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Background Sarcopenia and osteoporosis frequently co‐occur in the elderly and have common pathophysiological determinants. Slit guidance ligand 3 (SLIT3) has been recently discovered as a novel therapeutic factor against osteoporosis, and a SLIT3 fragment containing the second leucine‐rich repeat domain (LRRD2) had a therapeutic efficacy against osteoporosis. However, a role of SLIT3 in the skeletal muscle is unknown. Methods Skeletal muscle mass, strength, and/or physical activity were evaluated in Slit3 −/−, ovariectomized, and aged mice, based on the measurements of muscle weight and grip strength, Kondziella's inverted hanging test, and/or wheel‐running test. Skeletal muscles were also histologically evaluated by haematoxylin and eosin staining and/or immunofluorescence. The ovariectomized and aged mice were intravenously injected with recombinant SLIT3 LRRD2 for 4 weeks. C2C12 cells were used to know cellular effects of SLIT3, such as in vitro myogenesis, fusion, cell viability, and proliferation, and also used to evaluate its molecular mechanisms by immunocytochemistry, immunoprecipitation, western blotting, real‐time PCR, siRNA transfection, and receptor‐ligand binding ELISA. Results Slit3‐deficient mice exhibited decreased skeletal muscle mass, muscle strength, and physical activity. The relative masses of gastrocnemius and soleus were lower in the Slit3 −/− mice (0.580 ± 0.039% and 0.033 ± 0.003%, respectively) than those in the WT littermates (0.622 ± 0.043% and 0.038 ± 0.003%, respectively) (all, P

Rationale Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain. Aim We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment. Sample-size estimates We aim to randomize 668 patients (334 per arm), 1:1. Methods and design We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP Study outcomes The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0–2 vs. 3–6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months. Discussion The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP Clinical trial registration ClinicalTrials.gov Identifier: NCT04205305.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Background and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion.Methods Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization.Results Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032).Conclusions The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Author's summary We sought to determine neurological outcomes following stroke in patients with left atrial appendage occlusion (LAAO) or non-vitamin K antagonist oral anticoagulant (NOAC) treatment for non-valvular atrial fibrillation (NVAF). Left atrial appendage closure significantly reduced stroke severity and lowered the risk of disabling stroke at 12 months post-event compared to NOAC after adjusting for multiple demographic and cardiovascular risk factors (odds ratio, 0.23; 95% confidence interval, 0.07–0.71; p=0.01). Thus, LAAO may yield more favorable outcomes in NVAF patients experiencing subsequent stroke than NOAC treatment, even in patients with increased risk of cardio- and cerebrovascular events., Background and Objectives Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment. Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results mRS scores were significantly lower in LAAO patients at 3 (p

Objective It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Methods Ten-week-old C57Bl/6 mice (n=338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1-4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1-3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed microCT thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. Results We observed a higher volume of carotid thrombus after dabigatran cessation at 1-3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through arachidonic acid or thrombin, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤3 day) cessation of NOAC therapy, compared with longer-term (≥5 days) cessation, tended to be associated with relatively high stroke severity. Interpretation We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. This article is protected by copyright. All rights reserved.

BACKGROUND AND PURPOSE The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS Patients were categorized on the basis of their BMI into underweight (BMI

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p

Background Endovascular treatment has been considered a good alternative to surgery for symptomatic vertebral artery origin stenosis (VAOS) due to the high risk of morbidity associated with surgery. The purpose of this study was to evaluate the feasibility and efficacy of insertion of the closed-cell, self-expandable Carotid Wallstent for the treatment of VAOS. Methods The records of 72 patients with VAOS refractory to adequate medication who were treated by endovascular treatment with the Carotid Wallstent from December 2006 to November 2018 were retrospectively evaluated. Results Of the 72 patients, 43 presented with transient ischemic attacks. Forty-seven patients (65.3%) manifested other brachiocephalic stenoses; of these, 40 patients had occlusion, hypoplasia, or stenosis of the contralateral vertebral artery. Overall technical success (defined as 20% or less residual stenosis) was 100%. Procedure-related complications ( n = 8, 11.1%) included sudden asystole ( n = 1), acute in-stent thrombosis ( n = 3), minor stroke ( n = 3), and stent shortening ( n = 1). All complications were resolved without permanent neurological deficit. Angiographic follow-up (mean, 13.0 months) was achieved in 49 patients and revealed in-stent restenosis in 1 patient (2.0%) and stent malposition by shortening in 2 patients (4.1%). Follow-up records were available in 57 patients (mean 15.6 months). Three of the 57 patients ( n = 3, 5.3%) had recurrent symptoms of vertebrobasilar ischemia and none was retreated. Conclusions Endovascular treatment of symptomatic VAOS using the closed-cell, self-expandable Carotid Wallstent is technically feasible and effective in alleviating patient symptoms and for improving vertebrobasilar blood flow.

We investigated whether there was an annual change in outcomes in patients who received the thrombolytic therapy or endovascular treatment (EVT) in Korea. This analysis was performed using data from a nationwide multicenter registry for exploring the selection criteria of patients who would benefit from reperfusion therapies in Korea. We compared the annual changes in the modified Rankin scale (mRS) at discharge and after 90 days and the achievement of successful recanalization from 2012 to 2017. We also investigated the determinants of favorable functional outcomes. Among 1230 included patients, the improvement of functional outcome at discharge after reperfusion therapy was noted as the calendar year increased (p &lt, 0.001). The proportion of patients who were discharged to home significantly increased (from 45.6% in 2012 to 58.5% in 2017) (p &lt, 0.001). The successful recanalization rate increased over time from 78.6% in 2012 to 85.1% in 2017 (p = 0.006). Time from door to initiation of reperfusion therapy decreased over the years (p &lt, 0.05). These secular trends of improvements were also observed in 1203 patients with available mRS data at 90 days (p &lt, 0.05). Functional outcome was associated with the calendar year, age, initial stroke severity, diabetes, preadmission disability, intervals from door to reperfusion therapy, and achievement of successful recanalization. This study demonstrated the secular trends of improvement in functional outcome and successful recanalization rate in patients who received reperfusion therapy in Korea.

Objectives A significant proportion of patients with acute minor stroke have unfavorable functional outcome due to early neurological deterioration (END). The purpose of this study was to evaluate the applicability of machine learning algorithms to predict END in patients with acute minor stroke. Patients and methods We collected clinical and neuroimaging information from patients with acute minor stroke with NIHSS score of ≤ 3. Early neurological deterioration was defined as any worsening of NIHSS score within 3 days after admission. Unfavorable functional outcome was defined as a modified Rankin Scale score of ≥ 2. We also compared clinical and neuroimaging information between patients with and without END. Four machine learning algorithms, i.e., Boosted trees, Bootstrap decision forest, Deep neural network, and Logistic Regression, were selected and trained by our dataset to predict early neurological deterioration Results A total of 739 patients were included in this study. 78 patients (10.6%) experienced END. Among 78 patients with END, 61 (78.2%) had unfavorable functional outcome at 90 days after stroke onset. On multivariate analysis, the initial NIHSS score (P = 0.003), hemorrhagic transformation (P = 0.010), and stenosis (P = 0.014) or occlusion (P = 0.004) of a relevant artery were independently associated with END. Of the four machine learning algorithms, Boosted trees, Deep neural network, and Logistic Regression can be used to predict END in patients with acute minor stroke (Boosted trees: accuracy = 0.966, F1 score = 0.8 and area under the curve = 0.934, Deep neural network :0.966, 0.8, and 0. 904, and Logistic Regression : 0.966, 0.8, and 0.885). Conclusions This study suggests that machine learning algorithms that integrate clinical and neuroimaging information can be used to predict END in patients with acute minor stroke. Further studies based on larger, multicenter datasets are needed to predict END accurately for designing treatment strategies and obtaining favorable functional outcome.

IntroductionPrior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset.Materials and methodsWe enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses.ResultsOf the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses.ConclusionsIn patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

Background The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs. Materials and Methods We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups. Results Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p Conclusion Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.

Background and Purpose— We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods— This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results— In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm 3 ; P P 3 . In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm 3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions— Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Summary Background CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. Methods We did this pragmatic, multicentre, randomi s ed controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15–44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analy s is was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Findings Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI −0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Interpretation Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Funding Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea.

As populations continue to age worldwide, sarcopenic obesity has heightened interest due to its medical importance. Although much evidence now indicates that n-3 fatty acids (FAs) may have beneficial effects on body composition including fat and muscle, their exact mechanisms have not yet been elucidated. Because free FA receptor 4 (FFA4) has been reported to be a receptor for n-3 FAs, we hypothesized that the protective role of n-3 FAs on body composition could be mediated by FFA4. To test this possibility, we generated mice overexpressing n-3 FAs but lacking FFA4 by crossing fat-1 transgenic (fat-1 Tg+) and FFA4 knockout (Ffar4 -/-) mice. Because fat-1 Tg+ mice, in which n-6 is endogenously converted into n-3 FAs, contain high n-3 FA levels, they could be a good animal model for studying the effects of n-3 FAs in vivo. Male and female littermates were included in high-fat-diet- (HFD) and ovariectomy-induced models, respectively. In the HFD model, male fat-1 Tg+ mice had a lower percentage of fat mass and a higher percentage of lean mass than their wild-type littermates only when they had the Ffar4 +/+ not the Ffar4 -/- background. Female fat-1 Tg+ mice showed less increase of fat mass percentage and less decrease of lean mass percentage after ovariectomy than wild-type littermates. However, these effects on body composition were attenuated in the Ffar4 -/- background. Taken together, our results indicate that the beneficial effects of n-3 FAs on body composition were mediated by FFA4 and thus suggest that FFA4 may be a potential therapeutic target for modulating sarcopenic obesity.

Background and purpose Patients who have acute stroke symptoms present on awakening are ineligible for standard intravenous thrombolysis due to the unclear onset time of symptoms. Some of these wake-up stroke (WUS) patients may benefit from endovascular recanalization. This study aimed to evaluate clinical predictors of outcomes from endovascular recanalization in WUS patients. Methods Forty-one WUS patients with internal carotid (ICA) or middle cerebral artery (MCA) occlusion treated with endovascular recanalization were reviewed. Regression analysis was performed to measure clinical predictors of outcomes from endovascular recanalization in WUS patients. Results The mean initial NIHSS score was 16.41 ± 4.96 (5–24). The mean symptom recognition-to-door time (SRDT) was 108.85 ± 65.80 (19–230) min. Successful recanalization (TICI 2b-3) was achieved in 29 patients (70.7%). Thirty-four patients improved on NIHSS (amount 7.59 ± 4.84, range; 1–17) at 7 days after recanalization. At 90 days after recanalization, a mRS of ≤2 was achieved in 19 patients (46.3%) and a mRS of ≤3 was achieved in 24 patients (58.5%). No symptomatic intracerebral hemorrhage occurred. Multivariate regression analysis identified SRDT (P = 0.019), successful recanalization (P = 0.005), and hypertension (P = 0.013) were factors associated with an improvement of the NIHSS score. For a good functional outcome at 90 days, SRDT (P = 0.036) and initial NIHSS score (P = 0.016) were found to be significant predictors. Conclusions The results of this study suggest that the SRDT is an independent predictor of both an improvement of NIHSS score and a good functional outcome in endovascular recanalization for WUS patients.

Objective To date, no controlled studies on the treatment of carotid artery dissection (CAD) have been reported. The purpose of this study was to demonstrate the technical feasibility and clinical efficacy of stent-supported angioplasty (SSA) as primary treatment for acute stroke due to CAD. Methods A review of medical records identified 21 patients who underwent SSA as primary treatment for acute stroke related to CAD between 2008 and 2014. The inclusion criteria were recent transient ischemic attack (n = 7, 33.3%) or acute infarct (n = 14, 66.7%) due to CAD (≥70% narrowing) with hemodynamic impairment. Technical success rates, complications, and angiographic and clinical outcomes were analyzed retrospectively. Results SSA was technically successful in all patients. Of 21 patients, 8 (38.1%) showed an additional intracranial occlusion. Intracranial recanalization to a thrombolysis in cerebral infarction ≥2b flow was achieved in 50% of the cases. Procedure-related mortality was 4.8%, and morbidity was 9.5%. Five (35.7%) of 14 patients presenting with an acute infarct showed significant improvement (decrease in National Institutes of Health Stroke Scale score of ≥4 points compared with admission score) at 7 days after SSA. During the observation period (mean, 20.5 months), stroke recurrence occurred in only 1 patient (5%), resulting in an annual stroke risk of 2.9%. A favorable outcome (modified Rankin Scale score ≤2) was achieved in all 7 patients with a transient ischemic attack (100%) and in 7 of 14 patients with an acute infarct (50%) at the 90-day follow-up. Conclusion Our results provide evidence that SSA is a feasible and effective strategy as primary treatment for steno-occlusive CAD patients with significant hypoperfusion or a large penumbra.

Background This study investigated the clinical value of interleukin-6 (IL-6), pentraxin 3 (PTX3), and procalcitonin (PCT) in patients with sepsis and septic shock diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods Serum levels of IL-6, PTX3, and PCT were measured in 142 enrolled subjects (51 with sepsis, 46 with septic shock, and 45 as controls). Follow-up IL-6 and PTX3 levels were measured in patients with initial septic shock within 24 h of hospital discharge. Optimal cut-off values were determined for sepsis and septic shock, and prognostic values were evaluated. Results Serum IL-6 levels could discriminate sepsis (area under the curve [AUC], 0.83–0.94, P P = 0.008). IL-6 was an independent risk factor for 28-day mortality among overall patients (hazard ratio, 1.0004; 95% confidence interval, 1.0003–1.0005; p = 0.024). In septic shock patients, both the initial and follow-up PTX3 levels were consistently significantly higher in patients who died than in those who recovered (initial p = 0.004; follow-up P Conclusions The diagnostic and prognostic value of IL-6 was superior to those of PTX3 and PCT for sepsis and septic shock.

Objective. Appropriate regional transport protocol for out-of-hospital cardiac arrest (OHCA) patients is important for achiev-ing favorable outcomes in a certain com-munity. This study aimed to investigate the effect of transported hospital resources on the neurologic outcome after OHCA. Methods. We categorized cardiac receiv-ing centers (CRC) in our community into two levels (primary [P-CRC] and definite CRC [D-CRC]) according to the hospital resources that were identified by the Hos-pital Assessment Survey in 2015. OHCA patients with presumed cardiac etiology resuscitated by emergency medical service providers between 2012 and 2014, were enrolled in the study. The main exposure was the level of CRC. The primary end-point was discharge with good neurologic outcomes. We compared outcomes be-tween CRCs after adjusting for potential confounders. Results. Among the 9,912 patients, 5,876 were transported to P-CRC and 4,036 to D-CRC from 2012 to 2014. Patients admit-ted to D-CRC showed better neurologic outcome than those admitted to P-CRC (6.2% vs 1.5%, p

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF). Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groups Results: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1–17)], followed by the warfarin withdrawal group [11, IQR (1–14, 18)], the no antithrombotic group [5, IQR (1–13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1–10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384–8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group. Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes.

The 2016 Surviving Sepsis Campaign guidelines suggest guiding resuscitation to normalize lactate levels in patients with sepsis-associated hyperlactatemia as a marker of tissue hypoperfusion. This study evaluated the prognostic value of lactate levels and lactate clearance for 30-day mortality in patients with sepsis and septic shock diagnosed in the emergency department.We performed a retrospective cohort study of sepsis patients with initial lactate levels of ≥2 mmol/L. All patients met the Sepsis-3 definitions. The prognostic value of 6-hour lactate levels, 6-hour lactate clearance, 6-hour lactate metrics (≥2 mmol/L), and lactate clearance metrics (

The Sewol ferry disaster is one of the most tragic events in Korea’s modern history. Among the 476 people on board, which included Danwon High School students (324) and teachers (14), 304 passengers died in the disaster (295 recovered corpses and 9 missing) and 172 survived. Of the rescued survivors, 72 were attending Danwon High School, located in Ansan City, and residing in a residence nearby. Because the students were young, emotionally susceptible adolescents, both the government and the parents requested the students be grouped together at a single hospital capable of appropriate psychiatric care. Korea University Ansan Hospital was the logical choice, as the only third-tier university-grade hospital with the necessary faculty and facilities within the residential area of the families of the students. We report the experiences and the lessons learned from the processes of preparing for and managing the surviving young students as a community-based hospital. (Disaster Med Public Health Preparedness. 2017;11:389–393)

Background: Carotid endarterectomy (CEA) is the standard treatment modality for the prevention of stroke in patients with carotid stenosis. This study reports our experiences during CEA with routine awake tests under regional anesthesia (RA) combined with light sedation by dexmedetomidine infusion. Materials and Methods: We retrospectively reviewed 23 patients who had undergone CEA between April 2013 and June 2015. All patients underwent the awake test during CEA with cervical plexus block and light sedation by continuous dexmedetomidine infusion. Results: Mean operation and clamp times were 108.5 ± 20.1 min and 30.1 ± 6.9 min, respectively. Selective shunt placement was performed in three patients (13.0%). There were no cases of perioperative stroke, myocardial infarction, or death. There were no occurrences of residual stenosis, thrombosis, or dissection. One patient had a hypoglossal nerve injury but fully recovered before discharge. Mean (± standard deviation) hospital stay was 7.5 ± 2.6 days. There were no incidences of death, stroke, or restenosis during a mean follow-up period of 9.2 ± 8.8 months. Conclusions: RA with dexmedetomidine infusion appears to be a safe and feasible option. A lower shunt placement rate and favorable patient outcomes were observed following the awake test during CEA.

Biomarkers are valuable tools for the prediction of mortality in patients with sepsis. However, the use of a single biomarker to predict patient outcomes is challenging owing to the complexity and redundancy of the immune response to infections.We aimed to conduct a prospective observational analysis to investigate the prognostic value of pentraxin 3, interleukin 6, procalcitonin, and lactate combined in predicting the 28-day mortality rate in patients with sepsis or septic shock (n = 160; sepsis, 78; sepsis shock, 82). Two methods (the frequency sum of values above the cutoff, and the multivariate logistic regression model) were used to assess the prognostic value of the biomarker combination.In the receiver operating characteristic curve analyses, the combination of the 4 biomarkers was better than the Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality rate, regardless of whether the frequency sum of values above the cutoff or the multivariate logistic model was used for the analysis. The addition of the SOFA score to the biomarker combination did not result in a better performance for the prediction of mortality.The combined biomarker approach showed good performance in predicting 28-day all-cause mortality among patients diagnosed with either sepsis or septic shock according to the Sepsis-3 definitions. Furthermore, it was superior to the SOFA score in predicting mortality.

The aim of this study was to determine the frequency, clinical and radiological features, and efficacy of clinical evaluation and perfusion-weighted imaging (PWI) for the prediction of final stroke in patients with DWI/MRI-negative posterior circulation stroke (PCS) presenting acute dizziness/vertigo. From our comprehensive prospective stroke registry of acute ischemic stroke during a 7-year period, we identified 1846 consecutive patients with PCS, 850 of whom presented with acute dizziness/vertigo. Of these 850 patients, initial DWI-MRI was negative in 35 (4.1%). In these 35 patients, dizziness/vertigo was acute prolonged in 31 and recurrent transient in 4. Focal neurological signs or profound imbalance were present in 16/35 or 18/34, respectively. Spontaneous nystagmus was absent in 21/35; the HINTS protocol (head impulse, nystagmus, and test-of-skew) was not applicable to them. In 12/26 patients, PWI was positive and the same time as DWI was negative. The usual site of lesion was the lateral medulla (n = 18). Twenty-nine patients (83%) had small strokes, while 19 (54%) had large vessel strokes. The sensitivity of systematic clinical evaluation adopting neurological examination, HINTS plus, and assessment of equilibrium was 83%, for prediction of final stroke and 100% when combined with PWI. An integrated approach using systematic neurological and neuro-otological examinations combined with PWI accurately diagnoses PCS presenting with acute dizziness/vertigo. Although most patients with acute vertigo and MRI-negative PCS have small brainstem strokes, about a half have large vessel stroke with greater risk of progression requiring prompt treatment.

Background Using high-resolution magnetic resonance imaging (HR-MRI), we investigated the impact of basilar artery plaques that were not detected by magnetic resonance angiography (MRA) on the functional outcomes of patients with acute pontine infarction. Methods A total of 40 patients with acute pontine infarction and normal basilar findings on MRA prospectively underwent HR-MRI for detection of basilar artery plaques. A relevant plaque was defined as one on the dorsal side of basilar artery, the same side of the ischemic lesion, and the same axial slices of the ischemic lesion. We analyzed the relationship between the relevant basilar artery plaques and the functional outcomes at 3 months. Results The initial National Institutes of Health Stroke Scale score (3.5 versus 2.0, P = .012), and the incidences of neurological deterioration (42.9% versus 6.3%, P = .031) and unfavorable functional outcome (71.4% versus 12.5%, P = .001) were higher in patients with relevant basilar artery plaques than in those without. On multiple regression analysis, the relevant basilar artery plaque was a significant and independent predictor of unfavorable functional outcome (odds ratio, 6.662; 95% confidence interval, 1.117-39.735; P = .037). Conclusions The presence of a relevant basilar artery plaque was closely related with unfavorable functional outcome in patients with acute pontine infarction even if the patients’ MRA showed normal basilar findings.

Background and purpose: In this study, we investigated the stroke severity was associated with the prior antithrombotic medication including novel Vitamin K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). Methods: We included 801 consecutive acute ischemic stroke or transient ischemic attack patients with NVAF who were admitted to 6 hospitals between August 2013 and January 2017 in the present study. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). Prior antithrombotics before index stroke were categorized into 5 groups: no antithrombotics, only antiplatelet, warfarin with international normalized ratio (INR) Results: A total of 801 acute ischemic stroke or transient ischemic stroke patients with NVAF were enrolled. Among the 801 patients, the 34 (4.2%) had been treated with warfarin with INR ≥2, 146 (18.2%) with warfarin with INR ≥2, 70 (8.7%) with NOACs, 347 (43.3%) with only antiplatelet, and 204 (25.5%) without any antithrombotics. The median NIHSS score was 5 (IQR 1-14). Compared with the no antithrombotics group (9.5, IQR 2-16), the NIHSS was lower in the warfarin with INR ≥2 (4, 1-7.3) and the only antiplatelet group (4, IQR 1-12), while the warfarin with INR Conclusions: Our data indicate that the prior anticoagulation was related with milder initial stroke severity in patients with NVAF.

Background and purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). Coronary screening is recommended in patients with high risks for CAD. It remains uncertain which group of stroke patients need evaluation for asymptomatic CAD, and which evaluation tool is appropriate for stroke patients. We investigated whether the coronary artery calcium (CAC) scores could predict significant CAD in patients with acute stroke and which stroke patients need a screening test for significant CAD. Methods: Among consecutive stroke patients between September 2011 and August 2013, a total of 1143 patients who underwent multiple detector CT coronary angiography and cerebral angiography were included. Atherosclerotic stenosis ≥ 50% or obstruction was classified as significant stenosis in coronary and cerebral arteries. Patients were grouped into four subgroups on the basis of CAC score: 0, 0.1-99.9, 100-399.9, and ≥ 400. Presence of hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking were considered as risk factors. Results: Of 1143 patients, significant stenosis was detected in 164 patients (14.3%) in the internal carotid artery (ICA), 279 (24.4%) in the vertebrobasilar artery (VBA), and 81 (7.1%) in the both ICA and VBA. Significant coronary artery stenosis in at least one coronary artery was detected in the 398 patients (34.8%). Two or more risk factors and one or more significant stenosis in the ICA or VBA were considered as screening criteria for choosing potential CAD patients according to AUC analysis. As the CAC score increased, odd ratio for significant CAD remarkably increased (2.1678, CI 1.0152 to 4.6290 for CAC score 0, 5.7193 ,CI 2.9192 to 11.2051 for 0 Conclusion: Two or more risk factors and one or more significant stenosis in the ICA or VBA can be used to choose patients with stroke who need to perform a screening test predicting significant CAD. CAC score also can be used as a screening to perform coronary artery evaluation even in the patients without documented cerebral atherosclerosis.

Piceatannol, a polyphenol which exhibits anticancer activities, is found in grapes, red wine and berries. It has been shown to inhibit several transcription factor pathways. The present study was conducted to determine whether oral administration of piceatannol inhibits mammary tumor progression. 4T1 mammary carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c mice. Starting 1 day later, piceatannol (10- or 20-mg/kg body weight/day) was administered by oral gavage for 30 days. Piceatannol treatment reduced tumor growth. In tumor tissues, piceatannol treatment reduced the expression of transcription factors P-NFκB p65, P-STAT3 and HIF-1α and multiple proteins involved in regulation of cell cycle progression (Ki67, cyclin D1, cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration. Piceatannol significantly increased apoptotic cells and expression of both Bax and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition, piceatannol reduced the number and volume of pulmonary tumor nodules and expression of MMP-9 in both lung and tumor. It also reduced tissue levels of cytokines/chemokines, including M-CSF and MCP-1. In vitro results revealed that piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte migration, which was suppressed by a CCR2 antibody. These results indicate that alteration in tumor microenvironment (macrophages, transcription factors, etc.) is an important mechanism by which piceatannol inhibits tumor proliferation, angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor growth and metastasis.

Objective Collateral flow is important for ischemic brain tissue after an acute occlusion of the cerebral artery. The purpose of this study was to evaluate baseline collateral flow, on CT angiography (CTA), as a predictor of functional outcome in patients who had endovascular recanalization, after acute pure first segment (M1) occlusion of the middle cerebral artery (MCA). Methods Thirty patients with acute pure M1 occlusion treated by endovascular recanalization, who were ineligible for intravenous thrombolysis or resistant to intravenous thrombolysis, were reviewed. The relationship between baseline collateral flow, on CTA, and functional outcome, was analyzed. In addition, other factors affecting clinical outcome were assessed. Results The mean NIHSS score on admission was 16.87±4.86 (7–24). The mean time interval between onset of stroke symptoms and recanalization was 324.37±68.38 (210–463)min. Successful recanalization (TICI 2b-3) was achieved in 18 patients (60%). Twenty-seven of 30 patients improved their NIHSS score (mean 8.4); NIHSS score 8.9±5.4 (median 10, range 0–16) at seven days. Two patients had aggravated symptoms and one patient had no change on the NIHSS score. At 90 days after recanalization, a modified Rankin Scale (mRS) of ≤3 was achieved in 15 patients (50%) and a mRS of ≤2 was achieved in nine patients (30%). Symptomatic intra-cerebral hemorrhage occurred in two patients (6.7%). Multivariate regression analysis showed an initial NIHSS score ( p =0.004), grade of baseline collateral flow on CTA ( p =0.025), presence of diabetes mellitus ( p =0.037), and TICI scale ( p =0.049) were factors associated with an improved NIHSS. For the mRS at 90 days, only the grade of the baseline collateral flow on CTA was associated with a good functional outcome ( p =0.013). Conclusions The results of this study suggest that the grade of baseline collateral flow, on CTA, is an independent predictor of functional outcome for endovascular recanalization of acute pure M1 occlusion of the middle cerebral artery.

We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Dear Sir: Shortening the interval between hospital arrival and thrombolytic treatment is critical to improve the efficacy of the treatment because of its time-sensitive effect [1]. Decision-making by patients or their families is an essential step during the process of thrombolytic treatment. In an emergency situation, decision-making by patients or their families relies mostly on the physician’s explanation concerning the benefits and risks of thrombolytic treatment. In this regard, a physician’s concise, standardized, and easily understandable explanation of the thrombolytic treatment is important for the process of decision-making and for obtaining informed consent from patients or their family. We investigated how a protocol using decision-making support (DMS) for patients and their families could reduce door-to-needle time in acute stroke. We have previously shown that quality improvement activity using a computerized physician order entry could reduce time from hospital arrival to evaluations and intravenous (IV) tissue plasminogen activator (tPA) [2-4]. While performing continuous quality improvement activity to further improve the process, we have found that the most common reason of treatment delay was waiting informed consent [5]. Therefore, we developed a protocol for DMS using standardized scrip and visual decision aid. The standardized script was developed for physicians who are responsible for providing explanations regarding thrombolysis treatment and then obtaining informed consent from patients or their families. The visual decision aid (http://stroke.ucla.edu/workfiles/VDA-for-TPA.pdf) was used by physicians to help explain the benefits and risks of IV tPA treatment to candidates for this treatment. This protocol was implemented from January 2010. All consecutive patients who visited the emergency department and were treated with IV tPA within the 3-hour time window were included in this study. The effect of DMS was investigated by comparing the door-to-needle time before (the pre-DMS group, January 2007–December 2009) and after (post-DMS group, January 2010–December 2012) the implementation of the DMS protocol. Demographic factors and time intervals were compared using the Mann–Whitney U test and the chi-square test. The possible reasons for delay were identified if the door-to-needle time was longer than 40 minutes. To determine factors associated with a door-to-needle time >40 minutes, multivariable logistic regression analysis was performed. Age, sex, and variables with P

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background and Purpose: Patients who have acute stroke symptoms present on awakening are ineligible for standard intravenous thrombolysis due to the unclear onset time of symptoms. Some of these wake-up stroke (WUS) patients may benefit from endovascular recanalization. This study aimed to evaluate clinical predictors of outcomes from endovascular recanalization in WUS patients. Methods: Forty-one WUS patients with internal carotid (ICA) or middle cerebral artery (MCA) occlusion treated with endovascular recanalization were reviewed. Regression analysis was performed to measure clinical predictors of outcomes from endovascular recanalization in WUS patients. Results: The mean initial NIHSS score was 16.41 ± 4.96 (5-24). The mean symptom recognition-to-door time (SRDT) was 108.85 ± 65.80 (19-230) minutes. Successful recanalization (TICI 2b-3) was achieved in 29 patients (70.7%). Thirty-four patients improved on NIHSS (amount 7.59 ± 4.84, range; 1-17) at 7 days after recanalization. At 90 days after recanalization, a mRS of ≤ 2 was achieved in 19 patients (46.3%) and a mRS of ≤ 3 was achieved in 24 patients (58.5%). No symptomatic intracerebral hemorrhage occurred. Multivariate regression analysis identified SRDT (P=0.019), successful recanalization (P=0.005), and hypertension (P=0.013) were factors associated with an improvement of the NIHSS score. For a good functional outcome at 90 days, SRDT (P=0.036) and initial NIHSS score (P=0.016) were found to be significant predictors. Conclusions: The results of this study suggest that the SRDT is an independent predictor of both an improvement of NIHSS score and a good functional outcome after endovascular recanalization in WUS patients.

Background and Purpose Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process. Methods After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared. Results The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]. Conclusions PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

This study was investigate the influences of wild haw ( Crataegus pinnatifida BUNGE) on lowering blood urea nitrogen (BUN) and creatinine concentrations in dyslipidemic rats. Four groups of rats were fed different diets for 5 weeks: basal diet (BD group), nondyslipidemic diet+feral haw extract (NDF group), dyslipidemic diet (DLD group), dyslipidemic diet+feral haw extract (DFH group). BUN, creatinine and uric acid concentrations were significantly higher in the DLD group than in the BD group. However, DFH group significantly lowered BUN, creatinine and uric acid concentrations compared to the DLD group. Amylase activity was significantly lower in the DLD group than in the BD group, while DFH group significantly higher compared to the DLD group. Lipase activity was also also significantly lower in the DLD group than the other group. Accordingly, these results suggest that haw extract could be effective for improving kidney function in dyslipidemic rats. Key words : Crataegus pinnatifida

To examine the effects of high-fat diet (HFD) on melanoma progression, HFD-fed C57BL/6N mice were subcutaneously injected with syngeneic B16F10 melanoma cells. At 3 weeks post-injection, the tumors were resected; the mice were then sacrificed at 2 weeks post-resection. HFD stimulated melanoma growth and lymph node (LN) metastasis as well as tumor and LN lymphangiogenesis. Lipid vacuoles in the tumor and M2-macrophage (MΦ)s in the adipose and tumor tissues were increased in HFD-fed mice. CCL19 and CCL21 contents were higher in LNs than in tumors. HFD increased both CCL19 and CCL21 levels in LNs and CCR7 in tumors. Adipose tissue-conditioned media (CM) from HFD-fed mice enhanced lymphangiogenesis, and mature adipocyte (MA)/M2-MΦ co-culture CM markedly stimulated the tube formation of lymphatic endothelial cell (LEC)s and B16F10 migration. Monocyte migration was moderately stimulated by B16F10 or MA CM, but tremendously stimulated by B16F10/M2-MΦ co-culture CM, which was enhanced by MA/B16F10/M2-MΦ co-culture CM. The co-culture results revealed that MAs increased CCL2, M-CSF and CCR7 mRNAs in B16F10s; vascular endothelial growth factor (VEGF)-D mRNA in M2-MΦs; and CCL19, CCL21 and VEGF receptor (VEGFR)3 mRNA in LECs. M2-MΦs increased CCL2, M-CSF and VEGF-A mRNAs in B16F10s, whereas B16F10s increased VEGF-C mRNAs in M2-MΦs and VEGFR3 mRNA in LECs. These results indicate that in HFD-fed mice, MA-induced CCL2 and M-CSF in tumor cells increase M2-MΦs in tumor; the crosstalk between tumor cells and M2-MΦs further increases cytokines and angiogenic and lymphangiogenic factors. Additionally, MA-stimulated CCL19, CCL21/CCR7 axis contributes to increased LN metastasis in HFD-fed mice.

With the emerging risks of drug-resistant viruses and pandemic influenza, rapid and accurate detection of influenza viruses and determination of their subtypes is a crucial component of patient management. This study evaluated the performance of the Verigene respiratory virus plus nucleic acid (Verigene RV+) test for the detection of influenza A/B and subtype determination compared it with conventional molecular methods. Nasopharyngeal swabs were collected from 228 patients with influenza-like illness (influenza A (n = 67), 2009-H1N1 (n = 21), influenza B (n = 80), mixed A & B (n = 3), mixed RSV A and influenza (n = 3), and influenza-negative (n = 54)). Patient samples were analyzed by Influenza A/B one-step typing (Seegene, Seoul, Korea), Seeplex RV15 ACE Detection (Seegene), Nanosphere Verigene RV+ assay (Nanosphere, Northbrrook, IL) and virus culture. Out of 228 samples, 109 (47.8%) were positive by culture, and an additional 65 (28.5%) were positive by Seeplex RV15 ACE Detection, Influenza A/B one-step typing or Nanosphere Verigene RV+ assay. In comparison tests with Seeplex RV15 ACE Detection RT-PCR, the sensitivity of the Verigene RV+ kit for detection of the influenza A, 2009-H1N1, influenza B, and mixed A & B was 97.1%, 100%, 100%, and 100%, respectively. The specificity of the Verigene RV+ was 100% for all types. The concordance between Verigene RV+ and Influenza A/B one-step typing for H1, H3, H1/H3 mixed, and 2009-H1N1 was 100% (26/26), 100% (35/35), 100% (4/4), and 100% (21/21), respectively. The Verigene RV+ assay showed acceptable sensitivity and specificity for detection and subtyping of influenza viruses compared with the conventional RT-PCR method. J. Med. Virol. 87: 18–24, 2015. © 2014 Wiley Periodicals, Inc.

We previously reported that a high-fat diet (HFD) and M2-macrophages induce changes in tumor microenvironments and stimulate tumor growth and metastasis of 4T1 mammary cancer cells in BALB/c mice. In this study, we attempted to determine whether benzyl isothiocyanate (BITC) inhibits HFD-induced changes in tumor progression and in tumor microenvironments. Four groups of female BALB/c mice (4-week-old) were fed on a control diet (CD, 10 kcal% fat) and HFD (60 kcal% fat) containing BITC (0, 25, or 100 mg/kg diet) for 20 weeks. Following 16 weeks of feeding, 4T1 cells (5 × 104 cells) were injected into the mammary fat pads, and animals were killed 30 d after the injection. HFD feeding increased solid tumor growth and the number of tumor nodules in the lung and liver, as compared to the CD group, and these increases were inhibited by BITC supplementation. The number of lipid vacuoles, CD45+ leukocytes and CD206+ M2-macrophages, expression of Ki67, levels of cytokines/chemokines, including macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1, and mRNA levels of F4/80, CD86, Ym1, CD163, CCR2, and M-CSF receptor were increased in the tumor tissues of HFD-fed mice, and these increases were inhibited by BITC supplementation. In vitro culture results demonstrated that BITC inhibited macrophage migration as well as lipid droplet accumulation in 3T3-L1 cells. These results suggest that suppression of lipid accumulation and macrophage infiltration in tumor tissues may be one of the mechanisms by which BITC suppresses tumor progression in HFD-fed mice. © 2014 Wiley Periodicals, Inc.

Objective Intracranial stenting is a possible option as a rescue strategy for acute secondary division (M2) occlusion of middle cerebral artery (MCA) when intravenous thrombolysis is ineffective or contraindicated. Methods We reviewed 10 patients of acute M2 occlusion treated by intracranial stenting who were ineligible for intravenous thrombolysis or resistant to intravenous thrombolysis. All patients underwent intracranial stenting with the Wingspan stent system. We analyzed clinical and angiographic outcomes. Results The mean NIHSS score on admission was 13.8 points (range 6–23). The occlusion sites were located in the superior division (n = 4, left: 3, right: 1), the middle division (n = 1, right) and the inferior division (n = 5, all: right) of MCA. The mean time interval from stroke symptom onset to stenting was 348.9 ± 90.4 min. Successful recanalization was achieved in all patients. No intracranial hemorrhage, vessel perforations or dissections occurred in any patient. One patient developed acute thrombosis in distal ICA of the stented side at 4 days after a stent placement and was managed with mechanical thrombectomy. All patients improved on the NIHSS (mean amount: 8.8) and to the NIHSS score of 5 ± 4.6 (median 4.5, range 0–15) at 7 days. At discharge, an mRS of ≤3 was achieved in 8 patients (80%) and an mRS of ≤2 was achieved in 6 patients (60%). Conclusions Endovascular recanalization with a Wingspan stent can be a safe and feasible procedure for acute M2 occlusion when intravenous thrombolysis is ineffective or not available.

Background: Novel dietary agents for colon cancer prevention and therapy are desired. Kaempferol, a flavonol, has been reported to possess anticancer activity. However, little is known about the molecular mechanisms of the anticancer effects of kaempferol. The aim of this study was to determine the inhibitory effect of kaempferol on growth factor-induced proliferation and to elucidate its underlying mechanisms in the HT-29 human colon cancer cell line. Methods: To assess the effects of kaempferol and/or growth factors [insulin-like growth factor (IGF)-I and heregulin (HRG)-β], cells were cultured with or without 60 μmol/L kaempferol and/or 10 nmol/L IGF-I or 20 μg/L HRG-β. Cell proliferation, DNA synthesis, and apoptosis were determined by a cell viability assay, a [3H]thymidine incorporation assay, and Annexin-V staining, respectively. Western blotting, immunoprecipitation, and an in vitro kinase assay were conducted to evaluate expression and activation of various signaling molecules involved in the IGF-I receptor (IGF-IR) and ErbB3 signaling pathways. Results: IGF-I and HRG-β stimulated HT-29 cell growth but did not abrogate kaempferol-induced growth inhibition and apoptosis. Kaempferol reduced IGF-II secretion, HRG expression and phosphorylation of Akt and extracellular signal-regulated kinase (ERK)-1/2. Kaempferol reduced IGF-I- and HRG-β-induced phosphorylation of the IGF-IR and ErbB3, their association with p85, and phosphatidylinositol 3-kinase (PI3K) activity. Additionally, kaempferol inhibited IGF-I- and HRG-β-induced phosphorylation of Akt and ERK-1/2. Conclusions: The results demonstrate that kaempferol downregulates activation of PI3K/Akt and ERK-1/2 pathways by inhibiting IGF-IR and ErbB3 signaling in HT-29 cells. We suggest that kaempferol could be a useful chemopreventive agent against colon cancer.

Objective Transient anterograde amnesia is occasionally observed in a number of conditions, including migraine, focal ischemia, venous flow abnormalities, and after general anesthesia. The inhalation anesthetic, isoflurane, is known to induce transient anterograde amnesia. We examined the involvement of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in the underlying mechanisms of the isoflurane-induced transient anterograde amnesia. Methods Adult male Sprague-Dawley rats were divided into three groups : the control group, the 10 minutes after recovery from isoflurane anesthesia group, and the 2 hours after recovery from isoflurane anesthesia group (n=8 in each group). The rats in the isoflurane-exposed groups were anesthetized with 1.2% isoflurane in 75% nitrous oxide and 25% oxygen for 2 hours in a Plexiglas anesthetizing chamber. Short-term memory was determined using the step-down avoidance task. BDNF and TrkB expressions in the hippocampus were evaluated by immunofluorescence staining and western blot analysis. Results Latency in the step-down avoidance task was decreased 10 minutes after recovery from isoflurane anesthesia, whereas it recovered to the control level 2 hours after isoflurane anesthesia. The expressions of BDNF and TrkB in the hippocampus were decreased immediately after isoflurane anesthesia but were increased 2 hours after isoflurane anesthesia. Conclusion In this study, isoflurane anesthesia induced transient anterograde amnesia, and the expressions of BDNF and TrkB in the hippocampus might be involved in the underlying mechanisms of this transient anterograde amnesia.

Background A greater intake of vegetables and fruits has been linked to a reduced incidence of colon cancer. Flavonoids are polyphenolic compounds which are broadly distributed in fruits and vegetables and display a remarkable spectrum of physiological activities, including anti-carcinogenic effects. The objective of this study was to determine the mechanisms by which kaempferol, a flavonol present in tea, apples, strawberries, and beans, inhibits the growth of HT-29 human colon cancer cells. Methods To examine the effects of kaempferol on cell cycle progression in HT-29 cells, cells were treated with various concentrations (0-60 μmol/L) of kaempferol. Cell proliferation and DNA synthesis were evaluated by MTT assay and [(3)H]thymidine incorporation assay, respectively. Fluorescence-activated cell sorting analyses were conducted to calculate cell cycle phase distribution. Western blot analyses and in vitro kinase assays were used to estimate the expression of proteins involved in the regulation of cell cycle progression and the activity of cyclin-dependent kinase (CDK)s, respectively. Results Kaempferol decreased viable cell numbers and [(3)H]thymidine incorporation into DNA of HT-29 cells in a dose-dependent manner. Kaempferol induced G1 cell cycle arrest within 6 h and G2/M arrest at 12 h. Kaempferol inhibited the activity of CDK2 and CDK4 as well as the protein expression of CDK2, CDK4, cyclins D1, cyclin E, and cyclin A, and suppressed the phosphorylation of retinoblastoma protein. Additionally, kaempferol decreased the levels of Cdc25C, Cdc2, and cyclin B1 proteins, as well as the activity of Cdc2. Conclusions The present results indicate that kaempferol induces G1 and G2/M cell cycle arrest by inhibiting the activity of CDK2, CDK4, and Cdc2. The induction of cell cycle arrest may be one of the mechanisms by which kaempferol exerts anti-carcinogenic effects in colon cancer cells.