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Milena Fronza Broering,1,2 Pedro Leonidas Oseliero Filho,3,4 Pâmela Pacassa Borges,1 Luis Carlos Cides da Silva,3 Marcos Camargo Knirsch,5 Luana Filippi Xavier,1 Pablo Scharf,1 Silvana Sandri,1 Marco Antonio Stephano,5 Fernando Anselmo de Oliveira,6 Ibrahim M Sayed,2 Lionel Fernel Gamarra,6 Soumita Das,2 Márcia CA Fantini,3 Sandra HP Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; 2Department of Biomedical and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA; 3Department of Applied Physics, Physics Institute, University of Sao Paulo, São Paulo, Brazil; 4Materials Innovation Factory, University of Liverpool, Liverpool, MSY, UK; 5Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; 6Instituto do Cérebro, Instituto Israelita de Ensino e Pesquisa, Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein, São Paulo, SP, BrazilCorrespondence: Sandra HP Farsky, Email sfarsky@usp.brIntroduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology.Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut.Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 μg; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis.Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results.Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non-invasive IBD therapy. Keywords: annexin A1, SBA-15, oral route, tissue recovery, inflammation

Introduction: IBD-Disk is a simple, easy-to-use, and self-administered analogue visual tool for assessing disability in patients with Inflammatory Bowel Disease (IBD). However, it has not yet been validated in Italian. This study aims to validate IBD-Disk in an Italian cross-sectional multicentre study., Methods: This study was conducted in eight IBD centres from February 2023 to October 2023. After forward-backwards translation of IBD-Disk into Italian, patients consecutively completed IBD-Disk (at baseline and after 7 days), IBD-Disability Index (IBD-DI) and IBDQ-32 for quality of life., Results: We enrolled 767 patients (377, 49,2% CD; 390, 50,8% UC) who completed the IBD-Disk [median score of 30 (IQR=11-52)]. Internal consistency was excellent, with Cronbach's α of 0.92 (95%CI=0.92-0.92). To evaluate the validity, the IBD-Disk was compared with the IBD-DI and IBDQ-32, revealing a significant positive correlation of 0.70 (95% CI=0.66-0.73; p<0.001) and 0.83 (r=0.83, 95% CI=0.80-0.85; p<0.001), respectively. The intraclass correlation coefficient (ICC) was 0.84 (95% CI=0.82-0.86) for test-retest. Female gender, clinically active IBD and the presence of extraintestinal manifestations led to higher IBD-Disk scores., Conclusion: This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying IBD-related disability. This validation facilitates its integration into the daily clinical management of IBD patients., Competing Interests: Conflict of interest All authors declare no conflict of interest regarding this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Janus kinase inhibitors (JAKis) represent a fundamental therapeutic tool for the treatment of patients with immune-mediated inflammatory diseases. Although JAKis are often considered a homogeneous class of drugs whose members are thought to be largely interchangeable, there are significant differences in their efficacy and safety profiles. This narrative review analyzes the pharmacokinetic and pharmacodynamic differences among JAKIs, highlighting their clinical relevance based on the most recent available evidence. The article aims to provide rheumatologists, gastroenterologists and dermatologists with practical guidance for choosing the most appropriate JAKi for each patient, given the lack of evidence-based recommendations on this topic, to improve clinical outcomes. Due to its preferential action on JAK1, intestinal metabolization and proven absence of impact on male fertility, filgotinib may be characterized by an improved benefit/risk ratio compared with other less selective JAKis., Competing Interests: AA declares he received consulting/advisory board fees from AbbVie, Alfa-Sigma, Astra Zeneca, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Roche, Sanofi, Samsung Bioepis, Sandoz, Takeda, Tillots Pharma; speaker’s fees from AbbVie, AG Pharma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Janssen, Lionealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals; and research grants from MSD, Takeda, Pfizer, Biogen. MFa has acted as a consultant for: AbbVie, Celgene, Celltrion, Gilead, Pfizer, MSD, Bristol-Meyer, Takeda, Janssen-Cilag, Roche, Galapagos, Biogen; Sandoz, Eli-Lilly, Teva, Giuliani, he has received financial support for research from Janssen-Cilag, Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Antonioli, Armuzzi, Fantini and Fornai.)

Background and Aims: Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The European consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid, comparative, pragmatic studies in inflammatory bowel diseases [BDs]., Methods: Statements were issued by a panel of 11 European experts in IBD management and trial methodology, on four main topics: [I] study design; [II] eligibility, recruitment and organisation, flexibility; [III] outcomes; [IV] analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement [1 to 9; cut-off ≥7 for approval] with the statements by 18 additional European experts in IBD., Results: At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: seven for study design; six for eligibility, recruitment and organisation, flexibility; eight for outcomes; and four for analysis., Conclusions: Pragmatic, randomised, clinical trials can address important questions in IBD clinical practice, and may provide complementary, high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality, pragmatic, clinical trials that can aid decision making in choosing a management strategy for IBDs., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC 50 value of 4.8 μg/mL compared to 11.5 μg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management., Competing Interests: Declaration of competing interest The authors of this manuscript, entitled “Exploring Asphodelus microcarpus as a Source of Xanthine Oxidase Inhibitors: Insights from In Silico and In Vitro Studies,” declare the following interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The nutritional status in inflammatory bowel disease (IBD) is often impaired, and adherence to the Mediterranean diet (MedDiet) remains under-investigated. The aim of this study was to assess diet quality (DQ) and adherence to MedDiet in a cohort of Sardinian IBD patients. We conducted a case-control study in which 50 Crohn's disease (CD) and 50 ulcerative colitis (UC) patients were matched with 100 healthy controls each. The Diet Quality Index (DQI-I) and Medi-Lite were used to assess DQ and adherence to MedDiet, respectively. Subgroup analysis by disease characteristics and use of advanced therapies were also carried out. DQI-I scored significantly lower in IBD, independently of disease localization and behavior (CD) and disease extent (UC): [DQI-I: CD 34.5 (IQR 33-37) vs. CTRL 40 (IQR 38.5-43) p < 0.0001; UC 34.5 (IQR 33-37) vs. CTRL 42 (IQR 40-44) p < 0.0001]. Medi-Lite scores were significantly lower in stricturing and ileo-colonic CD and in extensive UC: [Medi-Lite CD 7.5 (IQR 7-9)] vs. CTRL 9 (IQR 7-10) p = 0.0379]; [UC 8 (IQR7-10) vs. CTRL 9 (IQR 8-10.5) p = 0.0046]. IBD patients had a low DQ independently of disease type and phenotype. Patients with ileo-colonic stenosing CD or extensive UC had lower MedDiet adherence, suggesting that its benefits may be mitigated by low acceptance in specific subgroups.

Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA., Competing Interests: Declaration of competing interest FSM served as an advisory board member and/or received lecture grants from AbbVie, Biogen, Lionhealth s.r.l., Ferring, Galapagos, Janssen, Pfizer, Samsung Bioepis, and Takeda Pharmaceuticals. FC served as consultant to: Abbvie, MSD, Takeda, Janssen, Roche, Celgene, Bristol-Meyers Squibb, Galapagos, Gilead, Pfizer, Mundipharma, Galapagos, Biogen, Ferring, Eli-Lilly, Nestlè, Lionhealth; received lecture fees from Abbvie, Ferring, Takeda, Allergy Therapeutics, Janssen, Pfizer, Biogen, Galapagos, Sandoz, Eli-Lilly; received unrestricted research grants from Giuliani, Sofar, MSD, Takeda, Abbvie, Celltrion, Pfizer, Actial. CB served as consultant for Takeda, MSD, Ferring, Galapagos, Pfizer, Janssen and AbbVie. RC served as speaker and received consultant fee from Abbvie, Lilly, Galapagos, Pfizer, MSD, Janssen, UCB, Novartis, Fresenius, Accord. FC received research support from AbbVie, Eli Lilly, Novartis, Pfizer; Consulting and speaking fees from AbbVie, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. SDA: consulting and speaking fees from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, MSD Italy, Novartis, Pfizer and UCB. MCF has acted as a consultant for: AbbVie, Celgene, Celltrion, Gilead, Pfizer, MSD, Bristol-Meyer, Takeda, Janssen-Cilag, Eli-Lilly, Roche, Galapagos, Biogen; he has received financial support for research from Janssen-Cilag, Pfizer. SF: consultancy fees and/or Advisory member for Takeda, Galapagos, Abbvie, Pfizer, Janssen-Cilag. FI received honoraria or consulting fees from Abbvie, Eli-Lilly, Galapagos, Janssen, and Pfizer. CP has received consultancy fees and educational grants from Galapagos Pfizer, Janssen-Cilag Takeda, Chiesi, Sofar, Sandoz, Zambon. GP: research grants, consultation, and/or speaking from Abbvie, Alfasigma, Amgen, BMS, Fresenius Kabi, Galapagos, GSK, Lilly, Pfizer, UC. DP: speaker's fee/advisory board from Janssen, Pfizer, Galapagos, Takeda, MSD, AbbVie, Biogen. AR: advisory board and consultant for Abbvie, Takeda, Janssen, MSD, Pfizer, Sandoz, Galapagos. SS: consultancy, lecture fees, and advisory board for AbbVie, Arena, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, and Takeda. AV: lecture fees from Abbvie, Janssen-Cilag, Takeda, Pfizer, Zambon, Lionhealth; consultant for Abbvie, Janssen-Cilag, Takeda, Pfizer, Ferring, Celltrion. AA: consulting/advisory board fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Mylan, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, Tillots Pharma; speaker's fees from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix; research grants from MSD, Takeda, Pfizer, Biogen. AO served as an advisory board member for AbbVie, Ferring, Galapagos, MSD, Janssen, Pfizer, Takeda Pharmaceuticals, and received lecture grants from AbbVie, Ferring, Lionhealth s.r.l., MSD, Sofar, Chiesi, Janssen, Pfizer, and Takeda Pharmaceuticals. LB, AC, MSC, EL, PM, CS, MZ have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

(1) Background : Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians' awareness of the issue and the current status of IMID management. (2) Methods : A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results : A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions : While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

In inflammatory bowel disease (IBD), the loss of immune tolerance against gut microbiota causes chronic inflammation and the progressive accumulation of organ damage in genetically susceptible individuals. In the elderly, IBD is often characterized by a different disease behavior when compared with pediatric and young adult disease. Besides disease behavior, another aspect of the multifaceted impact of age on elderly IBD course is increased susceptibility to infections. In this context, age-of-onset-dependent IBD behavior and clinical course are two major contributors to immune system senescence and change of gut microbiota in older subjects. Here, we review the available literature linking immunosenescence and age-dependent changes in the gut microbiota composition to IBD pathogenesis speculating on their possible implications in disease expression in this age class.

Background and Aims: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process., Methods: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3., Results: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects., Conclusions: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents., Aim: The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines., Methods: We used the Delphi panel methodology to gather the IBD experts' views and achieve consensus for clinical recommendations on introducing and maintaining anti-TNF therapy for patients with IBDs., Results: Twelve recommendations achieved a high level of consensus in two assessment rounds by 52 (1st round) and 47 (2nd round) IBD experts., Conclusion: In many clinical situations, the early use of anti-TNF therapy is recommended. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients, thus providing the opportunity to increase access to biological therapy., Competing Interests: Conflict of interest Ardizzone,S. received consulting and advisory board fees and/or research support from AbbVie, MSD, Ferring, Janssen, Takeda, Zambon, Sofar, Pfizer, Biogen, Galapagos, Sandoz, Celltrion. Armuzzi,A. received consulting/advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker's fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix; research support from MSD, Takeda, Pfizer and Biogen. Caprioli,F. served as consultant to Abbvie, MSD, Takeda, Janssen, Roche, Celgene, Bristol-Meyers Squipp, Galapagos, Gilead, Pfizer, Mundipharma, Biogen; received lecture fees from Abbvie, Ferring, Takeda, Allergy Therapeutics, Janssen, Pfizer, Biogen. and unrestricted research grants from Giuliani, Sofar, MSD, Takeda, Abbvie, Celtrion, Pfizer. Castiglione,F. received lecture grants and/or served as an advisory board member from Takeda, Pfizer, Biogen, Sandoz, Janssen, Fresenius. Danese, S. received consulting fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor. Daperno,M. received adivory bord or speaker fees from: Janssen, Takeda, Pfizer, Cellgene, Roche, Abbvie, Biogen, SOFAR, Chiesi, Ferring; received consultancy fees from: Quintiles/Clario. Fantini,M.C. received consultancy fees from Abbvie, Takeda, Jannsen-Cilag, Pfizer, Sandoz, Biogen, Galapagos, Bristol-Mayers Squibb, MSD; Research grants from Pfizer and Jannsen-Cilag. Fries,W. received speaker fees/research grants and served as an advisory board member from Pfizer, Biogen, Ferring, Janssen, Takeda, Abbvie, and Zambon. Principi,M. served as advisory board and received lecture fee from MSD, Abbvie, Janssen, Pfizer, Takeda. Savarino,E. served as speaker for Abbvie, AGPharma, Alfasigma, Dr Falk, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco Gionchetti,P. received honoraria or consultation fees from: Janssen, Abbvie, Pfizer, Celgene, Takeda, Ferring, MSD, Alfa-Sigma, Amgen, Gilead, Arena, Galapagos, Celltrion, Biogen; participation in company sponsored speaker's bureau: Abbvie, Janssen, Takeda, Ferring, Msd, Sofar, Chiesi, Biogen., (Copyright © 2023. Published by Elsevier Ltd.)

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory disorder encompassing ulcerative colitis and Crohn's disease can be disabling and often requires lifelong treatment and follow-up. Digital health technologies and distance-management tools are less costly alternatives for IBD management and clinical monitoring. This review discusses how telephone/videoconference appointments enable treatment optimization from an early disease stage, provide complementary value-based patient care and educational resources, and allow consistent follow-up with a high standard of care. Replacing/supplementing traditional clinical consultations with telemedicine reduces healthcare utilization costs and the need for in-person consultations. The COVID-19 pandemic has accelerated the evolution of telemedicine in IBD, with several studies conducted since 2020 reporting high levels of patient satisfaction. Home-based injectable formulations coupled with telemedicine may become permanently embedded in healthcare systems in the post-pandemic period. While telemedicine consultations are well-accepted by many patients with IBD, they do not suit all patients or are not preferred (e.g., by elderly who do not have the means or ability to understand the associated technology). Ultimately, use of telemedicine should be decided by the patient and careful consideration is required to ensure that the patient is willing and capable of a successful remote visit., Competing Interests: Conflict of interest Massimo Claudio Fantini has received speaker and consultancy fees from AbbVie, Takeda, Janssen-Cilag, Pfizer, Sandoz, Biogen, Galapagos, Bristol-Myers Squibb, and MSD; and research grants from Pfizer and Janssen-Cilag. Sara Onali has received speaker fees from AbbVie, Takeda, Janssen, Amgen, Galapagos and Norgine. Erica Loddo and Amalia Di Petrillo declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Inflammatory bowel disease, whose major forms are Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gut due to the loss of tolerance toward antigens normally contained in the gut lumen. G protein-coupled receptor (GPR) 120 has gained considerable attention as a potential therapeutic target for metabolic disorders due to its implication in the production of the incretin hormone glucagon-like peptide 1 and the secretion of cholecystokinin. Recent studies have also highlighted the role of GPR120 in regulating immune system activity and inflammation. GPR120, expressed by intestinal epithelial cells, proinflammatory macrophages, enteroendocrine L cells, and CD4+ T cells, suppresses proinflammatory and enhances anti-inflammatory cytokine production, suggesting that GPR120 might have a pivotal role in intestinal inflammation and represent a possible therapeutic target in inflammatory bowel disease. This narrative review aims at summarizing the role of GPR120 in the maintenance of intestinal homeostasis through the analysis of the most recent studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que's binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.

Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-α and IL-6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolin-mediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF-α, IL-6, IL-1β and TGF-β1 levels in LPS-stimulated macrophages. These results support the hypothesis that the co-delivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD)., Aims: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD., Methods: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted., Results: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay., Conclusion: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice., Competing Interests: ES has served as speaker for Abbvie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Reckitt Benckiser, SILA, Sofar, Unifarco. DP has received speaker’s fee from Takeda, Pfizer, MSD, Janssen, MSD, and a grant from Amgen and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lenti, Scribano, Biancone, Ciccocioppo, Pugliese, Pastorelli, Fiorino, Savarino, Caprioli, Ardizzone, Fantini, Tontini, Orlando, Sampietro, Sturniolo, Monteleone, Vecchi, Kohn, Daperno, D’Incà, Corazza and Di Sabatino.)