BMC Gastroenterol
· 2026 Jun · PMID 42321620
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BACKGROUND: Fatty liver is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the mediating role of the triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio (THR) in this associa...BACKGROUND: Fatty liver is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the mediating role of the triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio (THR) in this association remains unclear. This study aimed to evaluate the impact of fatty liver on diabetes risk and explore the mediating effect and predictive performance of THR. METHODS: This secondary analysis included 15,453 non-diabetic participants from the NAGALA cohort. Fatty liver was diagnosed using ultrasonography, and T2DM was defined as a fasting plasma glucose level ≥ 7 mmol/L, hemoglobin A1c level ≥ 6.5%, or self‑report. THR was calculated as triglycerides (mmol/L) divided by HDL-C (mmol/L). Cox regression, mediation analysis, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Over a median follow-up of 5.4 years, 373 (2.4%) participants developed diabetes. Fatty liver was associated with a significantly increased risk of diabetes [adjusted hazard ratio (HR) 2.88; 95% confidence interval (CI) 2.22-3.73; P < 0.001]. The association was more pronounced in women and younger individuals (< 45 years). Fatty liver was also significantly associated with a higher THR (adjusted β 0.35; P < 0.001). Compared with the lowest THR quartile (< 0.30), the highest quartile (> 0.90) showed an adjusted HR of 2.08 (95% CI 1.27-3.40) for diabetes. THR mediated 11.63% (95% CI 6.80-19.58%) of the fatty liver-T2DM association, with significant mediation in men but not in women. THR yielded an area under the curve (AUC) of 0.75 (95% CI 0.72-0.77) for predicting diabetes, with a sensitivity of 69.71% and specificity of 68.58% at an optimal cutoff value of 0.75. CONCLUSIONS: Fatty liver is significantly associated with an increased risk of diabetes, and THR statistically explains part of this association, particularly in men. THR demonstrates moderate predictive value and may serve as a useful biomarker for risk stratification in patients with diabetes.
Nikparast A, Sepehrinia M, Zamanian N
… +4 more, Razaz JM, Tabatabaeyan A, Hadi S, Homayounfar R
BMC Gastroenterol
· 2026 Jun · PMID 42321612
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BACKGROUND: Diet is a key modulator of gut microbiota and may influence the development of metabolic dysfunction-associated steatotic liver disease (MASLD). The Dietary Index for Gut Microbiota (DI-GM) has been proposed...BACKGROUND: Diet is a key modulator of gut microbiota and may influence the development of metabolic dysfunction-associated steatotic liver disease (MASLD). The Dietary Index for Gut Microbiota (DI-GM) has been proposed to capture the overall capacity of diet to promote a favorable gut microbial profile. Prospective evidence linking DI-GM to MASLD risk remains limited. METHODS: This prospective analysis included 5,058 adults without MASLD at baseline from the Monitoring of Metabolic Diseases Risk Factors in Tehran (MMRT) study. Dietary intake was assessed using a validated 125-item food frequency questionnaire. The five-year incidence of MASLD was evaluated using multivariable logistic regression models, and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were conducted to assess potential effect modification. Sensitivity analyses examined the robustness of results after excluding participants with substantial weight gain and after additional adjustment for metabolic and dietary factors. Mediation analyses were performed to explore potential pathways underlying the observed associations. RESULTS: Over five years of follow-up, 562 participants developed MASLD. Higher DI-GM scores were associated with a lower likelihood of incident MASLD. In the fully adjusted model, individuals in the highest quartile of DI-GM had 42% lower odds of MASLD compared with those in the lowest quartile (OR:0.58; 95%CI:0.42-0.80; P-trend < 0.01). Each one-standard-deviation increment in DI-GM score was associated with reduced odds of MASLD (OR:0.72; 95%CI:0.65-0.81;P-value < 0.001). The inverse association was more pronounced among women and participants aged ≥ 45 years (P-interaction < 0.01). Mediation analyses suggested that CAP, HOMA-IR, and serum vitamin D partially explained the association. CONCLUSIONS: Greater adherence to a diet supportive of gut microbiota, as reflected by higher DI-GM scores, was associated with a lower five-year risk of MASLD. These findings highlight the potential role of microbiota-related dietary patterns in MASLD prevention.
Chen Z, Huang H, Tao H
… +4 more, Wu R, Xu Z, Zhan Q, Li Z
BMC Gastroenterol
· 2026 Jun · PMID 42321604
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BACKGROUND: Gastric cancer (GC) remains a significant global health burden due to its high incidence and mortality, especially in China. This study aimed to evaluate the performance of combined serological assessment of...BACKGROUND: Gastric cancer (GC) remains a significant global health burden due to its high incidence and mortality, especially in China. This study aimed to evaluate the performance of combined serological assessment of pepsinogen (PG) and Helicobacter pylori (H. pylori) antibodies for identifying gastric precancerous conditions. METHODS: From November 2016 to September 2019, an observational cohort study was performed to evaluate serum levels of PG and H. pylori antibodies. Among 19,879 participants, four groups were defined based on serological status: Group A (PG/ H. pylori), Group B (PG/ H. pylori), Group C (PG/ H. pylori), and Group D (PG/ H. pylori). Participants from Groups C and D were included in the analysis, while individuals from Groups A and B were randomly selected at a 3:1 ratio relative to Groups D and C, respectively. In total, 1,152 subjects underwent endoscopic and histopathological assessment. RESULTS: Group C demonstrated significantly elevated odds of atrophic gastritis (AG) (OR = 1.98; 95% CI: 1.17-3.26) and intestinal metaplasia (IM) (OR = 1.40; 95% CI: 0.73-2.67) compared to Group A. In the gastric corpus, the odds of AG and IM were 5.0 and 6.8 times higher, respectively, in Group C versus Group A. CONCLUSION: Combined serological assessment of PG and anti- H. pylori IgG improves the identification of gastric precancerous conditions, with particularly enhanced performance in the gastric corpus.
BACKGROUND: Risankizumab and ustekinumab are biologics targeting the interleukin-23 pathway through distinct mechanisms (selective p19 versus shared p40 inhibition). Both are key options for moderate-to-severe Crohn's di...BACKGROUND: Risankizumab and ustekinumab are biologics targeting the interleukin-23 pathway through distinct mechanisms (selective p19 versus shared p40 inhibition). Both are key options for moderate-to-severe Crohn's disease, but comparative evidence remains limited. We aimed to evaluate their relative efficacy and safety using direct and indirect evidence to inform treatment decisions. METHODS: We searched major databases for randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn's disease comparing risankizumab or ustekinumab with placebo or each other. Random-effects models were used for pairwise meta-analyses, and a Bayesian network meta-analysis (NMA) integrated direct and indirect evidence. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: Nine RCTs (N.=4814) were included. Versus placebo, risankizumab significantly improved clinical remission (odds ratio [OR] 2.24, 95% CI: 1.73-2.91) and response (OR=2.70, 95% CI: 2.02-3.61). Ustekinumab also increased remission (OR=2.14, 95% CI: 1.68-2.73) and response (OR=2.16, 95% CI: 1.67-2.80). In the NMA, risankizumab ranked highest for remission (SUCRA 96.9%) and response (98.1%), while ustekinumab occupied intermediate positions. Both agents were well tolerated; risankizumab ranked more favorably for serious adverse events and serious infections, whereas ustekinumab ranked slightly higher for total adverse events. CONCLUSIONS: Risankizumab and ustekinumab were both effective and generally well tolerated in moderate-to-severe Crohn's disease. Risankizumab showed a more favorable efficacy pattern for remission and response and ranked more favorably for serious adverse events, whereas overall safety profiles were otherwise broadly comparable. These findings support treatment selection according to clinical priorities.
Suzuki T, Sugimoto M, Kojima M
… +4 more, Kudo M, Kobayashi S, Ishii G, Gotohda N
BMC Gastroenterol
· 2026 Jun · PMID 42316056
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BACKGROUND: The reported incidence of clinically-relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) ranges from 10% to 40%. Identification of risk factors for POPF may enable individuali...BACKGROUND: The reported incidence of clinically-relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP) ranges from 10% to 40%. Identification of risk factors for POPF may enable individualized modification of surgical techniques and postoperative management strategies. This study aimed to elucidate the clinico-histopathological characteristics associated with CR-POPF after DP. METHODS: A total of 186 patients who underwent DP were investigated. Pancreatic thickness at the planned transection site was measured using preoperative computed tomography. Histopathological findings of the pancreatic stump, including branched pancreatic duct (BPD) density and fibrosis ratio, were assessed quantitatively using morphometric analysis. Risk factors for CR-POPF were analyzed. RESULTS: The incidence of CR-POPF was 33%. Factors associated with CR-POPF included pancreatic thickness ≥ 11.7 mm (odds ratio [OR] 3.736; p < 0.001), BPD density ≥ 2.5/100 mm² (OR 5.173; p < 0.001), and fibrosis ratio < 4.4% (OR 2.596; p = 0.041). Patients with pancreatic thickness ≥ 11.7 mm showed higher BPD density (2.5 vs. 1.8/100 mm²; p = 0.002) and lower fibrosis ratio (3.2% vs. 3.6%; p = 0.022). CONCLUSION: Greater pancreatic thickness, higher BPD density, and lower fibrosis ratio at the transection site were associated with CR-POPF after DP. As high BPD density and low fibrosis ratio were also associated with increased pancreatic thickness, these findings suggest that anatomical and histopathological pancreatic features may be jointly related to the risk of CR-POPF.
BMC Gastroenterol
· 2026 Jun · PMID 42316031
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BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymatic disorder, typically associated with hemolytic anemia. However, emerging evidence points to its involvement in a wider...BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymatic disorder, typically associated with hemolytic anemia. However, emerging evidence points to its involvement in a wider range of physiological processes, including the regulation of oxidative stress, immune defense, and epithelial repair which could lead to various manifestations. This is the first report of association between G6PD deficiency and perianal abscess and fistula. CASE PRESENTATION: A 16-year-old male with a five-year history of recurrent perianal abscess and fistula presented with renewed symptoms despite prior surgical management. His mother and brother had also reportedly been diagnosed with perianal abscess and fistula. Laboratory findings showed anemia and elevated inflammatory markers, while imaging revealed an intersphincteric fistula tract. Colonoscopy exhibited focal active ileitis without granulomas. Whole-exome sequencing identified a hemizygous pathogenic/likely pathogenic mutation in the G6PD gene (c.653 C > T), suggesting a genetic contribution to the chronic inflammatory process. CONCLUSIONS: This case highlights a possible association between G6PD deficiency and recurrent perianal abscess and fistula. Impaired immune response and epithelial repair linked to G6PD dysfunction may contribute to chronic perianal disease. Further studies are warranted to clarify this potential relationship.
BMC Gastroenterol
· 2026 Jun · PMID 42316027
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BACKGROUND: Primary gastrointestinal epithelioid angiosarcoma (EAS) is an extremely rare and aggressive malignancy. Due to its epithelioid morphology and aberrant cytokeratin expression, it frequently mimics poorly diffe...BACKGROUND: Primary gastrointestinal epithelioid angiosarcoma (EAS) is an extremely rare and aggressive malignancy. Due to its epithelioid morphology and aberrant cytokeratin expression, it frequently mimics poorly differentiated carcinoma, creating significant diagnostic challenges. Furthermore, the molecular landscape of primary EAS, particularly regarding MYC status, remains underrecognized compared to radiation-associated angiosarcomas. CASE PRESENTATION: An 82-year-old man presented with refractory melena and severe anemia. Imaging revealed multifocal lesions involving the stomach and small intestine. The patient underwent a laparoscopic exploration and multiple segmental resections. Histologically, the tumors consisted of epithelioid cells arranged in solid sheets with extensive hemorrhage. Immunohistochemistry showed strong positivity for CD31, ERG, and CD34, accompanied by diffuse CKpan expression, mimicking carcinoma. Crucially, despite the absence of prior radiotherapy, Next-Generation Sequencing (NGS) of the gastric lesion identified significant MYC gene amplification (copy number 6.7) and a PTPRD nonsense mutation. The patient died three months after surgery. CONCLUSIONS: This case highlights a critical diagnostic pitfall: primary EAS can diffusely express cytokeratins. More importantly, our findings challenge the traditional view that MYC amplification is exclusive to secondary, radiation-associated angiosarcomas. We propose that MYC amplification can act as a driver in primary EAS and may serve as a biomarker for aggressive clinical behavior.
Chen Y, Chen P, Li G
… +3 more, Fu SB, Cheng YL, Huang SP
BMC Gastroenterol
· 2026 Jun · PMID 42310586
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BACKGROUND: Electronic gastroscopic examination (EGE) is the most effective and reliable method for the screening and diagnosis of upper gastrointestinal diseases. Prolonged prohibition of drinking water before EGE may l...BACKGROUND: Electronic gastroscopic examination (EGE) is the most effective and reliable method for the screening and diagnosis of upper gastrointestinal diseases. Prolonged prohibition of drinking water before EGE may lead to discomfort in patients. AIM: To identify whether water-deprivation duration can be safely minimized in unsedated EGE for middle-aged/elderly patients without gastric emptying disorders. METHODS: A total of 252 middle-aged and elderly patients who underwent unsedated EGE at the Shaanxi Cancer Hospital endoscopy center were randomly assigned to three groups: the control group (drinking 200 ml of warm water 6 h before EGE), Experimental group A ( 200 ml of warm water 2 h before EGE), and Experimental group B ( 200 ml of warm water 1 h before EGE). Prior to EGE, patient discomfort and anxiety levels were assessed 15 min beforehand. Residual gastric volume (RGV) and clarity of the visual field (EVFC) during EGE were also evaluated. RESULTS: The Experimental groups showed lower scores for thirst, dryness of the mouth, nausea, vomiting, and weakness than the control group. No significant intergroup differences were observed in EVFC and RGV qualified rates among the two experimental groups and the control group. However, Experimental group B showed an unfavorable downward trend in RGV qualified rate. No adverse events such as aspiration occurred in either group. CONCLUSION: For middle-aged and elderly patients without gastric emptying disorders, drinking 200 ml of warm water 2 h prior to EGE is recommended. This strategy improves patients' comfort and mood, and maintains normal EVFC and RGV. Even though 1-hour water intake results in no statistically significant differences in RGV and EVFC, it presents an unfavorable trend of reduced RGV qualified rate.
BMC Gastroenterol
· 2026 Jun · PMID 42310577
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BACKGROUND: Inflammatory Bowel Disease (IBD) is a chronic and recurrent gastrointestinal disorder that adversely affects patients' quality of life. The influence of daily dietary behaviors and meal regularity on gastroin...BACKGROUND: Inflammatory Bowel Disease (IBD) is a chronic and recurrent gastrointestinal disorder that adversely affects patients' quality of life. The influence of daily dietary behaviors and meal regularity on gastrointestinal symptoms and quality of life remains under-investigated. The study aimed to evaluate dietary intake, dietary habits, and meal patterns of the IBD patients and based on this data, to determine their gastrointestinal symptoms, quality of life, and depression status. METHODS: This cross-sectional study was conducted at Istanbul University Cerrahpaşa Medical Faculty Hospital and included adults aged 18-75 years with a confirmed diagnosis of IBD attending routine outpatient follow-up visits. Data were collected using a sociodemographic and clinical data form, a 24-Hour Dietary Recall, IBD Quality of Life Questionnaire (IBD-QoL), Beck Depression Inventory II (BDI-II), Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: A total of 50 patients with IBD were included (30 Crohn's disease and 20 Ulcerative colitis). The mean age was 39.5 ± 13.49 years and the mean BMI was 24.82 ± 5.39 kg/m². Most patients (82%) reported consuming foods that worsened their symptoms, primarily legumes (21%), milk (14.3%), and raw vegetables (10.9%). Conversely, 50% identified foods that alleviated symptoms, mainly yogurt (18.2%) and cooked vegetables (18.2%), cooked meat (7.6%). Dietary analysis revealed intake below recommended levels for fiber, vitamins B1, B2, B6, C, folate, potassium, calcium, magnesium, and iron. Meal skipping was reported by 20% of patients with Ulcerative colitis and 40% with Crohn's disease. Patients who skipped meals had higher gastrointestinal symptom scores than those with regular meal patterns. Additionally, higher depression scores were associated with lower quality of life and more severe gastrointestinal symptoms. CONCLUSION: The study found that dietary intake and meal patterns in individuals with IBD are associated with their quality of life and gastrointestinal symptoms. A balanced and regular diet may be associated with reduced gastrointestinal symptoms and improved quality of life in IBD patients.
Yu S, Zhu Q, Yu C
… +3 more, Liu J, Han RPS, Xiang Y
BMC Gastroenterol
· 2026 Jun · PMID 42310554
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OBJECTIVE: Based on multidimensional data analysis, potential biomarkers for ulcerative colitis were screened, and the effects of curcumin chitosan microspheres on the expression of key targets in ulcerative colitis and...OBJECTIVE: Based on multidimensional data analysis, potential biomarkers for ulcerative colitis were screened, and the effects of curcumin chitosan microspheres on the expression of key targets in ulcerative colitis and their role in alleviating inflammation were observed. METHODS: Potential biomarkers related to UC progression were identified through differential expression analysis (using the limma package, with |log2FC| > 1 and corrected P < 0.05), weighted gene coexpression network analysis, and three machine learning algorithms (LASSO, random forest, SVM-RFE) on the basis of the datasets GSE107499 and GSE87473 in the GEO database. The core genes selected through this process were externally validated via the independent dataset GSE47908. A UC mouse model was constructed using 6-8-week-old C57BL/6 mice, and CCM was applied to the UC mice. Colonic tissues were collected for pathological examination and determination of inflammatory factor levels. Changes in the protein expression of the core genes were detected via immunohistochemistry. RESULTS: After rigorous screening and external validation, four core genes were finally identified: FCN3, FGR, HSD11B1 and PIM2. CCM treatment improved pathological damage and inflammatory factor levels in the colon tissue of UC mice, and the protein expression levels of FCN3, FGR, HSD11B1 and PIM2 in the colon tissue were inhibited. CONCLUSION: Four potential targets of UC, namely, FCN3, FGR, HSD11B1, and PIM2, were identified. CCM may improve the degree of the UC inflammatory response by downregulating the expression of key genes.
Ren X, Liu Z, Wang Y
… +3 more, Guo P, Cheng S, Zhang R
BMC Gastroenterol
· 2026 Jun · PMID 42310552
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BACKGROUND: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but response is highly variable. The systemic metabolic impact of TACE and its connection...BACKGROUND: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but response is highly variable. The systemic metabolic impact of TACE and its connection to tumor-intrinsic factors governing efficacy remain poorly understood. We hypothesized that by comparing host fecal metabolomics with tumor transcriptomics, we could identify convergent pathways suggestive of a gut-liver axis signature of TACE response. METHODS: We performed untargeted fecal metabolomics in a prospective paired cohort of 30 HCC patients sampled before TACE and again on post-TACE day 4, an early time point selected to capture acute ischemic, inflammatory, and metabolic perturbations after embolization. To characterize tumor-intrinsic programs associated with efficacy, we analyzed the independent public transcriptomic dataset GSE104580 containing pre-treatment tumors from TACE responders and non-responders. Cross-cohort integration was conducted at the pathway level to identify convergent biological themes. For metabolomics, paired univariate testing with Benjamini-Hochberg false discovery rate (FDR) correction and Variable Importance in Projection (VIP) > 1 from PLS-DA were used; for transcriptomics, differential expression used adjusted p < 0.05 and |log2FC|> 1, followed by GSEA. RESULTS: TACE induced a shift in the fecal metabolome, with significant enrichment of glycerophospholipid metabolism, together with changes in bile acid-related metabolites and tryptophan/vitamin B6-related metabolites. Lysophosphatidylcholines (LysoPCs), including LysoPC (22:4), and bile acid-related metabolites were increased after TACE, consistent with acute treatment-associated tissue metabolic perturbation. Independent transcriptomic analysis revealed that responder tumors were enriched for primary bile acid biosynthesis, fatty acid degradation, and tryptophan metabolism, with higher expression of CYP7A1, ACOX1, IDO1, and TDO2, whereas non-responders were enriched for Cell cycle, DNA replication, and ribosome-related programs. Because the metabolomics and transcriptomics datasets were derived from separate cohorts, these convergent findings support a pathway-level cross-cohort model rather than direct patient-level tumor-fecal linkage. CONCLUSION: Our comparative analysis suggests a potential gut-liver axis signature associated with TACE efficacy. We therefore present fecal LysoPC as a candidate non-invasive pharmacodynamic readout of acute post-TACE tissue injury and host-microenvironmental perturbation rather than a tumor-necrosis-specific biomarker. Likewise, the convergence on bile acid and tryptophan metabolism suggests that a responder-associated tumor metabolic phenotype may be relevant to TACE sensitivity. These findings offer potential non-invasive biomarkers and highlight new therapeutic targets to enhance TACE efficacy.
BMC Gastroenterol
· 2026 Jun · PMID 42310547
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BACKGROUND: Real-time endoscopic diagnosis of Helicobacter pylori infection remains challenging and often requires biopsy-based testing, delaying treatment decisions. Although deep learning (DL) approaches have shown pro...BACKGROUND: Real-time endoscopic diagnosis of Helicobacter pylori infection remains challenging and often requires biopsy-based testing, delaying treatment decisions. Although deep learning (DL) approaches have shown promise, most prior studies have relied on retrospective datasets or image-enhanced modalities, limiting their applicability to routine white-light endoscopy. We aimed to develop and prospectively validate a research-stage DL model for H. pylori detection using only standard white-light endoscopic images. METHODS: In this single-center prospective study, consecutive adults undergoing diagnostic gastroscopy were enrolled. Six standardized gastric images per patient were targeted under standard white-light endoscopic imaging. Histopathology from antral and corpus biopsies served as the reference standard. An EfficientNet-B0-based DL model was developed to classify H. pylori infection at the patient level by aggregating image-level predictions. Model performance was assessed using five-fold cross-validation within the development cohort, followed by evaluation in an independent temporally separated validation cohort (70% development / 30% temporal validation). RESULTS: A total of 172 patients (1,000 images) were included; 94 patients (54.7%) were H. pylori-positive. In five-fold cross-validation, the model achieved a patient-level AUC of 0.901 (95% CI: 0.863-0.936), with 85.1% sensitivity and 81.4% specificity. In the independent temporal validation cohort (n = 52; prevalence 48.1%), the AUC was 0.889 (95% CI: 0.793-0.960), with 84.0% sensitivity and 85.2% specificity. Aggregating predictions across multiple gastric views improved discrimination compared with single-image inference. CONCLUSION: In this prospective study, a deep learning model using routine white-light endoscopic images demonstrated reasonable patient-level discrimination for H. pylori detection, including in an independent temporally separated validation cohort. At present, the model should be viewed as a research and decision-support tool rather than a standalone diagnostic system. Multicenter external validation and prospective video-based studies are warranted before routine clinical deployment.
Knauss A, Gabel M, Kaufmann C
… +14 more, Loges L, Rath T, Atreya R, Radtke D, Grapp H, Gerlach K, Thoma OM, Eckstein M, Gessner A, Bartels N, Schmid B, Tripal P, Weigmann B, Neurath MF
Gastroenterology
· 2026 Jun · PMID 42309263
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BACKGROUND AND AIMS: Effector T lymphocytes have been shown to play a key role in inflammatory bowel diseases (IBD). However, the molecular pathways controlling their metabolism and functional activity remain poorly defi...BACKGROUND AND AIMS: Effector T lymphocytes have been shown to play a key role in inflammatory bowel diseases (IBD). However, the molecular pathways controlling their metabolism and functional activity remain poorly defined. We aimed to elucidate the role of the immune checkpoint receptor TIM3 for T cell signalling in IBD. METHODS: We combined experimental colitis models in TIM3-deficient mice with analyses of human IBD and control samples. Blood and mucosal T cells were assessed using multi-colour flow cytometry, cytokine profiling, and untargeted metabolomics. Single-cell sequencing data were analysed. The TIM3 ligand galectin-9 was used to study TIM3 function. RESULTS: TIM3 expression was higher on blood Th1 cells and mucosal Th17 cells in IBD patients compared to controls, with levels being particularly high in anti-TNF refractory patients. Mice lacking TIM3 showed exacerbated oxazolone colitis and increased effector T cell activation. Metabolome profiling and functional analyses revealed that TIM3 signaling functions as an immunometabolic regulator, suppressing adenosine deaminase and the purine degradation pathway to keep effector T cells in an exhausted PD1+ state. However, insufficient availability of the TIM3 ligand galectin-9 limited effective TIM3 signalling in chronic inflammation. Treatment with galectin-9 ameliorated experimental colitis via adenosine deaminase inhibition. Moreover, in IBD T cells, galectin-9 induced an immunometabolic switch associated with reduction of terminally exhausted Th17 cells. CONCLUSION: TIM3 plays a key role in the immunometabolism of effector T cells in colitis by suppressing adenosine deaminase and the purine degradation pathway. Targeting the immunometabolic functions of effector T cells via TIM3 activation emerges as a promising strategy for chronic intestinal inflammation.
BACKGROUND: Early-onset gastric cancer (EOGC), diagnosed before age 45, demonstrates distinct clinicopathological features and poorer prognosis. Current screening strategies lack sensitivity in young populations, while H...BACKGROUND: Early-onset gastric cancer (EOGC), diagnosed before age 45, demonstrates distinct clinicopathological features and poorer prognosis. Current screening strategies lack sensitivity in young populations, while Helicobacter pylori (H. pylori) virulence genotypes (e.g., cagA, vacA) remain underutilized in risk stratification. To develop and validate a diagnostic model combining clinical characteristics and H. pylori virulence serological detection of virulence factors to optimize EOGC risk stratification. METHODS: In this multicenter case-control study, 200 histologically confirmed EOGC patients and 600 age-matched controls (non-malignant gastric conditions) were enrolled from LiShui Hospital (2023-2024). Clinical parameters, H. pylori infection status (13C-urea breath test), and virulence genotypes (cagA, vacA; ELISA) were analyzed. Multivariable logistic regression identified independent risk factors, followed by risk score development and internal validation (1000 bootstrap replicates). RESULTS: EOGC patients exhibited higher prevalence of persistent epigastric pain (68.5% vs. 32.1%; P<0.001), significant weight loss (6.2 vs. 2.1 kg; P<0.01), and H. pylori infection (85.0% vs. 52.3%; P<0.001). Virulent genotypes were enriched in EOGC: cagA+ (72.5% vs. 45.6%; P<0.01) and vacA s1/m1 (65.0% vs. 38.2%; P<0.01). The final model included five predictors: persistent pain (adjusted odds ratio [aOR]=2.85, 95% CI:1.92-4.23), cagA+ (aOR=3.12, CI: 2.01-4.85), anemia (Hb<110 g/L; aOR=2.34, CI: 1.56-3.51), thrombocytosis (>300×10/L; aOR=1.98, CI: 1.32-2.96), and weight loss >2.1 kg (aOR=2.57, CI: 1.21-2.73). A score ≥3 indicated high risk, achieving 86.5% sensitivity and 82.3% specificity (AUC=0.89, CI: 0.85-0.93). CONCLUSIONS: This novel model integrates accessible clinical and microbiological markers to stratify EOGC risk with high accuracy, providing a cost-effective tool for prioritizing endoscopic evaluation in young symptomatic individuals.
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic conditions associated with gastrointestinal inflammation and a wide range of extraintestinal manifestations. While conventi...Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic conditions associated with gastrointestinal inflammation and a wide range of extraintestinal manifestations. While conventional treatments primarily address intestinal inflammation, many patients continue to experience chronic pain, psychological comorbidities, and functional gastrointestinal symptoms, highlighting the need for integrated therapeutic strategies. This narrative review explores the potential of neurofeedback (NFB) as a non-invasive therapeutic approach for managing symptoms frequently observed in IBD, including musculoskeletal pain, anxiety, depression, post-traumatic stress symptoms (PTSS), and gut-brain axis dysfunction. In the absence of direct evidence on neurofeedback in IBD populations, we examined data from clinical trials conducted in conditions that are frequently comorbid with or symptomatically overlap with inflammatory bowel disease, including fibromyalgia, irritable bowel syndrome (IBS), chronic pain syndromes, and affective or trauma-related disorders. We focused on outcomes related to chronic pain, psychological well-being, and gastrointestinal function, examining NFB protocols primarily targeting alpha, theta, and sensorimotor rhythms, which have shown promising results in improving symptom severity and autonomic regulation. These findings support the rationale for investigating NFB as a potential adjunctive therapy in IBD, particularly for patients with residual or refractory extraintestinal symptoms. However, as none of the available studies specifically involve patients with IBD, the evidence base remains indirect. Moreover, current findings are limited by small sample sizes, heterogeneous methodologies, and variable outcome measures in the studied populations, making it difficult to draw definitive conclusions regarding the efficacy of NFB in this context. Future research should include large-scale, randomized controlled trials conducted directly in IBD cohorts, along with protocol standardization and individualized approaches based on neurophysiological profiles. Clarifying the therapeutic potential of NFB in this population could open new avenues for non-pharmacological, patient-tailored interventions within integrative care frameworks.