Abstract Number: LBA23 Endovascular treatment of large vessel occlusion stroke caused by infective endocarditis

Introduction Infective endocarditis (IE) often presents as an acute ischemic stroke (AIS) secondary to a thromboembolic event leading to large vessel occlusion (LVO). These patients are at significant risk for intracerebral hemorrhage when given intravenous thrombolytics (IT) and are therefore better candidates for mechanical thrombectomy (MT). Current reports in the literature are divided on the safety of MT in this setting and no randomized control studies exist. With the advent of modern thrombectomy devices, we believe MT might be safe in this patient population. Methods Here we report a patient with IE who presented with LVO stroke (MCA syndrome) and underwent MT leading to first‐pass Thrombolysis inCerebral Infarction (TICI) score of 3 revascularization. In addition to presenting our case, we did a comprehensive review of the current literature on this topic. Results A thirty‐year‐old female with a history of cocaine abuse presented with acute onset left hemiplegia, dysarthria, and rightward gaze deviation. NIHSS was 19 and she presented 90 minutes from her last known well time . Computed Tomography (CT) head and CT perfusion imaging demonstrated a large MCA distribution stroke, an AlbertaStrokeProgram Early CT Score (ASPECTS) of 10, with significant perfusion mismatch of right MCA territory. CT angiography (CTA) confirmed a proximal large vessel occlusion (LVO) at the proximal M1. On initial assessment, the patient was febrile with a temperature of 40 degrees Celsius with a high clinical suspicion for IE; therefore, intravenous thrombolytic was not administered. MT was performed with one pull of stent retrieval under aspiration led to a successful opening of the vessel with TICI score of 3. Positive cocaine on urine toxicology was noted as well as, two sets of gram‐positive blood cultures which later resulted in Staph Aureus, oxacillin susceptible, unremarkable transthoracic echo, but with TEE demonstrating vegetative thickening within atrial aspects of both anterior andposterior mitral valve leaflets(Figure1). On hospital day two, magnetic resonance imaging of the brain shows small acute infarct with no bleed. The patient underwent a mitral valve replacement on hospital day nine. The patient was discharged to rehabilitation facilities with an NIHSS of two for mild left facial droop and mild left arm weakness; her degree of disability was measured as a modified Rankin Scale (mRS) one at 3 months. Conclusions In case IE is suspected, giving IV tPA (tissue‐type plasminogen activator) is contraindicated as it increases the chance of hemorrhagic complications and when LVO is confirmed in the setting of AIS, MT might be safe and effective to be considered

Endovascular Treatment of Large Vessel Occlusion Strokes Caused by Infective Endocarditis: A Systematic Review, Meta-Analysis, and Case Presentation

Thromboembolic events such as acute ischemic strokes are frequently seen in patients with infective endocarditis (IE). It is generally recommended that the administration of intravenous thrombolytics is avoided in these patients as they might encounter a higher risk of intracranial hemorrhages. In this setting, particularly with a large vessel occlusion (LVO), a mechanical thrombectomy may be an alternative option. In this systematic review and meta-analysis, we aimed to investigate the outcomes and safety of mechanical thrombectomies for LVO stroke patients secondary to IE. A search strategy was developed and we searched PubMed, Scopus, Web of Sciences, and Embase using the words “infective endocarditis”, “stroke”, and “mechanical thrombectomy”. Including 6 studies and 120 patients overall, this study showed that a mechanical thrombectomy might reduce the National Institute of Health Stroke Scale (NIHSS), with a weighted mean difference of −3.06 and a 95% CI of −4.43 to −1.70. The pooled rate of symptomatic intracranial hemorrhages and all-cause mortality were also determined to be 15% (95% CI: 4–47%) and 34% (95% CI:14–61%), respectively. The results of this study showed that a mechanical thrombectomy might be an effective and reasonably safe option for the treatment of LVO strokes caused by IE. However, more large-scale studies are needed to consolidate these results

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research

Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling

Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy