Santa Cruz de Tenerife, Spain
Santa Cruz de Tenerife, Spain

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Lorente L.,Hospital Universitario Of Canarias | Martin M.M.,Hospital Universitario Nuestra Senora Candelaria | Abreu-Gonzalez P.,University of La Laguna | Sole-Violan J.,Hospital Universitario Dr Negrin | And 7 more authors.
PLoS ONE | Year: 2014

Objective: Higher values of red blood cell distribution width (RDW) have been found in non-surviving than in surviving septic patients. However, it is unknown whether RDW during the first week of sepsis evolution is associated with sepsis severity and early mortality, oxidative stress and inflammation states, and these were the aims of the study. Methods: We performed a prospective, observational, multicenter study in six Spanish Intensive Care Units with 297 severe septic patients. We measured RDW, serum levels of malondialdehyde (MDA) to assess oxidative stress, and tumour necrosis factor (TNF)-α to assess inflammation at days 1, 4, and 8. The end-point was 30-day mortality. Results: We found higher RDW in non-surviving (n = 104) than in surviving (n = 193) septic patients at day 1 (p = 0.001), day 4 (p = 0.001), and day 8 (p = 0.002) of ICU admission. Cox regression analyses showed that RDW at day 1 (p<0.001), 4 (p = 0.005) and 8 (p = 0.03) were associated with 30-day mortality. Receiver operating characteristic curves showed that RDW at day 1 (p<0.001), 4 (p<0.001), and 8 (p<0.001) could be used to predict 30-day mortality. RDW showed a positive correlation with serum MDA levels at day 1 and day 4, with serum TNF-α levels at days 4 and 8, and with SOFA score at days 1, 4 and 8. Conclusions: The major findings of our study were that non-surviving septic patients showed persistently higher RDW during the first week of ICU stay than survivors, that RDW during the first week was associated with sepsis severity and mortality, that RDW during the first week could be used as biomarker of outcome in septic patients, and that there was an association between RDW, serum MDA levels, and serum TNF-α levels during the first week. © 2014 Lorente et al.


Lorente L.,Hospital Universitario Of Canarias | Martin M.,Hospital Universitario Nuestra Senora Candelaria | Plasencia F.,Hospital Universitario Of Canarias | Sole-Violan J.,Hospital Universitario Dr Negrin | And 9 more authors.
Critical Care | Year: 2013

Introduction: Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study.Methods: This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFα, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman's rank correlation coefficient or Spearman's rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission.Results: Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (χ2= 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ = -0.19; P = 0.002), MMP-10 (ρ = 0.55; P <0.001), TNFα (ρ = 0.56; P <0.001), IL-10 (ρ = 0.48; P <0.001) and PAI-1 (ρ = 0.49; P <0.001).Conclusion: The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance. © 2013 Lorente et al.; licensee BioMed Central Ltd.


Lorente L.,Hospital Universitario Of Canarias | Martin M.M.,Hospital Universitario Nuestra Senora Candelaria | Abreu-Gonzalez P.,University of La Laguna | Dominguez-Rodriguez A.,Hospital Universitario Of Canarias | And 7 more authors.
Critical Care | Year: 2013

Introduction: There is a hyperoxidative state in sepsis. The objective of this study was to determine serum malondialdehyde (MDA) levels during the first week of follow up, whether such levels are associated with severity during the first week and whether non-surviving patients showed higher MDA levels than survivors during the first week.Methods: We performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in 328 patients (215 survivors and 113 non-survivors) with severe sepsis at days one, four and eight of diagnosis, and in 100 healthy controls. The primary endpoint was 30-day mortality and the secondary endpoint was six -month mortality. The association between continuous variables was carried out using Spearman's rank correlation coefficient. Cox regression analysis was applied to determine the independent contribution of serum MDA levels on the prediction of 30-day and 6-month mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated as measures of the clinical impact of the predictor variables.Results: We found higher serum MDA in septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001) of diagnosis than in healthy controls. Serum MDA was lower in surviving than non-surviving septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001). Serum MDA levels were positively correlated with lactic acid and SOFA during the first week. Finally, serum MDA levels were associated with 30-day mortality (HR = 1.05; 95% CI = 1.02-1.09; p = 0.005) and six-month mortality (hazard ratio (HR) = 1.05; 95% CI = 1.02-1.09; p = 0.003) after controlling for lactic acid levels, acute physiology and chronic health evaluation (APACHE)-II, diabetes mellitus, bloodstream infection and chronic renal failure.Conclusions: To our knowledge, this is the largest series providing data on the oxidative state in septic patients to date. The novel finding is that high serum MDA levels sustained throughout the first week of follow up were associated with severity and mortality in septic patients. © 2013 Lorente et al.; licensee BioMed Central Ltd.


Lorente L.,Hospital Universitario Of Canarias | Martin M.M.,Hospital Universitario Nuestra Senora Candelaria | Gonzalez-Rivero A.F.,Hospital Universitario Of Canarias | Ferreres J.,Hospital Clinico Universitario Of Valencia | And 5 more authors.
PLoS ONE | Year: 2014

Objective: Apoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients.Methods: We performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality.Results: Non-surviving patients (n = 80) showed higher serum CCCK-18 levels (P<0.001) than survivors (n = 144). Multiple logistic regression analysis showed that serum CCCK-18 levels>391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449-4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96-4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores.Conclusions: The major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients. © 2014 Lorente et al.


PubMed | University of La Laguna, Hospital Universitario Of Canarias, Hospital Universitario Nuestra Senora Of Candelaria and Hospital Universitario Nuestra Senora Candelaria
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.


PubMed | Hospital Universitario La Paz, Hospital Universitario Nuestra Senora Candelaria, Hospital Universitario Of Canarias, Hospital San Jorge Of Huesca and 2 more.
Type: | Journal: Journal of critical care | Year: 2016

Higher caspase 3 activity has been found in lymphocytes of septic patients than of healthy controls. However, an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients has not been previously demonstrated, and this was the main objective of the present study.This is an observational study of 216 patients with severe sepsis in 6 Spanish intensive care units. We collected serum samples at moment of severe sepsis diagnosis to determine levels of caspase 3 and caspase-cleaved cytokeratin (CCCK) 18. End point was 30-day mortality.We found higher serum caspase 3 levels (P<.001) and caspase-cleaved cytokeratin 18 (P=.001) in nonsurvivors (n=76) than in survivors (n=140). Multiple binary logistic regression analysis showed that serum caspase 3 levels greater than 0.25 ng/mL were associated with 30-day mortality (odds ratio, 6.51; 95% confidence interval, 3.32-12.77; P<.001). Receiver operating characteristic analysis showed that the area under the curve to predict 30-day mortality for serum caspase 3 levels was 0.73 (95% confidence interval, 0.67-0.79; P<.001).The major novel findings of our study were that there is an association between serum caspase 3 levels at moment of severe sepsis diagnosis and mortality in septic patients and that serum caspase 3 levels could be used as prognostic biomarker, and further studies are needed to corroborate these findings.


PubMed | Hospital Universitario Nuestra Senora Candelaria, Hospital Universitario Dr Negrin, Hospital Universitario Of Canarias, Hospital San Jorge Of Huesca and 2 more.
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

The association between interleukin (IL)-6 promoter polymorphism (-174 G/C), circulating IL-6 levels and mortality in septic patients has scarcely been addressed, and then only in studies of small sample size, and a direct association among them has not been previously reported. Therefore, the purpose of our study was to determine whether this association exists. An observational, prospective and multicenter study including severe septic patients was undertaken and serum IL-6 levels at severe sepsis diagnosis and IL-6 promoter polymorphism (-174 G/C) were determined. The end-point of the study was 30-day mortality. The study included 263 patients with the following genotypes of IL-6 promoter polymorphism (-174 G/C): 123 (46.8%) GG, 110 (41.8%) GC and 30 (11.4%) CC. CC homozygous patients showed lower sepsis-related organ failure assessment (SOFA) score, serum IL-6 levels and mortality at 30 days compared to those with other genotypes (GC or GG). On regression analysis, CC homozygous patients showed lower 30-day mortality than those with genotype GG (odds ratio = 0.21; 95% CI = 0.053-0.838;


PubMed | Hospital Universitario Of Canarias, Hospital Universitario Nuestra Senora Of Candelaria and Hospital Universitario Nuestra Senora Candelaria
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301-73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%-84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.


PubMed | Hospital Universitario Nuestra Senora Candelaria, Hospital Universitario Dr Negrin, Hospital Universitario Of Canarias, Hospital San Jorge Of Huesca and 3 more.
Type: Journal Article | Journal: Journal of critical care | Year: 2016

Substance P (SP) is a peptide of the tachykinins family involved in the inflammatory response. Circulating SP levels have been assessed in septic patients in 2 previous studies with a small number of subjects (61 and 42 patients, respectively), and there were no significant differences in SP levels at the moment of sepsis diagnosis between surviving and nonsurviving patients. The main goal of this study was to determine a possible relationship between serum SP levels and patient outcome in the largest cohort of severe septic patients analyzed so far.We performed an observational, prospective, multicenter study in 6 Spanish intensive care units. Serum SP levels were measured at the moment of severe sepsis diagnosis in 238 patients. The end point of the study was 30-day mortality.We found that surviving septic patients (n = 153) showed higher serum SP levels than did nonsurvivors (n = 85). Multiple logistic regression analysis showed that serum SP levels higher than 350 pg/mL were associated with survival at 30 days (odds ratio, 0.43; 95% confidence interval, 0.24-0.77; P = .005) after controlling for serum lactic acid levels and Sepsis-related Organ Failure Assessment score.The major new finding of our study was that serum SP levels were associated with mortality in severe septic patients.


PubMed | Hospital Universitario Nuestra Senora Candelaria, Hospital Universitario Dr Negrin, University of Zaragoza, Hospital Universitario Of Canarias and 3 more.
Type: Journal Article | Journal: Journal of critical care | Year: 2016

The comparison of oxidative phosphorylation system capacities between septic patients and control subjects has been scarcely analyzed and only in studies with small sample size (fewer than 40 septic patients and 40 controls). Thus, the objective of this study was to compare platelet respiratory complex IV (CIV) activity between severe septic patients and healthy individuals in a larger series (including 198 severe septic patients and 96 healthy controls).A prospective, multicenter, observational study was carried out in 6 Spanish intensive care units. We obtained blood samples from 198 severe septic patients at day 1, 4, and 8 of the severe sepsis diagnosis and 96 sex- and age-matched healthy control individuals and determined platelet CIV-specific activity. The end point of the study was 30-day mortality.Control individuals showed higher platelet CIV-specific activity (P < .001) than surviving (n = 130) or nonsurviving (n = 68) severe septic patients at day 1, 4, and 8 of severe sepsis diagnosis.The major finding of our work, involving the largest series to date of severe septic patients with data on oxidative phosphorylation system capacity, was that surviving and nonsurviving septic patients showed lower platelet CIV-specific activity during the first week of sepsis than healthy controls.

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