[JOURNAL] HEPATOLOGY
Sun
200 papers
Acetazolamide-Responsive Exertion-Triggered Episodic Ataxia in DHDDS-Related Congenital Disorder of Glycosylation.
Muniswamy JKR, Selvido L, Van Zele E … +3 more , Satyanarayana R, Morava E, Muthusamy K
Mov Disord Clin Pract · 2026 Jul · PMID 42394283 · Publisher ↗
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The Changing Etiological Landscape of Liver Cancer in the Era of Metabolic Disease.
Zhou XD, Huang DQ, Sebastiani G … +1 more , Zheng MH
Liver Int · 2026 Aug · PMID 42394245 · Publisher ↗
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Feminizing Therapy in People With Klinefelter Syndrome and Gender Incongruence: Considerations for Treatment Without Testosterone Blockers.
Kroon M, Klooker TK, Hannema SE … +1 more , Den Heijer M
Andrology · 2026 Jul · PMID 42394191 · Publisher ↗
BACKGROUND: Klinefelter syndrome (KS; 47, XXY) usually involves male sex development and gender identity. Small studies suggest gender incongruence may be more common in KS, but feminizing gender‑affirming hormone therap...
BACKGROUND: Klinefelter syndrome (KS; 47, XXY) usually involves male sex development and gender identity. Small studies suggest gender incongruence may be more common in KS, but feminizing gender‑affirming hormone therapy in this group has been scarcely reported. OBJECTIVES: To evaluate current feminizing hormone therapy in individuals with KS and the number of individuals with KS attending our gender clinic. MATERIALS AND METHODS: We conducted a care evaluation of individuals with KS referred to the Center of Expertise on Gender Dysphoria (Amsterdam UMC) between February 1972 and May 2025, collecting data on KS diagnosis, testosterone use, referral age, feminizing hormone therapy, and hormone concentrations. RESULTS: Eight (0.12%) people had KS. Median age at KS diagnosis was 25.3 years (IQR 16.9-37.5, n = 8), and at gender clinic intake 45.3 years (IQR 34.2-52.2, n = 8). Among estradiol users, median age was 45.7 years (IQR 42.4-57.1, n = 6). None of those retaining their testes use testosterone blockers (follow‑up: median 5.4 years (3.6-7.7), n = 5). DISCUSSION: In KS, estradiol alone may sufficiently suppress testosterone. KS prevalence in our cohort does not exceed that of the general population. CONCLUSION: Given KS‑related hypogonadism, estradiol monotherapy may be an appropriate first‑line feminizing hormone therapy, avoiding routine use of testosterone blockers.
Unveiling the Cellular and Molecular Insights into Ulcerative Colitis Pathogenesis through Integrative Multi-omics and Functional Experiments.
Han Y, Xiao J, Yi J
Comb Chem High Throughput Screen · 2026 Jul · PMID 42393888 · Publisher ↗
INTRODUCTION: Single-cell RNA sequencing (scRNA-seq) enables the detection of cellular heterogeneity in ulcerative colitis (UC). But there is still inadequate evidence to unravel the causal relationship between different...
INTRODUCTION: Single-cell RNA sequencing (scRNA-seq) enables the detection of cellular heterogeneity in ulcerative colitis (UC). But there is still inadequate evidence to unravel the causal relationship between differentially expressed genes (DEGs) and UC pathogenesis. This study aimed to comprehensively explore genomic, transcriptomic, proteomic, and scRNA-seq data to provide valuable insights into the molecular basis of UC and identify potential candidate biomarkers. MATERIALS AND METHODS: The GSE125527 single-cell RNA sequencing (scRNA-seq) dataset was subjected to quality control, dimension reduction, and cell identification using the Seurat package. DEGs specific to different cell types were identified. Mendelian randomization (MR) analysis was used to explore the causal relationship between feature DEGs and UC based on data derived from genome-wide association studies (GWAS) (ieu-a-32, 20,464 normal controls and 6968 UC patients), including expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL). Multi-omics data were integrated to verify the genetic regulatory relationships. Further validation of the final hub gene was performed in vitro and in vivo. RESULTS: By analyzing the scRNA-seq dataset, we obtained 48,576 cells that were annotated into 5 different subtypes. A total of 1,905 DEGs were identified in different single-cell subsets. With these DEGs as exposure factors and the GWAS data of UC as outcomes, along with eQTL and pQTL analysis, FCN1 and ING4 were determined to be causally associated with UC. Both genes were effective in differentiating between UC patients and healthy controls. Furthermore, ING4 was lowly expressed in UC intestinal tissues and in LPS-treated intestinal epithelial cells, and it was involved in inflammatory responses. An in vitro functional experiment demonstrated that the knockdown or overexpression of ING4 could regulate the phosphorylation-induced activation of the NF-κB pathway and affect the release of the inflammatory factor iNOS, thereby triggering the occurrence and development of UC. DISCUSSION: From a genetic causality perspective, ING4 emerges as a candidate gene with genetically supported relationship to UC, linking immune-related regulatory variation to epithelial inflammatory responses, while its precise tissue- and cell-type specific mechanisms remain to be clarified. CONCLUSION: This study emphasizes the importance of integrating multi-omics data in the exploration of UC pathogenesis. These findings position ING4 as a promising candidate biomarker and a potential molecule of therapeutic interest for UC.
Clinicopathologic and Molecular Analysis of Traditional Serrated Adenoma and Its Possible Precursor Lesions With Special Reference to RSPO Fusion Status: A Large Case Series From Single Institution.
Kadomatsu Y, Saito T, Kamba E … +2 more , Murakami T, Yao T
Am J Surg Pathol · 2026 Jul · PMID 42393851 · Publisher ↗
Colorectal serrated lesions are divided into hyperplastic polyps (HP), sessile serrated lesions (SSL), and traditional serrated adenomas (TSA) in the sixth edition of the WHO classification. In 2018, superficially serrat...
Colorectal serrated lesions are divided into hyperplastic polyps (HP), sessile serrated lesions (SSL), and traditional serrated adenomas (TSA) in the sixth edition of the WHO classification. In 2018, superficially serrated adenoma (SuSA) was proposed as a new subtype of colorectal serrated lesions and a possible precursor of traditional serrated adenoma (TSA). However, tumorigenesis in the serrated pathway remains uncertain. In this study, 271 colorectal serrated lesions (13 SuSAs and 258 TSAs) were collected, and the clinicopathologic features, including the coexistence of possible precursor components (SuSA/SSL/HP), and molecular features (RSPO fusion and KRAS/BRAF mutation status) were investigated. In 13 SuSAs, RSPO fusion was detected in 13 cases, and KRAS mutations were detected in 9 cases. Among the 258 TSAs, RSPO fusion and KRAS and BRAF mutations were detected in 103, 92, and 102 cases, respectively. RSPO fusion-positive TSAs harbored KRAS and BRAF mutations in 62 (60%) and 18 (17%) cases, respectively, and were accompanied by SuSA/SSL/HP in 31/4/4 cases, respectively. KRAS-mutated TSAs exhibited RSPO fusion in 62 cases (67%), accompanied by SuSA/SSL/HP in 29/1/1 cases, respectively. BRAF-mutated TSAs exhibited RSPO fusion in 18 (18%) cases and SuSA/SSL/HP in 2/20/12 cases, respectively. These findings indicate that SuSA could be a possible precursor of TSA with KRAS mutation and RSPO fusion, whereas SSL and HP (microvesicular hyperplastic polyp) are possible precursors of TSA with BRAF mutation. RSPO fusions are more strongly associated with KRAS mutation and SuSA than with BRAF mutation and SSL/HP in serrated pathway tumorigenesis.
Early risk stratification of late-onset sepsis in very preterm infants by intestinal microbiota profiling: a multicenter case-control validation study.
Frerichs NM, de Kroon RR, van Schajik Y … +20 more , El Manouni El Hassani S, van Wesemael AJ, de Boode WP, Cossey V, Hulzebos CV, van den Akker CHP, Raets MMA, d'Haens EJ, Vijlbrief D, van Weissenbruch MM, de Jonge WJ, de Boer NK, van Goudoever JB, Beggs AD, Quraishi MN, Davids M, Mondal S, Acharjee A, Niemarkt HJ, de Meij TGJ
Gut Microbes · 2026 Dec · PMID 42393826 · Publisher ↗
Intestinal bacterial translocation to the bloodstream is a route of infection for late-onset sepsis (LOS) in preterm infants, highlighting the potential of fecal microbiota profiling for early risk stratification. We aim...
Intestinal bacterial translocation to the bloodstream is a route of infection for late-onset sepsis (LOS) in preterm infants, highlighting the potential of fecal microbiota profiling for early risk stratification. We aimed to identify and validate LOS-specific gut microbiota signatures. Fifty-eight preterm infants (gestational age < 30 weeks) with blood culture-proven LOS (excluding coagulase-negative ) were matched to controls (1:1) across three cohorts (Discovery (DC) = 18; Validation 1 and 2; VC1 = 12, VC2 = 28). Fecal samples collected up to 10 days before LOS onset underwent 16S rRNA gene sequencing. Microbial composition, diversity, and discriminatory taxa were compared across LOS subgroups. Random Forest (RF) models were trained in DC and validated in VC1/VC2. Microbiota variation was largely explained by LOS pathogen (R = 17%, < 0.001). Infants with non-staphylococcal and -LOS showed a temporal increase in relative abundance of . The RF model distinguishing LOS from controls displayed the highest discriminatory performance (AUC = 0.99/0.78/0.61 for DC/VC1/VC2) compared to non-staphylococcal LOS (AUC = 0.96/0.46/0.41). Our findings demonstrate profound microbiota shifts preceding -LOS, with higher discriminatory ability compared to non-staphylococcal-LOS. While pathogen-specific microbiota-based risk stratification may offer added clinical value, reduced validation performance highlights the limited generalizability and underscores the need for future research before clinical translation.
Gallstone ileus developing two months after endoscopic papillary large balloon dilatation: a case report.
Matsuzaki Y, Matsumoto K, Oyama S … +7 more , Saito H, Fujimoto H, Kameyama A, Murayama D, Igarashi T, Arakura N, Kiyosawa K
J Med Case Rep · 2026 Jul · PMID 42393767 · Full text
BACKGROUND: Gallstone ileus is a rare clinical entity causing bowel obstruction, and transpapillary migration of gallstones after endoscopic retrograde cholangiopancreatography is exceptionally uncommon. Although endosco...
BACKGROUND: Gallstone ileus is a rare clinical entity causing bowel obstruction, and transpapillary migration of gallstones after endoscopic retrograde cholangiopancreatography is exceptionally uncommon. Although endoscopic papillary large balloon dilatation is an effective procedure that dilates the Vater's papilla to remove larger size calculi, gallstone ileus following the procedure as a complication has rarely been reported in the literature. CASE PRESENTATION: We present the case of an 89-year-old Japanese woman diagnosed with acute cholangitis due to choledocholithiasis, exhibiting epigastric pain, nausea and jaundice. She was treated with endoscopic procedure, including papillary large balloon dilatation, but attempts at stone extraction were unsuccessful. Two months later, the patient was readmitted with acute cholangitis, likely secondary to biliary stent occlusion; however, retrospective review of the computed tomography revealed multiple common bile duct stones as well as a large intrajejunal foreign body consistent with a stone. One day after undergoing urgent endoscopic procedure, she developed recurrent vomiting and was diagnosed with gallstone ileus due to impaction of the stone in the ileum. Following failed endoscopic disimpaction, urgent surgery was performed, and the stone was manually fragmented into several pieces and pushed distally without the need for enterotomy. She was discharged from the hospital on eighth day after the operation. CONCLUSION: To our knowledge, this is one of the very few cases of gallstone ileus occurring after endoscopic papillary large balloon dilatation. When extraction of a large common bile duct stone is difficult even after endoscopic papillary large balloon dilatation, additional treatment strategies should be considered, given the potential risk of delayed spontaneous passage and subsequent gallstone ileus.
Spatial anchoring of lipid metabolism shapes immune fate in the tumor microenvironment.
Zheng S, Tan Z, Bao Y … +2 more , Gong X, Zhong X
Lipids Health Dis · 2026 Jul · PMID 42393736 · Full text
Cancer metabolic reprogramming has typically been regarded as a cell-autonomous process; however, this perspective fails to fully capture the intricacies of immunosuppression and treatment resistance within the heterogen...
Cancer metabolic reprogramming has typically been regarded as a cell-autonomous process; however, this perspective fails to fully capture the intricacies of immunosuppression and treatment resistance within the heterogeneous and spatially organized tumor microenvironment (TME). While the metabolism of all major nutrients is subject to spatial constraints, lipid metabolism exhibits a unique and pronounced sensitivity due to the hydrophobic nature of lipids, which necessitates a specialized network of carrier proteins and organelles for their transport, storage, and signaling. We propose a model of spatio-specific lipid-immune regulatory programs that connects the intrinsic metabolic drivers of cancer cells with the spatial architecture of the TME, While grounded in existing literature, several of the mechanistic connections we describe represent a conceptual framework and working hypotheses that require direct experimental testing in the tumor microenvironment. Our investigation focuses on how three distinct spatial niches, the hypoxic core, invasive margin, and perivascular area, shape diverse lipid metabolic profiles through their unique physicochemical conditions and cellular compositions. Metabolic states specific to location determine the destiny and role of infiltrating immune cells, shaping an immune network significantly impacted by spatial positioning. Additionally, we investigate the potential of this spatial framework in identifying niche-specific biomarkers and developing novel combination therapies.
Extracellular vesicle-mediated GALNT1/RPRD1A glycosylation axis drives immune escape and peritoneal metastasis in gastric cancer.
Jin G, Zhang J, He Q … +3 more , Chang S, Dong Z, Shi Y
J Exp Clin Cancer Res · 2026 Jul · PMID 42393735 · Full text
BACKGROUND: Peritoneal metastasis represents one of the most lethal clinical manifestations of gastric cancer (GC) and is closely associated with immune evasion. Extracellular vesicles (EVs) have emerged as critical medi...
BACKGROUND: Peritoneal metastasis represents one of the most lethal clinical manifestations of gastric cancer (GC) and is closely associated with immune evasion. Extracellular vesicles (EVs) have emerged as critical mediators of tumor-immune communication; however, the molecular mechanisms by which EV-associated glycosylation regulates immune escape and metastatic dissemination remain largely undefined. METHODS: EVs derived from highly metastatic GC cells were isolated and functionally characterized in vitro and in humanized immune system mouse models. Their clinical relevance was evaluated using paired human GC specimens. Underlying mechanisms were investigated through genetic manipulation, lectin-based glycosylation assays, and immune cell co-culture experiments. RESULTS: We identified GALNT1 as an EV-enriched glycosyltransferase that promotes GC cell invasion and suppresses CD8 T-cell activation. Mechanistically, GALNT1-dependent O-GalNAc glycosylation of RPRD1A was associated with increased RPRD1A protein abundance without altering its mRNA expression. Increased RPRD1A acted as a key downstream effector driving immune escape and peritoneal metastasis. Clinically, GALNT1 and RPRD1A were significantly upregulated in GC tissues, positively correlated with each other, associated with reduced T-cell infiltration, and predictive of poor prognosis. In humanized mouse models, EV-mediated transfer of GALNT1 accelerated peritoneal dissemination and impaired antitumor immunity, whereas disruption of the GALNT1/RPRD1A axis restored T-cell infiltration and suppressed metastatic progression. CONCLUSIONS: These findings identify an EV-driven GALNT1/RPRD1A glycosylation axis as a previously unrecognized mechanism underlying immune escape and peritoneal metastasis in GC and support this pathway as a potential therapeutic target for advanced disease.
Technical and clinical feasibility of single-use gastroscopy with real-time AI-based quality monitoring and single-use colonoscopy: a prospective two-center study.
Lv Y, Xu L, Gong W … +5 more , Zhu Y, Xu W, Xia G, Zhang Z, Zhi F
Biomed Eng Online · 2026 Jul · PMID 42393687 · Full text
BACKGROUND: Single-use gastrointestinal endoscopes eliminate the need for post-procedure reprocessing and have become an area of interest in endoscopic device development and quality management. However, clinical data on...
BACKGROUND: Single-use gastrointestinal endoscopes eliminate the need for post-procedure reprocessing and have become an area of interest in endoscopic device development and quality management. However, clinical data on their use in routine gastrointestinal endoscopy remain limited. This prospective, two-center, single-arm study evaluated the feasibility and short-term safety of single-use gastroscopy performed with ENDOANGEL, an artificial intelligence (AI)-based real-time quality monitoring system, and single-use colonoscopy in routine gastrointestinal endoscopy. Formal AI-based quality scoring was applied to gastroscopy, whereas ENDOANGEL-related colonoscopy indicators were recorded descriptively. RESULTS: A total of 120 participants were enrolled, including 60 who underwent gastroscopy and 60 who underwent colonoscopy. Imaging of predefined anatomical sites was successful in all participants in both groups (60/60 in each group; 95% CI 94.0-100.0%). All procedures were completed without conversion to reusable endoscopes. The overall image quality scores were 39.2 ± 0.8/40 for gastroscopy and 31.3 ± 0.8/32 for colonoscopy. Mean total procedure times were 9.3 ± 2.7 min and 12.6 ± 3.1 min, respectively. No device malfunction, device defect, or procedure-related adverse event was observed during the procedure or within 24 h after endoscopy. In gastroscopy, all ENDOANGEL-assisted examinations achieved the maximum procedural score, and ENDOANGEL-based assessment agreed with manual assessment of imaging success and procedure completion. In colonoscopy, ENDOANGEL-related cecal intubation reminders agreed with manual assessment in all procedures, and withdrawal-speed alerts were recorded in 4 of 60 procedures. CONCLUSION: Single-use gastroscopy with real-time AI-based quality monitoring and single-use colonoscopy were feasible in routine gastrointestinal endoscopy and showed a favorable short-term safety profile within 24 h. AI-related findings should be interpreted as feasibility and agreement data for gastroscopy and as descriptive process-monitoring observations for colonoscopy. Further controlled studies are needed to compare single-use and reusable systems and to clarify the clinical role of AI-based process monitoring in single-use endoscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100045101. Retrospectively registered on April 6, 2021.
Predictive factors and nomogram for post-endoscopic retrograde cholangiopancreatography pancreatitis.
Yuan H, Wang H
BMC Gastroenterol · 2026 Jul · PMID 42393582 · Full text
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone of minimally invasive diagnosis and treatment for pancreaticobiliary diseases. However, post-ERCP pancreatitis (PEP), the most common com...
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone of minimally invasive diagnosis and treatment for pancreaticobiliary diseases. However, post-ERCP pancreatitis (PEP), the most common complication, occurs with a relatively high incidence and can lead to organ failure or even death in severe cases. The effectiveness of existing preventive measures is highly dependent on accurate risk stratification, while empirical clinical judgment lacks consistency, underscoring the urgent need for objective and individualized predictive tools. OBJECTIVE: To identify independent risk factors for PEP and to construct a nomogram prediction model for individualized risk assessment in patients undergoing ERCP. METHODS: Clinical data from 289 patients who underwent ERCP at Jinzhong First People's Hospital between January 2020 and October 2025 were retrospectively analyzed. Patients were divided into PEP and non-PEP groups according to the consensus diagnostic criteria. Univariate analysis was performed to compare demographic characteristics, clinical factors, procedural details, and laboratory parameters between the two groups. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection, followed by multivariate logistic regression analysis to identify independent risk factors for PEP. A nomogram prediction model was constructed based on these factors. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) in the training cohort (n = 202) and validation cohort (n = 87). RESULTS: The incidence of PEP in this cohort was 10.73% (31/289). Multivariate logistic regression analysis identified five independent risk factors for PEP: sphincter of Oddi dysfunction, history of pancreatitis, pancreatic duct opacification, difficult cannulation, and guidewire access to the pancreatic duct (≥ 3 times). Elevated total bilirubin (TBil) level was identified as an independent protective factor against PEP. The nomogram incorporating these factors demonstrated excellent predictive performance, with AUC values of 0.922 (95%CI: 0.865-0.980) in the training cohort and 0.915 (95%CI: 0.878-0.951) in the validation cohort. Calibration curves showed good agreement between predicted probabilities and actual observations (Hosmer-Lemeshow test P > 0.05), and DCA confirmed the model's clinical utility across a wide range of threshold probabilities. CONCLUSION: The nomogram model constructed in this study integrates six easily accessible clinical and operational factors, provides an effective and reliable tool for individualized prediction of PEP risk. This model can assist clinicians in early identification of high-risk patients, facilitating targeted preventive interventions and potentially improving the safety of ERCP procedures.
Associations between childhood behavior and current cognitive and emotional function in adults with irritable bowel syndrome-a cross sectional retrospective study.
Billing J, Pfabigan DM, Steinsvik EK … +3 more , Lied GA, Berentsen B, Lundervold AJ
BMC Gastroenterol · 2026 Jul · PMID 42393543 · Full text
BACKGROUND: Childhood behavior may influence emotional regulation and cognitive processing capacities in adulthood. Associations between childhood behavior and present emotional and cognitive functions in adults with Irr...
BACKGROUND: Childhood behavior may influence emotional regulation and cognitive processing capacities in adulthood. Associations between childhood behavior and present emotional and cognitive functions in adults with Irritable Bowel Syndrome (IBS) are not yet established. OBJECTIVE: To explore relationships between retrospectively reported childhood behavior and current emotional and cognitive function in adults with IBS vs healthy controls (HCs). METHODS: Adults with IBS (n = 57) and HCs (n = 38) completed the Wender Utah Rating Scale (WURS) to assess childhood behavior. Emotional functioning was assessed with the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). WURS responses were subjected to principal component analysis (PCA) to identify underlying factors, which were then examined for associations with current emotional and cognitive functioning. RESULTS: The WURS PCA yielded four factors: (1) Behavioral Self-Regulation and Social Functioning (2) Emotional Reactivity and Temperament, (3) Psychological Vulnerability and Distress, and (4) Academic/Cognitive Challenges. IBS patients scored significantly higher than healthy controls on Factors 3 and 4. Significant correlations were found between Factor 3 and HADS in the HC group, and between Factor 4 and RBANS in the IBS group. CONCLUSIONS: This study demonstrates that IBS patients report more childhood psychological vulnerability and academic/cognitive challenges than controls, and that these retrospectively reported behaviors show distinct associations with adult cognitive functioning. The findings suggest that developmental trajectories, such as neurocognitive traits and early stress-related mechanisms, contribute to the heterogeneity of IBS. TRIAL REGISTRATION: The project is registered at www. CLINICALTRIALS: gov (#NCT04296552), first submitted 2020.03.04.
Rapid Gastric Emptying: Insights from a Large Cohort Study on a Controversial Disorder.
El Hayek M, Bali A, Moktan V … +4 more , Montenegro M, Accurso JM, Cangemi DJ, Lacy BE
Dig Dis Sci · 2026 Jul · PMID 42393488 · Publisher ↗
INTRODUCTION: Rapid gastric emptying (RGE) is conventionally defined as ≥ 70% emptying of a standardized solid meal at 1 h using gastric emptying scintigraphy (GES). However, this threshold is not universally adopted, an...
INTRODUCTION: Rapid gastric emptying (RGE) is conventionally defined as ≥ 70% emptying of a standardized solid meal at 1 h using gastric emptying scintigraphy (GES). However, this threshold is not universally adopted, and variability exists in how accelerated gastric emptying is defined in practice. We aimed to better characterize patients with conventionally defined RGE as well as those with accelerated emptying not meeting this threshold, and to evaluate what clinical differences exist across varying degrees of accelerated gastric emptying. METHODS: We identified a cohort of 258 adult patients (≥ 18 years old) with increased gastric emptying (≥ 30% emptied at 1 h) at a tertiary medical center. Patients with a history of esophageal, gastric or thoracic surgery were excluded. Patients were stratified into three cohorts based on 1-h gastric emptying percentages: 30-49%, 50-69%, and ≥ 70%. Manual chart review was performed to extract data on demographics, medications, laboratory values, GES indications, and management changes resulting from GES findings. RESULTS: The majority of patients (n = 205, 79.4%) were in the 30-49% emptying cohort. Only 10 patients (3.9%) met the conventional threshold of ≥ 70% emptying at 1 h. The most common indications for GES were nausea (39.1%), vomiting (33.7%), and abdominal pain (25.6%), with no statistically significant differences in indications across the 3 cohorts. Furthermore, there were no differences in age, sex, BMI, comorbidities, medications, or management changes between the cohorts. CONCLUSIONS: RGE that meets current consensus criteria is uncommon in clinical practice. Clinical characteristics and interventions were similar among cohorts with different degrees of accelerated emptying. The current cutoff of ≥ 70% emptying at 1 h may not represent a clinically distinct phenotype, emphasizing the need for better criteria to guide diagnosis and management.
Efficacy and safety of a novel oral anti-vasculogenic mimicry agent, CVM-1118, in advanced well-differentiated neuroendocrine tumors: a Phase IIa trial.
Yen CJ, Chen MH, Chen YY … +10 more , Bai LY, Chen JS, Hsieh JC, Shih YH, Wu IC, Chen YL, Chen CM, Chao TY, Chu YW, Chien DS
Br J Cancer · 2026 Jul · PMID 42393461 · Publisher ↗
BACKGROUND: Highly vascularised neuroendocrine tumours (NETs) are attractive targets for foslinanib (CVM-1118), which disrupts vasculogenic mimicry and induces apoptosis via tumour necrosis factor receptor-associated pro...
BACKGROUND: Highly vascularised neuroendocrine tumours (NETs) are attractive targets for foslinanib (CVM-1118), which disrupts vasculogenic mimicry and induces apoptosis via tumour necrosis factor receptor-associated protein 1. We evaluated the efficacy and safety of CVM-1118 in advanced NETs. METHODS: Patients with grades 1-2, well-differentiated lung, gastrointestinal, or pancreatic NETs, refractory or intolerant to one or more standard therapies and progressing within 6 months, received CVM-1118 (200-300 mg orally twice daily) in 28-day cycles. Primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Of 43 enroled participants, 35 were efficacy-evaluable; most had grade 2 pancreatic (63%) or gastrointestinal (34%) NETs with two prior therapies. Median PFS was 10.5 months (95% CI, 5.6-22.3). ORR was 3%, DCR was 77%, and median OS was not reached (95% CI, 23.8-NR). Sensitivity analysis in the full analysis set (N = 43) showed a PFS estimate broadly aligned with the primary analysis (median, 8.4 months); patients with prior everolimus, sunitinib, or peptide receptor radionuclide therapy (N = 22; median, 8.3 months) showed similar findings. Treatment-related adverse events occurred in 44%, mostly grades 1-2, with no serious events. CONCLUSIONS: CVM-1118 demonstrates favourable efficacy and safety in advanced NETs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03600233.
Prospective evaluation of oxygen saturation endoscopic imaging for radiotherapy response in head and neck cancer.
Tomizawa K, Motegi A, Hirata H … +18 more , Yamashita H, Sunakawa H, Yoda Y, Okano W, Enokida T, Fujisawa T, Nakamura M, Hojo H, Abe S, Sakuramachi M, Igaki H, Saito Y, Sakashita S, Matsuura K, Tahara M, Yano T, Zenda S, Akimoto T
Commun Med (Lond) · 2026 Jul · PMID 42393379 · Publisher ↗
BACKGROUND: We developed an endoscopic imaging technology, oxygen saturation imaging (OS imaging), to assess real-time tissue oxygenation levels. However, its clinical impact remains unclear. This prospective observation...
BACKGROUND: We developed an endoscopic imaging technology, oxygen saturation imaging (OS imaging), to assess real-time tissue oxygenation levels. However, its clinical impact remains unclear. This prospective observational study evaluated the association between pretreatment tumor oxygen saturation (StO) quantified by OS imaging and the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) receiving radiotherapy (RT). METHODS: The primary endpoint was the association between pretreatment tumor StO and complete response rate at 8 weeks after RT completion. Secondary endpoints were the impact of StO on 1-year overall survival, progression-free survival, and local failure rates. RESULTS: Of 50 patients with HNSCC enrolled from 2019 to 2022, 42 who underwent RT and OS imaging are analyzed. Of those, 41 received concurrent platinum-based chemotherapy. Median pretreatment StO is significantly lower in tumor tissue than in normal mucosa (61% vs. 66%, respectively). Complete response rates at 8 weeks after RT are not significantly different between the hypoxia (StO ≤ 61%, n = 22) and non-hypoxia (StO > 61%, n = 20) groups (86% vs. 100%, respectively). After a median follow-up of 36 (range: 9-53) months, the hypoxia group has significantly worse 1-year overall survival (91% vs. 100%), progression-free survival (77% vs. 95%), and local failure (18% vs. 5%) rates than the non-hypoxia group. CONCLUSIONS: Despite not meeting the primary endpoint, our findings suggest that pretreatment tumor StO is correlated with 1-year outcomes after RT, and OS imaging may be useful for identifying RT-resistant hypoxic tumors in HNSCC.
Docosahexaenoic acid alleviates DSS-induced colitis by regulating the gut microbiota and restoring the gut barrier.
Wang S, Hu S, Yan Y … +4 more , Wu L, Tang L, Hu Y, Wang W
Int Microbiol · 2026 Jul · PMID 42393343 · Publisher ↗
Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has well-recognized anti-inflammatory activity; however, the mechanisms underlying its protective effects in inflammatory bowel disease (IBD) r...
Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has well-recognized anti-inflammatory activity; however, the mechanisms underlying its protective effects in inflammatory bowel disease (IBD) remain incompletely understood. In this study, we investigated the effects of DHA in a dextran sulfate sodium (DSS)-induced mouse model of colitis and examined whether these effects were mediated by the gut microbiota. DHA administration markedly alleviated DSS-induced colitis, as indicated by reduced body weight loss, disease activity, mortality, colon shortening, histological injury, intestinal barrier disruption, and colonic inflammatory responses. 16 S rRNA gene sequencing showed that DHA reshaped the gut microbial community and increased the abundance of beneficial taxa, including Bifidobacterium. Antibiotic cocktail (ABX)-mediated microbiota depletion largely abolished the protective effects of DHA, whereas fecal microbiota transplantation (FMT) from DHA-treated donors transferred resistance to DSS-induced colitis to recipient mice. DHA also restored tight junction protein expression and increased the frequency of colonic regulatory T cells in a microbiota-dependent manner. These findings indicate that DHA alleviates experimental colitis by modulating the gut microbiota, restoring intestinal barrier integrity, and regulating mucosal immune homeostasis. DHA may therefore represent a promising dietary strategy for the prevention or adjunctive treatment of ulcerative colitis (UC).
Dysphagia Lusoria: A Rare Cause of Dysphagia.
Shibli F, Mari A, Farah A
Dysphagia · 2026 Jul · PMID 42393299 · Publisher ↗
Abstract loading — click title to view on PubMed.
Single-cell analyses of liver and blood reveal distinct immune cell signatures of HBV-related HCC patients.
Li Y, Wang W, Zeng A … +4 more , Zheng X, Lyu L, Ding H, Wang S
Sci Rep · 2026 Jul · PMID 42393223 · Full text
Chronic hepatitis B virus (HBV) infection is a major etiological driver of hepatocellular carcinoma (HCC) and is accompanied by profound immune dysregulation that shapes disease progression and therapeutic responsiveness...
Chronic hepatitis B virus (HBV) infection is a major etiological driver of hepatocellular carcinoma (HCC) and is accompanied by profound immune dysregulation that shapes disease progression and therapeutic responsiveness. However, the extent to which systemic immunity reflects the tumor immune microenvironment (TIME) in HBV-related HCC (HBV-HCC) remains incompletely defined. Here, we used mass cytometry (CyTOF) to resolve immune heterogeneity across peripheral blood mononuclear cells (PBMCs), tumor tissues, and matched adjacent non-tumor (paracancer) tissues in treatment-naïve HBV-HCC. PBMCs, tumor tissues, and paracancer tissues were collected from 12 treatment-naïve HBV-HCC patients and profiled by CyTOF. Nine major immune lineages/clusters were quantified and compared across compartments. Immune-cell distributions were correlated with virological and clinicopathological features (HBV DNA status, serum alpha-fetoprotein [AFP], tumor differentiation) and 5-year clinical outcomes. Public transcriptomic datasets were further leveraged for external validation of CD8A/CD8B-associated prognostic signals. HBV-HCC exhibited marked systemic-local immune compartmentalization. PBMCs were enriched for naïve CD8⁺ T cells and natural killer (NK) cells, whereas paracancerous tissues showed higher abundance of myeloid-derived suppressor cells (MDSCs) and memory CD8⁺ T cells. In contrast, HCC tissues were characterized by increased neutrophils and regulatory T (Treg) cells, together with a more activated and immunosuppressive marker profile in HCC-associated MDSCs. HBV DNA-positive patients showed higher intratumoral expression of naïve CD8⁺ T cells and Tregs than HBV DNA-negative patients, with the increase being most evident in HCC tissues relative to matched paracancerous tissues. Clinically aggressive phenotypes, including high AFP, poor differentiation, and postoperative recurrence, were characterized by neutrophil expansion accompanied by reduced PD-1⁺ dendritic cells (PD-1⁺ DCs) and decreased naïve/memory CD8⁺ T-cell subsets. Although higher CD8A/CD8B expression in public datasets predicted improved survival, CyTOF indicated that abundant intratumoral CD8⁺ infiltration could coexist with systemic and intratumoral immunosuppression and functional exhaustion, consistent with the recognized challenge of reinvigorating exhausted intrahepatic immunity. HBV-HCC is defined by profound immune heterogeneity across blood, tumor, and adjacent non-tumor compartments. Distinct immune signatures associate with virological activity, tumor aggressiveness, and long-term outcomes, providing a rationale for immune-based patient stratification and for combinatorial immunotherapy strategies targeting both myeloid-driven suppression and dysfunctional T-cell immunity.
Choline-dependent methionine metabolism supports leukemia progression.
Saha N, Lachowski L, Franzen F … +16 more , Alibeckoff S, Vitvitsky V, Kumar R, Hutchings M, Kandarpa M, Hu H, Ropa J, Aitken MJL, Chiang MY, Zhang L, Lyssiotis CA, Carty SA, Talpaz M, Gupta SV, Banerjee R, Muntean AG
Commun Biol · 2026 Jul · PMID 42393218 · Publisher ↗
Tumor cells must occupy and thrive in a competitive microenvironment marked by limited metabolites, including essential amino acids like methionine. Using a leukemia suppression model and CRISPR screening, we found that...
Tumor cells must occupy and thrive in a competitive microenvironment marked by limited metabolites, including essential amino acids like methionine. Using a leukemia suppression model and CRISPR screening, we found that the choline transporter SLC44A1 is overexpressed in leukemia patients and impacts leukemogenesis. Choline is an important nutrient for membrane synthesis and less commonly contributes to the methionine cycle. A metabolic analysis demonstrated that metabolites of the methionine pathway are significantly elevated in leukemic cells. Surprisingly, dietary restriction of methionine accelerated leukemogenesis in vivo. Choline can serve as an alternative source for methionine via the enzymatic activity of CHDH and BHMT. Under restrictive methionine conditions, BHMT and CHDH are significantly upregulated. In vivo, BHMT and CHDH are necessary for leukemia progression where they utilize choline as an alternative source to satisfy increased methionine demand. This pathway represents a vulnerability in cancer cells that may be exploited for therapeutic intervention.
Efficacy of heat-treated postbiotic Lacticaseibacillus rhamnosus in patients with functional bowel disorders: a randomized, double-blind, placebo-controlled clinical trial.
Kim D, Bang WY, Jung YH … +4 more , Yang J, Moon JS, Shin J, Shin M
Sci Rep · 2026 Jul · PMID 42393211 · Full text
Functional bowel disorders (FBDs) are characterized by chronic abdominal discomfort, altered bowel habits, and bloating, impairing quality of life. Current treatments, including dietary interventions and laxatives, have...
Functional bowel disorders (FBDs) are characterized by chronic abdominal discomfort, altered bowel habits, and bloating, impairing quality of life. Current treatments, including dietary interventions and laxatives, have limited effectiveness and raise safety concerns. Although probiotic-based interventions have gained attention, their mechanisms remain poorly understood. This randomized, double-blind, placebo-controlled pilot trial tested the heat-treated postbiotic Lacticaseibacillus rhamnosus IDCC 3201 (RHT) over an 8-week period in patients with FBDs (RHT, n = 19; placebo, n = 15). Outcomes were measured using the IBS Symptom Severity Scale (IBS-SSS) and IBS Quality of Life (IBS-QOL) questionnaire. Results suggested that the RHT group showed reductions in IBS-SSS scores, alongside improvements in IBS-QOL and bowel activity across physical and psychosocial domains. Gut microbiota profiling revealed decreased Klebsiella pneumoniae and increased beneficial taxa, including Fusicatenibacter saccharivorans and Bacteroides caccae. Metabolomics analysis revealed progressive alterations in the RHT group, with clear distinction from baseline by week 8. Amino acid metabolism-related metabolites increased, whereas inflammation-associated eicosanoids decreased. These findings suggest that RHT alleviates FBD symptoms and improves quality of life by modulating gut microbiota and fecal metabolome, supporting its potential as a postbiotic-based therapeutic strategy.
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