The micronutrient content in standard enteral mixtures should be closer to the dietary reference values for a healthy population since standard enteral diets are formulated for subjects with no ...special nutritional needs. This study compares the micronutrient content of the most common enteral nutrition (EN) formulas with European dietary reference values (DRVs) for healthy population.
Sixty-two nutritionally complete enteral formulas were considered. The micronutrient content was calculated by multiplying the value reported on the nutritional information panel of each formula by the daily dose usually prescribed. The comparison between the micronutrient content of all enteral formulas evaluated and the DRVs indicates that daily fluoride and vitamin K requirements were not covered, while an oversupply of many other micronutrients was provided. Moreover, in some enteral formulas, at a dose of 2000 Kcal/day, zinc and vitamin A content exceeded the tolerable upper limits and, for one diabetes-specific enteral formula, the chromium content exceeded the relevant European standards in both 1500 and 2000 Kcal/day diets.
Most enteral formulas evaluated are generally suitable for patients on long-term total EN and formulas with higher content of a specific micronutrient may be a useful tool for patients affected by specific clinical conditions, at least for a period of time, then switching to standard enteral mixtures. The availability of nutritional enteral formulas, well balanced also for micronutrient intake, will further improve individualized treatments, particularly for patients on long-term total EN.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The WHO Global Action Plan for the Prevention of non-communicable diseases (NCDs) recommends a 30% relative reduction in mean population salt/sodium intake. The study assessed the trend in the ...habitual salt intake of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urinary sodium excretion, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU’ SALUTE national surveys.
Data were from cross-sectional surveys of randomly selected age and sex–stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian Regions distributed in North, Centre and South of the Country. Urinary sodium and creatinine measurements were carried out in a central laboratory. The analyses included 942 men and 916 women examined in 2008–2012, and 967 men and 1010 women examined in 2018–2019. The age-standardized mean daily population salt (sodium chloride) intake was 10.8 g (95% CI 10.5–11.1) in men and 8.3 g (8.1–8.5) in women in 2008–2012 and respectively 9.5 g (9.3–9.8) and 7.2 g (7.0–7.4) in 2018–2019. A statistically significant (p<0.0001) salt intake reduction was thus observed over 10 years for both genders, and all age, body mass index (BMI) and educational classes.
The average daily salt intake of the Italian general adult population remains higher than the WHO recommended level, but a significant reduction of 12% in men and 13% in women has occurred in the past ten years. These results encourage the initiatives undertaken by the Italian Ministry of Health aimed at the reduction of salt intake at the population level.
•In Italian adults a significant reduction in salt intake has occurred over 10 years.•This reduction was independent of gender, age, BMI category and educational levels.•The salt intake in Italy remains definitely higher than recommended by WHO.•Salt intake remains higher in men, in overweight/obese and less education persons.
Abstract Objective High selenium status has been associated with adverse cardiometabolic outcomes in selenium-replete populations such as the US. In populations with lower selenium status such as in ...Italy, there is little epidemiological evidence about the association of selenium with cardiometabolic risk factors. We therefore examined cross-sectional and prospective relationships of serum selenium concentrations with cardiometabolic risk factors including blood pressure, diabetes and blood lipids in the Olivetti Heart Study. Methods The study population consisted of 445 adult male individuals for whom baseline serum selenium measurement and cardiometabolic risk factors at baseline (1994–1995) and follow-up examination (2002–2004: average follow-up = 8 years) were available. Serum selenium was measured by atomic absorption spectrophotometry. Results Average serum selenium concentration at baseline was 77.5 ± 18.4 μg/L. In cross-sectional analyses, serum selenium levels were positively associated with serum total cholesterol ( p for trend <0.0001) and prevalent diabetes ( p for trend <0.05). In prospective analysis, serum selenium at baseline was likewise a strong predictor of serum total cholesterol ( p = 0.002) and LDL-cholesterol ( p = 0.001) at follow-up, after adjustment for age, BMI, cigarette smoking, physical activity, and lipid-lowering medication. These associations, however, were no longer significant after additional adjustment for baseline blood lipids. Selenium at baseline did not predict changes in total cholesterol levels between the baseline and follow-up examinations β -coefficient (±SE) = 0.09 ± 0.12 ( p = 0.46). Conclusion These findings corroborate previous cross-sectional associations of high selenium status with adverse blood lipid profile and diabetes. However, prospective analyses do not support the causality of these relations. Randomized and experimental evidence is necessary to clarify the mechanisms underlying the observed cross-sectional associations.
Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic ...therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.
Abstract
Introduction: Hepatocellular carcinoma (HCC) is the fastest rising and fourth leading cause of cancer death worldwide. While new therapeutic modalities have been recently approved, treatment ...response and survival in patients remain poor. Claudin-1 (CLDN1) is a cell membrane protein mediating cell-cell adhesion, fate and differentiation. While the function of CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 in HCC remains unexplored. Aim and methods: Using humanized monoclonal antibodies (mAbs) targeting specifically the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems we aimed to investigate the role of CLDN1 as therapeutic target for treatment of HCC. Results: Targeting non-junctional CLDN1 robustly suppressed tumor growth in a large series of patient-derived model systems, including multicellular tumorspheres and patient-derived xenograft (PDX) mouse models. In vivo and ex vivo studies further suggested synergistic efficacy in combination with sorafenib. Mechanistic studies revealed that CLDN1 mAbs suppressed tumor cell proliferation, invasion and stemness by interfering with Src, Wnt-β-catenin and STAT3 signaling. Treatment with humanized anti-CLDN1 mAbs is considered to be safe, as administration in non-human primates and mouse models did not reveal any major toxicity even when high doses largely exceeding the therapeutic need were repeatedly applied. Conclusion: Our results provide robust pre-clinical proof-of-concept for humanized CLDN1-specific mAbs for treatment of HCC. The unique and differentiated mechanism of action has the potential to break the plateau of limited response and survival offered by currently approved therapies.
Citation Format: Natascha Roehlen, Marion Muller, Sara Cherradi, Frank Juehling, Francois H.T. Duong, Nuno Almeida, Fabio Del Zompo, Mirian Fernandez, Tobias Riedl, Hussein El Saghire, Antonio Saviano, Sarah Durand, Clara Ponsolles, Marine Oudot, Emanuele Felli, Patrick Pessaux, Irwin Davidson, Emilie Crouchet, Patrick Laquerriere, Mathias Heikenwälder, Roberto Iacone, Markus Meyer, Greg Elson, Tamas Schweighoffer, Catherine Schuster, Laurent Mailly, Joachim Lupberger, Thomas F Baumert. Claudin-1 is a therapeutic target for hepatocellular carcinoma abstract. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P153.
Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an ...in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade.
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•Molecular phenotyping stratifies compounds based on pathway profiles•Molecular phenotyping detects false-positive hits in a phenotypic screen•Molecular phenotyping correlates pathway activity patterns with phenotypic readouts•Molecular phenotyping can be powered by preclinical and clinical data
Drawnel and Zhang et al. show that quantitative mRNA sequencing of pathway reporter genes can be powered by translational information and classifies compound responses. Adopting this technique in drug discovery could permit biomedically relevant compound screening, increasing likelihood of clinical impact.
Adults with Crohn’s disease (CD) may be at risk of micronutrient insufficiency in clinical remission through restrictive eating, malabsorption, abnormal losses or inflammation. This systematic review ...synthesises the literature on micronutrient insufficiency in CD in clinical remission in terms of the prevalence of low circulating micronutrient concentrations and as a comparison against a healthy control (HC). Studies were included if the population was predominantly in remission. A total of 42 studies met the inclusion criteria; 12 were rated as low quality, leaving 30 studies covering 21 micronutrients of medium/high quality that were included in the synthesis. Vitamins D and B12 were the most frequently reported nutrients (8 and 11); there were few eligible studies for the remaining micronutrients. The prevalence studies were consistent in reporting individuals with low Vitamins A, B6, B12 and C, β-carotene, D, Magnesium, Selenium and Zinc. The comparator studies were inconsistent in finding differences with CD populations; Vitamin D, the most reported nutrient, was only lower than the HC in one-quarter of the studies. Adult CD populations are likely to contain individuals with low levels of one or more micronutrients, with the most substantial evidence for Vitamins D and B12. The studies on other micronutrients are of insufficient number, standardisation and quality to inform practice.
•The negative effects of malnutrition on the prognosis of hospitalized patients are now well documented.•Unfortunately, there is still little awareness and knowledge by health care professionals ...about this complication.•This study described the gradual improving in the years of medical consciousness on the potential risks for malnutrition on the patient prognosis.
The negative effects of malnutrition on the prognosis of hospitalized patients are well documented; however, less known is the awareness and knowledge of health care professionals about this complication. The aim of this study was to evaluate the trend of the requests for nutritional consultation in years and the prescription of artificial nutrition (AN), for adult patients at a university hospital in southern Italy in the years 2004, 2008, 2012, and 2016 to assess the progress of medical teams concerning awareness of hospital malnutrition.
This was a retrospective study that evaluated the time trend of nutritional consultation requests and related prescription of AN, for adult patients at a university hospital in southern Italy in the years 2004, 2008, 2012, and 2016. Of 112 233 inpatients, 2505 received a nutritional consultation with the prescription of AN.
The number of patients on AN increased from 507 of 33 240 (1.52%) in 2004 to 730 of 29 195 (2.5%) in 2008 (P < 0.001), remaining almost stable in 2012 and 2016.
The request for AN was quite equally distributed between surgical (51.5%) and medical wards (48.5%), with a prevalence among patients with oncologic diseases (806 patients 65.6%). As for nononcologic diseases, 20.4% involved the gastrointestinal tract and 6.3% the nervous system.
Throughout the 12 y of observation, parenteral nutrition was the main prescribed support (59.8%) followed by oral nutritional supplements (26.1%) and enteral nutrition (9.3%). Mean nutritional intervention duration was 11 d (±10.8 d).
The request of AN for hospitalized patients increased over time, probably owing to improved medical consciousness of the potential risks for malnutrition and the availability of a specialized clinical nutrition team.
Background
Twenty‐four‐hour urinary creatinine excretion (24hUCrE) is strongly correlated with skeletal muscle mass (SMM). This study suggests how to exploit the power of the SMM‐24hUCrE correlation ...to assess the accuracy of 24hUCrE measurement.
Methods
Four hundred and sixty‐six men, a subgroup of participants in the 2002‐2004 follow‐up examination of the Olivetti Heart Study, performed a 24‐h urine collection to measure 24hUCrE and underwent bioelectrical impedance analysis to evaluate SMM. Linear regression analysis between 24hUCrE and SMM was used to calculate the muscle‐creatinine equivalence and to develop an equation to predict the 24hUCrE depending on SMM. The accuracy of the 24hUCrE measurement was assessed using the change in the SMM‐24hUCrE correlation coefficient upon variation in the percentage deviation (%D) between the measured and predicted 24hUCrE.
Results
The calculated muscle‐creatinine equivalence was 1 g of 24hUCrE = 22.73 kg of SMM. The %Ds and the corresponding SMM‐24hUCrE correlation coefficients were as follows: %D = 3.0, r = .997; %D = 4.7, r = .989; %D = 8.1, r = .963; %D = 10.5, r = .940; %D = 12.6, r = .909; %D = 18.9, r = .825; %D = 25.8, r = .707; %D = 33.5, r = .595; %D = 41.4, r = .453.
Conclusion
The increase in %D corresponds to a reduced correlation between muscle mass and creatinine excretion, which indicated a poor performance in the measurement of the 24hUCrE. For studies on single individuals, where small variations in 24hUCrE could be significant, a %D up to 12.6% is suggested; on the other hand, a wider %D interval could be acceptable for population studies.
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