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Hai-Hua Chuang,1– 3 Chi-Hung Liu,4 Chao-Yung Wang,5 Yu-Lun Lo,6 Guo-She Lee,7,8 Yi-Ping Chao,4,9 Hsueh-Yu Li,10 Terry BJ Kuo,11 Cheryl CH Yang,11 Liang-Yu Shyu,12 Li-Ang Lee10,11 1Department of Family Medicine, Chang Gung Memorial Hospital, Taipei Branch and Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 2Department of Industrial Engineering and Management, National Taipei University of Technology, Taipei, Taiwan; 3Genomic Medicine Institute & Obesity Institute, Geisinger Medical, Danville, PA, USA; 4Department of Neurology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 5Department of Cardiology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 6Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 7Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 8Department of Otolaryngology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; 9Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan; 10Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 11Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; 12Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, TaiwanCorrespondence: Li-Ang LeeDepartments of Otorhinolaryngology-Head and Neck Surgery, Sleep Center, Chang Gung Memorial Hospital, Linkou Main Branch, No. 5, Fu-Hsing Street, Guishan District, Taoyuan, 33305, TaiwanTel +886 33281200 ext. 3972Fax +886 33979361Email 5738@cgmh.org.twBackground: Obstructive sleep apnea (OSA) and snoring have been reported to be modifiable risk factors for thick carotid intima-media thickness (CIMT) and carotid atherosclerosis, which are closely linked to cardiovascular disease.Methods: This cross-sectional study prospectively recruited 70 participants with OSA and without a history of carotid artery disorder, who primarily sought surgical Intervention. OSA and snoring were assessed with the Epworth Sleepiness Scale, Snore Outcomes Survey, polysomnography, and snoring sound recording. The carotid arteries were evaluated with ultrasonography and divided into three types of carotid artery profiles (normal carotid artery, thick CIMT, or significant carotid atherosclerosis). Multivariate linear/logistic/categorical regressions were performed with the forward selection approaches/logistic least absolute shrinkage and selection operator, as appropriate.Results: Normalized snoring sound energy (301– 850 Hz) was independently associated with the carotid intima-media thickness (regression coefficient [β] = 0.01, standard error [SE] = 0.004, P = 0.03; R2 = 0.067) and type of carotid profile (β = 0.40, SE = 0.09, P < 0.001; R2 = 0.156). Normalized snoring sound energy (4– 300 Hz) (β = − 0.10, SE = 0.04, P = 0.01) and female sex (β = 1.90, SE = 0.94, P = 0.04) were independently related to the presence of carotid stenosis (R2 = 0.159). The optimal regression model of the type of carotid artery profile included normalized snoring sound energy (301– 850 Hz) (β = 0.33, SE = 0.14, P = 0.03), snoring time (β = 0.26, SE = 0.13, P = 0.047), female sex (β = 0.26, SE = 0.13, P = 0.047), and increased age (β = 0.20, SE = 0.10, P = 0.04) under the control of the Snore Outcomes Survey score, 3% oxygen desaturation index, snoring sound energy (4– 1500 Hz), normalized snoring sound energy (851– 1500 Hz), cigarette smoking, and hyperlipidemia (R2 = 0.427).Conclusion: Our findings suggested that snoring sound characteristics are associated with carotid artery profiles among early OSA patients who cannot be noticed by ultrasound because organic changes of the carotid artery have not yet started. Future studies are warranted to verify the clinical significance of the results.Keywords: atherosclerosis, common carotid artery, categorical regression, obstructive sleep apnea, snoring, ultrasound

The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS.A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke.The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively).Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke.ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

PURPOSE OF THE REPORT In vivo tau PET imaging could help clarify the spatial distribution of tau deposition in Alzheimer disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo F-APN1607 tau PET studies in patients with AD. METHODS We applied tau tracer in 12 normal controls (NCs) and 10 patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements, and disease severity were documented. Regional SUV ratios (SUVRs) from F-AV-45 (florbetapir), F-APN1607 PET images, and regional gray matter (GM) atrophic ratios were calculated for further analysis. RESULTS Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all P's < 0.01) with medium to large effect sizes (0.44-0.75). The SUVRs from F-APN1607 PET imaging showed significant correlations with the Alzheimer's Disease Assessment Scale (ADAS-cog) scores (all P's < 0.01) and strong correlation coefficients (R ranged from 0.54 to 0.68), even adjusted for age and sex effects. Finally, the SUVRs from F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal, and occipital regions slowly increased. The combined SUVRs from amyloid, tau PET, and regional GM atrophic ratio showed regional specific patterns as the ADAS-cog scores increased. CONCLUSIONS Our findings suggest that the F-APN1607 tau tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition, and GM atrophy in the progression of AD.

Background: Antiplatelet use on the risk of intracerebral hemorrhage (ICH) in patients with Alzheimer’s disease (AD) has not yet been completely elucidated. Objective: This large epidemiologic study aims to estimate the risk of ICH in AD patients treated with antiplatelet therapy (APT). Methods: Using data from Taiwan’s National Health Insurance Research Database, ICH risk in APT-treated AD patients with a validated diagnosis (N = 824) was determined. AD without APT and non-AD with and without APT comparison cohorts were selected. To adjust for confounders and competing risk of death, inverse probability of treatment weighting using propensity scores and competing risks regression (CRR) were applied. Cox proportional hazards regression analysis estimated ICH risk in all cohorts comparing with non-AD without APT. Results: Among the 824 AD patients with APT, 79.6% were prescribed aspirin. ICH incidence rates in the AD (with/without APT) and non-AD (with/without APT) cohorts were 2.88/2.70 and 2.24/1.20 per 1,000 person-years, respectively. Overall, AD with (adjusted hazards ratio (aHR), 2.29; 95% CI, 1.19–4.38) and without (aHR, 1.97; 95% CI, 1.08–3.61) APT and non-AD with APT (aHR, 1.80; 95% CI, 1.34–2.42) were at a higher risk and had elevated subdistribution HR obtained from CRR than non-AD without APT controls. However, the risk was comparable between the AD cohorts with and without APT (HR, 1.16; 95% CI, 0.51–2.66). Conclusions: Our study indicated both the APT and non-APT users in AD population yielded higher ICH risks. However, whether APT use potentiate the risk of ICH in AD patients may warrant further evaluation.

Background: The objective is to study whether the cardiovascular protective effects of colchicines could be applied to non-cardiogenic ischemic stroke (IS) patients. Patients and Methods: Non-cardiogenic IS patients were identified from the National Health Insurance Research Database. Eligible patients were divided into chronic and non-chronic use categories based on their long-term status of colchicine use. The non-chronic use category was subdivided into (1) non-user and (2) new user groups while the chronic use category was divided into (3) former user and (4) long-term user groups according to the patient’s recent status of colchicine use. Inverse probability of treatment weights for propensity scores was used to balance the baseline characteristics. The primary outcome was recurrent IS, which was compared within the non-chronic use and chronic use categories. Results: In the non-chronic use category, the number of patients was 355,498 and 912 in the non-user and new user groups, respectively. In the chronic use category, the number of patients was 4737 and 4354 in the former user and long-term user groups, respectively. In the non-chronic use category, patients in the new user group had a marginally lower risk of recurrent IS at 6-months (subdistribution hazard ratio [SHR], 0.95, 95% confidence interval [CI], 0.94–0.97) and 2-years (SHR, 0.92, 95% CI, 0.91–0.93) follow up. In the chronic use category, patients in the long-term user group also had a marginally lower risk of recurrent IS at 6-months (SHR, 0.87, 95% CI, 0.86–0.88) and 2-years (SHR, 0.87, 95% CI, 0.86–0.88) follow up. The effect of colchicine on the reduced risk of recurrent IS was more favorable in patients who also used statins. Conclusions: Recent colchicine use in acute non-cardiogenic IS patients is associated with marginal fewer incidences of recurrent IS. Patients with concurrent statin use may have more profound protective effects.

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were 6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20–0.76) and IS/SE (HR = 0.12, 95% CI = 0.03–0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34–0.93) and IS/SE (HR = 0.26, 95% CI = 0.09–0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70, 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94, group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99, group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality.

Background Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear. Methods and findings Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. Conclusions The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population., Chi-Hung Liu and co-workers study associations between antihypertensive medication prescriptions and dementia risk in people with type 2 diabetes., Author summary Why was this study done? The drug of choice for antihypertensive treatment, and its association with dementia in patients with both type 2 diabetes mellitus (T2DM) and hypertension, is a valid question worthy of further investigations. Angiotensin receptor blockers (ARBs) modulate the renin–angiotensin–aldosterone system and potentially associate with cognitive preservation, but internal comparisons of the cognitive protective effects of different ARBs have not previously been performed. Telmisartan is the only ARB that, at a clinical dose, has agonistic effects on peroxisome proliferator-activated receptor γ (PPAR-γ), which maintains insulin sensitivity, reduces insulin resistance, and potentially has a protective impact on dementia. What did the researchers do and find? Using the electronic health records of the National Health Insurance Research Database of Taiwan between 1997 and 2013, we studied whether telmisartan was associated with a lower incidence of dementia compared to other ARBs in patients with T2DM and hypertension. Using telmisartan was associated with a lower risk of dementia diagnosis compared to using non-telmisartan ARBs (2.19% versus 3.20%). What do these findings mean? Telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any ischemic stroke events in an East-Asian population. Further work will be needed to investigate the observed association, owing to the limitations inherent in this observational study.

Background: Severe headaches, projectile vomiting, focal neurological deficits and early onset seizure are regarded as early warning symptoms of subarachnoid hemorrhage (SAH). Earlier diagnosis based on such warning symptoms theoretically would improve the clinical prognosis. However, it is still not clear whether the prognosis is correlated with early warning symptoms. Here, we reviewed warning symptoms and other predictive factors in the emergency room (ER) setting and examined their correlations with mortality. Methods: Ninety saccular aneurysmal SAH cases were reviewed in a single medical center between January 2011 and December 2013. We examined differences in mortality rate related to warning symptoms, SAH scales, onset-to-ER time, hydrocephalus, and aneurysm size, location, and complexity. Logistic regression analyses were performed to determine the correlations of warning symptoms and other predictive factors with mortality. Receiver operating characteristic (ROC) curve analysis was used to calculate the area the under curve (AUC) of SAH mortality prediction tools. Results: Warning headache, projectile vomiting, the Hunt and Hess scale, Fisher scale, World Federation of Neurological Surgeons (WFNS) grading scale, and modified WFNS (m-WFNS) scale, body mass index, aneurysm complexity and hydrocephalus were significantly different between the survivors and the decedents. The warning headache and WFNS grade were strongly correlated with mortality. The rate of prognostic prediction improved from 90.4% to 94.6% when warning headache was additionally evaluated. Conclusions: With growing healthcare costs and recognition of the value of palliative care, early identification via warning headache and a detailed clinical history review is necessary for cases of aSAH. Keywords: Warning headache, SAH, WFNS, Survival rate

There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.

Objective The impact of antithrombotic agents on patients with primary intracerebral hemorrhage (ICH) remains controversial, especially patients who require emergent craniotomy. This study was undertaken to evaluate clinical outcomes in operated patients with ICH with and without previous antithrombotic agents. Methods This is a retrospective cohort study. Between January 2001 and December 2013, all patients with ICH who received emergent craniotomy and who were present in Taiwan's National Health Insurance Research Database were screened and divided into those with previous antiplatelet therapy, anticoagulant therapy, and nonantithrombotic therapy according to their health care claims data within 3 months of index admission. The primary end points included in-hospital mortality and complications and short-term outcome. Results Of 18,872 eligible patients, 16,251 (87.1%) did not receive any antithrombotic therapy, 2267 patients had antiplatelet therapy, and 354 patients had anticoagulation therapy. After propensity score matching, significantly more blood transfusions and craniectomies were identified in the patients with previous antithrombotic treatment compared with those undergoing nonantithrombotic therapy. Compared with the nonantithrombotic treatment cohort, patients under previous anticoagulant treatment had significantly higher in-hospital mortality (odds ratio, 2.12; 95% confidence interval, 1.45–3.10). Furthermore, during the 6-month follow-up period, previous anticoagulant therapy was independently associated with a greater risk of all-cause mortality (P = 0.001). The in-hospital and 6-month all-cause mortality of patients with previous antiplatelet treatment was not significantly different from patients with nonantithrombotic treatment. Conclusions These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated patients with ICH with previous antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF.Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF.Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25–0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21–0.79 for severe DWMLs].Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

Background To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT). Methods We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups. Results The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29–16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09). Conclusions HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years.

Summary Background The existence of vascular disease in patients with atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. It is unclear whether coronary artery disease (CAD) and/or peripheral artery disease (PAD) have similar presentations and complication rates. Aim To investigate thromboembolic events among patients with AF who have CAD, PAD or polyvascular disease. Methods Patients with a new diagnosis of AF without anticoagulation (n = 306,386) were identified from the National Health Insurance Research Database in Taiwan (2001–2013). Ischaemic stroke (IS), systemic thromboembolism (STE) and their combination (IS/STE) were compared in four groups (No-CAD/PAD, CAD-only, PAD-only, CAD + PAD), and secondarily in patients with only CAD versus only PAD. Last, we compared propensity score-matched patients with only CAD or PAD with those with CAD and PAD. Results There were 185,169 patients without CAD or PAD, 8113 patients with only PAD, 105,715 patients with only CAD, and 7389 patients with CAD and PAD eligible for analysis (mean ± SD follow-up 3.2 ± 3.2 years). The incidences of STE and IS/STE differed in the four groups, with the highest in the CAD + PAD group and the lowest in the No-CAD/PAD group. The proportions of IS and STE also varied, with higher proportions of STE in patients with PAD, but higher proportions of IS in patients with CAD. After propensity score matching, the PAD-only group had significantly higher incidences of STE and IS/STE than the CAD-only group, across all levels of CHA2DS2-VASc score. Patients with CAD and PAD had a significantly higher incidence of STE and IS/STE than propensity score-matched patients with CAD or PAD. Conclusions PAD or CAD in patients with AF did not contribute equally to the risk prediction and presentation of IS and STE. Patients with polyvascular disease should be considered at higher risk than those with either condition.

Background Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. Methods Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. Results 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. Conclusions Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.

Background The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke. Methods We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < − 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables. Results Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke. Conclusion The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

Background: Atorvastatin 40mg (ATOR 40) and ezetimibe 10mg/simvastatin 20mg (EZ-SIM 20) have comparable reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond comparable reductions of LDL-C, especially for extremely CV risk patients.Methods: Between January 1, 2007 and December 31, 2013, a total of 3372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n=1686) matched with EZ-SIM 20 group (n=1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).Results: With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group.Conclusions: For T2DM patients after ACS or AIS, ATOR 40 may have lower risks of HUA, PCI and CABG than EZ-SIM 20.

Key Points Question Does the risk of dementia vary by type of androgen deprivation therapy among patients with prostate cancer? Findings In this cohort study of 23 651 patients with newly diagnosed prostate cancer between 2008 and 2015, there was no association of the use of gonadotropin-releasing hormone agonists or orchiectomy with increased dementia risk, while antiandrogen monotherapy use was associated with a 34% increased dementia risk compared with patients who did not receive androgen deprivation therapy. Meaning These findings suggest that the use of antiandrogen monotherapy, but not gonadotropin-releasing hormone agonist or orchiectomy, requires more attention with respect to subsequent risk of dementia., This cohort study examines the association between all-cause dementia, including Alzheimer disease, and different types of androgen deprivation therapy among patients with prostate cancer in Taiwan., Importance It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. Objective To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. Design, Setting, and Participants This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. Exposures Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. Main Outcomes and Measures The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. Results In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. Conclusions and Relevance In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.

Background: In vivo tau positron emission tomography (PET) imaging could help clarify the spatial distribution of tau deposition in Alzheimer’s disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo 18 F-APN1607 tau PET studies in patients with AD.Methods: We applied tau tracer in twelve normal controls (NCs) and ten patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements and disease severity were documented. Regional standardized uptake value ratios (SUVRs) from 18 F-AV-45 (florbetapir), 18 F-APN1607 PET images and regional gray matter (GM) atrophic ratios were calculated for further analysis.Results: Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all ps < 0.01) with medium to large effect sizes (0.44 - 0.75). The SUVRs from 18 F-APN1607 PET imaging showed significant correlations with the ADAS-cog scores (all ps < 0.01) and strong correlation coefficients (R squared ranged from 0.54 to 0.68), even adjusted for age and gender effects. Finally, the SUVRs from 18 F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal and occipital regions slowly increased. The combined SUVRs from 18 F-AV-45 PET, 18 F-APN1607 PET and regional GM atrophic ratio showed that uptake associated with the amyloid burden rapidly increased and reach a plateau, whereas uptake associated with tau depositions increased slowly and finally followed by regional GM atrophic ratios in most regions as the ADAS-cog scores increased. However, different regions exhibited various combinations of these patterns.Conclusions: Our findings suggest that the 18 F-APN1607 tau tracer showed a clear background without significant uptake in the basal ganglia or midbrain. Uptake of this tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition and GM atrophy in the progression of AD. Thus, the regional base of dynamic biomarker changes was observed in the current study.Trial registration: registration number (NCT03625128), date of registration( August 10, 2018), retrospectively registered.

Background and aim Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. Methods Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p p Results There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84–0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). Conclusions The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments.

Background and aims Statins improve clinical outcomes in patients with ischemic stroke but there is no evidence of the effect of continuing long-term statin therapy in patients with intracerebral hemorrhage (ICH). The aim of this study was to evaluate the impact of continuing statin after ICH. Methods Data on patients with ICH was retrieved from the National Health Insurance Research Database of Taiwan. The final population was separated into two groups according to those who continued and those who discontinued statin treatment. All-cause mortality and cardiovascular outcomes were analyzed after a 3 year follow-up after propensity score matching (PSM). Results Of the 114,101 patients with ICH, who were initially enrolled, 2468 patients with dyslipidemia and ICH were included. After PSM, the benefit of statin therapy on mortality appeared from 1 year to the end of the 3-year follow-up period after discharge (statin group versus non-statin group: 4.9% vs.12.3% at 1 year (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.26–0.57) and 12.9% vs. 25.3% at the end of the 3 year follow-up period (HR, 0.45; 95% CI, 0.35–0.58). Compared with the patients using lipophilic statins, those using hydrophilic statins had a significantly lower incidence of all-cause mortality (HR = 0.65, 95% CI = 0.43–0.99). There were no differences between those prescribed moderate-intensity statins and those prescribed high-intensity statins in terms of stroke and all-cause mortality (HR = 0.76; 95% CI = 0.40–1.46). Conclusions There was a lower risk of all-cause mortality following ICH in patients who continued statin treatment compared with those without statin treatment, especially in those treated with hydrophilic statins.

Background The 18F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer’s disease and corticobasal syndrome. In addition, 18F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore 18F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke. Results Fifteen patients received 18F-THK-5351 positron emission tomography (PET) and diffusion tensor imaging (DTI) approximately 3 months after ischemic stroke. A region of interest (ROI) was placed in the peri-ischemic area and was mirrored on the contralateral side as the control, and a proportional value was derived from the ratio of the peri-ischemic ROI value over the mirrored ROI value. Increased 18F-THK-5351 retention was observed in the areas around and remote from the stroke location. The proportional 18F-THK-5351 values were negatively correlated with the proportional fractional anisotropy values (r = − 0.39, P = 0.04). Conclusion 18F-THK-5351 PET imaging provides a potential tool for in vivo visualization of the widespread ischemia-related changes associated with a microstructural disruption in recent ischemic stroke patients. Electronic supplementary material The online version of this article (10.1186/s13550-018-0417-1) contains supplementary material, which is available to authorized users.

The time to maximum of the residue function (TMax) has been employed to identify the penumbra in acute ischemic stroke. Cognitive impairment in patients with Carotid Artery Stenosis (CAS) has been attributed to chronic cerebral hypoperfusion. The study aimed to examine whether cognitive impairment can be detected based on a preliminary TMax cutoff in patients with unilateral CAS.Fifty unilateral CAS patients underwent dynamic susceptibility contrast MR perfusion. The preliminary TMax cutoff (3 seconds) was derived on the basis of the upper limit of 95% confidence interval of TMax in the Middle Cerebral Artery (MCA) contralateral to the CAS side. All patients were allocated to the Right-delayed group (n=18), Left-delayed group (n=12), and Nondelayed group (n=20) by the cutoff. Cognitive assessment was also administered on all patients and 22 healthy volunteers.No significant interhemispheric mean TMax differences of the Non-delayed group were noted (p=0.75), but the mean TMax of ipsilateral MCA was significantly longer than that of the contralateral MCA of the Left- and Right-delayed groups (ps0.001), respectively. Compared to healthy volunteers, the Right-delayed group performed significantly worse on most of the visuospatial tests (ps0.04), while the Left-delayed group performed significantly worse on most of the verbal tests (ps0.05). The performance of the Non-delayed group on all cognitive domains was similar to that of healthy volunteers (ps0.07).TMax can be used to differentiate the chronic hypoperfusion state in unilateral CAS patients. Prolonged TMax in the MCA of either hemisphere may lead to lateralized impairment in cognition functions in patients with unilateral CAS.

Causes of death in both ischemic stroke (IS) and hemorrhagic stroke (HS) subtypes are not comprehensively studied. Between 2008 and 2011, we enrolled 11 215 first-ever stroke patients from the Stroke Registry of Chang-Gung Healthcare System and linked these data to the national death registry. The main causes of death in each stroke subtype were assessed. Patients with HS had higher overall mortality than IS (32.0% vs 18.1%, P < .001). In IS subtypes, large-artery atherosclerosis plus cardioembolism had the worst mortality (40.7%, P < .001). Stroke was the leading cause of death in both IS and HS within the first year. Stroke remained the major cause of death in HS, but cancer was the leading cause of death in IS after the first year. After excluding the patients with previous cancer history, cancer was still an important cause of death in IS and HS, particularly in the IS subtypes of small vessel occlusion, stroke of undetermined etiology, and transient ischemic attack.

Background and purpose Fabry disease is an X-linked disease, and enzyme-based screening methods are not suitable for female patients. Methods In total, 1000 young stroke patients (18-55 years, 661 with ischaemic stroke and 339 with hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay was used to detect 26 Fabry related mutation genes. The frequency of Fabry disease in young stroke was reviewed and compared between Asian and non-Asian countries. Results Two male patients with ischaemic stroke were found to have a genetic mutation of IVS4+919G>A. There was no α-galactosidase A (GLA) gene mutation in female patients. The frequency in Asian stroke patients was 0.62% (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic stroke and 1.40% for hemorrhagic stroke reported in western countries. Conclusion IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke patients. Fabry disease is more frequent among non-Asian patients compared to Asian patients.

Background and Purpose: This study proposed a machine learning method for identifying ≥50% stenosis of the extracranial and intracranial arteries. Patients and methods A total of 8211 patients with both carotid ultrasound and cerebral angiography were enrolled. Support vector machine (SVM) was employed as the machine learning classifier. Carotid Doppler parameters and transcranial Doppler parameters were used as the input features. Feature selection was performed using the Extra-Trees (extremely randomized trees) method. Results For the machine learning method, the sensitivities and specificities of identifying stenosis of the extracranial arteries were 88.5%–100% and 96.0%–100%, respectively. The sensitivities and specificities of identifying stenosis of the intracranial arteries were 71.7%–100% and 88.9%–100%, respectively. Conclusions The SVM classifier with feature selection is an efficient method for identifying the stenosis of both intracranial and extracranial arteries. Comparing with traditional Doppler criteria, this machine learning method achieves up to 20% higher in accuracy and 45% in sensitivity, respectively.

Background: Obstructive sleep apnea (OSA) increases the risk of Alzheimer’s disease (AD), and inflammation may be involved in the early pathogenesis of AD in patients with OSA. However, the potential pathways between OSA and AD have yet to be established. In this study, we aimed to investigate differential expressions of AD-associated genes in OSA patients without evident AD or dementia. Methods: This prospective case-control study included five patients with severe OSA and five age and sex-matched patients with non-severe OSA without evident dementia who underwent uvulopalatopharyngoplasty between 1 January 2013 and 31 December 2015. The expressions of genes associated with AD were analyzed using whole-exome sequencing. Unsupervised two-dimensional hierarchical clustering was performed on these genes. Pearson’s correlation was used as the distance metric to simultaneously cluster subjects and genes. Results: The expressions of CCL2, IL6, CXCL8, HLA-A, and IL1RN in the patients with severe OSA were significantly different from those in the patients with non-severe OSA and contributed to changes in the immune response, cytokine−cytokine receptor interactions, and nucleotide-binding oligomerization domain-like receptor signaling pathways. Conclusions: Inflammation may contribute to the onset of AD and physicians need to be aware of the potential occurrence of AD in patients with severe OSA.

Acupuncture is widely used for improving poststroke care. Knowing the condition of meridian can help traditional Chinese medicine (TCM) doctors make a tailored choice of acupoints for every patient. The establishment of an objective meridian energy measurement for acute ischemic stroke that can be used for future acupuncture treatment and research is an important area in stroke-assisted therapy. In this study, a total of 102 subjects diagnosed with acute ischemic stroke within 7 days of onset were recruited, and the meridian energy analysis device (MEAD) was used to record the meridian electrical conductance (MEC) values of twelve meridians on unaffected and affected limbs. We found that the MEC value of the twelve meridians on the affected limbs was significantly higher than that on the unaffected limbs (P=0.001). Compared with the unaffected limbs, there was a higher value of MEC on the affected limbs of the lung meridian, heart meridian, pericardium meridian, and small intestine meridian, with significant differences (P<0.05, P<0.001, P<0.001, and P<0.05, respectively). Further analysis revealed that the MEC values of both Yin and Yang meridians of the affected limbs were significantly higher than those of the unaffected limbs (P=0.001 and P<0.05, respectively). Meanwhile, the mean of the index of sympathovagal balance in patients with acute ischemic stroke (5.49 ± 4.21) was higher than the normal range (1–1.5), indicating autonomic imbalance. The results of this study are consistent with TCM theory as well as clinical observation and pathological mechanisms, suggesting that the measurement of MEC values may be used as a supplementary diagnostic method for acupuncture in patients with acute ischemic stroke.

Objective: To test whether strokes increase around the time of cancer diagnosis, we comprehensively examined the correlations of cancer and stroke by employing a population-based cohort study design. Methods: One million people insured under the Taiwan's National Health Insurance program in 2005 were randomly sampled to create the study's dataset. According to the presence of cancer and/or stroke, patients were separated into cancer and stroke, cancer-only, and stroke-only groups. Diagnoses of cancer, stroke, and comorbidities were defined according to ICD9-CM codes. Cancer and non-cancer populations were matched by age at cancer diagnosis, gender, and stroke risk factors, and each patient with cancer was matched with two non-cancer controls nested in the same year of cancer diagnosis. The hazards of stroke and cumulative incidences within a year after cancer diagnosis were evaluated using Fine and Gray's subdistributional hazard model. Results: The temporal distribution of first-ever stroke in patients with both cancer and stroke was a sharpened bell shape that peaked between 0.5 years before and after cancer diagnosis. Frequencies of stroke were further adjusted by number of cancer survivors. The monthly event rate of stroke remained nested around the time of cancer diagnosis in all strokes. Brain malignancies, lung cancer, gastric cancer, prostate cancer, and leukemia patients obtained higher ratio of stroke, while breast cancer and thyroid cancer patients had low percentage of combining stroke. When compared to non-cancer matched control, the hazard of stroke within one year after cancer diagnosis was increased by cancer at a subdistributional hazard ratio of 1.72 (95% confident interval 1.48 to 2.01; p < 0.0001). Conclusions: Cancer increased the risk of stroke and stroke events were nested around the time of cancer diagnosis, occurring 0.5 years prior to cancer on average regardless of stroke type.

Introduction: The multiphase computed tomography angiography (mCTA) is superior to the noncontrast computed tomography (NCCT) in selecting patients that would benefit from mechanical thrombectomy following an acute ischemic stroke (AIS). It remains unclear whether the longer examination time of mCTA worsens outcomes of intravenous recombinant tissue plasminogen activator (IV r-tPA) or increases the risk of hemorrhagic transformation (HT) compared to NCCT in Asian stroke patients. Methods: Between January 2011 and December 2017, 199 AIS patients receiving IV r-tPA with initial National Institute of Health Stroke Scale (NIHSS) scores between 6 and 25 were enrolled in a single medical center. Onset-to-needle time (ONT), door-to-needle time (DNT), and creatinine levels before and after thrombolysis were recorded. We evaluated NIHSS scores 2, 24 h after treatment, and at discharge, the modified Rankin Scale (mRS) at discharge, and mortality rate. The presence of HT was reviewed within 7 days after thrombolysis. Results: DNT, perithrombolysis creatinine levels, NIHSS, and mRS scores at the emergency room were similar between the NCCT and mCTA groups. ONT was shorter in the mCTA group. AIS patients got more significant neurologic improvement (NIHSS decrease ≥4) after thrombolysis and physically independent (mRS ≤2) at discharge in the mCTA group. Mortality rates, symptomatic, and total HT rates were similar between the NCCT and mCTA groups. Conclusion: Comparing to NCCT, mCTA-based IV r-tPA would not delay DNT nor worsen the outcome. Furthermore, mCTA provides more information for early identification of candidates for mechanical thrombectomy in Asian AIS patients.

Background: Brain 18F-AV-45 amyloid positron emission tomography (PET) in Taiwanese patients with familial Alzheimer's disease with the amyloid precursor protein (APP) p.D678H mutation tends to involve occipital and cerebellar cortical areas. However, tau pathology in patients with this specific Taiwan mutation remains unknown. In this study, we aimed to study the Tau PET images in these patients. Methods: Clinical features, brain magnetic resonance imaging/computed tomography (MRI/CT), and brain 18F-THK-5351 PET were recorded in five patients with the APP p.D678H mutation and correlated with brain 18F-AV-45 PET images. We also compared the tau deposition patterns among five patients with familial mild cognitive impairment (fMCI), six patients with sporadic amnestic mild cognitive impairment (sMCI), nine patients with mild to moderate dementia due to Alzheimer's disease (AD), and 12 healthy controls (HCs). All of the subjects also received brain 18F-AV-45 PET. Results: The nine patients with sAD and six patients with sMCI had a positive brain AV-45 PET scans, while the 12 HCs had negative brain AV-45 PET scans. All five patients with fMCI received a tau PET scan with the age at onset ranging from 46 to 53 years, in whom increased standard uptake value ratio (SUVR) of 18F-THK-5351 was noted in all seven brain cortical areas compared with the HCs. In addition, the SUVRs of 18F-THK-5351 were increased in the frontal, medial parietal, lateral parietal, lateral temporal, and occipital areas (P < 0.001) in the patients with sAD compared with the HCs. The patients with fMCI had a significant higher SUVR of 18F-THK-5351 in the cerebellar cortex compared to the patients with sMCI. The correlations between regional SUVR and Mini-Mental State Examination score and between regional SUVR and clinical dementia rating (sum box) scores within volumes of interest of Braak stage were statistically significant. Conclusion: Tau deposition was increased in the patients with fMCI compared to the HCs. Increased regional SUVR in the cerebellar cortical area was a characteristic finding in the patients with fMCI. As compared between amyloid and tau PET, the amyloid deposition is diffuse, but tau deposition is limited to the temporal lobe in the patients with fMCI.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

BackgroundStroke is prevalent in patients with chronic kidney disease (CKD) and is associated with high mortality, but the causes of death after stroke among different CKD stages are not well known.AimsWe aimed to investigate whether the severity of CKD would impact on the causes of death after first-ever stroke.MethodsThis retrospective multicenter cohort study included stoke patients with CKD between 2007 and 2012. The cause of death and date of death were ascertained by linking the National Death Registry Database of Taiwan. Clinical outcomes, 1-month, and 1-year mortality rates, and major causes of death were compared according to five CKD stages (G1 to G5) in the ischemic and hemorrhagic stroke separately.ResultsOf these patients, 9,878 were first-ever ischemic stroke (IS) patients, and 1,387 were first-ever hemorrhagic stroke (HS) patients. Patients with CKD G5 had the highest one-year mortality rate with hazard ratio 5.28 [95%CI, 3.94–7.08] in IS and 3.03 [95%CI, 2.03–4.54] in HS when compared to G1 patients. Leading causes of one-year death after IS were stroke, cancer, and pneumonia in early (G1-3) CKD patients, while diabetes mellitus, CKD, and stroke itself contributed to the major mortality in CKD G5 patients. An inverse association between eGFR decrement and the proportion of deaths caused by stroke itself was observed in CKD G2-5 patients after IS. Stroke was the leading cause of one-year death among all CKD patients after HS.ConclusionsAsides from high mortality, late-stage CKD patients had different causes of death from early CKD patients after stroke. This study highlights the need to imply different treatment strategies in late-stage CKD post-stroke patients to improve their prognosis.

Supplemental Digital Content is available in the text, Atrial fibrillation (AF) is a major independent risk factor of stroke and anticoagulation therapy is needed in patients with AF after ischemic stroke. However, the detection rate of AF is low after ischemic stroke. Developing a prediction model for newly diagnosed AF after ischemic stroke will help to assess the subclinical AF. We identified 98,103 patients with diabetes mellitus (DM) and 261,893 patients without DM, who were not AF history and admitted for newly ischemic stroke from the National Health Insurance Research Database in Taiwan. The prediction model for 3-year incidence of AF after ischemic stroke was derived from multivariate logistic regression and also the accuracy rate of the prediction model was compared with CHA2DS2-VASC and CHADS2 scores as a reference. Four thousand nine hundred seventy six patients in the DM cohort and 16,127 patients in the non-DM cohort developed AF during 3 years of follow-up. The variables in the point-based prediction model for non-DM patients (range: -3–28), included age, heart failure, coronary artery disease, gout, obstructive pulmonary disease, hypertension, female, and statin use, while those for DM patients (range: -2–30) included age, heart failure, coronary artery disease, chronic kidney disease, hypertension, obstructive pulmonary disease, and statin use. Compared to the CHADS2 and CHA2DS2-VASc scoring systems, this scoring system was better at predicting 3-year risk of AF after ischemic stroke in both cohorts. This model might be useful in evaluating the benefit of insertable cardiac monitor implantation and anticoagulation agents in individual patients after ischemic stroke.

Background: Previous clinical trials showed a significant difference in efficacy and safety among antiplatelets in acute ischemic stroke (IS). The present study wished to compare the efficacy and safety head-to-head between cilostazol and clopidogrel in chronic IS. Methods: This open prospective cohort study recruited chronic IS patients with an index hospitalization between 2001 and 2013 from Taiwan National Health Insurance Research Database. In the 504,191 hospitalized patients, patients who had missing information and history of atrial fibrillation or rheumatic heart disease, received mechanical valve replacement or anticoagulants, expired during the index hospitalization, received follow-up ⩽6 months, or had recurrent stroke within 6 months after index stroke were excluded. Results: Among the 15,968 eligible patients, 502 patients who consistently received either cilostazol or clopidogrel from the 7th month after the index stroke were included for analysis after propensity score matching. The 3-year primary outcomes showed similar frequency of recurrent IS, all-cause mortality, and acute myocardial infarction (AMI), and similar frequency of intracerebral hemorrhage, gastrointestinal bleeding, and major bleeding between the cilostazol and clopidogrel groups. Subgroup analysis revealed that patients with a history of hypertension or gastrointestinal bleeding had a trend of having lower frequency of recurrent IS or major bleeding, respectively, in the cilostazol group. Conclusion: The present real-world study demonstrated no significant difference in efficacy and safety between cilostazol and clopidogrel in chronic IS. However, cilostazol might be better than clopidogrel in patients with a history of hypertension or gastrointestinal bleeding.

BACKGROUND The amyloid AV-45 (florbetapir) positron emission tomography (PET) has been used in the study of the familial Alzheimer's disease (FAD) with the D678H amyloid precursor protein (APP) mutation. In addition, the progress of the disease remains unknown. OBJECTIVE We aim to investigate the progression rate of amyloid accumulation in FAD patients with this mutation by neuroimages analysis. METHODS The clinical course, changes in cognitive function, brain magnetic resonance imaging (MRI) and 18F-AV-45 PET scan were investigated in FAD patients and sporadic AD (sAD) patients. We compared the amyloid deposition pattern in serial brain 18F-AV-45 PET scan among the FAD, familial mild cognitive impairment (FMCI), and sMCI and sAD patients. RESULTS Seven familial patients received a follow-up survey. The follow up duration for brain AV-45 PET was from 1.54 to 3.61 years. In 4 FMCI patients, an increased regional SUVR was noted, and the annual change rates were increased from 1.03% to 18.82%. However, a decreased regional SUVR was noted in 3 FAD patients and the annual change rates were from -2.62% to -16.03%. As compared with the sAD and sMCI patients, the annual change rate is statistically significant in FAD and FMCI patients respectively. CONCLUSIONS The data indicate a biphasic course with an initial increase and then a decrease of SUVR in brain amyloid PET scan in familial APP mutation patients. The data also reveal that the novel Taiwan APP (D678H) mutation has a more amyloid burden than the sAD patients, particularly in an MCI stage.

Introduction The novel D678H amyloid precursor protein (APP) gene mutation has been called the “Taiwan mutation”. The study aims to identify amyloid deposition patterns and clinical features associated with this mutation. Methods we analyzed the clinical manifestations, brain neuroimages and 18F-AV-45 positron emission tomography (PET) findings in symptomatic patients and asymptomatic subjects with the autosomal-dominant Alzheimer's disease (AD). We compared the amyloid deposition pattern among 10 patients with genetically-positive familial cognitive decline (CD), 18 patients with sporadic CD, and 19 healthy controls. Results The clinical features were the early onset of memory impairment in all 10 patients and cerebral amyloid angiopathy in 3 patients. The characteristic results of brain 18F-AV-45 PET included the highest standard uptake value ratio (SUVR) in the occipital and cerebellar cortical areas in the genetically-positive CD patients. In subgroup analysis, the familial AD patients had a decreased amyloid SUVR trend in most areas except for cerebellar cortex compared to those with familial mild cognitive impairment. Conclusion Our data indicate that the familial D678H gene mutation have resulted in a more potent amyloid burden than in the patients with sporadic AD patients. The high amyloid uptake in the occipital area is characteristic of the specific Taiwan APP gene.

Background: Low lipid level is associated with better cardiovascular outcome. However, lipid paradox indicating low lipid level having worse outcomes could be seen under acute injury in some diseases. The present study was designed to clarify the prognostic significance of acute-phase lipid levels within 1 day after admission for stroke on mortality in first-ever statin-naïve acute ischemic stroke (IS) and hemorrhagic stroke (HS).Methods: This observational study was conducted using the data collected from Stroke Registry In Chang-Gung Healthcare System (SRICHS) between 2009 and 2012. Patients with recurrent stroke, onset of symptoms >1 day, and history of the use of lipid-lowering agents prior to index stroke were excluded. Stroke was classified into IS and hypertension-related HS. The primary outcomes were 30-day and 1-year mortality identified by linkage to national death registry for date and cause of death. Receiver operating characteristic (ROC) curve analysis and multivariate Cox proportional hazard models were used to examine the association of lipid profiles on admission with mortality.Results: Among the 18,268 admitted stroke patients, 3,746 IS and 465 HS patients were eligible for analysis. In IS, total cholesterol (TC)

BACKGROUND We compared the clinical outcomes of low and standard dose recombinant tissue Plasminogen Activator (rtPA) treatment in Acute Ischemic Stroke (AIS) patients receiving Endovascular Mechanical Thrombectomy (EVT). METHODS Between April 01, 2015 and September 30, 2017, all AIS patients admitted to the Linkou and Chiayi Chang Gung Memorial Hospital were retrospectively reviewed. Patients with large vessel occlusions, who underwent bridging therapy with rtPA and EVT, were further enrolled. The enrolled patients were categorized into low (0.6-0.7 mg/kg; LD) or standard dose (0.9 mg/kg; SD) group based on the dose of rtPA they received. Baseline characteristics, reperfusion status, and clinical outcomes were compared between the two groups. RESULTS Forty-two patients were enrolled in the final analyses, including 13 in the LD and 29 in the SD group. In all groups analyzed, the frequencies of moderate to severe and severe stroke at discharge were significantly decreased compared to those at stroke onset (p < 0.01). Compared to the SD group, patients of the LD group had a similar rate of mortality (LD vs. SD; 0% vs. 3.4%, p = 1.00), and comparable frequencies of functional independence at 3 months after stroke onset (LD vs. SD; 33.3% vs. 44.8%, p = 0.50). The rates of symptomatic intracerebral hemorrhage were also similar between the two groups (LD vs. SD; 0% vs. 6.9%, p =1.00). CONCLUSIONS Compared to standard dose treatment, low dose rtPA may have similar clinical efficacy and safety outcomes in AIS patients receiving bridging therapy.

Objective Neural disruption and cognitive impairment have been reported in patients with carotid stenosis (CS), but carotid artery stenting (CAS) may not contribute to the cognitive recovery. Although functional hyper-connectivity is one of the physiological over-compensation phenomena in neurological diseases, the literature on the cognitive influence of functional hyper-connectivity in CS patients is limited. We aimed to investigate the longitudinal changes of hyper-connectivity after CAS and its association with cognition in CS patients. Methods Thirteen patients with unilateral CS and 17 controls without CS were included. Cognitive function was evaluated at baseline, and resting-state functional MRI was performed 1 week before and 1 month and 1 year after CAS. Comparisons of functional connectivity (FC) between CS patients and controls in multiple brain networks were performed. Results In patients before CAS, FC in the cerebral hemispheres ipsilateral and contralateral to CS was mainly decreased and increased, respectively, compared with normal controls. Part of the FC alterations gradually recovered to the normal condition after CAS. The stronger FC abnormality (both hypo- and hyper-connectivity compared with normal controls) was associated with poorer cognitive performances, especially in memory and executive functions. Conclusion The study demonstrated the lateralization of hyper-connectivity and hypo-connectivity in patients with unilateral CS in contrast to the FC in normal controls. These FC alterations were associated with poor cognitive performances and tended to recover after CAS, implying that hyper-connectivity is served as a compensation for neural challenge., Highlights • Cerebral hypoconnectivity on functional MRI is lateralized to carotid stenosis side. • Cerebral hyperconnectivity is in regions contralateral to carotid stenosis side. • Abnormal connectivity gradually returns back to normal after carotid stenting. • Hypo- and hyper-connectivity associate with poor cognitive performances. • Hyperconnectivity could be served as a compensation for neural challenge.

Background We hypothesized that the inflammatory markers (IM) could be the independent predictors of Carotid Stenosis Progression (CSP) after Carotid Artery Stenting (CAS). Methods Between 2010 and 2012, 122 patients undergoing cervicocranial revascularization in our hospital were prospectively recruited. Patients undergoing revascularizations other than CAS were excluded. Carotid duplex ultrasonography was performed before and at 1 week, 6 months (6M), 1 year, and 2 years after CAS. IM levels were recorded before CAS and were followed up immediately and 6M after CAS. The data was analyzed retrospectively. Patients were categorized into the Progression Group (PG) and Nonprogression Group (NPG) based on the presence or absence of CSP, including in-stent restenosis (ISR) and worsening contralateral carotid stenosis. Receiver operating characteristic and multivariate logistic regression analyses were conducted. Results In Total, 77 patients were enrolled. The frequency of CSP was 24.7% (ISR: 14.3%; worsening contralateral carotid stenosis: 14.3%). Compared with the NPG, the PG had lower E-selectin levels before CAS [PG vs. NPG, 47.90 (42.80, 64.90) vs. 68.25 (52.08, 92.30); p = .01] and a nonreduced E-selectin levels at 6M after CAS [PG vs. NPG, 7.65 (-2.45, 25.75) vs. -16.10 (-33.45, 1.65); p = .002]. The E-selectin changes between 6M after and before CAS had highest predictive accuracy on CSP (area under the curve = 0.74, p = .002). The optimal cut-off level was a 2.95 ng/mL decrease and the adjusted odds ratio for CSP was 10.16 (p = .001). Conclusion The E-selectin changes between 6M after and before CAS are independent predictors of CSP.

This study aimed to investigate the clinical predictors of unfavorable prognosis in patients with venous catheter-related cerebral air embolism.An extensive review of English literature was performed to obtain reports on cerebral air embolism published between January 1982 and July 2014 through PubMed, Journal at Ovid, and Web of Science using the Mesh terms and keywords "cerebral air embolism" and "cerebral gas embolism." Reports not fulfilling the diagnosis of cerebral air embolism and iterant articles were excluded. Demographics, clinical manifestations, and imaging findings were recorded. The air distribution on initial brain computed tomography (CT) was recorded as gyriform air (GF), cavernous sinus bubble, venous sinus bubble, and parenchymal and subarachnoid bubble. The enrolled subjects were further divided into favorable and unfavorable outcome groups for analyses.Of the 33 cases enrolled, 31 had documented follow-up outcomes, including 14 with favorable and 17 with unfavorable prognoses. Patients with unfavorable outcome had older onset age (67.5 ± 15.8 versus 46.7 ± 17.0 years, P.001), higher frequency of GF on brain CT (58.8% versus 0%, P.01), initial consciousness disturbance (100% versus 42.9%, P.001), and hemiparesis (100% versus 42.9%, P.001), but lower frequency of cardiopulmonary symptoms (5.9% versus 64.3%, P.01). In patients with central venous catheter-related cerebral air embolism, the retrograde mechanism had a tendency for worse outcomes (43.8% versus 0%, P = .023).In patients with venous catheter-related cerebral air embolism, the presence of GF on brain CT imaging, old age, initial conscious disturbance, and hemiparesis may predict unfavorable outcomes.

Background Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population. Methods This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching. Results We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p

Background Atrial flutter ( AFL ) has been identified to be equivalent to atrial fibrillation ( AF ) in terms of preventing ischemic stroke, although differences exist in atrial rate, substrate, and electrophysiological mechanisms. This study aimed to investigate differences in clinical outcomes between nonvalvular AF and AFL . Methods and Results AF and AFL patients without any prescribed anticoagulation were enrolled from a 13‐year national cohort database. Under series exclusion criteria, ischemic stroke, heart failure hospitalization, and all‐cause mortality were compared between the groups in real‐world conditions and after propensity score matching. We identified 175 420 patients in the AF cohort and 6239 patients in the AFL cohort, and the prevalence of most comorbidities and frequency of medications were significantly higher in the AF group than the AFL group. In the real‐world setting the AF patients had higher incidence rates of ischemic stroke, heart failure hospitalization, and all‐cause mortality than the AFL patients (all P AF cohort was 1.63‐fold higher than in the AFL cohort ( P AF cohort was 1.70‐fold higher than in the AFL cohort ( P AF cohort was 1.08‐fold higher than in the AFL cohort ( P =0.002). Conclusions There were differences between AF and AFL in comorbidities and prognosis with regard to ischemic stroke, heart failure hospitalization, and all‐cause mortality.

Background Several coexisting diseases have been reported in patients with moyamoya vasculopathy (MMV), but studies of quasi-moyamoya disease (quasi-MMD) are rare. This study aims to investigate the frequency of known coexisting diseases in patients with quasi-MMD and to compare quasi-MMD with moyamoya disease (MMD). Methods Between 2000 and 2011, we retrospectively screened patients with International Classification of Diseases, Ninth Revision , code of 4375 (MMD) in the Health Information System of our hospital. The vascular images of each patient were confirmed by 2 neurologists and 1 neuroradiologist based on the diagnostic criteria of Japan Ministry of Health and Welfare. We excluded the patients with missing images and erroneous diagnosis. Demographics, coexisting diseases, laboratory data, treatment, and recurrent strokes were recorded. The eligible patients were divided into quasi-MMD and MMD groups according to the presence or absence of coexisting diseases. Results MMV was found in 90 patients including 37 (41.1%) quasi-MMD and 53 (58.9%) MMD. Atherosclerosis (32.4%) and thyroid disease (29.7%) were the leading coexisting diseases in quasi-MMD. Patients with MMD became symptomatic in a bimodal age distribution, whereas patients with quasi-MMD became symptomatic in a single-peak distribution. The prognosis of recurrent strokes was similar between quasi-MMD and MMD based on Kaplan–Meier analysis. Conclusions A bimodal distribution of onset age was noted in MMD, whereas a single-peak distribution was found in quasi-MMD. Coexisting diseases were usually underevaluated but were more common than expected in patients with MMV. Atherosclerosis and thyroid diseases were the leading coexisting diseases in different preferential age.

Background and purpose Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke. Methods Between January 2009 and December 2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr), these patients were divided into dehydrated (BUN/Cr ≥ 15) and non-dehydrated (BUN/Cr

We enrolled 221 patients with elective carotid artery stenting (CAS). Patients with contralateral carotid stenosis exceeding 50%, insufficient vertebral artery (VA) flows, or angioplasty at subclavian artery were excluded. All patients underwent serial cerebral ultrasound studies. Of the 116 included patients, the direction of ophthalmic artery (OA) flow was forward in 74 patients while reversed in 42. The reversed flow group had worse ipsilateral stenosis, higher hemoglobin, and cardiac output. After CAS, the reversed flow group had an immediate recovery of ipsilateral internal carotid artery flow volume (FV; P < .0001), time average velocity (TAV) of middle cerebral artery ( P = .02), and normalization of OA flow. The forward flow group had gradual decrement in TAV of contralateral anterior cerebral artery ( P = .01) and total FV of VA ( P = .001). Our results suggest CAS improves cerebral hemodynamics through different ways regardless of the direction of OA flow.

Objective. Thallium toxicity induces cellular injury through impaired Na-K-ATPase activity. The aim of this study was to investigate functional imaging and the long-term clinical-imaging correlations of thallium toxicity. Materials and methods. We measured thallium concentrations in blood, urine, stools, and hair of a 48-year-old woman and a 52-year-old man (patients 1 and 2) in the first 3 months after exposure to thallium containing water, and studied their neuropsychological functions. Using fluorodeoxyglucose positron emission tomography (18FDG PET) scans, we examined the brain involvement and correlated the image findings with the clinical presentations. Results. On the 1st, 30th, and 61st days after exposure, the thallium concentrations in patient 1 were 2056, 311, and 7.5 μg/L in the blood, and 11400, 4570, and 36.4 μg/L in the urine. The concentrations in patient 2 were 956, 235, and 15.6 μg/L in the blood, and 11900, 2670, and 101 μg/L in the urine. On the 40th, 50th and 89th days after exposure,...