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 (Cmin) 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 Cmin determinations in the non-ECMO group and nine patients with 27 voriconazole Cmin determinations in the ECMO group were recruited. The ECMO group had lower Cmin (0.38 ± 2.98 vs. 3.62 ± 3.88, p < 0.001) and higher infratherapeutic Cmin 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 Cmin values. When comparing pre- and post-therapeutic drug optimisation samples from the ECMO group, the dose required to achieve therapeutic Cmin 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.

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.

Ceftolozane/tazobactam for difficult-to-treat Gram-negative infections: A real-world tertiary hospital experience.

OBJECTIVE: To evaluate the real-world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult-to-treat infections caused by multi-drug resistant Gram-negative microorganisms, including carbapenem-resistant Pseudomonas aeruginosa. METHODS: Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi-drug resistant Gram-negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all-cause mortality within 30 days of follow-up. RESULTS AND DISCUSSION: 96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra-abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital-acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem-resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30-day all-cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%). WHAT IS NEW AND CONCLUSION: C/T showed a favourable clinical profile for difficult-to-treat multidrug-resistant and carbapenem-resistant Gram-negative infections, regardless of the source of infection.

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.

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.

Phytosterolemia and γ-glutamyl transferase in adults with parenteral nutrition: Fish versus vegetal lipids: A randomized clinical trial.

OBJECTIVES: Fish oil (FO)-based lipid emulsions (LEs) have been reported to prevent hepatic dysfunction in patients treated with parenteral nutrition (PN). We studied patients with alterations of γ-glutamyl transferase (GGT) associated with the administration of PN containing olive/soybean (O/S)-based LE. The aim of this study was to determine whether the strategy of reducing the lipid dose by 50%, by changing to an FO-based LE, reduced plasma levels of phytosterols (PS) and GGT more effectively and safely, than the strategy of reducing lipid contribution by 50% while maintaining the same LE composition. METHODS: A randomized double-blind clinical trial was carried out in patients with normal initial GGT, who after a minimum of 1 wk of daily PN (0.8 g/kg of O/S-based LE) presented with GGT values twice the upper normal value. At the time of randomization 1:1, lipids were reduced to 0.4 g/kg daily. Group A maintained O/S LE and group B changed to FO LE. The primary endpoints were reduction of plasmatic PS and GGT on day 7 after randomization, performed in the study population per protocol by Student's t test and simple linear regression. Secondary outcomes included alkaline phosphatase (AP), alanine transaminase (ALT), and total bilirubin (BIL), and safety variables. RESULTS: Nineteen patients were included. On day 7 after randomization, GGT and AP values were higher in the O/S group (n = 10; GGT: median [Med], 4.99; interquartile range [IQR], 4.09; AP: Med, 2.59 µkat/L; IQR 1.74) than in the FO group (n = 9; GGT: Med, 2.26 µkat/L; IQR, 1.07; AP: Med, 1.2 µkat/L; IQR 1.44). Although there were no differences in ALT and BIL values, the ALT decrease was larger and more statistically significant in the FO group than in the O/S group (P = 0.009). Total PS (Med, 21.10 µg/mL; IQR, 5.50) in the O/S group was higher than in the FO group (Med, 13.4 µg/mL; IQR, 10.65; P = 0.002). Significant decreases in PS and their fractions were observed, with the exception of campesterol and stigmasterol. CONCLUSION: Plasma accumulation of PS and high values of GGT, AP, and ALT can be prevented with the exclusive administration of FO-based LE.

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.

Determinación de fitoesteroles en emulsiones lipídicas para nutrición parenteral / Phytosterol determination in lipid emulsions for parenteral nutrition

Objetivo: La presencia de fitoesteroles en emulsiones lipídicas de origen vegetal se ha relacionado con la aparición de alteraciones de los parámetros de la función hepática. El objetivo es determinar la presencia de fitoesteroles en las emulsiones registradas en el mercado farmacéutico. Método: Se analizaron tres-cuatro lotes no consecutivos de seis marcas distintas de emulsiones lipídicas (Clinoleic(R), Intralipid(R), Lipofundina(R), Lipoplus(R), Omegaven(R) y Smoflipid(R)) y las diferencias en contenido de fitoesteroles totales entre marcas y entre lotes se estudiaron estadísticamente (ANOVA de un factor, aproximación no paramétrica de Kruskal-Wallis y análisis post hoc Scheffé; p < 0,05). Resultados: Se encontró ausencia de fitoesteroles en el preparado Omegaven(R) con aceite de pescado. El contenido más alto de fitoesteroles (422,4 ± 130,5 µg/mL) coincidió con el porcentaje más alto de aceite de soja (Intralipid(R)). En el resto de las emulsiones se detectaron concentraciones de fitoesteroles entre 120 y 210 µg/mL, relacionadas con el contenido de aceite de soja. Se observaron diferencias estadísticamente significativas entre todas las marcas de emulsiones lipídicas (F = 42,97; p = 0,000) y entre lotes no consecutivos. Clinolenic(R) (F = 23,59; p = 0,000); Intralipid(R) (F = 978,25; p = 0,000); Lipofundina(R) TCL/TCM (F = 5,43; p = 0,045); Lipoplus(R) (F = 123,53; p = 0,000),; y Smoflipid(R) (16,78; p = 0,000). Excepto en el caso de la Lipofundina(R) TCL/TCM las diferencias entre lotes fueron marcadas. Conclusiones: Las emulsiones lipídicas registradas en el mercado farmacéutico español contienen cantidades variables de fitoesteroles en función de la marca comercial y el lote. La determinación del contenido de fitoesteroles, actualmente no declarados, permitiría desarrollar estrategias para prevenir o tratar la aparición de estas alteraciones

Objective: The presence of phytosterols in vegetal lipid emulsions has been associated with alterations of liver function tests. Determination of phytosterols content, currently undeclared, would allow the development of strategies to prevent or treat these alterations. Method: 3-4 non-consecutive batches of 6 lipid emulsions from different providers (Clinoleic(TM), Intralipid(TM), Lipofundina(TM), Lipoplus(TM), Omegaven(TM) and Smoflipid(TM)) were analyzed. Differences in total phytosterol assay between providers and batches were statistically studied by a one-way ANOVA and Kruskal-Wallis non-parametric approximation and post hoc Scheffé test (p < 0.05). Results: The absence of phytosterols was confirmed in Omegaven(TM), emulsion based on fish oil. The highest assay of phytosterols (422.4 ± 130.5 µg/mL) has been related with the highest percentage of soya bean oil in Intralipid. In the remaining emulsions, concentrations were from 120 to 210 µg/mL related to the percentage of soya bean oil. Statistically significant differences of phytosterol content in lipid emulsions were observed among different providers (F = 23.59; p = 0.000) as well as among non-consecutive batches. Clinolenic(TM) (F = 23.59; p = 0.000), Intralipid(TM) (F = 978.25; p = 0.000), Lipofundina(TM) TCL/TCM (F = 5.43; p = 0.045), Lipoplus(TM) (F = 123.53; p = 0.000) and Smoflipid(TM) (16.78; p = 0.000). Except for Lipofundina(TM) TCL/TCM, the differences between batches were marked. Conclusions: Lipid emulsions, registered on Spanish pharmaceutical market, contain variable quantities of phytosterols dependent on commercial brand and batch

[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.

Phytosterol determination in lipid emulsions for parenteral nutrition.

OBJECTIVE: The presence of phytosterols in vegetal lipid emulsions has been  associated with alterations of liver function tests. Determination of phytosterols  content, currently undeclared, would allow the development of strategies to  prevent or treat these alterations. METHOD: 3-4 non-consecutive batches of 6 lipid emulsions from different providers (Clinoleic, Intralipid, Lipofundina, Lipoplus, Omegaven and Smoflipid) were analyzed. Differences in total phytosterol assay between providers and batches were statistically studied by a one-way ANOVA and Kruskal-Wallis non-parametric approximation and post hoc Scheffé test (p < 0.05)Results: The absence of phytosterols was confirmed in Omegaven, emulsion  based on fish oil. The highest assay of phytosterols (422.4 ± 130.5 µg/mL) has  been related with the highest percentage of soya bean oil in Intralipid. In the  remaining emulsions, concentrations were from 120 to 210 µg/mL related to the  percentage of soya bean oil. Statistically significant differences of phytosterol  content in lipid emulsions were observed among different providers (F = 23.59;  p = 0.000) as well as among non-consecutive batches. Clinolenic (F = 23.59; p  = 0.000), Intralipid (F = 978.25; p = 0.000), Lipofundina TCL/TCM (F = 5.43; p  = 0.045), Lipoplus (F = 123.53; p = 0.000) and Smoflipid (16.78; p = 0.000).  Except for Lipofundina TCL/TCM, the differences between batches were marked. CONCLUSIONS: Lipid emulsions, registered on Spanish pharmaceutical market,  contain variable quantities of phytosterols dependent on commercial brand and  batch.

Objetivo: La presencia de fitoesteroles en emulsiones lipídicas de origen vegetal se ha relacionado con la aparición de alteraciones de los parámetros de la  función hepática. El objetivo es determinar la presencia de fitoesteroles en las  emulsiones registradas en el mercado farmacéutico.Método: Se analizaron tres-cuatro lotes no consecutivos de seis marcas  distintas de emulsiones lipídicas (Clinoleic®, Intralipid®, Lipofundina®,  Lipoplus®, Omegaven® y Smoflipid®) y las diferencias en contenido de  fitoesteroles totales entre marcas y entre lotes se estudiaron estadísticamente  (ANOVA de un factor, aproximación no paramétrica de Kruskal-Wallis y análisis  post hoc Scheffé; p < 0,05).Resultados: Se encontró ausencia de fitoesteroles en el preparado Omegaven® con aceite de pescado. El contenido más alto de fitoesteroles (422,4 ± 130,5  µg/mL) coincidió con el porcentaje más alto de aceite de soja (Intralipid®). En el resto de las emulsiones se detectaron concentraciones de fitoesteroles entre 120  y 210 µg/mL, relacionadas con el contenido de aceite de soja. Se  observaron diferencias estadísticamente significativas entre todas las marcas de  emulsiones lipídicas (F = 42,97; p = 0,000) y entre lotes no consecutivos.  Clinolenic® (F = 23,59; p = 0,000); Intralipid® (F = 978,25; p = 0,000);  Lipofundina® TCL/TCM (F = 5,43; p = 0,045); Lipoplus ® (F = 123,53; p =  0,000),; y Smoflipid® (16,78; p = 0,000). Excepto en el caso de la  Lipofundina® TCL/TCM las diferencias entre lotes fueron marcadas.Conclusiones: Las emulsiones lipídicas registradas en el mercado farmacéutico español contienen cantidades variables de fitoesteroles en función  e la marca comercial y el lote. La determinación del contenido de fitoesteroles, actualmente no declarados, permitiría desarrollar estrategias para prevenir o tratar la aparición de estas alteraciones.

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

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

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) + fish (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% vs39.5% 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.

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 signifiativas 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.

Hospital malnutrition screening at admission: malnutrition increases mortality and length of stay.

INTRODUCTION: Malnutrition is common in patients admitted to hospital and is associated with morbidity and mortality. We conducted a study to assess the prevalence of nutritional risk, risk factors associated and its consequences in a third-level hospital. METHODS: This is a prospective nutritional screening study of hospitalized patients evaluated within the first 72 hours of admission, by Malnutrition Universal Screening Tool (MUST) and Short Nutritional Assessment Questionnaire (SNAQ) screening tests. The variables recorded included demographic, anthropometric, hospitalization and clinical data. RESULTS: Out of 409 patients, 12.7% and 15.3% were nutritionally at risk according to MUST and SNAQ, respectively, with the highest prevalence in critical care units (33.3%; 25.5%), amongst oncologic patients (17.5%; 28.4%) and those with higher Charlson comorbidity indices (CCI). Length of stay (LOS) was longer in patients at severe malnutrition risk (15.4 vs 9.9 days for MUST; 13.3 vs 9.9 days for SNAQ). Mortality was higher in those with high malnutrition risk (66.7% vs 10.9% for MUST; 50.0% vs 14.2% for SNAQ). Multivariate analysis showed that malnutrition was associated with CCI and mortality. Risk factors associated with LOS were admission as emergencies for both MUST and SNAQ tests. CONCLUSIONS: The prevalence of malnutrition is high in patients on admission to a third-level hospital, with a higher prevalence in critical care units, amongst oncologic patients and those with a higher CCI. Malnutrition is associated with longer LOS and higher mortality. The systematic clinical use of screening tools enables to detect patients at risk of malnutrition and take appropriate action.

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)

Hospital malnutrition screening at admission: malnutrition increases mortality and length of stay / Cribado de la desnutrición hospitalaria en la admisión: la desnutrición aumenta la mortalidad y la duración de la estancia hospitalaria

Introduction: Malnutrition is common in patients admitted to hospital and is associated with morbidity and mortality. We conducted a study to assess the prevalence of nutritional risk, risk factors associated and its consequences in a third-level hospital. Methods: This is a prospective nutritional screening study of hospitalized patients evaluated within the first 72 hours of admission, by Malnutrition Universal Screening Tool (MUST) and Short Nutritional Assessment Questionnaire (SNAQ) screening tests. The variables recorded included demographic, anthropometric, hospitalization and clinical data. Results: Out of 409 patients, 12.7% and 15.3% were nutritionally at risk according to MUST and SNAQ, respectively, with the highest prevalence in critical care units (33.3%; 25.5%), amongst oncologic patients (17.5%; 28.4%) and those with higher Charlson comorbidity indices (CCI). Length of stay (LOS) was longer in patients at severe malnutrition risk (15.4 vs 9.9 days for MUST; 13.3 vs 9.9 days for SNAQ). Mortality was higher in those with high malnutrition risk (66.7% vs 10.9% for MUST; 50.0% vs 14.2% for SNAQ). Multivariate analysis showed that malnutrition was associated with CCI and mortality. Risk factors associated with LOS were admission as emergencies for both MUST and SNAQ tests. Conclusions: The prevalence of malnutrition is high in patients on admission to a third-level hospital, with a higher prevalence in critical care units, amongst oncologic patients and those with a higher CCI. Malnutrition is associated with longer LOS and higher mortality. The systematic clinical use of screening tools enables to detect patients at risk of malnutrition and take appropriate action (AU)

Introducción: la desnutrición es común en los pacientes ingresados en el hospital y se asocia a morbi/mortalidad. El objetivo de este estudio es evaluar la prevalencia de riesgo nutricional, factores de riesgo asociados y sus consecuencias en un hospital de tercer nivel. Métodos: estudio prospectivo de cribado nutricional de pacientes hospitalizados evaluados dentro de las primeras 72 horas de ingreso, mediante las herramientas Malnutrition Universal Screening Tool (MUST) y Short Nutritional Assessment Questionnaire (SNAQ). Las variables registradas incluyen datos demográficos, antropométricos, de hospitalización y clínicos. Resultados: de los 409 pacientes entrevistados, 12,7% y 15,3% presentaban riesgo nutricional según MUST y SNAQ, respectivamente, con una mayor prevalencia en la Unidad de Cuidados Intensivos (UCI) (33,3%; 25,5%), pacientes oncológicos (17,5%; 28,4%) y aquellos con mayor índice de comorbilidad de Charlson (ICC). La estancia hospitalaria fue mayor en pacientes en riesgo de desnutrición severa (15,4 vs. 9,9 días para MUST; 13,3 vs. 9,9 días para SNAQ), así como la mortalidad (66,7% vs. 10,9% para MUST; 50,0% vs. 14,2% para SNAQ). El análisis multivariante mostró una asociación entre desnutrición e ICC y mortalidad. Los factores de riesgo asociados con estancia hospitalaria fueron ingreso por urgencias para ambos tests. Conclusiones: la prevalencia de desnutrición en pacientes al ingreso a un hospital de tercer nivel es alta, siendo mayor en las UCI, entre pacientes oncológicos y con mayor ICC. La desnutrición se asocia con mayor estancia hospitalaria y mayor mortalidad. El uso clínico sistemático de herramientas de detección puede ayudar a identificar pacientes en riesgo de desnutrición y tomar las medidas apropiadas (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.