Evidence-Based Medicine

Research Appraisals

Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.

Showing 26 appraisals

Systematic ReviewEvidence: Weak
15CEBM

Journal of advanced research

Machine learning for food flavor prediction and regulation: models, data integration, and future perspectives.

BACKGROUND: Flavor is a central attribute of food quality, shaping consumer preferences and market performance. Traditional evaluation methods, such as sensory panels and basic assays, are often constrained by subjectivity, low throughput, and limited scalability. With the rise of high-throughput technologies and multimodal datasets, machine learning (ML) has emerged as a promising tool for deciphering and regulating complex flavor systems. AIM OF REVIEW: This review examines current flavor detection techniques and the application of ML across diverse domains. It compares supervised learning models (SVM, DT), ensemble algorithms (XGBoost, LightGBM), and deep learning approaches (CNN, ANN). This review also discusses the contribution of three major data dimensions to flavor prediction, as well as future prospects in the field. ML enables precise flavor prediction, compound screening, and real-time process control. To support these tasks, researchers have developed integrated analytical systems that combine electronic nose (E-nose), electronic tongue (E-tongue), gas chromatography-mass spectrometry (GC-MS), and gas chromatography-ion mobility spectrometry (GC-IMS). Ensemble learning and deep learning models show strong performance when handling complex, nonlinear datasets. Explainable artificial intelligence (XAI) tools such as Shapley Additive Explanations (SHAP) improve model transparency by linking predictions to underlying features. ML models further enhance both prediction accuracy and generalizability. Innovations such as attention mechanisms, graph neural networks, and digital twins support dynamic flavor modulation. ML also aids in identifying key flavor compounds and genotype-phenotype relationships, accelerating breeding and formulation. KEY SCIENTIFIC CONCEPTS OF REVIEW: ML is opening up new technological avenues in flavor science, with significant potential to predict and control flavor formation mechanisms, verify product authenticity, and support the targeted design of flavor-active compounds that align with consumer expectations for sensory appeal.

2 July 2026

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Systematic ReviewEvidence: Moderate
65CEBM

Life sciences

Intermittent fasting and cardiometabolic responses under cardiac stress: a systematic review of preclinical studies

Intermittent fasting (IF) has emerged as a dietary strategy with benefits that extend beyond weight management and glycemic control. Although growing evidence supports its favorable effects on cardiometabolic health, the impact of IF under conditions of cardiac stress remains poorly characterized. Since clinical trials cannot ethically expose patients to acute cardiac stress during IF protocols, preclinical models are essential to elucidate its potential cardioprotective mechanisms. This systematic review aimed to synthesize the preclinical evidence on the effects of IF in models of cardiac stress. Following a registered protocol (PROSPERO:#CRD42023466215), we searched databases for preclinical studies evaluating IF under cardiac stress. Models included atherosclerosis induction, diet modulation, hypercholesterolemic mice, doxorubicin-induced cardiotoxicity, pulmonary arterial hypertension, myocardial infarction, ischemia-reperfusion injury, among others. All IF regimens, encompassing variations in timing, frequency, and type, were considered. Clinical trials, observational studies, reviews, meta-analyses, updates, guidelines were excluded. Thirty-two studies involving 451 predominantly male animals were included. Approximately 80% reported that IF improved cardiovascular outcomes, reducing blood pressure, cardiac hypertrophy, fibrosis, and ischemic injury while enhancing vascular and metabolic function. Mechanistically, IF protects the heart under stress by downregulating NF-κB, IL-1β, and TNF, and activating SIRT3 and AMPK pathways, improving mitochondrial function, lipid metabolism, and cardiac energy homeostasis. Cardioprotective benefits were dependent on fasting duration and regimen, emphasizing the importance of metabolic context. In conclusion, IF appears to enhance cardiovascular resilience under stress through multiple metabolic and molecular pathways. These findings support further clinical investigation of IF as a potential adjunct strategy for cardiometabolic protection under stress.

15 June 2026

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Systematic ReviewEvidence: Moderate
60CEBM

Current atherosclerosis reports

Comparative Efficacy of Nutraceuticals on Endothelial Function: A Systematic Review and Network Meta-Analysis

PURPOSE OF REVIEW: This network meta-analysis (NMA) compares the efficacy of dietary interventions in improving flow mediated dilation (FMD) as a measure of endothelial function among individuals with cardiovascular diseases (CVDs) and hypertension. This work can be a basis for the design of future clinical trials and for the development of evidence-based nutritional guidelines to improve cardiovascular outcomes. RECENT FINDINGS: The most substantial improvements in FMD were observed with magnesium (MD: 8.17; CoE: High), vitamin D3 (MD: 7.84; CoE: High), flaxseed (MD: 7.39; CoE: Low), barberry (MD: 6.64; CoE: Moderate), folic acid (MD: 3.36; CoE: Low), and omega-3 (MD: 1.83; CoE: Very low). Sensitivity analyses confirmed the robustness of these findings. Several dietary interventions, particularly magnesium and vitamin D₃, have been shown to improve endothelial function in individuals with CVDs and hypertension. These findings highlight the potential role of nutritional strategies as adjunct therapies for preserving vascular health. TRIAL REGISTRATION: Systematic review registered with PROSPERO, registration number CRD420251041093.

14 June 2026

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Systematic ReviewEvidence: Strong
85CEBM

Pediatric surgery international

Early vs. delayed feeding after pediatric gastrointestinal surgery: a systematic review and meta-analysis

BACKGROUND: The adoption of early feeding after pediatric gastrointestinal surgery remains inconsistent due to concerns regarding anastomotic safety. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted comparing early enteral feeding (initiation within 48 h) with delayed feeding in patients < 18 years undergoing intestinal anastomosis or stoma reversal. RESULTS: Eight trials comprising 704 patients (323 early feeding, 381 delayed) were included across neonatal and pediatric elective surgical populations. Early feeding significantly shortened hospital length of stay (mean difference - 3.53 days; 95% CI - 4.35 to - 2.71) and reduced time to full feeds (mean difference - 3.15 days; 95% CI - 3.89 to - 2.40). There was no significant difference in anastomotic leakage (log risk ratio - 0.36; 95% CI - 1.23 to 0.51; I²=0%) or postoperative vomiting (log risk ratio - 0.02; 95% CI - 0.41 to 0.38). Early feeding was also associated with fewer wound infections (log risk ratio - 0.85; 95% CI - 1.48 to - 0.22). CONCLUSIONS: Overall, early enteral feeding after pediatric gastrointestinal surgery appears safe and confers clinically meaningful benefits by accelerating nutritional recovery, reducing infectious complications, and shortening hospitalization, supporting its incorporation into pediatric postoperative care pathways.

13 June 2026

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Systematic ReviewEvidence: Moderate
60CEBM

PloS one

Probiotics, synbiotics and berberine in Type 2 diabetes mellitus: A systematic review, meta-analysis, and molecular dynamics simulation study

BACKGROUND: Type 2 diabetes mellitus is characterized by impaired regulation of blood glucose. Probiotics, synbiotics, and berberine (BBR) have been proposed as adjunctive interventions, but their overall effectiveness remains uncertain. OBJECTIVE: To evaluate the effects of these interventions on glycemic control and to explore a potential molecular interaction of BBR with a key carbohydrate-digesting enzyme. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted. Pooled effects were estimated for fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) using random-effects models. A subgroup analysis compared probiotics with placebo. An exploratory computational analysis examined the interaction of BBR with α-glucosidase. RESULTS: More than 30 trials involving over 2,000 participants were included. The pooled analysis showed significant but modest reductions in FPG (-0.71 mmol·L ⁻ ¹) and HbA1c (-0.19%), with substantial between-study variability. Probiotics alone also reduced FPG (approximately -0.80 mmol·L ⁻ ¹) and HbA1c (approximately -0.21%) compared with placebo. Computational analysis indicated weaker enzyme binding for BBR than for the reference inhibitor acarbose. CONCLUSIONS: Probiotics, synbiotics, and BBR provide statistically significant but clinically modest improvements in glycemic control. These findings support their use as adjunctive, rather than primary, therapeutic options and highlight the need for larger and longer trials with standardized interventions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251116387, identifier CRD420251116387.

30 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

European respiratory review : an official journal of the European Respiratory Society

Nutrition and growth of primary ciliary dyskinesia patients: a systematic review.

BACKGROUND: Growth, nutritional status and intake can be crucial for the management and prognosis of chronic lung diseases, including primary ciliary dyskinesia (PCD); yet research in PCD is scarce. In this study, we systematically reviewed the existing literature and summarised the evidence on growth, nutritional status and intake of patients with PCD. METHODS: We conducted searches in Medline, Embase, Scopus and PubMed limited to the past 20 years, due to changes in the diagnosis of PCD. Eligible studies included cross-sectional, case-control and prospective studies, and case series with >5 people that reported on the growth, nutritional status or intake of patients with PCD. We performed additional searches through reference list checking and in medRxiv for relevant preprints. The review was registered in PROSPERO (CRD420251065699). RESULTS: 50 studies were included in the qualitative synthesis. We observed variability in growth-related outcomes, with some studies reporting reduced z-score for height, body weight or BMI, while others reported no growth differences in patients with PCD. The prevalence of undernutrition ranged from 4 to 11%; underweight ranged from 0 to 50%. Overweight and obesity estimates ranged from 3 to 25%. The prevalence of vitamin D insufficiency was 54%, while deficiency was reported in 18-26% of study participants. Only three studies reported on the nutritional intake of patients with PCD. DISCUSSION: We observed considerable variability in growth-related outcomes and a lack of nutritional intake-related data in patients with PCD. The findings we noted related to malnutrition and vitamin D insufficiency/deficiency are alarming and warrant further investigation.

29 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

Acta oncologica (Stockholm, Sweden)

Change in skeletal muscle mass during systemic cancer treatment: a systematic review and meta-analysis

BACKGROUND AND PURPOSE: Loss of skeletal muscle mass (SMM) is common during systemic cancer treatment, but the magnitude and variability across cancer and treatment types remain uncertain. We aimed to describe changes in SMM during systemic cancer treatment supported by pooled quantitative estimates. PATIENTS/MATERIAL AND METHODS: We systematically searched PubMed, Embase, and Web of Science until April 2025 for longitudinal studies reporting SMM during chemotherapy and/or immunotherapy (± targeted therapy) in patients with cancer (PROSPERO CRD42022308388). Standardized mean changes (SMC) were pooled in random-effects meta-analyses using the restricted maximum-likelihood estimator with Hartung-Knapp adjustment. Heterogeneity was assessed using I². Risk of bias was assessed with the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Seventy-eight studies (n = 10,502; 52% male; median age 64 years [interquartile range, IQR: 34-77]) were included. Meta-analysis across cancers showed an association between systemic cancer treatment and decline in SMM (59 studies; n = 6,373; SMC = -0.24, 95% confidence interval [CI]: -0.29 to -0.20; I² = 92%), corresponding to -5% over a median interval of 90 (IQR: 71-129) days among studies (62%) reporting assessment intervals. Declines were most pronounced during chemotherapy (± targeted therapy). INTERPRETATION: Declines in SMM are frequently observed during systemic cancer treatment, particularly during chemotherapy (± targeted therapy), although effect sizes were generally small per Cohen's thresholds. However, substantial heterogeneity limits interpretation of a single pooled estimate. Prospective studies with standardized methods are needed to clarify trajectories, mechanisms and clinical implications of SMM loss.

28 May 2026

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observationalEvidence: Weak
55CEBM

Otolaryngologia polska = The Polish otolaryngology

Leveraging large language models to audit perioperative total laryngectomy care: anesthetic, nutritional, and complication profiles in a real‑world cohort

&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Total laryngectomy (TL) remains the standard treatment for advanced la‑ ryngeal cancer, and its perioperative management requires close collaboration within a multidisciplinary team, including anaesthesiologists and clinical nutritionists.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim:&lt;/strong&gt; The aim of this study was to analyse the perioperative course of patients un‑ dergoing TL from both an anaesthesiologist's and a nutritionist's perspective, with a particular focus on the feasibility and performance of structured data extraction from electronic medical records using large language models (LLMs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods:&lt;/strong&gt; We performed a single‑centre retrospective analysis of 43 consecutive patients undergoing TL (ICD‑9 codes 30.32, 30.39, 30.41, 30.49) be‑ tween January 2024 and April 2026. Clinical data, including physician notes (n = 845), nursing notes (n = 2578), discharge summaries (n = 173), and consultations (n = 123), were subjected to structured extraction using large language models (gemma-3-31Bit/gemma-4-26B-it). Demographics, tumour stage, length of stay (LOS), periopera‑ tive nutrition, pharmacotherapy, postoperative complications, temporal laboratory trends, and rehabilitation were analysed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The cohort comprised 35 men (81%) and 8 women (19%), with a mean age of 66.4 9.8 years; pT4a (49%) and pN0 (82%) predominated. Median LOS was 15.0 days (IQR 13.1-16.5). Enteral nutrition via nasogastric tube was used in 95% of patients, and oral intake was initiated at a median of postoperative day 13. Multimodal anal‑ gesia based on intravenous paracetamol (60%), ketoprofen (47%), and metamizole (40%) was routinely employed, while strong opioids were used in only 5% of pa‑ tients. Postoperative complications occurred in 22.5% of cases, with pharyngocuta‑ neous fistula (PCF) being the most frequent (12.5%). In‑hospital mortality was 0%, and overall mortality during a median 12‑month follow‑up was 2.3%. CRP peaked on postoperative day 3 (mean 114 mg/L). Pharmacologic VTE prophylaxis was admi‑ nistered in 65% of patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; In TL patients, enteral feeding forms the backbone of nutritional sup‑port, and multimodal analgesia provides effective pain control, whereas VTE pro‑phylaxis and other modifiable elements of perioperative care warrant optimization within prehabilitation and ERAS-based protocols.&lt;/p&gt;&lt;p&gt;&amp;nbsp;&lt;/p&gt.

26 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

European journal of pediatrics

Gut microbiota-modulating interventions in paediatric type 1 diabetes: a systematic review and meta-analysis

To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and CENTRAL were searched from inception to 28 February 2026 for randomised controlled trials of oral probiotics, prebiotics, or synbiotics in participants aged ≤ 19 years with type 1 diabetes. Primary outcomes were glycated haemoglobin, fasting blood glucose, total daily insulin dose, and C-peptide. Immune-inflammatory, microbiota-related, intestinal permeability, and safety outcomes were narratively synthesised. Twelve randomised controlled trials involving 808 paediatric participants were included. Interventions varied in formulation, dose, and duration. Pooled analyses showed significant reductions in glycated haemoglobin and fasting blood glucose, whereas no significant effects were found for total daily insulin dose or C-peptide. Immune-inflammatory, microbiota-related, and intestinal permeability outcomes suggested possible benefits, but reporting was inconsistent and quantitative pooling was not feasible. Overall, the evidence was limited by substantial clinical and methodological heterogeneity. Conclusion: Gut microbiota-modulating interventions may improve glycaemic control in children and adolescents with type 1 diabetes, particularly glycated haemoglobin and fasting blood glucose. However, current evidence is insufficient to support any specific formulation, dose, or duration, and larger well-designed paediatric trials are still needed. What is Known: • Gut microbiota-modulating interventions are biologically plausible adjunctive strategies in paediatric type 1 diabetes. • Earlier paediatric reviews included few randomised trials and reported inconsistent glycaemic findings. What is New: • This updated review included 12 randomised controlled trials involving 808 children and adolescents. • It adds a structured synthesis of immune-inflammatory, microbiota/barrier, metabolite-related and safety outcomes beyond glycaemic endpoints.

26 May 2026

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Randomised Controlled TrialEvidence: Moderate
75CEBM

Journal of ethnopharmacology

Efficacy and safety of medicine-food homology Shenqi paste in older adults with diabetic sarcopenia: A randomized, double-blind, placebo-controlled trial

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic sarcopenia (DS), an emerging diabetes complication, poses an increasing challenge to the elderly population. Shenqi paste (SQP) consists of 8 medicine-food homology substances: Astragalus membranaceus (Fisch.) Bge., Codonopsis pilosula (Franch.) Nannf., Polygonatum sibiricum Red., Dioscorea opposita Thunb., Poria cocos (Schw.) Wolf, Eucommia ulmoides Oliv., Hordeum vulgare L., and Ophiopogon japonicus (L.f.) Ker Gawl. SQP has shown potential benefits for sarcopenia in clinical practice. Its efficacy and safety in DS have not been validated in a randomized controlled trial. AIM OF THE STUDY: This study aimed to evaluate the efficacy, safety, and limitations, and provide insights into methods and strategies for utilizing SQP in DS management. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, community-dwelling older adults (≥60 years) with DS and spleen-kidney deficiency syndrome were allocated 1:1 to receive either SQP or placebo paste for 12 weeks. Primary outcomes were skeletal muscle mass index (SMI), handgrip strength, and five-time chair stand test (FCST) duration. Secondary outcomes included health-related scales and biochemical indicators. Assessments were conducted at the baseline (T0), week 6 (T1), and week 12 (T2). Safety evaluation included blood routine, liver and kidney function tests. Intention-to-treat analysis was applied to the primary outcomes data from all participants, with per-protocol analysis for sensitivity. Generalized estimating equations with covariate adjustment and t-tests or Wilcoxon rank-sum tests were used for statistical analysis. RESULTS: Of 90 randomized participants, the SQP group showed greater improvements in handgrip strength (T2: interact p < 0.001), SMI (T2: interact p < 0.001), and FCST (T2: interact p < 0.001) versus control. Secondary outcome measures of 74 participants, including frailty, nutrition, physical activity, sleep quality, depression, and TCM syndrome scores, significantly improved (p < 0.05), with significant fasting blood glucose reduction (T2: interact p = 0.018) and C-reactive protein decrease (T2: interact p < 0.001). There was no statistically significant difference in the change in the difference between the two groups in fasting insulin, glycated hemoglobin and insulin resistance index before and after intervention (p > 0.05). Within-group analysis demonstrated significant reductions of SQP group in inflammatory cytokines, and sarcopenia-related biomarkers (p < 0.001) post-intervention. No serious adverse events occurred. CONCLUSION: A 12-week SQP intervention enhanced muscle mass, strength, function, and metabolic and inflammatory profiles in older adults with DS, with good tolerability, supporting its potential as a safe, complementary therapy.

23 May 2026

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Randomised Controlled TrialEvidence: Moderate
75CEBM

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Nutritional prehabilitation in patients with head and neck cancer: an evidence mapping analysis

BACKGROUND: Head and neck cancer patients are often at high risk of malnutrition due to the disease and its treatment, and pretreatment nutritional prehabilitation is an important strategy for improving prognosis; however, the existing evidence still needs to be systematically synthesized. PURPOSE: To systematically describe and evaluate the evidence related to pretreatment nutritional prehabilitation in patients with head and neck cancer through evidence mapping to provide a basis for clinical practice. METHODS: Computerized searches of CNKI, Wan-fang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, Embase, and CINAHL were performed from the time of database construction to May 2025, to include systematic review/meta-analysis of nutritional prehabilitation of patients with head and neck cancer, randomized controlled trials, and observational studies. The Risk of Bias Tool, Newcastle-Ottawa Scale (NOS), and AMSTAR-2 scale were used to evaluate the methodological quality of the included studies, respectively, and the current status of the studies was demonstrated using a combination of text and graphs. RESULT: Then, 6 systematic evaluations/meta-analyses, 13 randomized controlled trials, and 4 observational studies were finally included. The largest number of studies was published in China, and all study populations consisted exclusively of patients with head and neck cancer. Interventions include pretreatment immunonutritional interventions, nutritional risk screening-guided interventions, standard enteral nutritional support, disease-specific nutritional formula support, nutritional counseling, and pretreatment swallow training. The outcome indicators mainly focused on the patients' nutritional status, complication rates, length of hospital stay, body weight, and BMI, etc. However, the methodological quality of the included studies needs to be improved. The results of the studies all showed that nutritional prehabilitation benefits the prognosis of patients with head and neck cancer. CONCLUSION: Overall evidence suggests that nutritional prehabilitation can improve patients' nutritional status and enhance their prognosis and quality of life, showing beneficial effects. More high-quality, large-sample clinical studies should be conducted in the future to guide the clinical implementation of nutritional prehabilitation.

21 May 2026

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Systematic ReviewEvidence: Strong
100CEBM

Journal of the American Heart Association

Effect of Different Types of Whole Dietary Pulses on Established Therapeutic Lipid Targets for Cardiovascular Risk Reduction: An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Although dietary pulses are recognized by major clinical practice guidelines to reduce cholesterol and coronary heart disease risk, intake is low. There are no health claims for any pulse for cholesterol reduction, which could support uptake. We therefore conducted a systematic review and dose-response meta-analysis of randomized trials of the effect of different types of whole dietary pulses on lipid targets. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2025 for trials ≥3 weeks. The primary outcome was low-density lipoprotein-cholesterol. Secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Thirty-eight trials (52 trial comparisons, n=2095) with a median of 6 weeks and dose of 130 g/d (0.5-0.67 cup/d) showed that whole dietary pulses decreased low-density lipoprotein-cholesterol (mean difference, -0.14 mmol/L [95% CI, -0.19 to -0.08]), non-high-density lipoprotein-cholesterol (-0.22 mmol/L [95% CI, -0.30 to -0.14]), apoB (apolipoprotein B) (-0.08 g/L [95% CI, -0.13 to -0.03]) and high-density lipoprotein-cholesterol (-0.03 mmol/L [95% CI, -0.05 to -0.01]) with no effects on other lipids. Analyses by pulse type showed similar results. A linear inverse relationship was shown for beans up to 1 cup/d for low-density lipoprotein-cholesterol (coefficient, -0.25 mmol/L/0.5 cup [95% CI, -0.48 to -0.02]) and non-high-density lipoprotein-cholesterol (-0.45 mmol/L/0.5 cup [95% CI, -0.71 to -0.18]). Grading of Recommendations Assessment, Development, and Evaluation was moderate-to-high for all outcomes, except apoB (very low). CONCLUSIONS: Whole dietary pulses likely result in small important-to-moderate reductions in lipid targets and trivial reductions in high-density lipoprotein-cholesterol. Similar effects were observed across pulse types with an inverse dose-response gradient for beans up to 1 cup/d. Future studies on chickpeas, dried peas, and lentils are warranted. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023432826; Unique identifier: CRD42023432826.

20 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

Journal of global health

Folate and global health review series, part 3: syntheses on cardiovascular, cerebrovascular, and metabolic diseases.

BACKGROUND: Cardiovascular and metabolic diseases account for an increasing share of morbidity and mortality globally. Folic acid supplementation has been linked to a lowered risk of stroke and some metabolic indicators due to its involvement in homocysteine and one-carbon metabolism and its role in the production of nitric oxide; however, the evidence on these associations is inconclusive. METHODS: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects from inception to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (dietary intake, supplementation, or blood concentrations) with any cardiometabolic outcome. We performed screening, data abstraction, and risk of bias assessment in duplicate, and assessed the credibility of the evidence using predefined criteria. RESULTS: We identified 113 unique associations from 49 reviews. The included syntheses mostly had low risk of bias of and provided pooled risk estimates from intervention trials or prospective cohorts. A larger volume of evidence was available for composite cardiovascular outcomes, coronary heart disease, and stroke compared to other outcomes. No association reached a convincing or highly suggestive level of credibility. Six directional associations and five null associations met the criteria for a suggestive level of credibility. Three dose-response relationships, all at suggestive levels of credibility, supported an association between higher dietary folate intake and a reduced risk of coronary heart disease and stroke. CONCLUSION: The available evidence on the association between folate status and cardiometabolic outcomes primarily focuses on secondary prevention of cardiometabolic diseases and substantially underrepresents low- and middle-income countries. More large-scale studies are warranted to validate a relationship between folate status and cardiometabolic events or indicators. Overall, the evidence landscape around folate and cardiometabolic diseases appears to be limited both in volume and scope. REGISTRATION: PROSPERO: CRD42021265041.

12 May 2026

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Systematic ReviewEvidence: Moderate
70CEBM

Journal of burn care & research : official publication of the American Burn Association

Metabolic and Immunomodulatory Effects of α-Ketoglutarate in Burn Injuries: A Systematic Review

Severe burns unleash a hyper-catabolic and immunosuppressive state that erodes lean tissue and delays repair. Alpha-ketoglutarate (α-KG), usually delivered enterally as the dipeptide ornithine α-ketoglutarate (OKG), feeds the tricarboxylic-acid cycle, donates nitrogen for amino-acid synthesis, and modulates collagen formation and immunity. We systematically appraised the biological mechanisms, delivery strategies, and clinical outcomes associated with α-KG/OKG in burn care to clarify its therapeutic value and translational readiness. A PRISMA-2020-compliant search of PubMed, EMBASE, Web of Science, Cochrane, and Google Scholar up to May 2025 identified clinical, in vivo, and relevant in vitro studies linking α-KG or OKG with thermal injury. Study quality was assessed using the Newcastle-Ottawa Scale, SYRCLE Risk-of-Bias tool, and Oxford Levels of Evidence. Fifteen studies published between 1984 and 2024 met inclusion criteria, including clinical, animal, and mechanistic work, most conducted in France. Across studies, OKG supplementation replenished glutamine and arginine pools, improved nitrogen balance, preserved muscle mass, and promoted wound healing through enhanced collagen synthesis and immune modulation. Clinical data confirmed improved nitrogen retention, reduced muscle breakdown, and faster wound closure. Preclinical studies further showed that α-KG preconditioning enhances stem cell-driven regeneration and vascularization. Additional effects, such as improved glucose tolerance and hepatic enzyme preservation, suggest some benefits occur independently of glutamine pathways. This review highlights α-KG and OKG as promising adjuncts to enhance metabolic recovery, wound repair, and immune competence after burns. Evidence supports improved nitrogen balance and healing, but findings remain limited by heterogeneity and small cohorts, warranting renewed and well-powered studies.

11 May 2026

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otherEvidence: Moderate
80CEBM

The Proceedings of the Nutrition Society

Good practices and common pitfalls of machine learning in nutrition research

Machine learning is increasingly being utilised across various domains of nutrition research due to its ability to analyse complex data, especially as large datasets become more readily available. However, at times, this enthusiasm has led to the adoption of machine learning techniques prior to a proper understanding of how they should be applied, leading to non-robust study designs and results of questionable validity. To ensure that research standards do not suffer, key machine learning concepts must be understood by the research community. The aim of this review is to facilitate a better understanding of machine learning in research by outlining good practices and common pitfalls in each of the steps in the machine learning process. Key themes include the importance of generating high-quality data, employing robust validation techniques, quantifying the stability of results, accurately interpreting machine learning outputs, adequately describing methodologies, and ensuring transparency when reporting findings. Achieving this aim will facilitate the implementation of robust machine learning methodologies, which will reduce false findings and make research more reliable, as well as enable researchers to critically evaluate and better interpret the findings of others using machine learning in their work.

4 May 2026

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Systematic ReviewEvidence: Moderate
60CEBM

Journal of the International Society of Sports Nutrition

Effects of nutritional interventions on competitive performance and dose‒response relationships among esports players of different skill levels: a systematic review and three-level meta-analysis

BACKGROUND AND OBJECTIVES: Esports place exceptional demands on neuropsychological capacities; however, a systematic and quantitative synthesis of the specific efficacy of nutritional interventions across various tasks and competitive populations remains absent. This study aims to evaluate the impact of nutritional supplementation on cognitive function and competitive performance in esports players and to explore key moderating variables. METHODS: Electronic databases, including Web of Science, PubMed, and Scopus, were searched (up to January 25, 2026). Thirteen randomized controlled trials (RCTs) met the inclusion criteria. A three-level random-effects model was employed to calculate the pooled effect size (Hedges' g), with sources of heterogeneity explored through subgroup analyses and meta-regression. RESULTS: Nutritional interventions significantly enhanced esports-related performance (g = 0.92), with the most pronounced benefits observed in processing speed (g = 1.18) and executive function (g = 1.06). Subgroup analyses revealed significant gains in both professional (g = 0.97) and amateur groups (g = 0.92), while the improvement in first-person shooter (FPS) games (g = 0.96) appeared to surpass that in multiplayer online battle athlete (MOBA) games. Meta-regression indicated no significant linear correlation between caffeine dosage and effect size. GRADE assessment categorized the quality of evidence mostly as "low" to "moderate." CONCLUSIONS: Nutritional interventions demonstrate significant potential for optimizing multidimensional cognitive performance in esports players, particularly in enhancing fundamental reaction speed and high-level decision-making processes. While the findings exhibit a degree of robustness, their practical application should be cautiously evaluated within specific competitive contexts due to current limitations in evidence certainty and significant interstudy heterogeneity. Future research characterized by gender balance and mechanistic orientation with long-term intervention protocols is warranted to elevate the level of clinical evidence.

27 Apr 2026

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otherEvidence: Weak
35CEBM

Nutricion hospitalaria

Refeeding syndrome ‒ What we know and what remains to be explored.

Background: refeeding syndrome (RS) is a serious metabolic complication that occurs upon reintroducing nutrition to malnourished individuals. Although formally recognized for more than 70 years, significant gaps in its understanding remain. Objective: to conduct a narrative review on the current state of knowledge regarding RS, its recent advances, existing gaps, and future perspectives. Methods: an integrative review was conducted using articles published between 2000 and 2024 from international databases, following a systematic methodology of literature search, selection, and analysis. Results: the main pathophysiological mechanisms of RS, its multisystemic clinical manifestations, current diagnostic criteria, and risk-based therapeutic strategies were identified. Despite advances in biomarkers and personalized nutrition, challenges remain in early diagnosis, prevention, and treatment, especially in vulnerable populations. Conclusions: RS continues to pose a complex clinical challenge that requires standardized protocols, identification of reliable biomarkers, and increased clinical research, particularly in underrepresented regions such as Latin America. Prevention, based on a multidisciplinary approach, is important to reducing its impact. Introducción: el síndrome de realimentación (SR) es una complicación metabólica grave que ocurre tras reintroducir la nutrición en personas desnutridas. Aunque formalmente reconocido desde hace más de 70 años, aún existen importantes lagunas en su comprensión. Objetivo: realizar una revisión narrativa sobre el estado actual del conocimiento del SR, sus avances recientes, las brechas existentes y las perspectivas futuras. Métodos: se realizó una revisión integrativa de artículos publicados entre 2000 y 2024 en bases de datos internacionales, siguiendo una metodología sistemática de búsqueda, selección y análisis de la literatura. Resultados: se identificaron los principales mecanismos fisiopatológicos del SR, sus manifestaciones clínicas multisistémicas, los criterios diagnósticos actuales y las estrategias terapéuticas basadas en el riesgo. A pesar de los avances en términos de biomarcadores y nutrición personalizada, persisten desafíos en el diagnóstico precoz, la prevención y el tratamiento, especialmente en las poblaciones vulnerables. Conclusiones: el SR sigue siendo un reto clínico complejo que exige protocolos estandarizados, identificación de biomarcadores fiables y una mayor investigación clínica, especialmente en regiones poco estudiadas como América Latina. La prevención basada en un enfoque multidisciplinario es clave para reducir su impacto.

25 Apr 2026

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Randomised Controlled TrialEvidence: Weak
60CEBM

European journal of pediatrics

Different doses of vitamin A supplementation as adjuvant treatment for pneumonia in children: a network meta-analysis of randomized controlled trials

UNLABELLED: While previous meta-analyses have established a link between vitamin A supplementation and outcomes in children with pneumonia, the efficacy and safety of different dosing regimens remain unclear. Existing evidence is predominantly based on single-dose trials, creating a critical knowledge gap. We systematically searched PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and VIP databases from their inception to December 2025. Study searches were independently carried out in December 2025 by two reviewers. Two researchers used the Cochrane risk of bias tool to independently assess the quality of the included studies. Data analysis was conducted through the "netmeta" package in R software (version 4.3.3). Twenty-five trials involving 3116 patients were included. Network meta-analysis revealed that medium-dose vitamin A supplementation was most effective in reducing the duration of fever and cough. Low-to-medium doses were consistently associated with better clinical outcomes than high-dose regimens. However, evidence regarding safety outcomes remained limited and inconclusive. CONCLUSION: Low-to-medium dose vitamin A supplementation appears superior to high-dose regimens for alleviating clinical symptoms in children with pneumonia. However, the evidence is limited by high heterogeneity, indirect comparisons between dose groups, and poor reporting of adverse events. Future trials should prioritize direct dose-comparisons and rigorous safety monitoring to refine dosing guidelines. WHAT IS KNOWN: • Pneumonia poses a significant threat to the health and lives of children. Vitamin A supplementation plays an adjuvant role in the treatment of pneumonia in children. • There are currently divergent conclusions in the research regarding the optimal dosage of vitamin A, particularly with regard to the safety of high-dose supplementation and the effectiveness of low-dose supplementation. WHAT IS NEW: • This study revealed that medium-to-low-dose vitamin A supplementation appears to be more effective than high-dose therapy in alleviating the primary symptoms of childhood pneumonia. • This study also suggests that children in developed regions have higher baseline serum retinol levels, which may diminish the marginal benefits of high-dose supplementation and may even predispose them to its immunosuppressive effects.

22 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
80CEBM

Journal of gastrointestinal cancer

Effect of Probiotics on the Clinical Outcome and Inflammatory Response in Gastric Cancer Surgery: A Double Blinded Randomized Control Trial

BACKGROUND AND AIM: Gut dysbiosis contributes to postoperative complications and worsens the inflammatory and immune dysfunction in gastric cancer (GC) patients. Probiotics may mitigate these effects by modulating gut microbiota. This study aimed to evaluate the effect of probiotics on the length of hospital stay, other post-operative clinical outcomes, nutritional status, inflammatory and immune markers in patients undergoing gastrectomy for gastric cancer. METHODS: This was a single-centred, prospective, double blinded, placebo-controlled trial. Participants were patients who underwent open gastrectomy for gastric cancer. Participants were randomized to receive probiotics or placebo for 10 days starting on postoperative day (POD) 1. Blood samples were collected preoperatively and POD 10 to assess haemoglobin, total counts, albumin, IL6, TNFα, and IgA. Clinical outcomes including time to first flatus, first passage of stools, oral diet resumption and length of hospital stay (LOHS). Postoperative complications were monitored for 30 days and classified using the Clavien-Dindo system. RESULTS: Of 42 participants (22 probiotic, 20 placebo), baseline characteristics were comparable. The probiotic group had a significantly shorter median LOHS (9 vs. 12 days, p<0.05), earlier time to first passage of flatus (2.6 vs. 4.3 days, p<0.05), earlier time to first passage of stools (3.6 vs. 5.7 days, p<0.05), and oral diet resumption (3.6 vs. 5.7 days, p<0.05). No significant differences were observed in inflammatory markers (TLC, IL-6, TNF-α), immune markers (IgA), nutritional status (albumin, haemoglobin), or postoperative complications (p>0.05). CONCLUSION: Postoperative probiotic supplementation reduced LOHS and improved gastrointestinal recovery in GC patients undergoing gastrectomy, but did not significantly affect inflammatory, immune, or nutritional markers.

20 Apr 2026

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Systematic ReviewEvidence: Moderate
75CEBM

Human fertility (Cambridge, England)

The global evaluation of the effects of antioxidants on seminal outcomes in infertile men: a systematic review and meta-analysis

The aim of the current review is to summarise information from publications on the impact of antioxidants on seminal outcomes in infertile men. A systematic search was performed in the five valid databases (Scopus, PubMed, Medline, Embase, and Web of Science) utilizing two sets of keywords up to September 2025, according to the PRISMA approach. Of the 11749 papers identified, 101 papers were included in this review, for a total of 11889 infertile men. Sperm concentration, normal sperm morphology, progressive sperm motility, and total sperm motility, were considerably higher in experimental groups compared with control groups. Both sperm concentration (106 mL-1) and total motility (%) were higher in experimental groups compared to control groups with an overall pooled standardised mean difference (SMD) of 2.33 (95% CI: 1.73, 2.94) for sperm concentration and SMD of 1.62 (95% CI: 1.20, 2.04) for total motility (%). Subgroup analysis demonstrated that duration of treatments of more than 6 months were more effective than those of less than 3 months. Based on the findings of this review, no definitive recommendation can be made regarding the use of antioxidants as a therapy for male infertility, and further research is necessary.

16 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
65CEBM

Journal of affective disorders

The effects of Omega-3 supplementation on stress, anxiety, depression, sleep quality, and everyday memory in individuals with psychological distress: A randomized, double-blind, placebo-controlled trial

BACKGROUND/OBJECTIVES: Psychological stress, anxiety, depression, memory impairment, and poor sleep quality are prevalent issues that affect individuals' quality of life and overall health. Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested to have mood-regulating effects. However, there is lack of data on the effect of omega-3 supplementation on depression, stress, anxiety, everyday memory, and sleep quality on Saudi population. Therefore, this study aimed to evaluate the impact of omega-3 supplementation on stress, anxiety, depression, everyday memory, and sleep quality in individuals with severe psychological distress. METHODS: A randomized, double-blind, placebo-controlled trial was conducted involving 64 participants with high levels of stress, anxiety, depression, memory issues and with poor quality of sleep with 32 allocated to the intervention group and 32 to the control group. The participants received either omega-3 supplementation (500 mg EPA + 250 mg DHA) or a placebo daily for three months. Pre- and post-intervention assessments were conducted using validated scales, including the Perceived Stress Scale (PSS), Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Everyday Memory Questionnaire (EMQ). RESULTS: Significant improvements were observed in the intervention group regarding stress, anxiety, depression, sleep quality, and memory outcomes (p < 0.001 for PSS, GAD-7, PHQ-9, PSQI, and EMQ). Between-group comparisons showed statistically significant reductions in post-intervention scores for the intervention group versus the control group. Regression analysis revealed strong predictive relationships between pre- and post-scores, particularly for stress and depression. CONCLUSIONS: Omega-3 supplementation resulted in notable psychological and cognitive improvements, suggesting its potential as a safe and effective adjunct for managing stress, mood disorders, and sleep disturbances among participants with psychological distress. Further research should explore how individual responses are influenced by baseline inflammation and omega-3 status. CLINICALTRIALS: gov: NCT07157241.

16 Apr 2026

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otherEvidence: Weak
70CEBM

Scientific reports

Effect of glucose on medium chain triglyceride induced ketosis in healthy adults in a randomized, double-blind, controlled study

Although medium-chain triglycerides (MCT) stimulate and carbohydrates inhibit ketone body synthesis, their quantitative interaction in humans is not well defined. This randomised, controlled, double-blind crossover study investigated how increasing glucose doses affects C8-MCT-induced ketone body synthesis after overnight fasting. Eleven healthy young woman (22.5 ± 1.9 years) received a constant dose of tricaprylin (99% C8; 0.2 g/kg bodyweight) combined with increasing glucose doses (0.2-0.6 g/kg bodyweight). In additional interventions, both C8-MCT and glucose were increased in parallel. Plasma β-hydroxybutyrate (βHB), glucose, and insulin were measured for up to 300 min post-dose. Indirect calorimetry in a subset and side effects were monitored. C8-MCT significantly increased βHB concentrations at low and medium glucose doses compared with control, but not at highest glucose dose. When both substrates were increased equally (1:1 ratio), ketone body synthesis increased. βHB was negative correlated with increasing glucose dosing at constant C8-MCT dosing, while parallel increases in both substrates showed a positive moderate correlation between βHB and C8-MCT doses. No dose-dependent side effects occurred. Overall, ketone body synthesis declines with rising glucose intake. It remains unclear whether a C8-MCT: glucose ratio of 1:3 represents a metabolic cut-off or whether glucose intake becomes excessive due to linear effects.Trial registration This study was prospectively registered in the German Clinical Trials Register (DRKS ID DRKS00035373 https//www.bfarm.de/EN/BfArM/Tasks/GermanClinicalTrialsRegister/_node.html ).

12 Apr 2026

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Systematic ReviewEvidence: Moderate
65CEBM

Psychological medicine

Interventions to prevent antipsychotic-induced weight gain and metabolic complications in individuals with a first-episode psychosis and minimal antipsychotic exposure: a systematic review and meta-analysis

BACKGROUND: Rapid weight gain commonly occurs following the onset of first-episode psychosis (FEP), leading to cardiometabolic disease. Most weight gain in FEP occurs in the first 3 months of treatment, offering a critical window for prevention. Despite this, most studies aiming to prevent antipsychotic-induced weight gain include people with chronic illness or people who have had lengthy exposure to antipsychotic medication. We aimed to synthesize and analyze the literature on interventions aimed at preventing antipsychotic-induced weight gain. METHODS: We conducted a systematic review in PsycInfo, MEDLINE, CINAHL, and EMBASE of studies that examined the effectiveness of interventions in preventing antipsychotic-induced weight gain in FEP. We examined their effect on weight gain and a range of cardiometabolic markers. RESULTS: We screened 2,092 articles, 13 of which were eligible. Behavioral interventions, all three of which consisted of a multidisciplinary team approach, resulted in a mean of 3.05 kg less weight gain than treatment-as-usual (95% CI 1.36 kg to 4.73 kg). Pharmacological interventions displayed marked clinical and statistical heterogeneity, with each of the seven trials in adults using a different pharmacological intervention. Few studies collected comprehensive data on metabolic health. Only two pharmacological studies, and five studies in total, have been published since 2010. CONCLUSIONS: Despite the importance of preventing weight gain in FEP, there have been few recent studies investigating this topic. Our results indicate that multidisciplinary team interventions are effective in preventing weight gain in FEP and should be offered to all patients.

11 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
70CEBM

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

A trifold prehabilitation model prior to induction chemotherapy in patients with leukemia: a randomized controlled trial

PURPOSE: A trifold prehabilitation program that integrates exercise, nutritional support, and psychological care has not yet been incorporated into routine care for leukemia patients prior to induction chemotherapy. This study aimed to evaluate the safety and feasibility of this trifold intervention and to further examine its potential impact on physical fitness, nutritional risk, and psychological health. METHODS: In a single-blind, parallel-group randomized trial, 86 newly diagnosed leukemia patients at a tertiary hospital in China were randomly assigned to a 12-week prehabilitation group (n = 43) or usual care (n = 43). Primary outcomes were recruitment, attrition, and safety. Secondary outcomes included the 6-min walk test (6MWT), exercise self-efficacy, cancer-related fatigue (CRF), anxiety, depression, and nutrition. Assessments occurred at baseline (T0), pre-chemotherapy (T1), and 1 (T2) and 3 months (T3) post-chemotherapy. RESULTS: The recruitment rate was 60.14%, with an attrition rate of 20.93%, and no serious adverse events occurred. Compared with controls, the intervention group showed significantly greater improvements in 6-min walk distance and cancer-related fatigue from T1 to T3 (all p < 0.05). Improvements in exercise self-efficacy were significant at T2 and T3 but not at T1. Nutritional status improved at T3 (p = 0.033). Anxiety and depression levels were consistently lower across all follow-up points (p < 0.01). CONCLUSIONS: This study demonstrates that prehabilitation is safe, feasible, and potentially beneficial for physical, nutritional, and psychological outcomes in leukemia patients. TRIAL REGISTRATION: China Clinical Trials Registration Platform: ChiCTR2500105061, date of registration: June 27, 2025 (retrospectively registered).

10 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
60CEBM

Gut

High versus gradually increasing energy nutrition in the early phase of acute pancreatitis (GOULASH): a multicentre double-blind randomised clinical trial

BACKGROUND: Acute pancreatitis (AP) is among the most common gastrointestinal diseases requiring hospitalisation, often with severe outcomes and no disease-specific therapy. Nutritional support has been proven to improve outcome, but little is known regarding optimal timing and composition. OBJECTIVE: This clinical trial aimed to compare high (30 kcal/kg/day, high energy (HE)) versus gradually increasing energy (0 increased to 30 kcal/kg/day over 4 days, low energy (LE)) strategies for enteral nutritional support in AP. DESIGN: This was a multicentric, double-blind, randomised clinical trial, enrolling patients with AP regardless of predicted severity (January 2017 to April 2023). The primary outcome was a combination of mortality and severe acute pancreatitis (Revised Atlanta Criteria); secondary outcomes included severity, rate of infection, organ failure and pain relapse. Interim analysis was planned after 50% enrolment. The Benjamini-Hochberg false discovery rate (FDR) method was used to correct p value for multiple testing. RESULTS: The trial was stopped early after enrolling 636 patients. Interim analysis showed that the primary outcome showed no difference between groups in the modified intention-to-treat (mITT) population (HE: 28/312, 9.0% vs LE: 18/307, 5.7%, p(uncorrected/corrected)=0.19/0.42). Secondary outcomes showed no difference in the mITT analysis. Without correction for multiplicity testing, results favoured a low gradual energy strategy in terms of organ failure (HE: 52/312, 16.7% vs LE: 28/307, 9.1%, p(uncorrected)=0.007) and pain relapse (80/312, 27.1% vs 54/307, 19.0% p(uncorrected)=0.03) but showed no differences between groups after correction for multiple testing (p=0.13 and p=0.23, respectively). It was determined that the superiority of the intervention would not be shown even with an increased sample size, and thus the trial was terminated based on a post hoc decision on ethics and futility. CONCLUSION: Based on this early terminated trial, a high-energy strategy for early nutrition in pancreatitis does not decrease mortality/severity, but potentially increases organ failure and pain relapse rate. TRIAL REGISTRATION NUMBER: ISRCTN63827758.

8 Apr 2026

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otherEvidence: Moderate
60CEBM

Clinical nutrition ESPEN

Artificial intelligence in clinical nutrition. A narrative review.

The rapid integration of Artificial Intelligence (AI) into healthcare, particularly clinical nutrition, holds transformative potential for enhanced diagnostics, risk prediction, and personalized therapeutic support. However, many clinicians lack sufficient understanding of AI principles, capabilities, and limitations, which may hinder adoption, lead to inappropriate use, or result in missed opportunities to enhance patient care. This narrative review aims to provide an accessible overview of foundational AI concepts, such as machine learning, deep learning, and large language models, and their practical applications in clinical nutrition. While AI offers immense promise in advancing nutritional care, its successful implementation requires clinicians to be adequately prepared to engage with these technologies. Education programs tailored to healthcare professionals, interdisciplinary collaboration between AI experts and clinicians, and robust ethical oversight are critical to ensure responsible and effective integration. By equipping clinicians with the necessary knowledge and tools, AI can serve as a powerful ally in delivering personalized and patient-centered nutritional care while maintaining human expertise at the forefront of decision-making.

2 Apr 2026

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