Inflammatory Bowel Disease and Colorectal Cancer.

Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.

Prevalence, characteristics, management, and outcomes of difficult-to-treat inflammatory bowel disease.

BACKGROUND AND AIM: Criteria for "difficult-to-treat" Inflammatory Bowel Disease (IBD) (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD. METHODS: We conducted a retrospective study in two tertiary centers in Italy. RESULTS: Among 1736 IBD patients treated with biologics/advanced small molecules, 430 (24.8%) met at least one DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action.In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (OR 6.55, 1.93-40.98, p=0.011; and OR 10.12, 3.01-63.14, p=0.002, respectively). In Crohn's disease (CD), multiple localizations (L3+L4) (OR 3.04, 1.09-8.34, p=0.03), stricturing (OR 2.24, 1.52-3.34, p<0.001) and penetrating (OR 2.33, 1.55-3.53, p<0.001) behaviors, and perianal disease (OR 2.49, 1.75-3.53, p<0.001) were the main risk factors for DTT.Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74, 1.27-2.41 p=0.001) but protective in UC (OR 0.65, 0.45-0.93 p=0.019).The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%).Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence. CONCLUSIONS: DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.

The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases.

Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.

Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment.

The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn's disease and ulcerative colitis.

Small Bowel Cancer in Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that frequently affects the small bowel. Individuals diagnosed with CD are at increased risk of developing bowel cancer compared to the general population. Small bowel cancer is a rare but significant CD complication. Adenocarcinoma represents the most prevalent of these neoplasms, followed by neuroendocrine tumors and sarcomas. The primary risk factors identified are being of the male sex, disease duration, previous surgical intervention, perianal disease, and chronic inflammation. The precise etiology remains unclear. Another crucial issue concerns the role of immunomodulators and advanced therapies. By inhibiting inflammation, these therapies can reduce the risk of cancer, which is often initiated by the inflammation-dysplasia-adenocarcinoma sequence. In accordance with the most recent guidelines, it is not necessary to conduct surveillance in patients with small bowel cancer among CD patients, as it is considered a rare disease. Nevertheless, it is of significant importance for gastroenterologists to be aware of this potential CD complication, as well as the patients who are most at risk of developing it. The purpose of this review is to provide a comprehensive overview of CD-SBC, focusing on epidemiology, etiopathogenesis, risk factors, diagnosis, and the role of advanced therapies in CD-SBC.

A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities.

Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.

Immunity in digestive diseases: new drugs for inflammatory bowel disease treatment-insights from Phase II and III trials.

BACKGROUND: Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), continues to challenge treatment paradigms. Advancements in therapeutic options have been have been driven by Phase 2 and 3 clinical trials of new drug classes, particularly sphingosine-1-phosphate (S1P) modulators and interleukin-23 (IL-23) inhibitors. METHODS: This review synthesizes findings from Phase 2 and 3 clinical trials conducted up to early 2024, focusing on the impact of S1P modulators and IL-23 inhibitors on IBD management. Drugs such as ozanimod, etrasimod, risankizumab, mirikizumab, guselkumab, and brasikumab were evaluated for their efficacy and safety profiles. RESULTS: S1P modulators, such as ozanimod and etrasimod, effectively regulate immune cell trafficking to reduce inflammation and several trials highlight their clinical effectiveness in both inducing and maintaining remission in IBD, highlighting its long-term safety and sustained therapeutic effects. Additionally, IL-23 inhibitors including risankizumab, mirikizumab, and guselkumab, which disrupt key inflammatory cytokine pathways, have already shown significant effectiveness in inducing and maintaining remission in both CD and UC, with favorable safety profiles across multiple studies, suggesting their potential as critical components in managing IBD. CONCLUSIONS: The clinical trials indicate that both S1P modulators and IL-23 inhibitors offer promising therapeutic benefits and maintain strong safety profiles, positioning them as potential cornerstone treatments for IBD. Despite these advancements, further exploration into long-term safety and the development of personalized treatment strategies is essential for maximizing clinical outcomes.

Vedolizumab versus ustekinumab in Crohn's disease with prior anti-tumor necrosis factor failure: an updated meta-analysis.

Ustekinumab and vedolizumab are key treatment options for Crohn's disease patients who fail anti-tumor necrosis factor (TNF) therapy. This updated meta-analysis aims to compare the efficacy and safety of these two drugs. We performed a systematic review in PubMed, Embase , and Cochrane databases searching for randomized and nonrandomized studies comparing vedolizumab versus ustekinumab in patients with Crohn's disease with previous anti-TNF failure or intolerance. The primary outcome was steroid-free clinical remission (SFR) at the pos-induction (12-16 weeks) and maintenance period (48-52 weeks). The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I2 statistics. This meta-analysis included 11 studies and 2724 patients. There was a significant difference favoring ustekinumab in SFR at pos-induction (OR, 1.44; 95% CI, 1.11-1.88; P  = 0.006; I2  = 27%) and maintenance periods (OR, 1.86; 95% CI, 1.23-2.82; P  = 0.003; I2  = 80%), in clinical remission at pos-induction period (OR, 2.04; 95% CI, 1.58-2.63; P  < 0.001; I2  = 3%), and in treatment discontinuation due to adverse events (OR, 0.31; 95% CI, 0.16-0.60; P  < 0.001; I2  = 0%). In patients with Crohn's disease with prior anti-TNF failure, ustekinumab showed higher SFR during both the pos-induction and maintenance period and a lower rate of treatment discontinuation due to adverse events.

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

BACKGROUND AND AIMS: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. METHODS: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. RESULTS: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. CONCLUSION: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.

BACKGROUND: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection. METHODS: This international, randomised controlled trial was done in six hospitals and tertiary care centres in the Netherlands and Italy. Eligible patients were aged 16 years or older and had Crohn's disease that was previously confirmed by endoscopy in the terminal ileum or ileocolic region (L1 or L3 disease), with an imaging update in the past 3 months (ultrasound, MRI, or CT enterography). Eligible patients were scheduled to undergo primary ileocolic resection with ileocolic anastomosis. Enrolled patients were assigned by use of simple random allocation (1:1) to either extended mesenteric resection (intervention) or conventional mesenteric sparing resection (control). The primary endpoint was endoscopic recurrence 6 months after surgery. Analyses were done in all patients with primary endpoint data, excluding those who had no anastomosis, a postoperative diagnosis other than Crohn's disease, or withdrew consent. This trial was registered with ClinicalTrials.gov, NCT04538638. FINDINGS: Between Feb 19, 2020, and April 24, 2023, we assessed 217 patients for eligibility. 78 patients were excluded due to failure to meet the inclusion criteria or refusal to participate. 139 patients were enrolled and randomly assigned to either extended mesenteric resection (n=71) or mesenteric sparing resection (n=68). All 139 patients underwent surgery. Six patients were excluded after random assignment due to withdrawal of consent (n=2), postoperative diagnosis other than Crohn's disease (n=2) and no anastomosis performed (in case of a stoma; n=2). Two patients were lost to follow-up, and two more patients deviated from the protocol by undergoing investigations other than endoscopy 6 months after. 133 patients were included in the baseline analysis (67 in the extended resection group and 66 in the sparing resection group) of whom 57 (43%) were male. Baseline characteristics were similar between the groups, and median patient age was 36 years (IQR 25-54). 131 patients were analysed for the primary outcome. There was no difference between groups in the rate of endoscopic recurrence at 6 months after surgery (28 [42%] of 66 patients in the extended mesenteric resection group vs 28 [43%] of 65 patients in the mesenteric sparing resection group, relative risk 0·985, 95% CI 0·663-1·464; p=1·0). Five (8%) of 66 patients in the extended mesenteric resection group had anastomotic leakage within the 30 days after surgery, as did one (2%) of 65 in the mesenteric sparing group. Postoperative complications of Clavien-Dindo grade IIIa or higher were reported in seven (11%) patients in the mesenteric resection group and five (8%) in the mesenteric sparing group. INTERPRETATION: Extended mesenteric resection was not superior to conventional resection with regard to endoscopic Crohn's disease recurrence. These data support the guideline-recommended mesenteric sparing approach. FUNDING: Topconsortia voor Kennis en Innovatie-Topsector Life Sciences & Health.

Evaluating the pharmacokinetics of upadacitinib for the treatment of moderate-to-severe Crohn's disease.

INTRODUCTION: Janus kinases (JAK) are enzymes involved in signaling pathways that activate the immune system. Upadacitinib, an oral small molecule, is the first JAK inhibitor approved by FDA and EMA for the treatment of moderately to severely active Crohn's disease (CD), following successful phase II and III trials. Compared to other JAK inhibitors, upadacitinib has a high selectivity toward JAK1. This characteristic could improve its efficacy and safety. AREAS COVERED: This review provides an overview of the available knowledge on the pharmacokinetics of upadacitinib as induction and maintenance therapy for CD. EXPERT OPINION: The approval of newer targeted small molecules drug, including JAK inhibitors, marked a significant advancement in terms of effectiveness. In fact, the oral administration, the rapid absorption, the excellent bioavailability and the short serum time of maximum concentration are some of the advantages compared to biologics. The selective inhibition of JAK1 by upadacitinib allows for high efficacy while maintaining a reliable safety profile.

Positioning risankizumab in the treatment algorithm of moderate-to-severe Crohn's disease.

Risankizumab is a humanized monoclonal antibody that inhibits the p19 subunit of IL-23 cytokine. Recently it has been approved for the treatment of patients with moderate-to-severe Crohn's disease (CD). We conducted a scoping review to summarize the available data on risankizumab and to define its positioning in the treatment algorithm of CD. Pubmed, Embase and Scopus databases were searched up to Oct 31, 2023 to identify studies reporting efficacy and safety data of risankizumab in patients with CD. Risankizumab is an effective and safe drug for the management of patients with moderate-to-severe CD. It could be used as first-line therapy in biologic-naive patients and in patients who have previously failed other biological therapies.

When we eat the food is processed and absorbed by the gastrointestinal tract. Sometimes, in some people, the gastrointestinal tract gets inflamed, causing problems like tummy ache and diarrhea: this condition is called Crohn's disease. To help turn off this inflammation and make people with Crohn's disease feel better, there's a new treatment called risankizumab. Risankizumab binds to the proteins in the body that cause inflammation and blocks their effects. This helps to reduce gastrointestinal inflammation and relieve its symptoms. Scientific studies have shown that is effective, safe, and it starts working quickly. Patients using this treatment do not have to go to the hospital every time. After three times in the outpatient's clinic, they can continue the treatment comfortably at home using a small device that sticks to the body and administers the medicine.

Accuracy of Information given by ChatGPT for Patients with Inflammatory Bowel Disease in Relation to ECCO Guidelines.

BACKGROUND: As acceptance of artificial intelligence [AI] platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of inflammatory bowel disease [IBD] remains unclear. METHODS: In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: [1] Crohn's disease [CD], ulcerative colitis [UC], and malignancy; [2] maternal medicine; [3] infection and vaccination; and [4] complementary medicine. Responses given by ChatGPT were assessed for accuracy [1-completely incorrect to 5-completely correct] and completeness [3-point Likert scale; range 1-incomplete to 3-complete] by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines. RESULTS: In terms of accuracy, most replies [84.2%] had a median score of ≥4 (interquartile range [IQR]: 2) and a mean score of 3.87 [SD: ±0.6]. For completeness, 34.2% of the replies had a median score of 3 and 55.3% had a median score of between 2 and <3. Overall, the mean rating was 2.24 [SD: ±0.4, median: 2, IQR: 1]. Though groups 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the four question groups [Kruskal-Wallis test p > 0.05]. However, statistical analysis for the different individual questions revealed a significant difference for both accuracy [p < 0.001] and completeness [p < 0.001]. The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning. CONCLUSION: This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinics and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.

Gut Microbiota Metabolites: Unveiling Their Role in Inflammatory Bowel Diseases and Fibrosis.

In recent years, there has been a growing focus on the intricate interplay between the gut microbiota and host health, specifically in the context of inflammatory bowel diseases (IBDs). The gut microbiota produces a diverse array of metabolites, influencing the host's immune response and tissue homeostasis. Noteworthy metabolites, such as short-chain fatty acids, bile acids, and indoles, exert significant effects on intestinal inflammation and fibrosis. This review integrates current research findings to clarify the mechanisms through which gut microbiota metabolites contribute to the progression of IBD and fibrosis, offering insights into potential therapeutic targets and strategies for managing these intricate gastrointestinal conditions. The unraveling of the complex relationship between gut microbiota metabolites and inflammatory processes holds promise for the development of targeted interventions that could lead to more effective and personalized treatment approaches for individuals affected by IBD and subsequent intestinal fibrosis.

Ultrasound remission after biologic induction and long-term endoscopic remission in Crohn's disease: a prospective cohort study.

Background: The Bowel Ultrasound Score (BUSS) accurately detects therapy-related changes by using the Simple Endoscopic Score for Crohn's disease (SES-CD) as the reference standard. We aimed to evaluate ultrasound remission as a treatment target and its prediction for long-term endoscopic remission. Methods: This single-centre prospective observational study, based at a tertiary referral centre in Milan, Italy, enrolled, between March 1, 2018, and January 31, 2021, adult patients with active CD (SES-CD >2) who were starting biologics. Colonoscopy and IUS was performed at baseline and at 12 months (mean 12.8 ± 4.2). The primary outcome was the predictive value of ultrasound remission at week 12 (BUSS ≤3.52) for long-term endoscopic remission at 12 months. The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was also calculated and optimal cut-point to detect endoscopic remission was identified through ROC analysis. Findings: 93 patients with CD were included. Of these, 22 patients (24%) achieved endoscopic remission. Week 12 ultrasound remission predicted endoscopic remission (59% compared with 41% of the patients who were not in ultrasound remission; OR 9.93, 95% CI 3.10-31.80; p < 0.001), while week 12 calprotectin values (<50, <100, <250 µg/g) did not. Week 12 ultrasound activity was associated with failure to achieve long-term endoscopic remission (NPV 87%, PPV 54%). IBUS-SAS cut-off to discriminate endoscopic remission was 22.8 (AUC 0.906). ROC curve comparison showed no-significant difference between BUSS and IBUS-SAS (p = 0.46) for detecting endoscopic remission. Interpretation: Early ultrasound remission predicts long-term endoscopic remission, making it a valuable early treatment target for clinical practice and in clinical trials. Larger multicentre validation studies are warranted to confirm these findings. Funding: None.

The learning curve for using intestinal ultrasonography.

BACKGROUND AND AIMS: Intestinal ultrasonography (IUS) is challenging to learn. This prospective study examined how the accuracy of IUS increases with operator experience ("learning curve") and if prior abdominal ultrasound experience facilitates the learning process. METHODS: The study included two trainees with limited abdominal ultrasound experience (< 50 exams) and two with extensive experience (> 500 exams). Each trainee performed 99 examinations and reported four IUS findings. An expert sonographer repeated the exam, and concordance (k) between the expert and trainees was assessed in three consecutive testing periods of 33 exams each. RESULTS: A progressive improvement in concordance was observed for all IUS findings from Period 1 to Period 3, overall and for both groups of trainees, although those with experience in abdominal ultrasound had faster learning curves. The minimum number of examinations required to achieve concordance with the expert operator for detecting increased bowel wall thickness was 84 and detecting bowel dilatation was 79. However, a minimum of 97 examinations was necessary to achieve concordance for detecting intra-abdominal complications, considered an advanced IUS competence. CONCLUSION: Basic competence in IUS can be acquired with relatively few examinations, while advanced competence requires more extensive training, particularly for gastroenterologists without abdominal ultrasound experience.

The gut-brain axis: Correlation of choroid plexus volume and permeability with inflammatory biomarkers in Crohn's disease.

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.

Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study.

BACKGROUND AND AIMS: Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy. METHODS: Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk. RESULTS: Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18-8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19-1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06-2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03-2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7. CONCLUSIONS: A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.

The role of filgotinib in ulcerative colitis and Crohn's disease.

Filgotinib is an oral small molecule that selectively inhibits JAK1. It is already approved for the treatment of moderately to severely active ulcerative colitis (UC). Ongoing studies are evaluating the efficacy and safety of filgotinib in Crohn's disease (CD). The purpose of this review is to summarize the available data regarding filgotinib in the management of UC and CD. We used Pubmed, Embase and clinicaltrials.gov websites to search all available data and currently ongoing studies regarding the efficacy and safety of filgotinib in inflammatory bowel diseases. Filgotinib is an effective and safe drug for the management of biologic-naive and biologic-experienced patients with moderate-to-severe UC. The same efficacy results have not been achieved in CD.

Filgotinib is an oral medication that inhibits the activity of the JAK1 enzyme. It has received approval from the European Medicines Agency for the treatment of moderate-to-severe ulcerative colitis, a condition characterized by inflammation in the lower part of the digestive tract. Filgotinib has a rapid mechanism of action and is effective at relieving the symptoms of ulcerative colitis and maintaining this improvement. However, its use is recommended with caution in patients who have risk factors such as heart and blood vessel issues, active smoking, a history of cancer, or those who are elderly (over 65 years old), and only when there are no other viable treatment options available. Although filgotinib was also studied for managing moderate-to-severe Crohn's disease, a chronic inflammatory condition affecting the digestive system, it did not pass phase III clinical trials and will not be available for this indication.

Treat-to-Target and Regular Surveillance of Inflammatory Bowel Disease Are Associated with Low Incidence and Early-Stage Detection of Malignancies: A Retrospective Cohort Study.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), increase the risk of malignancies, particularly colorectal cancer (CRC). We aimed to assess the incidence of malignancies in IBD patients managed using a treat-to-target approach and recommended surveillance. We retrospectively searched the electronic databases of two tertiary IBD centers in Milan from 2010 to 2019 for new diagnoses of malignancy in patients with pre-existing IBD. A total of 5239 patients with a follow-up of 19,820 years were included. In total, 71 malignancies were diagnosed in 70 patients (38 CD, 32 UC) with a mean age of 52.9 years, of whom 64% were former or active smokers. The annual incidence of all malignancies was 358 per 100,000 patient years (95% CI 275-444), and the standardized incidence rate (SIR) was 0.93 (95% CI 0.73-1.16). Gastrointestinal cancers were the most frequent (n = 17, 23.9%), in particular, CRC (n = 9), with an incidence of 45 per 100,000 (95% CI 15-74) and an SIR of 1.18 (95% CI 0.54-2.09). CRC occurred mainly in UC patients (6/8), while small bowel cancer was seen in CD patients (5/9). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers. No significant difference in incidence was found between CD or UC. Death occurred in nine patients (11%) and was due to cancer in eight of these cases, two of which were IBD-related. Most malignancies included in the surveillance were diagnosed at early (I-II) stages (20 vs. 4, p < 0.05). In patients with IBD, treat-to-target and strict surveillance were associated with a low incidence of cancer, similar to that of the general population, and the detection of malignancies at an early stage.