bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract T P58: TPA Contraindications have Little Impact on Thrombolysis Outcomes
Authors: Parker Sarah , Ali Yasmin , Nair Deepak , McNeil Clayton , Mathews Maureen , Jahnel Jan , Swanson-Devlin Teresa , Beck Judith , Wang David 
Published: March 2022

Treatment with tPA is effective in patients with acute ischemic stroke but is only given to ~4% of patients. Part of what limits the use of tPA in acute stroke is the list of recognized contraindications (CIs) to tPA. Many of these CIs have little or no evidence describing how they may affect the safety of tPA. At the OSF Saint Francis comprehensive stroke center we have relaxed our definition of who can qualify for tPA.
Aggressively limiting what is considered a contraindication to tPA allows more patients to be treated safely and effectively.
We reviewed 218 patients who received tPA at our center from July 2010 to July 2014 to determine how many had one of 19 recognized CIs. Admission and discharge NIHSS, discharge MRS, discharge disposition and symptomatic ICH rates were compared in patients with CIs and those without.
Ninety (41%) of our patients were found to have one or more contraindication to tPA. There were a total of 157 CIs. The most common contraindication was NIHSS greater than 22 or less than 4 with 37 patients. The mean decrease in NIHSS from admission to discharge was 4 points in patients with CIs and those without CIs. There was no significant difference in the 43% of patients with CIs and the 42% of patients without CIs who had a good outcome on discharge defined as a discharge MRS of 0-2. There was no significant difference between the 64.8% of patients discharged to home or to rehab in the patients with CIs and the 66.1% of patients discharged to home or rehab who did not have CIs. There was also no significant difference between the 1% of patients with CIs who had symptomatic intracerebral hemorrhage and the 2% of patients without CIs with symptomatic intracerebral hemorrhage.
When making the decision to treat acute ischemic stroke with tPA, the risks & benefits of treating vs not treating should be weighed as they apply to each individual patient. Given our findings, we feel there is evidence that many contraindications to tPA should have less weight when making such decisions. This may increase the number of eligible patients who would receive treatment for stroke.
Abstract W MP7: Good Outcomes After Endovascular Therapy For Ischemic Stroke In Octogenarians Are Consistently Present If Final Infarct Volume Is Less Than 20 Cubic Centimeters
Authors: Giurgiutiu Dan-Victor , Jadhav Ashutosh P , Aghaebrahim Amin , Jankowitz Brian T , Ducruet Andrew F , Jovin Tudor G 
Published: March 2022

Background and Purpose:
Octogenarians are thought to have uniformly poor outcomes following endovascular therapy for stroke. We sought to verify whether this contention hold true when low final infarct volumes (FIV) are achieved following endovascular reperfusion.

Methods:
Retrospective analysis of an acute stroke endovascular database. Inclusion criteria: age ≥ 80, anterior circulation large vessel occlusion stroke, available outcomes and post procedural MRI allowing for FIV analysis.

Results:
A total of 1298 patients were identified of which 192 (15%) were octogenarians. Of those 95 with available brain MRI and follow up data were included. Baseline: Median age: 83, female: 67%, median admission NIHSS: 16.4, and median time to treatment: 4.7 hours. Occlusion location: M1 in 71 (73%), M2 in 7 (7%), ICA terminus in 17 (17%), and tandem occlusions in 9 (8.8%) of cases. Atrial fibrillation was found in 57% of cases. Median ASPECTS: 9.

Successful recanalization rate (TICI 2b, 3) was achieved in 74%, with a favorable outcome (mRS 0-2) in 23 patients (24%). Median FIV was 38.4 cc (mean 72.2 cc). In patients with favorable outcome, median FIV was 15 cc (interquartile range- IQR 2.4 to 24.5 cc), versus 55.8 cc (IQR 21.1 to 120.5 cc), p=0.0007 in patients with poor outcomes. In 31 patients (32.5%), the FIV was < 20 cc, and of those patients 14 (45%) had a favorable outcome, while only 9 (14%) of patients with FIV > 20 cc achieved favorable outcome, p=0.001. Mean ASPECTS in patients with FIV of < 20 cc was 9.23, versus 8.38 with FIV > 20 cc, p=0.0013.
In multivariate analysis, predictors of good outcome included FIV of < 20 cc (odds ratio (OR) 6.6, 95% CI 1.4-27.1), successful recanalization (OR 15.9, 95% CI 1.4 to 1.9), but not age, admission NIHSS, time to treatment or occlusion location.

Conclusions:
Final infarct volumes of < 20 cc after endovascular acute stroke intervention in octogenarians are associated nearly half of the times with good outcomes while larger final infarcts rarely result in good outcomes. Different baseline infarct thresholds may be necessary when selecting octogenarians vs younger stroke patients for endovascular therapy.
Abstract W P105: Lipopolysaccharide Exacerbates Stroke Severity and Compromises Mitochondrial Function in Cerebral Endothelium
Authors: Ren Xuefang , Doll Danielle N , Hu Heng , Sun Jiahong , Lewis Sara E , Rellick Stephanie L , Simpkins James W 
Published: March 2022

Stroke is the fourth leading cause of death in the U.S, with many cases leading to severe disabilities. Statistics reports present that more than 40% of ischemic stroke patients have recent prior infections. Acute infections initiate rapid inflammation and can be a trigger for acute ischemic stroke in people. Ischemia-reperfusion injury following ischemic stroke induces blood-brain barrier (BBB) breakdown, hyperpermeability and brain edema. Cerebral vascular endothelial cells (CVEC) lining the BBB play a key role in fluid leakage into the brain tissue. The expression of toll-like receptor 4 (TLR4, specific for bacteria-sourced lipopolysaccharide, LPS) on CVEC implicates that acute bacterial infections may directly target CVEC and regulate BBB permeability and integrity. High mitochondrial contents in BBB capillaries suggest mitochondrial mechanisms are important to maintain BBB integrity.
In order to test the hypothesis that bacterial infections regulate BBB permeability via mitochondrial mechanisms in stroke, we designed a series of studies both in vivo and in vitro. First, we used LPS challenged mice, then evaluated stroke outcomes including: infarct size, neurological deficits, BBB permeability and infiltration of neutrophils in the brain after transient middle cerebral artery occlusion (tMCAO). Second, we treated cultured CVEC with various concentrations of LPS and evaluated their mitochondrial function. Third, we impaired mitochondrial function in CVEC and investigated the BBB permeability in vitro.
Our results demonstrated that LPS (100ug/kg) prior to tMCAO administration significantly exacerbates stroke infarct volume, BBB permeability and neutrophil infiltration in the brain, and worsens neurological deficits in murine experimental stroke in vivo. In vitro, LPS significantly impaired mitochondrial oxidative phosphorylation and decreased maximal respiration and spare capacity in CVEC. Finally, pharmacological inhibition of mitochondria respiration disrupted tight junctions in CVEC monolayers and increased CVEC monolayer permeability in vitro.
These data are particularly important because they suggest a novel mitochondrial mechanism of the interactions between stroke and infections on BBB integrity.
Abstract W P112: Effects of Acute versus Post-acute Systemic Delivery of Neural Progenitor Cells on Neurological Recovery and Brain Remodeling After Focal Cerebral Ischemia in Mice
Authors: Doeppner Thorsten R , Kaltwasser Britta , Theli Mahesh K , Bretschneider Eva , Bähr Mathias , Hermann Dirk M 
Published: March 2022

Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests.
Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared to transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain-barrier (BBB), reduction of microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity.
Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment.
Abstract W P236: Role of Leukocyte Cathepsin G in an Atherothrombotic Stroke Model
Authors: Schunke Kathryn J , Koehler Raymond C , Faraday Nauder 
Published: March 2022

The majority of ischemic strokes in humans are caused by atheroemboli that originate from extracranial vessels, activate platelets and produce thrombi that occlude intracranial vessels. Most of the current stroke models do not simulate the mechanisms of endogenous thrombus interaction with blood elements, the vascular wall and its extracellular matrix, and thus do not translate well for the study of atherothrombotic mechanisms. To overcome these shortcomings, we developed an atherothrombotic stroke model. We used this model to determine the pathophysiologic role of leukocyte cathepsin G, a serine protease with pro-thrombotic properties, in stroke and to determine its suitability as a molecular target for therapy. We hypothesized that deficiency of cathepsin G will reduce intravascular thrombus formation, decrease infarct volume and improve neurobehavioral deficit in a mouse atherothrombotic stroke model.
Male C57Bl/6 (WT) and cathepsin G knockout mice (CG-/-) were used. A PE8 catheter was advanced into the ICA near the MCA origin and a reduction in cortical laser-Doppler flow was induced after a series of intra-arterial injections of collagen, a platelet activator and component of ruptured atherosclerotic plaque. Mice were sacrificed 3h post-collagen injection for histologic examination, or 48h post-collagen for infarct volume quantification and neurobehavioral assessment.
Gross examination of excised brains 3h post-collagen revealed thrombi within the main ICA in 71% (5/7) of WT mice and 0% of CG-/- mice (p=0.005), branches of the ICA in 0 WT mice and 29% (2/7) of CG-/- mice (p=0.13), in the main MCA in 43% (3/7) of WT mice and 0 CG-/- mice (p=0.05), and distal branches of the MCA in 100% (7/7) of WT and CG-/- mice. Immunofluorescence microscopy confirmed that platelets and fibrin were major components of these thrombi. Cerebral infarct in WT mice was 33% ± 9% of hemispheric volume and 19% ± 1% in CG-/- mice (p=0.02). Neurobehavioral deficit 48h post-collagen was reduced in CG-/- mice compared to WT.
Using a novel atherothrombotic stroke model, these data reveal an important role of cathepsin G in cerebrovascular thrombus formation and a novel mechanism linking inflammatory cells to ischemic brain injury- a link commonly observed in human clinical studies.
Abstract W P426: Vascular Filling Defect Shape and Density Of Thrombus In CT/CT-Angiography Predict Results Of Thrombectomy
Authors: Cardona Pedro , Quesada Helena , Lara Blanca , Cano Luis , Rubio Francisco , Aja Lucia , Barranco Roger , Escrig Ana M. , Mora Paloma 
Published: March 2022

BACKGROUND:
In acute thromboembolic stroke, mechanical recanalization with retrieval stents may result in immediate flow restoration and improve prognosis of patients. However, in up to 20% of cases, mechanical thrombectomy with stent retrievers results in poor angiographic outcomes (TICI 0-2a). Radiological findings on baseline CT scan and CT-angiography could predict recanalization rate and clinical outcome after thrombectomy.

METHODS:
We performed a retrospective analysis of patients with acute MCA or TICA occlusion treated with thrombectomy using retrievable stents between July 2010 to May 2014. We analyzed thrombus attenuations (Hounsfield Units, HU) in baseline noncontrast CT (NCCT), and shape of vascular filling defect in CT-angiography (CTA) that we correlate with arteriography study. Successful recanalization was considered with TICI 2b-3.

RESULTS:
A total of 183 patients were analyzed (142 had a M1 segment occluded, 25 a M2 and 16 a TICA occlusion on the admission CTA). Fifty-three percent of patients had received previously rtPA.

The mean age was 64.5 years+/-12 (46% women).The median NIHSS at presentation was 17 (range 6-26). Recanalization TICI 2b-3 was achieved in 78% of patients. Symptomatic hemorrhage occurred in 8% and good 90-day functional outcome (mRS ≤2) was achieved by 54%. Eighty percent of patients had a hyperdense thrombus evident on the baseline NCCT (mean 61+/-26 HU). In receiver operating characteristic (ROC) analysis attenuations of the clots was associated with higher rate of recanalization TICI 2b-3 ( AUC=0.782; p:0.001).
The shape of vascular filling defect contacting the thrombus by CTA (hook, sharp and abrupt shapes) correlates exactly in 98.5% with angiography series. Recanalization rates (TICI2b-3) were significant different in hook shape compared with sharp and abrupt shape group (85% vs 25%; p:0.001). Patients with hook shaped defect were associated with better clinical outcome compared with other shapes of filling defects (90 days mRS 0-2: 71% vs 38%, p:0.001).

CONCLUSIONS:
We found a significant association between characteristics of thrombus by NCCT/CTA and successful recanalization (TICI 2b-3). Shape and attenuation of thrombus could be predictive of technical success of thrombectomy.
Abstract 58: Ultra early CT-Perfusion May Overestimate Initial Infarct Core. The Ghost Infarct Core Concept
Authors: Boned Sandra , Tomasello Alejandro , Padroni Marina , Coscojuela Pilar , Cabero Jordi , Rodriguez-Luna David , Pagola Jorge , Muchada Marian , Rubiera Marta , Sanjuan Estela , Juega Jesus M. , Molina Carlos , Ribó Marc 
Published: March 2022

Identifying infarct core or irreversible infarct on admission is essential in order to establish the amount of salvageable tissue and indicate reperfusion therapies. CT perfusion (CTP) has been reported to be useful differentiating the penumbra as the mismatch between infarct core and hypoperfused brain. Infarct core is established on CTP as the severely hypoperfused areas, however the correlation between hypoperfusion and infarct core may be time dependent and not always true as it is not a direct tissue damage indicator.
We aim to characterize those cases in which admission core lesion on CTP does not reflect an infarct on follow-up imaging.

Methods:
We studied patients with ICA/MCA occlusion who underwent CTP on admission but received endovascular thrombectomy based on initial non-contrast CT ASPECTS≥7. Admission infarct core was measured on initial CBV-CTP and final infarct on follow-up imaging. We defined ghost infarct core (GIC) as: initial core - final infarct>10cc. Time from symptom onset to CTP was recorded. Recanalization (TICI2b3) was assessed after thrombectomy.

Results:
79 patients were studied: ICA/MCA occlusion 21/58, median NIHSS 17(11-20), mean time from symptoms to CTP: 218±143minutes. Recanalization rate was: 77% Mean CBV infarct core was 44±59cc, and mean final infarct volume was 38±70cc. 30 patients (38%) presented a GIC>10cc and 22(29%) a GIC>20cc. GIC>10cc was associated with recanalization (TICI2b3:44 Vs 17%; p=0.034), admission glicemia (<185mg/dl:42% Vs 0%; p=0.028) and time to CTP (185:26%; p=0.033). An adjusted logistic regression model showed time from symptom to CTP imaging 10cc (OR: 2.89, 95%CI: 1.04-8.09). Similar results were observed if infarct core was defined with CBF maps.

Conclusion:
CT perfusion may overestimate final infarct core especially in the early window from symptom onset. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who may still benefit from reperfusion.
Abstract TMP83: Modifiable Factors Influencing Timely Carotid Endarterectomy among Stroke Prevention Clinic Patients
Authors: Gocan Sophia , Bourgoin Aline , Blacquiere Dylan , Shamloul Rany , Stotts Grant 
Published: March 2022

For optimal stroke prevention following transient ischemic attack or minor stroke, international best practice guidelines recommend carotid endarterectomy for appropriate candidates as soon possible, with a target of less than two weeks. Research has demonstrated however, that delays to surgery occur frequently, in part due to complex clinical care processes. The goal of our study was to identify modifiable factors which could improve timely access to urgent carotid endarterectomy.
A retrospective chart review was competed, examining transient ischemic attack /stroke patients assessed in four regional Stroke Prevention Clinics between 2011 and 2014, who subsequently underwent carotid endarterectomy. Descriptive statistics were used to examine patient characteristics and time points to carotid surgery. A thematic analysis was performed to identify key factors which enhanced or delayed timelines to carotid endarterectomy. These themes were further analyzed to determine avoidable delays and key success factors.
Seventy-five records were eligible for study inclusion. Completion of carotid endarterectomy within two weeks was achieved for 21% of patients. Six key themes were identified including patient response to stroke, first health care contact, surgical fitness, resource capacity and physician availability (neurology or surgery). Forty four percent of patients did not present to medical attention the day of symptom onset contributing substantially to avoidable delays in care. Furthermore, 79% of patients experienced delays in access to vascular imaging, neurologist assessment and surgical bookings. Success was influenced by distinct triage, rapid diagnostic testing, and physician accessibility strategies. This often required divergence from standard clinical practices and interdepartmental collaboration.
Delayed patient presentation was the most common reason for delayed carotid endarterectomy which highlights the importance of ongoing public awareness strategies. Significant clinical delays were also noted at each step where patients required imaging or consultation. In order to reach carotid endarterectomy benchmarks, quality enhancement approaches will require coordinated, multifaceted care innovations.
Abstract TP104: A Novel
in vitro
Model of Cerebral Ischemia Using Patient-derived Induced Pluripotent Stem Cells
Authors: Page Shyanne , Munsell Alli , Alahmad Abraham 
Published: March 2022

Stroke constitutes the 5th cause of death in the United States and an important cause of morbidity. During ischemic stroke injury, the blood-brain barrier (BBB, part of the neurovascular unit) is compromised as brain microvascular endothelial cells (BMECs) loose their tight junctions complexes, resulting in the loss of the barrier function, unrestricted entrance of water and ions inside the brain parenchyma and neuronal cell death by excitotoxicity and cerebral edema formation.
Despite the important effort to find neuroprotective agents capable to partially improve neuronal cell survival and restore the BBB function, our ability to translate findings from animal studies to clinical trials is still hampered by an important failure rate. One of the possible caveats we hypothesize that contributes to such important failure rate is the absence of a pre-clinical human model capable to ease the translation. We speculate that a human in vitro model of the neurovascular unit encompassing human BMECs, neurons and astrocytes may help improve such translation.
In this study, we describe a novel in vitro model based on human induced pluripotent stem (iPSCs) cells. Using IMR90-c4 as an iPSC line, we were capable to differentiate BMECs, astrocytes and neurons.
Using oxygen-glucose deprivation (OGD stress), we were able to demonstrate the ability of our iPSC-derived BMECs to respond to such injury by a loss of the cell barrier function similarly, such cellular response was similar to hCMEC/D3 monolayers (an immortalized human BMEC line commonly used). In contrast, iPSC-derived astrocytes showed a remarkable compliance to prolonged OGD stress, showing some consistency with the previous literature. In the other hand, preliminary data obtained with iPSC-derived neurons displayed a rapid decrease in cell viability and increase in cell death suggesting similarities with studies using primary neural cell cultures.
Taken together, we document a differentiation protocol capable to obtain pure iPSC-derived BMECs, astrocytes and neurons lineages allowing us to investigate the cellular and molecular response to stroke injury in vitro. Such model may provide an interesting alternative model to improve our probability to identify novel stroke neuroprotective drug candidates.
Abstract TP411: Banner Health Stroke Coordinator Collaboration Lowers Door to Needle Times for the Banner Health System of Primary Stroke Centers
Authors: Bremer Jane A , Duke Kimberley A , Holland Donna L , Lombardo Carmen , Wikas Angie , Smith Evelyn , Liable Deborah A , Milakovich Rebecca D 
Published: March 2022

Background and Purpose:
The Banner Health (BH) System includes 7 hospitals that are certified as Primary Stroke Centers (PSCs) by The Joint Commission. Each PSC employs a Stroke Coordinator to oversee the stroke program, monitor data, and ensure compliance with Joint Commission standards. Many of the Coordinators struggled with unique difficulties and barriers within their individual programs. In October 2012, the Stroke Coordinators decided to form a committee and meet monthly with a focus on standardizing processes within the stroke programs across the BH System. This collaboration and sharing of common struggles and best practices has led to a decrease in door-to-needle times throughout the BH System and an increase in the utilization rate of this emergency treatment.

Methods:
The BH Stroke Coordinator Committee objectives:

-Stroke Core Measure review and development of a consistent process to resolve outliers
-Standardization of stroke alert and Core Measure tracking mechanisms
-Implementation of consistent metric reporting
-Sharing of best practices
-Joint Commission standard compliance
The Stroke Coordinator Committee reports to the BH System Interdisciplinary Neuroscience Clinical Consensus Group (Neuro CCG). The Neuro CCG approves revisions and updates to stroke care as indicated from the Stroke Coordinator Committee at the BH System level.

Results:

Conclusion:
Collaboration among the Stroke Coordinators and standardization of stroke care across the BH system resulted in lowering the average door-to-tPA times and increasing the tPA utilization across all 7 BH Primary Stroke Centers.