bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP198: Reducing Stroke Readmissions
Authors: Douglas Jessica , Ramsey Heather , Venters Kelly , Parker Amber
Published: June 2021

Background and Purpose:
Hospital readmissions have become a priority focus for healthcare organizations. According to the Centers for Medicare and Medicaid, 20% of all patients who are discharged from a hospital will be readmitted within thirty days (CMS, 2015). This not only has a negative impact for the patient, but also imposes a financial impact on the healthcare organization. Baseline data from 2014 at Lake Cumberland Regional Hospital (LCRH) showed a stroke readmission rate of 9.6%. The purpose was to decrease stroke readmissions through development of a discharge call process that targets risk factors for readmission and ensures transition from hospital care to post-discharge follow-up.

Methods:
The discharge call process was implemented in June 2014. Calls were conducted by the facility’s stroke educator. All stroke program participants excluding discharges to nursing homes, rehabilitation center, or hospice were included in the discharge call process. Minimally, 3 attempts per patient were made to conduct the phone call within 3 days of discharge. In addition, the Lake Cumberland Area Stroke Support Group was established in May 2016 for stroke survivors and their caregivers.

Results:
Stroke readmission rates at LCRH decreased to 7.9% in 2015 and further declined to 1.6% as of 2nd quarter 2016. Interventions completed as a result of the discharge phone call process include: expediting follow-up appointments, collaborating with primary care practitioner for needed prescriptions, clarifying discharge instructions, reinforcing stroke education, and scheduling additional follow-up calls to provide assistance when needed.

Conclusions:
Stroke readmission rates decreased from 9.6% in 2014 to 1.6% through second quarter of 2016. Multiple opportunities were discovered to close the communication gap between hospital care and primary care follow-up. Maintaining contact post-discharge is needed to transition from the hospital to home care.
Abstract TP202: Association of Rs7961894 with Mean Platelet Volume in Patients with Acute Ischemic Stroke
Authors: Miller Malgorzata , Henninger Nils , Umeton Renato , Slowik Agnieszka
Published: June 2021

Introduction:
Mean platelet volume (MPV) is a marker of platelet function and elevated MPV was found to be an independent risk factor for death after myocardial infarct in patients with coronary artery disease. Higher MPV was associated with increased risk of ischemic stroke, yet there is insufficient data regarding the role of MPV as a marker of outcome in patients with ischemic stroke. The variability of platelet indices in humans is largely determined by genetic factors and rs7961894 located within intron 3 of WDR66 gene showed the strongest association with MPV in all genome wide association (GWA) studies in the European population.

Aim:
To determine the association of rs7961894 with MPV in patients with acute ischemic stroke and to assess whether rs7961894 and MPV could be markers of one year mortality in different stroke subtypes.

Material and methods:
For 426 adults with first-ever ischemic stroke MPV was measured within 72h of stroke onset and single nucleotide polymorphism genotyping of rs7961894 was performed accordingly (RT-PCR, Applied Biosystems). Epidemiologic and clinical characteristics (including TOAST classification), laboratory findings as well as one year mortality data were collected for each participant.

Results:
Allele T and genotypes CT and TT of the rs7961894 polymorphism were associated with the highest (>11.5fL) MPV quartile (Chi
2
test, p<0.01). MPV was significantly higher in patients with genotype TT as compared to CT and CC genotype (12.0±0.24fL vs. 11.10±0.15fL and 10.77±0.05fL, respectively, ANOVA, p <0.005 with Tukey HSD post-hoc test, Figure 1).

Conclusions:
Allele T of rs7961894 polymorphism is associated with increased MPV in the recessive and dominant model and patients with genotype TT have significantly higher MPV as compared to the rest of the population study. Further analysis is currently being conducted to determine the association of MPV and rs7961894 polymorphism with one year mortality and stroke subtypes.
Abstract TP214: Low Diagnostic Yield of Routine Cerebrospinal Fluid Analysis in Patients with Juvenile Stroke
Authors: Prakapenia Alexandra , Puetz Volker , Barlinn Kristian , Barlinn Jessica , Siepmann Timo , Pallesen Lars-Peder , Winzer Simon M , Koehler Anne , Reichmann Heinz
Published: June 2021

Background:
The diagnostic value of cerebrospinal fluid (CSF) analysis in identification of stroke etiology in patients with juvenile stroke remains not well studied. We sought to determine the frequency and underlying causes of pathological CSF-findings in juvenile stroke patients who underwent CSF-analysis as part of their diagnostic work-up.

Methods:
We retrospectively abstracted data from consecutive (01/2008 to 12/2015) patients aged 18 to 45 years with acute ischemic stroke or transient ischemic attack. Routine work-up included MRI with dissection-sensitive sequences, Holter-ECG, transthoracic and transesophageal echocardiography, duplex ultrasound of extra- and intracranial arteries and screening for coagulopathies, vasculitis and Fabry disease. CSF-analysis was routinely performed in patients with hitherto cryptogenic stroke. We assessed frequency and causes of pathological CSF-findings including microbiological and virological abnormalities, and their impact on the choice of specific therapy for secondary stroke prevention.

Results:
Among 379 juvenile patients with acute ischemic stroke or transient ischemic attack, CSF analysis was performed in 201 patients (53%). Of these, 26 patients (13%) had CSF pleocytosis (leucocyte cell count ≥5 Mpt/l). CSF-pleocytosis was rated false positive (e.g. traumatic lumbar puncture, reactive pleocytosis due to acute stroke) after exclusion of specific conditions in 23 of these patients. Only 2 patients with CSF-pleocytosis (1% of patients who underwent CSF analysis) had specific CSF-findings (Lyme disease and neurosyphilis with consecutive cerebral vasculitis) as a cause of stroke and subsequent impact on secondary stroke prevention therapy. One patient had serological evidence of chronic infection with Mycoplasma pneumoniae that was rated as a contributing factor to stroke pathophysiology.

Conclusions:
The diagnostic yield of routine CSF-analysis in juvenile stroke patients was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.
Abstract TP216: Subtle Cardiovascular Measures in Young-onset Cryptogenic Ischemic Stroke: A Prospective Case-control Study
Authors: Martinez-Majander Nicolas , Gordin Daniel , Pirinen Jani , Sinisalo Juha , Lehto Mika , Liebkind Ron , Kivioja Reetta , Tatlisumak Turgut , Groop Per-Henrik , Putaala Jukka
Published: June 2021

Background:
Worldwide, ≈1.3 million annual ischemic strokes (IS) occur in young adults (<50 years of age), of which up to 50% remain cryptogenic after a complete diagnostic work-up. In a pilot case-control study, we studied the value of arterial stiffness and related subendocardial viability in the search of underlying pathophysiology in these patients.

Methods:
We prospectively enrolled 51 patients aged 18-49 with recent imaging-positive cryptogenic IS and 51 age- and sex-matched stroke-free controls (NCT01934725). Measurements were done with an applanation tonometry (SphygmoCor). Augmentation Index (AIx) served as a measure of stiffness in small arteries. Aortic and brachial pulse wave velocities (aPWV; bPWV) reflected stiffness in large and intermediate-sized arteries, respectively. Subendocardial viability ratio (SEVR) was derived from radial artery waveform measures, reflecting myocardial oxygen supply and demand. Related-samples statistics were applied for univariate case-control analyses and linear regression to explore the relationship between parameters with significant association in case-control analysis.

Results:
AIx, aPWV, bPWV, heart rate, and systolic or diastolic blood pressures did not differ statistically between patients and controls. Mean SEVR was significantly lower in patients compared with controls (148±35 vs. 161±29, P=0.003). In patients, higher heart rate was inversely associated with SEVR (P<0.001). Age, sex, migraine with and without aura, smoking, and systolic and diastolic blood pressure showed no independent association with SEVR.

Conclusions:
To our knowledge, this is the first report to show an association between SEVR and stroke. Yet unrecognized subtle cardiovascular pathology may play a role in early-onset cryptogenic IS.
Abstract TP217: Intra-arterial Verapamil Can Help Differentiate Reversible From Non-reversible Vasculopathy
Authors: Vallin Eileen C , Serrone Joseph C , Betts Aaron M , Tackla Ryan D , Abruzzo Todd , Ringer Andrew J , Grossman Aaron W
Published: June 2021

Introduction:
Cerebral angiography (DSA) is commonly used to characterize small vessel vasculopathy, yet it is difficult to establish etiology by angiographic patterns alone.

Hypothesis:
Responsiveness to intra-arterial verapamil (IA-V) can help differentiate etiology of small vessel vasculopathy by characterizing it as reversible or non-reversible.

Methods:
We performed a retrospective analysis from 2013-15 of patients referred for DSA to evaluate cerebral vasculopathy. We characterized symptoms, radiographic findings, angiographic pattern and responsiveness to IA-V, if given, as well as biopsy and follow-up angiography.

Results:
Thirty-three patients were identified (70% female; mean age 47.7). Presenting symptoms were headache (48%), focal neurologic deficit (45%), cognitive impairment (30%) and seizure (18%). Three patients presented in the post-partum period. Radiographic findings included infarct (42%), cortical subarachnoid hemorrhage (33%) and cerebral edema (3%). Arteriopathy was present on DSA in 19 of 33 patients (58%). Twelve patients had smooth segmental narrowing, 6 had irregular narrowing, 1 had diffuse narrowing. IA-V was administered in 12 of the 19 patients with arteriopathy (63%), including 9 of 12 with smooth segmental, 2 of 6 with irregular, and the patient with diffuse narrowing. Of 9 patients with smooth segment narrowing that received IA-V, 8 exhibited a vasodilatory response (89%). In 1 of these patients, superficial temporal artery biopsy was normal. Follow-up DSA was performed in 4 of the 8 patients with verapamil-responsive arteriopathy at a median time of 86 days. All 4 had angiographic resolution of their arteriopathy, consistent with reversible cerebral vasoconstriction syndrome. The 3 patients with irregular or diffuse narrowing who received IA-V did not exhibit vasodilatory response or have follow-up angiography. In 3 patients with irregular narrowing, brain biopsy was performed; 1 revealed CNS vasculitis, 2 were normal, consistent with atherosclerosis.

Conclusion:
Our series is consistent with reports of patients with reversible vasculopathy exhibiting a response to IA vasodilators. Response to IA-V may better characterize small vessel vasculopathy than angiographic pattern alone.
Abstract TP218: Peripheral Neutrophil and Lymphocyte Dynamics Following Acute Ischemic Stroke
Authors: Petrone Ashley B , King Dana E
Published: June 2021

Introduction:
An improper immune response has been shown to increase mortality following acute ischemic stroke (AIS), and targeting the immune system may offer a critical, novel treatment option in AIS. Recently, several immune-modulating agents, such as neutrophil inhibitory factor (UK-279, 276) showed promise in preclinical AIS models; however, either failed or were detrimental in clinical trials. One potential reason for their failure may be an improper time of administration, due to a lack of characterization of a healthy versus a detrimental peripheral immune profile following AIS. The aim of this study is to characterize the pattern of peripheral neutrophil and lymphocyte expression and neutrophil-lymphocyte ratio (NLR) following AIS.

Hypothesis:
We hypothesized that patients with mild AIS or good functional outcome following AIS will display an elevated NLR from 0-48 hours due to increased neutrophil activation, followed by a reduction in NLR from 48-96 hours due to an increase in lymphocyte activation.

Methods:
We analyzed data from 300 AIS patients for this study. White blood cell differentials were used to record neutrophil and lymphocyte percentages at several time points during hospitalization and to calculate NLR. AIS patients were grouped by severity using their National Institutes of Health Stroke Score (NIHSS) at admission and by functional outcome using their Modified Rankin Scale (MRS) at discharge.

Results:
Regardless of severity or outcome, patients have an elevated neutrophil percentage from 0-48 hours following AIS. From 48-96 hours following AIS, patients with mild AIS or MRS 0-2 have a significant decrease in neutrophil percentage, with a concordant increase in lymphocyte percentage compared to severe AIS patients. Further, NLR at discharge is significantly higher in severe AIS patients or patients with MRS>2 (p=0.014).

Conclusion:
In conclusion, our study is the first to describe the patterns of peripheral neutrophil and lymphocyte expression in the acute phase of AIS. These findings may shed light on the failure of UK-279,276 in clinical trial. This study also provides support for the use of the NLR as a prognostic marker, especially at ~48 hours following AIS, compared to the traditional assessment at admission.
Abstract TP228: Continuous Non-invasive Blood Pressure versus Oscillometric Assessment in Acute Care After Intracerebral Hemorrhage, Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Koehler Anne , Siepmann Timo , Winzer Simon , Simon Eric , Pallesen Lars-Peder , Barlinn Jessica , Reichmann Heinz , Puetz Volker , Bodechtel Ulf , Barlinn Kristian , Ziemssen Tjalf
Published: June 2021

Introduction:
Uncontrolled arterial hypertension increases the risk of intracerebral hemorrhage (ICH) in acute ischemic stroke (AIS) patients treated with intravenous tPA and may lead to hematoma progression in patients with primary ICH. While arterial blood pressure (aBP) is commonly monitored using intermittent oscillometric measurements, vascular unloading based assessment (VUA) allows noninvasive continuous (beat-to-beat) aBP monitoring with a finger cuff. We hypothesized that VUA monitoring is feasible in post thrombolysis and ICH care and shows diagnostic agreement with intermittent oscillometric assessment.

Methods:
Consecutive patients with either AIS receiving intravenous tPA or ICH were prospectively monitored for 24 hours following the index event using VUA monitoring and contralateral oscillometric aBP measurement every 30 minutes. Bland Altman Plot and linear regression were conducted to define diagnostic agreement.

Results:
We enrolled 24 AIS patients (10 males, aged 74±15 years, mean±standard deviation) receiving tPA and 24 ICH patients (16 males, aged 67±16 years). Mean systolic aBP assessed via VUA was higher and mean diastolic aBP was lower compared to oscillometric assessment in the entire population (systolic: 147 ± 23 mmHg vs. 144 ± 34, p=0.004; diastolic: 75 ± 14 mmHg vs. 77 ± 20 mmHg vs, p=0.004) There was a positive association between VUA and oscillometric aBP profiles (systolic aBP: coef. 0.24, p<0.005; diastolic aBP: coef. 0.31, p<0.005; figure). However, diagnostic agreement analysis was inconclusive. (Bland Altman Plot)

Conclusions:
Although VUA and oscillometric aBP profiles were positively associated in our study, diagnostic agreement between the techniques was not sufficient to recommend implementation of VUA in clinical practice.

Figure
Abstract TP239: The Influence of Cerebral Microbleeds on Blood Pressure Control in Acute Intracerebral Haemorrhage
Authors: Khurana Dheeraj , Rajendiran Ramalingam , Singh Paramjeet , Ahuja Chirag
Published: June 2021

Background:
Cerebral microbleeds(CMBs) represent microangiopathy in intracerebral hemorrhage(ICH). Their association with BP control-ability in ICH has not been studied.

Objectives:
To study influence of CMBs on blood pressure control in acute ICH presenting within 24 hours of symptom onset

Methods:
Acute ICH presenting within 24 hours of symptom onset were prospectively enrolled from April ’15 to May ’16 if they fulfilled major inclusion [age>18, GCS >8 (M >4)] and exclusion (Lobar bleed,ICH due to anticoagulants,Pregnancy, Contraindications for MRI) criteria.A baseline brain CT and CT angio was done.Brain MRI(3T) was done within 24 hours of admission to assess CMBs. Blood pressure lowering was carried out as per guidelines with a target SP<140mmHg.The target BP was attempted to be achieved in 24 hours.Based on BP control,patients were divided into two groups: a)Easy(E) and b)Difficult(D) based on control achieved within 7 hours.CMB assessor was blinded to the clinical condition and treatment.

Results:
25 patients were recruited in the study.Mean age was 58.6± 9.69 yrs with 52% females.Median time from symptom onset(TFSO) at presentation was 11.15 hrs(IQR 7.1-17.15).68% patients presented after 12 hours of onset.88% patients were hypertensives most(81.8%) being poorly compliant to treatment.Baseline Mean GCS was12±2.39;Systolic BP(SBP):187.76±21.95;Diastolic BP(DBP):110±13.22. 56% patients had basal gangla hemorrhage, 44% thalamic and 24% had midline shift. 80% had CMBs on SWI-MRI: 90% predominantly deep, 5% infratentorial and 5% lobar.Target BP was achieved in all patients within 24 hours. "E" group had 52% while rest were in "D"group."D" patients were likely to be smokers,had higher mortality at 1 month(p=0.052),had greater number of deep CMBs(p<0.001). Deeper location of CMBs was associated with smoking and higher ICH scores.On multivariate logistic regression, deep CMBs were significantly associated with poor blood pressure control after adjusting for all variables.(p=0.022;AOR:2.134,95%CI:1.117-4.077)

Conclusion:
CMBs may impose an influence on blood pressure control in acute spontaneous ICH with a predominant deep location being predictive of difficult to control BP and thereby may require aggressive measures to control BP
Abstract TP246: Emergency Medical Services Survey of a Low-cost, Ambulance-based System for Mobile Neurological Assessment: The iTREAT Study
Authors: Clark William M , Chiota-McCollum Nicole A , Cote Jack , Schneider Brett J , Pitchford Haydon , Gunnell Brian S , Lindbeck George M , Perina Debra G , O’Connor Robert E , Chapman Smith Sherita N , Solenski Nina J , Worrall Bradford B , Southerland Andrew M
Published: June 2021

Introduction:
Modern advances in acute stroke care place an added emphasis on accurate prehospital diagnosis and triage. As part of the Improving Treatment with Rapid Evaluation of Acute Stroke via mobile Telemedicine (iTREAT) study, we assessed the EMS provider experience with a novel system for mobile telestroke assessment.

Methods:
We developed a 12-question survey with input from local participants in an EMS Council serving rural counties in central Virginia. Providers rated the iTREAT system on feasibility for acute stroke triage, potential effectiveness in prehospital neurological assessment, and interactions with prehospital care. All survey responses were voluntary and anonymous.

Results:
Since initiation of live patient enrollment, we have completed 34 ambulance-based telestroke encounters with the iTREAT system. Among 7 participating agencies, 19 EMS providers have served as tele-presenters during the telestroke assessment, and 17 EMS providers completed the voluntary survey. Of the respondents, 71% were certified EMS providers for over 5 years. Regarding technical feasibility, 69% experienced issues related to maintaining a video connection, 41% with logging in to the videoconferencing application, and 18% powering on the tablet. Of technical challenges, 41% of providers resolved the issue on their own, 18% with guidance from study staff, and 24% could not resolve the issue. Concerning patient care, 23% felt the system interfered, 35% were neutral, and 41% felt there was no interference. The majority of respondents (71%) agreed that the iTREAT system is feasible for acute stroke triage, and an effective tool (59%) for prehospital neurological assessment. In commentary, EMS participants emphasized the system’s utility in rural areas.

Conclusion:
This survey of the EMS experience with a low-cost, ambulance-based system for prehospital telestroke assessment reveals both technical challenges and clinical promise. Importantly, technical issues are mostly solvable in real time and correctable for further system refinement. As a novel tool for prehospital neurological assessment and acute stroke triage, the initial EMS evaluation supports further investigation of clinical efficacy, particularly in rural and underserved areas.
Abstract TP260: Causes of Delayed Diagnosis of Vertebrobasilar Stroke Patients After Arrival at Emergency Room
Authors: Jeong Hye Seon , Kim Soo Young , An Ha Kyeu , Yu Hee Seon , Yoon Na Young , Shin Jong Wook , Song Hee-Jung , Kim Jei
Published: June 2021

Introduction:
Dizziness is a main symptom caused by ischemic insult to vertebrobasilar vessels as well as peripheral vertigo. So, proper diagnosis and management is often delayed in the vertebrobasilar ischemic patients. The present study was to evaluate factors related with the delayed diagnosis among vertebrobasilar infarction patients suffered from dizziness as initial main symptom.

Methods:
We reviewed clinical and radiologic data of 166 patients, who suffered from dizziness and/or vertigo as initial symptom and diagnosed finally as acute infarction on cerebellum and/or brainstem. First, we classified patients by incorrect triage as peripheral vertigo for the patients by first triage doctor of emergency room. Then, we evaluated time intervals from arrival at emergency room to first examination by a neurologist, to first brain image, and to final diagnosis as ischemic stroke of each group of patients. Type of initial symptoms including dizziness only or dizziness plus focal neurologic deficits were also compared between the groups. Finally, factors related with the incorrect triage of the included patients were analyzed using multivariate analysis.

Results:
The time from ER arrival to examination by a neurologist (221.0±158.7 vs. 56.0±76.8 min,
p
<0.001), to first image (232.4±182.1 vs. 58.2±77.0 min,
p
<0.001), and to final diagnosis (367.2±179.7 vs. 151.3±94.1 min,
p
<0.001) were significantly delayed in incorrect triage group. More patients in incorrect triage group showed dizziness only at presenting ER (52% vs. 13%,
p
<0.001). Among the focal neurologic signs defined by neurologists in incorrect triage group, Tandem abnormality was most frequently observed (29%). On multiple regression analysis, presence of chronic kidney disease (Odd ratio (OR) 15.7, 95% CI 1.4-175.6,
p
=0.026), isolated dizziness symptom (OR 13.5, 95% CI 3.3-55.3,
p
<0.001).

Conclusions:
In the present study, presence of chronic kidney disease and initial presenting symptom were the main cause of delaying diagnosis of vertebrobasilar infarction patients in ER. Additionally, Tandem gait should be performed for the dizzy patients to avoid delaying diagnosis of ischemic stroke.
Abstract TP265: AATF Protects Neuron Against Ischemia via Regulating PAR/AIF Pathway
Authors: Jin Wei , Xu Wei , Chen Jing , Zhang Xiaoxiao , Ren Chuancheng
Published: June 2021

Abstract:
Apoptosis antagonizing transcription factor (AATF) exerts an effect against oxidative stress, DNA damage and cellular apoptosis. However, its role in neuronal ischemia or hypoxia damage has not been elucidated yet. Present study investigated the neuroprotective roles and mechanisms of AATF under ischemia and hypoxia in vivo and in vitro. Focal cerebral ischemia of rat was generated by distal middle cerebral artery occlusion (dMCAO) model, SH-SY5Y cells were used to generate oxygen glucose deprivation (OGD) model in vitro. Western blot and immunofluorescent staining were used to investigate the expression changes of AATF. CCK-8 and LDH were performed to evaluate cellular survival and cytotoxicity. Overexpression and interference lentivirus vectors were performed to regulate the expression of AATF in SH-SY5Y cells. DHE staining that measured by flow cytometry was performed to investigate cellular superoxide anion levels. 8-OHdG expression and AP sites measurement were used to evaluate DNA damage. DNA Ladder and TUNEL staining were employed to evaluate DNA fragmentation. MNNG and DPQ were respectively used to agitate or antagonist caspase-3 independent PCD (programmed cell death) pathway, STS and Z-VAD-fmk were respectively used to agitate or antagonist caspase-3 dependent PCD pathway. Western blot was performed to investigate the expression of Poly(ADP-ribose) polymers (PAR) and apoptosis inducing factor (AIF) in different cellular components, Co-IP (co-immunoprecipitation) was used to test the interaction of AIF, H2AX and CypA (Cyclophilin A). We found that AATF was increased in cortical neurons after brain ischemia (P<0.001). Besides, AATF was upregulated in OGD-treated SH-SY5Y cells in a time-dependent manner (P=0.007). Additionally, overexpressing AATF ameliorated OGD-induced cellular death (P < 0.001) and cytotoxicity (P = 0.001), and AATF interference exacerbated OGD-induced cellular death (P=0.033) and cytotoxicity (P=0.006). We also found that AATF overexpression suppressed cellular DNA fragmentation (P=0.003) but did not ameliorate oxidative stress and DNA damage. Moreover, we discovered that overexpressing AATF suppressed PAR/AIF signaling pathway via binding with AIF.
Abstract TP270: Interleukin-6 Receptor Inhibition with Tocilizumab Ameliorates Ischemic Stroke Damage in Mice
Authors: Hudobenko Jacob , Verma Rajkumar , McCullough Louise
Published: June 2021

Introduction:
In stroke patients higher plasma IL-6 levels are correlated with larger infarct volume, increased stroke severity and poor long term prognosis. IL-6 signaling may be detrimental in the periphery with high serum levels linked to detrimental outcomes. However, direct brain injection of IL-6 blocking antibodies increase deficits suggesting that therapeutic agents may need to block the peripheral rise in IL-6 without altering brain IL-6. This study sought to determine if Tocilizumab, an FDA approved drug that blocks IL-6 receptors and therefore inhibits the peripheral effects of IL-6, while having low blood brain barrier permeability; would result in reduced infarct and leukocyte infiltration after ischemic stroke.

Methods:
Experiments utilized young (8 week; 20-25g) C57BL/6J male mice to examine neuroprotection, leukocyte infiltration and IL-6 activation post-ischemia. Stroke was induced by 60 min of transient right middle cerebral artery occlusion under anesthesia followed by reperfusion for 3 days. Four hours after the onset of ischemia all mice were randomly assigned into two groups and given an intraperitoneal injection of either Tocilizumab (13 day half-life) at a dose of 6 mg/kg body weight or saline vehicle as a control. The mice underwent behavioral testing to evaluate the effects of Tocilizumab on stroke recovery, testing evaluated motor/sensory deficits, anxiety and locomotor activity. Mice were sacrificed and used to either assess leukocyte infiltration and activation using IHC or infarct measurement using TTC staining.

Results:
Tocilizumab not only ameliorated the severity of ischemic injury but also reduced behavioral deficits in mice after stroke. Treatment led to a significant reduction (p<0.05 vs saline) in infarct size. The results with the corner test, a sensorimotor function test, and neurological deficit scores further supported the beneficial effect of the drug. Immunohistochemical analysis displayed attenuated microglia activation in the tocilizumab treatment group suggesting that tocilizumab lowers immune system response to stroke by mediating the response of IL-6. This study demonstrates that inhibition of the IL-6 receptor with Tocilizumab may be a potential therapeutic approach for stroke treatment.
Abstract TP271: Leukemia Inhibitory Factor Differentially Regulates Its Receptor in the Brain and Immune System After Stroke
Authors: Davis Stephanie M , Collier Lisa A , Fazal Jawad A , Britton Michael , Leonardo Christopher C , Ajmo Craig T , Pennypacker Keith R
Published: June 2021

Objective:
To identify how leukemia inhibitory factor (LIF) regulates antioxidant neuroprotective and anti-inflammatory signaling through the expression and trafficking of its receptor (LIFR).

Hypothesis:
LIF treatment after stroke confers neuroprotection by increasing protein expression and membrane localization of LIFR in neural cells and splenocytes.

Methods:
Genomatix software was used to identify binding sites for the LIF-dependent transcription factors specificity protein 1 (Sp1) and myeloid zinc finger-1 (MZF-1) in the LIFR promoter. Male Sprague-Dawley rats underwent middle cerebral artery occlusion or sham surgery and injected with PBS or LIF (125 μg/kg) (n=8 per group) at 6, 24 and 48 h post-MCAO. Levels of LIFR, MZF-1, and Sp1 were measured using western blotting. Immunohistochemistry was used to determine localization of Sp1, LIF receptor, MZF-1, and superoxide dismutase 3, a LIF-inducible enzyme.

Results:
LIF (1.494 OD ± 0.161) significantly increased brain LIFR levels in ipsilateral tissue at 72 h after stroke compared to sham surgery (0.299 OD ± 0.060) and PBS treatment (0.399 OD ± 0.154) (0.0281 OD ± 0.011, p<0.01). Splenic LIFR levels decreased significantly after LIF (0.170 OD ± 0.010) treatment compared to PBS (0.228 OD ± 0.285, p<0.05) and sham rats (0.329 OD ± 0.031, P<0.001). LIFR was localized to neuronal nuclei but translocated to the cell membrane after injury. After LIF treatment, MZF-1 and Sp1 co-localized with superoxide dismutase 3 in cortical neurons. LIF significantly increased MZF-1, but not Sp1, in spleen tissue (0.158 OD ± 0.038) compared to PBS (0.109 OD ± 0.044) and sham (0.090 OD ± 0.018).

Conclusions:
Injury increases membrane localization of LIFR in neurons while LIF increases its receptor’s expression and Sp1/MZF-1 in stroke-injured neurons. As a part of its anti-inflammatory action, LIF causes downregulation of LIFR in the spleen after stroke.
Abstract TP275: “Touch-and-Go”: Touching of Endothelial Cells by Endothelial Progenitor Cells Increases Activation of Pro-survival ERK1/2 Signaling
Authors: Mandeville Emiri T , Chen Su Jing , Hayakawa Kazuhide , Arai Ken , Lo Eng H
Published: June 2021

Background:
Cell-based therapies can potentially promote neurological repair for CNS diseases including stroke. Pre-clinical data showed improved infarct volume and neurological scores following injection of Endothelial progenitor cells (EPCs). However relatively few EPCs were found in infarct areas, and mechanisms by which injected EPCs enhance neovascularization are largely unknown. In this study, we hypothesized that circulating EPCs would positively impact intracellular signaling cascades in rat brain endothelial cells (RBECs) even by short-duration contact due to activation of pro-survival ERK1/2 cascades.

Methods:
Primary RBECs and EPCs were isolated from rat brain and spleen, respectively. These cells were cultured separately, and 10 days later, cultured EPCs were transferred to plates of cultured RBECs. After 1 or 10 min incubation with cell-culture plate shaking, EPCs were washed from the plates and RBECs were subjected to western blot analysis to assess ERK1/2 phosphorylation. As a negative control for EPCs, we prepared neutrophils from different rats.

Results:
We confirmed that our RBECs and EPCs were viable in vitro by LDH assay and these cells were positive for their cell-type markers assessed by immunostaining. Ten min incubation of EPCs phosphorylated ERK1/2 in RBECs in an EPC-number-dependent manner, whereas identical conditions of neurtrophil incubation did not. Importantly, only 1 min incubation with EPCs significantly upregulated ERK cascades in RBECs. Remaining EPCs on RBEC surfaces may not contribute to ERK1/2 phosphorylation because very few EPCs were observed after washout. In addition, experiments by the same procedure without RBECs did not show ERK phosphorylation.

Conclusion:
We demonstrated increased activation of pro-survival ERK1/2 signaling in RBECs following short-duration incubation of EPCs. Results suggest that circulating EPCs may not need to be integrated into existing blood vessels to promote neovascularization. Rather, short-duration interactions between EPCs and RBECs may provide a “Touch-and-Go” stimulus that supports brain endothelial cells to make favorable environments for neovascularization.
Abstract TP28: Defining Large Vessel and Routing Criteria for Endovascular Patients
Authors: Martin Coleman , Hawkins Angela , Olds Karin , Akhtar Naveed , Holloway William
Published: June 2021

Background:
Five recently published randomized trials of endovascular therapy versus medical management, including intravenous thrombolysis, demonstrated strong positive data in support endovascular thrombectomy procedures. The American Heart Association/American Stroke Association released a focused update to specifically incorporate the findings of these trials. Implementing the care these studies show as beneficial requires a mechanism to rapidly transfer large vessel occlusion patients from primary stroke centers to those offering thrombectomy.

Purpose:
The purpose of the project was to streamline stroke work-up across the various levels of stroke hospitals and to apply rapid routing practices when transferring stroke patients between facilities. We evaluated the changes in stroke systems of care, with an emphasis on the role of pre-hospital stroke triage, inter-hospital transfer, and the two main levels of stroke center certification (primary and comprehensive).

Methods:
The system stroke steering team, defined four primary processes to reduce transfer times. These included 1) benchmarks for hospital door in to door out times of transferring centers 2) scripted transfer verbiage to designated time critical patients 3) large vessel stroke criteria definitions 4) pre-notification of the endovascular team to treat potential patients presenting with stroke. A reduction in time between initial patient contact and arterial puncture times and measures of patient outcomes were used as indicators of effectiveness.

Results:
The implementation of four process improvements for large vessel stroke patients was associated with improved treatment times. Mean door to recanalization times decreased from 224 minutes in 2014 to 112 minutes, thus far in 2016. Stroke treatment rates for tPA increased from 19.8% in 2013 to 22.7% in 2016, and endovascular treatment rates of 14.6% to 18.1% in the same time period. Conversely, complication rates from stroke treatment declined within the same period from 7.4% to 3.8%.

Conclusion:
Within a metropolitan health system, using the above multimodal approach to streamline the transfer of patients from primary to comprehensive centers decreases latency to treatment and is associated with improved outcomes.
Abstract TP286: Improving Core Measure Compliance in Stroke Chameleon Patients
Authors: Gribko Michele , McLeod Ann Marie , Libman Richard B , Wright Paul , Katz Jeffrey M
Published: June 2021

Background:
Patients presenting with altered mental status, syncope, and other non-localizing complaints may be subsequently diagnosed with minor ischemic or hemorrhagic strokes. These patients, termed stroke chameleons, are typically admitted to non-neurology units (NNUs) with a non-stroke diagnosis and are more likely to fall-out on stroke core measures (SCM). Early identification of these patients should improve SCM compliance and promote better care.

Methods:
A performance improvement initiative was implemented to elevate SCM compliance overall by targeting patients admitted to NNUs in a comprehensive stroke center. A nurse practitioner was dedicated to scan the electronic medical record for potential stroke chameleons on NNUs and review radiology reports to confirm a stroke diagnosis. A SCM checklist was utilized to reinforce SCM adherence with the patient’s providers and nurses. SCM compliance for 24 months pre and 12 months post intervention was compared using data entered into the Get With The Guideline-Stroke database.

Results:
Over the 3-year study period, 3,355 patients were discharged with a stroke diagnosis. Comparing pre to post intervention periods, 522/2129 (24.5%) vs. 401/1226 (32.7%) patients were admitted to NNUs. Distribution of pre- and post intervention stroke diagnoses were ischemic/TIA 381 (73.0%) vs. 319 (79.6%) and hemorrhagic 141 (27.0%) vs. 82 (20.4%). For NNU patients, the initiative had a statistically significant impact on stroke education documentation (45.5% pre vs. 67.0% post; p=0.0006). In addition, compliance improved for smoking cessation (77.8% to 81.2%), early antithrombotics (84.0% to 85.3%), VTE prophylaxis (90.8% to 94.7%), and discharge antithrombotic therapy (98.7% to 100%), although none were statistically significant.

Conclusion:
Dedicating resources to identify stroke chameleons early, and focusing compliance efforts on NNUs, significantly improved compliance with stroke education. Other SCM showed numerical improvements, but did not reach statistical significance. Especially in centers with high volumes of stroke chameleons, attention and efforts directed at this population raises the quality of care provided to all hospitalized stroke patients.
Abstract TP290: Comparison of Risk-Adjusted 30-day Mortality Models by Claims Data in Acute Ischemic Stroke With vs Without Adjustment for Stroke Severity: J-ASPECT Study
Authors: Kamitani Satoru , Nishimura Kunihiro , Kada Akiko , Sayama Tetsurou , Arimura Kouichi , Nishimura Ataru , Kurogi Ryouta , Kurogi Ai , Nakamura Fumiaki , Miyamoto Yoshihiro , Onozuka Daisuke , Hagihara Akihito , Ogasawara Kuniaki , Shiokawa Yoshiaki , Miyachi Shigeru , Yoshimura Sinichi , Toyoda Kazunori , Nakagawara Jyouji , Matsuda Shinya , Okuchi Kazuo , Aruga Toru , Ono Junichi , Iihara Koji
Published: June 2021

Introduction:
Reports on hospital-specific, risk-standardized outcomes using claims data on acute ischemic stroke are increasing. However, these reports sometimes fail to account for stroke severity.

Hypothesis:
Hospital-specific, risk-adjusted mortality rating without accounting for stroke severity are altered after including initial severity for ischemic strokes.

Methods:
The health insurance claims data known as the Japanese Diagnosis Procedure Combination/Per Diem Payment Systems between April 1, 2013 and May 31, 2014 was obtained from 332 certified training institutions in Japan. The hospital-specific, risk-adjusted 30-day mortality rate was calculated using a hierarchical logistic regression model. We developed two models, with and without initial levels of consciousness (LOC), and compared them to assess the impact of stroke severities on hospital-specific mortalities. The hospital-specific mortalities with and without LOC were ranked and groped into 3 categories (top 20%, middle 60%, and bottom 20%), and then compared across the two models. We used an integrated discrimination improvement (IDI) index to measure how the model with LOC reclassified patients compared with the model without LOC. Patients with deep comas were excluded from the analyses.

Results:
We analyzed 64,569 acute ischemic stroke patients. Crude 30-day mortality was 3.9% , the mean age was 74.1±1.3 years, 41.2% were women, 70.8% had hypertension, 29.2% had diabetes mellitus, 79.9% had a Charlson comorbidity index score greater than 5, 3.7% had severe LOC (coma/semi-coma) and 8.1% had modestly impaired LOC. Among hospitals ranked in the top 20% of performers without LOC, 26.9% were ranked in the middle 60% when LOC was adjusted. Among the bottom 20% of performers without LOC, 21.2% were ranked in the middle 60% when LOC was adjusted. The hospital-specific, risk-adjusted 30-days mortality model with LOC had a significantly better IDI index score than the model without LOC (IDI, 0.09; P<0.001).

Conclusions:
Adding the metric of stroke severity to a hospital-specific, risk-adjusted 30-day mortality model based on claims data was associated with model improvement and changes of mortality-based performance rankings.
Abstract TP298: Rapid Response Team Utilization for Inpatient Stroke Codes
Authors: Agrawal Kunal , Tainter Christopher R , Hemmen Eema , Botts Emily , Paulson Debra , Minokadeh Anushirvan , Hemmen Thomas M , Sell Rebecca E
Published: June 2021

Introduction:
Rapid response teams (RRTs) are a way to provide rapid assessment and early intervention for inpatients with clinical deterioration, including those with acute stroke. The goal of this study is to examine the accuracy and outcomes of inpatient stroke code RRT activations within a hospital system.

Methods:
A retrospective chart review was performed for all RRT activations called for inpatient stroke codes within the UC San Diego Healthcare System from January 1, 2014 to November 30, 2015. Relevant variables included: clinical symptoms at the time of RRT initiation, neuroimaging modality (CT, CTA, MRI), IV rt-PA and/or endovascular therapy (ET), event diagnosis, and discharge disposition. We compared patients with diagnosis of stroke (AIS, ICH, SAH, other) versus non-stroke diagnosis. Diagnosis was determined by independent adjudication of provider documentation and corresponding acute and follow-up neuroimaging.

Results:
285 of 2336 (12.2%) RRT activations were for stroke code. Ultimately, 31.2% (n=89) were diagnosed with stroke (61 AIS [68.5%], 17 ICH [19.1%], 2 SAH [2.3%], 2 epidural [2.3%] and 7 subdural hematomas [7.9%]). Of stroke codes, neuroimaging was used more often in patients diagnosed with stroke including CT (97.8% vs 89.3%, p=0.03), CTA (42.7% vs 29.6%, p=0.04), and MRI (28.1% vs 16.3%, p=0.03). Discharge disposition was home in 18.0% vs. 36.2% (p=0.001), skilled nursing facility in 22.5% vs. 27.6% (p=0.001), and inpatient rehabilitation in 11.2% vs. 3.6% (p=0.001). In-hospital mortality was higher in those with stroke (22.5% vs 10.7%, p=0.001). Only 18 patients (6.3%) received acute recanalization therapies (4 IV rt-PA, 12 ET, 2 both).

Conclusions:
Relatively few RRT stroke code activations diagnosed acute stroke and few received IV rt-PA and ET. Further studies are needed to better quantify the benefit of RRT in stroke code, explore additional benefits beyond acute recanalization therapies, and consider more targeted assessment for better resource utilization.
Abstract TP302: Improvement of Endovascular Stroke Care Performance After Transition From MRI/A to an CTP-based Imaging Protocol
Authors: Ortega Gutierrez Santiago , Samaniego Edgar , Overton Angela , Nagaraja Nandakumar , Pieper Connie , Rindels Erin , Derdeyn Colin , Policeni Bruno , Hasan David , Rossen James , Hayakawa Minako , Olalde Heena , Adams Harold , Leira Enrique
Published: June 2021

Background and Purpose:
The 2015 Focused Update for the Acute Ischemic Stroke Guidelines emphasized the importance of rapid patient selection, optimization of endovascular procedures and organizations of systems of care. Our institution, which has been performing endovascular procedures using a rapid MRI/MRA imaging protocol, transitioned in 2015 to a CT/CTA/CTP imaging protocol. The goal of the study is to evaluate the impact of the transition to CTP on endovascular performance, as measured by door to imaging time and door to skin puncture, and the improvement of the neurological deficit measured by NIHSS difference at admission and discharge.

Methods:
All endovascular procedures performed from January 2014 to May 2016 were reviewed from our prospective database. CT perfusion was performed with injection of 40 cc iodinated contrast and 40 seconds acquisition time. The CTA images were generated from the CT perfusion. Demographics, endovascular performance and discharged status were obtained. Continuous variables were assessed for normality by the Kolmogorov-Smirnov test. Non-parametric data were reported as median and analysed using the Kruskal-Wallis test or Wilcoxon Ranks test.

Results:
A total of 91 thrombectomies were initially identified. The median age was 65 (IQR:53-77) with 52% males. 78% were anterior circulation strokes (ACS). Although the overall number of stroke admission remained relatively stable, the proportion of thrombectomies duplicated every year (23/1003 in 2014 vs. 38/1159 in 2015 vs. 32/632 until May 2016). Door to advance imaging median time (52 mins vs 24 mins vs.25 minutes; p=0.023) and door to skin puncture median time (130 mins vs. 100 mins vs. 81 mins; p=0.007) demonstrated significant differences in the ACS. A significant improvement in NIHSS at discharge was noted after implementation of the protocol (18 to 8; p=0.001 in 2015 and 17.5 to 8 in 2016; p=0.006 vs. 14 to 9 in 2014; p=0.777).

Conclusion:
Transition to CT-based imaging protocols was associated with improvement in the delivery of endovascular acute care in a Comprehensive Center used to acute MRI imaging despite the logistic challenges and lack of familiarity with the new technique. Transition to CT-based imaging is a reasonable approach to improve endovascular care.
Abstract TP304: The Challenge of Stroke Transitions from the Healthcare Provider’s Perspective: A Qualitative Study
Authors: Fritz Michele , Hughes Anne , Woodward Amanda , Freddolino Paul , Reeves Mathew J
Published: June 2021

Background:
Inadequate transitional care contributes to poor patient outcomes including hospital readmissions, delayed recovery, and reduced quality of life. We report perspectives from healthcare providers on challenges and stroke educational needs which were collected to inform an intervention study designed to improve stroke transitions following discharge to home.

Methods:
During the development phase of the Michigan Stroke Transitions Trial (MISTT), a randomized trial testing a Social Work Case Management (SWCM) intervention, we convened 4 stakeholder meetings with healthcare providers. We aimed to understand provider perspectives regarding patient and system-level challenges and to identify patient educational needs. Michigan providers, including social workers, nurses, neurologists, physiatrists, rehabilitation therapists, and managers were invited to attend the focus groups. Transcriptions were analyzed for common patient and system-level challenges (themes) using qualitative methods and educational needs were determined.

Results:
Thirty-four providers, representing hospitals, rehabilitation facilities, nursing homes, and home healthcare agencies, attended the 4 meetings. They identified 43 patient-level, 36 healthcare-level, and 13 community-level challenges. The most common challenges were related to medical follow-up (n=10), consistency of care planning across settings (n=10), ability of patients to retain information (n=10), and unrealistic patient expectations (n=10). The most common stroke educational needs were stroke signs and symptoms recognition (n=10), post-stroke expectations (n=10), stroke risk factors (n=9), and post-stroke depression (n=9). Common medication topics included strategies for medication management (n=13), understanding the importance of medications (n=12), managing side effects (n=7), and communicating with physicians (n=5).

Conclusion:
These data were essential in directing the scope and organization of the MISTT case management intervention. Addressing common challenges and targeting stroke educational needs offers the best opportunity for in-home transitional support to maximize stroke recovery during the early transitional period.