Micronutrient deficiency and supplements in schoolchildren and teenagers.

PURPOSE OF REVIEW: The essential micronutrients are corner stones in the functional and physical development. Early deficiency has life-long consequences. While awareness about iron deficiency is relatively high, it remains lower for other micronutrients. This review aims at reporting on recent data and attracting attention to the high prevalence of micronutrient deficiencies in school-age and adolescent individuals. RECENT FINDINGS: Iron deficiency anaemia remains highly prevalent worldwide and the most frequent deficiency but can be corrected with simple tools ranging from food fortification, nutritional intervention, and to supplements. The link between micronutrient (MN) deficiency and neurobehavioral disorders is increasingly established and is worrying even in Western countries. Paediatric individuals are prone to imbalanced diets and picky eating behaviour, and their diets may then become incomplete: the highest risk for deficiency is observed for iron, zinc and vitamin D. SUMMARY: There is not much new information, but rather confirmation of the importance of health policies. Well conducted randomized controlled trials confirm that deficiencies can be corrected efficiently including with food fortification, and result in clinical benefits. Individual complementation should be considered in children and adolescents with proven deficiency.

ESPEN practical short micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. The importance of MNs in common pathologies is recognized by recent research, with deficiencies significantly impacting the outcome. OBJECTIVE: This short version of the guideline aims to provide practical recommendations for clinical practice. METHODS: An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL for the initial guideline. The search focused on physiological data, historical evidence (for papers published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: The limited number of interventional trials prevented meta-analysis and led to a low level of evidence for most recommendations. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90 % of votes. Altogether the guideline proposes 3 general recommendations and specific recommendations for the 26 MNs. Monitoring and management strategies are proposed. CONCLUSION: This short version of the MN guideline should facilitate handling of the MNs in at-risk diseases, whilst offering practical advice on MN provision and monitoring during nutritional support.

Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. METHODS: Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. RESULTS: The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. CONCLUSION: Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Personalized nutrition therapy in critical care: 10 expert recommendations.

Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.

ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit.

Following the new ESPEN Standard Operating Procedures, the previous 2019 guideline to provide best medical nutritional therapy to critically ill patients has been shortened and partially revised. Following this update, we propose this publication as a practical guideline based on the published scientific guideline, but shortened and illustrated by flow charts. The main goal of this practical guideline is to increase understanding and allow the practitioner to implement the Nutrition in the ICU guidelines. All the items discussed in the previous guidelines are included as well as special conditions.

An update on essential micronutrients in critical illness.

PURPOSE OF REVIEW: Numerous micronutrients are involved in antioxidant and immune defence, while their blood concentrations are frequently low in critically ill patients: this has fuelled many supplementation trials. Numerous observational, randomized studies have been published, which are presented herein. RECENT FINDINGS: Micronutrient concentrations must be analysed considering the context of the inflammatory response in critical illness. Low levels do not always indicate a deficiency without objective micronutrients losses with biological fluids. Nevertheless, higher needs and deficiencies are frequent for some micronutrients, such as thiamine, vitamins C and D, selenium, zinc and iron, and have been acknowledged with identifying patients at risk, such as those requiring continuous renal replacement therapy (CRRT). The most important trials and progress in understanding have occurred with vitamin D (25(OH)D), iron and carnitine. Vitamin D blood levels less than 12 ng/ml are associated with poor clinical outcomes: supplementation in deficient ICU patients generates favourable metabolic changes and decreases mortality. Single high-dose 25(OH)D should not be delivered anymore, as boluses induce a negative feedback mechanism causing inhibition of this vitamin. Iron-deficient anaemia is frequent and can be treated safely with high-dose intravenous iron under the guidance of hepcidin to confirm deficiency diagnosis. SUMMARY: The needs in critical illness are higher than those of healthy individuals and must be covered to support immunity. Monitoring selected micronutrients is justified in patients requiring more prolonged ICU therapy. Actual results point towards combinations of essential micronutrients at doses below upper tolerable levels. Finally, the time of high-dose micronutrient monotherapy is probably over.

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study.

INTRODUCTION: Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. METHODS: Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. RESULTS: The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. CONCLUSION: Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. REGISTRY: CORONA IMMUNITAS:: ISRCTN18181860.

Nutritional and metabolic characteristics of critically ill patients admitted for severe toxidermia.

INTRODUCTION: Drug-induced toxidermia is an idiosyncratic adverse skin reaction that may become life-threatening in a small portion of patients, requiring intensive care unit (ICU) admission. The treatment recommendations are extrapolated from those of major burns, while prospective data remain sparse. The objective was to observe the application of these recommendations in patients treated in a burn ICU. METHOD: Retrospective cohort study including patients requiring ICU between 2006 and 2020 in a tertiary university hospital. INCLUSION CRITERIA: Age >18 years. Patients were categorized as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), or other toxidermia. VARIABLES: severity scores, body surface area (BSA) involvement, nutritional and metabolic variables, trace element status, outcome variables. Descriptive statistics: median [IQR]. RESULTS: Altogether 35 patients were included (27 SJS/TEN and 8 "other"), aged 58 [48; 69] years. Skin involvement was 45% [30; 60] of body surface, 17 patients required mechanical ventilation, and length of ICU stay was 16 [6.5; 26] days. Hospital mortality was 23%. Fluid resuscitation requirements were moderate, despite intense inflammation (admission CRP (144 [89; 218] mg/L). The first 2 weeks' energy and protein intakes were below recommendations (p < 0.0001), lowest with oral feeding. Indirect calorimetry showed high energy expenditure in 11 patients (30.4 [23.9; 35.5] kcal/kg) resulting in negative energy balances (mean -245 kcal/day). Copper and zinc levels were below reference range during the first week, the low copper values being a novel finding. CONCLUSION: Trace elements should be monitored. The cohort was underfed with intakes lower than our ICU protocols, partly explained by short intubation times, and mucocutaneous involvement complicating the management and placement of feeding tubes. Oral feeding was least efficient and may become an indication for supplemental parenteral nutrition in the absence of an enteral feeding tube. CLINICALTRIALS: gov Identifier: NCT05320653.

Impact of ß-hydroxy-ß-methylbutyrate (HMB) in critically ill patients on the endocrine axis - A post-hoc cohort study of the HMB-ICU trial.

BACKGROUND: ß-hydroxy-ß-methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D. METHODS: Post-hoc analysis of the study HMB-ICU, a randomized, placebo-controlled double-blind trial. INCLUSION CRITERIA: Intensive care unit (ICU) patients depending on mechanical ventilation on day 3 with functional gastrointestinal tract. Patients were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on, for 30 days. Blood samples were collected on days 4 and 15. We determined the GH, C-peptide, 25-OH vitamin-D, and IGF-1. Statistics by ANCOVA. RESULTS: Blood samples of 26 patients were available on day 4, and 23 on day 15. While age and severity of disease did not differ, diabetes was more frequent in the HMB group (p = 0.041), and obesity was more frequent in the placebo group (p = 0.021). Glucose intake, blood glucose (BG) and amount of insulin to maintain blood glucose between 6 and 8 mM did not differ between groups. There was no difference between groups for C-peptide, GH, IGF-1, and 25-OH vitamin-D. IGF-1 increased significantly from day 4-15 (p = 0.026) in both groups. CONCLUSION: Subject to possible insufficient power of the study, we did not reach conclusive results. HMB intervention does not affect significantly the plasma concentrations of insulin, GH/IGF axis activity, C-peptide, and 25-OH vitamin-D. GOV IDENTIFIER: NCT03628365.

Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis.

BACKGROUND: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females. METHODS: In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA. RESULTS: Critically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations. CONCLUSIONS: The present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Post Intensive Care Syndrome (PICS) physical, cognitive, and mental health outcomes 6-months to 7 years after a major burn injury: A cross-sectional study.

OBJECTIVES: The Post Intensive Care Syndrome (PICS) has been described in intensive care (ICU) survivors, being present in 50% of patients surviving 12 months, with well-defined risk factors. Severely burned patients combine many of these risk factors, but the prevalence of PICS has not yet been documented in burns. The study aimed to answer this question and identify associations of PICS with clinical characteristics. METHODS: Cross-sectional descriptive study of major burn survivors admitted to the burn ICU between 2013 and 2019. Main inclusion criteria: major burns>20 %BSA and ICU admission. The PICS components were assessed using three questionnaires: 1) Physical with Burn Specific Health Scale-Brief (BSHS-B); 2) Cognitive health with MacNair Cognitive Difficulties Self-Rating Scale (CDS); 3) Mental health with the Hospital Anxiety and Depression Scale (HADS) questionnaire. PICS was considered present if at least one component out of three was abnormal. Data as mean±SD. RESULTS: Among the 288 patients admitted during the period, 132 met the inclusion criteria: 53 patients were finally enrolled. They were aged 44 ± 18 years at the time of injury and burned 24 ± 20 BSA % and stayed 25 ± 44 days in the ICU. PICS was identified in 35 patients (66 %): more than one component was altered in 21 patients (60 %). Principal risk factors were more than 3 general anesthetics, prolonged mechanical ventilation (>4 days), ICU stay (>8 days), and hospital stay (>25 days) CONCLUSION: PICS occurred in 66 % of major burns with two or three components affected simultaneously in 60 %, i.e. more frequently than in general ICU patients.

Pitfalls in the interpretation of blood tests used to assess and monitor micronutrient nutrition status.

Assessment of micronutrient (MN) status is of particular importance in patients who require medical nutrition therapy, especially those requiring parenteral nutrition. Blood testing is generally the only tool available in clinical settings to assess MN status. However, using plasma or serum concentration faces pitfalls mainly because of the impact of inflammation that diverts the MNs from the circulating compartment. This review aims to review the blood tests that are useful and provide information about how to integrate functional markers of status to reach a clinically relevant diagnosis. Most impacted, with a significant and proportional decrease in plasma concentrations, are iron, selenium, zinc, thiamin, folic acid, cobalamin, and vitamins A, C, and D; copper is the only MN for which the plasma concentration increases. Therefore, a surrogate marker of inflammation, C-reactive protein, must always be determined simultaneously. Validated intracellular and functional tests are proposed to improve status assessment. A protocol is suggested for tests required both on commencing and during nutrition support. A timely turnaround of analysis is essential for results to be clinically useful. In some cases, the appropriate provision of MNs should be commenced before results have been obtained to confirm the clinical assessment. Laboratory tests of MN status are an area prone to misuse and misinterpretation. The appropriate use and interpretation of such tests are essential to ensure the correct management of nutrition problems.

Computer customization errors compromised the optimization of trace element repletion dose after major burns.

BACKGROUND & AIMS: Major burns develop acute trace element (TE) deficiencies due to exudative losses of copper, selenium, and zinc from the wounds. A repletion strategy has been shown to decrease infectious and surgical complications. The TE doses have been adapted over time and the last adaptation, was not followed by the expected changes. The study aims at identifying the causes of the failure. METHODS: Retrospective cohort study including critically ill major burns patients admitted to intensive care with burns exceeding 20% of body surface area (BSA). Period A (2011-2015) included patients admitted before the dose change, and Period B patients after (2017-2020). Demographic variables, daily TE delivery, and weekly TE blood levels were extracted from the computerized information system (CIS). RESULTS: Altogether 71 patients completed the inclusion criteria (Periods A and B: 42 and 29 patients respectively). They were aged 38 (32) years and burned 35 (30) % BSA, with no severity differences. Comparing periods A and B, copper (p = 0.046) and selenium (p = 0.031) blood levels were significantly lower in B. The dose value extracted from CIS was as planned. Customization error was found: TE salts' weight had been entered instead of elemental weight in molar units. CONCLUSION: The lower TE repletion doses administered since 2017 resulted in a significant decrease in blood levels of Cu and Se. A CIS customisation error, confusing salt weight and elemental weight was the source of the error. A systematic quality control is crucial to identify systemic errors, as is the use of the standard international units.

Clinical nutrition issues in 2022: What is missing to trust supplemental parenteral nutrition (SPN) in ICU patients?

A multidisciplinary group of international physicians involved in the medical nutrition therapy (MNT) of adult critically ill patients met to discuss the value, role, and open questions regarding supplemental parenteral nutrition (SPN) along with oral or enteral nutrition (EN), particularly in the intensive care unit (ICU) setting. This manuscript summarizes the discussions and results to highlight the importance of SPN as part of a comprehensive approach to MNT in critically ill adults and for researchers to generate new evidence based on well-powered randomized controlled trials (RCTs). The experts agreed on several key points: SPN has shown clinical benefits, resulting in this strategy being included in American and European guidelines. Nevertheless, its use is heterogeneous across European countries, due to the persistence of uncertainties, such as the optimal timing and the risk of overfeeding in absence of indirect calorimetry (IC), which results in divergent opinions and barriers to SPN implementation. Education is also insufficient. The experts agreed on actions needed to increase evidence quality on SPN use in specific patients at a given time point during acute critical illness or recovery.