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.

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

Introduction: Liver 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 methods: Prospective observational study. Simple linear and stepwise multiple linear regression tests and interactions were performed. Results: Nineteen 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 < 0.001), stigmasterol (p < 0.001), interleukin-10 (IL-10) × total phytosterols (Phyt) (p < 0.009), tumor necrosis factor-α (TNF-α) × Phyt (p < 0.002), IL-10 × sitosterol (p < 0.002), TNF-α × sitosterol (p < 0.001), IL-10 × campesterol (p < 0.033), IL-10 (p < 0.006 and p < 0.015), TNF-α (p < 0.048 and p < 0.027). Increases in alanine aminotransferase (ALT) were associated with Phyt (p < 0.006), lanosterol (p < 0.016), C-reactive protein (CRP) × campesterol (p < 0.001), interleukin-6 (IL-6) × stigmasterol (p < 0.030), CRP (p < 0.08), and IL-6 (p < 0.042). Alkaline phosphatase (AP) increases were associated with CRP (p < 0.002). Discussion: Inflammation 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 (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-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-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-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 ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-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.

Genetic factors associated with alterations in liver function test results in adult hospitalized patients treated with parenteral nutrition: A substudy of a clinical trial.

OBJECTIVES: The presence of phytosterols in vegetable-based lipid emulsions has been associated with alterations in the results of liver function tests (LFTs). Serum levels of phytosterols are under strict genetic control. T-allele carriers in rs41360247 and C-allele carriers in rs4245791 of ABCG8genes are associated with higher phytosterolemia. The objective of this study was to determine the association between these single-nucleotide polymorphisms (SNPs) and LFT result alterations in an adult hospitalized population treated with parenteral nutrition. METHODS: This is a substudy of a previous clinical trial (EudraCT 2014-003597-17). It included adult hospitalized patients who had received at least 7 d of parenteral nutrition with 0.8 g/kg/d of an olive/soybean lipid emulsion, randomized 1:1 to receive the same olive/soybean emulsion or 100% fish oil at a dose of 0.4 g/kg/d for 7 d. Plasma phytosterols and their fractions, rs41360247 and rs4245791 of ABCG8 genes, and LFT were determined. Analyses of variance were performed to determine the association between the SNPs and LFT values, as well as total phytosterol values and their fractions. Simple linear regressions were performed to analyze LFT variations and the different interactions of the SNPs studied with phytosterols and their fractions. Interactions of the synergic variable plasma phytosterol and its fractions with SNPs allow us to study the interaction of the SNPs with phytosterols with a regression. RESULTS: We included 19 participants. In the multivariate model, total phytosterols, sitosterol, and lanosterol were positively associated with increases in γ-glutamyltransferase. Significant increases with stigmasterol were associated with the T allele of rs41360247, whereas campesterol showed only a tendency to increase that was not significant. Increases in alkaline phosphatase were associated with T-rs41360247 independent of the presence of phytosterols. With stigmasterol, C-allele carriers of rs4245791 showed a tendency to increase, and also for sitosterol and lanosterol, although independent of the SNP analyzed. Increases in alanine aminotransferase were positively associated with total phytosterol and sitostanol, whereas lanosterol and stigmasterol were associated with the presence of the T allele of rs41360247. CONCLUSIONS: With both SNPs rs41360247 and rs4245791, the alteration in parameters of liver function in adult patients with short-term parenteral nutrition is conditional.

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients.

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

Cohort Multicenter Study on the Role of Medications in Parenteral Nutrition-Related Alteration of Liver Function Tests in Adults.

BACKGROUND: Our objective was to assess in non-critically-ill adult inpatients receiving parenteral nutrition (PN) the risk of developing liver function test (LFT) alterations when receiving concomitant possibly hepatotoxic medications or others reported to improve LFTs during PN. METHODS: A multicenter retrospective analysis of prospectively collected data was performed on patients receiving PN. Two groups were recruited: group LALT (patients with any LFT alterations during PN), and group NOLALT (patients without such alterations). Exclusion criteria were previous sepsis, shock, renal failure, hyperglycemia, LFT alteration, or biliopancreatic surgical procedures. Medications were classified into 2 categories: medications reported to improve LFTs during PN (n = 8) and possibly hepatotoxic medications (n = 54), including a subgroup of possibly highly hepatotoxic medications (n = 30). RESULTS: The study included 200 patients, 136 (68.0%) in the LALT group. The groups differed in the number of patients requiring surgical intervention ≤7 days before PN (LALT, 94 [69.1%]; NOLALT, 29 [45.3%]; P < .002) and those receiving possibly hepatotoxic medications (LALT, 126 [92.6%]; NOLALT, 45 [70.3%]; P < .001). Variables in the final Cox regression model were possibly hepatotoxic medications, odds ratio (OR) 3.310 (1.678-6.530); surgical intervention prior to PN, OR 1.861 (1.277-2.711); baseline triglyceridemia, OR 1.005 (1.001-1.009); and creatinine, OR 1.861 (1.043-3.323). CONCLUSIONS: Patients who received PN and concomitantly possibly hepatotoxic medications had a 3-fold risk of developing LFT alterations. Medications reported to improve LFTs had no effect. The use of possibly hepatotoxic medications during PN was associated with LFT alterations.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Programa de nutrición parenteral domiciliaria: 32 años de experiencia clínica / A home parental nutrition program: 32 years of clinical experience

Introducción: la nutrición parenteral domiciliaria (NPD) es una técnica compleja que implica un seguimiento multidisciplinar. Objetivos: análisis descriptivo de todos los pacientes incluidos en el programa de NPD. Métodos: estudio retrospectivo de los pacientes con NPD entre 1985 y 2017 en nuestro centro, un hospital universitario terciario. Resultados: analizamos 61 pacientes (32 hombres, edad media: 51,2 años). La patología de base más frecuente fue la neoplasia (32,8%), siendo el síndrome de intestino corto (SIC) la principal indicación de NPD (70,5%). Recibieron NPD parcial 45 pacientes y total, 16. El tipo de catéter más empleado fue el venoso tunelizado. Veinte pacientes la suspendieron por ingesta oral completa (19 los primeros cinco años), 26 por exitus (18 los primeros cinco años) y 15 la mantienen. La neoplasia fue la causa de muerte más frecuente (46,2%) y en un 15,4%, la hepatopatía asociada a NPD. La duración mediana de la NPD fue de 25 meses (1-394), siendo en 24 pacientes mayor a cinco años (ocho fallecidos, solo uno de causa oncológica no relacionada con la NPD). Un 54% presentaron infecciones de catéter, aislándose Staphylococcus coagulasa negativo en el 55,2%, con una tasa de infección de 1,04 por 1,000 días de cateterización. Conclusiones: la NPD es una estrategia terapéutica útil en el fracaso intestinal. El SIC es la indicación más frecuente en nuestra casuística. La patología de base, como la neoplasia, determinará el pronóstico. La infección por catéter es la complicación más frecuente, por lo que es necesario reforzar la educación sanitaria y la profilaxis antiséptica

Introduction: home parenteral nutrition (NPD) is a complex technique that involves multidisciplinary follow-up. Objectives: descriptive analysis of all patients included in the NPD program. Methods: retrospective study of patients with NPD between 1985 and 2017 in our center, a tertiary university hospital. Results: we analyzed 61 patients (32 men, mean age: 51.2 years). The most common underlying pathology was neoplasia (32.8%), with short bowel syndrome (SIC) being the main indication of NPD (70.5%). Forty-five patients received partial NPD and 16 total. The tunnelled vein catheter was the most common venous access used. 20 patients suspended it for complete oral intake (19 the first 5 years), 26 were deceased (18 the first 5 years) and 15 maintain it. Neoplasia was the most frequent cause of death (46.2%) and in 15.4% liver disease was associated with NPD. The median duration of NPD was 25 months [1-394]; being in 24 patients longer than 5 years (8 dead, only 1 for oncologic cause not related to the NPD). Fifty-four per cent had catheter infections, being isolated 55.2% Staphylococcus coagulase negative, with an infection rate of 1.04 per 1000 days of catheterization. Conclusions: NPD is a useful therapeutic strategy in intestinal failure. The SIC is the most frequent indication in our case study. The underlying pathology, such as neoplasia, will determine the prognosis. Catheter infection is the more frequent complication, so it is necessary to strengthen health education and antiseptic prophylaxis

[A home enteral nutrition program: 32 years of clinical experience]. / Programa de nutrición parenteral domiciliaria: 32 años de experiencia clínica.

INTRODUCTION: Introduction: home parenteral nutrition (NPD) is a complex technique that involves multidisciplinary follow-up. Objectives: descriptive analysis of all patients included in the NPD program. Methods: retrospective study of patients with NPD between 1985 and 2017 in our center, a tertiary university hospital. Results: we analyzed 61 patients (32 men, mean age: 51.2 years). The most common underlying pathology was neoplasia (32.8%), with short bowel syndrome (SIC) being the main indication of NPD (70.5%). Forty-five patients received partial NPD and 16 total. The tunnelled vein catheter was the most common venous access used. 20 patients suspended it for complete oral intake (19 the first 5 years), 26 were deceased (18 the first 5 years) and 15 maintain it. Neoplasia was the most frequent cause of death (46.2%) and in 15.4% liver disease was associated with NPD. The median duration of NPD was 25 months [1-394]; being in 24 patients longer than 5 years (8 dead, only 1 for oncologic cause not related to the NPD). Fifty-four per cent had catheter infections, being isolated 55.2% Staphylococcus coagulase negative, with an infection rate of 1.04 per 1000 days of catheterization. Conclusions: NPD is a useful therapeutic strategy in intestinal failure. The SIC is the most frequent indication in our case study. The underlying pathology, such as neoplasia, will determine the prognosis. Catheter infection is the more frequent complication, so it is necessary to strengthen health education and antiseptic prophylaxis.

INTRODUCCIÓN: Introducción: la nutrición parenteral domiciliaria (NPD) es una técnica compleja que implica un seguimiento multidisciplinar. Objetivos: análisis descriptivo de todos los pacientes incluidos en el programa de NPD. Métodos: estudio retrospectivo de los pacientes con NPD entre 1985 y 2017 en nuestro centro, un hospital universitario terciario. Resultados: analizamos 61 pacientes (32 hombres, edad media: 51,2 años). La patología de base más frecuente fue la neoplasia (32,8%), siendo el síndrome de intestino corto (SIC) la principal indicación de NPD (70,5%). Recibieron NPD parcial 45 pacientes y total, 16. El tipo de catéter más empleado fue el venoso tunelizado. Veinte pacientes la suspendieron por ingesta oral completa (19 los primeros cinco años), 26 por exitus (18 los primeros cinco años) y 15 la mantienen. La neoplasia fue la causa de muerte más frecuente (46,2%) y en un 15,4%, la hepatopatía asociada a NPD. La duración mediana de la NPD fue de 25 meses (1-394), siendo en 24 pacientes mayor a cinco años (ocho fallecidos, solo uno de causa oncológica no relacionada con la NPD). Un 54% presentaron infecciones de catéter, aislándose Staphylococcus coagulasa negativo en el 55,2%, con una tasa de infección de 1,04 por 1,000 días de cateterización. Conclusiones: la NPD es una estrategia terapéutica útil en el fracaso intestinal. El SIC es la indicación más frecuente en nuestra casuística. La patología de base, como la neoplasia, determinará el pronóstico. La infección por catéter es la complicación más frecuente, por lo que es necesario reforzar la educación sanitaria y la profilaxis antiséptica.

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.

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.

Multicenter study of parenteral nutrition in non-critically ill elderly patients compared to younger patients - Study IAIOS-PN (Incidence and Assessment of Iatrogenesis in Older Subjects receiving Parenteral Nutrition).

OBJECTIVE: this study assessed the incidence of hyperglycemia, hypertriglyceridemia, and liver function test (LFT) alterations among patients older and younger than 65 years receiving parenteral nutrition (PN). A secondary objective was to compare the incidence of any of these three events. MATERIAL AND METHODS: inclusion criteria were non-critically ill adult inpatients receiving PN for ≥ 7 days in 15 hospitals in Spain. Exclusion criteria were hyperglycemia, hypertriglyceridemia, LFT alterations, sepsis, shock, pancreatic/hepatobiliary surgery, renal failure, diabetes mellitus (DM) type 1, insulin-treated DM type 2, acute DM complications, or obesity prior to PN. Patients were classified into groups YOUNG (aged 35-64) and OLD (aged 65-95). RESULTS: this study recruited 200 patients. Group YOUNG included 63 (31.5%) patients and OLD, 137 (68.5%). Hyperglycemia appeared in 37 (18.5%) patients, eight (12.7%) in group YOUNG and 29 (21.2%) in group OLD (p = 0.174). Hypertriglyceridemia appeared in only one (0.7%) patient. LFT alterations appeared in 141 (70.5%) patients, 44 (69.8%) in group YOUNG and 97 (70.8%) in group OLD (p = 1.000). The model for hyperglycemia included DM type 2, previous surgical procedure, and use of hyperglycemia-inducing medications. The model for LFT alteration included previous surgical procedure, amount of lipids and amino acids, medications causing LFT alterations and a trend for age group. The model for any event included surgical procedure, DM type 2, and medications causing alterations. CONCLUSION: patients of ≥ 65 years receiving PN had similar incidences of hyperglycemia, hypertriglyceridemia, and LFT alterations as younger patients. Additionally, older patients had trends toward lower LFT alterations.

[Endocrine disruptors in artificial nutrition]. / Disruptores endocrinos en nutrición artificial.

Phthalates are chemical compounds classified as endocrine disruptors which are present in practically every environment of daily life. In the field of artificial nutrition, they are relevant because they are found as plasticizers in infusion lines made with PVC. They are lipophilic molecules which weakly pair with PVC and, therefore, they are easily extracted by the fatty compounds that are part of both the parenteral and enteral nutrition, as various studies show. As endocrine disruptors, they directly affect the reproductive organs because of their antiandrogenic and estrogenic effects. They promote inflammation and oxidative stress and they are also related to the development of obesity, asthma, neurological and ophthalmic disorders, cholestasis and other gastrointestinal disorders. The legislation establishes the highest recommended exposure level for daily exposure; however, in the medical environment the exposure follows a different pattern, more occasional with very high peaks, for which there are no established thresholds, that is why it is recommended to avoid exposure whenever possible. The industry is working on the development of alternative plasticizers, for which the use experience is still limited. Currently, in the field of artificial nutrition it is recommended to use phthalate-free intravenous and enteral infusion lines.

Multicenter study of parenteral nutrition in non-critically ill elderly patients compared to younger patients - Study IAIOS-PN (Incidence and Assessment of Iatrogenesis in Older Subjects receiving Parenteral Nutrition) / Estudio multicéntrico de nutrición parenteral en pacientes ancianos no críticos comparados con pacientes más jóvenes - Estudio IAIOS-PN (Incidencia y Valoración de Yatrogenia en Sujetos Ancianos que reciben Nutrición Parenteral)

Objective: this study assessed the incidence of hyperglycemia, hypertriglyceridemia, and liver function test (LFT) alterations among patients older and younger than 65 years receiving parenteral nutrition (PN). A secondary objective was to compare the incidence of any of these three events. Material and methods: inclusion criteria were non-critically ill adult inpatients receiving PN for ≥ 7 days in 15 hospitals in Spain. Exclusion criteria were hyperglycemia, hypertriglyceridemia, LFT alterations, sepsis, shock, pancreatic/hepatobiliary surgery, renal failure, diabetes mellitus (DM) type 1, insulin-treated DM type 2, acute DM complications, or obesity prior to PN. Patients were classified into groups YOUNG (aged 35-64) and OLD (aged 65-95). Results: this study recruited 200 patients. Group YOUNG included 63 (31.5%) patients and OLD, 137 (68.5%). Hyperglycemia appeared in 37 (18.5%) patients, eight (12.7%) in group YOUNG and 29 (21.2%) in group OLD (p = 0.174). Hypertriglyceridemia appeared in only one (0.7%) patient. LFT alterations appeared in 141 (70.5%) patients, 44 (69.8%) in group YOUNG and 97 (70.8%) in group OLD (p = 1.000). The model for hyperglycemia included DM type 2, previous surgical procedure, and use of hyperglycemia-inducing medications. The model for LFT alteration included previous surgical procedure, amount of lipids and amino acids, medications causing LFT alterations and a trend for age group. The model for any event included surgical procedure, DM type 2, and medications causing alterations. Conclusion: patients of ≥ 65 years receiving PN had similar incidences of hyperglycemia, hypertriglyceridemia, and LFT alterations as younger patients. Additionally, older patients had trends toward lower LFT alterations

Objetivo: valorar la incidencia de hiperglicemia, hipertrigliceridemia y alteraciones de los parámetros bioquímicos hepáticos (PBH) en pacientes mayores de 65 años frente a pacientes más jóvenes con nutrición parenteral (NP). El objetivo secundario fue comparar la incidencia de cualquiera de los tres eventos. Material y métodos: se incluyeron adultos no críticos hospitalizados que recibieron NP durante siete días o más en 15 hospitales españoles. Se excluyeron pacientes con hiperglicemia, hipertrigliceridemia, alteración de los PBH, sepsis, shock, cirugía biliopancreática, insuficiencia renal, diabetes tipo 1 o tipo 2 insulinodependiente, complicaciones diabéticas agudas y obesidad previas a la NP. Los pacientes se clasificaron en dos grupos: YOUNG (35-64 años) y OLD (65-95 años). Resultados: se incluyeron 200 pacientes; 63 (31,5%) en el grupo YOUNG y 137 (68,5%) en el OLD. Se detectó hiperglicemia en 37 (18,5%) pacientes, ocho (12,7%) en el grupo YOUNG y 29 (21,2%) en el OLD (p = 0,174). Solo hubo un caso (0,7%) de hipertrigliceridemia. Alteraciones de PBH aparecieron en 141 (70,5%) pacientes, 44 (69,8%) en el grupo YOUNG y 97 (70,8%) en el OLD (p = 1,000). El modelo para hiperglicemia incluyó como variables diabetes tipo 2, cirugía previa y el uso de medicamentos hiperglucemiantes. El modelo para alteración de PBH incluyó cirugía previa, dosis de lípidos y aminoácidos y medicaciones hepatotóxicas. Hubo una tendencia a menor alteración por la edad. El modelo global para cualquier evento incluyó cirugía previa, diabetes tipo 2 y medicaciones que causen las alteraciones estudiadas. Conclusión: los pacientes de 65 años o más que recibieron NP tuvieron incidencias similares de hiperglicemia, hipertrigliceridemia y alteración de PBH a las de los pacientes más jóvenes. Hubo una tendencia a menor alteración de PBH en los pacientes mayores

Disruptores endocrinos en nutrición artificial / Endocrine disruptors in artificial nutrition

Los ftalatos son unos compuestos químicos clasificados como disruptores endocrinos que están presentes en prácticamente todos los entornos de la vida cotidiana. En el campo de la nutrición artificial son relevantes porque se encuentran como plastificantes en las líneas de infusión elaboradas con PVC. Son moléculas lipófilas que se unen débilmente al PVC y, por lo tanto, se extraen fácilmente por los compuestos lipídicos que forman parte de la nutrición tanto parenteral como enteral, tal y como demuestran diversos estudios. Como disruptores endocrinos, afectan directamente a los órganos reproductivos debido a sus efectos antiandrogénicos y estrogénicos. Favorecen la inflamación y el estrés oxidativo y también se relacionan con el desarrollo de obesidad, asma, alteraciones neurológicas y oftalmológicas, colestasis y otras alteraciones gastrointetinales. La legislación establece unos rangos máximos de exposición que están pensados para la exposición diaria; sin embargo, en el entorno médico la exposición sigue un patrón diferente, más puntual y con picos muy altos, para los cuales no hay márgenes descritos, por lo que se recomienda evitar la exposición siempre que sea posible. La industria trabaja en el desarrollo de plastificantes alternativos para los cuales la experiencia de uso es todavía limitada. Actualmente, en el campo de la nutrición artificial se recomienda utilizar líneas de infusión tanto intravenosa como enteral libres de ftalatos

Phthalates are chemical compounds classified as endocrine disruptors which are present in practically every environment of daily life. In the field of artificial nutrition, they are relevant because they are found as plasticizers in infusion lines made with PVC. They are lipophilic molecules which weakly pair with PVC and, therefore, they are easily extracted by the fatty compounds that are part of both the parenteral and enteral nutrition, as various studies show. As endocrine disruptors, they directly affect the reproductive organs because of their antiandrogenic and estrogenic effects. They promote inflammation and oxidative stress and they are also related to the development of obesity, asthma, neurological and ophthalmic disorders, cholestasis and other gastrointestinal disorders. The legislation establishes the highest recommended exposure level for daily exposure; however, in the medical environment the exposure follows a different pattern, more occasional with very high peaks, for which there are no established thresholds, that is why it is recommended to avoid exposure whenever possible. The industry is working on the development of alternative plasticizers, for which the use experience is still limited. Currently, in the field of artificial nutrition it is recommended to use phthalate-free intravenous and enteral infusion lines

Selección de emulsiones lipídicas en nutrición parenteral: parámetros bioquímicos y hematológicos / Lipid emulsion selection in parenteral nutrition. Biochemical and hematological paramaters

Introducción: el patrón de ácidos grasos (AG) de las emulsiones lipídicas (EL) utilizadas en nutrición parenteral (NP) condiciona diferentes respuestas fisiológicas. Objetivos: estudiar si los criterios clínicos de prescripción de EL en NP establecidos en nuestro protocolo abierto y basados en recomendaciones se correlacionan con marcadores bioquímicos y hematológicos iniciales. Métodos: estudio observacional retrospectivo de cuatro años. Se recogieron variables demográficas, clínicas, nutricionales y analíticas al inicio de la NP. Se realizó un análisis uni y multivariante para estudiar la asociación entre los valores iniciales de los parámetros bioquímicos y hematológicos (PBHE) y el tipo de emulsión lipídica empleada. Resultados: de los 1.558 pacientes, 460 pacientes (29,5%) tenían PBHE al inicio de la NP y utilizaron mayoritariamente las combinaciones soja (AS) + triglicéridos de cadena media (MCT) + oliva (AO) + pescado (AP) (37,4%) y AS+MCT+AO (35,6%). Se encontraron diferencias estadísticamente significativas en el patrón EL utilizado entre los pacientes con y sin PBHE: patrón de AG con AP 44,8% vs. 39,5%, respectivamente. Las situaciones clínicas con proteína C-reactiva (PCR) elevada se asociaron con mayor uso de EL con AP: AS+AO+AP (OR: 4,52 [IC 95%: 1,43-13,91] y AS+MCT+AO+AP (OR: 3,34 [IC 95%: 2,10-5,33]). En situaciones clínicas complejas asociadas con paciente crítico se utilizó EL con MCT: afectación hepática (AS+MCT OR: 2,42 [IC 95%: 1,03-5,68]) y afectación renal (AS+MCT+AP OR: 3,34 [IC 95%: 1,12-9,99]). Conclusiones: la inclusión protocolizada de PBHE al inicio de la NP permite complementar criterios clínicos y metabólicos en la elección de la EL (AU)

Introduction: Lipid emulsions (LE) are a component of parenteral nutrition (PN) and its fatty acid (FA) profile determines various physiological responses. Objectives: To assess the adequacy of a clinical not restricted protocol in the choice of LE by studying complementary biochemical and hematological parameters (BHP) at the beginning of the PN. Methods: A 4-year retrospective observational study of LE administered to patients with PN. Demographic, clinical, nutritional and analytical variables at the beginning of the PN were collected. Univariate and multivariate analyses were performed to study the correlation between the initial clinical and biochemical parameters and the LE profile used. Results: Four hundred and sixty patients (29.5%) out of 1,558 had BHP at the beginning of PN and used mainly the LE combinations soybean (SO) + medium-chain triglycerides (MCT) + olive (OO) + fi sh (FO) (37.4%) and SO + MCT + OO (35.6%). Statistically significant differences on the LE pattern were observed between patients with and those without initial BHP (44.8% vs 39.5% received FO, respectively). Conditions regularly associated with elevated C-reactive protein (CRP) were associated with increased use of FO LE: SO+OO+FO (OR: 4.52 [95% CI: 1.43-13.91]) and SO+MCT+OO+FO (OR: 3.34 [95% CI: 2.10-5.33]). In those complex conditions related with the critical patient MCT were used: hepatic failure (SO+MCT OR: 2.42 [95% CI: 1.03-5.68]) and renal failure (SO+MCT+FO OR: 3.34 [95% CI: 1.12-9.99]). Conclusions: The use of BHP at the beginning of PN treatment allows complementing the clinical and metabolic criteria in LE selection (AU)

Impact of intravenous lipid emulsions on liver function tests: Contribution of parenteral fish oil.

OBJECTIVE: Lipids in parenteral nutrition (PN) have been linked to liver damage. The aim of this study is to 1) determine whether the incidence of alterations in liver function tests (LFTs) changes over time among hospitalized adult patients receiving PN; 2) evaluate whether the alteration in LFTs varies with the pattern of lipid administration; and 3) study the relationship between LFT alterations and fish oil (FO) emulsions. METHODS: Patients treated with PN over 4 y were included. Demographic, clinical, nutritional, and analytical variables were collected. LFTs (γ-glutamyl transferase [GGT], alkaline phosphatase [AP], alanine aminotransferase [ALT], and total bilirubin [BIL]) were collected during PN treatment. Differences in LFTs were studied with t tests for paired samples. To match the type of lipid with each of the LFTs studied, four multivariate statistical models were performed. Significance was reported with the 95% confidence interval (CI) at p < 0.05 (two-tailed). RESULTS: We studied 1555 patients. LFT alterations at baseline were high and increased during PN treatment except ALT. GGT and AP showed significant increases from baseline values. In the multivariate study, daily dose of FO (g·kg(-1)·d(-1)) was associated with a significant decrease in GGT (B = -11.189; 95% CI, -19.799 to -2.578) and in AP (B = -5.250; 95% CI, -10.263 to -0.237). Daily dose of vegetal oil (g/kg) had a tendency for a significant increase in GGT (B = 0.441; 95% CI, -0.107 to 1.039) and AP (B = 0.312; 95% CI, -0.023 to 0.648). CONCLUSIONS: GGT and AP increased throughout the clinical course of PN administration. These alterations had a multifactorial component. The administration of FO was associated with a significant decrease in the levels of GGT and AP.

The relationship between the parenteral dose of fish oil supplementation and the variation of liver function tests in hospitalized adult patients.

BACKGROUND: Hepatic dysfunction is a complication associated with parenteral nutrition (PN). Our primary objective was to study the relationship between doses of intravenous fish oil (FO) emulsion in PN and the variation in the main liver function tests (LFTs) in hospitalized PN-treated adults. As a secondary objective, we studied the safety of FO administration. METHODS: We conducted a retrospective study in adult patients receiving FO supplementation in PN. Demographic, nutritional and safety variables were collected. Variation of LFTs was defined as the difference between values just before the first administration of FO and values at the end of PN. A multiple linear regression was performed to study the association between PN-lipids (FO or vegetable) and the variation of each LFT; the following variables were used to adjust the effect of lipids: sepsis, length of stay in the intensive care unit and lipids dose. Student t-test was used to study safety variables. Data were analyzed using SPSS 19.0. RESULTS: Patients (53, median age 68 years (24-90); 62% men) with the principal diagnosis of digestive neoplasm (42%) received PN for a median of 19 (7-75) days. In the multivariate analysis, the amount of FO was related to a decrease in gamma-glutamyl transferase (GGT) (B = -2.23;CI95 % = -4.41/-0.05), a decrease in alkaline phosphatase (AP) (B = -1.23;CI95 % = -2.07/-0.37), and a decrease in alanine aminotransferase (ALT) (B = -0.82; CI95 % = -1.19/-0.44). No differences were found in safety variables. CONCLUSIONS: GGT, AP and ALT improved with FO PN-supplementation. Moreover, the improvement was greater when the doses of FO were higher. FO administration in PN is safe.

Artificial nutritional support in cancer patients after esophagectomy: 11 years of experience.

Esophageal cancer represents a high-risk group of patients. This study determines the association of artificial nutrition with morbidity, mortality, and survival and studies clinical situations that determine the choice between enteral (EN) and parenteral support (PN). This retrospective single-center study compared 2 periods: 1) treatment centered in surgical process with discretionary demand of support, and 2) elective therapeutic and nutritional interventions were systematized. Risks factors that determined use of PN and survival were included in 4 multivariate regression models: 2 logistic, 1 multinomial, and a survival Cox analysis. Significance determined with 95% confidence interval (CI) of 95%; inclusion criteria was P < 0.1. During an 11-yr period, 175 patients were studied. Artificial nutrition consisted of 45 jejunostomy EN, 28 PN, and 102 both. Risk factors that conditioned PN were first period (OR: 2.41; 95% CI: 1.13-5.14), stay in intensive care unit (ICU) >3 days (OR: 1.70; 95% CI: 0.93-3.71), and surgical reintervention (OR: 3.83; 95% CI: 0.94-16.95). Risk factors associated with mortality were first period (OR: 22.7; 95% CI: 2.31-172.05), respiratory infection (OR: 11.23; 95% CI: 2.33-55.5) and coloplasty surgery (OR: 13.16; 95% CI: 2.11-83.33). Longer survival was associated with second period (OR: 2.36; 95% CI: 1.38-4.05) and lower neoplasm staging (OR: 1.43; 95% CI: 1.21-1.69). A multidisciplinary management that includes nutritional support of esophagectomized patients is 1 of the factors that improves survival. Protocol implies greater use of EN; PN remains an important nutritional therapy.

A randomised study on the clinical progress of high-risk elective major gastrointestinal surgery patients treated with olive oil-based parenteral nutrition with or without a fish oil supplement.

n-3 Fatty acids have clinical benefits. The primary aim of the present study was the assessment of infection in patients who underwent major high-risk elective gastrointestinal surgery receiving postoperatively fish oil (FO)-supplemented parenteral nutrition (PN), compared with those receiving a standard olive oil (OO) emulsion. The secondary aims were the assessment of anti-inflammatory response and evaluation of tolerance and safety of these emulsions. A prospective, randomised, double-blind study was performed in patients requiring at least 5 d of PN. An isoenergetic and isoproteic formula was administered: group A received OO alone, while group B received OO that was partially replaced with FO (16.6 %, w/w). End points were outcome measures (mortality, sepsis, infection, hospitalisation days and PN duration), inflammatory response (C-reactive protein (CRP), prealbumin and leucocytes) and safety (TAG and glucose metabolism, and liver and kidney function). Statistical analysis was done using Student's t test and Fisher's exact test (P < 0.05). Twenty-seven patients were evaluated, with thirteen patients receiving FO. In this group, a significantly lower incidence of infections was found (23.1 v. 78.6 %, P = 0.007). CRP, prealbumin and leucocytes were not significantly different between the groups. There were no differences in safety parameters. We conclude that high-risk surgical patients receiving FO-supplemented PN for 5 d present a lower incidence of infection. Emulsions were safe and well tolerated.