bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 417: The Prognostic Value of Lactate in Cardiac Intensive Care Unit Patients With and Without Cardiac Arrest
Authors: Burstein Barry , Vallabhajosyula Saraschandra , Ternus Bradley , Kashani Kianoush , Barsness Gregory W , Jentzer Jacob C
Published: June 2021

Introduction:
Lactate is a known prognostic marker in critically ill patients, including patients with shock and cardiac arrest (CA). We sought to describe the association between admission lactate and hospital mortality in cardiac intensive care unit (CICU) patients, particularly those with CA.

Methods:
We retrospectively evaluated adult patients admitted to a tertiary care CICU from January 1, 2007, to April 30, 2018, with measured lactate on admission. We examined hospital mortality as a function of admission lactate level in patients with and without CA. Multivariable logistic regression was used to determine predictors of hospital mortality in the overall cohort, after adjustment for clinical characteristics, therapies, and illness severity.

Results:
We included 3,042 patients with a median age of 70 years (IQR 60-80), including 40.5% (n=1,233) females. There were 789 patients (26.1%) with a diagnosis of CA. The median APACHE-4 predicted mortality was 24.2% (IQR 10.9-50.7), and 50.8% (n=1546) were treated with vasoactive infusions. The median lactate on admission was 1.8 mmol/L (IQR 1.1-3.0). CICU mortality occurred in 478 (15.7%) patients) and hospital mortality occurred in 706 (23.2%) patients. Hospital mortality rose progressively as a function of admission lactate (
Figure
). On univariable analysis, lactate was associated with increased hospital mortality among the overall cohort (OR 1.36, CI 1.31-1.42, P < .001; AUROC 0.71), patients with CA (OR 1.33 (95% CI 1.25-1.41, P < .01; AUROC 0.73), and patients without CA (OR 1.27, CI 1.21-1.34, P < .01; AUROC 0.64). On multivariable analysis, lactate was one of the most significant predictors of hospital mortality (adjusted OR 1.13 per mmol/L, 95% CI 1.08-1.18, P < .001).

Conclusions:
Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, especially those with CA. The prognostic value of lactate levels may help inform clinicians caring for CICU patients.
Abstract 425: A Sign of ST-Segment Elevation Predicts Type 1 Myocardial Infarction in Patients Resuscitated From Cardiac Arrest
Authors: Kotoku Nozomi , Higuma Takumi , Ishibashi Yuki , Kaihara Toshiki , Kuwata Shingo , Koga Masashi , Mitarai Takanobu , Kamijima Ryo , Yoneyama Kihei , Tanabe Yasuhiro , Akashi Yoshihiro J
Published: June 2021

Introduction:
Emergent coronary angiogram (CAG) followed if necessary by percutaneous coronary intervention (PCI) are currently a standard strategy in patients resuscitated from cardiac arrest with acute myocardial infarction (MI), especially in patients with ST-segment elevation myocardial infarction (STEMI). Spontaneous MI is related to a coronary plaque disruption with resulting intraluminal thrombosis, which is defined as type 1 MI by the universal definition of MI. For type 1 MI, the management includes early CAG and revascularization as appropriate. The aim of this study was to identify the predictor of type 1 MI in patients resuscitated from cardiac arrest.

Methods and Results:
A total of 74 patients who underwent immediate CAG after successful resuscitation from in-hospital and out-of-hospital cardiac arrest between January 2015 and December 2016 were analysed. Based on immediate CAG, 44 patients (59.5%) were diagnosed as type1 MI, and 39 (88.6%) of these patients underwent primary PCI after immediate CAG. A sign of ST-segment elevation after resuscitation was more frequently observed in patients with type 1 MI than in those without (71.1% vs. 6.9%, p<0.01). Prevalence of ventricular fibrillation or pulseless ventricular tachycardia as an initial rhythm did not differ between patients with and without type 1 MI (71.1% vs 62.1%, p=0.454). Even after adjusted for possible confounders, ST-segment elevation remained associated with type 1 MI (odds ratio: 89.0, 95% confidence interval 4.3 to 1824.7: p<0.01). Diagnosis by ST-segment elevation resulted in sensitivity of 71.1%, specificity of 93.1%, positive predictive value of 94.1% and negative predictive value of 67.5% for type 1 MI.

Conclusions:
Among patients who had been successfully resuscitated after cardiac arrest, ST-segment elevation on electrocardiography was a powerful predictor for type1 MI. A sign of ST-segment elevation is useful for rule in decision-making to determine the early invasive strategy.
Abstract 427: Sudden ECG Rhythm Changes After Return of Spontaneous Circulation in Porcine Models of Cardiac Arrest
Authors: Koller Allison C , Salcido David D , Genbrugge Cornelia , Menegazzi James J
Published: June 2021

Background:
Observation of the electrocardiogram (ECG) immediately following return of spontaneous circulation (ROSC) in resuscitated swine has revealed the interesting phenomenon of sudden ECG rhythm changes (SERC) that occur in the absence of pharmacological, surgical, or other medical interventions.

Objective:
We sought to identify, quantify, and characterize post-ROSC SERCs in successfully resuscitated swine.

Methods:
We reviewed all LabChart data from resuscitated approximately four-month-old swine used for various experimental protocols from 2006 to 2019. We identified those that achieved sustained ROSC and analyzed the entire post-ROSC period for evidence of a SERC in the ECG, arterial and venous pressure tracings. Presence or absence of a SERC was confirmed independently by two reviewers (ACK, DDS). We measured the time from ROSC to first SERC, analyzed the following metrics and calculated the change from 60 sec pre-SERC (or from ROSC if less than 60 sec) to 60 sec post-SERC: heart rate, central arterial pressure (CAP), and central venous pressure (CVP).

Results:
A total of 52 pigs achieved and sustained ROSC. Of these, we confirmed at least one SERC in 25 (48.1%). Two pigs (8%) had two unique SERC events. Median (IQR) time from ROSC to first SERC was 3.8 (1.0-6.9) min (range: 16 sec to 67.5 min). Mean (SE) heart rate changed by 51.7 (6.22) bpm. Mean heart rate decreased in 60% of cases. Mean (SE) CAP changed by 20.9 mmHg and mean (SE) CVP changed by 1.1 (0.24) mmHg. Mean CAP decreased in 72% of cases and mean CVP increased in 68%. Figure 1 shows an illustrative case with: red channel CAP (top), blue channel CVP (second from top), green channel CPP (second from bottom), and pink channel ECG (bottom).

Conclusions:
SERC occurs in nearly half of all cases with sustained ROSC and can occur multiple times per case. First SERC occurs within the first 4 minutes following ROSC. Heart rate, CAP and CVP change around the moment of SERC.

Figure 1. SERC Case
Abstract 438: Synchronization of Chest Compressions During Pseudo Electro-Mechanical Dissociation Improves Blood Pressures Relative to Standard Chest Compressions
Authors: Lampe Joshua W , Gould Jeff R , Moodie Karen L , Soucy Zachary P , Burrage Peter S , Paradis Norman A
Published: June 2021

Introduction:
The treatment of pseudo electro-mechanical dissociation (P-EMD) with standard chest compressions leads to periods where the chest compressions and heart-beat are in phase and periods where the chest compression and heart-beat are out of phase. We hypothesized that synchronized chest compressions will improve hemodynamics relative to standardized chest compressions during P-EMD.

Methods:
Eight animals underwent surgical preparation and were exposed to hypoxia to induce P-EMD. The treatment period was divided into eight 45 sec epochs during which the P-EMD was left untreated or was treated with standard chest compressions or chest compressions synchronized to the R-wave in the ECG. For each epoch of CPR in each animal, we measured the rate of change in the hemodynamics over the last half of the epoch using linear regression. ANOVA modeling was used to compare changes in hemodynamics as a function of treatment.

Results:
The rate of change in coronary perfusion pressure (CPP), minimum right atrial pressure (RAPmin), and maximum right atrial pressure (RAPmax) was larger during synchronized compressions than during standard compressions or untreated P-EMD. The rate of change in AOPmin was larger during both treatments than during untreated P-EMD. Other differences in the rate of change were not detected between standard chest compressions and untreated P-EMD. Numerical results are shown in the table below. RAPmax decreased over time, while the other measures increased.

Conclusions:
Synchronized chest compressions improved several blood pressure metrics over time during P-EMD, while standardized chest compressions only improved AOPmin. While some of the changes are modest, they were sustained over 20 seconds, suggesting that continued delivery of synchronized chest compressions could result in clinically meaningful improvement in blood pressures.

Table 1. ANOVA comparison of blood pressures as a function of treatment
Abstract 450: Rapid Cycle Deliberate Practice Improves Critical Item Retrieval From Crash Cart
Authors: Cotteral Julia , Kekkonen Keri , Fidler Richard L
Published: June 2021

Introduction:
Unfamiliarity with crash cart contents contributes to decreased patient safety. There is no standardization of crash carts organization or contents. Initial moments of an emergency are critical and especially stressful. Responders familiar with the available equipment may be more efficient in retrieval and utilization of supplies.

Methods:
This study investigated the effects of Rapid Cycle Deliberate Practice (RCDP) as a training tool to increase familiarity with crash carts and contents, through a challenge of timed retrieval and assembly of critical items needed in response to in-hospital cardiac arrest (IHCA). Individuals were randomly assigned to one of four experimental groups to further identify efficient education methods.

Hypothesis:
RCDP predicted to improve retrieval performance and participant group assigned to hands-on discovery of the crash cart would show most improvement.

Results:
75 interdisciplinary participants averaged total time for retrieval of 12 critical care items with completion of 4 corresponding tasks of 327 seconds decreased to 104 seconds from round 1 to 2. Secondly, average number of drawer pulls to retrieve items went from 14.8 to 10.5. The item most infrequently found in the 60 seconds allotted in round 1 was the intraosseous access kit (14/75, 18.67%). Connection of the defibrillator electrodes to the defibrillator device failed completion by 23 participants (30.67%) in the 60-second round 1. Retrieval of intraosseous access kit and connection of defibrillator electrodes was successful by all participants in round 2.

Conclusions:
Findings highlight the importance of training staff on available emergency equipment, with the expectation that increased familiarity and decreased response times will correlate to improved patient IHCA outcomes. Furthermore, findings indicate a need for standardization of crash cart organization across units and facilities.
Abstract 466: Consideration of an Optimal Educational Strategy for High-Quality Cardiopulmonary Resuscitation and Chest Compression Fraction in Basic Life Support Simulation Training
Authors: Sekiguchi Hiroshi , Saito Kanako , Fukami Masataka , Taira Takayuki , Ouchi Gen , Tamaki Yuichiro , Fukuda Tatsuma , Hanashiro Kazuhiko , Hanashiro Kazuhiko , Yoshikazu Kawazuma , Yonemoto koji , Nakajima Shigeyoshi , Terada Taizo , Kukita Ichiro
Published: June 2021

Introduction:
The American Heart Association (AHA) is pursuing higher-quality simulation training with the goal of “Optimizing educational strategies for healthcare providers” as one of the Science Gaps in the 2015 Cardiac Arrest Guidelines. The latest guidelines suggest that increasing CCF as much as possible during CPR increases the chance of ROSC. However, in simulation training, it is important to evaluate the percentage of CCF and maintain high-quality CPR. We evaluated CPR for 10 minutes in a “High-Performance Teams Activity” of an AHA-BLS course using the HQCPR quotient and CCF indexes.

Methods:
We measured the rhythm chest compressions (CCs), duration of two breaths, and chest rise two times using a bag valve mask, interruption and alternation time of CC, CC resumption time after AED (shock or no shock), and CCF, which was calculated from CPR recorded for 10 minutes using the video camera. This data was evaluated using the criteria of high-quality CPR based on AHA-BLS guidelines comprising 7 items, such as “100-120 frequency per min for CC,” and the HQCPR quotient was determined. The HQCPR quotient and CCF of each team were analyzed using logistic analysis. Moreover, the BLS techniques of each teams, such as the rhythm CCs were compared with the CCF of each teams, respectively. This study was approved by the Ethics Committee of Ryukyu University and the Japan ACLS Association.

Results and Conclusions:
Overall, 48 teams comprising 215 subjects participated in the study. The HQCPR achievement rate for the 48 teams was 65.9%. There was no correlation between the HQCPR quotient and CCF (R2 = 0.0003). In simulation training, the CCF height did not necessarily guarantee high-quality CPR (Figure 1). In particular, as CCF increased, the duration of two breaths decreased (R2 = 0.46). An adverse effect of breaths for a very short time was noted. We propose that it is essential to evaluate CCF with HQCPR quotient to achieve “Optimizing educational strategies for healthcare providers.”
Abstract 474: Higher Mortality From Cardiac Arrest in North Carolina versus Washington State and Denmark: Implications for Improving Systems of Care
Authors: Moeller Sidsel , Malta Hansen Carolina , Dupre Matthew , Rea Tom , Van Diepen Sean , Monk Lisa , Tyson Clark , McNally Bryan , Starks Monique A , Fordyce Christopher , Shin Jenny , Folke Fredrik F , Torp-pedersen Christian , Jollis James , Granger Christopher B
Published: June 2021

Introduction:
Survival from out-of-hospital cardiac arrest (OHCA) remains low and with major regional variation. This study explored differences in patients, care, and survival in patients with OHCA in North Carolina (NC), Washington State (WA), and Denmark.

Methods:
We identified a total of 17,277 adult patients with OHCA from the Cardiac Arrest Registry to Enhance Survival (CARES) registry and the Danish Cardiac Arrest Register of presumed cardiac cause from 2013-2014. Patients were categorized into three regions: two states in the United States (NC, 9.1 million inhabitants, WA, 7.5 million inhabitants) and the country of Denmark (5.8 million inhabitants). Outcomes of cardiopulmonary resuscitation (CPR) and defibrillation performed by either professional first responder or lay bystanders prior to emergency medical service (EMS) arrival, as well as overall survival. Data were analyzed using multivariable logistic regression analyses adjusted for age, sex, calendar year, location of arrest and witnessed status.

Results:
Patients in NC and WA were younger and had more racial variation compared to Denmark. Survival was 9.3% in NC, 14.5% in WA and 13.3% in Denmark. Using the Danish cohort as reference, the odds for bystander CPR and defibrillation in NC (CPR: OR 0.41, 95%CI 0.38-0.44; defibrillation: OR 0.30, 95%CI 0.23-0.38) and WA (CPR: OR 0.71, 95%CI 0.65-0.77; defibrillation: OR 0.41, 95%CI 0.31-0.53) were lower, respectively. CPR and defibrillation performed by either a bystander or a professional first responder prior to EMS arrival were higher in NC (CPR: OR 2.67, 95%CI 2.43-2.93; defibrillation: OR 2.72 95%CI 2.30-3.21), but not in WA (CPR: OR 1.01, 95%CI 0.92-1.11; defibrillation OR 0.73, 95%CI 0.58-0.90), respectively. Compared with Denmark, survival was lower in NC (OR 0.39, 95%CI 0.34-0.45) and WA (OR 0.83, 95%CI 0.72-0.95).

Conclusion:
Survival following OHCA was higher in Denmark and WA than in NC, and was associated with higher rates of bystander CPR and defibrillation. However, CPR and defibrillation prior to EMS arrival, mainly from professional first responders, was significantly higher in NC. A combination of both bystander and first responder interventions may be the optimal approach to improve outcomes of cardiac arrest.
Pro Re Nata Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity-Matched Cohort Study
Authors: Mohandas Rajesh , Chamarthi Gajapathiraju , Bozorgmehri Shahab , Carlson Jeremy , Ozrazgat-Baslanti Tezcan , Ruchi Rupam , Shukla Ashutosh , Kazory Amir , Bihorac Azra , Canales Muna , Segal Mark S.
Published: June 2021

Physicians routinely order blood pressure (BP) medications on an as needed basis or pro re nata to control BPs in hospitalized patients. We hypothesized that treatment of inpatients, who do not have a hypertensive emergency, with the use of antihypertensive medication on an as needed basis could lead to adverse outcomes. Four thousand two hundred nineteen patients who received BP medications on an as needed basis in addition to scheduled antihypertensive medications were matched 1:1 using propensity matching to those who received only scheduled BP medications. Compared with the propensity-matched cohort, patients who received antihypertensive medications on an as needed basis were more likely to experience abrupt lowering of systolic BPs (odds ratio, 2.05 [95% CI, 1.56–2.71],
P
<0.001), acute kidney injury (odds ratio, 1.24 [95% CI, 1.09–1.42],
P
=0.002), and ischemic stroke (odds ratio, 8.5 [95% CI, 1.96–36.79];
P
<0.001). The use of as needed antihypertensive medication was also associated with increased in-hospital mortality (odds ratio, 2.36 [95% CI, 1.26–4.41];
P
=0.001) and an increase in the median length of stay (4.7 versus 2.9 days;
P
<0.001). In addition, ischemic events were more likely in those who had an abrupt drop in BPs, and the risk was increased in proportion to the number of doses of as needed BP medications administered. The use of as needed antihypertensive medication is associated with an abrupt drop in BPs, increased risk of ischemic events, in-hospital mortality, and longer length of stay. We suggest that the routine use of as needed antihypertensive medication should be discouraged.
All Roads Lead to Rome (the Heart): Cell Retention and Outcomes From Various Delivery Routes of Cell Therapy Products to the Heart
Authors: Li Junlang , Hu Shiqi , Zhu Dashuai , Huang Ke , Mei Xuan , López de Juan Abad Blanca , Cheng Ke
Published: June 2021

In the past decades, numerous preclinical studies and several clinical trials have evidenced the feasibility of cell transplantation in treating heart diseases. Over the years, different delivery routes of cell therapy have emerged and broadened the width of the field. However, a common hurdle is shared by all current delivery routes: low cell retention. A myriad of studies confirm that cell retention plays a crucial role in the success of cell‐mediated cardiac repair. It is important for any delivery route to maintain donor cells in the recipient heart for enough time to not only proliferate by themselves, but also to send paracrine signals to surrounding damaged heart cells and repair them. In this review, we first undertake an in‐depth study of primary theories of cell loss, including low efficiency in cell injection, “washout” effects, and cell death, and then organize the literature from the past decade that focuses on cell transplantation to the heart using various cell delivery routes, including intracoronary injection, systemic intravenous injection, retrograde coronary venous injection, and intramyocardial injection. In addition to a recapitulation of these approaches, we also clearly evaluate their strengths and weaknesses. Furthermore, we conduct comparative research on the cell retention rate and functional outcomes of these delivery routes. Finally, we extend our discussion to state‐of‐the‐art bioengineering techniques that enhance cell retention, as well as alternative delivery routes, such as intrapericardial delivery. A combination of these novel strategies and more accurate assessment methods will help to address the hurdle of low cell retention and boost the efficacy of cell transplantation to the heart.
Abstract 29: Porcine Decellularized Heart Tissue Enhance the Expression of Contractile Proteins in Human Cardiomyocytes and Differentiated Cardiac Progenitor Cells
Authors: Huby Anne-Cecile , Beigi Farideh , Xiang Qian , Gobin Andrea , Taylor Doris
Published: June 2021

Tissue engineering is an evolving tool for repair of cardiovascular damage, in particular after myocardial infarction. Currently, most studies are focused on providing gel or thin synthetic matrices to provide structural support for injured valves, or ventricle. But little is known about how cardiac cells (eg, endothelial cells [ECs], cardiomyocytes [CMs] and cardiac progenitor cells [CPCs]) are modified by an exposure to a scaffold much less how a xenogeneic scaffold may affect cell physiology or function. Our study was designed to examine the effect of rat or pig collagen matrix and decellularized left ventricle extracellular matrix (dECM) tissues on the phenotype of human cardiac cells.

Human ECs, CMs and CPCs derived from IPs cells (Cellular Dynamics International) were cultured singly or together on rat or pig collagen matrices or on dECM. Protein and gene expression was investigated by immunohistochemistry, histology and real time PCR.

All 3 cell types survived on both types of support when delivered singly or together. Endothelial cell PECAM-1 expression was enhanced on decellularized tissues particularly on rat matrix. Cardiomyocyte contractile protein expression did not differ with support type, whereas CPC contractile protein gene expression increased on both decellularized tissues more so on pig matrix. Additionally, when the cells were co-cultured, single cell type gene expression was modified.

Our study showed that human cardiac cells are influenced by the structural support on which they are cultivated. Cardiac ECM enhanced the expression of contractile proteins and endothelial markers but matrix species had minimal influence on this effect. Furthermore, cell co-culture altered gene expression suggesting cell communication is intact on the matrix. This study shows that cell phenotype and behavior is impacted by the tissue matrix to a greater degree than occurs with a simple one protein support and suggests complex decellularized matrix may be superior to successfully engineer cardiac constructs with intact physiology. Additionally, the successful differentiation of IPs cells into cardiomyocytes on decellularized matrix opens avenue to build tissue engineer constructs from patients with heart disease as a screening tool.
Abstract 376: Sam68 Suppresses Autophagy in Macrophages and Promotes Atherosclerosis
Authors: Shi Jiawei , Han Shuling , Zhou Junlan , Yang Liu , Arnone Baron , Boriboun Chan , He Congcong , Qin Gangjian
Published: June 2021

Background:
Recent experimental evidence suggests that autophagy inhibits the pathogenesis of atherosclerosis. The Src-associated substrate during mitosis of 68 kDa (Sam68) belongs to the family of KH domain RNA binding protein; its role in macrophage autophagy and atherosclerosis has not been studied.

Methods & Results:
In Raw264.7 macrophage cell line, lentivirus-shRNA mediated knockdown of Sam68 (Sam68-KDn) led to a reduced level of LC3-I, LC3-II, and p62/sqstm1 proteins at basal culture condition, however, to a faster accumulation of these proteins with Bafliomycin A1 (autolysosome inhibitor) treatment, indicating an accelerated autophagy flux. Consistently, Sam68-KDn HeLa/GFP-LC3 cells displayed more autophagosome punctae counts (by immuno-fluorescent microscopy) and greater LC3-II specific median fluorescent intensity (by flow cytometry) than control HeLa/GFP-LC3 cells when treated with Bafliomycin A1. Notably, quantitative RT-PCR analyses revealed that Sam68-KDn did not alter mRNA expression of known major autophagy related genes (MAP1LC3B, SQSTM1, BECN1, Atg5, Atg7 and Atg12). Following induction of autophagy with different treatments including starvation (EBSS), Rapamycin (100nM), LPS (10ng/ml) and ox-LDL (50μg/ml), the autophagy flux was increased to a greater extent in Sam68-KDn cells than in control non-targeting cells. When treated with oxLDL and AcLDL, Sam68-KDn Raw264.7 cells and Sam68-null (Sam68-/-) peritoneal macrophages formed fewer foam cells and produced lesser amount of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) than control cells with an intact Sam68. Furthermore, the Sam68-/- peritoneal macrophages displayed an enhanced cholesterol efflux as compared to wild-type control cells. Lastly, ApoE-/-Sam68-/- mice developed a significantly smaller area of atherosclerotic lesions in the aorta and aortic valves than ApoE-/- mice after Western diet feeding for 12 weeks.

Conclusions:
Sam68 suppresses autophagy in macrophages, which may contribute to the development of atherosclerosis.
Abstract 133: Effectiveness of a Stem Cell-derived Therapeutic Factor Concentrate in a Mouse Embolic Stroke Model
Authors: Johnstone Brian H , Hoda Nasrul , Pandya Chirayu , Vaibhav Kumar , Fatima Sumbul , March Keith L , Hess David C
Published: June 2021

Background:
Early clinical trials of cell-based therapies in stroke have been very encouraging; however, technical hurdles may prevent widespread adoption. The salutary effects appear to be through release of “trophic” factors and immunomodulators which affect host repair and protection responses. We are developing a novel stroke therapy which is a clinically compliant cell-free, therapeutic factor concentrate (TFC) derived from adipose stem cell conditioned medium (ASC-CM). We will present data from a murine embolic stroke model study to determine the potential for clinical translation of TFC.

Methods:
Embolic stroke was induced in C57/Bl6 male mice (16 - 18 wks old) by delivering 9 - 10 mm clot into the middle cerebral artery (MCA) territory. Mice were randomly picked up for the intravenous treatments (either vehicle or 20/50/100 uL of TFC; N= 10/group) immediately after stroke. Neurological deficits were evaluated at 48 hrs post stroke, and mice were also tested for the somatosensory functions using adhesive tape removal test (ATT) at 72 hrs before the sacrifice for TTC-stained infarct analysis. Statistical significance was determined at P < 0.05.

Results:
Our data demonstrate a clear dose dependent response, with the highest dose tested (100 uL; ~4 mg total protein/kg body weight) being the most effective in the embolic stroke model. While the low-dose (20 uL; 0.8 mg/kg) did not show an effect in any outcomes measured, the middle dose (50 uL, ~2 mg/kg) was effective but less so than the highest dose (100 uL). TFC at 100 uL significantly improved neurological outcomes on Bederson scale, and also somatosensory function as determined by ATT. There was also a trend toward improved survival after stroke in 100 uL TFC treated group. Most importantly, while the 50 uL dose reduced the infarction volume by ~20%, the effect was >50% reduction with 100 uL treatment. TFC at any dose did not show any adverse effects such as the hemorrhagic transformation.

Conclusion:
TFC is a potential therapy to improve post-stroke outcomes. We are repeating these studies with ovariectomized female mice and extending the studies to 1 month. Future studies with this model will test TFC (1) in combination with IV-tPA, (2) with delayed delivery (up to 24 hours post-stroke), (3) and in aged animals.
Abstract 170: Role of Patent Foramen Ovale in First and Recurrent Childhood Cryptogenic Arterial Ischemic Stroke
Authors: Shih Evelyn K , Natarajan Shobha , Falkensammer Christine , Beslow Lauren A , Messe Steven R , Ichord Rebecca N
Published: June 2021

Background:
Numerous studies in adults have reported a robust association between patent foramen ovale (PFO) and cryptogenic arterial ischemic stroke (AIS), particularly in younger adults. The association between PFO and stroke in children has not been well characterized and the clinical significance of identifying a PFO in a child with first or recurrent cryptogenic stroke is currently unknown.

Methods:
We performed a retrospective case control analysis of a 10-year prospectively enrolled cohort of children with acute AIS who underwent transthoracic echocardiogram (TTE) as part of their diagnostic evaluation. We compared PFO prevalence in children with cryptogenic stroke to those with known stroke etiologies and to non-stroke controls. We also assessed stroke recurrence risk in children with vs without PFO and assessed PFO features that may confer higher stroke risk.

Results:
Of 119 children with first-ever AIS, 59 had TTE available for central review, of which 17 were cryptogenic and 42 had a known cause. PFO prevalence was higher in the cryptogenic stroke group (X, 24%) compared to both the known stroke etiology group (Y, 6%,
p
= 0.05) and non-stroke controls (Z, 8%,
p
= 0.05). However, 2 year recurrence free survival rates in stroke patients with PFO did not differ from those without PFO (HR 1.58, 95% CI 0.18-13.62,
p
= 0.68). PFOs in children with AIS vs controls had numerically more right-to-left shunt at rest (7 vs 0) and atrial septal aneurysm (4 vs 0) but the study was underpowered to look at these factors.

Conclusions:
In our prospectively enrolled cohort of children with AIS, we found the prevalence of PFO to be higher in children with cryptogenic stroke compared to healthy controls and non-cryptogenic stroke patients. The implication of PFO for risk of recurrence and optimal secondary preventative treatment remains uncertain and require further study.
Abstract 174: Headache Presentation in Childhood Arterial Ischemic Stroke Differs by Arteriopathy Subtype
Authors: Billinghurst Lori L , Hills Nancy K , Jastrzab Laura , Wintermark Max , deVeber Gabrielle A , Fullerton Heather J , Dowling Michael ,   The VIPS Investigators
Published: June 2021

Introduction:
Headache is common at onset of arterial ischemic stroke (AIS), with rates between 10-50%. Adult studies suggest that headache prevalence relates to stroke etiology, with highest rates observed in dissection. We hypothesized that children with arteriopathy-related stroke may have higher rates of headache than those without.

Methods:
Children (29 days -18 years) with AIS enrolled in the prospective, international Vascular Effects of Infection in Pediatric Stroke (VIPS) study were analyzed for presence of headache at stroke ictus. Cases were subjected to a rigorous, centralized process for diagnostic confirmation of AIS and radiographic classification of arteriopathy as definite, possible or absent. Site investigators abstracted data from medical records regarding stroke presentation details. Headache at stroke ictus was classified as present, absent or unclear.

Results:
We included all 355 VIPS cases in this secondary analysis. Headache was uncommon in subjects < 3 yo (5/90, 6%) but was present in nearly half of those ≥ 3 yo (108/265, 46%). Excluding those with an unclear headache presentation (n=31), there was no significant difference in headache at stroke ictus in children ≥ 3 yo with definite (46/92, 50%), possible (15/24, 63%) or absent (60/118, 51%) arteriopathy (p=0.53). However, in those with definite arteriopathy, a difference was found in sub-classification, with headache prevalence highest in dissection and transient cerebral arteriopathy of childhood (TCA) (70% each) (p>0.001). Acute headache was uncommon in children with moyamoya (12%).

Conclusion:
No difference was found in headache prevalence in children with and without definite or possible arteriopathy. However, in children with definite arteriopathy, headache was more common in TCA and dissection. This may reflect a higher degree of nociceptive afferent activation in these childhood AIS subtypes and may provide clues to underlying pathophysiologic mechanisms.
Abstract 215: Does the CT Angiography Spot Sign Identify Intracerebral Hemorrhage Patients More Likely to Benefit From Intensive Blood Pressure Reduction?
Authors: Morotti Andrea , Brouwers Bart H , Romero Javier M , Jessel Michael J , Vashkevich Anastasia , Schwab Kristin , Afzal Rauf , Cassarly Christy , Greenberg Steven M , Hebert Martin Renee’ , Qureshi Adnan I , Rosand Jonathan , Goldstein Joshua N ,   On behalf of ATACH-II and NETT Investigators
Published: June 2021

Background and Purpose:
the computed tomography angiography (CTA) spot sign is a strong predictor of intracerebral hemorrhage (ICH) expansion, and may mark those most likely to benefit from intensive blood pressure (BP) reduction. The Spot Sign score in restricting ICH growth (SCORE-IT) study analyzed whether intensive BP reduction improved outcome in Spot Sign positive patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) clinical trial.

Methods:
In ATACH-2, patients with ICH were randomly assigned to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment within 4.5 h from stroke onset. This analysis included patients with a CTA performed within 8 hours from onset. The association between intensive BP lowering, ICH expansion and functional outcome was investigated with a multivariable logistic regression model.

Results:
133 subjects met the inclusion criteria, of whom 53 (39.9%) had a spot sign and 24/123 (19.5%) experienced ICH expansion. A total of 56/123 patients had a 90 day modified Rankin scale (mRS) >3 (45.5%). Among Spot positive patients, 74.1% of those in the intensive BP lowering group had poor outcome, compared with 50.0% of those in the standard group (p=0.31). After adjustment for potential confounders, intensive BP lowering was not associated with a significant reduction of ICH expansion (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.27 - 2.51, p = 0.74) or improved functional outcome (OR for mRS>3 1.24, 95% CI 0.53 - 2.91, p = 0.62) in spot sign positive ICH patients.

Conclusions:
We found no evidence that ICH patients with a spot sign specifically benefit from intensive BP reduction.
Abstract 29: The Association Between General Anesthesia and Outcome of Endovascular Thrombectomy in Pooled Data From Five Randomized Trials
Authors: Campbell Bruce C , van Zwam Wim , Goyal Mayank , Menon Bijoy K , Dippel Diederik W , Demchuk Andrew , Dávalos Antoni , Majoie Charles B , Brown Scott , Saver Jeffrey L , Jovin Tudor G , Hill Michael D , Mitchell Peter J ,   HERMES Investigators
Published: June 2021

Background and purpose:
General anesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies. We examined the association between GA and thrombectomy outcomes in pooled data from five randomized trials.

Methods:
Patient-level data were pooled from trials comparing endovascular thrombectomy (predominantly using stent retrievers) with standard care in anterior circulation ischemic stroke patients (HERMES Collaboration): MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA. The primary outcome was ordinal analysis of modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models.

Results:
Of 1287 patients, 634 were allocated to endovascular thrombectomy and general anesthesia was used in 153/609 (25%) of endovascular-treated patients with anesthesia information available. Although dysphasic patients are sometimes felt to be less co-operative and require GA, the rate of GA was 25% in both right and left hemisphere patients. At baseline, GA and non-GA patients had similar age, NIHSS and time to randomization. Endovascular thrombectomy was associated with increased odds of improved functional outcome at 3 months, regardless of whether GA (cOR 1.73 95%CI 1.10-2.72, p=0.02) or non-GA (cOR 2.61 95%CI 2.01-3.40, p<0.001) was used. The odds of improved outcome were, however, significantly greater for those treated under non-GA (OR 1.59 95%CI 1.12-2.26, p=0.01). Pneumonia was more common in the GA group (16% vs 9% p=0.03). Rates of vessel perforation were similar in GA (0.7%) vs non-GA patients (1.8%, p=0.52). Delay between randomization and reperfusion was greater in GA versus non-GA patients (median 98 vs 75 min, p<0.001).

Conclusions:
Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment is still worthwhile in those who require anesthesia for medical reasons.
Abstract 37: ASPECTS and Stratified Outcomes After Endovascular Therapy in the Trevo Retriever Registry: Benefit in Low ASPECTS
Authors: Liebeskind David S , Woolf Graham W , Xiang Bin , Shields Ryan , Veznedaroglu Erol , English Joey , Baxter Blaise W , Budzik Ronald F , Bartolini Bruno M , Krajina Antonin , Sarraj Amrou , Narata Ana Paula , Miller Tim , Grobelny Thomas , Gupta Rishi , Jadhav Ashutosh , Nogueira Raul G ,   for the Trevo Retriever Registry Investigators
Published: June 2021

Background:
Most endovascular stroke therapy studies and subsequent guidelines restrict intervention based on ASPECTS. A wide range of ASPECTS scores may be encountered in practice and individual patient benefit may be realized even at low ASPECTS. We examined large-scale data on outcomes after endovascular therapy, stratified by baseline ASPECTS in the Trevo Retriever Registry.

Methods:
The independent Imaging Core Lab of the Trevo Retriever Registry prospectively determines ASPECTS on baseline imaging acquired immediately prior to endovascular thrombectomy. ASPECTS scores and regional involvement were analyzed with respect to site of arterial occlusion, effect of time from symptom onset, co-morbidities and clinical outcomes, based on ASPECTS strata.

Results:
Baseline ASPECTS data was reviewed by the Imaging Core Lab in 426 subjects with anterior circulation stroke enrolled in the Trevo Retriever Registry, as of July 2016. Mean age was 68.8 ± 13.7 yrs, with 20.9% > 80 years old. Baseline NIHSS was median 15.0 (10.0, 19.0). Onset to CT was median 3.8 (1.5, 9.0) hrs, with median ASPECTS of 8.0 (7.0, 9.0), ranging from 3-10. Baseline ASPECTS 0-7 occurred in 118/426 (27.7%) subjects, including 39.0% of ICA, 27.1% M1 and 16.9% M2/3 arterial occlusions at angiography. Baseline clinical variables predicting ASPECTS included age and NIHSS, whereas the ASPECTS score was mildly associated with final TICI2C reperfusion (r=0.24, p<0.001). Subsequent symptomatic ICH was 1.7% with baseline ASPECTS 0-7 versus 2.0% with ASPECTS 8-10. The distribution of mRS at 90 days based on individual ASPECTS strata from 10 to 3 revealed a trend to worse outcomes with lower ASPECTS, yet good outcomes (mRS 0-2) were 60.7% (ASPECTS 10), 55.3% (9), 60.2% (8), 54.9% (7), 55.1% (3-6).

Conclusions:
Discrete ASPECTS strata may influence outcomes of endovascular therapy conducted in routine practice around the world, yet individuals with low ASPECTS may still achieve reasonable outcomes.
Abstract 65: Effects of Immediate Blood Pressure Reduction on Two-Year Mortality and Major Disability in Patients With Acute Ischemic Stroke
Authors: He Jiang , Zhang Yonghong , Xu Tan , Wang Dali , Chen Chung-Shiuan , Sun Yingxian , Chen Jing ,   the CATIS investigators
Published: June 2021

Although elevated blood pressure (BP) is very common in patients with acute ischemic stroke, the management of hypertension among them remains controversial. We tested the effect of immediate BP reduction on two-year mortality and major disability in acute ischemic stroke patients. The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit. Mean SBP was reduced by 21.8 in the treatment group and 12.7 mm Hg in the control group within 24 hours after randomization (P<0.001). Mean SBP was 137.3 mm Hg in the treatment group and 146.5 in the control group at day 7 after randomization (P<0.001). At two-year follow-up, study outcomes were obtained in 1945 (95.4%) participants in the treatment group and 1925 (94.7%) in the control group. 78.8% of the patients in the treatment group and 72.6% in the control group reported the use of antihypertensive medications (p<0.001). SBP was 138.8 mmHg in the antihypertensive treatment group and 139.7 in the control group (p=0.02). Among patients in the antihypertensive treatment group, 24.5% (476/1945) died or had a major disability, compared with 22.1% (425/1925) in the control group (odds ratio 1.14 [95% CI 0.99 to 1.33], p=0.078). Hazard ratios for all-cause mortality (1.01 [0.81, 1.25], p=0.95), recurrent stroke (0.91 [0.73, 1.13], p=0.40), and vascular events (0.97 [0.79, 1.19], p=0.76) were not statistically significant comparing the antihypertensive treatment group to the control group. The effect of antihypertensive treatment did not differ by pre-defined subgroups. In conclusion, among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years.
Abstract TMP4: Serial ASPECTS from Baseline to 24 Hours: Impact of Endovascular Therapy in STRATIS
Authors: Liebeskind David S , Woolf Graham W , Mueller-Kronast Nils H , Aziz-Sultan M A , Froehler Michael T , Klucznik Richard P , Saver Jeffrey L , Sanossian Nerses , Zaidat Osama O , Haussen Diogo C , Hellinger Frank R , Yavagal Dileep R , Yao Tom L , Jahan Reza ,   for the STRATIS Investigators
Published: June 2021

Background:
Serial ASPECTS of ischemic stroke lesion evolution from baseline to 24-hours has been established as an effective surrogate endpoint in endovascular therapy. The use of this imaging shift has not been implemented beyond thrombectomy trials to estimate impact of endovascular therapy in large-scale registry data.

Methods:
The STRATIS Imaging Core Lab, blind to all clinical data, independently determined ASPECTS scores on baseline and 24-hour studies. ASPECTS regional involvement and resulting total scores were analyzed in anterior circulation occlusions in STRATIS. Statistical analyses calculated the proportion of subjects with 0 ASPECTS score shift and separately, those with shifts >4, 5, 6 points. Clinical predictors of ASPECTS shift and regional involvement were determined.

Results:
Baseline ASPECTS (n=517) was 8.2 ± 1.59 (median 8.0 (2, 10)) and 24-hour ASPECTS (n=547) was 6.0 ± 2.92 (median 7.0 (0, 10)). Serial ASPECTS (n=487) revealed change of -2.1 ± 2.41 (median-1.0 (-10, 3)). Absolutely no change in ASPECTS, or 0 shift from baseline to 24 hours, occurred in 157/487 (32%). Substantial ASPECTS decline of ≥4 occurred in 117/487 (24%), with ≥5 in 76/487 (16%) and ≥6 in 51/487 (10%). ASPECTS decline was linked with baseline collaterals (ASITN 4 (n=19; -0.9 ± 1.05); 3 (n=117; -0.8 ± 1.21); 2 (n=140; -2.6 ± 2.27); 1 (n=29; -3.6 ± 2.34); 0 (n=10; -4.2 ± 3.08)) and the degree of subsequent reperfusion (oTICI 3 (n=63; -1.1 ± 1.94); 2B (n=282; -1.9 ± 2.32); 2A (n=103; -3.4 ± 2.38); 1 (n=2; -3.0 ± 1.41); 0 (n=10; -4.0 ± 2.75)). Baseline predictors of ≥6 ASPECTS decline included previous TIA (OR 3.10 (95%CI 1.32, 7.31), diabetes (OR 2.23 (95%CI 1.22, 4.07)) and baseline NIHSS (OR 1.10 (95%CI 1.03, 1.16).

Conclusions:
Frozen ASPECTS or 0 shift from baseline to 24 hours occurs in about 1/3 of all cases treated with endovascular therapy in a large-scale registry. Poor collaterals, prior TIA, diabetes and elevated baseline NIHSS may be important predictors of those likely to experience infarct evolution despite reperfusion, identifying optimal candidates for neuroprotection with endovascular therapy.
Abstract TMP8: Predictors of Large Vessel Occlusion in Kaiser Stroke EXPRESS Program
Authors: Klingman Jeffrey G , Kim Anne C , Hatfield Meghan , Wilson Benjamin , Klingman Lauren , Nguyen-Huynh Mai N ,   on behalf of KPNC Stroke FORCE team
Published: June 2021

Background:
In 2015, trials showed that rapid endovascular stroke treatment (EST) of qualified patients with large vessel occlusion (LVO) resulted in improved outcomes over treatment with IV tPA alone. In 2015, Kaiser Permanente Northern California (KPNC) redesigned its acute stroke care work flow for its 21 stroke centers, which included expedited IV t-pa treatment, rapid CTA investigation, expedited transfer of appropriate patients for EST. We assessed for predictors of LVO post-implementation.

Methods:
The KPNC Stroke EXPRESS program was live in all centers by January 2016. Using clinical data for 1/1/16 - 7/10/16, we evaluated the frequency and locations of LVO, and patient characteristics of those with LVO. Multivariate logistic regression was used to examine whether age, gender, race, or an NIHSS ≥ 8 are predictors of LVO.

Results:
There were 2,204 tele-stroke alert cases from the ED. Among 993 (39.3%) that proceeded as likely acute stroke, 812 (81.8%) were evaluated with CTA. Out of those who had a CTA, 152 (18.7%) were found to have LVO as followed: 27 (17.8%) ICA, 87 (57.2%) M1, 24 (15.8%) M2, 6 (4.0%) basilar, 5 (3.3%) PCA, and 3 (2.0%) vertebral. Of those with LVO, 97 (63.8%) were treated with EST. Patients with LVO had a higher median NIHSS (15 vs. 5 in those without LVO). Neglect (27% vs. 7%) and gaze deviation (16% vs. 1%) were more likely to be seen among those with LVO and treated with EST compared to those without LVO. In multivariate analysis, age (OR=1.02, 95% CI 1.00 - 1.03, p=0.01) and NIHSS ≥8 (OR = 4.99, 95% CI 3.32- 7.49, p < 0.001) were associated with LVO. PPV for NIHSS ≥8 was 75.7%.

Conclusions:
In our large multi-ethnic population of acute stroke patients, a relatively small percentage (19%) was found to have LVO and only a subset qualified for EST. Predictors of LVO included NIHSS ≥8, increasing age, and presence of neglect and gaze preference. Given the low numbers of patients brought in for acute stroke treatment who ended up with a LVO requiring EST, further research is needed to assess a given system’s ability to rapidly evaluate and transfer as appropriate for EST rather than paramedic based diversion.