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Background: Pomegranate (Punica granatum) can be used to prepare a bioactive extract exerting anti-inflammatory activities. Clinical studies demonstrated an improvement in clinical response in inflammatory bowel disease (IBD) patients when pomegranate extract (PG) was taken as a complement to standard medications. However, the molecular mechanisms underlying its beneficial effects are still scarcely investigated. This study investigates the effect of PG on bacterial biofilm formation and the promotion of mucosal wound healing. Methods: The acute colitis model was induced in C57BL/6N mice by 3% dextran sodium sulfate administration in drinking water for 5 days. During the recovery phase of colitis, mice received saline or PG (200 mg/kg body weight) by oral gavage for 11 days. Colitis was scored daily by evaluating body weight loss, bleeding, and stool consistency. In vivo intestinal permeability was evaluated by fluorescein isothiocyanate-conjugated dextran assay, bacterial translocation was assessed by fluorescence in situ hybridization on tissues, whereas epithelial and mucus integrity were monitored by immunostaining for JAM-A and MUC-2 markers. Bacterial biofilm formation was assessed using microfluidic devices for 24 or 48 h. Primary fibroblasts were isolated from healthy and inflamed areas of 8 IBD patients, and Caco-2 cells were stimulated with or without PG (5 μg/mL). Inflammatory mediators were measured at the mRNA and protein level by RT-PCR, WB, or Bio-plex multiplex immunoassay, respectively. Results: In vivo, PG boosted the recovery phase of colitis, promoting a complete restoration of the intestinal barrier with the regeneration of the mucus layer, as also demonstrated by the absence of bacterial spread into the mucosa and the enrichment of crypt-associated fibroblasts. Microfluidic experiments did not highlight a specific effect of PG on Enterobacterales biofilm formation, even though Citrobacter freundii biofilm was slightly impaired in the presence of PG. In vitro, inflamed fibroblasts responded to PG by downregulating the release of metalloproteinases, IL-6, and IL-8 and upregulating the levels of HGF. Caco-2 cells cultured in a medium supplemented with PG increased the expression of SOX-9 and CD44, whereas in the presence of HGF or plated with a fibroblast-conditioned medium, they displayed a decrease in SOX-9 and CD44 expression and an increase in AXIN2, a negative regulator of Wnt signaling. Conclusions: These data provide new insight into the manifold effects of PG on promoting mucosal homeostasis in IBD by affecting pathogen biofilm formation and favoring the regeneration of the intestinal barrier through the regulation of the crosstalk between epithelial and stromal cells.

The increasing armamentarium of drugs for inflammatory bowel disease (IBD) requires a direct comparison of different therapeutic options in order to guide physicians in the choice of the most appropriate treatment for their patients. Head-to-head trials, considered the gold standard in comparative research in IBD, allow to compare different therapies in the same population and setting, but also to evaluate different treatment strategies. Although head-to-head trials including biologics and immunosuppressive therapy in IBD have been performed decades ago, the interest in these direct comparisons is growing since the publication of the first randomized controlled trial directly comparing biologic agents with different molecular targets. This review provides an overview of the past and current IBD head-to-head trials, considering their respective strengths and limitations in a real-life setting.

Background: Intestinal fibrosis and subsequent strictures represent an important burden in inflammatory bowel disease (IBD). Both the detection and evaluation of the degree of fibrosis in stricturing Crohn’s disease (CD) are important when deciding the best therapeutic strategy (medical anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness as a biomarker of intestinal fibrosis. Objective: The aim of this review is to discuss the ability and current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion: Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample size. The first type of USE investigated was strain elastography, while shear wave elastography has been introduced recently. Despite the heterogeneity of the methods of the studies, USE has been proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing this technique in current practice, further studies with larger sample sizes are needed. In addition, the use of homogeneous parameters, the assessment of reproducibility, and the identification of validated cut-off values are essential.

Crohn's disease (CD) and ulcerative colitis (UC) are immune-mediated disorders characterized by a chronic inflammation, with intermittent exacerbations of symptoms and inflammation. In both diseases, medical treatment has made revolutionary steps forward. Nevertheless, surgery is still required in many cases due to inefficacy of multiple medical therapies. It is not clear whether surgery rates in inflammatory bowel diseases (IBD) are currently decreasing despite all improvements.Multidisciplinary management is critical in surgical patients to improve long-term outcomes. Endoscopy plays a crucial role, both before and after surgery, in planning therapeutic strategies and stratifying risk of recurrence. Aim of this review is to provide a deeper insight into the central role of endoscopy in the postoperative management of IBD patients, focusing on recent research advances, future challenges and unresolved questions.Both UC and CD surgical patients need endoscopy to define the correct therapeutic choice, predict subsequent disease course and adopt the correct surveillance strategy. In the next future, newer endoscopic techniques could be systematically applied in IBD patients after surgery, to assess early postoperative inflammation, response to treatment, or, regarding UC, to provide enhanced pouch surveillance, allowing for early detection of inflammation and dysplasia.

Background Smoking has detrimental effects on Crohn's disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD). Aim To understand the patients' perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients. Methods The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking. Results In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products. Conclusion This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.

Introduction: Several biological drugs and a new small molecule are available for the treatment of Crohn's disease and ulcerative colitis. However, to date, no reliable predictors of response to treatment have yet been identified. Areas covered: We focused on studies evaluating the therapeutic management of patients with chronic inflammatory bowel diseases in order to identify any predictive factors of response to drugs and to guide therapeutic decisions based on patient and disease characteristics. Expert opinion: The heterogeneity of literature data, the main retrospective nature of the scientific evidence, and the lack of comparative head-to-head trials are the most relevant limitations for identifying factors predicting drug response. In the near future, a personalized approach to patients with chronic inflammatory diseases will be based on patient's profile to define not only the best drug to use, but also the appropriate follow-up, and the possibility of home care.

Introduction: Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract. Dysregulated innate and adaptive immune pathways contribute to intestinal inflammation in IBD, and cytokines, including IL-12 and IL-23, play a key role. The blockade of both IL-12 and IL-23 may have an impact on different pathways of inflammation and could be effective for the treatment of inflammatory bowel diseases.Ustekinumab is a fully human IgG1kappa monoclonal antibody which binds to the shared p40 protein subunit of IL-12 and -23. It is currently approved for several immune-mediated diseases such as moderate to severe plaque psoriasis, psoriatic arthritis, and Crohn's disease, and has shown promising results in UC.Areas covered: A review of the literature was performed to understand several aspects including the role of IL-12 and -23 in UC, the potential therapeutic role of ustekinumab in inflammatory bowel disease, and the positioning of ustekinumab in the therapeutic algorithm of UC, based on extrapolated data from available randomized clinical trials.Expert opinion: Ustekinumab is effective and safe in UC, and shows potential advantages compared to other drugs in moderate-to-severe UC.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are lifetime chronic and progressive disorders of poorly known etiology. Over the past few decades, new therapeutic approaches, including early and more aggressive intervention with immunomodulators and biological agents have offered the possibility of a favorable modification in the natural history of inflammatory bowel diseases. Area covered: Here, we review the literature about the effectiveness of early detection and intervention in adult inflammatory bowel diseases patients. Expert commentary: Detecting and managing early stages of inflammatory bowel diseases represents an effective strategy to avoid disease progression in selected patients. Primary care physicians may play a key role in attaining these outcomes by recognizing the signs and symptoms early and making timely referrals. Moreover, early therapeutic intervention with complete disease control may allow dose reduction or even treatment withdrawal in the maintenance phase, reducing side effects, costs, and also improving quality of life.

Over the past decades, the treatment of inflammatory bowel diseases (IBD) has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. This top-down approach has been correlated with favorable short and long-term outcomes, but it has also brought with it concerns regarding potential infectious complications. This large IBD population treated with immune-modifying therapies, especially if combined, has an increased risk of severe infections, including opportunistic infections that are sustained by viral, bacterial, parasitic, and fungal agents. Viral infections have emerged as a focal safety concern in patients with IBD, representing a challenge for the clinician: they are often difficult to diagnose and are associated with significant morbidity and mortality. The first step is to improve effective preventive strategies, such as applying vaccination protocols, adopt adequate prophylaxis and educate patients about potential risk factors. Since viral infections in immunosuppressed patients may present atypical signs and symptoms, the challenges for the gastroenterologist are to suspect, recognize and diagnose such complications. Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients' lives. This practical review supports this standard of care to improve knowledge in this subject area.

The climate crisis is an unprecedented existential threat that causes disturbing emotions, such as anxiety. However, relatively little is known about how people cope with climate anxiety, how it influences mental health and well-being, and whether it is relevant for climate (in)action. Recently, Clayton and Karazsia measured climate anxiety as a “clinically significant anxious response to climate change” (2020, p. 9) that may impair human well-being and functioning. To gain a more nuanced understanding of the phenomenon from an empirical psychological perspective, we translated the Climate Anxiety Scale into German and assessed potential correlates in a large German-speaking quota sample (N=1011, stratified by age and gender). Overall, people reported low levels of climate anxiety. Climate anxiety correlated positively with anxiety and depressiveness, avoidance of climate change in everyday life, and the frustration of basic psychological needs. It correlated negatively with climate-relevant self-protective strategies and denial. While unrelated to ideological beliefs, stronger climate anxiety was associated with pro-environmental intentions and support for climate policies. We were not able to replicate the scale’s original factor structure. Thus, we encourage researchers to rework the scale and include an emotional factor in future research efforts.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. In the last few years, the development of biological agents targeting cytokines and receptors involved in IBD pathogenesis has led to better outcomes and has improved the course of the disease. Despite their effectiveness, drugs such as tumor necrosis factor (TNF) inhibitors, anti-Interleukin-12/23 and anti-integrins, do not induce a response in about one-third of patients, and 40% of patients lose response over time. Therefore, more efficient therapies are required. Recent studies showed that TL1A (Tumor necrosis factor-like cytokine 1A) acts as a regulator of mucosal immunity and participates in immunological pathways involved in the IBD pathogenesis. In this review article, we analyze the role of TL1A as a new potential target therapy in IBD patients.

Endoscopy plays a key role in the management of inflammatory bowel disease (IBD). There is an increased need for quality assurance programs that evaluate the quality, safety and patient experiences of endoscopy, by assessing procedural and clinical outcomes.This review aims to summarize the most important quality indicators of endoscopy in IBD patients and could serve as the basis to improve quality endoscopic procedures and patients' perception of endoscopy in the future. However, further studies and consensus reports are necessary to standardize the quality of care in the endoscopy unit of all IBD centers.Developing an understanding of the patient-reported perception is important for both clinicians and patients, as it facilitates patient engagement with their care. Moreover, implementing education in reporting is crucial f and the use of verifiable databases, generated from electronic reporting systems, should be encouraged rather than unverified self-reporting, to have greater validity for documenting and to formally evaluate endoscopic practice data with audits. The use of artificial intelligence may improve the quality of endoscopy, by increasing the adenoma detection rate and helping endoscopists in the challenging differentiation between inflammatory and neoplastic lesions.

Introduction: Biosimilars represent great potential in cost saving and re-investment opportunities in healthcare and allow patients greater access to effective mAbs. Infliximab biosimilars are succ...

Introduction: Biosimilars present a considerable potential to reduce costs related to clinical management allowing health-care providers to reinvest this money, leading to a wider access to an effective biological treatment with monoclonal antibodies (mAb). Infliximab biosimilars have already been incorporated in daily clinical practice and are currently used in all indications for which the reference product (RP) was approved. Areas covered: In the next few years, also adalimumab biosimilars will become available for the treatment of inflammatory bowel disease (IBD). In fact, several of them (ABP501, BI 695501, GP2017, and SB5) have been approved by the European Medicines Agency (EMA) with the same indications of the reference product (Humira ®). Initial preclinical data proved a strong similarity between all biosimilars and the RP. Moreover, phase 3 studies in rheumatoid arthritis and psoriasis showed no differences in terms of efficacy, safety, and immunogenicity. Data on IBD patients are urgently needed. Expert opinion: Biosimilars of adalimumab showed equivalent clinical efficacy to the RP in other immunemediated diseases. However, defining the ideal patient’s profile to receive or to be switched to a biosimilar, choosing one biosimilar vs. another, or cross-switching among biosimilars, will become the next challenge in IBD.

The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.