Ahmed SalmanInternal Medicine Department, Faculty of Medicine, Cairo University, Cairo, EgyptCorrespondence: Ahmed Salman, Internal Medicine Department, Faculty of Medicine, Cairo University, Al-Saray Street, El Manial, Cairo, 11956, Egypt, Tel +20 100 046 8664, Email awea84@kasralainy.edu.egAbstract: Eosinophilic gastritis (EoG) and eosinophilic duodenitis (EoD) are chronic, immune-mediated gastrointestinal disorders in which tissue eosinophil density is both an accessible biomarker and a common trial endpoint. Recent targeted studies have shown trial-level divergence between objective endpoints and patient-reported outcomes. This narrative review examines mechanisms, measurement tools, conventional treatment, and biologic studies published or registered through October 2026. In a 26-patient benralizumab trial, histologic remission occurred in 77% of treated patients and 8% of placebo recipients, yet symptom and endoscopic changes were not statistically different. In the DEGAS trial, dupilumab improved histology and endoscopy at 12 weeks, while the symptom change did not differ significantly from placebo. Two Phase 3 lirentelimab trials with registry-posted results met histologic endpoints without significant symptom benefit. Paired individual data are needed to establish within-person discordance. These findings do not make eosinophils unimportant. They show that target engagement, biological disease control, patient status, treatment success, and durability answer different questions. We propose a provisional framework that separates biological disease activity, structural damage, and patient status; treats burden and safety as modifiers of treatment success; and applies duration as a temporal qualifier. The framework favors domain-specific reporting and named discordance states over a single remission score. Patchy disease, variable microscopic field geometry, shallow mucosal sampling, nonspecific symptoms, and limited EoD-specific validation remain important constraints. Patient-informed international consensus and prospective longitudinal testing are needed before the proposed states can guide routine care.Keywords: eosinophilic gastritis, eosinophilic duodenitis, biologic therapy, treatment outcome, remission induction
Serge Chooklin, Serhii ChuklinSurgical Department, Saint Paraskeva Medical Center, Lviv, UkraineCorrespondence: Serge Chooklin, Email chooklin_serge@hotmail.comAbstract: Acute pancreatitis is a heterogeneous inflammatory disease in which severe forms are frequently complicated by intestinal barrier failure, dysbiosis, bacterial translocation, infected necrosis, systemic inflammation, and organ dysfunction. Growing clinical and experimental evidence suggests that the gut microbiota may contribute to disease progression and represents a potential, although incompletely validated, therapeutic target. Importantly, acute pancreatitis–associated dysbiosis involves not only taxonomic shifts but also functional metabolic reprogramming, including reduced short-chain fatty acid production, altered microbial bile acid transformation, and disturbances in amino acid and lipid metabolism that may contribute to barrier dysfunction and systemic inflammation. This review synthesizes current evidence on microbiota-oriented strategies in acute pancreatitis, with emphasis on clinical applicability, mechanistic rationale, and safety. This narrative review integrates clinical guidelines, randomized trials, meta-analyses, cohort studies, metagenomic and metabolomic investigations, and experimental studies published mainly between 2002 and 2026. Among clinically supported strategies, early oral or enteral nutrition has the strongest evidence base and may help preserve mucosal integrity while limiting the ecological consequences of fasting and critical illness. Antimicrobial stewardship is also fundamental, because unnecessary antibiotic exposure may aggravate dysbiosis, impair colonization resistance, and promote resistant organisms. Selective digestive decontamination has historical clinical evidence but is not established for routine contemporary practice. Prebiotics, dietary fibers, postbiotics, and metabolite-oriented approaches are mechanistically promising, but clinical evidence remains limited. GV-971 is currently supported predominantly by preclinical experimental data. Probiotics and synbiotics require caution, particularly in predicted severe disease, because clinical benefits are inconsistent and important safety concerns have been reported. Fecal microbiota transplantation and washed microbiota transplantation remain investigational and should not be used routinely outside controlled protocols. At present, microbiota-oriented management should prioritize evidence-based supportive measures, particularly early oral or enteral nutrition and rational antimicrobial use. Future studies should combine clinical outcomes with standardized microbiome, metabolome, barrier, and resistance endpoints to determine whether direct microbiota modulation can become a safe and reproducible component of personalized therapy.Keywords: acute pancreatitis, gut microbiota, intestinal barrier, enteral nutrition, antimicrobial stewardship, short-chain fatty acids
Anne-Mette Haase,1,* Jens Kelsen,1,* Jørgen Agnholt,1,2,* Mia Bendix3,*1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2National Center of Autoimmune Diseases, Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Medicine, Regional Hospital Randers, Randers, Denmark*These authors contributed equally to this workCorrespondence: Anne-Mette Haase, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark, Email annehaas@rm.dkObjective: Remission in patients with inflammatory bowel disease appears to plateau at 30– 50% within the first year of biological monotherapy. Patients with Crohn’s disease (CD) and ulcerative colitis (UC) on monotherapy with biologics or small molecules may face this therapeutic ceiling, not reaching remission in relation to bowel inflammation and/or extraintestinal manifestations (EIM). Dual therapy, combining two advanced therapies, has been proposed for this challenging population. We aimed to investigate real-life safety, steroid free- and clinical response in dual therapy.Materials and Methods: Medical records from September 2018 to September 2023 were reviewed for CD and UC patients undergoing dual therapy with biologics and/or small molecules due to refractory bowel inflammation or EIM in outpatient gastroenterology clinics at Aarhus University Hospital and Regional Hospital Randers. Patients treated for at least three months were included and followed until treatment discontinuation or the end of the study. Patient characteristics, clinical outcomes, adverse events, and clinical response data were collected at baseline and follow-up.Results and Conclusions: Seventy-four patients (47 with CD and 27 with UC) received a total of 79 dual therapies. The median dual therapy duration was 488 days for CD and 412 days for UC. The most common combinations were adalimumab/ustekinumab in CD (46%) and adalimumab/vedolizumab in UC (35%). Clinical response at follow-up was achieved in 50% of CD patients and 45% of UC patients and steroid-free follow-up in 80% of CD patients and 52% of UC patients. Severe adverse events (SAEs) occurred in eight out of 79 dual therapies. Treatment failure and adverse events within the first three months of dual therapy were not included. This study demonstrates substantial rate of clinical response and an acceptable safety profile in complex IBD patients receiving dual therapy. Still, the risk of SAEs must be balanced against the therapeutic benefit.Keywords: Crohn’s disease, ulcerative colitis, biological therapy, dual therapy, safety
Raffaele Buono,1 Marzia La Franca,1 Paolo Girardi,2 Marco Di Pascoli11Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine – DIMED, University of Padova, Padova, Italy; 2Department of Environmental Sciences, Informatics and Statistics, Ca’ Foscari University of Venice, Venice, ItalyCorrespondence: Marco Di Pascoli, Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine – DIMED, University of Padova, Padova, Italy, Email marco.dipascoli@unipd.itBackground and Aims: While systemic arterial pressure typically declines with advancing cirrhosis, the relationship between arterial hypertension (AH) and clinical outcomes in compensated cirrhosis is not defined. We aimed to investigate the association between AH and non-invasive markers of portal hypertension and liver-related complications.Methods: We conducted a retrospective cohort study including 189 patients with compensated liver cirrhosis, stratified according to history of AH. Clinical, laboratory, endoscopic, and outcome data, including cirrhosis decompensation, liver transplantation, and mortality, were collected. Median follow-up time was 5 years, IQR 3.2– 5.0 years. Spleen diameter was assessed at baseline and serially during follow-up.Results: Of the 189 patients, 111 had a history of AH. Compared with non-hypertensive patients, those with AH were older, had higher platelet counts, smaller spleen diameter, and fewer indirect signs of portal hypertension, including esophageal varices, congestive gastropathy, and portosystemic shunts (all p < 0.05). During follow-up, spleen size remained stable in hypertensive patients, whereas a progressive increase in spleen diameter was observed in patients without AH. Despite these differences, no significant differences were found between groups in terms of cirrhosis decompensation or overall mortality. However, patients without AH had a significantly higher rate of liver transplantation (p = 0.008).Conclusion: In compensated cirrhosis, AH is associated with fewer indirect signs of portal hypertension, including smaller and stable spleen size. These findings support the concept that patients with AH exhibit a distinct hemodynamic phenotype, characterized by less pronounced portal hypertensive state and circulatory dysfunction.Keywords: liver cirrhosis, arterial hypertension, portal hypertension, splenomegaly
Colorectal cancer (CRC) remains a major global health concern, and experimental animal models continue to play a key role in understanding its development and in evaluating preventive and therapeutic strategies. Among these, the 1,2-dimethylhydrazine (DMH)-induced rat model is widely used; however, substantial variability in dosing regimens and study design has limited consistency across studies. The present systematic review aimed to synthesize existing evidence on DMH-induced colorectal carcinogenesis in rats, with particular attention to how dose, duration, and route of administration influence pathological outcomes. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science from January 2010 to December 2025. Eligible studies were screened and analyzed based on predefined inclusion criteria. Data were extracted on induction protocols, histopathological findings, and study characteristics. Across the 430 included studies, notable heterogeneity was observed in experimental protocols. Nevertheless, certain patterns emerged. Higher-dose, shorter-duration regimens were more frequently associated with early preneoplastic lesions such as aberrant crypt foci (ACF), whereas lower-dose, longer-duration protocols tended to be linked with more advanced tumor development. Subcutaneous administration appeared to provide more consistent results compared to other routes. These findings suggest that the choice of protocol should be guided by the intended stage of carcinogenesis under investigation. Importantly, the interpretation of these findings should be approached with caution. Many studies lacked detailed reporting of methodological parameters, and quantitative synthesis was limited by incomplete data. As such, the proposed framework should be viewed as a practical guide rather than a definitive standard. In conclusion, DMH-induced CRC models in rats remain valuable but highly sensitive to experimental design. Greater standardization and more rigorous reporting are needed to improve reproducibility and strengthen the translational relevance of future studies.
