Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

NOTCH2NLC GGC Repeat Expansion in Patients With Vascular Leukoencephalopathy.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID), caused by GGC (guanine-guanine-cytosine) repeat expansion in NOTCH2NLC, has several clinical and radiological features akin to cerebral small vessel disease (cSVD). The present study tested the hypothesis that NOTCH2NLC GGC expansion may contribute to cSVD. METHODS: One hundred and ninety-seven unrelated patients with genetically unsolved vascular leukoencephalopathy without NOTCH3, HTRA1, and mitochondrial m.3243A>G mutations and 730 healthy individuals were screened for NOTCH2NLC GGC repeat expansion using repeat-primed polymerase chain reaction, fragment analysis, Southern blot analysis, or nanopore sequencing with Cas9 (CRISPR associated protein 9)-mediated enrichment. The clinical and neuroimaging features of the patients were compared between individuals with and without NOTCH2NLC GGC repeat expansion. RESULTS: Six of the 197 (3.0%) patients with unsolved vascular leukoencephalopathy and none of the controls carried the GGC repeat expansion (P=0.00009). Skin biopsy of 1 patient revealed eosinophilic, ubiquitin-positive, and p62-positive intranuclear inclusions in the cells of sweat gland and capillary, providing pathologic evidence for the involvement of small vessels in NIID. For the 6 patients, gait disturbance and cognitive decline were common manifestations with a median onset age of 65 (59-69) years. They all had multiple neuroimaging features suggestive of cSVD, including diffuse white matter hyperintensities, lacunes, and enlarged perivascular space in all 6 patients, cerebral microbleeds in 5, and old intracerebral hemorrhage in 4. Four patients had linear hyperintensity in the corticomedullary junction on diffusion-weighted imaging-the characteristic neuroimaging feature of NIID. There was no difference in the severity of cSVD imaging features between the patients with and without the GGC expansion but more pronounced brain atrophy in the patients with the GGC expansion. CONCLUSIONS: NOTCH2NLC GGC repeat expansion accounted for 3% of genetically unsolved Taiwanese vascular leukoencephalopathy cases after excluding participants with cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). NIID should be considered in patients manifesting cSVD, especially in those with characteristic neuroimaging feature of NIID.

Patient and hospital characteristics associated with do-not-resuscitate/do-not-intubate orders: a cross-sectional study based on the Taiwan stroke registry.

BACKGROUND: Previous studies of do-not-resuscitate (DNR) or do-not-intubate (DNI) orders in stroke patients have primarily been conducted in North America or Europe. However, characteristics associated with DNR/DNI orders in stroke patients in Asia have not been reported. METHODS: Based on the Taiwan Stroke Registry, this nationwide cross-sectional study enrolled hospitalized stroke patients from 64 hospitals between 2006 and 2020. We identified characteristics associated with DNR/DNI orders using a two-level random effects model. RESULTS: Among the 114,825 patients, 5531 (4.82%) had DNR/DNI orders. Patients with acute ischemic stroke (AIS) had the highest likelihood of having DNR/DNI orders (adjusted odds ratio [aOR] 1.76, 95% confidence interval [CI] 1.61-1.93), followed by patients with intracerebral hemorrhage (ICH), and patients with subarachnoid hemorrhage (SAH) had the lowest likelihood (aOR 0.53, 95% CI 0.43-0.66). From 2006 to 2020, DNR/DNI orders increased in all three types of stroke. In patients with AIS, women were significantly more likely to have DNR/DNI orders (aOR 1.23, 95% CI 1.15-1.32), while patients who received intravenous alteplase had a lower likelihood (aOR 0.74, 95% CI 0.65-0.84). Patients with AIS who were cared for by religious hospitals (aOR 0.55, 95% CI 0.35-0.87) and patients with SAH who were cared for by medical centers (aOR 0.40, 95% CI 0.17-0.96) were significantly less likely to have DNR/DNI orders. CONCLUSIONS: In Taiwan, DNR/DNI orders increased in stroke patients between 2006 and 2020. Hospital characteristics were found to play a significant role in the use of DNR/DNI orders.

Incomplete Recovery from the Radiocontrast-Induced Dysregulated Cell Cycle, Adhesion, and Fibrogenesis in Renal Tubular Cells after Radiocontrast (Iohexol) Removal.

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-ß1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

Function-based dementia severity assessment for vascular cognitive impairment.

BACKGROUND/PURPOSES: Unimpaired activities of daily living (ADL) is essential for the diagnosis of normal cognition and mild cognitive impairment. However, diagnosis according to this concept is difficult to apply to patients comorbid with motor dysfunction. We aim to use a novel ADL questionnaire for operationally diagnosing unimpaired ADL in vascular cognitive impairment with no dementia (VCIND). METHODS AND PARTICIPANTS: This was a retrospective cohort study with both cross-sectional and long-term follow-up analysis. Patients with cerebrovascular disease with normal cognition (CVDNC), VCIND, and vascular dementia (VaD) were analyzed. Cutoff scores for differentiating different stages of cognitive impairment were compared between the new History-based Artificial Intelligent ADL questionnaire (HAI-ADL) and other tools. RESULTS: A total of 596 individuals were analyzed, including 40 CVDNC, 167 VCIND, 218 mild, 119 moderate, and 52 severe-dementia patients. The cutoff scores for determining unimpaired ADL in VCIND were 8.5, 3.5, 5, 100, and 60 in HAI-ADL, CDR-SB, IADL, BI, and CASI, respectively. HAI-ADL had the highest correlations with CDR-SB and the CDR staging system compared to other tools. Four models of progression rates from CVDNC/VCIND to VaD revealed it was much higher in the group with HAI-ADL > 8.5 compared to those with HAI-ADL≦8.5 with odds ratios of 3.75, 3.66, 3.31, and 2.77, respectively. CONCLUSION: Our study showed that HAI-ADL provides an operational determinates unimpaired ADL which is necessary for the diagnosis of VCIND. The predictive value for progression to dementia was proved by a long-term follow-up analysis of the research cohort.

Utility of apolipoprotein measurements in predicting incident type 2 diabetes: A Chinese cohort study.

BACKGROUND/PURPOSE: There is conflicting data regarding the utility of measuring apolipoproteins in addition to traditional lipid measures in risk assessment of cardiometabolic diseases. The aim of this study was to determine whether apolipoprotein measurements can improve the ability to predict the future development of type 2 diabetes beyond what is possible based on traditional type 2 diabetes risk factors and clinical routine lipid measurements. METHODS: A total of 4,223 Chinese adults without diabetes were followed for a mean duration of 5.42 years. The hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to analyze the longitudinal associations of apolipoprotein B (apo B), apolipoprotein A-I (apo A-I), and the apo B/apo A-I ratio with the risk of type 2 diabetes. Further, the analysis of the area under receiver operating characteristics curves (AUC) was performed to test the predictive value of apolipoprotein measurements. RESULTS: After adjusting for potential confounders, the HRs of diabetes consistently showed an increasing trend across both the apo B and the apo B/apo A-I ratio quartiles (p for trend = 0.004). In analyses of AUC, the predictive ability for type 2 diabetes risk for the apo B and the apo B/apo A-I ratio was superior to that of routine lipid and lipoprotein measurements. CONCLUSION: Apolipoprotein measurements significantly predict diabetes risk in an Asian population. Furthermore, the predictive ability of apo B alone to detect diabetes was comparable with that of the apo B/apo A-I ratio and better than the routine lipid measurements.

Reduced risk of stroke following cholecystectomy: A nationwide population-based study.

BACKGROUND AND AIM: Gallstones and stroke are common diseases worldwide. The relationship between gallstones and stroke has been documented in the literature. In this work, to characterize the risk of stroke among gallstone patients with and without cholecystectomy, we investigated the effects of cholecystectomy in a nationwide population-based retrospective cohort study. METHODS: Data were obtained from Taiwan's National Health Insurance Research Database. The study comprised 155 356 gallstone patients divided into two groups: those with and without cholecystectomy. RESULTS: During the study period (2000-2012), 19 096 (17.8/1000 person-years) gallstone patients without cholecystectomy and 11 913 (10.6/1000 person-years) gallstone patients with cholecystectomy had a stroke. Following gallstone removal, the patients exhibited a significant decrease in the risk of overall stroke (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.59-0.61), ischemic stroke (HR = 0.59, 95% CI = 0.58-0.61), and hemorrhagic stroke (HR = 0.56, 95% CI = 0.53-0.59). Asymptomatic and symptomatic gallstone patients had lower overall stroke risk after cholecystectomy (HR = 0.64, 95% CI = 0.62-0.67 and HR = 0.57, 95% CI = 0.56-0.59) than did asymptomatic gallstone patients without cholecystectomy. CONCLUSIONS: This population-based cohort study demonstrated that cholecystectomy is related to reduce the risk of overall stroke, ischemic stroke, and hemorrhagic stroke. Preventive measures for stroke may be considered for gallstone patients, particularly those presenting risk factor(s) for stroke.

An Informant-Based Simple Questionnaire for Language Assessment in Neurodegenerative Disorders.

BACKGROUND/AIMS: Language dysfunction is a crucial feature of brain disorders. This study investigated language dysfunction in patients with dementia with or without parkinsonism by using an informant-based simple questionnaire. METHODS: Language dysfunction in normal controls (NCs), and patients with Parkinson disease (PD), Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), or Alzheimer disease (AD) were analyzed and compared. RESULTS: A total of 1,662 individuals were studied: 285 NCs, 157 PD patients, 161 PDD patients, 248 DLB patients, and 811 AD patients. Patients with PD displayed higher frequency of language dysfunction in several language domains than NC. Patients with PDD and DLB showed higher frequency of language dysfunction in most of the language domains than those with AD. A composite score of our simple questionnaire was comparable with the score for the language domain of the Cognitive Abilities Screening Instrument (CASI) in different stages of dementia due to Lewy body diseases or not. CONCLUSION: Our study showed that the informant-based simple questionnaire is a practical screening tool and is comparable with the language subscale of CASI. This tool can be applied in clinical practice and in the registration platform for rapid language dysfunction screening.

Gender difference in the association and presentation of visual hallucinations in dementia with Lewy bodies: a cross-sectional study.

OBJECTIVE: Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). We investigated gender differences in the association and presentation of VHs in DLB. METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on dementia was performed. Cumulative frequency, 1-month frequency, and phenomenology of VHs were summarized and compared between female and male patients with DLB. Gender differences in the factors associated with VHs were investigated in patients with and without hallucinations. RESULTS: A total of 152 patients including 65 (42.8%) women and 87 (57.2%) men were analyzed. The cumulative and 1-month frequencies of VHs were 60% and 55.4%, respectively, in women and 44.8% and 41.4%, respectively, in men. Adjusting for age and disease severity resulted in the inclusion of more women in the VH group [odds ratio (OR) = 2.33, p = 0.028)] than in the non-VH group. In female participants, older age (OR = 9.16, p = 0.003) and higher neuropsychiatric inventory score (OR = 4.89, p = 0.009) were associated with VHs, whereas in male participants, more severe dementia stage (clinical dementia rating 2-3 versus clinical dementia rating 0.5, OR = 6.22, p = 0.008) and higher rates of using antipsychotics (OR = 9.64, p = 0.047) were associated with VHs. CONCLUSION: The frequencies of 1-month and cumulative VHs were high in DLB, which indicated a high prevalence as well as a high persistency of VHs in DLB. The patterns of factors associated with VHs differed between female and male patients. Copyright © 2017 John Wiley & Sons, Ltd.

Protective effect of wogonin on endotoxin-induced acute lung injury via reduction of p38 MAPK and JNK phosphorylation.

Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017.

Gallstone disease and the risk of stroke: a nationwide population-based study.

BACKGROUND: Gallstone disease (GD) and stroke share a number of risk factors including diabetes and hyperlipidemia. This nationwide population-based study was designed to estimate the risk of stroke after a diagnosis of GD. METHODS: Data were obtained from the Taiwan National Health Insurance Research Database. A total of 135,512 patients with a diagnosis of GD and 271,024 age- and gender-matched non-GD control patients were included to assess the risk of stroke using Cox proportional hazard regression. RESULTS: During the study period (2000-2003), 12,234 (153.67/10,000 person-years) strokes occurred among the GD patients, and 20,680 (114.83/10,000 person-years) among the controls. The diagnosis of GD carried a higher risk of developing ischemic and hemorrhagic stroke, with a hazard ratio (HR) of 1.28 and 1.33 (95% confidence interval [CI], 1.25-1.31 and 1.25-1.41, both P < .0001), respectively. Stroke risk was increased in both genders but at a higher rate in younger age. The GD group had significantly higher prevalence rate of comorbidities that are known stroke risk factors, including hypertension, diabetes, and coronary artery disease. Stroke risk was higher in the GD group with or without any of these comorbidities. CONCLUSIONS: In this population-based longitudinal follow-up study, GD carried a significantly higher stroke risk, particularly for younger age with or without stroke risk factors. Stroke preventive measures maybe needed for patients with GD, especially those of younger age and with stroke risk factor(s).

The effect of different patient education methods on quality of bowel cleanliness in outpatients receiving colonoscopy examination.

AIMS: To investigate the effectiveness of an educational film intervention on the quality of bowel cleanliness of outpatients receiving colonoscopy examinations and also to understand the related factors affecting bowel cleanliness. METHOD: This is a quasi-experimental design. One hundred four patients in the experimental group and 114 patients in the control group are the participants in this study. An 8-minute "Preparation for Bowel Cleanliness" educational film was made based on clinical experience and references to related literature. We adopted a valid Aronchick scale evaluate bowel cleanliness. RESULTS: The patients in the experimental group had significantly better bowel cleanliness compared to the control group (80.8% vs. 48.2%, p<.001). Logistic regression showed that the experimental group, gender, and experience with colonoscopy were potentially important factors that may affect bowel cleanliness. CONCLUSIONS: The "Preparation for Bowel Cleanliness" educational film provides simple and easy-to-follow methods for the preparation of cleaning the colon and related information.

Predicting ischemic stroke patients' prognosis changes using machine learning in a nationwide stroke registry.

Accurately predicting the prognosis of ischemic stroke patients after discharge is crucial for physicians to plan for long-term health care. Although previous studies have demonstrated that machine learning (ML) shows reasonably accurate stroke outcome predictions with limited datasets, to identify specific clinical features associated with prognosis changes after stroke that could aid physicians and patients in devising improved recovery care plans have been challenging. This study aimed to overcome these gaps by utilizing a large national stroke registry database to assess various prediction models that estimate how patients' prognosis changes over time with associated clinical factors. To properly evaluate the best predictive approaches currently available and avoid prejudice, this study employed three different prognosis prediction models including a statistical logistic regression model, commonly used clinical-based scores, and a latest high-performance ML-based XGBoost model. The study revealed that the XGBoost model outperformed other two traditional models, achieving an AUROC of 0.929 in predicting the prognosis changes of stroke patients followed for 3 months. In addition, the XGBoost model maintained remarkably high precision even when using only selected 20 most relevant clinical features compared to full clinical datasets used in the study. These selected features closely correlated with significant changes in clinical outcomes for stroke patients and showed to be effective for predicting prognosis changes after discharge, allowing physicians to make optimal decisions regarding their patients' recovery.

Association between exposure to particulate matter and incidence of Parkinson's disease: A nationwide cohort study in Taiwan.

Objective: Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson's disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide. Methods: We utilized data from the Taiwan National Health Insurance Research Database, which was spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1st, 2005) until the occurrence of PD or the end of the study period (December 31st, 2017). Participants who had a prior diagnosis of PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD, we employed a Cox regression to estimate the hazard ratio with a 95% confidence interval (CI). Results: A total of 454,583 participants were included, with a mean (SD) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20-1.23) per interquartile range increase in exposure (10.17 µg/m3) when adjusting for both SO2 and NO2. Conclusion: We provide further evidence of an association between PM2.5 exposure and risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Onset headache predicts good outcome in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke. METHODS: A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache. RESULTS: Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52-0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus -0.20; P=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28-2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72-0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups. CONCLUSIONS: By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.

Minimal amount of exercise prevents incident dementia in cognitively normal older adults with osteoarthritis: a retrospective longitudinal follow-up study.

Robust evidence suggests that regular exercise, including walking more than 6000 steps, is effective for preventing dementia; however, such activity is less feasible in older people with osteoarthritis (OA) or other motor disabilities. Therefore, we aimed to test whether the minimal amount of exercise (MAE) could help prevent dementia in older adults with OA. A retrospective longitudinal study was performed and a non-demented cohort (≥ 50-years-old) of 242 people (155 [64.0%] non-converters and 87 [36.0%] converters) from three centers in Taiwan was analyzed with a mean follow-up of 3.1 (range 0.3-5.9) and 2.9 (range 0.5-6.0) years, respectively. MAE was defined as walking for approximately 15-30 min or 1500-3000 steps. Rate of MAE (0, 1-2, or ≥ 3) within one week were defined as MAE-no, MAE-weekly, or MAE-daily, respectively. The incidence rates of dementia were compared between groups. Multivariate logistic regression and Cox proportional hazards analyses were used to study the influence of MAE on dementia occurrence. Age, education, sex, activities of daily living, neuropsychiatric symptoms, cognition, multiple vascular risk factors, and related medications were adjusted. Compared to the MAE-no group, the odds ratios for the incidents of dementia were 0.48 and 0.19 in the MAE-weekly and MAE-daily groups, respectively. In addition, older age, poorer cognition, poorer ADL performance, and congestive heart failure increased the incidence of dementia. Daily and weekly MAE prevented dementia in older adults with OA. As such, an informative public health policy may help promote adequate exercise in at-risk groups.

Cholesterol Paradox in Older People with Type 2 Diabetes Mellitus Regardless of Lipid-Lowering Drug Use: A Cross-Sectional Cohort Study.

Lipid-lowering drugs (LLDs) have protective effects against coronary artery disease (CAD) and cerebrovascular disease (CVD); however, a paradoxical association with cholesterol has been identified in several diseases, such as diabetes, dementia, and atrial fibrillation. We aimed to analyze the association between LLDs and cholesterol levels in older adults with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled consecutive patients aged ≥50 years from three centers in Taiwan. A multiple logistic regression model was used, and odds ratios (ORs) for different levels of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) compared with the highest level were adjusted for age, triglyceride level, sex, comorbidities, and medications. Among the 3688 participants, 572 with and 676 without T2DM used LLDs. After adjusting for age and sex, the non-T2DM group demonstrated better medical conditions, cognition, and daily function than the T2DM group, regardless of LLD use. Compared to the highest TC level (≥240 mg/dL), ORs were significantly increased as TC levels decreased. A similar pattern of T2DM prevalence was observed in LDL-C levels. Older people with T2DM demonstrated low cognitive and daily functions. Significantly reduced TC and LDL levels were associated with a higher T2DM prevalence in older adults regardless of LLD use. T2DM was associated with impaired cognitive and daily functioning. A higher prevalence of T2DM in older people with low cholesterol levels raises doubt surrounding cognition and daily function being jeopardized when the "lower is better" strategy is applied for the secondary prevention of CAD or CVD.

Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.