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A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass

Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cf...

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Autores principales: Ishay, Shlomo Yaron, Abu-Tailakh, Muhammad, Raichel, Lior, Hershenhoren, Tal F., Matsa, Menahem, Lev-Ran, Oren, Gideon, Sahar, Douvdevani, Amos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612555/
https://www.ncbi.nlm.nih.gov/pubmed/36301964
http://dx.doi.org/10.1371/journal.pone.0276443
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author Ishay, Shlomo Yaron
Abu-Tailakh, Muhammad
Raichel, Lior
Hershenhoren, Tal F.
Matsa, Menahem
Lev-Ran, Oren
Gideon, Sahar
Douvdevani, Amos
author_facet Ishay, Shlomo Yaron
Abu-Tailakh, Muhammad
Raichel, Lior
Hershenhoren, Tal F.
Matsa, Menahem
Lev-Ran, Oren
Gideon, Sahar
Douvdevani, Amos
author_sort Ishay, Shlomo Yaron
collection PubMed
description Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cfDNA) and histones are released by inflammatory cells and damaged tissue and act as DAMPs. We sought to characterize the changes in circulating cell-free DNA (cfDNA) levels during CPB. Primary outcomes were renal failure, ventilation time (>18 hr), length of stay (LOS) in the intensive care unit (ICU) (>48hr), hospital LOS (>15 days), and death. We looked for associations with blood tests and comparison to standard scores. In a prospective cohort study, we enrolled 71 patients undergoing non-emergent coronary artery bypass grafting. Blood was drawn at baseline, 20 and 40 minutes on CPB, after cross-clamp removal, and 30 minutes after chest closure. cfDNA was measured by our fast fluorescent method. Baseline cfDNA levels [796 (656–1063) ng/ml] increased during surgery, peaked after cross-clamp removal [2403 (1981–3357) ng/ml] and returned to baseline at recovery. The difference in cfDNA from 20 to 40 minutes on CPB (ΔcfDNA 40–20) inversely correlated with peripheral vascular disease (PVD), longer ventilation time, and longer ICU and hospital length of stay (LOS). Receiver operating characteristic (ROC) curve of ΔcfDNA 40–20 for long ICU-LOS (>48hr) was with an area under the curve (AUC) of 0.738 (p = 0.022). ROC AUC of ΔcfDNA 40–20 to long Hospital LOS (>15 days) was 0.787 (p = 0.006). Correction for time on CPB in a multivariate logistic regression model improved ROC-AUC to 0.854 (p = 0.003) and suggests that ΔcfDNA 40–20 is an independent risk factor. To conclude, of measured parameters, including STS and Euroscore, the predictive power of ΔcfDNA 40–20 was the highest. Thus, measurement of ΔcfDNA 40–20 may enable early monitoring of patients at higher risk. Further studies on the mechanism behind the negative association of ΔcfDNA 40–20 with PVD and outcomes are warranted.
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spelling pubmed-96125552022-10-28 A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass Ishay, Shlomo Yaron Abu-Tailakh, Muhammad Raichel, Lior Hershenhoren, Tal F. Matsa, Menahem Lev-Ran, Oren Gideon, Sahar Douvdevani, Amos PLoS One Research Article Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cfDNA) and histones are released by inflammatory cells and damaged tissue and act as DAMPs. We sought to characterize the changes in circulating cell-free DNA (cfDNA) levels during CPB. Primary outcomes were renal failure, ventilation time (>18 hr), length of stay (LOS) in the intensive care unit (ICU) (>48hr), hospital LOS (>15 days), and death. We looked for associations with blood tests and comparison to standard scores. In a prospective cohort study, we enrolled 71 patients undergoing non-emergent coronary artery bypass grafting. Blood was drawn at baseline, 20 and 40 minutes on CPB, after cross-clamp removal, and 30 minutes after chest closure. cfDNA was measured by our fast fluorescent method. Baseline cfDNA levels [796 (656–1063) ng/ml] increased during surgery, peaked after cross-clamp removal [2403 (1981–3357) ng/ml] and returned to baseline at recovery. The difference in cfDNA from 20 to 40 minutes on CPB (ΔcfDNA 40–20) inversely correlated with peripheral vascular disease (PVD), longer ventilation time, and longer ICU and hospital length of stay (LOS). Receiver operating characteristic (ROC) curve of ΔcfDNA 40–20 for long ICU-LOS (>48hr) was with an area under the curve (AUC) of 0.738 (p = 0.022). ROC AUC of ΔcfDNA 40–20 to long Hospital LOS (>15 days) was 0.787 (p = 0.006). Correction for time on CPB in a multivariate logistic regression model improved ROC-AUC to 0.854 (p = 0.003) and suggests that ΔcfDNA 40–20 is an independent risk factor. To conclude, of measured parameters, including STS and Euroscore, the predictive power of ΔcfDNA 40–20 was the highest. Thus, measurement of ΔcfDNA 40–20 may enable early monitoring of patients at higher risk. Further studies on the mechanism behind the negative association of ΔcfDNA 40–20 with PVD and outcomes are warranted. Public Library of Science 2022-10-27 /pmc/articles/PMC9612555/ /pubmed/36301964 http://dx.doi.org/10.1371/journal.pone.0276443 Text en © 2022 Ishay et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ishay, Shlomo Yaron
Abu-Tailakh, Muhammad
Raichel, Lior
Hershenhoren, Tal F.
Matsa, Menahem
Lev-Ran, Oren
Gideon, Sahar
Douvdevani, Amos
A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title_full A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title_fullStr A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title_full_unstemmed A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title_short A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass
title_sort prospective cohort study of dynamic cell-free dna elevation during cardiac surgery with cardiopulmonary bypass
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612555/
https://www.ncbi.nlm.nih.gov/pubmed/36301964
http://dx.doi.org/10.1371/journal.pone.0276443
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