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1.
Medicine (Baltimore) ; 103(19): e37924, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728516

RATIONALE: Marfan syndrome (MFS), which is a dominantly inherited connective tissue disease resulting from a mutation in the FBN1 gene, exhibits variable manifestations affecting the cardiovascular, musculoskeletal, ophthalmologic, and pulmonary systems. Notably, neurologic deficiency, which involves ischemic or hemorrhagic stroke, is a rare but severe manifestation. The safety of rt-PA treatment for ischemic stroke caused by MFS is still under discussion. PATIENT CONCERNS: In the current report, we discuss 3 atypical MFS cases presented as acute ischemic stroke, compared to those exhibiting cardiovascular and musculoskeletal abnormalities. DIAGNOSES: Three patients were diagnosed with acute ischemic stroke accompanied by MFS based on clinical manifestations, imaging examinations, and genetic testings. INTERVENTIONS: The first case underwent intravenous thrombolytic therapy with rt-PA, the second case received antiplatelet therapy, and the third case received anticoagulant therapy and perfusion therapy. OUTCOMES: The neurologic deficiency of all three patients showed improvement upon discharge, and there were no symptoms of recurrence observed during the follow-up period. LESSONS SUBSECTIONS: MFS is a rare etiology in young people with embolic stroke of undetermined source. Physicians should take MFS into consideration when they observe the characteristic symptoms during a consultation. The potential pathogenesis of ischemic stroke secondary to MFS may include cardio-embolism, arterial dissection, and hypoperfusion. Although intravenous thrombolysis is a promising therapy to treat acute ischemic stroke, further examinations should be conducted to rule out contraindications in patients with a suspicion of MFS.


Ischemic Stroke , Marfan Syndrome , Humans , Marfan Syndrome/complications , Marfan Syndrome/diagnosis , Ischemic Stroke/etiology , Ischemic Stroke/diagnosis , Male , Adult , Female , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Tissue Plasminogen Activator/administration & dosage , Anticoagulants/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use
2.
Open Heart ; 11(1)2024 May 08.
Article En | MEDLINE | ID: mdl-38719499

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.


Atrial Fibrillation , Electrocardiography, Ambulatory , Ischemic Stroke , Humans , Female , Male , Aged , Retrospective Studies , Electrocardiography, Ambulatory/instrumentation , Electrocardiography, Ambulatory/economics , Electrocardiography, Ambulatory/methods , Ischemic Stroke/economics , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Ischemic Stroke/prevention & control , Ischemic Stroke/etiology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/economics , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , Atrial Fibrillation/mortality , United States/epidemiology , Anticoagulants/economics , Anticoagulants/administration & dosage , Time Factors , Middle Aged , Follow-Up Studies , Cost-Benefit Analysis , Aged, 80 and over , Health Care Costs
3.
Tunis Med ; 102(4): 217-222, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38746961

INTRODUCTION: Ischemic Stroke in young adults is a real public health problem; it's a major cause of disability, alters quality of life and has a great socio-economic impact. AIM: determine risk factors and specify the etiology of arterial ischemic stroke in young Tunisian adults. METHODS: In this 5 years retrospective study (2015-2020), we included all young adults (18-50 years) admitted for arterial ischemic stroke (AIS). Risk factors were registered and analyzed. All patients were investigated using a standard protocol: biological tests, brain imaging, carotid ultrasound and cardiac assessment. Additional investigations were carried out at the discretion of the treating physician. The cause of ischemic stroke was classified according to the TOAST criteria. RESULTS: We collected 200 patients with AIS. The mean age was 41.37 years ± 6.99. Traditional vascular risk factors were observed in more than 1/4 patients. A definite cause of stroke was identified in 120 patients. Cardio-embolic causes were the most common among our patients (19%) followed by atherosclerosis of the large arteries (11.5%). Other determined etiologies were found in 27.5% of patients. The etiology remained unclear in 40% of cases: undetermined despite complete investigation in 17.5%, undetermined and incompletely investigated 14.5 % and more than one potential pathomechanisms in 8%. CONCLUSION: Through this study, we demonstrated the diversity of etiology of stroke in young Tunisian adults. Changes of lifestyle are responsible for the occurrence of the traditional risk factors at an early age. Rheumatic heart diseases remain a frequent cause of AIS in our area.


Ischemic Stroke , Humans , Tunisia/epidemiology , Adult , Male , Ischemic Stroke/epidemiology , Ischemic Stroke/etiology , Ischemic Stroke/diagnosis , Female , Middle Aged , Young Adult , Retrospective Studies , Risk Factors , Adolescent , Brain Ischemia/epidemiology , Brain Ischemia/etiology , Brain Ischemia/diagnosis
4.
Brain Behav ; 14(5): e3537, 2024 May.
Article En | MEDLINE | ID: mdl-38715443

OBJECTIVE: Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90-day interval in AIS patients. METHODS: A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). RESULTS: Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90-day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90-day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p-overall = .011). CONCLUSIONS: Including RC as a contributing element may refine the prediction of poor 90-day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.


Cholesterol , Ischemic Stroke , Humans , Male , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Female , Aged , Middle Aged , Prognosis , Cholesterol/blood , Risk Factors , Cholesterol, LDL/blood
5.
J Am Heart Assoc ; 13(9): e032645, 2024 May 07.
Article En | MEDLINE | ID: mdl-38700029

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.


Black or African American , Blood Pressure , Hypertension , Ischemic Stroke , White People , Humans , Male , Female , Aged , Ischemic Stroke/ethnology , Ischemic Stroke/epidemiology , Ischemic Stroke/diagnosis , Ischemic Stroke/physiopathology , Blood Pressure/physiology , Middle Aged , White People/statistics & numerical data , Hypertension/ethnology , Hypertension/physiopathology , Hypertension/epidemiology , Hypertension/diagnosis , Black or African American/statistics & numerical data , Risk Factors , Kentucky/epidemiology , Health Status Disparities , Ohio/epidemiology , Time Factors , Aged, 80 and over , Prevalence
6.
J Am Heart Assoc ; 13(9): e033316, 2024 May 07.
Article En | MEDLINE | ID: mdl-38639371

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.


Fibrinolytic Agents , Healthcare Disparities , Ischemic Stroke , Thrombolytic Therapy , Humans , Female , United States/epidemiology , Male , Ischemic Stroke/drug therapy , Ischemic Stroke/ethnology , Ischemic Stroke/diagnosis , Aged , Middle Aged , Thrombolytic Therapy/trends , Thrombolytic Therapy/statistics & numerical data , Healthcare Disparities/trends , Healthcare Disparities/ethnology , Adult , Aged, 80 and over , Young Adult , Adolescent , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/administration & dosage , Inpatients , Time Factors , Administration, Intravenous , Insurance Coverage/statistics & numerical data
7.
J Am Heart Assoc ; 13(9): e032471, 2024 May 07.
Article En | MEDLINE | ID: mdl-38641856

BACKGROUND: Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta-analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90-day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. METHODS AND RESULTS: Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90-day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random-effects meta-analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90-day stroke recurrence was 8.6% (95% CI, 6.5-10.7), reducing by 0.60% (95% CI, 0.09-1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5-8.0) when compared with non-dual antiplatelet trial arms (7.2%, 95% CI, 4.7-9.6) and observational studies 10.6% (95% CI, 7.0-14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference - score ≤3: 8.6% (95% CI, 6.0-11.1), score ≤4: 8.4% (95% CI, 6.1-10.6), as did excluding studies with n<500%-7.3% (95% CI, 5.5-9.0). CONCLUSIONS: The risk of recurrence after minor ischemic stroke is declining over time but remains important.


Observational Studies as Topic , Recurrence , Humans , Time Factors , Ischemic Stroke/epidemiology , Ischemic Stroke/diagnosis , Risk Factors , Randomized Controlled Trials as Topic , Risk Assessment , Stroke/epidemiology , Platelet Aggregation Inhibitors/therapeutic use , Severity of Illness Index
8.
Korean J Intern Med ; 39(3): 469-476, 2024 May.
Article En | MEDLINE | ID: mdl-38632895

BACKGROUND/AIMS: The reimbursement policy for cryptogenic stroke (CS) was expanded in November 2018 from recurrent strokes to the first stroke episode. No reports have demonstrated whether this policy change has affected trends in implantable loop recorder (ILR) utilization. METHODS: We identified patients who received an ILR implant using the Korea Health Insurance Review and Assessment Service database between July 2016 and October 2021. Patients meeting all the following criteria were considered to have CS indication: 1) prior stroke history, 2) no previous history of atrial fibrillation or flutter (AF/AFL), and 3) no maintenance of oral anticoagulant for ≥4 weeks within a year before ILR implant. AF/AFL diagnosed within 3 years after ILR implant or before ILR removal was considered ILR-driven. RESULTS: Among 3,056 patients, 1,001 (32.8%) had CS indications. The total ILR implant number gradually increased for both CS and non-CS indications and the number of CS indication significantly increased after implementing the expanded reimbursement policy. The detection rate for AF/AFL was 26.3% in CS patients over 3 years, which was significantly higher in patients implanted with an ILR within 2 months after stroke than those implanted later. CONCLUSION: The expanded coverage policy for CS had a significant impact on the number of ILR implantation for CS indication. The diagnostic yield of ILR for AF/AFL detection seems better when ILR is implanted within 2 months than later. Further investigation is needed to demonstrate other clinical benefits and the optimal ILR implantation timing.


Ischemic Stroke , Humans , Republic of Korea , Male , Female , Middle Aged , Aged , Ischemic Stroke/diagnosis , Databases, Factual , Time Factors , Insurance, Health, Reimbursement , Retrospective Studies , Atrial Fibrillation/diagnosis , Atrial Fibrillation/economics , Electrocardiography, Ambulatory/instrumentation , Electrocardiography, Ambulatory/economics , Adult
9.
BMC Anesthesiol ; 24(1): 139, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38609861

BACKGROUND: While serum Ca has proven to be a reliable predictor of mortality across various diseases, its connection with the clinical outcomes of ischemic stroke (IS) remains inconclusive. Our research aimed to explore the relationships between serum total Ca (tCa) and serum ionized Ca (iCa) and mortality among acute IS (AIS) patients. METHODS: We gathered data from 1773 AIS patients in the Medical Information Mart for Intensive Care Database IV, including baseline demographic data, comorbidities, vital signs, laboratory-based data, and scoring systems. Endpoints for the study encompassed 30-d, 90-d, and 365-d all-cause mortalities. Employing restricted cubic spline Cox regression, we explored potential nonlinear relationships between admission serum iCa and tCa levels and mortality. Participants were categorized into four groups based on serum iCa and tCa quartiles. Multivariable Cox regression analysis was then conducted to evaluate the independent association of iCa and tCa quartiles with all-cause mortality. RESULTS: The restricted cubic spline revealed a U-shaped association between iCa and 30-d and 90-d mortality (P<0.05), while the relationship between iCa and 365-d mortality was linear (P<0.05). After adjusting for confounders, multivariable Cox analysis demonstrated that the lowest serum iCa level quartile was independently associated with increased risks of 30-d, 90-d, and 365-d mortality. Similarly, the highest serum iCa level quartile was independently associated with increased risks of 30-d and 90-d mortality, but not 365-d mortality. Notably, serum tCa level showed no association with increased risks of 30-d, 90-d, and 365-d mortality. CONCLUSIONS: Our findings suggest that serum iCa, rather than tCa, is linked to ischemic stroke prognosis. Both high and low serum iCa levels are associated with poor short-term prognosis, while only low serum iCa is associated with poor long-term prognosis in AIS patients.


Calcium , Ischemic Stroke , Humans , Ischemic Stroke/diagnosis , Prognosis , Critical Care , Intensive Care Units
10.
Swiss Med Wkly ; 154: 3633, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38579294

BACKGROUND: Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort. METHODS: This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers. RESULTS: Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes. CONCLUSIONS: In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov. REGISTRATION NUMBER: NCT00878813.


Atherosclerosis , Brain Ischemia , Ischemic Stroke , Lipoprotein(a) , Stroke , Humans , Arteries , Atherosclerosis/complications , Biomarkers , Ischemic Stroke/diagnosis , Lipoprotein(a)/blood , Lipoprotein(a)/chemistry , Prospective Studies , Risk Factors , Stroke/complications , Switzerland/epidemiology
11.
J Neuroimmune Pharmacol ; 19(1): 15, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38647743

Acute ischemic stroke (AIS), commonly known as stroke, is a debilitating condition characterized by the interruption of blood flow to the brain, resulting in tissue damage and neurological deficits. Early diagnosis is crucial for effective intervention and management, as timely treatment can significantly improve patient outcomes. Therefore, novel methods for the early diagnosis of AIS are urgently needed. Several studies have shown that bioactive molecules contained in extracellular vesicles, especially circRNAs, could be ideal markers for the diagnosis of many diseases. However, studies on the effects of exosomes and their circRNAs on the development and prognosis of AIS have not been reported extensively. Therefore, we explored the feasibility of using circRNAs in plasma brain-derived exosomes as biomarkers for AIS. By high-throughput sequencing, we first identified 358 dysregulated circRNAs (including 23 significantly upregulated circRNAs and 335 significantly downregulated circRNAs) in the plasma brain-derived exosomes of the brain infarct patient group compared to those of the noninfarct control group. Five upregulated circRNAs (hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808, and hsa_circ_0000097) were selected for further validation via Real-Time Quantitative Reverse Transcription PCR (qRT‒PCR) in a larger cohort based on the exclusion criteria of log2FC > 1, p < 0.05 and measurable expression. We found that the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were significantly upregulated in AIS patients and could serve as potential biomarkers for AIS with high specificity and sensitivity. Moreover, the expression levels of hsa_circ_0007290, hsa_circ_0049637, hsa_circ_0000607, hsa_circ_0004808 and hsa_circ_0000097 were also found to be positively correlated with National Institutes of Health Stroke Scale (NISS) and modified Rankin scale (mRS) scores, which indicated that the presence of these circRNAs in plasma brain-derived exosomes could also determine the progression of AIS.


Biomarkers , Exosomes , Ischemic Stroke , RNA, Circular , Humans , Exosomes/genetics , Exosomes/metabolism , RNA, Circular/genetics , RNA, Circular/blood , Ischemic Stroke/blood , Ischemic Stroke/genetics , Ischemic Stroke/diagnosis , Biomarkers/blood , Male , Female , Middle Aged , Aged , Brain/metabolism
12.
Aging (Albany NY) ; 16(7): 6314-6333, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38575196

BACKGROUND: Coagulation system is currently known associated with the development of ischemic stroke (IS). Thus, the current study is designed to identify diagnostic value of coagulation genes (CGs) in IS and to explore their role in the immune microenvironment of IS. METHODS: Aberrant expressed CGs in IS were input into unsupervised consensus clustering to classify IS subtypes. Meanwhile, key CGs involved in IS were further selected by weighted gene co-expression network analysis (WGCNA) and machine learning methods, including random forest (RF), support vector machine (SVM), generalized linear model (GLM) and extreme-gradient boosting (XGB). The diagnostic performance of key CGs were evaluated by receiver operating characteristic (ROC) curves. At last, quantitative PCR (qPCR) was performed to validate the expressions of key CGs in IS. RESULTS: IS patients were classified into two subtypes with different immune microenvironments by aberrant expressed CGs. Further WGCNA, machine learning methods and ROC curves identified ACTN1, F5, TLN1, JMJD1C and WAS as potential diagnostic biomarkers of IS. In addition, their expressions were significantly correlated with macrophages, neutrophils and/or T cells. GSEA also revealed that those biomarkers may regulate IS via immune and inflammation. Moreover, qPCR verified the expressions of ACTN1, F5 and JMJD1C in IS. CONCLUSIONS: The current study identified ACTN1, F5 and JMJD1C as novel coagulation-related biomarkers associated with IS immune microenvironment, which enriches our knowledge of coagulation-mediated pathogenesis of IS and sheds light on next-step in vivo and in vitro experiments to elucidate the relevant molecular mechanisms.


Biomarkers , Ischemic Stroke , Machine Learning , Humans , Ischemic Stroke/genetics , Ischemic Stroke/diagnosis , Ischemic Stroke/immunology , Biomarkers/metabolism , Blood Coagulation/genetics , ROC Curve , Actinin/genetics , Support Vector Machine , Male
13.
PLoS One ; 19(4): e0302227, 2024.
Article En | MEDLINE | ID: mdl-38656987

BACKGROUND/AIM: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. MATERIALS AND METHODS: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. RESULTS: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. CONCLUSIONS: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.


Ischemic Stroke , Nomograms , Humans , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Male , Female , Aged , Middle Aged , Risk Factors , Aged, 80 and over , Prognosis , Critical Illness/mortality
14.
J Stroke Cerebrovasc Dis ; 33(6): 107707, 2024 Jun.
Article En | MEDLINE | ID: mdl-38561166

OBJECTIVES: We studied quality of life, functional outcome, depression, and fatigue of ischemic stroke patients treated with or without thrombolysis seven years post-stroke. MATERIALS AND METHODS: A total of 204 ischemic stroke patients treated with or without thrombolysis during 2013-2015. After seven years the 136 survivors were assessed with telephone interview, which included questions about subjective quality of life (European Quality of Life-5 Dimensions), depression, fatigue with Fatigue Severity Scale, functional ability assessed with Barthel Index and Modified Rankin Scale, living conditions, need of care, and medical aids. RESULTS: At admission patients with thrombolysis had higher National Institutes of Health Stroke Scale scores compared with those not treated with thrombolysis. At seven years post-stroke, 99% of alive patients answered the questionnaires. There were no group differences concerning functional outcome, quality of life, depression, fatigue, or insomnia. The Barthel Index was normal in both groups. The quality of life was good in both groups without group differences in any domains. Of all patients, 68% reported no problems in usual activities, and 61% were without pain. Anxiety or depression were experienced by 19% of all stroke patients, while fatigue was present in 32% of cases. CONCLUSIONS: Seven years post-stroke the quality of life was good and functional outcome remained in good level in both study groups. One third experienced fatigue, while every fifth experienced depression. The thrombolysis treatment seems to protect from decreased quality of life, fatigue, and decreased mobility, self-care, and usual activities despite more severe stroke.


Depression , Disability Evaluation , Fatigue , Fibrinolytic Agents , Functional Status , Ischemic Stroke , Quality of Life , Recovery of Function , Thrombolytic Therapy , Humans , Female , Male , Aged , Fatigue/etiology , Fatigue/physiopathology , Fatigue/diagnosis , Fatigue/drug therapy , Thrombolytic Therapy/adverse effects , Time Factors , Middle Aged , Treatment Outcome , Depression/diagnosis , Depression/etiology , Depression/drug therapy , Depression/psychology , Ischemic Stroke/physiopathology , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Ischemic Stroke/therapy , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Aged, 80 and over , Activities of Daily Living , Risk Factors
15.
Heart ; 110(11): 768-774, 2024 May 10.
Article En | MEDLINE | ID: mdl-38569853

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.


Blood Pressure , Ischemic Stroke , Humans , Male , Female , Ischemic Stroke/physiopathology , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Aged , Blood Pressure/physiology , Time Factors , Middle Aged , Risk Factors , Prognosis , Hypertension/physiopathology , Hypertension/complications , Risk Assessment/methods , Aged, 80 and over , Blood Pressure Monitoring, Ambulatory/methods
16.
J Stroke Cerebrovasc Dis ; 33(6): 107711, 2024 Jun.
Article En | MEDLINE | ID: mdl-38580158

OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.


Hemorrhage , Ischemic Stroke , Platelet Aggregation Inhibitors , Precision Medicine , Thrombelastography , Humans , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Female , Male , Aged , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Middle Aged , Treatment Outcome , Risk Factors , Hemorrhage/chemically induced , Predictive Value of Tests , Drug Resistance , Aspirin/adverse effects , Aspirin/administration & dosage , Aspirin/therapeutic use , Retrospective Studies , Clopidogrel/adverse effects , Clopidogrel/administration & dosage , Clopidogrel/therapeutic use , Blood Platelets/drug effects , Clinical Decision-Making , Drug Substitution , Risk Assessment , Aged, 80 and over , Time Factors , Platelet Function Tests
17.
J Stroke Cerebrovasc Dis ; 33(6): 107713, 2024 Jun.
Article En | MEDLINE | ID: mdl-38583545

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.


Databases, Factual , Decompressive Craniectomy , Ischemic Stroke , Humans , Decompressive Craniectomy/trends , Female , Retrospective Studies , Male , Middle Aged , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Ischemic Stroke/therapy , Aged , Time Factors , Treatment Outcome , Risk Factors , United States/epidemiology , Risk Assessment , Respiration, Artificial/trends , Aged, 80 and over
18.
J Stroke Cerebrovasc Dis ; 33(6): 107716, 2024 Jun.
Article En | MEDLINE | ID: mdl-38604350

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.


Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Ischemic Stroke , Metformin , Humans , Metformin/therapeutic use , Metformin/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Treatment Outcome , Risk Factors , Male , Aged , Female , Middle Aged , Risk Assessment , Time Factors , Recovery of Function , Disability Evaluation , Aged, 80 and over , Functional Status
19.
J Stroke Cerebrovasc Dis ; 33(6): 107718, 2024 Jun.
Article En | MEDLINE | ID: mdl-38604352

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.


Cognition , Cognitive Dysfunction , Humans , Male , Female , Aged , Middle Aged , Singapore/epidemiology , Risk Factors , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/epidemiology , Time Factors , Memory , Risk Assessment , Prognosis , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Neuropsychological Tests , Attention , Stroke/diagnosis , Stroke/complications , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/psychology
20.
J Stroke Cerebrovasc Dis ; 33(6): 107536, 2024 Jun.
Article En | MEDLINE | ID: mdl-38636322

INTRODUCTION: Numerous diseases have been found to be associated with the lactate-to-albumin ratio (LAR), as confirmed by existing research. This study aims to investigate the relationship between LAR within 24 hours of admission and a 28-day mortality rate in patients manifesting ischemic stroke. METHODS: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with acute ischemic stroke (AIS) who were admitted to the intensive care unit. The primary outcome entailed evaluating the ability of LAR to predict death at 28-day of hospital admission in patients with AIS. RESULTS: A total of 502 patients with ischemic stroke were enrolled in the study, of which 185 (36.9 %) died within 28 days after hospital admission. We identified a linear association between LAR and mortality risk. Compared with the reference group (first LAR tertile), the 28-day mortality was increased in the highest tertile; the fully adjusted HR value was 1.21 (1.08 to 1.40). the Area Under the Curve (AUC) value for LAR was 58.26 % (95 % CI: 53.05 % - 63.46 %), which was higher than that for arterial blood lactate (AUC = 56.88 %) and serum albumin (AUC = 55.29 %) alone. It was not inferior even when compared to SOFA (AUC = 56.28 %). The final subgroup analysis exhibited no significant interaction of LAR with each subgroup (P for interaction: 0.079 - 0.848). CONCLUSION: In our study, LAR emerged as a promising predictor of all-cause mortality in acute ischemic stroke patients within 28 days of admission.


Biomarkers , Critical Illness , Ischemic Stroke , Lactic Acid , Predictive Value of Tests , Serum Albumin, Human , Humans , Male , Female , Aged , Retrospective Studies , Middle Aged , Biomarkers/blood , Critical Illness/mortality , Time Factors , Ischemic Stroke/mortality , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Lactic Acid/blood , Risk Factors , Prognosis , Risk Assessment , Serum Albumin, Human/analysis , Aged, 80 and over , Databases, Factual , Cause of Death , Patient Admission , Hospital Mortality
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