bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 26: Tcf7l1 Intrinsically Contributes to Cardiac Lineage Establishment
Authors: Liang Rui , Liu Yu 
Published: July 2021

T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) proteins are critical downstream effectors of the canonical Wnt pathway. Tcf7l1 is the most abundant among the four TCF/LEF proteins and acts as a key regulator of self-renewal in ESCs. It negatively modulates the expression level of pluripotent genes, and prepares the epiblast for transition to lineage specification. Tcf7l1-/- embryos show a range of defects related to axis misinduction. Some severely affected embryos lack the heart and somites. Because of defective axis induction, whether Tcf7l1 intrinsically contributes to cardiac development is unknown. Earlier work in our lab established that TCF/LEF proteins cooperate with Oct4 in driving the transcription of the cardiac mesoderm factor Mesp1, but the responsible TCF/LEF protein is not identified.
Here, we have built ESC systems to conditionally manipulate Tcf7l1 expression in a Tcf7l1-/- background. A combination of tTA/tet-O-Tcf7l1 transgenes allows us to temporally “knockout” Tcf7l1 with doxycycline, while a combination of rtTA/tet-O-Tcf7l1 transgenes allows us to temporally activate Tcf7l1 expression with doxycycline. We found that “knockout” of Tcf7l1 on day 4 during ESC differentiation caused decreased expression in cardiac genes including Tbx5, Nkx2-5, and α-MHC, without affecting the expression of Goosecoid, Eomes, and Brachyury, markers of mesendoderm development. Tcf7l1-/- ESCs showed slower progression toward mesoderm formation, but temporally activated Tcf7l1 induced cardiac gene expression after mesoderm was formed. Tcf7l1 ChIP-PCR demonstrated that Tcf7l1 bound to cis-regulatory regions of core cardiac transcription factor genes. Our data suggest that Tcf7l1 intrinsically contributes to cardiac lineage development through activating Mesp1 and downstream cardiac transcription factors.
Abstract 300: Topical Application of IcyHot Reduces Myocardial Infarct Size in Rodents by a TRPA1-dependent Mechanism
Authors: Wu Yun , Lu Yao , Gross Eric R 
Published: July 2021

Toxic reactive aldehydes are formed during ischemia-reperfusion. The ion channel transient receptor potential ankryin 1 (TRPA1) is irreversibly modified by reactive aldehydes which can cause calcium influx and cell death. Here we tested whether topically applied creams containing a reversible TRPA1 agonist could reduce myocardial infarct size.

Male Sprague-Dawley rats 8-10 weeks age were subjected to an
in vivo
myocardial ischemia-reperfusion model of 30 minutes of left anterior descending (LAD) coronary artery ischemia followed by 2 hours reperfusion. Prior to ischemia, rats were untreated or had 1g of cream applied to the abdomen. The creams tested were IcyHot, Bengay, Tiger Balm, or preparation H (Fig. 1A). Hearts were negatively stained for the area at risk and the infarct size was determined by using TTC staining (Fig. 1B). A subset of rodents prior to receiving IcyHot also received an intravenous bolus of the TRPA1 antagonist TCS-5861528 (1mg/kg) or AP-18 (1mg/kg).

Interestingly, both IcyHot and Bengay reduced myocardial infarct size compared to untreated rodents (Fig. 1C and 1D IcyHot: 41±3%*, Bengay: 50±2%* versus control 62±1%, n=6/group, *P<0.001). Both preparation H and Tiger Balm failed to reduce myocardial infarct size (Tiger Balm: 63±2%, preparation H 59±2%). Giving a TRPA1 antagonist prior to IcyHot also blocked the reduction in infarct size. Our additional data also indicates the methyl salicylate (mint) in IcyHot and Bengay is the agent that limits myocardial infarct size.
Since IcyHot and Bengay are safely used by humans, targeting TRPA1 by using products such as these could be quickly translatable and widely used to reduce ischemia-reperfusion injury.
Whole-Body Circulatory Autoregulation and Hypertension
Authors: COLEMAN THOMAS G. , GRANGER HARRIS J. , GUYTON ARTHUR C. 
Published: July 2021

A possible cause of elevated arterial pressure involves the interrelationship between autoregulation of blood flow and control of arterial blood pressure. An autoregulatory response could theoretically result in an elevated arterial pressure and an elevated peripheral resistance with normal or nearly normal cardiac output. Several experimental studies support this theory.
Autoregulation of blood flow has been observed in a number of the body's tissues, and the summated effect, whole-body autoregulation, has been demonstrated in areflex dogs. An increase in cardiac output precedes an increase in total peripheral resistance, and a decrease in cardiac output precedes a decrease in total peripheral resistance. The gain of the system was calculated to be slightly greater than three. This same hemodynamic pattern, that is, an increase in cardiac output preceding an increase in resistance, has been observed at the onset of hypertension. We have observed increases in cardiac output at the beginning of salt-induced hypertension in dogs and at the beginning of hypertension secondary to fluid volume expansion in anephric patients, while other investigators have observed this hemodynamic pattern in a number of instances, including labile hypertension, perinephritis hypertension, and Goldblatt hypertension. The increased cardiac output can be caused by several factors, although in many instances the cause appears to be fluid retention.
A hemodynamic response suggesting the involvement of whole-body autoregulation, that is, a decrease in cardiac output precedes a decrease in peripheral resistance, has been observed in the reversal of hypertension. Dehydrating overhydrated (and hypertensive) anephric patients and unclipping the renal artery in Goldblatt hypertension elicits this pattern, as well as administration of diuretics or several other antihypertensive drugs to hypertensives.
Theoretically, the role of the kidney in hypertension is either to initiate the autoregulatory response by causing fluid retention or to allow the autoregulatory response to occur by preventing the loss of fluid in the face of an elevated arterial pressure.
Abstract TP343: In-hospital Stroke: Patterns Of Care, Clinical Characteristics And Outcomes
Authors: Alves Monique B , Jaures Michele , Nogueira Paula S , Miranda Renata C , Laselva Claudia R , Coelho Fernando M , Silva Gisele S 
Published: July 2021

Epidemiological and clinical features of patients with in-hospital stroke are not well described in the literature. Our aim was to compare clinical characteristics and outcomes of patients who experienced a stroke during hospital admission with those who were admitted by the emergency department (ED)
Retrospective analysis of prospectively collected data from medical records. Clinical and demographic findings were analyzed. Modified Rankin Scale (mRs) was performed at discharge. We included patients who were admitted to a tertiary hospital with any disease and suffered an ischemic stroke (IS), intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) during admission and those that were admitted by the ED from Feb-09 to Jun-12.
We evaluated 501 patients. A total of 11.1% had in-hospital stroke (IHS). In patients with IHS, IS was more frequent 75,8%, followed by ICH 16.0% and SAH 8.9%. Patients who had IHS were similar to those who were admitted by the ED in age, type of stroke, gender and in the use of CT scan for diagnosis. Stroke was more severe in patients with IHS, NIHSS [7.0 (1-9) x 3.0 (3-15), p=0.007]. The median time between admission and stroke was 2.5 days [0,25-6]. When symptoms onset were noticed, 37.7% of the patients were on a regular ward, 32.1% in the ICU, 21.1% in a step down unit (21.1%) and 17.8% in the OR or interventional suite. A total of 39.3% of the patients were admitted for elective surgery, 23.2% for treatment of an infectious, 19.6% for cardiac diseases, 3.6% for cancer treatment and 10.7% for neurological diseases. Patients with IHS and those admitted by the ED were similar in the prevalence of stroke risk factors and in the frequency of complications rates. Thrombolysis rate was similar between the two groups. The mean length of stay was higher in IHS group [20 days 9-47 x 8 days 4-16, p<0.01]. Functional outcome measured by the mRs ≤ 2 at discharge was worse in patients with IHS [37.5% x 68.8%, p<0.005]. Patients with IHS had a higher chance of dying (OR3.52 [95% CI 1,85-6,69]).
In conclusion, patients with IHS had a worse prognosis and higher in-hospital mortality when compared to patients admitted because of an incident stroke. This is probably explained by more severe strokes in the IHS group in association with the presence of previous comorbidities
Abstract WP107: Optogenetic Stimulation of Human Neural Stem Cell Grafts In Ischemic Brain
Authors: Daadi Marcel , Lee Soo Yeun , Bajar Bryce , Lo Maisie , Ramakrishnan Charu , Sun Guohua , Deisseroth Karl , Steinberg Gary 
Published: July 2021

Optogenetically engineered neural stem cells (NSCs) provide a targeted approach to probe the role of neural circuits NSC-based cell therapy in experimental stroke models. A large body of work provides evidence that the therapeutic benefits of NSC grafts are mediated by replacement of cells lost to injury or disease and by secretion of neurotrophic and regenerative factors. Currently the potential of the grafted cells to modulate local circuits and to modify motor performances in animal model of ischemic brain injury is not well understood. This study explores whether optogenetic stimulation of NSC grafts will modulate neural differentiation and integration into the local circuitry.
We isolated multipotent NSCs from human embryonic stem cells. The NSCs were transduced with lentiviral vectors carrying the channelrodopsin-2 (ChR2) gene fused with enhanced yellow fluorescent protein (ChR2-EYFP) under the EF1alpha promoter. The ChR2 expression and response of the NSC progeny to blue light stimulation (470 nm) was confirmed in vitro. To test the function of these cells in stroke model, Sprague Dawley rats were subjected to middle cerebral artery occlusion (65 minutes). One week later, immunosuppressed rats received transplantation of NSCs (2 x 105) into the ischemic boundary zone in the striatum. Chronic optogenetic stimulation of the grafted cells was carried out daily after transplantation for 1 month. Five animal groups were established: vehicle, vehicle with stimulation, NSC transplant with chronic stimulation, NSC transplant without chronic stimulation and NSC with control (non-ChR2) vector. Animals in all groups were tested weekly for their motor performance through testing spontaneous forelimb use during lateral exploratory movement and the vibrissae-elicited forelimb-placing test. Preliminary results suggest that animals that received chronic stimulation showed an enhanced sensorimotor performance in comparison to animals that did not receive stimulation. The effects of long-term optogenetically-controlled stimulation of the grafted cells on the cellular differentiation and functional recovery in animals with ischemic brain injury will be presented.
Abstract WP31: Asymmetrical Internal Veins Sign In Acute Ischemic Stroke: A New Marker For Poor Collateral Circulation.
Authors: Dinia Lavinia , Carrera David , Raquel Delgado-Mederos , Joan Martí-Fàbregas , Munuera Del Cerro Josep Lluis 
Published: July 2021

INTRODUCTION:
Changes in venous drainage imaging have been directly related to parenchymal damage in acute ischemic stroke during endovascular treatment. Venous asymmetry assessed by CT prior to treatment may be directly related to delayed flow in the hypoperfused territory.

We investigated the prevalence of asymmetry in internal cerebral vein (AIV) drainage and its correlation with collateral flow in patients with acute ischemic stroke by a multimodal CT protocol.

Subjects and methods:
We retrospectively evaluated clinical and radiological data of 29 consecutive patients with acute anterior circulation ischemic stroke within 6 hours from symptoms onset. Collateral status was graded as good or poor depending on the extent of contrast visualized distal to the occlusion on CT angiography (CTA). Presence and AIV (analyzed by density units, time to peak and volume) and arterial collateral score were blinded assessed on CT perfusion (PCT), CTA source images (CTASI) and MIP reconstructions.

Results:
We included 29 patients, with a median age of 77 ± 15 y, and 31% of them were men. Median baseline NIHSS was 11 ± 7. Mean infarct ASPECTS was 9.3 ± 1 and size 2 cm3 ± 4. Asymmetrical veins were present in 33% of patients. This sign was more prevalent in patients with proximal occlusions than in distal occlusions (67% versus 33%) and in patients with poor collaterals compared to those with good collaterals (62% versus 29%).

AIV was significantly associated with increasing age (p= 0.03), increasing baseline NIHSS (p= 0.02) and poor collaterals (p=0.01).
Presence of AIV reached high specificity (93%) and good sensitivity (66%) for poor arterial collaterals prediction (p=0.001).

Conclusion:
Impairment of venous circulation, assessed by means of AIV, is present in one third of the patients and was associated with stroke severity and low effectiveness of collateral flow.

Presence of internal veins asymmetry is highly specific in detecting poor collateral circulation in acute stroke and may be a predictor of clinical and radiological severity, possibly useful for patients selection in planning reperfusion therapy strategies.
Abstract WP333: A Simplified Score to Predict Stroke Risk in Nonvalvular Atrial Fibrillation
Authors: Garrard Clare T , Amin Mahesh , Hakki Abdul H 
Published: July 2021

The widely used
CHADS2
score has been validated to predict the annual stroke risk (SR) in patients with non-valvular atrial fibrillation (AF). The
CHA2DS2-VASc
score incorporates 5 more risk factors including female gender, age 65 to 74 years, and peripheral arterial disease (PAD), prior myocardial infarct or aortic plaque. The two schemes have different SR and require separate tables to calculate SR
(Table 1)
.

Table 1
An acronym
(AFIB)2S4
+
PaF2 (Table 2)
is presented to predict SR that increases with higher scores, simplifies memorization of the score, incorporates all known risk factors and more accurately predicts SR without the use of tables.

Table 2
The SR per 100 patient-years is calculated by adding
(AFIB)2S4
+
PaF2
scores. For example if all are positive including age 75 years then the SR is 15%, while if all are negative, including age <65 and male gender, then the SR is 0.

To determine the predictive accuracy of the three scores, we reviewed the records of 100 consecutive patients admitted with acute cerebrovascular events and AF. The results showed 83% would have been classified as moderate to high risk (score>1) by
CHADS2
, 95% by
CHA2DS2-VASc
, and 99% by
(AFIB)2S4
+
PaF2.
(P <0.012).

Conclusion:
Compared to the
CHADS2
, and
CHA2DS2-VASc
,
(AFIB)2S4
+
PaF2
more accurately predicts risk of acute cerebrovascular events in patients with AF.

It is easy to remember and does not require the use of tables to assess SR in AF. Further studies are needed for validation.
PEN ©
Abstract WP339: Reducing Door-to-Needle Time for Acute Ischemic Stroke Thrombolysis in a Community Hospital
Authors: Linzey Jennifer , Shilling-Brewer Janet , Thibodeaux Mariaelena , Cory William , Berger Paulo , Neil William 
Published: July 2021

Reducing door-to-needle time [DTNT] for delivery of IV t-PA to acute ischemic stroke [AIS] patients improves functional outcome [1, 2]. Our community hospital sought to evaluate methods for improving DTNT in a non-academic center.
Weekly debriefings of all AIS cases were conducted to develop process improvement strategies using a rapid cycle test of change model; which allows for quickly implementing changes in organizational structure [3].
Paired t-test was used to compare mean DTNT before and after implementation of changes.
First, stroke patients arriving by ambulance were transferred directly to CT scan, eliminating the time delay of gurney transfers. The stroke team then started formal stroke debriefs, wherein areas for improvement were sought on an individual basis. In response to a delay due to IV tubing issues, pharmacy included tubing with the t-PA. Next, the algorithm was changed to allow ED staff to order t-PA while neurologist was en route. Later, a neurologist was assigned to be on-site at the hospital for immediate response. Pharmacy began hand delivering t-pa after a delivery delay due to miscommunication. After triage delays for atypical strokes, ED began pre-shift nursing messages and displayed posters that emphasized atypical stroke symptoms. Pharmacy designated one phone number to quickly communicate t-PA was to be given. The process improvements resulted in a significant reduction of average monthly DTNT by 7.56 minutes (p = 0.02) (Figure 1).
Weekly debriefings of AIS cases lead to policy changes which significantly reduced DTNT in our community hospital.

Saver, J.L., et al.: The “Golden Hour” and Acute Brain Ischemia; Stroke. 2010;41:1431-1439

Lees KR, et al: Time to treatment with intravenous alteplase and outcome in stroke; Lancet. 2010 May 15;375(9727):1695-703.

Langley G.L.: The Improvement Guide: A Practical Approach to Enhancing Organizational Performance 2009, 2
nd
ed. Jossey Bass, San Francisco
Abstract T P142: Mortality and Stroke Recurrence in Obese Stroke Patients: The Obesity Paradox in a London-Based Population
Authors: Gomes Filomena , Emery Peter W , Weekes Christine E 
Published: July 2021

INTRODUCTION

Several studies have shown a paradoxical association between body mass index (BMI) and mortality after stroke. However, the association between BMI, waist circumference (WC) and mortality and stroke recurrence is unclear.
This study aimed to determine the associations between BMI, WC and mortality and stroke recurrence at 6 months post stroke.

METHODS

Patients were recruited from consecutive admissions at 2 hyper-acute stroke units in London and were classified into 4 categories of BMI (underweight, normal weight, overweight and obese) and quartiles of WC. Outcomes were obtained for each patient through a national database that contains details of all hospital admissions.
Chi-square tests were used to compare mortality and stroke recurrence rates. Cox Proportional Hazards Models were used to compare mortality risk and survival curves between different BMI categories and WC quartiles.

RESULTS

Of 543 recruited patients, 51% were males and 87% had an ischaemic stroke, with a mean age of 74.7 years (range 22-99).

There were significant inverse associations between BMI and WC and risk of mortality at 6-months post-stroke (see table) (
p=0.001
and
p=0.04,
respectively). After adjusting for possible confounders (age, ethnicity, gender, severity and type of stroke, stroke risk factors), these associations were attenuated (
p=0.06
for BMI and
p=0.
11
for WC).

No significant differences were found in stroke recurrence rates between BMI groups (underweight 3.7%, normal weight 3.8%, overweight 4.5%, obese 2.8%; p=0.91) or WC quartiles (Q1 2.8%, Q2 5.1%, Q3 3.5%, Q4 3.6%; p=0.83).

CONCLUSION

After a stroke, being obese and having a larger waist circumference was associated with reduced mortality but did not affect the risk of a recurrent stroke.
Abstract T P276: Calling Stroke Alert: Does It Make a Difference in the Chain of Survival?
Authors: Small Cristine W , Price Donald L , Ferguson Jeffrey D , Madubeze Lawrence I , Freeman Susan D 
Published: July 2021

Purpose:
To determine whether the stroke alert process results in improved outcomes, as reflected in door to lytic times and other outcome measures.

Introduction:
The diagnosis and treatment of stroke is time-sensitive and should be inclusive of all seven D’s in the “chain of survival” - Detection, Dispatch, Delivery, Door, Data, Decision and Drug (Adams, Stroke, 2007). Early stroke activation is part of the “Delivery” which incorporates transport and management by Emergency Medical Services (EMS).

Clinical suspicion of stroke by EMS resulted in a process of early activation which was labeled “Stroke Alert.” This expedited the code stroke process upon arrival, preparing the hospital based stroke team to provide immediate triage and evaluation. The goal was to improve clinical efficiency and possibly clinical outcomes.

Methods:
• Implementation of a notification process from EMS to ED - Stroke Alert

• Incorporated Stroke Alert to include Stroke Response Team (SRT) nurses January 22, 2011
• Retrospective review of internal stroke database (January 22, 2011 to July 2013) for comparative analysis of Stroke Alerts called versus those where no stroke alert was called
• Evaluate clinical outcomes directly related to Stroke Alert process

Results:
From January 22, 2011 to July 2013:

Stroke Alert Called:
• 37 t-PA patients and 14 of those, 37.8%, met the 60 minute benchmark
• Average Door to Lytic time - 65 minutes Stroke Alert NOT Called:
• 35 t-PA patients and 10 of those, 28.6% met the 60 minute benchmark
• Average Door to Lytic time - 79 minutes

Conclusions:
The ability for a SRT to meet the golden hour of stroke benchmark occurs more frequently when a Stroke Alert is called to the SRT nurse. Future plans include review of stroke severity scores, length of stay (LOS), and discharge disposition, to determine the impact a Stroke Alert may have on clinical outcomes.
Abstract W MP31: Thrombotic and Hemorrhagic Complications After Pipeline Embolization - A Platelet Aggregation and Transcranial Doppler Study
Authors: Raychev Radoslav , Tateshima Satoshi , Vinuela Fernando , Jahan Reza , Gonzalez Nestor , Szeder Viktor , Bagude Amit , Konstas Angelos , Duckwiler Gary 
Published: July 2021

In this study, we sought to determine the correlation between the pre-treatment platelet aggregation, and the respective occurrence of thrombotic and hemorrhagic complications after pipeline embolization device (PED) for treatment of intracranial aneurysms. In addition, we evaluated the cerebral hemodynamics and the presence of silent emboli after PED placement in some patients utilizing transcranial Doppler (TCD).

Methods:
We analyzed the clinical and imaging characteristics of 46 consecutive patients who underwent 48 PED procedures. All patients received double antiplatelet therapy with Clopidogrel 75mg and Aspirin 325mg daily for at least 3 days prior to the planned procedure. Platelet aggregation testing was performed in 41/48 (86%) procedures. Based on the initial ADP % inhibition, patients were divided in 3 groups in the present study: 1) poor responders: <50%, 2) satisfactory responders: 50-75%, and 3) over-responders: > 75%

Results:
Hemorrhagic complications requiring escalation of care occurred in 15% (7/48) of all procedures, including 3 patients with symptomatic ICH. 2/3 ICHs occurred in a remote vascular territory in reference to the treated aneurysm, one of which was fatal. Thrombotic complications occurred at a rate of 13% (6/48), of which 3 (9%) were symptomatic. Permanent complication-related morbidity and mortality at 6 months was 4% (2/48).

Of all patients with available platelet aggregation testing (n=41), 13 (31%) were poor Clopidogrel responders. Of those, 6 were switched to an alternative antiplatelet regimen. Thrombotic complications occurred mostly in the poor responders group who had no change in their regimen (27% vs. 4%; p=0.05).
Intracranial hemorrhage occurred entirely in the over-responders group, (0% vs. 14%; p=0.08). None of the TCD demonstrated presence of silent emboli. In addition, 10/11 patients had elevated flow velocities after the PED placement.

Conclusions:

1. Pre-treatment Clopidogrel response, measured by ADP % inhibition may predict thrombotic and/or hemorrhagic complications after PED placement.
2. Distal embolization likely occurs mostly during, but not after the procedure as suggested by the TCD data in this study.