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.

Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications.

Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients' quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Most of the molecular targeted biological therapies developed over the last two decades were based on evidence that specific cytokines may be involved in these immune diseases. Despite pro-inflammatory cytokine pathways sharing the pathogenesis of both articular and gut diseases (i.e., tumor necrosis factor and interleukin-23), several other cytokines (i.e., interleukin-17) may be differently involved in the tissue damage process, depending on the specific disease and the organ involved in inflammation, making difficult the identification of a therapeutic plan that is efficacious for both inflammatory manifestations. In this narrative review, we comprehensively summarize the current knowledge on cytokine involvement in spondyloarthritis and inflammatory bowel diseases, underlining similarities and differences among their pathogenetic pathways; finally, we provide an overview of current and potential future treatment strategies to simultaneously target both articular and gut immune disorders.

Checkpoint Inhibitor-Induced Colitis: From Pathogenesis to Management.

The advent of immunotherapy, specifically of immune checkpoint inhibitors (ICIs), for the treatment of solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one-third of patients treated with ICIs may de velop immune-related adverse events, and the gastrointestinal tract is often affected by different grades of mucosal inflammation. Checkpoint inhibitors colitis (CIC) presents with watery or bloody diarrhea and, in the case of severe symptoms, requires ICIs discontinuation. The pathogenesis of CIC is multifactorial and still partially unknown: anti-tumor activity that collaterally effects the colonic tissue and the upregulation of specific systemic inflammatory pathways (i.e., CD8+ cytotoxic and CD4+ T lymphocytes) are mainly involved. Many questions remain regarding treatment timing and options, and biological treatment, especially with anti-TNF alpha, can be offered to these patients with the aim of rapidly resuming oncological therapies. CIC shares similar pathogenesis and aspects with inflammatory bowel disease (IBD) and the use of ICI in IBD patients is under evaluation. This review aims to summarize the pathogenetic mechanism underlying CIC and to discuss the current evidenced-based management options, including the role of biological therapy, emphasizing the relevant clinical impact on CIC and the need for prompt recognition and treatment.

Mental Illnesses in Inflammatory Bowel Diseases: mens sana in corpore sano.

Background and aims: Inflammatory bowel diseases (IBD) are chronic disorders associated with a reduced quality of life, and patients often also suffer from psychiatric comorbidities. Overall, both mood and cognitive disorders are prevalent in chronic organic diseases, especially in the case of a strong immune component, such as rheumatoid arthritis, multiple sclerosis, and cancer. Divergent data regarding the true incidence and prevalence of mental disorders in patients with IBD are available. We aimed to review the current evidence on the topic and the burden of mental illness in IBD patients, the role of the brain-gut axis in their co-existence, and its implication in an integrated clinical management. Methods: PubMed was searched to identify relevant studies investigating the gut-brain interactions and the incidence and prevalence of psychiatric disorders, especially of depression, anxiety, and cognitive dysfunction in the IBD population. Results: Among IBD patients, there is a high prevalence of psychiatric comorbidities, especially of anxiety and depression. Approximately 20-30% of IBD patients are affected by mood disorders and/or present with anxiety symptoms. Furthermore, it has been observed that the prevalence of mental illnesses increases in patients with active intestinal disease. Psychiatric comorbidities continue to be under-diagnosed in IBD patients and remain an unresolved issue in the management of these patients. Conclusions: Psychiatric illnesses co-occurring in IBD patients deserve acknowledgment from IBD specialists. These comorbidities highly impact the management of IBD patients and should be studied as an adjunctive therapeutic target.

Sporadic non-ampullary duodenal adenomas: efficacy and outcomes of endoscopic resection.

BACKGROUND AND AIMS: Sporadic non-ampullary duodenal adenomas (SNDAs) are often referred to tertiary centers because of the challenges in endoscopic resection. There is a paucity of data on both technical and clinical outcomes. The aim of our study was to evaluate the efficacy and safety of endoscopic resection for the treatment of SNDA in two western centers. METHODS: This is a retrospective study reporting data of a cohort of patients referred for resection of SNDA between 2013 and 2017. Patients with familial adenomatous polyposis or ampullary lesions were excluded from present analysis. Outcomes considered for this study were technical success, adverse events, recurrence and need for surgery. RESULTS: 120 patients (mean age 66 ± 11.9 years, 64male) were enrolled in the study. Mean size of the lesions was 23.3 mm (range 5-80). Fifty-six en-bloc endoscopic mucosal resection (EMR) (46.6%), 41 piecemeal EMR (pEMR) and 23 endoscopic submucosal dissection were performed. Intra-procedural perforation was observed in 4 patients (3.3%). Fourteen post-procedural (11.6%) adverse events were recorded. All post-procedural perforations occurred in lesions > 30 mm. Recurrence was observed in 11 patients (9.5%) during a mean follow-up of 29 months. All recurrences were successfully managed endoscopically. 119 patients were still alive at last follow-up. CONCLUSION: Endoscopic resection can be successfully carried out in majority of patients. Size > 30 mm seems to be the predictor of high adverse events risk.

Relief of jaundice in malignant biliary obstruction: When should we consider endoscopic ultrasonography-guided hepaticogastrostomy as an option?

BACKGROUND: Since it was first described in 2001, endoscopic ultrasonography-guided biliary drainage (EUS-BD) has emerged as an alternative procedure for achieving an endoscopic internal drainage in case of endoscopic retrograde cholangiopancreatography (ERCP) failure. Biliary drainage can be achieved by either a transduodenal extrahepatic approach through EUS-guided choledochoduodenostomy (EUS-CDS), or a transgastric intrahepatic approach, namely EUS-guided hepaticogastrostomy (EUS-HGS) which already holds a remarkable place in the treatment of patients with malignant biliary obstruction. DATA SOURCES: For this review we did a comprehensive search of PubMed/MEDLINE from inception to May 31, 2021 for papers with a significant sample size (at least 20 patients enrolled) dealing with EUS-HGS. Data on technical success, clinical success and rate of adverse events were collected. RESULTS: A total of 22 studies with different design, comprising 874 patients, were included. Technical success was achieved in about 96% of cases (ranging from 65% to 100%). Clinical success was obtained in almost 91% of cases (ranging from 76% to 100%). Overall rate of adverse events was 19% (ranging from 0% to 35%). Abdominal pain, self-limiting pneumoperitoneum, bile leak, cholangitis, bleeding, perforation and intraperitoneal migration of the stent were the most common. CONCLUSIONS: Despite both safety and efficacy profile, at the moment HGS still remains a challenging procedure at every single step and must therefore be conducted by a very experienced endoscopist in interventional EUS and ERCP procedures, who is able to deal with the possible severe adverse events of this procedure. A rapid introduction in clinical practice of dedicated devices is desiderable.

Underwater cap-assisted endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy: a pilot study.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy (SAA) is technically challenging and associated with a significant number of failures. We examined the feasibility and efficacy of a novel technique for the management of bile duct stones (BDSs), called underwater cap-assisted ERCP (u-ERCP). METHODS : Between June 2019 and February 2020 all patients with SAA with jaundice or cholangitis secondary to BDSs who underwent u-ERCP were enrolled. The u-ERCP technique combines the underwater advancement of a pediatric colonoscope with a transparent cap fitted on the tip of the endoscope. We evaluated the technical success, clinical success, and adverse events associated with u-ERCP. RESULTS : We describe the technique itself and our initial experience in six patients. A complete and successful procedure was carried out in all patients, with the occurrence of no adverse events. None of the patients needed additional treatments for recurrence of symptoms during the follow-up period. CONCLUSIONS : u-ERCP can be considered as a promising alternative for successful endoscopic management of biliary disease in patients with SAA.

Coronavirus (COVID-19) outbreak: what the department of endoscopy should know.

Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection.

Management of Post-Operative Crohn's Disease: Knowns and Unknowns.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing-remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20-30% of subjects may not experience endoscopic POR and that 40-50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient's risk of recurrence) or starting therapy after confirming endoscopic POR 6-12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options.

Reporting of Magnetic Resonance Enterography in Inflammatory Bowel Disease: Results of an Italian Survey.

Background/Objectives: Inflammatory bowel diseases (IBDs) are chronic disorders that require close monitoring with imaging techniques such as magnetic resonance enterography (MRE). Standardization of radiological reports is crucial for the optimal management of IBD. We surveyed Italian radiologists regarding their experiences with MRE examinations and reporting for IBD. Methods: All members of the Italian Society of Medical and Interventional Radiology (SIRM) were invited to complete an anonymous questionnaire in April 2023. Comparison tests between variables were assessed using the χ2 test or Fisher exact test according to the least frequency group. Significance level was set for p-value < 0.05. Results: A total of 253 radiologists responded to the survey. Around 70% of the respondents declared personal clinical experience with IBD. Great agreement with the items included and described for both disease activity (i.e., intestinal wall thickness, presence of mucosal ulcers, presence of edema, mucous enhancement) and complications was reported. One-third of the respondents regularly used a structured MRE report. Centers with a high number of IBD patients per year (>1000) mostly used 3 T scanners or both 1.5 T and 3 T scanners (p < 0.001). The incorporation of scores of disease activity was associated with university and high-volume hospitals (p < 0.001). Conclusions: This survey highlighted the current routine practice and experience of MRE reports of IBD patients among Italian radiologists. We found deficiencies in the use of radiological scores in MRE reports and attendance at IBD multidisciplinary meetings.

Management of proctitis in ulcerative colitis and the place of biological therapies.

INTRODUCTION: Approximately 20-30% of the patients with ulcerative colitis (UC) may present with isolated proctitis. Ulcerative proctitis (UP) is a challenging condition to manage due to its significant burden in terms of disabling symptoms. AREAS COVERED: PubMed was searched up to March 2024 to identify relevant studies on UP. A comprehensive summary and critical appraisal of the available data on UP are provided, highlighting emerging treatments and areas for future research. EXPERT OPINION: Patients with UP are often undertreated, and the disease burden is often underestimated in clinical practice. Treat-to-target management algorithms can be applied to UP, aiming for clinical remission in the short term, and endoscopic remission and maintenance of remission in the long term. During their disease, approximately one-third of UP patients require advanced therapies. Escalation to biologic therapy is required for refractory or steroid dependent UP. For optimal patient care and management of UP, it is necessary to include these patients in future randomized clinical trials.

Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.

Fibro-Stenosing Crohn's Disease: What Is New and What Is Next?

Fibro-stenosing Crohn's disease (CD) is a common disease presentation that leads to impaired quality of life and often requires endoscopic treatments or surgery. From a pathobiology perspective, the conventional view that intestinal fibro-stenosis is an irreversible condition has been disproved. Currently, there are no existing imaging techniques that can accurately quantify the amount of fibrosis within a stricture, and managing patients is challenging, requiring a multidisciplinary team. Novel therapies targeting different molecular components of the fibrotic pathways are increasing regarding other diseases outside the gut. However, a large gap between clinical need and the lack of anti-fibrotic agents in CD remains. This paper reviews the current state of pathobiology behind fibro-stenosing CD, provides an updated diagnostic and therapeutic approach, and finally, focuses on clinical trial endpoints and possible targets of anti-fibrotic therapies.

Atherosclerotic cardiovascular diseases in inflammatory bowel diseases: to the heart of the issue.

Atherosclerotic cardiovascular disease and stroke are the leading causes of morbidity and mortality worldwide. Along to the traditional risk factors for these diseases, chronic inflammation is known to be an important player in accelerating the process of atherosclerosis, which can result in an increased incidence of arterial thromboembolic events. As in other chronic inflammatory diseases, in the past few years, several studies suggested that subjects affected by inflammatory bowel diseases (IBD) may also be at an incremented risk of atherosclerotic disease, especially during the periods of disease's flare. Therefore, IBD treatment may assume an important role for achieving both disease remission and the control of the atherosclerotic risk. In this article we aimed to perform a comprehensive review on evidence on the increased risk of arterial thromboembolic events in patients affected by IBD and discuss the potential role of IBD therapy in reducing this risk.

Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections.

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.

Artificial intelligence and inflammatory bowel disease: Where are we going?

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, are chronic and relapsing conditions that pose a growing burden on healthcare systems worldwide. Because of their complex and partly unknown etiology and pathogenesis, the management of ulcerative colitis and Crohn's disease can prove challenging not only from a clinical point of view but also for resource optimization. Artificial intelligence, an umbrella term that encompasses any cognitive function developed by machines for learning or problem solving, and its subsets machine learning and deep learning are becoming ever more essential tools with a plethora of applications in most medical specialties. In this regard gastroenterology is no exception, and due to the importance of endoscopy and imaging numerous clinical studies have been gradually highlighting the relevant role that artificial intelligence has in inflammatory bowel diseases as well. The aim of this review was to summarize the most recent evidence on the use of artificial intelligence in inflammatory bowel diseases in various contexts such as diagnosis, follow-up, treatment, prognosis, cancer surveillance, data collection, and analysis. Moreover, insights into the potential further developments in this field and their effects on future clinical practice were discussed.

Exploring the link: Porto-sinusoidal vascular disorder and inflammatory bowel disease - A comprehensive narrative review.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions involving the portal venules and sinusoids, independent of the presence of portal hypertension (PH), and for which liver biopsy is essential for diagnosis. PSVD has been shown to be common in patients with immune-mediated diseases, including inflammatory bowel disease (IBD). The association between PSVD and the use of thiopurines and thioguanine in patients with IBD has been well established. In addition, research suggests an association between PSVD and IBD, even in cases where patients haven't been exposed to specific medications, probably related to changes in intestinal permeability. The identification and management of patients with known IBD and PSVD is a challenge for gastroenterologists. This narrative review aims to summarize the currently available data on the association between IBD and PSVD and provide practical suggestions for the management of this group of patients.