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The relationship between the differential protective effect of salt substitute between hypertensive and normotensive individuals and the use of cardiovascular medications remains unclear. This study involved 4211 individuals with a history of stroke or hypertension who participated in the Salt Substitute and Stroke Study (SSaSS) from 120 villages in Shanxi Province. The aim of this study was to investigate the differences in major adverse cardiovascular events and blood pressure changes between the salt substitute and the regular salt group in the subgroups of participants taking different antihypertensive medications. Mixed models were employed and adjusted for the cluster effect (village) and potential confounding variables. During the average follow-up period of 4.66 years, a significantly protective effect of salt substitute on reducing the risk of cardiovascular events was observed in the participants who taking antihypertensive medications (rate ratio: 0.81, 95% CI: 0.68 to 0.95. p = 0.011), whereas no significant effect in participants not taking antihypertensive medications (rate ratio: 0.91, 95% CI: 0.62 to 1.32, p = 0.612). Significant effects to lower systolic blood pressure of the salt substitutes were observed in the participants who took different antihypertensive medications. This study emphasized that the use of salt substitutes might enhance the efficacy of anti-hypertensive medications in lowering blood pressure and reducing the risk of adverse cardiovascular events., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The SSaSS (Salt Substitute and Stroke Study) has shown that use of a potassium-enriched salt lowers the risk of stroke, total cardiovascular events, and premature death. The effects on cause-specific cardiac outcomes are reported here., Methods: SSaSS was an unblinded, cluster-randomised trial assessing the effects of potassium-enriched salt compared with regular salt among 20 995 Chinese adults with established stroke and older age and uncontrolled hypertension. Post hoc efficacy analyses were performed using an intention-to-treat method and a hierarchical Poisson regression model adjusting for clustering to obtain rate ratios and 95% CIs. We assessed acute coronary syndrome, heart failure, arrhythmia, and sudden death., Results: Over a mean 4.74 years follow-up, there were 695 acute coronary syndrome events, 454 heart failure events, 230 arrhythmia events, and 1133 sudden deaths recorded. The rates of events were lower in potassium-enriched salt group for all outcomes but CIs were wide for most: acute coronary syndrome (6.32 versus 7.65 events per 1000 person-years; rate ratio, 0.80 [95% CI, 0.65-0.99]); heart failure (9.14 versus 11.32 events per 1000 person-years; rate ratio, 0.88 [95% CI, 0.60-1.28]); arrhythmia (4.43 versus 6.20 events per 1000 person-years; rate ratio, 0.59 [95% CI, 0.35-0.98]); and sudden death (11.01 versus 11.76 events per 1000 person-years; rate ratio, 0.94 [95% CI, 0.82-1.07]; all P >0.05 with adjustment for multiple comparisons)., Conclusions: These results suggest that use of potassium-enriched salt is more likely to prevent than cause cardiac disease but the post hoc nature of these analyses precludes definitive conclusions., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02092090., Competing Interests: Disclosures The Salt Substitute and Stroke Study was funded by grants APP1164206 and APP1049417 from the National Health and Medical Research Council of Australia. Salt substitute was donated by Jiangsu Sinokone Technology Co Ltd for years 3 and 4 of the trial. The other authors report no conflicts.

The Salt Substitute and Stroke Study (SSaSS) demonstrated significant reductions in systolic blood pressure (SBP), and the risk of stroke, major cardiovascular events and total mortality with the use of potassium-enriched salt. The contribution of sodium reduction versus potassium increase to these effects is unknown. We identified four different data sources describing the association between sodium reduction, potassium supplementation and change in SBP. We then fitted a series of models to estimate the SBP reductions expected for the differences in sodium and potassium intake in SSaSS, derived from 24-h urine collections. The proportions of the SBP reduction separately attributable to sodium reduction and potassium supplementation were calculated. The observed SBP reduction in SSaSS was -3.3 mmHg with a corresponding mean 15.2 mmol reduction in 24-h sodium excretion and a mean 20.6 mmol increase in 24-h potassium excretion. Assuming 90% of dietary sodium intake and 70% of dietary potassium intake were excreted through urine, the models projected falls in SBP of between -1.67 (95% confidence interval: -4.06 to +0.73) mmHg and -5.33 (95% confidence interval: -8.58 to -2.08) mmHg. The estimated proportional contribution of sodium reduction to the SBP fall ranged between 12 and 39% for the different models fitted. Sensitivity analyses assuming different proportional urinary excretion of dietary sodium and potassium intake showed similar results. In every model, the majority of the SBP lowering effect in SSaSS was estimated to be attributable to the increase in dietary potassium rather than the fall in dietary sodium., (© 2024. The Author(s).)

The moderate formation of the fibrotic scar plays an important role in functional recovery after stroke. M2a macrophages have been identified as an important source of early fibrosis after cerebral ischemia. However, the underlying mechanisms by which macrophages interact with fibroblasts in this context remain largely unknown. Therefore, our study aimed to further investigate the potential mechanisms underlying the effects of macrophages on fibroblasts following ischemic stroke. In vitro and in vivo, recombinant rat interleukin 4 (IL4) was used to induce macrophages to polarize into M2a macrophages. In vitro, primary Sprague-Dawley newborn rat meningeal-derived fibroblasts were treated with PU.1 knockdown, the PU.1 inhibitor DB1976 or the mTOR inhibitor rapamycin, which were then co-cultured with M2a macrophage conditioned medium (MCM). In vivo, Sprague-Dawley adult rats were infected with negative control adenoviruses or PU.1-shRNA adenoviruses. Ten days after infection, an injury model of middle cerebral artery occlusion/reperfusion (MCAO/R) was constructed. Subsequently, IL4 was injected intracerebroventricularly to induce M2a macrophages polarization. In vitro, M2a MCM upregulated PU.1 expression and promoted the differentiation, proliferation, migration and extracellular matrix generation of fibroblasts, which could be reversed by treatment with the PU.1 inhibitor DB1976 or PU.1 knockdown. In vivo, PU.1 expression in fibroblasts was increased within ischemic core following MCAO/R, and this upregulation was further enhanced by exposure to IL4. Treatment with IL4 promoted fibrosis, increased angiogenesis, reduced apoptosis and infarct volume, as well as mitigated neurological deficits after MCAO/R, and these effects could be reversed by PU.1 knockdown. Furthermore, both in vivo and in vitro studies showed that IL4 treatment increased the levels of phosphorylated Akt and mTOR proteins, which were markedly decreased by PU.1 knockdown. Additionally, the use of an mTOR inhibitor rapamycin obviously suppressed the migration and differentiation of fibroblasts, and Col1 synthesis. In conclusion, our findings suggest for the first time that M2a macrophages, at least in part, regulate fibrosis and affect the outcome after cerebral ischemic stroke via the PU.1/mTOR signaling pathway in fibroblasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Stroke stands as the second leading cause of death worldwide. Currently, extensive research has been conducted on stroke risk factors. However, when stroke patients contend with multiple risk factors, the impact on clinical indicators remains uncertain., Objectives: This study seeks to investigate potential significant variations among distinct ranges of clinical indicators in instances where stroke patients experience multiple risk factors and various ischemic stroke subtypes., Material and Methods: The research encompassed 440 stroke patients admitted to the First People's Hospital of Wenling City, Zhejiang Province, China. These patients were classified based on the type and quantity of risk factors and subtypes of ischemic stroke they presented. The χ 2 test was employed to assess the relationship between the risk of comorbid diseases and clinical indicators in stroke patients., Results: The results of our study have underscored a significant correlation between various comorbid risk factors in stroke patients and the patients' age (P < 0.010). Furthermore, we observed noteworthy disparities in the plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ between patients devoid of risk factors and those presenting with comorbid risk factors associated with stroke. Significant differences in INF-γ were observed between the two subtypes of ischemic stroke, namely lacunar infarction and cardioembolic stroke., Conclusion: Age is correlated with an elevated risk of stroke. Individuals exhibiting multiple stroke risk factors and diverse ischemic stroke subtypes commonly present with abnormal lipid levels and imbalances in Th1/Th2 cytokines. These factors significantly contribute to the onset and progression of stroke. Furthermore, inflammatory responses, particularly those induced by atherosclerosis, play a pivotal role in the genesis of stroke and exert a substantial influence on its prognosis., (© 2024. The Author(s).)

Objectives: To investigate the relationship between the number of valvular insufficiency (VI) and emergency hospitalization or mortality in maintenance hemodialysis (HD) patients., Methods: The maintenance HD patients with cardiac ultrasonography were included. According to the number of VI ≥ 2 or not, the patients were divided into two groups. The difference of emergency hospitalized for acute heart failure, arrhythmia, acute coronary syndrome (ACS) or stroke, cardiovascular mortality, and all-cause mortality between the two groups were compared., Results: Among 217 maintenance HD patients, 81.57% had VI. 121 (55.76%) patients had two or more VI, and 96 (44.24%) with one VI or not. The study subjects were followed up for a median of 47 (3-107) months. At the end of the follow up, 95 patients died (43.78%), of whom 47 (21.66%) patients died because of cardiovascular disease. Age (HR 1.033, 95% CI 1.007-1.061, P = 0.013), number of VI ≥ 2 (HR 2.035, 95% CI 1.083-3.821, P = 0.027) and albumin (HR 0.935, 95% CI 0.881-0.992, P = 0.027) were independent risk factors for cardiovascular mortality. The three parameters were also independent risk factors for all-cause mortality. The patients with number of VI ≥ 2 were more likely to be emergency hospitalized for acute heart failure (56 [46.28%] vs 11 [11.46%], P = 0.001). On the contrary, the number of VI was not associated with emergency hospitalized for arrhythmia, ACS or stroke. Survival analysis results showed that probability of survival was statistically different in the two groups (P < 0.05), no matter based on cardiovascular mortality or all-cause mortality. Based on age, number of VI ≥ 2 and albumin, nomogram models for 5-year cardiovascular and all-cause mortality were built., Conclusions: In maintenance HD patients, the prevalence of VI is prominently high. The number of VI ≥ 2 is associated with emergency hospitalized for acute heart failure, cardiovascular and all-cause mortality. Combining age, number of VI ≥ 2, and albumin can predict cardiovascular and all-cause mortality., (© 2023. The Author(s).)

Since metabolic dysregulation is a hallmark of both stroke and Alzheimer's disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabolic networks of the these diseases is still lacking. In this study, we integrated single-cell RNA sequencing datasets of ischemic stroke (IS), hemorrhagic stroke (HS) and AD models to construct metabolic flux profiles at the single-cell level. We discovered that the three disorders cause shared metabolic shifts in endothelial cells. These altered metabolic modules were mainly enriched in the transporter-related pathways and were predicted to potentially lead to a decrease in metabolites such as pyruvate and fumarate. We further found that Lef1, Elk3 and Fosl1 may be upstream transcriptional regulators causing metabolic shifts and may be possible targets for interventions that halt the course of neurodegeneration., (© 2023. Springer Nature Limited.)

Cerebral ischemic stroke is one of the leading causes of human death. The fibrous scar is one of major factors influencing repair in central nervous system (CNS) injury. Silencing information regulator 2-related enzyme 1 (Sirt1) can regulate peripheral tissue and organ fibrosis. However, it is unclear how the fibrous scar forms and is regulated and it is unknown whether and how Sirt1 regulates the formation of the fibrous scar after cerebral ischemic stroke. Therefore, in the present study, we examined the effects of Sirt1 on the formation of the fibrotic scar after middle cerebral artery occlusion/reperfusion (MCAO/R) injury in vivo and on the transforming growth factor β1 (TGF-β1)-induced meningeal fibroblast fibrotic response in vitro, and we explored the molecular mechanisms underlying the Sirt1-regulated fibrosis process in vitro. We found that MCAO/R injury induced fibrotic scar formation in the ischemic area, which was accompanied by the downregulation of Sirt1 expression. The overexpression of Sirt1 reduced the infarct volume, improved Nissl body structure and reduced neurons injury, attenuated formation of fibrotic scar, upregulated growth associated protein43 (GAP43) and synaptophysin (SYP) expression, and promoted neurological function recovery. Similarly, Sirt1 expression was also downregulated in the TGF-β1-induced fibrosis model. Sirt1 overexpression inhibited fibroblast migration, proliferation, transdifferentiation into myofibroblasts, and secretion of extracellular matrix(ECM) by regulating the deacetylation of lysine at K49 and K120 sites of 14-3-3ζ in vitro. Therefore, we believe that Sirt1 could regulate fibrous scar formation and improve neurological function after cerebral ischemic stroke through regulating deacetylation of 14-3-3ζ., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke characterized by high mortality and morbidity rates with no effective treatment. TGF-β/ALK-5 signaling is reported to participated in the regulation of blood-brain barrier (BBB) integrity in the inflammation pain model, the effects of transforming growth factor (TGF)-β1 and the potential mechanisms on BBB after ICH have not been fully elucidated. Herein, we have demonstrated that peripheral administration of TGF-β1 reduces brain edema and ameliorated BBB injury after ICH. Consistent with previous results, TGF-β1 is shown to promote activation of anti-inflammatory microglia and reduce the inflammatory response after ICH. Furthermore, TGF-β1 administration improves long-term outcomes after ICH. Our data suggest that TGF-β1 may be a promising therapeutic agent for ICH., Competing Interests: Declarations of competing interest None, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Stroke is the leading cause of disability globally in need of novel and effective methods of rehabilitation. Intermittent theta burst stimulation (iTBS) has been adopted as a Level B recommendation for lower limb spasticity in guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Nonetheless, the methodological differences and deficits of existing work bring about heterogenous results and therefore limit the universal clinical use of rTMS in lower extremity (LE) rehabilitation. The variation of stimulated targets across motor cortex contributes mainly to these heterogeneities. This narrative review includes studies of rTMS on LE motor function rehabilitation in patients after stroke until now. Some analyses of brain imaging and electromagnetic simulation and quantification through computational modeling were also performed. rTMS appears capable of fostering LE motor rehabilitation after stroke, but the actually stimulated targets are considerably bias making it difficult to confirm effectiveness. The main reason for this phenomenon is probably inaccurate targeting of motor cortical leg representation. An underlying updated method is proposed as Individual-Target TMS (IT-TMS) combined with brain imaging. rTMS is a promising validated method for LE function regaining. Future studies should systematically compare the effects of IT-TMS with traditional rTMS using large samples in random clinical trials. This article is categorized under: Neuroscience > Clinical Neuroscience., (© 2022 The Authors. WIREs Cognitive Science published by Wiley Periodicals LLC.)

As an add-on drug approved for Parkinson's disease treatment, safinamide has multiple functions, such as selective and reversible monoamine oxidase-B inhibition, voltage-sensitive sodium/potassium channel blockage, and glutamate release inhibition. Meanwhile, safinamide shows tremendous therapeutic potential in the context of other central nervous system diseases (e. g. ischaemic stroke, amyotrophic lateral sclerosis, depression, etc.). In this work, [ 18 F]safinamide, which is safinamide labelled by the positron-emitting radionuclide [ 18 F]fluorine, was synthesized automatically based on iodonium ylide precursors with high radiochemical yield and high molar activity. Density functional theory was applied to calculate the Gibbs free energy change during iodonium ylide-mediated fluorination and to interpret the effect of tetraethylammonium (TEA + ) as the counter cation in these reactions to improve the nucleophilicity of [ 18 F/ 19 F]fluoride. In addition, positron emission tomography studies on Sprague Dawley rats were carried out to determine the imaging characteristics, pharmacokinetics, and metabolism of the [ 18 F]safinamide radiotracer. The results displayed the complete biodistribution of the radiotracer, especially in rat brains, and revealed that [ 18 F]safinamide has moderate brain uptake, rapid and reversible binding kinetics, and good stability., (© 2022 Wiley-VCH GmbH.)

Spot urine specimens have been used to estimate 24 h urinary sodium (Na) excretion (24UNaV) and potassium (K) excretion (24UKV). However, the validity is limited for 24UNaV and unknown for 24UKV in stroke patients, using the existing formulas. Herein, we developed and validated a new formula for 24UNaV and 24UKV by spot urine specimens in stroke patients. Spot and 24 h urine samples were collected from 970 stroke patients. The models of 24UNaV and 24UKV were developed using stepwise multivariate linear regression in 689 patients. The performance of different formulas was internally validated in 281 patients at the population and individual levels. The obtained new formulas were: (1) estimated 24UNaV (mmol/day): -0.191 × Age + 4.349 × BMI + 0.229 × Spot Na + 1.744 × Spot Na /Spot creatinine (Cr) + 41.492 (for male); -1.030 × Age + 2.011 × BMI + 0.143 × Spot Na + 1.035 × Spot Na /Spot Cr + 147.159 (for female); and (2) estimated 24UKV (mmol/day): -0.052 × Age + 0.410 × BMI + 0.031 × Spot K + 33.280 × Ln (spot K /spot Cr ) - 5.789 × Ln (spot Na /spot Cr ) - 1.035 (for male); -0.235 × Age + 0.530 × BMI + 0.040 × Spot K + 30.990 × Ln (spot K/ spot Cr ) - 7.837 × Ln (spot Na /spot Cr ) + 4.318 (for female). The new formula obtained the lowest mean bias (5.17 mmol/day for 24UNaV and 0.85 mmol/day for 24UKV) and highest proportion at the cutoff under the ±30% level for the estimation of 24UNaV (59.43%) and 24UKV (70.11%). The new formula provides a meaningful exploration to estimate 24UNaV and 24UKV in stroke patients by using spot urine specimens.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases., (© 2021. Higher Education Press.)

Background: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention., Methods: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models., Results: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P =0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective., Conclusions: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.

Ischemic stroke is one of the major causes of death and disability in the world. Currently, most patients cannot choose intravenous thrombolysis or intravascular mechanical thrombectomy because of narrow therapeutic windows and severe complications. Stem cell transplantation is an emerging treatment and has been studied in various central nervous system diseases. Animal and clinical studies showed that transplantation of mesenchymal stem cells (MSCs) could alleviate neurological deficits and bring hope for ischemic stroke treatment. This article reviewed biological characteristics, safety, feasibility and efficacy of MSCs therapy, potential therapeutic targets of MSCs, and production process of Good Manufacturing Practices-grade MSCs, to explore the potential therapeutic targets of MSCs in the process of production and use and provide new therapeutic directions for ischemic stroke., (© 2022. The Author(s).)

Background: A considerable number of stroke survivors suffered from cognitive impairment, and more than one third of stroke survivors are affected at 3 and 12 months after the stroke. Although the published systematic reviews suggest that acupuncture can help improve post-stroke cognitive dysfunction, the power of the results is low due to study limitations. Therefore, this review is necessary to analyze the effect of acupuncture on cognitive impairment after stroke and to provide evidence for cognitive impairment in stroke., Methods: This study will be carried out in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions. According to the pre-established search strategy (PICOS framework), all the literature will be obtained from online databases including Cochrane Central Register of Controlled Trials in the Cochrane Library, Medline (via PubMed), EMBASE (via embase.com), CINAHL (via EBSCOhost), China National Knowledge Infrastructure database, WanFang Database, Chinese Science and Technology Periodical Database, and Sino-Med Database from inception until December 31, 2021 with no language limitations. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. The data needed will be extracted independently by 2 authors according to a table of data extraction. Any inconsistencies in literature screening and data collection will be resolved to reach a consensus via discussion with a third author. Risk of bias for each study will be assessed using risk of bias tool. RevMan5.3 will be used to analyze the data. Heterogeneity will be identified and measured by Chi2. Subgroup analyses and sensitivity analysis will be carried out. Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the evidence for each outcome., Conclusion: The results of this study will provide a theoretical basis for the clinical use of electro-acupuncture to treat cognitive dysfunction after stroke., Unique Inplasy Number: INPLASY202210038., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain., Methods: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia., Results: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76)., Conclusions: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.)., (Copyright © 2021 Massachusetts Medical Society.)

Introduction: Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Reducing dietary salt consumption is a potentially cost-effective way to reduce blood pressure and the burden of CVD. To date, economic evidence has focused on sodium reduction in food industry or processed food with blood pressure as the primary outcome. This study protocol describes the planned within-trial economic evaluation of a low-sodium salt substitute intervention designed to reduce the risk of stroke in China., Methods and Analyses: The economic evaluation will be conducted alongside the Salt Substitute and Stroke Study: a 5-year large scale, cluster randomised controlled trial. The outcomes of interest are quality of life measured using the EuroQol-5-Dimensions and major adverse cardiovascular events. Costs will be estimated from a healthcare system perspective and will be sought from the routinely collected data available within the New Rural Cooperative Medical Scheme. Cost-effectiveness and cost-utility analyses will be conducted, resulting in the incremental cost-effectiveness ratio expressed as cost per cardiovascular event averted and cost per quality-adjusted life year gained, respectively., Ethics and Dissemination: The trial received ethics approval from the University of Sydney Ethics Committee (2013/888) and Peking University Institutional Review Board (IRB00001052-13069). Informed consent was obtained from each study participant. Findings of the economic evaluation will be published in a peer-reviewed journal and presented at international conferences., Trial Registration Number: ClinicalTrials.gov Registry (NCT02092090)., Competing Interests: Competing interests: Between 24 months and 48 months, salt substitute in SSaSS has been provided by Jiangsu Sinokone Technology Co for free., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao)., Methods: A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019. Structured questionnaires were administered, and physical examinations were performed in the same manner for cases and controls. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischaemic stroke. An additive model was used to study the interaction between the modifiable risk factors and ethnicity with R software., Results: Higher high-sensitivity C-reactive protein levels (OR 50.54, 95%CI 29.76-85.85), higher monthly family income (4.18, 2.40-7.28), increased frequency of hot pot consumption (2.90, 1.21-6.93), diabetes mellitus (2.62, 1.48-4.62), a higher apolipoprotein (Apo)B/ApoA1 ratio (2.60, 1.39-4.85), hypertension (2.52, 1.45-4.40) and moderate-intensity physical activity (0.50, 0.28-0.89) were associated with ischaemic stroke. There was an additive interaction between the ApoB/ApoA1 ratio and ethnicity in the Tujia and Miao populations with first-ever ischaemic stroke (the relative excess risk due to the interaction was 5.75, 95% CI 0.58 ~ 10.92; the attributable proportion due to the interaction was 0.65, 95% CI 0.38 ~ 0.91; the synergy index was 3.66, 95% CI 1.35 ~ 9.93)., Conclusions: This is the first case-control study examining modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China. Some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.

Background and Purpose: Post-stroke fatigue (PSF) is a common neuropsychiatric affective symptom occurring after stroke. Evidence indicates activated inflammatory pathways are involved in modulating the stroke and fatigue. High-sensitivity C-reactive protein (hs-CRP) is one of the most sensitive indicators of inflammation. Our aim was to estimate the association between plasma hs-CRP and PSF after acute ischaemic stroke., Methods: In all, 212 acute ischaemic stroke patients were consecutively recruited within the first 14 days after stroke onset and followed up for 6 months. Plasma hs-CRP levels were assayed by enzyme linked immunosorbent assay. Fatigue severity was assessed using the Fatigue Scale for Motor and Cognitive Functions. A score ≥ 43 is defined as PSF., Results: Sixty-eight stroke patients (32.1%) were diagnosed with PSF at 6 months' follow-up. In the patients with PSF, plasma hs-CRP levels were significantly higher compared with those in non-PSF patients (t = -8.524, P ≤ 0.001). In multivariate analyses, plasma levels of hs-CRP were independently associated with PSF at 6 months (odds ratio 3.435, 95% confidence interval 2.222-5.309; P ≤ 0.001) after adjusting other recorded variables. Based on the receiver operating characteristic curve, the optimal cut-off value of plasma hs-CRP levels as an indicator for the prediction of PSF was projected to be 0.52 mg/dl, which yielded a sensitivity of 77.9% and a specificity of 74.3%, with the area under the curve 0.794 (95% confidence interval 0.725-0.864; P ≤ 0.001)., Conclusion: Elevated plasma hs-CRP levels at admission were associated with PSF 6 months after stroke, suggesting that these alterations might predict the development of PSF in stroke patients., (© 2020 European Academy of Neurology.)

Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) - 1.63, 95% confidence intervals (CI) - 2.73 to - 0.53, I 2  =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I 2  = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I 2  = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up., Competing Interests: Disclosures After 24 months, salt substitute has been provided by Jiangsu Sinokone Technology Co. Ltd for free. The company does not participate in any aspect of the study design or implementation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The findings on the association between elevated plasma homocysteine levels and the risk of the trial of org 10172 in acute stroke treatment (TOAST) of ischemic stroke have been inconsistent in Chinese. So far, there is no meta-analysis about the association between Hcy and the TOAST subtypes of ischemic stroke in Chinese. This study; therefore, aimed to evaluate whether elevated homocysteine levels are associated with the TOAST subtypes of ischemic stroke using a meta-analysis., Materials and Methods: A systematic search of electronic databases were conducted for studies reporting homocysteine levels in ischemic stroke and the TOAST of ischemic stroke to April 18, 2018. The data were extracted after the application of inclusion and exclusion criteria. All the data were analyzed using Stata software version 9.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables., Results: Thirteen studies comprising 3114 participants (2243 patients and 871controls) met the eligibility criteria and were included in the meta-analysis. The meta-analysis revealed that the ischemic stroke group had significantly higher levels of homocysteine than controls (SMD = 1.15, 95% CI = 0.85-1.45, P < .05). The subgroup analyses suggested that the groups of patients with large-artery atherosclerosis, small-vessel occlusion, cardioembolism, stroke of other determined etiology and stroke of undetermined etiology had significantly higher levels of homocysteine compared to those in the control group (large-artery atherosclerosis: SMD = 2.12, 95% CI = 1.40-2.84, P < .05; small-vessel occlusion: SMD = 1.10, 95% CI = 0.72-1.48, P < .05; CE: SMD = 1.17, 95% CI = 0.64-1.71, P < .05; stroke of other determined etiology: SMD = 0.88, 95% CI = 0.53-1.24, P < .05; stroke of undetermined etiology: SMD = 1.50, 95% CI = 0.66-2.33, P < .05, respectively)., Conclusion: This meta-analysis found that ischemic stroke patients and the TOAST of ischemic stroke patients in Chinese had significantly higher homocysteine levels than the controls, suggesting that serum homocysteine levels may be a risk factor for ischemic stroke and the TOAST subtypes of ischemic stroke in Chinese.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen and nitrogen species (RONS) following ischemic insult is known as a key factor in exacerbating brain damage. Thus, RONS scavengers that can block excessive production of RONS have great therapeutic potential. Herein, we propose an efficient treatment strategy in which an artificial nanozyme with multienzyme activity drives neuroprotection against ischemic stroke primarily by scavenging RONS. Specifically, through a facile, Bi 3+ -assisted, template-free synthetic strategy, we developed hollow Prussian blue nanozymes (HPBZs) with multienzyme activity to scavenge RONS in a rat model of ischemic stroke. The comprehensive characteristics of HPBZs against RONS were explored. Apart from attenuating oxidative stress, HPBZs also suppressed apoptosis and counteracted inflammation both in vitro and in vivo, thereby contributing to increased brain tolerance of ischemic injury with minimal side effects. This study provides a proof of concept for a novel class of neuroprotective nanoagents that might be beneficial for treatment of ischemic stroke and other RONS-related disorders.

Objective: To observe the effect difference between acupuncture combined with electroacupuncture (EA) and simple acupuncture for hand spasm in stroke patients., Methods: Sixty patients were randomly assigned into an acupuncture group and a combination group, 30 cases in each one. Patients in the two groups were treated with acupuncture at the affected Jianyu (LI 15), Binao (LI 14), Jianliao (TE 14), Quchi (LI 11), Shousanli (LI 10), Waiguan (TE 5), Futu (ST 32), Liangqiu (ST 34), Xuehai (SP 10), Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Yinlingquan (SP 9), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3), and the points at the middle of all the dorsal muscles between metacarpal bones. EA with discontinuous wave was used in the combination group at Waiguan (TE 5) and the middle point of the dorsal muscle between the second and the third metacarpal bones. The treatment was given for 40 min, once a day for 3 courses, five treatment per week, 4 weeks as a course. The modified Ashworth scale (MAS), the Fugl-Meyer finger motor function rating scale and the modified Barthel index (BI) were observed before and after treatment in the two group., Results: The MAS scores after treatment significantly decreased compared with those before treatment in the two groups (both P <0.05), with lower score in the combination group ( P <0.05). The Fugl-Meyer scores and BI scores after treatment increased in the two groups (all P <0.05), with higher scores in the combination group (both P <0.05)., Conclusion: EA combined with acupuncture can more apparently alleviate hand spasm, promote the recovery of hand function, improve the quality of life for stroke patients than simple acupuncture.

Lowering sodium intake with a reduced-sodium, added potassium salt substitute has been proved to lower blood pressure levels. Whether the same strategy will also reduce the risks of vascular outcomes is uncertain and controversial. The SSaSS has been designed to test whether sodium reduction achieved with a salt substitute can reduce the risk of vascular disease. The study is a large-scale, open, cluster-randomized controlled trial done in 600 villages across 5 provinces in China. Participants have either a history of stroke or an elevated risk of stroke based on age and blood pressure level at entry. Villages were randomized in a 1:1 ratio to intervention or continued usual care. Salt substitute is provided free of charge to participants in villages assigned to the intervention group. Follow-up is scheduled every 6months for 5years, and all potential endpoints are reviewed by a masked adjudication committee. The primary end point is fatal and nonfatal stroke, and the 2 secondary endpoints are total major cardiovascular events and total mortality. The study has been designed to provide 90% statistical power (with 2-sided α = .05) to detect a 13% or greater relative risk reduction for stroke. The power estimate assumes a primary outcome event rate of 3.5% per year and a systolic blood pressure difference of 3.0mm Hg between randomized groups. Recruitment is complete and there are 20,996 participants (about 35 per village) that have been enrolled. Mean age is 65years and 49% are female. There were 73% enrolled on the basis of a history of stroke. The trial is well placed to describe the effects of salt substitution on the risks of vascular disease and death and will provide important policy-relevant data., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair.

Unlabelled: This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury., Methods: Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation., Results: Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest., Conclusion: Spatiotemporal PET imaging with (18)F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia-reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Introduction: Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH., Materials and Methods: We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE., Results: Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups., Conclusions: Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy., Methods: Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality., Results: There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001)., Conclusions: Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: There are multiple clinical and radiographic factors that influence outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS). We sought to derive and validate an outcome prediction score for AIS patients undergoing ERT based on readily available pretreatment and posttreatment factors., Methods: The derivation cohort included 511 patients with anterior circulation AIS treated with ERT at 10 centers between September 2009 and July 2011. The prospective validation cohort included 223 patients with anterior circulation AIS treated in the North American Solitaire Acute Stroke registry. Multivariable logistic regression identified predictors of good outcome (modified Rankin score ≤2 at 3 months) in the derivation cohort; model β coefficients were used to assign points and calculate a risk score. Discrimination was tested using C statistics with 95% confidence intervals (CIs) in the derivation and validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and plots of observed to expected outcomes. We assessed the net reclassification improvement for the derived score compared to the Totaled Health Risks in Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct volume measurements was also performed to identify whether these radiographic predictors improved the model compared to simpler models., Results: Good outcome was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and validation cohorts, respectively. Combining readily available pretreatment and posttreatment variables, we created a score (acronym: SNARL) based on the following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20; 0 points: >20), age (2 points: <60 years; 1 point: 60-79 years; 0 points: >79 years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3) and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The SNARL score demonstrated good discrimination in the derivation (C statistic 0.79, 95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI 0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04). Compared with the THRIVE score, the SNARL score resulted in a net reclassification improvement of 34.8%., Conclusions: Among AIS patients treated with ERT, pretreatment scores such as the THRIVE score provide only fair prognostic information. Inclusion of posttreatment variables such as reperfusion and symptomatic hemorrhage greatly influences outcome and results in improved outcome prediction., (© 2014 S. Karger AG, Basel.)

Background and Purpose: Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches., Methods: A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care., Results: A total of 442 consecutive patients of mean age 66 ± 14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008)., Conclusions: Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

Purpose: Advanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP) or MRI compared with non-contrast CT (NCT) in a multicenter cohort., Materials and Methods: This is a retrospective study of 10 stroke centers who select patients for endovascular treatment using institutional protocols. Approval was obtained from each institution's review board as only de-identified information was used. We collected demographic and radiographic data, selected time intervals, and outcome data. ANOVA was used to compare the groups (NCT vs CTP vs MRI). Binary logistic regression analysis was performed to determine factors associated with a good clinical outcome., Results: 556 patients were analyzed. Mean age was 66 ± 15 years and median National Institutes of Health Stroke Scale score was 18 (IQR 14-22). NCT was used in 286 (51%) patients, CTP in 190 (34%) patients, and MRI in 80 (14%) patients. NCT patients had significantly lower median times to groin puncture (61 min, IQR (40-117)) compared with CTP (114 min, IQR (81-152)) or MRI (124 min, IQR (87-165)). There were no differences in clinical outcomes, hemorrhage rates, or final infarct volumes among the groups., Conclusions: The current retrospective study shows that multimodal imaging may be associated with delays in treatment without reducing hemorrhage rates or improving clinical outcomes. This exploratory analysis suggests that prospective randomised studies are warranted to support the hypothesis that advanced modality imaging is superior to NCT in improving clinical outcomes.

Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB), in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI), nuclear medicine imaging, and optical imaging (OI). Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke.

Background: Reperfusion therapy for acute ischemic stroke (AIS) is rapidly evolving, with the development of multiple endovascular modalities that can be used alone or in combination., Objective: To determine which pharmacologic or mechanical modality may be associated with increased rates of recanalization., Methods: A cohort of 1122 patients with AIS involving the anterior circulation treated at 13 stroke centers underwent intra-arterial (IA) therapy within 8 hours of symptom onset. Demographic information, admission National Institutes of Health Stroke Scale (NIHSS), mechanical and pharmacologic treatments used, recanalization grade, and hemorrhagic complications were recorded., Results: The mean age was 67 ± 16 years and the median NIHSS was 17. The sites of arterial occlusion before treatment were M1 middle cerebral artery (MCA) in 561 (50%) patients, carotid terminus in 214 (19%) patients, M2 MCA in 171 (15%) patients, tandem occlusions in 141 (13%) patients, and isolated extracranial internal carotid artery occlusion in 35 (3%) patients. Therapeutic interventions included multimodal therapy in 584 (52%) patients, pharmacologic therapy only in 264 (24%) patients, and mechanical therapy only in 274 (24%) patients. Patients treated with multimodal therapy had a significantly higher Thrombolysis in Myocardial Infarction 2 or 3 recanalization rate (435 patients [74%]) compared with pharmacologic therapy only (160 patients, [61%]) or mechanical only therapy (173 patients [63%]), P<.001. In binary logistic regression modeling, independent predictors of Thrombolysis in Myocardial Infarction 2 or 3 recanalization were use of IA thrombolytic OR 1.58 (1.21-2.08), P<.001 and stent deployment 1.91 (1.23-2.96), P<.001., Conclusion: Multimodal therapy has significantly higher recanalization rates compared with pharmacologic or mechanical therapy. Among the individual treatment modalities, stent deployment or IA thrombolytics increase the chance of recanalization., (Copyright © 2011 by the Congress of Neurological Surgeons)

Background and Purpose: Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT., Methods: A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death., Results: The mean age was 66+/-15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63-3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23-2.30; P<0.0001) compared with conscious sedation., Conclusions: Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Objective: Atrial fibrillation (AF) may be present within a subset of patients with presumed cryptogenic TIA or stroke and remains undetected by standard diagnostic methods. We hypothesized that AF may be an under-recognized mechanism for cryptogenic TIA/stroke., Methods: A consecutive series of 56 patients with cryptogenic TIA/stroke was analyzed after diagnostic evaluation and Mobile Cardiac Outpatient Telemetry (MCOT) for up to 21 days. Demographic, radiographic, echocardiographic, and MCOT results were reviewed. Predictors of AF detection by MCOT were determined by univariate analysis including Student t test and Fisher exact tests and multivariate analysis., Results: The median MCOT monitoring duration was 21 (range 5-21) days resulting in an AF detection rate of 23% (13/56). AF was first detected after a median of 7 (range 2-19) days of monitoring. Twenty-seven asymptomatic AF episodes were detected in the 13 patients, of which 85% (23/27) were <30 seconds and the remaining 15% (4/27) were 4-24 hours in duration. Diabetes was predictive of AF detection by both univariate (p = 0.024) and multivariate analysis (OR 6.15; 95% CI 1.16 to 32.73; p = 0.033)., Conclusions: There is a high rate of atrial fibrillation (AF) detection by Mobile Cardiac Outpatient Telemetry (21 days) in patients with cryptogenic TIA/stroke that may be related to extended monitoring duration, patient selection, and inclusion of all new onset AF episodes. Brief AF episodes (<30 seconds) may be biomarkers of more prolonged and clinically significant AF.