bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 20: Role of IRF5-IRF4 Regulatory Axis in Microglial Polarization After Neonatal Stroke
Authors: Mirza Mehwish A , Xu Yan , McCullough Louise D , Liu Fudong
Published: July 2021

Background:
Perinatal arterial ischemic stroke (PAIS) is an important cause of neonatal death and long-term disability. Once PAIS occurs, microglia are activated and innate immune responses are mounted in the brain. Microglial activation is characterized as M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype depending on the progression of brain injury. Recent studies with adult models of peripheral inflammation have found that interferon regulatory factor 5 (IRF5) regulates expression of pro-inflammatory cytokines, while IRF4 controls M2 macrophage polarization. The balance of the IRF5-IRF4 regulatory axis is critical in establishing M1/M2 macrophage phenotypes; however, it is unknown if microglial activation is regulated by the same mechanism in neonatal brains after PAIS. We hypothesize that IRF5-IRF4 regulatory axis directs M1/M2 microglial polarization and manipulation of the axis confers neuroprotection against PAIS.

Methods:
IRF5/IRF4 inducible conditional knockout (ICKO) mice in which IRF5 or IRF4 was deleted specifically in microglia by Tamoxifen induction were subjected to 60-minute Rice-Vanucci Modeling (RVM) at post-natal day 10 (P10) to induce PAIS. Stroke outcomes were evaluated at 7d of RVM. C57BL6 P10 pups will also be used for examination of microglial activation and IRF5/IRF4 expression by flow cytometry (FC), RT-PCR, IHC, and western blotting.

Results:
Microglia exhibited high levels of M2 marker CD206 at 3d and M1 marker MHCII at 7d of PAIS by FC analysis (n= 6st, 3sh/gp). IRF4 mRNA in FC-sorted microglia was upregulated 24h after stroke and peaked at 3d, but declined to baseline at 7d. Conversely, IRF5 was not upregulated until 3d and peaked at 7d. Correspondingly, IRF4 and IRF5 expression in the nuclear fraction was increased at 3d and 7d respectively. Similar patterns of IRF5/IRF4 expression was seen in Iba-1
+
cells in the brain by IHC (n= 8st, 4sh/gp). IRF4 ICKO mice had worsened stroke outcomes while IRF5 ICKO showed protective effects 7d after PAIS.

Conclusions:
PAIS led to a transient M2 phenotype of microglia that switched to M1 polarization at a later time. IRF5-IRF4 regulatory axis plays an important role in mediating M1/M2 polarization of microglia and is a promising target of interventional therapy for PAIS.
Abstract 210: The Risk Of A Diagnosis Of Cancer After Ischemic Stroke: Two Year Follow-up Study Of 3247 Cancer Free Ischemic Stroke Patients
Authors: Qureshi Adnan I , Malik Ahmed A , Saeed Omar , Adil Malik M , Suri Fareed K
Published: July 2021

Background:
Subclinical cancer can manifest as a thrombo-embolic event and may be detected at a later interval in ischemic stroke survivors.

Objective:
To determine the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors.

Methods:
An analysis of 3680 adults with non-disabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. We calculated age adjusted rates of incidence of cancer among ischemic stroke survivors and calculated the standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity.

Results:
A total of 3247 patients (mean age (±SD) of 66 (±11); 2013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 month, 1 year, and 2 years, respectively. The age adjusted annual rate of cancer in patients with ischemic stroke over 1 year after recruitment was 581.8/100,000 persons which was higher than the age adjusted cancer rate of 486.5/100,000 persons in the general population (SIR 1.2, 95% CI 1.16-1.24). The age adjusted annual rate continued to be higher in patients with ischemic stroke over 2 years after recruitment (1301.7/100,000 versus 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6). There was a higher risk for death (OR 3.1, 95% CI, 1.8-5.4), fatal/disabling stroke or death (OR 2.3, 95% CI 1.4-3.7), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders.

Conclusions:
The annual rate of age adjusted cancer incidence was higher among ischemic stroke patients compared with general population. The risk of mortality was three folds greater among stroke survivors who developed incident cancer.
Abstract 221: Regional Vulnerability within White Matter tracts to White Matter Hyperintensities: a Diffusion Tensor Imaging Tractography Study
Authors: Maillard Pauline , Seshadri Sudha , Beiser Alexa , Himali Jayandra , DeCarli Charles
Published: July 2021

Background:
Characterizing the impact of cerebral white matter (WM) damage on age related cognitive decline is of growing interest. White matter hyperintensities (WMH) and reduced microstructural WM integrity, as expressed by diffusion tensor imaging (DTI), have been associated with increased risk of clinically cognitive decline in the elderly, but the regional vulnerability within certain WM tracts to WMH is not well understood. Characterizing the implication and interactions of microstructural integrity and WMH within specific WM tracts would further elucidate mechanisms of cognitive decline in normal aging.

Methods:
410 cognitively normal individuals from the Offspring Framingham Heart Study, aged 72.5±7.5 ([54.2; 104.9]), received a comprehensive clinical evaluation and brain MRI including FLAIR and DTI sequences. WM tractography was performed from DTI using FSL tools, resulting in 27 fiber tracts maps for each subject. WMHs were detected on FLAIR scans using a standardized protocol and coregistered to the subject DTI space. The mean fractional anisotrophy (mFA) within each tract was computed. Superimposition of WMH masks onto fiber tracts maps was used to calculate the overlap ratio of WMH (WMHor) within each tract. For each tract, mFA was regressed against the age and tract size and resulting residuals related to WMHor using a linear regression model.

Results:
The highest rates of WMHor were found within the thalamic radiations (range: [0- 28%]) and the inferior longitudinal fasciculi ([0- 29%]). Lower mFA was independently associated with larger WMHor within almost all association and projection fibers (p values<0.05). Correcting for the overall WMH burden did not significantly alter the results.

Discussion:
Regional mean FA has been previously associated with the overall WMH burden. We extended this finding by showing that, independently of the overall WM injury, microstructural WM integrity was associated with WMH within specific fiber tracts. Further investigations are needed to detangle the impact of specific tract disruption from that of more generalized subtle WM injury on cognitive decline.
Abstract 23: Predictors of Early Neurological Deterioration in the Single Small Subcortical Infarctions
Authors: Jeong Han-Gil , Kim Beom Joon , Yang Mi Hwa , Kim Seongheon , Han Moon-Ku , Bae Hee-Joon
Published: July 2021

Background:
Early neurological deterioration (END) occurs in ≥20% of single small subcortical infarctions (SSSIs; axial diameter ≤20 mm in the perforator territories) and deters functional recovery. SSSIs are supposed to have two distinct pathological processes including microvasculopathies of arteriolar walls and the localized atherosclerosis of the upstream arteries. We hypothesized that the occurrence of END in the SSSIs differs according to the pathological processes.

Methods:
From a total of 4961 stroke cases between July 2007 and July 2013, we assessed 587 patients with SSSI within 48 hours of onset. END was assessed prospectively as a quality improvement program of stroke care. Functional outcomes after stroke were also collected prospectively by telephone or face-to-face interview. Independent reviewers rated neuroimaging characteristics with the acceptable inter-rater reliability including relevant artery stenosis (0 - 50% stenosis of the adjacent arteries on MR angiography), branched atheromatous lesion (≥4 consecutive axial cuts or extension from the basal surface of brainstem), white matter hyperintensities, old lacunar infarction and cerebral microbleeds.

Results:
END occurred in 79 (13.5%) cases, including 6 recurrences (8%), 66 progressions (84%) and 7 other causes (9%). Symptomatic hemorrhagic transformation was not documented. NIHSS score was increased when END occurred by 2.3 ± 1.4 points. END patients had higher frequency of having mRS score 3 - 6 at 3 months than those without END (49% vs. 23%). In the multivariable analyses, relevant artery stenosis (adjusted OR 1.91, 95% CI 1.13 - 3.21) and branch atheromatous lesion (2.98; 1.80 - 4.93) had significantly higher odds of having END. However, such association was not detected in the stigmas of small vessel diseases.

Conclusions:
Relevant artery stenosis and branch atheromatous lesions were significantly associated with the occurrence of END in SSSIs, which suggest a potential contribution of the localized atherosclerotic process to the END in SSSIs. Our results suggest that precautionary measures might be utilized for SSSI patients with higher atherosclerotic burdens.
Abstract 31: The Angiotensin Type 2-receptor Agonist, Compound 21, Provides Neuroprotection After Ischemia Reperfusion Injury Through Interleukin 10 Upregulation
Authors: Fouda Abdelrahman Y , Alhusban Ahmed , Ergul Adviye , Fagan Susan C
Published: July 2021

Introduction:
We and others have shown that the angiotensin type 2 (AT2) receptor agonist, compound 21 (C21), provides neuroprotection and enhances recovery in rodent stroke models yet the mechanism involved is not known. Moreover, C21 treatment is associated with an anti-inflammatory response. Here we tested the hypothesis that C21 mediates neuroprotection by upregulating the neuroprotective and anti-inflammatory cytokine interleukin (IL)-10. Methods: Wistar rats (n=16) were subjected to 3 h MCA suture occlusion and treated at reperfusion with C21 (0.03 mg/kg) ± IL-10 neutralizing antibody (0.1 μg/kg) both given I.P. Endpoints at 24 h included: Infarct size, behavioral outcome, and molecular analysis. Primary rat neurons were used to test the direct neuroprotective effect of C21 in vitro. Results (Table): C21 treatment upregulated IL-10 expression (1797±89 vs 1333±84 pg/mg) and increased IL-10 downstream survival signals, STAT3 and AKT phosphorylation, in the stroked hemisphere compared to saline. Anti-IL-10 co-treatment blocked the C21 induced reduction in infarct size and inflammatory/apoptotic markers, and blunted the improvement in behavioral outcome, as well as survival signal activation. In vitro (n=4), C21 treatment failed to directly protect ischemic neurons against oxygen glucose deprivation/reperfusion (OGD/R) insult as measured by LDH release (other cell death markers are to be analyzed), but was able to upregulate IL-10 in normoxic neurons (0.3±0.02 vs 0.23±0.01) suggesting a potential indirect neuroprotective effect. Conclusion: C21 provides acute neuroprotection after ischemia reperfusion injury through neuronal IL-10 upregulation. Further understanding of the mechanism of action will pave the way for translating C21 and future AT2 agonists to the clinical stroke setting.
Abstract 34: Cognitive Outcomes Following Intracranial Injection of SB623 Cells in Patients with Stable Ischemic Strokes
Authors: Kenmuir Cynthia L , Reddy Vivek K , Stilley Carol , Zeifert Penelope , Steinberg Gary K , Kondziolka Douglas S , Lunsford L. D , Schwartz Neil E , Yankee Ernest , Wechsler Lawrence R
Published: July 2021

Background:
Ischemic stroke remains a major cause of disability with 90% of patients achieving no improvement after 90 days. The primary objective of this study was to evaluate the safety and feasibility of intraparenchymal administration of SB623 cells in chronic stroke. SB623 cells are adult bone-marrow-derived cells transfected with a plasmid encoding the intracellular domain of Notch-1 and have been shown to secrete factors that protect neurons in animal models.

Methods:
Patients with hemiparesis from stable subcortical ischemic stroke and NIHSS > 7 received intracranial injection of 2.5, 5 or 10 million SB623 cells. Clinical outcome measures including NIHSS, MRS, ESS, FMA and cognitive testing including Rey verbal learning and figure copy, digit vigilance, digit-symbol coding, trails, logical memory, word association, Stroop interference and letter-number sequencing were recorded at baseline and then repeated at 6 and 12 months.

Results:
18 patients were enrolled, 11 had complete data available for analysis. There was improvement from 0-12 months in Rey verbal learning (p = 0.033); and from 0-6 months in categorical word association (p = 0.014), which was affected by cell dose (p = 0.043). Patients with cortical versus deep infarcts showed more improvement on Rey figure immediate (p = 0.01) and delayed recall (p = 0.014), and digit-symbol coding (p = 0.042). Patients with left-sided infarcts showed more improvement on logical memory (T1 p = 0.038, T2 p = 0.008), but worsened performance on letter number sequencing (p = 0.046).

Conclusions:
Intraparenchymal injection of SB623 cells in chronic ischemic strokes resulted in improvement of some measures of cognitive function. Further investigation of cognitive function in stem cell therapy for stroke is warranted.
Abstract 38: Intensive Monitoring of Cardiac Function and Extravascular Lung Water Predicts Outcome of Tako-tsubo Cardiomyopathy after Subarachnoid Hemorrhage
Authors: Mutoh Tatsushi , Kazumata Ken , Taki Yasuyuki , Inoue Kentaro , Suzuki Akifumi , Ishikawa Tatsuya
Published: July 2021

Takotsubo cardiomyopathy (TCM) is a life-threatening systemic consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics and related outcome are not well-understood. We aimed to investigate the TCM-induced cardiac function by transpulmonary thermodilution and its impact on clinical outcome of SAH.
Forty-six
consecutive SAH patients who developed TCM and treated surgically or endovascularly were analyzed retrospectively. Patients were divided into two groups of LVEF <40% (TCM with LV dysfunction) and LVEF ≥40% (TCM without LV dysfunction). Cardiac function index (CFI) and extravascular lung water index (ELWI) were monitored by transpulmonary thermodilution. Transpulmonary thermodilution-derived CFI was correlated significantly with echocardiographic left ventricular ejection fraction (LVEF) (
r
= 0.82,
P
<0.0001). The CFI between day 0 to day 7 was significantly lower in patients with LV dysfunction (LVEF <40%) than in patients with LVEF ≥40% (
P
<0.05). CFI had a better ability than cardiac output to detect cardiac dysfunction (LVEF <40%) (Area under the curve: 0.85 ± 0.02;
P
<0.001). A CFI value of <4.2 min
-1
had a sensitivity of 82% and specificity of 84% for detecting LVEF <40%. The CFI <4.2 min
-1
was associated with delayed cerebral ischemia (DCI) (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.33-2.86;
P
= 0.004) and poor 3-month functional outcome on modified Rankin Scale of 4-6 (OR, 1.87; 95% CI, 1.06-3.29;
P
= 0.02). An ELWI >14 mL/kg after day 4 increased the risk of poor functional outcome at 3-month follow-up (OR, 2.10; 95% CI, 1.11-3.97;
P
= 0.04).
In conclusion,
prolonged cardiac dysfunction and pulmonary edema increased the risk of DCI and poor 3-month functional outcome in patients with SAH suffering from TCM. Serial measurements of CFI and ELWI by transpulmonary thermodilution may provide an easy bedside method of detecting early changes of the cardiopulmonary function in directing proper post-SAH treatment.
Abstract 40: Transcriptome and DNA Methylation Changes in Patients with Subarachnoid Hemorrhage Undergoing Remote Ischemic Preconditioning
Authors: Nikkola Elina , Ko Arthur , Connolly Mark J , Ooi Yinn Cher , Pajukanta Päivi , Gonzalez Nestor
Published: July 2021

Background:
Remote ischemic conditioning (RIC) is a phenomenon by which brief periods of sublethal ischemia in one tissue confers protection from ischemia to distant tissues. We hypothesize that RIC triggers a cascade of integrated gene expression and methylation changes, leading to neuroprotection in subarachnoidal hemorrhage (SAH) patients. Our goal was to identify and compare changes in DNA methylation and gene expression profiles before and after RIC.

Methods:
Patients enrolled in a clinical trial of RIC after SAH, receiving RIC by limb cuff transient ischemia sessions. Fourteen SAH patients (64% female, mean age 51) underwent 3-4 RIC sessions and gave a blood sample before and after RIC, seven days apart. The transcriptome analysis of whole blood was performed using paired-end, 100-bp RNA-sequencing. We employed STAR and HTSeq to align and count reads; EdgeR to normalize the counts and detect differential expression (DE); and David to search for functional categories of the DE genes. Genome-wide DNA methylation profiles were assessed using reduced representation bisulfite sequencing (RRBS); Bismark with Bowtie to align the RRBS data, and the differential methylation analysis package (DMAP) to call the methylation status of CpG sites. Bedtools was used to overlap the DE genes with differentially methylated regions.

Results:
Of the 12,411 genes passing QC, 168 genes were differentially expressed after RIC (FDR<0.05). These genes were enriched for pathways involving mitosis and nuclear division (P50% after RIC in at least one individual. Of the 8,069 sites, 723 were differentially methylated (Bonferroni P<0.05). Our overlap analysis showed that 88 of the significantly altered methylation sites resided in 39 DE genes, including CEACAM8 and CRISP3, both implicated previously for stroke.

Conclusions:
Our data suggest that RIC alters expression of a specific set of genes involved in stroke via changes in regional DNA methylation. Further studies are warranted to replicate these pilot results.
Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment
Authors: Graff-Radford Jonathan , Roberts Rosebud , Madhavan Malini , Rabinstein Alejandro , Cha Ruth , Vemuri Prashanthi , Kantarci Kejal , Mielke Michelle , Lowe Val , Gunter Jeffrey , Senjem Matthew , Pankratz Vernon S , Knopman David , Petersen Ronald C , Jack Clifford
Published: July 2021

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.
Abstract 6: Resting-state Functional Connectivity Changes After Stroke Rehabilitation Using Closed Loop Neurofeedback
Authors: Nair Veena A , Young Brittany M , Nigogosyan Zack , Remsick Alex , Weber Sonya , Diffee Kayla , Walton Leo , Tyler Mitch , Sattin Justin , Edwards Dorothy F , Williams Justin , Prabhakaran Vivek
Published: July 2021

Introduction:
Brain-computer interface (BCI)-EEG is a promising intervention for improving motor function after stroke. However, brain changes following intervention on a BCI-EEG system are not yet fully understood. We examined changes in resting state functional connectivity (RSFC) MRI in the motor network defined by 6 key regions in the left and right primary motor cortex (M1), left and right supplementary motor area (SMA), and left and right premotor cortex (PMC). Additionally, we investigated brain-behavior correlation between rsFC and a battery of outcome measures including the Barthel Index (BI), the Stroke Impact Scale(SIS), and the Action Research Arm Test (ARAT).

Methods:
Fifteen stroke patients with persistent mild to severe upper extremity impairment following ischemic stroke received intervention using BCI-EEG and were tested before (T1) and at 2-3 weeks (T2) mid intervention. 11 of these patients were also tested a third time at 4-6 weeks at the end of intervention (T3). Eyes closed, 10 minute resting fMRI and anatomical scans were acquired on a GE 3T MRI scanner. Right hemisphere stroke patients’ scans were flipped so that as a group the lesion was in the left (L) hemisphere and the impaired limb right (R). Seed region based connectivity analyses were performed to examine changes in RSFC over time and in inter-hemispheric and intra-hemispheric connectivity, and correlations between brain changes and behavioral changes were investigated.

Results:
BCI-EEG intervention led to significant increase in intra-hemispheric connectivity (p = .03) from T1 to T3. Inter-hemispheric connectivity increased from T1 to T3, trending towards significance (p = .06). Significant positive correlations were observed between changes in RSFC (L.M1 and L.PMC, L.M1 and R.PMC, L.SMA and R.PMC, and R.PMC and R.SMA) and change in upper extremity BI score (p ranging from .01 to .001); changes in RSFC between L.PMC and R.PMC correlated with hand strength on the SIS (p = .03). A trend was observed between increase in RSFC (L.M1 and R.PMC) and increase in total ARAT score but this was not significant.

Conclusions:
Results suggest that BCI-EEG intervention facilitate changes in RSFC in the motor network in stroke patients and these changes are associated with improved outcomes.
Abstract 61: Seasonal Variation of In-Hospital Mortality in Patients with Acute Ischemic Stroke
Authors: Kumar Nilay , Garg Neetika , Khunger Monica , Venkatraman Anand
Published: July 2021

Background and objectives:
Seasonal patterns in incidence and mortality are well known for cardiovascular diseases (CVD) including acute myocardial infarction and arrhythmias. It is unclear whether in-hospital mortality in patients with acute ischemic stroke (AIS) exhibits seasonal variation.

Methods:
We searched the 2011 Nationwide Inpatient Sample for discharges with a principal diagnosis of AIS using the ICD-9 codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91 and 437.1. Seasonal variation in in-hospital mortality was tested using logistic regression with admission season and month as categorical predictors in separate models. In addition to annual variation, we tested for the “July effect” of increase in mortality in teaching hospitals.

Results:
There was an estimated 467, 849 discharges for AIS of which 21,149 (4.53%) died in the hospital. Compared to summer months, the risk of in-hospital mortality was 12.6% higher in winter and 10.2% higher in the fall (p=0.004 for winter vs. summer, p=0.024 for fall vs. summer). Compared to August, mortality was 18.20% higher in January (p=0.026 for comparison) and 24.3% higher in December (p=0.003 for comparison) (Table shows odds ratio of death compared to reference season/month). We did not find any evidence of a “July effect” of increased mortality, often attributed to new trainees, in teaching hospitals (p=0.830 for June vs. July)

Conclusions:
In a large national database of hospital discharges related to AIS, mortality was significantly higher in colder months compared to warmer months. Our study adds to the growing body of evidence that links winter season to worse outcomes in CVD.
Abstract 68: Palliative Care Is Underutilized in Patients with Severe Intracerebral Hemorrhage
Authors: Sisson April , Albright Karen C , Peck Michelle , Nguyen Linh M , Lyerly Michael , Sands Kara A , Boehme Amelia K , Harrigan Mark
Published: July 2021

Background and Purpose:
Palliative care is an essential part of ICH care, particularly in patients with high ICH scores given their poor prognosis. Palliative care involves consultation by the Palliative Care Service and includes de-escalation of care, changing code status, and making pain and symptom relief the central goal of management.

Methods:
We performed a retrospective review of consecutive patients presenting to our tertiary care center from 2008-2013 with primary ICH. Demographic and clinical data were collected. Our sample included only patients who died or were transferred to hospice. We examined the proportion of patients that received an inpatient palliative care consult and compared this group to patients who did not receive an inpatient palliative care consult. Patients were categorized by ICH score.

Results:
Of the 99 ICH patients who died or were discharged to hospice, only 23% received a palliative care consult. Figure 1 displays death, predicted death, and palliative care consult proportions by ICH score. Patients that received a Palliative Care consult were older (mean age 65 vs. 73, p=0.018) and more frequently had evidence of infection (32% vs. 13%, p=0.038); no other significant differences were found between groups.

Conclusions:
In our sample of ICH patients, 23% of patients received a palliative care consult. In those with high ICH scores utilization was only 28%, despite 30 day expected mortality of 97% or greater. This raises concern that palliative care may be underutilized in patients who may benefit from it the most.
Abstract 79: Evidence to Maintain the SBP treatment threshold at 140 mmHg for Stroke Prevention in Persons Aged 60 Years or Older Without Diabetes Mellitus or Chronic Kidney Disease: The Northern Manhattan Study (NOMAS)
Authors: Dong Chuanhui , Rundek Tatjana , Marquez Chensy , Wright Clinton B , Elkind Mitchell S , Sacco Ralph L
Published: July 2021

Background:
In 2014, the Eighth Joint National Committee recommended increasing target systolic blood pressure (SBP) from 140 to 150 mm Hg in persons aged ≥ 60 years without diabetes mellitus (DM) or chronic kidney disease (CKD). The evidence from population-based studies supporting the change was sparse. In a race/ethnically diverse prospective cohort, we examined incident stroke risk by SBP level in those aged ≥ 60 years without stroke, DM, or CKD at baseline.

Methods:
In the Northern Manhattan Study, there were 1706 participants aged ≥ 60 years and free of stroke, DM, and CKD at baseline. Incident strokes were identified through annual follow-up and adjudicated by two vascular neurologists. Cox proportional hazard models were used to estimate the multivariable-adjusted hazard ratio (HR) for baseline SBP categories and stroke risk.

Results:
At baseline, mean age was 72±8 years, 37% were male, 25% non-Hispanic white, 26% non-Hispanic black, and 49% Hispanic; 41% were on antihypertensive medication, and 43% had SBP <140 mm Hg, 20% 140-149 mm Hg, and 37% ≥150 mm Hg. With a median follow-up of 13 years, 167 participants developed a stroke. The crude stroke incidence was greater among individuals with SBP ≥150 mm Hg (10.0 per 1000 person-years) and SBP 140-149 (12.2) compared to those with SBP<140 (6.2). After adjustment for age, sex, race-ethnicity and medication use, participants with SBP 140-149 mm Hg had increased risk of stroke (HR, 1.7; 95% CI, 1.2-2.6) compared with those with SBP <140 mm Hg, and the increased risk remained in those without medication use (1.7; 1.0-3.0). Stratified analysis showed that the increased risk was seen in Hispanics (2.4; 1.3-4.7) and non-Hispanic blacks (2.0; 1.0-4.2) but not in non-Hispanic whites (0.8; 0.3-1.8).

Conclusions:
In a prospective diverse cohort, SBP 140-149 mm Hg was associated with an increased stroke risk, compared to those with SBP <140 mm Hg, in individuals aged 60 years or older without DM or CKD, in particular in Hispanics and non-Hispanic blacks. Raising the threshold for hypertension treatment could have a detrimental effect on stroke risk reduction especially among minority populations.
Abstract 9: Clinical Effectiveness of Statin Therapy after Ischemic Stroke: Primary Results from the PROSPER Study
Authors: O'Brien Emily C , Greiner Melissa A , Xian Ying , Fonarow Gregg C , Olson DaiWai M , Schwamm Lee H , Bhatt Deepak L , Smith Eric E , Maisch Lesley , Hannah Deidre , Lindholm Brianna , Peterson Eric D , Pencina Michael J , Hernandez Adrian F
Published: July 2021

Background:
Evidence for statin use comes primarily from select clinical trial populations that are often younger without comorbidities. Stroke patients and their caregivers are in need of real-world effectiveness data to better inform decision-making on statin use after stroke.

Methods:
PROSPER is a PCORI-funded research program designed with stroke survivors to evaluate the effectiveness of therapies post-stroke. We linked data from Get With The Guidelines-Stroke patients >65 years of age to Medicare claims to capture post-discharge outcomes. Primary outcomes prioritized by patients were: 1) Home time (days alive and out of acute or post-acute care) and 2) Major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, all-cause readmission, CV readmission, and hemorrhagic stroke. We used negative binomial and Cox models to evaluate discharge statins and outcomes with inverse probability weighting (IPW) to adjust for baseline differences by treatment group.

Results:
Of 77,468 statin-naïve ischemic stroke patients hospitalized from 2007-2011, n=54,991 (71%) were discharged on statin therapy. Compared with those not receiving a statin, patients receiving a statin were younger and more likely to be smokers. Unadjusted rates of MACE, mortality and CV readmission within 2 years were lower for statin patients compared with those not receiving a statin. After IPW adjustment, statin therapy was associated with 28 more days of home time in the 2-year post-discharge period (P <.001), 9% lower hazard of MACE (P <.001), 16% lower hazard of mortality (P <.001), and 7% lower hazard of readmission (P <.001). Statin use was not associated with increased risk of hemorrhagic stroke (P=0.56).

Conclusions:
In a real-world population of older statin-naïve ischemic stroke patients, discharge statin therapy was associated with more days spent at home during the 2-year period after hospitalization and lower risk of both MACE and all-cause mortality.
Abstract NS13: Post Stroke Depression and Fatigue are Independently Related to Sleep Disturbances in Acute and Sub-acute Stroke Patients
Authors: Choi Kwon Smi , Suh Minhee , Kim Jong S
Published: July 2021

Post-stroke sleep disturbances (PSSD) is common and is associated with unfavorable clinical outcomes. The purpose of this study was to evaluate the characteristics of PSSD and how depression and fatigue affect PSSD in hospitalized and 3 months post stroke patients.

Methods:
Patients who were hospitalized with stroke at the Asan Medical Center were evaluated. The duration and latency of nighttime sleep, the frequency of waking after sleep onset, and daytime sleepiness were evaluated during the hospitalization and also 3 months post stroke. An actigraph was also performed. The location, circulation and laterality of each lesion were determined using MRI. Depression and fatigue were assessed using the Beck Depression Inventory and the Fatigue Severity Scale, respectively. For environmental factors, the equipment used at the bedside, and the number of other patients in the same room in acute stage and the place of residence, and the number of other person sharing the room in chronic stage were recorded.

Results:
A total of 282 patients completed the study. The mean age of the patients was 62.3(± 12.76). Sixty (21.3%) reported sleep duration <6 h/night and 110 (39.0%) reported more daytime sleepiness than prior to the stroke. In 54 patients who wore actigraph, self-reported sleep duration was significantly correlated with time in bed measured with an actigraph (
r
=.407,
p
=.002). Quality of nighttime sleep was independently related to cortical lesion location (p=.002), diabetes mellitus (p=.020), and depression (p<.001) whereas increased daytime sleepiness was independently associated with subcortical lesion location (p=.031), fatigue (p=.001), and quality of nighttime sleep (p=.001). In chronic stage, 151 patients completed the study. PSSD persisted in the majority of the patients (75%) and the related factors to PSSD were also similar as compared to those in acute stage.

Conclusions:
PSSD are common in acute and chronic stroke patients. . Although brain lesion and diabetes mellitus were associated with nighttime PSSD, depression was the most powerful factor predicting nighttime sleep disturbances. Post-stroke daytime sleep was more closely associated with fatigue and subcortical lesion location.
Abstract NS16: What’s Important for Post-Stroke Community Re-integration? Viewpoints of Stroke Survivors and Service Providers in Ontario, Canada
Authors: Jermyn Darren , Montgomery Phyllis , Mossey Sharolyn , Bailey Patricia , Nangia Parveen , Egan Mary , Verrilli Sue
Published: July 2021

Background:
Stroke is a leading cause of disability worldwide. Stroke survivors living in the community require regular, ongoing, and coordinated services to prevent deterioration and maximize health outcomes. Published evidence, often conducted in large urban centres, suggests that community reintegration services are an important component of care for stroke survivors. This evidence, however, often does not address the particular challenges inherent in servicing stroke survivors who reside in smaller urban and rural contexts.

Purpose:
The purpose of this study was to gain an understanding of the priorities that are needed to support stroke recovery and community reintegration from the perspectives of survivors and service providers living in four geographic districts in Northeastern Ontario, Canada.

Methods:
Using Q methodology, 45 service providers, and 43 stroke survivors and their family caregivers ranked 30 theoretical statement cards. Each card identified a feature specific to stroke recovery, community navigation and community reintegration. These statements were generated through a review of health care literature and qualitative data collected from interviews with stroke survivors. Q analysis of the priority ranked statements involved centroid factor analysis and varimax rotation.

Results:
The three discrete viewpoints of survivors were Role of Skilled Navigators, Survivors as Co-navigators, and Striving for Well-being. The survivors’ consensus perspective, labelled Quality Service, identified the importance of timeliness and appropriateness of service. The three discrete viewpoints for service providers were Role of Skilled Navigators, Survivor-centered Practices, and Optimizing Survivors’ Resources. The consensus perspective of service providers was labelled Involvement of Family Carers. Findings were consistent across all 4 geographic districts.

Conclusion:
This research suggests that survivors’ and providers’ conceptualized role of community navigators is focused on building upon the strengths and capacity of survivors through cooperative inquiry with multiple stakeholders. A time-sensitive, appropriate, and family involved service structure supports survivor-centric community reintegration.
Abstract NS23: Changing State-wide Stroke Practice: The QASC Implementation Project
Authors: Middleton Sandy , Comerford Daniel , Lydtin Anna , Dale Simeon , Cadilhac Dominique , D'Este Cate , McElduff Patrick , Hill Kelvin , Cheung N Wah , Levi Christopher , Longworth Mark , Ward Jeanette , Quinn Claire ,   on behalf of the QASC Implementation Working Groupand Steering Committee
Published: July 2021

Background:
The Quality in Acute Stroke Care (QASC) Trial
1
determined that a multidisciplinary supported, nurse-initiated, evidence-based intervention involving supported implementation of clinical protocols to manage fever, hyperglycaemia and swallowing (FeSS protocols) following stroke decreased death and dependency by 16% (p=0.002); reduced temperatures (p=0.001) and glucose levels (p=0.02); and improved swallowing management (p=<0.001). Yet, upscale and spread of even proven interventions on a state-wide level is challenging.

Aim:
To implement the FeSS protocols from the QASC Trial in all 36 stroke services in NSW, Australia.

Method:
Our 14 month translational project replicated the intervention from the original QASC Trial. We conducted barrier and enabler assessments and an educational workshop, engaged local opinion leaders, used reminders, and provided ongoing site champion support. Participating sites audited 40 pre-, and 40 post- implementation medical records using the National Stroke Foundation clinical audit web-based tool.

Results:
All (n=36, 100%) sites participated in the medical record audit (100% response rate) providing data for a total of 2144 patients (pre-implementation: n= 1062; post-implementation: n=1082). Significantly increased proportions of patients received care according to the fever (pre: 69%; post: 78%; p=0.0031), hyperglycaemia (pre: 23%; post: 34%; p=0.0085), and swallowing (pre: 42%; post: 51%; p=0.0331) protocols post-implementation.

Conclusion:
Our results provide rare evidence of successful research translation of Class 1 Level B evidence across an entire state in a short time-frame and in the real world of clinical practice.
Abstract NS7: Presenting Symptoms and Response to Dysphagia Screen Predict Unfavorable Outcome in Acute Ischemic Stroke Patients Who Do Not Receive IV tPA Due to Mild and Rapidly Improving Stroke Symptoms
Authors: Camp Deborah , Bryant Katja , Zimmermann Susan , Brasher Cynthia. , Connelly Kerrin M , Dunn Joshu , Frankel Michael , Ido Moges , Lugtu James ,   Georgia Stroke Professional Alliance, Nahab Fadi
Published: July 2021

Background & Purpose:
Studies have shown that patients who do not receive IV t-PA due to mild and rapidly improving stroke symptoms (MaRISS) are often not discharged home. The purpose of this study was to identify whether presenting symptoms and response to initial dysphagia screen can predict which patients not treated with IV tPA due to MaRISS have an unfavorable outcome.

Methods:
Acute ischemic stroke (AIS) patients presenting to hospitals participating in the Georgia Coverdell Acute Stroke Registry and not treated with IV t-PA due to MaRISS alone from January 1, 2009 through December 31, 2013 were included in this analysis. Patients who were unable to ambulate or needed assistance to ambulate prior to admission were excluded. Presenting symptoms and response to dysphagia screen were collected from retrospective chart review at participating hospitals. Multivariable regression analysis was used to identify factors associated with a lower likelihood of favorable outcome, defined as discharge to home. During the study period, < 1% of patients presenting to participating hospitals with MaRISS within the 3 hour time window received IV t-PA.

Results:
Of 841 AIS patients who did not receive IV-tPA due to MaRISS [median NIHSS 1 (Q1-Q3: 0-3)], 160 (19%) did not have a favorable outcome. Factors associated with lower likelihood of a favorable outcome included increasing NIHSS score (per unit OR 0.89, 95% CI 0.84 to 0.93), weakness as the presenting symptom (OR 0.50, 95% CI 0.30 to 0.84), and a failed dysphagia screen (OR 0.43, 95% CI 0.23 to 0.80).

Conclusion:
Nearly 1 in 5 AIS patients presenting with MaRISS were not discharged to home. Among AIS patients who present with MaRISS and do not receive IV thrombolytic therapy, baseline characteristics including increasing NIHSS score and weakness as a presenting symptom, and a failed dysphagia screen were all associated with a lower likelihood of discharge to home. Given the low rate of patients presenting during the study period, a prospective randomized trial to evaluate IV t-PA treatment focusing on this subgroup of patients is warranted.
Abstract T MP1: The Pittsburgh Collateral Ratio: A Novel Method to Assess Collateral Circulation Status in Acute Mca Occlusions
Authors: Abdelnour Carla , Rangaraju Srikant , Streib Christopher , Aghaebrahim Nima , Delfyett William , Jovin Tudor , Jadhav Ashutosh
Published: July 2021

Introduction:
Collateral status is a robust predictor of recanalization and clinical outcome in acute ischemic stroke and numerous collateral grades exist to evaluate it (many of which are qualitative or semi-quantitative) being CT angiography (CTA)-based collateral grading the most frequently used. We attempt to quantitatively assess collateral grade based on a comparison between contrast filling proximal and distal to a medial cerebral artery (MCA) occlusion.

Material and methods:
We retrospectively reviewed the data of patients with M1 MCA occlusions referred to our center between January 15, 2006 and January 15, 2014. The Pittsburgh Collateral Ratio (PCR) was determined by calculating the mean Hounsfield Units (HU) in regions of interest (ROI) in the MCA, both pre and post-thrombus at the time of maximal opacification of the vessel (PCR = HU post-thrombus/ HU pre-thrombus). Ipsilateral (iPCR) and contralateral (cPCR) ratios were calculated. Two independent reviewers (CA and WD) graded pre-treatment CTA collateral status as good (the entire MCA reconstitutes with contrast) and poor (partial or no reconstitution of the distal MCA). PCR was compared to CTA collateral status and associated with good outcome (mRS 0-2 at 3 months) by logistic regression analysis.

Results:
Fifty one patients were included (mean age 65±3 yrs, median initial NIHSS 17 [IQR 14-21]). Strong correlation between PCR and CTA collateral grade was observed (iPCR: Pearson’s R=-0.796, p<0.001, cPCR: Pearson’s R=-0.64, p<0.001). iPCR was highly predictive of good collateral status (AUC 0.89, p<0.001) and iPCR ≥ 0.6 had a 100% sensitivity and 64% specificity for good collateral status. In multivariate analysis after controlling for age, NIHSS and ivTPA, iPCR was an independent predictor of good outcome (p=0.02).

Conclusions:
The PCR is a simple and accurate method to evaluate collateral circulation status in MCA occlusion patients and further validation of this score in larger cohorts is warranted.
Abstract T MP102: Hotline Use for Recruitment Support in Acute Stroke Trials: Lessons learned To Date in Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II
Authors: France Kathryn A , Qureshi Mushtaq , Thomas Jessy , Abbott Emily , Brau Logan , Qureshi Adnan I
Published: July 2021

Background:
Use of hotline services for clinical support and safe operation of a research trial is common and important. The value of such services has not been objectively assessed within the context of a large acute stroke clinical trial.

Methods:
The use of three different hotline services have been tested, and cell and Email- options have also been explored for their advantages. US and Non-US sites are provided access to central hotline services, but for efficiency a local network for managing calls is established in each region. All sites may access both data management and the trial PI via hotline services when needed and this is supported by other technologies in addition. A means for supporting overall trial communications in light of these interactions has been developed and valuable insights are gained.

Results:
Data gathered from 211 calls logged at the Clinical Coordinating Center through the course of the ATACH-II trial have been summarized: Total Calls Reviewed: 211; Year 2 of trial: 92 calls, Year 3 of trial: 100 calls. Calls received midnight to 8 AM: 19 (9.0%), 8 AM - 5 PM 130 (61.6 %) 5 PM - 12:00 PM 65 (30.8%). Issues Resolved in < 5 min 143/211 (67.8%) Taking > 30 min to resolution 51/211 (24.2%). Purpose of calls: Eligibility 89 (42.2%). protocol compliance including drug management: 77 (36.5%%), randomization/emergency randomization: 16 (7.6%), protocol deviation:13 (6.2%), technological difficulties: 12 (5.7%), AE/SAE: 9 (4.3%), Subject enrollments directly associated with calls: 57 (20.8% of domestic subjects); excluded candidates directly associated with calls: 46 (% not available).

Conclusions:
In an international trial requiring rapid enrollment of subjects with intracerebral hemorrhage, the role of direct support via a hotline and other immediate communications means has proven to be instrumental in maintaining good protocol compliance and supporting enrollment by site team members .
Abstract T MP114: Hyperlipidemia and Statin Use: Is There an Effect on Mortality Following an Ischemic Stroke?
Authors: Yeramaneni Samrat , Kleindorfer Dawn , Sucharew Heidi , Alwell Kathleen , Moomaw Charles , Flaherty Matthew , Woo Daniel , Adeoye Opeolu , Ferioli Simona , De Los Rios La Rosa Felipe , Martini Sharyl , Mackey Jason , Khatri Pooja , Kissela Brett , Khoury Jane
Published: July 2021

Background:
Prior treatment with stain use is associated with reduced risk of arterial ischemic stroke (AIS) occurrence and recurrence. Recent studies report elevated lipid levels are associated with improved survival in AIS patients. We investigated the association of hyperlipidemia and statin use on all-cause mortality in AIS patients.

Methods:
All AIS patients, age ≥ 20 years (n=3898) residing within the Greater Cincinnati/Northern Kentucky region in 2005 and 2010 were included in the analysis. Based on prior medical history of hyperlipidemia or elevated fasting LDL levels during hospitalization (HLD) and statin use at baseline and/or discharge, patients were categorized as follows. Group1: no HLD and no statin use, Group2: HLD and no statin use, Group3: HLD and statin use. Covariates included age, BMI, baseline stroke severity (NIHSS), history of: hypertension, heart disease, diabetes, end-stage renal disease, dementia, prior stroke, and smoking. Multivariable logistic regression was used to estimate the odds of mortality, at 30- and 90-days and 1-, 2- and 3-years post stroke.

Results:
There were 22%, 21%, and 56% patients in groups 1, 2, and 3 respectively. Those in groups 2 and 3 were significantly younger, heavier, more likely to be male and have hypertension, diabetes, heart disease, and severe stroke, but less likely to have atrial fibrillation, dementia, and prestroke disability compared to patients in group 1. In unadjusted and adjusted analyses, patients in group 3 showed lower odds of mortality at all the time points compared to patients in groups 1 and 2. Patients in group 2 also showed lower odds of mortality at all the time points compared to patients in group 1 (Table).

Conclusions:
A pre-morbid diagnosis of HLD is associated with lower mortality in AIS patients, irrespective of statin use. Statin use appears to be associated with additional improved survival.