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1.
Monogenic Causes of Strokes.
Chojdak-Łukasiewicz, J, Dziadkowiak, E, Budrewicz, S
Genes. 2021;(12)
Abstract
Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.
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2.
Fasting blood glucose and risk of Stroke: A Dose-Response meta-analysis.
Shi, H, Ge, Y, Wang, H, Zhang, Y, Teng, W, Tian, L
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3296-3304
Abstract
BACKGROUND & PURPOSE A growing number of studies have shown that fasting blood glucose is related to the risk of stroke, however, the dose-response association between fasting blood glucose and the risk of stroke is still unclear. Accordingly, we conducted a dose-response meta-analysis to evaluate the relationship between fasting blood glucose and the risk of stroke by summarizing cohort studies. METHODS PubMed and Embase databases were searched for related studies (until October 2020). Cohort studies examining the influence of fasting blood glucose on stroke risk were summarized. A dose-response relationship was determined using a random-effect model. RESULTS Eighteen cohort studies involving 2,555,666 participants were included. The pooled relative risk for the high-versus-low categories was 1.79 (95% CI: 1.68-1.91) in all people, and 1.16 (95% CI: 1.11-1.21) in non-diabetic people. In addition, there was a non-linear relationship between fasting blood glucose and stroke risk. The incidence of stroke was reduced to its lowest point when fasting blood glucose level was 70-100 mg/dL. CONCLUSION Fasting blood glucose was positively related to stroke risk, with a non-linear dose-response relationship.
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3.
Sex- related differences in the factors associated with outcomes among patients with strokes of undetermined source: a hospital-based follow-up study.
Yan, L, Huangfu, C, Yang, N, Li, R, Yang, X, Feng, Y, Xuan, L, Wang, Q, Meng, Y, Hou, X, et al
Postgraduate medicine. 2021;(4):428-435
Abstract
Objective: Sex-related differences are well established among stroke patients, including the incidence and prevalence of stroke being higher among men than among women. However, the sex-related factors for differences in the outcomes of strokes of undetermined source (SUSs) have not been well described, especially in the Chinese population. We assessed the sex-related differences in the factors associated with outcomes among patients with SUSs in China.Method: Between January 2011 and December 2018, we recruited 205 patients diagnosed with SUSs from Kailuan General Hospital (China). The clinical features, risk factors, and outcome data were collected for the patients at 3 and 12 months after their strokes.Results: There were higher frequencies of hyperlipidemia (27.8% vs. 26.4%), smoking (41.4% vs. 5.6%), and alcohol consumption (21.8% vs. 0%) for male patients than for female patients. However, women were more likely than men to have hypertension (63.9% vs. 46.6%), diabetes (27.8% vs. 20.3%), and atrial fibrillation (9.7% vs. 5.3%); they were also more likely to be obese (16.7% vs. 12.0%). There were no significant differences in outcome between the sexes. Among men, severe strokes were associated with higher case fatality and disability risks at 12 months after stroke onset; hyperlipidemia was a risk factor for recurrence within 3 months of the initial stroke. Among women, severe strokes also increased the risk of disability; in women, high total cholesterol (TC) and age were associated with poor outcomes.Conclusion: The factors associated with outcomes in SUS differed by sex. For male patients, more severe stroke and hyperlipidemia were associated with poor outcomes in SUS. Risk factors for poor outcomes in female patients were stroke severity, age, and TC level. These findings suggest that taking measures to manage blood lipid levels and severe stroke among patients with SUS is important for both male and female patients and is crucial for reducing the burden of stroke in China.
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4.
A scoping review of PhotoVoice for people with post-stroke aphasia.
Dietz, A, Mamlekar, CR, Bakas, KL, McCarthy, MJ, Harley, D, Bakas, T
Topics in stroke rehabilitation. 2021;(3):219-235
Abstract
BACKGROUND PhotoVoice is a qualitative research methodology designed to engage and empower marginalized members of a community and/or to understand community needs. PhotoVoice seems aphasia-friendly because it relies on personal photographs to convey opinions regarding prespecified topics. However, PhotoVoice is based on a procedure referred to as the SHOWeD method. Participants are asked to reflect upon their photos by discussing (1) what they See, (2) what is Happening, (3) the relation to Our life, (3) Why the issue or condition exists, and then to (4) explain what can be Done to address the issue(s) at hand. Due to the linguistic demand required to convey complex thoughts and ideas inherent in this methodology, adaptations are likely required to successfully implement with people who have aphasia. AIMS A scoping review was conducted to summarize the current literature regarding the use of PhotoVoice with people who have aphasia, to address two questions:(1) Are people with post-stroke aphasia included in PhotoVoice studies?(2) What, if any, modifications are required to address post-stroke aphasia and motor impairments? MAIN CONTRIBUTION This scoping review revealed that researchers often exclude people with aphasia from post-stroke PhotoVoice research. Three studies outlined adaptations that allowed successful implementation with people who have post-stroke aphasia. CONCLUSIONS Further inquiry regarding how best to adapt PhotoVoice for people with aphasia will facilitate their ability to be included in community-based research. This is an important step in ensuring that all post-stroke stakeholders are involved in projects related to social justice and policy for stroke survivors.
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5.
Intermittent Theta Burst Stimulation (iTBS) for Treatment of Chronic Post-Stroke Aphasia: Results of a Pilot Randomized, Double-Blind, Sham-Controlled Trial.
Szaflarski, JP, Nenert, R, Allendorfer, JB, Martin, AN, Amara, AW, Griffis, JC, Dietz, A, Mark, VW, Sung, VW, Walker, HC, et al
Medical science monitor : international medical journal of experimental and clinical research. 2021;:e931468
Abstract
BACKGROUND Research indicates intermittent theta burst stimulation (iTBS) is a potential treatment of post-stroke aphasia. MATERIAL AND METHODS In this double-blind, sham-controlled trial (NCT01512264) participants were randomized to receive 3 weeks of sham (G₀), 1 week of iTBS/2 weeks of sham (G₁), 2 weeks of iTBS/1 week of sham (G₂), or 3 weeks of iTBS (G₃). FMRI localized residual language function in the left hemisphere; iTBS was applied to the maximum fMRI activation in the residual language cortex in the left frontal lobe. FMRI and aphasia testing were conducted pre-treatment, at ≤1 week after completing treatment, and at 3 months follow-up. RESULTS 27/36 participants completed the trial. We compared G0 to each of the individual treatment group and to all iTBS treatment groups combined (G₁₋₃). In individual groups, participants gained (of moderate or large effect sizes; some significant at P<0.05) on the Boston Naming Test (BNT), the Semantic Fluency Test (SFT), and the Aphasia Quotient of the Western Aphasia Battery-Revised (WAB-R AQ). In G₁₋₃, BNT, and SFT improved immediately after treatment, while the WAB-R AQ improved at 3 months. Compared to G₀, the other groups showed greater fMRI activation in both hemispheres and non-significant increases in language lateralization to the left hemisphere. Changes in IFG connectivity were noted with iTBS, showing differences between time-points, with some of them correlating with the behavioral measures. CONCLUSIONS The results of this pilot trial support the hypothesis that iTBS applied to the ipsilesional hemisphere can improve aphasia and result in cortical plasticity.
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6.
Advances in the Development of Biomarkers for Poststroke Epilepsy.
Liang, M, Zhang, L, Geng, Z
BioMed research international. 2021;:5567046
Abstract
Stroke is the main cause of acquired epilepsy in elderly people. Poststroke epilepsy (PSE) not only affects functional recovery after stroke but also brings considerable social consequences. While some factors such as cortical involvement, hemorrhagic transformation, and stroke severity are associated with increased seizure risk, so far that remains controversial. In recent years, there are an increasing number of studies on potential biomarkers of PSE as tools for diagnosing and predicting epileptic seizures. Biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), glutamate, and S100 calcium-binding protein B (S100B) in blood are associated with the occurrence of PSE. This review is aimed at summarizing the progress on potential biomarkers of PSE.
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7.
The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis.
Liu, X, Fang, JC, Zhi, XY, Yan, QY, Zhu, H, Xie, J
Neurorehabilitation and neural repair. 2021;(6):550-560
Abstract
Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor (BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG-Val/Val, GA-Val/Met, AA-Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.
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8.
Treatments-Preventive.
Sandset, EC, Goldstein, LB
Stroke. 2021;(3):1118-1120
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9.
Gliflozins for the prevention of stroke in diabetes and cardiorenal diseases: A meta-analysis of cardiovascular outcome trials.
Zhao, LM, Huang, JN, Qiu, M, Ding, LL, Zhan, ZL, Ning, J
Medicine. 2021;(39):e27362
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Abstract
BACKGROUND Individual randomized trials are not powered to assess the relationship between use of sodium-glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials. METHODS Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Meta-analysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins. RESULTS We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55-0.84) and MACE (HR 0.77, 95% CI 0.69-0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86-1.16) and MACE (HR 0.94, 95% CI 0.86-1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82-1.07) in T2D patients regardless of HF status (Psubgroup = .684) and ASCVD status (Psubgroup = .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83-0.96) in T2D patients regardless of HF status (Psubgroup = .428) and ASCVD status (Psubgroup = .423). Canagliflozin (HR 0.84, 95% CI 0.69-1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54-0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85-1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk. CONCLUSIONS Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk.
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Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF): Design and Rationale: From the COMBINE AF (A Collaboration between Multiple institutions to Better Investigate Non-vitamin K antagonist oral anticoagulant use in Atrial Fibrillation) Investigators.
Carnicelli, AP, Hong, H, Giugliano, RP, Connolly, SJ, Eikelboom, J, Patel, MR, Wallentin, L, Morrow, DA, Wojdyla, D, Hua, K, et al
American heart journal. 2021;:48-58
Abstract
BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date. DESIGN COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771). CONCLUSION In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.