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1.
Lancet Respir Med ; 8(3): 267-276, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32043986

RESUMO

BACKGROUND: There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS: We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS: Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION: Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING: Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.

3.
J Clin Immunol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828694

RESUMO

Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) is an indispensable enzyme for the activation of the lectin pathway of complement. Its deficiency is classified as a primary immunodeficiency associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity. In Europeans, MASP-2 deficiency, due to homozygosity for c.359A > G (p.D120G), occurs in 7 to 14/10,000 individuals. We analyzed the presence of the p.D120G mutation in adults (increasing the sample size of our previous studies) and children. Different groups of patients (1495 adults hospitalized with community-acquired pneumonia, 186 adults with systemic lupus erythematosus, 103 pediatric patients with invasive pneumococcal disease) and control individuals (1119 healthy adult volunteers, 520 adult patients without history of relevant infectious diseases, and a pediatric control group of 311 individuals) were studied. Besides our previously reported MASP-2-deficient healthy adults, we found a new p.D120G homozygous individual from the pediatric control group. We also reviewed p.D120G homozygous individuals reported so far: a total of eleven patients with a highly heterogeneous range of disorders and nine healthy controls (including our four MASP-2-deficient individuals) have been identified by chance in association studies. Individuals with complete deficiencies of several pattern recognition molecules of the lectin pathway (MBL, collectin-10 and collectin-11, and ficolin-3) as well as of MASP-1 and MASP-3 have also been reviewed. Cumulative evidence suggests that MASP-2, and even other components of the LP, are largely redundant in human defenses and that individuals with MASP-2 deficiency do not seem to be particularly prone to infectious or autoimmune diseases.

5.
J Crit Care ; 54: 94-98, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401543

RESUMO

PURPOSE: DNA and RNA oxidative damage occurs during sepsis. Higher urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels (from oxidation of guanosine from DNA) have been found in non-surviving patients than in surviving septic patients. However, the relation between DNA and RNA oxidative damage and mortality in septic patients has never been published; thus, the objective of this study was to determine the existence of this association. METHODS: This prospective and observational study including septic patients was conducted in 8 Spanish Intensive Care Units. Serum concentrations of the three oxidizied guanine species (OGS) (8-OHdG from DNA, 8-hydroxyguanosine from RNA, and 8-hydroxyguanine from DNA or RNA) were determined, and malondialdehyde (to estimate lipid peroxidation) in the diagnosis of sepsis. Mortality at 30 days was the end-point study. RESULTS: Non-surviving patients (n = 78) compared to surviving patients (n = 139) showed higher serum concentrations of OGS (p = .004) and malondialdehyde (p < .001). Simultaneously, an association between serum OGS concentrations and mortality in logistic regression analysis was found (OR = 1.105; 95% CI = 1.024-1.193; p = .01), and a positive correlation between serum levels of OGS and malondialdehyde (rho = 0.21; p = .002). CONCLUSIONS: The new findings from our study were that oxidative DNA and RNA damage in septic patients was associated with mortality and lipid peroxidation.

6.
Int J Dermatol ; 58(5): 577-581, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30548854

RESUMO

BACKGROUND: Recent epidemiological studies suggest that past data where superficial spreading melanoma was by far the most common subtype of melanoma may not reflect current patterns of sun exposure or other risk factors more involved in other subtypes of melanoma as lentigo maligna (LM) or lentigo maligna melanoma (LMM). METHODS: In order to measure the current situation in our country, all cases of LM and LMM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007, were recorded. RESULTS: Although for the global period LM/LMM represented only 8.4% of cases, an increasing trend in this percentage was observed throughout the study period (from 6.9% [27 cases] in 2000 to 13.1% [94 cases] in 2007). Also, an increasing incidence of LM/LMM was observed, especially in chronically sun-exposed areas (85.5% involving the head and neck region). During the 8 years of the registry, the mean Breslow thickness of LMM remained stable. However, the increase in the number of LM (in situ) cases was significantly higher than the increase of the invasive ones. CONCLUSIONS: An important observation from this data is that aging of population and current sun exposure patterns could keep increasing the incidence of LM/LMM, which may become an important public healthcare problem, over the other histological subtypes. In order to establish primary or secondary preventive measures to the LM/LMM risk-population, it is imperative to highlight the importance of chronic sun damage as a melanoma risk factor, and not only sunburn, most commonly addressed in melanoma prevention campaigns.


Assuntos
Sarda Melanótica de Hutchinson/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia
7.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 36(9): 539-543, nov. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-176829

RESUMO

Objective: The comparison on mitochondrial function between severe septic patients and healthy control subjects according to mitochondrial deoxyribonucleic acid (mtDNA) haplogroup has not been previously reported; and this was the objective of the current study. Methods: Prospective, multicenter, observational study. We obtained blood samples from 198 severe septic patients at days 1, 4 and 8 of severe sepsis diagnosis and from 96 sex- and age-matched healthy controls to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The endpoint of the study was 30-day mortality. Results: We included 198 severe septic patients (38 with mtDNA haplogroup JT and 160 with mtDNA haplogroup non-JT) and 96 healthy control subjects (16 with mtDNA haplogroup JT and 80 with mtDNA haplogroup non-JT). We have no found statistically significant differences in platelet CIV specific activity between healthy controls and survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis; and the remaining severe septic patients showed lower platelet CIV specific activity than healthy controls with the same mtDNA haplogroup. Conclusions: The new finding of our study was that survivor severe septic patients and healthy controls with mtDNA haplogroup JT showed no different platelet Civ specific activity


Objetivo: La comparación en la función mitocondrial entre pacientes con sepsis grave y sujetos sanos según el haplogrupo del ácido desoxirribonucleico mitocondrial (ADNmt) no se ha reportado previamente; y este fue el objetivo del estudio. Métodos: Estudio prospectivo, multicéntrico y observacional. Obtuvimos muestras sanguíneas de 198 pacientes con sepsis grave en los días 1, 4 y 8 del diagnóstico de la sepsis grave y de 96 sujetos sanos para determinar el haplogrupo del ADNmt y la actividad del complejo respiratorio mitocondrial IV (CIV) en plaquetas circulantes. La variable resultado principal del estudio fue la mortalidad a los 30 días. Resultados: Se incluyeron 198 pacientes con sepsis grave (38 con haplogrupo JT del ADNmt y 160 con otro haplogrupo del ADNmt) y 96 sujetos sanos (16 con haplogrupo JT del ADNmt y 80 con otro haplogrupo del ADNmt). No encontramos diferencias estadísticamente significativas en la actividad de CIV plaquetaria entre los sujetos sanos y los pacientes sépticos supervivientes con haplogrupo JT del ADNmt en los días 1, 4 y 8 del diagnóstico de la sepsis grave; y el resto de los pacientes sépticos presentaron menor actividad de CIV plaquetaria que los sujetos sanos con su mismo haplogrupo del ADNmt. Conclusiones: El nuevo hallazgo de nuestro estudio fue que los pacientes sépticos y sujetos sanos con haplogrupo JT del ADNmt no tenían diferencias en la actividad de CIV plaquetaria


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mitocôndrias/genética , Mitocôndrias/metabolismo , Sepse/sangue , Sepse/fisiopatologia , Plaquetas , Estudos Prospectivos , Estudos de Casos e Controles , Sepse/mortalidade , Espanha/epidemiologia , Unidades de Terapia Intensiva
8.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 36(9): 544-549, nov. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-176830

RESUMO

Objective: Higher serum melatonin levels have previously been found in patients with severe sepsis who died within 30 days of diagnosis than in survivors. The objective of our study were to determine whether serum melatonin levels during the first seven days of severe sepsis diagnosis could be associated with sepsis severity and mortality. Methods: Multicentre study in eight Spanish Intensive Care Units which enrolled 308 patients with severe sepsis. We determined serum levels of melatonin, malondialdehyde (as biomarker of lipid peroxidation) and tumor necrosis factor-alpha at days 1, 4 and 8 of severe sepsis diagnosis. The study's primary endpoint was 30-day mortality. Results: A total of 103 patients had died and 205 survived at 30 days of severe sepsis diagnosis, with the non-survivors presenting higher serum melatonin levels at days 1 (p < 0.001), 4 (p < 0.001) and 8 (p < 0.001) of severe sepsis diagnosis than the survivor patient group. The multiple logistic regression analysis found that serum melatonin levels at days 1, 4 and 8 of severe sepsis diagnosis (p < 0.001, p = 0.01 and p = 0.001, respectively) were associated with mortality adjusted for age, serum lactic acid, SOFA score and diabetes mellitus. Conclusions: The novel and more interesting findings of our study were that serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality


Objetivo: Previamente se han encontrado mayores niveles séricos de melatonina en pacientes con sepsis grave que fallecían en los primeros 30 días del diagnóstico de la sepsis grave en comparación con los supervivientes. Los objetivos de nuestro estudio fueron determinar si los niveles séricos de melatonina durante la primera semana del diagnóstico de la sepsis grave están asociados con la gravedad y mortalidad de la sepsis. Métodos: Estudio multicéntrico en 8 Unidades de Cuidados Intensivos españolas con 308 pacientes con sepsis grave. Se determinaron niveles séricos de melatonina, malondialdehído (como biomarcador de peroxidación lipídica) y factor de necrosis tumoral-alfa en los días 1, 4 y 8 del diagnóstico de la sepsis grave. Consideramos la mortalidad a 30 días como la variable resultado principal del estudio. Resultados: Un total de 103 pacientes estaban fallecidos y 205 vivos a los 30 días del diagnóstico de la sepsis grave, y los fallecidos presentaron superiores niveles séricos de melatonina en los días 1 (p < 0.001), 4 (p < 0.001), y 8 (p < 0.001) del diagnóstico de la sepsis grave que los supervivientes. En el análisis de regresión logística múltiple encontramos que los niveles séricos de melatonina en los días 1, 4 y 8 del diagnóstico de la sepsis grave (p < 0.001, p = 0.01 and p = 0.001, respectively) estaban asociados con la mortalidad controlando por la edad, niveles séricos de ácido lactico, SOFA score y diabetes mellitus. Conclusiones: Los nuevos y más interesantes hallazgos de nuestro estudio son que los niveles séricos de melatonina durante la primera semana del diagnóstico de la sepsis grave están asociados con la gravedad y la mortalidad de la sepsis


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Sepse/sangue , Sepse/mortalidade , Melatonina/sangue , Biomarcadores/sangue , Índice de Gravidade de Doença , Estudos Prospectivos , Estudo Observacional
9.
J Crit Care ; 47: 139-144, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981999

RESUMO

PURPOSE: Higher circulating total antioxidant capacity (TAC) concentrations have been found in non-survivor than in survivor septic patients at moment of sepsis diagnosis. The objectives of this study were to determine whether serum TAC levels during the first week of sepsis are associated with lipid peroxidation, sepsis severity, and sepsis mortality, and whether could be used as a prognostic biomarker. METHODS: This prospective and observational study with 319 septic patients admitted to Intensive Care Units was carried out in 8 Spanish hospitals. We determined serum concentrations of malondialdehyde (to estimate lipid peroxidation) and TAC at days 1, 4 and 8 of sepsis. Mortality at 30 days was the end-point study. RESULTS: We found that serum TAC concentrations at days 1, 4 and 8 could predict 30-day mortality according to ROC curve analyses (p < 0.001), that were associated with 30-day mortality according to regression analyses (p < 0.001), and that were associated with serum levels of malondialdehyde and SOFA score. CONCLUSIONS: The new findings of our study were that serum TAC levels during the first week of sepsis are associated with lipid peroxidation, sepsis severity, and sepsis mortality, and that could be used as a prognostic biomarker.


Assuntos
Antioxidantes/análise , Cuidados Críticos , Sepse/sangue , Sepse/mortalidade , Idoso , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão
10.
Enferm Infecc Microbiol Clin ; 36(9): 539-543, 2018 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29054538

RESUMO

OBJECTIVE: The comparison on mitochondrial function between severe septic patients and healthy control subjects according to mitochondrial deoxyribonucleic acid (mtDNA) haplogroup has not been previously reported; and this was the objective of the current study. METHODS: Prospective, multicenter, observational study. We obtained blood samples from 198 severe septic patients at days 1, 4 and 8 of severe sepsis diagnosis and from 96 sex- and age-matched healthy controls to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The endpoint of the study was 30-day mortality. RESULTS: We included 198 severe septic patients (38 with mtDNA haplogroup JT and 160 with mtDNA haplogroup non-JT) and 96 healthy control subjects (16 with mtDNA haplogroup JT and 80 with mtDNA haplogroup non-JT). We have no found statistically significant differences in platelet CIV specific activity between healthy controls and survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis; and the remaining severe septic patients showed lower platelet CIV specific activity than healthy controls with the same mtDNA haplogroup. CONCLUSIONS: The new finding of our study was that survivor severe septic patients and healthy controls with mtDNA haplogroup JT showed no different platelet Civ specific activity.


Assuntos
DNA Mitocondrial/genética , Haplótipos , Mitocôndrias/fisiologia , Sepse/fisiopatologia , Adulto , Idoso , DNA Mitocondrial/sangue , DNA Mitocondrial/classificação , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação Oxidativa , Prognóstico , Estudos Prospectivos , Sepse/sangue , Sepse/genética , Sepse/mortalidade , Sobreviventes
11.
Enferm Infecc Microbiol Clin ; 36(9): 544-549, 2018 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29198774

RESUMO

OBJECTIVE: Higher serum melatonin levels have previously been found in patients with severe sepsis who died within 30 days of diagnosis than in survivors. The objective of our study were to determine whether serum melatonin levels during the first seven days of severe sepsis diagnosis could be associated with sepsis severity and mortality. METHODS: Multicentre study in eight Spanish Intensive Care Units which enrolled 308 patients with severe sepsis. We determined serum levels of melatonin, malondialdehyde (as biomarker of lipid peroxidation) and tumor necrosis factor-alpha at days 1, 4 and 8 of severe sepsis diagnosis. The study's primary endpoint was 30-day mortality. RESULTS: A total of 103 patients had died and 205 survived at 30 days of severe sepsis diagnosis, with the non-survivors presenting higher serum melatonin levels at days 1 (p<0.001), 4 (p<0.001) and 8 (p<0.001) of severe sepsis diagnosis than the survivor patient group. The multiple logistic regression analysis found that serum melatonin levels at days 1, 4 and 8 of severe sepsis diagnosis (p<0.001, p=0.01 and p=0.001, respectively) were associated with mortality adjusted for age, serum lactic acid, SOFA score and diabetes mellitus. CONCLUSIONS: The novel and more interesting findings of our study were that serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality.


Assuntos
Melatonina/sangue , Sepse/sangue , Idoso , Comorbidade , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/mortalidade , Índice de Gravidade de Doença , Espanha/epidemiologia , Fator de Necrose Tumoral alfa/sangue
12.
Intensive Care Med ; 43(11): 1660-1667, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28936675

RESUMO

BACKGROUND: Spontaneous breathing trials (SBT) can be exhausting, but the preventive role of rest has never been studied. This study aimed to evaluate whether reconnection to mechanical ventilation (MV) for 1 h after the effort of a successful SBT could reduce the need for reintubation in critically ill patients. METHODS: Randomized multicenter trial conducted in 17 Spanish medical-surgical intensive care units (Oct 2013-Jan 2015). Patients under MV for longer than 12 h who fulfilled criteria for planned extubation were randomly allocated after a successful SBT to direct extubation (control group) or reconnection to the ventilator for a 1-h rest before extubation (rest group). The primary outcome was reintubation within 48 h. Analysis was by intention to treat. RESULTS: We recruited 243 patients randomized to the control group and 227 to the rest group. Median time from intubation to SBT did not differ between groups [5.5 (2.7, 9.6) days in the control group vs. 5.7 (2.7, 10.6) in the rest group; p = 0.85]. Reintubation within 48 h after extubation was more common in the control than in the rest group [35 (14%) vs. 12 (5%) patients; OR 0.33; 95% CI 0.16-0.65; p < 0.001]. A multivariable regression model demonstrated that the variables independently associated with reintubation were rest [OR 0.34 (95%CI 0.17-0.68)], APACHE II [OR 1.04 (1.002-1.077)], and days of MV before SBT [OR 1.04 (1.001-1.073)], whereas age, reason for admission, and type and duration of SBT were not. CONCLUSION: One-hour rest after a successful SBT reduced the rates of reintubation within 48 h after extubation in critically ill patients. Trial registration Clinicaltrials.gov identifier NCT01915563.


Assuntos
Extubação/métodos , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Desmame do Respirador/métodos , APACHE , Idoso , Extubação/efeitos adversos , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Análise de Intenção de Tratamento , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/etiologia , Índice de Gravidade de Doença , Fatores de Tempo
13.
Int J Mol Sci ; 18(7)2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28714876

RESUMO

Previously, researchers found higher serum substance P (SP) concentrations in survivors of severe sepsis than in non-survivors at the time of severe sepsis diagnosis. The objectives of our current study were to determine whether there is an association between serum SP levels during the first week and sepsis mortality, sepsis severity, serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10, and whether serum SP levels during the first week could be used as a biomarker of sepsis mortality. We determined serum concentration of SP, TNF-α, and IL-10 at days 1, 4, and 8. The end-point of the study was mortality at 30 days. We found that non-survivor (n = 104) compared to survivor patients (n = 206) showed lower serum SP levels at days 1, 4, and 8 (p < 0.001). Multiple logistic regression analyses showed an association between 30-day mortality and serum SP levels at days 1, 4, and 8 (p < 0.001) controlling for SOFA score, diabetes mellitus, age, and lactic acid levels. The most interesting findings of our study were that there is an association between serum SP levels during the first week and sepsis mortality, and that serum SP levels during the first week could be used as a biomarker of sepsis mortality.


Assuntos
Sepse/sangue , Sepse/mortalidade , Substância P/sangue , Humanos , Interleucina-10/sangue , Estimativa de Kaplan-Meier , Modelos Logísticos , Curva ROC , Sobreviventes , Fator de Necrose Tumoral alfa/sangue
14.
J Crit Care ; 41: 177-182, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28570959

RESUMO

INTRODUCTION: Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non-survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker?. This study was developed to answer these asks. METHODS: Study from 6 Spanish Intensive Care Units with 291 severe septic patients. There were determined serum levels of sCD40L and tumor necrosis factor (TNF)-alpha during the first week. The end-point study was 30-day mortality. RESULTS: We found that serum sCD40L at days 1, 4, and 8 could predict mortality at 30days, and are associated with mortality. CONCLUSIONS: The novel findings of our study were that there were higher serum sCD40L levels persistently during the first week in non-survivor than in survivor patients, that there is an association between serum sCD40L levels during the first week and sepsis mortality, and that serum sCD40L levels during the first week could be used as sepsis mortality biomarker.


Assuntos
Ligante de CD40/sangue , Mortalidade Hospitalar , Sepse/sangue , Sepse/mortalidade , Idoso , Biomarcadores/sangue , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sobreviventes , Fator de Necrose Tumoral alfa/sangue
15.
Clin Chem Lab Med ; 55(10): 1621-1629, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28282291

RESUMO

BACKGROUND: Caspase-cleaved cytokeratin (CCCK)-18 is a protein released into the blood during apoptosis. Higher circulating CCCK-18 concentrations have been found in non-survivor than in survivor septic patients at moment of sepsis diagnosis. The following questions arise now: (1) How are serum CCCK-18 levels during the first week of sepsis? (2) Is there an association between sepsis severity and mortality and serum CCCK-18 levels during the first week? The aims of this study were to answer these questions. METHODS: Multicenter study with 321 severe septic patients from eight Spanish intensive care units. We determined serum concentration of CCCK-18, tumor necrosis factor (TNF)-α, and interleukin (IL)-10 during the first week. Our end-point study was 30-day mortality. RESULTS: Non-survivor (n=108) compared to survivor patients (n=213) showed higher serum CCCK-18 levels at days 1, 4 and 8 (p<0.001). ROC curve analyses showed that serum CCCK-18 levels at days 1 (AUC=0.77; 95% CI=0.72-0.82), 4 (AUC=0.81; 95% CI=0.76-0.85) and 8 (AUC=0.83; 95% CI=0.78-0.88) could predict mortality at 30 days (p<0.001). Logistic regression analyses showed that serum CCCK-18 levels at days 1 (OR=4.367; 95% CI=2.491-7.659), 4 (OR=10.137; 95% CI=4.741-21.678) and 8 (OR=8.781; 95% CI=3.626-21.268) were associated with 30-day mortality (p<0.001). We found a positive correlation between CCCK-18, SOFA, and lactic acid at days 1, 4 and 8. CONCLUSIONS: Non-survivor septic patients showed persistently during the first week higher serum CCCK-18 levels than survivor patients, and there is an association between sepsis severity and mortality and serum CCCK-18 levels during the first week.


Assuntos
Caspases/metabolismo , Queratina-18/sangue , Sepse/diagnóstico , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Interleucina-10/sangue , Estimativa de Kaplan-Meier , Queratina-18/metabolismo , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sepse/mortalidade , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
16.
Int J Mol Sci ; 17(11)2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27834822

RESUMO

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; p = 0.03) or GC (hazard ratio = 0.28; 95% CI = 0.074-1.037; p = 0.06). The most important results of our study were that CC might be a favorable genotype in septic patients showing lower serum IL-6 levels and lower risk of death within 30 days.


Assuntos
Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Sepse/diagnóstico , Sepse/genética , Adulto , Idoso , Feminino , Expressão Gênica , Homozigoto , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Regiões Promotoras Genéticas , Estudos Prospectivos , Análise de Regressão , Sepse/sangue , Sepse/mortalidade , Análise de Sobrevida
17.
J Crit Care ; 34: 103-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27288619

RESUMO

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Assuntos
Caspase 3/sangue , Queratina-18/sangue , Sepse/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/mortalidade , Espanha , Sobreviventes
18.
J Crit Care ; 33: 95-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26936038

RESUMO

OBJECTIVE: The influence of mitochondrial deoxyribonucleic acid (mtDNA) haplogroup or oxidative phosphorylation system (OXPHOS) function on survival of septic patients has been scarcely studied. However, the association between mtDNA haplogroup, OXPHOS capacity at diagnosis of severe sepsis, and survival has been not previously reported, and that was the objective of the present study. METHODS: This was a prospective, multicenter, observational study. Blood samples from 198 patients at diagnosis of severe sepsis were analyzed to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The end point of the study was 30-day survival. RESULTS: Septic patients with mtDNA haplogroup JT showed higher 30-day survival than those with mtDNA haplogroup non-JT (31/38 [81.6%] vs 99/160 [61.9%]; P= .02). Septic patients with mtDNA haplogroup JT showed higher platelet CIV specific activity than those with mtDNA haplogroup non-JT (P= .002). CONCLUSIONS: The main novel finding of our study, including the largest series providing data on platelet CIV specific activity according to mtDNA haplogroup in severe septic patients, was that those with mtDNA haplogroup JT showed higher survival and higher platelet CIV specific activity at diagnosis of severe sepsis than patients with mtDNA haplogroup non-JT.


Assuntos
DNA Mitocondrial/genética , Fosforilação Oxidativa , Sepse/genética , Idoso , Cuidados Críticos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Haplótipos/genética , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/metabolismo , Sepse/mortalidade , Espanha , Taxa de Sobrevida
19.
PLoS One ; 10(6): e0129565, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26066833

RESUMO

OBJECTIVE: Two studies have reported that patients with the 4G/4G genotype of the plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease, and the other included 88 adult patients with septic shock. Thus, the objective of this study was to determine whether there is an association between carriage of the 4G/4G genotype, plasma PAI-1 concentrations and mortality in a large series of adult septic patients. METHODS: An observational, prospective, multicenter study was carried out in six Spanish Intensive Care Units including severe septic patients. We determined the PAI-1 4G/5G polymorphism and plasma PAI-1 concentrations in all patients. The end-points of the study were 30-day and 6-month mortality. RESULTS: We included a total of 260 patients, 82 (31.5%) with 4G/4G, 126 (48.5%) with 4G/5G and 52 (20.0%) with 5G/5G genotype. Multivariate logistic regression analysis showed that the 4G/4G genotype was associated with higher mortality at 30 days (Odds Ratio = 1.95; 95% CI = 1.063-3.561; p = 0.03) and at 6 months (Odds Ratio = 2.19; 95% CI = 1.221-3.934; p = 0.01), and that higher plasma PAI-1 concentrations were associated with higher mortality at 30 days (Odds Ratio = 1.01; 95% CI = 1.002-1.022; p = 0.02) at 6 months (Odds Ratio = 1.01; 95% CI = 1.003-1.023; p = 0.01). Multivariate linear regression analysis showed that increased plasma PAI-1 concentrations were associated with the PAI-1 4G/4G genotype (regression coefficient = 4.82; 95% CI = 3.227 to 6.406; p<0.001). CONCLUSIONS: The major findings of our study, to our knowledge the largest series reporting data about 4G/5G polymorphism of the PAI-1 gene, plasma PAI-1 concentrations and mortality in septic patients, were that septic patients with the 4G/4G genotype had higher plasma PAI-1 concentrations and higher risk of death than those with 4G/5G or 5G/5G genotypes.


Assuntos
Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Sepse/genética , Sepse/mortalidade , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Estudos Prospectivos , Espanha , Análise de Sobrevida
20.
J Crit Care ; 30(5): 924-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26072386

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The major new finding of our study was that serum SP levels were associated with mortality in severe septic patients.


Assuntos
Sepse/mortalidade , Substância P/metabolismo , Idoso , Biomarcadores/sangue , Cuidados Críticos , Feminino , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Sepse/sangue
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