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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.)

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

Background and Purpose: A large spectrum of neurologic disease has been reported in patients with coronavirus disease 2019 (COVID-19) infection. Our aim was to investigate the yield of neuroimaging in patients with COVID-19 undergoing CT or MR imaging of the brain and to describe associated imaging findings., Materials and Methods: We performed a retrospective cohort study involving 2054 patients with laboratory-confirmed COVID-19 presenting to 2 hospitals in New York City between March 4 and May 9, 2020, of whom 278 (14%) underwent either CT or MR imaging of the brain. All images initially received a formal interpretation from a neuroradiologist within the institution and were subsequently reviewed by 2 neuroradiologists in consensus, with disputes resolved by a third neuroradiologist., Results: The median age of these patients was 64 years (interquartile range, 50-75 years), and 43% were women. Among imaged patients, 58 (21%) demonstrated acute or subacute neuroimaging findings, the most common including cerebral infarctions (11%), parenchymal hematomas (3.6%), and posterior reversible encephalopathy syndrome (1.1%). Among the 51 patients with MR imaging examinations, 26 (51%) demonstrated acute or subacute findings; notable findings included 6 cases of cranial nerve abnormalities (including 4 patients with olfactory bulb abnormalities) and 3 patients with a microhemorrhage pattern compatible with critical illness-associated microbleeds., Conclusions: Our experience confirms the wide range of neurologic imaging findings in patients with COVID-19 and suggests the need for further studies to optimize management for these patients., (© 2020 by American Journal of Neuroradiology.)

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.

Background: Visceral infarctions appear to be more common in patients with embolic stroke subtypes, but their relation to troponin elevation remains uncertain., Methods: Among patients with acute ischemic stroke enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011 to 2016, we included those with troponin measured within 24 hours from stroke onset and a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. A troponin elevation was defined as a value exceeding our laboratory's upper limit of normal (.04 ng/ mL) in the absence of a clinically recognized acute ST-segment elevation myocardial infarction. Visceral infarction was defined as a renal or splenic infarction as ascertained by a single radiologist blinded to patients' other characteristics. Multivariable logistic regression was used to evaluate the association between elevated troponin and visceral infarction., Results: Among 2116 patients registered in CAESAR from 2011 to 2016, 153 patients had both a troponin assay and a contrast-enhanced abdominal computed tomographic scan, of whom 33 (21%) had an elevated troponin and 22 (14%) had a visceral infarction. The prevalence of visceral infarction was higher among patients with an elevated troponin (30%; 95% confidence interval [CI], 16%-49%) than among patients without an elevated troponin (10%; 95% CI, 5%-17%) (P = .003). After adjustment for demographics and comorbidities, we found a significant association between elevated troponin and visceral infarction (odds ratio, 3.9; 95% CI, 1.5-10.4)., Conclusions: Among patients with acute ischemic stroke, elevated troponin was associated with visceral infarction. Our results demonstrate that poststroke troponin elevation may indicate the presence of underlying embolic sources., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background It is uncertain whether there is an association between left ventricular (LV) ejection fraction ( LVEF ) or LV wall motion abnormality and embolic stroke of undetermined source ( ESUS ). Methods and Results We performed a retrospective, cross-sectional study of patients with acute ischemic stroke enrolled in the CAESAR (Cornell Acute Stroke Academic Registry) from 2011 to 2016. We restricted this study to patients with ESUS and, as controls, those with small- and large-artery ischemic strokes. LVEF had to be above 35% to be considered ESUS . In a secondary analysis, we excluded patients with ESUS who had any evidence of ipsilateral carotid atherosclerosis. Multiple logistic regression was used to evaluate whether LVEF or LV wall motion abnormality was associated with ESUS . We performed a confirmatory study at another tertiary-care center. We identified 885 patients with ESUS (n=503) or small- or large-artery strokes (n=382). Among the entire cohort, LVEF was not associated with ESUS (odds ratio per 5% decrement in LVEF , 1.0; 95% CI, 1.0-1.1) and LV wall motion abnormality was not associated with ESUS (odds ratio, 0.9; 95% CI, 0.5-1.6). The results were identical in our confirmatory study. In our secondary analysis excluding ESUS patients with any evidence of ipsilateral carotid atherosclerosis, there was an association between LVEF and ESUS (odds ratio per 5% decrement in LVEF , 1.2; 95% CI, 1.0-1.5; P=0.04). Conclusions Among the entire cohort, no association existed between LVEF or LV wall motion abnormality and ESUS ; however, after excluding ESUS patients with any evidence of ipsilateral carotid atherosclerosis, lower LVEF appeared to be associated with ESUS .