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1.
Cell ; 184(2): 460-475.e21, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33278358

RESUMEN

SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection.


Asunto(s)
Antiinflamatorios/administración & dosificación , Azetidinas/administración & dosificación , Tratamiento Farmacológico de COVID-19 , COVID-19/inmunología , Macaca mulatta , Infiltración Neutrófila/efectos de los fármacos , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Animales , COVID-19/fisiopatología , Muerte Celular/efectos de los fármacos , Degranulación de la Célula/efectos de los fármacos , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/inmunología , Quinasas Janus/antagonistas & inhibidores , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Activación de Linfocitos/efectos de los fármacos , Macrófagos Alveolares/inmunología , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad , Linfocitos T/inmunología , Replicación Viral/efectos de los fármacos
2.
AJR Am J Roentgenol ; 215(4): 839-842, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32298149

RESUMEN

OBJECTIVE. Coronavirus disease (COVID-19) is a global pandemic. Studies in the radiology literature have suggested that CT might be sufficiently sensitive and specific in diagnosing COVID-19 when used in lieu of a reverse transcription-polymerase chain reaction test; however, this suggestion runs counter to current society guidelines. The purpose of this article is to critically review some of the most frequently cited studies on the use of CT for detecting COVID-19. CONCLUSION. To date, the radiology literature on COVID-19 has consisted of limited retrospective studies that do not substantiate the use of CT as a diagnostic test for COVID-19.


Asunto(s)
Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Betacoronavirus , COVID-19 , Humanos , Pandemias , SARS-CoV-2
3.
Chest ; 160(4): 1492-1511, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33957099

RESUMEN

BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown. RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior? STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ2 test, and multivariable analyses were used for statistical analysis. RESULTS: A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC. INTERPRETATION: EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding.


Asunto(s)
Lesión Pulmonar Aguda/diagnóstico por imagen , Hemorragia/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Vapeo/efectos adversos , Lesión Pulmonar Aguda/etiología , Adolescente , Adulto , Anciano , Dronabinol/administración & dosificación , Sistemas Electrónicos de Liberación de Nicotina , Femenino , Hemorragia/etiología , Humanos , Lesión Pulmonar/diagnóstico por imagen , Lesión Pulmonar/etiología , Linfadenopatía/etiología , Masculino , Persona de Mediana Edad , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Psicotrópicos/administración & dosificación , Tomografía Computarizada por Rayos X , Adulto Joven
4.
J Am Coll Radiol ; 17(6): 786-790, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31930981

RESUMEN

PURPOSE: The purpose of this study was to determine how often a second-opinion interpretation of interstitial lung disease (ILD) by an academic cardiothoracic radiologist is discordant with the initial interpretation by a nonacademic radiologists and how often the clinical diagnosis determined by multidisciplinary consensus agrees with the initial and second-opinion interpretations. METHODS: This retrospective study included 364 consecutive second-opinion CT examination reports of imaging from nonacademic radiology practices from July 2014 to May 2016. The second-opinion interpretations, provided by seven fellowship-trained cardiothoracic radiologists, were compared with the initial interpretations and the clinical diagnoses determined by multidisciplinary consensus. RESULTS: Two hundred ninety-six consecutive reports met the inclusion criteria, and two hundred had findings of ILD. The initial interpretations lacked specific diagnoses in 41% of reports, but the second-opinion reports lacked specific diagnoses in only 7%. When a diagnosis was provided, the second-opinion diagnosis disagreed with the initial interpretation in 25% of cases. The clinical-consensus diagnosis was concordant with that of the academic radiologists 85% of the time but concordant with the initial interpretation only 44% of the time. The academic radiologists' diagnostic sensitivity was higher than that of the initial radiologists for the four most common diagnoses: usual interstitial pneumonitis (0.91 versus 0.4), sarcoidosis (0.94 versus 0.60), hypersensitivity pneumonitis (0.79 versus 0.17), and nonspecific interstitial pneumonitis (0.72 versus 0.14). CONCLUSIONS: Academic cardiothoracic radiologists were more likely to provide specific diagnoses for ILD, and these diagnoses were more likely to be concordant with the multidisciplinary consensus.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Derivación y Consulta , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Variaciones Dependientes del Observador , Radiólogos , Estudios Retrospectivos
5.
Radiol Clin North Am ; 58(3): 503-516, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32276700

RESUMEN

Because of a recent increase in survival rates and life expectancy of patients with congenital heart disease (CHD), radiologists are facing new challenges when imaging the peculiar anatomy of individuals with repaired CHD. Cardiac computed tomography and magnetic resonance are paramount noninvasive imaging tools that are useful in assessing patients with repaired CHD, and both techniques are increasingly performed in centers where CHD is not the main specialization. This review provides general radiologists with insight into the main issues of imaging patients with repaired CHD, and the most common findings and complications of each individual pathology and its repair.


Asunto(s)
Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Humanos , Adulto Joven
6.
bioRxiv ; 2020 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-32995780

RESUMEN

Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.

7.
Curr Treat Options Cardiovasc Med ; 21(10): 51, 2019 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-31473870

RESUMEN

PURPOSE OF REVIEW: The purpose of this review is to analyze the long-term prognostic value of stress perfusion cardiovascular magnetic resonance (CMR) in patients with suspected or known coronary artery disease (CAD). RECENT FINDINGS: Stress perfusion CMR provides high diagnostic accuracy for detection of CAD, with high sensitivity and relatively lower specificity. A normal stress perfusion CMR examination is highly predictive of overall low patient risk. Conversely, abnormal stress perfusion CMR results are associated with mortality and increased risk for adverse cardiac-related events. Stress perfusion CMR is a useful and robust tool for risk reclassification across different CAD risk categories, and most significant for patients of intermediate risk. Stress CMR is reliable for excluding clinically significant coronary artery disease in patients presenting with low-risk acute chest pain. An ischemic burden threshold of less than 1.5 cardiac segments has been found to be most appropriate for safe deferral from revascularization therapy. A stress perfusion CMR-guided strategy has been shown to be noninferior compared to fractional flow reserve (FFR) for revascularization in patients with stable CAD. In clinical practice, CMR offers a multiplicity of useful techniques besides stress perfusion which may add significant prognostic value when combined with the findings of the stress test itself. Stress perfusion CMR is an accurate noninvasive diagnostic test for patients with suspected CAD and provides strong prognostic value across different risk categories.

8.
Curr Probl Diagn Radiol ; 45(4): 265-70, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26810714

RESUMEN

The purpose of the article is to determine if miscentering affected dose with use of automated tube voltage selection software. An anthropomorphic phantom was imaged at different table heights (centered in the computed tomography [CT] gantry, and -6, -3, +3, and +5.7cm relative to the centered position). Topogram magnification, tube voltage selection, and dose were assessed. Effect of table height on dose also was assessed retrospectively in human subjects (n = 50). When the CT table was positioned closer to the x-ray source, subjects appeared up to 33% magnified in topogram images. When subjects appeared magnified in topogram images, automated software selected higher tube potentials and tube currents that were based on the magnified size of the subject rather than the subject׳s true size. Table height strongly correlated with CT dose index (r = 0.98, P < 0.05) and dose length product (r = 0.98, P < 0.05) in the phantom study. Transverse dimension in the topogram highly correlated with dose in human subjects (r = 0.75-0.87, P <0.05). Miscentering results in increased dose due to topogram magnification with automated voltage selection software.


Asunto(s)
Errores Médicos/estadística & datos numéricos , Fantasmas de Imagen , Dosis de Radiación , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Programas Informáticos , Adulto Joven
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