bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocular and Mucocutaneous Sequelae among Survivors of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Togo
Authors: Saka Bayaki , Akakpo Abla Séfako , Teclessou Julienne Noude , Mahamadou Garba , Mouhari-Toure Abas , Dzidzinyo Kossi , Diori Adam Nouhou , Maneh Nidain , Prince-Agbodjan Sabin , Kombaté Koussake , Balo Komi , Tchangai-Walla Kissem , Pitché Palokinam
Published: January 2019

Aim. The aim of this study was to assess ocular and mucocutaneous sequelae among SJS/TEN survivors and identify risk factors of ocular sequelae. Patients and Method. Late complications among SJS/TEN survivors were assessed using 2 methods: a retrospective assessment of medical records only or a retrospective assessment of medical records and physical examination of survivors who were contacted by phone. Results. Between January 1995 and December 2017, 177 cases of SJS/TEN (138 cases of SJS, 29 cases of TEN, and 10 cases SJS/TEN overlap) were admitted into two university hospitals of Lomé (Togo). There were 113 women and 64 men, with an average age of 31.7±13.0 years (range: 5 to 80 years). The most used drugs were antibacterial sulfonamides (35.6%) and nevirapine (24.3%). HIV serology was positive in 68 (59.1%) of the 115 patients tested. Sixty-four (52,5%) of the 122 patients, who had been examined by an ophthalmologist during the acute stage, had acute ocular involvement, which was mild in 27.9% of patients, moderate in 13.1%, and severe in 11.5%. We recorded 17 deaths (i.e., three cases of SJS, 12 of TEN, and two of SJS/TEN overlap), including 11 cases of HIV infected patients. Of the 160 SJS/TEN survivors, only 71 patients were assessed 6 months after hospital discharge. Among them, forty-three (60.6%) patients had sequelae. Concerning mucocutaneous sequelae, the main lesions were diffuse dyschromic macules (38.0% of patients) and ocular sequelae were dominated by decreased visual acuity (14.1% of patients). In multivariate analysis, exposure to sulfadoxine (odds adjusted ratio = 5.95; 95%CI= [1.36-31.35]) and moderate (adjusted odds ratio = 5.85; 95%CI = [1.23-31.81]) or severe (adjusted odds ratio = 48.30; 95%CI = [6.25-1063.66]) ocular involvement at acute stage were associated with ocular sequelae. Conclusion. Ocular and mucocutaneous sequelae are common in SJS/TEN survivors. Exposure to sulfadoxine and severity of acute ocular involvement are risk factors of ocular sequelae.
Genetic Variability and Correlation Coefficients of Major Traits in Early Maturing Rice under Rainfed Lowland Environments of Nepal
Authors: Tiwari Dev Nidhi , Tripathi Santosh Raj , Tripathi Mahendra Prasad , Khatri Narayan , Bastola Bishwas Raj
Published: January 2019

Genetic variability is the fundamental requirement of any crop breeding program to develop superior cultivars. The objective of this study was to estimate the genetic variability and find out the correlation among the different quantitative traits of rainfed early lowland rice. The experiment was conducted consecutively two years during 2015 and 2016 in wet season across the four different locations in Regional Agricultural Research Station, Khajura, National Wheat Research Program, Bhairahawa, National Maize Research Program, Rampur, and National Rice Research Program, Hardinath, along the Terai region of Nepal representing subtropical agroclimate. Seven genotypes including Hardinath-1 as standard check variety were evaluated in the randomized complete block design with three replications. Various quantitative traits were measured to investigate the variability and correlation coefficients. All the genotypes and locations showed significant variations for all the traits considered. Genotypic coefficient of variation was lower than phenotypic coefficient of variation for all traits studied. The magnitudes of genotypic coefficient of variations were relatively higher for grain yield, 1000-grain weight, and days to heading. The highest broad sense heritability of 94% was recorded in days to maturity and the lowest heritability of 16% was observed in plant height. Positive and highly significant correlations were found both in genotypic and phenotypic levels between days to heading and days to maturity (rg=0.9999 ⁎⁎, rp=0.997 ⁎⁎), days to heading and grain yield (rg =0.9999 ⁎⁎, rp= 0.9276 ⁎⁎), and days to maturity and grain yield (rg =0.9796 ⁎⁎, rp=0.9174 ⁎⁎). However, negative and highly significant genetic correlation was observed between plant height and 1000-grain weight (rg = -0.9999 ⁎⁎). Thus results indicated that days to heading, days to maturity, grain yield, 1000-grain weight demonstrating higher heritability and remarkable genetic advance could be considered the most appropriate traits for improvement and selection of trait to achieve stable and high yielding early rice genotypes under rainfed environments.
New Gene Markers of Angiogenesis and Blood Vessels Development in Porcine Ovarian Granulosa Cells during Short-Term Primary Culture In Vitro
Authors: Chermuła Błażej , Brązert Maciej , Iżycki Dariusz , Ciesiółka Sylwia , Kranc Wiesława , Celichowski Piotr , Ożegowska Katarzyna , Nawrocki Mariusz J. , Jankowski Maurycy , Jeseta Michal , Antosik Paweł , Bukowska Dorota , Skowroński Mariusz T. , Brussow Klaus P. , Bruska Małgorzata , Pawelczyk Leszek , Zabel Maciej , Nowicki Michał , Kempisty Bartosz
Published: January 2019

The physiological processes that drive the development of ovarian follicle, as well as the process of oogenesis, are quite well known. Granulosa cells are major players in this occurrence, being the somatic element of the female gamete development. They participate directly in the processes of oogenesis, building the cumulus-oocyte complex surrounding the ovum. In addition to that, they have a further impact on the reproductive processes, being a place of steroid sex hormone synthesis and secretion. It is known that the follicle development creates a major need for angiogenesis and blood vessel development in the ovary. In this study, we use novel molecular approaches to analyze markers of these processes in porcine granulosa cultured primarilyin vitro.The cells were recovered from maturesus scrofaspecimen after slaughter. They were then subjected to enzymatic digestion and culture primarily for a short term. The RNA was extracted from cultures in specific time periods (0h, 24h, 48h, 96h, and 144h) and analyzed using expression microarrays. The genes that exhibited fold change bigger than|2|, and adjusted p-value lower than 0.05, were considered differentially expressed. From these, we have chosen the members of “angiogenesis,” “blood vessel development,” “blood vessel morphogenesis,” “cardiovascular system development,” and “vasculature development” for further selection.CCL2, FGFR2, SFRP2, PDPN, DCN, CAV1, CHI3L1, ITGB3, FN1,andLOXwhich are upregulated, as well asCXCL10, NEBL, IHH, TGFBR3, SCUBE1, IGF1, EDNRA, RHOB, PPARD,andSLITRK5genes whose expression is downregulated through the time of culture, were chosen as the potential markers, as their expression varied the most during the time of culture. The fold changes were further validated with RT-qPCR. The genes were described, with special attention to their possible function in GCs during culture. The results broaden the general knowledge about GC’sin vitromolecular processes and might serve as a point of reference for furtherin vivoand clinical studies.
Dynamical Model Identification for a Small-Scale Unmanned Helicopter Using an Integrated Approach
Authors: Ma Rui , Ding Li , Liu Kailei , Wu Hongtao
Published: January 2019

This article presents an integrated approach for the parameter identification of a small-scale unmanned helicopter. With the flight experiment data collection and preprocessing, a hybrid identified algorithm combining the improved artificial bee colony algorithm and prediction error method is proposed to obtain the unknown dynamical parameters of the linear model. The proposed algorithm is valid to use thanks to an adaptive search equation, a novel probability-scaling method, and a chaotic operator and has a good performance in search speed and quality. Afterwards, we design a wind tunnel test to modify the main rotor time constant of the identified model. The identified accuracy and feasibility of the proposed approach are verified by making a time-domain comparison with three other algorithms. Results show that the dynamical characteristics of the helicopter can be determined accurately by the identified model. And the proposed approach is propitious to enhance the reliability and availability of the identified dynamical model.
Adaptive Output Feedback Stabilization of Random Nonlinear Systems with Unmodeled Dynamics Driven by Colored Noise
Authors: Cui Mingyue
Published: January 2019

This paper focuses on the problem of adaptive output feedback stabilization for random nonlinear systems with unmodeled dynamics and uncertain nonlinear functions driven by colored noise. Under the assumption of unmodeled dynamics having enough stability margin, an adaptive output feedback stabilization controller is designed based on a reduced‐order observer such that the state of the closed‐loop system has an asymptotic gain in the 2‐th moment (AG‐2‐M) and the mean square of the output can be made arbitrarily small by tuning parameters. A simulation example is used to illustrate the effectiveness of the control scheme.
Effect of Brittle Mineral Size on Hydraulic Fracture Propagation in Shale Gas Reservoir
Authors: Gao Wei , Iqbal Javed , Xu Dan , Sui Haoyue , Hu Ruilin
Published: January 2019

The properties of brittle minerals have great effect on the morphology of postfracturing network in shale reservoirs in the southeastern Ordos Basin, China. In order to study the effect of brittle mineral size distributions on the fracture parameters, the concrete cubes of 300 mm × 300 mm × 300 mm in size with four distinct brittle mineral sizes of 2.36 mm, 0.425 mm, 0.15 mm, and 0.075 mm were investigated under large-sized triaxial hydraulic fracturing test. The effect mechanism of aggregate on the fracture properties of shale was studied using ultrasonic technique, photosensitive electron microscope, and numerical simulation. The test results obtained for each specimen (both disturbed and undisturbed conditions) indicate that brittle mineral size has significant effect on the fracture extension. The tensile strength, fracture toughness, and fracture pressure were found to decrease with a decrease in maximum brittle mineral size when the maximum brittle mineral size is smaller than 0.425 mm. In addition to this, the degree of attenuation difference also follows the similar trend. Observed fracture morphology reveals that with an increase in maximum size of brittle mineral specimen, the tortuous and complicated cracking path generation increases. These findings would be very helpful in order to better understand the behavior of shale under hydraulic fracturing test.
Differential Molecular Modeling Predictions of Mid and Conventional Dialysate Flows
Authors: Leypoldt John K. , Prichard Sarah , Chertow Glenn M. , Alvarez Luis
Published: January 2019

Background: High dialysate flow rates (QD) of 500–800 mL/min are used to maximize urea removal during conventional hemodialysis. There are few data describing hemodialysis with use of mid-rate QD (300 mL/min). Methods: We constructed uremic solute (urea, beta2-microglobulin and phosphate) kinetic models at varying volumes of distribution and blood flow rates to predict solute clearances at QD of 300 and 500 mL/min. Results: Across a range of volumes of distribution a QD of 300 mL/min generally yields a predicted urea spKt/V greater than 1.2 during typical treatment times with a small difference in urea spKt/V between a QD of 300 and 500 mL/min. A larger urea KoA dialyzer and 15 min of additional time narrows the urea spKt/V difference. No substantial differences were observed regarding the kinetics of beta2-microglobulin and phosphate for QD of 300 vs. 500 mL/min. Conclusion: A QD of 300 mL/min can achieve urea clearance targets. Hemodialysis systems using mid-rate QD can be expected to provide adequate hemodialysis, as currently defined.
Subclinical Nasal and Lung Lymphocytosis in Ulcerative Colitis
Authors: Marvisi Maurizio , Balzarini Laura , Mancini Chiara , Ramponi Sara , Marvisi Chiara , Maffezzoni Enrico
Published: January 2019

Background: Extraintestinal manifestations are common in ulcerative colitis (UC). Data regarding pulmonary and nasal mucosa involvement are sparse. Objectives: The aim of the study was to evaluate, by using induced sputum (IS) and nasal cytology (NC), the cytological pattern of the lung and nose in patients with UC. Materials and Methods: We enrolled 15 consecutive subjects from the outpatient department with a recent diagnosis of UC. On the same day of enrollment, we performed a global spirometry, including a lung diffusing capacity test, IS analysis, and evaluation of NC. Results: IS analysis showed an increase in lymphocytes in UC patients when compared to those of controls (2.8 ± 0.9 vs. 0.2 ± 0.4%; p < 0.01). NC showed a similar increase in lymphocytes (12.5 ± 5.30 vs. 3.5 ± 4.0%; p < 0.01). We found a positive correlation between lymphocyte counts in IS and NC (r = 0.775; p < 0.001) and between lymphocytes in IS and NC and grade of intestinal inflammation (r = 0.603, p = 0.015; r = 0.60, p = 0.013). Conclusions: Our data demonstrated that UC patients may have a subclinical nasal and lung lymphocytosis.
A Placebo-Controlled, Randomized Trial of Enarodustat in Patients with Chronic Kidney Disease Followed by Long-Term Trial
Authors: Akizawa Tadao , Nangaku Masaomi , Yamaguchi Takuhiro , Arai Masanobu , Koretomo Ryosuke , Matsui Atsushi , Hirakata Hideki
Published: January 2019

Background: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis. Methods: Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10.0–12.0 g/dL in reference to a dose adjustment algorithm (Period 2). Results: In the correction group, Hb level increase rate per week increased in a dose-response manner. The proportion of subjects in the conversion group who maintained Hb levels within ± 1.0 g/dL of baseline did not differ between each enarodustat arm and placebo arm during Period 1. Over 70% of subjects in both groups maintained Hb levels within the target range at the end of treatment in Period 2. The mean prescribed doses were 3.58 and 3.74 mg/day in the correction group and the conversion group, respectively. Enarodustat was associated with decreases in hepcidin and ferritin and increased total iron-binding capacity and was generally well tolerated. Conclusions: Enarodustat corrects and maintains Hb levels in anemic patients with CKD not on dialysis.
Abstract 52: Inflammatory Biomarkers Correlate With Etiology in Childhood Arterial Ischemic Stroke
Authors: Fullerton Heather J , Hills Nancy K , Wintermark Max , Norris Philip , Heitman John , Keating Sheila , Owen Rachel ,   The VIPS Investigators
Published: January 2019

Introduction:
Etiologies of childhood arterial ischemic stroke (AIS) are heterogeneous, yet most cases fall into one of three subtypes: arteriopathic, cardioembolic, or idiopathic. Circulating inflammatory mediators could play a role in the pathogenesis of each subtype, whether through inflammatory injury to arterial or cardiac endothelium, or by promoting thrombosis.

Hypothesis:
Patterns of post-stroke serum inflammation in children will differ by etiologic subtype.

Methods:
From the “Vascular effects of Infection in Pediatric Stoke” (VIPS) study cohort (355 cases of AIS, ages 29 days through 18 years), we selected cases centrally classified as arteriopathic (N=119), spontaneous cardioembolic (N=58; excluding peri-procedural cardioembolic AIS), or idiopathic (N=82). We used Luminex assays to measure serum concentrations (pg/mL) of 20 inflammatory biomarkers selected for their correlation with adult AIS or arteriopathy in other settings. We compared analyte concentrations across the three etiologic subtypes in unadjusted and adjusted analyses.

Results:
Serum samples were collected at a median of 5.5 days post-stroke (IQR 3, 10 days). Compared to children with idiopathic AIS, those with cardioembolic AIS had higher levels of four analytes (IL-6, IL-8, IL-10, IP-10), even after adjustment for age, sex, infarct volume, and other potential confounders (Table). Children with arteriopathic AIS, on the other hand, had higher levels of two analytes (IL-10, IP-10), and lower levels of another two (fractalkine, MCP-1).

Conclusion:
Patterns of post-AIS serum inflammation differ by stroke subtype in children, and may provide clues to stroke pathogenesis. We will perform network analyses using unsupervised machine learning approaches to elucidate these patterns further.
Abstract TMP120: Sildenafil Treatment of Vascular Dementia in Aged Rats
Authors: Zacharek Alex , Venkat Poornima , Chopp Michael , Landschoot-Ward Julie , Chen Jieli
Published: January 2019

Background and Purpose:
Vascular Dementia (VaD) caused by silent or mini strokes, affects cognition and memory predominantly in the elderly. Sildenafil, a cGMP-specific phosphodiesterase type 5 inhibitor mediates vasodilation. In this study, we tested the therapeutic effects of Sildenafil on cognitive decline, white matter (WM) damage, autophagy and inflammatory response associated with a model of VaD in aged rats.

Methods:
Male, 16-18 month old Wistar rats were subjected to a multiple microinfarction (MMI) induced VaD model and were treated daily with or without Sildenafil (2mg/Kg, i.p) starting at 24 hours after MMI for 28 days (n=7/group). A battery of cognitive tests was performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation, Western blot and PCR assays.

Results:
Compared to aged-control, aged-MMI rats exhibit significant (p<0.05): 1) short term memory loss, long term memory deficits and anxiety like behavior, respectively; 2) increased brain inflammatory factor expression such as IL-1β, MCP-1 and thrombin; 3) increased brain WM/axonal damage as well as increased autophagy in the brain. Compared to aged-MMI control rats, Sildenafil treatment in aged-MMI rats significantly (p<0.05): 1) improves short and long term memory as well as decreases anxiety like behavior; 2) improves spatial learning and memory; 3) increases axon and myelin density in the corpus callosum and white matter bundles in the striatum; 4) increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum; 5), increases synaptic protein expression in the cortex and striatum as well as increases water channel protein Aquaporin-4 expression around cerebral blood vessels; 6) decreases inflammatory factors MCP-1, IL-1β and thrombin expression as well as decreases MMI induced autophagy indicated by LC3A and Beclin-1 expression.

Conclusions:
MMI in aged rats induces significant WM damage, autophagy, and inflammatory responses which lead to decline in cognition and memory. Sildenafil treatment increases white matter remodeling, synaptic plasticity, decreases autophagy and exerts anti-inflammatory effects which in concert may contribute to the improvement in cognition and memory.
Abstract TMP45: Association of Late Functional Improvement With 5-Year Post-stroke Outcomes: A Population-based Cohort Study
Authors: Ganesh Aravind , Luengo-Fernandez Ramon , Rothwell Peter M ,   Oxford Vascular Study
Published: January 2019

Background:
We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one in four patients with ischaemic stroke, more commonly in lacunar strokes. It is unknown whether this late improvement is associated with better long-term clinical or health economic outcomes.

Methods:
In 1-year ischaemic stroke survivors of the Oxford Vascular Study (OXVASC; 2002-2014), we examined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We used Cox regressions adjusted for age, sex, 3-month disability, and stroke subtype (lacunar vs non-lacunar) to examine the association of late functional improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points between 3-12 months) with 5-year mortality and institutionalization (admission to nursing or residential care home). We used similarly adjusted generalized linear models to examine the association with 5-year health/social-care costs. Analyses were restricted to patients capable of showing improvement per the relevant scale (mRS>0, RMI<15, BI<20).

Results:
Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, of whom 319 (28.1%) demonstrated late functional improvement between 3-12 months post-stroke. 1-year survivors who demonstrated late functional improvement between 3-12 months per the mRS had lower 5-year mortality (aHR 0.68, 95%CI 0.51-0.91, p=0.009), were less likely to be institutionalized at 5-years (aHR 0.48, 0.33-0.72, p<0.001), and incurred lower 5-year health/social-care costs (margin -$17,524, -24,763 to -10,284, p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (e.g. for 5-year mortality: aHR 0.69, 0.49-0.96, p=0.026) and on examining late functional improvement per the RMI and/or BI (e.g. for 5-year mortality with RMI: aHR 0.64, 0.46-0.87, p=0.004).

Conclusions:
Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization rates, and health/social-care costs. These findings should motivate patients and clinicians to maximize late recovery in routine practice, and consider access to rehabilitative services for at least 1-year post-stroke.
Abstract TP23: The Impact of Procedure Time on Clinical Outcome in Endovascular Treatment for Acute Ischemic Stroke
Authors: Enomoto Yukiko , Yoshimura Shinichi , Sakai Nobuyuki , Yamagami Hiroshi ,   Rescue-Japan Registry 2 investigators
Published: January 2019

Introduction:
Time from onset to reperfusion is highly associated with better clinical outcome in acute ischemic stroke, however, optimal endovascular-procedural time limit is uncertain. We performed this study to determine the relationship among procedure time and clinical outcomes in acute ischemic stroke patients undergoing endovascular treatment.

Methods:
We analyzed the data from the Recovery by the Endovascular Salvage for Cerebral Ultra-acute Embolism (RESCUE) - Japan Registry 2, a prospective multicenter registry in Japan between 0ct 2014 and Jan 2017. Among the patients undergoing endovascular treatment, 1249 patients whose procedure time was clear were included for this analysis and classified into 2 groups based on time from puncture to reperfusion (extended group; >120minutes [n=120], normal group; <120 minutes [n=1129]).

Results:
The median procedure time was 160 minutes in extended group and 50 minutes in normal group. Extended group had more atherosclerotic etiology (27.5% vs. 12.6%, p<.01) and internal carotid artery occlusion (45% vs. 31%, p<.01) compared with shorter group. The rates of successful recanalization (TICI 2b/3; 74% vs. 89%, p<.05) and favorable outcome (mRS 0-2 at 90days ; 23 % vs. 44%, p<.05) were lower in extended group.

Conclusions:
Long procedure time did not contribute to the improvement of clinical outcome. This study emphasized the need for procedure time guidelines for endovascular treatment for acute ischemic stroke.
Abstract TP426: Description of Early Hematoma Expansion Trajectory and Rate of Expansion in Patients With Intracranial Hemorrhage
Authors: Burgos Adrian M , Vilaisaktipakorn Pitchamol , Shkirkova Kristina , Sanossian Nerses , Saver Jeffrey L , Villablanca Pablo , Starkman Sidney , Liebeskind David S ,   FAST-MAG Investigators and Coordinators
Published: January 2019

Introduction:
Expansion of intracerebral hemorrhage (ICH) is associated with increased disability and mortality. The trajectory and rate of hematoma expansion (HE) have not been well described. We evaluated ultra-early baseline and follow up CT and MRI scans to describe the direction and rate of expansion.

Methods:
We analyzed consecutive ICH patients enrolled in the multicenter, NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial with baseline and follow up imaging between 6 to 48 hours. HE was defined as growth more than 33% or more than 6mL. Topographic locations were determined using x-, y-, and z- coordinates on OsiriX software. Direction of HE was described by a change in coordinates and correlated with anatomic location. Hematoma growth (HG) rate was described as hematoma volume divided by symptoms onset to scan time in hours. HE rate was described as change in hematoma volume between initial and follow up imaging divided by the time lapse in hours.

Results:
There were 387 patients with intracerebral hemorrhage enrolled in the FAST-MAG clinical trial. 260 patients had initial and follow up imaging without undergoing hematoma evacuation. The median age was 64, 176 (66.7%) were male. 97 patients were on antiplatelets and 25 were on anticoagulation. Median SBP on admission was 178 and median DBP was 95. 80 (30.7%) patients demonstrated hematoma expansion. The most common location observed was the basal ganglia (69.6%). These hemorrhages tend to expand in all x-, y- and z- coordinates with the greatest change in z- expanding cortically through the corona radiata. There is a high rate of intraventricular hemorrhage (51.5%). Average HG rate was 18.09mL/hr (17.9) and the average HE rate was 1.37mL/hr (1.86). Interestingly, basal ganglia and thalamic hemorrhages had higher rates of expansion. Both HG rate and HE rate were influenced by changes in blood pressure and use of antiplatelets or anticoagulantion.

Conclusion:
Hematoma expansion location can be predicted based on the location of the initial hemorrhage location. Hematoma trajectory and HE rate can help predict poor outcomes in ICH.
Abstract TP446: Predictors of Surgical Intervention in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Chen Ching-Jen , Ding Dale , Ironside Natasha , Buell Thomas J , Southerland Andrew M , Flaherty Matthew , Walsh Kyle B , Coleman Elisheva R , Woo Daniel , Worrall Bradford B ,   ERICH Investigators
Published: January 2019

Objective:
Despite no clear evidence from randomized trials, surgical intervention of spontaneous intracerebral hemorrhage (ICH) still occurs. We sought to describe the characteristics of patients undergoing surgical intervention in ICH.

Methods:
Data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study were analyzed, and ICH patients were categorized into surgical intervention or nonoperative management groups. Patients with primary intraventricular hemorrhage (IVH) and those without data regarding the use of surgical intervention data were excluded. Multivariable models were developed to identify predictors of surgical intervention.

Results:
The study cohort comprised 2,947 patients, and surgical intervention was performed in 289 (10%). Younger age (p<0.001), lower baseline modified Rankin Scale score (mRS; p<0.001), higher admission Glasgow Coma Scale (GCS; p=0.007), larger ICH volume (p<0.001), infratentorial ICH location (p<0.001), lobar ICH location (p<0.001), lack of IVH (p=0.001), ICP monitoring (p<0.001), and mannitol use (p<0.001) were independent predictors of surgical intervention. Younger age (p<0.001), lower baseline mRS score (p=0.002), larger ICH volume (p<0.001), lobar ICH location (p<0.001), ICP monitoring (p<0.001), and mannitol use (p<0.001) were independent predictors of surgical interventions in supratentorial ICHs. Larger ICH volume (p<0.001), ICP monitoring (p<0.001), and mannitol use (p=0.005) were independent predictors of surgical interventions in infratentorial ICHs.

Conclusion:
We identified multiple factors associated with surgical intervention for patients with ICH. Younger age, good neurological function at baseline, large ICH volume on presentation, and lobar or infratentorial hematomas were independently associated with surgical intervention in ICH patients. Additional studies are necessary to determine the risk to benefit profile of ICH surgery.
Abstract TP535: Degree of Cognitive Impairment Based on Subarachnoid Hemorrhage-Associated Early Brain Injury
Authors: Lara-Angulo Melissa , Geraghty Joseph R , Moustafa Bayan , Husain Muhammad R , Oparowski Matthew , Castillo Norma , Testai Fernando D
Published: January 2019

Introduction:
Cognitive impairment is common after aneurysmal subarachnoid hemorrhage (aSAH), however differences between low and high grade aSAH is less well defined. In this study we investigated the contribution of aSAH-associated early brain injury (EBI) to neurocognitive decline.

Methods:
We retrospectively studied aSAH patients admitted to a tertiary referral center (group 1). EBI was defined as mild, moderate, or severe based on baseline Hunt and Hess score (1-2 vs. 3 vs. 4-5, respectively). Cognition was assessed by the Montreal Cognitive Assessment (MoCA) administered by blinded personnel prior to hospital discharge. Sociodemographic characteristics and pertinent complications, including use of ventricular diversion, vasospasm, delayed neurologic deterioration, and cerebral infarct were recorded. Ischemic stroke (group 2) and non-neurological patients (group 3) served as controls. MoCA scores were compared using ANCOVA adjusting for baseline differences.

Results:
Groups 1, 2, and 3 included 84, 43, and 25 patients, respectively. There was no difference in sex but there was a difference in age (52.2±12.2, 60.5±14.9, 52.2±7.0 years, p=0.008). MoCA scores (mean±SD) for groups 1, 2, and 3 were 20.0±5.2, 20.0±5.4, and 23.6±5.0. These differences were statistically different after adjustment for age and level of education (p=0.001). In pairwise analysis, MoCA scores for aSAH patients were similar to ischemic stroke but lower than for non-neurologic patients. Among aSAH patients, the rate of mild, moderate, and severe EBI were 71%, 21%, and 8% (MoCA scores 20.7±5.3, 18.2±4.9 and 18.3±4.2, respectively). No significant differences in MoCA scores were noted based on EBI severity. Also, the scores of aSAH patient with mild EBI were comparable to ischemic stroke but lower than for non-neurological controls.

Conclusion:
Cognitive decline is commonly seen in aSAH survivors irrespective of the EBI severity. The cognitive decline observed in mild EBI patients highlights an underappreciated degree of cognitive decline in individuals who are otherwise expected to have good outcomes. Cognitive screening in low-grade aSAH patients is warranted.
Abstract TP555: Early Rehabilitation in Aneurysmal Subarachnoid Hemorrhage Patients is Associated With Better Cognitive Outcomes and Shorter ICU Stay
Authors: George Pravin
Published: January 2019

Early rehabilitation is associated with improved outcomes in some neurological conditions. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have prolonged ICU and hospital stays with delayed rehabilitation. We aimed to study the effect of early rehabilitation on patient reported outcomes, length of stay in the ICU as well as 90-day physical function and cognition. This was a pilot randomized controlled study of aSAH patients, 10 experimental and 10 controls, with Hunt-Hess grades I - IV, who underwent endovascular embolization or surgical clipping. Demographic, clinical, radiographic and cost characteristics were collected. The experimental group underwent a rehabilitation program on the day after aneurysm repair with increased visits by physical and occupational therapists, increased out-of-bed time, utilization of a bedside ergometer, and a number of cognitive exercises. A 29-question Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey was given to the patient in the week of discharge as well as at 30 and 90 days after discharge. A Montreal Cognitive Assessment (MoCA) was performed at one-week post-ictus, 30 and 90 days. Baseline demographic, clinical and radiological characteristics were similar between both groups and there were no adverse events related to mobilization. Median ICU length of stay was significantly decreased in the experimental group (3.5 vs 10.5 days, p=0.037), as was the overall cost of care. PROMIS-29 results revealed more fatigue in the control group at one week prior to discharge (p=0.026) and more sleep disturbances in the control group at 30-days post discharge (p=0.032). Other PROMIS-29 outcomes of physical function, depression, anxiety, and pain were not different between the groups. Baseline mean MoCA scores were similar, but experimental group had greater improvement at both 30 (+4.6 vs +0.9, p=0.007) and 90 (+5.4 vs +1.8, p=0.031) days. Excellent outcome by modified Rankin Scale scores (0-1) was not significant different between the two groups (90% experimental, 50% controls, p=0.14). Early rehabilitation in aSAH patients is feasible and is associated with shorter ICU stay, less cost and improved cognitive outcomes at 30 and 90 days. A larger study is needed to confirm these findings.
Abstract TP585: Long-Term Outcomes in Unruptured Brain Arteriovenous Malformation Patients: The Multicenter Arteriovenous Malformation Research Study (MARS)
Authors: Kim Helen , Al-Shahi Salman Rustam , Flemming Kelly D , Flint Alexander C , Hess Christopher P , Hetts Steven , Krings Timo , Laakso Aki , Lanzino Giuseppe , Lawton Michael T , McCulloch Charles E , Mohr Jay P , Morgan Michael K , Moy Claudia S , Nakaji Peter , Pereira Victor M , Sgarabotto Ribeiro Diego , Stapf Christian , Stefani Marco A , Zaroff Jonathan G , Zhao Yuanli
Published: January 2019

Introduction:
Accurately balancing risks of interventional treatment and intracranial hemorrhage (ICH) in the untreated course of unruptured brain arteriovenous malformation (uBAVM) patients is critical for optimal management. Observational studies of uBAVM afford an opportunity to address important gaps and previous criticisms of randomized data to help guide treatment decisions and assess long-term risk/benefit ratio. We previously published an individual patient data meta-analysis (IPDMA) in 4 MARS cohorts and identified ICH presentation and increasing age as significant predictors of ICH during follow-up, but was not powered to detect predictors in those with uBAVM. Thus, the goals of this project are to identify risk factors for ICH in uBAVMs, to estimate the risk with precision, and to create personalized, risk-prediction models.

Methods:
MARS is an international, multi-center study of 11 cohorts with target enrollment of 4,500 uBAVM patients ascertained through population-based or referral-based studies. We are harmonizing both retrospective and prospective data, including clinical, lifestyle, imaging, and angiographic factors. Treatments, complications, and functional outcomes (physician and patient-reported) will be updated annually between 2018-2022. We propose to: 1) identify predictors of outcome in uBAVMs using IPDMA; 2) test whether long-term outcomes differ by treatment using statistical approaches for causal inference and unbiased estimates; 3) compare treatment outcomes in randomized and non-randomized data to address generalizability; and 4) validate models and provide a novel tool for calculating individualized risks. Eligible sites have: a) prior BAVM publications; b) data from a minimum of 100 uBAVM patients; c) agree to random outcome adjudication; and d) agree to MARS data sharing policy.

Discussion:
The NIH-funded MARS consortium will provide important and comprehensive characterization of the untreated and treated course of uBAVMs, using large observational datasets and sophisticated epidemiological approaches. The data and models generated will be a useful resource for decision-making. We welcome participation from eligible sites with longitudinal data on uBAVM patients
Abstract TP73: Perfusion Values in Ischemic Core Depend on Time from Onset in Acute Stroke
Authors: Yoshie Tomohide , Jiang Hongquan , Yu Yannan , Honda Tristan , Trieu Harry , Scalzo Fabien , Jahan Reza , Starkman Sidney , Sharma Latisha , Yoo Bryan , Rao Neal , Hinman Jason , Duckwiler Gary , Nour May , Szeder ViKtor , Tateshima Satoshi , Colby Geoffrey , Hosseini Mersedeh B , Raychev Radoslav , Kim Doojin , Saver Jeffrey L , Liebeskind David S ,   the UCLA Reperfusion Therapy Investigators
Published: January 2019

Introduction:
Infarct core in perfusion imaging is defined by rCBF regardless of time from onset.

Hypothesis:
Perfusion values and optimal perfusion thresholds for ischemic core depend on onset-to-imaging time.

Methods:
Prospectively collected date for consecutive patients treated with IV t-PA and/or endovascular thrombectomy was analyzed retrospectively. Inclusion criteria were (1) patients with ICA or M1 occlusion (2) underwent both DWI and PWI (3) onset time was clear. Ten places of ROI were set in the same place of ADC and PWI images. These ROI were separated into two groups; low ADC (ADC<620) and normal ADC area (ADC>620). In each area we investigated relationship between time to imaging from onset and each PWI values (rCBF, rCBV, MTT and Tmax). ROC curve analysis for ADC<620 was also performed and compared AUC of early (time from onset to imaging <180 min) and late group (>180 min).

Results:
Sixty-six patients meet inclusion criteria and 660 ROI was analyzed. 164 ROI were low ADC and 496 ROI were normal ADC. There were statistically significant relationships between time from onset to imaging and rCBF (p=0.0051), rCBV (p<0.0001), MTT (p=0.0001) and Tmax (p<0.0001) in low ADC area. In contrast, no relationship was found in normal ADC area between time and each MRP values. ROC analysis for ADC<620 showed rCBF had the highest AUC. However, AUC in late group was significantly higher than early group (0.927 vs 0.850, p=0.0055) and optimal thresholds was different between early and late group.

Conclusions:
Perfusion values on PWI depend on time only in low ADC area. The accuracy and optimal thresholds for ischemic core in perfusion image depend on time.
Abstract TP81: Time-Domain Near-Infrared Spectroscopy in Acute Ischemic Stroke Patients
Authors: Giacalone Giacomo , Zanoletti Marta , Re Rebecca , Germinario Bruno , Contini Davide , Spinelli Lorenzo , Torricelli Alessandro , Roveri Luisa
Published: January 2019

Background:
cerebral microcirculation might reveal important prognostic information for acute ischemic stroke. Time-Domain Near-Infrared Spectroscopy (TD-NIRS) is an advanced optical technique that estimates quantitatively and non-invasively the oxygenation in microcirculation of cerebral outer layers at the bedside of the patient. We aimed to measure hemoglobin species and tissue oxygen saturation in acute ischemic stroke patients comparing them to controls according to brain areas and large vessel recanalization status.

Methods:
TD-NIRS measurements within 24 h of stroke onset (1
st
time point) and after 24 h (2
nd
time point) were performed on anterior circulation stroke patients classified as lacunar and recanalized or non-recanalized partial/total anterior circulation syndrome. Fiducial markers categorized the brain region below each TD-NIRS probe as ischemic or non-stroke areas. We evaluated the concentration of deoxyhemoglobin (HbR), oxyhemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO
2
) and assessed differences compared to control subjects and according to large vessel occlusion.

Results:
TD-NIRS measurements were performed on 47 acute ischemic stroke patients. At 1
st
time point the ischemic area had higher HbR and HbT compared to controls in both recanalized (p=8.2·10
-4
; p=0.03) and non-recanalized patients (p=4.9·10
-3
, p=0.03), but lower StO
2
only in recanalized patients (p=0.015). The ischemic area of recanalized patients had higher concentration of HbR, HbO, HbT compared to the ipsilateral non-stroke area (p=0.01; p=3.6·10
-3
; p=2.0·10
-3
). The same pattern was observed at 2
nd
time point. Recanalized patients had lower mean StO
2
in the ipsilateral hemisphere compared to non-recanalized patients at both time points (p=0.016, p=0.011).

Conclusions:
TD-NIRS can be performed during routine Stroke Unit activity and it is able to detect significant differences in hemoglobin species in large vessels ischemic stroke patients compared to controls. Data suggest that StO
2
could serve as surrogate functional marker of the metabolic activity of the rescued brain tissue.
Abstract WMP57: Geographic Disparities in Stroke and Life Expectancy Significantly Attributable to Ambient PM2.5 Pollution Across the Counties of the United States
Authors: Liu Longjian ,   for Air Quality and Population Health Rsch Group
Published: January 2019

Background:
We aimed to test the hypotheses that ambient particulate matter (PM2.5) is significantly associated with the risk of stroke mortality and life expectancy (LE) reduction, and the degrees of these associations differ across the counties and regions of the United States (U.S).

Methods:
Annual average county-level data (n=1561 counties) from U.S. Centers for Disease Control and Prevention, and Environmental Protection Agency on PM2.5 measures in 2005-2010, age-adjusted stroke mortality in adults aged ≥35 in 2013-2015, and LE in 2010, as well as % of poverty rate, number of primary care physicians per 1000 residents (as a marker of healthcare support) and county-level % of rural population as covariates were analyzed using linear and multilevel hierarchical regression analyses.

Results:
Significant county-level variations in annual average PM2.5 levels (range: 7.2-14.7 ug/
3
), stroke mortality (30.1-219.0 per 100,000 population in males, and 35.0-249.0 in females), and LE (65.0-81.7 years in males and 72.7-85.0 in females) were observed across the nation. Population-weighted PM2.5 levels were significantly and positively associated with stroke mortality in males (r=0.49, p<.0001), and in females (r=0.42, p<.0001), and negatively associated with LE in males (r=-0.39, p<.0001) and females (r=-0.37, p<.0001). Adjusted multilevel analysis indicates that PM2.5 was significantly associated with stroke mortality rates (β=1.27, p<.0001) in both sexes, and with LE in males (β=-0.18, p=<.001), and in females (β=-0.09, p<.001). The adverse impacts of PM2.5 were even worse in counties with higher % of poverty rates and poorer healthcare support compared to their counterparts. Analyses by regions indicate that the highest risk of PM2.5 for stroke (assessed by regression coefficients) was shown for males and females living in the South, followed by Midwest, Northeast, and West. Similar results of the risk of PM2.5 for LE reduction were observed across the regions.

Conclusion:
The study, using U.S. national representative datasets provides new and important evidence that geographic disparities in stroke mortality and LE are significantly attributable to ambient PM2.5 pollution across the nation.
Abstract WP10: Impact of Prior Intravenous Thrombolysis on the Outcome of Emergent Carotid Stenting in Acute Stroke Patients With Tandem Occlusion: A Collaborative Pooled Analysis
Authors: Anadani Mohammad , Spiotta Alejandro M , Piotin Michel , Turjman Francis , Steglich-Arnholm Henrik , Holtmannspötter Markus , Taschner Christian , Eiden Sebastian , Haussen Diogo C , Nogueira Raul G , Papanagiotou Panagiotis , Boutchakova Maria , Siddiqui Adnan , Lapergue Bertrand , Dorn Franziska , Cognard Christophe , Killer Monika , Mangiafico Salvatore , Ribo Marc , Psychogios Marios N , Labeyrie Marc A , Mazighi Mikael , Biondi Alessandra, , Lauzon Steven , Richard Sébastien , Anxionnat René , Bracard Serge , Gory Benjamin ,   On Behalf of TITAN (Thrombectomy in TANdem Lesions) Investigators
Published: January 2019

Background:
Acute tandem occlusion (ATO) management is technically challenging and was not sufficiently evaluated in trials. There is evidence suggesting the efficacy and safety of emergent carotid stenting in conjunction with mechanical thrombectomy (MT) for ATO treatment. However, the safety of carotid stenting (CS) post intravenous tPA (IVT) treatment remains unclear.

Objective:
to report the safety and functional outcomes of emergent CS post IVT, and compare it to non-IVT patients.

Methods:
This was a retrospective multicenter international TITAN collaboration including 18 endovascular databases. In the present analysis, patients were included if they presented with acute ischemic stroke (AIS) due to ATO and were treated with CS in conjunction with MT. ATO was defined as an extracranial internal carotid artery (ICA) lesion (complete occlusion or stenosis >=90%) and an intracranial proximal occlusion (distal ICA and/or first or second segment of the middle cerebral artery). Outcome measures included final mTICI score, 90 day-modified Rankin Scale (mRS), mortality, procedural complications, and symptomatic intracerebral hemorrhage. Mixed effects logistic model was used to determine the predictors of each outcome

Results:
Among 454 patients with ATO, 289 were treated with CS and included in the present analysis. One hundred seventy-five patients (60%) of the included patients received IVT prior to MT. Onset to groin was shorter in the IVT group (259 ±251 vs. 353±238; p=0.013). Otherwise, there was no difference in baseline characteristics between the two groups. Heparin use during procedure was less in IVT group (20% vs. 54%; p<0.001). With respect to the outcome, there was no significant difference in the rate of successful recanalization (mTICI 2b-3), complete recanalization (mTICI 3), and favorable outcome (90-day mRS 0-2) between two groups. In addition, there was no difference in rate of sICH or procedural complications between two groups. In a mixed logistic regression model adjusting for potential confounders, IVT was not a predictor of sICH, successful recanalization or favorable outcome.

Conclusion:
Emergent CS in association with MT after IVT was safe and was not associated with an increased risk of sICH or procedural complications.
Abstract WP107: Early Recurrence of Ischemic Stroke in Alteplase-treated Patients: The ENCHANTED Study
Authors: Yoshimura Sohei , Carcel Cheryl , Delcourt Candice , Wang Xia , Torii-Yoshimura Takako , Lindley Richard I , Chalmers John , Anderson Craig S ,   the ENCHANTED Investigators
Published: January 2019

Introduction:
Early recurrence of acute ischemic stroke (AIS) predicts adverse outcome, but there is uncertainty about the predictors after intravenous alteplase. We aimed to determine the predictors of stroke/transient ischemic attack (TIA) and their prognostic significance among ENCHANTED participants.

Methods:
ENCHANTED was an international, randomized, open-label, blinded-endpoint trial of low- versus standard-dose intravenous alteplase in AIS patients. Log-rank test and multivariable analysis with cox-regression models were used to assess the association of baseline characteristics and stroke/TIA recurrence and of functional outcome (modified Rankin scale [mRS] scores 2-6) at 90 days.

Results:
Among 3297 AIS participants, 103 (3%) had early recurrent AIS/TIA, which was predicted by recruitment in South America (hazard ratio 1.75, 95%CI 1.04-2.94), history of coronary artery disease (1.67, 1.03-2.72) and extra/intra-cranial vessel stenosis (2.94, 1.49-5.81), premorbid mRS ≥1 (1.63, 1.04-2.55), lipid lowering therapy (1.66, 1.03-2.67), multiple ischemic brain imaging lesions (2.33, 1.50-3.61), and cardioembolic stroke (1.58, 1.02-2.46). Early recurrence was independently associated with poor functional outcome (odds ratio 4.76, 95%CI 2.63-8.42).

Conclusions:
After treatment with intravenous alteplase, early recurrence of cerebral ischemic events complicates recovery and residual disability. Better targeting of preventive strategies in those at high risk, specifically those with cardioatherosclerosis and cardioembolic disease, may improve outcome from AIS.