Serum Fas levels during first week of sepsis are associated with severity and mortality.

INTRODUCTION: The aim of our study was to explore whether there is an association of serum sFas (cell death apoptosis receptor) concentrations during the first week of sepsis with sepsis severity and sepsis mortality. METHODS: In this observational study, septic patients were recruited. Serum sFas concentrations were determined on days 1, 4, and 8 of sepsis diagnosis. Thirty-day mortality was the outcome variable. RESULTS: Surviving patients (n = 181) compared to non-survivors (n = 101) presented lower serum sFas levels on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001), and lower SOFA on day 1 (p < 0.001), day 4 (p < 0.001) and day 8 (p < 0.001). Logistic regression analyses showed associations between 30-day mortality and serum sFas levels controlling for SOFA on day 1 (OR = 1.005; 95% CI = 1.003-1.007; p < 0.001), day 4 (OR = 1.044; 95% CI = 1.029-1.060; p < 0.001) and day 8 (OR = 1.012; 95% CI = 1.002-1.022; p = 0.02). CONCLUSIONS: The association of serum sFas concentrations during the first week of sepsis with sepsis severity and sepsis mortality were our new findings.

Mortality prediction of septic patients by blood caspase-8 levels.

We have not found data about blood caspase-8 concentrations (initiator caspase in the extrinsic pathway of apoptosis) during follow-up of sepsis and this was the objective of our study. We included septic patients. Serum caspase-8 concentrations were determined at days 1, 4, and 8 of sepsis diagnosis. We registered mortality at 30 days. Nonsurviving patients (n = 89) in respect to surviving patients (n = 160) showed higher serum caspase-8 levels at days 1 (P < 0.001), 4 (P <0.001), and 8 (P <0.001) of sepsis diagnosis. Serum caspase-8 levels on day 1, day 4, and day 8 had an area under curve for the prediction of 30-day mortality of 68% (60%-75%, P<0.001), 72% (62%-82%, P<0.001), and 81% (73%-90%, P<0.001). Thus, that blood caspase-8 concentrations at any time during the first week of sepsis were higher in non-survivor than in survivor patients and that were able to predict mortality were new findings in our study.

Mortality of spontaneous intracerebral haemorrhage patients and high serum caspase-8 concentrations.

PURPOSE: Apoptotic changes in brain samples have been found in haematoma areas of patients with spontaneous intracerebral haemorrhage (SIH) undergoing surgical haematoma evacuation. However, circulating caspase-8 concentrations in SIH patients have not been described. Thus, we carried out this study with the aim to explore whether there is an association of circulating caspase-8 concentrations and mortality in patients with SIH. METHODS: We included patients with severe and supratentorial SIH. We established that the SIH was severe if Glasgow Coma Scale (GCS) was lower than 9. Intensive Care Units from 5 Spanish hospitals carried out the recruitment of patients of this observational and prospective study. We registered serum caspase-8 levels at moment of severe SIH diagnosis and 30-day mortality. RESULTS: Surviving (n = 41) in respect to non-surviving SIH patients (n = 38) showed lower serum caspase-8 levels (p < 0.001). The area under the curve to estimate 30-day mortality ability by serum caspase-8 levels was 0.75 (95% CI = 0.64-86; p < 0.001). Kaplan-Meier analysis found that patients with serum caspase-8 levels > 17.8 ng/mL showed higher death risk (Hazard ratio = 3.9; 95% CI = 1.99-7.63; p < 0.001). Multiple logistic regression analysis revealed the association of serum caspase-8 concentrations (controlling for intracerebral haemorrhage score, midline shift and early haematoma evacuation) with mortality at 30 days (Odds Ratio = 1.048; 95% CI = 1.018-1.079; p = 0.002). CONCLUSIONS: The association of serum caspase-8 concentrations with mortality of SIH patient mortality is the main of novel findings that have been revealed in our study.

Obesity and metabolic syndrome induce hyperfiltration, glomerulomegaly, and albuminuria in obese ovariectomized female mice and obese male mice.

OBJECTIVE: Obese patients with metabolic syndrome have a high risk of chronic kidney disease. The prevalence of obesity, metabolic syndrome, and insulin resistance increase in women after menopause, as does the risk of chronic kidney disease. This may indicate an interaction between obesity, metabolic syndrome, and menopause in the induction of renal damage. However, the pathogenesis of kidney disease in postmenopausal obese women is poorly understood. METHODS: We investigated the interaction of an obesogenic diet and menopause on renal dysfunction in ovariectomized and non-ovariectomized lean (n = 8 and 17) and obese (n = 12 and 20) female mice. Obese (n = 12) and lean (n = 10) male mice were also studied. Glucose metabolism, insulin resistance, and kidney function were evaluated with gold standards procedures. Changes in kidney histology and lipid deposition were analyzed. Females had a lower number of glomeruli than males at baseline. RESULTS: Only female ovariectomized obese animals developed insulin resistance, hyperglycemia, and kidney damage, evidenced as glomerulomegaly, glomerular hyperfiltration, and increased urinary albumin excretion, despite a similar increase in weight than obese non-ovariectomized female mice. Male obese mice developed hyperglycemia, insulin resistance, and hyperfiltration without major renal histological changes. Males on high fat diet showed higher renal lipid content and females on high fat diet (ovariectomized or non-ovariectomized) showed higher total cholesterol content than males. CONCLUSIONS: In mice, there is a clear interplay between obesity, metabolic syndrome, and menopause in the induction of kidney damage.

Video Summary : http://links.lww.com/MENO/A803 .

Baseline Levels of Vitamin D in a Healthy Population from a Region with High Solar Irradiation.

The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as "optimal" and those shown by the healthy population but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D (25(OH)D) in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and, who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th; 95th percentile, 14.3; 45.8) ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30 ng/mL, 23.4% below 20 ng/mL and 6.4% below 15 ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20 ng/mL, or even ≥30 ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20 ng/mL and close to 15 ng/mL as adequate for the general population.

Serum Levels of B-cell Lymphoma-2 Anti-Apoptotic Protein and Malignant Middle Cerebral Artery Infarction Mortality.

INTRODUCTION AND GOAL: There is scarce and contradictory data on B-cell lymphoma 2 (Bcl2), member of the Bcl-2 antiapoptotic molecules family of intrinsic apoptosis pathway, in ischemic stroke patients. The objective of this study was to determine whether there is an association between blood Bcl2 concentrations and mortality of ischemic stroke patients. MATERIAL AND METHODS: Five Intensive Care Units participated in this prospective and observational study of patients with severe malignant middle cerebral artery infarction (MMCAI). Severe MMCAI was diagnosed when acute infarction was present in 50% or more of said region and with a Glasgow Coma Scale (GCS) score of less than 9 points. Serum samples were collected at the time of MMCAI diagnosis. FINDINGS: Higher serum Bcl2 concentrations (p = 0.001), lower platelet count (p = 0.01) and lower GCS (p = 0.002) were found in non-survivors (n = 28) than in MMCAI survivors (n = 28). Serum Bcl2 levels had an area under the curve for mortality prediction of 75% (95% CI = 62%-88%; p < 0.001). Patients with serum Bcl2 levels > 43.6 ng/mL had higher mortality rate according to Kaplan-Meier analysis (Hazard ratio=10.0; 95% CI = 3.4-29.5; p < 0.001). Multiple logistic regression showed an association between serum Bcl2 and mortality at 30 days (OR = 1.041; 95% CI = 1.006-1.077; p = 0.02) controlling for GCS and platelet count. CONCLUSIONS: This study reports for the first time the higher blood Bcl2 concentrations in non-surviving ischemic stroke patients than in survivors and the association between elevated blood Bcl2 and mortality in ischemic stroke patients.

Serum B cell lymphoma-2 concentrations and mortality of patients with spontaneous intracerebral hemorrhage.

OBJECTIVE: There is scarce data on B cell lymphoma 2 (Bcl2), a member of the Bcl-2 family of antiapoptotic molecules of the intrinsic apoptosis pathway, in patients with spontaneous intracerebral hemorrhage (SIH). In one study, higher serum Bcl2 levels were found in patients with SIH than in healthy subjects. Thus, the objective of our study was to compare serum Bcl2 levels in surviving and non-surviving SIH patients. METHODS: Patients with severe supratentorial SIH (defined as Glasgow Coma Scale < 9) admitted from the Intensive Care Units of five Spanish hospitals were included in this observational and prospective study. Serum levels of Bcl2L were determined at the time of diagnosis. Thirty-day mortality was the end-point study. RESULTS: Non-surviving (n = 38) compared to surviving patients (n = 41) had higher intracerebral hemorrhage (ICH) score (p = 0.001), midline shift (p = 0.003), and serum Bcl2 levels (p < 0.001). In addition, non-surviving compared to surviving patients had lower early hematoma evacuation rate (p = 0.03). We found 77% area under curve in mortality prediction for serum Bcl2 levels (95% CI = 0.66-88%; p < 0.001). Patients showing serum Bcl2 levels > 16.5 ng/mL had higher risk of death according to analysis of Kaplan-Meier (HR = 5.2; 95% CI = 2.5-10.6; p < 0.001). An association, after control for ICH score, midline shift, and early hematoma evacuation, was found between serum Bcl2 levels and 30-day mortality (OR = 1.090; 95% CI = 1.030-1.154; p = 0.003) in the multiple logistic regression. CONCLUSIONS: As far as we know, our study is the first one reporting higher serum Bcl2 levels in non-surviving than in surviving SIH patients and the association between serum Bcl2 levels and SIH mortality.