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Background: Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population. Methods: A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions. Results: Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54–74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1–4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P P =0.01), dyslipidemia (56.4% versus 40.0%, P =0.01), and coronary artery disease (22.8% versus 11.3%, P =0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0–3] versus 1.5 mm [IQR 0–2.6], P P P =0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P =0.02). Conclusions: Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.

The current undergraduate radiology education predominantly integrates radiology with other disciplines during preclerkship years and is often taught by nonradiologists. Early exposure to radiology and profound understanding of scientific fundamentals of imaging modalities and techniques are essential for a better understanding and interest in the specialty. Furthermore, the COVID-19 pandemic-related impact on in-person medical education aggravated the need for alternative virtual teaching initiatives to provide essential knowledge to medical students.The authors designed an online 7-session course on the principles of imaging modalities for medical students and fresh graduates in the United States and abroad. The course was delivered online and taught by radiologists from different US institutions. Pretests and posttests were delivered before and after each session, respectively, to assess change in knowledge. At the end of the course, a survey was distributed among students to collect their assessment and feedback.A total of 162 students and interns initially enrolled in the program by completing a sign-up interest form. An average of 65 participants attended each live session, with the highest attendance being 93 live attendees. An average of 44 attendees completed both the pretest and posttest for each session. There was a statistically significant increase in posttest scores compared with pretest scores ( P0.01) for each session; on average, the posttest scores were 48% higher than the pretest scores. A total of 84 participants answered the end-of-course survey. A total of 11% of the respondents described themselves as first year, 17% as second year, 18% as third year, 21% as fourth year, and 33% as "other." Attendees were enrolled in medical schools across 21 different countries with 35% of the respondents studying medicine in the United States. More than 76% of the respondents stated that they "strongly agree" that the program increased their understanding of radiology, increased their interest in radiology, and would be useful in their clinical practice in the future. Eighty-three percent of the respondents stated that they "strongly agree" that "this course was a worthwhile experience." Particularly, more than 84% of the respondents stated that among the most important components in enhancing their understanding of radiology were "the interpretation of normal imaging" and "interpretation of clinical cases." Ninety-two percent of the respondents stated that "the amount of effort to complete the requirements for this program was just right." Participants were also asked to rate each of the 8 sessions using the following scale: poor = 1 point, fair = 2, good = 3, and excellent = 4. The average rating for all 8 sessions was 3.61 points (SD = 0.55), which translates to 96% of the sessions being rated good or excellent. Eighty percent of the participants reported that the topics presented in the program were "excellent and clinically important to learn," and 20% of the participants reported that the topics presented were "good and somewhat important to learn." The participants were asked to evaluate their confidence regarding basic radiology skills before and after the program using the following scale: not confident at all = 1 point, somewhat confident = 2, moderately confident = 3, and very confident = 4. Figure 2 summarizes the responses of the participants.An online course to teach the fundamentals of imaging modalities could be delivered through a webinar format to medical students and interns in several countries to address the potential gaps in radiology education, therefore increasing their understanding of the different imaging modalities and their proper use in medicine.

To study healthcare avoidance behavior in pilots related to fear of aeromedical certificate loss.Voluntary participation in an anonymous survey distributed to U.S. pilots.A total of 3765 pilots were included in the analysis. There were 56.1% of pilots (n = 2111) who reported a history of healthcare avoidance behavior due fear for losing their aeromedical certificate. There were 45.7% who sought informal medical care (n = 1721) and 26.8% who misrepresented/withheld information on a written healthcare questionnaire for fear of aeromedical certificate loss (n = 994).Aircraft pilots may participate in healthcare avoidance behavior related to fear of losing their aeromedical certificate. Further work is necessary to address pilot healthcare avoidance.

Introduction: Small studies have suggested that eptifibatide (EPT) may be safe in acute ischemic stroke (AIS) following IV thrombolysis (tPA) or during endovascular therapy (EVT) for large vessel occlusion (LVO), however larger studies are called upon to evaluate the safety of EPT use in this setting. Methods: A stroke center registry (09/2015-12/2020) of consecutive adults who had undergone EVT for LVO was queried. Patients treated with EPT were matched with 3 control groups based on known factors associated with intracranial hemorrhage (ICH) risk - age, early infarct size (Alberta Stroke Program Computed Tomography Scale [ASPECTS] score), and number of thrombectomy passes. ICH, parenchymal hematoma (PH-2), symptomatic ICH (sICH), and 90-day modified Rankin Scale (mRS) score were compared between matched groups. Results: A total of 236 patients were included, 59 of whom (25%) received EPT. IV tPA was non-significantly more utilized in EPT patients (41%, p=0.22). Rate of any ICH was similar between groups (p=0.23), while PH-2 was significantly more frequent with EPT (21% v. 7% v. 3% v. 0%; p= 0.0001). There were no significant differences in sICH (7% EPT v. 7% v. 5% v. 2%; p=0.57), 90-day mRS (p=0.84), or 90-day mortality (p=0.92) between EPT and control groups. Conclusion: In this single center analysis, EPT during EVT was associated with a higher rate of PH-2 grade hemorrhages but not with differences in sICH, 90-day mRS, or 90-day mortality. Larger prospective studies are needed to confirm these findings.

Introduction: Ipsilateral nonstenotic ( Methods: Consecutive stroke patients at our center (2019-2021) with unilateral, anterior ESUS were categorized into the following mutually exclusive etiologies: (1) nonstenotic ipsilateral ICA plaque (≥3mm), (2) atriopathy (sex-adjusted mod-to-severe atrial enlargement) & (3) PFO. Clinical and diagnostic results were compared between patients in each group, and against those with “true ESUS” (who failed to meet criteria for these 3 groups). Results: Of 133 included patients, there was minimal overlap between the mutually exclusive ESUS etiologies (2 having nonstenotic plaque + atriopathy, and 1 having atriopathy + PFO). Older patients more frequently had atriopathy, while patients with PFO had fewer vascular risk factors when compared to the other groups (padj≤0.1; Table). Patients with nonstenotic plaque had more frequent tobacco use (p=0.06), more severe white matter disease (p=0.07), and greater ipsilateral v. contralateral plaque (p Conclusions: Certain clinical and radiographic features may be useful in predicting the proximal source of occult cerebral emboli, and can be used for cost-effective outpatient diagnostic testing.

Background: Nonstenotic internal carotid artery (ICA) plaque as a mechanism of embolic stroke of undetermined source (ESUS) is controversial. Studies show an inverse relationship between cardioembolic stroke risk and nonstenotic plaque in ESUS patients. We explored this relationship using left atrial enlargement (LAE) as a marker of cardioembolic stroke predisposition. Methods: A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried. ESUS diagnosis was based on an embolic stroke pattern without an identifiable source on imaging and ≥24hrs of telemetry. Descriptive statistics were used to differentiate clinical, laboratory, and imaging predictors of sex adjusted LAE. Results: Of the 4155 patients screened, 273 (7%) met the inclusion criteria. Compared to patients without LAE, those with LAE were older (68y vs 62y, p Discussion: Clinically relevant ipsilateral ICA plaque was more frequent in this ESUS cohort, regardless of LAE. When stratified by age, younger patients had greater ipsilateral ICA plaque burden and less LAE. While nonstenotic plaque and LAE frequently co-exist, younger ESUS patients were at greater risk of nonstenotic plaque than the elderly, who were at greater risk of LAE.

Introduction: Conduction disturbance after transcatheter aortic valve replacement (TAVR) remains a common complication. Predictive tools to identify conduction disturbance requiring pacing are limited. Our main objective was to develop a deep learning model to predict the need for a permanent pacemaker. Hypothesis: An electrocardiogram (ECG) based deep learning algorithm can predict the need for permanent pacemaker post TAVR. Methods: We evaluated patients who had TAVR at Mayo Clinic between June 2010 and May 2021. Digital ECGs done on the TAVR date or within 24 hours post procedure were partitioned into training, validation, and testing datasets. We trained a deep learning algorithm on the training data and optimized hyperparameters against the validation data. All model performance metrics are based on the reserved test data that were estimated once model architecture was optimized. Need for permanent pacemaker, defined as pacemaker placement due to development of conduction disturbance post TAVR and at least 1% ventricular pacing on device interrogation done at least 2 weeks post pacemaker implantation, was the training target. Results: A total of 3021 patients were evaluated for inclusion and 2,407 cases were available for modeling (exclusions: prior pacemaker (n=419), unsuccessful TAVR (n=27) and no ECG within the pre-specified period (n=168)). Overall, the median age was 82 (Q1: 76, Q3: 86) and 41% were female. In the withheld test data, 15% had a permanent pacemaker with at least 1% ventricular pacing. The algorithm detected the need for pacemaker in the test set with an AUC of 0.83 (95% CI: 0.73 to 0.92). Accuracy, sensitivity, specificity, positive and negative predictive were 80%, 72%, 81%, 41% and 94%, respectively. Conclusions: This study demonstrates the ability of a deep learning model based on ECG data to assist in making the decision to implant a pacemaker following TAVR with a high negative predictive value. Larger validation studies are warranted.

Introduction : In‐hospital stroke (IHS) is defined as stroke that occurs during hospitalization for non‐stroke conditions. We aimed to understand the timing of symptom recognition for patients who experienced IHS and its impact on the care they receive. Methods : A prospective, single center registry of adult patients (9/20/19‐2/28/21) was queried for acute anterior circulation IHS. Indications for hospitalization, delays from last known well (LKW) to symptom recognition, imaging, and treatment were explored. Results : Of 928 consecutively evaluated adults with acute stroke, 85 (9%) developed an anterior circulation IHS, 39 (46%) of whom were female, with a median age of 67 years (IQR 60–76) and median NIHSS of 15 (IQR 4–22). Sixty‐eight (80%) had a >1 hour delay from last known well to symptom recognition. Two patients (2%) received IV thrombolysis, although another 38 (45%) would have been eligible if not for a delay in symptom recognition. An ICA, M1, or M2 occlusion was observed in 18 patients (21%), 7 of whom were treated at a median of 174 minutes after LKW (IQR 65–219). Compared to the 11 patients who did not undergo thrombectomy with large vessel occlusion, those who underwent thrombectomy had non‐significantly shorter delays from LKW until neuroimaging (median 85 [IQR 65‐162] vs. 216 [IQR 133‐507], p = 0.12). Conclusions : While uncommon, patients with IHS experience delays in symptom recognition and treatment, which lead to exclusion from acute care treatment such as thrombolysis and thrombectomy. Earlier detection with more frequent nursing assessments or advanced neuromonitoring devices in at‐risk patients may reduce delays in care.

Introduction: Sudden cardiac arrest is a leading cause of mortality in the United States, with over 475,000 people dying annually. Bystander CPR significantly improves the odds of neurologically intact survival, yet nationally is performed in only 46% of out of hospital cardiac arrests. Significant regional variation exists in the performance of bystander CPR, with our community performing lower than national norms (26%). We sought to assess our community’s awareness of current American Heart Association (AHA) recommendations and the perceived barriers to performing bystander CPR. Methods: Adult study volunteers were recruited within the community (Norfolk, VA; pop. 244,703) and completed a 15-question anonymous survey that assessed knowledge of AHA recommendations, willingness to perform, and perceived barriers to performing CPR. Results: A total of 1,017 respondents completed all or part of the survey (40% male; 60% female). Knowledge of the importance of CPR was high. Of the respondents, 78% (n=708) indicated they would know if CPR was required, 84% (n=756) recognized the importance of performing CPR on a person who is unconscious and not breathing, and 89% (n=733) agreed CPR should not be delayed until the arrival of an ambulance. Though 70% (n=597) of respondents indicated they had been previously trained to perform CPR, only 44% (n=397) had been trained to perform “hands-only” CPR. Several barriers to performing CPR were identified. Forty-nine percent of respondents (n=402) believed they must perform “mouth to mouth” during CPR while 32% (n=284) were concerned they could catch a disease. Fear of doing something wrong while performing CPR was a concern for 28% (n=257). Twenty-six percent (n=237) reported concerns about the legal consequences of performing CPR. Conclusions: Though the importance of bystander CPR is well recognized in our community, misunderstandings regarding requirements and risks continue to exist. Education efforts should focus on increasing community awareness of current AHA recommendations.

Inflammation is a key component in the pathogenesis of cardiometabolic disease. Certain anti-inflammatory compounds may improve atherosclerotic disease risk by modulating systemic and vascular inflammation. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may represent a dietary mechanism for improving cardiometabolic health through reduction of inflammation. We hypothesized that n-3 PUFA supplementation would reduce the inflammatory response to evoked endotoxemia in healthy humans. In the Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia study (FFAME Study), we recruited healthy individuals (N=60; age 18-45; BMI 18-30; 43% Female; 65% Caucasian, 20% African, 15% Asian ancestry) randomized to one of three treatment groups; n-3 PUFA (Lovaza 465mg EPA/375mg DHA) supplemented at either 900mg per day or 3,600mg per day, or placebo. An additional arm of the study included a fenofibrate treatment group, not included here. Participants were treated for ∼8 weeks then admitted to the research center for an endotoxin challenge of lipopolysaccharide (LPS) 0.6ng/kg intravenously. Multiple clinical and biochemical variables were assessed throughout, and analyzed using RM-ANOVA with Bonferroni post-hoc tests for between group differences. Compared to placebo, high-dose (P The specific anti-inflammatory properties of n-3 PUFA appear to be dose-specific, with high doses (3,600mg/day) leading to attenuation of the inflammatory response to evoked endotoxemia, while lower doses (900mg/day) do not reduce the inflammatory response despite similar reductions in plasma lipids.

Introduction: Inflammation plays a crucial role in the pathophysiology of cardiometabolic disease. Some experimental data and clinical trials suggest that PPAR-α activation and fibrate therapy suppress inflammation in humans, potentially promoting anti-atherogenic actions. Human experimental endotoxemia provides a controlled model for the study of atherogenic inflammatory responses and their modulation in vivo . We hypothesized that fenofibrate would suppress the inflammatory responses to endotoxin (LPS) in healthy humans. Methods: In the Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia study, 36 healthy volunteers (mean age 26 ± 7 years; mean BMI 24 ± 3 kg/m 2 ; 56% male; 72% Caucasian, 19% African, 8% Asian ancestry) were randomized to fenofibrate 145 mg or placebo daily. After 8 weeks of treatment, subjects underwent a low-dose LPS challenge (0.6 ng/kg intravenous bolus). Anthropometric, clinical, and blood measures were collected at baseline, pre-LPS, and serially for 24 hours after LPS exposure. Results: Compared to placebo, fenofibrate reduced total cholesterol (170 ± 35 to 137 ± 31 mg/dL, p=0.009) and tended to decrease triglycerides (78 ± 40 to 57 ± 23 mg/dL, p=0.611) prior to LPS. LPS induced a modest clinical response with increased temperature, heart rate, and blood pressure ( p p p p =0.08 for both). Conclusions: PPAR-α modulation with fenofibrate did not attenuate clinical or inflammatory responses during low-grade human endotoxemia. These data suggest the anti-inflammatory properties of fenofibrate at clinically-relevant dosing are limited.