to inform the design of future implementation strategies. ISRCTN, ISRCTN12464275. Registered on 13 March 2018.

Development and application of the TFA macrosimulation model a case study of modelling the impact of trans fatty acid (TFA) elimination policies in Brazil.

The consumption of trans-fatty acids (TFA) is directly associated with cardiovascular disease risk and is responsible for a significant health burden globally. The policy strategies for reducing TFA include limiting their content in foods and eliminating partially hydrogenated oils (PHO) in the market. This study aims to describe a comparative risk assessment macrosimulation model and to apply this tool to estimate the potential reductions in CVD mortality gained from the compared scenarios of TFA reductionelimination in Brazil. We developed and implemented a comparative risk assessment macrosimulation model estimates the potential CVD mortality reduction (coronary heart disease - CHD- and stroke) if TFA intake is reduced in diets. The TFA macrosimulation model estimates the change in the annual number of NCD deaths between baseline with current TFA consumption levels and alternate or counterfactual scenarios, such as considering different limits to TFA content in foods and the elimination of PHO in Brazil in 2018. The model incorporated additional outputs related to other impacts of TFA reduction on DPP, such as Years of Life Lost, Years of Productive Life Lost, and related economic impacts of premature deaths. In 2018, a 2% limit for TFA in the oils and fats and a 5% limit of TFAs for other foods could avert or postpone approximately 2,000 deaths (UI 95% 1,899-2,142) and save US$ 32.1 million savings in productivity losses to the economy associated to premature deaths. An intermediate scenario, applying a 2% limit of TFA in all food products In Brazil could prevent or postpone approximately 6,300 deaths (UI 95% 5,925-6,684) and the premature deaths prevented would represent US$ 100.2 million in economic saving. Finally, by banning PHO, approximately 10,500 deaths could be prevented or postponed (UI 95% 9,963 - 10,909), corresponding to US$ 166.7 million in savings to the economy because of premature deaths. The TFA macrosimulation model can efficiently compare different policy scenarios for trans fats reduction policies at the country level and proves that the elimination of PHOs from the food market in Brazil may significantly reduce the health burden of trans fatty acids in the country compared to other policy options. The model also represents a useful public health tool to support TFA reduction and elimination policies in other countries.

Study protocol of transcranial electrical stimulation at alpha frequency applied during rehabilitation A randomized controlled trial in chronic stroke patients with visuospatial neglect.

A frequent post stroke disorder in lateralized attention is visuospatial neglect (VSN). As VSN has a strong negative impact on recovery in general and independence during daily life, optimal treatment is deemed urgent. Next to traditional stroke treatment, non-invasive brain stimulation offers the potential to facilitate stroke recovery as a complementary approach. In the present study, visual scanning training (VST the current conventional treatment) will be combined with transcranial alternating current stimulation (tACS) to evaluate the additive effects of repeated sessions of tACS in combination with six-weeks VST rehabilitation. In this double-blind randomized placebo-controlled intervention study (RCT), we will compare the effects of active tACS plus VST to sham (placebo) tACS plus VST, both encompassing 18 VST training sessions, 40 minutes each, during 6 weeks. Chronic stroke patients with VSN (> 6 months post-stroke onset) are considered eligible for study participation. In total 22 patients are needed for the study. The primary outcome is change in performance on a cancellation task. Secondary outcomes are changes in performance on a visual detection task, two line bisection tasks, and three measures to assess changes in activities of daily living. Assessment is at baseline, directly after the first and ninth training session, after the last training session (post training), and 1 week and 3 months after termination of the training (follow-up). If effective, a tACS-VST rehabilitation program could be implemented as a treatment option for VSN. ClinicalTrials.gov registration number NCT05466487 registration date July 18, 2022 retrospectively registered httpsclinicaltrials.govct2showNCT05466487.

SOX-1 antibodies in a patient with Crohns disease a case report.

The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohns Disease (CD) with ensuing neurological symptoms. A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohns Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure a few days later she died, due to ensuing septic shock and Multiple Organ Failure. Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

Amorfrutin B Protects Mouse Brain Neurons from HypoxiaIschemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation.

Amorfrutin B is a selective modulator of the PPARγ receptor, which has recently been identified as an effective neuroprotective compound that protects brain neurons from hypoxic and ischemic damage. Our study demonstrated for the first time that a 6-h delayed post-treatment with amorfrutin B prevented hypoxiaischemia-induced neuronal apoptosis in terms of the loss of mitochondrial membrane potential, heterochromatin foci formation, and expression of specific genes and proteins. The expression of all studied apoptosis-related factors was decreased in response to amorfrutin B, both during hypoxia and ischemia, except for the expression of anti-apoptotic BCL2, which was increased. After post-treatment with amorfrutin B, the methylation rate of the pro-apoptotic Bax gene was inversely correlated with the protein level, which explained the decrease in the BAXBCL2 ratio as a result of Bax hypermethylation. The mechanisms of the protective action of amorfrutin B also involved the inhibition of autophagy, as evidenced by diminished autophagolysosome formation and the loss of neuroprotective properties of amorfrutin B after the silencing of Becn1 andor Atg7. Although post-treatment with amorfrutin B reduced the expression levels of Becn1, Nup62, and Ambra1 during hypoxia, it stimulated Atg5 and the protein levels of MAP1LC3B and AMBRA1 during ischemia, supporting the ambiguous role of autophagy in the development of brain pathologies. Furthermore, amorfrutin B affected the expression levels of apoptosis-focused and autophagy-related miRNAs, and many of these miRNAs were oppositely regulated by amorfrutin B and hypoxiaischemia. The results strongly support the position of amorfrutin B among the most promising anti-stroke and wide-window therapeutics.

Some neighbors are more interfering Asymmetric priming by stroke neighbors in Chinese character recognition.

Chinese is a visually complex logographic script that consists of square-shaped characters, with each character composed of strokes. Previous masked priming studies using single-character Chinese stroke neighbors (i.e., visually similar characters differing in only one or two strokes, e.g., ) have shown facilitatory or inhibitory priming effects. We tested whether the mixed pattern of stroke neighbor priming might be an instance of asymmetry in priming that has been observed previously with Japanese kana and Latin alphabets. Specifically, a prime lacking a stroke (or line segment) that is present in the target speeds up the recognition of its stroke neighbor almost as much as the identity prime (e.g., - -), but not the converse (e.g., - >> -). Two experiments, one using a character match task and the second using lexical decision, showed a robust asymmetry in priming by stroke neighbors. The results suggest that the early letter identification process is similar across script types, as anticipated by the Noisy Channel model, which regards the first stage of visual word recognition as a language-universal perceptual process.

Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating AxlRac1 Signaling in Subarachnoid Hemorrhage Mice.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1.

Teleneurocritical Care for Patients with Large Vessel Occlusive Ischemic Stroke Treated by Thrombectomy.

Teleneurocritical care (TNCC) provides 247 virtual treatment of patients with neurological disease in the emergency department or intensive care unit. However, it is not known if TNCC is safe, effective, or associated with similar outcomes compared with in-person neurocritical care. We aim to determine the effect of daily inpatient consults from TNCC on the outcomes of patients with large vessel occlusive acute ischemic stroke treated by thrombectomy. A multicenter, retrospective cohort of consecutive patients ≥ 18 years old with acute ischemic stroke from a large vessel occlusion treated by thrombectomy were identified from 2018 to 2021 within a telehealth network of an integrated not-for-profit health care system in the United States. The primary end point was good functional outcome, i.e., modified Rankin Scale 0-3, at the time of hospital discharge in patients receiving in-person neurocritical care versus TNCC. A total of 437 patients met inclusion criteria, 226 at the in-person hospital (median age 67, 53% women) and 211 at the two TNCC hospitals (median age 74, 49% women). The rate of successful endovascular therapy (modified Thrombolysis in Cerebral Infarction score 2b-3) was not different among hospitals. Good functional outcome at discharge was similar between in-person neurocritical care and TNCC (in-person 31.4% vs. TNCC 33.5%, odds ratio 0.88, 95% confidence interval 0.6-1.3 p 0.64). Only National Institutes of Health stroke scale and age were multivariable predictors of outcome. There were no differences in mortality (9.3% vs. 13.2%, p 0.19), intensive care unit length of stay (2.1 vs. 1.9 days, p 0.39), or rate of symptomatic intracerebral hemorrhage (6.8% vs. 6.6%, p 0.47) between in-person neurocritical care and TNCC. Teleneurocritical care allows for equivalent favorable functional outcomes compared with in-person neurocritical care for patients with acute large vessel ischemic stroke receiving thrombectomy. The standardized protocols used by TNCC in this study, specifically the comprehensive 247 treatment of patients in the intensive care unit for the length of their stay, may be relevant for other health systems with limited in-person resources however, additional study is required.

Accuracy of automated intracerebral hemorrhage volume measurement on non-contrast computed tomography a Swedish Stroke Register cohort study.

Hematoma volume is the strongest predictor of patient outcome after intracerebral hemorrhage (ICH). The aim of this study was to validate novel fully automated software for quantification of ICH volume on non-contrast computed tomography (CT). The population was defined from the Swedish Stroke Register (RS) and included all patients with an ICH diagnosis during 2016-2019 in Region Skåne. Hemorrhage volume on their initial head CT was measured using ABC2 and manual segmentation (Sectra IDS7 volume measurement tool) and the automated volume quantification tool (qER-NCCT) by Qure.ai. The first 500 were examined by two independent readers. A total of 1649 ICH patients were included. The qER-NCCT had 97% sensitivity in identifying ICH. In total, there was excellent agreement between volumetric measurements of ICH volumes by qER-NCCT and manual segmentation by interclass correlation (ICC 0.96), and good agreement (ICC 0.86) between qER-NCCT and ABC2 method. The qER-NCCT showed volume underestimation, mainly in large (> 30 ml) heterogenous hemorrhages. Interrater agreement by (ICC) was 0.996 (95% CI 0.99-1.00) for manual segmentation. Our study showed excellent agreement in volume quantification between the fully automated software qER-NCCT and manual segmentation of ICH on NCCT. The qER-NCCT would be an important additive tool by aiding in early diagnostics and prognostication for patients with ICH and in provide volumetry on a population-wide level. Further refinement of the software should address the underestimation of ICH volume seen in a portion of large, heterogenous, irregularly shaped ICHs.

Association between thyroid cancer and cardiovascular disease risk a nationwide observation study.

Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (< 65 and ≥ 65 years old). This observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with a follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. SIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (< 65, ≥ 65 years), and different follow-up years. After excluding 128 individuals (< 20 years or ≥ 85 years old) and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years among thyroid cancer patients, the observed number of new CHD events was 70 IS, 30 and AF, 20, respectively. The SIR was significantly higher for CHD (SIR, 1.57 95% confidence interval CI 1.2-1.93) among thyroid cancer patients compared with the age- and sex-specific standardized population. However, the association between thyroid cancer and the risks of IS (SIR, 0.74 95% CI 0.47-1), cardiovascular disease (SIR, 0.88 95% CI 0.7-1.05), and atrial fibrillation (SIR, 0.74 95% CI 0.42-1.06) were insignificant. Moreover, stratification by age < 65 or age ≥ 65 years old and by sex for CHD suggested that the diagnosis of thyroid cancer in the young may attenuate the CHD risk (SIR, 2.08 95% CI 1.5-2.66), and the CVD risk was constant among both men (SIR, 1.63 95% CI 1.03-2.24) and women (SIR, 1.53 95% CI 1.06-1.99). The patients had persistent higher CHD risk for 5 years after cancer diagnosis. Thyroid cancer survivors have a substantial CHD risk, even at long-term follow-up, especially in those patients < 65 years old. Further research on the association between thyroid cancer and CHD risk is warranted.

Vexed mutations promote degeneration of dopaminergic neurons through excessive activation of the innate immune response.

The hallmark of Parkinsons disease (PD) is the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. We previously completed a screen identifying genes associated with the progressive degeneration of DA neurons. Here we describe the role of a previously uncharacterized gene, CG42339, in the loss of DA neurons using Drosophila Melanogaster. CG42339 mutants display a progressive loss of DA neurons and locomotor dysfunction, along with an accumulation of advanced glycation end products (AGEs) in the brain. Based on this phenotype, we refer to CG42339 as vexed. We demonstrate that vexed is specifically required within cortex glia to maintain neuronal viability. Loss of vexed function results in excessive activation of the innate immune response in the brain, leading to loss of DA neurons. We show that activation of the innate immune response leads to increased nitric oxide signaling and accumulation of AGEs, which ultimately result in neurodegeneration. These results provide further insight into the relationship between the role of the immune response in the central nervous system and how this impacts neuronal viability.

Improving stroke clinical guideline adherence in an Australian hospital using a clinician-led implementation process.

Private hospitals in Australia manage 11% of acute and 48% of rehabilitation stroke admissions, yet little is known about implementation of stroke clinical guidelines in this setting. Clinical guidelines recommend that acute stroke patients be co-located in a stroke unit in a geographically defined area, rather than dispersed across the hospital. To investigate post-intervention adherence to clinical guidelines for stroke management, and to explore staff barriers and facilitators to guideline implementation. Observational study before-and-after local implementation of Australian stroke clinical guidelines. The primary outcome was a change in the proportion of patients who were physically co-located in an acute stroke unit. Secondary outcomes included changes in adherence to additional acute and rehabilitation guideline criteria, and staff identification of barriers and facilitators to guide implementation. Data were collected from medical record audits, health service information and staff surveys. Co-location in an acute stroke unit did not change significantly after guideline implementation (49% adherence pre-intervention and 54% post-intervention). Across acute and rehabilitation wards, 15% (1172) of guideline criteria improved (p < .05). These related to assessments of swallowing and neglect, presence of a stroke care co-ordinator and occupational therapist, post-discharge care plan, provision of patient education and return to driving. Facilitators to guideline implementation included staff education, collaboration, and dissemination of user-friendly stroke policies. Stroke clinical guideline implementation led to a favorable uptake of some criteria, yet not all. Implementation was assisted by staff education, user-friendly stroke policies and multidisciplinary team collaboration. ANZCTR registration number ACTRN12616000646448 (httpwww.ANZCTR.org.auACTRN12616000646448.aspx).

Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults A Nationwide Population-Based Study.

Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults. Using data from the Korean National Health Insurance Service database, patients age between 20 and 39 years, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate-to-heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 gwk at the health examination each year and calculating the sum of 4 years (0-4). The main outcome was incident stroke and its subtypes, ischemic stroke, and hemorrhagic stroke during the follow-up period. Of 1 536 668 patients (mean age of 29.5 years, 71.5% male, and median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1,000 person-years). After multivariable adjustment, patients with alcohol burden scores of 2, 3, and 4, who consumed more than 105 gwk of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (hazard ratio HR 1.19, 95% CI 1.05-1.34 for 2 HR 1.22, 95% CI 1.09-1.38 for 3 HR 1.23, 95% CI 1.10-1.38 for 4) compared with those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10-1.54 for 2 HR 1.42, 95% CI 1.21-1.67 for 3 HR 1.36, 95% CI 1.16-1.59 for 4) compared with a burden score of 0. Young adults who engaged in moderate-to-heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

Association between non-HDLC and 1-year prognosis in patients with spontaneous intracerebral haemorrhage a prospective cohort study from 13 hospitals in Beijing.

Previous studies suggested an inverse association between lipoprotein cholesterols and bleeding risk, while limited data were available about the predictive value of lipoproteins on intracerebral haemorrhage (ICH). Our recent research series showed that higher non-high-density lipoprotein cholesterol (non-HDLC) was an independent predictor of favourable 3-month outcome in ICH patients, we thus aimed to further investigate the association between non-HDLC levels and 1-year functional outcomes after ICH. Prospective multicentre cohort study. 13 hospitals in Beijing, China. A total of 666 ICH patients were included between December 2014 and September 2016. Non-HDLC was calculated by subtracting HDL-C from total cholesterol. Patients were then grouped by non-HDLC levels into three categories <3.4 mmolL, 3.4-4.2 mmolL and ≥4.2 mmolL. Both the univariate and multivariate logistic regressions were used to assess the association between non-HDLC levels and 1-year unfavourable functional outcomes (modified Rankin Scale ≥3) in ICH patients. Moreover, sensitivity analysis was performed in ICH patients without statin use after admission. There were 33.5% (223666) ICH patients identified with unfavourable functional outcomes at 1-year follow-up. In the univariate analysis, patients who achieved non-HDLC levels above 4.2 mmolL had a 49% decreased risk of 1-year poor prognosis (OR 0.51, 95% CI 0.33 to 0.81). However, non-HDLC did not retain its independent prognostic value in multivariate analysis, the fully adjusted OR values were 1.00 (reference), 1.06 (0.63, 1.79) and 0.83 (0.45, 1.54) from the lowest to the highest non-HDLC group. Moreover, statin use after ICH onset made no difference to the long-term prognosis. Non-HDLC was not an independent predictor for 1-year functional outcome in ICH patients, irrespective of poststroke statin use. The predictive value of well-recognised confounding factors was more dominant than non-HDLC on long-term prognosis.

Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2 a systematic review and meta-analysis of cohort studies in Europe.

As mortality from coronavirus disease 2019 (COVID-19) is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age-gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations. We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including death, hospitalisation, intensive care unit (ICU) admission and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11 June 2021 in Ovid Medline and Embase. Results are presented as odds ratios with 95% confidence intervals and absolute risk differences in deaths per 1000 COVID-19 patients. We included 88 cohort studies with age-gender-adjusted data from 6 653 207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes and end-stage renal disease. Evidence of highmoderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke and liver disease. The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of nonpharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.

Gardening Is Associated with Better Cardiovascular Health Status Among Older Adults in the United States Analysis of the 2019 Behavioral Risk Factor Surveillance System Survey.

Gardening benefits health in older adults, but previous studies have limited generalizability or do not adequately adjust for sociodemographic factors or physical activity (PA). We examined health outcomes, fruits and vegetables (FV) intake, and 10-year mortality risk among gardeners and exercisers compared with nonexercisers. Cross-sectional data of noninstitutionalized US adults in the 2019 Behavioral Risk Factor Surveillance System was collected via landline and cellular phone survey. Adults 65 years and older reporting any PA (n 146,047) were grouped as gardeners, exercisers, or nonexercisers. Outcomes included cardiovascular disease (CVD) risk factors, mental and physical health, FV intake, and 10-year mortality risk. Summary statistics were calculated and adjusted logistic regression models were conducted to calculate adjusted odds ratios (aORs) and 95% CIs, accounting for the complex survey design. The sample included gardeners (10.2%), exercisers (60.0%), and nonexercisers (30.8%). Gardeners, compared with nonexercisers, had significantly lower odds of reporting all studied health outcomes and higher odds of consuming 5 or more FV per day (CVD aOR 0.60, 95% CI 0.53 to 0.68 stroke aOR 0.55, 95% CI 0.47 to 0.64 heart attack aOR 0.63, 95% CI 0.55 to 0.73, high cholesterol aOR 0.86, 95% CI 0.79 to 0.93 high blood pressure aOR 0.74, 95% CI 0.68 to 0.81 diabetes aOR 0.51, 95% CI 0.46 to 0.56 body mass index ≥25 aOR 0.74, 95% CI 0.68 to 0.80 poor mental health status aOR 0.50, 95% CI 0.43 to 0.59 poor physical health status aOR 0.35, 95% CI 0.31 to 0.39 5 or more FV per day aOR 1.56, 95% CI 1.40 to 1.57 high 10-year mortality risk aOR 0.39, 95% CI 0.36 to 0.42). Male and female gardeners had significantly lower odds of reporting diabetes even when compared with exercisers. Among adults 65 years and older, gardening is associated with better CVD health status, including lower odds of diabetes. Future longitudinal or interventional studies are warranted to determine whether promoting gardening activities can be a CVD risk reduction strategy.

Automated Quantification of Compartmental Blood Volumes Enables Prediction of Delayed Cerebral Ischemia and Outcomes After Aneurysmal Subarachnoid Hemorrhage.

The role of hemorrhage volume in risk of vasospasm, delayed cerebral ischemia (DCI), and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH) is well established. However, the relative contribution of blood within individual compartments is unclear. We present an automated technique for measuring not only total but also volumes of blood in each major compartment after SAH. We trained convolutional neural networks to identify compartmental blood (cisterns, sulci, and ventricles) from baseline computed tomography scans of patients with SAH. We compared automated blood volumes against traditional markers of bleeding (modified Fisher score mFS, Hijdra sum score HSS) in 190 SAH patients for prediction of vasospasm, DCI, and functional status (modified Rankin Scale) at hospital discharge. Combined cisternal and sulcal volume was better correlated with mFS and HSS than cisternal volume alone (ρ 0.63 vs. 0.58 and 0.75 vs. 0.70, P < 0.001). Only blood volume in combined cisternal plus sulcal compartments was independently associated with DCI (OR 1.023 per mL, 95% CI 1.002-1.048), after adjusting for clinical factors while ventricular blood volume was not. Total and specifically sulcal blood volume was strongly associated with poor outcome (OR 1.03 per mL, 1.01-1.06, P 0.006 and OR 1.04, 1.00-1.08 for sulcal) as was HSS (OR 1.06 per point, 1.00-1.12, P 0.04), while mFS was not (P 0.24). An automated imaging algorithm can measure the volume of bleeding after SAH within individual compartments, demonstrating cisternal plus sulcal (and not ventricular) blood contributes to risk of DCIvasospasm. Automated blood volume was independently associated with outcome, while qualitative grading was not.

Meningeal macrophages protect against viral neuroinfection.

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II

Identification of The Unique Subtype of Macrophages in Aneurysm Lesions at the Growth Phase.

Recent experimental studies have defined intracranial aneurysms as a macrophage-mediated chronic inflammatory disease affecting intracranial arteries. Although there are various subtypes in macrophages, what type of macrophages is present in lesions during the disease development remains to be elucidated. The previously-established aneurysm model of rats was used. Macrophages were labeled with the fluorescent protein and isolated by a laser-microdissection method. The comprehensive gene expression profile analyses and gene ontology analyses was then done to identify a macrophage subtype present in lesions at the growth phase. The gene expression profile data of total 52 macrophages infiltrating into the lesions was acquired. The principal component analysis revealed the monotonous macrophage subtype. By comparing the profile identified with one from in vitro-differentiated M0 or M1 macrophages, the macrophages in the lesions were belonged to the simple and unique subtype. Because the perception of signaling from nervous system was highlighted as up-represented terms through gene ontology analyses, the macrophage subtype in lesions at the growth phase might be differentiated under the influence of nervous system in the microenvironment. The histopathological examinations supported the above notion by confirming the presence of nerves in the adventitia. The findings from the present study have provided the useful insights about the macrophage subtype in aneurysm lesions at the growth phase and also proposed its ability as a therapeutic target.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.

To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. Across the study period, 12.7% of AIS admissions had previousactive cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males4.8% females4.0%) and increased with age up to age 70-79 years (30-39 years 1.4% 70-79 years5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison 0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of headneck, skinbone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

Feasibility of deconvolution-based multiphase CT angiography perfusion maps in acute ischemic stroke Simulation and concordance with CT perfusion.

Integration of CT perfusion (CTP) with requisite non-contrast CT and CT angiography (CTA) stroke imaging may allow efficient stroke lesion volume measurement. Using surrogate images from CTP, we simulated the feasibility of using multiphase CTA (mCTA) to generate perfusion maps and assess target mismatch profiles. Patients with acute ischemic stroke who received admission CTP were included in this study. Four CTP images (surrogate mCTA, one pre-contrast and three post-contrast, starting at the arterial peak then at 8 s intervals) were selected according to the CTP arterial time-density curve to simulate non-contrast CT and mCTA images. Cerebral blood flow (CBF) and Tmax maps were calculated using the same model-based deconvolution algorithm for the standard CTP and surrogate mCTA studies. Infarct and penumbra were delineated with CBF < 20% and Tmax > 6 s threshold, respectively. Classification accuracy of surrogate mCTA target mismatch (infarct <70 ml penumbra ≥15 ml mismatch ratio ≥1.8) with respect to standard CTP was assessed. Agreement between infarct and penumbra volumes from standard CTP and surrogate mCTA maps were evaluated by Bland-Altman analysis. Of 34 included patients, 28 had target mismatch and 6 did not by standard CTP. Accuracy of classifying target mismatch profiles with surrogate mCTA was 79% with respect to that from standard CTP. Mean ± standard deviation of differences (standard CTP minus surrogate mCTA) of infarct and penumbra volumes were 9.8 ± 14.8 ml and 20.1 ± 45.4 ml, respectively. Surrogate mCTA ischemic lesion volumes agreed with those from standard CTP and may be an efficient alternative when CTP is not practical.

The impact of the approval of prothrombin complex concentrates for vitamin K antagonist-related intracerebral hemorrhage A retrospective study.

This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage. We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physicians discretion (previous dose group). After approval, we adopted the manufacturers recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality. Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups. After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage however, there was no apparent difference in clinical outcomes.

Use of A Systemic Inflammatory Response Index to Predict Non-Traumatic Non-Aneurysmal Subarachnoid Hemorrhage Patient Outcomes.

Patients who suffer from non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH) episodes still face a risk of clinical complications and poor outcome. As the systemic inflammatory response index (SIRI) has recently been shown to offer value as a tool capable of predicting aneurysmal SAH (aSAH) patient outcomes, this study was designed to gauge SIRI prognostic utility in naSAH patients. Clinical findings and outcome data for 111 naSAH patients were analyzed, with patients being separated into high- and low-SIRI groups. The modified Rankin scale (mRS) was used to compare 3-month outcomes in these patients, with mRS scores of 0-1 and 2-6 respectively corresponding to functional outcomes that were favorable and unfavorable. The association between SIRI levels and clinical outcomes was assessed using receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and logistic regression approaches. Of the 111 patients included in this study, 38 (34.2%) exhibited poor outcomes. An optimal SIRI cut-off of 6.478 × 10 SIRI values may offer utility as a novel tool for predicting clinical outcomes in naSAH patients during the early stages of disease.

Historic redlining in Columbus, Ohio associated with stroke prevalence.

Racial disparities exist in stroke and stroke outcomes. In an ecologic study, using the Home Owners Loan Corporation (HOLC) redlining scores, as indicator of historic racialized lending practices, we hypothesized that census tracts with high historic redlining are associated with higher stroke prevalence. Weighted historic redlining scores (HRS) were calculated using the proportion of 1930s HOLC residential security grades contained within 2010 census tract boundaries of Columbus, Ohio. Stroke prevalence (adults >18) was obtained at the census tract-level from the CDCs 500 Cities Project. Sociodemographic census tract level data (American Community Survey 2014-2018) were considered mediators in the causal association between historic redlining and stroke prevalence and were not controlled for in regression analysis. HRS and stroke prevalence associations were evaluated with and without adjustment for proportion of census tract 65 years and older. Census tracts in the highest quartile of HRS (greater redlining) had 1.73% higher stroke prevalence compared to those in the lowest quartile (95% CI0.41,3.05) adjusting for proportion 65 years and older. No other interquartile differences were observed. Historic redlining practices are a form of structural racism that established geographic systems of disadvantage and consequently, poor health outcomes. Our findings demonstrate disparate stroke prevalence by degree of historic redlining in census tracts across Columbus, Ohio.

Endovascular thrombectomy with or without intravenous thrombolysis in acute basilar artery occlusion ischemic stroke A meta-analysis.

It is poorly understood if endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) better facilitates clinical outcomes in patients with acute basilar artery occlusion (BAO) ischemic stroke. A systematic literature review and meta-analysis was completed to investigate the outcomes of EVT with IVT versus direct EVT alone in acute BAO. Data was collected from the literature and pooled with the authors institutional experience. The primary outcome measure was 90-day modified Rankin sale (mRS) of 0-2. Secondary measures were successful post-thrombectomy recanalization defined as mTICI ≥2b, 90-day mortality, and rate of symptomatic ICH. Our institutional experience combined with three multicenter studies resulted in a total of 1,127 patients included in the meta-analysis. 756 patients underwent EVT alone, while 371 were treated with EVTIVT. Patients receiving EVTIVT had a higher odds of achieving a 90-day mRS of ≤ 2 compared to EVT alone (OR 1.50, 95% CI 1.15 to 1.95, P 0.002, I On meta-analysis, EVT with bridging IVT results in superior 90-day functional outcomes and lower 90-day mortality without increase in symptomatic ICH. These findings likely deserve further validation in a randomized controlled setting.

Neurogenic cardiac outcome in patients after acute ischemic stroke The brain and heart connection.

Neurogenic cardiac impairment can occur after acute ischemic stroke (AIS), but the mapping of the neuroanatomic correlation of stroke-related myocardial injury remains uncertain. This study aims to identify the association between cardiac outcomes and middle cerebral artery (MCA) ischemic stroke, with or without insular cortex involvement, as well as the impact of new-onset atrial fibrillation (AF) after AIS on recurrent stroke. Serial measurements of high sensitivity troponin T (TnT), brain natriuretic peptide (BNP), electrocardiography (ECG), echocardiogram, and cardiac monitoring were performed on 415 patients with imaging confirmed MCA stroke, with or without insular involvement. Patients with renal failure, recent cardiovascular events, or congestive heart failure were excluded. One hundred fifteen patients (28%) had left MCA infarcts with insular involvement, 122 (29%) had right MCA infarcts involving insular cortex, and 178 (43%) had no insular involvement. Patients with left MCA stroke with insular involvement tended to exhibit higher BNP and TnI, and transient cardiac dysfunction, which mimicked Takotsubo cardiomyopathy in 10 patients with left ventricular ejection fraction (LVEF) of 20-40%. Incidence of new-onset AF was higher in right MCA stroke involving insula (39%) than left MCA involving insula (4%). Nine out of fifty-three patients with new-onset AF were not on anticoagulant therapy due to various reasons none of them experienced recurrent AF or stroke during up to a 3-year follow-up period. Statistically significant correlations between BNP or TnT elevation and left insular infarcts, as well as the incidence of AF and right insular infarcts, were revealed using linear regression analysis. The present study demonstrated that acute left MCA stroke with insular involvement could cause transient cardiac dysfunction and elevated cardiac enzymes without persistent negative outcomes in the setting of health baseline cardiac condition. The incidence of new-onset AF was significantly higher in patients with right MCA stroke involving the insula. There was no increased risk of recurrent ischemic stroke in nine patients with newly developed AF who were not on anticoagulant therapy, which indicated a need for further research on presumed neurogenic AF and its management.

Excessive supraventricular ectopic activity and future onset of atrial fibrillation in patients with cryptogenic stroke.

Although evidence has shown the association of excessive supraventricular ectopic activity (ESVEA) with future development of atrial fibrillation (AF), this relationship is not yet fully understood. This study examines whether ESVEA can predict the future onset of AF, in patients presenting with cryptogenic stroke. A retrospective cohort of 124 non-AF, consecutive patients, hospitalized for cryptogenic stroke between 2014 and 2015, was retrieved. 24-h inpatient monitoring with Holter was employed to reveal ESVEA, defined as the presence of more than 20 premature atrial complexes per hour (PACsh) on average, or a more than 5 s duration of the longest supraventricular run (LSVR). After a median follow-up period of 5.2 years, the patients were examined for AF. From initial 124 patients, 12 died and one was lost during follow-up. For the total of 111 patients finally included, the median age was 56 years and 25.2% were females. The overall baseline median CHA2DS2-VASc score was 3. AF was found in 13 (11.71%) patients. Patients who were finally diagnosed with AF had a significantly higher number of PACsh and a longer median LSVR duration at baseline (16.67 vs. 0.21, p < 0.001 and 3 vs. 0 s, p < 0.001, respectively). The presence of ESVEA was also significantly more frequent among AF patients (46.15%, 95%CI 17.78%-74.22%) compared to non-AF ones (6.1%, 95%CI 1.3%-10.7%, p < 0.001). Excessive atrial ectopy, detected with 24 h inpatient Holter monitoring, is a significant indicator of future development of AF in patients presenting originally with a cryptogenic stroke.

The burden of heat-related stroke mortality under climate change scenarios in 22 East Asian cities.

Stroke is a leading cause of death and disability in East Asia. Owing to the aging population and high prevalence of stroke, East Asia might suffer a disproportionately heavy burden of stroke under the changing climate. However, the evidence relevant is still limited in this area. To evaluate the stroke mortality risk due to heat exposure in East Asia and predict its burden under various future climate change scenarios. We conducted a multi-center observational study and collected data from 22 representative cities in three main East Asian countries (i.e., China, Japan, and South Korea) from 1972 to 2015. The two-stage time-series analyses were applied to estimate the effects of heat on stroke mortality at the regional and country level. We further projected the burden of heat-related stroke mortality using 10 global climate models (GCMs) under four shared socioeconomic pathway and representative concentration pathway (SSP-RCP) scenarios, including SSP1-RCP1.9, SSP1-RCP2.6, SSP2-RCP4.5, and SSP5-RCP8.5 scenarios. In the present study, a total of 287,579 stroke deaths were collected during the warm season. Heat was significantly associated with an increased risk of stroke mortality. Overall, compared with the 2010 s, the heat-related attributable fraction (AF) was projected to increase in the 2090 s, with increments ranging from 0.8 % to 7.5 % across various climate change scenarios. The heat-related AF was projected to reach 11.9 % (95 % empirical confidence interval eCI 6.1 %, 17.5 %) in the 2090 s under the SSP5-RCP8.5 scenario in China, while the corresponding estimates were 6.6 % (95 % eCI 2.5 %, 11.0 %) and 5.1 % (95 % eCI 1.2 %, 9.1 %) for Japan and South Korea, respectively. Climate change will exacerbate the burden of heat-related stroke mortality but with considerable geographical heterogeneity in East Asia.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mgkg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mgkg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n 49) and moderate-dose (n 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval CI, 0.32-3.00 P .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18 95% CI, 0.30-4.88 P .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

Mild Traumatic Brain Injury Induces Time- and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability.

Mild traumatic brain injury (mTBI) produces subtle cerebrovascular impairments that persist over time and promote increased ischemic stroke vulnerability. We recently established a role for vascular impairments in exacerbating stroke outcomes 1 week after TBI, but there is a lack of research regarding long-term impacts of mTBI-induced vascular dysfunction, as well as a significant need to understand how mTBI promotes stroke vulnerability in both males and females. Here, we present data using a mild closed head TBI model and an experimental stroke occurring either 7 or 28 days later in both male and female mice. We report that mTBI induces larger stroke volumes 7 days after injury, however, this increased vulnerability to stroke persists out to 28 days in female but not male mice. Importantly, mTBI-induced changes in blood-brain barrier permeability, intravascular coagulation, angiogenic factors, total vascular area, and glial expression were differentially altered across time and by sex. Taken together, these data suggest that mTBI can result in persistent cerebrovascular dysfunction and increased susceptibility to worsened ischemic outcomes, although these dysfunctions occur differently in male and female mice.

Experiences and needs of older adults at different stages of cerebral infarction based on trajectory theory-A qualitative study.

In recent years, stroke has become the second leading cause of death worldwide, and the incidence and mortality of ischemic stroke have increased significantly. This study mainly aimed to explore the experiences and needs of older adults at different stages of cerebral infarction based on the chronic illness trajectory theory. Data were collected from 22 older adults experiencing the onset, acute, and stable stages of stroke through semi-structured interviews and were analyzed using Colaizzis descriptive phenomenological approach. Multiple themes and subthemes emerged on the experiences and needs of older adults at different stages of cerebral infarction based on the three dimensions of the long-term disease trajectory theory illness-related work, biographical work, and everyday life work. Seven themes were extracted for illness-related work, six for biographical work, and eight for everyday life work. The treatment, nursing, and rehabilitation of cerebral infarction are complex. This study indicated that patients after cerebral infarction have different experiences and needs for illness-related work. They also have distinctive and dynamically changing demands for biographical work and everyday life work. The experiences and needs of older patients with cerebral infarction changed dynamically at different stages of the disease. Healthcare professionals should develop effective interventions targeting these needs at various disease stages, provide patients with continuous support to shape their disease trajectories, and maintain patients stability.

Mangiferin exerts neuroprotective effects against focal cerebral ischemia in mice by regulating NF-κB signaling pathway.

Mangiferin is a natural free radical scavenging antioxidant that induces excitation of the central nervous system. However, the mechanism of neuroprotective effect of mangiferin on focal cerebral ischemia has not been fully investigated. The aim of this study was to investigate the protective effect of mangiferin on focal cerebral ischemia in mice. Middle cerebral artery occlusion (MCAO) was performed to investigate the effect of mangiferin on focal cerebral ischemia. Mice were randomly divided into 5 groups sham, MCAO, MCAO 5 mgkg mangiferin, MCAO 20 mgkg mangiferin and MCAO 5 mgkg nimodipine. Neurobehavioral scores, brain edema, brain injury scores, relative infarct size and expression of some inflammatory factors in the brain were evaluated. NF-κB pathway was detected by Western blotting and immunofluorescence. The results showed that mangiferin effectively attenuated MCAO-induced brain injury, including improvement of neurological impairment, reduction of brain edema, and reduction of infarct size. Compared with the MCAO group, mangiferin significantly inhibited MCAO-induced neuroinflammation, which can be proved by reduced expression levels of TNF-α, IL-1β, iNOS and COX-2. In addition, we found that phosphorylation of IκBα was inhibited and the expression of NF-κB p65 in the nucleus was reduced after the addition of mangiferin. Our study suggested that mangiferin exerts neuroprotective effects on focal cerebral ischemia in mice by regulating the NF-κB signaling pathway. Mangiferin may be an effective treatment for cerebral ischemia and other neurological disorders.

Investigating gender-based differential item functioning on the Kansas City Cardiomyopathy Questionnaire (KCCQ) using qualitative content analysis.

The purpose of this study is to evaluate potential gender-based differences in interpreting the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and to explore if there are aspects of health-related quality of life (HRQOL) not captured by the KCCQ-23 that are important to assess in men andor women with heart failure (HF). Patients ≥ 22 years of age with clinician-diagnosed HF and left ventricular ejection fraction ≤ 40% were recruited from two academic medical centers to participate in semi-structured concept elicitation and cognitive debriefing interviews. Enrollment was stratified by patient-identified gender (half womenhalf men). All interviews were conducted over the phoneweb and audio recorded. Interviews were transcribed and descriptive qualitative content analysis was used to summarize findings overall and by gender. Twenty-five adults (56% women) diagnosed with HF participated. The average age was 67 years (range 25-88). Women attributed a wider variety of symptoms to HF than men. Some participants had difficulty differentiating whether their experiences were due to HF, side effects of their medications, or age. We found very little evidence that participants interpreted KCCQ-23 items differently based on gender. Overall, our findings indicate that interpretation of the KCCQ-23 items were similar in men and women. However, some modifications to items may improve clarity of interpretation for a wide range of patients.

Percutaneous left atrial appendage occlusion impact on left atrial deformation indices.

Percutaneous left atrial appendage occlusion (LAAO) is an accepted alternative to thromboprophylaxis in patients with atrial fibrillation (AF) who are (i) intolerant to oral anticoagulation (OAC) (e.g. life-threatening haemorrhage), (ii) non-adherent to OAC, or (iii) at a high bleeding risk with OAC. Improvement in LA mechanics was shown post-LAAO in the LAFIT-LARIAT study, using the Lariat device. No significant change was seen in LA mechanics after LAAO with the Watchman device in the LAFIT-Watchman study. The impact of LAAO with the Amplatzer or Amulet device on LA deformation mechanics has not been investigated. To evaluate the impact of LAAO with the Amplatzer or Amulet device on echocardiographic LA deformation indices. All patients undergoing percutaneous LAAO from 2013 to 2021 at a single centre were included from an ongoing clinical registry. LA reservoir (ε 28 LAAO recipients (mean age 73 ± 12 years, 68% male) were analysed. 5 (18%) patients had AF pre- or post-procedure. After a mean follow-up of 1.6 ± 1.4 months, the mean LA ε No significant improvement in LA mechanical function was seen after LAAO with the Amplatzer or Amulet device. Different LAAO devices therefore appear to have divergent effects on LA deformation, the clinical implications of which may warrant further study.

Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis.

The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100).

Feasibility, Safety, and Technical Success of the Flying Intervention Team in Acute Ischemic Stroke Comparison of Interventions in Different Primary Stroke Centers with those in a Comprehensive Stroke Center.

Prompt endovascular care of patients with ischemic stroke due to large vessel occlusion (LVO) remains a major challenge in rural regions as primary stroke centers (PSC) usually cannot provide neuro-interventional services. Objective The core content of the Flying Intervention Team (FIT) project is to perform thrombectomy on-site at a local PSC after the neuro-interventionalist has been transported via helicopter to the target hospital. An important and so far unanswered question is whether mechanical thrombectomy can be performed as safely and successfully on-site as in a specialized comprehensive stroke center (CSC). Comparison of 100 FIT thrombectomies on site in 14 different PSCs with 128 control thrombectomies at 1 CSC (79 drip-and-ship, 49 mothership) performed by a single interventionalist with respect to technical-procedural success parameters, procedural times, and complications. There were no significant differences between the two groups in terms of technical success (95.0% successful interventions in FIT group vs. 94.5% in control group, p 0.60) and complications (3% major complications in FIT vs. 1.6% in control group, p 0.47). Regarding time from onset to groin puncture, there was no difference between FIT and the entire control group (182 vs. 183 min, p 0.28), but a trend in favor of FIT compared with the drip-and-ship control subgroup (182 vs. 210 min, p 0.096). Airborne neuro-interventional thrombectomy service is a feasible approach for rural regions. If performed by experienced neuro-interventionalists, technical success and complication rates are comparable to treatment in a specialized neuro-interventional department.

Nurse-led Telehealth Intervention for Rehabilitation (Telerehabilitation) Among Community-Dwelling Patients With Chronic Diseases Systematic Review and Meta-analysis.

Chronic diseases are putting huge pressure on health care systems. Nurses are widely recognized as one of the competent health care providers who offer comprehensive care to patients during rehabilitation after hospitalization. In recent years, telerehabilitation has opened a new pathway for nurses to manage chronic diseases at a distance however, it remains unclear which chronic disease patients benefit the most from this innovative delivery mode. This study aims to summarize current components of community-based, nurse-led telerehabilitation programs using the chronic care model evaluate the effectiveness of nurse-led telerehabilitation programs compared with traditional face-to-face rehabilitation programs and compare the effects of telerehabilitation on patients with different chronic diseases. A systematic review and meta-analysis were performed using 6 databases for articles published from 2015 to 2021. Studies comparing the effectiveness of telehealth rehabilitation with face-to-face rehabilitation for people with hypertension, cardiac diseases, chronic respiratory diseases, diabetes, cancer, or stroke were included. Quality of life was the primary outcome. Secondary outcomes included physical indicators, self-care, psychological impacts, and health-resource use. The revised Cochrane risk of bias tool for randomized trials was employed to assess the methodological quality of the included studies. A meta-analysis was conducted using a random-effects model and illustrated with forest plots. A total of 26 studies were included in the meta-analysis. Telephone follow-ups were the most commonly used telerehabilitation delivery approach. Chronic care model components, such as nurses-patient communication, self-management support, and regular follow-up, were involved in all telerehabilitation programs. Compared with traditional face-to-face rehabilitation groups, statistically significant improvements in quality of life (cardiac diseases standard mean difference SMD 0.45 95% CI 0.09 to 0.81 P.01 heterogeneity X This review showed that telerehabilitation programs could be beneficial to patients with chronic disease in the community. However, better designed nurse-led telerehabilitation programs are needed, such as those involving the transfer of nurse-patient clinical data. The heterogeneity between studies was moderate to high. Future research could integrate the chronic care model with telerehabilitation to maximize its benefits for community-dwelling patients with chronic diseases. International Prospective Register of Systematic Reviews CRD42022324676 httpswww.crd.york.ac.ukprosperodisplayrecord.phpRecordID324676.

Concordance Between Patient-Reported Health Data and Electronic Health Data in the ADAPTABLE Trial.

Patient-reported health data can facilitate clinical event capture in pragmatic clinical trials. However, few data are available on the fitness for use of patient-reported data in large-scale health research. To evaluate the concordance of a set of variables reported by patients and available in the electronic health record as part of a pragmatic clinical trial. Data from ADAPTABLE (Aspirin Dosing A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic clinical trial, were used in a concordance substudy of a comparative effectiveness research trial. The trial randomized 15 076 patients with existing atherosclerotic cardiovascular disease in a 11 ratio to low- or high-dose aspirin from April 2016 through June 30, 2019. Concordance of data was evaluated from 4 domains (demographic characteristics, encounters, diagnoses, and procedures) present in 2 data sources patient-reported data captured through an online portal and data from electronic sources (electronic health record data). Overall agreement, sensitivity, specificity, positive predictive value, negative predictive value, and κ statistics with 95% CIs were calculated using patient report as the criterion standard for demographic characteristics and the electronic health record as the criterion standard for clinical outcomes. Of 15 076 patients with complete information, the median age was 67.6 years (range, 21-99 years), and 68.7% were male. With the use of patient-reported data as the criterion standard, agreement (κ) was high for Black and White race and ethnicity but only moderate for current smoking status. Electronic health record data were highly specific (99.6%) but less sensitive (82.5%) for Hispanic ethnicity. Compared with electronic health record data, patient report of clinical end points had low sensitivity for myocardial infarction (33.0%), stroke (34.2%), and major bleeding (36.6%). Positive predictive value was similarly low for myocardial infarction (40.7%), stroke (38.8%), and major bleeding (21.9%). Coronary revascularization was the most concordant event by data source, with only moderate agreement (κ 0.54) and positive predictive value. Agreement metrics varied by site for all demographic characteristics and several clinical events. In a concordance substudy of a large, pragmatic comparative effectiveness research trial, sensitivity and chance-corrected agreement of patient-reported data captured through an online portal for cardiovascular events were low to moderate. Findings suggest that additional work is needed to optimize integration of patient-reported health data into pragmatic research studies. ClinicalTrials.gov Identifier NCT02697916.

Dawn of a new Day - A brief History of Stroke Treatment in Iceland.

Here we will briefly review the main influential factors and milestones in the history of stroke care in Iceland. Over the last few decades the treatment of ischemic stroke has revolutionized in many ways and so has the general mindset of those providing it. This review article is partly based upon interviews with Icelandic doctors that partook in the development. Looking back at this history it is clear that, in many ways, the medical care in Iceland was at the forefront in implementing those emerging new treatments in stroke care. This is mainly on account of ambitious and hard working individuals that were not easily dissuaded but firmly believed in the possibility of better outcomes for their stroke patients.

Lipoprotein(a) and the risk of recurrent events in patients with acute myocardial infarction treated by percutaneous coronary intervention.

The role of Lipoprotein(a) (Lpa) in risk stratification following an acute myocardial infarction (AMI) is still debated. We aimed to investigate whether elevated Lp(a) levels in patients with AMI treated by percutaneous coronary intervention (PCI) are associated with worse outcomes. We designed a retrospective registry including patients with AMI undergoing PCI. The occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as death from cardiovascular causes, recurrent myocardial infarction, unplanned coronary revascularization and stroke, was assessed at follow up and compared between patients with high (≥ 30 mgdl) and low (< 30 mgdl) Lp(a) levels. Cox proportional hazard analysis was performed in order to assess independent predictors of MACCE. During a 3-year period (2018-2020) we identified 634 patients with AMI treated by PCI and known Lp(a) blood levels follow up visits were performed in 414 patients (median length 29 months 19-38). Median Lp(a) level was 18 mgdl 8-42. The incidence of MACCE was significantly higher in high as compared to low Lp(a) group (log-rank p0.018). The following independent predictors were identified at multivariate Cox regression Lp(a) ≥30 mgdl (HR 1.82 95% CI 1.04-3.19, peripheral artery disease (HR 4.62 95% CI 2.50-8.54), number of diseased coronary vessels (HR 1.51 95% 1.03-2.24 and presence of a coronary chronic total occlusion at coronary angiography (HR 3.46 95% CI 1.77-6.76). In this study, Lp(a) values ≥30 mgdl were associated to worse outcomes in patients with AMI receiving PCI. Lp(a) could represent a useful tool to identify patients at high risk of recurrent events.

Kidney in VHL disease Early clear cell proliferation occurs in the distal tubular system.

Renal clear cell carcinoma commonly occurs in patients with von Hippel‑Lindau disease (VHL). Kidneys of VHL disease patients (VHL kidneys) contain an abundance of independent clear cell proliferation events that have been hypothesized to represent precursor structures of clear cell carcinoma. In the present study, it was tried to identify the site of origin of clear cell proliferation, and the immunophenotype of clear cells. Using 3D histological tracking, the topographic origin of microscopic clear cell proliferation was investigated by identification of informative structures of interest and immunohistochemical staining for cluster of differentiation 10 (CD10) and cytokeratin 7 (CK7) in consecutive serial sections. In addition, the CD10CK7 immunophenotype of proliferating clear cells was evaluated. Clear cell proliferation uniformly occurred in the distal tubular system. Some clear cell proliferation, however, revealed proximal tubule immunophenotype. It was concluded that early proliferation of VHL‑deficient clear cells occurs in the distal tubular system. Despite the association with the distal tubular system, the immunohistochemical profile of early clear cell proliferation may be inconsistent with its distal tubular origin.

The CRYOSTAT2 trial The rationale and study protocol for a multi-Centre, randomised, controlled trial evaluating the effects of early high-dose cryoprecipitate in adult patients with major trauma haemorrhage requiring major haemorrhage protocol activation.

To describe the protocol for a multinational randomised, parallel, superiority trial, in which patients were randomised to receive early high-dose cryoprecipitate in addition to standard major haemorrhage protocol (MHP), or Standard MHP alone. Blood transfusion support for trauma-related major bleeding includes red cells, plasma and platelets. The role of concentrated sources of fibrinogen is less clear and has not been evaluated in large clinical trials. Fibrinogen is a key pro-coagulant factor that is essential for stable clot formation. A pilot trial had demonstrated that it was feasible to deliver cryoprecipitate as a source of fibrinogen within 90 min of admission. Randomisation was via opaque sealed envelopes held securely in participating Emergency Departments or transfusion laboratories. Early cryoprecipitate, provided as 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g fibrinogen supplementation), was transfused as rapidly as possible, and started within 90 min of admission. Participants in both arms received standard treatment defined in the receiving hospital MHP. The primary outcome measure was all-cause mortality at 28 days. Symptomatic thrombotic events including venous thromboembolism and arterial thrombotic events (myocardial infarction, stroke) were collected from randomisation up to day 28 or discharge from hospital. EQ5D-5Land Glasgow Outcome Score were completed at discharge and 6 months. All analyses will be performed on an intention to treat basis, with per protocol sensitivity analysis. The trial opened for recruitment in June 2017 and the final patient completed follow-up in May 2022. This trial will provide firmer evidence to evaluate the effectiveness and cost-effectiveness of early high-dose cryoprecipitate alongside the standard MHP in major traumatic haemorrhage.

Memory decay and generalization following distinct motor learning mechanisms.

Motor skill learning is considered to arise out of contributions from multiple learning mechanisms, including error-based learning (EBL), use-dependent learning (UDL), and reinforcement learning (RL). These learning mechanisms exhibit dissociable roles and engage different neural circuits during skill acquisition. However, it remains largely unknown how a newly formed motor memory acquired through each learning mechanism decays over time and whether distinct learning mechanisms produce different generalization patterns. Here, we used variants of reaching paradigms that dissociated these learning mechanisms to examine the time course of memory decay following each learning and the generalization patterns of each learning. We found that motor memories acquired through these learning mechanisms decayed as a function of time. Notably, 15 min, 6 h, and 24 h after acquisition, the memory of EBL decayed much greater than that of RL. The memory acquired through UDL faded away within a few minutes. Motor memories formed through EBL and RL for given movement directions generalized to untrained movement directions, with the generalization of EBL being greater than that of RL. In contrast, motor memory of UDL could not generalize to untrained movement directions. These results suggest that distinct learning mechanisms exhibit different patterns of memory decay and generalization.

The best and worst of times in therapy development for myasthenia gravis.

Within the last 5 years, the US Food and Drug Administration (FDA) has approved complement and neonatal Fc receptor (FcRN) inhibitors for treatment of generalized myasthenia gravis, and several other therapies are in late-stage clinical trials or under regulatory review. However, questions about which patients are most likely to benefit from which therapies, and the relative effectiveness of these very expensive drugs, has resulted in uncertainty around the place that they should occupy in the existing therapeutic armamentarium. MGNet (a Rare Diseases Clinical Research Consortium funded by the National Institute of Neurological Diseases and Stroke) held two meetings during the 14th International Conference of the Myasthenia Gravis Foundation of America to discuss the most critical needs for clinical trial readiness and biomarker development in the context of therapy development for myasthenia gravis. Herein we provide a summary of these discussions, but not a consensus opinion, and offer a series of recommendations to guide focused research in the most critical areas. We welcome ongoing discussion through comments on this work.

The HeartMate 3 left ventricular assist device as a strategy to bridge to transplant.

Recent changes in the market for left ventricular assist devices have resulted in the HeartMate 3 (HM3) being the only commercially-available device. This study evaluates the outcomes of patients with a HM3 waitlisted for and undergoing orthotopic heart transplantation (OHT). Patients waitlisted for isolated OHT with a HM3 or undergoing OHT after bridge-to-transplant (BTT) with a HM3 between 2015 and 2021 were identified from the UNOS registry and included in this study. Propensity matching was used to compare outcomes of BTT-HM3 versus primary OHT. A total of 1321 patients supported with a HM3 underwent OHT during our study period. Unadjusted 30-day, 90-day, and 1-year survival following OHT in the BTT-HM3 cohort was 96.5%, 94.4%, and 90.7%, respectively. In propensity-matched analysis, 1103 BTT-HM3 patients were compared with 1103 primary OHT patients. Rates of post-OHT stroke were higher in the BTT-HM3 group (4.4% vs. 2.0%, p .001). The BTT-HM3 group had lower 30-day survival (96.2% vs. 97.4%, p .033) although 90-day (94.2% vs. 95.3%, p .103) and 1-year survival (90.4% vs. 91.7%, p .216) were comparable. A total of 1251 patients were supported with a HM3 at the time of OHT listing during the study period. At the time of this analysis, 60 (4.5%) remained on the waitlist, 991 (75.0%) underwent OHT, and 119 (9.0%) died or clinically deteriorated with waitlist removal. The HM3 is a viable method for BTT with acceptable waitlist outcomes. Although 1-year survival is comparable to primary OHT, early outcomes are worse, suggesting that refinement of patient selection and perioperative management is prudent to optimizing outcomes.

Endovascular therapy for acute ischemic stroke after cardiac surgery Why not

There are few publications regarding the use of endovascular therapy (EVT) for the treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) after cardiac surgery. In the manuscript entitled Endovascular Thrombectomy for Large Vessel Occlusion Acute Ischemic Stroke after Cardiac Surgery, Gupta et al. report their experience with EVT for AIS after cardiac surgery.

Associations of short- and long-term mortality with admission blood pressure in Chinese patients with different heart failure subtypes.

It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short- and long-term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women mean age, 68.8 years), we assessed the risk of 30-day, 1-year, and long-term (> 1 year) mortality with 1-SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow-up of 4.1 years, 1341 patients died. The 30-day, 1-year, and long-term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable-adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long-term mortality (hazard ratio, 1.11 95% CI, 1.02-1.22 p .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long-term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04-1.29 p .007) and .89 (95% CI, .80-.99 p .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1-year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all-cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.

On- versus off-pump CABG in octogenarians A propensity-matched analysis from the UK National Database.

Coronary artery bypass grafting (CABG) remains a good revascularization strategy in octogenarians with excellent clinical outcomes and quality of life postoperatively. However, the benefits of off-pump over on-pump CABG in the elderly population are still controversial. We investigated this issue in the UK National Audit database. We retrospectively analyzed all octogenarians undergoing nonemergency, isolated CABG from 1996 to 2019. Propensity score matching (PSM) was conducted to adjust for imbalance in the baseline characteristics between the off-pump and on-pump groups. Primary outcome was in-hospital mortality and postoperative cerebrovascular accidents. Secondary outcomes were bleeding requiring reoperation, deep sternal wound infection, and postoperative dialysis. A total of 6436 patients were included for analysis. No differences were observed between off- and on-pump group in-hospital mortality (4% vs. 3.8%, p .89), return to theater rate (5.4% vs. 6.2%, p .16) and incidence of deep sternal wound infection (1.1% vs. 1.6%, p .34). However, octogenarian undergoing off-pump CABG were less likely to experience postoperative transient ischemic attack (TIA)stroke (1.4% vs. 2.3%, p .004) but more likely to require renal dialysis (4.8% vs. 3.5%, p .03). The data show similar in-hospital mortality in octogenarians regardless of the revascularization technique used. Off-pump when compared with on-pump CABG is associated with a lower incidence in postoperative neurological events but a higher need for renal dialysis.

Prediction of functional results of percutaneous coronary interventions with virtual stenting and quantitative flow ratio.

The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown. We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI). This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years. We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve AUC 0.856 0.804-0.909, p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC 0.712 0.555-0.869, p 0.041), being similar to that of actual post-PCI FFR (AUC 0.691 0.512-0.870, p 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio HR 12.9 2.32-71.3, p 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR 16.98 2.33-123.29, p 0.0051). rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events. Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560.

The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction Insights From the PARADISE-MI Trial.

In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitrilvalsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitrilvalsartan on coronary outcomes in patients with AMI. We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitrilvalsartan (97103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. Patients were randomly assigned at a median of 4.4 3.0-5.8 days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitrilvalsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 95% CI, 0.74-0.99, In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitrilvalsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. URL httpswww. gov Unique identifier NCT02924727.

Contemporary Incidence and Burden of Cerebral Venous Sinus Thrombosis in Children of the United States.

The incidence of cerebral venous thrombosis (CVT) in children of the United States is unknown, and it is uncertain how the burden of CVT hospitalizations in children changed over the last decade. We conducted a retrospective cohort study using the State Inpatient Database and Kids inpatient database. All new CVT cases in children (0-19 years) in the New York 2006 to 2018 State Inpatient Database (n705), and all cases of CVT in the entire US contained in the 2006 to 2019 Kids inpatient database (weighted n6115) were identified using validated Across the study period, 48.2% of all incident CVT cases and 44.6% of all CVT admissions nationally were in girls. Of all incident cases, 27.2% were infants and 65.8% of these infants were neonates. Average incidence across the study period was (1.1100 000year, SE0.04) but incidence in infants (6.4100 000year) was at least 5 times the incidence in other age groups (1-4 years 0.7100 000year, 15-19 years 1.2100 000year). Incidence and national burden of CVT admissions was higher in girls in adolescents 15 to 19 years, but overall burden was higher in boys in other age groups. Age- and sex-standardized CVT incidence increased by 3.8% annually (95% CI, 0.2%-7.6%), while the overall burden of admissions increased by 4.9% annually (95% CI, 3.6%-6.2%). CVT incidence in New York and national burden of CVT increased significantly over the last decade.

Diurnal Differences in Immune Response in Brain, Blood and Spleen After Focal Cerebral Ischemia in Mice.

The immune response to acute cerebral ischemia is a major factor in stroke pathobiology. Circadian biology modulates some aspects of immune response. The goal of this study is to compare key parameters of immune response during the activeawake phase versus inactivesleep phase in a mouse model of transient focal cerebral ischemia. Mice were housed in normal or reversed light cycle rooms for 3 weeks, and then they were blindly subjected to transient focal cerebral ischemia. Flow cytometry was used to examine immune responses in blood, spleen, and brain at 3 days after ischemic onset. In blood, there were higher levels of circulating T cells in mice subjected to focal ischemia during zeitgeber time (ZT)1-3 (inactive or sleep phase) versus ZT13-15 mice (active or awake phase). In the spleen, organ weight and immune cell numbers were lower in ZT1-3 versus ZT13-15 mice. Consistent with these results, there was an increased infiltration of activated T cells into brain at ZT1-3 compared with ZT13-15. This proof-of-concept study indicates that there are significant diurnal effects on the immune response after focal cerebral ischemia in mice. Hence, therapeutic strategies focused on immune targets should be reassessed to account for the effects of diurnal rhythms and circadian biology in nocturnal rodent models of stroke.

Blood Pressure Control Targets and Risk of Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP <120 mmHg displayed reduced risk of recurrent ICH (adjusted hazard ratio AHR, 0.74 95% CI, 0.59-0.94) and major adverse cardiovascular and cerebrovascular events (AHR, 0.69 95% CI, 0.53-0.92). All-cause mortality (AHR, 0.76 95% CI, 0.57-1.03) and vascular mortality (AHR, 0.68 95% CI, 0.45-1.01) did not differ significantly. Among participants aged >75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 95% CI, 1.02-1.85 and AHR, 1.36 95% CI, 1.03-1.78, respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.

mTOR (Mammalian Target of Rapamycin) Hitting the Bulls Eye for Enhancing Neurogenesis After Cerebral Ischemia

Ischemic stroke remains a leading cause of morbidity and disability around the world. The sequelae of serious neurological damage are irreversible due to bodys own limited repair capacity. However, endogenous neurogenesis induced by cerebral ischemia plays a critical role in the repair and regeneration of impaired neural cells after ischemic brain injury. mTOR (mammalian target of rapamycin) kinase has been suggested to regulate neural stem cells ability to self-renew and differentiate into proliferative daughter cells, thus leading to improved cell growth, proliferation, and survival. In this review, we summarized the current evidence to support that mTOR signaling pathways may enhance neurogenesis, angiogenesis, and synaptic plasticity following cerebral ischemia, which could highlight the potential of mTOR to be a viable therapeutic target for the treatment of ischemic brain injury.

Cerebroprotective Role of

FTO (fat mass and obesity-associated protein) demethylates Adult male and female C57BL6J mice were injected with FTO adeno-associated virus 9 (intracerebral) at 21 days prior to inducing transient middle cerebral artery occlusion. Poststroke brain damage (infarction, atrophy, and white matter integrity) and neurobehavioral deficits (motor function, cognition, depression, and anxiety-like behaviors) were evaluated between days 1 and 28 of reperfusion. FTO overexpression significantly decreased the poststroke m These results demonstrate that FTO-dependent m

Subarachnoid Hemorrhage During Pregnancy and Puerperium A Population-Based Study.

Pregnancy-related subarachnoid hemorrhage (pSAH) is rare, but it causes high mortality and morbidity. Nevertheless, data on pSAH are limited. The objectives here were to examine the incidence trends, causes, risk factors, and outcomes of pSAH in a nationwide population-based cohort study in Finland covering 30 years. We performed a retrospective population-based cohort study and nested case-control study in Finland for the period 1987-2016 (Stroke in Pregnancy and Puerperium in Finland). The Medical Birth Register was linked to the Hospital Discharge Register to identify women with incident stroke during pregnancy or puerperium. A subcohort of women with SAH is included in this analysis. The temporal connection of SAH to pregnancy and clinical details were verified from patient records. The unadjusted incidence of pSAH was 3.21 (95% CI, 2.46-4.13) per 100 000 deliveries. No significant increase occurred in the incidence throughout the study period. However, the age of the mother had a significant increasing effect on the incidence. In total, 77% of patients suffered an aneurysmal pSAH, resulting in death in 16.3% of women and with only 68.2% achieving good recovery (modified Rankin Scale score 0-2) at 3 months. Patients with nonaneurysmal pSAH recovered well. The significant risk factors for pSAH were smoking (odds ratio, 3.27 1.56-6.86), prepregnancy hypertension (odds ratio, 12.72 1.39-116.46), and pre-eclampsiaeclampsia (odds ratio, 3.88 1.00-15.05). The incidence of pSAH has not changed substantially over time in Finland. The majority of pSAH cases were aneurysmal and women with aneurysm had considerable mortality and morbidity. Counseling of pregnant women about smoking cessation and monitoring of blood pressure and symptoms of pre-eclampsia are important interventions to prevent pSAH.

Burden of cardiovascular disease attributable to particulate matter pollution in the eastern Mediterranean region analysis of the 1990-2019 global burden of disease.

Particulate matter pollution is the most important environmental mediator of global cardiovascular morbidity and mortality. Air pollution evidence from the Eastern Mediterranean Region (EMR) is limited, owing to scarce local studies, and the omission from multinational studies. We sought to investigate trends of particulate matter (PM2.5)-related cardiovascular disease (CVD) burden in the EMR from 1990 to 2019. We used the 1990-2019 global burden of disease methodology to investigate total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and disability-adjusted life years (DALYs) and cause-specific CVD mortality in the EMR. The average annual population-weighted PM2.5 exposure in EMR region was 50.3 μgm3 95% confidence interval (CI)42.7-59.0 in 2019, which was comparable with 199 048.1 μgm3 (95% CI 36.5-65.3). This was despite an 80% reduction in household air pollution (HAP) sources since 1990. In 2019, particulate matter pollution contributed to 25.67% (95% CI 23.55-27.90%) of total CVD deaths and 28.10% (95% CI 25.75-30.37%) of DALYs in the region, most of which were due to ischaemic heart disease and stroke. We estimated that 353 071 (95% CI 304 299-404 591) CVD deaths in EMR were attributable to particulate matter in 2019, including 264 877 (95% CI 218 472-314 057) and 88 194.07 (95% CI 60 149-119 949) CVD deaths from ambient PM2.5 pollution and HAP from solid fuels, respectively. DALYs in 2019 from CVD attributable to particulate matter was 28.1% when compared with 26.69% in 1990. The age-standardized death and DALY rates attributable to air pollution was 2122 per 100 000 in EMR in 2019 and was higher in males (2340 per 100 000) than in females (1882 per 100 000). The EMR region experiences high PM2.5 levels with high regional heterogeneity and attributable burden of CVD due to air pollution. Despite significant reductions of overall HAP in the past 3 decades, there is continued HAP exposure in this region with rising trend in CVD mortality and DALYs attributable to ambient sources. Given the substantial contrast in disease burden, exposures, socio-economic and geo-political constraints in the EMR region, our analysis suggests substantial opportunities for PM2.5 attributable CVD burden mitigation.

A continuous statistical-geometric framework for normative and impaired gaits.

A quantitative analysis of human gait patterns in space-time provides an opportunity to observe variability within and across individuals of varying motor capabilities. Impaired gait significantly affects independence and quality of life, and thus a large part of clinical research is dedicated to improving gait through rehabilitative therapies. Evaluation of these paradigms relies on understanding the characteristic differences in the kinematics and underlying biomechanics of impaired and unimpaired locomotion, which has motivated quantitative measurement and analysis of the gait cycle. Previous analysis has largely been limited to a statistical comparison of manually selected pointwise metrics identified through expert knowledge. Here, we use a recent statistical-geometric framework, elastic functional data analysis (FDA), to decompose kinematic data into continuous amplitude (spatial) and phase (temporal) components, which can then be integrated with established dimensionality reduction techniques. We demonstrate the utility of elastic FDA through two unsupervised applications to post-stroke gait datasets. First, we distinguish between unimpaired, paretic and non-paretic gait presentations. Then, we use FDA to reveal robust, interpretable groups of differential response to exosuit assistance. The proposed methods aim to benefit clinical practice for post-stroke gait rehabilitation, and more broadly, to automate the quantitative analysis of motion.

Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world.

We report on a 116-year-old Japanese woman who was the first officially documented supercentenarian to be autopsied in the world. She lived a remarkably healthy life until suffering cerebral infarction at 109 years of age. She became Japans oldest person at 113 years and died in 1995 from colon cancer at 116 years 175 days. Her medical records show the delayed onset of stroke, cancer, dementia, and heart disease and the importance of appropriate medical treatment and intensive dedicated care provided during the last stage of her life. She was the longest-lived person in Japan for 21 years from 1993 until 2014. The neuropathological findings of her autopsied brain were briefly reported in the Japanese literature in 1997. In this study, we reinvestigated her brain and spinal cord in more detail. Severe cerebrovascular lesions and cervical spondylotic myelopathy were found to be the main causes of her disability. Although the density of senile plaques was relatively high, the distribution of neurofibrillary tangles was limited. Ghost tangles and argyrophilic grains were mild. The mildness of tau pathological changes in her neurons, in other words the resistance of neurons to tau pathology, may be a factor responsible for her longevity.

Tonic extracellular glutamate and ischaemia glutamate antiporter system x

In stroke, the sudden deprivation of oxygen to neurons triggers a profuse release of glutamate that induces anoxic depolarization (AD) and leads to rapid cell death. Importantly, the latency of the glutamate-driven AD event largely dictates subsequent tissue damage. Although the contribution of synaptic glutamate during ischaemia is well-studied, the role of tonic (ambient) glutamate has received far less scrutiny. The majority of tonic, non-synaptic glutamate in the brain is governed by the cystineglutamate antiporter, system x

Bilateral Lower Limb Training for Post-stroke Survivors A Bibliometric Analysis.

Stroke is one of the most disabling conditions affecting the middle-aged population all around the world. This study aims to explore the rehabilitation of stroke patients using bibliometric analysis, which includes statistical analysis of recent articles, books, and other kinds of publications, to assess scientific output and determine the significance of scientific investigations in terms of both quality and quantity. In this study, an analysis of global trends in research in bilateral lower limb training for training balance and walking for patients in the subacute stage post-stroke between 1988 and 2021 was done. All the articles were obtained from PubMed databases. CiteSpace software was used to analyze the relationship between publications and country, journals, institutions, authors, references, and the keywords used. A total of 160 publications were included in the analysis. There was a tremendous increase in the research of physiotherapy intervention in patients who had residual disability post-stroke with a publication rate of 7.1 articles per year of publications. The use of the sophisticated PubMed database to extract articles allowed for a thorough and powerful bibliometric analysis of stroke rehabilitation research published between 1988 and 2020. In general, the number of studies on bilateral training has increased in recent decades. This historical overview of rehabilitation for post-stroke survivors will serve as a valuable starting point for future study into possible collaborators, focus issues, and trends. This bibliometric analysis highlights the potential value of exercise therapy for stroke survivors in creating more effective hemiplegia rehabilitation programs. This research may encourage the use of strengthening in the therapeutic therapy of hemiplegia balance. The groundwork will be laid for future research on strengthening stroke to be organized and given top priority.

Long-Term Neurological Sequelae Among Severe COVID-19 Patients A Systematic Review and Meta-Analysis.

Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models. We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR 4.53 95% CI 2.37-8.65 p<0.00001 I

Thrombolysis in an Acute Ischemic Stroke Patient on Direct Anticoagulant Therapy Outside of the Traditional Time Window A Case Report.

A stroke is a life-threatening medical condition that could be disabling if left untreated. Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) can be effective when initiated in an acute stroke, but their benefit is time-dependent and their use may be restricted by contraindications (CIs) such as anticoagulation therapy. The critical therapeutic time window, which was previously limited to 4.5-6 hours, is now extended to 24 hours in selected patients due to the development of advanced neuroimaging techniques. Herein, we discuss the case of a 50-year-old patient on rivaroxaban who developed acute ischemic stroke (AIS) and was treated successfully with intravenous recombinant tissue plasminogen activator thrombolysis more than six hours after the time he was last seen well (LSW). Our case demonstrates the importance of advanced neuroimaging techniques in identifying AIS candidates for IVT andor MT with late or unknown time windows as well as the importance of case-by-case assessment when challenged by theoretical contraindications for thrombolysis.

Hiccup The Striking Manifestation of Hyponatremia Due to Ischemic Stroke-Induced Cerebral Salt Wasting Syndrome (CSWS).

Among many clinical symptoms, hiccups are an infrequent presentation of hyponatremia. Hyponatremia indicates a serum sodium level of less than 135 mmoll, the most common reported electrolyte abnormality. Cerebral salt wasting syndrome is a less common cause of hyponatremia, which can arise from a spectrum of brain pathology. This case report brings attention to a case of hyponatremia due to cerebral salt wasting syndrome in a 76-year-old man who suffered from an ischemic stroke. The hyponatremia appeared vaguely, with only a hiccup as a symptom.

Reversible Cerebral Vasoconstriction Syndrome and Ischemic Stroke Secondary to Peripartum Cardiomyopathy - Report a Rare Case.

Acute cardioembolic stroke is a rare presentation of peripartum cardiomyopathy. We present an unusual case of peripartum cardiomyopathy, that subsequently developed cardioembolic ischemic stroke and reversible cerebral vasospasms. A 26-year-old G1P1 caucasian woman presented to the emergency department 10 days after a spontaneous vaginal delivery with the clinical and physical presentation of acute heart failure. Brain natriuretic peptide (BNP) level was >8000 pgmL. Transthoracic echocardiogram (TTE) demonstrated global left ventricular hypokinesis, reduced ejection fraction (EF) 22% with grade I diastolic dysfunction and apical thrombus. On hospital day two of her heart failure exacerbation admission, a code stroke was activated for aphasia and confusion. She received an IV tissue plasminogen activator (tPA) and underwent a mechanical thrombectomy. On hospital day three, she developed worsening of neurological symptoms, and a computed tomography (CT) angiogram revealed vasospasm in the region of the left middle cerebral artery (MCA), which subsequently resulted in nimodipine therapy. Furthermore, her hospital course was complicated by persistent hypotension, and with our concern for vasospasm that was noted in the CT angiogram instead of guideline-directed therapy for heart failure, digoxin was given to control heart rate and to improve cardiac output. Ultimately, her neurological symptoms improved, and she was discharged on hospital day 10. This case highlights the combination of rare presentations - postpartum cardiomyopathy, ischemic stroke, and reversible cerebral vasospasms, which suggests that the time and size of the stroke are of the essence in terms of promptness of aggressive treatment.

Isolated Medial Rectus Palsy in a Patient After Percutaneous Transluminal Coronary Angioplasty.

Diplopia, a very common ophthalmic complaint, is a potential first sign of severe pathology. Here, we present a case of an atypical midbrain infarction targeting the lateral subnucleus of the oculomotor nuclear complex that manifested as diplopia with no additional symptoms of a stroke episode. Axial diffusion-weighted and coronal T2-weighted magnetic resonance imaging showed an infarct in the rostral midbrain affecting the subnucleus of the medial rectus located ventrally. Diffusion-weighted imaging was used to diagnose the medial rectus nucleus infarct.

Oculomotor Nerve Palsy as a Manifestation of Immune Thrombocytopenic Purpura A Case Report.

Immune thrombocytopenic purpura (ITP) is caused by alterations in the immune system resulting in platelet destruction. It often manifests clinically with bleeding or on routine lab work revealing thrombocytopenia in asymptomatic individuals. Neurologic manifestations of this condition are sparsely documented in the literature. Among the symptoms reported were case reports of ischemic strokes, transient ischemic attacks, mononeuropathy multiplex, and polyneuropathy as neurological complications from immune thrombocytopenic purpura. Isolated cranial nerve palsies are uncommon. The following case describes a patient with immune thrombocytopenic purpura who presented with an isolated cranial nerve III palsy. A 55-year-old presented with pain in the right eye that was found in a downward and lateral gaze paralysis. There was no evidence of central or peripheral neurovascular etiology on imaging. However, workup revealed isolated thrombocytopenia with platelets <2000ml

Balloon-Expandable TAVR Bioprostheses Area or Perimeter Sizing A Prospective Pilot Study.

In TAVR, area sizing is used for balloon-expandable (BE) valves, whereas self-expanding valves are sized to annulus perimeter. For BE valves, this seems illogical these frames force a circular shape even on an ellipsoid annulus. This can potentially lead to relative undersizing when area sizing is being applied. We developed a perimeter-based sizing algorithm to evaluate the safety and feasibility of perimeter sizing for the Myval BE valve. In this prospective single-center study, 60 patients with severe aortic stenosis treated with the Myval BE valve were included. Perimeter sizing was used with limited oversizing of 3.7% ± 1.3% compared to the annulus perimeter. After TAVR, clinical outcomes were evaluated at 30 days and 1 year. An echocardiographic follow-up took place at 30 days. At 30 days, the need for PPI and stroke occurred in 2% and 3% of the patients, respectively. Moreover, cardiac death and moderate-severe PVL were absent. At 1-year, cardiac death and stroke were observed in 3% and 8% of the patients, respectively. In 33.3% of the patients, a larger valve size was implanted compared to the valve size calculated by area sizing. Perimeter sizing with the Myval BE valve leads to substantial use of larger valve sizes and favorable clinical outcomes, with low PPI and the absence of significant PVL. A randomized controlled trial is being planned to prove the superiority of this alternative sizing method.

Imaging of hypochlorous acid in mitochondria using an asymmetric near-infrared fluorescent probe with large Stokes shift.

Small-molecule near-infrared (NIR) imaging facilitates deep tissue penetration, low autofluorescence, non-invasive visualization, and a relatively simple operation. As such it has emerged as a popular technique for tracking biological species and events. However, the small Stokes shift of most NIR dyes often results in a low signal-to-noise ratio and self-quenching due to crosstalk between the excitation and emission spectra. With this research, we developed a NIR-based fluorescent probe WD-HOCl for hypochlorous acid (HOCl) detection using the NIR dye TJ730 as the fluorophore, which exhibits a large Stokes shift of 156 nm, with no crosstalk between the excitation and emission spectra. It contains acyl hydrazide as the responsive group and a pyridinium cation as the mitochondria-targeting group. The fluorescence intensity of WD-HOCl was enhanced by 30.1-fold after reacting with HOCl. Imaging studies performed using BV-2 cells indicated that WD-HOCl could be used for endogenous HOCl detection and imaging in living cells exposed to glucose and oxygen deprivationreperfusion. Finally, we demonstrated that inhibiting the expression of NOX2 reduced the HOCl levels and the severity of oxidative stress during stroke in a mouse model.

Systemic sclerosis with cerebral infarction and severe stenosis of internal carotid artery and coronary artery A case report.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microangiopathy, extensive fibrosis and autoantibody production. It is generally believed that microvascular disease is the hallmark of SSc. Macrovascular involvement is not initially considered as a feature of SSc, but its mortality is high, which should not be ignored. Up to the present, SSc patients with cerebral involvement and multiple macrovascular stenosis have been rarely described. We herein report a case of cerebral infarction and severe stenosis of the internal carotid artery and coronary artery associated with SSc.

Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.

The unique environment of the brain and retina is tightly regulated by blood-brain barrier and the blood-retinal barrier, respectively, to ensure proper neuronal function. Endothelial cells within these tissues possess distinct properties that allow for controlled passage of solutes and fluids. Pericytes, glia cells and neurons signal to endothelial cells (ECs) to form and maintain the barriers and control blood flow, helping to create the neurovascular unit. This barrier is lost in a wide range of diseases affecting the central nervous system (CNS) and retina such as brain tumors, stroke, dementia, and in the eye, diabetic retinopathy, retinal vein occlusions and age-related macular degeneration to name prominent examples. Recent studies directly link barrier changes to promotion of disease pathology and degradation of neuronal function. Understanding how these barriers form and how to restore these barriers in disease provides an important point for therapeutic intervention. This review aims to describe the fundamentals of the blood-tissue barriers of the CNS and how the use of transgenic animal models led to our current understanding of the molecular framework of these barriers. The review also highlights examples of targeting barrier properties to protect neuronal function in disease states.

The presence and impact of multimorbidity clusters on adverse outcomes across the spectrum of kidney function.

Multimorbidity (the presence of two or more chronic conditions) is common amongst people with chronic kidney disease, but it is unclear which conditions cluster together and if this changes as kidney function declines. We explored which clusters of conditions are associated with different estimated glomerular filtration rates (eGFRs) and studied associations between these clusters and adverse outcomes. Two population-based cohort studies were used the Stockholm Creatinine Measurements project (SCREAM, Sweden, 2006-2018) and the Secure Anonymised Information Linkage Databank (SAIL, Wales, 2006-2021). We studied participants in SCREAM (404,681 adults) and SAIL (533,362) whose eGFR declined lower than thresholds (90, 75, 60, 45, 30 and 15 mLmin1.73m Chronic conditions became more common and clustered differently across lower eGFR categories. At eGFR 90, 75, and 60 mLmin1.73m Patterns of multimorbidity and corresponding risk of adverse outcomes varied with declining eGFR. While diabetes and cardiovascular disease are known high-risk conditions, chronic pain and depression emerged as important conditions and associated with adverse outcomes when combined with physical conditions.

Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery.

The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) andor left ventricular ejection fraction (LVEF) decrease. We retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes. 300 patients were enrolled 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death andor PMI whereas they were associated with LVEF decrease ≥ 10% (p value < 0.005 at any time interval), in particular hs-cTn I values at 9-12 h post-operatively. A hs-cTn I cutoff of 5556 ngL, a value 281 (for males) and 479 (for females) times higher than the URL, at 9-12 h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%. Hs-cTn I at 9-12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.

Clinical profiles, comorbidities, and treatment outcomes of stroke in the medical ward of Dessie comprehensive specialized hospital, Northeast Ethiopia a retrospective study.

Undoubtedly, stroke is expanding as a global public health issue. Stroke-related deaths are attributable to modifiable risk factors. A demographic shift in Ethiopia increased the prevalence of stroke risk factors. Furthermore, there is limited relevant information available about stroke. Therefore, the current study sought to evaluate the clinical profiles, comorbidities, and treatment outcomes of stroke in the medical ward of Dessie comprehensive specialized hospital. A retrospective cross-sectional study design was employed among stroke patients. The study included medical records with complete patient information and a stroke diagnosis that had been verified using imaging techniques. Using simple random sampling, 344 medical records were selected, 312 of which met the requirements for inclusion. The frequency and percentage of sociodemographic characteristics and other variables were described using descriptive statistics. The patients were 59.2 ± 14.6 years old on average. About 14.7% of the study participants were chat chewers. Of stroke victims, about 52.2% had sensory loss and limb weakness. Nearly 44.9% of the patients had hemiplegia or hemiparesis when they were first seen, and 25.3% were unconscious. Hypertension (63.1%), atrial fibrillation (15.1%), and structural heart diseases (12.5%) were the frequently seen co-morbidities in stroke patients. About 35.8% of the patients had fully recovered and were released go from the hospital without suffering any repercussions. However, hospital deaths from stroke accounted for 21.8% of cases. Stroke fatalities usually involved hypertension, atrial fibrillation, and structural heart disorders. Sensory deficits, limb weakness, and mentation loss were all common clinical presentations in stroke patients. In particular, hypertension, atrial fibrillation, and structural heart diseases were commonly seen as comorbidities in stroke patients. Stroke mortality was high in the hospital. Thus, establishing promotive, preventive, curative, and rehabilitative strategies is indispensable.

Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease.

Peripheral artery disease (PAD) patients have an increased cardiovascular risk despite pharmacological treatment strategies. Biomarker research improving risk stratification only focused on known atherothrombotic pathways, but unexplored pathways might play more important roles. To explore the association between a broad cardiovascular biomarker set and cardiovascular risk in PAD. 120 PAD outpatients were enrolled in this observational cohort study. Patients were followed for one year in which the composite endpoint (myocardial infarction, coronary revascularization, stroke, acute limb ischemia and mortality) was assessed. Patient data and blood samples were collected upon inclusion, and citrated platelet-poor plasma was used to analyze 184 biomarkers in Olink Cardiovascular panel II and III using a proximity extension assay. Fifteen patients reached the composite endpoint. These patients had more prior strokes and higher serum creatinine levels. Multivariate analysis revealed increased plasma levels of protease-activated receptor 1 (PAR1), galectin-9 (Gal-9), tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) and interleukin 6 (IL-6) to be most predictive for cardiovascular events and mortality. Positive regulation of acute inflammatory responses and leukocyte chemotaxis were identified as involved biological processes. This study identified IL-6, PAR1, Gal-9, TNFRSF11A as potent predictors for cardiovascular events and mortality in PAD, and potential drug development targets.

Prognostic value of right ventricular strain and peak oxygen consumption in heart failure with reduced ejection fraction.

Our purpose is to evaluate the combined predictive value of cardiopulmonary exercise testing (CPET) and echocardiographic evidence of left ventricular (LV) and right ventricular (RV) strain in predicting mortality and heart transplant (HTx) in a series of outpatients with heart failure with reduced ejection fraction (HFrEF). A retrospective cohort study of 66 patients with HFrEF (median age, 57 years 51% women) who underwent CPET and echocardiography (up to 90 days apart) to assess prognosis. The primary outcome was a composite of death and need for HTx. At a median follow-up of 27 20-39 months, 19 patients (29%) experienced the primary outcome. In unadjusted analysis, most echocardiographic and CPET parameters were associated with the primary outcome, including percentage of predicted peak oxygen consumption (ppVO

Therapeutic plasma exchange in multiple sclerosis patients with an aggressive relapse an observational analysis in a high-volume center.

An evidence-based treatment for a Multiple Sclerosis (MS) relapse is an intravenous administration of 3-5 g of Methylprednisolone. In case of insufficient effect or corticosteroids intolerance, the therapeutic plasma exchange (TPE) is indicated. To assess the clinical effect of TPE in treatment of relapse in patients with relapsing-remitting MS (RRMS), we enrolled 155 patients meeting the following criteria (study period January 2011 to February 2021) (1) age > 18, (2) RRMS according to the McDonald´s 2017 criteria, (3) MS relapse and insufficient effect of corticosteroidscorticosteroids intolerance, (4) baseline EDSS < 8. Exclusion criteria (1) progressive form of disease, (2) history of previous TPE. Following parameters were monitored EDSS changes (before and after corticosteroid treatment, before and after TPE EDSS after TPE was assessed at the next clinical follow-up at the MS Center), and improvement of EDSS according to the number of procedures and baseline severity of relapse. 115 females (74%) and 40 males (26%) were included. The median age was 41 years (IQR 33-47)-131 patients underwent the pulse corticosteroids treatment and TPE, while 24 patients underwent only TPE without any previous corticosteroid treatment. Median baseline EDSS was 4.5 (IQR 3.5-5.5), median EDSS after finishing steroids was 4.5 (IQR 4.0-5.5). EDSS prior to the TPE was 4.5 (IQR 4-6), EDSS after TPE was 4.5 (IQR 3.5-5.5). We observed a significant improvement in the EDSS after TPE (p < 0.001). Sex differences were seen in TPE effectiveness, with median improvement of EDSS in females being -0.5 (IQR 1-0) and in males being 0 (IQR -0.5 to 0), p 0.048. There was no difference in EDSS improvement by age category 18-30 years, 31-40 years, 41-50 years, > 50 (p 0.94), nor by total TPE count (p 0.91). In this retrospective study of patients with an aggressive relapse and insufficient effect of intravenous corticosteroid treatment, a significant effect of TPE on EDSS improvement was observed. There was no significant difference in TPE effectivity according to the number of procedures, age, nor severity of a relapse. In this cohort, TPE was more effective in females.

The Effects of Trunk and Extremity Functions on Activities of Daily Living, Balance, and Gait in Stroke.

The primary aim is to investigate the effect of the trunk, upper extremity, and lower extremity functions on activities of daily living (ADL), balance, and gait. The second aim is to investigate the effect of trunk position sense on trunk control. Thirty-six patients with chronic stroke were included in the study. The Trunk Impairment Scale (TIS), Barthel Index (BI), Berg Balance Scale (BBS), and 2-minute walking test (2MWT) were used for the assessment of trunk function, ADL, balance, and gait respectively. The Stroke Rehabilitation Assessment of Movement upper extremity (STREAM-UE) and lower extremity (STREAM-LE) sub-scales were used to evaluate extremity functions. The trunk position sense was measured with a digital inclinometer. The mean age of the participants was 58.8 ± 12.6 years. In multiple regression analysis, TIS values were found to have a positive effect on BI and BBS (p < 0.05), and STREAM-LE values have a positive effect on BBS and 2MWT (p < 0.05). STREAM-UE values were no significant effect on BI, BBS, or 2MWT (p > 0.05). Trunk position sense was found to have a positive effect on TIS (p < 0.05). The results of this study showed that trunk functions are more related to ADL and balance than extremity functions. Therefore, trunk training should be included as a basic application in physiotherapy programs for stroke patients.

Use of fish oil and mortality of patients with cardiometabolic multimorbidity A prospective study of UK biobank.

Cardiometabolic multimorbidity (CMM) has risen as a global issue of public health, with an in-creasing prevalence and more severe clinical prognosis. This study aimed to estimate the association between use of fish oil and mortality among patients with CMM. In this prospective study based on UK Biobank, participants with ≥2 of cardiometabolic diseases (CMDs, including coronary heart disease CHD, diabetes, hypertension, and stroke in this study) at recruitment were included. Use of fish oil was derived from touchscreen questionnaires at baseline. All-cause and cardiovascular mortality were accessed via electronic health-related records. Kaplan-Meier curves and flexible parametric Royston-Parmar proportion-hazard models were fitted to assess the as-sociations of fish-oil use with all-cause, cardiovascular mortality, and related life expectancy alterations. Among 30 068 participants from UK Biobank (67.9% men mean age 61.75 years), 5357 deaths were reported during 12.03 years of follow-up. For patients with CMM, use of fish oil was associated with a 17% lower risk of all-cause mortality (95% confidence interval 95% CI 0.78-0.88, P < 0.001), and 19% lower risk of cardiovascular mortality (95% CI 0.72-0.90, P < 0.001) in multivariable-adjusted models. At 45 years old, using fish oil was associated with 1.66 years of life expectancy gained. Among patients with CMM, use of fish oil was associated with a significantly reduced risk of all-cause, cardiovascular mortality, and prolonged life expectancy.

Status and transition of normal-weight central obesity and the risk of cardiovascular diseases A population-based cohort study in China.

Cardiovascular disease (CVD) has become a growing public health concern. Normal weight central obesity (NWCO) has emerged as a potential risk factor for cardiometabolic dysregulation. To date, the association between NWCO and new-onset CVDs remains unclear. We aimed to evaluate the associations of NWCO and its longitudinal transitions with cardiovascular risks in middle-aged and older Chinese. Data were from the China Health and Retirement Longitudinal Study 2011-2018. NWCO was defined as the combination of a body mass index (BMI) of <24.0 kgm NWCO and transition from NWNCO to NWCO are associated with higher risks of CVDs. Identification and prevention of NWCO may be useful in the management of CVDs.

Hand robotic devices in neurorehabilitation A systematic review on the feasibility and effectiveness of stroke rehabilitation.

Robot-assisted therapy is a relatively new intervention, increasingly used in the rehabilitation treatment of stroke patients. It allows to increase the number of repetitions in the performance of specific tasks movements. For this review, a search was carried out between August and October 2021 in the PubMed, Web of Science, Scopus, Cochrane, PEDro and OTseeker databases, selecting a total of six randomized controlled trials where robot-assisted hand therapy was used in stroke rehabilitation. Studies agree that robot-assisted hand therapy has benefits in all phases of stroke rehabilitation that translate into motor and functional improvements of the upper limb and improvements in hemispatial neglect.

Design and optimization of two-degree-of-freedom parallel four pure-slide- and four parallel quadrilateral-pair precision positioning platform.

Aiming at the complex structure, small output displacement, and low positioning accuracy of the two-degree-of-freedom (2-DOF) precision positioning platform, theoretical analyses and experimental tests are carried out so that the platform has the characteristics of compact structure, large output stroke, and high positioning accuracy. First, to optimize the structural parameters of the positioning platform, a modeling method to improve the modeling accuracy of the compliant mechanism of the positioning platform is proposed. A static model of the positioning platform based on Euler-Bernoulli beam theory and the sixth-order compliance matrix method is established, and the accuracy of the model is verified by simulation. In addition, the single-objective genetic optimization algorithm is used to optimize the structural size parameters of the positioning platform, and the optimal solution set of the structural size parameters of the positioning platform is obtained by taking the displacement amplification rate of the positioning platform as the optimization target. Finally, according to theoretical and simulation analysis and optimization results, an experimental prototype was fabricated, and a series of experimental tests were carried out on the working stroke, displacement magnification, and output stiffness. The experimental results show that the displacement magnification of the positioning platform reaches 3.39, the positioning stroke is 89.2 × 85.9 µm

A novel two-degrees of freedom (2-DOF) piezo-driven positioning platform with the working stroke being over 20 cm.

Multi-degrees of freedom piezo-driven precision positioning platforms with large working strokes are demanded in many research fields. Although many multi-degrees of freedom piezo-driven positioning platforms have been proposed, few of them can achieve both large working stroke and high speed, which hinders their applications. In this study, a two-degrees of freedom piezo-driven positioning platform was proposed by stacking two identical stick-slip piezoelectric actuators. To simplify the practical implementation of a large working stroke, the actuator employed a special structure, in which the compliant mechanism and the slider were connected together as a mover and the guide rail was fixed as a stator. The working stroke of the actuator can be increased easily by increasing only the length of the guide rail without changing the output performances. By designing a lever-type compliant mechanism (LCM) on the side surface of the slider, a large loading space was obtained. Theoretical calculation and finite element analysis of the LCM were performed in detail. As the structures of these two stick-slip piezoelectric actuators are the same, only the output performances of the upper actuator (x direction) were tested as an example. Experimental results indicated that the upper actuator had a stable bi-direction motion with a working stroke being over 20 cm. The maximum speeds along the positive x and negative x directions reached 17.864 and 18.73 mms, and the resolutions were 100 and 230 nm, respectively. Furthermore, the vertical loading capacity was larger than 60 N.

Thrombus migration in ischemic stroke due to large vessel occlusion a question of time.

Thrombus migration (TM) is frequently observed in large vessel occlusion (LVO) ischemic stroke to be treated by endovascular thrombectomy (EVT). TM may impede complete recanalization and hereby worsen clinical outcomes. This study aimed to delineate factors associated with TM and clarify its impact on technical and functional outcome. All patients undergoing EVT due to LVO in the anterior circulation at two tertiary stroke centers between October 2015 and December 2020 were included. Source imaging data of all individuals were assessed regarding occurrence of TM by raters blinded to clinical data. Patient data were gathered as part of the German Stroke Registry, a multicenter, prospective registry assessing real-world outcomes. Technical outcome was assessed by modified Thrombolysis in Cerebral Infarction scale (mTICI). Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. The study consisted of 512 individuals, of which 71 (13.8%) displayed TM. In adjusted analyses, TM was associated with longer time from primary imaging to reassessment in the angio suite (aOR 2.37 (1.47 to 3.84) per logarithmic step) and intravenous thrombolysis (IVT aOR 4.07 (2.17 to 7.65)). In individuals with IVT, a needle-to-groin time >1 hour was associated with higher odds for TM (aOR 2.60 (1.20 to 5.99)). TM was associated with lack of complete recanalization (aOR TM is associated with IVT and longer time between sequential assessments of thrombus location. Consequently, TM may be of high relevance in patients with drip-and-ship treatment.

Readmission Risk after COVID-19 Hospitalization A Moderation Analysis by Vital Signs.

Readmission to the hospital after hospitalization with coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality. Hospital clinicians may identify the presence of a patients comorbid conditions, overall severity of illness, and clinical status at discharge as risk factors for readmission. Objective data are lacking to support reliance on these factors for discharge decision making. The objective of our study was to examine risk factors for readmission to the hospital after COVID-19 hospitalization and the impact of vital sign abnormalities, within 24 hours of discharge, on readmission rates. In total, 2557 COVID-19-related hospital admissions within the Lifespan Health System, a large multicenter health system (Rhode Island), of 2230 unique patients aged 18 years and older, occurring from April 1, 2020 to December 31, 2020 were analyzed. Risk factors associated with readmission within 30 days were identified and analyzed using Cox regression. A moderation analysis by vital signs at discharge on the risk of readmission was performed. Clinical factors associated with readmissions included existing cardiovascular conditions (risk ratio 2.32, 95% confidence interval CI 1.10-4.90) and pulmonary disease (risk ratio 3.25, 95% CI 1.62-6.52). The absence of abnormal vital signs within 24 hours of discharge was associated with decreased 30-day readmission rates (risk ratio 0.70, 95% CI 0.52-0.94). Elevated C-reactive protein and d-dimer values and in-hospital complications including stroke, myocardial infarction, acute renal failure, and gastrointestinal bleeding were not associated with an increased risk of readmission. In moderation analysis, the presence of normal vital signs within 24 hours of discharge was associated with decreased readmission risk in patients who had primary risk factors for readmission including pulmonary disease (risk ratio 0.80, 95% CI 0.65-0.99), psychiatric disorders, and substance use (risk ratio 0.70, 95% CI 0.52-0.94). Comorbid conditions, including pulmonary and cardiovascular disease, are associated with readmission risk after COVID-19 hospitalization. The normalization of vital signs within 24 hours of discharge during COVID-19 hospitalization may be an indicator of readiness for discharge and may mitigate some readmission risk conferred by comorbid conditions.

Multiparametric Neuroimaging and Its Association with Non-Contrast Computed Tomography in Late-Window Large Vessel Occlusion Acute Stroke.

Endovascular treatment (EVT) for acute ischemic stroke (AIS) between 6 and 24 h is established as a standard of care among patients selected by multiparametric neuroimaging. We aimed to explore neuroimaging parameters in late-window large vessel occlusion (LVO) patients and its association with non-contrast computed tomography (NCCT) findings. We included consecutive AIS patients within 6-24 h from the symptoms onset with LVO. We described multiparametric imaging findings, the rate of patients who fulfilled imaging perfusion criteria according to the DAWN and DEFUSE-3 trials that define the computed tomography perfusion mismatch (CTP-MM) group and its association with NCCT focused on Alberta Stroke Program Early CT Score (ASPECTS). We also analyzed the association between neuroimaging parameters and the clinical outcome determined by the 90-day modified Rankin scale (mRS). We included 206 patients, of them, 176 (85.4%) presented CTP-MM and 184 (89.3%) presented an ASPECTS ≥6 on admission. The rate of CTP-MM was 90.8% in patients with ASPECTS ≥6, compared with 40.9% in those with low ASPECTS. ASPECTS was moderately correlated with ischemic core determined by cerebral blood flow <30% volume (rS -0.557, p < 0.001). In EVT-treated patients (185, 89.8%), after adjusting for identifiable confounders, the presence of CTP-MM was a predictor of 90-day functional independence (OR 3.38 95% CI 1.01-11.29 p 0.048). We did not find an association between CTP-MM and 90-day functional disability (ordinal mRS shift, aOR 1.39 95% CI 0.58-3.34 p 0.459). A great majority of patients who presented a LVO in the late window fulfilled guidelines imaging criteria to undergo EVT, especially those with high ASPECTS (≥6). Our data suggest that NCCT with CT angiography could be a reasonable approach for AIS treatment selection also in the late window.

Predictive Value of Pediatric Stroke Diagnoses in Administrative Data A Systematic Literature Review.

Administrative healthcare data are frequently used for studying incidence, prevalence, risk factors, and outcome of pediatric stroke. However, the accuracy of these data sources is uncertain. The aim of this study was to systematically analyze published data on the positive predictive value (PPV) and sensitivity of diagnoses used to identify pediatric stroke patients in administrative data. This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed and Embase for studies, published in year 2000 or later, describing the PPV or sensitivity of diagnoses used to identify children with stroke in administrative data. The search was performed on June 9, 2022. Studies written in other languages than English, with less than 30 participants, and conference abstracts were excluded. Eight studies were included after full-text review from 2,475 potentially eligible records. These included 3,137 children. All studies reported data from high-income countries. Reported PPVs varied considerably across studies and stroke subtypes acute ischemic stroke, range 0.27-0.89 cerebral venous thrombosis, range 0.45-0.72 spontaneous subarachnoid hemorrhage, range 0.52-0.83 and spontaneous intracerebral hemorrhage, range 0.62-0.66. One study examined sensitivity of an ICD-9 search compared to a radiology report search and found that the ICD search had poor sensitivity (33%). Caution is recommended in the use and interpretation of nonvalidated administrative data for pediatric stroke. Data on the PPV and sensitivity of pediatric stroke diagnoses in administrative data remain limited and are only available from high-income countries.

The scale transformed power prior for use with historical data from a different outcome model.

We develop the scale transformed power prior for settings where historical and current data involve different data types, such as binary and continuous data. This situation arises often in clinical trials, for example, when historical data involve binary responses and the current data involve some other type of continuous or discrete outcome. The power prior, proposed by Ibrahim and Chen, does not address the issue of different data types. Herein, we develop a new type of power prior, which we call the scale transformed power prior (straPP). The straPP is constructed by transforming the power prior for the historical data by rescaling the parameter using a function of the Fisher information matrices for the historical and current data models, thereby shifting the scale of the parameter vector from that of the historical to that of the current data. Examples are presented to motivate the need for such a transformation, and simulation studies are presented to illustrate the performance advantages of the straPP over the power prior and other informative and noninformative priors. A real dataset from a clinical trial undertaken to study a novel transitional care model for stroke survivors is used to illustrate the methodology.

USE OF Β-ADRENOBLOCKERS IN PATIENTS WITH HEART FAILURE AND CONCOMITANT THYROID PATHOLOGY (LITERATURE REVIEW AND OWN OBSERVATIONS).

The systematization of literature data on the use of β-adrenoblockers in patients with heart failure and concomitant thyroid pathology was carried out, and the results of our own study were presented. It has been suggested that the final chapter in the history of the use of β-adrenoblockers in patients with heart failure with reduced left ventricular ejection fraction and thyroid pathology has not yet been written. Further studies are needed, including pharmacogenetic ones. The use of a selective β-adrenoblockers - bisoprolol in patients with chronic heart failure with reduced left ventricular ejection fraction and concomitant low triiodothyronine syndrome does not lead to a decrease in the frequency of rehospitalization due to decompensation. At the same time, the frequency of rehospitalization in the group of patients with heart failure without low triiodothyronine syndrome is higher at a dose of 1.25-5.0 mg of bisoprolol compared with a higher dose. The effect of bisoprolol is reversed in patients with low triiodothyronine syndrome the risk of re-hospitalization increases when the dose of bisoprolol is exceeded, there is a decrease in the serum level of triiodothyronine, an increase in thyroxine levels, a decrease in the ratio of triiodothyronine thyroxine further increase in the cavities of the heart and decrease in size. Probably, in patients with heart failure, against the background of low triiodothyronine syndrome, it is not advisable to titrate the dose of bisoprolol above 5 mg, and the time to titrate the drug to the indicated dose should be more than 63 days. Today it can be argued that, in general, recommendations for the use β-adrenoblockers in patients with chronic heart failure with reduced left ventricular ejection fraction apply to patients with concomitant thyroid dysfunction, subject to the above restrictions.

Sleep and wake cycles dynamically modulate hippocampal inhibitory synaptic plasticity.

Sleep is an essential process that consolidates memories by modulating synapses through poorly understood mechanisms. Here, we report that GABAergic synapses in hippocampal CA1 pyramidal neurons undergo daily rhythmic alterations. Specifically, wake inhibits phasic inhibition, whereas it promotes tonic inhibition compared to sleep. We further utilize a model of chemically induced inhibitory long-term potentiation (iLTP) to examine inhibitory plasticity. Intriguingly, while CA1 pyramidal neurons in both wake and sleep mice undergo iLTP, wake mice have a much higher magnitude. We also employ optogenetics and observe that inhibitory inputs from parvalbumin-, but not somatostatin-, expressing interneurons contribute to dynamic iLTP during sleep and wake. Finally, we demonstrate that synaptic insertion of α5-GABAA receptors underlies the wake-specific enhancement of iLTP at parvalbumin-synapses, which is independent of time of the day. These data reveal a previously unappreciated daily oscillation of inhibitory LTP in hippocampal neurons and uncover a dynamic contribution of inhibitory synapses in memory mechanisms across sleep and wake.

Usage of RePlay as a Take-Home System to Support High-Repetition Motor Rehabilitation After Neurological Injury.

Stroke is a leading cause of chronic motor disability. While physical rehabilitation can promote functional recovery, several barriers prevent patients from receiving optimal rehabilitative care. Easy access to at-home rehabilitative tools could increase patients ability to participate in rehabilitative exercises, which may lead to improved outcomes. Toward achieving this goal, we developed RePlay a novel system that facilitates unsupervised rehabilitative exercises at home. RePlay leverages available consumer technology to provide a simple tool that allows users to perform common rehabilitative exercises in a gameplay environment. RePlay collects quantitative time series force and movement data from handheld devices, which provide therapists the ability to quantify gains and individualize rehabilitative regimens. RePlay was developed in C using Visual Studio. In this feasibility study, we assessed whether participants with neurological injury are capable of using the RePlay system in both a supervised in-office setting and an unsupervised at-home setting, and we assessed their adherence to the unsupervised at-home rehabilitation assignment. All participants were assigned a set of 18 games and exercises to play each day. Participants produced on average 698 ± 36 discrete movements during the initial 1 hour in-office visit. A subset of participants who used the system at home produced 1593 ± 197 discrete movements per day. Participants demonstrated a high degree of engagement while using the system at home, typically completing nearly double the number of assigned exercises per day. These findings indicate that the open-source RePlay system may be a feasible tool to facilitate access to rehabilitative exercises and potentially improve overall patient outcomes.

TAVR nemesis of NOACs

Data on non-vitamin K antagonist oral anticoagulants (NOACs) in transcatheter aortic valve replacement (TAVR) patients are controversial. In patients without atrial fibrillation (AF), rivaroxaban showed enhanced ischemia and bleeding as compared to standard of care. ENVISAGE showed enhanced bleeding in AF patients as compared to vitamin K antagonist (VKA). Only apixaban was non-inferior but failed superiority regarding bleeding in AF patients after TAVR. One could hypothesize that this might be due to pharmacokinetics of NOACs. Therefore, we compared outcome in rivaroxabanedoxaban (once-daily) and apixaban (twice-daily) treated patients. 568 patients with indication for permanent oral anticoagulation due to AF undergoing TAVR were analyzed via inverse probability of treatment weighting. Valve academic research consortium complications during 30-day follow-up were assessed. Bleeding complications were similar in once-daily and twice-daily NOACs (major 22 (7.5%) vs. 14 (5.3%), p 0.285 minor 66 (22.4%) vs. 46 (17.4%), p 0.133). Complications did not change when splitting the cohort in the different agents apixaban, rivaroxaban and edoxaban. These findings remained robust after multivariate analysis. In summary, twice-daily and once-daily NOACs did not differ regarding bleeding complications in a hypothesis generating real-world cohort of TAVR patients with AF.

Safety, Efficiency, and Efficacy of Protocolized Contrast-Enhanced Imaging in Acute Stroke Evaluation.

Computed tomography angiography and perfusion studies have increasingly become a part of acute stroke evaluation. However, the volume, benefit, and scope of need for imaging is sometimes debated. This study evaluated the safety, efficiency, and efficacy of changes to the acute stroke evaluation protocol at our academic institution. Previously, contrast-enhanced imaging was opt-in and ordered upon suspicion of large vessel occlusion. This was subsequently transitioned to one where contrast-enhanced imaging was automatically ordered for all patients with opt-out of imaging if felt appropriate. We performed a retrospective, case-control study that included patients evaluated for acute stroke management before and after the protocol change. Six hundred forty-seven patients met criteria for study involvement, of which 258 were in the preprotocol and 389 in the postprotocol group. There was no significant difference in rate of acute kidney injury and no delay in door-to-needle time. There was significant improvement in door-to-groin puncture times (49.9 minutes) for typical cases and increase in monthly rate of endovascular therapy (EVT). Protocolization of contrast-enhanced imaging for acute stroke evaluation proved safe with respect to renal function, did not delay door-to-needle time, improved door-to-groin puncture time, and lead to higher rates of EVT.