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.

Management of Home Parenteral Nutrition: Complications and Survival.

BACKGROUND AND AIMS: Parenteral nutrition (PN) has become an efficient, safe, and convenient treatment over years for patients suffering from intestinal failure. Home PN (HPN) enables the patients to have a high quality of life in their own environment. The therapy management however implies many restrictions and potentially severe lethal complications. Prevention and therapy of the latter are therefore of utmost importance. This study aims to assess and characterize the situation of patients with HPN focusing on prevalence of catheter-related complications and mortality. METHODS: Swiss multicentre prospective observational study collecting demographic, anthropometric, and catheter-related data by means of questionnaires every sixth month from 2017 to 2019 (24 months), focusing on survival and complications. Data were analysed using descriptive statistics. Logistic regression models were fitted to investigate association between infection and potential co-factors. RESULTS: Seventy adult patients (50% women) on HPN were included (≈5 patients/million adult inhabitants/year). The most common underlying diseases were cancer (23%), bariatric surgery (11%), and Crohn's disease (10%). The most prevalent indication was short bowel syndrome (30%). During the study period, 47% of the patients were weaned off PN; mortality rate reached 7% for a median treatment duration of 1.31 years. The rate of catheter-related infection was 0.66/1,000 catheter-days (0.28/catheter-year) while the rate of central venous thrombosis was 0.13/1,000 catheter-days (0.05/catheter-year). CONCLUSION: This prospective study gives a comprehensive overview of the adult Swiss HPN patient population. The collected data are prerequisite for evaluation, comparison, and improvement of recommendations to ensure best treatment quality and safety.

Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines.

It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 µmol/l DHA, 1467 ± 362 µmol/l EPA, and 9.8 ± 1.1 µmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53+/+, bax-/-) and HT-29 (p53-/0, bax+/+) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and/or necrosis. The cytotoxic potential of LIPUFU was confirmed in vivo by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases.

Evaluating the TARGET and EAT-ICU trials: how important are accurate caloric goals? Point-counterpoint: the pro position.

PURPOSE OF REVIEW: Controversies about the adequate amount of energy to deliver to critically ill patients are still going on, trying to find if hypocaloric or normocaloric regimen is beneficial in this population. Our purpose is to review recent publications using or not indirect calorimetry. RECENT FINDINGS: Numerous studies have compared hypocaloric to normocaloric regimen using predictive equations. However, these equations have been demonstrated to be inaccurate in most of the cases. Some recent PRCT using indirect calorimetry are finding some advantages to isocalorie regimens, but others not. Timing of the nutrition respecting or not the early substrate endogenous production, use of an adequate amount of protein, respect of the daily variability of needs may explain the divergent results observed. SUMMARY: Indirect calorimetry should be used to define the energy expenditure of the patient and to determine its requirements. More studies comparing isocalorie to hypocalorie regimens with fixed protein intake are necessary to confirm the observational and some of the PRCT-positive studies.

Nutrition of the COVID-19 patient in the intensive care unit (ICU): a practical guidance.

Five to 10% of the coronavirus SARS-CoV-2-infected patients, i.e., with new coronavirus disease 2019 (COVID-19), are presenting with an acute respiratory distress syndrome (ARDS) requiring urgent respiratory and hemodynamic support in the intensive care unit (ICU). However, nutrition is an important element of care. The nutritional assessment and the early nutritional care management of COVID-19 patients must be integrated into the overall therapeutic strategy. The international recommendations on nutrition in the ICU should be followed. Some specific issues about the nutrition of the COVID-19 patients in the ICU should be emphasized. We propose a flow chart and ten key issues for optimizing the nutrition management of COVID-19 patients in the ICU.

Cellular circadian period length inversely correlates with HbA1c levels in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: The circadian system plays an essential role in regulating the timing of human metabolism. Indeed, circadian misalignment is strongly associated with high rates of metabolic disorders. The properties of the circadian oscillator can be measured in cells cultured in vitro and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed to discover whether molecular properties of the circadian oscillator are altered as a result of type 2 diabetes. METHODS: We assessed molecular clock properties in dermal fibroblasts established from skin biopsies taken from nine obese and eight non-obese individuals with type 2 diabetes and 11 non-diabetic control individuals. Following in vitro synchronisation, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. RESULTS: We observed a significant inverse correlation (ρ = -0.592; p < 0.05) between HbA1c values and circadian period length within cells from the type 2 diabetes group. RNA sequencing analysis conducted on samples from this group revealed that ICAM1, encoding the endothelial adhesion protein, was differentially expressed in fibroblasts from individuals with poorly controlled vs well-controlled type 2 diabetes and its levels correlated with cellular period length. Consistent with this circadian link, the ICAM1 gene also displayed rhythmic binding of the circadian locomotor output cycles kaput (CLOCK) protein that correlated with gene expression. CONCLUSIONS/INTERPRETATION: We provide for the first time a potential molecular link between glycaemic control in individuals with type 2 diabetes and circadian clock machinery. This paves the way for further mechanistic understanding of circadian oscillator changes upon type 2 diabetes development in humans. DATA AVAILABILITY: RNA sequencing data and clinical phenotypic data have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the European Bioinformatics Institute (EBI) and the Centre for Genomic Regulation (CRG), ega-box-1210, under accession no. EGAS00001003622.

Feeding should be individualized in the critically ill patients.

PURPOSE OF REVIEW: Any critical care therapy requires individual adaptation, despite standardization of the concepts supporting them. Among these therapies, nutrition care has been repeatedly shown to influence clinical outcome. Individualized feeding is the next needed step towards optimal global critical care. RECENT FINDINGS: Both underfeeding and overfeeding generate complications and should be prevented. The long forgotten endogenous energy production, maximal during the first 3 to 4 days, should be integrated in the nutrition plan, through a slow progression of feeding, as full feeding may result in early overfeeding. Accurate and repeated indirect calorimetry is becoming possible thanks to the recent development of a reliable, easy to use and affordable indirect calorimeter. The optimal timing of the prescription of the measured energy expenditure values as goal remains to be determined. Optimal protein prescription remains difficult as no clinically available tool has yet been identified reflecting the body needs. SUMMARY: Although energy expenditure can now be measured, we miss indicators of early endogenous energy production and of protein needs. A pragmatic ramping up of extrinsic energy provision by nutrition support reduces the risk of overfeeding-related adverse effects.

High-intensity exercise is associated with a better nutritional status in anorexia nervosa.

OBJECTIVE: Our aim is to investigate the links between duration and intensity of exercise and the nutritional status in terms of body composition in acute anorexia nervosa (AN) patients. METHOD: One hundred ninety-one hospitalized women suffering from AN were included. Exercise duration and intensity were assessed using a semistructured questionnaire. Body composition was measured using bioelectrical impedance. Linear multiple regression analyses were carried out using body mass index, fat-free mass index, and fat mass index as dependent variables and including systematically exercise duration, exercise intensity, and other confounding variables described in the literature that were significantly associated with each dependent variable in univariate analysis. RESULTS: A lower BMI was linked to lower exercise intensity, AN restrictive type, and presence of amenorrhea. A lower FFMI was linked to lower exercise intensity, older age, AN restrictive type, and premenarchal AN. Duration of exercise was not linked to the nutritional status. CONCLUSIONS: Exercising at higher intensity in AN is associated with a better nutritional status, thus, a better resistance to starvation. The impact of therapeutic physical activity sessions, adapted in terms of exercise intensity and patient's clinical status, should be evaluated during nutrition rehabilitation.

Parenteral nutrition in intensive care patients: medicoeconomic aspects.

PURPOSE OF REVIEW: Parenteral nutrition (PN) alone or as supplemental parenteral nutrition (SPN) has been shown to prevent negative cumulative energy balance, to improve protein delivery and, in some studies, to reduce infectious morbidity in ICU patients who fail to cover their needs with enteral nutrition (EN) alone. RECENT FINDINGS: The optimization of energy provision to an individualized energy target using either early PN or SPN within 3-4 days after admission has recently been reported to be a cost-saving strategy mediated by a reduction of infectious complications in selected intensive care patients. SUMMARY: EN alone is often insufficient, or occasionally contraindicated, in critically ill patients and results in growing energy and protein deficit. The cost benefit of using early PN in patients with short-term relative contraindications to EN has been reported. In selected patients SPN has been associated with a decreased risk of infection, a reduced duration of mechanical ventilation, a shorter stay in the ICU. Altogether four studies have investigated the costs associated with these interventions since 2012: two of them from Australia and Switzerland have shown that optimization of energy provision using SPN results in cost reduction, conflicting with other studies. The latter encouraging findings require further validation.

Prolonged Versus Short-Duration Use of Nasogastric Tubes in Patients with Head and Neck Cancer During Radiotherapy Alone or Combined Chemoradiotherapy.

To compare safety and effectiveness of prolonged (>28 days) versus short duration (≤28 days) use of nasogastric tube for enteral nutrition and weight loss prevention during curative radiotherapy with or without concurrent chemotherapy or cetuximab for head and neck cancer patients. We performed a retrospective study and database review of all patients at our center, treated with radiotherapy for head and neck cancer receiving enteral nutrition by nasogastric tube. Type of treatment, weight and body mass index changes, and related complications (gastroesophageal reflux, pneumonia, ulcer, feeding tube obstruction, or dislocation) were documented. Comparison between patients with prolonged (>28 days, group A) and short duration (≤28 days, group B) of EN through nasogastric tube was performed. Data expressed as mean ± SD or median (min; max) values as appropriate, and analyzed by ANOVA repeated measures and Kaplan-Meier estimates. We identified 114 patients who fulfilled the inclusion criteria. Among them, 10% were treated with radiotherapy alone, while 90% received concurrent chemotherapy or cetuximab. Ninety-four patients (82%, group A) had a nasogastric tube in place for a period >28 days and 20 (18%, group B) for ≤28 days during treatment. Patients were mainly men (86 patients, 75%), with a median age of 61 years (range 49-73) and advanced stage IV disease in most cases (87 patients, 76%) without differences between both groups (p = 0.53, 0.47, and 0.30, respectively). Treatment discontinuation did not occur within both groups. Fifty-six patients (49%) developed complications, without a significant difference between both groups (P = 0.23). Body weight and BMI changes did not differ during EN (-0.8 ± 4.5 and -0.3 ± 1.6), the oncological treatment (-5.3 ± 4.0 and -1.8 ± 1.4), or 6 months after the end of treatment (-0.6 ± 4.4 and -0.2 ± 1.5). Our findings suggest that prolonged enteral nutrition by nasogastric tube is safe and effective in preventing weight loss during curative radiotherapy or radio-chemotherapy for head and neck cancer.

[Fasting during health and diseases]. / Le jeûne dans la santé et pendant la maladie.

Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despite few randomized controlled studies, therapeutic fasting is prescribed in various chronic diseases, as diabetes, hypertension and also cancer. Fasting is applied to lose weight in overweight and obese patients. However, weight loss is often associated with fat-free mass loss. Chronic caloric restriction has been associated with longevity in animal studies, while it has been poorly studied in humans to date. Good quality studies are needed to better understand the effects of fasting on health and diseases.

Le jeûne volontaire, intermittent ou continu, religieux ou thérapeutique, connaît un engouement grandissant. Malgré la rareté des études randomisées et contrôlées chez l'homme, le jeûne thérapeutique est souvent proposé dans certaines pathologies chroniques, telles que le diabète de type 2, l'hypertension artérielle et le cancer. Il est aussi pratiqué dans le but de maigrir chez les sujets en surpoids ou obèses. Sa pratique n'est pas sans risques. La perte de poids est souvent associée à une perte de masse maigre, facteur de mauvais pronostic. Enfin, alors que la restriction calorique est associée à la longévité dans certaines études animales, ses effets ont été peu étudiés chez l'homme. Des études cliniques de bonne qualité sont nécessaires pour une meilleure évaluation des effets du jeûne sur la santé et lors de maladies.

The ADAPP trial: a two-year longitudinal multidisciplinary intervention study for prostate cancer frail patients on androgen deprivation associated to curative radiotherapy.

BACKGROUND: Androgen deprivation (AD) therapy combined to radiotherapy (RT) is a curative therapeutic option for patients with non-metastatic locally advanced or aggressive intermediate prostate cancer (PC), though with a range of nutritional, physical, and psychological side effects. A multidisciplinary care program was created to help frail patients to prevent and manage those side effects. MATERIAL AND METHODS: We conducted a longitudinal interventional study in frail patients, presenting either cardiovascular/pulmonary comorbidities, old age (≥75 years), vulnerability ratings, or balance impairment. Patients were treated by AD and RT and, benefited from nutritional coaching, supervised biweekly 45 minute physical training, and psychological counseling for two years. Treatment outcomes included PC-related quality of life (QoL), body mass index, fat mass index, and fat-free mass index derived from bioelectrical impedance analysis, Six-Minute Walk Test, Timed Up&Go, handgrip strength, Hospital Anxiety and Depression scale, Mini Mental State Examination. Measures were repeated after zero, three, six, nine, 12, 18, 24 months, and 12-months post-study follow-up. A prospective mixed-model design was used to assess longitudinal outcome. RESULTS: Regression analyses revealed no significant change over the two years, including post-study follow-up. Means of QoL, nutritional, physical, as well as psychological variables remained stable over more than two years in the 35 men aged 74 (range 68-76) years. CONCLUSION: The expected side effects of AD and RT were not observed in frail PC patients who followed this multidisciplinary care program.

Can calculation of energy expenditure based on CO2 measurements replace indirect calorimetry?

BACKGROUND: Methods to calculate energy expenditure (EE) based on CO2 measurements (EEVCO2) have been proposed as a surrogate to indirect calorimetry. This study aimed at evaluating whether EEVCO2 could be considered as an alternative to EE measured by indirect calorimetry. METHODS: Indirect calorimetry measurements conducted for clinical purposes on 278 mechanically ventilated ICU patients were retrospectively analyzed. EEVCO2 was calculated by a converted Weir's equation using CO2 consumption (VCO2) measured by indirect calorimetry and assumed respiratory quotients (RQ): 0.85 (EEVCO2_0.85) and food quotient (FQ; EEVCO2_FQ). Mean calculated EEVCO2 and measured EE were compared by paired t test. Accuracy of EEVCO2 was evaluated according to the clinically relevant standard of 5% accuracy rate to the measured EE, and the more general standard of 10% accuracy rate. The effects of the timing of measurement (before or after the 7th ICU day) and energy provision rates (<90 or ≥90% of EE) on 5% accuracy rates were also analyzed (chi-square tests). RESULTS: Mean biases for EEVCO2_0.85 and EEVCO2_FQ were -21 and -48 kcal/d (p = 0.04 and 0.00, respectively), and 10% accuracy rates were 77.7 and 77.3%, respectively. However, 5% accuracy rates were 46.0 and 46.4%, respectively. Accuracy rates were not affected by the timing of the measurement, or the energy provision rates at the time of measurements. CONCLUSIONS: Calculated EE based on CO2 measurement was not sufficiently accurate to consider the results as an alternative to measured EE by indirect calorimetry. Therefore, EE measured by indirect calorimetry remains as the gold standard to guide nutrition therapy.

Overview on nutritional issues in bariatric surgery.

PURPOSE OF REVIEW: In the context of the worldwide obesity epidemic, bariatric surgery is the only therapy associated with a sustainable weight loss and to midterm prevention of obesity-related complications. However, nutritional and behavioral multidisciplinary medical preparation, as well as long-term postoperative nutritional follow-up, is strongly advised to avoid postoperative surgical, nutritional, or psychiatric complications. RECENT FINDINGS: Due to a long history of restrictive diets and large body weight fluctuations, preoperative nutritional assessment and correction of vitamin and trace elements deficiencies are mandatory. A rapid and massive weight loss induces the loss of muscle mass and fat-free mass that could lead to malnutrition and osteoporosis. Dietetic counseling is advised to prevent postoperative food intolerance syndrome, malnutrition, and weight regain. Protein intake should be at least 60 g/day. Planned and structured physical exercise should be systematically promoted to maintain muscle mass and bone health. SUMMARY: Bariatric surgery is mostly successful if patients are well prepared and monitored. The perfect patients' selection remains difficult in the absence of well defined predictive criteria of success. Future research is needed to define optimal perioperative nutritional management and its influence on long-term outcome, including quality of life and healthcare-related costs.

Parenteral nutrition in the ICU setting: need for a shift in utilization.

PURPOSE OF REVIEW: The difficulties to feed the patients adequately with enteral nutrition alone have drawn the attention of the clinicians toward the use of parenteral nutrition, although recommendations by the recent guidelines are conflicting. This review focuses on the intrinsic role of parenteral nutrition, its new indication, and modalities of use for the critically ill patients. RECENT FINDINGS: A recent trial demonstrated that selecting either parenteral nutrition or enteral nutrition for early nutrition has no impact on clinical outcomes. However, it must be acknowledged that the risk of relative overfeeding is greater when using parenteral nutrition and the risk of underfeeding is greater when using enteral nutrition because of gastrointestinal intolerance. Both overfeeding and underfeeding in the critically ill patients are associated with deleterious outcomes. Thus, early and adequate feeding according to the specific energy needs can be recommended as the optimal feeding strategy. SUMMARY: Parenteral nutrition can be used to substitute or supplement enteral nutrition, if adequately prescribed. Testing for enteral nutrition tolerance during 2-3 days after ICU admission provides the perfect timing to start parenteral nutrition, if needed. In case of absolute contraindication for enteral nutrition, consider starting parenteral nutrition carefully to avoid overfeeding.

Parenteral or enteral nutrition: do you have the choice?

PURPOSE OF REVIEW: The review focuses on the use of parenteral nutrition and enteral nutrition in critically ill patients to optimize the nutrition care throughout the ICU stay. The key message is: you have the choice! RECENT FINDINGS: Enteral nutrition has been recommended for critically ill patients, whereas parenteral nutrition has been considered harmful and to be avoided. However, recent studies have challenged this theory. They demonstrated that enteral nutrition is frequently associated with energy and protein undernutrition, whereas parenteral nutrition becomes deleterious only if overfeeding is induced. Measuring energy expenditure by indirect calorimetry, in most cases, enables accurate determination of the energy needs to optimize the prescription of nutrition. Protein targets should also be considered for adequate feeding. Parenteral nutrition can be used as a supplement or as an alternative to enteral nutrition in case of gastrointestinal intolerance, to enable adequate energy, and protein provision. SUMMARY: Parenteral nutrition is a powerful tool to optimize nutrition care of critically ill patients to improve clinical outcome, if prescribed according to the individual needs of the patients. After 3-4 days of attempt to feed enterally, enteral nutrition or parenteral nutrition can be used alternatively or combined, as long as the target is reached with special attention to avoid hypercaloric feeding.

Impact of Hypocaloric Hyperproteic Diet on Gut Microbiota in Overweight or Obese Patients with Nonalcoholic Fatty Liver Disease: A Pilot Study.

BACKGROUND: NAFLD is likely to become the most common cause of chronic liver disease. The first-line treatment includes weight loss. AIMS: To analyze the impact of a hypocaloric hyperproteic diet (HHD) on gut microbiota in NAFLD patients. METHODS: Fifteen overweight/obese patients with NAFLD were included. At baseline and after a 3-week HHD (Eurodiets(®), ~1000 kcal/day, ~125 g protein/day), we measured gut microbiota composition and function by shotgun metagenomics; body weight; body composition by bioelectrical impedance analysis; liver and visceral fat by magnetic resonance imaging; plasma C-reactive protein (CRP); and liver tests. Results between both time points, expressed as median (first and third quartile), were compared by Wilcoxon signed-rank tests. RESULTS: At baseline, age was 50 (47-55) years and body mass index 34.6 (32.4, 36.7) kg/m(2). HDD decreased body weight by 3.6 % (p < 0.001), percent liver fat by 65 % (p < 0.001), and CRP by 19 % (p = 0.014). HDD was associated with a decrease in Lachnospira (p = 0.019), an increase in Blautia (p = 0.026), Butyricicoccus (p = 0.024), and changes in several operational taxonomic units (OTUs) of Bacteroidales and Clostridiales. The reduced liver fat was negatively correlated with bacteria belonging to the Firmicutes and Bacteroidetes phyla (a Ruminococcaceae OTU, r = -0.83; Bacteroides, r = -0.73). The associated metabolic changes concerned mostly enzymes involved in amino acid and carbohydrate metabolism. CONCLUSIONS: In this pilot study, HHD changes gut microbiota composition and function in overweight/obese NAFLD patients, in parallel with decreased body weight, liver fat, and systemic inflammation. Future studies should aim to confirm these bacterial changes and understand their mode of action. TRAIL REGISTRATION: Under clinicaltrials.gov: NCT01477307.

[Oral nutritive supplements : efficiency and clinical use in community-dwelling patients]. / Suppléments nutritifs oraux : efficacité et aspects pratiques en ambulatoire.

Undernutrition represents a wide-spread clinical state in outpatients and inpatients. It is associated with a high morbidity and mortality, an impaired quality of life, and increased healthcare costs. Early diagnosis and treatement help to reduce these medical and economic consequences. Oral nutritive supplements (ONS) are simple, effective and economic medical treatments to fight against undernutrition. However, they are insufficiently used for outpatients because of lack of knowledge. This article reviews the impact of ONS, their indications and contraindications and their modalities of prescription and focuses especially on community-dwelling patients.

La dénutrition est un état clinique répandu chez les personnes hospitalisées et ambulatoires. Elle augmente la morbi-mortalité, les coûts et diminue la qualité de vie. Un diagnostic et une prise en charge précoces permettent de diminuer ses conséquences médico-économiques. Les suppléments nutritifs oraux (SNO) sont un traitement médical simple, efficace et économique pour lutter contre la dénutrition. Ils sont peu utilisés chez les patients ambulatoires, car méconnus. Cet article précise l'impact des SNO, les indications et les contre-indications, et les modalités de prescription, en se focalisant sur les patients ambulatoires.