Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 7 appraisals
The Journal of clinical endocrinology and metabolism
The effects of glucose-dependent insulinotropic polypeptide on net splanchnic blood flow in lean humans.
CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with potent vasoactive and metabolic effects in adipose tissue, but its effects on splanchnic blood flow (SBF) in humans remain unclear. Investigating potential regional differences is important for understanding the vascular actions of GIP in humans. OBJECTIVE: The aim of this study was to examine the effects of GIP on SBF, both independently and in combination with hyperglycemia and hyperinsulinemia. METHODS: In a randomized, controlled crossover study, 8 healthy, lean male participants underwent 4 separate experimental conditions. The interventions included intravenous infusions of either GIP at a rate of 1.5 pmol-1 kg-1 minute-1 or saline, administered alone or in combination with a hyperglycemic and hyperinsulinemic clamp, respectively. Splanchnic blood flow was measured by Fick's Principle after catheterization of a hepatic vein, using indocyanine green as indicator. RESULTS: Splanchnic blood flow remained comparable across all experimental conditions, including GIP and saline infusions, both with and without the hyperglycemic and hyperinsulinemic clamp (P = .42). CONCLUSION: Under the applied conditions, GIP does not appear to play a substantial role in the acute regulation of net SBF, either alone or in combination with induced hyperglycemia and hyperinsulinemia.
17 July 2026
Read appraisal →European journal of nutrition
Nutrition interventions in women with polycystic ovary syndrome: a systematic review.
PURPOSE: This systematic review aimed to synthesize current evidence on the effects of various dietary interventions on anthropometric, metabolic, hormonal, inflammatory, and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). METHODS: The review followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42025641781). Searches were conducted in PubMed, Cochrane Library, EBSCO, Science Direct, Web of Science, National Thesis Center, Google Scholar, and DergiPark Academic for studies published between February 2015 and February 2025. Experimental and observational studies were included if they evaluated the independent effect of dietary interventions in adult women with PCOS. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. RESULTS: A total of 38 studies were included, covering interventions such as calorie-restricted diets, low-glycemic index/load diets, ketogenic diets, intermittent fasting, dietary approaches to stop hypertension, Mediterranean-style, and other diets. Most dietary interventions demonstrated beneficial effects on body weight, body mass index, and waist circumference, as well as improvements in insulin sensitivity, reproductive hormone regulation, and menstrual regularity. However, findings related to lipid metabolism, inflammatory markers, and oxidative stress outcomes were inconsistent. CONCLUSION: Current evidence indicates that dietary interventions are crucial in improving the management of metabolic, anthropometric, hormonal, and clinical outcomes in women with PCOS. Nevertheless, the heterogeneity of dietary approaches, study designs, and outcome measures highlights the need for long-term randomized controlled trials to establish more conclusive recommendations.
30 June 2026
Read appraisal →Nature communications
Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids
Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, we here develop a deep learning algorithm tailored for cell type-specific drug repurposing screening. In parallel, we perform a survival drug screen in a yeast model of Leigh. The two approaches independently converge on azole compounds, two of which - talarozole and sertaconazole - rescue neuronal morphogenesis in Leigh neurons and lower lactate release and improve growth rate in Leigh midbrain organoids. Mechanistically, these compounds modulate the retinoic acid pathway and membrane-associate lipid metabolism. The findings highlight azoles as promising candidates for Leigh and demonstrate the potential of combining in silico screens with human brain organoids as new approach methodologies (NAMs) to advance the discovery of therapeutics addressing rare neurodevelopmental disorders.
22 Apr 2026
Read appraisal →Food & function
Regular black tea kombucha consumption is associated with improved insulin resistance and increased ADIPOQ expression in adults with obesity: a pre-post clinical trial
Kombucha is a fermented beverage obtained by a Symbiotic Culture of Bacteria and Yeast (SCOBY). Although in vitro and animal studies suggest that kombucha has anti-inflammatory and anti-obesogenic properties, no clinical trials have confirmed that. In this pre-post clinical intervention study, we aimed to evaluate whether regular black tea kombucha consumption would impact metabolic, inflammatory, and oxidative stress markers; body weight and composition; and obesity-associated genes in individuals with and without obesity. This study follows the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) guidelines. Individuals with normal weight (Group 1; n = 20) and with obesity (Group 2; n = 16) received 200 mL of black tea kombucha for 8 consecutive weeks. Blood and subcutaneous adipose tissue (SAT) were collected at the baseline (T0) and after 8 weeks of intervention (T8). Most inflammatory (hs-CRP, IFN-γ, TNF-α, and IL-4, IL-6, IL-8, IL-10, and IL-12p70) and oxidative stress markers (FRAP, MDA, and NO) showed significant changes over time following the intervention. However, interaction analyses revealed that responses to kombucha consumption differed between groups for only a limited number of variables: body weight, conicity index, HOMA-IR, and hs-CRP. An upregulation of the gene ADIPOQ in the SAT (p = 0.0481) was also observed, alongside a positive correlation between the BMI and PPARγ (r = 0.58; p = 0.030), and between HOMA-IR and both NFκB (r = 0.73; p = 0.002) and SREBF1 (r = 0.66; p = 0.010). In conclusion, metabolic and inflammatory pathways may respond differently to kombucha consumption depending on the obesity status. The results are mainly attributed to the high number and diversity of phenolic compounds identified in the black tea kombucha, which confer a high antioxidant capacity to the beverage.
15 Apr 2026
Read appraisal →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
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Reconstruction of human metabolic models with large language models
Genome-scale metabolic models (GEMs) have become essential tools for understanding human metabolism. Here, we introduce Human2, a consensus human GEM with enhanced precision and biological relevance, which leverages large language models (LLMs) and GitHub Action checks to streamline automated, efficient, and collaborative curation. Human2 supports the reconstruction of tissue- and organ-specific models tailored to sex- and age-specific human groups. By integrating transcriptomic, proteomic, and kinetic data, we reveal distinct metabolic features across these groups, such as significant differences in arachidonic acid and leukotriene metabolism. The specific models were integrated into a dynamic whole-body framework, marking an enzyme-constrained dynamic model that simulates interorgan metabolite exchanges under varying nutritional states, from feeding to fasting. Our work highlights the transformative role of LLMs in GEM reconstruction and introduces a whole-body dynamic simulation that integrates kinetic data, offering a powerful resource for multiscale human metabolism modeling.
10 Apr 2026
Read appraisal →Journal of medical Internet research
Artificial Intelligence, Connected Care, and Enabling Digital Health Technologies in Rare Diseases With a Focus on Lysosomal Storage Disorders: Scoping Review
BACKGROUND: Rare diseases affect more than 300 million people globally, and only about 5% have approved therapies. Lysosomal storage disorders (LSDs) exemplify the diagnostic and long-term care complexity typical of rare diseases, and digital health technologies (DHTs), especially artificial intelligence (AI) and connected care (CC), are emerging tools to support LSD management. OBJECTIVE: We aimed to map and synthesize peer-reviewed and gray literature from the past decade on DHTs relevant for LSD care, with a primary analytic focus on AI-enabled and CC solutions and a contextual mapping of other enabling DHTs. Evidence distribution was charted by population, care-journey phase, and outcome domains to identify gaps, methodological limitations, and timely priorities relevant for research, clinical practice implementation, and policies. METHODS: We conducted a scoping review guided by a population, concept, context framework and operationalized through a Population, Intervention, Comparison, and Outcome (PICO)-informed data-charting structure to map study characteristics and reported outcomes, without causal or effectiveness assumptions and without risk-of-bias assessment. We searched PubMed, Google Scholar, and ClinicalTrials.gov for studies published between October 2015 and September 2024, complemented by AI-assisted discovery tools for citation extension. Reproducibility logs (search strings, run dates, filters, and stepwise counts) were maintained. Of 1751 records retrieved, 245 were included. Evidence was charted by LSD population, intervention class (AI, CC, and other enabling DHTs), outcome domains (patient, health care, and societal), and phase of the care journey. RESULTS: Among 245 included records, 92.2% (226/245) were peer-reviewed, and 7.8% (19/245) were gray literature; no completed and published randomized controlled trials or LSD-specific systematic reviews were identified, with evidence dominated by small, single-center observational studies. Overall, 40 peer-reviewed records reported AI-driven DHTs, 89 reported CC DHTs, and 144 reported other enabling DHTs (some multilabeled). Evidence was concentrated mostly in Gaucher and Fabry diseases. Nearly half of the mapped literature focused on screening and diagnosis, with fewer records addressing treatment intensification, rehabilitation, and end-of-life care. Outcomes were predominantly health care delivery performance measures, with fewer patient and societal outcomes. AI applications mainly supported diagnostic decision support, phenotyping, monitoring, tracking, and risk stratification; CC commonly involved telemedicine, remote monitoring, and patient-engagement platforms; enabling DHTs included interoperable data systems, registries, and digital infrastructures. CONCLUSIONS: The evidence base is appreciable for a niche field and reflects growing interest in AI and CC for LSD care, but heterogeneity and methodological limitations preclude inferences on effectiveness or routine implementation. This evidence map highlights relatively stronger areas and gaps, providing a structured foundation to inform timely expert consensus-building and research prioritization. Key priorities include interoperable data infrastructures and data availability, prospective multicenter evaluations, transparent reporting of algorithms and workflows, and implementation-relevant outcomes to support safe, equitable, and scalable adoption aligned with evolving European Union and global rare-disease priorities.
4 Apr 2026
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