bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Total Enteral Feeding versus Conventional Enteral Feeding in Stable Very-Low-Birth-Weight Infants: A Randomised Controlled Trial
Authors: Nangia Sushma , Vadivel Vinoth , Thukral Anu , Saili Arvind
Published: January 2019

Objective: To evaluate the effect of early total enteral feeding (ETEF) when compared with conventional enteral feeding (CEF) in stable very-low-birth-weight (VLBW; 1,000–1,499 g) infants on the postnatal age (in days) at attaining full enteral feeds. Methods: In this unblinded randomised controlled trial, 180 infants were allocated to an ETEF (n = 91) or a CEF group (n = 89). Feeds were initiated as total enteral feeds in the ETEF group and as minimal enteral nutrition (20 mL/kg) in the CEF group. The rest of the day’s requirement in the CEF group was provided as parenteral fluids. The primary outcome was postnatal age at attaining full enteral feeds. The secondary outcomes included episodes of feed intolerance, incidence of sepsis and necrotising enterocolitis (NEC), and duration of hospital stay. Results: The baseline variables including birth weight and gestational age were similar in the two groups. The infants of the ETEF group attained full enteral feeds earlier than those of the CEF group (6.5 ± 1.5 vs. 10.1 ± 4.1 days postnatal age; mean difference –3.6 [–4.5 to –2.7]; p < 0.001). Total episodes of feed intolerance and clinical sepsis were fewer, with a shorter duration of hospital stay, in the ETEF group (15.5 vs. 19.6 days) (p = 0.01). The incidence of NEC was similar in the two groups. Conclusion: ETEF in stable VLBW infants results in earlier attainment of full feeds and decreases the duration of hospital stay without any increased risk of feed intolerance or NEC.
Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety
Authors: Zhao Zhiying , Yao Shuxia , Li Keshuang , Sindermann Cornelia , Zhou Feng , Zhao Weihua , Li Jianfu , Lührs Michael , Goebel Rainer , Kendrick Keith M. , Becker Benjamin
Published: January 2019

Background: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. Methods: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Results: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. Conclusions: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
Phronesis and the Knowledge-Action Gap in Moral Psychology and Moral Education: A New Synthesis?
Authors: Darnell Catherine , Gulliford Liz , Kristjánsson Kristján , Paris Panos
Published: January 2019

This article has two aims. First, to offer a critical review of the literatures on two well-known single-component solutions to the problem of a gap between moral knowledge and moral action: moral identity and moral emotions. Second, to take seriously the rising interest in Aristotle-inspired virtue ethics and character development within the social sciences: approaches that seem to assume that the development of phronesis (practical wisdom) bridges the gap in question. Since phronesis is a multicomponent construct, the latter part of this article offers an overview of what those different components would be, as a necessary precursor to operationalising them if the phronesis hypothesis were to be subjected to empirical scrutiny. The idea of a neo-Aristotelian multicomponent solution to the “gappiness problem” invites comparisons with another multicomponent candidate, the neo-Kohlbergian four-component model, with which it shares at least surface similarities. Some space is thus devoted to the proposed theoretical uniqueness of a phronesis-based multicomponent model vis-à-vis the neo-Kohlbergian one. Our main conclusion is that – weaknesses in its developmental psychological grounding notwithstanding – operationalising the phronesis model for the purposes of instrument design and empirical inquiry would be a feasible and potentially productive enterprise.
Clearance of Magnesium in Peritoneal Dialysis Patients: A Single-Center Study
Authors: Li Guiyan , Zhang Li , Ren Haibin , Huang Baodi , Mao Chunxia , Zhou Annan
Published: January 2019

Objective: This retrospective study aimed to investigate the clearance of magnesium (Mg) in peritoneal dialysis (PD) patients and its influencing factors. Methods: The demographic information, clinical characteristics and laboratory data of the patients were collected. According to the corrected serum Mg (cS-Mg) concentration, patients were divided into 3 groups including hypomagnesemia (Mg2+ < 0.77 mmol/L, group A), normal serum Mg concentration (0.77 mmol/L ≤ Mg2+ ≤1.03 mmol/L, group B), and hypermagnesemia (Mg2+ > 1.03 mmo/L, group C). Results: One hundred and fifteen patients were enrolled, and their mean 24 h-peritoneal Mg clearance was 39.75 ± 17.42 mg. The mean normalized peritoneal Mg clearance rate was 1.82 ± 0.82 L/day/1.73 m2. Twenty-four-hour peritoneal Mg clearance of group A was significantly lower than that of group C (p < 0.05). Bivariate correlation analysis showed that cS-Mg was positively correlated with peritoneal dialysate Mg concentration (p < 0.01). cS-Mg was negatively correlated with the normalized peritoneal Mg clearance rate (p < 0.05). The normalized peritoneal Mg clearance rate was positively correlated with prealbumin (p < 0.05), daily peritoneal protein loss (p < 0.01) and the normalized PD-creatinine clearance rate (p < 0.01). The normalized peritoneal Mg clearance rate was also negatively correlated with the normalized renal-creatinine clearance rate (p < 0.01). Furthermore, cS-Mg of patients with continuous ambulatory PD (CAPD) was significantly lower than that of patients with daytime ambulatory PD (DAPD, p < 0.01). The normalized peritoneal Mg clearance rate of patients with CAPD was significantly higher than that of patients with DAPD (p < 0.01). Moreover, among the patients with different peritoneal transport characteristics of peritoneal equilibration test, the normalized peritoneal Mg clearance rate of high average transport patients was significantly higher than that in those with low transport, low average transport and high transport (p < 0.05). Conclusions: Serum Mg could be partly cleared by PD. The peritoneal Mg clearance was positively related with serum Mg concentration, which was concentration-dependent. Peritoneal Mg clearance was negatively correlated with the residual renal function, while being positively correlated with the nutritional status and daily peritoneal protein loss. Peritoneal Mg clearance was higher in patients with high transport characteristics or CAPD.
Study on the Prevalence of Vascular Calcification in Different Types of Arteries and Influencing Factors in Maintenance Peritoneal Dialysis Patients
Authors: Niu Qingyu , Zhao Huiping , Wu Bei , Tsai Shihming , Wu Jian , Zhang Meng , Lu Lixia , Qiao Jie , Men Chuncui , Zuo Li , Wang Mei
Published: January 2019

Objective: To investigate the occurrence of vascular calcification (VC) in different types of arteries in patients with maintenance peritoneal dialysis (PD) patients and its influencing factors. Methods: This study enrolled PD patients with stable status who has received PD treatment for more than 6 months in Peking University People’s Hospital. We used plain X-ray films of abdomen, pelvis, and hands to quantitatively evaluate VC of large artery (abdominal aorta, iliac artery), medium artery (femoral artery, radial artery), and small artery (finger arteries). Two radiologists read and scored radiographs blindly. Demographic data, clinical characteristics, Charlson comorbidity index (CCI), baseline and time-average laboratory indices including parameters of calcium phosphorus metabolism, serum albumin, PD adequacy were collected. A logistic regression model was used to estimate the influencing factors of different sites of VC. Results: (1) 154 PD patients were enrolled in this study: seventy-eight males, mean age was 60.4 ± 13.9 years, and median PD duration was 24 (16.39) months. The major primary disease was diabetic nephropathy (39%). (2) Among the 154 PD patients, the proportion of calcification of large artery was the highest (found in 100 patients, accounting for 64.9%); then the medium artery (66, 42.9%); and 15 of small artery, accounting for 9.7%. (3) Logistic regression showed that older age, longer dialysis duration, lower baseline serum intact parathyroid hormone (iPTH), and higher CCI scores were independent risk factors of large artery calcification (p < 0.05), and higher CCI scores, higher baseline serum triglycerides (TG), lower baseline serum iPTH, and time-average iPTH were independent risk factors of medium and small arteries. Conclusions: In PD patients, the occurrence of large artery calcification was higher than others. Among different sites of VC, the abdominal aortic calcification was most likely to occur, and the proportion of small artery calcification was low. Calcification of medium and small arteries can exist alone without calcification of large artery. Large artery calcification was more likely to occur in patients with older age, longer dialysis duration, lower baseline serum iPTH levels and higher CCI scores. Patients with higher CCI scores, higher baseline TG and lower baseline iPTH, and time-average iPTH were more likely to develop small and medium artery calcification.
Sclerostin/Receptor Related Protein 4 and Ginkgo Biloba Extract Alleviates β-Glycerophosphate-Induced Vascular Smooth Muscle Cell Calcification By Inhibiting Wnt/β-Catenin Pathway
Authors: Wang Jian , Qiu Xiaobo , Xu Tianhua , Sheng Zitong , Yao Li
Published: January 2019

Background: Abnormal mineral metabolism in patients with chronic kidney disease (CKD) may lead to vascular calcification, which is markedly associated with adverse events, including ischemic cardiac diseases and all-cause cardiovascular mortality. Thus, preventing and treating vascular calcification play an important role in improving the prognosis of CKD patients. Objectives: To investigate the potential functions of sclerostin and low-density lipoprotein receptor-related protein 4 (Lrp4) in alleviating the β-glycerophosphate (β-GP)-induced vascular smooth muscle cell (VSMC) calcification, and the protective effect of Ginkgo biloba extract (GBE). Methods: VSMC were extracted from Sprague-Dawley rat aorta and cultured in medium. The VSMCs were divided into 3 groups: (1) Negative control group, (2) β-GP group, in which the VSMCs were treated with β-GP, and (3) GBE and β-GP group, where the VSMCs were treated with both β-GP and GBE. The calcium nodules within the cells were examined by using Alizarin red S staining. The mRNA expression levels of β-catenin and bone gamma-carboxyglutamic-acid-containing proteins (BGP) were detected by real-time PCR. The protein levels of sclerostin and Lrp4 were determined by Western blot. Results: Alizarin red S staining showed that the VSMCs in β-GP group had a distinct orange-red precipitate when compared with VSMCs in the negative control group, while the orange-red precipitate of the GBE and β-GP group was significantly reduced compared to the β-GP group. Real-time PCR showed that the mRNA levels of β-catenin and BGP in VSMCs of β-GP group were significantly higher than those of the negative control group (p < 0.05); while they were significantly reduced in VSMCs of the GBE and β-GP group (p < 0.05). Western blot results showed that the expression of sclerostin in the β-GP group was significantly higher than that in the control group (p < 0.05), whereas Lrp4 was significantly lower than in control group (p < 0.05). Sclerostin in GBE and β-GP group was significantly reduced (p < 0.05), but Lrp4 was significantly elevated when compared with that of the β-GP group (p < 0.05). Conclusion: β-GP induced VSMC calcification by activating the Wnt/β-catenin signaling pathway. Sclerostin and Lrp4 were involved in β-GP-induced VSMC calcification and play an important role. GBE could alleviate VSMC calcification induced by β-GP through inhibiting the Wnt/β-catenin signaling pathway.
Effect of Assertive Community Treatment for Patients with Substance Use Disorder: A Systematic Review
Authors: Penzenstadler Louise  , Soares Carina , Anci Eleonora , Molodynski Andrew , Khazaal Yasser
Published: January 2019

Purpose: Substance use disorders (SUD) are an important health issue internationally. Traditional outpatient programmes often do not adequately address the substantial medical and social needs and in addition many patients have difficulties accessing the care needed. The assertive community treatment (ACT) model was originally developed for patients with a severe mental illness but has been adapted for patients with SUD by integrating specific SUD treatments into the traditional ACT model. This paper aims to assess the effectiveness of ACT for patients with SUD on a number of measures. Methods: We performed a systematic review of ACT interventions for patients with SUD by analyzing randomized controlled studies published before June 2017 found on the electronic databases PsychINFO, MEDLINE, PsychARTICLES. Eleven publications using 5 datasets were included in the analysis. Quality of studies was analyzed using the JADAD scale or Oxford quality scoring system. Outcome measures used were substance use, treatment engagement, hospitalization rates, quality of life, housing status, medication compliance and legal problems. Patients included in the studies had a diagnosis of SUD. Two datasets included homeless patients and 2 datasets included patients with high service use. Results and Conclusions: The results of the very few existing randomized control studies are mixed. Treatment engagement was higher for ACT in 4 datasets. One dataset reported higher service contact rates for the ACT group than for controls. In 2 datasets a positive effect on hospitalization rates was found. Higher fidelity to the ACT model appears to improve outcomes. Substance use reduced only in half of the datasets, of which only one showed a significant reduction in the ACT group. Overall, ACT is a promising approach that may be useful for promoting treatment engagement for patients with SUD. According to earlier studies on patients with severe mental illness, patients with high inpatient service use benefit most from this assertive approach. We hypothesize that a similar high need user group among patients with SUD might benefit most from ACT. Further research is needed to examine which types of clinical interventions might help difficult-to-engage patients with addictions.
Everolimus and Bevacizumab in the Management of Recurrent, Progressive Intracranial NF2 Mutated Meningioma
Authors: Mathew Thomas Vinay , Bindal Poorva , Vredenburgh James J.
Published: January 2019

Meningiomas are primary CNS tumors that arise from the arachnoid layer of the meninges. Genomic sequencing has revealed that NF2 mutations are the most common genetic alteration seen in meningiomas. Meningiomas although usually low grade, can sometimes progress to high grade. A patient who had several recurrences of meningiomas since childhood presented with recurrent headaches. Imaging showed that he had another recurrence of a meningioma. He underwent surgery for resection of the meningioma and histopathology showed NF2 mutation. He was started on everolimus and bevacizumab with good effect. Studies have shown that NF-2 mutated meningiomas have a good response to everolimus and bevacizumab with increased progression-free survival time and progression-free survival time at 6 months.
Surgery for Prolactinomas to Date
Authors: Buchfelder Michael , Zhao Yining , Schlaffer Sven-Martin
Published: January 2019

While in the past surgery for prolactinomas was a competitive option to medical treatment with dopamine agonists, to date the indications for operations are restricted to only a few specific situations. However, if a patient is intolerant to medical treatment or if the drugs are not sufficiently effective in terms of lowering prolactin levels or tumor shrinkage, surgery should always be considered. In microprolactinomas, operations can achieve excellent prolactin normalization rates. In tumors difficult to treat, the combination of surgical tumor resection and long-term medical treatment supports better control of the disease. The individual indications, results, techniques, and complications of operations for prolactinomas are briefly reviewed in this paper.
C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function
Authors: Wang Yong , Dembowsky Klaus , Chevalier Eric , Stüve Philipp , Korf-Klingebiel Mortimer , Lochner Matthias , Napp L. Christian , Frank Heike , Brinkmann Eva , Kanwischer Anna , Bauersachs Johann , Gyöngyösi Mariann , Sparwasser Tim , Wollert Kai C.
Published: January 2019

Background:

Acute myocardial infarction (MI) elicits an inflammatory response that drives tissue repair and adverse cardiac remodeling. Inflammatory cell trafficking after MI is controlled by C-X-C motif chemokine ligand 12 (CXCL12) and its receptor, C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 antagonists mobilize inflammatory cells and promote infarct repair, but the cellular mechanisms are unclear.

Methods:

We investigated the therapeutic potential and mode of action of the peptidic macrocycle CXCR4 antagonist POL5551 in mice with reperfused MI. We applied cell depletion and adoptive transfer strategies using lymphocyte-deficient
Rag1
knockout mice; DEREG mice, which express a diphtheria toxin receptor–enhanced green fluorescent protein fusion protein under the control of the promoter/enhancer region of the regulatory T (T
reg
) cell–restricted Foxp3 transcription factor; and dendritic cell-depleted CD11c-Cre iDTR mice. Translational potential was explored in a porcine model of reperfused MI using serial contrast-enhanced magnetic resonance imaging.

Results:

Intraperitoneal POL5551 injections in wild-type mice (8 mg/kg at 2, 4, 6, and 8 days) enhanced angiogenesis in the infarct border zone, reduced scar size, and attenuated left ventricular remodeling and contractile dysfunction at 28 days. Treatment effects were absent in splenectomized wild-type mice,
Rag1
knockout mice, and T
reg
cell–depleted DEREG mice. Conversely, treatment effects could be transferred into infarcted splenectomized wild-type mice by transplanting splenic T
reg
cells from POL5551-treated infarcted DEREG mice. Instructive cues provided by infarct-primed dendritic cells were required for POL5551 treatment effects. POL5551 injections mobilized T
reg
cells into the peripheral blood, followed by enhanced T
reg
cell accumulation in the infarcted region. Neutrophils, monocytes, and lymphocytes displayed similar mobilization kinetics, but their cardiac recruitment was not affected. POL5551, however, attenuated inflammatory gene expression in monocytes and macrophages in the infarcted region via T
reg
cells. Intravenous infusion of the clinical-stage POL5551 analogue POL6326 (3 mg/kg at 4, 6, 8, and 10 days) decreased infarct volume and improved left ventricular ejection fraction in pigs.

Conclusions:

These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell–primed splenic T
reg
cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting T
reg
cell function in vivo.
Abstract 1: DAWN versus Modified Clinical-ASPECTS Mismatch Selection for Stroke Endovascular Therapyin the Early and Late Time Windows
Authors: Bouslama Mehdi , Haussen Diogo , Grossberg Jonathan , Rodrigues Gabriel , Barreira Clara , Frankel Michael , Nogueira Raul
Published: January 2019

Background and Purpose:
Optimal patient selection for thrombectomy in large vessel acute ischemic stroke (LVOS) remain to be established. We evaluated the performance of imaging paradigms in a cohort of endovascularly-treated LVOS.

Methods:
Review of a prospectively collected database of endovascular patients with anterior circulation LVOS, adequate CTP maps, and NIHSS ≥10 from January 2014-June 2018 in a clinical setting where no specific ASPECTS or CTP criteria defined treatment selection. Patients were assessed for thrombectomy eligibility by each 2 mismatch criteria: DAWN Clinical-Core Mismatch (DAWN-CCM): between age-adjusted NIHSS and CTP-derived ischemic core volume and modified Clinical-ASPECTS Mismatch (mCAM) defined as ASPECTS 6-10 and one of the following criteria: NIHSS ≥ 10 and 0-1 Cortical-ASPECTS (M1-6 area) Involvement (any age);NIHSS ≥ 10 and 0-2 Cortical-ASPECTS (M1-6 areas) Involvement (and age < 80 years old);NIHSS ≥ 20 and 0-3 Cortical-ASPECTS (M1-6 areas) Involvement (and age < 80 years old). Clinical outcomes were compared.

Results:
591 patients qualified. mCAM had a higher inclusion rate as compared to the DAWN-CCM criteria (89.8%vs83.9%). The proportions of selected patients were statistically different between groups (p=0.01). Both mCAM(+) and DAWN-CCM(+) patients had higher rates of 90-day good outcomes (modified Rankin scale 0-2) compared to non-selected counterparts (53.2%vs21.3%,p<0.0001 and 52.5%vs35.5%,p=0.09 respectively). mCAM(+) had lower rates of 90-day mortality than mCAM(-) patients (17.5% vs 29.8%,p=0.04). However there was no difference in mortality between DAWN-CCM (+) and DAWN-CCM(-) patients (17.7% vs 25%,p=0.15). The abilities of mCAM and CCM to predict good outcomes were similar as assessed by the c-statistic, Akaike and Bayesian information criterion. Sensitivity analyses for the early (within 6H after symptom onset) and late (6-24H) time windows yielded similar results.

Conclusion:
mCAM and DAWN-CCM selection paradigms have similar inclusion rates and outcome discrimination ability. mCAM could represent a good substitute in centers where access to advanced imaging is more limited. Future studies are warranted.
Abstract 105: Obesity Induces Vascular Remodeling and Deteriorates Cognitive Function in Mice: Role of Pericytes
Authors: Coucha Maha , Barrett Amy C , Dalessandro Gabrielle A , Hafez Sherif , Ergul Adviye , Abdelsaid Mohammed A
Published: January 2019

30 million Americans of the United States population have diabetes. Additional 90 million people in the pre-diabetic stage. Insulin resistance and obesity are the hallmarks of prediabetes. Understanding the effect of obesity on cerebrovasculature is crucial to identify novel therapies to prevent cerebrovascular complications of diabetes including vascular cognitive impairment and dementia. We hypothesize that pericyte dysfunction in prediabetes causes vascular remodeling and pathological neovascularization that leads to vascular cognitive impairment and dementia. Methods, male and female mice were fed regular or a high fat diet (HFD) for 12 weeks. Insulin resistance (IR) was confirmed with a glucose tolerance test. Neovascularization indices were measured (Vascular density, tortuosity, and branching density) to assess cerebral integrity. Pericyte count and basement membrane thickness (BMT) were determined in the cerebral cortex. Learning and memory functions were evaluated using Water maze, Y-maze and novel object recognition (NOR). Pericyte (PC) were grown in high glucose (HG) to mimic prediabetes. Pericytes MMP9 activity, TIMP1 and PDGFR beta internalization were measured. Results, male and female mice fed with HFD showed a significant increase in body weight and IR as indicated by impaired glucose tolerance. 3D reconstructed images of cerebral cortex vasculature showed that HFD significantly increases neovascularization indices (P<0.05, n=5). TEM studies showed an increase in cerebrovascular BMT in HFD mice that was associated with significantly decreased in PCs count and TIMP-1 expression in the cerebral cortex. HFD led to significant deterioration of cognitive memory function in Water maze, Y maze, and NOR. (P<0.05, n=5). MMP9 activity and internalization of PDGFR beta were increased in HG-treated PCs that were accompanied by a decrease in TIMP1 expression. (P<0.05, n=4). Conclusion, obesity-induced pericyte dysfunction is associated with pathological cerebral vessel remodeling and impaired cognitive function. These studies illustrate the crucial role of pericyte dysfunction in prediabetes and identify pericytes as a potential therapeutic target for the treatment of cognitive impairment in diabetes.
Abstract 108: Direct Aspiration First Pass Technique versus Stent Retriever Thrombectomy in Basilar Artery Occlusion
Authors: Alemseged Fana , Yassi Nawaf , Diomedi Marina , Sallustio Fabrizio , Rocco Alessandro , Arba Francesco , Oxley Thomas , Morotti Andrea , Bush Steven , Yan Bernard , Dowling Richard J , Cavallini Anna , Nappini Sergio , Limbucci Nicola , Fifi Johanna , Gandini Roberto , Parsons Mark , Davis Stephen M , Mitchell Peter J , Campbell Bruce C ,   Batman Collaboration
Published: January 2019

Background:
Whether direct aspiration first pass technique (ADAPT) is associated with better clinical and procedural outcomes compared with stent retriever thrombectomy in basilar artery occlusion (BAO) is uncertain. We compared reperfusion and clinical outcomes between ADAPT and stent retriever thrombectomy (SR) in BAO.

Methods:
Clinical and procedural data of consecutive endovascular-treated stroke patients with BAO diagnosed on CT angiography from the multisite international Basilar Artery Treatment and MANagement (BATMAN) collaboration were retrospectively analysed. Good outcome was defined as modified Rankin Scale≤3 at 3 months; successful reperfusion as mTICI 2b-3 and complete reperfusion as TICI 3.

Results:
We included 107 BAO patients treated with mechanical thrombectomy [31 treated with first-line ADAPT and 76 with stent retriever or combined approach (“Solumbra technique”)]. An additional SR was used in 3/28 (11%) patients in the ADAPT group. Mean age was 67 (SD 14), median NIHSS 18 (IQR 7-29.5), 36% of patients received intravenous thrombolysis prior to mechanical thrombectomy. Median procedural time was 91min (IQR 49-132). Successful reperfusion was achieved in 87/107 (81%) of patients and good outcome was observed in 42/100 (42%) patients. Although a greater proportion of patients achieved successful reperfusion in the ADAPT group, this was not significant (ADAPT 87% vs SR 79%, p=0.4). Similarly, complete reperfusion occurred in 67% ADAPT vs 51% SR (p=0.2).14% of patients were treated beyond 6 hours in the ADAPT group vs 38% in the SR group (p=0.02). Procedural times were significantly shorter in the ADAPT group [52min (IQR 29-103.5) vs SR 99.5min (IQR 72-143); p<0.001)]. Rates of good outcome were significantly higher in patients treated with ADAPT (64% vs 40%, p=0.04). In ordinal regression analysis adjusted for age, NIHSS and time to treatment>6 hours, ADAPT remained associated with good outcome (cOR 3.4, 95%CI 1.3-8.6, p=0.01).

Conclusions:
ADAPT is associated with shorter procedural times and improved outcomes in comparison with stent retriever thrombectomy in BAO. Rates of successful reperfusion were similar in the two groups. Randomized controlled trials to determine the optimal endovascular technique are warranted.
Abstract 109: Thrombectomy is Safe for Dawn- and Defuse-3-Ineligible Patients Who Present Within the Extended Window: A Subgroup Analysis From the BEST Prospective Cohort Study
Authors: Siegler James E , Messé Steven R , Sucharew Heidi , Mehta Tapan , Arora Niraj , Starosciak Amy K , De Los Rios La Rosa Felipe , Barnhill Natasha R , Mistry Akshitkumar M , Patel Kishan , Assad Salman , Tarboosh Amjad , Dakay Katarina , Wagner Jeff , Bennett Alicia , Jagadeesan Bharathi , Streib Christopher , Weber Stewart A , Chitale Rohan , Volpi John J , Mayer Stephan A , Yaghi Shadi , Jayaraman Mahesh , Khatri Pooja , Mistry Eva
Published: January 2019

Background:
Recent data have demonstrated robust efficacy for endovascular thrombectomy in acute large vessel occlusion (LVO) up to 24h after symptom onset. Given the overwhelming benefit of this intervention in a highly selective, clinical trial population, it is plausible that a benefit may also be observed in some trial-ineligible patients.

Methods:
Using the BEST multi-center prospective cohort of consecutive patients who underwent thrombectomy for LVO, we compared DAWN and DEFUSE 3 trial-ineligible patients treated within 6-24 hours after last known normal (LKN) to trial-eligible patients, and to untreated controls from those trials. The co-primary outcomes were an early therapeutic response (decrease in NIHSS ≥10, or NIHSS 0-1 by 24h) and good functional outcome (90-day mRS 0-2). Secondary outcomes included change in NIHSS at 24h, intracerebral hemorrhage within 72h, and discharge to home or acute rehab.

Results:
Of 443 patients in the BEST cohort, 159 (36%) underwent endovascular therapy between 6-24 hours after LKN, of whom 71 (45%) were trial-ineligible. The most common trial exclusion criteria were M2 (53%) and multivessel occlusions (30%). Compared to trial-eligible patients, trial-ineligible patients were younger (median 63 vs. 72y, p=0.02) but had similar baseline NIHSS (median 14 vs. 15, p=0.28), ASPECTS scores (median 8 v. 8, p=0.69), times to recanalization (median 627 vs. 682 min, p=0.08), and rates of successful recanalization (TICI 2b/3, 83% v. 86%, p=0.57). Compared to DAWN untreated controls, BEST trial-ineligible patients were more likely to have an early therapeutic response (OR 2.02, 95%CI 1.00-4.06, p=0.049) and good functional outcome (OR 3.02, 95%CI 1.33-6.86, p=0.001). Compared to trial-eligible patients in BEST, trial-ineligible patients had similar improvements in 24h NIHSS (-2 vs. -4, p=0.33), rates of intracerebral hemorrhage (28% vs. 24%, p=0.54), and rates of discharge to home or rehab (77% vs. 73%, p=0.49).

Conclusion:
This multicenter prospective cohort demonstrates that thrombectomy for acute LVO within 24 hours in DAWN and DEFUSE 3 trial-ineligible patients is safe and may be effective. Treating these patients may be reasonable but our findings should be confirmed by additional randomized data trials.
Abstract 112: Brain Selective Hypothermia With Intra-arterial Cold Infusions Plus Early Normobaric Hyperoxygenation for Neuroprotection in Experimental Acute Ischemic Stroke
Authors: Wang Yi , Yang Xueyu , Patzwaldt Kristin , Castaneda Salvador , Martella Manuela , Quintanilla-Fend Leticia , Pichler Bernd , Ziemann Ulf , Poli Sven
Published: January 2019

Introduction:
Characterized by strong and brain-selective cooling performance paired with only minor (systemic) adverse effects, intra-arterial cold infusions (IACI) into brain-supplying arteries have been reported as neuroprotective in experimental acute ischemic stroke (AIS). Combining normobaric hyperoxygenation (NBHO) with IACI might potentiate neuroprotection by increasing oxygen supply and, at the same time, reducing metabolism during ischemia and mitigating oxidative stress during reperfusion.

Methods:
To investigate potentially synergistic effects, we tested NBHO+IACI vs. NBHO vs. IACI vs. controls in a transient (60 minutes) filament middle cerebral artery occlusion (MCAO) rat model (n = 16 per group). NBHO (100 % oxygen) was initiated 10 minutes after MCAO, continuous IACI (0 °C, 12 mL) into the internal carotid artery were started two minutes prior to reperfusion, both treatments were stopped (simultaneously) after 65 and 15 minutes. Infarct and edema growth were estimated by MRI incl. perfusion, diffusion and T2 during ischemia, at 24 hours and two weeks. Neurological tests were performed for functional outcome. NeuN, IB4 and GFAP staining was used to illustrate selective neuron loss (SNL), microglia activation and gliosis at two weeks. Effect of arterial on penumbral oxygenation was evaluated with pre/post-treatment blood gas analyses and MBA1 staining at 24 hours.

Results:
In accordance with previous studies, NBHO reduced infarct growth (primary endpoint; T2 infarct at two weeks minus perfusion ischemic core during MCAO) by 50 % vs. controls. Cerebral edema, penumbral oxygenation and functional outcome as well as SNL, microglia activation and gliosis were also improved or reduced. In contrast, IACI were not beneficial and no synergistic neuroprotection was found for NBHO+IACI.

Conclusions:
Our findings confirm strong NBHO-mediated neuroprotection in AIS, while IACI were not neuroprotective. Longer duration of brain-selective hypothermia might be the key, but IACI volume is the limiting factor. MRI, functional and histological results will be discussed in the context of current literature.
Abstract 114: Biomarkers for Patient Selection Improve Stroke Rehabilitation Trial Efficiency
Authors: Byblow Winston D , Barber P Alan , Ackerley Suzanne J , Smith Marie-Claire , Cramer Steve C , Stinear Cathy M
Published: January 2019

There is high inter-individual variability in recovery after stroke, which reduces statistical power in rehabilitation trials. This could be addressed by using biomarkers for patient selection. Corticospinal tract function assessed with transcranial magnetic stimulation (TMS) is a candidate biomarker for trials aiming to improve upper-limb motor recovery. Patients in whom TMS can elicit motor evoked potentials (MEPs) have a functionally intact lateral corticospinal tract and better motor recovery. We used an existing data set to estimate the sample sizes required to detect rehabilitation benefits on upper-limb motor performance 90 days after stroke. Baseline clinical assessments were made and MEP status of the paretic upper-limb determined within 7 days post-stroke. Upper-limb Fugl-Meyer (UE-FM) and Action Research Arm Test (ARAT) scores were obtained 90 days after stroke. Analyses were carried out for the full sample, and repeated for the MEP+ subset. Population estimates of the UE-FM and ARAT scores 90 days post-stroke were used to calculate the sample sizes required to detect clinically meaningful treatment effects of 7 points on the UE-FM and ARAT scores. Baseline and 90-day assessments were completed by 207 patients (103 women, mean 70.6 SD 15.1 years). The full sample and MEP+ subset (n=177) had similar demographic and baseline clinical characteristics. The estimated required sample sizes to detect treatment effects for MEP+ patients were only 27-29% of those for the full sample of patients. The estimated percentage of patients who are MEP+ was 85.5% (95%CI 81.2%-89.9%). Biomarkers could be used to enrich samples for stroke rehabilitation trials. Selecting patients on the basis of MEP status reduces variance, thereby reducing required sample size by around 75% without significantly limiting the pool of participants. Using biomarkers for patient selection could markedly increase rehabilitation trial sensitivity and efficiency, with associated decreases in costs and time required for completion.
Abstract 12: Day-to-Day Modest Drinking Rather Than Occasional Binge Drinking May Raise Risk of Ischemic Stroke
Authors: Yang Wookjin , Kang Dong-Wan , Gook Hyung Seok , Ha Sueyoung , Park Eun-Sun , Lee Seung-Hoon
Published: January 2019

Introduction:
Although it has been reported that amount of alcohol consumption has J-shaped association with ischemic stroke, it is yet to be concluded whether difference in drinking pattern affects the relationship. Given that drinking pattern may vary even among individuals with similar drinking amount, it is necessary to further assess the association between drinking pattern and ischemic stroke.

Methods:
The National Health Insurance Service-National Sample Cohort is a large-sized, standardized population cohort in Korea, which consists of randomly selected 2% of Koreans considering demographic characteristics. Drinking pattern was defined in 5 categories by frequency and quantity per occasion. Participants who reported to have rarely or never drunken alcohol were classified as abstainers. Those who drank less than 5 days per week were defined as social drinkers or episodic heavy drinkers, depending on whether the amount of alcohol consumed at one occasion exceeded a bottle of Soju (60g of alcohol). In the same way, participants drinking 5 days or more a week were classified as daily modest drinkers or daily heavy drinkers. We analyzed the relationship between drinking pattern and ischemic stroke occurrence.

Results:
A total of 286,256 eligible participants (mean age, 45 years; 148,985 men [52.0%]) were analyzed. Median follow-up period was 9.0 years. As reported in previous studies, social drinking had protective effect for ischemic stroke (HR, 0.88; 95% CI, 0.81-0.96). In participants who drink more, however, the drinking pattern influenced the results. Drinking modest amount of alcohol everyday significantly elevated the risk of ischemic stroke (HR, 1.16; 95% CI, 1.01-1.33), whereas episodic heavy drinking did not (HR, 0.90; 95% CI, 0.76-1.07).

Conclusions:
Risk of ischemic stroke may be influenced by drinking pattern. Particularly, daily modest drinkers may be at higher risk for ischemic stroke compared with intermittent excessive drinkers.
Abstract 120: Peripheral Nerve Stimulation to Enhance Upper Limb Motor Function in Stroke
Authors: Conforto Adriana B , Luccas Rafael , Menezes Isabella S , Machado Andre G , Mello Eduardo A , Assis Priscila S , Freitas Paloma F , Pires Danielle S , Peckham Paul H , Cohen Leonardo G
Published: January 2019

Introduction:
Peripheral sensory stimulation (PSS) administered for 2 hours prior to intensive task-oriented motor training delivered for 4 hours, over 10 days, leads to clinically significant benefits in subjects with stroke and moderate to severe upper limb motor impairment, compared to sham PSS. Whether similar results can be obtained with less intensive training programs remains to be determined.

Methods:
Twenty subjects with stroke in the chronic phase (>6m) and moderate to severe upper limb motor impairments were randomized to treatment with either 1.5h active PSS or sham, followed by functional electrical stimulation (FES) and task-specific training (TST) in sessions administered three times per week over six weeks. FES lasted for 30 minutes and TST, for 45 minutes. The primary outcome was the difference in performance in the Wolf Motor Function Test. The data were analyzed with a generalized estimating equations model with factors “group” (active or sham) and “time” (baseline, three and six weeks after starting treatment).

Results:
There were significant effects of “time” (Wald Chi-square = 16.5, p<0.001) and interaction between “group” and “time” (Wald Chi-square = 10.4, p=0.005) for the Wolf Motor Function Test, Functional Ability Scale. Post-hoc Bonferroni-corrected analyses showed a statistically significant improvement in performance between baseline and three weeks after beginning of treatment in the active (p=0.001) but not in the sham group (p=0.912). The difference between performance at baseline and six weeks after beginning of treatment almost reached statistically significance in the active (p=0.058) but not in the sham (p>0.999) group.

Conclusions:
These results are relevant for the design of larger clinical trials involving durations of interventions that are more easily implemented in clinical practice than rehabilitation protocols lasting for 6 hours per day. The study is ongoing.
Abstract 123: Underlying Pathologic Differentiation With Cerebral Microbleeds in Embolic Stroke of Undetermined Source
Authors: Kikuno Muneaki , Koga Masatoshi , Kanemaru Kodai , Ando Daisuke , Shiozawa Masayuki , Ueno Yuji , Kato Haruhisa , Aizawa Hitoshi , Ihara Masafumi , Toyoda Kazunori
Published: January 2019

Background and purpose:
The embolic stroke of undetermined source (ESUS) was introduced and expected the efficacy of anticoagulant. However, a large-scale clinical trial failed to reveal the superiority of rivaroxaban to aspirin. The heterogeneous pathology of ESUS may be a cause of this discrepancy. The prevalence of cerebral microbleeds (CMBs) is different among subtypes of ischemic stroke. In this study, we aimed to differentiate the underlying pathology of ESUS throughout analyzing CMBs.

Methods:
Acute ESUS patients who were admitted to our hospital between April 2014 and December 2016 were studied. In addition, findings of brain MRI including T2*-weighted imaging and transesophageal echocardiography (TEE) were collected to assess covert pathology of ESUS.

Results:
Of a total 1612 acute ischemic stroke patients, 221 (13.7%, 78 women, 71.9±12.7 years) met the criteria of ESUS and underwent brain MRI and TEE. Of these, 94 had CMBs (the CMB group) and 127 did not (the non-CMB group). The CMB group was more aged (75.3 ± 9.5 vs 69.5 ± 14.1 years, p=0.0006), more male (74.5% vs 57.5%, p=0.0104), and more hypertensive (94.7% vs 69.3%, p<0.0001) than the non-CMB group. Brain MRI revealed broader deep white matter hyperintensity (Fazekas grade 2-3; 61.7% vs 27.6%, p<0.0001) and periventricular hyperintensity (Fazekas grade 2-3; 77.7% vs 34.7%, p<0.0001) in the CMB group. TEE more frequently showed aortic complicated lesions of arch (thickness ≥4mm or with ulceration or mobile components; 50.0% vs 20.5%, p<0.0001) in the CMB group. Covert atrial fibrillation was detected less frequently in the CMB group (10.6% vs 21.3%, p=0.0448) during hospitalization. In a multiple logistic regression analysis, hypertension (OR 6.90, 95%CI 2.51-22.77, p<0.0001), deep white matter hyperintensity (2.29, 1.03-5.10, p=0.0428), periventricular hyperintensity (3.66, 1.63-8.49, p=0.0016), aortic complicated lesion (2.12, 1.03-4.41, p=0.0416), and atrial fibrillation (0.33, 0.12-0.80, p=0.0137) were independently associated with the CMB group.

Conclusions:
Because ESUS patients with CMBs more frequently had aortic complicated lesion and less frequently had atrial fibrillation than those without, CMBs may have a potential to discriminate underlying pathology of ESUS.
Abstract 125: Atrial Fibrillation Known Before Stroke or Detected After Stroke Shares Similar Risk of Ischemic Stroke Recurrence and Death
Authors: Yang Xiaomeng , Li Zixiao , Gu Hongqiu , Wang Chunjuan , Wang Yilong , Wang Yongjun
Published: January 2019

Objective:
To compare the risk of 1-year ischemic stroke recurrence and death between atrial fibrillation (AF) diagnosed after stroke (AFDAS), AF known before stroke (KAF) and sinus rhythm (SR).

Methods:
From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals voluntarily participating in the China National Stroke Registry II. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We explored the relationship between heart rhythm groups and 1-year ischemic stroke recurrence and death by using Cox regression adjusted for multiple covariates. Considering death is the competing risk of stroke recurrence, we used the competing-risks analysis of Fine and Gray to assess the association between heart rhythm and stroke recurrence.

Results:
Among 19604 ischemic stroke patients, 17727 had SR, 495 AFDAS, and 1382 KAF. At 1 year, 54 (10.9%) patients with AFDAS, 182 (13.2%) with KAF, and 1008 (5.7%) with SR had recurrent ischemic strokes (p< 0.0001). The mortality was 22.0% in patients with AFDAS , 22.1% in patients with KAF, and 7.0% in patients with SR (p< 0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was higher than that of SR (hazard ratio 1.48 [95% confidence interval 1.19, 1.85]; p = 0.0005) but not different from that of KAF (hazard ratio 1.09 [95% confidence interval 0.85, 1.40]; p = 0.51). The adjusted risk of 1-year death for AFDAS was also higher than that of SR (hazard ratio 1.60 [95% confidence interval 1.29, 2.00]; p <0.0001) and not different from that of KAF (hazard ratio 1.09 [95% confidence interval 0.85, 1.40]; p = 0.49).

Conclusions:
The higher 1-year ischemic stroke recurrence and mortality between AFDAS and SR together with the lack of difference between AFDAS and KAF suggest the similar potential risk of AFDAS.
Abstract 126: A Simple Classification of the Left Atrial Appendage Morphology Based on Stroke Risk: The LAA H/L Classification System
Authors: Yaghi Shadi , Chang Andrew , Kamel Hooman , Furie Karen , Elkind Mitchell S , Atalay Michael
Published: January 2019

Introduction:
The left atrial appendage (LAA) morphology is classified into 4 categories: chicken wing (CW), windsock, cactus, and cauliflower (cLAA-CS) (Figure) without established inter and intra-rater agreements. We aim to determine intra-rater and inter-rater agreements and relationship with embolic stroke subtypes using a new classification system vs. cLAA-CS.

Methods:
Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology were classified using the cLAA-CS (CW=low risk) and the new LAA-H/L system [Low risk morphology (LAA-L) defined an acute angle bend or fold from the proximal/middle portion of the LAA and LAA-H defined as all others]. We determined intra and inter-rater agreements for the two classification systems and the association between non-CW and LAA-H morphologies with embolic subtypes in our cohort and stroke in previous studies.

Results:
We identified 329 patients with a qualifying chest CT performed (126 cardioembolic subtype, 116 ESUS, and 87 non-cardioembolic subtypes). Intra and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85) vs. cLAA-CS (0.4 and 0.5). Using the LAA-H/L led to classifying 50 LAA morphologies that met criteria for CW as LAA-H (Figure). In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter and intrarater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes (Table).

Conclusion:
The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk stratify patients at risk for cardioembolic stroke.