BackgroundCritically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets.MethodsThe PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models.DiscussionThe PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04633421. Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.
MULTIFILE
BackgroundICU patients lose muscle mass rapidly and maintenance of muscle mass may contribute to improved survival rates and quality of life. Protein provision may be beneficial for preservation of muscle mass and other clinical outcomes, including survival. Current protein recommendations are expert-based and range from 1.2 to 2.0 g/kg. Thus, we performed a systematic review and meta-analysis on protein provision and all clinically relevant outcomes recorded in the available literature.MethodsWe conducted a systematic review and meta-analyses, including studies of all designs except case control and case studies, with patients aged ≥18 years with an ICU stay of ≥2 days and a mean protein provision group of ≥1.2 g/kg as compared to <1.2 g/kg with a difference of ≥0.2 g/kg between protein provision groups. All clinically relevant outcomes were studied. Meta-analyses were performed for all clinically relevant outcomes that were recorded in ≥3 included studies.ResultsA total of 29 studies published between 2012 and 2022 were included. Outcomes reported in the included studies were ICU, hospital, 28-day, 30-day, 42-day, 60-day, 90-day and 6-month mortality, ICU and hospital length of stay, duration of mechanical ventilation, vomiting, diarrhea, gastric residual volume, pneumonia, overall infections, nitrogen balance, changes in muscle mass, destination at hospital discharge, physical performance and psychological status. Meta-analyses showed differences between groups in favour of high protein provision for 60-day mortality, nitrogen balance and changes in muscle mass.ConclusionHigh protein provision of more than 1.2 g/kg in critically ill patients seemed to improve nitrogen balance and changes in muscle mass on the short-term and likely 60-day mortality. Data on long-term effects on quality of life are urgently needed.
MULTIFILE
Background & aims: Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2–4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. Methods: Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2–1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. Results: Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73–0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79–0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64–0.90 for 60-day mortality and HR 0.80, 95%CI 0.68–0.93 for 6-month mortality). Conclusions: Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.
Micro and macro algae are a rich source of lipids, proteins and carbohydrates, but also of secondary metabolites like phytosterols. Phytosterols have important health effects such as prevention of cardiovascular diseases. Global phytosterol market size was estimated at USD 709.7 million in 2019 and is expected to grow with a CAGR of 8.7% until 2027. Growing adoption of healthy lifestyle has bolstered demand for nutraceutical products. This is expected to be a major factor driving demand for phytosterols. Residues from algae are found in algae farming and processing, are found as beachings and are pruning residues from underwater Giant Kelp forests. Large amounts of brown seaweed beaches in the province of Zeeland and are discarded as waste. Pruning residues from Giant Kelp Forests harvests for the Namibian coast provide large amounts of biomass. ALGOL project considers all these biomass residues as raw material for added value creation. The ALGOL feasibility project will develop and evaluate green technologies for phytosterol extraction from algae biomass in a biocascading approach. Fucosterol is chosen because of its high added value, whereas lipids, protein and carbohydrates are lower in value and will hence be evaluated in follow-up projects. ALGOL will develop subcritical water, supercritical CO2 with modifiers and ethanol extraction technologies and compare these with conventional petroleum-based extractions and asses its technical, economic and environmental feasibility. Prototype nutraceutical/cosmeceutical products will be developed to demonstrate possible applications with fucosterol. A network of Dutch and African partners will supply micro and macro algae biomass, evaluate developed technologies and will prototype products with it, which are relevant to their own business interests. ALGOL project will create added value by taking a biocascading approach where first high-interest components are processed into high added value products as nutraceutical or cosmeceutical.
The seaweed aquaculture sector, aimed at cultivation of macroalgal biomass to be converted into commercial applications, can be placed within a sustainable and circular economy framework. This bio-based sector has the potential to aid the European Union meet multiple EU Bioeconomy Strategy, EU Green Deal and Blue Growth Strategy objectives. Seaweeds play a crucial ecological role within the marine environment and provide several ecosystem services, from the take up of excess nutrients from surrounding seawater to oxygen production and potentially carbon sequestration. Sea lettuce, Ulva spp., is a green seaweed, growing wild in the Atlantic Ocean and North Sea. Sea lettuce has a high nutritional value and is a promising source for food, animal feed, cosmetics and more. Sea lettuce, when produced in controlled conditions like aquaculture, can supplement our diet with healthy and safe proteins, fibres and vitamins. However, at this moment, Sea lettuce is hardly exploited as resource because of its unfamiliarity but also lack of knowledge about its growth cycle, its interaction with microbiota and eventually, possible applications. Even, it is unknown which Ulva species are available for aquaculture (algaculture) and how these species can contribute to a sustainable aquaculture biomass production. The AQULVA project aims to investigate which Ulva species are available in the North Sea and Wadden Sea which can be utilised in onshore aquaculture production. Modern genomic, microbiomic and metabolomic profiling techniques alongside ecophysiological production research must reveal suitable Ulva selections with high nutritional value for sustainable onshore biomass production. Selected Ulva spp lines will be used for production of healthy and safe foods, anti-aging cosmetics and added value animal feed supplements for dairy farming. This applied research is in cooperation with a network of SME’s, Research Institutes and Universities of Applied Science and is liaised with EU initiatives like the EU-COST action “SeaWheat”.
Chemo-enzymatic peptide synthesis is unique in enabling the fast and sustainable synthesis of cyclic peptides, complex peptides and functionalized mini-proteins. The starting materials are routinely obtained by solid-phase peptide synthesis. One of the starting materials requires an oxo-ester functionality for recognition by the enzymes active site. The SPPS-based synthesis of the oxo-ester functionality still suffers from significant byproduct formation and low overall synthesis yields. The solution to this is introduction of the oxo-ester functionality at the end of the SPPS via a so-called Passerini reaction. Such a process does not only result in a more efficient production of cyclic or long peptides, but also expand the scope towards proteins derived from biological synthesis (i.e. recombinant proteins). To highlight the relevance of this proposed methodology, we will demonstrate a site-selective modification of the pharmaceutically important drug insulin.
