PMC:7537941 / 13907-16198 JSON TXT

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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T28","span":{"begin":237,"end":241},"obj":"Body_part"},{"id":"T29","span":{"begin":368,"end":372},"obj":"Body_part"}],"attributes":[{"id":"A28","pred":"uberon_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A29","pred":"uberon_id","subj":"T29","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PubTator

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T84","span":{"begin":1136,"end":1147},"obj":"http://purl.obolibrary.org/obo/GO_0006412"},{"id":"T85","span":{"begin":2026,"end":2038},"obj":"http://purl.obolibrary.org/obo/GO_0006954"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

MyTest

{"project":"MyTest","denotations":[{"id":"33004529-18090375-29393007","span":{"begin":272,"end":274},"obj":"18090375"},{"id":"33004529-19740417-29393008","span":{"begin":276,"end":278},"obj":"19740417"},{"id":"33004529-11597289-29393009","span":{"begin":445,"end":447},"obj":"11597289"},{"id":"33004529-30477976-29393010","span":{"begin":1838,"end":1840},"obj":"30477976"},{"id":"33004529-27975101-29393011","span":{"begin":1907,"end":1909},"obj":"27975101"},{"id":"33004529-21887302-29393012","span":{"begin":1911,"end":1913},"obj":"21887302"},{"id":"33004529-18090375-29393013","span":{"begin":2071,"end":2073},"obj":"18090375"},{"id":"33004529-18460218-29393014","span":{"begin":2284,"end":2286},"obj":"18460218"},{"id":"33004529-20937093-29393014","span":{"begin":2284,"end":2286},"obj":"20937093"},{"id":"33004529-26673586-29393014","span":{"begin":2284,"end":2286},"obj":"26673586"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T59","span":{"begin":437,"end":443},"obj":"Phenotype"},{"id":"T60","span":{"begin":1103,"end":1112},"obj":"Phenotype"},{"id":"T61","span":{"begin":1188,"end":1194},"obj":"Phenotype"},{"id":"T62","span":{"begin":1205,"end":1214},"obj":"Phenotype"},{"id":"T63","span":{"begin":1306,"end":1315},"obj":"Phenotype"},{"id":"T64","span":{"begin":1601,"end":1610},"obj":"Phenotype"},{"id":"T65","span":{"begin":2060,"end":2069},"obj":"Phenotype"}],"attributes":[{"id":"A59","pred":"hp_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A60","pred":"hp_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A61","pred":"hp_id","subj":"T61","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A62","pred":"hp_id","subj":"T62","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A63","pred":"hp_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A64","pred":"hp_id","subj":"T64","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A65","pred":"hp_id","subj":"T65","obj":"http://purl.obolibrary.org/obo/HP_0002090"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

2_test

{"project":"2_test","denotations":[{"id":"33004529-18090375-29393007","span":{"begin":272,"end":274},"obj":"18090375"},{"id":"33004529-19740417-29393008","span":{"begin":276,"end":278},"obj":"19740417"},{"id":"33004529-11597289-29393009","span":{"begin":445,"end":447},"obj":"11597289"},{"id":"33004529-30477976-29393010","span":{"begin":1838,"end":1840},"obj":"30477976"},{"id":"33004529-27975101-29393011","span":{"begin":1907,"end":1909},"obj":"27975101"},{"id":"33004529-21887302-29393012","span":{"begin":1911,"end":1913},"obj":"21887302"},{"id":"33004529-18090375-29393013","span":{"begin":2071,"end":2073},"obj":"18090375"},{"id":"33004529-18460218-29393014","span":{"begin":2284,"end":2286},"obj":"18460218"},{"id":"33004529-20937093-29393014","span":{"begin":2284,"end":2286},"obj":"20937093"},{"id":"33004529-26673586-29393014","span":{"begin":2284,"end":2286},"obj":"26673586"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T78","span":{"begin":0,"end":13},"obj":"Sentence"},{"id":"T79","span":{"begin":14,"end":280},"obj":"Sentence"},{"id":"T80","span":{"begin":281,"end":380},"obj":"Sentence"},{"id":"T81","span":{"begin":381,"end":628},"obj":"Sentence"},{"id":"T82","span":{"begin":629,"end":812},"obj":"Sentence"},{"id":"T83","span":{"begin":813,"end":997},"obj":"Sentence"},{"id":"T84","span":{"begin":998,"end":1267},"obj":"Sentence"},{"id":"T85","span":{"begin":1268,"end":1445},"obj":"Sentence"},{"id":"T86","span":{"begin":1446,"end":1611},"obj":"Sentence"},{"id":"T87","span":{"begin":1612,"end":1736},"obj":"Sentence"},{"id":"T88","span":{"begin":1737,"end":1842},"obj":"Sentence"},{"id":"T89","span":{"begin":1843,"end":1915},"obj":"Sentence"},{"id":"T90","span":{"begin":1916,"end":1989},"obj":"Sentence"},{"id":"T91","span":{"begin":1990,"end":2291},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Anti-thrombin\nAT inactivates thrombin and factor Xa and has been shown to reduce systemic (after intravenous administration) and bronchoalveolar (after both intravenous and nebulised administration) thrombin and fibrin levels and reduce lung injury in preclinical models [42, 46]. However, the clinical data currently do not support using AT as a treatment to improve lung injury. The KyperSept trial of high-dose AT treatment in severe sepsis [47] showed no effect on 28-day mortality, and an increased risk of bleeding events in the AT-treated participants was observed, particularly in those who received concomitant heparin. Yet, a subgroup analysis revealed that the AT-treated group that had not received concomitant heparin had a 15% improvement in 90-day mortality compared to those treated with heparin. Nonetheless, a meta-analysis of 20 trials of a heterogeneous population of critically ill patients concluded that AT should be avoided owing to the risk of bleeding complications [45]. Natural or pharmacological thrombin inhibitors have not been tested in clinical trials in the setting of pneumonia and potential clinical translation has been inferred from studies of AT in sepsis, in which pneumonia is the leading cause in a large proportion of cases. In terms of extrapolation to COVID-19 pneumonia, we would propose that the current evidence would also argue against the use of AT, particularly if co-administered with heparin. Heparin alone, which exerts its anticoagulant effects via the activation of AT, is currently being evaluated in multiple trials in the context of COVID-19 pneumonia. This includes evaluation of a systemic prophylactic dose and a full therapeutic dose of low molecular weight heparin (LMWH). In H1N1 ARDS, anticoagulation with systemic heparin significantly reduced the high incidence of VTE [48]. Heparin also exerts anti-inflammatory and antiviral properties [49, 50]. However, the route of administration of heparin is likely to be critical. Nebulised heparin did not attenuate inflammation in a murine model of pneumonia [42], and, in clinical trials in patients with or at risk of ARDS, nebulised heparin had no major impact on physiological variables nor a beneficial effect on mortality, although it increased ventilator-free days [51–53]."}

PMC:7537941 / 13907-16198 JSONTXT

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PMC:7537941 / 13907-16198 JSON TXT