Blood Phytosterol Concentration and Genetic Variant Associations in a Sample Population

The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of ABCG8 and the r657152 SNV at the ABO blood group locus in a sample of a population treated at our hospital, and to determine whether these SNVs are related to plasma PS concentrations. The secondary objective was to establish the variables associated with plasma PS concentrations in adults. Participants completed a dietary habit questionnaire and a blood sample was collected to obtain the following variables: campesterol, sitosterol, sitostanol, lanosterol, stigmasterol, biochemical parameters, and the SNVs. In addition, biometric and demographic variables were also recorded. In the generalized linear model, cholesterol and age were positively associated with total PS levels, while BMI was negatively related. For rs4245791, homozygous T allele individuals showed a significantly lower campesterol concentration compared with C homozygotes, and the GG alleles of rs657152 had the lowest levels of campesterol compared with the other alleles of the SNV. Conclusions: The screening of certain SNVs could help prevent the increase in plasma PS and maybe PNALD in some patients. However, further studies on the determinants of plasma phytosterol concentrations are needed

Voriconazole Pharmacokinetics in Critically Ill Patients and Extracorporeal Membrane Oxygenation Support: A Retrospective Comparative Case-Control Study

Voriconazole, an antifungal agent, displays high intra- and inter-individual variability. The predictive pharmacokinetic (PK) index requires a minimum plasma concentration (C-min) in patient serum of between 1-5.5 mg/L. It is common to encounter fungal infections in patients undergoing extracorporeal membrane oxygenation (ECMO) support, and data regarding voriconazole PK changes during ECMO are scarce. Our study compared voriconazole PKs in patients with and without ECMO support in a retrospective cohort of critically-ill patients. Fifteen patients with 26 voriconazole C-min determinations in the non-ECMO group and nine patients with 27 voriconazole C-min determinations in the ECMO group were recruited. The ECMO group had lower C-min (0.38 & PLUSMN; 2.98 vs. 3.62 & PLUSMN; 3.88, p < 0.001) and higher infratherapeutic C-min values (16 vs. 1, p < 0.001) than the non-ECMO group. Multivariate analysis identified ECMO support (-0.668, CI95 -0.978--0.358) and plasma albumin levels (-0.023, CI95 -0.046--0.001) as risk factors for low C-min values. When comparing pre- and post-therapeutic drug optimisation samples from the ECMO group, the dose required to achieve therapeutic C-min was 6.44 mg/kg twice a day. Therapeutic drug optimisation is essential to improve target attainment

Inflammatory processes involved in the alteration of liver function biomarkers in adult hospitalized patients treated with parenteral nutrition

IntroductionLiver damage has been associated with the accumulation of phytosterols (PS) in patients treated with parenteral nutrition (PN). We aimed to study the association of inflammatory markers with liver function biomarker (LFB) alterations in patients treated with PN containing PS.Materials and methodsProspective observational study. Simple linear and stepwise multiple linear regression tests and interactions were performed.ResultsNineteen patients were included. In the multivariable model, determinations based on LFBs as dependent and phytosterols (and their fractions) as independent variables showed an association between increases in gamma-glutamyltransferase (GGT) and lanosterol (p &lt; 0.001), stigmasterol (p &lt; 0.001), interleukin-10 (IL-10) × total phytosterols (Phyt) (p &lt; 0.009), tumor necrosis factor-α (TNF-α) × Phyt (p &lt; 0.002), IL-10 × sitosterol (p &lt; 0.002), TNF-α × sitosterol (p &lt; 0.001), IL-10 × campesterol (p &lt; 0.033), IL-10 (p &lt; 0.006 and p &lt; 0.015), TNF-α (p &lt; 0.048 and p &lt; 0.027). Increases in alanine aminotransferase (ALT) were associated with Phyt (p &lt; 0.006), lanosterol (p &lt; 0.016), C-reactive protein (CRP) × campesterol (p &lt; 0.001), interleukin-6 (IL-6) × stigmasterol (p &lt; 0.030), CRP (p &lt; 0.08), and IL-6 (p &lt; 0.042). Alkaline phosphatase (AP) increases were associated with CRP (p &lt; 0.002).DiscussionInflammation in the presence of plasmatic PS seems to have a synergistic effect in impairing liver function, mainly altering GGT but also ALT

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (omega-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of omega-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-alpha (TNF-alpha), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of omega-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of omega-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) omega-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed

Risk factors of hepatic function alterations in hospitalized adult patients treated with short-term parenteral nutrition receiving the same lipid composition at the same dose

Abstract Background High doses and vegetable origin of lipid emulsions (LE) are prominent factors for liver test (LT) alterations in patients treated with parenteral nutrition (PN). This study aims to determine incidence of LT alterations, and risk factors related to these alterations in patients with short term PN with homogenous LE. Methods Adult non-critically ill hospitalized patients, with normal LTs at the beginning of PN, receiving 0.8 g/kg/day of an olive/soybean LE were included. A paired Student t-test was applied to compare final with initial LT values. LT variation (end vs start of PN) according to type of surgery and infection was studied by means of an analysis of the variance. Univariate and multivariate analyses were constructed to relate the variations of each of the 4 LTs with the adjustment variables. Results One hundred eighty one patients (66.57 ± 12.89 years; 72.4% men), 66.8% suffered from cancer. Final LT values increased from initial values for gamma-glutamyltransferase (GGT) 2.69 ± 2.49 μkat/L vs 0.55 ± 0.36 μkat/L, alkaline phosphatase (AP) 1.97 ± 1.49 μkat/L vs 1.04 ± 0.33 μkat/L, and alanine aminotransferase (ALT) 0.57 ± 0.92 μkat/L vs 0.32 ± 0.26 μkat/L. GGT and AP variations were associated with days of PN; GGT, AP and total bilirubin with surgical patients, AP variations with infection, and GGT with cancer. Multivariate analysis: elevation of GGT, AP and ALT was related to infection, days of PN and surgery. Conclusions Factors that increased the risk of LTs elevation during short term PN treatment were duration of PN, surgery, cancer, and infection associated with oxidative stress