Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis. DESIGN: HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo. RESULTS: HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo. CONCLUSION: This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

Predictive Value of Bowel Ultrasound in Crohn's Disease: A 12-Month Prospective Study.

BACKGROUND & AIMS: Mucosal healing is associated with better outcomes in Crohn's disease (CD). Colonoscopy is invasive and poorly tolerated. Bowel ultrasound (US) is a noninvasive tool that increasingly is being used for CD assessment. We assessed the predictive role of baseline bowel US findings on disease course in a large prospective cohort of CD patients for 12 months. METHODS: Ileocolonic CD consecutive patients were followed up for 12 months after performing bowel US. The negative course of CD, defined as the need for steroids and/or change of therapy and/or hospitalization and/or the need for surgery, was assessed. We evaluated this composite end point and subsequently considered each individual end point separately. Predictors of negative disease course were analyzed by logistic regression analysis. RESULTS: There were 225 ileal and/or colonic CD consecutive patients included in the study. We analyzed the association between baseline bowel US parameters and endoscopic activity (defined as a Simplified Endoscopic Activity score for CD > 2) to set up a noninvasive quantitative ultrasound-based score (bowel ultrasound score). The multivariable analysis identified the following independent predictors of a worse outcome throughout the 12-month period as follows: bowel ultrasound score greater than 3.52 (odds ratio [OR], 6.97; 95% CI, 2.87-16.93; P < .001), presence of at least 1 disease complication (stricture, fistula, abscess) at baseline bowel US (OR, 3.90; 95% CI, 1.21-12.53; P = .021), fecal calprotectin value of 250 µg/g or greater at baseline (OR, 5.43; 95% CI, 2.25-13.11; P < .001), and male sex (OR, 2.60; 95% CI, 1.12-6.02; P = .025). CONCLUSIONS: Bowel US predicts the 12-month course in CD.

Maintaining the Quality Standards of Care for Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

Since February 20, 2020, the SARS-COV2 infection has spread in Lombardy, and in the rest of the Italian regions, forcing our government to impose a national lockdown.1 Hospitals have been forced to adapt and to restructure their units to cope with this urgent new critical situation.2 Alternative solutions have been found to manage patients with inflammatory bowel disease (IBD), including remote monitoring, drug home delivery, limitations for infusion units, and patient education on measures to prevent infection,3 to maintain high-quality care.4.

Effects of low-dose aspirin on clinical outcome and disease progression in patients with gastroenteropancreatic neuroendocrine neoplasm.

Objective: The chemopreventive effect of aspirin (ASA) has been observed in the setting of colorectal cancer and other solid neoplasms. Recently, ASA has demonstrated a promising anti-proliferative effect on GEP-NENs in vitro. However, the direct anti-neoplastic impact of ASA on GEP-NEN clinical outcome is yet to be clarified. Materials and methods: All the GEP-NEN patients followed up in three European Centers from January 2005 to September 2016 were retrospectively enrolled. Patients taking ASA in doses of 75-100 mg daily for cardiovascular prevention for at least six months were evaluated. The possible association between ASA and disease grading, staging, primary site, OS and PFS were evaluated. Results: Two hundred fifty one patients were included (117 males, median age 63 years). Of these, 64 patients were prescribed with ASA. No clear impact on OS or PFS was observed in GEP-NEN patients taking ASA compared to those not taking it. ASA intake was related with the patients' older age. At Cox multivariate analysis, stage IV and Ki-67 resulted independent predictors for OS and PFS. In the setting of intestinal NENs, a suggestive, but not statistically significant, protective role of ASA on PFS was observed [HR 0.41 (95% CI: 0.13-1.29)]. Conclusions: Despite ASA showed promising anti-proliferative effects in vitro and a chemopreventive action in NENs has been reported, a clear impact of ASA on survival in NENs has not emerged from the present study. However, in the subgroup of patients with small-intestine NENs, ASA showed a trend toward a protective role.

Endoscopic ultrasound appearance of pancreatic serotonin-staining neuroendocrine neoplasms.

BACKGROUND/OBJECTIVES: The pancreatic localization of serotonin-staining neuroendocrine neoplasms is extremely rare. This is a retrospective study aimed at analyzing the endoscopic ultrasound appearance of pancreatic serotoninoma. METHODS: Between 2010 and 2016, all consecutive patients with histologically proven pancreatic serotoninoma who had undergone endoscopic ultrasound were enrolled. RESULTS: Eight patients (six F, median age 68.5 years) had a diagnosis of pancreatic serotoninoma and underwent endoscopic ultrasound examinations. Median diameter of the lesion was ten mm. The nodule echotexture was hypoechoic in seven out of eight cases. The most frequent localization was the pancreatic neck (four); in three cases, the tumor was located in the pancreatic head and in one in the body. In seven cases the tumor caused a main pancreatic duct dilation; in three cases also the secondary ducts were dilated. In one case a dilation of the common bile duct was observed. At contrast-enhanced endoscopic ultrasound no one showed the typical contrast-enhancement. Elastography (available in two patients) showed a rigid pattern of the lesion. CONCLUSIONS: From this case series a specific endoscopic ultrasound appearance resulted for pancreatic serotoninoma, different from other types of pancreatic neuroendocrine neoplasm, but it is difficult to differentiate it from a pancreatic adenocarcinoma or an intraductal papillary mucinous neoplasm.

Relevance of vitamin D deficiency in patients with chronic autoimmune atrophic gastritis: a prospective study.

BACKGROUND: Chronic autoimmune atrophic gastritis (CAAG) is an autoimmune disease characterized by hypo/achlorhydria. A role of CAAG in the pathogenesis of nutritional deficiencies has been reported, therefore we hypothesized a possible association between CAAG and 25-OH-Vitamin D [25(OH)D] deficiency. Aim of the present study is to evaluate the prevalence of 25(OH)D deficiency in CAAG patients. METHODS: 87 CAAG patients (71 females; mean age 63.5 ± 12.8 years) followed at our Centre from January 2012 to July 2015 were consecutively evaluated. 25(OH)D, vitamin B12, parathormone, and calcium were measured in all the CAAG patients. The results were compared with a control group of 1232 healthy subjects. RESULTS: In the CAAG group the mean 25(OH)D levels were significantly lower than in the control group (18.8 vs. 27.0 ng/ml, p < 0.0001). 25(OH)D levels < 20 ng/ml was observed in 57 patients, while levels < 12.5 ng/ml in 27 patients. A significant correlation between vitamin B12 values at diagnosis and 25(OH)D levels was observed (rs = 0.25, p = 0.01). Interestingly, the CAAG patients with moderate/severe gastric atrophy had lower 25(OH)D values as compared to those with mild atrophy (11.8 vs. 20 ng/ml; p = 0.0047). Moreover, the 25(OH)D levels were significantly lower in CAAG patients with gastric carcinoid as compared to those without gastric carcinoid (11.8 vs. 19.8 ng/ml; p = 0,0041). CONCLUSION: Data from the present study showed a significant reduction of 25(OH)D levels in CAAG patients and a possible impairment of vitamin D absorption in CAAG may be postulated. Any implication to the genesis of gastric carcinoids remains to be elucidated.

Impact of Vitamin D on the Clinical Outcome of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Report on a Series from a Single Institute.

BACKGROUND/AIMS: Vitamin D deficiency is hypothesized to represent a risk factor in several neoplasms. The aim of this study was to determine whether serum 25-hydroxyvitamin D (25-OHvitD) deficiency represents a risk factor for neuroendocrine neoplasms (NENs) and can be associated with overall survival (OS) and progression-free survival (PFS). METHODS: From 2010 to 2015, 138 patients with gastro- entero-pancreatic NENs (61 females; median age, 63 years) were included in the study. Serum 25-OHvitD levels, which were measured at baseline, were defined as deficient if ≤20 ng/mL. In such cases, 25-OHvitD supplementation was administered to the patients. The possible associations between 25-OHvitD levels and disease grading, staging, overall OS, and PFS were considered. Furthermore, the possible association between 25-OHvitD supplementation and PFS or OS was evaluated by Cox proportional hazards regression. RESULTS: Median 25-OHvitD levels were 12.9 ng/mL (range 2-32); in detail, 94 patients (68%) had ≤20 ng/mL, with 46 cases (33%) having ≤10 ng/mL. An inverse correlation was observed between 25-OHvitD levels and OS (p = 0.03, rs = -0.18) and PFS (p = 0.01, rs = -0.22). At Cox proportional hazards regression, mortality was not related to 25-OHvitD levels; however, there was an association between 25-OHvitD supplementation and OS (p < 0.002). CONCLUSIONS: Vitamin D deficiency is highly prevalent among NEN patients. 25-OHvitD supplementation potentially plays an important role in the correction of 25-OHvitD values, and has an influence on the clinical outcome. However, further studies are needed to confirm this observation.

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

OBJECTIVE: Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far. MATERIALS AND METHODS: From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria. RESULTS: The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence. CONCLUSIONS: The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.

Gastrinoma and neurofibromatosis type 2: the first case report and review of the literature.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors have occasionally been described in association with neurofibromatosis type 1, whereas an association with neurofibromatosis type 2 has never been reported. CASE PRESENTATION: This report refers to an Italian 69 year old woman with neurofibromatosis type 2 and a pancreatic gastrinoma. In the past she had encephalic meningiomas, a tongue schwannoma and bilateral acoustic neurinomas. She presented with weight loss and a long-term history of diarrhea, responsive to proton pump inhibitors. Upper gastrointestinal endoscopy revealed peptic ulcer of the duodenal bulb. Blood tests were normal, except for the elevation of plasma gastrin (1031 pg/ml; reference value <108) and chromogranin A (337 U/L; reference value <36). After secretin stimulation testing, the plasma gastrin level rose to 3789 pg/ml. The abdomen magnetic resonance imaging and gallium68-DOTATOC positron emission tomography scan demonstrated the presence of a 1.2 x 2 cm lesion in the pancreatic head and a liver metastatis. Pancreatic endoscopic ultrasound with fine needle aspiration revealed cytomorphologic features suggestive of pancreatic gastrinoma. Brain magnetic resonance showed a pituitary microadenoma. There was no evidence of hyperparathyroidism. The genetic test for multiple endocrine neoplasia type 1 syndrome mutation was negative. CONCLUSION: This report focuses on the first case of coexistence of gastrinoma with neurofibromatosis type 2. Although the clinical relevance of this association remains to be determined, our case report will surely give cause for due consideration.

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.

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 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.

Prevalence and natural history of potential celiac disease in adult patients.

OBJECTIVE: Potential celiac disease (PCD) is a form of CD characterized by positive endomysial/tissue transglutaminase antibodies and a preserved duodenal mucosa despite a gluten-containing diet (GCD); it can evolve into flat, active CD. This evolution is, however, not certain. Our aim was to retrospectively study the prevalence and the natural history of adult patients with PCD. METHODS: The clinical notes of all 47 patients with PCD attending our clinic between September 1999 and October 2011 were retrospectively reevaluated. To study their clinical features, patients with active CD, randomly selected and matched for sex and date of birth, served as controls. Symptoms, associated diseases, familiarity, and laboratory data at diagnosis were compared. RESULTS: Prevalence of PCD among all celiac patients directly diagnosed in our center was 42/187, (1/4.4, 18.3%, 95% confidence interval (CI) 13.3-23.4%). Age at diagnosis, laboratory data, prevalence of symptoms, associated diseases, and familiarity for CD did not differ between patients with PCD and those with active CD. Some patients with PCD maintained a normal duodenal mucosa for many years and their symptoms spontaneously improved despite maintaining a GCD. CONCLUSIONS: PCD is not a rare form of CD. Having found no difference at all in age at diagnosis and clinical features between PCD and active CD could suggest that PCD is not a prodrome of CD but is a separate entity that can only subsequently evolve into active CD.

Early Biological Therapy in Operated Crohn's Disease Patients Is Associated With a Lower Rate of Endoscopic Recurrence and Improved Long-term Outcomes: A Single-center Experience.

BACKGROUND: Two-thirds of Crohn's disease (CD) patients require surgery during their disease course. However, surgery is not curative, and endoscopic recurrence is observed in up to 90% of cases. Our aim was to investigate the impact of postoperative biological therapy on the incidence of endoscopic recurrence and long-term outcomes in CD patients. METHODS: This retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Milan, Italy) between 2014 and 2021. All consecutive CD patients who underwent surgery and colonoscopy at 6-12 months postoperatively were eligible for inclusion. RESULTS: A total of 141 patients were included (42.6% female, mean age 44 years). Median follow-up was 28 months. About one-third of patients were treated with biologics at baseline colonoscopy. A higher rate of endoscopic recurrence was detected in patients without biologic therapy at the time of colonoscopy compared with those treated (80.8% vs 45.2%, P < .0001). Hospitalization and surgery occurred more in untreated patients than in subjects undergoing biological therapy (12.1% vs 0.0%, P = .01). The Kaplan-Meier curves showed that the no treatment group at baseline had a >23.3% 5-year rate of hospitalization and surgery (log-rank P = .0221) and a >49.7% 5-year rate of medical therapy escalation (log-rank P = .0013) compared with the treatment arm. In the logistic regression model, absence of biologic therapy was independently associated with the risk of endoscopic disease recurrence (odds ratio, 0.22; 95% CI, 0.1-0.51; P = .0004). CONCLUSION: Operated CD patients treated early with biologics experience decreased rates of endoscopic recurrence and improved long-term outcomes.

New Technologies in Digestive Endoscopy for Ulcerative Colitis Patients.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the colon and rectum. Endoscopy plays a crucial role in the diagnosis and management of UC. Recent advancements in endoscopic technology, including chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and the use of artificial intelligence, have revolutionized the assessment and treatment of UC patients. These innovative techniques enable early detection of dysplasia and cancer, more precise characterization of disease extent and severity and more targeted biopsies, leading to improved diagnosis and disease monitoring. Furthermore, these advancements have significant implications for therapeutic decision making, empowering clinicians to carefully consider a range of treatment options, including pharmacological therapies, endoscopic interventions and surgical approaches. In this review, we provide an overview of the latest endoscopic technologies and their applications for diagnosing and monitoring UC. We also discuss their impact on treatment decision making, highlighting the potential benefits and limitations of each technique.

Use of IBD Drugs in Patients With Hepatobiliary Comorbidities: Tips and Tricks.

Advanced therapies (biologic agents and small molecules) for inflammatory bowel diseases (IBD) have radically changed the management of these diseases during the last decade. Data about these drugs in patients with hepatic disorders derive mainly from real-life studies, as these conditions often represent an exclusion criterion from pivotal drug developmental trials. However, IBD patients sometimes have concomitant liver diseases. Nonalcoholic fatty liver disease is the most prevalent hepatic comorbidity, whereas viral hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, and hepatic vascular disorders are less frequent. This review aimed at describing the real-life data about the use of advanced therapies for IBD in patients with concomitant hepatobiliary disorders. Hepatitis B virus and hepatitis C virus infections do not represent an absolute contraindication for novel IBD therapeutic agents. Data from the literature suggest a safe hepatobiliary profile of biologic agents and small molecules in the case of nonalcoholic fatty liver disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and portal vein thrombosis. Consequently, although the liver disease does not affect a different therapeutic approach in patients with concomitant IBD and liver disease, a close risk/benefit analysis for each drug should be performed in these patients, especially in cirrhotic patients and in the postliver transplant setting.

This review focuses on the efficacy and safety of IBD-approved biologic agents and small molecules in patients with common hepatobiliary disorders that may coexist in IBD patients, focusing in particular on liver-related side effects. Even if IBD treatment choices should not be substantially different based on the underlying liver disease, each agent's overall risk/benefit profile should be carefully considered, especially in cirrhotic patients and postliver transplant settings.

Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors.

INTRODUCTION: Janus kinase (JAK) inhibitors are an emerging class of small-molecule drugs, providing targeted therapy for a variety of diseases, and have made their way into the treatment of armamentarium of ulcerative colitis (UC) in recent years. AREAS COVERED: This review focuses on the pharmacokinetics, safety, and efficacy of selective JAK1 inhibitors in the treatment of moderate-to-severe UC. The PubMed database and clinicaltrials.gov were consulted using keywords - further expanded in the methods section. The search was focused on full-text publications in English. No publication date restrictions were imposed. EXPERT OPINION: JAK1 inhibitors are small-molecule drugs used in the treatment of ulcerative colitis and other immune mediated inflammatory diseases. They are orally bioavailable and have a rapid mechanism of action and no immunogenicity. JAK inhibitors can be used for the management of both naïve patients and biological-experienced patients.Particular attention should be paid to elderly patients or those with cardiovascular or oncological risk factors, in whom JAK inhibitors should be recommended only if no alternatives are available. In addition, JAK inhibitors have the potential to be combined with other biological drugs or small molecules for the management of difficult-to-treat cases.