Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 209 appraisals
The American journal of pathology
An Integrated Machine Learning and Genomic Framework for Precise Detection of Gastric Cancer
This study presents a novel integrative approach for the analysis of high-dimensional gene expression data, leveraging the complementary strengths of unsupervised clustering and supervised classification. Using K-means clustering, the data set is stratified into three distinct clusters, revealing intrinsic biological patterns and relationships. The resulting cluster assignments are subsequently used as pseudolabels to train machine learning models, including support vector machines, random forest, and a stacking ensemble classifier. To validate and enhance the robustness of clustering, complementary methods, such as hierarchical clustering and density-based spatial clustering of applications with noise (DBSCAN), are used, with results visualized through principal component analysis-driven dimensionality reduction. The high predictive accuracy achieved by the classifiers underlines the separability and reliability of the identified clusters. Furthermore, feature importance analysis highlighted key genetic determinants within each cluster, offering actionable insights into potential biomarkers and critical genomic features. This framework bridges the gap between exploratory unsupervised learning and predictive supervised modeling, providing a scalable and interpretable method for analyzing complex genomic data sets. Its applicability extends to biomarker discovery, patient stratification, and other precision medicine applications, emphasizing its utility in advancing genomic research and clinical practice.
3 Aug 2026
Read appraisal →Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Artificial Intelligence Tools for Gastrointestinal Research: A Practical Guide
Artificial intelligence (AI) tools, including large language models (LLMs) such as ChatGPT, Claude, and Gemini, are increasingly used in biomedical research. However, practical guidance for integrating these tools into the manuscript writing workflow remains limited. This narrative review provides a structured, step-by-step guide for gastrointestinal (GI) researchers and clinicians seeking to use AI responsibly across the stages of manuscript preparation.
2 Aug 2026
Read appraisal →Current opinion in critical care
Smart feeding: the role of artificial intelligence and integrated nutrition platforms in the ICU
PURPOSE OF REVIEW: Tremendous improvement in the use of artificial intelligence has opened new opportunities to analyze the data obtained from electronic health records and imaging. New technologies have tried to overcome obstacles to implement guidelines and recommendations. This review aims to describe the recent progress in the use of machine learning and new technologies in the field of nutrition of the critically ill. RECENT FINDINGS: Increase in data availability, ability to extract these data and analyze them using machine learning has allowed data scientists together with ICU specialists to improve nutritional screening and assessment and to predict occurrence of obstacles like enteral feeding intolerance or refeeding hypophosphatemia. In addition, new technologies can ensure nasogastric tube positioning and enteral feeding efficacy. Integrated platforms can integrate nutritional needs with most adequate prescriptions and modulate the nutritional administration according to the patient's tolerance and requirements. Analysis of continuous recording of imaging obtained from ultrasound can also predict gastric intolerance. SUMMARY: Using machine learning, numerous algorithms and nomograms have been suggested to predict enteral feeding intolerance but validation of these predictions is still required. New technologies integrating energy requirements and delivery of the optimal enteral feeding are very promising.
2 Aug 2026
Read appraisal →Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
Research progress of machine learning applications in gastric cancer diagnosis and therapy
Gastric cancer (GC), a malignant neoplasm originating from the gastric mucosal epithelium, represents one of the most prevalent cancers worldwide. Early detection is critical for improving treatment outcomes and patient prognosis. Recent advances in artificial intelligence (AI), particularly in machine learning, have introduced powerful computational and analytical capabilities that are increasingly being applied in GC research. Machine learning algorithms have shown considerable promise in enhancing the accuracy of GC diagnosis and optimizing therapeutic strategies. This review provides a concise overview of progress in machine learning applications within oncology, examines their current role and clinical utility in GC diagnosis and treatment, and highlights the transformative potential of machine learning in advancing GC management and patient care.
2 Aug 2026
Read appraisal →Journal of food science
Artificial Intelligence in Food-Nutrition-Health Research: From Multimodal Data Integration to Precision Intervention
Artificial intelligence (AI) is transforming food-nutrition-health research by enabling pattern recognition in complex, high-dimensional datasets that traditional hypothesis-driven approaches cannot address. This review systematically synthesizes research progress of AI across the food-nutrition-health continuum from 2020 to 2025. By examining 181 systematic reviews through PRISMA-guided selection, we provide a comprehensive overview and prospects across four dimensions: technical foundation, application scenarios, existing challenges, and future prospects. We propose a tripartite framework comprising (1) a data layer enabling multisource fusion of food composition, health monitoring, and individual characteristic data; (2) a technological layer of nondestructive testing (spectroscopy, nuclear magnetic resonance [NMR], imaging); and (3) an algorithmic layer progressing from machine learning to deep learning architecture. Key applications include food component analysis and safety detection; nutrition-disease association modeling; pathogen identification; and personalized dietary intervention systems. Despite rapid progress, critical challenges persist, insufficient model generalization across populations, algorithmic opacity limiting clinical trust, data privacy vulnerabilities, and lack of standardized multi-omics integration protocols. Future directions emphasize multimodal fusion models, explainable artificial intelligence (XAI), federated learning for privacy-preserving collaboration, gene-guided precision nutrition, and development of intelligent wearable devices and functional food. This review provides a roadmap for transitioning from population-averaged guidelines to dynamic, individualized health optimization through AI-enabled food system.
1 Aug 2026
Read appraisal →Acta oncologica (Stockholm, Sweden)
User perceptions of machine learning models as decision support for colorectal cancer multidisciplinary team conferences (AID-SIM-2): a qualitative simulation study.
BACKGROUND: Multidisciplinary team (MDT) conferences are considered a cornerstone of decision-making in cancer diagnostics and care. However, the current literature has not demonstrated improved patient outcomes based on the decisions of the MDT conferences. AIM: We aimed to evaluate how four different decision-support modalities impacted the decision-making process and the internal discussions in the MDTs in a multicenter simulation study, with a focus on user perceptions. METHODS: Four colorectal cancer centers with MDTs participated. We performed four simulations in each center. Each simulation used a different decision-support tool: (1) Current standard, (2) Current standard plus a prediction model, (3) A structured data presentation tool, and (4) A structured data presentation tool plus the prediction model. Clinician- and model-estimated risks were compared, the treatment suggestions from each site were compared, questionnaires about user perceptions were conducted after Simulations 2, 3, and 4 using a Google Form link, and a semi-structured interview was conducted at each site after the last simulation. RESULTS: Similar distributions of risk groups between clinicians and models were found; however, distinct discrepancies in predictions arose, particularly with higher-risk patients, highlighting the need for standardization for more complex clinical cases. The primary perceived benefit of decision support was increased standardization of care, independent of the individual physicians' personal views. However, participants emphasized the necessity of clinician autonomy to overrule tool suggestions when identifying clinical nuances not captured by the model. CONCLUSIONS: The colorectal cancer MDTs expressed a positive view regarding the use of prediction models and other forms of decision-support in their workflow. While clinicians and prediction models had similar risk score distributions, they diverged in the assessment of specific individual patients.
1 Aug 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Efficacy and safety of fecal microbiota transplantation in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment
BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease that is a growing public health challenge. Recent evidence showed that gut microbiota dysbiosis is involved in the pathogenesis of PD, prompting interest in fecal microbiota transplantation (FMT) as a potential disease-modifying intervention. This systematic review and meta-analysis aim to evaluate the efficacy and safety of FMT in patients with PD. METHODS: We conducted a systematic literature review using PubMed, Scopus, Web of Science, and the Cochrane Library till June 4, 2026, to identify RCTs comparing FMT with placebo or control interventions in PD. After removal of duplicates alongside title and abstract screening, followed by full-text screening, seven randomized controlled trials were included in this systematic review and meta-analysis. RESULTS: A total of seven randomized controlled trials (RCTs) with 318 subjects were analyzed. FMT was delivered via oral capsules, nasojejunal tubes, or colonoscopy, with follow-up periods ranging from 12 to 52 weeks. The meta-analysis indicated a notable short-term enhancement in daily motor activities, as assessed by MDSUPDRS Part II, after one month (mean difference - 2.19, 95% confidence interval - 4.32 to -0.06; P = 0.044). Nevertheless, no significant estimates were noted for MDS-UPDRS Part III, aggregate MDS-UPDRS scores, motor complications, non-motor symptoms, or overall life quality at any assessed time frame. Some individual studies reported gains in cognitive ability, anxious feelings, quality of life related to constipation, and certain PDQ-39 categories, although these improvements were not uniformly observed. Overall, FMT was well tolerated by participants, with adverse reactions mostly comprising mild, self-resolving gastrointestinal issues and no major safety risks. CONCLUSIONS: FMT is a safe treatment for individuals with PD and may offer modest short-term advantages in performing daily motor tasks. However, current evidence does not indicate lasting enhancements in overall motor capabilities, non-motor symptoms, or life quality. More extensive and sufficiently powered trials utilizing standardized FMT procedures and longer observation periods are necessary to elucidate the therapeutic benefits of FMT in Parkinson's disease.
1 Aug 2026
Read appraisal →JMIR cancer
Piloting a Clinical Decision Support System for Unintended Weight Loss in Primary Care: Mixed Methods Study on Early Cancer Detection
BACKGROUND: Delayed cancer diagnosis leads to poorer outcomes. Unintended weight loss (UWL) is a nonspecific symptom associated with cancer and other serious conditions, which can make it complex to identify the underlying cause. Clinical decision support systems (CDSSs) can provide evidence-based recommendations to facilitate timely investigation and diagnosis. OBJECTIVE: This study aimed to pilot the implementation of a CDSS for improving early cancer detection in primary care patients with UWL. METHODS: Five practices reviewed patients identified by the UWL CDSS. Staff were interviewed on the acceptability and feasibility of the CDSS. Interviews were analyzed thematically using 2 relevant frameworks: the acceptability of health care interventions and the sociotechnical model for evaluation of digital interventions framework. Clinical audits assessed the correct identification of UWL, follow-up rates, and patient characteristics. RESULTS: Of 60 patients identified by the CDSS as potentially having UWL, 36 (60%) had true UWL. Among the misclassified cases, most patients (16/55, 30%) were intentionally trying to lose weight; this intention was documented as free text in the clinical notes for 98% (58/60) of patients and in a structured field for only 20% of patients. Of the 36 patients, 5 (14%) were actively recalled by their practices for further follow-up; the others (31/36, 86%) were not recalled, as most were deemed already under appropriate follow-up. By 6 months, 94% (34/36) of the cohort had received follow-up care regardless of whether they had been formally recalled. One-third (12/36, 33%) of patients had no additional symptoms, while 36% (13/36) had recorded additional abdominal symptoms. Mental health conditions accounted for 19% of diagnoses linked to UWL consultation. Practice staff were generally receptive to the UWL CDSS concept. It was particularly appreciated by practices with strong quality improvement processes and prior CDSS experience. A high proportion of misclassified patients, poor workflow integration, and conflicting patients' agendas were cited as implementation barriers. CONCLUSIONS: Our study revealed challenges and potential benefits of implementing a CDSS for identifying patients with UWL at risk of cancer in primary care. While integration issues and misclassification of patients were noted, high rates of follow-up care were observed regardless of the CDSS. These high follow-up rates prompt consideration of whether they reflect Australian primary care and whether a CDSS with these characteristics is the most appropriate approach to support early cancer detection. Future research should focus on improving CDSS integration with existing workflows, enhancing correct identification through access to clinical notes and the use of more sophisticated digital methods (eg, AI). These findings highlight the potential of CDSS in improving patient care and the complexities involved in their successful implementation.
30 July 2026
Read appraisal →Histochemistry and cell biology
Molecular plasticity of LAMA3 across the disease spectrum: pathogenic mechanisms and clinical translation.
The laminin α3 chain, encoded by LAMA3, constitutes a principal component of laminin-332 (LN-332), an essential extracellular matrix (ECM) glycoprotein governing cell adhesion, proliferation, and tissue homeostasis. This systematic review consolidates current evidence on the molecular features and regulatory mechanisms of LAMA3, including its roles in PI3K/Akt, epithelial-mesenchymal transition (EMT), and Hippo-YAP signaling, as well as epigenetic and post-transcriptional modulation. Its context-dependent functions across distinct pathological states are delineated. In malignancies, including colorectal and ovarian cancers, LAMA3 functions as an oncogenic determinant that enhances invasion, metastatic dissemination, and chemotherapeutic resistance. In contrast, in hereditary diseases such as junctional epidermolysis bullosa (JEB) and chronic disorders such as idiopathic pulmonary fibrosis (IPF), LAMA3 deficiency or dysfunction constitutes a structural basis of tissue pathology. From a translational standpoint, elevated LAMA3 expression has been recognized as an independent prognostic indicator in pancreatic ductal adenocarcinoma, whereas LAMA3 promoter methylation is a candidate biomarker for platinum resistance in ovarian cancer. LAMA3-directed gene therapy for JEB has progressed to clinical evaluation. Current limitations in the field are critically examined, and emerging therapeutic approaches, including proteolysis-targeting chimeras (PROTACs), are discussed. Collectively, an integrated framework that connects LAMA3 biology with clinical applications is presented to inform future investigations and precision therapeutic strategies targeting this multifunctional molecule.
29 July 2026
Read appraisal →Biomedical physics & engineering express
BMSNet: a boundary-guided multi-scale polyp segmentation network
Accurate polyp segmentation in colonoscopy images is essential for computer-aided diagnosis and early colorectal cancer screening. However, this task remains challenging due to large variations in polyp size, shape, and texture, as well as blurred boundaries and low contrast between polyps and surrounding mucosa. To address these challenges, we propose boundary-guided multi-scale polyp segmentation network (BMSNet), a boundary-guided multi-scale network for accurate polyp segmentation. First, an Scale-Aware Modulation Meets Transformer-T backbone initialized with officially released pretrained weights is adopted to extract multi-level features efficiently. Then, a boundary prediction module is introduced to generate preliminary boundary priors through bidirectional feature interaction and differentiable Canny-based auxiliary supervision. Based on the generated boundary information, we design a boundary-guided feature enhancement module to refine feature representations. This module combines frequency-domain enhancement, multi-scale feature interaction, and boundary-guided modulation. Finally, a feature fusion unit is introduced to progressively integrate multi-scale features and generate the final segmentation prediction. Extensive experiments on five benchmark datasets demonstrate the effectiveness of the proposed method. On ClinicDB, Kvasir, ColonDB, ETIS, and CVC-300, BMSNet achieves Dice scores of 0.943, 0.920, 0.828, 0.825, and 0.913, respectively. These results indicate that BMSNet achieves competitive segmentation performance with moderate computational complexity under the evaluated experimental setting.
28 July 2026
Read appraisal →Signal transduction and targeted therapy
Mucosal immunity and vaccine development
The mucosal system, which includes the respiratory, gastrointestinal, and urogenital tracts, serves as a primary entry point for pathogens, with a unique immune microenvironment and specialized defense mechanisms. In recent years, especially following the onset of the COVID-19 pandemic, there has been increasing recognition of the importance of mucosal immunity, motivated by an enhanced comprehension of its fundamental mechanisms. Currently, strategies based on mucosal delivery systems to administer antigens and induce strong mucosal protective immunity have become a key focus in the development of mucosal vaccines. Compared with conventional intramuscular delivery, mucosal vaccination can simultaneously elicit a robust local mucosal response, effectively block pathogen entry into the local mucosa, and generate systemic immune responses to prevent symptomatic infections and severe disease. In addition, mucosal delivery offers advantages such as ease of administration and low invasiveness, making it a more widely acceptable approach to vaccination. In the present study, we conducted a systematic review of the mechanisms of mucosal immunity, the technological platforms for mucosal vaccines, and proposed a perspective on the challenges and future directions for the development of next-generation mucosal vaccines, with the goal of enhancing public knowledge and awareness regarding mucosal immunity and its possible effects on global health.
27 July 2026
Read appraisal →Medicine
Performance of DeepSeek V3 and ChatGPT-4o in answering esophageal cancer-related questions
Esophageal cancer remains a significant global health issue. ChatGPT-4o and DeepSeek V3 can provide the public with health-related knowledge about esophageal cancer. This study aimed to evaluate the accuracy of DeepSeek V3 and ChatGPT-4o in responding to health knowledge questions related to esophageal cancer. Fifty-two questions related to esophageal cancer were classified into themes of basic knowledge, diagnosis and molecular biology, management of local and locoregional diseases, management of advanced and metastatic diseases, clinical case analysis and patient frequently asked questions (FAQs). These questions were entered into DeepSeek V3 and ChatGPT-4o to obtain responses, and 2 experienced gastroenterologists independently evaluated the accuracy and temporal stability of each response. Overall, the scores of DeepSeek V3 and ChatGPT-4o on all questions were 4 (3-4), and there was no statistically significant difference between the 2 groups. The final scores of DeepSeek V3 in basic knowledge, diagnosis and molecular biology, management of local and locoregional diseases, management of advanced and metastatic diseases, clinical case analysis, and FAQs were 4 (3-4), 4 (3-4), 4 (3-4), 3 (3-4), 4 (4-4), and 4 (4-4), respectively, while the scores of ChatGPT-4o were 4 (3-4), 3 (2-4), 4 (3-4), 3 (3-4), 4 (4-4), and 4 (4-4), respectively. For temporal stability across 2 independent test runs, DeepSeek V3 presented inconsistent responses on 2 questions, and ChatGPT-4o on 1 question; no statistically significant differences were found in overall and subgroup scores between the 2 runs for both models (all P > .05). ChatGPT-4o and DeepSeek V3 showed favorable accuracy and comprehensive responses to most of the 52 esophageal cancer-related questions in this study, but our findings do not confirm their general reliability for esophageal cancer health information in routine clinical or public use.
27 July 2026
Read appraisal →Medicine
Comparative safety and effectiveness of stents in drainage of pancreatic fluid collections guided by endoscopic ultrasonography: A systematic review and network meta-analysis
BACKGROUND: Endoscopic ultrasonography-guided drainage is an effective treatment for pancreatic fluid collections (PFCs). However, the optimal stent strategy for endoscopic ultrasonography-guided drainage of PFCs is still unclear. This study aims to compare the clinical outcomes of different stent types to identify the best option. METHODS: Databases including PubMed, EMBASE, and Cochrane were searched up to August 2024. The analysis focused on comparisons between bi-flanged metal stents (BFMS), double-pigtail plastic stents (DPPS), fully covered self-expanding metal stents (FCSEMS), lumen-apposing metal stents (LAMS), and the combination of LAMS and DPPS (LAMS + DPPS). RESULTS: A total of 38 studies, involving 4265 patients with PFCs, were analyzed. In all of these patients, LAMS (risk ratio [RR]: 1.07, 95% confidence interval [CI]: 1.02-1.13) and BFMS (RR: 1.08, 95% CI: 1.01-1.15) showed higher clinical success rates compared with DPPS. LAMS + DPPS reduced infection rates compared with BFMS (RR: 0.32, 95% CI: 0.10-0.99), DPPS (RR: 0.19, 95% CI: 0.06-0.62), and FCSEMS (RR: 0.23, 95% CI: 0.07-0.76). Within the pancreatic pseudocysts subgroup, LAMS (RR: 1.08, 95% CI: 1.01-1.16) and LAMS + DPPS (RR: 1.24, 95% CI: 1.03-1.48) demonstrated higher clinical success rates compared with DPPS. Similarly, in the walled-off necrosis subgroup, LAMS (RR: 1.10, 95% CI: 1.02-1.17), LAMS + DPPS (RR: 1.19, 95% CI: 1.01-1.41), FCSEMS (RR: 1.14, 95% CI: 1.03-1.26), and BFMS (RR: 1.11, 95% CI: 1.03-1.20) all showed higher success rates compared with DPPS, with BFMS exhibiting a lower bleeding rate than DPPS (RR: 0.32, 95% CI: 0.18-0.99). CONCLUSION: Newer metal stents, including BFMS, LAMS, and LAMS + DPPS, offer advantages over plastic stents like DPPS alone. BFMS is preferable when bleeding risk is a concern, while LAMS + DPPS is more effective in reducing infection rates in PFCs.
26 July 2026
Read appraisal →Cell reports. Medicine
Toward generalizable prediction of cancer signal using a cell-free DNA language model.
Cell-free DNA can be used for early cancer detection, minimal residual disease monitoring, and post-treatment risk stratification. However, current assays are often designed for a single purpose and rely on deep or broad sequencing panels that capture only a small fraction of tumor-derived signals, limiting transferability, increasing cost, and reducing scalability. Fragmentia-AI is an artificial intelligence language model that learns fragment-level sequence patterns in tumor-derived cell-free DNA. Instead of focusing on mutations, it uses the structure of cell-free DNA to detect cancer signals in a partially panel-agnostic manner from ultra-low sequencing input, approximately 0.1%-1% of conventional depth. The model performs well across cancer types and clinical settings, including monitoring after surgery or immunotherapy, and in samples with low variant allele frequencies or no detected mutations. Fragment-level analyses identify shorter fragments and tumor-derived sequence patterns across panels of different sizes and ultra-low-pass whole-genome sequencing in multiple cohorts.
23 July 2026
Read appraisal →European journal of trauma and emergency surgery : official publication of the European Trauma Society
The association between pancreatic enzyme serum concentrations and blunt pancreatic trauma: a systematic review.
PURPOSE: Blunt pancreatic trauma is uncommon. When suspected, serum amylase and lipase are measured, but their diagnostic value remains uncertain. This systematic review evaluated the diagnostic performance of serum amylase and serum lipase in detecting blunt pancreatic trauma in adults. METHODS: MEDLINE, Embase, Scopus and Cochrane Central were searched for studies evaluating serum amylase and/or lipase in adults with blunt pancreatic trauma. Observational studies reporting diagnostic accuracy or clinical outcomes were included. Two reviewers independently screened studies and assessed risk of bias using the Newcastle-Ottawa Scale. RESULTS: Four observational studies met inclusion criteria. A total of 4937 patients with blunt abdominal trauma, including 150 with pancreatic injury were investigated. Two studies evaluated serum lipase alone and two compared amylase and lipase. Pancreatic injuries were graded according to the American or Japanese Association for the Surgery of Trauma. Early serum amylase measurement (< 90 min post-injury) demonstrated low sensitivity. In contrast, testing performed more than 3 h after injury has shown improved diagnostic accuracy with one study suggesting combined serum amylase and lipase testing can achieve a sensitivity of 85% and specificity of 100%. CONCLUSION: Early serum pancreatic enzymes measurement does not appear to aid initial management decisions following blunt abdominal trauma. Delayed testing (> 3-6 h), particularly using lipase or combined lipase and amylase showed improved diagnostic performance. Prospective multicentre validation is needed to define their role in guiding further imaging after equivocal or negative initial CT.
22 July 2026
Read appraisal →BMJ open
Endoscopic biopsy strategies for gastric ulcers: an updated systematic review
OBJECTIVE: To systematically summarise recent evidence on endoscopic biopsy for gastric ulcer. DESIGN: Systematic review of clinical studies. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science, CNKI and CiNii Research were searched for studies published from 2015 to May 2025. ELIGIBILITY CRITERIA: Original studies involving adults with endoscopically diagnosed gastric ulcers or ulcerative gastric lesions directly informing biopsy strategy were eligible if they evaluated biopsy timing, number, site or related diagnostic outcomes. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and assessed risk of bias using the Newcastle-Ottawa Scale. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively. RESULTS: Seven studies were included and grouped into four domains: biopsy timing, biopsy number, biopsy site and safety. Available data suggested that most malignancies may be identifiable at the initial endoscopy examination although repeat biopsy during ulcer healing or scarring might still detect some missed cancers. Evidence on the biopsy site remained limited and inconsistent, and findings from healed-phase ulcers further suggested that the anatomical site alone may be insufficient to guide biopsy strategy. Available studies also indicated that four well-targeted biopsies may be adequate for some depressed or polypoid lesions whereas more extensive sampling might be needed for infiltrative or otherwise suspicious lesions. Limited safety data did not show a clear increase in adverse events with broader biopsy strategies or the biopsy of stabilised bleeding ulcers. CONCLUSIONS: Contemporary evidence on endoscopic biopsy for gastric ulcers remains limited, heterogeneous and largely observational. Available data suggest that biopsy at initial endoscopy and adequate, lesion-targeted sampling may improve diagnostic yield, while follow-up and intensive sampling should be individualised according to endoscopic appearance, histological findings and clinical suspicion. PROSPERO REGISTRATION NUMBER: CRD420251157851.
21 July 2026
Read appraisal →Food & function
Efficacy of different dietary fibers for chronic idiopathic constipation: a systematic review and network meta-analysis
This study aims to compare the efficacy and safety of different dietary fiber subtypes in treating patients with chronic idiopathic constipation (CIC) through network meta-analysis (NMA). PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to October 23, 2025. The risk of bias was evaluated using the Cochrane RoB 2.0 tool, and treatment rankings were calculated using the surface under the cumulative ranking curve (SUCRA). 17 randomized controlled trials (RCTs) involving 1423 adults with CIC were included. NMA suggested that viscous soluble fibers were associated with greater efficacy compared with placebo in relieving defecation difficulty (high certainty, class 1), and were also associated with improvements in stool consistency and stool frequency relative to placebo (moderate certainty, class 1). According to SUCRA rankings, viscous soluble fibers tended to have a higher probability of favorable performance compared with other dietary fiber subtypes in improving straining during defecation (moderate certainty), stool frequency (low certainty), and stool consistency (low certainty), and was associated with a relatively favorable tolerability profile (moderate certainty). Insoluble dietary fibers showed the highest ranking probability for improvement in overall constipation symptom scores; however, this finding was supported by very low certainty evidence. Overall, the findings suggest that viscous soluble fibers have a higher probability of improving stool consistency, stool frequency, and straining during defecation. In contrast, insoluble fibers showed a relatively higher ranking for improvement in overall constipation symptom scores. These results support a symptom-oriented and individualized approach to dietary fiber selection in the management of CIC.
21 July 2026
Read appraisal →Pediatric surgery international
Pediatric colonic diverticulitis: clinical presentation, management, and review of the literature
Colonic diverticulitis is rare in the pediatric population and often presents with nonspecific symptoms that may be misdiagnosed as other causes of acute abdominal pain, such as appendicitis, leading to diagnostic uncertainty and variability in management. We report a case of pediatric colonic diverticulitis and present a systematic review to characterize its clinical presentation, diagnostic challenges and management. Clinical data for the index patient were retrospectively reviewed, and parental consent was obtained. A structured literature search was performed using PubMed, Scopus, and Embase. Studies reporting patients younger than 18 years were included. A 16-year-old male presented with right lower quadrant pain. CT suggested cecal diverticulitis. Worsening symptoms prompted diagnostic laparoscopy, revealing an inflamed diverticulum adjacent to a normal appendix. The postoperative course was uneventful. The review identified 27 studies including 101 patients. Median age was 14 years (IQR 12-16; range 3-17), with 57% male preponderance. Most cases involved a solitary right-sided diverticulum. CT correctly identified diverticulitis in 85%. Complicated disease occurred in 17%. In conclusion, in the pediatric age diverticulitis often arises from a solitary cecal diverticulum and can closely mimic appendicitis. Awareness may improve diagnosis, and uncomplicated cases can be treated conservatively with careful follow-up and appropriate clinical monitoring.
21 July 2026
Read appraisal →Science advances
Multistage microrobots with pH-responsive release of platelet membrane-coated nanoparticles
Targeted drug delivery in the gastrointestinal tract remains challenging because therapeutics must overcome multiple hierarchical barriers before reaching diseased tissue. Here, we present a multistage delivery platform that integrates magnetic microrobots, a pH-responsive protective coating, and platelet membrane-coated nanoparticles (PNPs) in one platform. A fillable design enables the formation of an internal magnetic layer for microrobot actuation, while the pH-responsive coating protects the cargo during transit and selectively degrades upon pH change, releasing cancer cell-targeting PNPs. In an in vitro colon cancer model that reproduces key gastrointestinal features, including flow, pH variation, and villi-like structures, this strategy increased nanoparticle retention and enhanced cancer cell cytotoxicity compared to nanoparticles administered alone. Ex vivo studies in porcine stomach and intestine further demonstrated robust locomotion on compliant and folded tissue surfaces. These results establish an environment-responsive hierarchical delivery strategy for more precise oral delivery in complex gastrointestinal settings.
20 July 2026
Read appraisal →Antonie van Leeuwenhoek
Advancements in the study of gut microbiome in disease diagnosis
This review summarizes disease-associated changes in gut microbial composition and evaluates the diagnostic performance of models constructed with different machine-learning algorithms. The review seeks to answer questions related to the relationship between the human gut microbiome and disease progression, how different machine learning algorithms affect disease diagnosis using gut microbiome data, and how disease-specific microbial communities impact diagnostic models. Multiple studies report that gut microbiome dysbiosis is commonly observed in many diseases, though patterns vary between conditions and cohorts. Large-scale computational analyses are increasingly applied to identify microbial signatures and to build diagnostic models; however, model performance often depends on data source, preprocessing and choice of algorithm. Overall, evidence indicates disease-associated shifts in gut microbial composition, and that diagnostic model accuracy is sensitive to cohort, sequencing and modeling choices. While certain taxa recur across studies for some diseases, heterogeneity between cohorts limits immediate clinical translation; thus, harmonized study designs and external validation are required. Future work should prioritize reproducible multi-cohort analyses, transparent reporting (e.g., PRISMA for reviews) and prospective validation before clinical deployment.
18 July 2026
Read appraisal →Inflammation research : official journal of the European Histamine Research Society ... [et al.]
Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review.
OBJECTIVE AND DESIGN: This systematic review synthesized evidence for a conserved lipopolysaccharide (LPS)-mediated pathogenic mechanism across diverse tissues and evaluated its potential relevance to peripheral neuropathy. METHODS: Studies were identified in which LPS was the independent exposure and pro-inflammatory, M1-like macrophage activation/polarization was an outcome. Structured evidence mapping was used to code in-vivo studies for direct measurement of prespecified steps along a proposed pathway: gut perturbation→barrier disruption→circulating LPS→systemic inflammation→tissue interface disruption→innate immune activation→M1-like macrophage skew→tissue dysfunction. Conditional concordance and downstream chain completeness scores were calculated. RESULTS: Mechanistic patterns were conserved between pulmonary, cardiac, renal, lymphatic, gastrointestinal, central nervous, adipose, osseous, urologic, dental, hepatic, uterine, and pancreatic tissues. Conditional concordance with the proposed pathway was high (mean 0.984 ± 0.053). Eleven studies assessed all downstream steps from LPS exposure to tissue dysfunction, each demonstrating full chain completeness. M1 macrophage skew (87%), innate immune activation (87%), and circulating LPS (82.6%) were the most frequently reported steps. CONCLUSIONS: These findings demonstrate conservation of LPS-driven M1-like macrophage polarization and tissue injury across systems, supporting the need to further investigate the biological plausibility of a gut-immune-nerve axis contributing to peripheral neuropathy.
18 July 2026
Read appraisal →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 →ACS applied materials & interfaces
The Evolving Landscape of Terahertz Biosensing: From Sensitivity to Precision
Terahertz (THz) spectroscopy has recently gained significant attention as a powerful tool for biomacromolecule detection due to its exceptional sensitivity in capturing molecular fingerprints, attributed to its unique wavelength range. THz biosensing platforms offer distinct advantages in identifying molecular rotational and vibrational states, making them effective for high-sensitivity, high-precision biomacromolecule analysis. This review highlights recent advancements in THz biosensing platforms, focusing on their spectroscopy interpretation and practical applications. We begin by introducing commonly used THz equipment and various metamaterials, followed by an overview of the key spectroscopy interpretation strategies for THz spectral analysis, including refractive index sensing and molecular fingerprint recognition. We also summarize the machine learning (ML) methods applied to enhance spectral analysis in THz biosensing platforms. Lastly, we provide an integrated perspective on the spectroscopy interpretation, clinical applications, and recent technological advancements in THz biosensing platforms, with an emphasis on how to construct a standardized THz-based biosensing workflow. We believe THz biosensing platforms hold immense potential to revolutionize molecular detection by enabling precise, label-free, and highly sensitive analysis of biomacromolecule interactions, paving the way for breakthroughs in medical diagnostics, environmental monitoring, and biochemical research.
17 July 2026
Read appraisal →Gut and liver
Data-Informed Intuition in Hepatology: Integrating Evidence, Context, and Clinical Reasoning
Artificial intelligence and data-driven models are changing hepatology, but expert clinical judgment remains essential. Liver diseases are complex and evolve over time, requiring reasoning that links numerical data with clinical context. We propose data-informed intuition (DII), a conceptual framework bridging evidence-based medicine with clinical experience and reflective reasoning. Instead of presenting a validated prediction model, it proposes DII as an integrative scaffold for clinical reasoning that can be examined and revised. DII is viewed as a trainable skill that improves with data feedback, not mere guesswork. Clinicians continually calibrate their judgment as patient information accumulates. In hepatology, DII helps interpret disease trajectories, adapt predictive scores to context, and handle uncertainty in liver transplantation, hepatocellular carcinoma, acute liver failure, and related conditions. The DII framework describes eight axes (time, rate, magnitude, pattern, context, causality, integration, and uncertainty) that make visible how data and intuition interact in clinical reasoning. Integrating DII into fellowship training and artificial intelligence-assisted systems could nurture clinicians who combine algorithmic precision with human insight. This perspective summarizes the conceptual basis, clinical uses, and educational value of DII, and outlines both a research agenda for its empirical testing and a path toward data-informed professionalism in hepatology.
15 July 2026
Read appraisal →Nutricion hospitalaria
Immunonutrition in surgical patients with colorectal cancer: a systematic review
Introduction: surgery in patients with colorectal cancer often leads to complications, affecting recovery, prolonging hospital stay, and impacting quality of life. Immunonutrition plays an important role by modulating the immune system and may contribute to the reduction of these complications. Objective: to assess the effect of immunonutrient supplementation on complications in surgical patients with colorectal cancer. Materials and methods: a literature search was conducted in PubMed, Web of Science, Embase, and Cochrane, following the PRISMA model. A total of 20 clinical trials and two observational studies published between 2000 and 2025 were selected, analyzing postoperative complications, physical or nutritional status, immune response, and length of hospital stay. Results: a reduction in postoperative complications was observed with combined immunonutrient supplementation (arginine, omega-3 fatty acids, nucleotides, L-alanine, and L-glutamine), particularly in wound infections. No benefits were found with isolated supplementation. Conclusion: combined immunonutrient administration may improve postoperative complications, especially wound infections, although results regarding hospital stay are inconsistent. Isolated supplementation with omega-3 fatty acids shows no benefit. Introducción: la cirugía en pacientes con cáncer colorrectal conlleva complicaciones, alterando la recuperación, alargando la estancia hospitalaria y afectando a la calidad de vida. La inmunonutrición ejerce una acción importante al modular el sistema inmunológico y podría mejorar estas complicaciones. Objetivo: evaluar el efecto de la suplementación con inmunonutrientes en las complicaciones en pacientes quirúrgicos por cáncer colorrectal. Material y métodos: se realizó una búsqueda bibliográfica en PubMed, Web of Science, Embase y Cochrane, siguiendo el modelo PRISMA. Se seleccionaron 20 ensayos clínicos y dos observaciones, publicados entre 2000 y 2025, que analizaron complicaciones posoperatorias, el estado físico o nutricional, la respuesta inmune y la duración de estancia hospitalaria. Resultados: se halló una reducción de las complicaciones posoperatorias con una suplementación combinada de inmunonutrientes como arginina, ácidos grasos omega-3, nucleótidos, L-alanina y L-glutamina, especialmente en infecciones de herida, sin beneficios en la administración aislada. Conclusión: la administración combinada podría mejorar las complicaciones posquirúrgicas, especialmente de la infección de la herida, con resultados contradictorios para estancia hospitalaria. La suplementación aislada de ácidos grasos n-3 no aporta beneficios.
15 July 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Physically intelligent capsule robots with embodied memory and logic in the gastrointestinal tract
Miniaturized medical robots offer a promising solution for minimally invasive measurements and interventions in the gastrointestinal (GI) tract. Clinical assessment of GI disorders is commonly guided by threshold-based physiological indicators, including pressure, temperature, and pH, which motivate event-triggered strategies for personalized medicine. However, identifying homeostatic dysregulation and enabling in-situ therapy remains challenging, because ingestible robotic systems must tightly integrate sensing, decision-making, and actuation under severe constraints of size, power, and biosafety. Inspired by the autonomy of microorganisms that operate without neural processing, this work introduces physically intelligent capsule robots (PI Capbots) that enable homeostatic monitoring and targeted delivery within the GI tract, without relying on centralized electronic control. Through embodied stimuli-responsive memory and logic, PI Capbots effectively distill rich, detailed, and redundant physiological information into a small set of decoupled and event-triggered outputs suitable for operations in in vivo environments. In each PI Capbot, multistable metamaterials encode intraluminal pressure as mechanical memory, programmable hydrogels implement orthogonal sensing and logic operations, and helical fibers enable multimodal locomotion. Ex vivo and in vivo studies in large animal models demonstrate the efficacy, robustness, and reproducibility of PI Capbots, highlighting its potential for their translational medical applications.
15 July 2026
Read appraisal →BMC oral health
The association between oral hygiene and metabolic dysfunction-associated steatotic liver disease - a systematic review
BACKGROUND: Given the increasingly evident links between oral health and systemic health, the aim of this review was to investigate whether oral hygiene practices influence the risk or progression of metabolic dysfunction-associated steatotic liver disease (MASLD). The findings support the potential importance of good oral hygiene and regular dental visits, especially for patients with MASLD. METHODS: This systematic review was registered with PROSPERO (CRD420251041530), and PubMed, Scopus, Embase and Web of Science were used for literature research up to June 2026. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, screening, study selection and quality check were performed using Rayyan and the Joanna Briggs Institute (JBI) critical appraisal checklists. Studies assessing the potential link between the frequency of oral hygiene procedures and the incidence, prevalence or progression of MASLD were selected for a systematic synthesis. The old terms non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) were considered as well. RESULTS: A total of 570 results were identified of which six studies met the inclusion criteria. Five of them reported a correlation between higher tooth brushing frequency and a lower incidence, prevalence or progression of NAFLD/NASH compared to individuals with lower tooth brushing frequency. Notably, one study revealed significantly worse liver parameters among NASH patients without regular dental visits than among those who visited a dentist more than once a year. CONCLUSIONS: An association between oral hygiene habits and NAFLD/NASH was found in all included studies. A greater frequency of daily tooth brushing as well as regular dental visits might have beneficial effects on both the development and progression of fatty liver disease. However, there is not enough evidence to establish causality yet and the impact of confounding factors must be further investigated. CLINICAL TRIAL REGISTRATION: Not applicable.
11 July 2026
Read appraisal →Journal of medicinal chemistry
Machine Learning-Based Models to Predict Drug-Induced Liver Injury (DILI) to Assist Medicinal Chemistry
Drug-induced liver injury (DILI) is a leading cause of drug failure and post-market withdrawals. Traditional preclinical methods fail to detect up to 40-45% of clinical hepatotoxicity cases. Computational approaches, particularly those based on machine learning and deep learning (DL), are emerging as promising tools to support medicinal chemistry and early drug discovery, though their predictive capabilities remain under active investigation. In this perspective, we review the development of DILI annotation data sets, tracing their growth from small collections to large, comprehensive resources. We also outline the evolution of computational methods, from simple descriptor-based models to advanced DL and ensemble approaches that incorporate interpretable features. Finally, we highlight recent efforts to integrate standardized causality frameworks, pharmacogenomics, and mechanistic models, aiming to connect computational advances with clinical relevance. This perspective provides valuable insight for researchers and promotes the development of more robust and consensual DILI prediction strategies.
10 July 2026
Read appraisal →Journal of gastrointestinal cancer
Radiomics Models as Tools for Predicting Genetic Mutations in Colorectal Cancer: A Systematic Review and Meta-Analysis
BACKGROUND: The evaluation of genetic mutations is crucial for personalized therapy in colorectal cancer (CRC), but the invasive tissue biopsy is subject to sampling bias and other complications. Radiomics has emerged as a non-invasive tool to predict these mutations from standard medical images. In this systematic review and meta-analysis, we aimed to evaluate the diagnostic accuracy and methodological quality of radiomics models for predicting key genetic mutations in CRC. METHODS: A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted in accordance with PRISMA guidelines. Studies evaluating radiomics models for predicting genetic mutations in CRC patients using pre-operative CT, MRI, or PET/CT were included. A meta-analysis of diagnostic accuracy was performed to calculate the pooled sensitivity, specificity. Methodological quality was assessed using the Radiomics Quality Score (RQS) and QUADAS-2 tools. RESULTS: Sixteen studies were included in the quantitative analysis. The pooled sensitivity and specificity were 0.75 (95% CI, 0.67-0.81) and 0.78 (95% CI, 0.70-0.85), respectively, with an overall AUC of 0.79. Subgroup analyses revealed that radio-clinical models integrating both clinical and radiomics features achieved superior sensitivity compared to models with only radiological input. However, the overall methodological quality of the included studies was low, with a mean RQS of 45%. CONCLUSION: Conventional radiomics models demonstrate promising results for the non-invasive prediction of genetic mutations in CRC, with sensitivity enhanced by the integration of clinical data. Despite this potential, significant methodological shortcomings and heterogeneity across studies highlight the need for standardized protocols and large-scale, prospective validation before these models can be translated into routine clinical practice.
10 July 2026
Read appraisal →International ophthalmology
The relationship between diabetic retinopathy and intestinal microbiota: a systematic review and meta-analysis
PURPOSE: The results of human observational studies on the correlation between gut microbiota and diabetic retinopathy (DR) are discrepant. This meta-analysis aimed to evaluate the specificity of the gut microbiota in DR patients compared to patients with type 2 diabetes mellitus (T2DM). METHODS: All published literature up to October 2024 was searched by two researchers on PubMed, Embase and Web of Science databases. Diversity and gut microbiota composition were the main outcomes. The meta-analysis was conducted in Review Manager (RevMan) Version 5.3. RESULTS: Eight studies, investigating gut microbiota by collecting stool samples, conducted in China and India were included in this meta-analysis, involving a total of 486 individuals in the T2DM (n = 258) and DR (n = 228) groups. No significant difference in alpha-diversity was observed between T2DM and DR patients. The pooled estimate showed that, at the phylum level, the abundances of Patescibacteria, and Synergistetes were significantly lower, and Verrucomicrobia were considerably higher in DR patients than in T2DM patients. At the genus level, DR patients had an increase in Bacteroides compared to T2DM. CONCLUSIONS: In this meta-analysis with a small number of studies and relatively high heterogeneity, changes in gut microbiota were associated with DR, commonly reflected by a reduction in beneficial species and an increase in pathogenic species influencing metabolic pathways.
10 July 2026
Read appraisal →Gut
Digital twins in IBD-bridging data, biology and trial innovation
Clinical trials in IBD face difficulties of escalating complexity, high costs and challenges in recruitment. Digital twins are virtual, data-driven replicas of individual patients that model disease trajectories and treatment responses, which offer a potential innovative change in the conduct of clinical trials in IBD. Built from multimodal datasets integrating clinical, molecular, imaging and real-world data, digital twins can generate synthetic control arms, enable adaptive randomisation and predict disease relapse or treatment response. Early studies across oncology, cardiology and endocrinology demonstrate their feasibility and potential to improve statistical power while reducing patient burden. However, the integration of digital twins into clinical trials in IBD will require rigorous validation frameworks, transparent data governance and attention to algorithmic bias and consent. In this review, we explore how digital twins may transform IBD research-from in silico simulation to adaptive, patient-centred trial design-and outline the regulatory, ethical and logistical challenges to be considered in order to successfully integrate them into future trials.
10 July 2026
Read appraisal →Cell host & microbe
Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial
Gut microbiota may influence antidepressant treatment outcomes, yet whether targeted modulation can enhance efficacy remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in patients with major depressive disorder, administering a 2-week course of fecal microbiota transplantation (FMT) capsules or placebo as an adjunct to escitalopram (ChiCTR2300071421). Remission rates at week 8 did not differ significantly between groups, but FMT produced greater reductions in Hamilton Depression Rating Scale, 17-item version (HAMD-17) scores at weeks 2 and 8. FMT was well-tolerated with a safety profile comparable to placebo. Multi-omics analyses show durable donor microbial engraftment and enrichment of beneficial Lachnospiraceae and Oscillospiraceae taxa. Microbial remodeling is accompanied by an increase in serum bile acids that correlate with the alleviation of depressive symptoms. Mediation analysis supports a bile-acid-mediated suppression of inflammatory pathways linking microbial changes to antidepressant effects. Overall, FMT may provide a safe avenue to enhance escitalopram efficacy through microbiota-directed regulation of bile-acid metabolism and inflammation.
10 July 2026
Read appraisal →Journal of gastrointestinal cancer
Tumour-Associated Neutrophils in Colorectal Cancer: a Systematic Review, Meta-analysis, and Comprehensive Literature Review
PURPOSE: Neutrophils are at the forefront of innate immune response. The prognostic impact of tumour-associated neutrophils (TANs) remains unclear. This study aimed to evaluate the prognostic role of TANs in colorectal cancer (CRC). METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Scopus to identify studies correlating TANs with time-to-event survival analysis in patients with stages I-IV CRC from the date of inception until April 2024. Articles were included if they involved the identification of TANs through hematoxylin-eosin (HE) or immunohistochemistry (IHC) and reported survival analysis. Data was collected from the tumour core (TC) and invasive margin (IM). The hazard ratios (HRs) were extracted from the study results. Heterogeneity was evaluated using Cochran's Q and I². Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Of 4,292 citations found, 18 studies fulfilled eligibility criteria, encompassing 7,406 patients. IHC was used to identify TANs in 12 trials, while six performed HE. Five studies included patients with disease stages I-III, and 13 had stages I-IV. High TANs at the IM were associated with improved OS (HR = 0.64, 95% Confidence Interval [CI] 0.50-0.81, I2 = 48%) and DFS (HR = 0.47, 95% CI 0.25-0.88, I2 = 32%). At the TC, high TANs showed a trend towards better OS (HR = 0.82, 95% CI 0.61-1.10, I2 = 83%) and DFS (HR = 0.48, 95% CI 0.21-1.07, I2 = 93%), although not statistically significant and with high heterogeneity. CONCLUSION: In this systematic review and meta-analysis, high TANs at the invasive margin (IM), the tumour-host interface, was associated with improved prognosis in CRC. In contrast, no statistically significant association was observed for high TANs at the tumour core (TC).
9 July 2026
Read appraisal →Food & function
Apples and apple-based products in the modulation of cardiometabolic and functional markers: a systematic review of human intervention studies.
Apple is one of the most widely consumed fruits worldwide, yet its effects on human health remain the subject of ongoing debate. The aim of the present review was to examine evidence from human intervention studies evaluating the impact of apples and apple-based products on functional and metabolic health markers. A total of 38 studies were included: 13 postprandial interventions, 22 medium- or long-term interventions, and 3 assessing both postprandial and chronic effects. Postprandial studies predominantly investigated the effects of apple consumption on blood glucose levels and plasma antioxidant capacity, whereas medium- or long-term interventions assessed a broader range of biomarkers related to cardiometabolic health, oxidative stress, vascular function, inflammation, and gut function. Overall, the findings suggest that apples and apple-based products may beneficially modulate glycaemia, antioxidant capacity, and vascular endothelial function mainly in short-term interventions, while medium/long-term studies reported an apparent improvement in gut microbiota composition. However, the current evidence remains insufficient to draw definitive conclusions. Additionally, substantial heterogeneity in study design, populations, and products tested limits the ability to generalize results. Nonetheless, apple consumption, consistent with fruit intake in general, represents an important component of a healthy and balanced diet, providing valuable nutrients and bioactive compounds whose intake should be encouraged. Therefore, further well-designed intervention studies, particularly in populations with cardiometabolic risk factors, are warranted to better clarify the role of apples and apple-derived products in human health. Future research should also aim to identify the effective amounts and specific bioactive components responsible for the observed effects, as well as to determine whether these benefits may vary according to the health status of the target population.
6 July 2026
Read appraisal →Food & function
Application of artificial intelligence in synbiotic and functional food development for precision nutrition
Synbiotic and functional food formulations modulate gut microbiota, SCFA production, immune signalling and metabolic pathways, yet current development pipelines remain largely empirical and constrained by nonlinear trade-offs among probiotic viability, prebiotic functionality and sensory acceptance. Artificial Intelligence (AI) and machine learning (ML) approaches offer data-driven strategies to support formulation, multi-objective optimization and functional assessment. This review systematically identified and critically synthesized literature published between 2020 and 2025 across five thematic domains: (i) formulation and ingredient selection; (ii) viability and shelf-life modelling; (iii) functional and antioxidant bioactivity assessment; (iv) sensory and consumer prediction; and (v) personalization and precision nutrition. Studies were identified through database searches and screened for relevance to synbiotics, functional foods, microbiome modulation and nutrition outcomes, following PRISMA 2020 guidelines. Current evidence indicates that AI can assist ingredient pairing, viability forecasting, sensory modelling and functional property prediction, often complementing conventional statistical tools such as Response Surface Methodology in multivariate design spaces. However, most implementations remain computational or pilot-scale, with minimal integration of microbiome-informed personalization, clinical endpoints or adherence outcomes. Major translational gaps include data heterogeneity, model interpretability, regulatory substantiation and scarcity of longitudinal evidence. AI should therefore be considered a complementary decision-support tool that can accelerate hypothesis generation and formulation refinement rather than substitute mechanistic validation or human trials. Bridging computational modelling with microbiome science and nutritional evidence may enable precision synbiotic strategies and next-generation functional food innovation.
6 July 2026
Read appraisal →International journal of medical informatics
Artificial intelligence in gastroenterology clinical practice: Scoping review of large language model applications.
BACKGROUND: Advances in artificial intelligence have brought renewed attention to tools that can work with the large amount of written information generated in clinical practice. Among these, large language models (LLMs) stand out for their ability to interpret and generate medical text in a flexible, context-aware way. Gastroenterology, like many specialties, produces a wide range of narrative and semi-structured data, and this has encouraged researchers to explore how LLMs might help clinicians manage everyday tasks. Recent studies have examined their potential contributions to patient education, communication between care teams and patients, decision support, and routine documentation, reflecting a growing interest in how these systems might fit into real-world clinical workflows. OBJECTIVE: This scoping review aimed to map current applications of LLMs in gastroenterology clinical practice, including subspecialty focus, study designs, model types, and reported outcomes. METHOD: Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2022 and August 2025. Eligible studies included original research assessing LLM applications in gastroenterology clinical practice. Data were extracted on subspecialty, application domain, LLM type, data source, and outcomes. We employed thematic analysis to address our primary research question. RESULTS: 73 out of 2895 studies identified in the initial search met the inclusion criteria. Six subspecialties and six application domains emerged from our review. Hepatology (20/73 studies, 27.3%) and endoscopy (17/73 studies, 23.2%) were the most represented subspecialties. The most frequently investigated application domains were patient education and communication (38 studies) and decision support and clinical guidance (24 studies). Most studies were simulation-based or literature-based cases, although an increasing number have used real-world clinical data, particularly in recent years. The majority evaluated general-purpose models such as GPT-3.5 and GPT-4, with some incorporating retrieval augmentation or fine-tuning. Reported outcomes varied by application domain and included measures of accuracy, concordance, completeness, relevance, safety, reliability, usability, user satisfaction, efficiency, time savings, and educational value. Commonly described limitations included variable reliability, incomplete responses, and challenges in generalizing from simulated to clinical settings. CONCLUSIONS: Research on LLMs in gastroenterology has expanded across multiple subspecialties and application domains. Current evidence is primarily based on simulation studies, with limited but growing evaluation using real-world clinical data. Further work is needed to assess performance in prospective and applied clinical contexts.
2 July 2026
Read appraisal →Journal of medical Internet research
Large Language Model Versus Multidisciplinary Team: Feasibility Study of Pancreatic Cancer Management Recommendations
Of 269 pancreatic cancer multidisciplinary team cases, 125 complete structured cases were evaluated. The chat interface model labeled ChatGPT-5.2 matched the multidisciplinary team's broad initial management category in 119 cases (95.2%, 95% CI 89.8%-98.2%). The end point was coarse, and the model was not version controlled, so findings only support supervised exploratory use.
2 July 2026
Read appraisal →European journal of nutrition
The effectiveness of a plant-based milk with fermented brown rice on constipation symptoms via gut microbiota modulation: a double-blind randomized controlled trial
PURPOSE: To evaluate the effects of a plant-based milk with fermented brown rice on constipation symptoms in patients with functional constipation and to identify post-intervention gut microbial alterations that may underlie potential mechanisms. METHODS: This is a randomized controlled trial among 100 participants with functional constipation. Participants were randomly assigned to the intervention group (plant-based milk with fermented brown rice, 2 bottles/day, 500 ml in total), or the control group (an isocaloric plant protein milk, equivalent dose) for 3 weeks. The primary outcome is complete spontaneous bowel movement (CSBM) rate, while secondary outcomes include score of individual symptoms assessment of constipation, bowel movement frequency (BMF), and gut microbial changes (metagenomics). RESULTS: A total of 99 participants completed the intervention. CSBM and BMF increased, and GSRS scores decreased over time in both groups, with no significant between-group differences. The plant-based milk with fermented brown rice relieved constipation symptoms more than the control group did, with significant between-group differences in straining, bloating and abdominal pain (all P < 0.05). The intervention group showed increases in 8 species, including three beneficial species in the genus Blautia, associated with relief of abdominal pain after the intervention. Meanwhile, machine learning models identified gut microbiota features predicting intervention responders. CONCLUSION: Our study did not find between-group difference in CSBM, while the plant-based milk with fermented brown rice showed greater effectiveness in relieving constipation symptoms and optimizing gut microbiota. Functional species benefiting intestinal health in response to the intervention were also identified. CLINICAL TRIAL REGISTRY: This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, ChiCTR2400088688).
30 June 2026
Read appraisal →BMJ open
Comparative diagnostic accuracy of image-enhanced endoscopy modalities and artificial intelligence-assisted endoscopy for gastric intestinal metaplasia and gastric dysplasia: protocol for a systematic review and diagnostic test network meta-analysis.
INTRODUCTION: Gastric intestinal metaplasia (GIM) and gastric dysplasia are critical precursors in the Correa cascade of gastric carcinogenesis. Although multiple image-enhanced endoscopy (IEE) modalities and artificial intelligence (AI)-assisted systems have been developed to improve their detection, the comparative diagnostic accuracy of these technologies remains unclear. Direct comparative studies are limited and conventional pairwise meta-analyses do not provide a coherent framework for comparing multiple diagnostic technologies. METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and PRISMA-Network Meta-Analysis guidelines. We will search MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library/Wiley), Web of Science Core Collection (Clarivate), Scopus (Elsevier), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception, without date or language restrictions. Eligible studies will be diagnostic accuracy studies evaluating IEE modalities (including narrow-band imaging with or without magnification, blue laser imaging, linked colour imaging and iScan) or AI-assisted endoscopy against histology. Comparative studies will form the primary evidence base for the diagnostic test network meta-analysis; single-arm studies will be summarised separately and will not contribute to the primary network estimates. The coprimary diagnostic parameters will be sensitivity and specificity for GIM and dysplasia. These will be analysed jointly using a hierarchical bivariate diagnostic test network meta-analysis with binomial likelihoods and correlated random effects. Diagnostic OR and area under the receiver operating characteristic curve will be treated as secondary summary measures. Two reviewers will independently screen, extract data and apply Quality Assessment of Diagnostic Accuracy Studies 2. Heterogeneity, transitivity and inconsistency will be assessed using prespecified clinical and methodological effect modifiers, model-based diagnostics and sensitivity analyses. The certainty of evidence will be assessed using Confidence in Network Meta-Analysis, with interpretation adapted to diagnostic accuracy outcomes. ETHICS AND DISSEMINATION: This study does not require ethical approval as it relies on secondary analysis of published literature. Findings will be disseminated through peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD420261363078.
29 June 2026
Read appraisal →Journal of gastrointestinal and liver diseases : JGLD
Colon Cleaning after Inadequate Bowel Preparation: A Pooled-data Analysis
BACKGROUND AND AIMS: An adequate bowel preparation is essential for performing high-quality ccolonoscopy; however, it remains ineffective for a certain percentage of patients. We conducted a literature search to identify evidence on salvage strategies following inadequate bowel preparation. METHODS: The search of medical literature was conducted using Medline and Google Scholar, restricted to studies published in English as a full paper. From retrieved studies, the success rate was calculated according to the rescue approaches used, including different oral- or device-assisted procedures, and pooling data of similar approaches. RESULTS: By considering data of 17 studies with 2,167 patients, an adequate colon cleaning was overall achieved in 79.3% (95%CI: 77.5-80.1). By grouping data of similar approaches, the success rate was 78.1% with oral high-volume polyethylene glycol (PEG), 75.3% with low-volume PEG, 82.5% with oral sennosides, and 84.6% following colonoscope or device-assisted preparation. CONCLUSIONS: Effective bowel cleansing is not achieved in nearly 20% of patients due to inadequate bowel preparation and although multiple approaches have been investigated, none has consistently provided adequate bowel preparation for all patients.
29 June 2026
Read appraisal →Medicine
Clinical outcome of revisional gastrectomy postgastric banding failure: A systematic review.
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has been widely used for obesity management; however, its long-term failure, due to complications such as band erosion, slippage, and inadequate weight loss, has necessitated revisional bariatric procedures. Revisional laparoscopic sleeve gastrectomy has emerged as a common alternative, yet its safety and efficacy remain debated. METHODS: A systematic review was conducted in accordance with PRISMA guidelines; this review was prospectively registered with Prospective Register of Systematic Reviews (CRD42024568094). A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases was performed up to July 19, 2024. Studies published in English that reported postoperative outcomes following revisional laparoscopic sleeve gastrectomy after failed LAGB were included. Data were extracted independently by 2 reviewers, focusing on patient demographics, complication rates (including leaks, bleeding, and infections), and nutritional outcomes. Quality assessment was performed using a standardized tool for observational studies, cohort and cross-sectional studies. RESULTS: Fifty studies involving a total of 16,192 patients were analyzed. Patients had a mean age between 30 and 50 years and a revision body mass index ranging from 33 to 52 kg/m2. Infection was reported in 9 studies, though incidence was low. Bleeding was examined in 30 studies, with mostly isolated cases; thrombosis was reported in only 1 study. Leak rates were reported in 39 studies, ranging from 0% to 8.1%, with stage-specific rates between 2.8% and 5.8%. Four studies noted nutritional deficiencies, including increased ferritin deficiency and some cases contributing to readmission. Overall complication rates were reported in 22 studies, averaging 9.95% and ranging from 0% to 37.5%. CONCLUSION: Revisional laparoscopic sleeve gastrectomy following failed LAGB appears to offer a safe and effective alternative, with acceptable complication rates and favorable weight loss outcomes. However, heterogeneity in study designs and patient characteristics underscores the need for standardized reporting and further research to optimize clinical protocols.
28 June 2026
Read appraisal →Public health research & practice
Optimising SMS content for bowel cancer screening participation in Australia: cross-sectional national survey findings.
OBJECTIVES AND IMPORTANCE OF STUDY: This study aimed to identify short message service (SMS) reminder content perceived as most likely to prompt bowel cancer screening, examine differences across sociodemographic subgroups, and explore preferences for timing and frequency. METHODS: Australian residents (N = 1016) aged 50-74 years completed an online survey rating five SMS reminders presented in random order. Outcomes included perceived usefulness, likelihood of encouraging kit return, likelihood of irritation and clarity. Preferences for timing and frequency were also assessed. Bayesian multilevel modelling (cumulative probit) compared ratings across SMS types, with effect sizes expressed as standard deviation (s.d.) differences in perceived likelihood that each SMS would encourage kit return compared with a reminder-only message. Interactions with age, gender, socioeconomic status and screening history were explored. RESULTS: Compared with a 'reminder-only' message, SMS content that encouraged storing the kit near the toilet (s.d. 0.44), conveyed general practitioner endorsement (s.d. 0.32) and gave instructions (s.d. 0.22) was more likely to prompt kit return. Responses varied slightly by age and area-level socioeconomic status. Most participants preferred two to three SMS reminders (mean 2.89, s.d. 6.73). CONCLUSIONS: SMS reminders using behavioural prompts and clear, concise content may support improved screening participation. Tailored SMS messages that reflect public preferences may increase kit return rates, support national screening goals and reduce bowel cancer mortality.
27 June 2026
Read appraisal →La Medicina del lavoro
Cadmium Exposure and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis
INTRODUCTION: Pancreatic cancer is a highly lethal malignancy with poor prognosis and limited treatment options. Environmental exposures, particularly to heavy metals such as cadmium, may contribute to its etiology. This systematic review and meta-analysis evaluated the association between cadmium exposure from different sources and pancreatic cancer incidence or mortality. METHODS: Following PRISMA guidelines, we searched PubMed, EMBASE, and Scopus. Eighteen studies comprising 20 risk estimates were included. Random-effects meta-analyses were conducted overall and stratified by exposure source, gender, region, study design, and outcome. Dose-response relationships were assessed using meta-regression of cadmium exposure measures. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Overall, cadmium exposure was associated with an increased risk of pancreatic cancer [relative risk (RR) = 1.69, 95% confidence interval (CI): 1.28-2.22]. Occupational exposure showed the most consistent association (RR = 1.38, 95% CI: 1.19-1.61), followed by urinary and blood/serum biomarkers. Risk was higher in men than in women, and in case-control than in cohort studies. Dose-response analysis did not reveal a linear trend. There was limited evidence of publication bias overall, though some asymmetry was observed for urinary cadmium studies (P = 0.045). CONCLUSION: Cadmium exposure was associated with pancreatic cancer risk, particularly in occupational and biomarker-based studies. While findings support a potential causal link, heterogeneity, residual confounding, and limited dose-response data necessitate cautious interpretation.
26 June 2026
Read appraisal →Reviews in the neurosciences
Probiotics and seizure susceptibility in preclinical epilepsy models: mechanistic insights from a systematic review and meta-analysis
The gut microbiota can affect neuronal excitability, inflammation, and oxidative balance via the gut-brain axis, shaping seizure susceptibility. To translate these findings into clinical approaches, a synthesis of preclinical microbiome-based evidence is needed. This systematic review and meta-analysis examined the putative anticonvulsant, anti-inflammatory, antioxidant, and neuroprotective effects of probiotics in rodent models. An extensive systematic search up to July 2025 identified eligible animal studies in which probiotics were administered in seizure models. Reported outcomes included seizure latency, duration, severity, and frequency, as well as inflammation, oxidative stress, and behavioral measures. Of the 24 studies that met the inclusion criteria, 19 provided sufficient data to be included in the meta-analysis. The most frequently used strains belonged to the Lactobacillus (e.g., acidophilus, casei, fermentum) and Bifidobacterium genera (e.g., bifidum, longum), with occasional synbiotic combinations. Probiotics significantly increased seizure latency (MD = 22.09; 95 % CI: 10.52 to 33.67) and reduced seizure severity (MD = -1.08; 95 % CI: -1.39 to -0.76) and duration (MD = -23.19; 95 % CI: -35.56 to -10.82). Probiotics significantly reduced IL-1β, IL-6, and TNF-α levels while MDA showed a nonsignificant trend toward reduction (p = 0.076). Behaviorally, improvements in spatial learning (p < 0.05) and reduced anxiety-like behavior (p < 0.001) were observed. Probiotic supplementation appears to exert anticonvulsant, anti-inflammatory, antioxidant, and behavioral benefits in preclinical epilepsy models, although the evidence is heterogeneous and limited to animal studies. Mechanistic evidence indicates modulation of the gut-brain axis, enhanced GABAergic signaling, and improved mitochondrial function. These findings support further investigation of specific probiotic formulations as promising adjunct candidates in well-designed, mechanism-driven clinical trials.
25 June 2026
Read appraisal →Current opinion in anaesthesiology
Traditional learning meets adaptive learning: the present and future of education in nonoperating room anesthesia.
PURPOSE OF REVIEW: Nonoperating room anesthesia (NORA) and continuing education in this setting are both in a state of change. Procedures performed outside the operating room, especially those that require nuanced anesthetic care, are becoming increasingly prevalent. Numerous new innovations are transforming care across NORA settings, especially within gastroenterology, interventional and neurointerventional radiology, and electrophysiology. Concurrently, education for NORA providers is rapidly evolving, influenced by technological advancements and artificial intelligence. RECENT FINDINGS: Traditional learning, a mode of education in which each learner receives essentially the same content, is now blending with adaptive learning, a field of precision education in which dynamic educational content is curated for individual learners, timed and paced to their preferences and progress, and coupled with artificial intelligence-generated feedback. The mainstays of traditional education for NORA providers remain relevant: content created by professional societies, podcasts, textbooks, and primary literature. Yet new, artificial intelligence-driven approaches for adaptive learning have entered the scene: clinical decision-making tools, literature review and knowledge mapping assistants, online platforms for precision education, virtual reality, and synthetic patients or avatars. SUMMARY: This article explores the blending of traditional and adaptive educational modalities in NORA continuing education and discusses the implications and obstacles for the future.
23 June 2026
Read appraisal →Journal of robotic surgery
Outcomes in laparoscopic versus robotic-assisted surgery for median arcuate ligament syndrome: a systematic review and meta-analysis
Median Arcuate Ligament Syndrome (MALS) is a rare condition caused by external compression of the coeliac artery by the median arcuate ligament (MAL), leading to postprandial abdominal pain, nausea, vomiting, and weight loss. This study aims to compare outcomes of robotic (RMALR) and laparoscopic (LMALR) MAL release. A systematic search of PubMed/MEDLINE, Scopus, and Embase databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare perioperative and postoperative outcomes of LMALR versus RMALR. Comparative studies including adult patients undergoing either approach were included. Outcomes assessed were conversion to open surgery, resolution of pain, length of admission, postoperative complications, symptom recurrence and time to recurrence. Five retrospective comparative studies comprising 158 patients were included. No differences were found between laparoscopic and robotic approaches in conversion to open, resolution of pain, postoperative complications, length of admission, or overall time to recurrence. However, RMALR showed a significantly longer time to symptom recurrence (9.04 months, 95% CI 4.18-13.89; p = 0.0003). Both LMALR and RMALR are safe and effective for MALS, with comparable perioperative and postoperative outcomes. The longer symptom-free interval after robotic surgery may reflect greater precision in dissection around the coeliac axis. However, further prospective studies with standardised follow-up are needed to validate these findings.
20 June 2026
Read appraisal →International journal of medical informatics
Automated Flow and local LLM-Driven clinical Context Engineering: Precision colorectal cancer recurrence registry
OBJECTIVE: This study develops and validates a deployable, privacy-preserving automated tool to address the labor-intensive nature of colorectal cancer (CRC) recurrence registration. Our tool utilizes a reproducible, two-stage 'Clinical Context Engineering' workflow to mimic expert clinical reasoning and overcome the limitations of handling longitudinal clinical data ambiguity. METHODS: We retrospectively studied 3053 CRC patients (2010-2018). A local Large Language Model (LLM) (Qwen3:14B) analyzed ∼ 19,900 pathology and ∼ 43,900 imaging reports using iterative, patch-based analysis ("raw LLM"). Clinical validation rules were applied to generate "rule-based LLM" output, enhancing explainability and trustworthiness. Both automated methods and the manual Taiwan Cancer Registry (TCR) database were compared against a 20% manual reference standard (N = 602). Full prompts and validation code are provided for complete reproducibility. RESULTS: Under a strict 60-day temporal tolerance, the Rule-Based LLM achieved 90.7% accuracy, comparable to standard TCR processes (92.0%), and 77.2% sensitivity. The application of clinical validation rules significantly improved specificity from 87.7% (Raw LLM) to 93.9% (Rule-Based LLM). In time window analysis, the Rule-Based LLM identified 87.1% of recurrences within 60 days of the reference date. CONCLUSION: Our locally deployed, privacy-preserving, and explainable Clinical Context Engineering framework offers a viable, non-inferior alternative to standard TCR processes, reducing workload while maintaining data quality and fostering trust in AI-assisted cancer registry automation.
16 June 2026
Read appraisal →Life sciences
The interplay of plant polysaccharide structure, gut microbiota metabolism, and host health: Mechanisms and perspectives
Plant polysaccharides, as natural biomolecules, possess the capability to modulate the structure and function of gut microbiota, subsequently influencing host health. Nevertheless, the molecular mechanisms underlying their interactions remain insufficiently understood. This article presents a systematic review of the impact of the chemical structure of plant polysaccharides, including monosaccharide composition and types of glycosidic bonds, on the metabolic preferences of gut microbiota. It emphasizes how structural variations in polysaccharides can promote the proliferation of specific gut microbiota, such as Bacteroidetes and Firmicutes. Additionally, the study analyzes critical enzymatic systems, including glycoside hydrolases (GHs) and polysaccharide lyases (PLs), alongside metabolic pathways associated with the production of short-chain fatty acids (SCFAs) that facilitate the degradation of plant polysaccharides by gut microbiota. Furthermore, it explores the influence of these metabolites on conditions such as obesity, diabetes, inflammatory bowel disease (IBD), and non-alcoholic fatty liver disease. The findings provide a robust theoretical framework for enhancing the utilization efficiency of bioactive polysaccharide components through targeted extraction and characterization techniques, thereby fostering potential advancements in innovative nutritional formulations and pharmacological applications.
16 June 2026
Read appraisal →Journal of hazardous materials
Biomarker-anchored screening of dietary microplastics via a gut microbiota-informed machine learning model
Microplastics (MPs) are increasingly recognized as emerging contaminants in the human diet, yet the absence of unified biomarker-anchored screening thresholds hampers quantitative risk assessment. This study establishes a gut microbiota-anchored machine learning framework that links Firmicutes/Bacteroidetes (F/B) ratio thresholds with real-world dietary MP exposure data, enabling a biomarker-anchored screening of dysbiosis-related signals associated with disease risk. Across the compiled disease cohorts, obesity provided the largest and most data-sufficient contrast in this dataset and was therefore selected as the anchor condition for threshold derivation. Receiver operating characteristic (ROC) analysis determined a model-derived screening cutoff for the F/B ratio (cutoff = 1.08), which was further used to define a three-tier risk classification system. A dataset comprising 558 dietary MP records from 129 studies across 25 countries was incorporated to predict food- and region-specific risk levels. Results reveal that seafood represents the dominant global dietary MP risk source, with mollusca contributing the highest predicted F/B-related risk signal. Spatial stratification indicates that the United States and Ecuador were classified into the highest model-derived tier based on national mean predicted F/B values, followed by high-risk regions such as Vietnam, Turkey, and Ireland, while countries in the Middle East and North Africa remain at moderate risk. These geographic contrasts suggest the combined influence of dietary structure and regional exposure intensity. Overall, we present a biomarker-anchored, machine-learning-enabled screening framework that links dietary MP exposure to predicted changes in a dysbiosis-associated indicator (F/B). This approach can support monitoring prioritization, identification of data gaps, and hypothesis generation for future validation studies.
15 June 2026
Read appraisal →Mammalian genome : official journal of the International Mammalian Genome Society
A novel biological function-based method for mining core genes in rare disease with limited cases
Conventional high - throughput sequencing data analysis methods, relying on large cohorts, are unsuitable for rare diseases with few cases and poor at explaining gene biological functions. This study proposes a biological-function-based method for mining core genes under limited-sample conditions. Using colorectal cancer (CRC) and its rare subtype signet-ring cell carcinoma (SRCC) as examples, differential expression analysis was performed separately for each SRCC sample against CRC samples. Shared genes obtained through progressive intersections were defined as the initial core gene set (List 1). Non-core genes were subjected to functional enrichment analysis, and pathway-associated genes were integrated to construct the non-core gene set. Two independent SRCC samples were subsequently used for secondary mining to obtain the final biologically significant core gene set (List 2). In addition, RankProd (RP), Robust Rank Aggregation (RRA), and an external mucinous adenocarcinoma dataset (GSE281917) were used for validation. First-round mining identified 246 core genes in SRCC, while secondary mining generated 66 and 65 biologically significant core genes from two validation samples with a high degree of overlap. RP identified 1,850 candidate genes and RRA identified 601 candidate genes, among which 64 genes overlapped with the 65 genes identified by this method. In the external mucinous adenocarcinoma dataset, first-round mining identified 144 core genes, while secondary mining generated 122 and 119 core genes with high overlap between validation samples. This method enables the identification of biologically significant core genes in rare diseases under limited-sample conditions, improves the biological interpretability of gene-mining results, demonstrates stable performance in both SRCC and external mucinous adenocarcinoma datasets, and provides a reliable experimental basis for the advancement of precision medicine in rare disease research.
15 June 2026
Read appraisal →Med (New York, N.Y.)
Sintilimab and lenvatinib plus hepatic arterial infusion chemotherapy and embolization as conversion therapy for uHCC: A phase 2 trial
BACKGROUND: Transarterial chemoembolization (TACE) or systemic treatments are recommended for unresectable hepatocellular carcinoma (uHCC) but have low conversion-to-resection rates. This single-arm phase II trial (PLATIC) aims to investigate the conversion efficacy of PD-1 inhibitor sintilimab, lenvatinib plus TACE and hepatic arterial infusion chemotherapy (TACE-HAIC) in uHCC. METHODS: 57 uHCC patients received 200 mg of sintilimab and lenvatinib (8/12 mg for body weight <60 kg or ≥60 kg) and TACE-HAIC every 3-4 weeks. The primary endpoint was conversion-to-resection rate. A historical-based cohort treated with TACE-HAIC was included as control. FINDINGS: After a median of three treatment cycles, 44 (77.2%; 95% confidence interval [CI], 0.64-0.87]) patients underwent conversion resection. The objective response rates were 80.7% (95% CI, 0.68-0.90) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and 43.8% (95% CI, 0.31-0.58) according to RECIST 1.1. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 37 (64.9%) patients; no treatment-related deaths were reported. Among the 44 patients receiving resection, the median progression-free survival (PFS) was 17.3 months, and the median overall survival (OS) was unavailable. After inverse probability of treatment weighting analysis, the PLATIC cohort exhibited longer PFS (hazard ratio [HR] = 0.55, 95% CI, 0.33-0.94; p = 0.020) and OS (HR, 0.50, 95% CI, 0.28-0.92; p = 0.029) than the historical cohort. CONCLUSIONS: Sintilimab, lenvatinib, and TACE-HAIC demonstrated favorable conversion-to-resection rates and acceptable TRAEs in uHCC. FUNDING: Supported by grants from the National Natural Science Foundation of China (no. 82172815 and 82272887) and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center (no. PT22040201).
14 June 2026
Read appraisal →Scientific reports
Performance of GPT-based large language models in hepatocellular carcinoma stratification: liver function assessment, BCLC staging, and treatment recommendations.
Large language models (LLMs) like GPT have been proposed to support complex clinical decision-making. This study evaluated the performance of GPT-based LLM in analyzing clinical, radiological, and laboratory data from patients with hepatocellular carcinoma (HCC) to assess liver function, assign BCLC stage, and recommend treatment. Data from 106 HCC patients (82% male, median age 65 [22-86]) were compiled into anonymized integrated reports. Four GPT-versions (4, o1, o3, 5.4) were prompted-using both short and long instructions-to calculate MELD, ALBI, and Child-Pugh scores, assign BCLC stage, and generate treatment recommendations based on current guidelines. Outputs were compared to expert consensus and tumor board decisions. Errors were categorized by type and source. Time and cost analyses compared GPT to clinical staff. All GPT versions achieved high accuracy (> 85%) in liver function assessment, with MELD calculation being the most error-prone. BCLC staging accuracy ranged from 46.2% (version 4) to 84.0% (o3), with misclassification of radiological reports as the main error source. Reasoning-optimized models (o1, o3) performed best for treatment recommendations, achieving an overall accuracy (correct suggestions and acceptable alternatives) of up to 90.6%. In 9-14% of cases, GPT suggestions were retrospectively more guideline-concordant than tumor board decisions. GPT processing was significantly faster and reduced costs by approximately 300- to 1300-fold compared to clinical staff. GPT-based LLMs show potential as decision-support tools for liver function assessment, BCLC staging, and treatment guidance in HCC. Particularly with reasoning-optimized models and detailed prompting, LLMs may serve as valuable adjuncts in multidisciplinary HCC workflows. However, a non-negligible error rate requires expert oversight and further model refinement.
14 June 2026
Read appraisal →Med (New York, N.Y.)
Neoadjuvant mFOLFOXIRI with or without cadonilimab versus mFOLFOX6 in locally advanced colorectal cancer: A randomized phase 2 trial (OPTICAL-2)
BACKGROUND: The efficacy of neoadjuvant chemotherapy combined with dual immune checkpoint blockade in proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced colorectal cancer (LACRC) remains uncertain. METHODS: In this open-label, randomized phase 2 trial (ClinicalTrials.gov: NCT05571644), eligible patients were randomly assigned (1:1:1) to receive 6 cycles of neoadjuvant mFOLFOXIRI plus cadonilimab, mFOLFOXIRI, or mFOLFOX6, followed by surgery and adjuvant chemotherapy. The primary endpoint was pathological complete response (pCR) in the intention-to-treat population. Secondary endpoints included major pathological response (MPR), safety, locoregional recurrence, disease-free survival, and overall survival. FINDINGS: Between July 2023 and August 2024, 123 patients were randomly assigned (41 per group). Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 (26.8% versus 9.8%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.04 to 13.24; p = 0.046), whereas mFOLFOXIRI alone did not (14.6% versus 9.8%; OR, 1.6; 95% CI, 0.4 to 6.7; p = 0.50). MPR rates were 68.3%, 46.3%, and 43.9%, respectively, and were significantly higher with mFOLFOXIRI plus cadonilimab than with mFOLFOX6 (p = 0.026). Downstaging to ypStage 0-I occurred in 66%, 45%, and 41% of patients in the three groups, respectively, and was significantly higher in the mFOLFOXIRI plus cadonilimab group (p = 0.027). Grade ≥3 adverse events were manageable, with liver enzyme elevation and neutropenia being the most common. CONCLUSIONS: Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 in LACRC, with a manageable safety profile, supporting further investigation. FUNDING: This work was funded by the National Science Fund for Distinguished Young Scholars (82425045) and the National Natural Science Foundation of China (82272800).
14 June 2026
Read appraisal →Journal of global health
Residential green space mitigates genetic susceptibility to incident irritable bowel syndrome in a prospective cohort of 376 749 individuals
BACKGROUND: Environmental exposures may influence irritable bowel syndrome (IBS) pathogenesis, but the interplay between genetic risk, residential green/blue space, and IBS incidence remains unexplored. METHODS: We aimed to study the association between green/blue space and incident IBS, and to assess effect modification by genetic susceptibility. The study included 376 749 UK Biobank participants at baseline. Residential green space was measured using the normalised difference vegetation index (NDVI), and blue space was defined by distance to the nearest water bodies. For time-to-event analyses, we used Cox proportional hazards models, polygenic risk scores (PRS), and mediation analysis to test gene-environment interactions. Results are presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: During a follow-up of 11.73 years, 7091 incident IBS cases were documented. Higher residential green space exposure was associated with reduced risk of incident IBS. Specifically, within a 1000 m buffer, each interquartile range (IQR) increase in NDVI corresponded to a 5% lower IBS risk (HR = 0.95; 95% CI = 0.91-0.98), with consistent effects observed at 800 m and 500 m buffers. Conversely, a greater distance to water bodies was associated with reduced IBS risk. Stratification by PRS revealed a significant interaction: increased green space (1000 m buffer) reduced IBS risk by 8% exclusively among high-genetic-risk individuals (HR = 0.92; 95% CI = 0.88-0.96), whereas no interaction was observed for blue space. Moreover, physical activity mediated the association between green space and IBS. CONCLUSIONS: Increased residential green space exposure is associated with reduced IBS incidence, particularly among individuals with high genetic susceptibility. These findings underscore the importance of urban greening as a public health strategy to mitigate IBS risk, highlighting the potential for targeted environmental interventions to offset genetic predispositions.
13 June 2026
Read appraisal →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
Read appraisal →BMJ open gastroenterology
Safety and efficacy of advanced combination therapies for treating inflammatory bowel disease in adults: a systematic review and meta-analysis
OBJECTIVES: To systematically synthesise available evidence on the safety of advanced combination therapy (ACT) in adults with inflammatory bowel disease (IBD), with secondary exploratory evaluation of efficacy outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of Embase (via Ovid), MEDLINE and PubMed were initially undertaken on 9 May 2025 and updated on 8 April 2026. Additional studies were identified through hand-searching and reference list screening. Eligible publications were restricted to those published between 1 January 2015 and 31 March 2026. ELIGIBILITY CRITERIA: We included randomised controlled trials as well as observational and descriptive studies. Conference abstracts, reviews, editorials and commentaries were excluded. Inclusion was restricted to publications in English. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and assessed risk of bias using Joanna Briggs Institute tools and Cochrane RoB-1. Pooled proportions of total adverse events (TAEs), serious adverse events (SAEs) and treatment discontinuations were calculated using random-effects meta-analysis. Subgroup analyses were conducted by drug class. Where meta-analysis was not appropriate, findings were narratively synthesised. RESULTS: Fifty-two studies (n=2022 participants) were included. The most frequent combinations were anti-TNFa plus integrin inhibitors and interleukin (IL) 23 plus integrin inhibitors. Pooled analyses demonstrated low rates of SAEs (eg, anti-TNFa plus integrin inhibitors: 2.7%, 95% CI 0.22% to 6.86%) and discontinuations (6.38%, 95% CI 2.36% to 11.58%), although heterogeneity was substantial and certainty of evidence was very low, with some analyses based on small sample sizes. CONCLUSION: ACT may be associated with low rates of SAEs in selected patients with refractory IBD; however, the evidence is limited by small sample sizes, heterogeneity and predominantly observational designs. Robust conclusions regarding safety and efficacy cannot be made due to very low GRADE certainty. PROSPERO REGISTRATION NUMBER: CRD420251025883.
13 June 2026
Read appraisal →Journal of ethnopharmacology
Revealing the temporal metabolic trajectory and potential pharmacodynamic substances of Da-Cheng-Qi Decoction in treating patients with acute pancreatitis: A serum metabolomics-based study
ETHNOPHARMACOLOGICAL RELEVANCE: Acute Pancreatitis (AP) is a pancreatic inflammatory disease lacking specific therapeutics. Da-Cheng-Qi Decoction (DCQD) has been proven to alleviate the severity and mortality of AP. However, its underlying mechanisms remain to be fully elucidated. AIM OF THE STUDY: This study aimed to explore DCQD's dynamic metabolic regulatory effects on AP patients and potential pharmacodynamic substances via serum metabolomics and serum pharmacochemistry analysis, with validation in animal models. MATERIALS AND METHODS: AP patients were randomized into conventional therapy (Con) and Con + DCQD groups. Fasting venous blood samples were collected at four time points (admission, 24 h/96 h post-admission, pre-discharge) for biochemical assays and UHPLC-Q-Exactive-Orbitrap-MS analysis. Metabolomics was used to screen AP-related biomarkers, evaluate the two regimens' reversal effects, and compare inter-group differences in metabolic recovery trajectories. Prototypes and metabolites of DCQD were identified, with potential pharmacodynamic substances screened via correlation analysis with AP biomarkers. L-arginine-induced SAP mouse model was used for validation. RESULTS: Serum amylase normalization and C-reactive protein decline were accelerated in Con + DCQD group. Both regimens reversed AP-related energy, amino acid, and lipid metabolic disorders. Adjuvant DCQD therapy accelerated inflammation alleviation and energy homeostasis restoration in early stage, and improved lipid metabolism more comprehensively in middle-to-late stage, with efficacy validated in SAP mice. Forty-eight and 35 blood-migrated components were identified in patients and mice, respectively, with 8 key pharmacodynamic substances screened. CONCLUSIONS: Integrating serum metabolomics and multi-time-point monitoring, this study delineated AP's metabolic recovery trajectory and clarified DCQD's efficacy and dynamic metabolic regulation, providing guidance for its clinical application.
12 June 2026
Read appraisal →Journal of ethnopharmacology
Exploring the molecular mechanism of Shenling baizhu formula in the treatment of ulcerative colitis via the cGMP-PKG signaling pathway
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by symptoms such as persistent diarrhea. Shenlingbaizhu Formula (SLBZ), a classical Chinese herbal formula with centuries of clinical application, has long been used to treat such gastrointestinal disorders. This historical efficacy provides a strong ethnopharmacological rationale for investigating its therapeutic potential and underlying mechanisms in UC. AIM OF THE STUDY: To elucidate the molecular mechanism by which SLBZ ameliorates UC by restoring the intestinal barrier via the sGC-cGMP-PKG signaling pathway. MATERIALS AND METHODS: To systematically investigate the therapeutic effects of SLBZ on UC, we established a dextran sulfate sodium (DSS)-induced colitis model in 57BL/6 mice. Comprehensive evaluations were conducted to assess intestinal barrier function and elucidate underlying mechanisms, including histological analysis, immunofluorescence staining of tight junction proteins, 16S rDNA sequencing for gut microbiota profiling, transcriptomic analysis for gene expression patterns, and Western blot validation of key proteins. Furthermore, a multi-tiered experimental strategy was employed, integrating molecular modeling, machine learning algorithms, graph neural network (GNN) approaches and in vitro experiments using Caco-2 cell monolayers, to systematically validate the sGC-cGMP-PKG signaling pathway and identify bioactive compounds responsible for SLBZ's therapeutic effects. RESULTS: SLBZ treatment markedly alleviated UC symptoms in mice and restored intestinal barrier function through dual mechanisms: upregulation of tight junction proteins (ZO-1/Occludin) and modulation of gut microbiota composition. Transcriptomic analysis pinpointed the cGMP-PKG signaling pathway as a central therapeutic target. Through an integrated approach combining molecular docking, machine learning (random forest algorithm), and deep neural network analysis, we identified soluble guanylate cyclase (sGC) as the primary molecular target, with Choerospondin emerging as a key bioactive component. Mechanistic investigations demonstrated that SLBZ robustly activated the sGC-cGMP-PKG axis both in vivo (colon tissues) and in vitro (Caco-2 cells), culminating in significant suppression of intestinal epithelial apoptosis. CONCLUSION: SLBZ alleviates UC by activating the sGC-cGMP-PKG pathway to restore intestinal barrier function through tight junction upregulation and microbiota modulation. Our study both validates SLBZ's traditional use and identifies this pathway as a novel therapeutic target for UC.
12 June 2026
Read appraisal →Physics in medicine and biology
Unsupervised multimodal deformable medical image registration based on feature perceptual contrast learning
Objective.Multimodal medical image registration has extensive applications in clinical diagnosis and is fundamental for a series of medical analysis tasks. However, the presence of modality differences makes the registration process challenging. Existing methods often employ modality-independent feature descriptors that are sensitive to noise, or attempt to bridge differences within networks, which typically results in translation inaccuracies and misaligned anatomical information.Approach.In this paper, we propose a novel unsupervised approach utilizing a Feature Perceptual Contrast Learning Network (FP-net) to learn descriptors that bridge modality differences while accurately capturing common details. We unify the feature representation of anatomical information under homogeneous and heterogeneous intensity distributions through local sampling-based feature perceptual contrast learning and image reconstruction learning. The trained FP-net is subsequently employed to drive an unsupervised registration framework without requiring ground-truth deformation fields.Main results.We extensively evaluated our method on two public benchmarks: the BraTS 2021 dataset for brain T2-T1 and T1-T1ce registration, and the Learn2Reg 2021 dataset for challenging abdominal CT-MR registration. By passing multimodal image pairs with shape differences through the fixed FP-net, we generate optimization gradients that successfully update the registration network. Quantitative evaluations demonstrate our method's superiority over state-of-the-art baselines. Specifically, our model achieved a dice similarity coefficient (DSC) of 76.3% and 77.7% in tumor-bearing T2-T1 and T1-T1ce tasks, respectively. Furthermore, in the complex abdominal CT-MR task, it reached a DSC of 50.1%, significantly improving structural alignment.Significance.Our method effectively shifts the burden of bridging the modality gap away from the registration network, enabling standard U-Net architectures to achieve state-of-the-art deformable registration. This provides a robust, accurate, and easily deployable unsupervised solution for complex clinical multimodal image analysis.
12 June 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study
PURPOSE: Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC). METHODS: OrigAMI-1 (ClinicalTrials.gov identifier: NCT05379595) is a phase Ib/II study evaluating amivantamab monotherapy in chemorefractory (2-3 prior lines) mCRC. Participants had centrally confirmed RAS/BRAF/EGFR ectodomain wild-type status, without ERBB2/HER2 amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1. RESULTS: By October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE. CONCLUSION: Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.
11 June 2026
Read appraisal →BMJ open
Prediction of ICU length of stay, hospital discharge outcomes and discharge location among ICU-admitted patients diagnosed with viral hepatitis using machine learning: a retrospective cohort study of the MIMIC-IV database
BACKGROUND: Hepatitis, a disease characterised by inflammation of the liver, is a leading global health challenge that contributes to over 1.3 million deaths annually, with hepatitis B and C accounting for many of these fatalities. Intensive care unit (ICU) management of patients is particularly challenging due to the complex clinical care and resource demands. Despite advancements in ICU predictive analytics, limited research has specifically addressed hepatitis patients, creating a gap in optimising care for this population. METHODS: This study focuses on predicting ICU length of stay (LoS), hospital discharge outcomes and discharge location for ICU-admitted viral hepatitis patients using a comparative assessment of machine learning (ML) models. Leveraging data from the Medical Information Mart for Intensive Care-IV database, which includes around 94 500 ICU patient records, this study uses sociodemographic details, clinical characteristics and resource utilisation metrics to develop predictive models such as Random Forest, Logistic Regression, Gradient Boosting Machines and Generalised Additive Model with Negative Binomial Regression. RESULTS: Among 3875 ICU-admitted hepatitis patients, Random Forest classification outperformed Logistic Regression in predicting discharge outcomes, achieving higher accuracy (0.87 vs 0.82) and greater discriminative ability (area under the receiver operating characteristic curve 0.95 vs 0.89). For ICU LoS prediction, Random Forest regression applied to log-transformed LoS demonstrated strong performance (R² up to 0.82), while the generalised additive model with negative binomial distribution explained approximately 76% of LoS variance. Prediction of discharge location yielded moderate performance across Gradient Boosting and multinomial logistic regression models (accuracy 0.55 and 0.56), reflecting challenges associated with multi-class imbalance. Variable importance analyses across ML models consistently identified medication counts, procedure counts, comorbidity burden, age, race and total LoS as the most influential predictors of discharge outcomes and discharge location. CONCLUSIONS: This study demonstrates the value of ML models for predicting clinical outcomes for hepatitis patients, including ICU LOS and hospital discharge status. The results underscore the influence of factors like race and age, revealing disparities that must be addressed in predictive care strategies. While the models show promise, challenges such as variability in prolonged stays and limited multiclass prediction accuracy point to the need for ongoing refinement and research.
11 June 2026
Read appraisal →Biochemical and biophysical research communications
Efferocytosis-related biomarkers and immune infiltration in pancreatic ductal adenocarcinoma based on single-cell sequencing and machine learning: a comprehensive bioinformatics analysis and experimental validation
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and lethal malignancy, with its complex tumor microenvironment (TME) severely limiting therapeutic efficacy. Efferocytosis, a key process by which macrophages clear apoptotic cells, has been demonstrated to influence tumor initiation and progression by modulating immune responses, promoting M2 polarization, and facilitating immune evasion. Yet, the function and predictive significance of genes linked to efferocytosis in PDAC are still not fully understood. METHODS: This study integrated TCGA-PDAC, GTEx, and GEO datasets with single-cell transcriptomics to screen and analyze expression patterns and functions of efferocytosis-related genes (ERGs) in PDAC. Differential analysis, single-cell clustering, cell communication, and pseudo-time analysis revealed heterogeneity in macrophage efferocytosis. Subsequently, a six-gene prognostic model (CD36, ITGAV, PANX1, PPARG, S100A4, THBS1) was constructed and validated using Cox and LASSO regression. Concurrently, GSEA pathway analysis, immune infiltration assessment, and immunotherapy response prediction were conducted. Key gene functions were validated through molecular docking, RT-qPCR, western blotting, and functional experiments. RESULTS: Single-cell analysis revealed that macrophages exhibit the highest efferocytic activity within the PDAC microenvironment, demonstrating significant subpopulation heterogeneity. Differential analysis identified 23 key intersecting genes, ultimately yielding a risk model comprising six core genes. The model exhibited strong predictive accuracy in both the training and validation groups (notable AUC). Additional examination showed that patients at high risk showed a heightened presence of pathways linked to the reprogramming of energy metabolism and inflammatory reactions, along with heightened genomic instability and immunosuppressive TME traits, suggesting a grim prognosis. Experimental validation confirmed that knockdown of THBS1 significantly inhibited the proliferation, migration, and invasion of PDAC cells. CONCLUSION: The research clarifies the diverse nature of macrophage efferocytosis in PDAC and its crucial function in the restructuring of TME. It establishes and validates a six-gene risk prediction model, clarifying the functional significance of core genes, including THBS1. These findings provide novel molecular tools for PDAC prognosis assessment and identify potential targets for immunotherapy and personalized treatment strategies.
11 June 2026
Read appraisal →Critical care explorations
Artificial Liver Support Effectively Removes Immunosuppressive Bile Acids From Circulation in Patients With Severe Liver Failure: A Proof of Concept Study
OBJECTIVE: Bile acids that induce immunosuppression through activation of the Takeda G protein-coupled receptor 5 (TGR5) have recently been identified in the circulation of patients with liver failure and sepsis. These bile acids are associated with increased susceptibility to infection and a high short-term mortality. Furthermore, TGR5 activation by bile acids has been implicated in the development of pruritus. However, therapies targeting TGR5-activating bile acids in patients have not yet been reported. This study investigates the effects of two artificial liver support systems, the Molecular Adsorbent Recirculating System (MARS) and the open albumin dialysis (OPAL). DESIGN: Proof of concept study, multicenter study. SETTING: University Hospital Jena, University Hospital Ulm, and University Hospital Münster, Germany. PATIENTS: Patients with severe liver failure, as defined by the Sequential Organ Failure Assessment hepatic sub-score (i.e., bilirubin > 12 mg/dL). INTERVENTIONS: Patients with severe liver failure were randomized to receive one session of MARS or OPAL for 8 hours, followed by crossover to the other treatment on the next day. MEASUREMENTS AND MAIN RESULTS: Bilirubin, circulating total and individual bile acids, albumin function, and TGR5 activation induced by circulating bile acids were assessed before and after each treatment session. Both OPAL and MARS significantly removed bilirubin, as well as individual and total bile acids from circulation. OPAL was superior to MARS in removing protein-bound lipophilic bile acids and restoring patients' albumin function (i.e., albumin-binding capacity, detoxification efficiency, and binding efficiency). TGR5 activation induced by circulating bile acids was reduced by 60% with OPAL compared with 39% with MARS (median values, p = 0.051). CONCLUSIONS: Artificial liver support systems effectively remove immunosuppressive bile acids from circulation. The clinical implications of bile acid reduction, however, require further study.
11 June 2026
Read appraisal →Bioorganic chemistry
In silico discovery and biological evaluation of a novel selective HDAC8 inhibitor featuring 1H-pyrazolo[3,4-b]pyridine scaffold
Histone deacetylase 8 (HDAC8), a pivotal epigenetic regulator orchestrating chromatin remodeling and transcriptional control, has emerged as a compelling anticancer target owing to its frequent dysregulation in malignancies. The development of isoform-selective inhibitors, however, confronts substantial challenges because of the pronounced structural conservation across HDAC isoforms. This study developed a high-efficiency drug screening pipeline primarily leveraging artificial learning (AI) models and molecular simulation techniques, and further evaluated the biological activity of computationally prioritized compounds through enzymatic inhibition assays and cellular experiments. The structurally novel compound Cmpd.16 was successfully identified, exhibiting promising inhibitory activity against HDAC8 (IC50 = 0.16 ± 0.01 μM) and moderately inhibited HCT116 cell proliferation mainly through the induction of apoptosis and G2/M phase cell cycle arrest. Subsequently, molecular dynamics simulations were employed to investigate the binding conformation of Cmpd.16 within the active pocket, and the key residues identified through free energy decomposition further elucidated the drug-target binding mode. Collectively, Cmpd.16, featuring 1H-pyrazolo[3,4-b]pyridine scaffold, was discovered via an efficient screening workflow, offering valuable insights to guide the rational design of HDAC8-targeted agents.
7 June 2026
Read appraisal →Techniques in coloproctology
Robotic versus laparoscopic TME for rectal cancer: meta-analysis of pathological quality indicators
BACKGROUND: Total mesorectal excision (TME) quality is a key determinant of oncological outcomes in rectal cancer. While robotic surgery offers technical advantages over laparoscopy in the confined pelvis, its superiority regarding pathological outcomes remains debated. We conducted a meta-analysis comparing robotic and laparoscopic TME focusing on quality indicators of TME and risk factors for incomplete TME. METHODS: A PROSPERO-registered systematic search of PubMed and EMBASE up to May 2025. Comparative studies reporting pathological outcomes of robotic versus laparoscopic TME were included. Primary endpoints were TME completeness, circumferential resection margin (CRM) positivity and distal resection margin (DRM) positivity. Secondary analysis included baseline characteristics (male gender, BMI, bulky tumours, distance to anal verge, neoadjuvant radiotherapy) and local recurrence rate. RESULTS: Fifty-six studies (27,648 patients; robotic 10,629, laparoscopic 17,019) were included. Robotic surgery was associated with significantly more complete TME specimens (OR 1.50, 95% CI 1.23-1.82, p < 0.001) and fewer positive DRMs (OR 0.68, 95% CI 0.48-0.97, p = 0.031). CRM positivity was comparable between groups (OR 0.93, 95% CI 0.77-1.12, p = 0.44). In random-effects analysis, there was a non-significant trend towards fewer local recurrences after robotic TME (OR 0.75, 95% CI 0.54-1.05, p = 0.09). Robotic cohorts more frequently included male patients, distal tumours and neoadjuvant chemoradiotherapy, suggesting preferential selection of technically challenging cases. CONCLUSIONS: Robotic TME is associated with higher specimen completeness and lower DRM positivity compared with laparoscopic TME, while CRM positivity and local recurrence rates appear broadly similar. These data support the use of robotics as a primary minimally invasive option for mid-low rectal cancer; however, as a result of low certainty of evidence, these findings should be interpreted cautiously. SYNOPSIS: This meta-analysis provides the most up-to-date synthesis of pathological outcomes comparing robotic and laparoscopic TME for rectal cancer, incorporating data from 56 studies including the recent REAL and COLRAR randomized trials. Unlike previous reviews, it exclusively analyses total mesorectal excision procedures, excluding partial or high anterior resections, thereby eliminating a major source of heterogeneity. The findings demonstrate that robotic TME is associated with higher specimen completeness and fewer positive distal margins, even in technically demanding mid- and low-rectal cancers, supporting the role of robotics as the preferred minimally invasive approach in mid-low, difficult tumours.
1 June 2026
Read appraisal →JMIR research protocols
Implementation of Mobile-Based Programs for Alcohol Cessation in the Treatment of Alcohol-associated Liver Disease: Protocol for a Type 1 Hybrid Implementation-Effectiveness Trial
BACKGROUND: The rising burden of alcohol-associated liver disease (ALD) calls for effective interventions. Alcohol cessation remains the only intervention known to reduce long-term ALD morbidity and mortality. Integrating treatment for alcohol use disorder with medical and hepatology care shows significant promise. OBJECTIVE: This study aims to conduct a randomized, controlled, type 1 hybrid implementation-effectiveness trial in patients with ALD to evaluate an evidence-based smartphone app for alcohol use disorder (Connections). The primary aim is to (1) compare the effectiveness of the Connections app plus usual care to the effectiveness of usual care alone on days of alcohol abstinence for patients with ALD and (2) assess the implementation of the Connections app in the ALD population using a multilevel model of system change to determine facilitators and barriers to the successful adoption of the app at the patient, provider, and clinic levels. METHODS: Study procedures were approved by the Institutional Review Board on March 13, 2024. Patients are recruited from General Hepatology and Multidisciplinary Clinics in Wisconsin and Michigan. Participants are randomized to an intervention (Connections + treatment as usual) or no intervention (treatment as usual). During the 6-month enrollment period, participants complete monthly e-surveys measuring alcohol consumption and quarterly e-surveys measuring patient health indicators and behaviors. Patients earn up to US $240 for participation. RESULTS: This study was funded in September 2023. Recruitment began in June 2024 and is ongoing. As of February 26, 2026, 144 participants have been enrolled in the study. Of these, 65 (45.1%) have completed all the study activities. We aim to recruit 298 participants through 2027, with analysis and results publication estimated in 2028. CONCLUSIONS: Implementation insights highlight the importance of flexibility and strong provider relationships. Challenges include reliance on technology, which limits access for patients with low digital literacy, and the risk of loss to follow-up. This trial is the first fully powered implementation-effectiveness study of a mobile health app for alcohol cessation in ALD, testing a new care model that integrates multidisciplinary expertise. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/94231.
1 June 2026
Read appraisal →Journal of gastrointestinal cancer
Durable Survival Outcomes After Liver Transplantation for Colorectal Liver Metastases: A Systematic Review and Single-arm Meta-analysis of Prospective Clinical Trials
BACKGROUND: Liver transplantation (LT) has emerged as a potential treatment option for selected patients with colorectal liver metastases (CRLM), but existing meta-analyses are limited by heterogeneous populations and mixed treatment modalities. METHODS: A systematic review and single-arm meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting outcomes following LT for CRLM were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS) at predefined time points. Secondary outcomes included adverse events. Pooled proportions were calculated using random-effects models with logit transformation and Hartung-Knapp adjustment. Heterogeneity was assessed using the I² statistic. RESULTS: Four prospective studies (1 RCT, 3 prospective cohorts) comprising 118 patients were included. Studies were conducted in Norway (SECA-I, n = 21; SECA-II, n = 15), the United Kingdom (n = 50), and a European multicentre RCT (TransMet, n = 32). Median age ranged from 55 to 58 years; all patients had liver-only metastases with resected primary tumors and had received pre-transplant chemotherapy. The pooled 3-year OS was 69% (95% CI, 52-82%; I² = 0.0%), and the pooled 5-year OS was 62% (95% CI, 36-83%; I² = 14.6%). The pooled 3-year PFS was 33% (95% CI, 7-76%), with substantial heterogeneity (I² = 62.8%). The pooled incidence of adverse events was 41% (95% CI, 25-60%; I² = 0.0%). Sensitivity analyses confirmed the robustness of pooled estimates. The retrospective literature also supported the finding that LT can achieve meaningful long-term survival in carefully selected patients. CONCLUSIONS: In carefully selected patients with CRLM, LT is associated with durable long-term survival and an acceptable safety profile, supporting further prospective evaluation and refinement of selection criteria.
31 May 2026
Read appraisal →Medicine
Burden of Helicobacter pylori infection in children and adults in Vietnam: A systematic review and meta-analysis of prevalence
BACKGROUND: Although Helicobacter pylori (H. pylori) prevalence has declined in many high-income countries, data from Vietnam remain limited and fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of H. pylori infection in Vietnamese adults and children. METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for observational studies published between January 2000 and September 2025. Eligible studies reported H. pylori prevalence in Vietnamese populations using validated diagnostic methods. Random-effects meta-analyses were used to calculate pooled prevalence estimates with 95% confidence intervals (CIs). Subgroup analyses were conducted by age group, geographic area, and study setting. RESULTS: Twenty-five studies met inclusion criteria, comprising 8204 adults and 4641 children. The pooled prevalence of H. pylori infection was 58.7% (95% CI: 49.9%-67.2%) in adults and 77.2% (95% CI: 67.1%-86.0%) in children, with high heterogeneity across studies (I2 > 98%, P < .001). Among adults, prevalence was 56.4% in those aged <50 years and 65.8% in those ≥50 years (P = .455). Prevalence was lower in rural areas (46.8%) compared to urban areas (60.7%) (P = .045), with no significant difference between community- and hospital-based settings (P = .723). Funnel plot assessment did not indicate evident publication bias. CONCLUSION: H. pylori infection remains common in the populations represented in this study, particularly among urban and healthcare-seeking groups in Vietnam. These findings underscore the need for expanded surveillance and monitoring to better characterize H. pylori infection patterns and inform appropriate response strategies.
31 May 2026
Read appraisal →Medicine
Associations of TyG-related indices with NAFLD-related outcomes: A systematic review and meta-analysis
BACKGROUND: The triglyceride-glucose (TyG) index and related composite indices have been increasingly studied as accessible metabolic markers for fatty liver disease. However, evidence remains difficult to interpret because different TyG-related indices have been evaluated across heterogeneous populations and nonalcoholic fatty liver disease (NAFLD)-related outcomes. We conducted a systematic review and meta-analysis to clarify the pooled associations that could be formally synthesized and to summarize the broader descriptive evidence. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, VIP Database, and China Biology Medicine Database from inception to December 2025. Observational studies evaluating the TyG index or related composite indices, including TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio, in relation to NAFLD-related outcomes were eligible. Random-effects meta-analyses were performed in R. Only studies with sufficient comparability in exposure operationalization, outcome definition, and effect-size reporting were quantitatively pooled; the remaining studies were retained in the descriptive synthesis. RESULTS: Nineteen studies involving 212,618 participants were included in the systematic review, including 16 cross-sectional studies and 3 cohort studies. Of these, 8 studies contributed to at least 1 quantitative synthesis. In continuous-scale analyses, higher TyG levels were associated with increased odds of NAFLD/steatosis (5 studies; pooled odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.55; I2 = 85.7%). In highest-versus-lowest analyses, the association remained significant (4 studies; pooled OR, 4.36; 95% CI, 3.39-5.61; I2 = 92.8%). TyG-body mass index (2 studies; pooled OR, 1.04; 95% CI, 1.03-1.05; I2 = 0.0%) and TyG-waist circumference (2 studies; pooled OR, 1.01; 95% CI, 1.01-1.01; I2 = 15.1%) were also positively associated with NAFLD/steatosis. TyG-waist-to-height ratio showed a positive association in supportive synthesis, but evidence for liver fibrosis and nonalcoholic steatohepatitis remained limited and was mainly descriptive. CONCLUSION: TyG-related indices were consistently associated with NAFLD/steatosis across the available literature. The basic TyG index had the broadest evidence base, whereas composite indices suggested possible additional value in selected settings. These markers may be useful for metabolic fatty liver risk stratification, but further studies with standardized outcome definitions and clearer exposure parameterization are needed.
31 May 2026
Read appraisal →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
Read appraisal →Progress in biomedical engineering (Bristol, England)
Wearable sensors for monitoring neurogenic dysphagia: a scoping review
Neurological disorders, such as Parkinson's disease and stroke, often lead to neurogenic dysphagia, a swallowing disorder that compromises nutrition and increases the risk of malnutrition, aspiration of food, and even death. Although instrumental assessments remain the gold standard for evaluating swallowing function, their invasiveness, cost, and reliance on specialized clinical facilities limit their routine use. A systematic search was conducted in PubMed, Scopus, IEEE Xplore, and Web of Science, including only peer-reviewed studies using non-invasive wearable devices for assessing and monitoring dysphagia in neurological disorders. The initial search identified 1669 records, and an updated search retrieved 128 additional records. After screening, 24 studies met the inclusion criteria. Accelerometers and surface electromyography sensors were the most frequently used, either alone or in multimodal configurations. Multimodal approaches generally provided more accurate and comprehensive assessments than single-sensor systems. However, validation with gold-standard methods was performed in only half of the studies, and considerable heterogeneity was observed in sensor placement, study protocols, and signal-processing strategies. Wearable sensing technologies represent a non-invasive and scalable solution for assessing neurogenic dysphagia. To enable clinical translation, future research should focus on standardized methodologies, robust validation, and the integration of artificial intelligence for more precise swallowing assessment in individuals with neurological disorders.
29 May 2026
Read appraisal →The New England journal of medicine
Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer
BACKGROUND: Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy and safety as first-line therapy in phase 2 studies involving patients with HER2-positive gastroesophageal adenocarcinoma. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival. RESULTS: At a median follow-up of 25.9 months, progression-free survival was longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons). Overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratio for death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004). At this interim analysis, overall survival did not differ significantly between zanidatamab-chemotherapy (median, 24.4 months) and trastuzumab-chemotherapy (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P = 0.06). The incidence of grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively. CONCLUSIONS: Zanidatamab plus chemotherapy, both with and without tislelizumab, led to longer progression-free survival than trastuzumab plus chemotherapy among patients with HER2-positive advanced gastroesophageal adenocarcinoma. At this interim analysis, overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy; further analyses are planned to assess zanidatamab-chemotherapy. Diarrhea was a common adverse event. (Funded by Jazz Pharmaceuticals and others; HERIZON-GEA-01 ClinicalTrials.gov number, NCT05152147.).
29 May 2026
Read appraisal →PloS one
One out of four patients with pancreatic cancer experience psychological symptoms: A systematic review and meta-analysis
The death rate from pancreatic cancer is one of the highest of all cancers, with increasing incidence every year over the past decades. As the prognosis remains extremely poor, this trend brings not only a growing clinical challenge, but also a significant psychological toll for patients. In comparison to other types of cancer, our understanding of the psychological burden of such a deadly disease is still limited. Recognizing and addressing the psychological aspects of pancreatic cancer are crucial for comprehensive patient care. We, therefore, aimed to quantify the psychological burden of patients with pancreatic cancer. We conducted a systematic search (PROSPERO: CRD42022288805) of MEDLINE, Cochrane, and Embase databases to identify articles reporting on the prevalence of psychological symptoms among patients with pancreatic cancer. The symptoms examined were depression, anxiety, distress, fatigue, sleep disturbances. Study quality for the included studies was assessed using the Joanna Briggs Institute tool. Relevant data were extracted and exported for quantitative synthesis. The meta-analysis of the proportion of symptoms with a 95% confidence interval (CI) was conducted using frequentist random-effects models. Subset analyses were performed based on the severity of depression. A total of 28 articles were included in the meta-analysis and 31 in the systematic review. Our results showed that the proportion of depression (19 studies; 78,930 patients) was 0.27 (95% CI: 0.18-0.39). The proportion for anxiety (18 studies; 26,538 patients) was 0.29 (95% CI: 0.16-0.46; for distress (6 studies; 2746 patients) 0.43 (95% CI: 0.25-0.63); for fatigue (7 studies; 11 338 patients) 0.40 (95% CI: 0.21-0.63); and for sleep disturbances (3 studies; 10,645) 0.31 (95% CI: 0.06-0.77). These findings highlight the urgent need to integrate psychological care into pancreatic cancer treatment. Future research should explore sources of heterogeneity to better identify which approaches provide the most psychological benefit and tailor interventions to patient needs accordingly.
28 May 2026
Read appraisal →JMIR cancer
Machine Learning-Based Survival Prediction Models for Young Patients With Gastric Cancer: Model Development and Validation Study
BACKGROUND: Despite a global decline in the incidence of gastric cancer (GC), the number of cases diagnosed among younger individuals continues to increase. Several studies have been conducted to develop predictive models of mortality in patients with GC. OBJECTIVE: We developed 3- and 5-year survival prediction models for young patients with GC based on machine learning-based survival modeling approaches. METHODS: Data from 813 young patients (≤50 years) diagnosed with GC between 2013 and 2015 were retrieved from the Gastric Cancer Public Staging Database. Among these 813 patients, data from 569 (70%) and 244 (30%) were allocated to the model training and testing datasets, respectively. Random survival forest, gradient boosting survival analysis, extra survival tree, and the Cox proportional hazards model were applied to predict survival outcomes at the 3- and 5-year time horizons. Model performance was assessed and quantified using the concordance index (C-index) metric. For the machine learning prediction models, the mean C-index values and corresponding 95% CIs were estimated across 100 repeated training iterations. RESULTS: For the random survival forest model, the C-index for predicting 3-year mortality was 95.89% (95% CI 95.80%-95.97%), whereas the C-index for predicting 5-year mortality was 91.82% (95% CI 91.68%-91.96%). In the gradient boosting survival analysis model, the C-index for predicting 3-year mortality was 95.32% (95% CI 95.31%-95.33%), and the C-index for predicting 5-year mortality was 89.98% (95% CI 89.95%-90.01%). For the extra survival tree model, the C-index for predicting 3-year mortality was 95.53% (95% CI 95.46%-95.60%), whereas the C-index for predicting 5-year mortality was 94.60% (95% CI 94.50%-94.70%). In addition, the Cox proportional hazards model showed a C-index of 94.15% for predicting 3-year mortality and 82.26% for predicting 5-year mortality. Tumor stage and tumor size were the primary predictive variables used to train the models for mortality prediction at different time points. Other variables exhibited varying levels of predictive contribution across different time points. CONCLUSIONS: These findings may facilitate the identification of high-risk young patients with GC who may benefit from more aggressive treatment strategies by enabling the prediction of mortality risk at different time points.
28 May 2026
Read appraisal →Cell reports
Artificial intelligence-driven donor-recipient gut microbiome matching for optimized fecal microbiota transplantation
Fecal microbiota transplantation (FMT) has emerged as a promising therapy for gastrointestinal diseases, yet its clinical efficacy remains individually variable. Here, we analyze multi-kingdom and functional profiles in pre- and post-FMT metagenomes from 515 FMTs across 30 cohorts and 12 diseases, in which 94 metagenomes from 44 FMTs are newly collected. We reveal a robust association between clinical efficacy and post-FMT microbiome convergence of recipients toward donors, across diseases. To predict post-FMT microbial convergence, we develop MOZAIC (Microbiome Matching Optimization via Artificial Intelligence), a framework that integrates multi-dimensional donor-recipient microbiota features. MOZAIC achieves an average area under the curve (AUC) of 0.88 and accuracy/recall >0.80 in forecasting microbiome convergence, with 78.7% accuracy in predicting clinical outcomes, and retrospectively simulates a 1.44-fold improvement (from 49.4% to 71.0%) in clinical response rates over baseline. This study establishes microbiome convergence as a key mediator of FMT and provides a scalable tool for precision matching in microbiota-based therapies.
28 May 2026
Read appraisal →Journal of radiation research
Deep learning-based dose prediction in proton beam therapy for hepatocellular carcinoma: comparison of network architectures and loss functions
In proton beam therapy (PBT) for hepatocellular carcinoma (HCC), deep learning (DL)-based dose prediction offers clinical value by providing immediate reference dose distributions as a guideline tool for treatment planners and enabling virtual PBT dose assessment at institutions lacking PBT facilities to support clinical decision-making. This study proposes a dose gradient-aware DL training approach and a beam arrangement-free framework that predicts dose distributions from computed tomography (CT) images and target/organs-at-risk structures without requiring beam arrangement inputs. Using data from 172 HCC patients, we systematically compared 20 DL models combining five architectures with four loss functions, including a novel dose gradient-aware loss capturing PBT-specific dose distribution characteristics arising from the Bragg peak. Prediction accuracy was evaluated using dose metrics for clinical target volume, planning target volume, and normal liver, 10% dose region volume assessment, visual examination, Dice similarity coefficient (DSC) for 10% dose region, and dose-volume histogram (DVH) analysis. DL models employing dose gradient-aware loss demonstrated reduced prediction errors in target volume dose metrics, achieved the lowest errors in 10% dose region volume when combined with U-Net (MAE: 35.4 cm3, RMSE: 51.3 cm3), attained the highest DSC (0.88 ± 0.05), showed the closest DVH agreement with clinical plans for both target structures and normal liver. A comprehensive evaluation consistently confirmed the superiority of dose gradient-aware loss across all metrics, demonstrating the importance of physics-informed, dose gradient-aware learning for accurate PBT dose distribution prediction. Particularly, DL models combining simple architectures with dose gradient-aware loss predicted doses that closely approximated clinical doses in PBT.
27 May 2026
Read appraisal →Journal of the International Society of Sports Nutrition
The effect of probiotic and synbiotic supplementation on sleep parameters in exercised population: a systematic review and synthesis without meta-analysis (SWiM) of randomized controlled trials
BACKGROUND: Sleep is crucial for recovery and optimal performance in athletes; however, poor sleep is common during periods of intensive training or competition. The microbiota-gut-brain axis suggests probiotics and synbiotics could modulate sleep, but evidence in exercised populations is limited. OBJECTIVE: To systematically review randomized controlled trials (RCTs) assessing the effects of probiotic and synbiotic supplementation on sleep in exercised populations, using a Synthesis Without Meta-analysis (SWiM) approach. METHODS: PubMed, Scopus, Web of Science, and ProQuest were searched up to September 2025. Eligible studies were RCTs including exercised individuals, testing probiotics or synbiotics, and reporting sleep outcomes. Data extraction, risk of bias assessment (RoB 2), and narrative synthesis followed SWiM guidelines. RESULTS: Six RCTs (n = 180) were included: four probiotic and two synbiotic interventions lasting 4-17 weeks. Populations included athletes from multiple sports across four continents. Nine of twelve primary sleep outcomes favored supplementation, with significant effects for probiotics (combined p < 0.01) and synbiotics (p < 0.001). Benefits were most consistent for subjective sleep quality and, in some cases, sleep latency. Secondary outcomes showed occasional reductions in stress, anxiety, and fatigue. CONCLUSION: Probiotic and synbiotic supplementation may improve sleep in exercised populations, especially perceived quality and latency. Evidence supports cautious, adjunctive use, but larger, standardized trials are needed to confirm effects.PROSPERO registration number: CRD420251151264.
26 May 2026
Read appraisal →Journal of gastrointestinal cancer
Trend of Adjuvant Radiation in Resected Pancreatic Ductal Adenocarcinoma: Evaluation of RTOG 0848 with a Large National Database
PURPOSE: Adjuvant radiation (AR) remains a controversial treatment modality for pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the findings of the RTOG 0848 trial assessing the benefits of adjuvant radiation in node-negative disease utilizing a national database. METHODS: Utilizing the National Cancer Database, all patients diagnosed with non-metastatic PDAC, who underwent pancreatectomy, were included (2004-2019). The trend of adjuvant radiation utilization was evaluated. Overall survival in a cohort of patients mimicking the RTOG 0848 protocol was examined as were clinicodemographic and pathologic predictors of adjuvant radiation. RESULTS: Overall rates of adjuvant radiation decreased from 45 to 12%, while neoadjuvant radiation rates simultaneously increased from 4 to 12%. Positive margins and nodal disease were the strongest predictors of adjuvant radiation receipt (OR 1.7[ 95% CI: 1.6-1.7] p < 0.001 and OR: 1.1 [95% CI: 1.1-1.2] p < 0.001; respectively). Both high-risk pathologic groups experienced a decline in the use of adjuvant radiation over time, even after exclusion of patients who received neoadjuvant radiation. After application of the RTOG 0848 criteria, improved overall survival was observed in patients with node-negative and positive margins (adjuvant radiation: 28.6 [95% CI: 25.4-31.8] vs 23.0 [95% CI: 19.4-26.7] months; p = 0.005). In the margin positive cohort, adjuvant radiation was significantly associated with reduced mortality (HR: 0.791 [95% CI: 0.7-0.9]; p < 0.001). CONCLUSION: Evaluation of RTOG 0848 in the setting of real-world data indicates a role for adjuvant radiation for patients with margin-positive, node-negative pancreatic cancer. This highlights the essential role of multidisciplinary discussions regarding patients with PDAC care.
26 May 2026
Read appraisal →European journal of pediatrics
Safety and efficacy of liposomal iron for iron deficiency anemia in pediatric population: A systematic review and meta-analysis of randomized controlled trials
Iron deficiency anemia (IDA) remains a public health problem in children. Conventional iron therapy is effective but often causes gastrointestinal adverse effects that reduce adherence. Liposomal iron has been developed to enhance absorption and improve tolerability. This systematic review and meta-analysis evaluated the efficacy and safety of liposomal iron compared with conventional iron formulations in pediatric patients with IDA. We searched PubMed, Scopus, Web of Science, and the Cochrane Library up to February 21, 2026 for randomized controlled trials (RCTs) comparing liposomal iron with conventional oral iron in children with IDA. Analyses were performed using R software with the meta package. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. Subgroup analyses according to follow-up duration. Four RCTs involving 454 children were included. At 6 months, liposomal iron produced a significantly greater increase in hemoglobin compared with conventional iron (MD 0.96 g/dL, 95% CI 0.09-1.82; P = 0.03), although heterogeneity was substantial (I2 = 92.9%). No significant differences were observed at earlier time points. Liposomal iron significantly reduced total iron-binding capacity (MD - 35.52 μg/dL; P < 0.0001) and increased mean corpuscular hemoglobin (MD 1.83 pg; P < 0.0001). Liposomal iron was associated with fewer adverse events (RR 0.29; P = 0.02) and lower risk of constipation (RR 0.56; P = 0.02).Conclusion: Liposomal iron offered better tolerability and was non-inferior to conventional iron for most hematologic outcomes. Evidence remains preliminary and larger RCTs are needed to confirm its efficacy in pediatric IDA.
26 May 2026
Read appraisal →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
Read appraisal →Journal of robotic surgery
Short-term outcomes of robot-assisted versus conventional minimally invasive esophagectomy for resectable esophageal cancer: a systematic review and meta-analysis
Robot-assisted minimally invasive esophagectomy (RAMIE) has emerged as an alternative to conventional minimally invasive esophagectomy (MIE) for esophageal cancer, but its short-term perioperative advantages remain uncertain. To compare early postoperative outcomes of RAMIE and MIE in patients with resectable esophageal cancer, this systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines. PubMed was searched for randomized controlled trials, propensity score-matched studies, and retrospective comparative studies published between January 2005 and December 2024. Adult patients undergoing RAMIE or conventional MIE for resectable esophageal cancer were included. Random-effects models were used to pool standardized mean differences and odds ratios with 95% confidence intervals. Study quality was assessed using the MINORS criteria and Cochrane RoB 2 tool. In addition, a post hoc GRADE assessment was carried out for key outcomes to evaluate the certainty of evidence. Forty-one studies involving 13,321 patients were included, of whom 4,327 underwent RAMIE and 8,994 underwent MIE. Compared with MIE, RAMIE was associated with lower blood loss, reduced conversion to open surgery, higher total lymph node yield, greater left recurrent laryngeal nerve lymph node harvest, fewer pulmonary complications, and lower overall postoperative morbidity. ICU stay and hospital stay were also e shorter after RAMIE, whereas operative time was longer. No significant differences were observed in R0 resection, anastomotic leak, recurrent laryngeal nerve palsy, cardiac complications, chyle leak, surgical site infection, or 30- and 90-day mortality. Post hoc GRADE assessment showed that the certainty of evidence was very low across key outcomes, mainly because of the predominance of non-randomized studies, substantial heterogeneity across several pooled analyses, and outcome-specific concerns regarding imprecision and publication bias. RAMIE is safe and may offer some short-term perioperative advantages over conventional MIE without clear evidence of increased major morbidity or short-term mortality. However, the certainty of evidence across key outcomes was very low, and the predominance of nonrandomized studies and substantial heterogeneity across several analyses warrant cautious interpretation. Further adequately powered randomized trials are required.
25 May 2026
Read appraisal →Hepatology communications
Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites-A randomized trial (MIDAS trial)
BACKGROUND: Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess. METHODS: In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications. RESULTS: One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups. CONCLUSIONS: Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.
25 May 2026
Read appraisal →Journal of gastrointestinal cancer
Optimal First-line Immune-related Therapy Selection for Advanced Gastric Cancer: A Systematic Review and Network Meta-analysis
PURPOSE: Although immune checkpoint inhibitors combined with chemotherapy improve survival in advanced gastric cancer (AGC), comparative evidence across first-line regimens remains insufficient. This study aimed to systematically evaluate their relative efficacy and safety. METHODS: PubMed, Embase, the Cochrane Library, Web of Science, and major conferences were searched up to February 28, 2025. Eligible RCTs comparing ICI-related regimens as first-line AGC treatment were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: Eleven RCTs involving 8,999 patients, six integrated strategies, and twelve specific regimens were included. Dual-target ICI-chemo and single ICI-chemo showed significant survival benefits over chemotherapy, whereas dual ICIs±chemo and single ICI alone did not. Dual-target ICI-chemo was associated with significantly better survival than both dual ICIs±chemo and single ICI±chemo. Among the specific regimens, cadon-chemo achieved the most favorable OS and PFS. No significant OS differences were observed among the single ICI-chemo regimens. In PD-L1-positive subgroups, both dual-target ICI-chemo and single ICI-chemo significantly improved survival compared with chemotherapy, with cadon-chemo being most effective in CPS ≥ 10 and CPS ≥ 1, and SHR1701-chemo in CPS ≥ 5. In the CPS < 5 subgroup, dual-target ICI-chemo significantly improved OS, while single ICI-chemo showed a trend toward benefit. However, no ICI-based strategy demonstrated benefit in CPS < 1. CONCLUSIONS: Dual-target ICI-chemo appears to be the most effective first-line strategy for AGC based on current indirect evidence, surpassing single ICI-chemo and dual ICI-based regimens. These findings support personalized therapy selection but await confirmation by head‑to‑head trials. Future studies should address CPS < 1 and explore optimized combinations to enhance outcomes.
25 May 2026
Read appraisal →Medicine
Survival prediction of colorectal cancer using 101 machine learning methods based on immune-related genes: A machine learning study
Colorectal cancer (CRC) is characterized by high incidence and mortality rates. Early identification of high-risk CRC patients and timely intervention are crucial for reducing mortality rates. This study aims to develop a prognostic model incorporating immune-related genes using 101 machine learning algorithms. We utilized data from 630 CRC patients in The Cancer Genome Atlas Program database and the Gene Expression Omnibus database as a validation set. We identified immune-related genes from the ImmPort repository and conducted differential gene expression analysis. We developed 101 machine learning models, including random survival forest, elastic net, LASSO, Ridge regression, stepwise Cox, Coxboost, partial least squares regression for Cox, supervised principal component analysis, generalized boosted modeling, and survival support vector machines. The model with the highest mean concordance index was selected as the optimal prognostic model. The Ridge regression model demonstrated the most robust performance with a mean concordance index of 0.67. Patients with higher immune-related gene risk score (IRGRS) had significantly lower survival rates (log-rank test, P < .001). Univariate and multivariate Cox regression analyses confirmed IRGRS as an independent prognostic factor. Nomograms successfully predicted overall survival at 1, 2, and 3 years. IRGRS correlated with immune cell infiltration levels and stromal activity in the tumor microenvironment. High IRGRS scores were associated with higher tumor immune dysfunction and exclusion scores, suggesting potential differences in response to immune checkpoint inhibitors. In addition, high IRGRS patients exhibited greater sensitivity to certain chemotherapy drugs. The IRGRS score is a potent predictor of survival in CRC patients. This study offers a new perspective for CRC prognosis and supports the development of personalized treatment strategies.
24 May 2026
Read appraisal →Medicine
Mechanisms linking primary biliary cholangitis and osteoporosis: A combined clinical and molecular analysis
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic liver disease, and osteoporosis (OP) is a prevalent comorbidity that aggravates the disease burden of PBC patients. Although the co-occurrence of the 2 diseases has been widely observed, the underlying molecular mechanisms remain unclear. Herein, we evaluated the causal link between PBC and OP using Mendelian randomization (MR) and explored shared molecular mechanisms through bioinformatics and machine learning. We performed two-sample MR using genome-wide association study summary data for PBC and OP from the Integrative Epidemiology Unit database. Inverse-variance weighting was used as the primary MR method, with heterogeneity and horizontal pleiotropy tests performed to exclude potential biases. To explore shared molecular mechanisms, we analyzed transcriptomic datasets from the Gene Expression Omnibus database, identified comorbidity-associated differentially expressed genes, and applied multiple machine learning algorithms for biomarker screening and validation, combined with immune infiltration analysis. Our study showed that MR demonstrated that PBC significantly increases the risk of OP, while transcriptomic analysis identified 36 shared differentially expressed genes enriched in key biological pathways such as ribonucleic acid splicing and ubiquitin-mediated proteolysis. Furthermore, using 3 machine learning algorithms, we identified 12 PBC-specific and 4 OP-specific diagnostic genes, whose intersection revealed vacuolar protein sorting 37 homolog C (VPS37C) as a common diagnostic biomarker. In both diseases, VPS37C exhibited an area under the receiver operating characteristic curve value >0.7, demonstrating its robust predictive performance. In addition, VPS37C expression was found to be significantly correlated with the infiltration landscape of multiple immune cell types in both PBC and OP. This study identified VPS37C as a shared diagnostic gene linking PBC and OP, providing new insights into their comorbidity at both genetic and immune levels. Our findings further elucidate the molecular mechanisms underlying the comorbidity of PBC and OP, offer novel clues for understanding their pathogenesis, and highlight promising diagnostic and therapeutic targets for clinical application.
24 May 2026
Read appraisal →BMC cancer
Efficacy and risk analysis of monotherapy and dual immunotherapy in dMMR/MSI-H metastatic colorectal cancer: a meta-analysis based on randomized controlled trials
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for metastatic colorectal cancer (mCRC) exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). However, the comparative efficacy and safety of monotherapy versus dual immunotherapy remain inadequately quantified. This meta-analysis aims to evaluate the benefits and risks of these strategies by quantitatively synthesizing data from randomized controlled trials (RCTs) to inform clinical decision-making. DESIGN: We systematically searched major databases (PubMed, Web of Science, Cochrane, Embase) from inception to September 2025 for relevant RCTs. Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and adverse events. Statistical analyses were performed using RevMan 5.3 and Stata 18.0. RESULTS: Six RCTs (1,460 patients) were included. Pooled analysis showed that PD-1/PD-L1 monotherapy significantly improved ORR compared with chemotherapy (OR = 1.52, 95% CI: 1.02-2.27, P = 0.04), based on two RCTs (n = 429), and demonstrated a significantly lower incidence of grade ≥ 3 adverse events (OR = 0.14, 95% CI: 0.08-0.23, P < 0.00001; 2 studies). Dual immunotherapy with nivolumab plus ipilimumab significantly improved ORR versus monotherapy (OR = 1.77, 95% CI: 1.25-2.49, P = 0.001), based on one RCT (n = 582), with a significantly increased toxicity risk (OR = 1.73, 95% CI: 1.22-2.44, P = 0.002). For PFS, KEYNOTE-177 (HR = 0.59, 95% CI: 0.45-0.79) and CheckMate 8HW (HR = 0.62, 95% CI: 0.48-0.81) showed significant benefits, while SAMCO-PRODIGE 54 and CheckMate 9 × 8 did not demonstrate statistically significant PFS improvement. OS hazard ratios across four studies ranged from 0.74 to 1.03, with all 95% confidence intervals crossing 1.0, indicating no statistically significant survival benefit in any individual study. DOR was consistently longer with immunotherapy, with median not reached for pembrolizumab versus 10.6 months for chemotherapy in KEYNOTE-177. CONCLUSIONS: Effect estimates for PFS, OS, and DOR generally favored immunotherapy; however, confidence intervals were wide and statistical significance was not consistently observed across trials. PD-1/PD-L1 monotherapy demonstrated a favorable safety profile and a statistically significant improvement in ORR compared with chemotherapy (OR = 1.52, 95% CI: 1.02-2.27, P = 0.04). Dual immunotherapy significantly improved ORR compared with monotherapy (OR = 1.77, 95% CI: 1.25-2.49, P = 0.001), but this benefit was accompanied by significantly increased toxicity (OR = 1.73, 95% CI: 1.22-2.44, P = 0.002) and did not consistently translate into statistically significant PFS or OS benefits across trials. These findings highlight the need for personalized risk-benefit assessment. Future research should focus on biomarker-driven patient selection and strategies to overcome resistance.
23 May 2026
Read appraisal →Journal of medical Internet research
Benchmarking Large Language Models and Prompt Engineering Strategies in Microsatellite Instability Cancers: Evaluation Study
BACKGROUND: The reliability of general-purpose large language models (LLMs) for complex clinical tasks in specialized domains such as microsatellite instability (MSI) cancers remains critically uncharacterized. The absence of a domain-specific benchmark to evaluate and guide the optimization of their capabilities across diverse clinical tasks poses unevaluated risks to patient safety. OBJECTIVE: This study aimed to develop and validate Microsatellite Instability Cancer Benchmark (MSIC-Bench), a novel, two-tiered benchmark for MSI cancer, covering both consensus and frontier knowledge. Using this framework, we aimed to systematically assess LLM performance across various prompting strategies, identify task-specific weaknesses, and reveal effective pathways for performance improvement. METHODS: We developed MSIC-Bench, a 511-question benchmark derived from clinical guidelines and a curated knowledge base. Three state-of-the-art LLMs (GPT-4o, [OpenAI], Gemini 2.5 Pro [Google], and Claude Opus 4 [Anthropic]) were evaluated using 4 prompting strategies, including vanilla, chain-of-thought, reflection of thoughts, and retrieval-augmented generation (RAG), under both multiple-choice and open-ended modalities. Performance was assessed on accuracy, safety (honesty), error composition, and token usage. RESULTS: LLMs demonstrated a significant "scaffolding effect," with accuracy dropping substantially in open-ended scenarios. For non-RAG strategies, the primary failure mode was an internal knowledge deficit. The integration of RAG proved to be the most effective intervention. A domain-aligned RAG strategy not only significantly improved accuracy in complex decision-making tasks but also fundamentally shifted the system's primary bottleneck from knowledge deficits to retrieval failures. In terms of safety, RAG induced a favorable shift from high-risk fabrications to safer refusals, though this introduced a safety-utility trade-off in the form of false refusals. Notably, our hybrid-RAG configuration, which combined both knowledge sources, demonstrated the most robust and generalizable performance across all tasks. CONCLUSIONS: Current LLMs lack the specialized knowledge required for reliable application in MSI oncology. A well-designed RAG architecture is the pivotal intervention to address this gap. However, its success is not automatic; it transforms the nature of system failure, making retrieval precision and knowledge base quality the new critical determinants of performance and safety. Our findings establish a clear directive for developing trustworthy clinical artificial intelligence: focus must shift toward optimizing the retrieval component and curating high-quality, comprehensive knowledge sources. MSIC-Bench provides a robust framework to guide these future efforts.
22 May 2026
Read appraisal →Journal of medical Internet research
Efficacy of Internet-Based Self-Help Interventions for Irritable Bowel Syndrome: Systematic Review and Meta-Analysis of Randomized Controlled Trials
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that reduces quality of life and causes a heavy medical burden. Internet-based self-help interventions are flexible and scalable, showing potential for IBS symptom improvement, but relevant evidence is fragmented and lacks systematic review. OBJECTIVE: This systematic review aimed to comprehensively evaluate the effects of internet-based self-help interventions on symptom severity, quality of life, and visceral sensitivity, as well as comorbid depressive and anxiety symptoms, in individuals with IBS. METHODS: Only randomized controlled trials evaluating internet-based self-help interventions for individuals with IBS were included. A literature search was conducted across PubMed, Embase, Web of Science, CINAHL Complete, PsycINFO, the Cochrane Library, and 4 Chinese databases on June 25, 2025, with an updated search on March 9, 2026. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Meta-analyses were performed with the Hartung-Knapp-Sidik-Jonkman-adjusted random-effects model. Effect sizes were reported as standardized mean differences (SMDs) with 95% CIs, and evidence certainty was evaluated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. RESULTS: A total of 17 randomized controlled trials from 7 countries were included, involving 2289 participants (predominantly female). Compared with control groups, internet-based self-help interventions were associated with a statistically significant improvement in IBS symptom severity (SMD -0.52, 95% CI -0.78 to -0.26, 95% prediction interval [PI] -1.46 to 0.42), quality of life (SMD 0.57, 95% CI 0.23 to 0.90, 95% PI -0.41 to 1.54), visceral sensitivity (SMD -0.55, 95% CI -0.89 to -0.21, 95% PI -1.43 to 0.33), and depressive symptoms (SMD -0.14, 95% CI -0.27 to -0.01, 95% PI -0.27 to -0.01). However, no statistically significant improvement was observed in anxiety symptoms (SMD -0.03, 95% CI -0.34 to 0.27, 95% PI -0.78 to 0.71). The certainty of evidence was rated as moderate to very low for all outcomes. CONCLUSIONS: This review synthesizes the latest evidence on internet-based self-help interventions for individuals with IBS disease-specific and comorbid psychological symptoms. It stands out by encompassing a diverse range of such interventions and incorporating visceral sensitivity as a key outcome. In doing so, it establishes a more comprehensive multi-outcome evidence base for IBS digital interventions, advancing the field by clarifying the potential of these interventions as viable alternatives to conventional treatments. For real-world practice, these findings can inform targeted strategies for primary care and telemedicine platforms, especially in resource-limited regions. However, this review is limited by moderate bias risk, high heterogeneity, and moderate to very low GRADE evidence certainty. A wide 95% PI suggests that effect variability is linked to contextual and population factors, so findings should be interpreted cautiously. Future research should prioritize technical support, patients' digital health literacy, and standardized intervention protocols to further validate clinical utility.
22 May 2026
Read appraisal →Journal of medical Internet research
Large Language Models in Colorectal Cancer Care and Clinical Decision Support: Systematic Review
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The complexity of guideline-concordant care and unstructured clinical data has driven demand for decision-support tools. Large language models (LLMs) show promise for processing clinical data and patient-provider communication, yet evidence is fragmented, and a CRC-specific synthesis across the full care continuum is lacking. OBJECTIVE: This systematic review evaluates the current applications, performance determinants, and clinical implications of LLMs across the continuum of CRC care. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), we searched 6 databases (PubMed, Embase, Web of Science, Scopus, CINAHL, Cochrane) through April 1, 2026. Eligible studies were peer-reviewed original investigations of LLMs on CRC tasks with extractable outcomes; reviews, editorials, and abstracts were excluded. Two reviewers assessed quality with QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), PROBAST (prediction model risk of bias assessment tool), and ROBINS-I (Risk of Bias in Nonrandomized Studies - of Interventions). Data on model types, applications, prompts, input/output formats, and outcomes were analyzed descriptively, with narrative synthesis per synthesis without meta-analysis (SWiM) guidelines. RESULTS: Of 8880 records, 37 studies met inclusion criteria (2023-2026), mostly from China and the United States, with GPT series most frequently evaluated. Overall risk of bias was low in 10/37 studies (27.0%), moderate in 14/37 (37.8%), unclear in 7/37 (18.9%), and high or serious in 6/37 (16.2%). Problematic domains included outcome measurement, intervention classification, patient selection, and lack of blinded assessment. LLMs showed utility in automating data extraction from clinical texts, supporting patient education, aiding diagnosis, and assisting clinical decision-making, with emerging visual interpretation and multimodal capacities. Domain-specific and multimodal models showed advantages over general-purpose models in certain tasks. Performance was significantly influenced by prompt design, from zero-shot queries to fine-tuning. Despite efficiency and outcome benefits, challenges persist regarding methodological quality, data privacy, and generalizability. CONCLUSIONS: This review provides an integrative framework synthesizing evidence across study designs and LLM categories in CRC care. Unlike prior reviews addressing gastroenterology broadly or limited to one design, it covers the full CRC continuum and, for the first time, comparatively evaluates general-purpose, domain-specific, and multimodal LLMs, clarifying how prompt engineering and heterogeneous metrics shape outcomes. Although findings support LLMs' clinical potential, results must be interpreted cautiously, given low overall evidence quality. Most studies lacked safeguards against bias-blinded assessment, confounder adjustment, or prospective multicenter validation. Substantial heterogeneity across tasks, LLM types, prompts, reference standards, and outcomes means reported advantages cannot be generalized. Future work should prioritize real-world integration via prospective multicenter validation, robust privacy frameworks, and rigorous human oversight. Amid rising global CRC burden and health care disparities, this review informs clinical translation, equitable scaling, and policy on LLM deployment.
22 May 2026
Read appraisal →Current obesity reports
Burden of Intrapancreatic Fat Deposition in Type 2 Diabetes and the Role of Obesity: A Systematic Review and Meta-Analysis
BACKGROUND: Growing evidence supports a role for high intrapancreatic fat deposition (IPFD) in the pathogenesis of type 2 diabetes mellitus (T2DM); however, the magnitude of this association and the extent to which it is influenced by body mass index (BMI), liver fat content (LFC), and age remain uncertain. OBJECTIVE: To quantitatively evaluate IPFD measured by magnetic resonance imaging (MRI) in individuals with T2DM and to investigate study-level factors contributing to between-study variability. METHODS: We systematically searched PubMed and Embase for observational studies comparing MRI-measured IPFD in individuals with T2DM versus non-diabetic controls, excluding studies in which IPFD quantification was performed using AI-based models. Pooled standardized mean differences (SMDs) were estimated using a restricted maximum likelihood approach with Hartung-Knapp adjustment. Heterogeneity was explored through subgroup, meta-regression, and sensitivity analyses. RESULTS: Thirty studies (n=3,980) were included. Individuals with T2DM had significantly higher IPFD than non-diabetic controls (SMD 1.13, 95% CI 0.74 to 1.51), with no significant differences when stratified by pancreatic region, MRI technique, geographic region, sample size, and risk of bias. In multivariable models, BMI remained the only consistent moderating covariate, and the excess IPFD in T2DM persisted after adjusting for BMI, LFC, and age (intercept=0.797, p=0.010, false discovery rate-adjusted p=0.018). Advanced heterogeneity exploration identified no structural outliers, and the pooled effect size remained consistent across multiple sensitivity analyses. CONCLUSION: T2DM is associated with substantially higher MRI-quantified IPFD, independent of study-level differences in BMI, LFC, and age. Although causality cannot be inferred, these findings support the hypothesis that IPFD may be involved in the underlying mechanism of T2DM. They also suggest that high IPFD could represent a metabolic hallmark, with potential implications for risk stratification and therapeutic targeting.
22 May 2026
Read appraisal →Journal of the Egyptian National Cancer Institute
Preclinical efficacy of drug delivery systems in colon cancer therapy: a systematic review and meta-analysis of in vivo animal studies
BACKGROUND: Drug delivery systems (DDS) offer a promising strategy to enhance the therapeutic index of chemotherapeutic agents in colon cancer by improving tumor targeting, circulation time, and controlled drug release. Despite extensive preclinical research, a quantitative synthesis evaluating the efficacy of DDS and the influence of design parameters remains lacking. METHODS: We conducted a systematic review and meta-analysis of preclinical in vivo studies assessing DDS-based chemotherapy in murine models of colon cancer. A comprehensive search of PubMed, EMBASE, Scopus, Google Scholar, Cochrane CENTRAL, and ClinicalTrials.gov was performed through October 15, 2025. Outcomes included tumor growth inhibition, with subgroup analyses examining the effects of DDS platform, chemotherapeutic agent, targeting strategy, ligand type, and route of administration. RESULTS: Twenty-three studies comprising 25 experiments and 539 animals were included. Overall, DDS-based therapies significantly reduced tumor growth compared with controls ((WMD: - 557.7; 95% CI: - 716.8 to - 398.5; I²=88%; p < 0.001) and free-drug administration ((WMD: - 276.3; 95% CI: - 367.6 to - 185.1; I²=78%; p < 0.001). Both targeted and non-targeted DDS significantly reduced tumor growth compared with free drug treatment, while targeted DDS showed significantly greater efficacy than non-targeted systems (WMD: - 240.3; 95% CI: - 399.4 to - 81.25; I²=59%; p = 0.003). Although no statistically significant differences were observed between DDS platforms or chemotherapeutic agent subgroups, micelle-based systems and DDS formulations incorporating SN-38 or doxorubicin tended to show greater tumor growth reduction. Intravenous administration demonstrated significantly greater efficacy than intraperitoneal delivery, while hyaluronic acid- and aptamer-based targeting strategies achieved the largest tumor growth inhibition. Risk-of-bias assessment indicated moderate methodological quality, with variability in reporting of randomization, blinding, and sample size calculations. CONCLUSIONS: DDS-based chemotherapy consistently improves antitumor efficacy in preclinical colon cancer models, with targeting strategy, platform type, chemotherapeutic agent, and administration route influencing outcomes. These findings support the rational design of DDS platforms and underscore their translational potential. Rigorous preclinical study design and standardized reporting of efficacy and safety are essential to facilitate clinical translation.
21 May 2026
Read appraisal →Journal of clinical pathology
AI triage of duodenal biopsies improves workflow
AIMS: To develop, deploy and evaluate artificial intelligence (AI) for triaging duodenal biopsies within a National Health Service (NHS) histopathology laboratory, with the aim of improving reporting turnaround times for clinically significant diagnoses. METHODS: The pathway was developed in the UK in an NHS laboratory. Rule-based automation software was used to find all newly scanned duodenal biopsy slides. Those with case numbers ending in an odd number were exported for AI triage and if they had significant AI predicted abnormalities they were prioritised for reporting. The cases with even numbers followed the routine reporting pathway. RESULTS: 313 cases (517 duodenal slides) were processed by the routine pathway, and 329 cases (533 duodenal slides) were processed by the AI triage pathway. AI processing took about 70 s per slide. The AI classifier had a sensitivity and positive predictive value (PPV) as follows: normal small bowel: 99.6%, 95.7%; coeliac disease: 86.7%, 100%; gastric heterotopia: 84.6%, 95.7%; adenoma: 88.9%, 88.9%; adenocarcinoma: 50.0%, 100%. In the AI triage workstream coeliac disease, and non-neoplastic abnormalities as a group, were reported quicker than in the standard workstream (6 days vs 10 days and 7 days vs 10 days, respectively, both p<0.005), but neoplastic lesions were not reported quicker. The cost of deployment and operation was reasonable. CONCLUSIONS: An NHS histopathology laboratory successfully developed and implemented an AI-based triage system for duodenal biopsies, achieving high diagnostic accuracy and significantly improving turnaround times for coeliac disease and non-neoplastic abnormalities as a group. This study demonstrates the feasibility and clinical value of locally developed AI tools within routine diagnostic practice.
21 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Sustained Action of Imapextide, A Glucagon-Like Peptide-1 Receptor Antagonist, in Healthy Volunteers
CONTEXT: After weight-loss surgery, some patients experience postbariatric hypoglycemia (PBH). Although PBH is customarily managed by dietary modifications with continuous glucose monitoring, advanced treatment options are needed. Imapextide is a sustained-action, selective, reversible glucagon-like peptide-1 (GLP-1) receptor antagonist designed for once-weekly administration for PBH treatment. OBJECTIVE: This work aimed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses (SAD/MAD) of imapextide in healthy volunteers (HVs). METHODS: This 3-part, phase 1, double-blind study enrolled healthy adults. In the SAD/MAD parts, randomly assigned participants (3:1) received subcutaneous imapextide (SAD, 10-200 mg; MAD, 10-30 mg once weekly, 4 doses) or placebo. The primary end point was safety/tolerability (treatment-emergent adverse events [TEAEs]). PK (SAD/MAD; time-to-maximal concentration [tmax] and half-life [t1/2]) and PD (MAD; GLP-1 and glycemic parameters during a mixed meal tolerance test [MMTT]) were assessed. Imapextide drug-drug interactions (DDIs) of OATP1B1/OATP1B3 inhibition and accelerated gastric emptying were evaluated with coproporphyrin-I, rosuvastatin, and acetaminophen. RESULTS: Overall, 69 HVs were randomly assigned (32 SAD, 23 MAD, 14 DDIs). Imapextide TEAE rates ranged from 33.3% to 50.0% (SAD), 33.3% to 100% (MAD), and 14.3% (DDIs) across cohorts. The most common TEAEs included injection site erythema (SAD, MAD) and injection site swelling (MAD). Imapextide exposure was dose proportional (median tmax 24-48 hours; mean t1/2 ∼90 hours). During the MMTT, imapextide increased GLP-1 concentrations at early time points, while effects on other glycemic parameters were variable. Minimal nonclinically relevant DDIs occurred with rosuvastatin. Imapextide slightly accelerated gastric emptying. CONCLUSION: Imapextide was generally well tolerated in HVs. PK findings supported weekly dosing. PD showed consistent effects on GLP-1 levels, supporting a potential role for imapextide in modulating PBH pathophysiology.
21 May 2026
Read appraisal →Scientific reports
Quantum machine learning for predicting anastomotic leak: a clinical study
Anastomotic leak is a life-threatening complication following colorectal surgery. This study benchmarks Quantum Neural Networks (QNNs) against hyperparameter-tuned classical models (logistic regression, multi-layer perceptrons, boosting algorithms) for anastomotic leak prediction. Using a 200-patient clinical dataset strictly bounded by a priori medical constraints, we simulated QNNs with ZZFeatureMap encoding and EfficientSU2/RealAmplitudes ansatze under realistic hardware noise. To ensure statistical reliability, performance metrics were averaged across 10 independent optimization runs. The EfficientSU2-BFGS configuration achieved the highest mean AUC of [Formula: see text], while RealAmplitudes with CMA-ES maximized Average Precision ([Formula: see text]). Crucially, at a fixed, clinically necessary sensitivity of [Formula: see text], specific QNN configurations achieved significantly higher specificity (up to [Formula: see text]) and Negative Predictive Value (up to [Formula: see text]) compared to classical models (maximum [Formula: see text] and [Formula: see text], respectively), effectively minimizing false positives. However, classical models maintained superior probability calibration for continuous risk stratification. We conclude that QNNs offer robust discriminative performance for clinical screening, warranting further validation on larger, independent cohorts.
20 May 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147)
PURPOSE: Detection of molecular residual disease using circulating tumor DNA (ctDNA) may enable postoperative risk stratification and guide adjuvant therapy. We evaluated the prognostic value of a tissue-free, epigenomic ctDNA assay in patients with stage III colon cancer (CC) enrolled in a phase III adjuvant chemotherapy trial. METHODS: Plasma samples were collected after surgery and before adjuvant infusional fluorouracil, leucovorin, and oxaliplatin alone or combined with cetuximab. ctDNA was analyzed using a tissue-free assay; in ctDNA-positive patients, tumor fraction (TF) was quantified and genotyping was performed with a 739-gene panel. Associations with disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS) were assessed using multivariable Cox models adjusted for covariates. RESULTS: Among 2,260 evaluable patients, 461 (20.4%) were ctDNA-positive with significantly higher detection in advanced T-/N-stage, high-grade, obstruction/perforation, and BRAFV600E tumors. At a median follow-up of 6.1 years, ctDNA positivity was independently associated with shorter TTR (hazard ratio [HR], 5.96 [95% CI, 5.11 to 6.96]), DFS (HR, 5.03 [95% CI, 4.36 to 5.81]), and OS (HR, 4.45 [95% CI, 3.76 to 5.27]; all P < .0001). The 5-year DFS was 27.7% (95% CI, 23.8 to 32.2) v 77.1% (95% CI, 75.1 to 79.1) in ctDNA-positive versus ctDNA-negative patients, and adverse prognostic impact was greater in lower T/N stage, low-risk, and dMMR subsets (interaction P = .0012-.041). Among ctDNA-positive patients, TF was nearly double in those who recurred or died (P = .0002) and stratified patients for TTR, DFS, and OS (all adjusted P < .002). Genotyping identified mutations in FLT1 (OR, 8.99) and PREX2 (OR, 7.73) genes that were most strongly associated with recurrence (P < .03). CONCLUSION: Evaluation of ctDNA in resected stage III CC using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, dMMR, and specific mutations defined poor prognostic groups among ctDNA-positive patients.
20 May 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603
JCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we report OS after long-term follow-up. Eligible patients with colorectal adenocarcinoma and an unlimited number of liver metastases were randomized to adjuvant mFOLFOX6 or hepatectomy alone. DFS was the primary endpoint, and OS was a secondary endpoint. Between March 2007 and January 2019, 151 and 149 patients were randomized to adjuvant chemotherapy and hepatectomy alone, respectively. At a median follow-up of 7.7 years for disease-free surviving patients, 54 (35.8%) and 51 (34.2%) patients had died in the respective arms, (hazard ratio [HR], 1.07 [95% CI, 0.73 to 1.57]). Five-year OS was 73.4% (95% CI, 65.5 to 79.7) and 80.1% (95% CI, 72.6 to 85.7) and 7-year OS was 69.4% (95% CI, 61.2 to 76.2) and 72.4% (95% CI, 64.2 to 79.1), respectively. One patient in the adjuvant chemotherapy arm possibly died of protocol treatment-related toxicity, and one in the hepatectomy-alone arm died of post-protocol treatment complications. Five-year DFS was respectively 49.7% (95% CI, 41.5 to 57.3) and 40.5% (95% CI, 32.5 to 48.3) in the adjuvant chemotherapy and hepatectomy-alone arms (HR, 0.72 [95% CI, 0.54 to 0.97]). Long-term OS did not differ with adjuvant mFOLFOX6 compared with hepatectomy alone in resectable CRLM. Adjuvant mFOLFOX6 may delay recurrence but did not improve long-term survival.
20 May 2026
Read appraisal →European journal of pediatrics
Development and validation of an explainable machine learning model for predicting surgical intervention in pediatric intestinal obstruction
Pediatric intestinal obstruction, a critical acute abdomen condition, carries a risk of intestinal necrosis. Decisions for urgent surgery lack standardized criteria. This study aimed to develop an explainable machine learning (ML) model to predict surgical indication, reducing diagnostic variability. A retrospective study included 642 children from our center (split into training/internal validation sets) and 137 from two external centers. Surgical indication was defined based on the presence of one or more of the following: evidence of peritonitis on physical examination, radiographic signs of strangulation, or failure of conservative management for > 24 h; in cases of diagnostic uncertainty, consensus among three senior physicians was used as the adjudication standard. We built models using 35 easily obtainable features across eleven algorithms and evaluated performance via AUC and other metrics. SHapley Additive exPlanations (SHAP) provided model interpretability, and an optimal probability threshold was established for clinical stratification. At the optimal threshold determined by maximizing the Youden index, the model achieved a sensitivity of 89% and a specificity of 99% in the internal validation set. The random forest model demonstrated the highest discriminative performance. A streamlined, interpretable model using the eight most important features (including vital sign dynamics and clinical markers) showed no evidence of overfitting based on the close agreement between training and validation performance metrics. It achieved AUCs of 0.988 (internal validation) and 0.981 (external validation). The model has been translated into a convenient clinical tool.Conclusion: Our explainable ML model demonstrates strong discriminative performance in predicting the need for surgery in pediatric intestinal obstruction and is strongly associated with intestinal necrosis. By mitigating the "black-box" concern through SHAP, it offers transparent, interpretable decision support to clinicians.
20 May 2026
Read appraisal →Journal of robotic surgery
Perioperative and oncological outcomes of robotic versus laparoscopic low anterior resection in younger rectal cancer cohorts: a systematic review and meta-analysis with narrative functional assessment
Robotic low anterior resection (R-LAR) has been proposed to overcome technical limitations of laparoscopy in rectal surgery. However, previous meta-analyses have evaluated mixed-age populations, and no meta-analysis has specifically investigated younger patients (aged < 65 years) undergoing low anterior resection. This study aimed to compare operative, short-term postoperative, and oncological outcomes between robotic and laparoscopic low anterior resection in this cohort. A systematic review and meta-analysis were conducted according to PRISMA 2020 and the Cochrane Handbook, with prospective registration in Prospero. PubMed, Scopus, and the Cochrane Library were searched up to January 2026. Comparative studies evaluating R-LAR versus L-LAR in younger rectal cancer cohorts, defined as studies with mean patient age ≤ 65 years, were included. Random-effects models were used to calculate pooled mean differences (MD), odds ratios (OR), and hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias was assessed using ROBINS-I and RoB2, and certainty of evidence using GRADE. A total of 16 studies were included. Compared with laparoscopy, R-LAR was associated with longer operative duration (MD 24.59 min, 95% CI 3.85-45.33, p = 0.02, I² = 96%), lower conversion to open surgery (OR 0.38, 95% CI 0.27-0.53, p < 0.0001, I² = 38%), lower overall complications (OR 0.84, 95% CI 0.73-0.97, p = 0.02, I² = 0%), lower 30-day mortality (OR 0.59, 95% CI 0.45-0.77, p = 0.006, I² = 0%), lower 30-day reoperation (OR 0.77, 95% CI 0.61-0.98, p = 0.04, I² = 0%), higher complete TME rates (OR 3.30, 95% CI 2.14-5.10, p = 0.003, I² = 0%) and shorter hospital stay (MD -0.82, 95% CI -1.50 to -0.13, p = 0.02, I²=97%). Estimated blood loss (p = 0.05) and major complications (p = 0.05) were borderline significant in favor of R-LAR. Anastomotic leakage (p = 0.17), postoperative ileus (p = 0.49), time to first flatus (p = 0.12), time to diet initiation (p = 0.10), CRM positivity (p = 0.56), lymph node yield (p = 0.09), local recurrence (p = 0.67), loop ileostomy (p = 0.56), disease-free survival (p = 0.53), and overall survival (p = 0.73) were comparable. The certainty of evidence ranged from very low to moderate. Functional outcomes were insufficient for pooling. Robotic low anterior resection in younger rectal cancer cohorts may improve several perioperative and technical outcomes without compromising oncological adequacy. Further high-quality studies are required to confirm these findings.
19 May 2026
Read appraisal →Current oncology reports
Impact of 18-FDG PET/CT on Multidisciplinary Decision-Making and Management in Abdominal Malignancies: A Systematic Review and Meta-Analysis
PURPOSE: To systematically review and assess the impact of 18 F-FDG PET/CT on multidisciplinary team (MDT) decision-making and management in adults with abdominal malignancies. MATERIALS & METHODS: We searched Ovid MEDLINE, Ovid Epub, Cochrane CENTRAL, EMBASE, and Scopus upto August 31, 2024, for studies including 18-FDG PET/CT and MDT management in abdominal malignancies in adult patients and describing pre- and post-PET/CT treatment plans or MDT decisions. Data extraction followed by independent two reviewer assessment using ROBINS-I framework. A random-effects meta-analysis of proportions was performed for studies reporting management change attributable to PET/CT. RESULTS: Fourteen studies met inclusion criteria, of which seven provided sufficient quantitative data for meta-analysis. A random-effects meta-analysis of the seven eligible quantitative studies showed that 21.8% of patients (95% CI: 10.6%-33.0%, p < 0.001; range: 8-36%) experienced a management change directly attributable to PET-based imaging. Between-study heterogeneity was substantial (I² ≈ 85%, p < 0.001). Reported management changes included cancellation or addition of planned surgery, modification of surgical extent, change in treatment intent between curative and palliative strategies, and alteration of systemic therapy or radiotherapy plans. Evidence on downstream outcomes such as survival, quality of life, and cost-effectiveness was limited and heterogeneous, precluding quantitative synthesis. CONCLUSION: PET/CT leads to a change in MDT management in roughly one in five patients with abdominal malignancies, often through re-staging and identification of occult metastases that alter treatment intent or surgical strategy. The magnitude of impact varies widely by clinical context and tumor type. 1. PET/CT identifies occult metastases and clarifies disease extent, allowing MDTs to avoid futile surgeries and appropriately shift between curative and palliative strategies. 2. Approximately one in five patients experience a meaningful change in management after PET/CT, demonstrating its significant influence on real-world treatment planning. 3. Incorporating PET/CT into MDT discussions enhances diagnostic confidence and supports more coordinated, evidence-based care across surgical, oncologic, and radiologic teams. By highlighting which patients benefit most, the findings support more efficient use of PET/CT, emphasizing the need for standardized outcome measures and prospective data to refine patient selection.
19 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Mortality risk and causes of death in exogenous Cushing's syndrome: a systematic review and meta-analysis
CONTEXT: Chronic oral glucocorticoids (GCs) are widely prescribed for multiple diseases. Although long-term GC exposure causes systemic toxicity, the magnitude, dose-response relationship, and causes of GC-associated mortality remain incompletely defined. OBJECTIVE: To quantify overall and cause-specific mortality associated with chronic oral GC exposure and evaluate dose-response relationships across underlying disease groups. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD42017067530). PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, and CINAHL were searched from 1945 to March 2019. Eligible studies reported standardized mortality ratios (SMRs) or absolute deaths among adults receiving chronic oral GCs. Random-effects meta-analysis and mixed-effects meta-regression were used to synthesize mortality and dose-response associations across GC exposure metrics, exposure duration, and disease subgroups. RESULTS: One-hundred and sixteen studies encompassing 128 cohorts and 51 380 patients were included. Chronic GC exposure was associated with excess mortality (pooled SMR 1.87; 95%CI 1.32-2.61; I2 74.0%). The pooled proportion of death was 12.0% (95%CI 10-14%). Mortality risk was highest in inflammatory diseases (30.0%) and the vasculitides (18.0%). Higher cumulative dose (≥5 g prednisolone-equivalent), average daily dose >5 mg/day, and higher initial dose were each independently associated with increased mortality. Cardiovascular disease was the leading causes of death (25.6%), followed by malignancy (15.7%) and infection (13.4%). CONCLUSION: Chronic oral GC exposure was associated with increased mortality across disease groups, with higher cumulative and early-treatment doses correlating with higher risk. However, causal attribution remains uncertain due to confounding by indication, limited disease-severity data, and exposure misclassification. These findings support GC stewardship and targeted cardiovascular and infection risk mitigation, rather than indiscriminate dose reduction.
19 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Effectiveness of survivorship programmes to enhance health-related quality of life of colorectal cancer survivors: a systematic review and meta-analysis of randomised controlled trials
PURPOSE: This study aimed to assess the effectiveness of the survivorship programmes by synthesising and analysing the available evidence to enhance health-related quality of life (HRQoL) amongst colorectal cancer (CRC) survivors. METHODS: Ten English-language databases were searched from inception to June 2025 in this systematic review and meta-analysis. All randomised controlled trials (RCTs) were included. Available data were pooled in a meta-analysis using RevMan (version 5.4.0). Two independent reviewers performed the database searches, extracted the data, assessed the methodological quality by using the Cochrane Risk-of-Bias tool (version 2) and evaluated the overall quality of findings by using Cochrane GRADE. RESULTS: A total of 22 RCTs involving 2949 CRC survivors were identified. The meta-analysis results (thirteen studies) indicated a significant improvement in the physical (standardised mean difference [SMD] = 0.52, 95% confidence interval [CI, 0.18, 0.86], P = 0.002, I2 = 88%) and mental domains of HRQoL (SMD = 0.4, 95% CI [0.06, 0.74], P = 0.02, I2 = 86%). Sensitivity analysis involved reducing the heterogeneity after removing one study. No publication bias was found. The overall quality of findings was from 'low' to 'moderate'. CONCLUSIONS: The detailed components of the survivorship programme can enhance HRQoL in physical and mental domains, indicating its potential as valuable evidence for health providers to support CRC survivors post-treatment. Future research should focus on expanding the delivery of such programme comprehensively by integrating mobile health into a nurse-led approach to optimise geographic diversity and improve social HRQoL.
19 May 2026
Read appraisal →Drug discoveries & therapeutics
Trends in the prescription of constipation medications in Japan (fiscal years 2019-2023): A nationwide baseline study prior to the 2023 clinical guidelines.
Constipation is a common gastrointestinal disorder that markedly affects health and quality of life. In Japan, magnesium-based and contact laxatives have long been widely prescribed. Since the launch of lubiprostone in November 2012, several new agents with novel mechanisms have been introduced, and their use has increased. However, to our knowledge, no nationwide study has examined their use. This study aimed to analyze nationwide trends and regional differences in the prescription of medications for constipation. We used data from the Japanese National Health Insurance Claims and Specific Health Checkup Database Open Data from fiscal years (FYs) 2019 to 2023, covering the period when all currently available constipation medications were on the market in Japan, and prior to the inclusion of the drug selection flowchart in the Evidence-Based Clinical Guidelines for Chronic Constipation 2023. Prescription trends were evaluated using defined daily doses per 1,000 inhabitants per day (DID), and regional variations were assessed using standardized claim ratios (SCRs). The DID for contact laxatives decreased during the study period, whereas the DID for other constipation medications increased. Magnesium oxide showed the smallest regional variation, whereas polyethylene glycol and linaclotide showed the largest variations in FY 2019 and FY 2023, respectively. Throughout the 5-year period, the highest SCRs for contact laxatives were observed in Akita, Iwate, and Aomori prefectures. Our findings provide a comprehensive nationwide picture of evolving constipation treatment patterns and regional variations in Japan, establishing baseline data for evaluating the impact of guideline dissemination and evidence accumulation on clinical practice.
18 May 2026
Read appraisal →Current allergy and asthma reports
Impact of IL-4/IL-13 Blockade with Dupilumab on the Microbiome in Type 2 Inflammatory Diseases: A Systematic Review
PURPOSE OF REVIEW: To systematically review current evidence on microbiota changes associated with dupilumab treatment across different anatomical sites in type 2 inflammatory diseases. RECENT FINDINGS: Fifteen studies were included, comprising two randomized trials and thirteen observational studies, mostly in atopic dermatitis, with fewer data in chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease. The skin was the most frequently investigated site, followed by the sinonasal tract and gut. Across skin studies, dupilumab was consistently associated with reduced Staphylococcus aureus, increased microbial diversity, and enrichment of commensal taxa. Sinonasal studies suggested shifts toward more eubiotic microbial communities. Gut evidence was limited, although one study suggested modulation of tryptophan metabolism-related pathways. Dupilumab appears to exert compartment-specific and disease-dependent effects on the microbiome. The strongest evidence concerns the skin and sinonasal compartments, whereas gut microbiota changes remain poorly defined. Further prospective studies are needed to assess microbiota signatures as potential biomarkers of response.
18 May 2026
Read appraisal →Journal of pharmacokinetics and pharmacodynamics
Development of a novel rabeprazole modified release formulation to reduce the dosing frequency: A trial and triumph with physiologically based biopharmaceutics modeling.
Advanced in silico tools, such as physiologically based biopharmaceutics models (PBBM) and physiologically based pharmacokinetic models (PBPK), play a pivotal role in model-informed formulation development (MIFD). In the present study, these methodologies were utilized in the development of a novel rabeprazole modified-release (MR) formulation for improved patient compliance by reducing the dosing frequency relative to existing delayed-release (DR) formulation. A MR formulation containing combination of delayed release and pulsatile release components was designed based on the hypothetical dissolution targets. A PBBM was first established using literature-derived clinical data and used to simulate the performance of formulations with varied dissolution profiles. Initial MR formulation prototypes (once a day) were evaluated in pilot-1 bioequivalence (BE) study against reference formulation (twice a day) but results indicated infra bioequivalence outcome. After pilot-1 study, the formulation and the dissolution method were optimized and then model was refined to predict the pilot 1 outcomes. The validated model was then employed to select suitable pilot-2 prototypes and to prospectively predict their BE outcomes under fasted and fed conditions. The predicted BE ratios were in good agreement with the observed pilot-2 study results. Therefore, the same model was used to make prospective predictions with increased subjects to understand the in vivo performance of pivotal test formulation and lead to the successful bioequivalence outcome, product commercialization, ultimately aiding in increased patient compliance. This work highlights the value of a model-informed strategy in accelerating formulation optimization, reducing development timelines and costs, and strengthening decision-making within pharmaceutical development programs.
18 May 2026
Read appraisal →Signal transduction and targeted therapy
HILL: the efficacy and safety of hepatic arterial infusion chemotherapy with the FOLFOX regimen combined with lenvatinib and the PD-L1 inhibitor durvalumab in unresectable hepatocellular carcinoma: a prospective, single-arm, phase 2 clinical trial
Despite numerous available treatment options, the overall prognosis for patients with unresectable hepatocellular carcinoma (uHCC) remains poor. This study aimed to evaluate the efficacy and safety of combining hepatic arterial infusion chemotherapy with FOLFOX (FOLFOX-HAIC), lenvatinib, and the PD-L1 inhibitor durvalumab in this population, with all uHCC patients receiving the triple-combination regimen as initial therapy. The primary objective was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. From August 2021 to September 2023, 40 uHCC patients were enrolled, with a median follow-up of 23.1 months (95% confidence interval [CI], 19.0-23.8); 3 deaths and 12 disease progressions were recorded. The median PFS was 15.8 months (95% CI, 8.3-23.3) with a 6-month PFS rate of 77.5% (95% CI, 63-90%), and 1- and 2-year OS rates were 97.5% and 94.0%, respectively. Per modified RECIST criteria, ORR was 75.0% (9 CR/pCR, 21 PR) and DCR was 95.0% (8 SD); median time to response (TTR) was 2.2 months and median duration of response (DOR) was 10.4 months. Seven patients (17.5%) underwent R0 conversion surgery, 3 (42.9%) achieving pCR. Safety was favorable: 85.0% had grade 1-2 adverse events, with grade 3 elevated alanine aminotransferase and thrombocytopenia each occurring in 2 patients (5.0%). No grade 4 adverse events were observed. Collectively, the triple-combination therapy of FOLFOX-HAIC, lenvatinib, and durvalumab exhibits promising therapeutic efficacy, favorable disease control, and a well-tolerated safety profile, providing a potential new treatment option for patients with uHCC. Trial number: NCT04961918.
18 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
PET/CT-Guided Neoadjuvant Tislelizumab plus Chemotherapy/Chemoradiotherapy for Resectable Esophageal Squamous Cell Carcinoma: RATIONALE-213 Final Analysis
PURPOSE: The aim of this study is to assess positron emission tomography/computed tomography (PET/CT)-guided neoadjuvant treatment with tislelizumab plus chemotherapy/chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: RATIONALE-213, a multicenter, open-label, two-cohort phase II study, enrolled 70 patients with resectable ESCC. After one induction chemotherapy cycle, patients were categorized as PET responders (PET maximum standardized uptake value decrease ≥35%) or PET nonresponders (<35%). Subsequently, all patients received three cycles of tislelizumab 200 mg intravenously. In addition, PET responders received chemotherapy and PET nonresponders received chemoradiotherapy as neoadjuvant treatment followed by surgery. The primary endpoint was the pathologic complete response (pCR) rate. RESULTS: As of October 25, 2024 (median follow-up 25.5 months), pCR rates were 30% [95% confidence interval (CI), 11.9-54.3] in PET responders and 34.4% (95% CI, 18.6-53.2) in PET nonresponders. Higher pCR rates were associated with higher baseline programmed cell death ligand 1 tumor area positivity scores in both cohorts. One-year disease-free survival rates were 79% and 74.2%, and event-free survival rates were 87.1% and 67.8%, respectively. Any-grade and grade ≥3 treatment-related adverse events (TRAE) occurred in 93.3% and 50% of PET responders and 97.5% and 82.5% of PET nonresponders, with no new safety signals. The most common grade ≥3 TRAE was decreased neutrophil count (36.7% and 70%, respectively). CONCLUSIONS: Tislelizumab with chemotherapy/chemoradiotherapy as neoadjuvant treatment for resectable ESCC yielded promising pCR rates and favorable survival outcomes with a tolerable safety profile in both PET/CT-guided responders and PET nonresponders.
18 May 2026
Read appraisal →Journal of gastrointestinal cancer
Long-term Outcomes of Protocol-based Neoadjuvant Selection and Liver Transplantation Versus Liver Resection for Perihilar Cholangiocarcinoma: A Systematic Review and Meta-analysis
BACKGROUND: Perihilar cholangiocarcinoma (CCA) is an aggressive malignancy that presents significant challenges in terms of diagnosis and treatment owing to its anatomical location. Liver resection and transplantation are the primary curative options; however, their long-term outcomes remain controversial. This study aimed to compare the long-term outcomes of protocol-based neoadjuvant selection and liver transplantation with liver resection for the management of perihilar cholangiocarcinoma. METHODS: A systematic review and meta-analysis were conducted according to the PRISMA guidelines. Electronic databases, including the Cochrane Library, PubMed/MEDLINE, and Embase, were searched for relevant clinical trials comparing liver transplantation with liver resection. RESULTS: Six studies comprising 768 patients (265 in the liver transplantation group and 503 in the liver resection group) were included. Liver transplantation was associated with significantly higher 5-year overall survival and 5-year disease-free survival. They also showed a higher 3-year disease-free survival rate. Patients in the liver transplantation group had a higher R0 resection rate. There were no significant differences in the 3- or 30-day postoperative mortality between the two groups. CONCLUSION: Liver transplantation was associated with improved long-term survival in highly selected patients; however, these findings are limited by significant selection bias and the retrospective study design. The apparent long-term benefit observed with LT must be interpreted cautiously because transplant series frequently report post-transplant rather than intention-to-treat outcomes.
18 May 2026
Read appraisal →Computers in biology and medicine
AI unleashed: A meta-analysis transforming radiological insights in diagnosing abdominal infections
INTRODUCTION: Artificial intelligence (AI)-based imaging modalities are next-generation diagnostic devices for abdominal infections that promise to provide enhanced diagnostic speed and accuracy. This systematic review and meta-analysis critically analyze the diagnostic accuracy of AI-assisted imaging modalities, including for appendicitis, pneumoperitoneum, and cholecystitis, to present a balanced estimate of their clinical utility. METHODS: A systematic literature search was undertaken in PubMed, Scopus, and Cochrane databases to search for studies that assessed the diagnostic accuracy of AI-based imaging modalities for abdominal infections. Eleven studies were included based on the inclusion criteria, and data were pooled for analysis. Diagnostic performance was measured by estimating sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), and area under the curve (AUC) using a random-effects model. Subgroup analyses were done to investigate the effect of infection type on diagnostic accuracy. RESULTS: AI-assisted imaging demonstrated an overall sensitivity of 0.891 (95% CI: 0.824-0.944) and specificity of 0.860 (95% CI: 0.784-0.922) for diagnosing abdominal infections. Subgroup analysis revealed that AI-aided computed tomography (CT) exhibited a sensitivity of 0.902 (95% CI: 0.850-0.948), while ultrasound (US) showed a sensitivity of 0.864 (95% CI: 0.792-0.922). The highest AUCs were observed for pneumoperitoneum (0.985) and appendicitis (0.947), underscoring AI's robust diagnostic capabilities across multiple pathologies. CONCLUSION: AI-imaging modalities significantly enhance diagnostic accuracy for abdominal infections, particularly for appendicitis and pneumoperitoneum. This meta-analysis underscores AI's clinical potential, though future research should prioritize multicenter studies to validate AI models' generalizability and ensure consistent performance across diverse healthcare settings.
17 May 2026
Read appraisal →Clinica chimica acta; international journal of clinical chemistry
AI in the Prediction of Hepatic Fibrosis Progression Using Non-Coding RNAs
Hepatic fibrosis is a dynamic and progressive condition that can lead to cirrhosis and hepatocellular carcinoma (HCC) if left untreated. Appropriate assessment of the disease progression of fibrosis is critical for early intervention and individualized treatment regimens. Traditional biopsy techniques are invasive and prone to sampling errors, highlighting the need for less invasive predictive techniques. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as key regulators of hepatic fibrogenesis and as a possible biomarker for disease staging and prognosis. The emergence of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has revolutionized the comprehensive large-scale analysis of transcriptomic data, enhancing the identification of ncRNA biomarkers and predictive modeling. The AI-based algorithms have been found to be more precise in anticipating fibrosis progression by means of integrating multi-omics data, ncRNA interaction networks, and by improving non-invasive diagnostic tools. This review involves the analysis of AI and ncRNA research in hepatic fibrosis, highlighting recent discoveries, possible challenges, and future opportunities. We address the necessity of standardization of data and clinical validation, as well as discuss the role of AI in identifying biomarkers of ncRNA, predicting the stage of fibrosis and risk stratification. ncRNA analysis with AI has a tremendous potential of transforming the diagnostics and prognostics of hepatic fibrosis, enabling precision hepatology.
17 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
Pembrolizumab Monotherapy in Sorafenib-Treated and Treatment-Naïve Advanced Hepatocellular Carcinoma: Long-Term Follow-up of the Open-Label, Phase II KEYNOTE-224 Study
PURPOSE: In the phase II KEYNOTE-224 study, pembrolizumab showed durable antitumor activity and manageable safety in participants with sorafenib-treated (cohort 1) or treatment-naïve (cohort 2) advanced hepatocellular carcinoma (HCC). We present data after a median follow-up of ∼7 years for cohort 1 and ∼5 years for cohort 2. PATIENTS AND METHODS: Adults with advanced HCC received pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity for ≤35 cycles. The primary endpoint was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Overall, 155 participants received ≥1 dose of pembrolizumab (cohort 1, n = 104; cohort 2, n = 51). The median follow-up was 83 months (range, 79.3-87.3) for cohort 1 and 58.8 months (range, 55.3-60.8) for cohort 2. The median OS was 13.2 months [95% confidence interval (CI), 9.7-15.3] and 16.9 months (95% CI, 8.3-23.1), respectively; 24- and 48-month OS rates were 31%/17% and 34%/20%, respectively. The median PFS was 4.9 months (95% CI, 3.5-7) and 4.3 months (95% CI, 2.1-7.8), respectively. Treatment-related adverse events occurred in 76 participants [73.1%; grade 3-5, 27 (26%)] in cohort 1 and 28 participants [54.9%; grade 3-5, 8 (15.7%)] in cohort 2. CONCLUSIONS: Pembrolizumab continued to show durable response and manageable safety in participants with advanced HCC with or without prior systemic therapy, with long-term effects on OS lasting beyond 48 months in some participants despite receiving study treatment for ≤2 years.
17 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
Allogeneic B7-H3-Targeted CAR Vδ1T-cell Therapy in Advanced Solid Tumors: A Phase I Study
PURPOSE: The aim of the study was to evaluate the safety, pharmacokinetics, and preliminary clinical activity of UTAA06, an "off-the-shelf" allogeneic B7-H3-targeted chimeric antigen receptor (CAR) Vδ1T-cell therapy, in patients with pretreated, advanced B7-H3-positive solid tumors. PATIENTS AND METHODS: In this first-in-human, phase I, dose-escalation study (NCT06372236), 10 patients with advanced solid tumors (including gastric, colorectal, hepatocellular, ovarian, and neuroendocrine cancers) were enrolled. Following lymphodepletion chemotherapy (cyclophosphamide and fludarabine), patients received UTAA06 infusion across three dose levels (5 × 108, 8 × 108, or 1 × 109 cells). The primary endpoint was safety. Secondary endpoints included pharmacokinetics and antitumor efficacy. RESULTS: UTAA06 demonstrated a manageable safety profile; no GVHD was observed, and cytokine release syndrome was limited to two transient grade 1 events. A single dose-limiting toxicity (grade 3 pneumonitis) was reported in one patient at the 5 × 108 cell dose level. Although UTAA06 demonstrated signals of biological activity, including transient reductions in serum tumor markers in 50% of patients, no objective response by RECIST v1.1 criteria was observed. Further analysis identified that the limited CAR T-cell persistence was likely driven by subclinical host-versus-graft rejection. CONCLUSIONS: This study provides clinical proof of concept for allogeneic B7-H3-targeted CAR-Vδ1T cells as a safe platform with low risk of GVHD and demonstrable biological activity in solid tumors. However, clinical efficacy was constrained by limited cellular persistence caused by host immune rejection. Future strategies are required to enhance the durability and therapeutic potential of this allogeneic approach.
17 May 2026
Read appraisal →European journal of cancer (Oxford, England : 1990)
Aflibercept and 5-FU vs. FOLFOX as 1st line treatment for older adults or frail elderly patients with metastatic colorectal cancer - The randomized phase 2 AIO / IKF ELDERLY trial (AIO-KRK-0117 / IKF 629)
BACKGROUND: Fluoropyrimidines + angiogenesis inhibitor or dose-reduced doublets are used for (frail) elderly patients with metastatic colorectal cancer (mCRC). This non-comparative trial evaluated two 1st line regimens for patients not eligible for full-dose combinations. METHODS: This open-label, multicenter, phase II study randomized untreated mCRC patients ≥ 70 years ± frailty 1:1 to dose reduced mFOLFOX7 in Arm A or aflibercept (4 mg/kg) plus dose reduced mLV5FU2 in Arm B. Primary endpoint was the 6-months PFS rate (PFS@6), secondary endpoints included safety, overall survival (OS), overall response rate (ORR), patient reported outcomes and overall treatment utility (OTU). FINDINGS: The full analysis population comprised 120 patients (62 Arm A, 58 Arm B; 63% male), with a median age of 78.5 years. 82% frail patients were included. PFS@6 was 68% [95%CI 56%;80%] in Arm A and 46% [32%;59%] in Arm B. Median PFS was 7.9 and 5.5 months, median OS was 20.4 and 19.0 months and ORR was 47% and 22% in Arm A and B, respectively. At 3 months, 52% in Arm A and 35% in Arm B had a good OTU. Most frequent grade ≥ 3 AEs in Arm B were hypertension (41%) and proteinuria (10%). More patients in arm B had treatment-related SAEs grade ≥ 3 (17% in arm B and 5% in arm A). INTERPRETATION: Both regimens were feasible in this (frail) elderly population. Dose-reduced mFOLFOX7 and, to a lesser extent, 5-FU/aflibercept showed good PFS and 3-month OTU. Although most patients were regarded frail, survival rates were promising, most likely due to effective further-line treatments.
17 May 2026
Read appraisal →Techniques in coloproctology
Bridging the gap: a systematic literature review and meta-analysis on the management of rectal wall defect after transanal excision
BACKGROUND: Transanal resection techniques have gained considerable importance in the treatment of benign and malignant rectal neoplasms. However, there is no definitive consensus on whether the rectal defect should be closed or left open after excision. We sought to provide an updated pooled analysis of the management of rectal wall defect after transanal excision. METHODS: In accordance with PRISMA and Cochrane guidelines, this meta-analysis was performed using the PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Google Scholar databases to identify studies comparing perioperative outcomes after rectal defect closure versus leaving the defect open following full-thickness (FT) excision. Odds ratios (ORs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Cochrane's Q test. Risk of bias and certainty of evidence were judged by ROBINS-I and GRADE, respectively. RESULTS: Six comparative studies meeting the inclusion criteria were included in the final analysis. Closing the rectal defect was associated with significantly reduced rectal bleeding (OR = 0.57, 95% CI: 0.35-0.94, p = 0.03; I2 = 26%) and re-admission rates (OR = 0.34, 95% CI: 0.16-0.76, p = 0.008; I2 = 0%) compared with the open group, while other outcomes were not significantly different. A prolonged operative time was noted when the rectal wall defect was sutured (SMD = 0.15, 95% CI: 0.03-0.28, p = 0.02; I2 = 44%). CONCLUSIONS: The present analysis revealed that both approaches are safe and technically feasible; however, closing the rectal wall defect after FT excision of rectal neoplasms was associated with lower bleeding and re-admission rates. Nevertheless, randomized studies with homogeneous protocols and consistent long-term outcome data are still needed to provide definitive answers.
17 May 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Is iron supplementation likely to impair linear growth and gut microbiota composition of Myanmar young children when complementary feeding is not optimized? A randomized controlled trial.
Iron deficiency, with or without anemia, remains a major public health concern among young children in Myanmar. While iron supplementation is widely recommended, its potential adverse effects on growth and gut microbiota warrant investigation, particularly in contexts of poor complementary feeding. To assess the effects of iron supplementation, with or without complementary feeding recommendations (CFRs), on micronutrient status, linear growth and gut microbiota composition among Myanmar children aged 12-23 months, a 24-week randomized controlled trial was conducted in Ayeyarwady Region of Myanmar. Fourteen clusters (villages/wards) were randomized to receive CFRs or not, and children within the clusters were randomized to receive daily aqueous iron or placebo, creating four arms: Placebo (n = 104), CFR (n = 112), Fe (n = 105) and CFRFe (n = 112) totalling 433 children. All intervention groups (CFR, Fe, CFRFe) improved haemoglobin and reduced anaemia risk compared with Placebo (AOR = 0.31 (0.15-0.62), 0.15 (0.07-0.32), 0.14 (0.07-0.31), respectively). CFR and CFRFe also improved zinc status. However, iron-alone (Fe) increased the stunting risk (AOR= 2.74 (1.04-7.23)), while CFRFe did not. No significant effects were observed on gut microbiota composition. Aqueous iron supplementation may impair linear growth when diets are not optimized; combining supplements with optimized complementary feeding may support healthier outcomes. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.
17 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
Circulating Tumor DNA Dynamics and Clinical Outcomes in Patients with Advanced Colorectal Cancer Treated with Cetuximab-Based Induction and Maintenance Treatment
PURPOSE: We investigated whether circulating tumor DNA (ctDNA) changes may be useful to assess clinical outcomes in patients with metastatic colorectal cancer (mCRC) randomized in the TIME-PRODIGE-28 trial comparing biweekly maintenance with cetuximab alone with observation after 4-month fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab induction chemotherapy. EXPERIMENTAL DESIGN: ctDNA samples were collected at four time points from baseline until disease progression during the first chemotherapy-free interval and analyzed using next-generation sequencing and methylation marker approaches. Progression-free survival (PFS) and overall survival (OS) from randomization were analyzed according to ctDNA kinetics and EGFR-MAPK pathway alterations. RESULTS: Among 139 randomized patients, 104 (74.8%) had paired samples available. Patients with negative baseline ctDNA remaining negative after 4-month induction chemotherapy had significantly longer PFS from randomization (9.6 months) as compared with patients with a ctDNA decrease of ≥80% (3.4 months) or a ctDNA decrease of <80% (2.1 months; P = 0.013). Patients with EGFR-MAPK pathway alterations identified either in tissue or baseline ctDNA had worse PFS and OS from randomization. Acquired alterations found in 17 of 63 (26.9%) patients at disease progression during the first chemotherapy-free interval were associated with worse OS from reintroduction of the full induction chemotherapy (14.9 vs. 19.4 months; P = 0.025). CONCLUSIONS: Our findings show the prognostic impact of both ctDNA kinetics and EGFR-MAPK pathway alteration dynamics following induction chemotherapy with FOLFIRI-cetuximab in patients with mCRC. Prospective studies evaluating ctDNA-guided treatment strategies are needed to validate the clinical utility of ctDNA monitoring to improve patient selection for first-line treatment de-escalation and anti-EGFR-based maintenance regimens, including treatment adaptation over time.
16 May 2026
Read appraisal →BMJ open gastroenterology
Development and validation of multivariable prognostic machine learning models to identify patients at risk for inadequate bowel preparation when undergoing colonoscopy: a prospective, multicentre study
OBJECTIVE: Inadequate bowel preparation impairs the accuracy of colonoscopy and increases the burden on patients and healthcare systems. Consequently, the quality of bowel preparation is an important quality indicator. We aim to develop and validate multivariable prognostic models for the identification of patients at risk of inadequate bowel preparation using machine learning (ML). METHODS: Demographic and clinical data from consecutive patients ≥18 years of age who underwent colonoscopy at six centres in Germany were prospectively collected. Adequate bowel preparation was defined as Boston Bowel Preparation Scale ≥6 with a value ≥2 in each colonic segment. We used statistical and ML methods to build prognostic models and to compare them to published models. RESULTS: Overall, we analysed 2652 patients, including 699 (26.4%) inpatient procedures. The mean patient age was 57.6 years (SD 16 years), and 48.9% were women. In 1401 (52.8%) patients, the indication was screening or surveillance, and 1035 (39%) patients had a first-time colonoscopy. The rate of inadequate bowel preparation was 16%. Sensitivities, specificities and areas under the curve of predictive models obtained by generalised boosting models, Ranger, support vector machine (radial), CatBoost and Net Regularised Generalised Linear Models were 0.51-0.86, 0.52-0.83 and 0.71-0.74, respectively. They were only marginally superior to a logistic regression model. All models had high negative predictive values >0.9 for inadequate bowel preparation. To detect one patient with inadequate bowel preparation, 8-10 patients need to be evaluated. CONCLUSIONS: Predictive models to identify patients at risk for inadequate bowel preparation obtained by ML showed comparable results compared with a logistic regression model. TRIAL REGISTRATION NUMBER: DRKS00018878.
16 May 2026
Read appraisal →Computers in biology and medicine
Artificial intelligence for metabolic dysfunction-associated steatotic liver disease diagnosis: A systematic review
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses significant diagnostic challenges. We conducted a systematic review of artificial intelligence (AI) applications in MASLD diagnosis, focusing on predictive modeling, screening, imaging analysis, and therapeutic assistance. Following PRISMA guidelines, we searched five databases (Web of Science, SciFinder, Elsevier ScienceDirect, EBSCOhost, Springer) for studies published January 2020-January 2026. Of 1247 initially identified records, 191 studies met inclusion criteria. AI models demonstrate high diagnostic performance across multiple modalities. Deep learning analysis of US, CT, and MRI enables automated steatosis quantification and fibrosis staging with accuracy comparable to expert interpretation. AI integration with multi-omics data facilitates novel biomarker discovery and therapeutic target identification. Despite these advances, model generalisability, standardization, and clinical integration remain challenges. AI holds substantial potential to transform MASLD diagnostics, but prospective validation and implementation strategies are needed before widespread clinical adoption.
16 May 2026
Read appraisal →Journal of robotic surgery
Robot-assisted versus laparoscopic distal pancreatectomy: an updated systematic review and meta-analysis including patient subgroups and meta-regression analyses
Robot-assisted distal pancreatectomy (RDP) was developed to overcome technical limitations of laparoscopic distal pancreatectomy (LDP), yet uncertainty persists regarding oncologic adequacy, learning-curve effects, and outcomes in high-risk subgroups. We synthesized current evidence to address these gaps. We systematically searched PubMed and EMBASE, in accordance with PRISMA guidelines, from inception to 2025 to identify comparative studies of RDP versus LDP. Using random-effects models, we calculated weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, and performed subgroup analyses, including pancreatic ductal adenocarcinoma (PDAC), along with meta-regression to explore heterogeneity sources. Sixty-four studies comprising 15,790 patients (5,723 RDP; 10,067 LDP; mean age 60.5 years; BMI 26.1 kg/m²) were included. RDP resulted in lower blood loss (WMD - 52.0 mL; p < 0.00001), fewer conversions (RR 0.49; p < 0.00001), and fewer unplanned splenectomies (RR 0.59; p < 0.0001). Operative time was longer (WMD + 24.06 min; p < 0.00001). Postoperative morbidity, POPF, PPH, infection, reintervention, and mortality were comparable. Length of stay was shorter with RDP (WMD - 0.57 days; p < 0.00001). Although lymph node yield appeared higher with LDP in the overall and PDAC cohorts, this difference was no longer significant in a sensitivity analysis, and R0 resection rates remained comparable. Costs were higher with RDP, with substantial heterogeneity. RDP and LDP demonstrate comparable safety and oncologic outcomes. RDP reduces blood loss, conversions, and splenectomy but increases operative time and cost. The operative time disadvantage likely reflects learning-curve. Selective use in high-risk and complex resections is supported; cost-effectiveness warrants further study.
15 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Effectiveness of comprehensive interventions including exercise and exercise-only interventions on postoperative ileus and recovery of intestinal function in patients with colorectal cancer: a systematic review and meta-analysis
PURPOSE: This systematic review and meta-analysis aimed to evaluate the effectiveness of postoperative or preoperative comprehensive interventions including exercise and exercise-only interventions on postoperative ileus (POI) incidence and the recovery of intestinal function in patients with colorectal cancer (CRC). METHODS: Electronic searches were conducted in 6 databases. Cohort and randomized-controlled trial (RCT) studies investigating the effects of postoperative or preoperative comprehensive interventions including exercise or exercise-only interventions on POI and the recovery of intestinal function in patients with CRC were included. RESULTS: Thirty-eight studies involving 13,124 patients were included. Postoperative comprehensive interventions including exercise significantly shortened the time to first flatus (standardized mean difference [SMD] = -1.38, 95% confidence interval [CI]: -1.87 to -0.89) and time to first defecation (SMD = -1.56, 95% CI: -2.20 to -0.92), but did not reduce POI incidence (odds ratio [OR] = 1.38, 95% CI: 0.43 to 4.47). While, postoperative exercise-only interventions showed no significant effect on intestinal recovery (SMD = -0.31, 95% CI: -1.21 to 0.58). Preoperative comprehensive interventions including exercise shortened the time to first flatus (SMD = -0.41, 95% CI: -0.66 to -0.17). Also, preoperative exercise-only interventions significantly reduced the incidence of POI (OR = 0.56, 95% CI: 0.46 to 0.67). CONCLUSIONS: Postoperative comprehensive interventions effectively promote intestinal recovery; however, postoperative exercise-only interventions may not promote the recovery of intestinal function. On the other hand, preoperative comprehensive interventions or exercise-only interventions may promote the recovery of intestinal function and prevent POI onset; however, the limited number of included studies prevented definitive conclusions.
15 May 2026
Read appraisal →Journal of medical Internet research
Leveraging Text Messaging and Behavior Theory to Improve Colorectal Cancer Screening in Federally Qualified Health Centers: Cohort Study
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Despite recommendations for screening to begin at the age of 45 years, significant disparities persist, particularly among medically underserved populations. OBJECTIVE: This study examines the effectiveness of SMS text messaging reminders in improving CRC screening rates across 2 large federally qualified health centers (FQHCs) serving vulnerable populations. METHODS: The study included 4822 adults aged ≥45 years, receiving care at 2 large FQHC networks in Texas and California. Participants were assigned to one of four groups: (1) control (no SMS text messages), (2) single-outreach SMS text overdue message, (3) three-week SMS overdue and reminder text messages, and (4) six-week SMS text messages that were informed by behavior theory. Data were collected from May 2023 to July 2024. The outcome measure was a binary indicator of whether the participant underwent 1 of 3 CRC tests, fecal immunochemical test, colonoscopy, and Cologuard, within 90 days of completing the SMS text messaging reminders. Independent variables included demographic, geographic, clinical, and primary care access variables. Multivariate logistic regression models were used to examine associations between CRC screening completion and the SMS text messaging reminder groups, adjusting for covariates. Adjusted odds ratios (aORs) and 95% CIs were reported. RESULTS: In the combined 3-test model, patients in the single-outreach SMS text message (aOR 1.22, 95% CI 1.00-1.47) and the 3-week SMS text message (aOR 1.27, 95% CI 1.05-1.53) groups had higher odds of completing the screening test compared to those in the control group. Within the fecal immunochemical test-only model, patients in the 3-week SMS text message group (aOR 1.25, 95% CI 1.00-1.56) were more likely to complete the screening test. Within the Cologuard-only model, patients in the 3-week SMS text message group (aOR 7.01, 95% CI 1.96-25.07) and the 6-week SMS text message group (aOR 5.75, 95% CI 1.53-21.61) had significantly higher odds of CRC screening completion. CONCLUSIONS: The findings highlight that moderate-frequency SMS text messaging reminders can effectively increase CRC screening rates in FQHCs; however, critical factors include the timing and frequency of these reminders. The 3-week intervention was associated with improved screening uptake, whereas the 6-week theory-informed intervention did not demonstrate a significant advantage over the control group, potentially reflecting a ceiling effect or message fatigue associated with more frequent messaging. Additionally, the study highlights unique screening patterns that contradict previous literature, underscoring the importance of a tailored approach for vulnerable communities.
15 May 2026
Read appraisal →PloS one
Evaluation of the diagnostic value of the Modified Evan's Blue Dye Test for assessing aspiration in tracheostomized critically ill patients: A systematic review and meta-analysis
Dysphagia and aspiration are common complications in tracheostomized critically ill patients. The Modified Evan's Blue Dye Test (MEBDT) is a non-invasive, bedside, adjunctive rule-in signal for aspiration when positive. However, its diagnostic accuracy compared to the gold standard Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in these patients remains unclear. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of the MEBDT for the detection of aspiration in tracheostomized critically ill patients. Study protocol was prospectively registered on PROSPERO (CRD:42023479920). A systematic search was performed across three databases (PubMed, Cochrane Central, and Embase), followed by a systematic screening process against predetermined selection criteria and included studies that provided data on the sensitivity and specificity of MEBDT versus FEES. The risk of bias and the level of evidence certainty in the included papers were assessed by the QUADAS-2 tool and GRADE approach respectively. Six out of 2227 screened studies were included. We found that MEBDT had a high specificity 95.42% (95% CI [67.38%, 99.53%]) and positive predictive value 95% (95% CI [81, 100]). In conclusion, the MEBDT can serve as a bedside adjunctive tool that indicates a potential aspiration risk when the result is positive. However, if the result is negative, further diagnostic assessments, like FEES, are recommended for high-risk patients.
15 May 2026
Read appraisal →Journal of robotic surgery
Robotic versus laparoscopic low anterior resection for rectal cancer: an updated systematic review and meta-analysis
Robotic surgery has increasingly been adopted for the treatment of rectal cancer. However, most previous meta-analyses included heterogeneous rectal procedures, limiting conclusions specific to low anterior resection. The present study aimed to provide an updated systematic review and meta-analysis comparing robotic versus laparoscopic low anterior resection for rectal cancer. This systematic review and meta-analysis was conducted according to PRISMA guidelines and recommendations from the Cochrane Handbook. PubMed, Scopus, and the Cochrane Library were systematically searched from inception to the most recent date. Comparative studies evaluating robotic low anterior resection (R-LAR) versus laparoscopic low anterior resection (L-LAR) for rectal cancer were included. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Certainty of evidence was evaluated using the GRADE approach. Thirty-three studies including 82,149 patients were analyzed (R-LAR: 56,290; L-LAR: 25,859). R-LAR was associated with a significantly lower conversion rate (OR 0.45, 95% CI 0.40-0.51, p < 0.00001, I²=28%), lower 30-day reoperation rate (OR 0.86, 95% CI 0.77-0.96, p = 0.01, I²=0%), reduced 30-day mortality (OR 0.65, 95% CI 0.52-0.82, p = 0.002, I²=0%), and higher rate of complete total mesorectal excision (OR 2.71, 95% CI 1.38-5.33, p = 0.01, I²=72%). Operative time was significantly longer in the robotic group (MD + 30.58 min, 95% CI 13.71-47.45, p = 0.001, I²=97%). No significant differences were observed for estimated blood loss, overall complications, major complications, anastomotic leakage, postoperative ileus, recovery parameters, length of hospital stay, readmission, circumferential margin positivity, lymph node yield, local recurrence, diverting ileostomy formation, disease-free survival, or overall survival. Robotic LAR may reduce conversion, reoperation, and short-term mortality and may improve completeness of total mesorectal excision, although operative time is longer. These findings suggest potential technical advantages of R-LAR, but high-quality randomized trials are required to determine whether these translate into meaningful clinical benefit.PROSPERO: CRD420261326600.
15 May 2026
Read appraisal →Gut
Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial)
BACKGROUND: Recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP) have limited preventive options beyond addressing the underlying aetiology. Statins, due to their anti-inflammatory properties, have been proposed as a potential prophylactic treatment. OBJECTIVE: We aimed to evaluate whether simvastatin could reduce the recurrence of pancreatitis. DESIGN: At 23 centres, we conducted a triple-blind, randomised, controlled, superiority trial enrolling patients with at least two episodes of RAP or CP flares in the previous 12 months. Participants were randomly assigned to receive simvastatin or placebo for 1 year. The primary endpoint was the recurrence of pancreatitis. The target sample size was 144 patients; however, an interim analysis was planned in the event of slow recruitment. RESULTS: A total of 85 patients (42.1% women) were included in the interim analysis. In the intention-to-treat analysis, no significant differences were observed regarding recurrence: 46.2% simvastatin versus 44.4% placebo; OR 1.07, 95% CI 0.43 to 2.66; p=0.88, or time to recurrence. No statistically significant differences were observed in recurrence in per-protocol analysis (35.5% simvastatin vs 41.9% placebo; OR 0.76, 95% CI 0.27 to 2.12; p=0.60). Development of diabetes mellitus was more frequent in the simvastatin group (4 vs 0 patients; OR not calculable, p=0.04). CONCLUSION: This trial, evaluating simvastatin versus placebo for the prevention of pancreatitis, did not demonstrate a reduction in recurrence rate, although results might be underpowered due to early termination. The relationship between statins in these patients and new-onset diabetes requires further investigation. TRIAL REGISTRATION NUMBER: NCT04021498.
14 May 2026
Read appraisal →Molecular neurobiology
Gut Microbiota Dysbiosis and Neuroinflammation in Alzheimer's Disease: a Systematic Review of Mechanistic Insights
This systematic review aims to identify microbial species associated with Alzheimer's disease and clarify how they influence Alzheimer's disease pathology, including immune system interactions and blood-brain barrier integrity. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 18 studies were analyzed, revealing significant differences in gut microbiota composition between patients with Alzheimer's disease and controls. Key findings include reduced beneficial bacteria, such as Faecalibacterium prausnitzii and Roseburia hominis and increased pro-inflammatory species like Escherichia coli. Mechanistically, Escherichia coli produces lipopolysaccharides, triggering the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha. This response correlates with elevated YKL-40 levels and reduced beneficial bacteria like Turicibacter. Additionally, reductions in butyrate-producing bacteria impair blood-brain barrier integrity, while bile acid metabolism disruptions impair signaling pathways, exacerbating amyloid-beta aggregation. These findings highlight the interplay between gut microbiota-derived metabolites and neuroinflammation, suggesting that targeting the gut microbiota for novel diagnostic and therapeutic approaches in Alzheimer's disease.
14 May 2026
Read appraisal →Lancet (London, England)
Long-term effects of colonoscopy screening on colorectal cancer incidence and mortality: a multicountry, population-based randomised controlled trial
BACKGROUND: We previously reported the 10-year effects of colonoscopy screening on colorectal cancer incidence and mortality. Here, we report the effects after 13 years of follow-up. METHODS: In this multicountry, population-based randomised controlled trial, 84 583 men and women aged 55-64 years at enrolment from Norway, Poland, and Sweden were randomly allocated (1:2) to colonoscopy screening or no screening and analysed. The primary outcomes were colorectal cancer incidence and mortality after 10-15 years of follow-up in intention-to-screen analyses, with first analysis after 10 years, and repeated every other year or at longer intervals. This trial is registered with ClinicalTrials.gov, NCT00883792, and is ongoing. FINDINGS: At 13 years of follow-up, colorectal cancer incidence was 375 colorectal cancers (1·46%) of 28 217 individuals in the screening group and 912 colorectal cancers (1·80%) of 56 366 individuals in the no-screening group. The risk ratio (RR) was 0·81 (95% CI 0·71-0·90) in intention-to-screen analyses and 0·55 (0·33-0·81) in per-protocol analyses. The risk for proximal colorectal cancer was 129 (0·51%) in the screening group versus 283 (0·56%) in the no-screening group (RR 0·91 [0·71-1·09]), and the risk for distal colorectal cancer was 224 (0·87%) in the screening group versus 563 (1·11%) in the no-screening group (RR 0·79 [0·65-0·89]; interaction p<0·0001). In men, the colorectal cancer risk was 214 (1·69%) of 14 154 in the screening group and 541 (2·19%) of 28 247 in the no-screening group (RR 0·77 [0·64 to -0·88]); in women, the risk was 161 (1·24%) of 14 063 in the screening group versus 371 (1·43%) of 28 119 in the no-screening group (RR 0·87 [0·70 to 1·02]; interaction p<0·0001). Colorectal cancer mortality was 106 (0·41%) of 28 217 in the screening group and 236 (0·47%) of 56 366 in the no-screening group (intention-to-screen RR 0·88 [0·68-1·08], per-protocol RR 0·70 [0·26-1·25]). The observed colorectal cancer mortality in the non-screening group (0·47%) was substantially lower than expected at the time of designing the trial (0·82%). INTERPRETATION: One colonoscopy significantly reduced colorectal cancer incidence but not mortality over 13 years. Colorectal cancer mortality was lower in both study groups than when the trial was designed. FUNDING: The Norwegian Research Council, the Nordic Cancer Union, the Norwegian Cancer Society, and the Health Fund of South-East Norway.
13 May 2026
Read appraisal →Journal of ethnopharmacology
Anti-inflammatory properties of Dendrobium: A systematic review of pharmacological mechanisms
ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Chinese Medicine (TCM), Dendrobium species have long been used to alleviate various inflammatory conditions, particularly those characterized by Yin deficiency with internal heat and stomach deficiency-heat, including impaired fluid production, stomach Qi dysfunction, and poor appetite. The inflammatory response is regulated by multiple signaling pathways that drive disease pathogenesis, making these pathways promising targets for anti-inflammatory therapy. Medicinal Dendrobium, enriched with anti-inflammatory bioactive constituents, exhibits substantial systemic anti-inflammatory activity. Its growing research interest stems from favorable properties such as low toxicity, broad therapeutic efficacy, and minimal risk of drug resistance. AIM OF THE STUDY: Medicinal Dendrobium and its bioactive constituents have demonstrated significant anti-inflammatory properties, underscoring their pharmacological potential. Nevertheless, substantial efforts remain an urgent priority to advance the translation of basic research findings into clinical applications. Therefore, pharmacological studies published within the past six years were systematically reviewed to elucidate the mechanisms by which Medicinal Dendrobium and its bioactive constituents modulate inflammatory processes, thereby evaluating their potential as multi-targeted natural anti-inflammatories. This will facilitate the translation of anti-inflammatory research on medicinal Dendrobium from basic research to clinical investigation, thereby laying a solid foundation for its eventual clinical application in managing inflammatory diseases. MATERIALS AND METHODS: A literature search and screening strictly followed the PRISMA 2020 guidelines and employed a predefined Boolean strategy. A comprehensive search was conducted across Web of Science, PubMed, Elsevier, ScienceDirect, Scopus, CNKI, Wanfang Data, Baidu Scholar, and Google Scholar. No language restrictions were applied; this review includes key findings from Chinese-language literature. The predefined keywords included "Dendrobium," "Shihu," "bioactive constituents," "anti-inflammatory," "cytokines," "signaling pathways," as well as their corresponding Chinese terms. Taxonomic validation was conducted using the World Flora Online (http://www.worldfloraonline.org) and the Medicinal Plant Names Services (http://mpns.kew.org) databases. RESULTS: Eight Medicinal Dendrobium species and their bioactive constituents-such as polysaccharides, alkaloids, flavonoids, bibenzyls, polyphenols and stilbenoids-exert anti-inflammatory effects by modulating multiple signaling cascades, including NF-κB, MAPK/NF-κB, TLR4/NF-κB, PI3K/AKT, Nrf2/HO-1, JAK/STAT, and AMPK/SIRT1 pathways, indicating their multi-target therapeutic potential for inflammatory diseases. This review further underscores the innovative role of Dendrobium in regulating these pathways and its potential for integration with conventional pharmacological treatments, supporting its synergistic use in precision medicine. CONCLUSIONS: Medicinal Dendrobium represents a promising ethnopharmacological resource, exhibiting broad-spectrum anti-inflammatory effects through multi-target, multi-pathway, and multi-organ mechanisms. To advance its modernization, therapeutic development, and clinical translation, future research should prioritize several key directions: establishing standardized quality control system and prioritizing the structures of core bioactive constituents; applying a multi-omics approach combined with artificial intelligence-assisted modeling, network pharmacology and advanced molecular imaging techniques to systematically map its systemic anti-inflammatory regulatory network; strengthening systematic pharmacokinetic and bioavailability studies; exploring precision and synergy delivery formulations; and conducting rigorous assessments of safety profiles and side-effect management. By focusing on these priorities, research can further elucidate the systemic anti-inflammatory mechanisms of medicinal Dendrobium, thereby bridging its traditional use with contemporary precision medicine, and supporting integrated interventions for complex inflammatory diseases.
12 May 2026
Read appraisal →Japanese journal of clinical oncology
Impact of intensity-modulated radiotherapy on survival and pulmonary toxicities for localized esophageal squamous cell carcinoma
OBJECTIVE: Definitive chemoradiotherapy (CRT) is a treatment strategy for localized esophageal squamous cell carcinoma (ESCC). Herein, we aimed to evaluate clinical outcomes of definitive CRT for ESCC. METHODS: We reviewed 127 patients who received definitive CRT for localized ESCC at our institution between January 2004 and December 2022. All patients received elective nodal irradiation with concurrent chemotherapy, primarily comprising cisplatin and 5-fluorouracil, during radiotherapy. Seventeen patients (13%) received intensity-modulated radiation therapy (IMRT) only, and 16 patients (13%) were treated with IMRT as a boost. The median total dose was 61.4 Gy. Approximately 80% of the patients had clinical stage III or higher disease. We analyzed overall survival (OS), progression-free survival (PFS), locoregional recurrence rate (LRR), prognostic factors, and adverse events. RESULTS: The median follow-up period was 13 months for all patients and 22 months for survivors. The 2-year OS, PFS, and LRR were 40.4%, 27.1%, and 30.8%, respectively. The overall complete response rate was 40.2%. On multivariate analysis, clinical stage 0-III (non-T4) (P < .001) and the use of IMRT (P = .034) were significantly associated with better OS. Pulmonary toxicity was significantly lower in the IMRT group (P = .049). CONCLUSIONS: IMRT for localized ESCC may improve prognosis and reduce pulmonary toxicity.
12 May 2026
Read appraisal →European radiology experimental
Reconstruction algorithms and arm positioning effects on abdominal CT image quality and radiation dose: a phantom study
OBJECTIVE: To evaluate the effects of arm positioning and reconstruction algorithms on radiation dose and image quality of abdominal CT. MATERIALS AND METHODS: Abdominal CT scans were performed using a customized body phantom at 100 kVp with automatic tube current modulation based on noise indices (NI) of 9, 11, and 13 across seven arm positions: arms up (AU), arms down (AD), arms down with one or two-layered air cushions (ADAC, ADAC2), arms on the belly (AB), and arms on the belly with one or two-layered air cushions (ABAC, ABAC2). Images were reconstructed using filtered back projection (FBP), iterative reconstruction, and deep learning-based reconstruction (DLIR). Radiation dose was recorded. Quantitative image quality metrics included image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), sharpness, and structural similarity. Qualitative assessment of sharpness, noise, artifacts, and overall image quality was performed using fixed-dose AU-FBP images as the reference standard. RESULTS: Compared with the AU position, radiation dose increased by up to 83% in non-AU configurations, with similar trends across all NI settings. In contrast, air cushion use caused only minor, configuration-dependent dose changes. Qualitatively, non-AU FBP images showed marked degradation, whereas DLIR enabled selected non-AU configurations to approach near-reference diagnostic quality. Air cushion-related benefits were modest overall but more apparent in AB than AD configurations. CONCLUSION: Arm positioning is the primary determinant of radiation dose and image quality in abdominal CT. When arm elevation is not feasible, DLIR effectively mitigates image quality degradation, while air cushions provide limited, configuration-dependent benefits. RELEVANCE STATEMENT: When arms cannot be raised during abdominal CT, avoiding arms-on-belly and using air cushions may help maintain image quality without substantially increasing radiation dose, while deep learning image reconstruction further enhances diagnostic performance under restricted positioning conditions. KEY POINTS: Arm positioning is a major determinant of radiation dose and image quality in abdominal CT. Arms-on-belly positioning produces poorer image quality despite increased radiation dose. DLIR improves image quality across arm positions but does not eliminate positioning-related degradation.
12 May 2026
Read appraisal →Journal of Crohn's & colitis
Safety of advanced therapies during pregnancy in women with immune-mediated inflammatory diseases: a systematic review and meta-analysis
BACKGROUND AND AIMS: We aimed to assess the safety of advanced therapies, excluding tumor necrosis factor inhibitors (anti-TNFs), for the treatment of immune-mediated inflammatory diseases (IMIDs), on pregnancy and neonatal outcomes. METHODS AND ANALYSIS: We performed a systematic review and meta-analysis. Study selection and data extraction were conducted independently by two reviewers. Primary outcomes included live births, major congenital malformations (MCMs), miscarriages, and stillbirths. Risk of bias was assessed using ROBINS-I, and the certainty of evidence was evaluated using GRADE. Meta-analyses of prevalence and odds ratios (ORs) comparing advanced therapies with anti-TNFs were conducted using fixed and random effect models. RESULTS: Of 14 661 manuscripts screened, 49 studies met the inclusion criteria: eight cohorts, nine case series, and 32 case reports. Most cohort studies were at a critical risk of bias. The majority of the available data related to ustekinumab (1324 exposed offspring) and vedolizumab (585 exposed offspring) whereas data on other biologics and JAK inhibitors were very limited. Pregnancies exposed to biologics had a pooled prevalence of 82.43% for live births, 0.55% for MCMs, 8.16% for miscarriage, and 0.00% for stillbirths. No significant differences in adverse pregnancy or neonatal outcomes were observed compared with women exposed to anti-TNFs. Overall, the level of evidence was very low, due largely to reliance on small observational studies and case reports. CONCLUSION: Current evidence does not suggest an increased risk of adverse pregnancy or neonatal outcomes with advanced therapies for IMIDs. However, larger, high-quality studies are needed, and these findings should be interpreted as hypothesis-generating.
12 May 2026
Read appraisal →Cancer immunology, immunotherapy : CII
Artificial intelligence-powered H&E-based quantification of spatial tumor-infiltrating lymphocyte distribution identifies prognostic immune niches in colorectal cancer
PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) is well established; however, existing approaches inadequately capture their spatial distribution. We investigated the prognostic implications of TIL spatial distribution in CRC using an artificial intelligence (AI)-based method. METHODS: A total of 202 patients with stage II-III CRC were included. TIL densities in intratumoral (iTIL) and stromal (sTIL) regions were quantified using AI-based analysis of hematoxylin and eosin (H&E)-stained images. Based on proximity to the tumor-stromal border (TSB), TILs were subclassified into core iTIL, bounding iTIL, bounding sTIL, and outermost sTIL. Immunoscore was calculated from CD3+ and CD8+ T-cell densities in the tumor center and invasive margin. RESULTS: Correlations between AI-based and pathologist assessments (iTIL: r = 0.57; sTIL: r = 0.70) were comparable to inter-pathologist correlations (iTIL: r = 0.47; sTIL: r = 0.70). In univariate Cox regression analysis, bounding iTIL, bounding sTIL, and outermost sTIL were significantly associated with recurrence-free survival (RFS), whereas core iTIL was not. Composite TIL and TSB scores were developed by incorporating the prognostically significant regions. In multivariable analysis, the TIL score (p = 0.001), TSB score (p < 0.001), and Immunoscore (p < 0.001) independently predicted RFS. In microsatellite instability-high tumors, only the TSB score remained prognostically significant. CONCLUSION: AI-powered spatial analysis of TILs, particularly the TSB score, demonstrated prognostic performance comparable to conventional Immunoscore, thereby supporting the value of spatial immune profiling and AI-driven analysis of H&E-stained slides for improved risk stratification in CRC.
11 May 2026
Read appraisal →European journal of medicinal chemistry
AI-driven identification of a selective dual function inhibitor blocking HK2 activity and HK2-VDAC1 interaction displaying enhanced anticancer efficacy under hypoxia
Selective inhibition of hexokinase 2 (HK2) represents a promising therapeutic strategy due to the pivotal role of HK2 in the Warburg effect, enhancement of glycolysis and anti-apoptosis via HK2-Voltage-Dependent Anion Channel 1 (VDAC1) protein-protein interaction. Moreover, HK2 initiates glycolysis to generate lactate, hence this central enzyme can be pharmacologically targeted to enhance therapy outcomes. Currently, no HK2 inhibitors (HK2is) exist in the clinic. Herein, we employed GCVec, an artificial intelligence (AI)-based compound-protein interaction (CPI) prediction tool, along with molecular docking, to identify the HK2i, 106. This compound exhibited an IC50 of 0.79 ± 0.07 μM and a consistent Kd of 0.41 ± 0.03 μM against HK2 enzyme. It also apparently blocked HK2-VDAC1 interaction as indicated by the disrupted colocalization of HK2-GFP and VDAC1-mCherry. Furthermore, 106 demonstrated enhanced anticancer efficacy under hypoxia in tumor cells with elevated HIF-1α/HK2 and VDAC1 levels. Compound 106 selectively targeted SW480 colorectal cancer cells with high HK2 expression, achieving a growth inhibition IC50 value of 5.00 ± 0.94 μM. Consistently, knockout of HK2 in these tumor cells significantly rescued the IC50 values and eliminated the glycolytic inhibition induced by 106. We further showed that 106 reduced lactate and ATP levels and induced markers of apoptosis, including increased p-AMPK/AMPK ratio and increased Bax levels, as well as decreased Bcl2 levels. Collectively, our findings highlight the potential of GCVec in identifying 106, a first in class dual-function HK2i which emerges as a promising lead compound for further development into a possible anticancer therapeutic agent.
11 May 2026
Read appraisal →Pediatric surgery international
Total versus partial fundoplication in children with gastroesophageal reflux disease: a systematic review and comparative meta-analysis of 2633 patients highlighting the trade-off between reflux control and postoperative dysphagia
INTRODUCTION: Gastroesophageal reflux disease (GERD) is a common condition in children requiring surgical intervention when medical therapy fails. Nissen (total) and Toupet (partial) fundoplications are the most frequently performed antireflux procedures; however, their comparative effectiveness and safety in the pediatric population remain uncertain. METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL from database inception to 2025. Eligible studies included randomized controlled trials and observational studies comparing total and partial fundoplication in patients younger than 18 years with GERD. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models in R software. RESULTS: Eighteen studies including 2,633 children were analyzed. Total fundoplication was associated with a significantly higher risk of postoperative dysphagia compared with partial fundoplication (RR 1.69; 95% CI 1.07-2.68; p = 0.024; I²=12%; n = 1,154), corresponding to an absolute risk increase of 5.7% and a number needed to harm (NNH) of 17. No significant difference was observed in reflux recurrence (RR 0.72; 95% CI 0.21-2.42; p = 0.59; I²=71% n = 834), although event rates were numerically lower after total fundoplication (6.8% vs. 13.7%), corresponding to an absolute risk reduction of 6.9% (NNT = 15). Intraoperative complications (RR 1.11; p = 0.84), postoperative complications (RR 1.49; p = 0.12), reoperation rates (RR 0.95; p = 0.88), and mortality (RR 1.09; p = 0.74) were comparable between procedures. CONCLUSIONS: Total and partial fundoplication demonstrate similar effectiveness for reflux control and overall safety in pediatric GERD. However, total fundoplication is associated with a higher risk of postoperative dysphagia, suggesting that partial fundoplication may offer functional advantages in selected patients.
10 May 2026
Read appraisal →Annals of medicine
A comprehensive review of regulatory mechanisms of novel enterotoxin genes in Staphylococcus aureus from meat sources
BACKGROUND AND AIMS: Meat-borne Staphylococcus aureus (S. aureus) remains a leading global foodborne pathogen harbouring novel enterotoxin genes (NEGs) encoding superantigenic toxins with conditionally enhanced pathogenicity, representing a critical food safety hazard. This review characterizes NEG features, pathogenic mechanisms, multi-layered regulatory networks, and identifies key research challenges. METHODS: We systematically searched PubMed, Embase and the Web of Science Core Collection to synthesize molecular and multi-omics evidence (ChIP-seq, RNA-seq, CRISPR-Cas9) characterizing NEG classification, pathogenic mechanisms, multi-level regulatory networks (transcriptional, post-translational, environmental), and geographical distribution patterns in meat-derived S. aureus. RESULTS: NEGs comprise superantigenic and tissue-targeting subgroups mediating pathogenicity via cytotoxicity, intestinal microenvironment disruption, and immune evasion. Regulation involves a complex network of Agr/σB/SarA/Rot-mediated transcriptional control, phosphorylation/lactylation modifications and environmental sensing, exhibiting marked geographical divergence. Current limitations include technical resolution constraints, insufficient physiological model fidelity and incomplete regulatory crosstalk elucidation. CONCLUSIONS: Future research should prioritize transcription factor interaction mechanisms, growth-toxin correlation prediction models and multi-omics-based network decipherment. This review provides a foundational framework for NEG research to inform food safety risk assessment and targeted contamination control strategies.
10 May 2026
Read appraisal →Signal transduction and targeted therapy
Total neoadjuvant chemotherapy combined with PD‑1 blockade and IL‑2 in MSS/pMMR locally advanced rectal cancer: short-term results of a prospective, single-arm phase II study
Neoadjuvant therapy has become a cornerstone in the management of locally advanced rectal cancer (LARC). In this single-arm, open-label phase II study, we evaluated the efficacy and safety of total neoadjuvant chemotherapy (TNT) using a CapOX regimen combined with a programmed cell death protein 1 (PD‑1) antibody (sintilimab) and interleukin‑2 (IL‑2) in patients with microsatellite stable (MSS)/defining proficient mismatch repair (pMMR) LARC. A total of 33 patients, aged 18-75 years, with rectal tumors located within 12 cm from the anal verge and staged as cT3/4N_anyM0 or cT_anyN⁺M0, were enrolled. Patients received a regimen consisting of oxaliplatin, sintilimab, capecitabine, and IL‑2 administered in a three‑week cycle, with response evaluations performed after every two cycles. Following six cycles of treatment, 33 patients underwent radical surgery, achieving a 100% R0 resection rate. The pathological complete response (pCR) rate was 42.4% (95% CI: 25.68-59.16%) while the remaining 19 patients (57.6%, 95% CI: 41.07-74.09%) were assessed as having a partial response. The tumor regression grades (TRG) were, TRG1: 3 cases (9.1%, 95% CI: 1.90-25.97%), TRG2: 14 cases (42.4%, 95% CI: 26.27-60.38%), and TRG3: 2 cases (6.1%, 95% CI: 0.73-20.37%), respectively. Surgical safety reported as no cases of grade B/C anastomotic leakage or bowel obstruction. Adverse events (AEs) were manageable, with a 21.2% incidence of grade 3 events and no grade IV/V events or treatment‑related deaths. With a median follow‑up of 25.5 weeks, no recurrences were observed. Analysis of blood and tissue samples from patients with different treatment outcomes revealed significant activation of CD8+ T cells, NK cells, and M1 macrophage subsets in the tumor microenvironment of patients achieving pCR. These compelling data demonstrate promising efficacy with a favorable safety profile in MSS/pMMR LARC. These findings warrant studies to validate this regimen as a novel treatment paradigm for rectal cancer. ClinicalTrials.gov registration: NCT06108596.
10 May 2026
Read appraisal →European journal of cancer (Oxford, England : 1990)
Stereotactic body radiotherapy versus hepatic resection for recurrent small hepatocellular carcinoma: A post-hoc analysis with propensity score adjustment from two randomized trials
BACKGROUND: Stereotactic body radiotherapy (SBRT) has been proven effective for treating small hepatocellular carcinoma (sHCC); however, the comparative efficacy of SBRT and surgical resection remains unknown. This analysis aims to compare the outcomes of SBRT and resection in treating recurrent sHCC. METHODS: Two randomized controlled trials enrolled recurrent sHCC undergoing resection (NCT01833286) or SBRT (NCT04047173). Patients with single recurrent HCC ≤ 5 cm were included in this study. The primary endpoint was local progression-free survival (LPFS). RESULTS: A total of 158 patients were included, with 83 and 75 patients assigned to the SBRT and resection cohorts, respectively. The cumulative 3-year LPFS rates were 84.3% (95% CI, 76.1-92.5) with SBRT and 76.8% (95% CI, 67.2-86.4) with resection, respectively (HR, 0.70 [95% CI, 0.35-1.40]; P = 0.311). The median progression-free survival time of the SBRT and resection group was 37.6 (95% CI, 26.0-49.2) and 26.3 (95% CI, 18.8-33.8) months, respectively, with no significant differences (HR, 0.80 [95% CI, 0.53-1.21]; P = 0.287). The 3-year overall survival rates were 90.3% (95% CI, 83.4-97.2) in the SBRT group, and 81.1% (95% CI, 76.5-90.1) in the resection group (HR, 0.53 [95% CI, 0.23-1.20]; P = 0.118). The comparison results remained consistent after adjusting for confounding variables. The incidences of adverse events were similar between the two groups (P = 0.695). CONCLUSIONS: SBRT provides satisfactory tumor control and long-term outcomes, comparable to those of resection. SBRT could be a potential alternative to resection in recurrent sHCC.
10 May 2026
Read appraisal →European journal of cancer (Oxford, England : 1990)
Sex differences in efficacy and toxicity of first-line treatment of metastatic colorectal cancer: An analysis of 18,041 patients in the ARCAD CRC database.
BACKGROUND: Greater toxicity of adjuvant chemotherapy in females has been reported previously, but the impact of patients' sex on chemotherapy (CT)+/-targeted therapies for non-resectable, metastatic colorectal cancer (mCRC) has remained unclear. We compared efficacy and toxicity of first-line chemotherapy, with or without targeted therapies, between male and female mCRC patients. METHODS: Twenty-seven randomized trials from the ARCAD CRC database were included. Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate, toxicity (according to NCI-CTCAE). Analyses were performed within three treatment groups: A) CT alone, B) CT+bevacizumab, and C) CT+epidermal growth factor receptor inhibitor. OS and PFS were estimated using Kaplan-Meier method. Associations with sex were assessed using study-stratified Cox models adjusted for age, performance status, body mass index, and CT backbone. RESULTS: Baseline data from 18,041 patients were analysed; among 15,271 included in outcome analyses, no sex differences in OS or PFS were observed. Adjusted OS hazard ratios (95% confidence interval) for females versus (vs.) males were: A: 1.01 (0.95-1.08, P = .69), B: 0.96 (0.89-1.04, P = .36), C: 0.97 (0.87-1.10, P = .67). Females experienced higher toxicity, including grade 1-4 and 3-4 nausea (71.8% vs. 60.5% and 7.5% vs. 4.8%), vomiting (47.7% vs. 35.5% and 6.6% vs. 4.4%), and neutropenia (52.4% vs. 44.4% and 29.2% vs. 18.8%) (P < .001). Conversely, rash (grade 1-4 and 3-4) was more frequent in males (29.6% vs. 24.3% and 5.1% vs. 3.7%, P < .001). CONCLUSIONS: Despite higher chemotherapy-related toxicity in females, treatment efficacy was similar between sexes. Rash was more common in males, highlighting that patients' sex modulates toxicity profiles in both directions. Strategies to reduce adverse events in female patients are warranted.
10 May 2026
Read appraisal →Medical image analysis
Diversity-driven MG-MAE: Multi-granularity representation learning for non-salient object segmentation
Masked Autoencoders (MAEs) have grown increasingly prominent as a powerful self-supervised learning paradigm. They are capable of effectively leveraging inherent image prior information and are gaining traction in the field of medical image analysis. However, their application to feature representations of the non-salient objects, such as microvasculature, accessory organs, and early-stage tumors-is fundamentally limited by dimensional collapse problem, which diminishes feature diversity critical for non-salient structure discrimination. To address this, we propose a Multi-Granularity Masked Autoencoder (MG-MAE) framework for feature diversity learning: (1) We extend the conventional MAE into a multi-granularity framework, a global branch reconstructs global pixels, with a local branch recovering Histogram of Oriented Gradients (HOG) features, enabling hierarchical representation of both coarse-grained and fine-grained patterns; (2) Critically, in the local branch, a diversity-enhanced loss function incorporating Nuclear Norm Maximization (NNM) constraint to explicitly mitigate feature space collapse through orthogonal embedding regularization; and (3) A Dynamic Weight Adjustment (DWA) strategy that dynamically prioritizes hard-to-reconstruct regions via entropy-driven gradient modulation. Comprehensive evaluations across five clinical benchmarks-CCTA139, BTCV, LiTS, ACDC, and MSD Pancreas Tumour datasets-demonstrate that MG-MAE achieves statistically significant improvements in Dice Similarity Coefficient (DSC) scores for non-salient object segmentation, outperforming state-of-the-art methods. The code is available at https://github.com/zhangbbin/mgmae.
9 May 2026
Read appraisal →Computers in biology and medicine
A decoction-inspired genetic algorithm and PPO reinforcement learning for intelligent molecular discovery: Anti-colorectal cancer candidates from the tiao-pi AnChang formula
BACKGROUND: Colorectal cancer (CRC) remains among the leading causes of cancer-related mortality worldwide. The TiaoPi AnChang Decoction (TPACD), a traditional Chinese herbal formula, has shown potential anti-CRC activity in preclinical studies (in vitro and in vivo); however, its active chemical basis and key target interactions remain unclear. The complex, multicomponent nature of TPACD poses significant challenges for systematically identifying and optimizing compounds. PURPOSE: This study aimed to establish an intelligent molecular discovery framework that integrates a decoction-inspired genetic algorithm (EGA) with proximal policy optimization (PPO)-based reinforcement learning to simulate the dynamic transformation and recombination processes underlying traditional herbal decoctions and to generate and prioritize in silico candidate molecules for further anti-CRC evaluation. STUDY DESIGN: A parallel molecular generation strategy was developed, comprising three algorithmic pathways, namely, the basic molecular generation algorithm (BMGA), enhanced molecular generation algorithm (EMGA), and intelligent molecular generation algorithm (IMGA), which represent progressive levels of structural diversity, biological relevance, and optimization capacity. METHODS: The EGA simulated the selection-transformation-recombination principles of decoction through adaptive mutation, fragment recombination, and a diversity-preserving selection procedure. PPO-based reinforcement learning further refined the molecular properties via a reward-guided exploration of the chemical space. The BMGA enabled baseline molecular generation; the EMGA incorporated affinity-based selection; and the IMGA achieved multiobjective optimization, integrating drug likeness, novelty, and toxicity filtering. The candidate molecules were validated by affinity prediction, QED scoring, and molecular docking. RESULTS: All three methods generated chemically valid and pharmacologically enhanced molecules relative to the original TPACD components. The EMGA provided improved biological affinity and exploration efficiency, whereas the IMGA achieved the highest overall performance level, with superior QED and docking stability, and predicted the CRC inhibition potential of the molecules. CONCLUSION: The proposed EGA-PPO framework effectively connects traditional decoction principles with modern AI-based drug design. The tri-algorithmic system (BMGA-EMGA-IMGA) provides a scalable and interpretable strategy for de novo molecular discovery, offering promising leads for acquiring natural product-derived CRC therapeutics.
9 May 2026
Read appraisal →Pancreas
Whole Metagenomic Profiling Identifies a Gut Microbial Signature for Chronic Pancreatitis via Machine Learning
BACKGROUND: Pancreatitis significantly alters the microbial composition of the oral and intestinal compartments, causing dysbiosis that may contribute to disease mechanisms and potentially serve as a basis for diagnosis or treatment. OBJECTIVE: To determine whether the oral or gut microbial signature can classify chronic pancreatitis (CP). METHODS: Stool samples (n=707) were collected from participants in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED). Samples were distributed among 200 healthy (HC), 310 CP, 49 acute pancreatitis (AP), and 148 recurrent acute pancreatitis (RAP). In addition, saliva samples were collected for a subset of participants (n=156). Whole genome sequencing was performed to assess microbiome composition. Machine learning algorithms were utilized to identify a signature with microbial features predictive of CP. RESULTS: Gut alpha diversity was significantly decreased in AP, RAP, and CP compared with HC, with CP exhibiting the lowest diversity. In contrast, oral microbial diversity showed no significant variation across groups. Beta diversity analysis revealed distinct gut microbiome compositions between HC and pancreatitis subtypes, with CP showing the most pronounced differences. Random forest models using gut microbial species demonstrated robust predictive performance for CP using a minimum of 10 species (Area under the curve-AUC: 0.834; accuracy: 0.774). Despite similarities in gut microbiome composition across pancreatitis subtypes, a unique gut microbial signature for CP was identified highlighting the microbiome's potential in CP diagnosis. CONCLUSION: Our study reveals a gut microbial signature predictive of CP using machine learning models in a large US multi-institutional cohort.
6 May 2026
Read appraisal →Cancer medicine
Predicting Prognosis for Gastric Cancer Patients Receiving Neoadjuvant Treatment With Body Composition-Based Deep Learning
BACKGROUND: This study sought to develop an innovative body composition (BC)-based deep learning (DL) model to precisely evaluate survival in gastric cancer (GC) patients undergoing neoadjuvant treatment (NT). MATERIALS AND METHODS: This retrospective study included GC patients undergoing NT from two centers. CT images both pre-NT and post-NT were preprocessed, focusing on the automatic segmentation of subcutaneous fat, visceral fat, and skeletal muscle regions using TotalSegmentator. Delta Radiomics features were extracted using Pyradiomics. After feature fusion and selection, the optimal model is Naive Bayes (Rad model). A hybrid DL model was developed by combining ResNet18 and Transformer networks for feature extraction. The Clinic_Rad_DL model was constructed by combining clinical features, radiomic signatures, and DL signatures. The ExtraTree classifier was used for the Clinic_Rad_DL model, while a separate Cox regression model was developed for survival analysis using the same features. RESULTS: A total of 356 patients (mean age, 59 ± 10 years; 264 males [74.2%]) were enrolled and divided into training, validation, and test sets in a 7:2:1 ratio. The DL model outperformed the Rad model. The Clinic_Rad_DL model outperformed both Rad model and DL model, with AUC of 0.915, 0.890, and 0.890 in training, validation, and test sets, respectively. The Cox proportional hazards model showed C-index of 0.806, 0.803, and 0.819, effectively stratifying patients into high- and low-risk groups with significant survival differences. CONCLUSION: The study developed and validated a BC-based DL model to predict survival in GC patients undergoing NT, offering potential for personalized treatment strategies in clinical practice.
5 May 2026
Read appraisal →Abdominal radiology (New York)
A CT-based 2.5D deep learning model for preoperative T-staging in gastric cancer: a retrospective multicenter study
PURPOSE: To develop and validate a 2.5D multi-angle deep learning (MADL) model for preoperative T-staging in patients with gastric cancer (GC) and to explore the predictive potential for survival outcome. MATERIALS AND METHODS: In this retrospective study, GC datasets from four centers were used to develop a quaternary for preoperative T-staging model by integrating CT images with nine 2D slicers and three angles (0°, + 45°, -45°) from transverse, sagittal, and coronal views. Diagnostic performance (accuracy, sensitivity, specificity, F1-score) were compared between the 2.5D MADL and radiologists. The prognostic potential of 2.5D MADL-derived features was evaluated using Kaplan-Meier analysis and multivariate Cox regression. RESULTS: A total of 433 patients were divided into the training (n = 346, mean age, 64.8 years ± 10.5 [SD]; 95 female) and the internal validation (n = 87, mean age, 63.0 years ± 11.9; 23 female) sets from Centers 1-3, and 41 patients (mean age, 64.6 years ± 8.9; 10 female) formed the external testing set from Center 4. The 2.5D MADL model exhibited excellent diagnostic performance for T-staging in external testing set (AUCs of T1-T4: 0.962, 0.722, 0.913, 0.962). For T1 staging, it outperformed radiologists in accuracy (95% vs. 83%), sensitivity (75% vs. 12%), and F1 score (86% vs. 22%) in external testing set. Survival analysis showed significant overall survival differences between high- and low-risk groups stratified (P < 0.001), with high-risk patients having shorter survival (HR = 1.632, 95% CI:1.239-2.150). CONCLUSION: The 2.5D MADL model achieves accurate and reliable preoperative T staging of gastric cancer, with performance comparable to radiologists and superior accuracy for early-stage disease.
5 May 2026
Read appraisal →European journal of nuclear medicine and molecular imaging
Machine learning models classifiers enable a strong prediction of radioembolization-induced liver disease, and define a new bilirubin threshold for selection of patients.
PURPOSE: Selective Internal Radiotherapy (SIRT) is an established treatment option for hepatocellular carcinoma (HCC). However, a major complication is radioembolization-induced liver disease (REILD). METHODS: This retrospective study, analyzed patients treated with SIRT for HCC to identify clinical factors associated with REILD and to predict treatment response. Machine learning (ML) methods were applied to two distinct cohorts to determine predictors of toxicity and response. RESULTS: Among 138 patients analyzed for REILD, ML identified bilirubin as a key predictor. A refined threshold of 26.5 µmol/L (1.55 mg/dL) was associated with toxicity risk. In the response cohort (136 patients), predictive performance was limited, nevertheless tumor dose appeared as the most frequent feature selected by the models. CONCLUSIONS: Bilirubin was confirmed as a critical factor for REILD prediction with the identification of a new threshold that may improve patient risk stratification. While tumor dose appears as the main predictor of treatment outcome, robust response models require additional features.
5 May 2026
Read appraisal →Abdominal radiology (New York)
Deep learning-based combined noise reduction and contrast enhancement for post-neoadjuvant pancreatic cancer CT: does improved image quality translate to better resectability assessment?
PURPOSE: To evaluate whether deep learning-based combined noise reduction and contrast enhancement reconstruction (DLR) improves image quality and resectability prediction accuracy compared to conventional iterative reconstruction (IR) in post-neoadjuvant pancreatic cancer CT assessment. METHODS: This retrospective study included 114 patients with pancreatic cancer following neoadjuvant therapy. Contrast-enhanced CT images were reconstructed using conventional IR and vendor-neutral ClariACE. Three abdominal radiologists independently assessed image quality (based on 8 parameters: tumor conspicuity, tumor margin, image noise, sharpness of the main pancreatic duct, arterial depiction, venous depiction, plasticity and overall image quality) and determined tumor resectability with confidence levels. Quantitative analysis included aortic and portal venous attenuation measurements and pancreas-to-tumor contrast-to-noise ratio (CNR). Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC) with DeLong's test. Sensitivity, specificity, accuracy, and reader confidence were compared using McNemar's test. RESULTS: DLR demonstrated significantly superior vessel enhancement (p < 0.001) and improved CNR (p < 0.001) versus conventional IR. Two readers consistently rated DLR images higher across all qualitative categories (p < 0.001) except plasticity, while the third reader favored DLR in five of eight parameters (p < 0.001 to 0.020). However, all readers noted increased artificial appearance in DLR images (p < 0.001). Despite image quality improvements, no significant differences were observed in resectability assessment accuracy (62.3%-65.8%), AUC values (0.485-0.520), or high-confidence diagnosis rates between reconstruction methods. CONCLUSION: Although deep learning-based combined noise reduction and contrast enhancement reconstruction significantly improved quantitative and subjective image quality metrics, it did not enhance diagnostic accuracy for predicting R0 resectability in post-neoadjuvant pancreatic cancer patients.
5 May 2026
Read appraisal →Journal of medical imaging and radiation sciences
Explainability-informed benchmarking of two deep learning models for organ-at-risk segmentation in MR-guided adaptive radiotherapy
INTRODUCTION/BACKGROUND: Segmentation of gastrointestinal (GI) organs-at-risk (OARs) is a critical yet time-consuming step in MR-guided adaptive radiotherapy (MRgRT), with manual delineation prone to inter- and intra-observer variability. While deep learning approaches have shown promise, their clinical adoption requires not only accuracy but also interpretability and reliability. This study benchmarks two widely used convolutional architectures, U-Net and Residual U-Net (ResUNet), for abdominal OAR segmentation, with an emphasis on explainability-oriented quantitative analysis. METHODS: An anonymized abdominal MRI dataset was used to train and evaluate U-Net and ResUNet using a 5-fold stratified group cross-validation strategy. Segmentation performance was assessed using the Dice Similarity Coefficient (DSC), Intersection-over-Union (IoU), and the 95th percentile Hausdorff Distance (HD95). Explainability was investigated using Gradient-weighted Class Activation Mapping (Grad-CAM) computed from the final convolutional layer of each network. To enable objective analysis beyond qualitative visualization, Grad-CAM activation maps were quantified using numerical localization metrics relative to ground-truth organ masks, including in-organ energy ratio, boundary energy ratio, pointing accuracy, activation Dice coefficient, centroid distance and activation entropy. Grad-CAM metrics were aggregated across gastrointestinal organs and averaged over the five validation folds. RESULTS: Both architectures demonstrated comparable segmentation performance across organs, with no statistically significant differences across evaluated metrics. Grad-CAM analysis showed similar region-level attention patterns, with in-organ activation ratios of 71.4 ± 8.6% for U-Net and 66.2 ± 9.1% for ResUNet, boundary energy ratios of 24.1 ± 4.9% and 21.8 ± 5.2%, respectively, and pointing accuracies exceeding 70% for both models. Uncertainty analysis based on inter-fold variability and boundary error dispersion indicated comparable stability and bounded worst-case behavior. DISCUSSION/CONCLUSION: By integrating performance, uncertainty and explainability quantitative indicators, this study provides an informed benchmarking of two deep learning models for abdominal OAR segmentation. The results suggest that both U-Net and ResUNet exhibit stable and interpretable behavior under the evaluated configurations, supporting their potential use in MR-guided adaptive radiotherapy workflows where reliability and clinical trust are essential.
4 May 2026
Read appraisal →Artificial intelligence in medicine
CL-MHAD: Contrastive Learning-based Multi-Hypergraph Aggregation and Diffusion model for prescription recommendation
Multiple syndrome-based prescription recommendations are significant for personalized diagnosis and treatment in Traditional Chinese Medicine (TCM). However, it remains a challenge to effectively extract and fuse multi-dimensional knowledge in herbs for accurate syndrome-based prescription recommendations. To address it, we propose CL-MHAD, a contrastive learning-based multi-hypergraph aggregation and diffusion model for prescription recommendation. Focusing on prescriptions, herbs, properties, and dosages, this model presents a multi-view hypergraph reconstruction mechanism, which employs a consistent Top-K neighbor strategy to generate affinity and feature matrices. Subsequently, a diffusion-enhanced method is proposed, utilizing multi-step propagation and weighted mapping to capture high-order relationships. Then, we propose a cross-view contrastive learning strategy to enhance discrimination and present a topology-aware random walk augmentation approach to alleviate data sparsity. An integrated loss function combining classification, contrastive, and augmentation losses is designed to optimize model performance. We evaluate CL-MHAD in a real-world clinical setting using Gastrointestinal Diseases (GID) as a case study. Extensive experiments, including comparative evaluations, ablation studies, and parameter sensitivity analyses, show that CL-MHAD achieves overall superior performance compared with representative baselines across multiple evaluation metrics. Specifically, the model achieves performance gains of 1.27% to 24.67% over representative baselines across all datasets. We further evaluate the model through dosage-syndrome interaction and data-sparsity robustness tests, with results demonstrating the effectiveness of our weighted fusion strategy and the model's superior stability. This study offers an effective solution and a promising paradigm for accurate syndrome-based prescription recommendations in TCM.
4 May 2026
Read appraisal →European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
Machine learning identifies a 10-gene signature predicting hepatocellular carcinoma recurrence and immune-metabolic reprogramming
BACKGROUND: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, with frequent recurrence after curative treatment. Conventional clinicopathological prognostic systems fail to capture the molecular heterogeneity underlying recurrence, highlighting the need for biologically informed biomarkers. METHODS: We developed a transcriptome-based prognostic model for HCC recurrence using a machine learning-guided feature selection strategy designed to reduce survival-time bias. LASSO-based gene selection was integrated with multivariable Cox regression, and model performance was assessed through stratified cross-validation and independent external validation. RESULTS: Analysis of the TCGA-LIHC cohort (n = 344) identified a stable 38-gene recurrence-associated signature (AUC: 0.715-0.847), which was distilled into a reproducible 10-gene classifier combined with tumor stage. This integrated model effectively stratified patients into high- and low-risk groups (log-rank P < 0.0001) and was independently validated in the HCCDB25 cohort (n = 158; P = 0.031). High-risk tumors exhibited an immune-excluded phenotype with reduced cytotoxic immune infiltration. Gene set enrichment analyses revealed progressive activation of proliferative signaling, metabolic dysregulation, and immune evasion pathways. CONCLUSIONS: The integrated 10-gene-plus-stage classifier is a robust and generalizable predictor of HCC recurrence, providing mechanistic insights into immune-metabolic reprogramming and highlighting potential implications for risk-informed patient stratification in future studies.
4 May 2026
Read appraisal →American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
Harnessing Artificial Intelligence for the Management of Patients With GI Cancers
Artificial intelligence (AI) has the potential of reshaping GI oncology by enabling more nuanced interpretation of complex clinical, imaging, and molecular data, while supporting more timely and patient-centered decisions. This article synthesizes perspectives across the GI cancer continuum, beginning with a framework for context-aware AI that emphasizes metadata, multimodal integration, and lifecycle quality and safety as foundations for trustworthy tools that clarify, rather than conceal, uncertainty. Next, AI in endoscopy is highlighted as an example in clinic practice, focusing on computer-aided detection and diagnosis systems that not only increase adenoma detection rates but also raise questions about surveillance burden, real-world effectiveness, and the balance between skill enhancement and potential deskilling of endoscopists. Another section explores how AI can help GI oncologists design, prioritize, and implement highly innovative clinical trials-particularly multi-omic and imaging-driven approaches-while envisioning a future in which far more patients participate in trials that align with their goals and values. The final section reviews emerging AI-enabled clinical trial matching pipelines, including large language model-based retrieval and prescreening tools that operate on real-world electronic health record and protocol data, and discusses challenges related to bias, privacy, explainability, and workflow integration. Together, these contributions argue that the greatest impact of AI in GI oncology will come from deliberately aligning technical capabilities with highly relevant patient-centered clinical questions, ethical governance, and implementation strategies that expand access to trials and improve outcomes for patients with GI malignancies.
2 May 2026
Read appraisal →The Journal of dermatological treatment
Modulation of mu-opioid pathway for the treatment of pruritus: a systematic review of 1,146 patients
BACKGROUND: Pruritus is a debilitating symptom and conventional therapies often provide incomplete relief. The μ-opioid receptor (MOR) pathway is a key regulator of itch, and μ-pathway-modulating agents are increasingly used off-label for refractory pruritus. AIM: This systematic review evaluates the efficacy, safety, and real-world use of μ-opioid pathway modulators for pruritus of dermatologic and systemic origin. METHODS: Following PRISMA guidelines (PROSPERO CRD420251207101), a comprehensive search of four databases identified 3,274 records, of which 69 studies met inclusion criteria, comprising 14 randomized controlled trials (RCTs; n = 795) and 55 non-randomized studies (n = 351). Owing to substantial clinical and methodological heterogeneity, findings were narratively synthesized. RESULTS: Five RCTs evaluated dermatologic conditions, including atopic dermatitis, prurigo nodularis, chronic urticaria, and lichen planopilaris, while nine RCTs assessed systemic pruritus, predominantly cholestatic and uremic pruritus. RCTs investigated oral or topical naltrexone, intravenous naloxone, nalmefene, and extended-release nalbuphine, with most demonstrating clinically meaningful reductions in pruritus intensity using validated itch scales. Non-randomized studies reported improvement across a wide range of dermatologic and systemic conditions, with adverse events generally mild and well tolerated. CONCLUSIONS: Overall, μ-opioid pathway modulators show promising efficacy with acceptable short-term safety across diverse pruritic conditions, although larger high-quality RCTs are required to define optimal dosing and support clinical translation.
2 May 2026
Read appraisal →Journal of investigative surgery : the official journal of the Academy of Surgical Research
Comparison of Functional Outcomes Between Robotic and Laparoscopic Surgery in Rectal Cancer Patients: Systematic Review and Meta-Analysis
BACKGROUND: Robotic and laparoscopic approaches are widely used for rectal cancer surgery. Although robotic systems provide enhanced visualization and dexterity, it remains unclear whether these advantages improve postoperative urinary and sexual function. METHODS: MEDLINE, Embase, Web of Science, and CENTRAL (2000-2025) were searched for studies comparing robotic and laparoscopic rectal cancer surgery. Outcomes included postoperative ileus, urinary retention, and urinary and sexual function. Random-effects meta-analysis was performed using RevMan. Study quality was assessed with MINORS, and certainty of evidence with GRADE. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Forty-four observational studies (6,121 patients) were included. Robotic surgery was associated with lower urinary retention, though this may reflect publication bias. No significant difference was found in postoperative ileus. Subgroup analyses at 3, 6, and 12 months showed no significant differences in urinary or sexual function. Although pooled results slightly favored robotic surgery, these effects were inconsistent, not sustained, and clinically modest. CONCLUSION: Robotic surgery may reduce urinary retention but shows no consistent functional superiority over laparoscopy. Outcomes at key follow-up points are comparable. As all studies were observational, evidence certainty is low, and findings should be interpreted cautiously. This study provides an updated and comprehensive synthesis of functional outcomes following robotic versus laparoscopic rectal cancer surgery, with a specific focus on clinically relevant time-point analyses (3, 6, and 12 months). Unlike prior meta-analyses, which often emphasize pooled outcomes across heterogeneous follow-up periods, this study demonstrates that no consistent or durable improvements in urinary or sexual function are observed at predefined postoperative intervals. Furthermore, by integrating GRADE-based certainty assessment, this work highlights that the current evidence is predominantly observational and of low to very low certainty. Importantly, the study incorporates contemporary evidence up to 2025, including recent systematic reviews and randomized data, and provides a clinically grounded interpretation by contextualizing effect sizes against minimal clinically important difference (MCID) thresholds. Collectively, this analysis offers a more cautious and clinically meaningful appraisal of functional outcomes, challenging assumptions of functional superiority associated with robotic rectal surgery.
2 May 2026
Read appraisal →The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B
Chronic hepatitis B remains a major global health challenge despite the advances in antiviral therapy. Although hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure, liver-related complications, particularly hepatocellular carcinoma, may still occur after viral clearance. This residual risk reflects the lasting impact of host and liver factors rather than ongoing viral activity. Conventional prediction models have attempted to stratify the residual risk after a functional cure but remain limited in their ability to guide individualized management. Recent advances in machine learning have enabled more precise risk stratification by capturing complex host-driven determinants of the long-term outcomes. These approaches support a shift from uniform surveillance toward risk-adaptive monitoring strategies. Nevertheless, post-cure management is emerging as a new clinical priority as more patients achieve a functional cure. Therefore, a functional cure should be viewed not as the end of the disease, but as the beginning of a phase requiring personalized risk assessment and surveillance.
28 Apr 2026
Read appraisal →Journal of ethnopharmacology
A multicenter, placebo-controlled clinical trial and preliminary experimental study exploring the efficacy of modified Banxia Xiexin Decoction in the treatment of advanced colorectal cancer
ETHNOPHARMACOLOGICAL RELEVANCE: Recent studies in China have increasingly focused on the evidence-based evaluation of malignant tumors, including colorectal cancer (CRC), leveraging the unique properties of herbal medicine. This has led to notable progress in the development of novel therapies. Clinical observations indicate that the modified Banxia Xiexin Decoction (mBXD) exhibits significant anti-cancer effects. However, well-designed clinical trials and foundational research in this field remain insufficient. AIMS OF THE STUDY: This study aims to assess the clinical efficacy and safety of mBXD in the treatment of advanced CRC, alongside preliminary in vivo and in vitro verification of its anti-CRC effects. METHODS: A clinical trial was conducted from October 2020 to October 2024 across 12 hospitals in Southwest China. Eligible participants were randomly assigned to either the mBXD group or the placebo group. Both groups received standard chemotherapy combined with targeted therapy; the mBXD group received mBXD granules (Ready-to-use), while the placebo group received a placebo. Treatment lasted for six months (six cycles). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and serum tumor markers. Efficacy was assessed every two cycles, with follow-ups conducted every three months after treatment completion until disease progression or death. This study is registered with the Chinese Clinical Trial (No. ChiCTR2100041643). Basic research included the establishment of a subcutaneous CT26 colon cancer model and the use of the HCT116 cell line, with mBXD interventions to monitor tumor growth and evaluate the viability, invasion, and migration of HCT116 cells. RESULTS: A total of 129 participants were enrolled. Compared to the placebo group, the mBXD group showed a 1.9-month and 2.8-month extension in PFS and OS, respectively, with a 17 % reduction in the risk of disease progression and a 15 % reduction in the risk of death (P = 0.341, 0.465). After two, four, and six cycles, the ORR and DCR in the mBXD group were 3.7-12.6 % and 1.2-18.5 % higher than those in the placebo group, respectively, with only the DCR after six cycles reaching statistical significance (P = 0.037). Moreover, serum levels of CEA and CA724 were significantly reduced in the mBXD group after four and six cycles (P ≤ 0.05). No severe adverse events were reported during the trial. Additionally, mBXD significantly inhibited subcutaneous tumor growth after 14 days of treatment (P < 0.05), and its drug-containing serum notably suppressed the viability, migration, and invasion of HCT116 cells. CONCLUSIONS: mBXD demonstrates clinical efficacy in prolonging PFS and OS, stabilizing tumor lesions, and reducing serum tumor marker levels in advanced CRC patients. The treatment is both safe and well-tolerated. Furthermore, mBXD significantly inhibits the growth of subcutaneous CT26 colon cancer and suppresses the viability, invasion, and migration of HCT116 cells.
28 Apr 2026
Read appraisal →PloS one
Effects of a spore-forming probiotic blend on bowel habits and physical well-being in adults with functional constipation: A randomized, double-blind, placebo-controlled trial
We aimed to evaluate the efficacy and safety of a spore-forming probiotic blend containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201, and Bacillus subtilis IDCC 1101 for improving bowel function and well-being in adults with functional constipation (FC). In a randomized, double-blind, placebo-controlled trial, 78 adults with FC (Rome IV criteria) received either probiotic blend (n = 40) or placebo (n = 38) daily for 4 weeks. Primary outcomes were changes in weekly spontaneous bowel movements (WSBM) and stool form. Secondary outcomes included physical functioning scores from the 36-Item Short Form Health Survey. The probiotic blend group showed significant improvements in irritant bowel movements (p = 0.0458), incomplete evacuation (p = 0.0374), and abdominal pain before defecation (p = 0.0090). Stool consistency shifted toward normal types (Bristol types 3-4, p = 0.0176). Physical functioning improved only in the probiotic blend group (p = 0.0300). Probiotic blend effectively alleviated symptoms of FC and improved physical well-being. Trial registration: Clinical Research Information Service (CRIS), KCT0010085.
28 Apr 2026
Read appraisal →Biomedical physics & engineering express
BiFUSE-UNet: a novel dual-encoder enhanced TransUNet for polyp segmentation
Polyps are abnormal protrusions that develop on the mucosal surface of the human body, arising from hyperproliferation or aberrant differentiation of mucosal tissue. While some polyps carry a risk of malignant transformation, timely intervention can halt this progression. Accurately segmenting polyp contours in medical images poses significant challenges, primarily due to the high heterogeneity in polyp appearance and morphology, blurry boundaries with background interference, and class imbalance coupled with data scarcity. To address these challenges, this paper presents BiFuse-UNet, a novel dual-encoder TransUNet architecture built upon a bidirectional fusion mechanism. Building upon the original TransUNet architecture, BiFuse-UNet incorporates several key modules. Firstly, a multi-axis attention module (MaxViT block) is integrated to form a dual-encoder structure, which extracts multi-scale local textural features across different dimensions and captures long-range dependencies through self-attention. Secondly, a Merge fusion module is designed, incorporating a Coordinate Attention module and the SaE block from SENetV2, to enhance the model's perception of local and detailed features. Finally, a Biformer module is introduced to strike an efficient balance between global semantics and local details, thereby improving the segmentation accuracy for subtle polyps and early-stage polyps with atypical morphology. Extensive evaluations on the Kvasir-SEG and CVC-ClinicDB dataset demonstrate that BiFuse-UNet achieves state-of-the-art segmentation performance, outperforming seven existing methods on key metrics such as the Dice coefficient, Recall, Precision, and IoU. The proposed model effectively mitigates the challenges of morphological heterogeneity, blurry boundaries, and background interference, leading to highly accurate pixel-level segmentation.
27 Apr 2026
Read appraisal →Annals of medicine
Construction of an XGBoost-SHAP-based malignant transformation risk prediction model for gallbladder polyps
BACKGROUND: To develop and validate a risk prediction model for malignant transformation in patients with gallbladder polyps (GBPs) using an interpretable machine learning framework and evaluate its predictive accuracy. METHODS: A retrospective cohort of 1,027 surgical patients was enrolled from Yantai Yuhuangding Hospital (training set: n = 933) and Shanghai Eastern Hepatobiliary Surgery Hospital (validation set: n = 94). Feature selection for the training set was performed using the least absolute shrinkage and selection operator (LASSO) regression method. A predictive model was constructed with the XGBoost machine learning algorithm and evaluated using Shapley Additive exPlanation (SHAP). RESULTS: LASSO regression identified five significant risk factors for malignant transformation in GBPs: presence of concomitant cholecystitis, polyp count, polyp base width, age, and maximum polyp diameter. The area under the receiver operating characteristic curve (AUC) was 0.862 (95% confidence interval [CI]: 0.8342-0.8893) in the training set and 0.777 (95% CI: 0.6804-0.8737) in the validation set. SHAP analysis illustrated the contribution of each factor. CONCLUSION: This study developed and validated a risk prediction model for malignant transformation in patients with GBPs. The model demonstrated favorable discrimination, calibration, accuracy, and clinical applicability. Integration with SHAP technology may assist clinicians in optimizing treatment and management strategies.
27 Apr 2026
Read appraisal →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
Read appraisal →Cell reports. Medicine
A metabolite-augmented FIB-4 machine learning panel achieves superior liver fibrosis staging in chronic liver disease
Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.
25 Apr 2026
Read appraisal →Antonie van Leeuwenhoek
Faecalibacterium prausnitzii and Akkermansia muciniphila: driving the multiple sclerosis-a systematic review
The gut microbiota (GM) is a complex microbial ecosystem, and its alteration contributes to the development of several diseases including multiple sclerosis (MS). Progressive research concerning neurodegenerative diseases and GM reveals that GM dysbiosis has been linked to fostering the development and progression of MS. Among existing bacteria, F.prausnitzii and A.muciniphila are key species implicated in this disease. Thus, the present study systematically reviewed and synthesized the research on the involvement of F. prausnitzii and A. muciniphila in MS patients versus healthy individuals. We systematically searched PubMed, MEDLINE, EMBASE, and Web of Science databases for relevant published articles from January 2010 till January 2023. Out of 400 articles, 16 met the required criteria. The included research investigations originated from the US, Germany, Norway, Egypt, Iran, Brazil, China, the UK, and Romania. Most publications reported decreased levels of F. prausnitzii and increased levels of A. muciniphila in MS patients compared to controls. This review underscored the importance of the F. prausnitzii and A. muciniphila in MS, which could explain the chronic inflammation that characterizes this disease and not only help in understanding its etiology and progression but also open new avenues for the treatment strategies focusing on gut health. Moreover, understanding the role of F. prausnitzii and A. muciniphila could lead to novel biomarkers for early detection and progression monitoring MS.
25 Apr 2026
Read appraisal →PloS one
Hepatitis C distribution across diverse population groups in the Eastern Mediterranean Region: An umbrella review
BACKGROUND: Hepatitis C virus (HCV) remains a major public health challenge in the Eastern Mediterranean Region (EMR), with prevalence varying across population groups. This umbrella review summarizes the distribution of HCV infection across diverse populations in the region. METHODS: We conducted an umbrella review of systematic reviews with meta-analyses reporting HCV prevalence in the EMR. PubMed, Web of Science, Scopus, Iranian databases, including Magiran and the Scientific Information Database (SID), were searched. Google Scholar was additionally screened to ensure comprehensive coverage. Pooled estimates were extracted across four population groups: apparently healthy individuals; those with clinical or healthcare-associated exposure risk; patients co-infected with hepatitis viruses or other liver-related diseases; and key populations at increased risk (groups disproportionately affected due to their behaviors and higher vulnerability). For time-period analyses, meta-analyses were grouped into two intervals (before 2015 vs. 2015 and after) based on the median year of data collection of primary studies. Pooled prevalence was calculated using a random-effects model in STATA version 17. RESULTS: A total of 55 meta-analyses were included. The pooled HCV prevalence was 31.0% (95% CI: 27.0-38.0) among key populations, and also 31.0% (95% CI: 12.0-49.0) among patients co-infected with other hepatitis viruses or liver-related diseases. Those with clinical or healthcare-associated exposure risk showed a prevalence of 28.0% (95% CI: 23.0-32.0), whereas the apparently healthy population had the lowest prevalence at 2.0% (95% CI: 1.0-2.0). Subgroup analysis indicated a decline in prevalence among clinically exposed populations after 2015, from 29% to 10%, coinciding with the direct-acting antivirals (DAAs) and strengthened infection-control practices. The highest prevalence was observed among key populations in Libya, healthcare-exposed populations in Morocco, and apparently healthy individuals in Egypt. CONCLUSION: Variation in HCV prevalence across populations in the EMR highlights the need for population-specific strategies to support progress toward World Health Organization elimination targets.
24 Apr 2026
Read appraisal →Cancer immunology, immunotherapy : CII
Envafolimab combined with lenvatinib and albumin-bound paclitaxel in previously treated advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: a prospective, phase II, multi-cohort trial
BACKGROUND: This single-center, open-label, exploratory trial aimed to investigate the efficacy and safety of envafolimab combined with lenvatinib and chemotherapy in previous treated advanced G/GEJ adenocarcinoma. METHODS: Eligible patients with HER2-negative, microsatellite stable (MSS) advanced G/GEJ adenocarcinoma who had progressed after first-line treatment were enrolled in this phase II trial. Patients without previously receiving PD-1/PD-L1 inhibitors were enrolled in Group A, and those who progressed on the first-line PD-1 inhibitors were included in Group B. Patients in both groups received envafolimab (200 mg, subcutaneous injection (sc), days 1 and 15, Q4W) combined with lenvatinib and albumin-bound paclitaxel (100 mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or refusal of continuation. The primary endpoint was objective response rate (ORR). RESULTS: A total of 30 patients were included for safety and efficacy analysis. As of data cutoff (Sep 14, 2024), the median follow-up was 17.0 months (IQR: 8.0-18.8) in Group A. The ORR was 60.0%, and the DCR was 100.0%. The mPFS was 8.2 months (95% CI 6.1-10.4) with mOS of 14.8 months (95% CI 7.4-22.2). With a median follow-up of 9.0 months (IQR: 6.1-16.2) in Group B, the ORR was 46.7%, and the DCR was 100.0%. The mPFS was 5.9 months (95% CI 3.8-8.1), and the mOS was 11.5 months (95% CI 3.1-19.9). The overall incidence of adverse events (AEs) of any grade was 100%. While Group A showed numerically better outcomes than Group B, there was no statistically significant difference in PFS (P = 0.629) or OS (P = 0.873) between the two groups. CONCLUSIONS: Second-line envafolimab-based combination therapy demonstrated promising effects in previously treated advanced GC, particularly in those who have not previously received ICIs.
23 Apr 2026
Read appraisal →PloS one
DSCANet: Integrating dual encoder and spatial cross-attention for polyp segmentation
Colonoscopy is a crucial clinical procedure for detecting colorectal polyps, which are strongly associated with the development of colon cancer. This endoscopic technique plays a vital role in both cancer prevention and early diagnosis. Accurate and efficient polyp segmentation is critical for enhancing the diagnostic reliability and clinical utility of colonoscopy. However, achieving precise segmentation presents significant challenges, primarily due to the diversity of polyps in their size and shape, coupled with poorly defined boundaries between polyps and surrounding tissues. To address these challenges, we propose a novel segmentation network, named DSCANet, which is a dual-branch encoder-structured network designed to efficiently fuse body and edge features for high-precision medical image segmentation. DSCANet integrates four key modules: a dual-branch encoder, a spatial cross-attention (SCA) module, a bipolar fusion (BF) module, and a flexible axis-attention (FAA) module. The dual-branch encoder consists of separate body and edge encoders, which extract respective features independently. The SCA module bridges the semantic gap between the two encoders' features. The BF module fuses the shallowest and deepest features, while the FAA module assists the decoder in extracting semantic information from high-level features. DSCANet achieved superior performance on multiple colorectal polyp segmentation datasets. The code is available at https://github.com/Shantdst/DSCANet.
23 Apr 2026
Read appraisal →The Analyst
Third-generation nanopore sequencing: advancing real-time pathogen detection and antimicrobial resistance surveillance in food safety applications
Foodborne diseases impact 600 million people annually, causing 420 000 deaths and over $110 billion in economic losses. Conventional pathogen detection methods take 3-7 days and lack sensitivity for low-abundance pathogens and antimicrobial resistance (AMR) genes. This review evaluates nanopore sequencing's potential in food microbiology, analyzing real-time pathogen detection, AMR surveillance, and performance versus traditional methods. A systematic review of 80 studies (2015-2025) revealed nanopore sequencing reduces detection time to <24 hours with 95-98% species identification accuracy and >90% AMR gene sensitivity, at $50-200 per sample versus $300-800 for traditional whole-genome sequencing. It enables multiplex pathogen detection, viable but non-culturable organism identification, and real-time AMR profiling. However, challenges include error rates of 8-15% in homopolymeric regions and the need for bioinformatics expertise. Addressing challenges, including error rates of 8-15% in homopolymeric regions and the need for bioinformatics expertise, requires strategic mitigation approaches. Despite limitations, advances in base-calling and workflows make nanopore sequencing a transformative tool for next-generation food safety surveillance.
23 Apr 2026
Read appraisal →Spinal cord series and cases
Early transanal irrigation in spinal cord injury-related neurogenic bowel dysfunction: preliminary insights.
STUDY DESIGN: Prospective, randomized, open-label, multicenter, parallel group study. OBJECTIVES: Neurogenic bowel dysfunction (NBD) is a common complication in spinal cord injury (SCI) patients, severely affecting quality of life. While transanal irrigation (TAI) has shown superior efficacy over conservative treatments (CT), its early adoption during the first hospitalization post-injury remains unexplored. This study aimed to compare early TAI initiation versus CT in managing NBD in SCI patients. SETTING: This study involved four spinal units across Italy. METHODS: SCI patients were randomized to receive TAI or CT during a four-week hospital stay, followed by continued treatment at home for 6 months. Bowel function, constipation, and continence were assessed using the Wexner scales, while quality of life was measured using the EQ-5D-5L and Spinal Cord Independence Measure (SCIM) questionnaires. Stool transit time and patient independence were also monitored. RESULTS: Twenty-two patients were enrolled, with the TAI group showing significant improvements in constipation (Wexner score reduction from 13.43 ± 4.24 at baseline to 7.55 ± 2.38 and 8.80 ± 4.16 at 4 weeks and 6 months, p = 0.02) and a trend toward continence improvement. A significant increase in the total SCIM score was observed in the TAI group (p = 0.02), particularly in respiratory and sphincter management. Quality of life improved in both groups, with a notable enhancement in self-care activities for the TAI group (p = 0.006). CONCLUSIONS: These preliminary results suggest early TAI adoption improves bowel management, especially constipation, and enhances patient independence. Larger studies are needed to validate these findings and assess long-term benefits.
22 Apr 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Nivolumab ± Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial
PURPOSE: There is no standard second-line therapy for gastroenteropancreatic (GEP) and lung large-cell neuroendocrine carcinoma (NEC) after the failure of platinum-based chemotherapy. This study aimed to investigate the efficacy of nivolumab ± ipilimumab. METHODS: The GCO-001-NIPINEC (ClinicalTrials.gov identifier: NCT03591731) trial was a noncomparative, open-label, phase II trial. The main inclusion criteria were age ≥18 years, performance status (PS) ≤2, advanced large- and small-cell GEP-NEC and large-cell lung NEC, and second- or third-line treatment for NECs refractory to platinum-based chemotherapy. Patients were randomly assigned (1:1) and stratified by age and PS to receive nivolumab (3 mg/kg/once every 2 weeks) ± ipilimumab (1 mg/kg/once every 6 weeks) for 2 years or until progression or unacceptable toxicity. The primary end point was objective response rate (ORR) at 8 weeks, assessed by investigators. RESULTS: A total of 185 patients (91 in the nivolumab arm and 94 in the nivolumab-ipilimumab arm) were enrolled between December 2018 and March 2021; 169 were analyzed (median age of 64.5 years, 71% male, 91% PS 0-1). The main primary tumor locations were lungs (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) regions. The ORR at 8 weeks was 7.2% (95% CI, 2.7 to 15.1]) in the nivolumab arm and 14.0% (95% CI, 7.4 to 23.1) in the nivolumab-ipilimumab arm. The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free and overall survival were approximately 2 months and 6 months in both arms. One treatment-related death occurred, in the nivolumab arm. The grade 3-4 adverse events (≥5%) were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%) in the nivolumab-ipilimumab arm. CONCLUSION: Nivolumab-ipilimumab could be a second-/third-line treatment option for patients with NECs. However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and/or associated with chemotherapy.
21 Apr 2026
Read appraisal →Journal of investigative surgery : the official journal of the Academy of Surgical Research
Acupoint Stimulation After Anesthesia Induction Does Not Decrease Nausea and Vomiting After Hepatectomy: A Multi-Center Double-Blinded Clinical Trial
INTRODUCTION: This study evaluated whether adding transcutaneous electrical acupoint stimulation (TEAS) to a double-antiemetic regimen during hepatectomy reduces the incidence of postoperative nausea and vomiting (PONV). METHODS: In this multicenter double-blinded randomized controlled trial conducted across three tertiary hospitals in China, patients scheduled for elective hepatectomy were randomized to either the TEAS group (stimulation at PC6 during surgery) or the control group (no stimulation). The primary outcome was the incidence of PONV within 24 h postoperatively. Key secondary outcomes included the severity of PONV and pain after surgery. RESULTS: Among 161 randomized patients, 159 completed the study. No significant difference was observed in the incidence of PONV within 24 h postoperatively between the TEAS and control groups (23.8% vs. 26.6%; OR, 95% CI: 0.86, 0.42-1.76). However, the TEAS group exhibited less patient controlled analgesia (PCA) attempts (2.7 vs 3.5) or deliveries (2.6 vs 3.5) by 24 h postoperatively. Recovery outcomes, including time to ambulation and to gastrointestinal function recovery, did not differ between groups. CONCLUSION: Intraoperative TEAS did not significantly reduce PONV incidence in hepatectomy patients receiving antiemetic therapy. Nonetheless, its potential to decrease the need for analgesics warrants further investigation to refine its role in perioperative care. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05396716), https://clinicaltrials.gov.
21 Apr 2026
Read appraisal →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
Read appraisal →Gut microbes
Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture
Patients with Clostridioides difficile infection have high colonic levels of primary bile acids, which are potent germinators of Clostridioides difficile. Several studies have suggested that re-establishing a normal bile acid composition is a key factor in fecal microbiota transplantation (FMT) for recurrent C. difficile infection, yet former studies supporting this lacked controls. In a subgroup from a randomized controlled trial, we compared the bile acid composition in patients with recurrent C. difficile infection treated with either FMT, a bacterial mixture, or vancomycin. The fecal bile acid content was analyzed several times before and after treatments. Furthermore, we used 16S rDNA gene sequencing to analyze the presence of some bacterial species involved in bile acid metabolism. Stool donors served as healthy controls. We observed a higher proportion of primary bile acids in patients with recurrent C. difficile infection than in donors, yet a donor-like dominance of secondary bile acids was observed after successful treatment in all groups. The shift seemed to occur earliest in the FMT group, followed by the vancomycin group, and the latest in the bacterial mixture group. In approximately half of the participants, the rise in secondary bile acids was timely associated with the detection of bile acid-transforming bacteria that were absent before treatment. Our findings indicate that FMT re-establishes the bile acid composition faster than vancomycin, reducing the time of susceptibility to recurrences of C. difficile infection. Hence, bacterial mixtures developed as an alternative to donor stool for treating recurrent C. difficile infection might benefit from including bile acid-metabolizing bacteria.
19 Apr 2026
Read appraisal →Nature communications
Donor-derived regulatory dendritic cell infusion and early immunosuppressive drug withdrawal in living-donor liver transplantation: a phase I/IIa trial
Operational tolerance (OT) following complete immunosuppression withdrawal (ISW) is rare ( ~ 13%) in eligible adult liver transplant recipients when initiated 1-2-years post-transplant. Regulatory dendritic cells (DCregs) promote transplant tolerance in pre-clinical models and attenuate immune effector cells in humans. Here, we completed a first-in-human phase I/IIa trial (2-year recruitment; 5 ± 0.5 years follow-up) to evaluate the feasibility, safety and preliminary efficacy of pre-emptive donor-derived DCreg (ddDCreg) infusion 7-days pre-transplant in 15 prospective living-donor liver recipients. Two patients were excluded from analysis for reasons unrelated to the study. ISW began one year post-transplant in candidates with a quiescent/permissive protocol biopsy. ddDCreg infusions were safe, reproducible, and well-tolerated. One-year post-transplant, 8/13 patients were eligible for ISW, 4 achieved complete ISW, 3 remained off all immunosuppression for >1 year. These 3 remained drug-free for 3.0 ± 0.17-years, reflecting a 37.5% OT rate in ISW-eligible recipients. Given the exploratory nature of this trial, additional studies to evaluate efficacy are needed. ClinicalTrials.gov registration number NCT03164265.
19 Apr 2026
Read appraisal →BMJ open
Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial
INTRODUCTION: Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence. METHODS AND ANALYSIS: This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years. ETHICS AND DISSEMINATION: The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences. EUDRACT NUMBER: 2023-5 08 316-27-00. TRIAL REGISTRATION NUMBER: NCT06398028. PROTOCOL VERSION: V.12, 18 March 2025.
18 Apr 2026
Read appraisal →Journal of the American College of Surgeons
Effect of Adhesion Barrier Use During Ladd Procedure for Intestinal Malrotation on Postoperative Midgut Volvulus and Postoperative Small-Bowel Obstruction: A Retrospective Cohort Study Using a National Inpatient Database
BACKGROUND: Postoperative midgut volvulus is a life-threatening complication after the Ladd procedure. An adhesion barrier to prevent postoperative small-bowel obstruction could increase postoperative midgut volvulus incidence due to reduced adhesions. We aimed to examine the effect of adhesion barrier use during Ladd procedures on postoperative midgut volvulus and postoperative small-bowel obstruction. STUDY DESIGN: We retrospectively identified patients younger than 18 years who underwent the Ladd procedure between July 2010 and March 2021, using a Japanese nationwide inpatient database. We used propensity score overlap-weighting analyses to compare reoperation for midgut volvulus, rehospitalization, and operation for small-bowel obstruction, mortality, total rehospitalization length, and total rehospitalization cost within 1 year after the Ladd procedure between patients in whom adhesion barrier was used (barrier group) and patients in whom it was not used (nonbarrier group). RESULTS: Of the 1,159 eligible patients, adhesion barrier was used in 314 and not used in 845 patients. The proportion of reoperations for midgut volvulus did not differ between the barrier and nonbarrier groups (3.5% vs 2.7%; risk difference 0.8%, 95% CI -1.9 to 3.5). The proportion of rehospitalization due to small-bowel obstruction was lower in the barrier group than in the nonbarrier group (2.6% vs 6.3%; risk difference -3.6%, 95% CI -6.6 to -0.8). No significant differences were observed in operation for small-bowel obstruction, mortality, and total length and cost of rehospitalization. CONCLUSIONS: The use of adhesion barrier during the Ladd procedure can prevent rehospitalization due to postoperative small-bowel obstruction without increasing the incidence of postoperative midgut volvulus.
17 Apr 2026
Read appraisal →Journal of agricultural and food chemistry
Dairy-Derived Aroma Release Modulated by Oral Mucin: In Vitro Study Insights from Multispectral, Computational Modeling, and Machine Learning
Salivary mucin plays a pivotal role in modulating aroma perception during dairy consumption. This study investigated the impact of mucin on the release of ten key milk fat-derived aroma compounds (including 3 aldehydes, 3 ketones, and 4 lactones) using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results demonstrated that mucin significantly inhibited the release of most compounds, including 2-heptanone, 2-nonanone, 2-pentadecanone, heptanal, δ-hexalactone, δ-octalactone, and δ-decalactone, with a maximum binding percentage of 34.79 ± 9.63%. Sensory analysis confirmed perceptible differences. Thermodynamic and spectroscopic data revealed that the binding was spontaneous and primarily driven by hydrophobic interactions and hydrogen bonds involving phenylalanine and tyrosine residues, which induced significant conformational changes in the mucin secondary structure. Shapley additive explanations analysis based on the support vector regression model identified the number of H-bond acceptors as the most critical molecular feature. These findings provide insights for modulating aroma perception in dairy products.
17 Apr 2026
Read appraisal →Computers in biology and medicine
A systematic review and benchmarking of modern metagenomic tools for taxonomic classification
Advancements in metagenomics have been driven by the continuous development of bioinformatic tools, particularly taxonomic classification software, which are central to the accurate characterization of microbial communities. However, establishing direct comparisons between these tools remains challenging due to variations in evaluation metrics, reference databases, and input data types. In this study, we present a systematic review of recently developed metagenomic taxonomic classification tools. Of the 31 identified tools, nine satisfied all functional and methodological criteria for the benchmark analysis. We evaluated their accuracy and computational performance using a standardized dataset derived from the NCBI RefSeq database. Our analysis revealed that most of these tools are domain-specific, each excelling in particular areas. Tools like TAMA, CAMITAX and PhyloFlash achieved higher accuracy for prokaryotic organisms, while ViWrap and PhaBOX achieved higher accuracy for viral classifications. SqueezeMeta achieved high F1 scores across most domains, though its assembly-based architecture limits effectiveness on highly diverse samples. MegaPath-Nano was least affected by increased mutation rates. The execution time varied widely among the tools, with domain-specific and machine learning-based tools generally being faster, while tools like BASTA had longer runtimes and lower accuracy. This review synthesizes performance results for current tools, providing an overview of their strengths and computational methodologies.
17 Apr 2026
Read appraisal →Cancer research
Mutant and Wild-Type RAS Cross-talk and Stoichiometric Deficiencies Are Determinants of Sensitivity to Targeted Therapies in KRASG12R Pancreatic Ductal Adenocarcinoma
UNLABELLED: Therapies targeting the RAF-MEK-ERK pathway are generally considered to have limited efficacy in KRAS-mutant cancers. However, specific KRAS mutants exhibit distinct behaviors. Notably, KRASG12R pancreatic ductal adenocarcinoma (PDAC) tumors have shown sensitivity to MEK inhibitors (MEKi) in combination with autophagy inhibitors, but a better understanding of the underlying mechanisms is needed to optimize this treatment strategy. Using a systems-level approach, we uncovered a mechanistic explanation for this phenomenon. Due to distinct biophysical properties, KRASG12R had an impaired ability to activate wild-type HRAS and NRAS (WT-RAS) compared with other KRAS mutants, such as KRASG12D. This reduced activation stemmed from the weaker interaction between KRASG12R and guanine exchange factors (SOS), as well as the tumor suppressor neurofibromin (NF1), crucial in regulating WT-RAS activity. The impaired ability to activate WT-RAS led to weaker holistic MAPK signaling in KRASG12R-driven tumors, which conferred increased sensitivity to MEKi. To substantiate the preclinical findings, the utility of MEKi in combination with the autophagy inhibitor hydroxychloroquine was analyzed in patients with KRASG12R-mutated metastatic PDAC. Five of the eight (62.5%) patients treated in first- or second-line settings had a progression-free survival exceeding 6 months. Three patients had impressive disease control: two had stable disease of 11 and 22.7 months, and one achieved a partial response with an 83% decrease in tumor size that lasted for 8.9 months. Overall, this work highlights how systems-based approaches in precision medicine can uncover mechanistic insights to guide the identification of patients with PDAC most likely to benefit from tailored therapeutic strategies. SIGNIFICANCE: The unique sensitivity of KRASG12R-mutant cancers to MEK inhibitors offers a critical advancement in understanding MAPK signaling and paving the way for precision-targeted therapies in previously untreatable contexts. See related commentary by Tiriac and Engle, p. 1817 See related article by Burge et al., p. 1854 See related article by Burge et al., p. 1868.
17 Apr 2026
Read appraisal →Journal of the International Society of Sports Nutrition
Effects of race distance and probiotics intervention on kidney, muscle, and gut injury and inflammation biomarker responses during running.
INTRODUCTION: Prolonged intense physical activity, such as long-distance running, may lead to systemic inflammation and cause organ injury, particularly to the kidneys. This study aimed to assess the impact of trail race running on kidney and muscle injury and gut inflammation biomarkers, and the potential mitigating effects of Lactiplantibacillus plantarum 299v (Lp299v) supplementation. METHODS: This randomized, double-blind, placebo-controlled study included 34 participants who completed 42 races, ranging from 20 to 164 km. Participants were divided into two groups, receiving either 40 bn CFU Lp299v or a placebo for 4 weeks before the race. Urine and fecal samples were collected pre- and post-race (immediately after, morning after and 24 h after the race) to measure biomarkers of muscle and kidney injury, and gut inflammation. Principal component analysis was used to create a single tubular kidney injury biomarker component variable (TKIBC1) positively associated with five separate tubular kidney injury biomarkers (MCP-1, KIM-1, GST-π, clusterin, and calbindin) at the three post-race time points. RESULTS: Running led to increased tubular and glomerular kidney injury markers, increased levels of fecal calprotectin, and, in some cases, elevated urine myoglobin levels. These effects were more pronounced in races ≥107 km (ultradistance). While Lp299v supplementation did not significantly influence TKIBC1, it was associated with a protective effect against gut inflammation. CONCLUSION: These findings suggest that prolonged intense exercise induces kidney and muscle injury as well as gut inflammation, with more severe effects observed in ultra-distance running. Lp299v may have some protective effects, particularly against gut inflammation, but further studies are needed to confirm these findings and explore the underlying mechanisms linking gut health and kidney injury during extreme physical exertion.
16 Apr 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
A Multicenter Phase II Randomized Controlled Trial Comparing 177Lu-Dotatate/Capecitabine Combination Treatment with 177Lu-Dotatate Monotherapy in Patients with Neuroendocrine Tumors
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-[DOTA0,Tyr3]octreotate (177Lu-Dotatate) is an effective and safe treatment for patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET). Whereas 177Lu-Dotatate prolongs progression-free survival (PFS) and preserves quality of life (QoL), objective response rates (ORR) remain limited. Capecitabine, as a radiosensitizer, could increase efficacy without increasing 177Lu-Dotatate activity. This phase II randomized controlled trial investigated the additional cytotoxic or radiosensitizing effect of capecitabine in combination with 177Lu-Dotatate. PATIENTS AND METHODS: Patients with advanced somatostatin receptor-positive GEP NET or bronchopulmonary NET were scheduled to receive four cycles of 7.4 GBq 177Lu-Dotatate and capecitabine or 177Lu-Dotatate alone. Capecitabine (1,650 mg/m2/day) was administered for 2 weeks from the start of each PRRT cycle. Primary endpoints were ORR, PFS, and median overall survival (OS). Secondary endpoints included biochemical response, adverse events, and QoL. RESULTS: A total of 111 of the 200 predefined patients were randomized for 177Lu-Dotatate/capecitabine (n = 50) or 177Lu-Dotatate (n = 61). According to the intention-to-treat analysis, the ORR was 32% for the 177Lu-Dotatate/capecitabine group versus 46% for the 177Lu-Dotatate group (P = 0.348). Treatment with 177Lu-Dotatate/capecitabine did not prolong median PFS (45.7 vs. 31.7 months, P = 0.629) or median OS (75.8 vs. 61.4 months, P = 0.530). Quality-adjusted life years (QALY) were lower in the 177Lu-Dotatate/capecitabine group (1.30 ± 0.48 vs. 1.47 ± 0.48, P = 0.014). CONCLUSIONS: In this prematurely closed phase II study, 177Lu-Dotatate/capecitabine did not improve ORR or prolong PFS and OS in patients with advanced NET compared with 177Lu-Dotatate alone and was associated with reduced QALY.
16 Apr 2026
Read appraisal →Journal of investigational allergology & clinical immunology
Dupilumab in Eosinophilic Gastrointestinal Disorders With Extraesophageal Involvement: A Pediatric Case Series and Systematic Review
Dupilumab has proven effective in the treatment of eosinophilic esophagitis (EoE) in randomized controlled trials. Its efficacy in other, less common and generally more severe eosinophilic gastrointestinal disorders (EGIDs) is scientifically plausible, although it has not been studied to date. Our objective was to describe published and our experience on the empirical use of dupilumab in patients affected by EGIDs with extraesophageal involvement. We retrospectively analyzed the medical charts of children diagnosed with extraesophageal EGIDs treated with dupilumab at our tertiary medical center. The Medline, Embase, and Cochrane databases were searched up to January 2025 for articles describing the use of dupilumab in patients with diagnosed or suspected extraesophageal EGID. Our cohort included 8 patients with a clinical and histological diagnosis of EGID and extraesophageal involvement. All of them had recurrent gastrointestinal symptoms refractory to standard treatments. Three patients had growth retardation. In all patients, symptoms and macroscopic and histological abnormalities, including eosinophilic infiltration, quickly improved after initiation of dupilumab. The systematic review identified 11 case reports (n=29 patients) of pediatric and adult patients with extraesophageal EGIDs treated with dupilumab. All 11 reports described significant clinical and histological improvement following therapy. Clinical experience suggests that dupilumab is effective in treating pediatric EGIDs with extraesophageal features. Given the rarity and high morbidity of these disorders, dupilumab could be considered a reasonable option while waiting for high-quality evidence from ongoing randomized controlled trials.
16 Apr 2026
Read appraisal →The Journal of clinical investigation
Carriage of rare APOB variants predisposes to severe steatotic liver disease and hepatocellular carcinoma
BACKGROUNDMetabolic dysfunction-associated steatotic liver disease (MASLD) has a substantial inherited component. Rare variants in apolipoprotein B gene (APOB) have been implicated in susceptibility to liver steatosis, but their role in disease progression and outcomes is unclear.METHODSWe investigated APOB rare variants in a case-control cohort of people with advanced MASLD versus healthy controls (n = 510 and 261, respectively), a family-based study (n = 43 and literature meta-analysis), the Million Veteran Program (MVP) cohort (n = 94,885), and the UK Biobank (UKBB) (n = 417,657).RESULTSIn the clinical cohort, APOB variants were enriched in people with advanced MASLD (OR 13.8, 95% CI: 2.7-70.7, P = 0.002) and associated with lower circulating lipids, but higher MASLD activity and fibrosis (P < 0.05). In the family study, APOB variants segregated with hepatic steatosis and fibrosis (P < 0.05). Cross-ancestry meta-analysis of the study cohorts yielded pooled ORs for cirrhosis and hepatocellular carcinoma (HCC) of 1.82, 95% CI: 1.33-2.49 and 3.53, 95% CI: 2.09-5.98, respectively. Variants affecting specifically ApoB100 had a 3-fold greater effect on hepatic lipid metabolism compared with those impairing also ApoB48 and were specifically protective against coronary artery disease (P < 0.05). The variants affected cirrhosis risk similarly, but ApoB48/100 had a larger effect on HCC (P < 0.05).CONCLUSIONSRare APOB variants predispose individuals to advanced MASLD and HCC, with distinct contributions from disrupted VLDL and chylomicrons secretion. These findings highlight the interplay between hepatic and intestinal lipid handling, suggesting that APOB genotyping may enhance MASLD risk stratification and patient identification.FUNDINGEuropean Union, Italian Ministry of Health, Swedish Research Council, Veterans Health Administration, NIH.
16 Apr 2026
Read appraisal →Signal transduction and targeted therapy
STRATEGIC-1: multiple-line, randomized, open-label GERCOR-PRODIGE-39 phase III trial in unresectable RAS/BRAF wild-type metastatic colorectal cancer
Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients with untreated, unresectable wild-type RAS/BRAFV600E mCRC. Patients were randomized (1:1) to FOLFIRI-cetuximab then mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab then FOLFIRI-bevacizumab followed by EGFR monoclonal antibody +/- irinotecan (arm B). The primary endpoint was the duration of disease control (DDC). Secondary endpoints were overall survival (OS), time to failure of strategy (TFS), progression-free survival (PFS), overall response rate (ORR), salvage surgery rate, safety, and health-related quality of life (HRQoL). Overall, 263 patients (arm A:131, arm B:132) were randomized. After 68.4 months of median follow-up (95% CI, 76.5-98.0), the median DDC was 22.8 months (95% CI, 20.4-28.8) in arm A and 23.5 months (95% CI, 17.9-26.3) in arm B (HR = 1.01, 95% CI, 0.76-1.34; log-rank P = 0.945). The median OS was 40.4 months (95% CI, 32.4-51.1) in arm A and 34.4 months (95% CI, 27.5-42.2) in arm B (HR = 1.30, 95% CI, 0.99-1.72). The ORR was higher in arm A (82.4% versus 65.4%) in the first-line group but not in the second-line group (20.7% versus 16.4%). Adverse events were consistent with the well-known safety profiles. STRATEGIC-1 did not meet its primary endpoint and was inconclusive in identifying the optimal treatment strategy in wild-type RAS/BRAFV600E mCRC.
16 Apr 2026
Read appraisal →Computers in biology and medicine
MIPHEI-ViT: Multiplex immunofluorescence prediction from H&E images using ViT foundation models
Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E Images), a U-Net-inspired architecture that leverages a ViT pathology foundation model as an encoder to predict mIF signals from H&E images using rich pretrained representations. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available OrionCRC dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on five independent datasets: HEMIT, PathoCell, IMMUcan, Lizard and PanNuke. On OrionCRC test set, MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.93 for Pan-CK, 0.83 for α-SMA, 0.68 for CD3e, 0.36 for CD20, and 0.28 for CD68, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that, for some molecular markers, our model captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.
15 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 →Hepatology communications
Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies
BACKGROUND: Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program. METHODS: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024. RESULTS: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months. CONCLUSIONS: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.
15 Apr 2026
Read appraisal →Biomedical physics & engineering express
A multi-task cross-attention strategy to segment and classify polyps
Polyps are the main biomarkers for diagnosing colorectal cancer. Their early detection and accurate characterization during colonoscopy procedures rely on expert observations. Nevertheless, such a task is prone to errors, particularly in morphological characterization. This work proposes a multi-task representation capable of segmenting polyps and stratifying their malignancy from individual colonoscopy frames. The approach employs a deep representation based on multi-head cross-attention, refined with morphological characterization learned from independent maps according to the degree of polyp malignancy. The proposed method was validated on the BKAI-IGH dataset, comprising 1200 samples (1000 white-light imaging and 200 NICE samples) with fine-grained segmentation masks. The results show an average IoU of 83.5% and a recall of 94%. Additionally, external dataset validation demonstrated the model's generalization capability. Inspired by conventional expert characterization, the proposed method integrates textural and morphological observations, allowing both tasks, polyp segmentation and the corresponding malignancy stratification. The proposed strategy achieves the state-of-the-art performance in public datasets, showing promising results and demonstrating its ability to generate a polyp representation suitable for multiple tasks.
14 Apr 2026
Read appraisal →International journal of pharmaceutics
From permeability to prediction: evolving strategies for evaluating oral drug absorption
Oral drug administration, preferred for patient compliance and convenience, encounters significant bioavailability challenges arising from complex physicochemical, physiological, and formulation-related barriers. Traditional models for evaluating absorption exhibit limitations in physiological relevance and predictive accuracy. This review critically examines evolving methodologies for oral drug absorption assessment, from classical permeability assays to emerging predictive platforms, emphasizing integration of mechanistic research with predictive modeling to advance intelligent platforms and clinical translation. While classical permeability models including parallel artificial membrane permeability assay (PAMPA), Caco-2, Ussing chambers, and intestinal perfusion remain indispensable for early screening, their limited physiological relevance and inability to elucidate mechanistic pathways constrain predictive accuracy. Mechanistic approaches such as lymphatic transport studies and advanced tracking techniques using fluorescence, Single Photon Emission Computed Tomography (SPECT), or Positron Emission Tomography (PET) imaging reveal critical biological pathways but suffer from scalability challenges. Emerging platforms provide transformative potential, as organoid-on-a-chip offer physiologically relevant and high-throughput alternatives, while integrated computational modeling enables multiscale prediction, from molecular interactions to systemic pharmacokinetics. Future oral absorption assessment requires converging in vitro biomimetics, computational modeling, and Artificial intelligence (AI) within unified platforms. Achieving this requires standardized in vitro models, robust data integration, and alignment with regulatory to accelerate translational drug development.
12 Apr 2026
Read appraisal →PloS one
Integrative bioinformatics and machine learning identify shared molecular mechanisms and diagnostic biomarkers between Helicobacter pylori infection and atrial fibrillation
BACKGROUND: Helicobacter pylori (H. pylori) infection and atrial fibrillation(AF) are major global health concerns. Emerging evidence has suggested a potentially chronic inflammation-mediated link between them, but the shared genetic mechanisms remain unclear. METHODS: We analyzed multidataset gene expression profiles from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment, and machine learning were employed to identify common genes, pathways, and diagnostic biomarkers. Protein-protein interaction (PPI) networks, drug-gene analysis, and molecular docking were used to identify hub genes and potential therapeutics. RESULTS: We identified 73 common differentially expressed genes (DEGs) between H. pylori infection and AF, which were predominantly enriched in immune-related processes including leukocyte activation, neutrophil migration, and myeloid cell-mediated immunity. Machine learning identified 15 and 23 key feature genes for H. pylori and AF, respectively, with S100A8 emerging as a shared diagnostic biomarker. Ten hub genes including TYROBP, ITGB2, and SPI1, were identified from the PPI network. Drug repositioning analysis suggested retinoic acid, indirubin, and ropivacaine as candidate therapeutics targeting these key hub genes. CONCLUSION: Our integrative analysis highlights the central role of immune-inflammatory pathways in linking H. pylori infection to AF. We propose S100A8 and other identified hub genes as potential biomarkers and therapeutic targets. The predicted candidate therapeutics, particularly retinoic acid, may offer novel avenues for intervention, warranting further experimental validation.
12 Apr 2026
Read appraisal →Vaccine
The safety and efficacy of in situ vaccine FOLactis for advanced hepatic malignancies.
BACKGROUND: Recent years have witnessed the emergence of a novel research direction in the field of tumor vaccines. An in situ vaccine known as FOLactis, comprised of genetically engineered Lactococcus lactis expressing a fusion protein of Fms-like tyrosine kinase 3 ligand (Flt3L) and co-stimulator OX40 ligand (OX40L), was developed by the Oncology Centre of Nanjing Drum Tower Hospital. The present study was designed to evaluate the efficacy and safety of combination therapy based on intratumoral injection of the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody in combination with immunoradiotherapy or low-dose chemotherapy in the treatment of advanced hepatic malignancies. METHODS: In this exploratory clinical study, patients with advanced hepatic malignancies were enrolled and randomly assigned to Group A and Group B, corresponding to different treatment regimens. The treatment regimen in Group A consisted of the in situ vaccine FOLactis combined with a PD-1 monoclonal antibody and immunoradiotherapy (5Gy/fraction×3fractions). In contrast, the regimen in Group B included the in situ vaccine FOLactis, a PD-1 monoclonal antibody, and low-dose chemotherapy (cisplatin plus vincristine). All treatments were given in 21-day cycles. The primary observation indicator of the study was the objective response rate (ORR) as defined by RECIST v1.1. Secondary observation indicators included the disease control rate (DCR) and the incidence of adverse events. RESULTS: A total of 18 eligible patients were included in the study. In Group A, the ORR and DCR for targeted lesions were 33.3%(95%CI:12.1-64.6%) and 77.8%(95%CI:45.3-96.1%), while the ORR and DCR for non-targeted lesions were 22.2%(95%CI:3.9-54.7%) and 66.7%(95%CI:35.4-87.9%), respectively. Targeted and non-targeted lesions in Group B did not reduce significantly, and their respective DCRs were 66.7%(95%CI:35.4-87.9%) and 22.2%(95%CI:3.9-54.7%). Patients in Group A experienced no significant adverse events. Patients in Group B experienced grade 1-2 hyperthermia as a side effect. CONCLUSIONS: The combination therapy based on the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody showed a certain degree of anti-tumor effect, and was safe and well tolerated in patients with advanced hepatic malignancies. TRIAL REGISTRATION: The Ethics Committee of Nanjing Drum Tower Hospital approved this study (approval number 2022-101-01). The associated trial is registered at ChiCTR.gov.cn (ChiCTR2200060660).
12 Apr 2026
Read appraisal →PloS one
Predicted meta-omics: A potential solution to multi-omics data scarcity in microbiome studies
Imbalances in the gut microbiome have been linked to conditions such as inflammatory bowel disease, diabetes, and cancer. While metagenomics and amplicon sequencing are commonly used to study the microbiome, they do not capture all layers of microbial functions. Other meta-omics data can provide more insights, but these are more costly and laborious to procure. The growing availability of paired meta-omics data offers an opportunity to develop machine learning models that can infer connections between metagenomics data and other forms of meta-omics data, enabling the prediction of these other forms of meta-omics data from metagenomics. We evaluated several machine learning models for predicting meta-omics features from various meta-omics inputs. Simpler architectures such as elastic net regression and random forests generated reliable predictions of transcript and metabolite abundances, with correlations of up to 0.77 and 0.74, respectively, but predicting protein profiles was more challenging. We also identified a core set of well-predicted features for each meta-omics output type, and showed that multi-output regression neural networks performed similarly when trained using fewer output features. Lastly, our experiments demonstrated that predicted features can be used for the downstream task of inflammatory bowel disease classification, with performance comparable to that of experimental data.
11 Apr 2026
Read appraisal →Signal transduction and targeted therapy
Irinotecan with trifluridine/tipiracil and bevacizumab for second-line metastatic colorectal cancer: a phase II multicenter study
Patients diagnosed with metastatic colorectal cancer (mCRC) face a constrained therapeutic landscape following the failure of initial treatment. This multicenter, single-arm, phase II trial (NCT06202001) aimed to assess the efficacy and safety of a novel second-line regimen comprising trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab. Patients with mCRC resistant to prior fluoropyrimidine and oxaliplatin-based chemotherapy were enrolled. Based on a preceding phase I trial, patients received biweekly cycles of oral TAS-102 (30 mg/m² twice daily, days 1-5), intravenous irinotecan (150 mg/m²), and intravenous bevacizumab (5 mg/kg). The primary outcome measure was the objective response rate (ORR). From October 2023 to August 2024, 60 patients were enrolled. As of December 2024, the ORR was 18.3% (2 complete and 9 partial responses), and the disease control rate (DCR) was 83.3%. The median progression-free survival (PFS) was 6.6 months (95% CI, 4.39-8.81), and the median overall survival (OS) was 17.3 months (95% CI, 13.55-21.05). Subgroup analyses indicated that prior resection of the primary tumor was associated with significantly longer median OS (21.9 vs. 16.2 months; p = 0.048) and PFS (8.9 vs. 5.2 months; p = 0.004). The most frequently reported treatment-related adverse events (TRAEs) were nausea (100%), neutropenia (86.7%), and anemia (83.3%). The predominant grade 3/4 TRAEs included neutropenia (48.3%), febrile neutropenia (8.3%), and diarrhea (6.7%). In conclusion, the combination of irinotecan, TAS-102, and bevacizumab shows encouraging efficacy and a manageable safety profile as a second-line therapy for mCRC, meriting further investigation.
11 Apr 2026
Read appraisal →A&A practice
Efficacy and Safety of Ketamine or Esketamine versus Fentanyl-Class Opioids as Adjuncts to Propofol for Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis
OBJECTIVE: Propofol is widely used for gastrointestinal (GI) endoscopies but may cause respiratory depression and hemodynamic compromise when used alone. Adjuncts such as ketamine or esketamine and fentanyl-class opioids (fentanyl, alfentanil, and sufentanil) are used to optimize sedation, yet their comparative efficacy and safety remain uncertain. This meta-analysis evaluated ketamine or esketamine plus propofol (KP regimens) versus fentanyl/alfentanil/sufentanil plus propofol (FP regimens). METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, Cochrane Library, and Google Scholar from inception to February 2025 for randomized controlled trials (RCTs). Eligible studies included patients undergoing GI endoscopy (Population), receiving ketamine or esketamine with propofol (Intervention), compared with fentanyl-class opioids with propofol (Comparison), and reporting outcomes including propofol dose, comfort, adverse events, recovery time, or procedure time (Outcomes). Risk of bias was assessed with the Cochrane tool. Heterogeneity was evaluated using Cochran's Q test and the I2 statistic, and clinical heterogeneity was considered based on study design and population differences. Sensitivity analyses were conducted to test robustness of findings. RESULTS: Fifteen RCTs (1492 participants) were included. KP regimens significantly reduced total propofol use compared with FP (mean difference [MD] -0.42; 95% confidence interval [CI] -0.66 to -0.19; P = .0005), with greater benefit observed for esketamine (p for subgroup = 0.001). No significant differences were found in sedation (MD 0.01; 95% CI -0.40 to 0.43; P = .95) or pain scores (MD 0.24; 95% CI -0.18 to 0.65; P = .26). Safety outcomes were comparable across groups, with no significant differences in desaturation, nausea/vomiting, bradycardia, or tachycardia, except for hypotension, which was lower with KP (risk ratio [RR] 0.56; 95% CI 0.39 to 0.82; P = .003). Recovery and procedure times were similar between groups. CONCLUSIONS: Both KP and FP regimens are effective and safe for GI endoscopy. KP regimens reduce total propofol requirements and significantly lower the risk of hypotension, while showing comparable sedation quality, analgesia, and recovery profiles to FP. These findings suggest KP may offer safety and dosing advantages, though larger standardized trials are needed to confirm its clinical superiority.
10 Apr 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Final Results of a Phase III Trial
PURPOSE: The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). METHODS: Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. RESULTS: A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group. CONCLUSIONS: The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.
10 Apr 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Transarterial Chemoembolization Combined With Camrelizumab and Rivoceranib for Unresectable Hepatocellular Carcinoma (CHANCE2005/CARES-005): A Randomized Phase II Trial
PURPOSE: Transarterial chemoembolization (TACE) alone has shown limited efficacy in improving survival among patients with unresectable hepatocellular carcinoma (HCC). This phase II trial compared TACE combined with camrelizumab (anti-PD-1 antibody) and rivoceranib (vascular endothelial growth factor receptor 2 inhibitor) versus TACE in unresectable HCC. METHODS: Patients with unresectable HCC (Barcelona Clinic Liver Cancer stage A to C without extrahepatic metastases) and Child-Pugh class A liver function were randomly assigned (1:1), stratified by macrovascular invasion, previous tyrosine kinase inhibitor treatment, and number of previous TACE procedures, to receive TACE combined with camrelizumab (200 mg once every 3 weeks) and rivoceranib (250 mg once daily; TACE-C-R) or TACE alone. The primary end point was progression-free survival (PFS) per composite criteria (progression per Response Evaluation Criteria in Cancer of the Liver version 5, transient deterioration to Child-Pugh class C, or TACE failure or refractoriness) in the intention-to-treat population. RESULTS: Between December 28, 2020, and October 29, 2023, 200 patients were randomly assigned (100 in each group). Median PFS per composite criteria was significantly longer with TACE-C-R than with TACE (10.8 months [95% CI, 8.8 to 13.7] v 3.2 months [95% CI, 2.4 to 4.2]; hazard ratio, 0.34 [95% CI, 0.24 to 0.50], P < .001). Grade ≥3 treatment-related adverse events occurred in 74.5% (70 of 94) of patients with TACE-C-R and 22.3% (23 of 103) of patients with TACE, with the most common being increased AST (29 [30.9%] and 13 [12.6%]) and increased ALT (23 [24.5%] and 14 [13.6%]). CONCLUSION: The addition of camrelizumab and rivoceranib to TACE showed statistically significant improvement in PFS for patients with unresectable HCC, with a manageable safety profile. Follow-up for further overall survival analysis is ongoing.
10 Apr 2026
Read appraisal →The New England journal of medicine
Setidegrasib in Advanced Non-Small-Cell Lung Cancer and Pancreatic Cancer
BACKGROUND: The KRAS p.G12D variant occurs in 5% of patients with non-small-cell lung cancer (NSCLC) and is the most common substitution variant in pancreatic ductal adenocarcinoma, occurring in 40% of patients, but no targeted therapies directed against this variant are currently approved for clinical use. Setidegrasib (ASP3082) is a first-in-class KRAS G12D-targeted protein degrader. METHODS: We conducted this phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of setidegrasib in patients with previously treated advanced solid tumors harboring KRAS p.G12D variants. The primary objectives were to evaluate the safety profile, as indicated by dose-limiting toxic effects and adverse events (the primary end points), and to determine the phase 2 dose. Setidegrasib was administered intravenously once weekly at doses of 10 to 800 mg. RESULTS: Overall, 203 patients were enrolled. Among the 76 patients who received setidegrasib at a dose of 600 mg, which was ultimately selected as the phase 2 dose, adverse events occurred during treatment in all the patients, with events of grade 3 or higher in 42%. Treatment-related adverse events occurred in 93% of the patients; the most common were transient infusion-related reactions (in 80%) and nausea (in 30%). Adverse events led to discontinuation in 2 patients. Among the 45 patients with NSCLC who received the 600-mg dose, 36% (95% confidence interval [CI], 22 to 51) had a partial response, the median progression-free survival was 8.3 months (95% CI, 4.1 to could not be estimated), and the estimated 12-month overall survival was 59% (95% CI, 40 to 74). Among the 21 patients with metastatic pancreatic ductal adenocarcinoma who received the 600-mg dose as second- or third-line treatment (of whom 67% received setidegrasib as third-line treatment), 24% (95% CI, 8 to 47) had a response, the median progression-free survival was 3.0 months (95% CI, 1.4 to 6.9), and the median overall survival was 10.3 months (95% CI, 4.2 to 13.0). CONCLUSIONS: Setidegrasib was associated with antitumor activity and a low incidence of treatment discontinuation due to adverse events in patients with previously treated advanced KRAS p.G12D-mutated NSCLC or pancreatic ductal adenocarcinoma. (Funded by Astellas Pharma; ClinicalTrials.gov number, NCT05382559.).
9 Apr 2026
Read appraisal →Journal of medical Internet research
Machine Learning in Predicting the Risk of Esophagogastric Variceal Bleeding Among Patients With Liver Cirrhosis: Systematic Review and Meta-Analysis
BACKGROUND: Liver cirrhosis (LC) can lead to several complications. Esophageal variceal bleeding (EVB) and esophagogastric variceal bleeding (EGVB) are particularly severe, leading to a high risk of mortality. Early identification of esophageal varices and esophagogastric varices is essential. Several studies have constructed prediction models for EVB and EGVB in patients with LC. However, robust systematic evidence to prove their performance is lacking. OBJECTIVE: We included original studies that developed prediction models for esophageal or gastric variceal bleeding in patients with LC under different modeling variables. This study aimed to review the predictive performance of various models for EVB or EGVB in patients with LC, providing insights into the development or updating of simplified scoring tools in the future. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched up to August 21, 2024, to collect original full-text studies on machine learning (ML) in the prediction of EVB and EGVB in patients with LC. The models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Subgroup analyses were carried out based on the modeling variables. RESULTS: In total, 21 studies were included, with 7011 patients with LC, among whom 1412 (20.14%) developed EVB and 733 (10.45%) developed EGVB. The meta-analysis results suggested that the pooled c-index, sensitivity, and specificity of the prediction model for predicting EVB in the validation set were 0.85 (95% CI 0.77-0.92), 0.93 (95% CI 0.87-0.96), and 0.66 (95% CI 0.46-0.82), respectively. The pooled c-index, sensitivity, and specificity of the prediction model for predicting EGVB in the validation set were 0.89 (95% CI 0.85-0.94), 0.77 (95% CI 0.66-0.85), and 0.81 (95% CI 0.67-0.90), respectively. The subgroup analysis based on modeling variables revealed that, for predicting EVB, the c-index in the validation set was 0.84 (95% CI 0.80-0.88) for models based on clinical features, 0.82 (95% CI 0.69-0.96) for radiomics-based models, 0.78 (95% CI 0.67-0.89) for models based on radiomics and clinical features, and 0.97 (95% CI 0.95-1.00) for models based on endoscopic features. Subgroup analyses based on modeling variables revealed that, for predicting EGVB, the c-index in the validation set was 0.91 (95% CI 0.86-0.96) for models based on clinical features and 0.85 (95% CI 0.75-0.96) for models based on radiomics and clinical features. CONCLUSIONS: ML methods are feasible for predicting EVB and EGVB in patients with LC. Nevertheless, the number of included original studies is limited. In the future, more studies with larger sample sizes are needed to promote the application of ML in the early assessment of EVB and EGVB in patients with LC in clinical practice.
9 Apr 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Real-world incidence of nausea and vomiting induced by antineoplastic agents: insights and future directions from the Japanese adverse drug event report database
PURPOSE: Antineoplastic treatment commonly leads to nausea and vomiting (NV), which considerably affects the quality of life and adherence to therapy of patients. This study aimed to analyze the incidence of NV induced by antineoplastic agents using the Japanese Adverse Drug Event Report (JADER) database and to explore novel antiemetic therapies for oral antineoplastic agents. METHODS: Data from April 2004 to March 2023 were extracted from the JADER database. The analysis considered guideline-recommended antiemetics and involved the temporal evaluation of cases with NV. The onset patterns of NV were analyzed for each oral antineoplastic agent. The reported odds ratio was used to identify adjunctive medications that showed inverse associations with these symptoms. RESULTS: A large number of NV cases were reported for platinum compounds and irinotecan. Among the oral agents, a notable incidence of NV was induced by antimetabolites and tyrosine kinase inhibitors. A decreasing trend in the use of single-agent antiemetic therapy was observed from 2010. Distinct NV patterns were identified. Silodosin and meropenem emerged as potential adjunct therapies to suppress NV induced by oral agents. CONCLUSION: Although there is a trend toward improvement in NV management with increased adherence to antiemetic therapies, a substantial gap remains between guidelines and actual practice. The need for tailored management strategies based on the onset patterns of NV for specific agents has been emphasized. Investigating the mechanisms underlying the antiemetic effects of adjunctive therapies, such as silodosin and meropenem, may pave the way for new antiemetic options for oral antineoplastic agents.
9 Apr 2026
Read appraisal →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
Read appraisal →Journal of Korean medical science
Effectiveness and Cost-Utility of Anti-Adhesion Agents in Intra-Abdominal Surgery Patients
BACKGROUND: Adhesive intestinal obstruction (AIO) is a common and critical complication of intra-abdominal surgery, often requiring preventative measures such as using anti-adhesion agents (AAA). However, despite their prevalence and significance, a notable lack of long-term and large-scale clinical evidence exists supporting the effectiveness and cost-utility of these agents. This study aimed to evaluate the effectiveness and cost-utility of applying AAA in patients undergoing intra-abdominal surgery. METHODS: This is a retrospective observational study utilizing the Korean National Health Insurance Database in combination with the data from the Clinical Data Warehouse collected from six university-affiliated hospitals in Korea. The study included patients who underwent intra-abdominal surgeries between April and December 2016, with 2-year follow-up. The effectiveness of AAA was assessed by the incidence rate of AIO, and cost-utility was evaluated through calculating quality-adjusted life years (QALYs) and direct costs. Subgroup and sensitivity analyses were conducted to confirm the consistency and robustness of the study findings. RESULTS: A total of 2,831 patients were included in the study. Among them, 1,365 (47.2%) received AAA while 1,466 (52.8%) did not. The group that received AAA exhibited a significantly lower incidence of AIO, with a rate of 12.4% compared to 18.5% in the non-user group. Utility scores were higher in the user group, averaging 1.992 QALYs versus 1.986 in the non-user group. Direct costs were significantly lower in the user group, totaling 3,794 USD, which is 1,330 USD less than those incurred by the non-user group. Subgroup and sensitivity analyses reinforced these findings, demonstrating consistent reductions in AIO incidence, increased QALYs, and decreased costs observed across various subgroups, particularly among older patients and those without chronic conditions. CONCLUSION: These findings highlight the clinical effectiveness and cost-utility of AAA in patients undergoing intra-abdominal surgery. By significantly reducing the incidence of AIO and lowering healthcare costs, these agents provide empirical evidence supporting their broader adoption in clinical practice. This study addresses critical gaps in the understanding of postoperative management and offers valuable insights that could inform future healthcare policies.
8 Apr 2026
Read appraisal →Pulmonology
Comparative diagnostic performance of advanced endoscopic techniques in suspected sarcoidosis: A systematic review and network meta-analysis
BACKGROUND: While various endoscopic techniques are used for minimally invasive tissue sampling in suspected sarcoidosis, comprehensive evidence comparing their diagnostic efficacy is limited, and the optimal approach remains unclear. RESEARCH QUESTION: Which endoscopic technique provides the greatest diagnostic advantage for sarcoidosis? STUDY DESIGN AND METHODS: We systematically searched 3 databases for studies published up to 22 April 2025. A network meta-analysis was conducted within a Bayesian framework, with diagnostic yield as the primary outcome. RESULTS: A total of 35 studies were included. Compared to TBLB, both EBUS-guided intranodal forceps biopsy (EBUS-IFB) (RR 3.50, 2.14-5.84) and EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) (RR 3.52, 1.97-6.48) showed higher diagnostic yield. SUCRA rankings placed EBUS-IFB (0.912) and EBUS-TMC (0.910) at the top, followed by EBUS-guided core needle biopsy (EBUS-CNB) (0.587), EUS-FNA (0.582), and EBUS-TBNA (0.560), EUS-B-FNA (0.498). Conventional techniques, including cTBNA (0.279), TBLB (0.168), and EBB (0.001), ranked lowest. All procedures had a favourable safety profile. CONCLUSIONS: In centres with appropriate expertise, EBUS-IFB and EBUS-TMC may offer superior diagnostic performance for sarcoidosis. However, given the low certainty of evidence, these conclusions should be interpreted with caution. Clinical decisions should be individualised, considering the patient's condition when determining the final diagnostic strategy.
8 Apr 2026
Read appraisal →Journal of ethnopharmacology
Unveiling the genus Taraxacum: From folk medicine to chemodiversity-driven pharmacological and toxicological outcomes-A systematic review
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Taraxacum (dandelion), belonging to the Asteraceae family, encompasses over 2800 species predominantly found in temperate to subtropical regions of the Northern Hemisphere. Dandelion has a long history as a functional food and traditional medicine in numerous countries, including China, Turkey, Spain, Italy, etc. Traditional application records indicate that dandelion might be used extensively to treat kidney stones, constipation, eczema, ulcers, inflammation, etc. However, the therapeutic application of different Taraxacum species varies significantly across regions, which may be influenced by local cultural and medical traditions. AIM OF THE REVIEW: This review provides a comprehensive summary of recent advancements in traditional applications, phytochemistry (highlighting 184 newly identified compounds), pharmacology, and toxicology, offering novel insights into both genus-wide characteristics of Taraxacum (covering 55 species) and species-specific differences. MATERIALS AND METHODS: A comprehensive search for relevant data was conducted using keywords such as "Taraxacum", "dandelion", "Taraxaci Herba", "pu gong ying", and others across multiple scientific databases, including Google Scholar, Web of Science, PubMed, ScienceDirect, Baidu Scholar, CNKI, online ethnobotanical databases, ethnobotanical monographs, The Plant List, Dictionary of Chinese Ethnic Medicine and considered data from 1972 to 2025. World Flora Online (http://www.worldfloraonline.org/) was utilized for confirming the correct species names of Taraxacum genus. The gathered information on the ethnobotanical usages, phytochemistry, pharmacology, and toxicology is comprehensively summarized in this paper. RESULTS: The literature review indicates that dandelion, a medicinal and edible plant, has been extensively utilized in traditional Chinese medicine since the 7th century. In Europe, its edible and medicinal properties began to be acknowledged and applied during the Middle Ages. In ethnomedical practice, dandelion has been used as diuretic, laxative, anti-inflammatory remedy, digestive aid, etc. Building on the 197 compounds reported from T. officinale, this review highlights over 180 newly identified compounds from 19 Taraxacum species, expanding the genus-wide catalog to more than 380 constituents. Recent toxicological and safety evaluations corroborate that T. officinale F.H.Wigg., T. mongolicum Hand.-Mazz., and T. lacistrum Sahlin possess a favorable safety profile. CONCLUSIONS: The genus Taraxacum is a promising medicinal and edible plant, exhibiting a range of biological activities, including anti-cancer, anti-inflammatory, and antioxidant effects. These properties align with its ethnobotanical usages, confirming its traditional use as diuretic, laxative, anti-inflammation, and digestive aid. However, research on its effects on neurodegenerative and cardiovascular diseases remains limited. Future studies should focus on in vivo experiments to explore the material basis and mechanisms underlying the therapeutic effects of dandelion species. Furthermore, current phytochemical and pharmacological research has overlooked several Taraxacum species with well-documented traditional uses. Investigating these understudied species is essential to fully elucidate the potential therapeutic value of the genus Taraxacum.
6 Apr 2026
Read appraisal →Medicine
Post-marketing signal detection of fruquintinib-associated adverse events using the FAERS database
Fruquintinib, a targeted therapeutic agent approved in 2018 for the treatment of metastatic colorectal cancer, is gradually being applied in an expanding range of clinical settings. Given the complexities associated with real-world dosing, a comprehensive evaluation of its safety profile is essential for optimizing clinical decision-making. We conducted a retrospective pharmacovigilance study utilizing a spontaneous reporting system. Reports related to Fruquintinib were extracted through a standardized data cleaning process and cross-validated using 3 complementary signal detection algorithms: proportional reporting ratio, Bayesian confidence propagation neural network, and reporting odds ratio (ROR). This approach was employed to systematically assess the drug's safety and identify potential adverse event signals. A total of 92 statistically significant safety signals were identified from 1188 independent cases included in the analysis, corresponding to 1836 adverse event reports. The signal distribution exhibited organ system specificity, with gastrointestinal reactions being the most prevalent category. These reactions primarily manifested as typical drug-related toxicities, including diarrhea and nausea. Other notable complications included neurological, respiratory, dermatological, renal, and cardiovascular events. Important aes not mentioned in the instructions, such as bone marrow suppression (ROR = 11.17), peripheral neuropathy (ROR = 4.24) and dehydration (ROR = 3.98), were also discovered. This study systematically characterizes the post-marketing safety profile of Fruquintinib through a multi-algorithm synergistic analysis, confirming that its safety profile aligns with the clinically expected outcomes based on its mechanism of action. Future research should focus on analyzing drug interaction mechanisms and exploring biomarkers to develop a precise risk-benefit assessment model.
5 Apr 2026
Read appraisal →PloS one
Clinical impact of broad- versus narrow-spectrum empiric therapy in acute cholangitis: A Japanese claims database study
The clinical benefit of broad-spectrum empiric therapy in patients with acute cholangitis is unclear. We aimed to evaluate the impact of broad-spectrum and narrow-spectrum empiric therapies on patient outcomes using a Japanese claims database. The study included patients who were diagnosed with acute cholangitis between April 2014 and August 2022, aged 18-99 years, received antibiotics, had blood cultures collected, and underwent biliary drainage. Patients who received empiric therapy with carbapenems, piperacillin/tazobactam, or fourth-generation cephalosporins were included in the broad-spectrum group, whereas others were included in the narrow-spectrum group. Of the 4,755 eligible patients, 3,377 were categorized into the narrow-spectrum group and 1,378 into the broad-spectrum group. In the multivariate logistic regression analysis, older age, higher Charlson Comorbidity Index, the presence of sepsis, and intensive care unit admission were associated with increased 30-day in-hospital mortality, whereas the receipt of broad-spectrum empiric therapy was not (adjusted odds ratio, 1.37 [95% confidence interval {CI}, 0.84-2.23]). In the propensity score matching analysis, there was also no association between the receipt of broad-spectrum empiric therapy and 30-day in-hospital mortality (odds ratio, 1.43 [95% CI, 0.82-2.50]). Furthermore, in the propensity score-matched cohort, the broad-spectrum group had longer duration of intravenous antibiotic therapy (median interquartile range [IQR]: 8 [6 -11] day vs. 9 [7 -13] day; difference 1 day [95% CI, 0.31-1.69 day]) and length of hospital stay (median [IQR]: 13 [9 -20] day vs. 16 [11 -25] day; difference 3 day [95% CI, 1.87-4.13 day]), compared with the narrow-spectrum group. In this large-scale study using a Japanese claims database, broad-spectrum empiric therapy was not associated with improved clinical outcomes, compared with narrow-spectrum empiric therapy. Therefore, the necessity of broad-spectrum empiric therapy may be limited in clinical practice, and narrow-spectrum empiric therapy may represent an effective treatment strategy for acute cholangitis.
5 Apr 2026
Read appraisal →Medicine
Neuroendocrine neoplasms diagnosed in the setting of inflammatory bowel disease: A systematic review and proposed management algorithm
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at higher risk of developing malignancies, including neuroendocrine neoplasms, but the specifics of that are not well known. We reviewed the existing literature to map the evidence surrounding this phenomenon. METHODS: Following PRISMA 2020 guidelines, we searched PubMed from inception to September 2024 for patients with gastrointestinal neuroendocrine neoplasms (NENs) and either Crohn disease (CD) or ulcerative colitis (UC). Eligible studies included case reports, case series, and larger retrospective IBD cohorts. We extracted demographic and clinical data including tumor grade, location, metastatic status, and mode of detection. Comparative analyses between UC and CD were performed using Fisher exact test, chi-square test, and independent t-tests. RESULTS: We identified 67 case studies with data available for a total of 108 patients (61.1% male), ranging from 14 to 87 years of age. The median duration from IBD diagnosis to NEN detection was 13 years. Fifty-five (50.9%) patients had CD and 53 (49.1%) had UC. UC patients were older at NEN diagnosis (mean 49 vs 40 years, P = .004) and had a higher metastatic rate (39.6% vs 18.2%, P = .019). Most NENs were low-grade (69.4%), while 20.4% were high-grade and 8.3% were mixed. The most common tumor locations were the rectum (29.6%) and appendix (27.8%), with rectal and colonic NENs more prevalent in UC and small bowel or appendiceal NENs more common in CD. At diagnosis, 71.3% of patients had localized disease. For high-grade NENs, 86.4% of cases were metastatic, compared to 9.3% for low-grade tumors. Only 10.2% of NENs were detected via endoscopic surveillance. CONCLUSIONS: NENs in IBD show distinct patterns by IBD type, with significant differences in tumor location, grade, and metastatic rates between UC and CD. These hypothesis-generating observations suggest heightened vigilance after approximately 10 years of IBD or around age 44, focusing on rectal lesions in UC and small bowel/appendiceal lesions in CD. Validation in prospective, population-based studies is needed before these findings can inform clinical practice.
4 Apr 2026
Read appraisal →Computer methods and programs in biomedicine
Application of artificial intelligence in colonoscopy imaging for polyp analysis-A systematic review
The colon is a major component of the digestive system, so early detection of colorectal polyps is essential in preventing colorectal cancer, which is a leading cause of cancer-related death worldwide. While colonoscopy remains the gold standard for polyp detection, its diagnostic accuracy is highly operator-dependent. Recent advances in Deep Learning (DL), a branch of Artificial Intelligence (AI), have shown substantial potential to improve colonoscopy image analysis by enhancing the accuracy, consistency, and objectivity of polyp detection, segmentation, and classification. Artificial intelligence-based systems have significantly reduced inter-observer variability and increased diagnostic efficiency, ultimately transforming the landscape of colorectal lesion assessment. This survey provides a comprehensive and critical analysis of the current status of deep learning applications in colorectal polyp analysis. We systematically review state-of-the-art methodologies across various DL architectures-including Convolutional Neural Networks (CNNs), transformer-based models, and hybrid approaches-and examine their performance on publicly available benchmark datasets. Additionally, we highlight the strengths and limitations of existing techniques, explore the clinical relevance of AI-assisted tools, and identify prevailing challenges such as data imbalance, real-time deployment, and generalizability across diverse populations and colonoscopy devices. By consolidating key advances and outlining future research directions, this review aims to serve as a valuable resource for researchers, clinicians, and developers seeking to leverage deep learning to enhance colorectal polyp detection, diagnosis, and clinical decision-making.
4 Apr 2026
Read appraisal →The American journal of gastroenterology
A Large Language Model Assistant for Summarizing Hepatology Referral Documents
INTRODUCTION: To use a large language model (LLM) to create accurate and useable summaries of patient records for clinicians triaging new hepatology referrals. METHODS: We developed a comprehensive list of data elements required to triage a new hepatology referral and engaged in an iterative prompt engineering process to instruct an LLM to extract relevant data from patient referral documents. The final prompt was used on 50 original patient records from June to July 2025 to generate corresponding artificial intelligence (AI) summaries, which were assigned to 2 providers to review and triage according to their usual process. We assessed time to triage original vs AI files and accuracy of the AI files. A linear mixed-effects model was used to determine an adjusted time ratio comparing the time to triage AI files vs original files. RESULTS: AI-generated summaries were significantly shorter than original files (median [interquartile range] 2 [2-3] vs 23 [10.2-38.8] pages, P < 0.001). AI summaries had high accuracy (median [interquartile range]: 94.6% [86.5%-97.3%]) with a low hallucination rate. Use of the AI summaries led to a 60% reduction in triage time (adjusted mean triage time of 37.2 seconds for AI files vs 94.2 seconds for original files, P < 0.001). DISCUSSION: The use of an LLM led to significantly reduced document length, maintained an appropriate level of accuracy, and led to a significant decrease in clinician time to review the patient record. Future steps involve creating a fully automated workflow that is integrated into the electronic health record for widespread use.
4 Apr 2026
Read appraisal →Yonsei medical journal
Deep Learning for Automated Tumor Segmentation of Rectal Cancer on T2-Weighted Magnetic Resonance Images
PURPOSE: To develop a deep learning (DL)-based automated segmentation model for rectal cancer on T2-weighted (T2W) magnetic resonance (MR) images. MATERIALS AND METHODS: A total of 458 patients who underwent baseline rectal MR imaging were retrospectively enrolled. An experienced radiologist labeled the tumor on each slice of the selected T2W axial images covering the entire tumor mass, and tumor volume was measured during labeling. Another radiologist labeled the rectum on the same images. Attention U-Net was trained on the T2W images from the training dataset to classify each voxel as tumor or non-tumor. Segmentation with or without rectum guidance was compared using evaluation metrics, including the Dice similarity coefficient (DSC), in the test dataset. RESULTS: The tumor segmentation DSC without rectum guidance was 73.35% (71.97-74.71); that with the predicted rectum was 71.79% (70.53-73.05); and that with the overlaid rectum was 75.52% (74.32-76.62), which was the highest among the three segmentation models. Tumor volume showed a positive correlation with tumor segmentation accuracy with the predicted rectum (r=0.333, p=0.001; overlaid rectum, r=0.319, p=0.002) and without rectum guidance (r=0.219, p=0.036). CONCLUSION: A DL-based automated segmentation model can predict RC with over 70% accuracy, which was further improved with overlaid rectum, and larger tumor volume.
4 Apr 2026
Read appraisal →Abdominal radiology (New York)
Artificial intelligence in gastric cancer: a systematic review of machine learning and deep learning applications
BACKGROUND: Gastric cancer (GC) remains a major global health concern, ranking as the fifth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide. Although early detection can increase the 5-year survival rate of early gastric cancer (EGC) to over 90%, more than 80% of cases are diagnosed at advanced stages due to subtle clinical symptoms and diagnostic challenges. Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has shown great promise in addressing these limitations. OBJECTIVES: This systematic review aims to evaluate the performance, applications, and limitations of ML and DL models in GC management, with a focus on their use in detection, diagnosis, treatment planning, and prognosis prediction across diverse clinical imaging and data modalities. METHODS: Following the PRISMA 2020 guidelines, a comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus for studies published between 2004 and May 2025. Eligible studies applied ML or DL algorithms for diagnostic or prognostic tasks in GC using data from endoscopy, computed tomography (CT), pathology, or multi-modal sources. Two reviewers independently performed study selection, data extraction, and risk of bias assessment. RESULTS: A total of 59 studies met the inclusion criteria. DL models, particularly convolutional neural networks (CNNs), demonstrated strong performance in EGC detection, with reported sensitivities up to 95.3% and Area Under the Curve (AUCs) as high as 0.981, often exceeding expert endoscopists. CT-based radiomics and DL models achieved AUCs ranging from 0.825 to 0.972 for tumor staging and metastasis prediction. Pathology-based models reported accuracies up to 100% for EGC detection and AUCs up to 0.92 for predicting treatment response. Cross-modality approaches combining radiomics and pathomics achieved AUCs up to 0.951. Key challenges included algorithmic bias, limited dataset diversity, interpretability issues, and barriers to clinical integration. CONCLUSION: ML and DL models have demonstrated substantial potential to improve early detection, diagnostic accuracy, and individualized treatment in GC. To advance clinical adoption, future research should prioritize the development of large, diverse datasets, implement explainable AI frameworks, and conduct prospective clinical trials. These efforts will be essential for integrating AI into precision oncology and addressing the increasing global burden of gastric cancer.
4 Apr 2026
Read appraisal →The Journal of pathology
Integrating artificial intelligence (AI) into colorectal cancer reporting
Artificial intelligence (AI) and deep learning (DL) are transforming cancer research and clinical care, with histopathology playing a central role in this transformation. In colorectal cancer (CRC), the second leading cause of cancer mortality world-wide, multimodal and vision-language models (VLMs) hold particular promise for enhancing the standardisation of histopathology reporting, the understanding of disease biology, and the discovery of novel prognostic indicators. Despite the availability of guidelines and reporting templates for essential prognostic indicators, variability remains in how key features such as TNM staging or tumour deposits are assessed and reported in routine clinical practice. AI-based tools have the potential to support refined extraction of established and extended features directly from whole-slide images. In parallel, recent studies have shown that DL models applied to pathology slides and associated AI-based biomarkers can outperform traditional histopathological prognostic indicators and uncover novel parameters, including tumour-adipocyte interactions, tumour-stroma ratio, and immune cell patterns at the invasive margin. Here, we review recent advances in both domains: AI-assisted standardisation of CRC pathology reporting and AI-driven identification of novel prognostic biomarkers. We highlight the need to refine and standardise CRC reporting practices and propose that a harmonised approach combining established pathology features with AI-derived prognostic indicators could refine risk assessment and improve outcomes for CRC patients. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
4 Apr 2026
Read appraisal →IEEE transactions on bio-medical engineering
Explainable Prediction of ICU Transfer in Acute Pancreatitis: A Neural Network Model With SHAP Interpretability for Clinical Decision Support
OBJECTIVE: Acute pancreatitis (AP) is a life-threatening disorder commonly observed in emergency departments. Patients with acute pancreatitis may necessitate transfer to the intensive care unit (ICU) if standard treatments prove ineffective. The development of a machine learning (ML) model that can precisely forecast the necessity for ICU admission in patients with acute pancreatitis might dramatically enhance in-hospital healthcare for patients. METHODS: For this study, data were extracted from the MIMIC-III Clinical Database Care-Vue subset (MIMIC-III v 1.4), Medical Information Mart for Intensive Care-IV (MIMIC-IV v 3.1), and eICU Collaborative Research Database (v 2.0). Fifteen features were identified through Boruta's algorithm, Least Absolute Shrinkage and Selection Operator (Lasso), and Recursive Feature Elimination (RFE) utilizing the XGBoost. RESULTS: Seven machine learning models, including Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Neural Network (NNET), etc. were developed based on these features. The neural network approach demonstrated the highest reliability, attaining an AUC of 0.891, sensitivity of 0.852, and specificity of 0.767 in the test set. Meanwhile, an interpretability assessment of the most robust models was performed utilizing SHapley Additive exPlanations (SHAP) to prioritize feature importance and elucidate the final model. This model has been deployed on a web platform: https://icupredict.shinyapps.io/shiny6/. CONCLUSIONS: The neural network model effectively predicted whether patients with AP would be transferred to the ICU, demonstrating optimal performance. SIGNIFICANCE: We developed an interpretable ML model for prediction of ICU admission in AP patients. It provides clinicians with a reliable tool for early identification and treatment.
4 Apr 2026
Read appraisal →Ann Med
Artificial intelligence-assisted diagnosis of early gastric cancer: present practice and future prospects
Gastric cancer (GC) occupies the first few places in the world among tumors in terms of incidence and mortality, causing serious harm to human health, and at the same time, its treatment greatly consumes the health care resources of all countries in the world. The diagnosis of GC is usually based on histopathologic examination, and it is very important to be able to detect and identify cancerous lesions at an early stage, but some endoscopists' lack of diagnostic experience and fatigue at work lead to a certain rate of under diagnosis. The rapid and striking development of Artificial intelligence (AI) has helped to enhance the ability to extract abnormal information from endoscopic images to some extent, and more and more researchers are applying AI technology to the diagnosis of GC. This initiative has not only improved the detection rate of early gastric cancer (EGC), but also significantly improved the survival rate of patients after treatment. This article reviews the results of various AI-assisted diagnoses of EGC in recent years, including the identification of EGC, the determination of differentiation type and invasion depth, and the identification of borders. Although AI has a better application prospect in the early diagnosis of ECG, there are still major challenges, and the prospects and limitations of AI application need to be further discussed.
1 Dec 2025
Read appraisal →Cancer Res
Artificial Intelligence and Multimodality Data Integration Decipher Tertiary Lymphoid Structure Maturity in Gastric Cancer
UNLABELLED: Tertiary lymphoid structures (TLS) are critical components of the tumor microenvironment in gastric cancer, but clinical assessment of TLSs is challenging. The development of automated annotation tools for histopathologic slide analysis could facilitate the identification of TLSs and enhance our understanding of the mechanisms driving TLS maturation. In this study, we generated a transformer-based deep learning model that enables quantitative characterization of TLS maturity from whole-slide images. Application of the model to a large gastric cancer cohort (n = 253) showed that higher TLS maturity correlated with improved patient survival. Integration of single-cell RNA sequencing data from 17 patients with gastric cancer combined with multiplex IHC, flow cytometry, and functional coculture assays identified a key immune circuit in mature TLSs involving CD8+ tissue-resident memory T cells, which recruit activated B cells via the CXCL13-CXCR5 axis to enhance tissue-resident memory T-cell cytotoxicity through granzyme B upregulation. Overall, this study established a clinically applicable artificial intelligence tool and uncovered key immune interactions that regulate TLS maturation and antitumor immunity in gastric cancer. SIGNIFICANCE: A deep learning model demonstrates that higher tertiary lymphoid structure maturity predicts improved gastric cancer patient survival and identifies a key immune circuit, offering a clinically applicable tool that could guide treatment. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI.
1 Dec 2025
Read appraisal →Gut Microbes
Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease
Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between the functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate the functional capability of gut microbiota to affect kidney function of DKD patients. A total of 990 subjects were enrolled consisting of a control group (n = 455), a type 2 diabetes mellitus group (DM, n = 204), a DKD group (n = 182) and a chronic kidney disease group (CKD, n = 149). Full-length sequencing of 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types of microbiota biomarkers have been created using a machine-learning (ML) method, namely relative abundance of a microbe, presence or absence of a microbe, and the hierarchy ratio between two different taxonomies. Four different panels of features were selected to be analyzed: (i) DM vs. Control, (ii) DKD vs. DM, (iii) DKD vs. CKD, and (iv) CKD vs. Control. These had accuracy rates between 0.72 and 0.78 and areas under curve between 0.79 and 0.86. Secondly, 13 gut microbiota biomarkers, which are strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by the ML algorithm and the differential abundance method were highly discriminatory. Finally, the predicted functional capability of a DKD-specific biomarker, Gemmiger spp. is enriched in carbohydrate metabolism and branched-chain amino acid (BCAA) biosynthesis. Coincidentally, the circulating levels of various BCAAs (L-valine, L-leucine and L-isoleucine) and their precursor, L-glutamate, are significantly increased in DM and DKD patients, which suggests that, when hyperglycemia is present, there has been alterations in various interconnected pathways associated with glycolysis, pyruvate fermentation and BCAA biosynthesis. Our findings demonstrate that there is a link involving the gut-kidney axis in DKD patients. Furthermore, our findings highlight specific gut bacteria that can acts as useful biomarkers; these could have mechanistic and diagnostic implications.
1 Dec 2025
Read appraisal →J Clin Oncol
Foundation Model for Predicting Prognosis and Adjuvant Therapy Benefit From Digital Pathology in GI Cancers
PURPOSE: Artificial intelligence (AI) holds significant promise for improving cancer diagnosis and treatment. Here, we present a foundation AI model for prognosis prediction on the basis of standard hematoxylin and eosin-stained histopathology slides. METHODS: In this multinational cohort study, we developed AI models to predict prognosis from histopathology images of patients with GI cancers. First, we trained a foundation model using over 130 million patches from 104,876 whole-slide images on the basis of self-supervised learning. Second, we fine-tuned deep learning models for predicting survival outcomes and validated them across seven cohorts, including 1,619 patients with gastric and esophageal cancers and 2,594 patients with colorectal cancer. We further assessed the model for predicting survival benefit from adjuvant chemotherapy. RESULTS: The AI models predicted disease-free survival and disease-specific survival with a concordance index of 0.726-0.797 for gastric cancer and 0.714-0.757 for colorectal cancer in the validation cohorts. The models stratified patients into high-risk and low-risk groups, with 5-year survival rates of 49%-52% versus 76%-92% in gastric cancer and 43%-72% versus 81%-98% in colorectal cancer. In multivariable analysis, the AI risk scores remained an independent prognostic factor after adjusting for clinicopathologic variables. Compared with stage alone, an integrated model consisting of stage and image information improved prognosis prediction across all validation cohorts. Finally, adjuvant chemotherapy was associated with improved survival in the high-risk group but not in the low-risk group (treatment-model interaction P = .01 and .006) for stage II/III gastric and colorectal cancer, respectively. CONCLUSION: The pathology foundation model can accurately predict survival outcomes and complement clinicopathologic factors in GI cancers. Pending prospective validation, it may be used to improve risk stratification and inform personalized adjuvant therapy.
1 Nov 2025
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