Background: and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. Methods: We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. Results: Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). Conclusion The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

The efficacy of endovascular treatment (EVT) in patients with posterior circulation stroke has not been proven. Two recent randomized controlled trials failed to show improved functional outcomes after EVT for posterior circulation stroke (PC-EVT). However, promising results for two additional randomized controlled trials have also been presented at a recent conference. Studies have shown that patients undergoing PC-EVT had a higher rate of futile recanalization than those undergoing EVT for anterior circulation stroke. These findings call for further identification of prognostic factors beyond recanalization. The significance of baseline clinical severity, infarct volume, collaterals, time metrics, core-penumbra mismatch, and methods to accurately measure these parameters are discussed. Furthermore, their interplay on EVT outcomes and the potential to individualize patient selection for PC-EVT are reviewed. We also discuss technical considerations for improving the treatment efficacy of PC-EVT.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background & Objective: Although the clinical manifestations and outcomes of lumbosacral plexopathy have been reported, the long-term outcomes are unclear. Therefore, we investigated clinical manifestations and long-term outcomes in patients with lumbosacral plexopathy in terms of the extent and etiology of the injury. Methods: We evaluated the clinical and electrodiagnostic data and outcomes of 23 patients with lumbosacral plexopathy in a retrospective longitudinal observational study. The enrolled subjects were divided into groups according to the etiology and extent of their injuries, and the clinical outcomes of each group 1 year after onset were investigated. Outcomes were classified as full recovery, able to walk, unable to walk, and follow-up loss. Results: The right lumbosacral plexus was involved in 11 patients, left lumbosacral plexus in 8, and both in 4. Among the 27 lumbosacral plexus lesions (4 patients had bilateral lesions), the upper lumbar plexus was involved in 6 cases, lower lumbosacral plexus in 12, and the entire lumbosacral plexus in 9. Thirteen cases arose from traumatic events, and the rest were non-traumatic. When the clinical outcomes of the groups were compared, non-traumatic cases had higher rates of full recovery than did traumatic cases. Those with lesions in the upper lumbar plexus had a higher rate of full recovery than the other groups. Conclusions: Non-traumatic etiology and upper lumbar plexus injury were associated with better outcomes. These results will be useful when planning treatment strategies and will increase our understanding of the prognosis for lumbosacral plexopathy

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203
Anisotropy ; Aspirin ; Atrophy ; Brain ; Cerebral Small Vessel Diseases ; Cognition ; Dementia ; Dementia, Vascular ; Diffusion Tensor Imaging ; Homeostasis ; Humans ; Korea ; Magnetic Resonance Imaging ; Outcome Assessment (Health Care) ; Perfusion ; Sample Size ; Stroke ; Stroke, Lacunar ; White Matter

Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS (10 µg/ml) in the presence or absence of a type 1 TACE inhibitor (1 µM) or type 2 TACE inhibitor (10 µM). LPS treatment induced increased serum creatinine, TNFα, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.
Acute Kidney Injury ; Angiotensins ; Animals ; Cell Survival ; Creatinine ; Cytokines ; Down-Regulation ; Epithelial Cells* ; Humans* ; Inflammation ; Kidney ; Lipocalins ; Mice ; Necrosis ; Neutrophils ; Oxidative Stress ; Protein Kinases* ; Reactive Oxygen Species* ; Receptor, Angiotensin, Type 1 ; Renin-Angiotensin System ; Tumor Necrosis Factor-alpha*

BACKGROUND AND OBJECTIVES: We assessed plaque erosion of culprit lesions in patients with acute coronary syndrome in real world practice. SUBJECTS AND METHODS: Culprit lesion plaque rupture or plaque erosion was diagnosed with optical coherence tomography (OCT). Intravascular ultrasound (IVUS) was used to determine arterial remodeling. Positive remodeling was defined as a remodeling index (lesion/reference EEM [external elastic membrane area) >1.05. RESULTS: A total of 90 patients who had plaque rupture showing fibrous-cap discontinuity and ruptured cavity were enrolled. 36 patients showed definite OCT-plaque erosion, while 7 patients had probable OCT-plaque erosion. Overall, 26% (11/43) of definite/probable plaque erosion had non-ST elevation myocardial infarction (NSTEMI) while 35% (15/43) had ST elevation myocardial infarction (STEMI). Conversely, 14.5% (13/90) of plaque rupture had NSTEMI while 71% (64/90) had STEMI (p<0.0001). Among plaque erosion, white thrombus was seen in 55.8% (24/43) of patients and red thrombus in 27.9% (12/43) of patients. Compared to plaque erosion, plaque rupture more often showed positive remodeling (p=0.003) with a larger necrotic core area examined by virtual histology (VH)-IVUS, while negative remodeling was prominent in plaque erosion. Overall, 65% 28/43 of plaque erosions were located in the proximal 30 mm of a culprit vessel-similar to plaque ruptures (72%, 65/90, p=0.29). CONCLUSION: Although most of plaque erosions show nearly normal coronary angiogram, modest plaque burden with negative remodeling and an uncommon fibroatheroma might be the nature of plaque erosion. Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion.
Acute Coronary Syndrome* ; Humans ; Membranes ; Myocardial Infarction ; Plaque, Atherosclerotic ; Rupture* ; Thrombosis ; Tomography, Optical Coherence ; Ultrasonography

BACKGROUND: The verbal fluency test consists of two separate tests of semantic fluency and phonemic fluency. The performance patterns of these tests differ with the type of dementia. We studied the patterns of verbal fluency between Alzheimer's disease (AD) and subcortical vascular dementia (SVaD), and assessed the clinical utility of these tests. METHODS: The 1,475 selected participants comprised 73 normal control subjects, 673 patients with amnestic mild cognitive impairment (aMCI), 535 AD patients, 42 patients with subcortical vascular mild cognitive impairment (svMCI), and 152 SVaD patients. We analyzed the z-score for the total number of animal items as a semantic fluency index and the z-score of the phonemic total score as a phonemic fluency index. RESULTS: The performance of semantic fluency was lower than that of phonemic fluency in all groups. The SVaD group showed the worst scores and abnormal performances on both tests, while the AD group presented abnormal performance only for semantic fluency. Dividing the patients with dementia according to severity revealed a different pattern between AD and SVaD for the clinical dementia rating (CDR) stage of 0.5. The performance of the AD group declined gradually with CDR. However, the SVaD group performed very poorly in both tests even for very mild dementia (CDR stage of 0.5). The aMCI and svMCI groups exhibited similar performance patterns. CONCLUSIONS: The pattern of semantic and phonemic fluency was not clinically useful at the MCI stage, but it could be helpful in differentiating AD and SVaD in the early stage of dementia.
Alzheimer Disease* ; Animals ; Dementia* ; Dementia, Vascular* ; Humans ; Mild Cognitive Impairment ; Semantics ; Task Performance and Analysis*

BACKGROUND AND PURPOSE: Patients with mild cognitive impairment (MCI) and their caregivers are concerned with the likelihood and time course of progression to dementia. This study was performed to identify the clinical predictors of the MCI progression in a Korean registry, and investigated the effects of medications without evidence, frequently prescribed in clinical practice. METHODS: Using a Korean cohort that included older adults with MCI who completed at least one follow-up visit, clinical characteristics and total medical expenses including prescribed medications were compared between two groups: progressed to dementia or not. Cox proportional hazards regression analysis was conducted. RESULTS: During the mean 1.42±0.72 years, 215 (27.63%) of 778 participants progressed to dementia. The best predictors were age [hazard ratio (HR), 1.036; 95% confidence interval (CI), 1.006–1.067; p=0.018], apolipoprotein ε4 allele (HR, 2.247; 95% CI, 1.512–3.337; p<0.001), Clinical Dementia Rating scale-sum of boxes scores (HR, 1.367; 95% CI, 1.143–1.636; p=0.001), Instrumental Activities of Daily Living scores (HR, 1.035; 95% CI, 1.003–1.067; p=0.029), and lower Mini-Mental State Examination scores (HR, 0.892; 95% CI, 0.839–0.949; p<0.001). Total medical expenses were not different. CONCLUSIONS: Our data are in accordance with previous reports about clinical predictors for the progression from MCI to dementia. Total medical expenses were not different between groups with and without progression.
Activities of Daily Living ; Adult ; Alleles ; Apolipoproteins ; Caregivers ; Cholinesterase Inhibitors ; Cohort Studies* ; Dementia ; Follow-Up Studies ; Humans ; Mild Cognitive Impairment*