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Background Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. Methods This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. Results Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. Conclusions Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Rapidly accumulating evidence supports the important role of gut microbiome in the regulation of mood, behaviour, appetite, gastrointestinal symptomology, and nutrient metabolism. These are all core features frequently altered in individuals with anorexia nervosa (AN). Current treatment recommendations for AN support the use of high-calorie diets as an essential part of nutritional rehabilitation, commonly achieved by elevating the fat content of the diet. However, in contrast to this approach, there is accumulating evidence suggesting the importance of balanced, high-fibre diets on the gut microbiome. Studies have demonstrated profound differences in the microbial composition of underweight people with AN and those of normal- or overweight individuals. Specific alterations vary widely between studies. It is thus far unclear to what extent the observed differences are brought on by iatrogenic effects of nutritional rehabilitation or the disorder itself. To date, only two studies have investigated the changes in the intestinal microbiota during nutritional rehabilitation and corresponding weight restoration. These studies suggest that the gut microbiome of AN patients was different to healthy controls both prior and following nutritional rehabilitation, though it is noted that these states were associated with lower and higher nutritional intakes, respectively. There is a clear need for further investigation regarding the effects of nutritional rehabilitation on the gut microbiome. Such research would provide insights into the potential role of gut microbiome in modulating the pathophysiology of AN and inform future treatment strategies.

PurposeChemotherapy-induced taste and smell alterations may have a negative impact on the quality of life and nutritional status. A prominent issue when dealing with taste and smell alterations and their consequences on food behavior and well-being lies in the variation arising from individual differences in chemosensory perceptions. The main aim of this study was to examine the effect of individuals’ variation in the severity of taste and smell alterations relative to the stage of chemotherapy on self-reported food behavior and food perception.MethodsEighty-nine cancer patients completed a questionnaire subdivided into two parts: a chemosensory part that allowed classification of patients in three groups (“no alterations,” “moderate alterations,” and “severe alterations”) and a food behavior part.ResultsThe results highlighted a negative impact of chemosensory alterations on food perception. Compared with patients without taste and smell alterations, patients with severe chemosensory alterations reported significantly more frequent food perception problems, including modification of the perceived taste of food, finding bad taste in all food, and being unable to perceive food taste. Whereas 72% of patients with severe alterations were in late stage, only 37% of patients were in late stage in the no alterations group, indicating an effect of the treatment stage on taste and smell alterations.ConclusionOur results underlie the importance of providing specific attention to the severity of chemotherapy-induced taste and smell alterations and considering the individual differences among patients for a better nutritional management.

Background/Objectives: Loop diuretics are among the most commonly used drugs in patients with heart failure with reduced ejection fraction (HFrEF). Higher doses of these diuretics are associated with poorer clinical status and may contribute to malnutrition. The study aims to assess the relationship between the use of high-dose loop diuretics and nutritional status in patients with HFrEF. Methods: The study included 353 hospitalized patients with HFrEF. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), the Geriatric Nutritional Index (GNRI), and the CONtrolling NUTritional status (CONUT). Patients were divided into three groups according to the daily dose of loop diuretics (defined as furosemide equivalent = 1 × furosemide dose and 2 × torsemide dose): low dose (LD), 40 mg/day or no treatment; medium dose (MD), 41–160 mg/day; or high dose (HD), >160 mg/day. Results: Of the evaluated patients, the mean MNA score was 23.31 ± 2.93 points, and 49.8% were at risk of malnutrition or malnourished. According to the MNA, patients in HD and MD groups had worse nutritional status than the LD group, similarly according to the GNRI. For CONUT, the differences were significant between all groups: nutritional status was the worst in the HD group, intermediate in the MD group, and the best in the LD group. Conclusions: The intake of loop diuretics, especially in high doses, correlates with an elevated risk of malnutrition in patients with HFrEF independently of sex, age, NYHA class, and left ventricular ejection fraction.

Background Home parenteral nutrition (HPN) can improve survival, quality of life, nutritional and functional status in cancer patients. Bioelectrical impedance analysis (BIA) is a non-invasive, validated method to assess body composition. The objective of this prospective single-arm study was to investigate the impact of HPN in advanced cancer patients receiving chemotherapy assessed by BIA, clinical and laboratory measures. Methods Adult malnourished cancer outpatients with solid tumors receiving anticancer treatments who were candidates for daily HPN were enrolled. Patients were assessed at baseline (T0), 60 (T1) and 90 days (T2) after HPN start. Assessments included anthropometric and clinical-oncological characteristics, performance status, inflammatory response and Patient-Generated Subjective Global Assessment (PG-SGA). Results Sixty-five advanced cancer patients were enrolled. Median overall survival was 317 days. Body weight, BMI, oral calorie and protein intake increased over time ( P  < 0.01). At T2 the proportion of well-nourished patients, Karnofsky performance status and modified Glasgow prognostic score were improved ( P  < 0.01), total body water was reduced ( P  = 0.04), and fat mass increased ( P  = 0.04). Reactance, resistance and phase angle were significantly associated with survival at T0, T1, and T2, respectively. At T2, PG-SGA category A was a predictor of survival ( P  < 0.0001). Conclusions After 90 days of HPN, patients experienced significantly improved nutritional status, performance status, prognostic score and some BIA measures. HPN may be an important therapy in oncology patients receiving chemotherapy. Longitudinal use of BIA may help track the effects of HPN and disease progression, potentially contributing to optimal global patient management.

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B 12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B 12 —were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

Anamorelin, a ghrelin receptor agonist, increases body weight and lean body mass (LBM); however, its effects on the gut microbiota remain unclear. Furthermore, the predictive value of nutritional scores, such as the Controlling Nutritional Status (CONUT) score, for anamorelin response is not established. This study aimed to evaluate the effects of anamorelin on body weight, quality of life (QOL), and gut microbiota in patients with advanced cancer and cachexia, and to clarify the predictive role of nutritional indicators. This single-center prospective observational study enrolled cachectic patients (non-small cell lung, pancreatic, gastric, or colorectal cancer) receiving anamorelin 100 mg/day with dietary counseling. Outcomes included change in body weight (baseline, 3, 6, 12 weeks), QOL (EORTC QLQ-C15-PAL), and gut microbiota diversity. The association between the baseline CONUT score and weight gain (>0 kg at 6 weeks) was analyzed. Sixteen patients were analyzed. Body weight significantly increased from baseline at weeks 3, 6, and 12 (mean change at 12 weeks: +2.61±0.72 kg, =0.008). In the eight patients assessed for QOL, the overall scale showed no significant change. The score for appetite loss (Q8) was 2.125±0.835 at 0 weeks 1.375±0.744 at 6 weeks (unadjusted =0.033). Gut microbiota alpha and beta diversity showed no significant change. A high baseline CONUT score (≥5) was associated with failure to gain weight in six weeks compared to a score <5 (87.5% of non-gainers had a high score 12.5%; unadjusted =0.01). In this pilot study, anamorelin significantly increased body weight and suggested an improvement in appetite in patients with cancer and cachexia. No significant changes in overall QOL or gut microbiota diversity were detected at 6 weeks. The finding that a high baseline CONUT score may predict a lack of short-term weight gain warrants further investigation.

•N-3 PUFAs prevent cachexia-related inflammation.•There is no strong evidence to favor EPA over DHA in cancer patients.•An EPA to DHA ratio of less than one shows the greatest benefit in cancer patients.•Supplementation compliance is better with n-3 PUFA tablets than with ONS.•Patients undergoing chemotherapy benefit most from n-3 PUFA supplementation. Chronic inflammation is a hallmark of cancer cachexia. Polyunsaturated fatty acids (ω-3 PUFAs): eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to contribute to the reduction of inflammation, preservation of lean body mass and total body weight, and reduction of cancer-related symptoms, such as anorexia or neuropathy. This systematic review aimed to assess whether the ratio of EPA to DHA used in supplementation in cancer patients matters in the context of the resolution of inflammation and reduction of the risk of cachexia. The analysis included 20 randomized clinical trials with acceptable quality identified from the Pubmed/MEDLINE database. The significant results concerning the resolution of inflammation or improvement in nutritional status were the highest in the case of a low EPA/DHA ratio, i.e., 67%, and decreased, reaching 50% and 36% for the moderate and high ratios, respectively. Most results concerning body weight from high and moderate EPA/DHA ratios showed no benefit or were insignificant. A significant benefit in reducing any reported inflammatory markers was seen in the low EPA/DHA ratio subgroup at 63%, in the moderate at 29%, and in the high ratio subgroup at 11%. The greatest benefit in CRP reduction was obtained by patients during chemotherapy. The review questions the anticachectic and anti-inflammatory effect of ω-3 PUFAs supplementation with doses of EPA higher than DHA. A population that particularly benefits from ω-3 PUFAs supplementation are patients undergoing chemotherapy for advanced cancer.

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with β-hydroxy-β-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6–3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. −0.36 (0.4), and 2.98 (0.5) vs. −0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.

Esophageal squamous cell carcinoma (ESCC) significantly affects nutritional status. While neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stage II/III ESCC, its impact on nutritional status and postoperative outcomes remains unclear. This study investigated the relationship between nutritional deterioration during NAC and outcomes following esophagectomy. This single-center retrospective study included 85 patients with thoracic ESCC who received NAC followed by esophagectomy between January 2019 and December 2023. The NAC regimens included cisplatin plus 5-fluorouracil (CF), administered with or without radiation, and docetaxel, cisplatin, and fluorouracil (DCF). Nutritional status and postoperative outcomes were evaluated. Of the 85 patients, 20 received DCF, 36 received CF alone, and 29 received CF with radiation. Nutritional deterioration was noted during NAC with significant decreases in Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), and hemoglobin-albumin-lymphocyte-platelet (HALP) score. Grade 3-4 hematologic toxicities correlated with reductions in GNRI and increases in neutrophil-lymphocyte ratio (NLR) ( =0.004 and 0.020, respectively). An increase in NLR post-NAC and decrease in PNI post-NAC were associated with prolonged hospital stays ( =0.024 and 0.042, respectively). Post-NAC NLR of 2.3 or over and HALP score below 20 were significantly associated with poorer overall survival ( =0.012 and <0.001, respectively). Although NAC reduces tumor burden and eliminates micrometastases, it potentially worsens nutritional status. Chemotherapy-induced hematologic toxicities are a risk factor for this decline. Therefore, comprehensive nutritional assessment and timely intervention during NAC are essential to optimize patient outcomes.