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Background: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain., Methods: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m 2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS)., Results: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25)., Conclusions: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy., Competing Interests: Declaration of competing interest Dr. Beyeler has received research support from the University of Bern, Switzerland. Dr. Navi has received personal fees for serving on an adjudication committee for MindRhythm Inc. Dr. Kamel reports serving as a PI for the ARCADIA trial (NIH/NINDSU01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; serving on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cardioembolism accounts globally for around 25% of ischemic strokes and is more often associated with higher rates of morbidity and mortality. Potential sources of cardioembolism into the intracranial circulation include paradoxic embolism, dysrhythmias, structural heart disease, and valvular heart disease. To identify the etiology of a patient's ischemic stroke, thorough investigation of the intracardiac structures, assessment of dysrhythmias, and consideration of high-risk events such as cardiac surgery are crucial. Treatment after cardioembolic stroke can be personalized based on the underlying cardioembolic source to minimize the risk of recurrent cerebral ischemic events., Competing Interests: Disclosure M.Y Yu and F.Z Caprio have no relevant disclosure. R.A. Bernstein has been a speaker and consultant for Medtronic, Astra Zeneca, Bristo Myers Squibb, Boehringer Ingelheim, and Abbott., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS)., Material and Methods: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase., Results: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke., Conclusions: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest to disclose regarding the manuscript entitled "Vertebral Artery Stump Syndrome: A Comprehensive Review of Diagnosis and Management," submitted for consideration for publication in Journal of Stroke Cerebrovascular Disease. We have no financial interests, research funding, employment or leadership roles, intellectual property rights, consultancies, or personal relationships that could potentially influence or be perceived to influence the content of this manuscript. We affirm that the work is original, has not been previously published or submitted elsewhere, and that we have not received any financial support or compensation for the preparation, writing, or submission of this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups., Materials and Methods: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test., Results: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients., Conclusions: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed., Competing Interests: Declaration of competing interest Dr Perera received grants from Bayer, which provided partial funding to Young ESUS, during the conduct of the study. Dr. Häusler reports personal fees from Bayer, which provided partial funding to Young ESUS study, during the conduct of the study. None of the other authors report any relevant competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: First, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes' etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality., Materials and Methods: All ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model., Results: 1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription., Conclusions: While atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke., Competing Interests: Declaration of competing interest The Authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis., Methods: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes., Results: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant., Conclusion: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Propensity for lesion lateralization in atrial fibrillation-related cardiac embolic stroke (AF-stroke) remains controversial. In this study, we compared the hemispheric differences among patients with AF-stroke and identified factors associated with lesion laterality., Methods: We retrospectively reviewed patients with acute AF-stroke admitted from January, 2017 to March, 2022. Patients were grouped based on whether lesions were right or left hemispheric in the anterior circulation territory, based on diffusion-weighted imaging. Factors associated with right-side propensity were analyzed., Results: Among 385 patients, the mean age was 74±11 years and 52.5 % were male. Right and left hemispheric lesions were observed in 189 (49.1 %) and 196 (50.9%) patients, respectively. In the multivariate analysis, enlarged left atrium (LA) (adjusted odds ratio [aOR]=1.03, 95% confidential interval [CI], 1.007-1.061; p=0.013) and single confluent lesion pattern (aOR= 1.55, 95% CI, 1.012-2.381; p=0.044) were associated with right hemispheric lesions., Conclusions: Enlarged LA and single confluent lesion pattern were strongly related to right-sided propensity in patients with AF-stroke., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The lack of superiority of anticoagulation over antiplatelet therapy in embolic stroke of undetermined source (ESUS) may be in part due to the misclassification of radiographic ESUS patterns as cardioembolic. In this imaging analysis, we sought to differentiate clinical and radiographic patterns of ESUS patients from patterns in patients with a highly probable cardioembolic source., Materials & Methods: A prospective registry of consecutive adults with acute infarction on diffusion-weighted magnetic resonance imaging was queried. Patients with infarctions due to small vessel disease, large vessel disease, and other causes were excluded. Multivariable logistic regression was used to identify independent predictors of two potentially embolic patterns: (1) multifocal and (2) cortical lesions, comparing patients with ESUS against those with atrial fibrillation (AF)., Results: Among 1243 screened patients, 343 (27.6%) experienced strokes due to ESUS or AF. Prior to the index stroke, patients with AF as compared to ESUS were older (median 75 vs. 65, p<0.01) and had more heart failure (25.9% vs. 8.4%, p<0.01). The odds of multifocal infarction were the same between patients with ESUS and both AF subtypes (p>0.05), however, cortical involvement was more associated with both AF versus ESUS (77.7% vs. 65.7%, P=0.02). A higher Fazekas grade of white matter disease was inversely associated with cortical infarction among included patients (aOR 0.77, 95% CI 0.62-0.96)., Conclusion: Cortical infarctions were twice as common among patients with AF versus ESUS. Subcortical infarct topography was strongly associated with chronic microvascular ischemic changes and therefore may not represent embolic phenomena. Larger-scale investigations are warranted to discern whether large or multifocal subcortical infarcts ought to be excluded from the ESUS designation., Competing Interests: Conflicts of Interest/Disclosures Dr. Siegler reports consulting fees (Ceribell) and for medicolegal work, and speakers bureau (AstraZeneca), all of which are unrelated to the present work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to determine whether oral anticoagulant therapy affects the severity of cerebral infarction at onset in elderly patients with non-valvular atrial fibrillation., Materials and Methods: This retrospective study included 330 elderly patients (aged ≥75 years) who were hospitalized for cardioembolic stroke due to non-valvular atrial fibrillation. Patients' medical history, stroke severity at onset (National Institutes of Health Stroke Scale score), and the prevalence of large vessel occlusion were compared between patients who received oral anticoagulant therapy (n = 109) and those who did not receive oral anticoagulant therapy (n = 221)., Results: Stroke severity was significantly lower in patients who received anticoagulants than in those who did not receive anticoagulants (6 versus 12; P = 0.021). Patients who did not receive anticoagulants had a significantly higher prevalence of large vessel occlusion (52% versus 37%; P = 0.010). After resampling based on propensity score matching, both median stroke severity (7 versus 12; P = 0.046) and large vessel occlusion prevalence (36% versus 57%; P = 0.019) were significantly lower in patients who received anticoagulant therapy., Conclusions: The results of this study suggest that elderly patients with non-valvular atrial fibrillation who are administered oral anticoagulant therapy before the onset of cerebral infarction develop less severe stroke than those who are not receiving oral anticoagulant therapy. Thus, oral anticoagulant therapy should be actively considered in patients with non-valvular atrial fibrillation as it does not only prevents cerebral embolism, but also reduces the risk of severe sequelae., Competing Interests: Declarations of interest I.D. received honoraria (e.g., lecture fees) from Bayer, Boehringer Ingelheim, and Daiichi Sankyo. T.O. received honoraria (e.g., lecture fees) from Bayer and Eisai. S.T. received honoraria (e.g., lecture fees) from Bayer, Eisai, and Daiichi Sankyo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified., Aims: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS., Materials and Methods: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample., Results: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors., Conclusions: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Embolic strokes of unknown source (ESUS) are common and often suspected to be caused by unrecognized paroxysmal atrial fibrillation (AF). An AI-enabled ECG (AI-ECG) during sinus rhythm has been shown to identify patients with unrecognized AF. We pursued this study to determine if the AI-ECG model differentiates between patients with ESUS and those with known causes of stroke, and to evaluate whether the AF prediction by AI-ECG among patients with ESUS was associated with the results of prolonged ambulatory cardiac rhythm monitoring., Materials and Methods: We reviewed consecutive patients admitted with acute ischemic stroke to a comprehensive stroke center between January 2018 and August 2019 and employed the TOAST classification to categorize the mechanisms of ischemia. Use and results of ambulatory cardiac rhythm monitoring after discharge were gathered. We ran the AI-ECG model to obtain AF probabilities from all ECGs acquired during the hospitalization and compared those probabilities in patients with ESUS versus those with known stroke causes (apart from AF), and between patients with and without AF detected by ambulatory cardiac rhythm monitoring., Results: The study cohort had 930 patients, including 263 patients (28.3%) with known AF or AF diagnosed during the index hospitalization and 265 cases (28.5%) categorized as ESUS. Ambulatory cardiac rhythm monitoring was performed in 226 (85.3%) patients with ESUS. AF probability by AI-ECG was not associated with ESUS. However, among patients with ESUS, the probability of AF by AI-ECG was associated with a higher likelihood of AF detection by ambulatory monitoring (P = 0.004). A probability of AF by AI-ECG greater than 0.20 was associated with AF detection by ambulatory cardiac rhythm monitoring with an OR of 5.47 (95% CI 1.51-22.51)., Conclusions: AI-ECG may help guide the use of prolonged ambulatory cardiac rhythm monitoring in patients with ESUS to identify those who might benefit from anticoagulation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The study aimed to investigate whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration and/or left atrial volume index (LAVI), as atrial cardiopathy biomarkers, were associated with infarct patterns on diffusion-weighted imaging in patients with embolic strokes of undetermined source (ESUS)., Materials and Method: We retrospectively evaluated patient with ESUS from our stroke registry between January 2018 and November 2019. Cut-off values for atrial cardiopathy biomarkers were defined as >250 pg/mL for NT-proBNP and >34 mL/m 2 for LAVI. Eligible patients were then assigned to 3 groups and infarct patterns were compared according to their atrial cardiopathy markers: Group 1 (no atrial cardiopathy markers), Group 2 (one marker), and Group 3 (both markers)., Results: Among 194 eligible patients with ESUS (76 women; mean age, 69.2 years), simultaneous increases of NT-proBNP concentration and LAVI were identified in 39 (20.1%). Group 3 had a significantly larger infarct volume, relative to Group 1 and Group 2 (P=0.043) Multivariable logistic regression analyses revealed that these patients (Group 3) were significantly more likely to have multi-territorial infarcts (adjusted odds ratio [aOR]: 3.03, 95% confidence interval [CI]: 1.05-8.72; P=0.04), a maximal lesion diameter >15mm (aOR: 4.51, 95% CI: 1.70-11.93; P=0.001), and large cortical infarctions (aOR: 4.17, 95% CI: 1.75-9.96; P=0.001)., Conclusion: We found that simultaneously increased values for NT-proBNP concentration and LAVI were independently associated with multi-territorial and large cortical infarct patterns in patients with ESUS. These findings suggest that NT-proBNP and LAVI may be useful biomarkers for identifying cardioembolic subtypes and guiding treatment selection in patients with ESUS., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Embolic stroke is a frequent complication of infective endocarditis yet lacks acute treatment as intravenous thrombolysis should be avoided due to high risk of intracerebral hemorrhage. Mechanical thrombectomy for large vessel occlusion may be a promising treatment but there is limited data on safety outcomes in infective endocarditis., Materials and Methods: In this multi-center retrospective case series, we reviewed data from patients with infective endocarditis-related large vessel occlusion who underwent mechanical thrombectomy in 9 US hospitals., Results: We identified 15 patients at 9 hospitals. A minority presented with signs suggesting infection (2 patients (14%) had fever, 7 (47%) were tachycardic, 2 (13%) were hypotensive, and 8 (53%) had leukocytosis). The median National Institute of Health Stroke Score decreased from 19 (range 9-25) at presentation to 7 post-thrombectomy (range 0-22, median best score post-thrombectomy), and the median modified Rankin Scale on or after discharge for survivors was 3 (range 0-6). Approximately 57% of patients had a modified Rankin Scale between 0 and 3 on or after discharge. Hemorrhagic transformation was observed in 7/15 (47%). The mechanical thrombectomy group had 2/9 petechial hemorrhagic transformation (22%), compared to 4/6 parenchymal hematomas (67%) in the tissue plasminogen activator + mechanical thrombectomy group., Conclusions: Our findings suggest that patients with large vessel occlusion due to infective endocarditis may not present with overt signs of infection. Mechanical thrombectomy may be an effective treatment in this patient population for whom intravenous thrombolysis should be avoided., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Experimental models have clearly demonstrated sex differences in the pathophysiology of stroke and prognosis, however clinical evidence remains elusive. In this study, we examined sex differences as a post hoc analysis of RELAXED (Recurrent Embolism Lessened by rivaroxaban, an anti-X agent, of Early Dosing for acute IS and TIA with atrial fibrillation) Study., Methods: We stratified study participants by sex and compared baseline and clinical characteristics as well as clinical outcomes. The primary outcome measure was a good outcome defined as a modified Rankin Scale score of 0-2 at 90 days after stroke. Secondary outcomes were mortality at 90 days, intracranial hemorrhage within 90 days, and recurrence of stroke or transient ischemic attack within 90 days. We constructed a logistic regression model to estimate the adjusted odds ratio of female patients compared with male patients for the primary and secondary outcomes., Results: Of 1303 patients, most were male (57.7%) with a mean age of 74.5 years. Female patients were older with a mean age of 80.6 ± 8.9 years and had significantly less frequent anticoagulation therapy before onset of stroke and more severe NIHSS scores. Good outcome was observed in 51.2% and 63.3% of the females and males (p < 0.0001). The adjusted odds ratio of a good outcome in females was 1.12 (95% confidence interval, 0.44-2.87) (p = 0.81). There were no sex differences in secondary outcomes., Conclusion: Adjusted regression analysis found no sex difference in the treatment outcomes at 90 days after stroke with non-valvular atrial fibrillation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Potential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke., Methods: We prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up., Results: Of 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively., Discussion: The MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The relationship between stroke etiology and clot pathology remains controversial., Materials and Methods: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed., Results: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots., Conclusions: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: In previous studies the risk of stroke recurrence has been associated with the left atrial appendage (LAA) morphology (non-chicken wing (NCW)), knowing those with a greater risk as malignant LAA. Recently, a simpler morphological classification has been suggested with two categories: Low-risk (LAA-L) and High-risk (LAA-H); which could be easier to apply and may correlate better with the risk of embolic stroke., Methods: Retrospective analysis from a registry of patients with recurrent cardioembolic strokes despite appropriate anticoagulant therapy, in which LAA morphology was studied with cardiac CT scan. LAA morphology was classified according to the four current categories and H-L morphology by the same cardiologist. Other variables associated with a high risk of stroke were also assessed, such as CHA 2 DS 2 -VASc score and left atrial (LA) size., Results: Twenty-six cases were included in the analysis. We identified 22 (84.6%) chicken wing (CW), 1 (3.8%) windsock and 3 (11.5%) cactus by the current classification system, while 15 (57.7%) were classified as LAA-H and 11 (42.3%) as LAA-L by the new system. Half of the 22 cases with CW morphology were considered LAA-H, whereas all NCW were also classified as LAA-H. LA diameter and area were significantly higher in cases with LAA-H morphology (p=0.03 and 0.014), and also in those CW and LAA-H, compared to those CW with LAA-L (p=0.035)., Conclusions: With this new classification system more than half of the cases of our malignant LAAs were classified as high-risk morphology. This morphology was also associated with an increased LA size., (Copyright © 2020 Elsevier Inc. All rights reserved.)