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Approximately one-quarter of strokes occur in individuals with prior stroke. Despite the advancement in secondary stroke prevention, the long-term risk of recurrent stroke has remained unchanged. The objective of this study was to identify metabolite risk markers that are associated with recurrent stroke. We performed targeted metabolomic profiling of 162 metabolites by liquid chromatography-tandem mass spectrometry in baseline plasma in a stroke case-cohort study nested within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, an observational cohort study of 30,239 individuals aged 45 and older enrolled in 2003–2007. Weighted Cox proportional hazard models were used to identify metabolites that had a differential effect on first-time versus recurrent stroke using an interaction term between metabolite and prior stroke at baseline (yes or no). The study included 1391 incident stroke cases identified during 7.1 ± 4.5 years of follow-up and 1050 participants in the random cohort sample. Among 162 metabolites, 13 candidates had a metabolite-by-prior stroke interaction at a p-value <0.05, with one metabolite, acetylglutamine, surpassing the Bonferroni adjusted p-value threshold (p for interaction = 5.78 × 10−5). In an adjusted model that included traditional stroke risk factors, acetylglutamine was associated with recurrent stroke (HR = 2.27 per SD increment, 95% CI = 1.60–3.20, p = 3.52 × 10−6) but not with first-time stroke (HR = 0.96 per SD increment, 95% CI = 0.87–1.06, p = 0.44). Acetylglutamine was associated with recurrent stroke but not first-time stroke, independent of traditional stroke risk factors. Future studies are warranted to elucidate the pathogenesis of acetylglutamine and recurrent stroke risk. [ABSTRACT FROM AUTHOR]

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) is a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets, and its association with renal outcomes remains unclear. In the REasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort, diet data were collected at baseline using food frequency questionnaires. Modified Poisson regression was used to examine the association of MIND diet with incident chronic kidney disease (CKD). In the REGARDS stroke case-cohort, 357 metabolites were measured in baseline plasma. Weighted linear regression was used to test associations between MIND diet and metabolites. Weighted logistic regression was used to test associations between MIND-associated metabolites and incident CKD. Mediation analyses were conducted to determine whether metabolites mediated the relationship between MIND diet and CKD. A higher MIND diet score was associated with a decreased risk of incident CKD (risk ratio 0.90, 95% CI (0.86–0.94); p = 2.03 × 10−7). Fifty-seven metabolites were associated with MIND diet (p < 3 × 10−4). Guanosine was found to mediate the relationship between MIND diet and incident CKD (odds ratio for indirect effects 0.93, 95% CI (0.88–0.97); p < 0.05). These findings suggest a role of the MIND diet in renal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic syndrome (MetS) increases the risk of cardiovascular disease and death. Previous '-omics' studies have identified dysregulated serum metabolites and aberrant DNA methylation in the setting of MetS. However, the relationship between the metabolome and epigenome have not been elucidated. In this study, we identified serum metabolites associated with MetS and DNA methylation, and we conducted bidirectional Mendelian randomization (MR) to assess causal relationships between metabolites and methylation. Methods: We leveraged metabolomic and genomic data from a national United States cohort of older adults (REGARDS), as well as metabolomic, epigenomic, and genomic data from a family-based study of hypertension (HyperGEN). We conducted metabolite profiling for MetS in REGARDS using weighted logistic regression models and validated them in HyperGEN. Validated metabolites were selected for methylation studies which fit linear mixed models between metabolites and six CpG sites previously linked to MetS. Statistically significant metabolite-CpG pairs were selected for twosample, bidirectional MR. Results: Forward MR indicated that glucose and serine metabolites were causal on CpG methylation near CPT1A [B(SE): -0.003 (0.002), p = 0.028 and B(SE): 0.029 (0.011), p = 0.030, respectively] and that serine metabolites were causal on ABCG1 [B(SE): -0.008(0.003), p = 0.006] and SREBF1 [B(SE): -0.009(0.004), p = 0.018] methylation, which suggested a protective effect of serine. Reverse MR showed a bidirectional relationship between cg06500161 (ABCG1) and serine [B(SE): -1.534 (0.668), p = 0.023]. Discussion: The metabolome may contribute to the relationship between MetS and epigenetic modifications. [ABSTRACT FROM AUTHOR]

Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke. Metabolites (n = 162) were measured in a case-control cohort nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 1,075 ischemic stroke cases and 968 random cohort participants. Cox models were adjusted for age, gender, race, and age-race interaction (base model) and further adjusted for the Framingham stroke risk factors (fully adjusted model). EFA identified fifteen metabolite factors, each representing a well-defined metabolic pathway. Of these, factor 3, a gut microbiome metabolism factor, was associated with an increased risk of stroke in the base (hazard ratio per one-unit standard deviation, HR = 1.23; 95%CI = 1.15–1.31; P = 1.98 × 10−10) and fully adjusted models (HR = 1.13; 95%CI = 1.06–1.21; P = 4.49 × 10−4). The highest tertile had a 45% increased risk relative to the lowest (HR = 1.45; 95%CI = 1.25–1.70; P = 2.24 × 10−6). Factor 3 was also associated with the Southern diet pattern, a dietary pattern previously linked to increased stroke risk in REGARDS (β = 0.11; 95%CI = 0.03–0.18; P = 8.75 × 10−3). These findings highlight the role of diet and gut microbial metabolism in relation to incident ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: While dietary intake is linked to stroke risk, surrogate markers that could inform personalized dietary interventions are lacking. We identified metabolites associated with diet patterns and incident stroke in a nested cohort from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Methods: Levels of 162 metabolites were measured in baseline plasma from stroke cases (n = 1,198) and random controls (n = 904). We examined associations between metabolites and a plant‐based diet pattern previously linked to reduced stroke risk in REGARDS. Secondary analyses included 3 additional stroke‐associated diet patterns: a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Southern diet. Metabolites were tested using Cox proportional hazards models with incident stroke as the outcome. Replication was performed in the Jackson Heart Study (JHS). Inverse odds ratio‐weighted mediation was used to determine whether metabolites mediated the association between a plant‐based diet and stroke risk. Results: Metabolites associated with a plant‐based diet included the gut metabolite indole‐3‐propionic acid (β = 0.23, 95% confidence interval [CI] [0.14, 0.33], p = 1.14 × 10−6), guanosine (β = −0.13, 95% CI [−0.19, −0.07], p = 6.48 × 10−5), gluconic acid (β = −0.11, 95% CI [−0.18, −0.04], p = 2.06 × 10−3), and C7 carnitine (β = −0.16, 95% CI [−0.24, −0.09], p = 4.14 × 10−5). All of these metabolites were associated with both additional diet patterns and altered stroke risk. Mediation analyses identified guanosine (32.6% mediation, p = 1.51 × 10−3), gluconic acid (35.7%, p = 2.28 × 10−3), and C7 carnitine (26.2%, p = 1.88 × 10−2) as mediators linking a plant‐based diet to reduced stroke risk. Interpretation: A subset of diet‐related metabolites are associated with risk of stroke. These metabolites could serve as surrogate markers that inform dietary interventions. ANN NEUROL 2023;93:500–510 [ABSTRACT FROM AUTHOR]

Background: After the initiation of the COVID-19 vaccination program in Thailand, thousands of patients have experienced unusual focal neurological symptoms. We report 8 patients with focal neurological symptoms after receiving inactivated virus vaccine, CoronaVac. Case series: Patients were aged 24–48 years and 75% were female. Acute onset of focal neurological symptoms occurred within the first 24 h after vaccination in 75% and between 1-7d in 25%. All presented with lateralized sensory deficits, motor deficits, or both, of 2–14 day duration. Migraine headache occurred in half of the patients. Magnetic resonance imaging of the brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deficits or structural brain injury. Discussions: Here, we present a case series of transient focal neurological syndrome following Coronavac vaccination. The characteristic sensory symptoms, history of migraine, female predominant, and abnormal functional brain imaging without structural changes suggest migraine aura as pathophysiology. We propose that pain related to vaccine injection, component of vaccine, such as aluminum, or inflammation related to vaccination might trigger migraine aura in susceptible patients. [ABSTRACT FROM AUTHOR]

We report a 66-year-old female patient who presented with acute onset of visual loss with relative afferent pupillary defect, hemineglect, hemihypesthesia, and apraxia. Magnetic resonance imaging of the brain demonstrated different stages of ischemic stroke in different vascular territories, suggesting cardiogenic embolism. Past history was significant for advanced-stage adenocarcinoma of the uterine cervix under chemoradiation treatment. On echocardiogram, vegetation at the aortic valve was observed. With the absence of evidence of infectious endocarditis, diagnosis of nonbacterial thrombotic endocarditis was made, and the patient was treated by long-term anticoagulant. This case is unique in terms of the adenocarcinoma cell type of cervical cancer, which is uncommon and has been rarely reported to be related to nonbacterial thrombotic endocarditis. [ABSTRACT FROM AUTHOR]

Background: Chulalongkorn Stroke Center is a comprehensive stroke center (CSC) located in Bangkok, Thailand. Our stroke network consists of different levels of spoke hospitals, ranging from community hospitals where thrombolytic treatment is not available, to those capable of onsite thrombolytic therapy. This study aimed to assess the time to treatment and outcomes among acute ischemic stroke patients who received thrombolytic treatment in the Chulalongkorn Stroke Network by 1.) Direct arrival at the CSC (mothership) 2.) Telestroke-assisted thrombolytic treatment with secondary transfer to the CSC (drip-and-ship) 3.) Referral from community hospital to the CSC for thrombolytic treatment (ship-and-drip).Methods: Acute ischemic stroke patients who received thrombolytic treatment during January 2016-December 2017 in the Chulalongkorn Stroke Network were studied. Time to treatment and clinical outcomes were compared among treatment groups.Results: There were 273 patients in the study including 147, 87, and 39 patients in mothership, drip-and-ship, and ship-and-drip paradigms, respectively. The door-to-needle-time (DTN) and onset-to-needle-time (OTN) times were significantly longest in ship-and-drip group (146.5 ± 62/205.03 ± 44.88 mins) compared to mothership (38 ± 23/155.2 ± 60.54 mins) and drip-and-ship (63.0 ± 44/166.09 ± 87 mins), P < 0.05. There was no significant difference regarding functional independence defined by modified Rankin Scale (mRS) ≤ 2 at 3 months (P = 0.12), in-hospital mortality (P = 0.37), mortality at 3 months (P = 0.73), and symptomatic intracerebral hemorrhage (P = 0.24) among groups.Conclusion: Thrombolytic treatment with drip and ship method under teleconsultation is feasible in Thailand. There was no difference of clinical outcome among the 3 treatment paradigms. However, DTN time and OTN time were longest in the ship-and-drip paradigm. [ABSTRACT FROM AUTHOR]

Concurrent acute ischemic stroke and acute myocardial infarction is an uncommon medical emergency condition. The challenge for the physicians regarding the management of this situation is paramount since early management of one condition will inevitably delay the other. We present two illustrative cases of "hyperacute simultaneous cardiocerebral infarction" who presented with simultaneous cardiocerebral infarction and arrived at the hospital within the thrombolytic therapeutic window for acute ischemic stroke of 4.5 h. We propose an algorithm for managing the patient with hyperacute simultaneous cardiocerebral infarction based on hemodynamic status and suggest close cardiac monitoring based on the site of cerebral infarction. [ABSTRACT FROM AUTHOR]

Background: Using movies has been accepted worldwide as a tool to help students learn medical professionalism. In the second year, a group of medical students conducted the “Cinemeducation” project to promote professionalism in the “Medical Ethics and Critical Thinking” course. Method: Five movies with professionalism issues were screened with 20-30 students attending each session. After the show, participants then were asked to reflect on what they had learned in terms of professionalism. Two students led group discussion emphasizing questioning and argumentation for 60 min. Additional learning issues emerging from each session were also explored in more depth and arranged into a report. Results: In the Cinemeducation Project, medical students have learned five main ethical issues in each film, which were the doctor-patient relationship, informed consent and clinical trials in patients, management of genetic disorders, patient management, and brain death and organ transplantation. In addition to issues of professionalism, they also developed critical thinking and moral reasoning skills. Conclusion: Using a case-based scenario in movies has proven to be an effective and entertaining method of facilitating students with learning on professionalism. [ABSTRACT FROM AUTHOR]

Background: Acute vertigo is a common presentation of inner ear disease. However, it can also be caused by more serious conditions, especially posterior circulation stroke. Differentiating between these two conditions by clinical presentations and imaging studies during the acute phase can be challenging. This study aimed to identify serum microRNA (miRNA) candidates that could differentiate between posterior circulation stroke and peripheral vertigo, among patients presenting with acute vertigo.Methods: Serum levels of six miRNAs including miR-125a-5p, miR-125b-5p, miR-143-3p, miR-342-3p, miR-376a-3p, and miR-433-5p were evaluated. Using quantitative reverse-transcription polymerase chain reaction (RT-qPCR), the serum miRNAs were assessed in the acute phase and at a 90 day follow-up visit.Results: A total of 58 patients with posterior circulation stroke (n = 23) and peripheral vertigo (n = 35) were included in the study. Serum miR-125a-5p (P = 0.001), miR-125b-5p (P <  0.001), miR-143-3p (P = 0.014) and miR-433-5p (P = 0.0056) were present at significantly higher levels in the acute phase, in the patients with posterior circulation infarction. Based on the area under the receiver operating characteristic curve (AUROC) only miR-125a-5p (0.75), miR-125b-5p(0.77), and miR-433-5p (0.71) had an acceptable discriminative ability to differentiate between the central and peripheral vertigo. A combination of miRNAs revealed no significant improvement of AUROC when compared to single miRNAs.Conclusion: This study demonstrated the potential of serum miR-125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to assist in the diagnosis of posterior circulation infarction among patients presenting with acute vertigo. [ABSTRACT FROM AUTHOR]