bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP312: Microglial Tmem119 Inhibits IRAK4 Activation and Confers Neuroprotection After Ischemic Stroke
Authors: Ngwa Conelius , Sharmeen Romana , Xu Yan , Li Jun , McCullough Louise D , Liu Fudong
Published: February 2024

Introduction:
Ischemic microglia trigger post-stroke inflammation leading to secondary neuronal death. Microglial responses are regulated through membrane protein signals that in turn activate inflammatory transcription factors. Transmembrane 119 (Tmem119) is a type 1A membrane protein that is exclusively expressed by microglia. It has been suggested that Tmem119 interferes with myeloid differentiation primary response 88 (MyD88)-interleukin-1 receptor-associated kinase 4 (IRAK4) axis that is involved in microglial activation. However, the exact role of Tmem119 in microglial activation has been elusive.

Hypothesis:
Tmem119 inhibits IRAK4 activation to suppress microglial pro-inflammatory responses and is protective against ischemic injury.

Methods:
Young (6-8-week-old) C57BL/6 WT mice were injected stereotaxically Lenti-Tmem119 to induce overexpression in microglia. Six weeks later, the mice were subjected to a 60-min middle cerebral artery occlusion (MCAO) model. Oxygen-glucose deprivation (OGD) was also performed in primary microglia cultures treated with Lenti-Tmem119 or Tmem119 siRNA. Western blotting was performed on brain homogenates or microglia cells respectively for expression of p-IRAK4. ELISA was conducted to measure cytokine levels in the plasma and cell culture supernatant.

Results:
p-IRAK4 protein levels were significantly lower in ischemic brains from Lenti-Tmem119 vs. Lenti-GFP injected mice (p=0.0035) at 3d after MCAO (n=4-6), accompanied by smaller infarct size in Lenti-Tmem119 injected mice. Cultured microglia treated with Lenti-Tmem119 or Tmem119 siRNA had decreased and increased expression of p-IRAK4 respectively than controls after OGD (p=0.0090 and p=0.0152 respectively, n=3-4). Pro-inflammatory cytokine (TNF-α, IL-1β, IL-6) levels were significantly lower in the plasma of Lenti-Tmem119 treated mice compared to controls. Levels of these cytokines were decreased or increased in microglia culture medium treated with Lenti-Tmem119 or Tmem119 siRNA respectively than in control treated medium.

Conclusion:
Tmem119 signaling regulates microglial inflammatory responses through interaction with IRAK4 and is beneficial to stroke.
Keywords:
Stroke; microglia; Tmem119; IRAK4; inflammation
Abstract WP316: Single-Cell RNA Sequencing Reveals a Massive Alteration in the Molecular Landscape of Microglia After Ischemic Stroke
Authors: del Águila Ángela , Zhang Ran , Dang Lihong , Yu Xinyuan , Sheng Huaxin , Yang Wei
Published: February 2024

Introduction:
Ischemic stroke, a prevalent and often devastating disease, remains poorly treated. Neuroinflammation is a key element of stroke pathophysiology and represents a promising therapeutic target. Among the central components driving neuroinflammation, microglia - the primary resident immune cells within the brain parenchyma - are key players in mediating the immune response in the stroke brain. However, how microglia respond to stroke is incompletely understood. In this study, we took advantage of a mouse genetic tool (ie, Tmem119-CreERT2), sorted microglia, and performed single-cell RNA sequencing (scRNA-seq) analysis using a mouse model of permanent stroke. Moreover, as stroke exhibits sexual dimorphism, we included both male and female mice.

Methods:
Young male and female Ai6/TMEM119-CreERT2;Ai6 (Tmem119-Ai6) mice with microglia labeled with ZsGreen underwent permanent middle cerebral artery occlusion (pMCAO) or sham surgery. On day 3 after stroke, ZsGreen+ cells (microglia) in the brain were isolated by FACS, and used for scRNA-seq analysis.

Results:
First, we confirmed that in Tmem119-Ai6 mice, expression of fluorescent ZsGreen was almost exclusively in microglia in the brain, with minimal presence in blood cells. Our unbiased scRNA-seq analysis of ZsGreen+ cells revealed 13 distinct microglial clusters after stroke. Importantly, 4 major stroke-related microglial clusters were identified. One cluster shared a gene signature with the reported disease-associated microglia (DAM) subset. The other 3 clusters were characterized by an interferon (IFN) response signature, a highly proliferative state, and a macrophage-like profile, respectively. RNA in situ hybridization analysis showed that cells from these clusters mainly resided within the stroke boundaries. Notably, our scRNA-seq data suggest no major sexual dimorphism in the microglial response to permanent stroke.

Conclusions:
This is the first scRNA-seq study with a focus on microglia in the context of sex and stroke. We propose that 4 microglial subsets may be deemed as common stroke-associated microglia. Future work will be designed to elucidate the functional significance of these subsets and their potential implications for stroke therapy.
Abstract WP318: Increased Synapse Elimination by Inflammatory Cells Contribute to Lon-Lasting Post-Stroke Memory Dysfunction in Aged Mice
Authors: Shabani nabikandi Zahra , Pan peipei , Li Qifeng , Wang Zhanqiang , Huo Kang , Su Hua
Published: February 2024

Background and Purpose:
Memory impairments are common after stroke. Memory dysfunction lasted longer in aged than in young mice, but the mechanisms are still unclear. Microglia maintain normal memory via removing excessive synapses and increase turnover of synaptic connections after stroke. Long-term memory deficits in aged mice may be associated with increased microglia in the brain.

Hypothesis:
Increased synapse removal by inflammatory cells contribute to the long-lasting post-stroke memory dysfunction of aged mice.

Methods:
Permanent distal middle cerebral artery occlusion (pMCAO) was induced in young and aged mice. The memory functions were analyzed weekly for 8 weeks by Y-maze test and at 8 weeks post stroke by novel objective recognition (NOR) test. Brain samples were collected 8 weeks after pMCAO induction. RNAseq analysis was performed to study gene expression profiles in peri-infarct area and hippocampus. Nissl staining was used to measure infarct volume and immunostaining was done to detect CD68
+
and GFAP
+
cells and synapse in peri-infarct region and hippocampus.

Results:
RNAseq data shown up-regulation of CD68, GFAP, pro-inflammatory cytokines, immune response, microglia chemotaxins and phagocytosis genes; and down-regulation of synaptic assembly and transmission, synaptic plasticity, and long-term potentiation genes in aged mice at peri-infarct region and ipsilateral hippocampi. Aged mice had larger infarct volumes, more CD68
+
and GFAP
+
cells in the peri-infarct region and ipsilateral hippocampi than young mice and had more CD68
+
cells in the ipsilateral than the contralateral hippocampi. In Y-maze test, aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than young stroke and sham operated aged mice. In the NOR test, aged stroke mice spent less time on the novel objects than young stroke and sham aged mice. Increased synaptophysin positive CD68
+
cells were detected in the hippocampi of aged stroke mice.

Conclusions:
Increase of synaptic elements by inflammatory cells contribute to the long-lasting post-stroke memory deficit in the aged mice, and reduction of neuroinflammation may improve their memory function.
Abstract WP320: Microemboli Model of Vascular Cognitive Impairment/Dementia (VCID) Presents With Long-Term Brain Tissue Hypoxia: Relevance to Endothelin-1 (ET-1)
Authors: Abdelsaid Kareem , Karakaya Eda , Li Alice , Edwards Jazlyn , JAMIL SARAH , Abdul Yasir , Li Weiguo , Ergul Adviye
Published: February 2024

Diabetes doubles the risk of VCID but the underlying reasons remain unclear. Given that diabetes mediates early endothelial dysfunction and activates the ET system, post-mortem brain ET-1 levels correlate with tissue hypoxia and disease severity in patients with dementia, and microemboli (ME) are more common in diabetic individuals, the goals of the current study were to investigate 1) the relationship between the brain ET system, hypoxia and neuroinflammation in a clinically relevant model of VCID, and 2) the impact of improving endothelial function on the ET system. At 10 weeks after the onset of diabetes, control and diabetic rats received cholesterol crystal ME (40-70 μm) injections and were monitored for 16 weeks. Another cohort received isosorbide mononitrate (ISMN, 75 mg/kg/day) and cilostazol (CZL, 60 mg/kg/day). Behavioral tests included novel object recognition (NOR) and Y-maze. After termination, brain tissue levels of ET-1/ETA/ETB, hypoxia markers myelin-associated glycoprotein (MAG), proteolipid protein-1 (PLP-1) and hypoxia-inducible factor-1α (HIF-1α), and microglia activation were analyzed by ELISA and immunoblotting. Diabetic animals had baseline deficits in certain cognitive domains that progressively worsened and treatment with (ISMN/CZL) prevented decline in cognitive function. HIF-1α levels were higher and MAG levels were lower in the ME cohorts indicating tissue hypoxia. MAG/PLP-1 ratio was even lower in diabetic ME animals (Table 1). ISMN/CZL treatment reduced HIF1α levels in the brain. While there was no dramatic change in plasma and brain tissue ET-1 levels, brain ET-1 levels correlated with HIF-1α (r
2
=0.53, p=0.0073) and MAG/PLP (r
2
=0.45, p=0.0167) in this model of VCID. The causal relationship between ET-1 and brain hypoxia, as well as neuroinflammation, needs further investigation. Strategies to improve vascular function by modulation of the ET system blockade can be a preventive and therapeutic strategy for VCID.
Abstract WP323: Late-Stage Degeneration Due to Middle-Cerebral Artery Occlusion Observed in White Matter Tracts and Specific Forebrain Regions in Middle-Aged Female Rats is Attenuated by mir20a-3p Treatment: A Magnetic Resonance-Diffusion Tensor Imaging and Conventional Morphometry Study
Authors: Sampath Dayalan , Singer Jacob , Gopalakrishnan Balaji , Hurst David A , Malone Robert , Noarbe Brenda P , Obenaus Andre , Sohrabji Farida
Published: February 2024

Introduction:
Our earlier studies show that the small non-coding RNA, mir20a-3p, is neuroprotective after stroke, and reduces sensory-motor impairments in the acute phase and cognitive decline in the long-term in female rats. Cognitive decline due to vascular diseases, such as stroke, is associated with volume loss in the cortex, the limbic structures and white matter tracts. In this study, we examined the volume of forebrain white matter tracts, cortical and limbic structures in animals with characterized cognitive impairment due to stroke, and the efficacy of microRNA treatment.

Methodology:
Middle-aged females were subjected to ischemic stroke using endothelin 1, injected adjacent to the left middle cerebral artery (MCA). Mir-20a-3p mimic (n=10) or scrambled oligo (n=8) was administered i.v. 4h, 24h and 70d post stroke. Animals were assessed periodically for cognitive performance up to 100d after stroke using both the cued fear conditioning test and the novel object recognition test (NORT). After perfusion fixation, T2 and diffusion tensor imaging (DTI) magnetic resonance imaging of the brain was performed. Thereafter, brains were processed for Weil myelin staining, followed by quantification of the corpus callosum and internal capsule.

Results:
Stroke resulted in impairment in both the cued fear conditioning test and the NORT, which was attenuated by mir-20a-3p treatment. Compared to sham (no-stroke) animals, volumetric analysis of DTI scans showed a significant reduction in the volume of substantia nigra (p<0.02) and the entorhinal cortex (P=0.0402) in stroke +scrambled group, but not in Stroke+ Mir20 treated group. White matter tracts showed a significant reduction in the corpus callosum and internal capsule volume in the ischemic hemisphere as compared to non-ischemic hemisphere in MCAo animals treated with the scrambled oligo. In contrast, sham and MCAo+Mir-20a-3p animals displayed no hemispheric differences in volume in either tract.

Conclusion:
Cognitive changes measured with remote fear memory retrieval and NORT were associated with volume reductions in the substantia nigra, the entorhinal cortex, and the major forebrain white matter tracts due to stroke. These stroke-induced deficits were attenuated in Mir-20-3p treated animals.
Abstract WP324: MCA/FeCl
3
Thromboembolic Model, an Easily Reproducible Model for COVID-19-Induced Embolic Cerebrovascular Complications
Authors: Corn Matthew R , Clifton Emily V , Heath Stan P , Hermanns Veronica C , Hafez Sherif S , Coucha Maha , Abdelsaid Mohammed A
Published: February 2024

COVID-19 neurological complications such as strokes and cognitive impairment have been reported. Yet the molecular mechanisms are under investigation. A mild and reproducible thromboembolic model will be a helpful tool for investigating COVID-thromboembolic complications. The aim of this study is to investigate the middle cerebral artery/ferric chloride (MCA/FeCl
3
) thromboembolic model as an easily and reproducible model for COVID-19-induced cerebrovascular embolic complications.

Methods:
SARS-CoV-2 spike-protein of the alpha variant were injected intravenously (4 ug/animal) in K18 (transgenic knock-in humanized ACE2 in epithelial cells). Seven days later, MCA/FeCl
3
thromboembolic model was induced in K18 mice by exposing the MCA and placing filter paper wet with FeCl
3
. Laser speckle imaging was used for the assessment of blood flow and recanalization after 1,2,6, and 24 hrs. TTC was used to assess the infarct volume. Cognitive function was assessed using a novel object recognition test. Cerebral vascular density and blood-brain barrier (BBB) were assessed by immunohistochemistry staining using Iso-B4 lectin and Occludin-5 antibody.

Results:
SARS-CoV-2 spike-protein caused a significant increase in the time required for vascular recanalization as detected by laser speckle imaging compared to control K18 mice. (P<0.05). In parallel, spike protein caused a significant increase in infarct size compared to control K18 mice (P<0.05). Our immunohistochemistry showed that spike protein decreased vascular density and increased vascular rarefaction compared to control K18 mice (P<0.05). A novel object recognition test showed that spike protein increased cognitive dysfunction compared to control (P<0.05). Western blot analysis showed that spike protein increased inflammatory markers and decreased BBB tight junction protein compared to control K18 mice (P<0.05).
In conclusion
, the MCA/FeCl
3
thromboembolic model is an easily reproducible mouse model to examine COVID-19-induced stroke and cerebrovascular complications.
Abstract WP326: Microclots, Erythrocytes, and the Coagulation Cascade in Long COVID
Authors: Walker Melanie , Venter Chantelle , Laubscher Gert J , Federico Emma , Pretorius Etheresia
Published: February 2024

Introduction:
The coagulation cascade in mammalian blood consists of a series of enzyme activation events in which proteins are activated in the next step of the cascade via limited proteolysis, resulting in polymerization of fibrin and the activation of platelets. The extrinsic, intrinsic, and common pathways are well-described. While typically protective, these pathways may also promote pathologic thrombosis, which is a leading cause of death and disability. An emerging concept is that COVID-induced endothelial injury initiates systemic activation of the extrinsic pathway, marked by direct protein-protein interactions with soluble fibrinogen molecules. In controlled in vitro settings, microclots can be induced using an array of substances including SARS-CoV-2 S1 spike protein. In this study, scanning electron microscopy (SEM) was used to visually demonstrate the detailed features of microclot interaction with erythrocytes at an ultrastructural level.

Methods:
SEM was performed on citrated whole blood of healthy individuals and patients with Long COVID. Whole blood smears from healthy controls and patients with Long COVID were placed on a glass coverslip, fixed in 4% formaldehyde, dehydrated in serial alcohol steps, coated with carbon and viewed with a scanning electron microscope (Carl Zeiss, Germany).

Results:
Proteolytic resistant fibrin microclots, spanning a size range of submicron to 200 μm, have a profound effect on the structure and function of erythrocytes (Figure 1).

Conclusion:
Long COVID microclots are characterized by an anomalous form of fibrin that is resistant to proteolysis (fibrinolysis). In addition to the possibility of microvascular ischemia, persistent microclots alter erythrocyte structure and may also entrap other proteins and stimulate production of various autoantibodies. Further study on the mechanism for microclot formation in Long COVID may lead to desperately needed novel treatment strategies.
Abstract WP44: Assessing Timely Care of WI's Critical Access Hospitals Acute Stroke Patients With a Speed and Efficiency Task Force
Authors: Bluma Dot , Bowser John , Abelt Susan , Erl Heidi , Pittenger Jeannie
Published: February 2024

Introduction:
Data indicates that rural residents are at 30% higher risk of stroke.
2
Thirty percent of Wisconsin’s (WI) residents live in a rural area and are more often served by smaller, critical access hospitals (CAH). WI Coverdell Stroke Program (Coverdell) data entry into Get With The Guidelines-Stroke® (GWTG) for 2022 shows 22.3% of stroke patient’s transfer from a spoke, often CAH, to a larger tertiary or hub hospital. To assist Coverdell participating (CAH) in timely care of acute stroke patients, Coverdell, American Heart Association® (AHA), and 32 CAH’s partnered to form a Speed and Efficiency Taskforce (TF).

Methods:
An agreed upon charter, framework and data goals were established in May 2022. Metrics of EMS pre-notification, arrival to CT, and door to needle (DTN) times were regularly reviewed. Evaluation of patients arriving within 4.5 hours of last known well (LKW), median DTN, and percent DTN < 60 minutes were analyzed in two arrival windows. Hypothesized differences when comparing arrival windows of 0700-1900 and 1901-0659 were that the 1901-0659 window would have extended treatment times due to lack of 24/7 CT coverage and LKW not validated from others.

Results:
Data analysis for 2022. N=179

• Arrival to CT: 10 minutes faster in 1901-0659 window

• Median DTN: 3 minutes faster in 0700-1900 window (71 vs 74 minutes respectively)

• % DTN within 60 minutes: 12% higher compliance in 0700-1900 window

Conclusions:
Coverdell CAH’s are initiating the CT in a timely manner. Times are lower for arrivals between 1901-0659, ruling out delays due to CT tech non-availability. Delays in DTN treatment times within 60 minutes of arrival are more significant in the 1901-0659 arrival timeframe. The potential causes are a delay in telestroke consult with decision to treat, internal hospital delays in mixing and delivering thrombolytics, CT availability, and family/significant others present. Further research regarding arrival time affecting treatment need to be considered.
Abstract WP49: Neuroscience Nurse Navigator Program Implementation: Impact on Inpatient & Outpatient Post Stroke Continuum
Authors: Patterson Michele J , MOORE TRACY , Blanchard Bonnie , Sanchez Briana
Published: February 2024

Background:
Comprehensive Stroke Program identified the need for a support system to ensure stroke patient [SP] follow-up [f/u] after discharge [DC] with [w/] Primary Care Physician [PCP] & specialized stroke services [SSS]: Neurology [NEURO] & Neurosurgery [NS]. The Neuroscience Nurse Navigator Program [NNN-P], implemented December 2019, included SP who received Alteplase [IV-A] or Mechanical Thrombectomy [MT]. Stroke order sets, revised 2020, included early DC planning [E-DC-P] for NNN-P coordination w/SSS & PCP offices, & updates to SP DC instructions. Individualized education included importance of f/u w/SSS & PCP & risk factor [RF] management, with barriers to care assessed. Contact information was verified with post DC calls at 3, 7, 30, & 90 days [d] w/Modified Rankin Score assessment [mRS-A] at 90d. SP satisfaction [SP-S] assessed via paper tool changed to Press Ganey in 2021.

Purpose:
Evaluate NNN-P impact on the Inpatient & Outpatient Post Stroke Continuum.

Method:
A retrospective review of 1,493 SP was conducted w/402 in the NNN-P. NNN-P records were reviewed for E-DC-P, days to f/u w/PCP & SSS, 90d mRS-A, & SP-S.

Results:
In the implementation year of 2020 there was an increase from 2019 in E-DC-P for PCP [60%], NEURO [38%], & NS [13%] w/an 18% increase in completed 90d mRS-A. The year after implementation showed an additional increase from 2020 in E-DC-P for PCP [28%], NEURO [32%], & NS [26%] w/a reduction in days to f/u for PCP [16d] & NEURO [20d]. In 2022 SP-S improved from 2021 for f/u instructions & RF [15%]. In 2023, sustained implementation, showed an overall increase from 2019 in E-DC-P for PCP [90%], NEURO [70%], & NS [57%] w/an overall reduction in days to f/u for NEURO [30d] & NS [16d] along w/improved SP-S for f/u instructions [27%] & RF [11%].

Conclusion:
The NNN-P established a support system that included coordination w/PCP & SSS offices as well as relationship building w/SP & family which resulted in improvement of timely f/u after DC, 90d mRS-A & SP satisfaction.
Abstract WP58: Intermittent Theta-Burst Stimulation Attenuates Oligodendrocytes Dysfunction and Alleviates Depression-Like Behaviors in Hypoxia-Ischemia Rats
Authors: Feng Yu , Huang Zhihai , Ma Xiaohui , Zong Xuemei , Zhang Quanguang
Published: February 2024

Rationale:
Perinatal hypoxic-ischemic (HI) brain injury is a significant cause of mortality and morbidity among newborns. Children who survive newborn hypoxic-ischemic encephalopathy (HIE) are at an increased risk of developing mood disturbances, characterized by neuronal injury and retarded myelin formation. To date, limited treatment methods are available to prevent or alleviate neurologic sequelae of HI. Intermittent theta-burst stimulation (iTBS) is considered a promising therapeutic tool for treating neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations.

Methods:
Postnatal day 10 Sprague-Dawley male and female rats were subjected to hypoxic (6% O
2
) conditions for 2 h after ligating the right common carotid artery. Transcranial application of iTBS (15 Gauss) was administered daily for seven consecutive days, starting either one day after HI insult (early iTBS) or 18 days after HI insult (late iTBS). Depression-like behaviors were examined 5 weeks after HI. The levels of oligodendrocyte progenitor cells (OPCs) proliferation, differentiation, and apoptosis, as well as the myelinating of oligodendrocytes (OLs) were measured and analyzed using immunofluorescence staining and automated western blot.

Results:
The male and female rats exposed to HI exhibited apparent OLs dysfunction, including a decrease in OPCs proliferation, a reduction in OPCs differentiation, diminished survival of OLs, and hindered myelination in the corpus callosum (CC) area. These alternations were concomitant with depression-like behaviors. Crucially, early iTBS treatment significantly alleviated HI-caused myelination damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment could not significantly impact these behavioral deficits.

Conclusion:
Our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms are suggested to be associated with the promoted the differentiation of OPCs and the alleviated myelination damage following iTBS administration.
Abstract WP65: Impact of Artificial Intelligence on Acute Ischemic Stroke Treatment in a Large Academic Healthcare System
Authors: Dohiem Mohamed , Sultny Abdallah , Al-Bayati Alhamza , Bhatt Nirav , Starr Matthew , Rocha Marcelo , Rios Rocha Lucas , Nogueira Raul G
Published: February 2024

Introduction:
We aimed to evaluate the impact of the implementation of a stroke triage artificial intelligence (AI) software on a large academic healthcare system.

Methods:
A retrospective study was conducted in our spoke and hub network comparing equal corresponding periods of pre- and post- Viz.ai implementation between January 2021 and December 2022. Door to needle, door to puncture (DTP), successful reperfusion rates, transfer rates, and clinical outcomes at discharge were compared.

Results:
The analysis encompassed a total of 5,456 patients including 2313 pre- and 2275 post-Viz.ai patients across 11 spokes and 416 pre- and 452 post-Viz.ai patients across 4 hubs. Among 868 patients undergoing EVT at the 4 hubs, there was no differences in baseline data except for a higher baseline NIHSS score in the post Viz.ai group. We found an overall absolute reduction of transfers by 60 cases equating to a statistically significant decrease of 2.3% (P=0.04). The results showed an overall decrease by 13.5 minutes (8.1%) which was not statistically significant (P=0.3). There was an overall statistically significant decrease of 6 minutes (9.5%) in DTP times from 63 (23-98) minutes to 57 (23-79) minutes (P=0.01). No other differences in outcomes were noted between both groups.

Conclusion:
The automatic AI software was able to show a notable impact in our hub and spoke mature network driven by decrease of unnecessary transfers, DIDO and DTP. These data support the role of AI software as an effective triaging tool in the stroke and hub networks. More studies are needed to confirm these results.
Abstract WP78: Large Vessel Occlusion Triage and Routing Utilized for Long-Distance Stroke Transports by Emergency Medical Services (LVO TRUST EMS)
Authors: Chionatos Rafail A , Valhuerdi Porto Camelia , Skeels Katelyn , Zebelean Devin , Leung Lester Y
Published: February 2024

Introduction:
Endovascular treatment (EVT) is the most effective therapy in acute ischemic stroke (AIS) with large vessel occlusion (LVO) but its practice is limited to comprehensive stroke centers (CSC). Previous studies have suggested that trained Emergency Medical Services (EMS) professionals can successfully detect LVO cases using a validated screening tool. For these cases, direct transfer to CSC bypassing community hospitals could lead to better outcomes.

Methods:
This is a retrospective cohort study from 01/01/2018-12/31/2022 of patients with suspected stroke transported by EMS providers from 14 community agencies (primarily fire paramedics) in Southeastern Massachusetts (EMS Region V). When stroke was suspected, EMS providers applied the Field Assessment Stroke Triage for Emergency Destination (FAST-ED) score to assess severity. Bypass of local community hospitals for direct transport to CSC was generally considered for patients with FAST-ED ≥4 and approval of the Region V EMS Medical Director, with the goal of early intervention for severe strokes. In addition to standard education on the use of the FAST-ED score, the EMS agencies received annual aggregate performance feedback and individual case feedback (when requested) from the CSC. Data were collected from the Electronic Health Record (EHR) on demographics, comorbidities, final diagnoses, FAST-ED scores, NIHSS and acute treatments. Descriptive statistics were performed to describe the accuracy of diagnosis and rates of treatment.

Results:
Among 166 triaged patients to go directly to CSC, 57.6% (95/166) were diagnosed with AIS, and 61.1% (58/95) of them were found to have LVO. There was a higher proportion of AIS or intracranial hemorrhage (ICH) in cases with higher FAST-ED scores. Only 23.4% (39/166) of the cases were diagnosed with stroke mimics, primarily related to lower FAST-ED scores. In total, 36.9% of patients with AIS received EVT: thrombectomy with standard window tPA (21.1%) or late presenter tPA (LKW ≥ 4.5 h, 1.1%), and without tPA (14.7%).

Conclusions:
A diverse group of community-based EMS services in Southeastern Massachusetts using a prehospital tool can identify patients with severe stroke, i.e. AIS due to LVO or ICH, with acceptable diagnostic accuracy.
Abstract WP81: Patient Characteristics Between Last Known Well and Symptom Onset Time: Patterns in the Time is Brain Study
Authors: Lalwani Dheeraj D , Scoleri Gianna , Mastrangelo Carissa , Rothfeld-Wehrwein Zach , Yadlapalli Vineetha , Zabinska Julia , Marshall Brandon D , Goedel William C , Bessey Sam , Dhand Amar , Sheth Kevin N
Published: February 2024

Background:
Acute reperfusion treatment reduces morbidity in Acute Ischemic Stroke (AIS). National guidelines use Last Known Well (LKW) estimates to determine eligibility. When LKW and symptom onset (SO) are “coupled,” treatment eligibility determination is easier. However, eligibility becomes complex when times are “decoupled,” such as in wake-up strokes. We aimed to understand social differences in AIS patients with coupled vs decoupled LKW and SO times.

Methods:
Time is Brain is an ongoing, multicenter study assessing effects of social network dynamics on pre-hospital delay in socioeconomically disadvantaged stroke patients. Demographics, stroke characteristics, tPA administration, LKW, and SO times were collected from electronic medical records or interviews from Jan to Jul 2023. Symptom onset-to-door (OTD) times were calculated. Fourteen out of seventy patients diagnosed with intracerebral hemorrhage or transient ischemic attack were excluded. Fifty-six were divided into Coupled or Decoupled LKW/SO conditions. Mann-Whitney U
,
and Fisher’s exact or Pearson X
2
tests were performed. Significance was defined as p<0.05.

Results:
Fifty-six patients diagnosed with AIS have been enrolled (mean age 67.0± 14.3, 54.3% Female, median NIHSS 2). 87.5% (n=49) self-identified as non-Hispanic and 17.9% (n=10) as Black. Fourteen patients had coupled and forty-two had decoupled LKW/SO times. Among those with decoupled times, 81.0% (n=34) had onset at home and 26.2% (n=11) awoke with symptoms. Cortical AIS was prevalent in both groups (58.8% v. 41.5%, p-value: 0.815). EMS use (58.8% v. 60.4%, p-value: 0.762) and tPA administration (23.5% v. 18.9%, p-value: 1.000) were comparable. Decoupled LKW/SO patients less commonly presented with dysarthria than coupled patients (29.4% v. 54.7%, p=0.036). Median OTD time of coupled v. decoupled groups was 458.5 v.105 min (IQR: 101.25-996.75 v. 60-390.0; p-value: 0.048).

Conclusions:
In our preliminary analysis of this multicenter cohort, three out of every four AIS stroke patients presented with decoupled LKW/SO times. Decoupling commonly occurred outside the wake-up stroke setting. Ongoing studies will discern patient-level social and clinical characteristics that describe these two important AIS populations.
Abstract WP87: To Walk-In or Not to Walk-In: Effects of ED Mode of Arrival on Acute Stroke Treatment and Hospitalization Outcomes in a Large Integrated Healthcare System
Authors: Nguyen-Huynh Mai N , Alexander Janet , Sax Dana , Zrelak Patricia A , Hatton Joeffrey , Sudhalkar Hemali , Klingman Jeff
Published: February 2024

Background:
Prior studies reported that only half of stroke patients arrived at emergency departments (ED) via emergency medical services (EMS). We sought to assess predictors of ED mode of arrival and its effects on acute stroke care and inpatient outcomes in a large racial-ethnically diverse cohort.

Methods:
In 2016, we launched a system-wide standardized telestroke program for 21 certified stroke centers. Non-cancelled stroke alerts included those patients who were potential candidates for further workup for acute ischemic stroke treatment. This study cohort included non-cancelled stroke alerts seen by Telestroke in 2021. Assessment included demographics, ED arrival mode , initial NIH Stroke Scale (NIHSS), neuroimaging results, IV thrombolytic, door-to-needle (DTN) time, large vessel occlusion (LVO), thrombectomy referral, hospital length of stay and discharge disposition. Clustered logistic regression was used to evaluate ED arrival mode’s effects on short-term outcomes.

Results:
Of the 7744 stroke alerts seen by Telestroke in 2021, 3264 (42.2%) were non-canceled. Among these, 2014 (61.7%) were in the early window (0-4.5 hours from last seen well). More of those arriving in the early window came via EMS compared to those seen in the extended window [1625 (80.7%) versus 729 (58.3%) respectively]. Among non-canceled ED stroke alerts, compared to patients who arrived via EMS, walk-in patients were younger, more Hispanic, had lower initial NIHSS scores, longer times for ED to contact Telestroke, slower DTN times, but less mortality [Table]. In multivariate analysis, walk-in patients were less likely to have a DTN time within 30 minutes (OR=0.37, 95% CI 0.25-0.34; p=<0.001).

Conclusions:
In our cohort, there were several differences between walk-in patients and those who arrived via EMS. Further research is needed to understand these differences, the reasons for choosing walk-in, and whether ED mode of arrival affects clinical outcomes.
Abstract WP89: National Assessment of Key Prehospital Stroke Care Practices and Their Association to Patient Characteristics
Authors: Green Alyssa M , Anderson Morgan K , Gage Christopher , van den Bergh Shea , Powell Jonathan , Panchal Ashish
Published: February 2024

Background:
Emergency medical service (EMS) clinicians provide time-sensitive care for patients with suspected stroke. While model evidence-based guidelines (EBG) exist, there is limited research on national adoption. Our objectives were to describe nationwide care delivery for suspected stroke patients and measure associations between guideline-compliant stroke care (GCSC) and patient characteristics.

Methods:
This retrospective analysis of the 2022 national ImageTrend Collaborate dataset evaluated 9-1-1 transported EMS incidents with primary impression of stroke. Included are advanced life support agencies with >6 annual strokes. Key components of GCSC from the National Model EMS Clinical Guidelines include documented stroke screen, 12-lead electrocardiogram, blood glucose (BG), onset time/last known well (LKW/Onset), pre-alert hospital notification, and scene time <15 minutes. Provision of GCSC was defined as providing at least five of the six components above. Multivariable logistic regression(OR,95%CI) used to describe the odds of GCSC adjusted for race/ethnicity, gender, and urbanicity.

Results:
In 2022, 43,555 events met inclusion criteria. Patients were commonly White (70.5%), female (52.3%), and with a median age 73 (IQR:62, 82). Most were in urban areas (88.2%) and had a dispatch complaint of stroke (56.1%). Key components of GCSC had varying degrees of compliance: stroke assessment (83.9%), LKW/Onset (93.7%), BG (85.1%), 12-lead (42.3%), pre-alert (58.7%) and on-scene time <15 minutes (58.9%). At least five components were completed in 43.0% of patients, and only 10.0% had all six. Adjusted odds of GCSC were higher for males (1.12,1.08-1.17), lower for Black/African American patients (0.71,0.67-0.76; referent: White), and lower for suburban and rural areas (0.52,0.48-0.56; 0.39,0.32-0.47; referent: urban).

Conclusion:
Prehospital GCSC delivery in the United States varies widely even with EBG’s providing a standardized approach. Variations in care are associated with gender, race, and urbanicity. Our results may be limited by reporting bias in the medical record. Future efforts may focus on agency-level implementation and documentation of these criteria to improve patient-based outcomes.
Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy
Authors: Pezzini Alessandro , Iacoviello Licia , Di Castelnuovo Augusto , Costanzo Simona , Tarantino Barbara , de Gaetano Giovanni , Zedde Marialuisa , Marcheselli Simona , Silvestrelli Giorgio , Ciccone Alfonso , DeLodovici Maria Luisa , Princiotta Cariddi Lucia , Paciaroni Maurizio , Azzini Cristiano , Padroni Marina , Gamba Massimo , Magoni Mauro , Del Sette Massimo , Tassi Rossana , De Franco Ivo Giuseppe , Cavallini Anna , Calabrò Rocco Salvatore , Cappellari Manuel , Giorli Elisa , Giacalone Giacomo , Lodigiani Corrado , Zenorini Mara , Valletta Francesco , Pascarella Rosario , Grisendi Ilaria , Assenza Federica , Napoli Manuela , Moratti Claudio , Acampa Maurizio , Grassi Mario ,   on behalf of the MUCH-Italy Investigators
Published: February 2024

BACKGROUND:

The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians.

METHODS:

In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the β-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores.

RESULTS:

Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56–0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58–0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65–0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64–0.74).

CONCLUSIONS:

Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.
Radial Versus Femoral Access for Mechanical Thrombectomy in Patients With Stroke: A Noninferiority Randomized Clinical Trial
Authors: Hernandez David , Requena Manuel , Olivé-Gadea Marta , de Dios Marta , Gramegna Laura Ludovica , Muchada Marian , García-Tornel Álvaro , Diana Francesco , Rizzo Federica , Rivera Eila , Rubiera Marta , Piñana Carlos , Rodrigo-Gisbert Marc , Rodríguez-Luna David , Pagola Jorge , Carmona Tomás , Juega Jesús , Rodríguez-Villatoro Noelia , Molina Carlos , Ribo Marc , Tomasello Alejandro
Published: February 2024

BACKGROUND:

Transfemoral access is predominantly used for mechanical thrombectomy in patients with stroke with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the noninferiority of radial access in terms of final recanalization.

METHODS:

The study was an investigator-initiated, single-center, evaluator-blinded, noninferiority randomized clinical trial. Patients with stroke undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5 mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (expanded Treatment in Cerebral Ischemia score, 2b–3) assigned by blinded evaluators. We established a noninferiority margin of −13.2%, considering an acceptable reduction of 15% in the expected recanalization rates.

RESULTS:

From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access and 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted 1 side risk difference [RD], −5.0% [95% CI, −6.61% to +13.1%]) showing noninferiority of transradial access. Median time from angiosuite arrival to first pass (femoral, 30 [interquartile range, 25–37] minutes versus radial: 41 [interquartile range, 33–62] minutes;
P
<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR, 28–74) versus radial: 59.5 (IQR, 44–81) minutes;
P
<0.050) were longer in the transradial access group. Both groups presented 1 severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (
P
=0.751).

CONCLUSIONS:

Among patients who underwent mechanical thrombectomy, transradial access was noninferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default first-line approach.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05225636.
Association of Assisted Reproductive Technology and Stroke During Hospitalization for Delivery in the United States
Authors: Dicpinigaitis Alis J. , Seitz Alison , Berkin Jill , Al-Mufti Fawaz , Kamel Hooman , Navi Babak B. , Pawar Anokhi , White Halina , Liberman Ava L.
Published: February 2024

INTRODUCTION:

Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data.

METHODS:

We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard
International Classification of Diseases, Tenth Revision
, Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users.

RESULTS:

Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all
P
<0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02–2.26);
P
<0.001).

CONCLUSIONS:

Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders.
On the identity of Dracocephalum breviflorum (Lamiaceae, Nepetoideae)
Authors: ZHANG RONG-QING , PATON ALAN J. , CHEN YA-PING , XIANG CHUN-LEI
Published: February 2024

As currently circumscribed, the genus Dracocephalum Linnaeus (1753: 594) includes the traditionally defined Hyssopus Linnaeus (1753: 569) and Lallemantia Fischer & Meyer (1840: 52), making it the second largest genus in subtribe Nepetinae (Nepetoideae, Lamiaceae), consisting of ca. 80 species (Chen et al. 2022). Morphologically, the genus is most similar to Nepeta Linnaeus (1753: 570), but it can be easily distinguished from the latter by its calyces with a thickened sinus-like fold between the bases of adjacent calyx lobes (Li & Hedge 1994; Harley et al. 2004). There are approximately 40 species of Dracocephalum distributed in China, of which 19 are endemic (Li & Hedge 1994; Chen et al. 2021, 2022). Among those endemic species, Dracocephalum breviflorum Turrill (1922: 154) was described on the basis of a specimen collected from Mount Everest area, southern Xizang (Tibet), China (A.F.R. Wollaston 255, K000911317). In the protologue, Turrill (1922) thought D. breviflorum is most similar to D. heterophyllum Bentham (1835: 738) but emphasized that the calyx morphology of the species (i.e., remarkably short and more distinctly 2-lipped than any previously known species of Dracocephalum) is unique in Dracocephalum. During our taxonomic revision of Dracocephalum in the Pan-Himalayan region, we found that D. breviflorum does not have a thickened sinus-like fold between the base of the calyx lobes, indicating it should be a member of the genus Nepeta. Given the importance of types in solving taxonomical issues (Wagensommer et al. 2016; Akhil et al. 2022; Perrino et al. 2023), we carefully compared the type specimens of both D. breviflorum and Nepeta coerulescens Maximowicz (1881: 529) (Fig. 1). In addition, we carried out observations of plants in the field (Fig. 2). The results of our research on herbarium specimens and in the field demonstrated that D. breviflorum and N. coerulescens are conspecific, and here we synonymize Dracocephalum breviflorum under Nepeta coerulescens.
Taxonomic notes on some neglected doryctine wasps (Hymenoptera: Braconidae) from Argentina described by J. Brèthes and E. Blanchard.
Authors: MARTÍNEZ JUAN JOSÉ , DIEZ FERNANDO
Published: February 2024

The type specimens of Austrodolops eremitae Blanchard, Doryctes ridiaschinae Brèthes, and Hormiopius ptericoptophagus Blanchard were studied and reclassified according to the current classification of the subfamily Doryctinae. The monotypic genera Austrodolops Blanchard and Hormiopius Blanchard are treated as junior synonyms of Allorhogas Gahan (syn. nov.) and Heterospilus Haliday (syn. nov.) respectively. Examination of the gall associated species D. ridiaschinae shows that it belongs in the genus Allorhogas. All species are redescribed and illustrated and the following new combinations are proposed: Allorhogas eremitae (Blanchard) (comb. nov.), Allorhogas ridiaschinae (Brèthes) (comb. nov.) and Heterospilus ptericoptophagus (Blanchard) (comb. nov.). Lectotypes are designated for all studied species and the genus Doryctes is excluded from the currently known Argentine fauna.
The Limnephilus bipunctatus Species Group in Turkey with the descriptions of two new species (Trichoptera, Limnephilidae)
Authors: SİPAHİLER FÜSUN
Published: February 2024

The Limnephilus bipunctatus Species Group in Turkey is studied with two new species, Limnephilus bayburt sp. n. from northeastern Turkey and Limnephilus bercalan sp. n. from eastern Turkey, described and illustrated. Four additional species, L. bipunctatus Curtis 1834, L. caucasicus Schmid 1955, L. malickyi Sipahiler 1992, and L. transcaucasicus Martynov 1909 are also redescribed and illustrated. Limnephilus transcaucasicus is a new record for the Turkish fauna.