Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study

Serrano-Gómez, Sergio Eduardo; Burgos-Angulo, Gabriel; Niño-Vargas, Daniela Camila; Niño, María Eugenia; Cárdenas, María Eugenia; Chacón-Valenzuela, Estephanía; McCosham, Diana Margarita; Peinado-Acevedo, Juan Sebastián; López, Marcos; Cunha, Fernando; Pazin‐Filho, Antônio; Ilarraza, Ramses; Schulz, Richard; Torres-Dueñas, Diego

doi:10.1177/0885066617732284

Cited by 11 publications

(21 citation statements)

References 41 publications

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“…Previous studies also demonstrated lower MMP-9 [ 8 , 9 , 15 ] and higher TIMP-1 [ 8 , 12 , 13 , 15 ] in nonsurvivors and in patients with higher disease severity scores [ 6 , 12 ]. Lorente et al [ 8 ] and Wang et al [ 13 ], as opposed to Martin et al [ 9 ] and Serrano-Gomez et al [ 14 ], supported our findings that MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio are good prognostic biomarkers of 28-day survival. A recent study by Niño et al, however, demonstrated that only TIMP-1 and not MMP-9 and MMP-9/TIMP-1 ratio was a good predictor of mortality in sepsis [ 15 ].…”

Section: Discussionsupporting

confidence: 90%

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

et al. 2018

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Background The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored. Materials and Methods Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded. Results Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels. Conclusions MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction.

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Section: Discussionsupporting

confidence: 90%

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

et al. 2018

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“…Analogous findings were reported for sepsis-associated organ dysfunction after major abdominal surgery by another study group [51]. Taking into account positive and negative predictive values, however, Serrano-Gomez et al found neither MMP-9, MMP-2, TIMP-1, TIMP-2 nor their respective ratios to have significant predictive values in mortality of sepsis patients [52]. The TIMP-1 has been associated with survival in several other critical diseases, including traumatic brain injury [53,54], cerebral infarction [55], graft versus host disease [56] and acute respiratory failure [57].…”

Section: Discussionsupporting

confidence: 62%

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival

Jordakieva

Budge-Wolfram

Budinsky

et al. 2020

Wien Klin Wochenschr

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Background Matrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP-2, MMP-9 and their inhibitors TIMP-1 and TIMP-2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU). Methods In a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the

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“…Thus, it is plausible to assume that MMPs and TIMPs in previous studies have been determined at a time-point when the patients have been more severely ill. This is probably the major explanation for the much higher mortality rates reported in previous studies: 13–34% overall sepsis or ICU mortality [ 25 , 29 ] and 12–33% 30-days mortality or 27% 90-day mortality in septic and/or critically ill patients [ 13 – 15 , 25 – 34 ] as compared to 13% and 18% mortality rates at 28 and 90 days in the present study.…”

Section: Discussionsupporting

confidence: 45%

“…No corresponding trend at was seen for TIMP-1. Previous reports have observed higher MMP-8 on [ 25 ] and TIMP-1 [ 13 , 23 , 25 , 29 ] at sepsis onset or ICU admission in non-surviving sepsis patients compared to surviving ones. Furthermore, two reports observed that critically ill non-surviving patients at ICU admission or in need of mechanical ventilation, as compared to surviving ones, presented higher MMP-8 and TIMP-1 levels [ 14 , 15 ] but indifferent MMP-8/TIMP-1 molar ratios [ 15 ].…”

Section: Discussionmentioning

confidence: 91%

“…solely acute respiratory distress syndrome [ 15 ] or multi-organ failure patients [ 32 ]. Moreover, many reports on MMPs and TIMPs in sepsis or critical illness have excluded immunocompromised patients or patients with malignancies or liver disease [ 13 , 15 , 26 , 27 , 29 ]. However, we are not aware of reports on MMPs or TIMPs levels in renal failure or of reports excluding patients with renal failure.…”

Section: Discussionmentioning

confidence: 99%

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Matrix metalloproteinase MMP-8, TIMP-1 and MMP-8/TIMP-1 ratio in plasma in methicillin-sensitive Staphylococcus aureus bacteremia

et al. 2021

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Background Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear. Methods MMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined. Results Altogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (p<0.01). Higher day 3 and 5 MMP-8 levels were associated to mortality at day 14 and 28 (p<0.01) and day 90 (p<0.05). Day 3 MMP-8 cut-off value of 203 ng/ml predicted death within 14 days with an area under the curve (AUC) of 0.70 (95% CI 0.57–0.82) (p<0.01). Day 5 MMP-8 cut-off value of 239 ng/ml predicted death within 14 days with an AUC of 0.76 (95% CI 0.65–0.87) (p<0.001). The results for MMP-8/TIMP-1 resembled that of MMP-8. TIMP-1 had no prognostic impact. In Cox regression analysis day 3 or 5 MMP-8 or day 3 MMP-8/TIMP-1 had no prognostic impact whereas day 5 MMP-8/TIMP-1 predicted mortality within 14 days (HR, 4.71; CI, 95% 1.67–13.3; p<0.01). Conclusion MMP-8 and MMP-8/TIMP-1 ratio were high 3–5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.

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Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study

Abstract: Although TIMP-1 showed higher sensitivity, specificity, and negative predictive value, with a representative population sample, we conclude that none of the evaluated biomarkers had significant predictive value for mortality.

Cited by 11 publications

References 41 publications

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival

Matrix metalloproteinase MMP-8, TIMP-1 and MMP-8/TIMP-1 ratio in plasma in methicillin-sensitive Staphylococcus aureus bacteremia

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