Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.344
Filtrar
1.
Cells ; 9(10)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998369

RESUMO

The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.


Assuntos
Infecções por Coronavirus/complicações , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pneumonia Viral/complicações , Proteína S/metabolismo , Trombose/etiologia , Imunidade Adaptativa , Animais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Hemostasia , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Trombose/sangue , Trombose/imunologia , c-Mer Tirosina Quinase/metabolismo
2.
Radiographics ; 40(6): 1574-1599, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001783

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Trombose/diagnóstico por imagem , Angiografia/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Artéria Pulmonar/diagnóstico por imagem , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Avaliação de Sintomas , Tromboembolia/sangue , Tromboembolia/etiologia , Trombose/sangue , Trombose/etiologia , Microangiopatias Trombóticas/diagnóstico por imagem , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos
3.
Ann Biol Clin (Paris) ; 78(5): 471-481, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026344

RESUMO

COVID-19 is associated with disturbances of hemostasis in the laboratory and an increased thrombotic risk. Routine laboratory tests - activated partial thromboplastin time (aPTT), prothrombin time, Clauss fibrinogen and D-dimers levels measurement - are used for the evaluation of the thrombotic risk and the monitoring of hemostasis, but are subject to several drawbacks that may affect the reliability and clinical relevance of the delivered results. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment. For instance, the issue of the monitoring of unfractionated heparin remains debated, the more so when there is a tremendous inflammatory response. This brief review considers the role of laboratory tests of hemostasis in the management of COVID-19 and discusses their main limitations to be kept in mind.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Hemostasia/fisiologia , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Trombose/diagnóstico , Trombose/etiologia , Trombose/prevenção & controle , Anticoagulantes/uso terapêutico , Betacoronavirus/fisiologia , Testes de Coagulação Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Monitoramento de Medicamentos/métodos , Hemostasia/efeitos dos fármacos , Humanos , Laboratórios Hospitalares , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Fatores de Risco , Trombose/epidemiologia
4.
Eur Heart J ; 41(32): 3038-3044, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882706

RESUMO

The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature. This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms. The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Endotélio Vascular/fisiopatologia , Estresse Oxidativo , Pneumonia Viral/complicações , Trombose/etiologia , Infecções por Coronavirus/epidemiologia , Citocinas/metabolismo , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Trombose/metabolismo , Trombose/fisiopatologia
6.
Am J Case Rep ; 21: e926915, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32963216

RESUMO

BACKGROUND Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis. Effective anticoagulation therapy may play a dominant role in the management of severe COVID-19 cases. CASE REPORT A 73-year-old man with a 6-day history of fever up to 38.5°C, dyspnea, cough, and fatigue was diagnosed with COVID-19. He had a past medical history significant for hypertension and coronary artery bypass grafting. Two days after hospital admission, the patient developed acute respiratory failure, requiring intubation, mechanical ventilation, and transfer to the intensive care unit (ICU). He received treatment including antibiotics, hydroxychloroquine, tocilizumab, vasopressors, prone positioning, and anticoagulation with enoxaparin at a prophylactic dose. After a 15-day ICU stay, the patient was hemodynamically stable but still hypoxemic; a transthoracic echocardiogram at that time, followed by a transesophageal echocardiogram for better evaluation, revealed the presence of a right atrium thrombus without signs of acute right ventricular dilatation and impaired systolic function. Since the patient was hemodynamically stable, we decided to treat him with conventional anticoagulation under close monitoring for signs of hemodynamic deterioration; thus, the prophylactic dose of enoxaparin was replaced by therapeutic dosing, which was a key component of the patient's successful outcome. Over the next few days he showed significant clinical improvement. The follow-up transesophageal echocardiogram 3 weeks after effective therapeutic anticoagulation revealed no signs of right heart thrombus. CONCLUSIONS The presented COVID-19 case, one of the first reported cases with evidence of right heart thrombus by transesophageal echocardiography, highlights the central role of diagnostic imaging strategies and the importance of adequate anticoagulation therapy in the management of severe COVID-19 cases in the ICU.


Assuntos
Infecções por Coronavirus/complicações , Ecocardiografia Transesofagiana/métodos , Átrios do Coração/diagnóstico por imagem , Cardiopatias/terapia , Pneumonia Viral/complicações , Síndrome Respiratória Aguda Grave/complicações , Trombose/terapia , Idoso , Terapia Combinada , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Tosse/diagnóstico , Tosse/etiologia , Cuidados Críticos/métodos , Progressão da Doença , Serviço Hospitalar de Emergência , Febre/diagnóstico , Febre/etiologia , Seguimentos , Grécia , Átrios do Coração/patologia , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologia , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/terapia , Índice de Gravidade de Doença , Trombose/diagnóstico por imagem , Trombose/etiologia , Resultado do Tratamento
7.
Crit Care ; 24(1): 559, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938471

RESUMO

Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management. In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue. However, substantive differences exist between these guidelines which can be difficult for clinicians. This review briefly summarizes the major societal guidelines and compares their similarities and differences. A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/terapia , Infecções por Coronavirus/complicações , Estado Terminal , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto , Trombose/etiologia , Trombose/terapia , Betacoronavirus , Humanos , Pandemias
8.
Crit Care ; 24(1): 561, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948243

RESUMO

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.


Assuntos
Infecções por Coronavirus/complicações , Estado Terminal , Hemorragia/etiologia , Pneumonia Viral/complicações , Trombose/etiologia , Betacoronavirus , Infecções por Coronavirus/terapia , Feminino , Hemorragia/terapia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Tromboelastografia , Trombose/terapia , Reino Unido
9.
Medicine (Baltimore) ; 99(36): e22084, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899083

RESUMO

RATIONALE: Dabigatran is a direct thrombin inhibitor that is widely used to prevent the formation of thrombus formation. Amiodarone can increase the plasma concentration of dabigatran. CES1 (carboxylesterase 1) and ABCB1 (ATP-binding cassette subfamily B member 1) genetic polymorphisms associate with the pharmacokinetics of dabigatran. PATIENT CONCERNS: A 62-year-old woman was admitted to the hospital due to chest tightness, fatigue, and discomfort despite long-term anticoagulation with dabigatran 110 mg twice daily for 6 months, with concomitant use of amiodarone. DIAGNOSES: Left atrial appendage thrombus formation with a history of atrial fibrillation. INTERVENTIONS: The clinician changed dabigatran to warfarin. To explore the causes of insufficient anticoagulation using dabigatran in this patient, we examined the ABCB1 and CES1 genes. Results showed that she carried ABCB1 variant alleles with 3 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs1045642, rs2032582) and CES1 variant alleles with 2 heterozygote SNPs (rs2244613, rs4580160). OUTCOMES: The left atrial appendage thrombus disappeared. LESSONS: Multiple mutations in the ABCB1 and CES1 genes may influence the pharmacokinetics of dabigatran and could have contributed to the thrombus formation in the left atrial appendage.


Assuntos
Apêndice Atrial/patologia , Fibrilação Atrial/complicações , Hidrolases de Éster Carboxílico/genética , Trombose/etiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Antitrombinas/administração & dosagem , Antitrombinas/farmacocinética , Apêndice Atrial/diagnóstico por imagem , Dabigatrana/administração & dosagem , Dabigatrana/farmacocinética , Feminino , Humanos , Pessoa de Meia-Idade , Trombose/prevenção & controle
10.
Clin Appl Thromb Hemost ; 26: 1076029620943293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735131

RESUMO

Since the onset of the global pandemic in early 2020, coronavirus disease 2019 (COVID-19) has posed a multitude of challenges to health care systems worldwide. In order to combat these challenges and devise appropriate therapeutic strategies, it becomes of paramount importance to elucidate the pathophysiology of this illness. Coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a dysregulated immune system and hypercoagulability. COVID-associated coagulopathy (CAC) was recognized based on profound d-dimer elevations and evidence of microthrombi and macrothrombi, both in venous and arterial systems. The underlying mechanisms associated with CAC have been suggested, but not clearly defined. The model of immunothrombosis illustrates the elaborate crosstalk between the innate immune system and coagulation. The rendering of a procoagulant state in COVID-19 involves the interplay of many innate immune pathways. The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system. Activated leukocytes potentiate a procoagulant state via release of intravascular tissue factor, platelet activation, NETosis, and inhibition of anticoagulant mechanisms. Additional pathways of specific relevance in CAC include cytokine release and complement activation. All these mechanisms have recently been reported in COVID-19. Immunothrombosis provides a comprehensive perspective of the several synergistic pathways pertinent to the pathogenesis of CAC.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/patologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Humanos , Imunidade Inata , Leucócitos/metabolismo , Leucócitos/patologia , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Trombofilia/imunologia , Trombofilia/virologia , Trombose/etiologia , Trombose/imunologia , Trombose/virologia
11.
Tohoku J Exp Med ; 251(4): 327-336, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32788506

RESUMO

After the first cases of COVID-19 appeared in Wuhan, China at the end of 2019, the disease quickly become a pandemic that has seriously affected the economic and health systems in more than 200 countries and territories around the world. Although most patients have mild symptoms or are even asymptomatic, there are patients who can develop serious complications such as acute respiratory distress syndrome or venous thromboembolism requiring mechanical ventilation and intensive care. Hence, it is important to identify patients with a higher risk of complications in a timely manner. Thus, the objective of this paper is to review the hematological laboratory parameters that consistently are altered in COVID-19 and to identify their relationship with the severity of the disease. According to 11 selected reports, the frequency of patients aged > 65 years is higher among subjects severely affected or deceased; likewise, males predominantly suffer from comorbidities such as hypertension, diabetes or obesity. Retrospective studies have identified alterations in various hematological and inflammatory parameters as part of the host's response to infection and a secondary increased risk of different thrombotic events. Among these altered parameters, D-dimer, C-reactive protein, and interleukin-6 have been tested as prognostic biomarkers due to their close relationship with the severity of the disease. Actually, they can reliably indicate the use of antithrombotic therapy at prophylactic or therapeutic doses (mainly D-dimer), as has already been established in those patients who, after an individualized assessment, appear to be at high risk for thrombotic events.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/sangue , Fibrinolíticos/uso terapêutico , Pandemias , Pneumonia Viral/sangue , Fatores Etários , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Biomarcadores , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/prevenção & controle , Testes de Coagulação Sanguínea , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemofilia A/complicações , Humanos , Inflamação , Interleucina-6/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Prognóstico , Risco , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombose/etiologia , Trombose/prevenção & controle
12.
BMJ Case Rep ; 13(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747597

RESUMO

We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.


Assuntos
Infecções por Coronavirus , Enoxaparina/administração & dosagem , Cardiopatias , Pandemias , Doença Arterial Periférica , Pneumonia Viral , Embolia Pulmonar , Trombose , Varfarina/administração & dosagem , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Deterioração Clínica , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Cardiopatias/terapia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/terapia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/terapia , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(31): e21554, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756213

RESUMO

BACKGROUND: Bioresorbable vascular scaffolds (BVS) completely resorb within 3 years after placement into the coronary artery. The safety and effectiveness of bioabsorbable scaffolds are of critical importance during this 3-year period. OBJECTIVE: We performed a meta-analysis to compare the safety and efficacy of BVS and second-generation drug-eluting stents (DES) at 3 years after implantation. METHODS: Published randomized trials comparing BVS to second-generation DES for the treatment of coronary artery disease were identified within PubMed, EMBASE, Cochrane Library, Web of Science, and relevant Web sites with publication dates through June 2019. The primary efficacy endpoint was target lesion failure. The primary safety endpoint was definite/probable stent/scaffold thrombosis. Secondary outcomes were cardiac death, target vessel myocardial infarction, ischemia-driven target lesion revascularization, and a patient-oriented composite end point. RESULTS: Six randomized controlled trials, with a total of 5,412 patients (BVS n = 3,177; DES n = 2,235), were included. At 3 years, BVS was associated with higher rates of target lesion failure (OR = 1.33, 95%CI: 1.10-1.60, P = 0.003) and definite/probable stent/scaffold thrombosis (OR = 3.75, 95% CI: 2.22-6.35, P < .00001)compared with DES. The incidence of target vessel myocardial infarction (OR = 1.68, 95% CI: 1.30-2.17, P < .0001), ischemia-driven target lesion revascularization (OR = 1.46, 95% CI: 1.14-1.86, P = .003), and the patient-oriented composite end point(OR = 1.20, 95% CI: 1.04-1.39, P = .01) were higher for those treated with BVS compared with DES. However, there was no significant difference in risk of cardiac death (OR = 0.94, 95%CI: 0.61-1.45, P = .79) between treatment groups. CONCLUSIONS: At the 3-year follow-up, BVS was inferior to second-generation DES in both safety and efficacy.


Assuntos
Implantes Absorvíveis/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Morte , Humanos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica/estatística & dados numéricos , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/etiologia
15.
Redox Biol ; 36: 101655, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738789

RESUMO

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.


Assuntos
Infecções por Coronavirus/metabolismo , NADPH Oxidase 2/metabolismo , Pneumonia Viral/metabolismo , Trombose/sangue , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2/química , Estresse Oxidativo , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Trombose/etiologia
18.
EBioMedicine ; 58: 102925, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32745993

RESUMO

BACKGROUND: Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. METHODS: Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry. PATIENT FINDINGS: Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. INTERPRETATION: These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. FUNDING: Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.


Assuntos
Infecções por Coronavirus/patologia , Armadilhas Extracelulares/metabolismo , Microvasos/patologia , Neutrófilos/metabolismo , Pneumonia Viral/patologia , Trombose/metabolismo , Células Cultivadas , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Humanos , Microvasos/metabolismo , Neutrófilos/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Trombose/etiologia , Trombose/patologia
19.
Arterioscler Thromb Vasc Biol ; 40(10): 2404-2407, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32762443

RESUMO

OBJECTIVE: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. CONCLUSIONS: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.


Assuntos
Infecções por Coronavirus/patologia , Células Endoteliais/citologia , Endotélio Vascular/patologia , Pneumonia Viral/patologia , Trombose/patologia , Doenças Vasculares/patologia , Autopsia , Biópsia por Agulha , Causas de Morte , Infecções por Coronavirus/mortalidade , Células Endoteliais/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pandemias , Pneumonia Viral/mortalidade , Medição de Risco , Trombose/etiologia , Trombose/mortalidade , Doenças Vasculares/mortalidade , Doenças Vasculares/fisiopatologia
20.
Blood ; 136(11): 1342-1346, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32766883

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state with a high incidence of thrombotic events during hospitalization; however, data examining rates of thrombosis after discharge are limited. We conducted a retrospective observational cohort study of discharged patients with confirmed COVID-19 not receiving anticoagulation. The cohort included 163 patients with median time from discharge to last recorded follow-up of 30 days (interquartile range [IQR], 17-46 days). The median duration of index hospitalization was 6 days (IQR, 3-12 days) and 26% required intensive care. The cumulative incidence of thrombosis (including arterial and venous events) at day 30 following discharge was 2.5% (95% confidence interval [CI], 0.8-7.6); the cumulative incidence of venous thromboembolism alone at day 30 postdischarge was 0.6% (95% CI, 0.1-4.6). The 30-day cumulative incidence of major hemorrhage was 0.7% (95% CI, 0.1-5.1) and of clinically relevant nonmajor bleeds was 2.9% (95% CI, 1.0-9.1). We conclude that the rates of thrombosis and hemorrhage appear to be similar following hospital discharge for COVID-19, emphasizing the need for randomized data to inform recommendations for universal postdischarge thromboprophylaxis.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Hemorragia/etiologia , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/complicações , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Trombose/patologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA