Severe septic patients with mitochondrial DNA haplogroup JT show higher survival rates: a prospective, multicenter, observational study.

OBJECTIVE: In a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients. METHODS: We conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score. RESULTS: Logistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival. CONCLUSIONS: The global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups.

The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis.

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.

Prognostic value of malondialdehyde serum levels in severe sepsis: a multicenter study.

OBJECTIVE: The oxidant/antioxidant state in septic patients has only been studied in small series. We wished to determine whether malondialdehyde (MDA) serum levels were associated with severity and 30-day mortality in a large series of patients with sepsis. METHODS: We performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in a total of 228 patients (145 survivors and 83 non-survivors) with severe sepsis and 100 healthy controls. RESULTS: Serum levels of MDA were higher in severe septic patients than in healthy controls. Non-surviving septic patients had higher MDA values than survivors. MDA serum levels were associated with severity markers (lactic acid, SOFA, APACHE-II) and coagulation indices. Regression analysis showed that MDA serum levels were associated with 30-day survival (Hazard ratio = 1.05; 95% confidence interval = 1.009-1.091; p = 0.016). Receiver operating characteristic analysis showed that the area under curve of MDA serum levels to predict 30-day survival was 0.62 (95% CI = 0.56-0.69; P = 0.002). The risk of death in septic patients with MDA serum levels above 4.11 nmol/mL was higher than in patients with lower values (Hazard Ratio = 2.43; 95% CI = 1.49-3.94; p<0.001). CONCLUSIONS: The novel findings of our study on severe septic patients, to our knowledge the largest series providing data on the oxidative state, are that elevated MDA serum levels probably represent an unbalanced oxidant state and are related with poor prognosis in patients with severe sepsis.

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

INTRODUCTION: CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. METHODS: This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. RESULTS: Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). CONCLUSIONS: In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

Consumo oculto de cocaína en urgencias neurológicas / No disponible

No disponible

Undisclosed cocaine use and chest pain in emergency departments of Spain.

AIMS: Illicit cocaine consumption in Spain is one of the highest in Europe. Our objective was to study the incidence of undisclosed cocaine consumption in patients attending in two Spanish Emergency Departments for chest pain. METHODS: We analysed urine samples from consenting consecutive patients attending ED for chest pain to determine the presence of cocaine, and other drugs, by semiquantative tests with fluorescence polarization immunoassay (FPIA). RESULTS: Of 140 cases, 15.7 presented positive test for drugs, and cocaine was present in 6.4%. All cocaine-positive patients were younger (p < 0.001); none was admitted to Hospital (p = 0.08). No significant differences in ED stay or need for hospitalization were found between cocaine-positive and negative patients. CONCLUSION: This finding in chest pain patients who consented to urine analysis suggests that the true incidence of cocaine use leading to such ED visits may be higher.

Consumo de cocaína y su relación con patología cardiaca y traumática atendida en un servicio de urgencias / Cocaine use and its relationship with cardiovascular pathology and trauma seen in an emergency department

Objetivo: Conocer la prevalencia de consumo de cocaína entre usuarios que consultan a un servicio de urgencias de un hospital de tercer nivel por patología traumática o cardiovascular, sin que exista una relación evidente de consumo y sin que el usuario hiciera explícito de manera espontánea dicho consumo, así como si dicho consumo se asocia a una mayor utilización de recursos sanitarios. Método: Entre octubre de 2005 y septiembre de 2006 se recogieron muestras de orina a los pacientes mayores de 16 años que acudieron a urgencias por un traumatismo de cualquier gravedad o un dolor torácico de probable causa cardiovascular. Se determinaron los niveles de cocaína en orina mediante ensayos semicuantitativos con tecnología de inmunoanálisis de polarización de la fluorescencia (FPIA).Resultados: Se obtuvieron 325 casos (206 traumatismos y 119 dolores torácicos). La prevalencia global de consumo no declarado de cocaína fue del 19,7% (18,9% para los traumatismos y 21% para el dolor torácico). En los traumatismos, la presencia de cocaína se asoció de forma significativa a una mayor petición de analítica (p < 0,05), en tanto que en el dolor torácico no se observaron diferencias en el consumo de recursos. Conclusiones: El consumo de cocaína no declarado entre los usuarios de un servicio de urgencias con patología cardiológica o traumática presenta una prevalencia alta. No parece que este hecho modifique en gran medida el gasto sanitario en la fase de atención aguda de estas patologías, cuando no son directamente el motivo de consulta del paciente (AU)

Objective: To determine the prevalence of cocaine use among patients seen in the emergency department of a tertiary hospital for trauma or cardiovascular disorders and in whom there was no obvious relationship with cocaine use and none was spontaneously declared by the patient. We also analyzed whether this substance abuse was associated with a greater use of health care resources. Material and methods: Between October 2005 and September 2006, urine samples were collected from patients over 16years of age who were seen in the emergency department for trauma of any severity or chest pain of probable cardiovascular origin. The cocaine levels were measured in urine using a semi quantitative fluorescence polarization immunoassay. Results: We studied 325 cases, 206 with trauma and 119 with chest pain. The overall prevalence of undisclosed use was19.7%; the prevalence was 18.9% among trauma patients and 21% among those with chest pain. In cases of trauma, cocaine use was significantly associated with more frequent requests for blood tests (P < .05), whereas no differences in the use of health care resources for chest pain patients were observed. Conclusions: There is a high prevalence of undisclosed cocaine use among patients attending an emergency department in relation to cardiovascular complaints or trauma. When cocaine use is not the direct reason for the patient’s visit, it does not appear to lead to a marked variation in health care costs during the acute phase of emergency treatment (AU)

Incidence and impact of undisclosed cocaine use in emergency department chest pain and trauma patients.

BACKGROUND: One of the highest rates of illicit cocaine consumption in Europe is in Spain. Our objective was to study the incidence and impact of undisclosed cocaine consumption in patients attending the emergency department (ED) for trauma or chest pain. METHODS: We analysed urine samples from consecutive patients attending the ED for trauma or chest pain to determine the presence of cocaine, cannabis, amphetamine/metaamphetamine and opioids by semiquantative tests with fluorescence polarization immunoassay (FPIA). RESULTS: Thirty percent of eligible patients participated. Of 75 cases, 61.3% had trauma and 38.7% chest pain; 25% presented a positive test for drugs. Cocaine was present in 13.3% and cannabis in the same proportion. No differences were found regarding positive cocaine test and chief complaint, ED or hospital stay, or additional tests. Cocaine-positive patients were significantly younger.