Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio.
<h4>Objective</h4>Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio diffe...
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2014
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oai:doaj.org-article:c5d58a36551747d19361f8c03dcf75562021-11-18T08:23:47ZAssociation of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio.1932-620310.1371/journal.pone.0094318https://doaj.org/article/c5d58a36551747d19361f8c03dcf75562014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24727739/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions.<h4>Methods</h4>Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality.<h4>Results</h4>We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8.<h4>Conclusions</h4>The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.Leonardo LorenteMaría M MartínJordi Solé-ViolánJosé BlanquerLorenzo LabartaCésar DíazJuan M Borreguero-LeónJosune OrbeJosé A RodríguezAlejandro JiménezJosé A PáramoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94318 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Leonardo Lorente María M Martín Jordi Solé-Violán José Blanquer Lorenzo Labarta César Díaz Juan M Borreguero-León Josune Orbe José A Rodríguez Alejandro Jiménez José A Páramo Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| description |
<h4>Objective</h4>Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions.<h4>Methods</h4>Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality.<h4>Results</h4>We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8.<h4>Conclusions</h4>The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome. |
| format |
article |
| author |
Leonardo Lorente María M Martín Jordi Solé-Violán José Blanquer Lorenzo Labarta César Díaz Juan M Borreguero-León Josune Orbe José A Rodríguez Alejandro Jiménez José A Páramo |
| author_facet |
Leonardo Lorente María M Martín Jordi Solé-Violán José Blanquer Lorenzo Labarta César Díaz Juan M Borreguero-León Josune Orbe José A Rodríguez Alejandro Jiménez José A Páramo |
| author_sort |
Leonardo Lorente |
| title |
Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| title_short |
Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| title_full |
Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| title_fullStr |
Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| title_full_unstemmed |
Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio. |
| title_sort |
association of sepsis-related mortality with early increase of timp-1/mmp-9 ratio. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/c5d58a36551747d19361f8c03dcf7556 |
| work_keys_str_mv |
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