Standardizing magnetic resonance enterography (MRE)-defined transmural healing (TH) remains challenging in Crohn’s disease (CD) despite its prognostic superiority. We aimed to evaluate seven conventional MRE-defined TH criteria and develop a machine-learning-optimized model for improved TH assessment. In this double-center study, 467 active CD patients with 1263 MRE scans were stratified into three cohorts. Cohort 1 (n = 341) enabled retrospectively dual-metric comparison (attainment rate/prognostic protection) of seven MRE-defined TH criteria. Leveraging their strengths, we developed five machine-learning models for TH assessment to identify the optimal one. Semi-external validation was performed in prospective Ustekinumab (n = 92) and Upadacitinib (n = 34) cohorts. Among seven conventional TH criteria, magnetic resonance index of activity (MaRIA), C-score, and simplified MaRIA (sMaRIA) demonstrated higher attainment rates (23.75
Intratumoral microbiota-related metabolites are emerging regulators of tumor immunity, yet their therapeutic potential remains largely unexplored. Here, indole-3-pyruvic acid (I3P), a Lactobacillus-associated tryptophan metabolite, is identified as a molecule associated with immunotherapy response in bladder cancer. Mechanistically, I3P suppresses macrophages ferroptosis and sustains CD8+ T cell activity through an AHR-NF-κB-SLC7A11 signaling axis that maintains macrophages redox homeostasis. Disruption of AHR or NF-κB signaling abolishes these effects. Notably, liposomal delivery of I3P facilitates efficient targeting of tumor-associated macrophages and enhances immunotherapy response without apparent toxicity. Together, these findings identify I3P as an immunoregulatory metabolite that potentiates anti-tumor immunity and support nanoparticle-mediated delivery as a promising strategy for immunotherapy sensitization in bladder cancer.
Background Measurement of Crohn disease (CD) activity is crucial for guiding treatment decisions. Super-resolution contrast-enhanced US (SRCEUS) is an emerging technique that can be used to assess vascularity at micrometer scale; however, its performance in differentiating CD activity stages is not yet known. Purpose To evaluate SRCEUS in the assessment of disease activity in participants with CD. Materials and Methods This prospective study included participants with CD involving the terminal ileum or colon who underwent intestinal SRCEUS imaging between January 2025 and June 2025. Participants were classified into remission/mild or moderate/severe activity groups based on the Simple Endoscopic Score for Crohn's Disease. B-mode US, color Doppler flow imaging (CDFI), conventional contrast-enhanced US (CEUS), and SRCEUS were performed. SRCEUS parameters were calculated. Logistic regression modeling, receiver operating characteristic analysis, and the DeLong test were used to evaluate and compare diagnostic performance. Results This study included 54 participants (mean age, 30 years ± 8.5 [SD]; 42 men). Key SRCEUS vascular parameters were higher in the moderate/severe activity group than the remission/mild activity group, including maximum density (mean, 63.4 ± 13.1 vs 51.1 ± 15.6; P = .003), mean density (mean, 26.9 ± 5.3 vs 21.1 ± 8.0; P = .007), mean velocity (mean, 40.2 mm/sec ± 27.3 vs 23.0 mm/sec ± 14.9; P = .01), vascular density ratio (mean, 73.2% ± 12.8 vs 38.5% ± 17.8; P < .001), and fractal dimension (mean, 1.7 ± 0.1 vs 1.5 ± 0.1; P < .001). SRCEUS performed well in distinguishing participants with remission/mild activity from those with moderate/severe activity (area under the receiver operating characteristic curve [AUC], 0.92; sensitivity, 94.1%; specificity, 95.0%). SRCEUS performed better than conventional CEUS (AUC, 0.78; P = .03). Clinical, B-mode US, CEUS, and SRCEUS parameters were included in a combined model, in which the International Bowel Ultrasound Segmental Activity Score and vascular density ratio were identified as influential factors. The combined model had an AUC of 0.94, demonstrating superior performance to both CDFI (AUC, 0.82; P = .04) and conventional CEUS (P = .002) and similar performance to SRCEUS (P = .51). Conclusion SRCEUS demonstrated excellent performance in differentiating CD activity through high-resolution depiction of microstructural changes, with superior performance to conventional CEUS. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Katwal and Chernyak in this issue.
Purpose This study evaluated the diagnostic accuracy of bowel ultrasound combined with inflammatory biomarkers for assessing ulcerative colitis disease activity. Materials and Methods The single-center derivation cohort retrospectively enrolled 60 ulcerative colitis patients from our institution who underwent colonoscopy and bowel ultrasound. Patients were stratified into active disease and remission groups. Bowel ultrasound parameters and clinical features were analyzed. Diagnostic performance was assessed using receiver operating characteristic curve analysis. The resulting model was externally validated from 35 patients at an independent tertiary hospital retrospectively. A nomogram was plotted for clinical application. Results In the derivation cohort (31 remission: age 42.6±18.3, male 48%; 29 active: age 44.4±14.5, male 48%), univariate analysis identified bowel wall thickness (cutoff value 3.95 mm), submucosal index (cutoff value 46.1%), bowel wall flow (cutoff value Grade 2), fecal calprotectin (cutoff value ≥200 μg/g), and erythrocyte sedimentation rate (cutoff value 26.5 mm/h) as significant predictors of disease activity. Bowel wall thickness and flow were independent risk factors. The combined model demonstrated an area under curve of 0.908 (0.829-0.986). External validation (19 remission, 16 active) provided preliminary evidence supporting the model's discriminative ability, showing an area under curve of 0.862 (0.743-0.981). The nomogram provided individualized risk prediction with acceptable calibration in both cohorts. Conclusion An integrated model combining bowel ultrasound and inflammatory biomarkers was developed and externally validated for the assessment of ulcerative colitis activity. The model, presented as a clinically practical nomogram, exhibits acceptable calibration, supporting its potential as a valuable non-invasive tool for patient management.
BACKGROUND/AIMS:The awareness, accessibility, and utilization of transabdominal intestinal ultrasound (IUS) in inflammatory bowel disease (IBD) management from both physicians' and patients' perspectives remains unclear in China. This nationwide cross-sectional survey aimed to gauge the current utilization of IUS, physician and patient perceptions and knowledge gap in IBD management across China. METHODS:A structured questionnaire, developed by the China IUS Group, was distributed to 612 physicians (69.8% of gastroenterologists, 28.0% of radiologists) from 38 tertiary hospitals and 1,154 IBD patients. RESULTS:A total of 91.7% of physicians expressed an intention to incorporate IUS into future clinical practice. However, while 69.3% of physicians reported IUS availability at their institutions, its utilization varied widely. Only 16.5% of physicians applied IUS to more than 75% of their IBD patients. Additionally, 27.1% of physicians reported receiving IUS training. Radiologists were more likely than gastroenterologists to consider IUS as a sensitive tool for evaluating treatment efficacy (48.3% vs. 19.4%, P< 0.001), intestinal wall fibrosis (33.7% vs. 27.4%, P< 0.001), intestinal fistula (27.9% vs. 11.2%, P< 0.001), abdominal abscesses (49.4% vs. 28.6%, P< 0.001), and disease severity (30.2% vs. 11.0%, P< 0.001). Patients expressed high satisfaction with IUS (76.1%), yet 39.2% had safety concerns. CONCLUSIONS:Despite growing recognition of IUS in China, its wide utilization in IBD management requires further promotion. The notable disparity between gastroenterologists and radiologists regarding IUS underscores the need for targeted, specialty-specific training. Strengthening patient education efforts is essential to further enhance patient acceptance of IUS.
Purpose:To investigate the feasibility of real-time shear wave elastography (SWE) in evaluating intestinal wall stiffness, and to establish the threshold SWE value of normal intestinal wall and explore the influencing factors of intestinal SWE. Method:659 subjects who underwent intestinal SWE and colonoscopy were retrospectively enrolled. The wall elasticity of colonoscopy-confirmed normal/abnormal intestinal segment was measured by transabdominal SWE. Measurement reliability was evaluated by the intraclass correlation coefficient (ICC). The threshold value of SWE in differentiating normal and abnormal intestine was determined using ROC curve analysis with the largest Youden index, and the diagnostic performance of this threshold was evaluated. We explored the effects of gender, age, depth and type of the targeted intestinal segment on the intestinal wall elasticity by t test and logistic linear regression analysis. Results:The technical success rate of SWE examination is 95.3 % (628/659). The mean SWE value of normal intestinal walls is (5.45 ± 1.34) kPa, which was significantly lower than that of abnormal ones (15.38 kPa±7.22, P < 0.001). Using 8.1 kPa as the threshold, the sensitivity and specificity were 93.5 % and 96.0 % with an AUC of 94.8 %. The overall ICC for SWE measurements was 0.933. Gender (ß=0.278, P = 0.013), depth (ß=0.220, P = 0.043) and type of the targeted segment (ß=0.522, P < 0.001) was associated with the SWE value of intestinal wall, but age was not (ß=0.050, P = 0.484). Conclusions:SWE is feasible in evaluating the stiffness of intestinal wall with high reliability. The SWE threshold value differentiating normal intestinal wall and abnormal intestinal wall is 8.1 kPa.
Background This study aimed to assess the role of intestinal ultrasound (IUS) in monitoring and predicting long-term bowel surgery in patients with ulcerative colitis (UC). Methods This retrospective study analyzed documented IUS examinations of UC patients from a prospective inflammatory bowel disease registry. A nomogram was constructed to predict bowel surgery based on factors identified by both multivariate Cox and logistic regression model. Model performance was assessed using receiver-operating characteristic (ROC) curves and decision curve analysis (DCA). Results A total of 171 patients were enrolled. Significant correlations were observed between IUS parameters and disease activity as assessed by colonoscopy, as well as with other inflammatory indices. During a median follow-up of 32 months, 12 patients (7.02%) underwent UC-related bowel surgery. Factors associated with bowel surgery identified by the Cox regression included the Limberg score (OR 3.86, 95% CI 0.98−15.26, p=0.054), steroids use (OR 7.31, 95% CI 0.85−62.51, p=0.069), perianal lesions (OR 37.19, 95% CI 1.94−712.34, p=0.016), and age at diagnosis (OR 1.08, 95%CI 1.02−1.13, p=0.007). A nomogram incorporating these factors was established. Both ROC curve and DCA analysis indicated that the nomogram, which included the Limberg score, had an area under the curve (AUC) of 0.872 and a C-Index of 0.875. The nomogram based on logistic regression analysis also showed good performance. Conclusion We developed and validated a prognostic nomogram incorporating the Limberg score to identify patients with UC most likely to require bowel surgery. This nomogram can improve risk stratification and aid personalized therapeutic decisions for UC patients.
BACKGROUND:Tumour-infiltrating lymphocytes (TILs) are strongly correlated with the prognosis and immunotherapy response in bladder cancer. The TIL status is typically assessed through microscopy as part of tissue pathology. Here, the authors developed Rad-TIL model, a novel radiomics model, to predict TIL status in patients with bladder cancer. MATERIAL AND METHODS:The authors enrolled 1089 patients with bladder cancer and developed the Rad-TIL model by using a machine-learning method based on computed tomography (CT) images. The authors applied a radiogenomics cohort to reveal the key pathways underlying the Rad-TIL model. Finally, the authors used an independent treatment cohort to evaluate the predictive efficacy of the Rad-TIL model for Bacillus Calmette-Guérin (BCG) immunotherapy. RESULTS:The authors developed the Rad-TIL model by integrating tumoral and peritumoral features on CT images and obtained areas under the receiver operating characteristic curves of 0.844 and 0.816 in the internal and external validation cohorts, respectively. Patients were stratified into two groups based on the predicted radiomics score of TILs (RSTIL). RSTIL exhibited prognostic significance for both overall and cancer-specific survival in each cohort (hazard ratios: 2.27-3.15, all P<0.05). Radiogenomics analysis revealed a significant association of RSTIL with immunoregulatory pathways and immune checkpoint molecules (all P<0.05). Notably, BCG immunotherapy response rates were significantly higher in high-RSTIL patients than in low-RSTIL patients (P=0.007). CONCLUSION:The Rad-TIL model, a noninvasive method for assessing TIL status, can predict clinical outcomes and BCG immunotherapy response in patients with bladder cancer.
Journal Article Corrected proof Utilization of Super-Resolution Contrast-Enhanced Ultrasonography in Diagnosing Intestinal Behçet's Disease With Enterovesical Fistula Get access Saidaitiguli Aihemaiti, MD, Saidaitiguli Aihemaiti, MD Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Zi-yin Ye, MD, Zi-yin Ye, MD Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Ren Mao, MD, Ren Mao, MD Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yu-jun Chen, MD Yu-jun Chen, MD Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Address correspondence to: Yu-jun Chen, MD, Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China ([email protected]). https://orcid.org/0000-0003-0888-5037 Search for other works by this author on: Oxford Academic PubMed Google Scholar Inflammatory Bowel Diseases, izaf040, https://doi.org/10.1093/ibd/izaf040 Published: 13 March 2025 Article history Received: 25 January 2025 Editorial decision: 12 February 2025 Corrected and typeset: 13 March 2025 Published: 13 March 2025
INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.
Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRP. aeruginosa) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N-acetylcysteine-ε-poly-l-lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro. Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDRP. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.
Background Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated.Methods We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells’ infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate.Results In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G–Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.Conclusions Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.
Natural polymer chitosan has many advantages, but the poor solubility limits its application. In this study, chitosan derivatives soluble in DCM, DMF, DMSO, H2O and other solvents were developed by introducing side chains into chitosan (CS). In addition, the fluorescent group on the side chain makes the chitosan derivative have the ability to detect 4-nitrophenol (4-NP). Firstly, a chain transfer agent containing C---C (N3-NS) was synthesized with naphthalimide as the fluorescence unit. Then, using AIBN as initiator, an extensively soluble polymer with fluorescent moiety TP-NVP was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) method using monomer N-vinyl pyrrolidone (NVP). Finally, the C ---C of TP-NVP was used to react with -NH2 on CS to prepare PVP-g-chitosan, so that more CS was "pulled" by TP-NVP into the solvent. The solubility of the synthesized CS-PVP probe can be adjusted by adjusting the amount of NVP, up to 17.6 mg/mL. At the same time, the synthesized CS-PVP had a good detection effect on 4-NP, and the detection limit (LOD) was 0.054 mu M. The HOMO-LUMO energy level of the probe was calculated by cyclic voltammetry (CV). In addition, CS-PVP was successfully loaded on a low background fluorescent test paper to achieve realtime visual intelligent determination of 4-NP in real samples with the help of a color scanning APP of a smartphone.
ABSTRACT Background We evaluated the mesenteric elasticity in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using shear wave elastography (SWE) and investigated its relationships with peritoneal function. Methods Patients were recruited in our peritoneal dialysis (PD) centre between 15 July 2019 and 31 December 2021 and followed up to 31 March 2022. Twelve chronic kidney disease (CKD) patients and nineteen healthy people were included as controls. Correlation, linear regression and Cox regression analyses were applied. Results Of the 218 PD patients, 104 (47.8%) were male. Their mean age was 48.0 ± 13.2 years and the median PD duration was 59.0 months [interquartile range (IQR) 17.0–105]. The median mesenteric SWE value was 8.15 kPa (IQR 5.20–16.1). The mesenteric SWE values of patients with a PD duration of <3 months [5.20 kPa (IQR 3.10–7.60)] were not significantly different from those of CKD patients [4.35 kPa (IQR 2.63–5.20), P = .17] and healthy controls [3.60 kPa (IQR 2.90–5.10), P = .13] but were lower than those of patients with a PD duration of 3 months–5 years [6.40 kPa (IQR 4.10–10.5), P < .001], 5–10 years [11.9 kPa (IQR 7.40–18.2), P < .001] and >10 years [19.3 kPa (IQR 11.7–27.3), P < .001]. Longer PD duration (β = 0.58, P < .001), high effluent interleukin-6 (β = 0.61, P = .001) and low effluent cancer antigen 125 (β = −0.34, P = .03) were independently associated with low mesenteric elasticity. The mesenteric SWE value was independently correlated with the dialysate:plasma creatinine ratio (β = 0.39, P = .01) and negatively correlated with the total daily fluid volume removed (β = −0.17, P = .03). High mesenteric SWE values were an independent risk factor for death-censored technique failure [adjusted hazard ratio 4.14 (95% confidence interval 1.25–13.7), P = .02). Conclusions SWE could be used to non-invasively characterize peritoneal textural changes, which were closely associated with changes in peritoneal function.
Overall survival (OS) was analyzed for different cellular resource of VISTA on immune cells (ICs) in Cohort Ⅵ UCB patients
Combination (combo) of VISTA mAb 13F3/sODN-dsRNA with TGF-β1mAb induced TME changes in MB49 mouse tumors
Overall survival (OS) was analyzed with the Kaplan-Meier method stratifying 144 Cohort II UCB patients according to high or low levels of VISTA+ endothelial cells (ECs, A), or tumor cells (TCs, B)
Combination (combo) of VISTA mAb 13F3 with sODN-dsRNA potentiated the proinflammatory effect of mouse derived macrophage in vitro
Objective: To investigate the feasibility of using shear-wave elastography (SWE) to measure the stiffness of the normal terminal ileum mesentery, and to establish its normal reference range.Methods: Ninety-five normal subjects and 22 patients with mesentery-related disease were included. The average Young's modulus of the normal terminal ileal mesentery was measured by SWE ultrasound. The thickness and the extent to which mesenteric fat extended around the intestinal circumference of the normal terminal ileum were also recorded. The normal reference range was established and the SWE values of normal and diseased subjects were compared.Results: Transabdominal SWE examination of the terminal ileum mesentery was successfully performed on 91 subjects (95.8 %). The mean extent range, thickness, and SWE value of the normal terminal ileum mesentery were 1/4 (1/5-1/3), 6.8 +/- 2.4 mm, and 4.3 +/- 2.1 kPa, respectively. These parameters did not differ significantly between genders, and across age and body mass index groups (all P > 0.05). The intra-and inter-operator consistencies were excellent for the replicated SWE measurements (0.801 [95 % confidence interval: 0.560-0.916] and 0.751 (95 % confidence interval: 0.388-0.900], respectively). The mean mesenteric elasticity in diseased subjects was 21.9 +/- 10.7 kPa, which was significantly higher than that in normal subjects (P < 0.001). The cut-off value for mesenteric elasticity was 9.3 kPa, with a sensitivity of 90 % and a specificity of 100 % (P < 0.001).Conclusion: SWE can be used to reliably evaluate the stiffness of the terminal ileum mesentery in normal subjects.