Ultrasensitive and Rapid Circulating Tumor DNA Liquid Biopsy Using Surface-Confined Gene Amplification on Dispersible Magnetic Nano-Electrodes.

Circulating tumor DNA (ctDNA) detection has been acknowledged as a promising liquid biopsy approach for cancer diagnosis, with various ctDNA assays used for early detection and treatment monitoring. Dispersible magnetic nanoparticle-based electrochemical detection methods have been proposed as promising candidates for ctDNA detection based on the detection performance and features of the platform material. This study proposes a nanoparticle surface-localized genetic amplification approach by integrating Fe3O4-Au core-shell nanoparticles into polymerase chain reactions (PCR). These highly dispersible and magnetically responsive superparamagnetic nanoparticles act as nano-electrodes that amplify and accumulate target ctDNA in situ on the nanoparticle surface upon PCR amplification. These nanoparticles are subsequently captured and subjected to repetitive electrochemical measurements to induce reconfiguration-mediated signal amplification for ultrasensitive (∼3 aM) and rapid (∼7 min) metastatic breast cancer ctDNA detection in vitro. The detection platform can also detect metastatic biomarkers from in vivo samples, highlighting the potential for clinical applications and further expansion to rapid and ultrasensitive multiplex detection of various cancers.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

U-shaped associations between glycated albumin and obesity and role of IL-10 in hyperacute ischemic stroke.

OBJECTIVE: There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). MATERIALS AND METHODS: We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1ß, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. RESULTS: The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). CONCLUSION: GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations.

Self-organized insulin-producing ß-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potential.

BACKGROUND: Human omentum-derived mesenchymal stem cells (hO-MSCs) possess great potential to differentiate into multiple lineages and have self-renewal capacity, allowing them to be utilized as patient-specific cell-based therapeutics. Although the use of various stem cell-derived ß-cells has been proposed as a novel approach for treating diabetes mellitus, developing an efficient method to establish highly functional ß-cells remains challenging. METHODS: We aimed to develop a novel cell culture platform that utilizes a fibroblast growth factor 2 (FGF2)-immobilized matrix to regulate the adhesion and differentiation of hO-MSCs into insulin-producing ß-cells via cell-matrix/cell-cell interactions. In our study, we evaluated the in vitro differentiation potential of hO-MSCs cultured on an FGF2-immobilized matrix and a round-bottom plate (RBP). Further, the in vivo therapeutic efficacy of the ß-cells transplanted into kidney capsules was evaluated using animal models with streptozotocin (STZ)-induced diabetes. RESULTS: Our findings demonstrated that cells cultured on an FGF2-immobilized matrix could self-organize into insulin-producing ß-cell progenitors, as evident from the upregulation of pancreatic ß-cell-specific markers (PDX-1, Insulin, and Glut-2). Moreover, we observed significant upregulation of heparan sulfate proteoglycan, gap junction proteins (Cx36 and Cx43), and cell adhesion molecules (E-cadherin and Ncam1) in cells cultured on the FGF2-immobilized matrix. In addition, in vivo transplantation of differentiated ß-cells into animal models of STZ-induced diabetes revealed their survival and engraftment as well as glucose-sensitive production of insulin within the host microenvironment, at over 4 weeks after transplantation. CONCLUSIONS: Our findings suggest that the FGF2-immobilized matrix can support initial cell adhesion, maturation, and glucose-stimulated insulin secretion within the host microenvironment. Such a cell culture platform can offer novel strategies to obtain functional pancreatic ß-cells from patient-specific cell sources, ultimately enabling better treatment for diabetes mellitus.

Association of non-sustained atrial tachycardia and its duration in 24-h Holter monitoring with embolic stroke of unknown source.

BACKGROUND AND PURPOSE: Although supraventricular ectopic beats (SVE), including premature atrial contractions (PACs) and non-sustained atrial tachycardia (NSAT), are frequent in the general population, some study results indicate that they are pathologic. SVE may predict undiagnosed atrial fibrillation or be associated with the embolic pattern of ischemic stroke. The aim of this study was to identify the indicators most associated with embolic stroke among the parameters that suggest the burden of SVE. METHODS: A total of 1920 consecutive acute ischemic stroke (AIS) patients were enrolled from two university hospitals. We defined embolic stroke of unknown source (ESUS) and small vessel occlusion (SVO) etiologies using stricter criteria than the existing conventional criteria. RESULTS: We enrolled 426 (SVO: 310 vs. ESUS: 116) patients who met the inclusion criteria. In the 24-h Holter monitoring parameters, total number of PACs and PAC-to-total beat ratio were not significantly different between the two groups. However, NSATs were more frequent, and the duration of the longest NSAT was longer in the ESUS group. Multivariate logistic regression revealed that high brain natriuretic peptide levels, presence of NSAT, history of previous stroke, and the longest NSAT duration significantly correlated with the ESUS etiology. CONCLUSION: The presence of NSAT and its duration are more important indicators of embolic stroke than the frequency of PACs is. Therefore, considering secondary prevention in AIS patients with ESUS, 24-h Holter monitoring parameters, such as the presence of NSAT and its duration, could be considered as potential sources of cardio-embolism.

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

BACKGROUND: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. AIMS: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. METHODS: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. RESULTS: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. CONCLUSION: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Multifunctional Nanoparticle Platform for Surface Accumulative Nucleic Acid Amplification and Rapid Electrochemical Detection: An Application to Pathogenic Coronavirus.

Of various molecular diagnostic assays, the real-time reverse transcription polymerase chain reaction is considered the gold standard for infection diagnosis, despite critical drawbacks that limit rapid detection and accessibility. To confront these issues, several nanoparticle-based molecular detection methods have been developed to a great extent, but still possess several challenges. In this study, a novel nucleic acid amplification method termed nanoparticle-based surface localized amplification (nSLAM) is paired with electrochemical detection (ECD) to develop a nucleic acid biosensor platform that overcomes these limitations. The system uses primer-functionalized Fe3O4-Au core-shell nanoparticles for nucleic acid amplification, which promotes the production of amplicons that accumulate on the nanoparticle surfaces, inducing significantly amplified currents during ECD that identify the presence of target genetic material. The platform, applying to the COVID-19 model, demonstrates an exceptional sensitivity of ∼1 copy/µL for 35 cycles of amplification, enabling the reduction of amplification cycles to 4 cycles (∼7 min runtime) using 1 fM complementary DNA. The nSLAM acts as an accelerator that actively promotes and participates in the nucleic acid amplification process through direct polymerization and binding of amplicons on the nanoparticle surfaces. This ultrasensitive fast-response system is a promising method for detecting emerging pathogens like the coronavirus and can be extended to detect a wider variety of biomolecules.

The usefulness of global longitudinal peak strain and left atrial volume index in predicting atrial fibrillation in patients with ischemic stroke.

Introduction: Detection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke. Methods: We prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI). Results: The mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P < 0.001) and a higher GLPS than those without AF (-14.0 vs. -17.3, P < 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, -14.6 vs. -18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03). Discussion: The LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.

Genotype and Phenotype Differences in CADASIL from an Asian Perspective.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2-6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.

Rapid and concise quantification of mycelial growth by microscopic image intensity model and application to mass cultivation of fungi.

The microbial food fermentation industry requires real-time monitoring and accurate quantification of cells. However, filamentous fungi are difficult to quantify as they have complex cell types such as pellet, spores, and dispersed hyphae. In this study, numerous data of microscopic image intensity (MII) were used to develop a simple and accurate quantification method of Cordyceps mycelium. The dry cell weight (DCW) of the sample collected during the fermentation was measured. In addition, the intensity values were obtained through the ImageJ program after converting the microscopic images. The prediction model obtained by analyzing the correlation between MII and DCW was evaluated through a simple linear regression method and found to be statistically significant (R2 = 0.941, p < 0.001). In addition, validation with randomly selected samples showed significant accuracy, thus, this model is expected to be used as a valuable tool for predicting and quantifying fungal growth in various industries.

M13 Virus Triboelectricity and Energy Harvesting.

Triboelectrification is a phenomenon that generates electric potential upon contact. Here, we report a viral particle capable of generating triboelectric potential. M13 bacteriophage is exploited to fabricate precisely defined chemical and physical structures. By genetically engineering the charged structures, we observe that more negatively charged phages can generate higher triboelectric potentials and can diffuse the electric charges faster than less negatively charged phages can. The computational results show that the glutamate-engineered phages lower the LUMO energy level so that they can easily accept electrons from other materials upon contact. A phage-based triboelectric nanogenerator is fabricated and it could produce ∼76 V and ∼5.1 µA, enough to power 30 light-emitting diodes upon a mechanical force application. Our biotechnological approach will be useful to understand the electrical behavior of biomaterials, harvest mechanical energy, and provide a novel modality to detect desired viruses in the future.

Differential effects of body mass index on domain-specific cognitive outcomes after stroke.

Although the obesity paradox is an important modifiable factor in cardiovascular diseases, little research has been conducted to determine how it affects post-stroke cognitive function. We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive outcomes, focusing on the subdivision of each frontal domain function in post-ischemic stroke survivors. A total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini Mental Status Examination (K-MMSE) and the vascular cognitive impairment harmonization standards neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonemic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles. The z-scores of K-MMSE at 3 months differed significantly between the groups after adjustment for initial stroke severity (p = 0.014). Global cognitive function in stroke survivors in the Q1 (the lowest quartile) BMI group was significantly lower than those in Q2 and Q4 (the highest quartile) BMI groups (K-MMSE z-scores, Q1: - 2.10 ± 3.40 vs. Q2: 0.71 ± 1.95 and Q4: - 1.21 ± 1.65). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.016 and p = 0.023 respectively). BMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.

Reversible Cerebral Vasoconstriction Syndrome Associated with Levonorgestrel-Releasing Intrauterine System.

Reversible cerebral vasoconstriction syndromes (RCVS) is a rare disease that is characterized by reversible multifocal stenosis of the cerebral arteries with various clinical manifestations. Though the pathomechanism of RCVS was unclear, we reported RCVS related to the levonorgestrel-releasing intrauterine system (IUS). A previous healthy 36-year-old woman had thunderclap headache after implanting the levonorgestrel-releasing IUS a year ago. In the serial angiography, we initially found left vertebra artery (VA), and then additionally new stenosis of both anterior cerebral arteries and middle cerebral arteries (MCA). Bilateral MCA stenosis improved but developed stenosis of right VA after a week. The mean flow velocities of both MCA increased in the first transcranial doppler (TCD), but normalized in the follow up TCD. Levonorgestrel might act as the vasoconstrictitve factor that increased the level of endothelin-1, diminished the release of NO and raised oxidative low-density lipoprotein (LDL). Although the exact pathological mechanisms for RCVS were not yet elucidated, this case might help clinicians understand the mechanisms of RCVS.

Effects of Glycemic Gap on Post-Stroke Cognitive Impairment in Acute Ischemic Stroke Patients.

BACKGROUND: Post-stroke hyperglycemia is a frequent finding in acute ischemic stroke patients and is associated with poor functional and cognitive outcomes. However, it is unclear as to whether the glycemic gap between the admission glucose and HbA1c-derived estimated average glucose (eAG) is associated with post-stroke cognitive impairment (PSCI). METHODS: We enrolled acute ischemic stroke patients whose cognitive functions were evaluated three months after a stroke using the Korean version of the vascular cognitive impairment harmonization standards neuropsychological protocol (K-VCIHS-NP). The development of PSCI was defined as having z-scores of less than -2 standard deviations in at least one cognitive domain. The participants were categorized into three groups according to the glycemic gap status: non-elevated (initial glucose - eAG ≤ 0 mg/dL), mildly elevated (0 mg/dL < initial glucose - eAG < 50 mg/dL), and severely elevated (50 mg/dL ≤ initial glucose - eAG). RESULTS: A total of 301 patients were enrolled. The mean age was 63.1 years, and the median National Institute of Health Stroke Scale (NIHSS) score was two (IQR: 1-4). In total, 65 patients (21.6%) developed PSCI. In multiple logistic regression analyses, the severely elevated glycemic gap was a significant predictor for PSCI after adjusting for age, sex, education level, initial stroke severity, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and left hemispheric lesion (aOR: 3.65, p-value = 0.001). Patients in the severely elevated glycemic gap group showed significantly worse performance in the frontal and memory domains. CONCLUSIONS: In conclusion, our study demonstrated that an elevated glycemic gap was significantly associated with PSCI three months after a stroke, with preferential involvement of frontal and memory domain dysfunctions.

Association between Geriatric Nutritional Risk Index and Post-Stroke Cognitive Outcomes.

BACKGROUND: It is not yet clear whether nutritional status is associated with post-stroke cognitive impairment (PSCI). We examined the geriatric nutritional risk index (GNRI) on the domain-specific cognitive outcomes 3 months after a stroke. METHODS: A total of 344 patients with acute ischemic stroke were included for the analysis. The GNRI was calculated as 1.489 × serum albumin (g/L) + 41.7 × admission weight (kg)/ideal body weight (kg) and was dichotomized according to the prespecified cut-off points for no risk and any risks. The primary outcome was PSCI, defined as having adjusted z-scores of less than -2 standard deviations in at least one cognitive domain: executive/activation, memory, visuospatial and language. Multiple logistic regression and linear regression analyses were performed to investigate the association between the GNRI and cognitive outcomes. RESULTS: Seventy (20.3%) patients developed PSCI 3 months after a stroke. The mean GNRI was 106.1 ± 8.6, and 59 (17.2%) patients had low (<98) GNRI scores. A low GNRI was independently associated with the PSCI after adjusting for age, sex, education, initial stroke severity, stroke mechanism and left hemispheric lesion (odds ratio, 2.04; 95% confidence interval, 1.00-4.14). The GNRI scores were also significantly associated with the z-scores from the mini-mental status examination and the frontal domain (ß = 0.04, p-value = 0.03; ß = 0.03, p-value = 0.03, respectively). CONCLUSIONS: A low GNRI was independently associated with the development of PSCI at 3 months after an ischemic stroke. The GNRI scores were specifically associated with the z-scores of the global cognition and frontal domain cognitive outcomes.

Blood pressure variability is related to faster cognitive decline in ischemic stroke patients: PICASSO subanalysis.

Blood pressure variability (BPV) is associated with higher cardiovascular morbidity risks; however, its association with cognitive decline remains unclear. We investigated whether higher BPV is associated with faster declines in cognitive function in ischemic stroke (IS) patients. Cognitive function was evaluated between April 2010 and August 2015 using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment in 1,240 Korean PICASSO participants. Patients for whom baseline and follow-up cognitive test results and at least five valid BP readings were available were included. A restricted maximum likelihood-based Mixed Model for Repeated Measures was used to compare changes in cognitive function over time. Among a total of 746 participants (64.6 ± 10.8 years; 35.9% female). Baseline mean-MMSE score was 24.9 ± 4.7. The median number of BP readings was 11. During a mean follow-up of 2.6 years, mean baseline and last follow-up MMSE scores were 25.4 ± 4.8 vs. 27.8 ± 4.4 (the lowest BPV group) and 23.9 ± 5.2 vs. 23.2 ± 5.9 (the highest BPV group). After adjusting for multiple variables, higher BPV was independently associated with faster cognitive decline over time. However, no significant intergroup difference in cognitive changes associated with mean systolic BP was observed. Further research is needed to elucidate how BPV might affect cognitive function.

Effect of molecular structure on phase transition behavior of rice starch with different amylose contents.

Phase transition behaviors in starch-water system and molecular structures of rice starches isolated from four Korean cultivars with different amylose contents were investigated and the importance of structural features affecting starch phase transitions was also explored. The Dodam starch with the highest average chain length of amylopectin (26.1), the highest proportion (24.3 %) of long chains (DP ≥ 37), and the lowest proportion (17.5 %) of short chains (DP 6-12) displayed the highest gelatinization and retrogradation temperatures. Enthalpies of ice freezing and melting, and glass transition temperature (Tg') of rice starches increased with increasing amylose content and decreasing proportion of short amylopectin chains because these structural features are related to a higher thermal stability of the starches. Ice melting temperature was also influenced by amylopectin chain structures. The results suggest that the phase transition behaviors of rice starches were highly influenced by their amylose content and amylopectin chain length distribution.

Personalized Consideration of Admission-Glucose Gap between Estimated Average and Initial Glucose Levels on Short-Term Stroke Outcome.

BACKGROUND: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term functional outcomes in acute ischemic stroke (AIS). METHODS: We enrolled patients with AIS or transient ischemic attack who had been admitted within 7 days of symptom onset to three stroke centers from May 2016 to December 2019. The admission-glucose gap between estimated average glucose levels (eAG) and initial glucose level (eAG-initial glucose) was categorized into four groups. The short-term functional outcome was evaluated using the modified Rankin Scale (mRS) score at 3 months after stroke onset and was dichotomized. RESULTS: Among 1332 included subjects, 548 (41.1%) had poor short-term functional outcomes. After adjusting for multiple variables, a severe negative glucose gap (eAG-initial glucose ≤ -50 mg/dL) was significantly associated with poor short-term functional outcome (OR, 1.573; 95% CI, 1.101-2.248). After dichotomizing glycemic control status, its significance was only maintained in the good glycemic control group (HbA1c < 6.5%) (OR, 1.914; 95% CI, 1.155-3.169). CONCLUSIONS: An elevated admission-glucose gap, in which the initial glucose level was much higher than the estimated glucose level was based on HbA1c, was associated with poor stroke prognosis. In addition to admission-glucose levels, glycemic control status at the time of stroke onset should be considered when predicting short-term stroke outcomes.

Cilostazol versus aspirin in ischemic stroke with cerebral microbleeds versus prior intracerebral hemorrhage.

BACKGROUND: In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect. AIMS: We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage). METHODS: In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death. RESULTS: Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01-0.60]; p = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52-4.90]; p = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant (pinteraction = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41-1.01]; p = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63-1.67]; p = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction (pinteraction = 0.165). CONCLUSIONS: Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed. CLINICAL TRIAL REGISTRATION: URL:http://www.clinicaltrials.gov. NCT01013532.