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[JOURNAL] GASTROENTEROLOGY

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Nutritional status in pediatric celiac disease: evaluation at diagnosis and during follow-up.

Yılmaz S, Çam Sİ

BMC Nutr · 2026 Jul · PMID 42401945 · Full text

INTRODUCTION: Celiac disease (CD) is a lifelong immune-mediated condition precipitated by gluten ingestion in genetically predisposed individuals, resulting in intestinal mucosal damage, impaired growth, micronutrient de... INTRODUCTION: Celiac disease (CD) is a lifelong immune-mediated condition precipitated by gluten ingestion in genetically predisposed individuals, resulting in intestinal mucosal damage, impaired growth, micronutrient deficiencies, among other gastrointestinal and extraintestinal symptoms. A gluten-free diet (GFD) contributes to the healing of the mucosa and improves nutrient absorption, although recovery patterns may vary. AIM: The present study aimed to determine changes in anthropometric parameters and micronutrient levels at diagnosis and at six and twelve months following the start of a GFD, and to investigate any associations between these changes and tissue transglutaminase IgA (tTG-IgA) status, the severity of mucosal damage, or clinical characteristics. METHODS: This retrospective investigation involved an assessment of pediatric individuals diagnosed with CD using anthropometric and micronutrient data collected at the point of diagnosis and at subsequent 6- and 12-month intervals following GFD. Dietary adherence was evaluated retrospectively using physician and dietitian follow-up notes, clinical assessment, and serial tTG-IgA measurements. RESULTS: Among 103 children (64% female), 56% had no comorbidities, and type 1 diabetes was the most common (15%). Height, weight, body mass index, and most micronutrient levels improved during follow-up period. Vitamin D deficiency remained present in 27% of patients at 12 months and overweight prevalence increased from 7.8% to 18.4% during follow-up. Individuals presenting with comorbid CD+type 1 diabetes demonstrated higher SDS for weight and height, and elevated hemoglobin concentrations. The incidence of seronegativity was 55% at six months and 73% at twelve months. CONCLUSION: Within a year, GFD enhances growth and resolves the majority of micronutrient deficiencies, however; ongoing nutritional monitoring is crucial due to persistent vitamin D deficiency and an increasing risk of overweight.

LAR/NMLR stratify mortality risk before and after checkpoint inhibitor pneumonitis in NSCLC: multi-state and time-dependent analyses.

Zhang Q, Xu Y, Liu J … +1 more , Wang Y

BMC Cancer · 2026 Jul · PMID 42401858 · Full text

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a clinically important immune-related adverse event in non-small cell lung cancer (NSCLC), but its time-varying occurrence complicates prognostic assessment. OBJECTIV... BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a clinically important immune-related adverse event in non-small cell lung cancer (NSCLC), but its time-varying occurrence complicates prognostic assessment. OBJECTIVE: This study evaluated whether baseline lactate dehydrogenase-to-albumin ratio (LAR) and neutrophil-monocyte-to-lymphocyte ratio (NMLR) were associated with CIP onset and mortality risk before and after CIP. METHODS: This retrospective cohort included adults with advanced or recurrent NSCLC treated with immune checkpoint inhibitors (ICIs) at Zhongshan Hospital (Xiamen), Fudan University, between 2021 and 2024. CIP incidence was estimated using cumulative incidence functions with death without prior CIP as a competing event. Transition-specific associations were evaluated using an illness-death multi-state model: CIP-free at-risk state after ICI initiation (state 0), post-CIP state (state 1), and death as the absorbing state (state 2). Overall survival (OS) was assessed using a time-dependent Cox model with CIP modeled as a time-varying exposure. Restricted cubic splines (RCS), calibration analyses, penalized sensitivity analyses, and benchmark comparisons with the lung immune prognostic index (LIPI) were performed. RESULTS: Among 202 patients, 24 developed CIP and 119 died during follow-up. In parsimonious transition-specific Cox models, cause-specific hazard ratios (csHRs) showed that zLAR and zNMLR were not associated with CIP onset, but were associated with death without prior CIP (0→2: zLAR csHR 1.22, 95% CI 1.00-1.50; zNMLR csHR 1.28, 95% CI 1.09-1.51) and death after CIP (1→2: zLAR csHR 2.47, 95% CI 0.93-6.57; zNMLR csHR 3.14, 95% CI 1.32-7.45). In the time-dependent Cox model, CIP was not significantly associated with mortality, whereas zLAR (HR 1.25, 95% CI 1.01-1.55) and zNMLR (HR 1.25, 95% CI 1.01-1.54) remained prognostic. Adding zLAR and zNMLR to the clinical base model increased the C-index from 0.623 to 0.682. The dual-outcome risk map showed partial separation between predicted CIP and death risks. CONCLUSION: Baseline LAR and NMLR were associated with mortality risk rather than the occurrence of CIP in ICI-treated NSCLC patients. These simple blood-based indices may help identify patients who require closer survival-oriented monitoring, while CIP risk should be assessed together with clinical pulmonary factors.

A primary care clinic on the frontline of early cancer detection: a retrospective observational study.

Yago Y, Hojo M, Shibuya T … +2 more , Tsujimoto T, Nagahara A

BMC Prim Care · 2026 Jul · PMID 42401800 · Full text

BACKGROUND: Early cancer detection is critical. In Japan, the cancer detection system is diverse, encompassing cancer screenings, health checks, and comprehensive medical checkups (Ningen-dock). However, early detection... BACKGROUND: Early cancer detection is critical. In Japan, the cancer detection system is diverse, encompassing cancer screenings, health checks, and comprehensive medical checkups (Ningen-dock). However, early detection pathways in primary care clinics remain unclear. This study aimed to investigate the current status of cancer detection and examine the clinical pathways leading to early diagnosis in a primay care clinic. METHODS: A retrospective observational study was conducted among cancer cases detected at a single primary care clinic in Japan between April 2009 and March 2023. In total, 17,942 patient charts were reviewed, representing 267,313 individual consultations during the study period. Data collected included cancer type, number, age, sex, smoking, comorbidities, detection pathways, and whether the cancer was early (without distant metastasis) or advanced (with distant metastasis). Multivariable logistic regression was performed to assess the associations between early cancer and both the detection pathways and follow-up by primary care physician. Univariate analyses were performed to evaluate associations between detection pathways and early cancer detection by cancer types. RESULTS: Three hundred forty-seven cases (29 types) were identified, comprising 283 early and 64 advanced. Early cancers had significantly higher detection rates through health screening-related, incidental or follow-up by primary care pathways (p < 0.05), whereas symptomatic detection was significantly less frequent (p < 0.05). For gastrointestinal and respiratory cancers, early detection was significantly associated with health screening-related (p < 0.05), whereas symptomatic detection predominated in advanced (p < 0.05). In hepatobiliary pancreatic, urinary, and other cancers, no significant differences were observed between early and advanced cancers in health screening-related; detection was mostly symptomatic. CONCLUSIONS: Cancer screening, health checks, comprehensive medical checkups, asymptomatic examinations, and follow-up by primary care physician might be associated with early cancer detection. However, certain cancer types presented difficulties for early detection. Studies discussing the overall picture of early cancer detection using real-world data from primary care clinics remain limited, and the findings of this study are expected to contribute to building a foundation for secondary prevention policies.

Synergistic anti-Helicobacter pylori efficacy of a molecularly identified Limosilactobacillus fermentum isolate in combination with multiple antibiotics.

Ali MMMM, Shady HMA, M SM … +1 more , Sayed HAE

BMC Microbiol · 2026 Jul · PMID 42401797 · Full text

BACKGROUND: Helicobacter pylori (H. pylori) is a Gram-negative gastric pathogen resistant to the acidic stomach environment through urease-mediated neutralization, enabling colonization of the gastric mucosa. It is a maj... BACKGROUND: Helicobacter pylori (H. pylori) is a Gram-negative gastric pathogen resistant to the acidic stomach environment through urease-mediated neutralization, enabling colonization of the gastric mucosa. It is a major cause of gastritis, peptic ulcer disease, and gastric cancer, and was classified as a Class I carcinogen by the International Agency for Research on Cancer (IARC) in 1994. Rising antibiotic resistance has limited the efficacy of conventional therapies, highlighting the need for alternative or adjunct antimicrobial strategies. METHODS: Forty lactic acid bacteria (LAB) isolates were screened for anti-H. pylori activity against twenty clinical H. pylori isolates previously recovered from gastric biopsies of Egyptian patients using neutralized cell-free supernatants (CFSs). The CFSs were evaluated alone and in combination with standard therapeutic antibiotics. The most potent CFS was subsequently evaluated for cytotoxic activity against colorectal adenocarcinoma (Caco-2) cells as a preliminary assessment of its potential anticancer-related properties. The CFS was then subjected to fast protein liquid chromatography (FPLC), and the active fraction was further analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to estimate its molecular weight. Following verification of its probiotic characteristics, the producer strain was identified by 16 S rRNA gene sequencing. RESULTS: Nine out of forty LAB isolates demonstrated anti-H. pylori activity, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 93.7 to 750 µg/mL. Combination assays demonstrated isolate-dependent interactions, with synergistic effects observed with clarithromycin (CLR), amoxicillin (AX), metronidazole (MET), tetracycline (TE), rifampicin (RA), and levofloxacin (LEV) against certain H. pylori isolate groups. L. fermentum strain M98, identified as the most potent isolate, exhibited the highest inhibitory activity both alone and in combination with antibiotics. The protein-enriched precipitate containing a putative bacteriocin exhibited cytotoxic activity against Caco-2 cells, with an IC₅₀ value of 19.73 ± 0.16 µg/mL. FPLC of its CFS yielded 22 protein fractions, three of which exhibited anti-H. pylori activity, suggesting the presence of bacteriocin-like compounds. Subsequent SDS-PAGE analysis of the active fraction revealed a prominent protein band of approximately 34 kDa. CONCLUSION: The CFS of L. fermentum strain M98 exhibits significant in vitro anti-H. pylori activity and enhances the efficacy of tested antibiotics, supporting its potential as an adjunct therapeutic agent against antibiotic-resistant H. pylori. In addition, LAB-precipitated proteins containing a putative bacteriocin demonstrated cytotoxic activity against Caco-2 cells, suggesting the presence of bioactive compounds with potential therapeutic value. Further in vivo investigations are warranted to confirm their safety, efficacy, and potential biomedical applications.

Abdominal obesity and leisure-time sedentary behavior in relation to gastroesophageal reflux disease risk: a prospective cohort study from the UK Biobank.

Sun L, Zhang S, Zhou Y … +9 more , Lv Y, Zheng Y, Shao L, Liang W, Jin X, Zhao H, Li C, Ye W, Song J

Sci Rep · 2026 Jul · PMID 42401731 · Full text

This study aimed to assess the associations of abdominal obesity and leisure-time sedentary behavior with the risk of gastroesophageal reflux disease (GERD), and to explore their combined effects and potential interactio... This study aimed to assess the associations of abdominal obesity and leisure-time sedentary behavior with the risk of gastroesophageal reflux disease (GERD), and to explore their combined effects and potential interactions. A total of 405,531 participants without GERD at baseline were included from the UK Biobank. Abdominal obesity was defined using sex-specific waist circumference thresholds. Self-reported sedentary time was dichotomized based on a 4.5-hour-per-day threshold identified using restricted cubic spline (RCS) analysis. Multivariable Cox proportional hazards models (Model 2) were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Joint exposure analyses and additive interaction measures were conducted. Over a median follow-up of 12.4 years, 26,089 new GERD cases were identified. In multivariable-adjusted models (Model 2), abdominal obesity was significantly associated with a higher risk of GERD (per 5 cm increase in waist circumference: HR = 1.06, 95% CI: 1.05-1.06). Each additional hour of daily self-reported sedentary time was associated with a 4% higher risk of GERD (HR = 1.04, 95% CI: 1.04-1.05). These associations remained consistent after further adjustment for potential mediators (Model 3). RCS analyses showed non-linear associations between both exposures and GERD risk. Participants with both abdominal obesity and sedentary time ≥ 4.5 h/day had the highest risk (HR = 1.42, 95% CI: 1.36-1.48). Additive interaction analysis did not provide evidence of a synergistic effect between the two exposures. Subgroup analyses suggested that the association between abdominal obesity and GERD was stronger in women, individuals under 60 years, and those with normal BMI. Abdominal obesity and self-reported sedentary behavior were independently associated with increased GERD risk. Although their co-occurrence was associated with the highest risk, no clear evidence of a synergistic interaction was observed. Interventions targeting either factor may help reduce GERD risk.

Washed microbiota transplantation is associated with short-term changes in selected spirometric parameters in patients with abnormal spirometry.

Huang L, Lu C, Hu Y … +7 more , Chen J, Chen A, Zhong C, Chen D, Qin Z, He X, Wu L

Sci Rep · 2026 Jul · PMID 42401711 · Full text

Gut microbiota may modulate pulmonary inflammation through the gut-lung axis. This study investigated the association between washed microbiota transplantation (WMT) and short-term changes in pulmonary function, inflamma... Gut microbiota may modulate pulmonary inflammation through the gut-lung axis. This study investigated the association between washed microbiota transplantation (WMT) and short-term changes in pulmonary function, inflammatory markers, and gut microbiota in patients with abnormal spirometric patterns. A total of 110 patients who underwent fecal microbiota transplantation, also referred to as WMT, were consecutively screened between March 2023 and January 2025. Of these, 47 patients with paired baseline and post-WMT spirometric data were included in the primary spirometric analysis. According to baseline spirometric patterns, WMT recipients were classified into an abnormal spirometric-pattern group (DG, n = 19) and a normal spirometric-pattern WMT-recipient group (HC, n = 28; HC denotes WMT recipients with normal spirometry rather than healthy community controls). In addition, 43 patients receiving conventional treatment without WMT were included as a non-WMT comparison group (CON). The WMT group underwent multi-course interventions with longitudinal monitoring of pulmonary function parameters, inflammatory markers, breath-holding time (BHT), and 36-Item Short Form Health Survey scores (SF-36). Gut microbiota composition and predicted functional profiles were analyzed using 16S rRNA gene sequencing. After one WMT course, DG patients showed increases in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Compared with the non-WMT comparison group, the change in FVC was greater in WMT recipients, whereas the between-group difference in FEV1 change was not statistically significant. Other spirometric indices, BHT, inflammatory markers, SF-36 scores, and microbiome-related findings were considered exploratory. Exploratory 16S rRNA gene sequencing identified differences in selected gut microbial taxa between WMT recipients with abnormal and normal spirometric patterns, including differences in Firmicutes, Faecalibacterium, and Alistipes. Predicted functional profiling suggested changes in glycerolipid metabolism-, Nod-like receptor signaling-, and bacterial chemotaxis-related functional potentials. WMT was associated with short-term changes in selected spirometric parameters, particularly FVC and FEV1, in patients with abnormal spirometric patterns. Changes in inflammatory markers, BHT, SF-36 scores, and microbiome-related findings were exploratory and hypothesis-generating. Further randomized, disease-specific studies with standardized pulmonary function testing and mechanistic validation are needed.

Curated endoscopic retrograde cholangiopancreatography images dataset.

Andrade AJ, Martins M, Ferreira A … +3 more , Araújo T, Lopes L, Alves V

Sci Data · 2026 Jul · PMID 42401597 · Publisher ↗

Endoscopic Retrograde Cholangiopancreatography (ERCP) is a key procedure in the diagnosis and treatment of biliary and pancreatic diseases. Artificial intelligence has been pointed as one solution to automatize diagnosis... Endoscopic Retrograde Cholangiopancreatography (ERCP) is a key procedure in the diagnosis and treatment of biliary and pancreatic diseases. Artificial intelligence has been pointed as one solution to automatize diagnosis. However, public ERCP datasets are scarce, which limits the use of such approach. To help address these limitations, this study aims to help fill this gap by providing a large and curated dataset. The collection is composed of 19.018 raw images and 19.317 processed sections from 1.602 patients. 5.519 images are labeled, which provides a ready-to-use dataset. All images were manually inspected and annotated by two gastroenterologists with more than 5 years of experience and reviewed by another gastroenterologist with more than 20 years of experience, all with more than 400 ERCP procedures annually. The utility and validity of the dataset is proven by a classification experiment. This collection aims to provide or contribute for a benchmark in automatic ERCP analysis and diagnosis of biliary and pancreatic diseases.

Pan-cancer profiling of CDH2 and a GSK3β-sensitive anti-proliferative effect in K562 chronic myeloid leukemia cells.

Zhou Y, Chen F, Yang W … +2 more , Yang Z, Qiu R

Sci Rep · 2026 Jul · PMID 42401590 · Full text

Chronic myeloid leukemia (CML) is driven by uncontrolled myeloid proliferation, yet underlying molecular mechanisms remain incompletely understood. This study investigated the pan-cancer expression profile of N-cadherin... Chronic myeloid leukemia (CML) is driven by uncontrolled myeloid proliferation, yet underlying molecular mechanisms remain incompletely understood. This study investigated the pan-cancer expression profile of N-cadherin (CDH2) and its potential role in suppressing proliferation in K562 CML cells, with an exploratory focus on the GSK3β/β-catenin axis. We combined in silico analyses (TCGA/GEO datasets) with functional assays in K562 cells. CDH2 expression was assessed across 31 cancer types. In K562 cells, we evaluated the effects of CDH2 overexpression on proliferation, cell cycle, apoptosis, and several proteins within the β-catenin/GSK3β network. CDH2 was significantly upregulated in 18 malignancies and downregulated in 10. It was associated with adverse overall survival in five solid tumors but favorable in KIRC. In acute myeloid leukemia (AML), higher CDH2 expression correlated with poor-prognosis cytogenetic risk (P = 0.008). CDH2 expression also correlated with macrophage/NK cell infiltration in some solid tumors. In K562 cells, CDH2 overexpression suppressed proliferation, induced cell cycle arrest and early apoptosis. This was accompanied by increased total β-catenin protein but a reduced nuclear-to-cytoplasmic β-catenin ratio, without consistent changes in canonical Wnt target gene expression. Notably, the GSK3 inhibitor CHIR-99,021 reversed the anti-proliferative effect of CDH2, whereas the β-catenin degrader MSAB did not rescue it. CDH2 exhibits context-dependent expression across malignancies. In K562 CML cells, CDH2 overexpression suppresses proliferation through a GSK3β-sensitive mechanism. However, the precise molecular mechanism remains unresolved. Our findings suggest that targeting GSK3β may represent a therapeutic vulnerability in this model.

Effectiveness and safety of mirikizumab in multirefractory ulcerative colitis: analysis from a real-world cohort.

Melotti L, Monicelli O, Dussias NK … +7 more , Pardi V, Jairath V, Hupé M, Salice M, Privitera Hrustemovic H, Gionchetti P, Rizzello F

Dig Liver Dis · 2026 Jul · PMID 42401516 · Publisher ↗

BACKGROUND: Mirikizumab is a selective anti-IL-23 monoclonal antibody approved for moderate-to-severe ulcerative colitis (UC). Evidence regarding its efficacy mostly derives from registration trials, as real-world data i... BACKGROUND: Mirikizumab is a selective anti-IL-23 monoclonal antibody approved for moderate-to-severe ulcerative colitis (UC). Evidence regarding its efficacy mostly derives from registration trials, as real-world data in multi-refractory populations remain limited. METHODS: We conducted an observational study including UC patients treated with mirikizumab. Clinical activity was assessed using the partial Mayo (pMayo) score at baseline, Week12 (W12), and Week24 (W24). Urgency, biomarkers, endoscopic activity and safety were evaluated. Steroid-free clinical remission (SFCR) was defined as pMayo≤1 without corticosteroids; clinical response as ≥3-point or ≥30% reduction. Changes over time were analyzed using paired non-parametric tests; logistic regression identified predictors of remission. RESULTS: One-hundred-twenty-three highly treatment-expierenced patients were included (median 3 prior advanced therapies, IQR 2-4). Most patients (89.0%) continued extended IV induction after W12. SFCR was achieved in 25.2% (31/123) at W12 and 31.3% (30/96) at W24, while clinical response occurred in 70.7% and 67.7%, respectively. Bowel urgency improved at W12 and W24 (p<0.001). Adverse events occurred in 20.3% of patients; the colectomy rate was 4.9%. Higher baseline pMayo and prior JAKi exposure were associated with lower remission. CONCLUSION: Mirikizumab showed encouraging effectiveness and safety in multirefractory UC. Prior JAKi exposure emerged as a potential negative predictor of remission; this hypothesis-generating signal warrants validation.

Novel approaches to liquid biopsy in pancreatic cancer.

Mannucci A, Puzzono M, Frattura A … +3 more , Prina D, Arcidiacono PG, Cavestro GM

Dig Liver Dis · 2026 Jul · PMID 42401515 · Publisher ↗

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An unusual gastric mass in a patient with human immunodeficiency virus infection.

Hattori A, Hamada Y, Nakagawa H

Dig Liver Dis · 2026 Jul · PMID 42401513 · Publisher ↗

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Association of metabolic dysfunction-associated steatotic liver disease onset age with risk of incident type 2 diabetes.

Huo Z, Li Y, Liu T … +8 more , Gui M, Zhao M, Jiang J, Chen S, Zhang S, Huang Z, Wu S, Wu S

Clin Gastroenterol Hepatol · 2026 Jul · PMID 42401250 · Publisher ↗

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a known risk factor for type 2 diabetes (T2D). However, whether MASLD onset age modifies T2D risk remains poorly understood. We aim... BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a known risk factor for type 2 diabetes (T2D). However, whether MASLD onset age modifies T2D risk remains poorly understood. We aimed to determine the association of MASLD onset age and risk of incident T2D in a large prospective cohort. METHODS: 58,814 MASLD- and T2D- free participants at the first health examination (2006-2007) in the Kailuan Study were included. By December 31, 2015, 29,016 new-onset MASLD cases were identified. Each MASLD case was randomly matched to a MASLD-free control by age (±1 years) and sex. After excluding participants who developed T2D within first 2 years of follow-up, 19,378 MASLD cases and 19,483 controls were included. All participants were followed for incident T2D until 31 December 2020. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 11.8 years, 2,301 incident T2D cases were documented. Compared with non-MASLD, MASLD patients with onset age < 40 years had the highest risk of T2D (HR=6.18, 95% CI: 4.28, 8.93), followed by gradually attenuated elevated risks in older onset age groups: 40-<50 years (HR = 3.29, 95% CI: 2.70, 4.00), 50-<60 years (HR = 3.14, 95% CI: 2.69, 3.66), 60-<70 years (HR = 2.94, 95% CI: 2.39, 3.62), and ≥ 70 years (HR = 2.17, 95% CI: 1.56, 3.01). CONCLUSION: MASLD onset at any age is associated with increased risk of T2D, with earlier onset conferring progressively greater risk. This highlights the importance of preventing, or at least delaying MASLD onset, particularly in young adults.

Randomized trial comparing 5-year follow-up of first-line infliximab to conventional therapy in paediatric Crohn's disease.

Vuijk SA, Jongsma MME, Cozijnsen MA … +18 more , van Pieterson M, de Meij TGJ, Groeneweg M, Wolters VM, van Wering H, Hojsak I, Kolho KL, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg-Roord S, Nienhuis JMP, Rizopoulos D, Escher JC, Samsom JN, de Ridder L

Clin Gastroenterol Hepatol · 2026 Jul · PMID 42401249 · Publisher ↗

BACKGROUND AND AIMS: The TISKids study previously demonstrated that first-line infliximab (FL-IFX) was more effective than conventional treatment in achieving clinical remission without treatment escalation at 52 weeks i... BACKGROUND AND AIMS: The TISKids study previously demonstrated that first-line infliximab (FL-IFX) was more effective than conventional treatment in achieving clinical remission without treatment escalation at 52 weeks in children with moderate-to-severe Crohn's disease (CD). We investigated 5-year outcomes. METHODS: The TISKids is a multicentre, open-label randomised controlled trial in newly diagnosed, untreated CD patients aged 3-17 years (wPCDAI>40). Patients were randomised to FL-IFX (five IFX infusions, then stopped) or conventional treatment (exclusive enteral nutrition or prednisolone). Both groups received azathioprine maintenance. The primary outcome was sustained clinical remission (wPCDAI<12.5, CDAI<150 or PGA remission) without additional CD-related therapy at 5 years. Secondary outcomes included time to (re)start IFX or another biological. RESULTS: One-hundred patients were randomised; six were lost to follow-up. At 5 years, sustained clinical remission without additional CD-related therapy was observed in 3/48 (6%) FL-IFX patients versus 1/46 (2%) of conventionally treated patients(p=0.617), whilst 42/48 (88%) in FL-IFX and 44/46 conventionally treated patients required additional CD-related treatment (p=0.271). Median time to (re)start of biologic therapy was 65 weeks [95%CI 53-122] for FL-IFX versus 31 weeks [95%CI 22-57] for conventional treatment (p=0.037). CONCLUSIONS: After 5-years follow-up in the TISKids trial, we found that almost all patients required additional CD-related treatment, irrespective of induction therapy with five infusion of FL-IFX or conventional treatment. FL-IFX delayed the need for additional biological treatment, indicating its potential as preferred treatment option for patients with moderate-to-severe CD at diagnosis. These findings underscore that patients with moderate-to-severe CD require early and maintained treatment with infliximab.

Reply to "Role of HBV genotype, monitoring, and events after cessation of nucleos(t)ide analogue therapy".

Dongelmans EJ, Janssen HLA

J Hepatol · 2026 Jul · PMID 42401243 · Publisher ↗

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Isolated Rectal Heterotopic Gastric Mucosa with Hemorrhage.

Ge CJ, Tang SS, Liu W

J Gastrointest Surg · 2026 Jul · PMID 42401230 · Publisher ↗

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MRI/MRCP and endoscopic ultrasound in pancreatobiliary disease: defining complementary roles in diagnostic and therapeutic decision-making.

Bolaños Bermúdez IA, Torres Castiblanco JL, Munive Gnecco AC … +2 more , Carta RP, Aguirre DA

Eur J Radiol · 2026 Jul · PMID 42401074 · Publisher ↗

MRI and magnetic resonance cholangiopancreatography (MRCP) remain foundational techniques for the evaluation of pancreatobiliary disease because they provide a comprehensive, non-invasive assessment of the pancreatic par... MRI and magnetic resonance cholangiopancreatography (MRCP) remain foundational techniques for the evaluation of pancreatobiliary disease because they provide a comprehensive, non-invasive assessment of the pancreatic parenchyma, biliary tree and surrounding structures. With optimized protocols, MRI/MRCP has high diagnostic performance for biliary obstruction, pancreatic cystic lesions and many inflammatory or neoplastic pancreatic disorders. Nevertheless, selected clinical scenarios remain challenging when findings are equivocal, discordant with biochemical or clinical suspicion, or insufficient to guide intervention. Endoscopic ultrasound (EUS) should therefore be understood not as a replacement for MRI/MRCP, but as a complementary problem-solving modality. Its incremental value is greatest when a specific unresolved question remains after cross-sectional imaging and when the result is likely to change management. Beyond high-resolution proximity-based imaging, EUS can provide tissue acquisition, cyst fluid analysis, molecular testing, contrast-enhanced assessment, elastography and selected therapeutic interventions. This revised review defines the complementary roles of MRI/MRCP and EUS in pancreatobiliary disease, with emphasis on small solid pancreatic lesions, pancreatic cystic lesions, pancreaticobiliary microlithiasis, autoimmune pancreatitis mimics, and therapeutic EUS applications. We also discuss MRI/MRCP protocol optimization, emerging deep learning-based MRI reconstruction, and the limitations of EUS in altered anatomy, gastric outlet obstruction, pancreatic tail lesions and multifocal neuroendocrine tumors. A practical selective imaging pathway is proposed to support clinically driven decision-making.

Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.

Du X, Cai Y, Zhang L … +12 more , Ji M, Sun Y, Ye A, Zhang H, Mo Q, Wang Z, Wang M, Li Y, Li T, Tang C, Ma J, Li Y

Phytomedicine · 2026 Jul · PMID 42401069 · Publisher ↗

BACKGROUND: Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which acinar-to-ductal metaplasia (ADM) and fibrosis form a vicious cycle, representing an early event in pancreatic carcinogenesis. Fa... BACKGROUND: Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which acinar-to-ductal metaplasia (ADM) and fibrosis form a vicious cycle, representing an early event in pancreatic carcinogenesis. Fangchinoline, a bisbenzylisoquinoline alkaloid from Stephania tetrandra, exhibits anti-inflammatory and anti-fibrotic properties, although its role in ADM-fibrotic lesions remains unknown yet. OBJECTIVE: To investigate the effects of fangchinoline on atypical hyperplasia of metaplastic ducts and pancreatic fibrosis, and to clarify its underlying mechanisms. METHODS: Network pharmacology, bioinformatics, molecular docking, dynamics simulations, and cellular assays were used to elucidate and verify the underlying mechanisms. A C57BL/6 J mouse model was used to elucidate the effects, hepatotoxicity, nephrotoxicity, and cardiotoxicity of fangchinoline. RESULTS: Fangchinoline alleviated caerulein-induced atypical hyperplasia of metaplastic ducts (64.3%) and reduced pancreatic fibrosis (70.8%). In terms of molecular mechanisms, it targeted bound to the kinase domains of proto-oncogene tyrosine-protein kinase SRC (SRC) and receptor tyrosine-protein kinase ERBB-2 (ERBB2), suppressed their phosphorylation, blocked the downstream focal adhesion kinase (FAK)/zinc finger E-box binding homeobox 1 (ZEB1) signalling, reversed epithelial-mesenchymal transition (EMT), attenuated cancer stemness properties, and reduced the secretion of pro-fibrotic factors. These actions disrupted the vicious cycle between ADM and fibrosis. CONCLUSION: Fangchinoline is a promising multi-target therapeutic candidate for atypical hyperplasia of metaplastic ducts and pancreatic fibrosis.

Tumor budding in colorectal cancer: partial EMT, microenvironmental remodeling, and metastatic competence.

Wang T, Fei H, Liu X … +4 more , Zhang L, Liang W, Wei X, Fei F

Biochem Biophys Res Commun · 2026 Jul · PMID 42401009 · Publisher ↗

Tumor budding (TB) is a pathological hallmark of malignant invasion at the invasive front of colorectal cancer (CRC) and provides a morphologic window into early dissemination. In the International Tumor Budding Consensu... Tumor budding (TB) is a pathological hallmark of malignant invasion at the invasive front of colorectal cancer (CRC) and provides a morphologic window into early dissemination. In the International Tumor Budding Consensus Conference (ITBCC) framework, buds are single tumor cells or clusters of up to four cells, graded by hotspot counting to support standardized evaluation. Evidence from histopathology, single-cell profiling, spatially resolved analyses, and functional models links TB to invasion-competent tumor states. TB often tracks partial epithelial-mesenchymal transition, with weakened cell-cell adhesion, E-cadherin loss, altered β-catenin localization, and activation of integrin signaling, cytoskeletal remodeling, and extracellular matrix (ECM) degradation while retaining epithelial features. Spatial/trajectory analyses suggest that budding-rich regions concentrate plastic, stem-like programs biased toward migration and stress tolerance and lie close to intravasation. The TB niche also shows immune and metabolic specialization, with constrained dendritic-cell maturation and antigen presentation, reduced or dysfunctional CD8 T-cell and NK-cell activity, and enrichment of tumor-associated macrophages and other suppressive myeloid programs. Hypoxia-driven glycolysis, lactate-associated acidification, adenosine signaling, and myeloid lipid-metabolic reprogramming can further stabilize invasive phenotypes and raise the threshold for immune control. Digital pathology and AI-enabled whole-slide analysis can improve scoring consistency and add spatial readouts linking TB patterns to immune contexture and stromal organization. Collectively, TB marks an interface between invasive tumor biology and the local microenvironment with direct relevance for risk stratification and therapeutic tailoring in CRC.

Dietary modulation of metabo-proteomic reprogramming by the EAT-lancet diet attenuates colorectal cancer risk.

Ye J, Zhao J, Wu H … +5 more , Ji H, Zhou S, Theodoratou E, Tsilidis KK, Li X

Clin Nutr · 2026 Jun · PMID 42400994 · Publisher ↗

BACKGROUND AND AIMS: The EAT-Lancet diet was developed to support both human health and environmental sustainability and has been linked to multiple chronic diseases. However, its associations with metabolic profiles and... BACKGROUND AND AIMS: The EAT-Lancet diet was developed to support both human health and environmental sustainability and has been linked to multiple chronic diseases. However, its associations with metabolic profiles and circulating proteins in colorectal cancer (CRC) have not been comprehensively evaluated. This study aimed to investigate the association between adherence to the EAT-Lancet diet and CRC risk and to explore potential metabolic, inflammatory, and proteomic pathways that may mediate this relationship. METHODS: We included 106,944 UK Biobank participants who completed at least two 24-h dietary recalls. Cox regression models were used to assess associations between adherence to the EAT-Lancet diet and CRC risk. Mediation analyses evaluated the potential mediating roles of body mass index, inflammation, metabolites, and circulating proteins, while enrichment and single-cell analyses explored potential underlying mechanisms. RESULTS: During a median follow-up of 13.54 years, 1591 CRC cases were recorded. Higher adherence to the EAT-Lancet diet was associated with a 12.2%-28.9% lower risk of CRC, with the strongest effects observed in individuals with medium genetic risk. These associations remained consistent across sensitivity and stratified analyses, and dose-response relationships were detected. The potential protective effects of the EAT-Lancet diet on CRC risk were comparable to those observed for the Mediterranean diet. Nine metabolites and nine proteins were significantly associated with all EAT-Lancet indices. Mediation analyses suggested that high body mass index (9.0%-18.0%), protein score (29.2%), and low-grade inflammation (INFLA score, 4.0%) partially mediated the relationship between dietary adherence and CRC risk. Circulating protein GGT1 was negatively associated with the diet, with lower levels linked to reduced CRC risk. Single-cell analysis showed GGT1 enrichment in immune and epithelial cells within CRC tumors. CONCLUSION: Our findings suggest that greater adherence to the EAT-Lancet diet is associated with lower CRC risk and favorable metabolic and protein profiles, supporting its potential as a sustainable and economically viable dietary strategy for CRC prevention. STATEMENT OF SIGNIFICANCE: This study is the first to comprehensively characterize the metabolic and proteomic signatures associated with adherence to the EAT-Lancet diet and to explore their potential mediating roles in colorectal cancer (CRC) risk. By integrating multi-omics analyses with dietary assessments, we identified novel molecular pathways-particularly involving GGT1 and immune-inflammatory signaling-through which the EAT-Lancet diet may influence CRC development, providing mechanistic insights that extend beyond previous epidemiologic findings.
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