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41.
Kaitlin Sawatzki Nichola J. Hill Wendy B. Puryear Alexa D. Foss Jonathon J. Stone Jonathan A. Runstadler 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(18)
Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic disease, one of whom was confirmed positive for SARS-CoV-2. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on viral and antibody assays. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein Spike (S) mutations associated with mustelids. While we found evidence that angiotensin-converting enzyme II provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin cleavage efficiency. These data support the idea that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. We propose two mechanistically grounded hypotheses for mustelid host adaptation of SARS-CoV-2, with possible effects that require additional investigation.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is a zoonotic member of Coronaviridae that emerged in 2019 as a major viral pandemic (1). As of February 2021, there have been ∼102 million confirmed COVID-19 cases globally and ∼2.2 million deaths (2). SARS-CoV-2 uses angiotensin I converting enzyme-2 (ACE2) as its primary cellular receptor for host entry and infection (3–5). In silico analyses of ACE2 genes in diverse mammalian species show that residues important to viral binding are moderately conserved between humans and several domestic animals, and a broad range of species have been demonstrated to be permissive to infection in vitro and in vivo (6–10).It is not yet known whether natural infection of animals plays a role in public health epidemiology or has the potential to establish endemic reservoirs and threaten wildlife. SARS-CoV-2 has been observed to be capable of natural human-to-animal reverse zoonoses, transmitting from infected individuals into mink (11), dogs (12), and felines (13–15). American mink (Neovison vison) are currently the only species observed to have natural human-to-animal spillover and onward transmission (11). To date, at least 27 mink farms in The Netherlands, Spain, Denmark, and United States have reported outbreaks, including at least one probable case of mink-to-human transmission (16, 17).SARS-CoV-2 has also been shown to productively infect several species, including ferrets and domestic cats, in vivo (9, 10, 18, 19). Ferrets (Mustela putorius furo) are of special relevance to laboratory studies of respiratory viruses like Influenza A virus and recapitulate clinical pathophysiological aspects of human disease. Given their susceptibility to experimental infection and onward transmission via direct and indirect contact, ferrets have been proposed as an animal model to study SARS-CoV-2 transmission. Based on in vivo data, we expect all naïve ferrets in direct contact with an infected ferret will 1) become infected, 2) have measurable viral shedding or RNA via oral swabs up to 19 d postinfection, and 3) seroconvert with measurable antibodies against SARS-CoV-2 receptor binding domain (RBD) (18, 19).In March 2020, during the first wave of the SARS-CoV-2/COVID-19 pandemic in the New England area, we developed a rapid response study to investigate the potential for human-to-animal spillover and onward transmission in domestic, farm, and wildlife species (CoVERS: Coronavirus Epidemiological Response and Surveillance). The goal of CoVERS is to understand whether and how SARS-CoV-2 transmission is occurring at these interfaces, to refine public health guidelines, investigate whether there are additional risks to animal or human health associated with spillover, and evaluate the potential for establishment of endemic reservoirs. In the CoVERS in-home study, participants are sent a “swab and send” kit, which provides materials and instructions to safely take longitudinal nasal and oral samples from their animals, store them in their freezers, and send them back for viral screening. This community science approach allows wide surveillance with no risk of human transmission, as kits are decontaminated and opened in biosafety cabinets. Here, we highlight one enrolled household that created an exceptional natural experiment with direct relevance to our understanding of SARS-CoV-2 reverse zoonosis and animal models of disease. 相似文献
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Philippe Généreux Nicolo Piazza Maria C. Alu Tamim Nazif Rebecca T. Hahn Philippe Pibarot Jeroen J. Bax Jonathon A. Leipsic Philipp Blanke Eugene H. Blackstone Matthew T. Finn Samir Kapadia Axel Linke Michael J. Mack Raj Makkar Roxana Mehran Jeffrey J. Popma Martin B. Leon 《Journal of the American College of Cardiology》2021,77(21):2717-2746
45.
Amir Ahmadi Jonathon Leipsic Kristian A. Øvrehus Sara Gaur Emilia Bagiella Brian Ko Damini Dey Gina LaRocca Jesper M. Jensen Hans Erik Bøtker Stephan Achenbach Bernard De Bruyne Bjarne L. Nørgaard Jagat Narula 《JACC: Cardiovascular Imaging》2018,11(4):521-530
Objectives
The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.Background
In patients with stable ischemic heart disease, FFR-guided revascularization, as compared with medical therapy alone, is reported to improve outcomes. Because morphological characteristics are the basis of plaque rupture and acute coronary events, a relationship between FFR and lesion characteristics may exist.Methods
This is a subanalysis of NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography), a prospective, multicenter study of 254 patients (age 64 ± 10 years, 64% male) with suspected stable ischemic heart disease; coronary computed tomography angiography including plaque morphology assessment, invasive angiography, and FFR were obtained for 383 lesions. Ischemia was defined by invasive FFR ≤0.80. Computed tomography angiography–defined morphological characteristics of plaques and their vascular location were used in univariate and multivariate analyses to examine their predictive value for invasive FFR. The distribution of various combinations of plaque morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR were examined.Results
The percentage of luminal stenosis, low-attenuation plaque (LAP) or necrotic core volume, left anterior descending coronary artery territory, and the presence of multiple lesions per vessel were the predictors of FFR. When grouped on the basis of degree of luminal stenosis, FFR-negative lesions had consistently smaller LAP volumes compared with FFR-positive lesions. The distribution of plaque characteristics in lesions with normal and abnormal FFR demonstrated that whereas FFR-negative lesions excluded likelihood of stenotic plaques with moderate to high LAP volumes, only one-third of FFR-positive lesions demonstrated obstructive plaques with moderate to high LAP volumes.Conclusions
In addition to the severity of luminal stenosis, necrotic core volume is an independent predictor of FFR. The distribution of plaque characteristics among lesions with varying luminal stenosis and normal and abnormal FFR may explain the outcomes associated with FFR-guided therapy. 相似文献46.
Andrew D. Choi Dustin M. Thomas James Lee Suhny Abbara Ricardo C. Cury Jonathon A. Leipsic Christopher Maroules Prashant Nagpal Michael L. Steigner Dee Dee Wang Michelle C. Williams Irfan Zeb Todd C. Villines Ron Blankstein 《Journal of Cardiovascular Computed Tomography》2021,15(1):2-15
Cardiovascular computed tomography (CCT) is a well-validated non-invasive imaging tool with an ever-expanding array of applications beyond the assessment of coronary artery disease. These include the evaluation of structural heart diseases, congenital heart diseases, peri-procedural electrophysiology applications, and the functional evaluation of ischemia. This breadth requires a robust and diverse training curriculum to ensure graduates of CCT training programs meet minimum competency standards for independent CCT interpretation. This statement from the Society of Cardiovascular Computed Tomography aims to supplement existing societal training guidelines by providing a curriculum and competency framework to inform the development of a comprehensive, integrated training experience for cardiology and radiology trainees in CCT. 相似文献
47.
Todd C. Villines Subhi J. Al’Aref Daniele Andreini Marcus Y. Chen Andrew D. Choi Carlo N. De Cecco Damini Dey James P. Earls Maros Ferencik Heidi Gransar Harvey Hecht Jonathon A. Leipsic Michael T. Lu Mohamed Marwan Pál Maurovich-Horvat Edward Nicol Gianluca Pontone Jonathan Weir-McCall Gudrun M. Feuchtner 《Journal of Cardiovascular Computed Tomography》2021,15(2):180-189
48.
Minkwan Kim Seung-Pyo Lee Soongu Kwak Seokhun Yang Yong-Jin Kim Daniele Andreini Mouaz H. Al-Mallah Matthew J. Budoff Filippo Cademartiri Kavitha Chinnaiyan Jung Hyun Choi Edoardo Conte Hugo Marques Pedro de Araújo Gonçalves Ilan Gottlieb Martin Hadamitzky Jonathon A. Leipsic Erica Maffei Hyuk-Jae Chang 《Journal of Cardiovascular Computed Tomography》2021,15(3):232-239
BackgroundThe association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).MethodsFrom a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.ResultsWith a 3.3-years’ median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm3/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm3/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.ConclusionsThe rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411. 相似文献
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50.
Vasvi Singh Andrew D. Choi Jonathon Leipsic Ayaz Aghayev James P. Earls Philipp Blanke Michael Steigner Leslee J. Shaw Phd Marcelo F. Di Carli Todd C. Villines Ron Blankstein 《Journal of Cardiovascular Computed Tomography》2021,15(1):16-26
The COVID-19 pandemic has affected patient care deliver throughout the world, resulting in a greater emphasis on efficiently and safety. In this article, we discuss the experiences of several North American centers in utilizing cardiac CT during the pandemic. We also provide a case-based overview which highlights the advantages of cardiac CT in evaluating the following scenarios: (1) patients with possible myocardial injury versus myocardial infarction; (2) patients with acute chest pain; (3) patients with stable chest pain; (4) patients with possible intracardiac thrombus; (5) patients with valvular heart disease. For each scenario, we also provide an overview of various societies recommendations which have highlighted the use of cardiac CT during different phases of the COVID-19 pandemic. We hope that the advantages of cardiac CT that have been realized during the pandemic can help promote wider adoption of this technique and improved coverage and payment by payors. 相似文献