Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC-QTOF-MS/MS platform.

Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n = 25) or without (n = 32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection.

Urinary Neutrophil Gelatinase-Associated Lipocalin as Predictor of Short- or Long-Term Outcomes in Cardiac Surgery Patients.

OBJECTIVES: To determine the ability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) to predict cardiac surgery-associated acute kidney injury (CSA-AKI), continuous renal replacement therapy (CRRT), mortality, and a composite outcome of major adverse kidney events at 365 days (MAKE365), and to investigate the influence of cardiopulmonary bypass (CPB) on NGAL release. DESIGN: A prospective observational study. SETTING: A single-center university hospital. PARTICIPANTS: A cohort of 288 adult cardiac surgery patients. INTERVENTIONS: uNGAL was measured at baseline, immediately after surgery, and on days 1 and 2 postoperatively. The authors used the recent Kidney Disease Improving Global Outcomes consensus criteria to define CSA-AKI. MEASUREMENTS AND MAIN RESULTS: CSA-AKI occurred in 36.1% of patients. uNGAL rapidly became significantly higher in patients who developed AKI, with peak value immediately after surgery (349.9 [76.6-1446.6] v 90.1 [20.8-328] ng/mg creatinine; p<0.001). No measure of uNGAL (peak, postsurgery, day 1 or 2 postsurgery) accurately predicted CSA-AKI, CRRT, mortality, or MAKE365. However, immediately after surgery, CPB induced greater uNGAL release compared with off-pump surgery (265.5 µmol/L [71-989.6] v 48.7 ng/mg creatinine [17-129.8]; p<0.001). Moreover, such early uNGAL release correlated with CPB duration (r = 0.505; p<0.001) but not with peak serum creatinine values on day 3 or 7 after surgery. CONCLUSIONS: uNGAL had a limited predictive ability for CSA-AKI or other relevant clinical outcomes after cardiac surgery and appeared to be more closely related to the use and duration of CPB. Thus, its levels may represent the aggregate effect of an inflammatory response to CPB as well as a renal response to cardiac surgery and inflammation.

Genome-wide linkage analysis for identifying quantitative trait loci involved in the regulation of lipoprotein a (Lpa) levels.

Lipoprotein Lp(a) levels are highly heritable and are associated with cardiovascular risk. We performed a genome-wide linkage analysis to delineate the genomic regions that influence the concentration of Lp(a) in families from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. Lp(a) levels were measured in 387 individuals belonging to 21 extended Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1 cM genetic map. The variance component linkage method was used to evaluate linkage and to detect quantitative trait loci (QTLs). The main QTL that showed strong evidence of linkage with Lp(a) levels was located at the structural gene for apo(a) on chromosome 6 (LOD score=13.8). Interestingly, another QTL influencing Lp(a) concentration was located on chromosome 2 with an LOD score of 2.01. This region contains several candidate genes. One of them is the tissue factor pathway inhibitor (TFPI), which has antithrombotic action and also has the ability to bind lipoproteins. However, quantitative trait association analyses performed with 12 SNPs in TFPI gene revealed no association with Lp(a) levels. Our study confirms previous results on the genetic basis of Lp(a) levels. In addition, we report a new QTL on chromosome 2 involved in the quantitative variation of Lp(a). These data should serve as the basis for further detection of candidate genes and to elucidate the relationship between the concentration of Lp(a) and cardiovascular risk.

[Treatment and control of cardiovascular risk in primary care in Spain. The PREVENCAT study]. / Tratamiento y control del riesgo cardiovascular en atención primaria en España. Estudio PREVENCAT.

BACKGROUND AND OBJECTIVE: The PREVENCAT study was designed to estimate the control of the main cardiovascular risk factors (CVRF) and their treatment in a sample of population having the diagnoses of hypertension (HT), type 2 diabetes mellitus (DM2) or hypercholesterolemia (HC) who was attended by primary care physicians in Spain. PATIENTS AND METHOD: Cross-sectional study in patients with HT, DM2 and/or HC, who were consecutively recruited. We describe the treatments for HT, DM2 and HC and analyze and the association between several potential predictors and the control of these CVRF. RESULTS: 2,649 patients were included in the study. 95% of HT patients were under treatment, as were 84% of DM2 and 71.4% of HC patients; most common drugs were diuretics, sulphonylureas and statins, respectively. Monotherapy was more frequent than combined therapy for hypertension treatment. The frequency of HT and DM2 treatment was similar among the subgroups defined by the presence or absence of the other two diagnoses. However, HC treatment was more common in the presence of DM2 (p = 0.001). Age, previous cardiovascular disease (CVD), DM2, obesity and sedentarism were all predictors of poor blood pressure control despite drug treatment. Age, previous CVD, HT and sedentarism were predictors of poor HC control. CONCLUSIONS: CVRF treatment was high although heterogeneous and not based on the best available evidence. DM2, previous CVD and obesity were associated with insufficient blood pressure control.

Fat distribution and metabolic abnormalities in HIV-infected patients on first combination antiretroviral therapy including stavudine or zidovudine: role of physical activity as a protective factor.

OBJECTIVE: To compare body composition, serum lipid profile, parameters of insulin secretion and endocrine measurements in HIV-1-infected patients whose first combination antiretroviral regimen differed only in a nucleoside reverse transcriptase inhibitor (NRTI). DESIGN AND SETTING: Cross-sectional study in an AIDS clinic of a university hospital. PATIENTS: One-hundred-and-fifty HIV-infected patients on long-term first highly active antiretroviral therapy including stavudine (n=75) or zidovudine (n=75). MAIN OUTCOME MEASURE: Fat wasting was assessed by physical examination. Regional fat distribution was estimated using calliper measurements of skinfold thickness at four sites. Central adiposity was assessed by measurement of waist-hip ratio. Fasting glucose, insulin, triglyceride, cholesterol and its fractions, testosterone, follicle stimulating hormone, luteinizing hormone levels, CD4 cell count and HIV viral load were determined. Daily caloric intake and physical activity level were also calculated. RESULTS: Total body fat was significantly lower in patients taking stavudine, whereas the lean body mass was not statistically different amongst both groups. Ninety-four patients (62.7%; 95% CI: 54.9-70.4%) had fat redistribution, being isolated lipoatrophy in 20 (13.3%; 95% CI: 7.9-18.8%), isolated lipohypertrophy in 33 (22.0%; 95% CI: 15.4-28.6%) and mixed syndrome in 41 (27.3%; 95% CI: 20.2-34.5%). There were not statistically significant differences between stavudine- and zidovudine-treated patients with respect to the overall prevalence of fat redistribution syndromes (P=0.34). The prevalence of lipoatrophy (OR=1.86; 95% CI: 0.58-6.33, P=0.37), lipohypertrophy (OR=0.65; 95% CI: 0.25-1.69, P=0.45) and mixed syndromes (OR=1.05; 95% CI: 0.43-2.54, P=0.93) was not statistically different in both groups of patients. The only independent predictor for the appearance of mixed syndrome and lipoatrophy was sedentarism (OR=4.418; 95% CI: 1.565-12.472, P=0.005) and (OR=4.515; 95% CI: 1.148-17.761, P=0.03), respectively. Independent predictors of lipohypertrophy were age (OR=1.138; 95% CI: 1.061-1.220, P<0.0001) and prior AIDS (OR=0.305; 95% CI: 0.100-0.931, P=0.04). There were no statistically significant differences between stavudine and zidovudine-based groups with respect to metabolic and hormonal parameters. CONCLUSION: The use of stavudine or zidovudine in the context of the first combination antiretroviral therapy is not associated either with an increased likelihood of lipid or gonadal hormones abnormalities, and although there was a trend to a lesser body fat content in the stavudine group, there was no increase in the overall likelihood of fat redistribution syndromes with respect to zidovudine group. Physical activity is a protective factor for the development of fat redistribution syndromes.

Impact of switching from lopinavir/ritonavir to atazanavir/ritonavir on body fat redistribution in virologically suppressed HIV-infected adults.

Changes in body fat distribution in virologically suppressed HIV-infected patients switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) were assessed. A prospective comparative study was conducted of 37 patients receiving LPV/r regimens switching to ATV/r with 46 patients continuing with LPV/r. Body composition was assessed with whole-body dual-energy x-ray absorptiometry (DXA). Abdominal CT scans were also performed in a subset of patients. Groups were comparable in baseline demographic, clinical, and anthropometric characteristics. After 12 months, peripheral fat did not change significantly, but an increase in trunk fat was observed only in the ATV/r group (0.87 kg, p = 0.021). The percentage of patients with an increase ≥20% in total fat was 37.8% and 15.2% in the ATV/r and LPV/r groups, respectively (p = 0.018). In the ATV/r group, the increase in trunk fat (9.4%) was significantly higher than in peripheral fat (3.7%) (p = 0.007), leading to a significant increase in fat mass ratio (3.76%, p = 0.028), whereas no significant differences were found among LPV/r patients. CT scans showed that abdominal fat increase corresponded to both visceral (28%, p = 0.008) and subcutaneous fat (42%, p = 0.008). These data suggest that switching from LPV/r to ATV/r is associated with increased trunk fat, both subcutaneous and visceral.