Colitis in a patient with familial Mediterranean fever: Is it Crohn's disease or ulcerative colitis?

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever.

Si-Ni-San alleviates intestinal and liver damage in ulcerative colitis mice by regulating cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS), a traditional Chinese medicinal formula derived from Treatise on Febrile Diseases, is considered effective in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice. However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. AIM OF THE STUDY: This study aimed to evaluate the effect, explore the bioactive ingredients and the underlying mechanisms of SNS in ameliorating ulcerative colitis (UC) and associated liver injury in dextran sodium sulphate (DSS)-induced mouse colitis models. MATERIALS AND METHODS: The effect of SNS (1.5, 3, 6 g/kg) on 3% DSS-induced acute murine colitis was evaluated by disease activity index (DAI), colon length, inflammatory cytokines, hematoxylin-eosin (H&E) staining, tight junction proteins expression, ALT, AST, and oxidative stress indicators. HPLC-ESI-IT/TOF MS was used to analyze the chemical components of SNS and the main xenobiotics in the colon of UC mice after oral administration of SNS. Network pharmacological study was then conducted based on the main xenobiotics. Flow cytometry and immunohistochemistry techniques were used to demonstrate the inhibitory effect of SNS on Th17 cells differentiation and the amelioration of Th17/Treg cell imbalance. LC-MS/MS, Real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting techniques were performed to investigate the oxysterol-Liver X receptor (LXRs) signaling activity in colon. Targeted bile acids metabolomics was conducted to reveal the change of the two major pathways of bile acid synthesis in the liver, and the expression of key metabolic enzymes of bile acids synthesis was characterized by RT-qPCR and western blotting techniques. RESULTS: SNS (1.5, 3, 6 g/kg) decreased the DAI scores, protected intestinal mucosa barrier, suppressed the production of pro-inflammatory cytokines, improved hepatic and splenic enlargement and alleviated liver injury in a dose-dependent manner. A total of 22 components were identified in the colon of SNS (6 g/kg) treated colitis mice, and the top 10 components ranked by relative content were regarded as the potential effective chemical components of SNS, and used to conduct network pharmacology research. The efficacy of SNS was mediated by a reduction of Th17 cell differentiation, restoration of Th17/Treg cell homeostasis in the colon and spleen, and the experimental results were consistent with our hypothesis and the biological mechanism predicted by network pharmacology. Mechanistically, SNS regulated the concentration of 25-OHC and 27-OHC by up-regulated CH25H, CYP27A1 protein expression in colon, thus affected the expression and activity of LXR, ultimately impacted Th17 differentiation and Th17/Treg balance. It was also found that SNS repressed the increase of hepatic cholesterol and reversed the shift of BA synthesis to the acidic pathway in UC mice, which decreased the proportion of non-12-OH BAs in total bile acids (TBAs) and further ameliorated colitis and concomitant liver injury. CONCLUSIONS: This study set the stage for considering SNS as a multi-organ benefited anti-colitis prescription based on the significant effect of ameliorating intestinal and liver damage, and revealed that derivatives of cholesterol, namely oxysterols and bile acids, were closely involved in the mechanism of SNS anti-colitis effect.

Uncovering the pharmacological mechanisms of Patchouli essential oil for treating ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemonis Herba has long been used in traditional Chinese medicine to treat inflammatory disorders. Patchouli essential oil (PEO) is the primary component of Pogostemonis Herba, and it has been suggested to offer curative potential when applied to treat ulcerative colitis (UC). However, the pharmacological mechanisms of PEO for treating UC remain to be clarified. AIM OF THE STUDY: To elucidate the pharmacological mechanisms of PEO for treating UC. METHODS AND RESULTS: In the present study, transcriptomic and network pharmacology approaches were combined to clarify the mechanisms of PEO for treating UC. Our results reveal that rectal PEO administration in UC model mice significantly alleviated symptoms of UC. In addition, PEO effectively suppressed colonic inflammation and oxidative stress. Mechanistically, PEO can ameliorate UC mice by modulating gut microbiota, inhibiting inflammatory targets (OPTC, PTN, IFIT3, EGFR, and TLR4), and inhibiting the PI3K-AKT pathway. Next, the 11 potential bioactive components that play a role in PEO's anti-UC mechanism were identified, and the therapeutic efficacy of the pogostone (a bioactive component) in UC mice was partially validated. CONCLUSION: This study highlights the mechanisms through which PEO can treat UC, providing a rigorous scientific foundation for future efforts to develop and apply PEO for treating UC.

Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

Endoscopic assessment of the J pouch in ulcerative colitis: A narrative review.

Patients with ulcerative colitis sometimes need a total colectomy with ileal pouch-anal anastomosis due to medically refractory disease or colitis-associated neoplasia. Up to 50% of patients with ulcerative colitis postoperatively develop pouchitis and the rate of chronic inflammatory pouch conditions requiring pouch excision or diverting ileostomy is reported to be 10%. In order to diagnose and monitor pouchitis, pouchoscopy is essential to assess endoscopic inflammatory findings of the J pouch and to survey neoplasia development, particularly in the remnant distal rectum. However, endoscopic protocols for the evaluation of the pouch may not be standardized worldwide and the reliability of existing disease activity indices for pouchitis has been questioned due to the lack of validation. Recently, reliable endoscopic scoring systems based on an observation of the anatomical location of the J pouch were reported and a significant association between the distribution pattern of endoscopic inflammation (i.e., endoscopic phenotype) and pouch outcomes was also uncovered. In this review, we discuss how to survey the J pouch using pouchoscopy, endoscopic indices for pouchitis disease activity, endoscopic phenotypes and classification, and the pathological mechanisms of pouchitis phenotype in patients with ulcerative colitis.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Duodenitis associated with ulcerative colitis and pouchitis after total colectomy successfully treated with upadacitinib: A case report.

A 27-year-old man had ulcerative colitis (UC) 1 year prior and underwent a colectomy and two-stage ileal pouch-anal anastomosis for medically refractory UC 6 months ago. He visited our department with epigastric pain and discomfort, increased stool frequency, and bloody diarrhea. Esophagogastroduodenoscopy revealed continuous diffuse friable mucosa, erosions, and edema in the duodenum, and pouchoscopy revealed multiple ulcers and purulent mucus adhesions. Based on endoscopic and pathological findings, the patient was diagnosed with duodenitis associated with UC and pouchitis, for which he received oral prednisolone (40 mg/day) and ciprofloxacin. The frequency of stools and occurrence of bloody diarrhea reduced, and epigastric pain and discomfort improved after 2 weeks. However, when prednisolone was discontinued, the symptoms worsened, albumin level decreased, and C-reactive protein level increased. Following this, we administered a 20 mg prednisolone sodium phosphate enema once daily, and the patient's symptoms improved. However, the symptoms relapsed when the enema was discontinued. Assuming that the patient had steroid-dependent duodenitis associated with UC and pouchitis, we initiated upadacitinib. His symptoms improved within a few days, and biomarkers returned to normal after 1 month. Nine months after initiating the upadacitinib treatment, endoscopic remission was achieved in the mucosa of the duodenum and pouch. The patient has been in clinical remission for 1 year without any adverse events.

Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.

Oral colon-targeted pH-responsive polymeric nanoparticles loading naringin for enhanced ulcerative colitis therapy.

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.

Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis.

Tofacitinib is an oral small-molecule Janus kinase (JAK) inhibitor that preferentially inhibits JAK1 and JAK3. Its efficacy in inducing and maintaining remission in ulcerative colitis (UC) as well as its safety profile has been demonstrated in multicenter, randomized, double-blind, placebo-controlled trials. Additionally, real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted, affirming its clinical efficacy in moderate-to-severe UC.

Game changer: How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis management.

Recent advancements in the treatment landscape of ulcerative colitis (UC) have ushered in a new era of possibilities, particularly with the introduction of Janus kinase (JAK)-signal transducer and activator of transcription inhibitors. These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes. With approved JAK inhibitors (JAKis), such as tofacitinib, filgotinib, and upadacitinib, clinicians now have powerful tools to modulate immune responses and gene expression, potentially revolutionizing the treatment algorithm for UC. Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission, presenting viable options for patients who have failed conventional therapies. Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy, particularly in patients with aggressive disease phenotypes or refractory to biologic agents. The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC, offering timely relief for patients with active disease and facilitating personalized treatment approaches. Despite safety concerns, including cardiovascular risks and infections, ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

Advanced CNN models in gastric cancer diagnosis: enhancing endoscopic image analysis with deep transfer learning.

Introduction: The rapid advancement of science and technology has significantly expanded the capabilities of artificial intelligence, enhancing diagnostic accuracy for gastric cancer. Methods: This research aims to utilize endoscopic images to identify various gastric disorders using an advanced Convolutional Neural Network (CNN) model. The Kvasir dataset, comprising images of normal Z-line, normal pylorus, ulcerative colitis, stool, and polyps, was used. Images were pre-processed and graphically analyzed to understand pixel intensity patterns, followed by feature extraction using adaptive thresholding and contour analysis for morphological values. Five deep transfer learning models-NASNetMobile, EfficientNetB5, EfficientNetB6, InceptionV3, DenseNet169-and a hybrid model combining EfficientNetB6 and DenseNet169 were evaluated using various performance metrics. Results & discussion: For the complete images of gastric cancer, EfficientNetB6 computed the top performance with 99.88% accuracy on a loss of 0.049. Additionally, InceptionV3 achieved the highest testing accuracy of 97.94% for detecting normal pylorus, while EfficientNetB6 excelled in detecting ulcerative colitis and normal Z-line with accuracies of 98.8% and 97.85%, respectively. EfficientNetB5 performed best for polyps and stool with accuracies of 98.40% and 96.86%, respectively.The study demonstrates that deep transfer learning techniques can effectively predict and classify different types of gastric cancer at early stages, aiding experts in diagnosis and detection.

Predictors of the efficacy of vedolizumab in patients with ulcerative colitis.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Vinegar-processed Schisandra Chinensis enhanced therapeutic effects on colitis-induced depression through tryptophan metabolism.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by its incurable nature and undefined etiology, which is often accompanied by a high prevalence of comorbid depression. The gut-brain axis has emerged as a promising treatment target in recent years. PURPOSE: This study aimed to investigate how vinegar-processed Schisandra Chinensis (VSC) enhances therapeutic effects on depressive behavior in chronic UC mice. METHODS: A chronic UC model was induced in mice using dextran sulfate sodium. The therapeutic effects of both raw and vinegar-processed Schisandra Chinensis on UC and associated depressive symptoms were assessed. Colonic mucosal damage was evaluated using hematoxylin and eosin (H&E) and Alcian blue staining. The integrity of the blood-brain barrier (BBB) and synaptic structures was visualized via transmission electron microscopy (TEM). Enzyme-linked immunosorbent assay (ELISA) was employed to quantify inflammatory cytokine levels in the colon, serum, and brain, while western blotting was performed for protein expression analysis. Additionally, metagenomic analysis was conducted to investigate gut microbiota composition. Nissl staining and immunofluorescence were used to assess hippocampal neuronal damage, and behavioral assessments including the morris water maze, open field test, forced swimming test and tail suspension test, were implemented to evaluate depressive states. Serum metabolites were analyzed using UPLC-MS/MS. RESULTS: Both raw and vinegar-processed Schisandra Chinensis significantly upregulated aryl hydrocarbon receptor (AhR), inhibited NF-κB p-p65 activation, and reduced levels of pro-inflammatory cytokine. These treatments also enhanced the expression of tight junction proteins, restored colonic mucosal and BBB integrity, alleviated damage to hippocampal neurons, and improved synaptic structure. Behavioral assessments indicated that VSC was particularly effective in ameliorating depressive-like behaviors in chronic UC mice. In the gut, both treatments reshaped the gut microbial composition, restoring the relative abundance of Duncaniella, Candidatus_Amulumruptor, Alistipes, Parabacteroides, Lachnospiraceae_bacterium, uncultured_Bacteroides_sp., Candidatus_Amulumruptor_caecigallinarius, with VSC showing more pronounced effects. Serum metabolomics revealed an increase in tryptophan levels and a decrease in kynurenine and xanthurenic acid levels with VSC, indicating that tryptophan metabolism shifted from the kynurenine pathway to the 5-HT or indole pathway. However, this phenomenon did not occur with Schisandra Chinensis (SC). CONCLUSION: This study demonstrated that the disruption of tryptophan metabolic balance served as a biological mechanism underlying the occurrence of depressive behaviors induced by UC. The application of SC following vinegar processing enhanced its regulatory effects on gut microbiota and tryptophan metabolism. This findings provided a new insight for the clinical management of gut-brain comorbidities.

Extraction, separation and efficacy of yam polysaccharide.

Yam is used as common herbal remedy in traditional Chinese medicine and is grown all over Asia. According to previous research, one of the primary bioactive components of yam is yam polysaccharide. To shed light on the mechanism of yam polysaccharide in ulcerative colitis (UC), a yam heteropolysaccharide named CYP-3a was isolated and purified using ultrasonic extraction, the trichloroacetic acid technique, DEAE cellulose-52 and a Sephadex G75 column. CYP-3a comprises rhamnus: arabinose:galactose:mannose:galacturonic acid glucuronic acid, with a molar ratio of 2.25:4.17:3.30:0.09:0.13:0.26. CCK-8 and ELISA analysis results showed that CYP-3a increased the number of dextran sodium sulphate (DSS)-induced Caco-2 cells and could reduce and inhibit their inflammatory response by lowering the amounts of secreted TNF-α and IL-6. Western blot data demonstrated that CYP-3a at various doses could suppress the endoplasmic reticulum stress-mediated apoptotic pathway generated by DSS-induced UC and down-regulate the protein levels of GRP78, CHOP and NF-κB.

[Survey on Patient Satisfaction with the Usability and Formulation of Budesonide Rectal Foam Following a Change in Head and Applicator Shape and Properties].

Budesonide Rectal Foam (BF) was introduced in 2017 and changed in November 2022 upon request, addressing the challenges encountered with liquid rectal formulations indicated for ulcerative colitis (UC). This formulation is an important agent in the treatment of rectal to sigmoid colon lesions in moderate UC. As the characteristics of the formulation of the rectal formulation are thought to influence patient satisfaction, a survey was conducted on the formulation and patient satisfaction among patients who used BF before and after the change. The survey spanned from January 2023 to May 2023. As the primary endpoint, the same patients were evaluated on the Visual Analogue Scale (VAS) for patient satisfaction. Significant variations in formulation usability and patient satisfaction were observed in 20 eligible patients before and after the change (p<0.05). Patient satisfaction with the formulation was strongly correlated with formulation usability, ease of pushing the head, and ease of insertion (r>0.7). The change in packaging was thought to improve the usability of the formulation and patient satisfaction. The formulation's usability and ease of insertion had a clear influence on satisfaction with the rectal formulation.

Biological treatment in chronic disease management: from asthma to ulcerative colitis. A review paper.

OBJECTIVE: Aim: The purpose of this article is to review the literature on the applicability of biologic agents, their mechanism of action, safety and factors affecting their choice in selected chronic conditions: asthma, psoriasis, ankylosing spondylitis and ulcerative colitis. PATIENTS AND METHODS: Materials and Methods: The electronic databases MEDLINE/PubMed and ScienceScholar were searched for studies published in English and Polish and indexed from 2018 to April 2024. Dodatkowo uwzgledniono Stanowisko Polskiego Towarzystwa Alergologicznego i Polskiego Towarzystwa Chorób Ukladu Oddechowego, rekomendacje Polskiego Towarzystwa Dermatologicznego, wytyczne Polskiego Towarzystwa Gastroenterologii i konsultanta krajowego w dziedzinie gastroenterologii oraz wytyczne Global Initiative for Asthma (GINA). CONCLUSION: Conclusions: 1. Biological therapy demonstrates a significant reduction in the severity of clinical symptoms and complications associated with a variety of disease entities. An additional value of this therapy is its effectiveness among patients who do not respond to traditional treatment strategies. 2. In the perspective of the future of biologic treatment, it is important to study potential interactions between biologic drugs and other therapeutic methods. 3. To maximize benefits while minimizing complications, requires an individualized approach for each patient.

Crohn's disease and ulcerative colitis share two molecular subtypes with different mechanisms and drug response.

BACKGROUND AND AIMS: Several therapies have been approved to treat crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease. METHODS: Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from six independent datasets and eight treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekimumab. RESULTS: Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found six S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and nine S1-specific cell types (cycling T, Tregs, cd8+ lamina propria, follicular B, cycling B plasma, inflammatory monocytes, inflammatory fibroblast, and post-capillary venules). Subtype S2 was associated with three modules related to metabolism functions and four cell types (immature enterocytes, transit amplifying, immature goblet and WNT5B+). The subtypes can be replicated in six independent datasets based on a 20-gene classifier. Furthermore, response rates to four treatments in subtype S2 were significantly higher than those in subtype S1. CONCLUSIONS: This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because two subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in IBD patients.

2-Stage and 3-stage restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis show comparable short- and long-term outcomes.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) represents the standard treatment for therapy-refractory, malignant or complicated ulcerative colitis (UC) and can be performed as a 2-stage or 3-stage procedure. This study aimed to compare the short- and long-term outcomes after 2- and 3-stage IPAA in patients with UC in our department. A retrospective analysis of 176 patients with UC who received 2- or 3-stage restorative proctocolectomy with IPAA at our institution from 2001 to 2021 was performed. Outcomes for short-term (morbidity, longer hospital stay, readmission) and long-term (pouch failure and quality of life) parameters were compared between the 2- and 3-stage procedure. Regarding short-term outcomes for all patients, in-hospital morbidity and readmission rates after any surgical stage were observed in 69% and 24%, respectively. Morbidity and readmission did not differ significantly between the 2- and 3-stage procedure in uni- and multivariate analysis. Median length of hospital stay for all stages was 17 days. The 3-stage procedure was identified as an independent factor for longer hospital stay (OR 3.8 (CI 1.3-10.8), p = 0.014). Pouch failure and failure of improved quality of life during long-term follow-up occurred both in 10% of patients, with no significant differences between the 2- and 3-stage procedure in uni- and multivariate analysis. Our data suggest that both the 2- and 3-stage proctocolectomy with IPAA demonstrate favourable and comparable postoperative short- and long-term outcomes, with a high rate of improved quality of life in patients with UC.

Activation of AMPK/SIRT1/FOXO3a signaling by BMS-477118 (saxagliptin) mitigates chronic colitis in rats: uncovering new anti-inflammatory and antifibrotic roles.

Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK/SIRT1/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK/SIRT1/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients.