PMC:7537941 / 17594-19543 JSON TXT

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LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T99","span":{"begin":591,"end":595},"obj":"Body_part"}],"attributes":[{"id":"A99","pred":"fma_id","subj":"T99","obj":"http://purl.org/sig/ont/fma/fma7195"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T35","span":{"begin":591,"end":595},"obj":"Body_part"}],"attributes":[{"id":"A35","pred":"uberon_id","subj":"T35","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T133","span":{"begin":352,"end":371},"obj":"Disease"},{"id":"T134","span":{"begin":399,"end":409},"obj":"Disease"},{"id":"T135","span":{"begin":596,"end":602},"obj":"Disease"},{"id":"T136","span":{"begin":641,"end":645},"obj":"Disease"},{"id":"T137","span":{"begin":745,"end":749},"obj":"Disease"},{"id":"T138","span":{"begin":1514,"end":1522},"obj":"Disease"},{"id":"T139","span":{"begin":1523,"end":1532},"obj":"Disease"}],"attributes":[{"id":"A133","pred":"mondo_id","subj":"T133","obj":"http://purl.obolibrary.org/obo/MONDO_0021113"},{"id":"A134","pred":"mondo_id","subj":"T134","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A135","pred":"mondo_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"},{"id":"A136","pred":"mondo_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A137","pred":"mondo_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A138","pred":"mondo_id","subj":"T138","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A139","pred":"mondo_id","subj":"T139","obj":"http://purl.obolibrary.org/obo/MONDO_0005249"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T174","span":{"begin":70,"end":73},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T175","span":{"begin":197,"end":206},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T176","span":{"begin":373,"end":375},"obj":"http://purl.obolibrary.org/obo/CLO_0050507"},{"id":"T177","span":{"begin":576,"end":586},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T178","span":{"begin":591,"end":595},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T179","span":{"begin":591,"end":595},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T180","span":{"begin":613,"end":614},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T181","span":{"begin":624,"end":626},"obj":"http://purl.obolibrary.org/obo/CLO_0050509"},{"id":"T182","span":{"begin":659,"end":660},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T183","span":{"begin":835,"end":836},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T184","span":{"begin":1319,"end":1322},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T185","span":{"begin":1354,"end":1355},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T186","span":{"begin":1452,"end":1453},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T187","span":{"begin":1463,"end":1464},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T188","span":{"begin":1819,"end":1827},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-PubTator

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T89","span":{"begin":564,"end":575},"obj":"http://purl.obolibrary.org/obo/GO_0050817"},{"id":"T90","span":{"begin":1805,"end":1827},"obj":"http://purl.obolibrary.org/obo/GO_0050819"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

MyTest

{"project":"MyTest","denotations":[{"id":"33004529-15891319-29393022","span":{"begin":373,"end":375},"obj":"15891319"},{"id":"33004529-17278083-29393023","span":{"begin":538,"end":540},"obj":"17278083"},{"id":"33004529-23433188-29393024","span":{"begin":647,"end":649},"obj":"23433188"},{"id":"33004529-24632673-29393025","span":{"begin":651,"end":653},"obj":"24632673"},{"id":"33004529-18565951-29393026","span":{"begin":760,"end":762},"obj":"18565951"},{"id":"33004529-16192478-29393027","span":{"begin":817,"end":819},"obj":"16192478"},{"id":"33004529-23826709-29393028","span":{"begin":1424,"end":1426},"obj":"23826709"},{"id":"33004529-17893198-29393029","span":{"begin":1829,"end":1831},"obj":"17893198"},{"id":"33004529-17893198-29393030","span":{"begin":1945,"end":1947},"obj":"17893198"}],"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":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T69","span":{"begin":284,"end":290},"obj":"Phenotype"},{"id":"T70","span":{"begin":352,"end":371},"obj":"Phenotype"},{"id":"T71","span":{"begin":520,"end":525},"obj":"Phenotype"},{"id":"T72","span":{"begin":784,"end":790},"obj":"Phenotype"},{"id":"T73","span":{"begin":1005,"end":1011},"obj":"Phenotype"},{"id":"T74","span":{"begin":1022,"end":1027},"obj":"Phenotype"},{"id":"T75","span":{"begin":1059,"end":1064},"obj":"Phenotype"},{"id":"T76","span":{"begin":1149,"end":1154},"obj":"Phenotype"},{"id":"T77","span":{"begin":1523,"end":1532},"obj":"Phenotype"},{"id":"T78","span":{"begin":1930,"end":1936},"obj":"Phenotype"}],"attributes":[{"id":"A69","pred":"hp_id","subj":"T69","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A70","pred":"hp_id","subj":"T70","obj":"http://purl.obolibrary.org/obo/HP_0002878"},{"id":"A71","pred":"hp_id","subj":"T71","obj":"http://purl.obolibrary.org/obo/HP_0031273"},{"id":"A72","pred":"hp_id","subj":"T72","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A73","pred":"hp_id","subj":"T73","obj":"http://purl.obolibrary.org/obo/HP_0100806"},{"id":"A74","pred":"hp_id","subj":"T74","obj":"http://purl.obolibrary.org/obo/HP_0031273"},{"id":"A75","pred":"hp_id","subj":"T75","obj":"http://purl.obolibrary.org/obo/HP_0031273"},{"id":"A76","pred":"hp_id","subj":"T76","obj":"http://purl.obolibrary.org/obo/HP_0031273"},{"id":"A77","pred":"hp_id","subj":"T77","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A78","pred":"hp_id","subj":"T78","obj":"http://purl.obolibrary.org/obo/HP_0100806"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

2_test

{"project":"2_test","denotations":[{"id":"33004529-15891319-29393022","span":{"begin":373,"end":375},"obj":"15891319"},{"id":"33004529-17278083-29393023","span":{"begin":538,"end":540},"obj":"17278083"},{"id":"33004529-23433188-29393024","span":{"begin":647,"end":649},"obj":"23433188"},{"id":"33004529-24632673-29393025","span":{"begin":651,"end":653},"obj":"24632673"},{"id":"33004529-18565951-29393026","span":{"begin":760,"end":762},"obj":"18565951"},{"id":"33004529-16192478-29393027","span":{"begin":817,"end":819},"obj":"16192478"},{"id":"33004529-23826709-29393028","span":{"begin":1424,"end":1426},"obj":"23826709"},{"id":"33004529-17893198-29393029","span":{"begin":1829,"end":1831},"obj":"17893198"},{"id":"33004529-17893198-29393030","span":{"begin":1945,"end":1947},"obj":"17893198"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T100","span":{"begin":0,"end":106},"obj":"Sentence"},{"id":"T101","span":{"begin":107,"end":377},"obj":"Sentence"},{"id":"T102","span":{"begin":378,"end":542},"obj":"Sentence"},{"id":"T103","span":{"begin":543,"end":821},"obj":"Sentence"},{"id":"T104","span":{"begin":822,"end":1033},"obj":"Sentence"},{"id":"T105","span":{"begin":1034,"end":1227},"obj":"Sentence"},{"id":"T106","span":{"begin":1228,"end":1533},"obj":"Sentence"},{"id":"T107","span":{"begin":1534,"end":1719},"obj":"Sentence"},{"id":"T108","span":{"begin":1720,"end":1949},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"In clinical studies, systemic, rather than nebulised, delivery of APC has had initially promising results. In the original landmark PROWESS study, intravenous infusion of rhAPC (drotrecogin alpha (activated) (DrotAA)) significantly reduced 28-day all-cause mortality in patients with sepsis (secondary to CAP) by 28% and reduced the resolution time of respiratory failure [22]. This resulted in the Infectious Diseases Society of America/American Thoracic Society recommending APC for the treatment of refractory septic shock due to CAP [62]. Although APC reduced coagulation activation and lung injury scores in a study of 27 patients with ARDS [63, 64], in a subsequent randomised controlled trial APC did not improve the clinical outcomes of ARDS patients [65] or of patients with sepsis and low of risk of death [66]. Furthermore, a meta-analysis of five studies involving 5101 participants concluded that APC was associated with higher risk of bleeding and should not be used in patients with severe sepsis or septic shock [67]. Importantly, the PROWESS-Shock study [55] failed to demonstrate an improvement in survival in patients with septic shock and eventually led to the withdrawal of DrotAA (Xigris) from the market. However, the significant differences in patient characteristics between the PROWESS trials has led to the recommendation that a trial of DrotAA should be repeated using an optimised study design [68], and this could include a trial in a less heterogeneous high-risk population, such as COVID-19 pneumonia. The preclinical and clinical data suggest nebulised rhAPC may not carry the same bleeding liability as intravenous administration and may be an appropriate route of drug administration. Alternatively, the bleeding risk could be mitigated using an rhAPC variant with \u003c10% anticoagulant activity [69], which in preclinical studies was as effective as wild-type APC in improving survival of mice in sepsis models [69]."}

PMC:7537941 / 17594-19543 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7537941 / 17594-19543 JSON TXT