bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP233: Patterns, Determinants and Outcomes of Ultra-Early Neurological Deterioration (U-END) in Acute Ischemic Stroke
Authors: Shkirkova Kristina , Wong Gregory , Weng Julius , Saver Jeffrey L , Starkman Sidney , Hamilton Scott , Liebeskind David S , Eckstein Mark , Stratton Samuel , Pratt Frank , Conwit Robin , Sanossain Nerses
Published: June 2021

Background:
The patterns and outcomes of deterioration during prehospital transport and the first phase of ED care are important for planning for diversion of acute cerebral ischemia (ACI) patients to designated stroke centers and design of prehospital treatment trials.

Methods:
We analyzed patients enrolled in the NIH Phase 3 Field Administration of Stroke Therapy - Magnesium (FAST-MAG) trial within 2h of last known well (LKW). Deterioration was defined as worsening by ≥2 on the Glasgow Coma Scale (GCS), performed serially by paramedics in the field, upon ED arrival, and after the early ED course.

Results:
Among 713 acute cerebral ischemia patients, age was 65.4 (±13.4), 45% female. Times from LKW to GCS assessments were: paramedic, 25 mins (IQR 15-46); ED arrival, 60 mins (IQR 48-82); and after early ED course, 83 mins (IQR 60-106). Overall, 16.3% experienced neurological deterioration, including 9.0% in prehospital phase only, 7.3% in early ED phase only, and none in both phases. Granular patterns of deficit progression were: Prehospital Sustained - prehospital deterioration, then stable early ED phase, 2.2% (16); Dippers - prehospital deterioration, then early ED improvement, 6.7% (48); Delayed - stable prehospital, then ED deterioration, 3.0% (22); and Peakers - prehospital improvement, then early ED deterioration, 4.2% (30) (Figure). Ischemic stroke patients who experienced any U-END had higher age, 73.2 vs 69.8, p<0.01; lower prehospital GCS scores, 14 (IQR 11-15) vs 15 (IQR 14-15), p<0.001; and greater prehospital focal weakness, LAMS 4.2 vs 3.6, p<0.001. U-END was associated with higher rates of disability or death (mRS 2-6) at 90 days, 77.8% vs 53.8%, p<0.001.

Conclusions:
Ultra-early neurological deterioration occurs in one-sixth of EMS-transported acute cerebral ischemia patients, and is associated with less favorable outcome. Early identification and effective management strategies are needed to reduce its occurrence.
Abstract TP241: Concordance of Pre-hospital Stroke Recognition by Medical Dispatchers and Paramedics in an Urban County
Authors: Brown Aliza , Bird Tommy M , Onteddu Sanjeeva , Balamurugan Appathurai , Skinner Robert D , Culp William C
Published: June 2021

Background:
Immediately after a stroke, the time it takes to reach a designated stroke center can determine the patient’s chances of recovery or permanent disability. In pre-hospital care, the first level of care occurs when 911 is called, second when the paramedics arrive and triage, and third, transport to the nearest primary stroke center (PSC). When emergency medical dispatchers (EMD) initially recognize stroke they provide critical stroke triage codes guiding the paramedic’s decision in appropriate hospital choice, saving time and improving patient recovery. This study assessed EMD and paramedic stroke recognition and performance in an urban area.

Hypothesis:
EMD recognition of stroke would provide paramedics adequate codes for correct recognition and influence transports to area primary stroke centers (PSCs).

Methods:
All emergency medical service (EMS) transports in an urban county area (392,664 population) during 2014 were retrospectively analyzed. The transports encompassed True/Negatives, False/Positives, False/Negatives and True/Positives for data on the number and percentages of EMS correctly identified stroke ground transport 911 calls. Dispatch impressions of calls were compared to paramedic decisions and confirmed by hospital ICD-9-CM billing codes 430-438. Transports to area PSC and non-PSC hospitals were determined.

Results:
Over 12 months, in N=40,171 total transports, EMDs impression of strokes were n=942 with 51.3% confirmed as strokes by paramedics. The other 47.6% of calls reported as strokes by EMDs were coded by paramedics as syncope/fainting, altered level of consciousness, abdominal pain, diabetic, behavioral, cardiac rhythm disturbance and seizures. Paramedic reported strokes were coded by dispatchers as 52.0% strokes/CVA or as headaches, sick person, unconscious/fainting, fall victim, chest pain, convulsions/seizures and breathing problems. Significantly more stroke-related deliveries were made to PSCs (55%, p<0.001) than other area facilities. Hospital confirmation by discharge data services of paramedic coded strokes provided a true positive predictive value of 44.8% and sensitivity of 25%.

Conclusion:
EMS dispatch and paramedic services could benefit from stroke recognition education.
Abstract TP244: Age-Related Disparities in Door-to-Needle Times: It’s Not What You Think
Authors: Burrell Christian J , Guilliams Kristin P , Williams Jennifer A , Heitsch Laura , Panagos Peter , Lee Jin-Moo , Ford Andria L
Published: June 2021

Introduction:
Delays in door-to-needle time (DNT) for tPA administration are associated with worse outcomes after acute ischemic stroke (AIS). Studies suggest tPA is safe and effective in young adults, though the effect of age on timeliness of tPA decision making is unknown. In the young adult population, lower frequency of stroke and higher frequency of stroke mimics may lead to DNT delays. We tested the hypothesis that DNT are longer in young adults with AIS.

Methods:
From 1/2009 to 3/2016, patient demographics and tPA metrics were prospectively collected on all tPA-treated patients at a large, urban academic hospital. Discharge diagnosis (including stroke mimics) and symptomatic intracranial hemorrhage (sICH) rates were collected by retrospective chart review. DNT was compared between young (age ≤ 45) and older adults (age > 45) and across four age groups: ≤45, 46-65, 66-85, and ≥86. Univariate analysis evaluated associations between DNT and baseline characteristics (age, race, sex, admission year, onset-to-arrival time, and admission NIHSS), followed by forward stepwise linear regression including variables with P<0.2 on univariate analysis.

Results:
Of 560 patients treated with tPA, 63 (11%) were age ≤45 and 497 (89%) were age > 45. Mean DNT was 63 minutes in young adults compared to 50 minutes in older adults (P=0.002). Across four age groups, DNTs were longer in young adults (P=0.027, Figure). In multivariable analysis, age ≤45 (P=0.012), lower NIHSS (P=0.006), and more remote admission year (P=0.001) independently predicted longer DNT. Stroke mimics were more frequent in young adults: 32% vs 7% (P<0.001), though mean DNT remained longer in young adults after excluding mimics: 63 vs 49 min (P=0.008). sICH rate was similar in both groups: 0% vs 4.2% (p=0.10).

Conclusions:
Despite established safety and efficacy of tPA in young adults, we found DNT delays in this population. Further studies are needed to confirm this finding and address age-related disparities in DNT.
Abstract TP247: Impact of Helicopter Emergency Medical Services Flights on Recombinant Tissue Plasminogen Activator (rtpa) Integrity
Authors: Faine Brett , Lentz Steven , Torner James , Dayal Sanjana , Olalde Heena , Leira Enrique
Published: June 2021

Introduction:
Inter-hospital transfer of ischemic stroke patients by Helicopter Emergency Medical Services (HEMS) is common in rural states. The administration of recombinant tissue plasminogen activator (rtPA) is often initiated at the outside hospital and continues during HEMS (drip and ship). Due to the unstable nature of rtPA after reconstitution in conjunction with strong, low frequency vibrations present during HEMS, there is potential for the physical integrity and thrombolytic activity of rtPA to be compromised during inter-hospital transfer.

Hypothesis:
Air ambulance transfer alters the antigen integrity of rtPA in ischemic stroke patients.

Methods:
Prospective cohort study of acute ischemic stroke patients receiving rtPA during air ambulance transfer to a comprehensive stroke center (CSC) (intervention group) compared to patients who presented directly to our CSC Emergency Department (control group). The duration of each flight was recorded to control for degree of exposure. To access the structural integrity and thrombolytic activity of rtPA, small residual samples (<0.5 mL) were taken from each patient’s vial after the infusion was completed. The structural integrity of rtPA antigen was evaluated with a specific rtPA protein ELISA.

Results:
Thirteen patients received rtPA and were transferred to our CSC via our air ambulance service. The mean flight time was 30.6±5.5 minutes. The mean concentration of rtPA in the control sample was 1.035±0.42 mg/mL. The mean difference in the concentration of the rtPA in the intervention group compared to the control group was 1.59±1.28 mg/mL.

Conclusions:
HEMS transfer appears to increase rtPA antigen concentrations possibly due to degradation. Future analysis will examine whether alteration in integrity of rtPA affects the thrombolytic activity.
Abstract TP249: Hospital Transfer Cost Savings From Triaging Selected Stroke Patients Directly to the Comprehensive Stroke Centers (CSCs) Courtesy of the Mobile Stroke Treatment Unit (MSTU)
Authors: Zafar Atif , Udeh Belinda , Reimer Andrew , Ramanathan Ramnath S , Vela-Duarte Daniel , Taqui Ather , Wisco Dolora , Winners Stacey , Buletko Andrew B , Organek Natalie , Hustey Fredrick , Hussain Shazam , Uchino Ken
Published: June 2021

Introduction:
The Mobile Stroke Treatment Unit (MSTU) is a novel onsite pre-hospital treatment team with all basic infra-structure to diagnose, emergently treat and hence timely triage acute ischemic and hemorrhagic stroke patients to either the primary stroke center (PSCs) or comprehensive stroke centers (CSCs). Recent evidence supports outcome benefits in favor of intra-arterial therapy (IAT) in large vessel strokes and transfers to neuro-critical care units for managing large strokes. This has resulted in a surge in transfers to CSCs summing additional transfer costs for patients not initially presenting to a CSC. This is the first ever study in the United States that utilizes a basic cost generation model to measure the economic benefits of MSTU triage directly to the CSCs by-passing PSCs, for the those patients requiring higher-level care.

Method:
Mobile Stroke Treatment Unit database was used to identify patients that stroke neurologists triaged to CSCs. These included all acute ICH, IAT candidates and severe strokes with ICU needs. We calculated the average costs of a typical primary stroke center emergency room visit and the cost of a critical care transport, generating a cost savings model.

Result:
Fifty two patients who were evaluated by stroke neurologists in the mobile stroke unit from July 2014 to October 2015 were adjudged candidates for comprehensive stroke centers. Twenty four (46%) of these were intra-cerebral hemorrhage (ICH) confirmed on portable head CT while the other 28 (54%) presented with major strokes with possible IA thrombectomy candidacy or anticipated Neuro ICU needs due to stroke severity. Eleven ICH and 13 ischemic stroke patients (46%) of the 52 patients by-passed PSC to be taken directly to comprehensive stroke centers with a potential of saving millions of dollars in costs and critical time.

Conclusion:
Even in a city with dense presence of comprehensive stroke centers, a large cohort of patients by-passed primary stroke centers with a potential of saving millions of dollars in costs and critical time. Future goals include evaluating for difference in outcome in this group of patients that by-passed PSC courtesy MSTU. Additionally, this needs to be replicated in other counties and cities before policy changes are proposed.
Abstract TP25: Increased Risk for Unfavorable Outcome in Patients with Pre-existing Disability Undergoing Endovascular Therapy
Authors: Leker Ronen R , Gavriliuc Pavel , Yagmur Nour Eddine , Gomori John M , Cohen Jose E
Published: June 2021

Background and Objectives:
Most studies evaluating endovascular therapy (EVT) for stroke only included patients without pre-existing disability. However, in real life many patients have pre-existing disability and whether they can benefit from EVT remains unknown.

Methods:
Patients with large vessel anterior circulation stroke were prospectively enrolled. Patients with no or mild disability (modified Rankin Scale [mRS] 0-2) were compared with patients presenting with pre-existing moderate disability (mRS≥3). Baseline demographics and risk factors, stroke severity (studied with the National Institutes of Health Stroke Scale [NIHSS]), imaging data including pre-treatment ASPECTS and ASPECTS collateral scores, as well as procedure related variables were accrued. Unfavorable outcome was defined as mRS≥4 at day 90.

Results:
Out of 100 enrolled patients, 85 had baseline mRS≤2 and 15 had pre-stroke mRS≥3. Patients with pre-existing mRS≥3 were significantly older (79.0±6 vs. 66.6±14, p=0.001) and more often had previous strokes (47% vs. 19%, p=0.04) and ASPECTS≤7 (33% vs. 12%, p=0.03). Patients with mRS≥3 at presentation were more likely to have poor outcome or death (OR 4.4 95%CI 1.3-15.0). Four of the patients with pre-existing moderate disability (27%) maintained their previous degree of disability. On multivariate analysis age (OR 1.1 95%CI 1.1-1.2), admission NIHSS (OR 1.2 95%CI 1-1.3) and complete recanalization (OR 0.2 95%CI 0.04-0.68) remained significant modifiers of poor outcome.

Conclusions:
Patients with pre-existing moderate disability have higher chances for sustaining unfavorable outcomes despite EVT. Nevertheless, some patients maintain the same level of moderate disability and therefore patients with pre-existing moderate disability should not be excluded from EVT.
Abstract TP252: Prehospital Stroke Scales as a Tool for Early Identification of Stroke and Transient Ischemic Attacks: A Cochrane Systematic Review
Authors: Walker Gregory B , Zhelev Zhivko , Frid handler Jon , Henschke Nicholas , Yip Samuel
Published: June 2021

Background:
Stroke remains among the leading causes of death and disability worldwide. The recent advances in acute stroke therapy further validate the need for an efficient ‘stroke system,’ of which the first step is rapid and accurate identification of stroke. Currently, there is no agreed upon standard prehospital stroke scale.

Methods:
In conjunction with the Cochrane Stroke Group we developed an electronic search strategy to identify relevant studies in MEDLINE. We then adapted it to seven other databases. Scales had to have been used in the emergency or prehospital setting, have a discharge diagnosis of stroke by a neurologist and needed to demonstrate at a minimum, the data needed to construct a two by two table. Our database search yielded 8479 references with 16 full texts articles and 4 abstracts (7 scales) meeting our inclusion criteria. We applied the Quadas-2 tool to eleiminate bias.

Results:
The ROSIER scale demonstrated the highest median sensitivity at 90% (95%CI, range 85%-97%) as well as the smallest confidence intervals. The LAPSS demonstrated the best pooled specificity, 91% (95%CI, range 84%-95%).

Conclusion:
In the acute stroke setting a highly sensitive scale for stroke identification is of great value. This Cochrane Systematic review demonstrated that of all currently validated scales, the ROSIER scale has the greatest sensitivity for detecting stroke in the the prehospital or emergency setting.
Abstract TP253: A Novel Prehospital Scale to Predict Candidates for Acute Stroke Thrombectomy : The Fukuoka Acute Stroke ThrombEctomy pRediction (FASTER) Scale
Authors: Miyazaki Yuichi , Tsumoto Tomoyuki , Matsuo Ryu , Ago Tetsuro , Kamouchi Masahiro , Yasaka Masahiro , Okada Yasushi , Kitazono Takanari
Published: June 2021

Background:
We aimed to design a prehospital scale to predict candidates for endovascular thrombectomy (CET) in patients with acute ischemic stroke (AIS).

Materials and methods:
In the Fukuoka Stroke Registry, we identified 3,470 patients with AIS who were transferred by emergency medical service within 24 hours of stroke onset and underwent intracranial vessel evaluation on admission from September 2007 to December 2015. CET were defined as patients with causative occlusion of internal carotid artery, middle cerebral artery, or basilar artery, and National Institute of Health Stroke Scale (NIHSS) score ≥ 6. The Fukuoka Acute Stroke ThrombEctomy pRediction (FASTER) scale was developed with NIHSS items based on the predictive importance derived from random forest analysis to predict CET. The discriminative performance was compared with other published scales for large vessel occlusion.

Results:
The FASTER scale was designed comprising of 4 NIHSS items : one point each was given for extinction and inattention (NIHSS subscore ≥ 1), best gaze (≥ 1), best language (≥ 1), and motor arm (≥ 2). Receiver operator curves demonstrated that the area under the curve of the FASTER scale was significantly larger than that of the Cincinnati Prehospital Stroke Severity Scale (0.907 vs 0.881, p<0.001), and not significantly different from that of the Rapid Arterial oCclusion Evaluation scale (vs 0.910, p= 0.68). The FASTER scale score ≥2 showed sensitivity of 88.4%, specificity 82.3%, positive predictive value 51.3%, and negative predictive value 97.1% for detecting CET.

Conclusion:
The FASTER scale is a simple and promising tool that can identify CET in the prehospital setting.
Abstract TP255: Designing a Pre-Arrival Stroke Notification System: Cincinnati Prehospital Stroke Scale versus Clinical Impression
Authors: English Stephen , Rabinstein Alejandro , Mandrekar Jay , Klaas James
Published: June 2021

Introduction:
Acute stroke pre-arrival notification by emergency medical services (EMS) allows hospital personnel to mobilize resources in advance, thereby improving treatment times and outcomes. However, criteria for pre-arrival notification vary by institution. In developing our own pre-arrival notification system, we aimed to determine whether objective measures, EMS clinical impression, or a combination of both best predicted accurate stroke team activation.

Methods:
Retrospective review of consecutive patients presenting to our institution via EMS with suspicion of acute stroke from 2014-2015. Data recorded included age, gender, time of symptom onset, glucose, Cincinnati Prehospital Stroke Scale (CPSS), Glasgow Coma Scale (GCS), and EMS impression. Univariate logistic regression was performed with acute stroke team activation in the emergency department (ED) as the endpoint.

Results:
130 patients met inclusion criteria. Of these, 88 prompted the ED provider to activate the acute stroke team. Of variables analyzed, CPSS was clinically and statistically significant (OR. 1.7, 95% CI 1.2-2.5, p=0.0035) on univariate analysis, with arm weakness being the most predictive component (OR 2.9, 95% CI 1.04-8.1, p=0.04). EMS impression was not statistically significant (p>0.05). We then performed sensitivity and specificity analyses of CPSS, EMS impression, and CPSS combined with EMS impression (Table). A CPSS score of 3 had the highest specificity, and CPSS score of 1 combined with EMS impression the highest sensitivity.

Conclusion:
CPSS was the key significant predictor of ED acute stroke team activation, and more specific than EMS clinical impression. By combining CPSS and EMS impression, sensitivity improved, but at the expense of specificity. This suggests that reproducible measurements and scores, such as CPSS, should be the main driver for stroke pre-notification systems and should be integrated systematically into EMS education programs.
Abstract TP264: MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke
Authors: Yang Xinxin , Liu Kai , Chen Jun , Yin Ke-Jie
Published: June 2021

MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
Abstract TP27: Impact of Mechanical Thrombectomy Device on the Thrombus Histology in Acute Embolic Stroke
Authors: Horie Nobutaka , Morofuji Yoichi , Sadakata Eisaku , Tateishi Yohei , Izumo Tsuyoshi , Morikawa Minoru , Tsujino Akira , Matsuo Takayuki
Published: June 2021

Background and Purpose:
Thrombus composition has been suggested to have a decisive impact on the outcome of patients treated by mechanical thrombectomy because of embolic stroke. The aim of this prospective study was to assess the impact of a mechanical thrombectomy device (Penumbra aspiration catheter vs. Stent retriever) on thrombus composition, which could affect flow impairment after reperfusion.

Methods:
Thrombi of consecutive stroke patients with large vessel occlusion were collected during intracranial mechanical recanalization. Mechanical thrombectomy device was used either Penumbra aspiration catheter or Stent retriever. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red blood cells and fibrin/platelets).

Results:
Of 65 cardio-embolic patients, Penumbra aspiration catheter was used in 27 patients, and Stent retriever was used in 38 patients. There was no significance in age, sex, occlusion vessel, NIH stroke scale, and onset to reperfusion time. The volume of thrombi was significantly larger in Penumbra group compared with that in Stent group (3.68 cm3 vs. 0.95 cm3, P<0.01). On the other hand, The percentage of fibrin component was significantly higher in Stent group (36.2% vs. 62.4%, P<0.01). Preoperative IV-tPA reduced the size of thrombi in Stent group, which was not seen in Penumbra group (0.46 cm3 vs. 1.26 cm3, P<0.01). Interestingly, preoperative susceptibility vessel sign on MR imaging correlated with the percentage of red blood cells in not Stent group but Penumbra group. Finally, new infarction on MR imaging was not different between two groups 24 hours after the treatment.

Conclusions:
Stent retriever could crush thrombus and reduce its size, which induce distal migration of the red blood cell component. However, it did not affect the final infarct lesion and outcome.
Abstract TP274: Activation of the Prostaglandin E
2
Receptor EP4 Reduces Blood-Brain Barrier Damage in a Rat Model of Ischemic Stroke
Authors: DeMars Kelly M , McCrea Austin O , Yang Changjun , Candelario-Jalil Eduardo
Published: June 2021

Ischemic stroke occurs when a clot forms in the cerebrovasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E
2
binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well characterized. In this study, we hypothesized that EP4 receptor activation reduces ischemic brain injury by reducing matrix metalloproteinase (MMP)-3/-9 production and blood-brain barrier (BBB) damage. Rats underwent transient ischemic stroke for 90 minutes. Animals received an intravenous injection of either the vehicle or L-902688, a highly specific EP4 agonist, at the onset of reperfusion. Brain tissue was harvested at 24 h. We established a dose-response curve and used the optimal dose that resulted in the greatest infarct reduction to analyze BBB integrity compared to vehicle-treated rats. The presence of IgG, a blood protein, in the brain parenchyma is a marker of BBB damage, and L-902688 (1 mg/kg; i.v.) dramatically reduced IgG extravasation. Consistent with these data, we assessed zona occludens-1, a tight junction protein integral to the maintenance of the BBB, and found it increased with L-902688 administration. With immunoblotting, qRT-PCR, and/or a fluorescence resonance energy transfer (FRET)-based activity assay developed by our group, we next measured MMP-3/-9 since they are key effectors of BBB breakdown in stroke. In the cerebral cortex, not only was MMP-3 activity significantly decreased, but L-902688 treatment also reduced MMP-9 mRNA, protein, and enzymatic activity. In addition, post-ischemic administration of the EP4 agonist significantly reduced pro-inflammatory cytokines IL-1β and IL-6 in the ischemic cortex. Our data show for the first time that pharmacological activation of EP4 with L-902688 is neuroprotective in ischemic stroke by reducing MMP-3/-9 and BBB damage.
Abstract TP277: Adropin is Profoundly Neuroprotective in Experimental Ischemic Stroke
Authors: Yang Changjun , DeMars Kelly M , Candelario-Jalil Eduardo
Published: June 2021

Adropin has been shown to improve peripheral endothelial dysfunction, reduce insulin resistance, and increase glucose utilization in obesity and diabetes. Although we showed that adropin reduces paracellular permeability of brain endothelial cells exposed to ischemia-like conditions, little is known of the effects of adropin in the brain. We hypothesized that adropin exerts neuroprotection through activation of endothelial nitric oxide synthase (eNOS)/NO signaling pathway and reduction of blood-brain barrier (BBB) damage. Male mice were subjected to permanent middle cerebral artery occlusion (MCAO) and treated intravenously with either vehicle or synthetic adropin (90, 900 and 2700 nmol/kg) at the onset of ischemia and sacrificed to determine infarct size at 48 h. Cellular localization of adropin was determined using immunofluorescence. Brain tissue was collected at 24 h after stroke to determine BBB damage, matrix metalloproteinase (MMP)-9 activity, and levels of tight junction proteins, eNOS, and gp91
phox
-containing NADPH oxidase. We determined the effects of a 3-h delayed administration on stroke outcomes to evaluate the translational value of adropin therapy. In the brain, adropin was expressed on endothelial cells and at a low level on astrocytes after stroke. Adropin given at the onset of MCAO dose-dependently reduced infarct size. More importantly, delaying adropin administration to 3 h post-MCAO profoundly reduced infarct size compared to vehicle-treated mice. Ischemia slightly increased eNOS phosphorylation at Ser1176, significantly increased gp91
phox
(a major source of reactive oxygen species), and reduced brain adropin levels. Adropin treatment induced a dramatic increase in eNOS phosphorylation, significantly reduced gp91
phox
levels, and restored endogenous adropin levels compared to the vehicle group. Additionally, adropin protected against a stroke-induced increase in MMP-9 activity, loss of zona occludens-1 and occludin, and BBB disruption as assessed by extravasated IgG and albumin. Collectively, these findings indicate that adropin-mediated neuroprotection in ischemic stroke may be through an increase in eNOS-derived NO bioavailability, reduction of gp91
phox
, and decreased MMP-9 activity and BBB damage.
Abstract TP282: High Mortality Among 30-Day Readmission After Stroke: Predictors and Etiologies of Readmission
Authors: McCormick Lauren , Modak Janhavi , Staff Ilene , Fortunato Gilbert , Nouh Amre
Published: June 2021

Background:
Although risk factors for readmission have been reported, the mortality risk is unclear. We sought to evaluate etiologies and predictors of 30-day readmission and determine the associated mortality risk.

Methods:
This is a retrospective case-control study evaluating stroke patients (hemorrhagic, ischemic or TIA) from January 2013-December 2014 and those readmitted within 30 days after index event; including 135 readmitted patients and 1,664 controls. Readmission for hospice or elective surgery were excluded. Socio-demographics, clinical variables and potential risk factors were assessed using chi-square test of proportions and multi variable logistic regression was performed to identify independent predictors of 30-day stroke readmission. Index mortality was compared to readmission mortality and odds associated with readmission was identified.

Results:
Overall, 67% of index stroke admissions were ischemic, 19% hemorrhagic, and 14% TIA. The 30-day readmission rate was 7.3%. The most common etiologies for readmission were infection (30%), recurrent stroke (17%), and cardiac complications (14%). Recurrent strokes presented earliest
(p=0.047)
and had a shorter index admission length of stay
(p=0.02.)
Risk factors for 30-day readmission included age > 75 (
p=0.04
), lack of spouse (
p=0.05
), living in a facility prior to index stroke (
p=0.033
), history of prior stroke (
p=0.02
), diabetes (
p=.018
), CHF (
p=<.0001
), atherosclerosis (
p=<0.01
), admission to non-stroke unit (
p=0.02
), non-home discharge status (
p<0.01
), and index admission to a non-neurology service was an independent predictor of 30-day readmission (p=<0.01). The overall mortality associated with 30-day readmission after stroke was higher as compared to index admission (37.3% vs 13.3% p =<0.01)
(OR 3.7 95%CI 2.5-5.3)
and was not influenced by recurrent stroke
(p=0.37)
.

Conclusion:
In our study, infection and recurrent stroke were most common causes and index admission to a non-neurology service was the strongest readmission predictor. The overall mortality is high and not influenced by recurrent stroke. Identifying high risk patients, ensuring appropriate level of service and early outpatient follow-up may help reduce 30-day readmission and risk of mortality.
Abstract TP284: Implementation of an Organized Stroke Care Program Reduced Door-to-needle Time in a Hospital in Mexico City
Authors: Calleja Juan , Martinez Jesus , Gutierrez Isabel
Published: June 2021

Introduction:
Reperfusion therapies are the optimal treatment for acute ischemic stroke (AIS). Their effectiveness is highly time-dependent. Worldwide, organized stroke care has shown to improve efficiency and quality of attention in stroke management. Neither reperfusion therapies or stroke center care have been widely implemented in Mexico. The objective of this study is to describe whether the implementation of a Stroke Care Program (ABC Stroke Center) improved time to treatment and adherence to Get With The Guidelines parameters on patients who underwent IV thrombolysis for AIS.

Hypothesis:
Implementation of an institutional Stroke Program lowers door-to-needle time (DNT) and improves adherence to stroke quality measures in patients treated with IV thrombolysis.

Methods:
The study included all patients with AIS diagnosis treated with IV thrombolysis between January 2010 and May 2016. We then compared patients admitted before and after June 2014 (start of the Stroke Program).

Results:
A total of 56 patients were included, 30 (53.6%) were admitted preintervention and 26 (46.4%) postintervention. All of them were treated with IV thrombolysis. All time parameters related to quality of attention were shorter in patients after the Stroke Program started. DNT was 21 minutes shorter in the Stroke Program group (mean 65 vs 86 min, p<0.03), and the number of patients within the DNT time goal of 60 minutes was larger postintervention (44.8 vs 29.6%, (95%CI 0.76 - 2.6, p=0.24)]. Adherence to stroke quality measures was more common in the Stroke Program group. Patients included after the start of the stroke program had a higher NIHSS score upon discharge. The probability of a good outcome (mRS<3) upon discharge was higher in the Stroke Program group (61.1% vs 31.4%) [RR = 1.9 (95%CI 1.17 - 3.38)].

Conclusions:
Implementation of a Stroke Care program diminished DNT significantly and improved adherence to stroke quality measures. This may result on better outcomes for AIS patients.
Abstract TP289: Code Neuro-Intervention a New Necessity: Reality of Shifting Stroke Care Paradigm
Authors: Suhan Laura , Panezai Spozhmy , Brar Jaskiran , Arango Audrey Z , Pullicino Anna , Kulhari Ashish , Mehta Siddhart , Kirmani Jawad F.
Published: June 2021

Background:
Various strategies have been implemented to reduce acute stroke treatment times. A unique code process pathway was designed at our hospital specifically to be activated by the stroke team for the purpose of rapidly assembling the Neurointerventional team.

Methods:
Code Neurointervention (NI), was designed and tested from January 2014 to April 2014 for all the patients who presented with ischemic strokes to our community based, university affiliated comprehensive stroke center. We retrospectively analyzed all patients who had Code NI called from May 1, 2014 to April 30, 2015 and compared them to patients who underwent acute endovascular treatment the prior year (Non Code NI). The following parameters were compared: decision to recanalization and door to recanalization times. Further analysis was done to compare patients presenting during business hours (Monday-Friday 8am-5pm) and off hours using GraphPad QuickCalcs Web site.

Results:
There were 28 Code NI; 14 were called during work hours and 14 during off hours. The previous year 25 patients underwent acute endovascular intervention; 12 during work hours and 13 during off hours. Mean decision to recanalization time was 106 (Code NI) vs 115 minutes (Non Code NI) (p<0.0.6) during work hours and 154 (Code NI) vs 139 minutes (Non Code NI) (p<0.37) during off hours. Mean door to recanalization time was 169 (Code NI) vs 173 minutes (Non Code NI) (p<0.85) during work hours and 252 (Code NI) vs 243minutes (Non Code NI) (p< 0.75) during off hours. Subset analysis of time parameters for patients in Code NI group showed mean decision to recanalization times of 106 minutes during work hours vs 154 minutes off work hours (p<0.004). Mean door to recanalization times were 169 minutes vs 251 minutes (p<0.0003), respectively.

Conclusion:
Institution of Code NI significantly improved intervention time parameters during work hours as compared to off hours. Rapid assembly of the neurointervention team, rapid availability of imaging and angiography suite likely contribute to these differences. Further initiatives, such as improving neurointervention staff availability during off hours or cross training other staff can further improve acute intervention time parameters.
Abstract TP301: Outlier Analysis of NIHSS Change in a Regional Database of Acute Ischemic Stroke
Authors: Rose Danny R , Grupke Stephen L , Fraser Justin F , Kitzman Patrick H , Elkins Kelley L , Wolfe Marc A , Morris Sarah N , Dobbs Michael R
Published: June 2021

Introduction:
Change in NIH Stroke Scale from admission to discharge has been proposed as an outcome-based method of assessing quality of care in the inpatient setting. Using the Kentucky Appalachian Stroke Registry database, statistical outliers were identified as potential targets for investigation. We aimed to use the analysis of this subset of patients to identify characteristics favoring exceptionally good or poor outcome.

Methods:
De-identified patient data was obtained from the Kentucky Appalachian Stroke Registry for all acute ischemic stroke patients from January 1, 2013 to December 31, 2014 using discharge diagnoses. Statistical process control methodology was used to identify hospitalizations with positive or negative NIHSS change more than three standard deviations from the mean. The statistical outliers underwent manual chart review to validate the data obtained from the registry and supplement it qualitatively to identify common characteristics. Chi-square tests were conducted to assess the association between patient characteristics and being a positive or negative outlier.

Results:
Positive outliers were less likely to have hypertension and more likely to have received intravenous thrombolysis. Negative outliers were more likely to have carotid stenosis. Both groups were more likely to have a diagnosis of cardiac arrhythmia and to have received mechanical thrombectomy.

Conclusions:
Gathering registry data regarding NIHSS outliers is a feasible and potentially useful tool in understanding and improving care. The absence of hypertension may represent positive predictive recovery potential in severe stroke. Patients with significant carotid disease on presentation may be at risk of neurological decline. Furthermore, patients with large vessel occlusions undergoing thrombectomy represent a high-variance population with the greatest improvements and greatest deteriorations during inpatient hospitalization.
Abstract TP303: Institutional Stroke Quality Improvement and Impact on Vascular Neurology Fellows Practice Patterns
Authors: Lynch John , Benson Richard , Hsia Amie , Leigh Richard , Nadareishvili Zurab , Luby Marie
Published: June 2021

Background and objectives:
The American Heart Association quality improvement (QI) program Target Stroke is focused on reducing door-to-needle (DTN) time for IV tissue plasminogen activator (tPA) therapy to ≤60 minutes. Multidisciplinary QI procedures similar to the Target Stroke best practices have been shown to improve DTN times at an MRI based program. Whether these strategies improve the performance of trainees is unclear. The objective of this study was to determine the impact of a multidisciplinary QI program on the practice patterns of vascular neurology (VN) fellows at an MRI based stroke program.

Methods:
Case logs from the NIH Stroke Program VN fellows (N=22) were reviewed from July 2008-July 2015. Data was collected for the following: total patients screened, patients triaged, stroke code proceeds, tPA treated cases, and door to needle time (DTN) for each patient treated including DTN ≤60 minutes. QI processes that included stroke team education and process changes were initiated in 2013 to improve stroke care at two hospitals where VN fellows provide clinical care. We compared VN fellow practice patterns before (2008-12) and after (2013-15) QI implementation.

Results:
A total of 5093 cases were reviewed for the study. From 2008-15, fellows screened a yearly average of 232 patients, triaged 54% (125) to acute imaging, and treated 7.8% (18) patients each year with IV tPA. VN fellow practice patterns after QI implementation (2013-15) improved for percent treated with IV tPA (5.8% vs. 9.9%, p<0.05), median DTN (83 vs. 71 min.; p<0.05), and percentage treated ≤60 minutes (11% vs. 40%; p<0.05). The mean number of patients screened was slightly higher before 2013 (238 vs. 225), and triage rates were similar (52.4% vs. 55%, p=0.58).

Conclusion:
The results of this study suggest that an institutional multidisciplinary QI stroke program can improve the practice patterns of VN fellows at an MRI based stroke program.
Abstract TP306: Risk of Stroke After ED Visits at Which No Diagnosis of TIA or Stroke was Recorded
Authors: Rosenman Marc , Oh Elissa , Richards Christopher T , Allen Norrina B , Capo-Lugo Carmen , Mendelson Scott , Madden Margaret , Muldoon Kathryn A , Holl Jane L , Naidech Andrew , Prabhakaran Shyam
Published: June 2021

Introduction:
Unrecognized, high-risk conditions like transient ischemic attack (TIA) are missed opportunities to initiate timely preventive treatment to reduce the risk of subsequent stroke, disability, and death. Up to 50% of patients with a TIA may have a subsequent disabling stroke, many within 30 days.

Hypothesis:
Among patients with an Emergency Department (ED) visit at which no diagnosis of TIA or stroke was recorded, analysis of electronic health record (EHR) data can help predict risk of subsequent stroke.

Methods:
We performed a retrospective cohort study of EHR data (2011-2015) from a high-volume comprehensive stroke center with an annual ED volume of >85,000. Patients age 60-89 years who were discharged to home from the ED in <24 hours without ICD-9 diagnosis of TIA or stroke were included for analysis. If patients had >1 qualifying index visit during the study period, we used the first. For each patient we determined presence or absence during the ED visit of a head CT and/or any of these strings in the ED chief complaint (“Symptoms”): slur, speech, aphasia, confuse, word, difficult, comprehen, weak, clumsy, clumsiness, droop, paralysis, move, moving, face, or facial (but not “facial injury”). In four mutually-exclusive categories, CT (Yes/No) by Symptoms (Yes/No), we calculated rate of stroke in the 30, 90, and 365-day periods after discharge from the ED. Ischemic stroke ascertainment was based on diagnostic codes at subsequent ED or hospital visits.

Results:
Among 40,450 patients, mean age was 69 years, and 59% were women. Race was 57% white, 15% African-American, 23% other, and 4% unknown. Numbers of patients and rates of stroke by category are shown in the table.

Conclusion:
This simple approach established a clinically meaningful risk gradient across four groups. Present and future work to refine this model may contribute to comparative effectiveness research that evaluates management and triage strategies for patients across the stroke risk spectrum.
Abstract TP317: Hyperglycemia Strongly Predicts Large Ischemic Infarct Growth Despite Full Endovascular Reperfusion
Authors: Bahr Hosseini Mersedeh , Woolf Graham W , Hinman Jason D , Raychev Radoslav , Latisha K Sharma Latisha K , Kim Doojin , Rao Rao , Starkman Sidney , Yoo Bryan , Jahan Reza , Szeder Viktor , Tateshima Satoshi , Duckwiler Gary R , Scalzo Fabien , Saver Jeffrey , Liebeskind David
Published: June 2021

Introduction:
Ischemic infarct core grows at variable rates despite early reperfusion. The purpose of this study was to determine the predictors of infarct growth despite full recanalization of a large vessel occlusion in acute ischemic stroke.

Method:
Patients with acute ischemic stroke due to ICA or MCA occlusion who received endovascular therapy with Thrombolysis in Cerebral Infarction scale (TICI) scores of 2b or greater were subsequently selected between July 2012 and May 2016. The Alberta Stroke Program Early CT Score (ASPECT) was measured on the initial CT or MRI upon arrival and subsequently on the 24-hour scan. The infarct growth (delta d) was measured as initial ASPECT minus 24-hour ASPECT. Large and small infarct growth was defined as delta d of >= to3 and < 3 respectively. The relationship between the infarct growth and baseline variables of blood glucose level(BG), time of symptoms onset to recanalization time and baseline ASPECT score were assessed using statistical analysis.

Results:
Total of 76 patients were included. 32% had large infarct growth (25/76). The initial ASPECT score was not significantly different between the the 2 subgroups of large and small delta d (7.5 vs 6, P= 0.97). Baseline BG level was significantly higher in the group with larger infarct growth (160 vs 128, P=0.006). The baseline BG level of more than 150 was found as the threshold between the 2 subgroups (P=0.0003). No association was found between the infarct growth and history of diabetes (P= 0.7).

Conclusion:
Our data suggests that infarct growth occurs in relatively high percentage of ischemic stroke patients despite early full reperfusion of the large vessel occlusion. We showed that baseline blood glucose level particularly levels of higher than 150 is significantly associated with larger infarct growth. Therefore, it can be used as a strong predictive value in early recognition of this patient population.
Abstract TP321: Strokes Occurring in the Hospital; Quality of Care and Outcome in a Tertiary Academic Medical Center
Authors: Kamal Haris , Lail Navdeep , Crumlish Annemarie , Ching Marilou , Sawyer Robert , Mowla Ashkan
Published: June 2021

Introduction:
Studies have shown that 4-17% of acute ischemic strokes (AIS) occur in the patients hospitalized for another reason.We present one of the largest single center data in the US on quality of care and outcome of in-hospital strokes from our large volume comprehensive stroke center at Buffalo general Hospital, Buffalo, NY.

Methods:
In a retrospective study, all patients who suffered an AIS after being admitted for another reason to our center from January 2006 till June 2015 were included in the study. Variables studied included demographics, comorbid illness, NIHSS on admission, clinical presentation and NIHSS at the time of stroke, location of infarction on brain imaging, location of the patient while stroke occurred, treatment undertaken, quality of care measures and outcome on discharge using modified Rankin Scale( mRS).

Results:
We found 53 patients who suffered AIS proven on brain imaging after being hospitalized for another reason in the study period. Twenty seven were females (51 %). Mean age was 69.4 (±13.1). Mean NIHSS on admission was 0. Mean NIHSS at the time of stroke was 10.1 (±9.72). Mean Time of symptom recognition to neuroimaging was 7 hours (±14.4 hours). Only in 4 patients (7.5%) head CT scans were done within 25 minutes from symptom recognition. Forty two (79%) underwent brain imaging within 6 hours of symptom recognition, out of them 11(26%) received intravenous thrombolysis (IVT) within the first 4.5 hours and 7 (17%) underwent intra-arterial thrombolysis (IAT). The patients admitted in the emergency room(ER) for other reasons or intensive care units(ICU) had more chance of being eligible for IVT or/and IAT from timing stand point compared to the patients admitted to the regular floors ( 44 % vs 25% ) . In 15 patients (28%), there was a delay in symptom recognition or treatment due to diagnosis uncertainty
.
The mean MRS on discharge 2.37 (± 2.16) with a mortality rate of 13%.

Conclusion:
Due to logistical problems, only a small number of patients with in-hospital strokes received brain imaging within the time window recommended by ASA/AHA guideline. We need to improve awareness of stroke symptoms among medical staff including nurses and non-neurology physicians which might leads to a more timely initiation of treatment and better outcome.