Enhanced versus standard hydration in acute ischaemic stroke: REVIVE - a randomised clinical trial.

RATIONALE: Early neurological deterioration (END) within 72 hours of stroke onset is associated with poor prognosis. Optimising hydration might reduce the risk of END. AIMS: To determine in acute ischaemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as whether it increased the incidence of early neurological improvement (secondary), at 72 hours after admissionSample Size Estimate: 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicentre, parallel-group, randomised controlled trial conducted at 4 hospitals from April 2014 to July 2020, with data analysed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischaemic stroke patients with measurable neurological deficits of onset within 12 hours of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ≥15 at point of admission were enrolled and randomised to 0.9% sodium chloride infusions of varying rates - enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 hours) versus standard hydration (60 mL/hour for 8 hours), followed by maintenance infusion of 40-80 mL/hour for the subsequent 64 hours. The primary outcome measure was the incidence of major early neurological deterioration at 72 hours after admission, defined as an increase in National Institutes of Health Stroke Scale of ≥4 points from baseline. RESULTS: 487 participants were randomised (median age 67 years; 287 females). At 72 hours: 7 (2.9%) in the enhanced-hydration arm and 5(2.0%) in the standard-hydration developed major early neurological deterioration (p=0.54). The incidence of minor early neurological deterioration and early neurological improvement did not differ between treatment arms. CONCLUSIONS AND RELEVANCE: Enhanced hydration ratio did not reduce END or improve short term outcomes in acute ischaemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).

Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition.

Background and objectives: Leukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains. Materials and methods: One hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia. Results: Carotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment. Conclusion: Left and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.

Oral presentation assessment and image reading behaviour on brain computed tomography reading in novice clinical learners: an eye-tracking study.

BACKGROUND: To study whether oral presentation (OP) assessment could reflect the novice learners' interpretation skills and reading behaviour on brain computed tomography (CT) reading. METHODS: Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students' reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. RESULTS: The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p < 0.001] improved after instruction. Both the scores of systematic OP ratings [0 vs.1 in both cases, p < 0.001] and eye-tracking studies (Case 1: 3.42 ± 0.62 and 3.67 ± 0.37 in TE, p = 0.001; Case 2: 3.42 ± 0.76 and 3.75 ± 0.37 in TE, p = 0.002) showed that the image reading behaviour changed before and after instruction. The results of linear mixed models suggested a significant interaction between instruction and area of interests for case 1 (p < 0.001) and case 2 (p = 0.004). Visual attention to the target lesions in the case 1 assessed by dwell time were 506.50 ± 509.06 and 374.38 ± 464.68 milliseconds before and after instruction (p = 0.02). However, the dwell times in the case 2, the fixation counts and the frequencies of accurate lesion diagnoses in both cases did not change after instruction. CONCLUSION: Our results showed OP performance may change concurrently with the medical students' reading behaviour on brain CT after a structured instruction.

Head and Neck Cancer Types and Risks of Cervical-Cranial Vascular Complications within 5 Years after Radiation Therapy.

Background and purpose: to investigate the frequency of cervical−cranial vascular complications soon after radiation therapy (RT) and identify differences among patients with various types of head and neck cancer (HNC). Methods: We enrolled 496 patients with HNC who had received their final RT dose in our hospital. These patients underwent carotid duplex ultrasound (CDU) for monitoring significant carotid artery stenosis (CAS). Brain imaging were reviewed to detect vertebral, intracranial artery stenosis, or preexisted CAS before RT. Primary outcome was significant CAS at the internal or common carotid artery within first 5 years after RT. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of significant CAS between the groups using Kaplan−Meier and Cox-regression analyses. Results: Compared to the NPC group, the non-NPC group had a higher frequency of significant CAS (12.7% vs. 2.0%) and were more commonly associated with significant CAS after adjusting the covariates (Adjusted hazard ratio: 0.17, 95% confident interval: 0.05−0.57) during the follow-up period. All the non-NPC subtypes (oral cancer/oropharyngeal, hypopharyngeal, and laryngeal cancers) were associated with higher risks of significant CAS than the NPC group (p < 0.001 respectively). Conclusion: Significant CAS was more frequently noted within 5 years of RT among the patients with non-NPC HNC than among the patients with NPC. Scheduled carotid artery surveillance and vascular risk monitoring should be commenced earlier for patients with non-NPC HNC. By contrast, vascular surveillance could be deferred to 5 years after RT completion in NPC patients.

Neurodegeneration and Vascular Burden on Cognition After Midlife: A Plasma and Neuroimaging Biomarker Study.

Background and Objectives: Neurodegeneration and vascular burden are the two most common causes of post-stroke cognitive impairment. However, the interrelationship between the plasma beta-amyloid (Aß) and tau protein, cortical atrophy and brain amyloid accumulation on PET imaging in stroke patients is undetermined. We aimed to explore: (1) the relationships of cortical thickness and amyloid burden on PET with plasma Aß40, Aß42, tau protein and their composite scores in stroke patients; and (2) the associations of post-stroke cognitive presentations with these plasma and neuroimaging biomarkers. Methods: The prospective project recruited first-ever ischemic stroke patients around 3 months after stroke onset. The plasma Aß40, Aß42, and total tau protein were measured with the immunomagnetic reduction method. Cortical thickness was evaluated on MRI, and cortical amyloid plaque deposition was evaluated by 18F-florbetapir PET. Cognition was evaluated with Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Dementia Rating Scale-2 (DRS-2). Results: The study recruited 24 stroke patients and 13 normal controls. The plasma tau and tau*Aß42 levels were correlated with mean cortical thickness after age adjustment. The Aß42/Aß40 ratio was correlated with global cortical 18F-florbetapir uptake value. The DRS-2 and GDS scores were associated with mean cortical thickness and plasma biomarkers, including Aß42/Aß40, tau, tau*Aß42, tau/Aß42, and tau/Aß40 levels, in stroke patients. Conclusion: Plasma Aß, tau, and their composite scores were associated with cognitive performance 3 months after stroke, and these plasma biomarkers were correlated with corresponding imaging biomarkers of neurodegeneration. Further longitudinal studies with a larger sample size are warranted to replicate the study results.

Total plaque score helps to determine follow-up strategy for carotid artery stenosis progression in head and neck cancer patients after radiation therapy.

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.

Hypothyroidism and risks of cerebrovascular complications among patients with head and neck cancer after radiotherapy.

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.

Cognitive Sequelae of Silent Ischemic Lesions Following Carotid Artery Stenting: Possible Role of Age-Related Moderation.

Background: The occurrence of ischemic lesions is common in patients receiving carotid artery stenting (CAS), and most of them are clinically silent. However, few studies have directly addressed the cognitive sequelae of these procedure-related silent ischemic lesions (SILs). Objective: In this study, we attempted to investigate the effects of SILs on cognition using a comprehensive battery of neuropsychological tests. Method: Eighty-five patients with unilateral carotid stenosis and 25 age-matched healthy volunteers participated in this study. Brain MRI was performed within 1 week before and 1 week after CAS to monitor the occurrence of post-CAS SILs. A comprehensive battery tapping reading ability, verbal and non-verbal memory, visuospatial function, manual dexterity, executive function, and processing speed was administered 1 week before and 6 months after CAS. To control for practice effects on repeated cognitive testing, the reliable change index (RCI) derived from the healthy volunteers was used to determine the cognitive changes in patients with carotid stenosis. Results: Among the 85 patients with carotid stenosis, 21 patients received medical treatment (MED group), and procedure-related SILs were noted in 17 patients (SIL+ group) but not observed in 47 patients (SIL- group) after undergoing CAS. Two-way (group × phase) ANOVA revealed that the volunteer group showed improved scores in most cognitive tests while only limited improvement was noted in the SIL- group. The MED and control groups tended to show improvement in the follow-up cognitive testing than the SIL+ group. However, most of the cognitive changes for each patient group did not exceed the upper or lower limits (z = ±1.0) of the RCI. Conclusions: Although the occurrence of procedure-related SILs is common in patients undergoing CAS, their impacts on cognitive changes after CAS may be limited. The practice effect should be taken into consideration when interpreting cognitive changes following CAS.

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

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.

Computed Tomography Angiography in Acute Stroke Patients Receiving Recombinant Tissue Plasminogen Activator: Outcome and Safety Evaluations in an Asian Population.

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.

Brain computerized tomography reading in suspected acute ischemic stroke patients: what are essentials for medical students?

BACKGROUND: Few systematic methods prioritize the image education in medical students (MS). We hope to develop a checklist of brain computerized tomography (CT) reading in patients with suspected acute ischemic stroke (AIS) for MS and primary care (PC) physicians. METHODS: Our pilot group generated the items indicating specific structures or signs for the checklist of brain CT reading in suspected AIS patients for MS and PC physicians. These items were used in a modified web-based Delphi process using the online software "SurveyMonkey". In total 15 panelists including neurologists, neurosurgeons, neuroradiologists, and emergency department physicians participated in the modified Delphi process. Each panelist was encouraged to express feedback, agreement or disagreement on the inclusion of each item using a 9-point Likert scale. Items with median scores of 7-9 were included in our final checklist. RESULTS: Fifty-two items were initially provided for the first round of the Delphi process. Of these, 35 achieved general agreement of being an essential item for the MS and PC physicians. The other 17 of the 52 items in this round and another two added items suggested by the panelists were further rated in the next round. Finally, 38 items were included in the essential checklist items of brain CT reading in suspected AIS patients for MS and PC physicians. CONCLUSIONS: We established a reference regarding the essential items of brain CT reading in suspected AIS patients. We hope this helps to minimize malpractice and a delayed diagnosis, and to improve competency-based medical education for MS and PC physicians.

Application of Meridian Electrical Conductance in the Setting of Acute Ischemic Stroke: A Cross-Sectional Study.

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.

The correlation of asymmetrical functional connectivity with cognition and reperfusion in carotid stenosis patients.

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.

Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Receiving Thrombectomy: Standard or Low Dose Therapy?

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.

Visualization of ischemic stroke-related changes on 18F-THK-5351 positron emission tomography.

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.

Academic outcomes of flipped classroom learning: a meta-analysis.

CONTEXT: The flipped classroom (FC), reversing lecture and homework elements of a course, is popular in medical education. The FC uses technology-enhanced pre-class learning to transmit knowledge, incorporating in-class interaction to enhance higher cognitive learning. However, the FC model is expensive and research on its effectiveness remains inconclusive. The aim of this study was to compare the efficacy of the FC model over traditional lecture-based (LB) learning by meta-analysis. METHODS: We systematically searched MEDLINE, PubMed, ERIC, CINAHL, EMBASE, reference lists and Association for Medical Education in Europe (AMEE) conference books. Controlled trials comparing academic outcomes between the FC and LB approaches in higher education were considered eligible. The main findings were pooled using a random-effects model when appropriate. RESULTS: Forty-six studies (9026 participants) were included, comprising four randomised controlled trials (RCTs), 19 quasi-experimental studies and 23 cohort studies. Study populations were health science (n = 32) and non health science (n = 14) students. The risk of bias was high (36/37 articles). Meta-analyses revealed that the FC had significantly better outcomes than the LB method in examination scores (post-intervention and pre-post change) and course grades, but not in objective structured clinical examination scores. Subgroup analyses showed the advantage of the FC was not observed in RCTs, non-USA countries, nursing and other health science disciplines and earlier publication years (2013 and 2014). Cumulative analysis and meta-regression suggested a tendency for progressively better outcomes by year. Outcome assessments rarely focused on behaviour change. CONCLUSIONS: The FC method is associated with greater academic achievement than the LB approach for higher-level learning outcomes, which has become more obvious in recent years. However, results should be interpreted with caution because of the high methodological diversity, statistical heterogeneity and risk of bias in the studies used. Future studies should have high methodological rigour, a standardised FC format and utilise assessment tools evaluating higher cognitive learning and behaviour change to further examine differences between FC and LB learning.

Core neurological examination items for neurology clerks: A modified Delphi study with a grass-roots approach.

BACKGROUND: With the evolution of treatments for neurological diseases, the contents of core neurological examinations (NEs) for medical students may need to be modified. We aimed to establish a consensus on the core NE items for neurology clerks and compare viewpoints between different groups of panelists. METHODS: First, a pilot group proposed the core contents of NEs for neurology clerks. The proposed core NE items were then subject to a modified web-based Delphi process using the online software "SurveyMonkey". A total of 30 panelists from different backgrounds (tutors or learners, neurologists or non-neurologists, community hospitals or medical centers, and different academic positions) participated in the modified Delphi process. Each panelist was asked to agree or disagree on the inclusion of each item using a 9-point Likert scale and was encouraged to provide feedback. We also compared viewpoints between different groups of panelists using the Mann-Whitney U test. RESULTS: Eighty-three items were used for the first round of the Delphi process. Of them, 18 without consensus of being a core NE item for the neurology clerks in the first round and another 14 items suggested by the panelists were further discussed in the second round. Finally, 75 items with different grades were included in the recommended NE items for neurology clerks. CONCLUSIONS: Our findings provide a reference regarding the core NE items for milestone development for neurology clerkships. We hope that prioritizing the NE items in this order can help medical students to learn NE more efficiently.

Changes in E-Selectin Levels Predict Carotid Stenosis Progression after Carotid Artery Stenting.

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.

A genome-wide association study links small-vessel ischemic stroke to autophagy.

Genome-wide association studies (GWAS) can serve as strong evidence in correlating biological pathways with human diseases. Although ischemic stroke has been found to be associated with many biological pathways, the genetic mechanism of ischemic stroke is still unclear. Here, we performed GWAS for a major subtype of stroke-small-vessel occlusion (SVO)-to identify potential genetic factors contributing to ischemic stroke. GWAS were conducted on 342 individuals with SVO stroke and 1,731 controls from a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 188 SVO stroke cases and 1,265 controls. Three SNPs (rs2594966, rs2594973, rs4684776) clustered at 3p25.3 in ATG7 (encoding Autophagy Related 7), with P values between 2.52 × 10-6 and 3.59 × 10-6, were identified. Imputation analysis also supported the association between ATG7 and SVO stroke. To our knowledge, this is the first GWAS to link stroke and autophagy. ATG7, which has been implicated in autophagy, could provide novel insights into the genetic basis of ischemic stroke.

Asymmetric Cerebrovascular Collateral Supply Affects Cognition in Patients with Unilateral Carotid Artery Stenosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ps<0.001), respectively. Compared to healthy volunteers, the Right-delayed group performed significantly worse on most of the visuospatial tests (ps<0.04), while the Left-delayed group performed significantly worse on most of the verbal tests (ps<0.05). The performance of the Non-delayed group on all cognitive domains was similar to that of healthy volunteers (ps>0.07). CONCLUSION: 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.