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Among patients with atrial fibrillation (AF) who have high risk of bleeding secondary to haematologic disorders, left atrial appendage (LAA) occlusion therapy has been shown to be an excellent alternative to long-term use of oral anticoagulation for thromboembolic stroke prevention. However, there remains a major concern of device-associated thrombosis post-procedure, that can lead to life-threatening embolic events. To this date, there is no systematic guideline for the selection and management of patients with haematological disorders with LAA occlusion therapy, especially in those with platelet disorders such as immune thrombocytopenia (ITP). Patients with platelet disorders are at a higher risk for bleeding; however, that does not prevent such patients from thromboembolic events secondary to AF. We present a case of ITP with permanent AF, where an LAA device was complicated by thrombus formation due to challenges faced with anticoagulation therapy.

Here is a case of a Pulmonary AVM in a female presenting with sudden onset of dizziness and vomiting most likely secondary to a paradoxical emboli causing an ischemic stroke of the cerebellum.

Aims Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. Methods Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx‐18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. Results Ang II‐induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood–brain barrier (BBB) leakage in Ang II‐induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. Conclusion Iron overload plays a key role in secondary bleeding after ICH in Ang II‐induced hypertensive mice. Iron chelation during the process of Ang II‐induced hypertension suppresses secondary bleeding after ICH., Iron accumulation in the brain tissues of Ang II‐induced hypertensive mice might exacerbate the loss of contractile VSMCs, enhance perivascular inflammation and BBB leakage. These factors might lead to increased vascular fragility and increased vulnerability to rupture, ultimately causing more secondary bleeding and subsequent HE after ICH.

Acute ischemic thromboembolic stroke is one of the most feared complications of atrial fibrillation (AF), and the risk increases with higher CHA2DS2-VASc scores. Postoperative atrial fibrillation (POAF) is common after noncardiac surgery, particularly after thoracic surgery, and can result in significant morbidity and mortality. We report the case of an 85-year-old female with a history of untreated hypertension (HTN) and no prior history of AF, who presented 5 days after an elective repair of a paraesophageal hernia with recurrence of a large type III paraesophageal hiatal hernia, AF, and subsequent acute thromboembolic ischemic stroke. Patient’s AF resolved shortly after treatment with calcium channel blocker. The risk of stroke is high in patients who develop AF and a period of 48 h after onset of AF is usually considered safe as the risk of stroke is low in this time period. However, this may not be the case during the perioperative period and preventive measures such as preoperative calcium channel blocker could be considered. Our case highlights that acute ischemic thromboembolic stroke might develop earlier tha 48 h after onset of POAF in patients undergoing paraesophageal hernia repair. Initiation of a calcium channel blocker should be considered during preoperative evaluation for patients undergoing paraesophageal hernia repairs, especially in those with untreated HTN.

Background Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC). Objective The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke. Methods Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized. Results Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases. In 80%, the LV lead was implanted down sPLSVC, and in 20%, sPLSVC was used to access the CS from the RA. Presumably because of unrecognized drainage from the CS to the LA, 1 patient had a stroke during implantation via sPLSVC. Conclusion When CS ostial abnormalities prevent access to the CS from the RA, sPLSVC can be used to successfully implant LV leads. In some, the CS partially drains into the LA and stroke can occur spontaneously or during lead intervention. It is important to distinguish sPLSVC associated with CS ostial abnormalities from isolated PLSVC.

Valvular heart disease affects more that 100 million people worldwide. Valvular replacement remains the only definite treatment for most of the patients with severe disease. Careful medical management and periodic follow-up of valve function is mandatory in order to prevent or diagnose prosthesis-related complications. We present a case of extensive mitral and aortic valve thrombosis and possible recurrent endocarditis in a 44-year-old woman non-adherent to anticoagulation therapy, presented with stroke. She also had a history of two mitral and aortic valvular heart replacement surgeries. Comprehensive and repeated imaging was used to evaluate and monitor the patient progression and outcome. Failure of adequate anticoagulation therapy to improve prosthesis function during hospitalization required third re-do surgery for mitral and aortic valve replacement with mechanical prosthesis.

Antithrombotic agents are widely used on the globe for prevention of thrombotic events such as atherothrombotic events and thromboembolic stroke in atrial fibrillation or for prevention and treatment of venous thromboembolism. However, the net clinical benefit of antithrombotic intervention may differ substantially in various sub-population of patients. Here, the authors attempt to address the risk of serious bleeding in East Asian as compared to the other regions of the world. The community-based epidemiological data suggest numerically higher risk of hemorrhage stroke in East Asian as compared to the globe. Importantly, the life-time risk of ischemic stroke in East Asia is higher than that of the globe. Regarding the serious bleeding risk in East Asians with the use of antithrombotic agents, various clinical trials and international registries provided conflicting information. It is hard to draw generalized conclusion, but there are some specific sub-population in East Asian with higher risk of specific serious bleeding events with the use of specific antithrombotic agents such as the risk of intra-cranial bleeding (ICH) with Vitamin K antagonists. Specific characteristics in East Asian such as higher prevalence of lacunar stroke may contribute higher risk of ICH in East Asian, but the detailed mechanism is still to be elucidated. In conclusion, further investigations are necessary to clarify the specific conditions where the risk of serious bleeding events in East Asian patients differ substantially compared to the global. In addition, further understanding of the mechanisms causing the different bleeding response in specific conditions in East Asian is awaited.

Introduction Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis (e.g. dilated cardiomyopathy), resulting in increased risk of thromboembolic complications. Historically, observational studies support the general safety and efficacy of warfarin for this indication. To date, limited data exists regarding the use of the direct oral anticoagulants (DOACs) for LV thrombus. Methods A retrospective cohort study utilizing electronic medical records was conducted from September 2012 - October 2018 at the University of Colorado Hospital System. Patients were included if they had any diagnosis of LV thrombus and received either a DOAC or warfarin within 90 days of diagnosis. The primary outcome was to determine the incidence of thromboembolic stroke in patients receiving a DOAC compared to warfarin. Secondary outcomes consisted of the composite incidence of thromboembolic events (stroke and systemic embolism), bleeding rates defined by the The Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria, and blood product administration. Chi square test was used to analyze categorical variables and the student's t-test and Wilcoxon Rank Sum test for continuous data. All statistical analyses were conducted using SAS. Results A total of 949 patients met inclusion, of whom 180 (19%) received a DOAC and 769 (81%) warfarin. Of the DOAC cohort, 77 (41.6%) received rivaroxaban, 79 (42.7%) apixaban, and 29 (15.7%) dabigatran. For baseline demographic information, see table 1. For the primary endpoint of new onset thromboembolic stroke on or within 90 days of LV thrombus diagnosis, no difference existed between treatment groups (DOAC: 7.8% vs warfarin: 11.7%, p=0.524). When compared to warfarin, no difference existed in the composite of thromboembolic events (33.1% vs 30.6%, P=0.524, respectively) or in GUSTO bleeding (11.1% vs 7.8%, p=0.397, for DOAC vs. warfarin, respectively). However, more patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p Conclusions Compared to warfarin, DOACs may be safe and efficacious for the treatment of LV thrombus, however further studies are warranted.

Background: Atrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke. Methods: EVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay. Results: Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes. Conclusions: Higher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) after stroke enhances C3a generation, which may abrogate the benefits of reperfusion. The C3aR antagonist SB290157 is neuroprotective following transient but not permanent middle cerebral artery occlusion (MCAo). SB290157 remains untested in thromboembolic (TE) models, which better approximate human stroke and also facilitate testing in combination with IVT. We hypothesized SB290157 would confer neuroprotection in TE stroke with and without “late” IVT. EXPERIMENTAL APPROACH: We used two different models of TE stroke to examine the efficacy of SB290157 alone and in combination with late IVT. We evaluated the benefit of SB290157 in attenuating post‐ischaemic behavioural deficits, infarction, brain oedema and haemorrhage. KEY RESULTS: Plasma C3a was elevated 6 hr after TE stroke alongside increased cerebrovascular C3aR expression, which was sustained to 4 weeks. Increased C3aR expression also was visualized in human ischaemic brain. In a photothrombotic (PT) stroke model, which exhibits rapid spontaneous reperfusion, SB290157 given at 1 hr post‐PT significantly improved neurofunction and reduced infarction at 48 hr. In an embolic (eMCAo) model, SB290157 administered at 2 hr improved histological and functional outcomes. Conversely, late IVT administered 4.5 hr post‐eMCAo was ineffective likely due to increased haemorrhage and brain oedema. However, SB290157 administered prior to late IVT ameliorated haemorrhage and oedema and improved outcomes. CONCLUSIONS AND IMPLICATIONS: We conclude that SB290157 is safe and effective with and without late IVT following TE stroke. Therefore, C3a receptor antagonist therapy represents a promising candidate for clinical translation in stroke, particularly as an adjuvant to IVT.

OBJECTIVE: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery.DESIGN: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed.PARTICIPANTS: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit.SETTING: Academic tertiary care medical center.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke.CONCLUSIONS: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery.

COVID-19 pneumonia has several complications, such as acute respiratory distress syndrome, septic shock, myocarditis, pulmonary embolism, and thromboembolic stroke. We present a case of a 71-year-old woman who was diagnosed with COVID-19 pneumonia and was found to have a pneumothorax, spontaneous pneumomediastinum (SPM), and subcutaneous emphysema without a history of lung disease. The pathophysiology of SPM and subcutaneous emphysema is likely caused by rupture of the alveolar membrane due to direct damage by COVID-19 infection and frequent cough-induced barotrauma.

IntroductionAtrial fibrillation (AF) is a major cardiovascular health problem: it is common, chronic and incurs substantial healthcare expenditure because of stroke. Oral anticoagulation reduces the risk of thromboembolic stroke in those at higher risk; but for a number of patients, stroke is the first manifestation of undetected AF. There is a rationale for the early diagnosis of AF, before the first complication occurs, but population-based screening is not recommended. Previous prediction models have been limited by their data sources and methodologies. An accurate model that uses existing routinely collected data is needed to inform clinicians of patient-level risk of AF, inform national screening policy and highlight predictors that may be amenable to primary prevention.Methods and analysisWe will investigate the application of a range of deep learning techniques, including an adapted convolutional neural network, recurrent neural network and Transformer, on routinely collected primary care data to create a personalised model predicting the risk of new-onset AF over a range of time periods. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the CPRD-AURUM dataset will be used for external geographical validation. Both comprise a sizeable representative population and are linked at patient-level to secondary care databases. The performance of the deep learning models will be compared against classic machine learning and traditional statistical predictive modelling methods. We will only use risk factors accessible in primary care and endow the model with the ability to update risk prediction as it is presented with new data, to make the model more useful in clinical practice.Ethics and disseminationPermissions for CPRD-GOLD and CPRD-AURUM datasets were obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences.Trial registration detailsA systematic review to incorporate within the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT04657900).

The ventricular non-compaction or spongy myocardium is a rare congenital cardiomyopathy which is caused by defective morphogenesis of myocardium during embryonic life. It is characterised by excessive, coarse trabeculations within ventricular myocardium beyond papillary muscle insertion which communicates freely with the ventricular cavity. This carries high risk for development of serious arrhythmia, thromboembolic stroke, pump failure etc. Isolated LV involvement is the most common presentation (68%) and biventricular involvement is the next most common presentation (22-38%). Isolated non-compaction of RV myocardium is a rare anomaly. We are hereby presenting such a case.

Heart valve replacements are commonly performed these days in India with mitral valve replacement being most common of all. Thromboemboli are a major source of morbidity in patients with prosthetic heart valves. The incidence of clinically recognizable events ranges from 0.6% to 2.3% per patient-year. Mechanical valve thrombosis is another common complication, incidence of which is estimated at 0.3% to 1.3% per patient-year in developed countries, but as high as 6% per patient-year in developing countries. Management of either complication in these patients requires adequate knowledge and clinical experience. We here describe a rare case of a patient who came to us with both complication of stuck mitral valve prosthesis and embolic stroke simultaneously. We here discuss the approach, monitoring and management of these patients, the clinical difficulties we faced in our case, immediate and short term prognosis of our patient.

Objective To assess different bridging anticoagulation therapies early after mechanical heart valve replacement (MHVR) in Chinese patients. Methods We performed a prospective, single-center, observational cohort study of 305 patients who underwent elective MHVR with different bridging anticoagulation regimens. Patients enrolled in the study were divided into three bridging therapy groups: the unfractionated heparin (UFH) group (n = 109), the low-molecular-weight heparin (LMWH) group (n = 97), and the UFH with sequential LMWH (UFH-LMWH) group (n = 99). All patients were followed for 4 weeks. Results Two patients experienced thromboembolic stroke events in the UFH group. The LMWH group was associated with an increase in the incidence of bleeding events compared with the UFH group (10.3% VS 2.8%; P = 0.03). With a comparison of LMWH and UFH group in secondary endpoints, the statistical test for significance indicated a trend of reduced ICU length of stay (P = 0.08), postoperative length of stay (P = 0.08) and time of achieving target INR (P = 0.06). The creatinine level (odds ratio = 1.03; 95% confidence interval = 1.01 to 1.05; P = 0.02) and hypertension (odds ratio = 3.72; 95% confidence interval = 1.35 to 10.28; P = 0.01) were risk factors for bleeding events. Conclusion For Chinese patients, the LMWH bridging anticoagulation presents the increased the incidence of bleeding events, but enables patients to benefit from achieving an early anticoagulation effect. Close follow-up and personalized management are required in patients with thromboembolic and bleeding risk factors. Trial registration Chinese Clinical Trial Registry ChiCTR1800019841. Registered 2 December 2018 retrospectively.

Physical exercise is known to reduce cardiovascular risk but its role in ischemic stroke is not clear. It was previously shown that an acute single bout of exercise reduced increased eNOS activation in the heart and reduced myocardial infarction. However, the impact of a single bout or short-term exercise on eNOS-induced neuroprotection after stroke was not previously studied. Accordingly, this study was designed to test the hypothesis that short-term acute exercise can provide “immediate neuroprotection” and improve stroke outcomes through induced eNOS activation. Male Wistar rats (300 g) were subjected to HIIT treadmill exercise for 4 days (25 min/day), break for 2 days, and then one acute bout for 30 min. Exercised animals were subjected to thromboembolic stroke 1 h, 6 h, 24 h, or 72 h after the last exercise session. At 24 h after stroke, control (sedentary) and exercised rats were tested for neurological outcomes, infarct size, and edema. The expression of active eNOS (p-S1177-eNOS) and active AMPK (p-T172-AMPK) was measured in the brain, cerebral vessels, and aorta. In an additional cohort, animals were treated with the eNOS inhibitor, L-NIO (I.P, 20 mg/kg), and stroked 1 h after exercise and compared with non-exercise animals. Acute exercise significantly reduced infarct size, edema, and improved functional outcomes, and significantly increased the expression of peNOS and pAMPK in the brain, cerebral vessels, and aorta. eNOS inhibition abolished the exercise-induced improvement in outcomes. Short-term acute preconditioning exercise reduced the neurovascular injury and improved functional outcomes after stroke through eNOS activation.

Internal carotid artery (ICA) stenosis, usually caused by atherosclerosis plaque, restricts the blood supply to the brain and causes cerebral ischemia. The plaque can be stable and asymptomatic, or it can cause embolization. An emboli can break from the plaque and travel to the blood vessels in the brain, causing a transient ischemic attack (TIA) or thromboembolic stroke. To reduce the risk of a stroke, estimation of the blood flow and stress distribution at the ICA stenosis is important. Common diagnostic methods, such as computed tomography (CT) and magnetic resonance imaging (MRI) are only able to provide a stenotic configuration. In addition, conventional image-based computational fluid dynamics (CFD) assumes the blood is a single-phase fluid, ignoring the circulating blood cell particles. This may result in an unreliable estimation of the blood flow and stress distribution at the ICA stenosis. Therefore, a multiphase particle-in-cell (MP-PIC) model was introduced to calculate the plasma flow and blood cell motion separately. The MP-PIC simulation showed a reverse flow, flow stagnation, and flow swigging at the stenosis that was not demonstrated by the single-phase model simulation. Thus, the blood cell motion caused significant temporal and spatial flow oscillation variations at the stenosis and must be considered in a hemodynamic simulation.

Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no-MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl−1, P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027 Tregs nl−1. Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE-2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl−1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012). Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl−1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery.

The poor clinical relevance of experimental models of stroke contributes to the translational failure between preclinical and clinical studies testing anti-inflammatory molecules for ischemic stroke. Here, we (i) describe the time course of inflammatory responses triggered by a thromboembolic model of ischemic stroke and (ii) we examine the efficacy of two clinically tested anti-inflammatory drugs: Minocycline or anti-CD49d antibodies (tested in stroke patients as Natalizumab) administered early (1 h) or late (48 h) after stroke onset. Radiological (lesion volume) and neurological (grip test) outcomes were evaluated at 24 h and 5 days after stroke. Immune cell responses peaked 48 h after stroke onset. Myeloid cells (microglia/macrophages, dendritic cells, and neutrophils) were already increased 24 h after stroke onset, peaked at 48 h, and remained increased—although to a lesser extent—5 days after stroke onset. CD8+ and CD4+ T-lymphocytes infiltrated the ipsilateral hemisphere later on (only from 48 h). These responses occurred together with a progressive blood-brain barrier leakage at the lesion site, starting 24 h after stroke onset. Lesion volume was maximal 24–48 h after stroke onset. Minocycline reduced both lesion volume and neurological deficit only when administered early after stroke onset. The blockade of leukocyte infiltration by anti-CD49d had no impact on lesion volume or long-term neurological deficit, independently of the timing of treatment. Our data are in accordance with the results of previous clinical reports on the use of Minocycline and Natalizumab on ischemic stroke. We thus propose the use of this clinically relevant model of thromboembolic stroke with recanalization for future testing of anti-inflammatory strategies for stroke.

Venomous snakes are found in every state and territory in Australia and are amongst the most dangerous in the world. Of Australia's snakes the Eastern Brown snake (Pseudonaja textilis) is responsible for the majority of the cases of envenomation and death. We describe a case of thromboembolic stroke associated with Eastern Brown snake envenomation in a 2-year-old boy. Following the incident, the boy has made a good recovery. Keywords: Snake bite, Stroke

Patient-centered care requires that treatments respond to the problematic situation of each patient in a manner that makes intellectual, emotional, and practical sense, an achievement that requires shared decision making (SDM). To implement SDM in practice, tools – sometimes called conversation aids or decision aids – are prepared by collating, curating, and presenting high quality, comprehensive, and up-to-date evidence. Yet, the literature offers limited guidance for how to make evidence support SDM. Here, we describe our approach and the challenges encountered during the development of Anticoagulation Choice, a conversation aid to help patients with atrial fibrillation and their clinicians jointly consider the risk of thromboembolic stroke and decide whether and how to respond to this risk with anticoagulation.

Takotsubo syndrome (TTS) is a poorly understood phenomenon that manifests as reversible myocardial damage. Despite the overall benign course of TTS, acute complications and significant mortality and morbidity are frequently encountered. However, the risk factors for developing such complications are not well determined. We present a case of reversible TTS within 48 hours after correction of cola-induced hypokalemia complicated by thromboembolic stroke. We present the patient's clinical presentation with imaging studies and discuss the case in light of related literature. A 62-year-old woman with a longstanding history of inadequate oral intake and excessively sweetened cola soft drinks consumption. Presented with progressive symmetrical quadriparesis and found to have severe hypokalemia with rhabdomyolysis, elevated troponin, and acute left ventricular dysfunction. The patient was diagnosed with TTS and hypokalemic paralysis. Her hospital course was complicated with an acute thromboembolic stroke of bilateral occipital lobes and left cerebellum. Takotsubo cardiomyopathy was reversible 48 hours after correction of severe hypokalemia. Cardiac ischemic workup was negative for any evidence of myocardial ischemia. In this presented case, TTS was revisable within 48 hours after the correction of cola-induced hypokalemia. However, patients with similar presentations might have a higher risk for in-hospital thromboembolic complications of TTS.

An ideal thromboembolic stroke model requires certain properties, including relatively simple surgical procedures with low mortality, a consistent infarction size and location, precipitation of platelet:fibrin intermixed blood clots similar to those in patients, and an adequate sensitivity to fibrinolytic treatment. The rose bengal (RB) dye-based photothrombotic stroke model meets the first two requirements but is highly refractory to tPA-mediated lytic treatment, presumably due to its platelet-rich, but fibrin-poor clot composition. We reason that combination of RB dye (50 mg/kg) and a sub-thrombotic dose of thrombin (80 U/kg) for photoactivation aimed at the proximal branch of middle cerebral artery (MCA) may produce fibrin-enriched and tPA-sensitive clots. Indeed, the thrombin and RB (T+RB)-combined photothrombosis model triggered mixed platelet:fibrin blood clots, as shown by immunostaining and immunoblots, and maintained consistent infarct sizes and locations plus low mortality. Moreover, intravenous injection of tPA (Alteplase, 10 mg/kg) within 2 h post-photoactivation significantly decreased the infarct size in T+RB photothrombosis. Thus, the thrombin-enhanced photothrombotic stroke model may be a useful experimental model to test novel thrombolytic therapies.

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration. This work was supported by grants from Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund “A Way to Achieve Europe” Health Strategic Action Program PI13/02258 and PI17/02123 (MC), PI20/00535 (IL), and Spanish Stroke Research Network RETICS RD12/0014/0010 (MC), and RD16/0019/0003 (JS), RD16/0019/0004 (MC), and RD16/0019/0009 (IL); from Regional Madrid Government B2017/BMD- 3688 (IL); from Spanish Ministry of Science and Innovation PID2019-106581RBI00 (MAM); from Leducq Foundation for Cardiovascular Research TNE-19CVD01 (MAM); and from Fundación La Caixa HR17_00527 (MAM). P. Comajoan was a recipient of a predoctoral fellowship from the University of Girona (IF-UdG 2015). Sí