BACKGROUND: Frailty is a multidimensional syndrome associated with poor outcomes and increased vulnerability, yet its assessment in inflammatory bowel diseases (IBD) remains challenging due to the absence of disease-spec...BACKGROUND: Frailty is a multidimensional syndrome associated with poor outcomes and increased vulnerability, yet its assessment in inflammatory bowel diseases (IBD) remains challenging due to the absence of disease-specific tools. AIMS: This study aimed to develop and validate the IBD Frailty Score, a tailored instrument for evaluating frailty in patients with Crohn disease (CD) and ulcerative colitis (UC). METHODS: In the development phase, 28 categorical items were included in the IBD Frailty Score. This tool was tested in an exploratory cohort of 121 IBD outpatients and later validated in a prospective multicenter cohort of 512 patients across four tertiary centers. Predictive factors of frailty were identified through univariate and multivariate analyses. RESULTS: The IBD Frailty Score was feasible, with an average administration time of ∼2 minutes. It correlated positively with the Fried Frailty Phenotype, IBD Disability Index, and Charlson Comorbidity Index and showed good reproducibility (rho = 0.78) and strong diagnostic accuracy (AUC = 0.79). A cut-off score of 4 reliably distinguished fit from frail patients. Increasing age, polypharmacy, history of extraintestinal manifestations, and higher disease activity were independent risk factors for frailty. CONCLUSIONS: The IBD Frailty Score is the first validated, disease-specific tool for assessing frailty in IBD. It is practical, reproducible, and correlates well with established measures.
BACKGROUND: Hepatitis E virus (HEV) infection remains a major cause of liver failure with high short-term mortality, yet predictive models incorporating systemic metabolic factors are limited. AIMS: We aimed to develop a...BACKGROUND: Hepatitis E virus (HEV) infection remains a major cause of liver failure with high short-term mortality, yet predictive models incorporating systemic metabolic factors are limited. AIMS: We aimed to develop a machine learning model incorporating systemic metabolic parameters for mortality prediction in HEV patients. METHODS: A total of 510 HEV patients from two medical centers were retrospectively enrolled and grouped into training, internal validation and external validation cohorts. Metabolic parameters (total cholesterol, HDL, LDL and diabetes) were integrated using SVM to generate a Metabolism Score. This score and other clinical variables (infection status, WBC, creatinine, age, platelet, albumin, TBIL, EGFR, INR, and GGT) were selected using LASSO regression. Five machine-learning models were developed to predict 28-day and 90-day mortality. RESULTS: Among all models, logistic regression (LR) showed the best performance, with AUROCs of 0.87, 0.98, and 0.84 for 28-day mortality and 0.86, 0.88, and 0.89 for 90-day mortality across the training, validation, and external cohorts, respectively. The LR model outperformed MELD, demonstrated good calibration and net clinical benefits, and was visualized as a nomogram. CONCLUSION: The LR model incorporating systemic metabolic factors accurately predicted short-term mortality in HEV patients and may facilitate early risk stratification and personalized management.
Faraci S, Rollo G, Alghisi F
… +12 more, Romano C, Gismondi A, Sepe AO, Cristiani L, Labriola F, Bramuzzo M, Torroni F, Mandato C, Dall'Oglio L, Caldaro T, De Angelis P, Balassone V
BACKGROUND: Chronic pancreatitis (CP) in children causes recurrent acute episodes and ductal changes that progressively impair pancreatic function. ERCP is used to manage ductal stenosis and obstruction, but evidence in...BACKGROUND: Chronic pancreatitis (CP) in children causes recurrent acute episodes and ductal changes that progressively impair pancreatic function. ERCP is used to manage ductal stenosis and obstruction, but evidence in pediatric CP is limited. AIMS: To assess the efficacy and safety of an ERCP-based management in children with genetically associated CP. METHODS: A multicentric retrospective study was performed in Italian referral centers, including consecutive children with genetically associated CP who underwent ERCP between October 2023 and June 2024. Clinical and procedural data, and outcomes were collected. Pancreatitis incidence rates before and after ERCP (PIRpre, PIRpost) were compared. RESULTS: Forty-two patients (mean age 8.1 ± 4.7 years; 61.9 % female) underwent ERCP, with a mean of 4.5 procedures per patient. All carried pathogenic variants, risk alleles, or VUS. Stents were placed in 34 patients, with upsizing in 41.2 %. Pancreatic duct stenosis was identified in 66.6 %. ERCP significantly reduced acute pancreatitis episodes (PIRpre 4.6 vs PIRpost 1.1; p = 0.0024), independently of stent placement. PEP occurred in 14.2 % of procedures, mostly mild; perforation, stent migration, and papillary bleeding were uncommon and managed conservatively. Mean follow-up time was 5.2 ± 2.7 years. CONCLUSION: ERCP significantly reduces the recurrence of pancreatitis episodes, potentially improving the quality of life.
BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) and gastric adenocarcinoma with enteroblastic differentiation (GAED) are rare and highly aggressive subtypes of gastric cancer (GC). AIMS: This study aimed to inve...BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) and gastric adenocarcinoma with enteroblastic differentiation (GAED) are rare and highly aggressive subtypes of gastric cancer (GC). AIMS: This study aimed to investigate the clinicopathological characteristics and prognostic outcomes of patients with HAS and GAED. METHODS: This multicenter retrospective study compared 107 patients with HAS/GAED with 428 patients with conventional GC (cGC) after 4:1 propensity score matching (PSM). The primary outcomes included disease-free survival (DFS), gastric cancer-specific survival (GCSS), and overall survival (OS). Survival analyses were performed using Cox proportional hazards models and Kaplan-Meier curves. RESULTS: With a median follow-up of 33 months, patients in the HAS/GAED group, compared with those in the cGC group, exhibited larger tumor size, poorer histological differentiation, higher preoperative carcinoembryonic antigen (CEA) levels, and a higher rate of human epidermal growth factor receptor 2 (HER2) overexpression (all P<0.05). Multivariate analysis identified elevated CEA levels, perineural invasion (PNI), and pathological N (pN) category as independent risk factors for poor prognosis, whereas postoperative chemotherapy was identified as a protective factor. The HAS/GAED group demonstrated significantly worse DFS (P<0.001), GCSS (P=0.001), and OS (P=0.028) compared with the cGC group. No significant prognostic differences were observed between patients with HAS and those with GAED. CONCLUSION: HAS and GAED are highly aggressive subtypes of GC, characterized by distinct clinicopathological features and an unfavorable prognosis.
BACKGROUND: Material deprivation (MD) is a key social determinant that may influence outcomes in cirrhosis, although its effect remains underdefined. AIMS: To assess the impact of MD on clinical outcomes in patients with...BACKGROUND: Material deprivation (MD) is a key social determinant that may influence outcomes in cirrhosis, although its effect remains underdefined. AIMS: To assess the impact of MD on clinical outcomes in patients with cirrhosis in a universal healthcare setting. METHODS: We retrospectively studied patients with cirrhosis residing in Genoa, first attending our Unit during 2016-2022, classified MD from residential address by prespecified criteria, and dichotomized MD into low and high via cluster analysis; we assessed modality of cirrhosis diagnosis, disease stage, follow-up adherence, hepatic decompensation requiring hospitalization, and overall survival. RESULTS: We studied 368 patients (68.5% male, median age 63 years), most with compensated disease (57.9%). Patients with low-MD were slightly older (64 years vs. 62 years; p<0.0001), more frequently diagnosed through screening (58.6% vs. 14.4%; p<0.001), and less likely to be lost to follow-up (8.3% vs. 15.5%; p<0.0001) compared to those with high-MD. The incidence of hepatic decompensation episodes requiring hospitalization was higher (incidence rate ratio: 1.95, CI 1.29-2.99) and overall survival was shorter (66.2 months, CI 59.6-72.7 vs. 93.7 months, CI 83.5-103.5) in patients with high-MD. CONCLUSION: MD significantly impacts clinical outcomes in patients with cirrhosis and is associated with worse prognosis, despite universal coverage.
BACKGROUND & AIMS: A significant subset of patients with acute pancreatitis (AP) who do not present with organ failure (OF) at admission nonetheless progress to severe acute pancreatitis (SAP). We aimed to develop and va...BACKGROUND & AIMS: A significant subset of patients with acute pancreatitis (AP) who do not present with organ failure (OF) at admission nonetheless progress to severe acute pancreatitis (SAP). We aimed to develop and validate a simple scoring system to predict progression to SAP specifically in AP patients without initial OF. METHODS: This study utilized a prospectively maintained AP database. Patients admitted without OF were included. Variable selection employed multivariable logistic regression, Boruta algorithm, and LASSO regression. A nomogram was developed, from which a simplified ACR score was derived. RESULTS: Of 3,813 eligible AP patients without OF at admission, 458 (12.0%) progressed to SAP. Six variables were independently associated with SAP progression. The resulting nomogram demonstrated strong discrimination, with AUCs of 0.834 (training), 0.833 (internal test), and 0.885 (external validation). The simplified ACR score (range 0-9) showed comparable performance (AUC 0.827, 95% CI: 0.807-0.846) and was significantly superior to APACHE II (AUC 0.655, p < 0.001), SIRS (AUC 0.732, p < 0.001) and BISAP (AUC 0.718, p < 0.001). Stratification into low- (0-3 points), intermediate- (4-6 points), and high-risk (7-9 points) groups revealed sharply increasing SAP incidence (2.9%, 16.5%, and 52.1%, respectively; p < 0.001) and worsening clinical outcomes. CONCLUSIONS: The ACR score, comprising six readily available clinical parameters, effectively stratifies the risk of SAP progression in AP patients without organ failure at admission.
Calabrese F, Pasta A, Furnari M
… +16 more, Bodini G, Grillo F, Mastracci L, Sorge A, Coletta M, Penagini R, Vecchi M, Marinoni B, Aldinio G, Pessarelli T, Visaggi P, De Bortoli N, Maniero D, Giannini EG, Savarino EV, Marabotto E
INTRODUCTION AND AIM: Guidelines recommend sampling 2-3 esophageal locations (4-6 biopsies) during EoE follow-up, but the optimal scheme is uncertain. We assessed whether two biopsies (distal, proximal) reliably classify...INTRODUCTION AND AIM: Guidelines recommend sampling 2-3 esophageal locations (4-6 biopsies) during EoE follow-up, but the optimal scheme is uncertain. We assessed whether two biopsies (distal, proximal) reliably classify activity versus three sites (distal, middle, proximal). METHODS: Retrospective analysis of EoE follow-up endoscopies (2020-2024, tertiary centers) with three-site histology. Active disease was defined as ≥15 eos/0.3 mm² in ≥1 site; sub-analyses used ≥6 and ≥1 eos/0.3 mm². We compared active/inactive classification for two-site (distal+proximal) versus three-site sampling. RESULTS: Among 634 histologic evaluations, 306 three-site sets and 293 two-site sets were positive at ≥15 eos/0.3 mm²; all 328 three-site negatives remained negative with two sites. Thus, omitting the middle site would miss 2.0 % of active disease. Two-site performance: accuracy 98.0 %, sensitivity 96 %, specificity 100 %, PPV 100 %, NPV 96 %, AUC 0.98 (95 % CI, 0.97-0.99), Cohen's κ 0.98. At ≥6 eos/0.3 mm², sensitivity 97 %, accuracy 98.6 %, AUC 0.98 (95 % CI, 0.98-0.99). At ≥1 eos/0.3 mm², sensitivity 99 %, AUC 0.99 (95 % CI, 0.98-0.99). CONCLUSIONS: In EoE follow-up, two-site (distal+proximal) biopsies provide classification nearly equivalent to three-site sampling, with only a 2 % miss rate for active disease when the middle site is omitted. This approach may reduce procedure time, patient discomfort, and costs while maintaining excellent diagnostic performance.
Precision oncology relies on precision diagnostics, and histopathological diagnosis, along with biomarker evaluation, currently represents the cornerstone for personalized treatment. In gastrointestinal neoplasms, diagno...Precision oncology relies on precision diagnostics, and histopathological diagnosis, along with biomarker evaluation, currently represents the cornerstone for personalized treatment. In gastrointestinal neoplasms, diagnostic assessment and molecular profiling are often performed on biopsy tissue, which may be quantitatively/qualitatively limited. Therefore, appropriate sample management is essential to avoid unnecessary waste and to obtain all the information necessary for treatment planning. Several factors may significantly impact biomarker testing: (i) pre-analytical issues; (ii) heterogeneity in biomarker expression; (iii) lack of standardization in biomarker testing and evaluation. Moreover, in the metastatic setting, inadequate/incomplete clinical information can lead to inappropriate sample handling, with negative implications. The application of appropriate guidelines in testing and reporting biomarker status according to clinical context is, therefore, strongly encouraged. In this position paper, the Italian Group of Gastrointestinal Pathologists (GIPAD), a section of the Italian Society of Pathological Anatomy and Cytology (SIAPeC-IAP), aims to summarize all the clinical and pathological requirements for adequate assessment of prognostic and predictive biomarkers in the gastrointestinal oncology patient, from biopsy acquisition to diagnostic reporting.
BACKGROUND: Acute liver failure (ALF) is a rapidly progressive and life-threatening condition that requires accurate risk stratification. Existing prognostic tools have limited sensitivity and generalizability. This stud...BACKGROUND: Acute liver failure (ALF) is a rapidly progressive and life-threatening condition that requires accurate risk stratification. Existing prognostic tools have limited sensitivity and generalizability. This study aimed to develop and externally validate a machine learning-based modeling framework for early in-hospital dynamic prediction of in-hospital mortality in patients with acute liver failure. METHODS: Patients with ALF were identified from the MIMIC-IV database, with an independent external cohort from Guangxi Medical University Cancer Hospital for validation. Eleven predictors were selected using LASSO regression and the Boruta algorithm. Seven ML models were trained and optimized through cross-validation and grid search. Model performance was assessed using discrimination, calibration, and decision curve analysis, with interpretability evaluated by SHAP. RESULTS: A total of 1,228 patients from MIMIC-IV and 108 external patients were included. Among all evaluated models, logistic regression demonstrated the most robust and stable performance, with AUCs of 0.802 in internal validation and 0.774 in external validation. Calibration and decision curve analyses demonstrated good clinical utility. SHAP identified temperature, vasopressor use, age, CRRT, and sedative/analgesic use as key predictors. A nomogram and online tool were developed for individualized risk prediction. CONCLUSION: This study presents an interpretable and externally validated ML model for predicting in-hospital mortality in ALF, providing a practical tool for early in-hospital dynamic risk stratification and clinical decision support.
BACKGROUND AND AIM: The benefit of combining linaclotide with polyethylene glycol (PEG) for improving bowel preparation quality and adenoma detection in patients at risk for inadequate bowel preparation remains uncertain...BACKGROUND AND AIM: The benefit of combining linaclotide with polyethylene glycol (PEG) for improving bowel preparation quality and adenoma detection in patients at risk for inadequate bowel preparation remains uncertain. This study aimed to evaluate its efficacy and safety. METHODS: From August 2022 to July 2023, a multicenter, randomized trial assigned participants to a 2-day linaclotide or placebo plus PEG regimen. The primary endpoints included adequate bowel preparation rate and mean number of adenomas detected per colonoscopy. RESULTS: The modified intention-to-treat (mITT) (n=672) and per-protocol (n=574) analyses showed no significant differences in adequate bowel preparation rates (mITT: OR 1.26, 95% CI 0.73-2.16, P=0.406; per-protocol: OR 1.46, 95% CI 0.80-2.66, P=0.222) or the mean number of adenomas (mITT: mean difference -0.02, 95% CI -0.19-0.15, P=0.832; per-protocol: mean difference -0.06, 95% CI -0.25-0.13, P=0.530) between groups. However, linaclotide and PEG increased the mean number of polyps in the right colon (0.54 ± 1.9 vs. 0.27 ± 0.8; mean difference -0.27, 95% CI -0.49- -0.05, P=0.016), particularly in patients aged ≥70 years (mean difference -1.30, 95% CI -2.48- -0.13, P=0.033). CONCLUSIONS: A 2-day linaclotide regimen failed to improve the primary endpoints of bowel preparation adequacy or adenoma detection in high-risk patients.
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer mortality in Asia, where histopathological diagnosis of endoscopic biopsy specimens remain challenging. METHODS: To address this challenge,...BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer mortality in Asia, where histopathological diagnosis of endoscopic biopsy specimens remain challenging. METHODS: To address this challenge, we developed an AI-based ESCC diagnostic system in biopsies (AI-EDS) using 1 104 H&E-stained whole slide images (WSIs) from one center, which were divided into three datasets at the patient level: 515 WSIs (including 226 malignancies) for training, 50 WSIs (22 malignancies) for validation, and 539 WSIs (149 malignancies) for internal testing. Lesion areas were annotated using an iPad-based system, and the DeepLab-v3 model, supported by a ResNet-50 backbone, was trained for analysis. AI-EDS was subsequently applied to 945 esophageal biopsy WSIs (351 malignancies) from four additional hospitals. Finally, we also assessed the model's performance on surgical resection and endoscopic submucosal dissection (ESD) specimens with a total of 173 WSIs (131 malignancies). RESULTS: The AI-EDS demonstrated high accuracy in distinguishing malignant from benign lesions in an internal test dataset, achieving an AUC of 0.986 (95.36% accuracy, 99.49% sensitivity, and 84.56% specificity). In multicenter validation across four external hospitals (945 WSIs), the system maintained strong performance (AUC range: 0.966-0.998). Notably, the AI-EDS matched diagnostic accuracy of junior pathologists (89%) while reducing interpretation time by more than half. Furthermore, the system demonstrated robust generalization capability in surgical resection and endoscopic submucosal dissection specimens (173 WSIs, AUC = 0.827). CONCLUSIONS: This multicenter validation confirms that the AI-EDS serves as a reliable, interpretable tool for computer-aided ESCC diagnosis, particularly valuable in resource-limited regions.
BACKGROUND AND AIMS: Cirrhosis progression from compensated to decompensated stage signals a deterioration in prognosis, with episodes of acute decompensation (AD) carrying a high risk of short-term mortality. Recently,...BACKGROUND AND AIMS: Cirrhosis progression from compensated to decompensated stage signals a deterioration in prognosis, with episodes of acute decompensation (AD) carrying a high risk of short-term mortality. Recently, the concept of non-acute decompensation (NAD) has emerged, representing a more insidious form of decompensation that is nonetheless associated with increased mortality. We aimed to evaluate the clinical impact of NAD in a hospital-referred hepatology population. METHODS: Single-center, retrospective, longitudinal observational study which included adult patients with compensated cirrhosis followed between 2013-2025. RESULTS: Data from 391 patients were analyzed, 72.1% male with a mean age of 59.9±11 years. Of those, 215 did not decompensate (ND), 121 developed NAD and 55 developed AD. The baseline independent predictors of NAD included a higher MELD score, lower serum albumin and non-compliance with the effective etiological treatment. AD was predicted by lower serum albumin, lower platelet count and non-compliance with the effective etiological treatment. Mortality was significantly higher in NAD (HR 10.82; p<0.001) and AD (HR 21.47; p<0.001) when compared with ND. CONCLUSIONS: Our data shows that both AD and NAD are independent predictors of mortality in cirrhosis, with the former associating more significantly than the latter. However, the occurrence of NAD, despite clinically silent, should be recognized as marker of poor prognosis.
Capasso M, Attanasio MR, Cossiga V
… +9 more, Montori M, Paccagnella A, Ricci M, Schiadà L, De Conte A, Mazzitelli F, Guarino M, Svegliati-Baroni G, Morisco F
BACKGROUND AND AIM: According to Baveno VII, non-invasive tests (NITs) should be used to rule in or out clinically significant portal hypertension (CSPH). The HVPG-3Parameters (-3P) showed good ability in the assessment...BACKGROUND AND AIM: According to Baveno VII, non-invasive tests (NITs) should be used to rule in or out clinically significant portal hypertension (CSPH). The HVPG-3Parameters (-3P) showed good ability in the assessment of severe portal hypertension (PH). Aims were to evaluate the HVPG-3P performance in prediction of endoscopic signs of PH and liver-related events (LRE), in comparison with other NITs (FIB- 4, ANTICIPATE, platelet count (PLT)/spleen-diameter). METHODS: The study retrospectively enrolled all patients with compensated advanced chronic liver disease (cACLD) who underwent upper-GI endoscopy. Any subsequently 24-months LRE was recorded. RESULTS: 291 cACLD subjects were recruited. Higher HVPG-3P, ANTICIPATE and FIB-4 and lower PLT/spleen-diameter were significantly associated with endoscopic signs of PH (p<0.001). To predict PH endoscopic signs, HVPG-3P showed good performance: comparable to ANTICIPATE (AUROC 0.744, 95%CI 0.68-0.80 vs 0.746, 95%CI 0.69-0.80); better than FIB-4 (0.68, 95%CI 0.62-0.74, p=0.02) and slightly lower than PLT/spleen ratio (0.786, 95%CI 0.73-0.83, p=0.003). In LRE prediction, HVPG-3P showed a good performance (AUROC 0.73, 95%CI 0.71-0.79), higher than the other NITs and with a high sensitivity (0.81, 95%CI 0.72-0.90) and negative predictive value (0.88, 95%CI 0.81-0.94). CONCLUSION: HVPG-3P is a simple tool for non-invasive prediction of endoscopic signs of PH and could be used to stratify the risk of LRE in ACLD patients.
BACKGROUND: Depression and anxiety were not only common but also with serious consequence in inflammatory bowel diseases (IBD) patients. The current study endeavors to define distinct depression and anxiety profiles of I...BACKGROUND: Depression and anxiety were not only common but also with serious consequence in inflammatory bowel diseases (IBD) patients. The current study endeavors to define distinct depression and anxiety profiles of IBD patients and identify central symptoms within different profiles to facilitate targeted interventions. METHODS: The research employed K-means Clustering to delineate the depression and anxiety profiles, followed by a repetition of the analysis using Latent Profile Analysis (LPA). Furthermore, network analysis was utilized to identify central symptoms within the various profiles. RESULTS: K‑means Clustering identified Cluster 1 (38.89%), Cluster 2 (45.33%) and Cluster 3 (15.78%), while LPA yielded the low-risk group (39.56%), the mild-risk group (44.22%) and the high-risk group (16.22%). A majority of patients in the three clusters were predominantly in a single LPA-derived patient class (96.1-99.0%). Network analysis revealed that connections within each symptom in PHQ-9 and GAD-7 were stronger than those between symptoms. Furthermore, PHQ 6 ("guilt"), PHQ2 ("sad mood")and GAD 7 ("feeling afraid") were identified as the central symptoms in Cluster 1. PHQ2 ("sad mood"), GAD 3("excessive worry") and GAD 1 ("nervousness") emerged as the central symptoms in Cluster 2. Additionally, GAD3 ("excessive worry"), GAD 4 ("trouble relaxing") and GAD 6("irritability") were identified as the central symptoms in Cluster 3. CONCLUSION: We defined three distinct depression and anxiety profiles among IBD patients and pinpointed central symptoms within each profile. These findings underscore the importance of directing research towards those central symptoms within each profile in order to develop targeted intervention strategies.