Search

Despite incredible growth in systems of care and rapidly expanding therapeutic options for people with inflammatory bowel disease, there are significant barriers that prevent patients from benefiting from these advances. These barriers include restrictions in the form of prior authorization, step therapy, and prescription drug coverage. Furthermore, inadequate use of multidisciplinary care and inflammatory bowel disease specialists limits patient access to high-quality care, particularly for medically vulnerable populations. However, there are opportunities to improve access to high-quality, patient-centered care. This position statement outlines the policy and advocacy goals that the American Gastroenterological Association will prioritize for collaborative efforts with patients, providers, and payors., (Copyright © 2024. Published by Elsevier Inc.)

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Histological assessment of endoscopic biopsies in inflammatory bowel disease [IBD] plays an important role in clinical management, investigative studies, and clinical trials. Scoring schemes consisting of multiple histological items and offering considerable precision are widely available. However, definitions of histological abnormalities are often inconsistent. Furthermore, interobserver variability for their recognition and assessment may be high. The European Crohn's and Colitis Organisation [ECCO] formed an expert panel to explore definitions of histological abnormalities in IBD, with the aim of improving the quality of diagnosis and facilitating development of scoring schemes. The process confirmed that the current definitions often have no evidence base and vary between sources. Using available evidence and expert knowledge, the panel produced a series of ECCO consensus position statements on histological features in IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

The humanized monoclonal anti-α4β7-integrin-antibody vedolizumab is one of several biologic therapeutic options in moderate-to-severe ulcerative colitis and Crohn's disease. Within the VISIBLE trial program, a novel subcutaneous application route was evaluated in addition to the already established intravenous form. In this position statement, the working group "Inflammatory Bowel Diseases" of the Austrian Society for Gastroenterology and Hepatology (OEGGH) summarizes the evidence regarding the subcutaneous application of vedolizumab. This work supplements a position paper on the value of vedolizumab as a first-line biologic that has already been published and offers useful recommendations for clinical practice., Competing Interests: Die Autoren erklären, dass die Erstellung dieses Positionspapieres finanziell von TAKEDA Austria unterstützt wurde und dass der Erstautor (S.R.) innerhalb der letzten 3 Jahre Vortragshonorare von TAKEDA Austria erhalten hat., (Thieme. All rights reserved.)

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: The utility of real-world data is dependent on the quality and homogeneity of reporting. We aimed to develop a core outcome set for real-world studies in adult patients with inflammatory bowel disease [IBD]., Methods: Candidate outcomes and outcome measures were identified and categorised in a systematic review. An international panel including patients, dietitians, epidemiologists, gastroenterologists, nurses, pathologists, radiologists, and surgeons participated in a modified Delphi consensus process. A consensus meeting was held to ratify the final core outcome set., Results: A total of 26 panellists from 13 countries participated in the consensus process. A total of 271 items [130 outcomes, 141 outcome measures] in nine study domains were included in the first-round survey. Panellists agreed that real-world studies on disease activity should report clinical, endoscopic, and biomarker disease activity. A disease-specific clinical index [Harvey-Bradshaw Index, Partial Mayo Score, Simple Clinical Colitis Activity Index] should be used, rather than physician global assessment. In ulcerative colitis [UC], either the UC Endoscopic Index of Severity or the Mayo Endoscopic Score can be used, but there was no consensus on an endoscopic index for Crohn's disease, nor was there consensus on the use of the presence of ulcers. There was consensus on using faecal calprotectin and C-reactive protein. There was no consensus on the use of histology in real-world studies., Conclusions: A core outcome set for real-world studies in IBD has been developed based on international multidisciplinary consensus. Its adoption will facilitate synthesis in the generation of real-world evidence., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders., Aim: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications., Methods: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available., Results: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children., Conclusions: There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Ulcerative colitis (UC) is one of the main forms of inflammatory bowel disease (IBD). Despite the widening range of drug treatment options, primary nonresponse, secondary loss of response as well as adverse events call for additional treatment alternatives.Tofacitinib is an oral small-molecule drug of the class of Janus kinase inhibitors which, in the European Union, was approved for the treatment of moderate to severe active UC in August 2018. This position paper, drawn up by the IBD Working Group of the Austrian Society of Gastroenterology and Hepatology, summarizes the mechanism of action, clinical development, marketing authorization status, efficacy and safety of tofacitinib. Also, by providing a synopsis of available data from both pivotal and post-marketing studies, clinical aspects of specific interest are highlighted and discussed.The available body of evidence indicates that tofacitinib is an additional effective medication for the treatment of UC that exhibits a good safety profile. This position paper aims at optimizing the safe and effective use of tofacitinib in daily clinical practice., (© 2022. The Author(s).)

Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

Background: Intestinal ultrasound is increasingly used for primary diagnosis, detection of complications and monitoring of patients with Crohn's disease and ulcerative colitis. Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different specialties. The current manuscript describes the features required for optimized reporting of intestinal ultrasound findings in inflammatory bowel disease (IBD)., Methods: An expert consensus panel of gastroenterologists, radiologists, pathologists, paediatric gastroenterologists and surgeons conducted a systematic literature search. In a Delphi- process members of the Kompetenznetz Darmerkrankungen in collaboration with members of the German Society for Radiology (DRG) voted on relevant criteria for reporting of findings in intestinal ultrasound. Based on the voting results statements were agreed by expert consensus., Results: Clinically relevant aspects of intestinal ultrasound (IUS) findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images., Conclusion: The current manuscript provides practical recommendations on how to standardize documentation and reporting from intestinal ultrasound findings in patients with IBD., Competing Interests: RA: Beratertätigkeit und/oder Honorare: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Ferring, Fresenius Kabi, Galapagos, Gilead, GlaxoSmithKline plc, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, Lilly, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepsis, Stelic Institute, Sterna Biologicals, Takeda Pharma, Tillotts Pharma AG, Viatris. DB: Fördermittel für ultraschallbezogene Veranstaltungen an der Charité – Universitätsmedizin Berlin und der University of Alberta von AbbVie, MSD, Hitachi, Toshiba und Canon eingeworben. Alle Mittel sind den genannten Institutionen zugeflossen. OB: Beratertätigkeit und/oder Honorare: Abbvie, AMGEN, Astellas Pharma, Bristol-Myers Squibb, Celltrion, Hexal, Dr. Falk Pharma, FERRING Arzneimittel, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Pfizer Pharma, Shield Therapeutics, Recordati, Takeda Pharma, Tillotts Pharma JD: Berater-/Vortrags-/Gutachtertätigkeiten für Abbvie, Shire/Takeda, Humana, Amgen, Hexal, Nestlé, Steigerwald/Bayer Vital, Nutricia Milupa und Ferring; Finanzierung wissenschaftlicher Untersuchungen für Centogene und Campro. Wisssenschaftspreise: Nestlé CM: Beratertätigkeit und/oder Honorare: Abbvie, Biogen, Ferring Arzneimittel GmbH, Galapagos, Gilead, Janssen, MSD Sharp & Dome GmbH, Pfizer, Roche, Samsung, Takeda Pharma GmbH, Vifor Pharma JM: keine Interessenkonflikte UH: Beratertätigkeit und/oder Honorare: Amgen, Biogen, BMS, Celltrion, Falk Foundation, Ferring, Fresenius, Janssen, MSD, Mundipharma, Mylan, Pfizer, Shield, Takeda, Vifor JJ: Beratertätigkeit und/oder Honorare: Abbvie, Janssen-Cilag, Galapagos, Intercept, Ferring, Takeda TK: Beratertätigkeit und/oder Honorare: Abbvie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Ferring Arzneimittel, Galapagos, Gilead, Janssen, MSD Sharp & Dome GmbH, Pfizer, Roche, Takeda Pharma, Vifor Pharma PK: Vortrags-/Beratertätigkeiten: AbbVie, Aesculap, Dr. Falk Pharma, Ethicon, Galapagos, Janssen-Cilag, MSD, Stryker, Takeda Pharma, Tillotts Pharma MV: Vortragshonorare von: FALK, Malesci, Menerini, Olympus, Janssen CS: Beratertätigkeit: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Ewopharma, Galapagos, Janssen-Cilag, MSD Sharp & Dohme, Norgine, Pfizer und Takeda; Vortragshonorare, Reiseunterstützung: Abbvie, Berlin Chemie, Biogen, CED Service, Ewopharma, Dr. Falk, Janssen-Cilag, med update, Merckle, MSD Sharp & Dohme, Norgine, Novartis, Olympus, Pentax, Pfizer, Shire, Shield Therapeutics und Takeda; Forschungsförderung: Abbvie, Olympus und Pentax JW: Vortrags-Honorare: Janssen-Cilag, Takeda Pharma, (Thieme. All rights reserved.)

Background: Bacterial culture is the gold standard for the diagnosis of invasive bacterial diseases (IBDs) but molecular methods are more specific and sensitive. Fresh liquid samples (FLSs) show patent limitations for shipping and storage. We aimed to evaluate the sensitivity and specificity of real-time polymerase chain reaction (PCR) performed on dried sample spots (DSSs) obtained from different biological fluids compared with real-time PCR or culture performed on FLSs., Methods: FLSs positive for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, Bordetella pertussis and/or Pseudomonas aeruginosa were spotted on filter paper. Real-time PCR was performed on both FLSs and DSSs and results were compared. The stability of the DSS results over time was evaluated., Results: Real-time PCR performed on 114 DSSs showed a specificity of 99.1% and a sensitivity of 91.2% for IBD diagnosis. A positive correlation was found between FLS cycle threshold (Ct) and DSS Ct (r=0.84; r2=0.71) with the Pearson statistical test and Bland-Altman analysis showing that 95% of the specimens were within agreeable limits. Although we observed a trend towards signal reduction over time in the DSSs, there was no statistical evidence of an increase in Ct values. Real-time PCR on DSSs was 2.2 times more sensitive than culture., Conclusions: Real-time PCR applied to DSSs may be a useful approach in different situations, such as IBD diagnosis, both for rural areas of low-income countries and family practitioners in various settings., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The complete and reliable documentation of endoscopic findings make up the crucial foundation for the treatment of patients with inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. These findings are, on the one hand, a prerequisite for therapeutic decisions and, on the other hand, important as a tool for assessing the response to ongoing treatments. Endoscopic reports should, therefore, be recorded according to standardized criteria to ensure that the findings of different endoscopists can be adequately compared and that changes in the course of the disease can be traced back. In consideration of these necessities, fifteen members of the Imaging Working Group of the German Kompetenznetz Darmerkrankungen have created a position paper proposing a structure and specifications for the documentation of endoscopic exams. In addition to the formal report structure, the recommendations address a large number of attributes of acute and chronic inflammatory alterations as well as endoscopically detectable complications, which are explained in detail and illustrated using exemplary images. In addition, more frequently used endoscopic activity indices are presented and their use in everyday clinical practice is discussed., Competing Interests: CS erhielt Beratungshonorare von AbbVie, Biogen, Ewopharma, Janssen-Cilag, MSD Sharp & Dohme, Pfizer und Takeda, AbbVie, Berlin Chemie, Biogen, Ewopharma, Dr. Falk, Janssen-Cilag, med update, Merckle, MSD Sharp & Dohme, Norgine, Novartis, Pfizer, Shire, Shield Therapeutics und Takeda sowie Forschungsunterstützung von AbbVie, Olympus und Pentax. OB erhielt Beratungshonorare von AbbVie, AMGEN, Hexal, Immundiagnostik, Dr. Falk Pharma, FERRING Arzneimittel, Janssen-Cilag, MSD Sharp & Dohme, Shield Therapeutics, Takeda Pharma, Tillotts Pharma sowie Referentenhonorare von AbbVie, Astellas Pharma, Biogen, Bristol-Myers Squibb, Dr. Falk Pharma, FERRING Arzneimittel, Janssen-Cilag, MSD Sharp & Dohme, Pfizer Pharma, Takeda Pharma. DCB hat keine Interessenkonflikte angegeben. MG erhielt Berater- bzw. Vortragshonorare von Janssen, Falk, MSD, Galapagos, AbbVie und Takeda. OD hat keine Interessenkonflikte angegeben. TK erhielt Beratungs- und Vortragshonorare von AbbVie, Allmiral, Arena Pharmaceuticals, Celgene/BMS, Celltrion, Ferring, Falk, Gilead Sciences, Galapagos, Janssen, Medtronic, Mundipharma, MSD, Pfizer, Shire, Sterna Biologicals, Takeda, Tillotts Pharma, JL hat folgende Verbindungen zu Unternehmen offenzulegen (Forschungsunterstützung: Vortragshonorar Berater/Gutachtertätigkeit) Medizinverlage Stuttgart; Celgene GmbH, Falk Foundation, Ferring Arzneimittel GmbH; Repha GmbH biologische Arzneimittel, Steigerwald Arzneimittelwerke GmbH, Sanofi, Dr. Willmar Schwabe; TechLab. JMa erhielt Beraterhonorar von AbbVie, Janssen-Cilag, Pharmacosmos und Takeda sowie Referentenhonorar und Reisekostenerstattungen von AbbVie, Cellgene, Falk Foundation, Ferring, Fujifilm, Janssen-Cilag, MSD, Pfizer und Takeda. WM erhielt Beratungshonorare von AbbVie, Amgen, Hexal, Janssen, MSD, Pfizer, Synformulas, Takeda, Vortragshonorare und Reiseunterstützung von AbbVie, alanta health service, Almirall, Aptalis, biogen, Falk, Gilead, Janssen, Pfizer, MSD, Takeda, Tillots, Vifor, Honorare für Studien von AbbVie, Janssen, MSD, Pfizer, Takeda. Er gibt Tätigkeiten in öffentlich-rechtlichen Gremien an als Mitglied der Vertreterversammlung der Landesärztekammer Saarland, der Beratungskommission der Prüfungsstelle für das Saarland, des beratenden Fachausschusses Fachärzte der KV Saarland, des Landesausschusses der Ärzte und Krankenkassen sowie des erweiterten Landesausschusses Saarland. Er ist abhängig beschäftigt im Konzern der alanta health group GmbH, Hamburg, und hält Aktien der Firmen AbbVie und Gilead. JMu macht folgende Angaben: Kooperationsvertrag mit Pentax, Vortragstätigkeiten für Pentax und Olympus, Vortragstätigkeiten für Helios Deutschland. MR erhielt Vortragshonorare von AbbVie, Janssen-Cilag und Ovesco. Der Arbeitgeber von AS erhielt Honorare für Vortrags- oder Beratungstätigkeit von AbbVie, Biogen, Cellgene, Falk Foundation, Pfizer, Janssen-Cilag, MSD, Pfizer und Takeda. TK erhielt Beratungshonorare von AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Hospira, Mundipharma, Dr. Falk Pharma GmbH, Gilead, Janssen, MSD Sharp & Dome GmbH, Novartis, Roche, Takeda Pharma GmbH und UCB sowie Referentenhonorare von AbbVie, Dr. Falk Pharma GmbH, Ferring Arzneimittel GmbH, MSD Sharp & Dome GmbH, Pfizer, Roche, Takeda Pharma GmbH und UCB. DW gibt Vortrags- und/oder Beratertätigkeiten für die Firmen AbbVie, Takeda, Janssen, MSD, Ferring, Celgene, Pharmacosmos, Celltrion, Tillotts Pharma und Falk Pharma an. RA hat folgende Verbindungen zu Unternehmen offenzulegen (Beratendes Gremium oder Komitee; Referententätigkeit; Beratungstätigkeit; Forschungsförderung): AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Cellgene, Celltrion Healthcare, Dr. Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda Pharma, Tillotts Pharma AG., (Thieme. All rights reserved.)

Objective: Uniform and standardised quality measurement allows care assessment and improvement. Following a pragmatic consensus method we aimed to agree on a selection of measurable quality indicators that can be used to assess, benchmark and gradually improve inflammatory bowel disease (IBD) care in Flanders., Methods: Of 49 structures, 135 processes and 37 outcome indicators identified through literature, 58 were preselected and reformulated into measurable outcome indicators by four IBD physicians. A larger expert group scored the 58 indicators on a 10-point importance scale twice, endorsed by patient and expert perspectives in between rounds. Additional items could be suggested. A final selection and subset of indicators with room for improvement were agreed upon during a consensus meeting., Results: Fifty indicators received an importance score of 7 or higher by ≥80% of the participants (seven IBD nurses, one abdominal surgeon, one chief medical officer and 31 IBD physicians including two paediatricians). Eight indicators scored highly important by 60-80%, two indicators reintroduced by patients and one newly suggested, were discussed during the consensus meeting. Among 26 participants, eight indicators were agreed to be added to the final selection. Of the 58 selected items, 19 were retained in the improvement subset, related to patient-reported outcomes, use of hospital services and survival, patient characteristics, monitoring of disease activity and remission, endoscopy guidelines, infection prevention, steroid and other medication use., Conclusion: Fifty-eight indicators were selected to assess IBD care in Flanders and a subset of 19 for use in clinical practice to steer quality improvement initiatives., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cytokines produced by immune cells contribute to the development and perpetuation of inflammatory bowel disease (IBD), namely Crohn's disease and ulcerative colitis, by regulating various aspects of the inflammatory response. Pro-inflammatory cytokines trigger chronic intestinal inflammation, tissue damage, carcinogenesis and perpetuation of disease and suppress the resolution of inflammation in IBD. The clinical success of antibodies that neutralize tumour necrosis factor (TNF) and the cytokine IL-12p40 in individuals with IBD has underscored this concept. Moreover, genetic and preclinical studies have emphasized the crucial role of IL-23 in IBD, leading to clinical approval of antibodies targeting this cytokine. Multiple studies have also investigated the administration of cytokines with assumed anti-inflammatory effects, but this approach has yet to show any real clinical benefit in individuals with IBD. Recent studies have targeted the cytokine network through the use of multi-cytokine blockers (for example, Janus kinase (JAK) inhibitors), IL-2-induced regulatory T cells or advanced combination therapies that use multiple cytokine blockers simultaneously (for example, anti-TNF along with anti-IL-23 antibodies). This Review will focus on our current understanding of how cytokines produced by innate and adaptive immune cells contribute to IBD pathogenesis and discuss how their modulation may inform future treatments for IBD., (© 2024. Springer Nature Limited.)

ABSTRACT Crohn’s disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

Aims: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy., Methods and Results: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies., Conclusions: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China., Methods: A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center., Results: A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers., Conclusion: The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center. Video Abstract., (© 2023. The Author(s).)

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialized and affluent areas in the Asia‐Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan‐Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up‐to‐date, evidence‐based approach to PIBD in the Asia‐Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine‐S‐methyltransferase (TPMT). The main considerations in the use of biologics in the Asia‐Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia‐Pacific region. [ABSTRACT FROM AUTHOR]

Background: Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD., Methods: This was a single-center prospective study of patients with IBD previously vaccinated with a three dose HepB series. Patients had a hepatitis B surface antibody (anti-HBs) drawn; if it was below 10 mIU/mL, they received a challenge dose of the HepB vaccine to assess for anamnestic response and sustained seroprotection. The primary outcome was to determine the rate of sustained seroprotection (anti-HBs ≥ 10)., Results: A total of 168 patients met inclusion criteria, mean age 35.7 years ± 13.6 standard deviation (SD). Initially 120 (71.4%) had anti-HBs ≥ 10 mIU/mL, with median anti-HBs of 37 mIU/mL (interquartile range 0-234); 48 (28.6%) needed a challenge dose, of which 34 responded with anti-HBs ≥ 10 mIU/mL. In total, 154 (91.7%) demonstrated sustained seroprotection to HepB. Those not seroprotected were more likely to have been vaccinated on immunosuppressive therapy or after their diagnosis of IBD., Conclusions: Most vaccinated patients with IBD maintain sustained seroprotection to HepB despite prolonged exposure to immunosuppression. This contradicts prior studies and shows that immunosuppression does not lead to loss of seroprotection., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study explored the variation in emerging adults' communication with gastroenterologists around the management of inflammatory bowel disease (IBD)., Methods: Nineteen emerging adults with IBD aged 18-25 and seven gastroenterologists participated in the study. Outpatient specialist consultations of consenting participants were audio-recorded and transcribed. Transcribed consultations were analysed in terms of the linguistic structure of the consultations and the gastroenterologist-patient role relationship., Results: Variations in the emerging adults' communication with their gastroenterologists stem partly from variation in their ability, opportunity, or need to contribute to the different phases of the consultation and partly from variations in the gastroenterologists' style of communication. Gastroenterologists differed in the construction of their role relationship with the patient, resulting in variations in employing empowering strategies including eliciting, exploring, and clarifying the patient's concerns, sharing clinical reasoning, and validating the patient experience. Variations were also observed in the length of appointments and the gastroenterologists' assessment and addressing of adherence issues. Techniques used by the gastroenterologist varied (1) from simply confirming adherence, to a comprehensive assessment of the patient's understanding of their management plan and their feedback, and (2) from use of persuasion to values calibration., Conclusions: Evidence-based consumer interventions and communication guidelines for clinicians are needed to address the identified variations in providing care to emerging adults living with chronic conditions., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

As the Editor-in-Chief of World Journal of Gastroenterology, every week prior to a new issues online publication, I perform a careful review of all encompassed articles, including the title, clinical and/or research importance, originality, novelty, and ratings by the peer reviewers. Based on this review, I select the papers of choice and suggest pertinent changes (e.g., in the title) to the Company Editors responsible for publication. This process, while time-consuming, is very important for assuring the quality of publications and highlighting important articles that Readers may revisit.

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed. [ABSTRACT FROM AUTHOR]

A new paper in the journal Development discusses the research conducted by J. Guillermo Sanchez and Jim Wells on the role of the transcription factor RFX6 in intestinal patterning. The authors derived human intestinal organoids from an individual with duodenal defects and a variant in the RFX6 gene. Through their study, they identified novel roles for RFX6 in intestinal development. The authors also discuss their use of induced pluripotent stem cell-derived organoids for disease modeling and their efforts to generate functional tissues for transplantation. [Extracted from the article]

Background: There is a need to improve psychological care for people with Inflammatory Bowel Diseases (IBD), noting the high psychosocial burden of disease., Aims: This study qualitatively explored the views of people living with IBD to help inform future co-design of services that better meet the psychological needs of consumers., Methods: Adults with IBD were recruited to attend virtual focus groups to discuss what they want most in an IBD-specific psychological service. The discussions were recorded and transcribed, and data were analyzed using conventional qualitative content analysis. Draft results were summarized midway and reviewed by remaining focus groups and a final expert consumer. A quantitative dataset was created of comment frequencies., Results: Thirty-one participants took part in the study: 10 focus groups were held with an average of three participants per group. The analysis identified 254 codes, 38 sub-categories and six categories. Five main categories were identified for an IBD-specific psychological service: People-Centered Healthcare (commented on by 90% of participants), Education and Preparation (83%), Social Connection (83%), Psychological Input (93%), and Accessible Services (97%). Results were summarized in a set of proposed clinical guidelines., Conclusions: The findings of this study identify important insights from people living with IBD regarding priorities for psychological services. IBD services should focus on improving education, addressing social connection, and integrating psychological input, as well as becoming more people-centered and accessible. It is hoped that IBD services consult the proposed clinical guidelines to inform co-designed service improvements., (© 2024. The Author(s).)

Despite the institution of an interdisciplinary Inflammatory Bowel Disease (IBD) centre is encouraged, how it may improve patient care is still unknown. In a 5-year period following organisation of an IBD centre, hospitalisations per patient/year decreased (0.41-0.17) and patients on biologics increased (7.7%-26.7%). Total number of hospitalisations (-18.4%) and length of hospitalisation (-29.4%) improved compared with a preceding 5-year period. These findings suggest that institution of an interdisciplinary IBD centre is associated with improved healthcare utilisation., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aim: The incidence of paediatric inflammatory bowel disease (IBD) continues to increase in both adults and children across the globe, with more than one third of the patients not responding to anti-tumour necrosis factor biologics and immune modulators. This narrative review provides an overview of novel pharmacological developments in the management of paediatric IBD, including new biological therapies., Methods: A PubMed Medline search was performed to include randomised controlled trials, retrospective and prospective observational studies, and relevant case reports of children with IBD published between 2018 and January 2023. Guidelines and protocols from relevant paediatric and adult gastroenterology societies, such as the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation, were also included. Non-pharmacological treatments including therapeutic diets and faecal microbiota transplantation were outside the scope of this work., Results: Early real-world evidence suggests that newer biologics and small molecules, such as anti-integrins, interleukin-12 and/or interleukin-23 inhibitors, Janus kinase and signal transducer and activator of transcription proteins inhibitors, are safe and effective in adult patients with IBD, with promising growing evidence for paediatric IBD., Conclusion: While many developments have been achieved with novel pharmacological treatments to manage IBD, ongoing research is required to confirm their effectiveness and safety in the paediatric age. Extending the licence of novel treatments to children will be crucial to tackle the increasing loss of response to conventional treatments. International guidelines will require timely updating to incorporate novel treatments within the existing protocols., (© 2023 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic., Methods: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded., Results: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 μg/g, hFC 595 vs. 47 μg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 μg/g, p = 0.003, hFC 57 vs. 40 μg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels., Conclusions: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Anemia is one of the most common extraintestinal manifestations of pediatric inflammatory bowel disease (IBD). We aimed to evaluate the prevalence of anemia in children newly diagnosed with IBD and assess the efficacy and safety of oral iron therapy over a 12-month follow-up period., Methods: This single-center, retrospective, observational cohort study included all children newly diagnosed with IBD at the Pediatric Gastroenterology Unit of Sapienza University of Rome from May 2015 to May 2019 presenting with anemia. At baseline, demographic, clinical, laboratory data (hemoglobin, mean corpuscular volume, serum iron, ferritin, transferrin levels, erythrocyte sedimentation rate, and C-reactive protein), and treatment received, were recorded. Clinical and laboratory data, as well as anemia therapy and adverse events (AEs), were collected every 3 months during the 1-year follow-up., Results: Eighty-nine out of 140 patients newly diagnosed with IBD presented with anemia (64%); 13 were excluded due to incomplete follow-up, thus 76 were included [median age 12.7 (interquartile range 9.8-15), 25 (33%) Crohn disease, 51 (67%) ulcerative colitis]. All patients received sucrosomial iron (SI) alone or in combination with intravenous ferric carboxymaltose. Treatment with SI was effective in 67 (88%) patients at the end of follow-up [37 (48%) within 3 months], regardless of anemia severity at baseline. No serious AEs related to SI treatment were reported., Conclusions: We confirmed a high prevalence of anemia at the time of the diagnosis of pediatric IBD. Our data suggest that SI is safe and effective, leading to anemia resolution in approximately half of the patients within 3 months., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Data on the phenotypes and disease outcomes of very early-onset inflammatory bowel disease (VEO-IBD) are limited. The aims of this study were to describe the clinical features, outcomes, and treatment response of VEO-IBD patients and to compare them with later-onset pediatric inflammatory bowel disease (P-IBD) patients., Methods: All consecutive patients aged 0-6 years who were diagnosed with Crohn disease (CD), ulcerative colitis, or IBD unclassified (IBD-U) at 2 academic hospitals from 2010 to March 2021 were included. They were compared to sex-matched IBD patients aged 6-17 years., Results: Two hundred thirty-two patients were included, 78 (34%) with VEO-IBD and 154 (66%) with P-IBD. IBD-U was the most common diagnosis in the VEO-IBD group compared to P-IBD (28% vs 3%, P < 0.001), while CD was predominant in older children (27% vs 52%, P < 0.001). The VEO-IBD group showed lower rates of clinical remission after induction with steroids compared to older children (82% vs 93%, P = 0.01), higher rates of steroid resistance (14% vs 5%, P = 0.02), and steroid dependence (27% vs 8%, P < 0.001). The number of patients who started anti-tumor necrosis factor (TNF)-α agents was similar between the groups. Anti-TNF-α retention was lower in the VEO-IBD group at 1 and 2 years (59% vs 85%, P = 0.003; 16% vs 55%, P < 0.001, respectively). Surgical risk appeared to be higher for VEO-IBD (32% vs 14%, P < 0.001)., Conclusions: When compared to P-IBD patients, patients with VEO-IBD may have a more severe disease course, a poorer response to steroids and anti-TNF-α agents, and require more frequent surgical procedures., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: Crohn's disease is a chronic gastrointestinal inflammatory disease with possible extraintestinal symptoms. There are predisposing genetic factors and even monogenic variants of the disorder. One of the possible genetic factors are variants of the DUOX2 gene. The protein product of the DUOX2 gene is a dual oxidase enzyme producing H 2 O 2 in the bowel. Reduced H 2 O 2 levels impact mucosal homeostasis and contribute to the development of inflammatory bowel disease. Thus far, only 19 patients with IBD with the DUOX2 variants have been described., Methods: Here we present a case report of an adolescent female diagnosed at eleven years of age with IBD that was subsequently reclassified as Crohn's disease. She was treated with immunosuppressants and biological therapy but experienced additional complications. Her peripheral blood lymphocyte DNA was studied using massive parallel sequencing. Detected variants were functionally studied., Results: Whole exome sequencing found two novel DUOX2 gene variants: a de novo variant c.3646C>T; p.R1216W and a maternally inherited variant c.3391G>A; p.A1131T which were initially classified as variants of unknown significance. However, follow-up functional studies demonstrated that both DUOX2 variants led to impaired H 2 O 2 generation, which led to their reclassification to the likely pathogenic class according to the ACMG.net. Therefore, we conclude that these variants are causative for the disease., Conclusions: Identifying novel variants in patients with Crohn's disease and their families is important for precision medicine approaches and understanding of the pathogenesis of likely "monogenic" rare forms of inflammatory bowel disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: Inflammatory bowel disease (IBD) is a global disease. We aim to summarize the latest epidemiological patterns of IBD at the national, regional and global levels to give well-deserved attention and outline facilitating measures to reduce the disease burden., Methods: We collected the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of IBD in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Disease Study 2019. We further calculated the estimated annual percentage change (EAPC) to qualify the temporal trends of IBD burden by sex, age and region over the past 30 years., Results: Globally, a total of 404.55 thousand incident cases, 4898.56 thousand prevalent cases, 41.00 thousand deaths and 1622.50 thousand DALYs of IBD were estimated in 2019. The age-standardized DALYs decreased from 27.2 in 1990 to 20.15 per 100,000 people in 2019, with an EAPC of -1.04. The high socio-demographic index regions presented pronounced age-standardized rates (ASRs) consistently over the last 30 years. The high-income North America had the highest ASRs in 2019, followed by Western Europe and Australasia. No gender difference was observed after being stratified by sex., Conclusions: The accumulated IBD patients are expected to increase in the future due to the increased rate of IBD in developing countries, and social aging in developed countries. Understanding the changes in epidemiological patterns helps to provide evidence to mitigate the rising burden of IBD., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder caused by mutations in either TTC37 or SKIV2L, usually leading to congenital diarrhea as part of a multisystem disease. Here, we report on the natural history of the disease for the largest UK cohort of patients with THES from 1996 to 2020. We systematically reviewed the clinical records and pathological specimens of patients diagnosed with THES managed in a single tertiary pediatric gastroenterology unit. Between 1996 and 2020, 13 patients (7 female and 6 male) were diagnosed with THES either by mutation analysis or by clinical phenotype. Two patients died from complications of infection. All patients received parenteral nutrition (PN) of which six patients were weaned off PN. All patients had gastrointestinal tract inflammation on endoscopy. Almost half of the cohort were diagnosed with monogenic inflammatory bowel disease (IBD) by the age of 11 years, confirmed by endoscopic and histological findings. Protracted diarrhea causing intestinal failure improves with time in all patients with THES, but monogenic IBD develops in later childhood that is refractory to conventional IBD treatments. Respiratory issues contribute to significant morbidity and mortality, and good respiratory care is crucial to prevent comorbidity., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Xylooligosaccharides riched in xylobiose and xylotriose exhibit various biological activities as prebiotics. However, the prebiotics of xylooligosaccharides for regulating the intestinal microbiota in colitis models has been rarely investigated. In this study, differences in prebiotic ability of xylooligosaccharides samples from paper mulberry branches using different methods, including autohydrolysis (termed as 170AH), sequent purification by polystyrene-divinylbenzene copolymer resin (termed as 170AH-XAD), and enzymatic hydrolysis using endo- β -1,4-xylanase (170AH-XAD-E) were investigated. Results revealed that 170AH-XAD-E possessing higher fractions of xylobiose and xylotriose exhibited the best performance in vitro by promoting the proliferation of Bifidobacterium adolescentis and Lactobacillus acidophilus , with utilization rates of 92.30% and 91.00%, respectively. Additionally, 170AH-XAD-E outperformed the other samples in increasing the species' abundance of in vivo intestinal microbiota in colitis mouse model induced by Escherichia coli. Furthermore, 170AH-XAD-E selectively promoted the growth of Bacteroides , while inhibiting the proliferation of Firmicutes , Proteobacteria , and Actinobacteriota. These abilities of 170AH-XAD-E may be due to its potential to upregulate the population of intestinal microbiota associated with the functional abundance of Cell wall/membrane/envelope biogenesis and Inorganic ion transport and metabolism. Overall, this work demonstrates that XOS with high contents of xylobiose and xylotriose possesses excellent potential as intestinal microbiota regulators and anti-colitis agents. [Display omitted] • Xylooligosaccharides riched with xylobiose and xylotriose enhance probiotic growth. • Xylooligosaccharides with higher xylobiose and xylotriose increase gut flora. • Xylooligosaccharides with higher xylobiose and xylotriose alleviate colitis. [ABSTRACT FROM AUTHOR]

Background/objectives: We analyzed the nationwide pediatric inflammatory bowel disease (PIBD) registry (1998-2016), to evaluate the nutritional status at the time of diagnosis., Subjects/methods: Nine types of nutritional status by the combination of weight-for-length (<2 years)/body mass index (>2 years) and length/height-for-age with three categories (<-2, -2 to 2, and >2 SD) were described. Malnutrition was defined by WHO criteria. Univariate and multivariate regression analysis was used to identify risk factors for malnutrition., Results: In total, 824 IBD patients (498 Ulcerative colitis (UC); 289 Crohn's Disease (CD); 37 Indeterminate Colitis (IC); 412 male; the median age 12.5 years) were eligible. The prevalence of eutrophy, wasting/thinness, stunting, overweight, tall stature, concurrent wasting/thinness and stunting, tall stature with overweight, tall stature with wasting/thinness, and short stature with overweight were 67.4%, 14.9%, 6.6%, 3.1%, 3.2%, 3.3%, 1.1%, 0.4%, and 0.1%, respectively. The prevalence of malnutrition was 32.7%, indicating a higher prevalence in CD (p < 0.001). Incidence of overweight was less common in the CD than UC and IC (p < 0.001). Multivariate analysis revealed that age of onset (>10 years), prepubertal stage, severe disease activity, perianal involvement, and high C reactive protein level were independently associated with malnutrition in pediatric IBD., Conclusion: We showed the frequency of nutritional impairment in PIBD. The percentage of overweight subjects was lower than the other studies. The age of onset, disease activity, CRP level, perianal involvement, and pubertal stage were associated with a higher risk for developing malnutrition. Our results also confirmed that CD patients are particularly vulnerable to nutritional impairment., Clinical Trial Number: ClinicalTrials.gov Identifier: NCT04457518., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases. Here we describe the methods and rationale for these studies., Methods and Rationale: The MANTA and MANTA-RAy studies included men (aged 21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases, respectively. Participants had no history of reproductive health issues, and the following semen parameter values (≥ 5th percentile of World Health Organization reference values) at baseline: semen volume ≥ 1.5 mL, total sperm/ejaculate ≥ 39 million, sperm concentration ≥ 15 million/mL, sperm total motility ≥ 40% and normal sperm morphology ≥ 30%. Each trial included a 13-week, randomized, double-blind, placebo-controlled period (filgotinib 200 mg vs placebo, up to N = 125 per arm), for pooled analysis of the week-13 primary endpoint (proportion of participants with ≥ 50% decrease from baseline in sperm concentration). All semen assessments were based on two samples (≤ 14 days apart) to minimize effects of physiological variation; stringent standardization processes were applied across assessment sites. From week 13, MANTA and MANTA-RAy study designs deviated owing to disease-specific considerations. All subjects with a ≥ 50% decrease in sperm parameters continued the study in the monitoring phase until reversibility, or up to a maximum of 52 weeks, with standard of care as treatment. Overall conclusions from MANTA and MANTA-RAy will be based on the totality of the data, including secondary/exploratory measures (e.g. sperm motility/morphology, sex hormones, reversibility of any effects on semen parameters)., Conclusions: Despite the complexities, the MANTA and MANTA-RAy studies form a robust trial programme that is the first large-scale, placebo-controlled evaluation of potential impacts of an advanced IBD and rheumatic disease therapy on semen parameters., Trial Registration: EudraCT numbers 2017-000402-38 and 2018-003933-14; ClinicalTrials.gov identifiers NCT03201445 and NCT03926195., (© 2022. The Author(s).)

Background: Female gender could be a cause of diagnostic delay in inflammatory bowel disease (IBD). The aim of this study was to investigate the diagnostic delay in women vs men and potential causes., Methods: This multicenter cohort study included 190 patients with recent diagnosis of IBD (disease duration <7 months). Reconstruction of the clinical presentation and diagnostic process was carried out in conjunction with the semistructured patient interview, review, and electronic medical records., Results: The median time from symptom onset to IBD diagnosis was longer in women than in men: 12.6 (interquartile range, 3.7-31) vs 4.5 (2.2-9.8) months for Crohn's disease (CD; P = .008) and 6.1 (3-11.2) vs 2.7 (1.5-5.6) months for ulcerative colitis (UC; P = .008). Sex was an independent variable related to the time to IBD diagnosis in Cox regression analysis. The clinical presentation of IBD was similar in both sexes. Women had a higher percentage of misdiagnosis than men (CD, odds ratio [OR], 3.9; 95% confidence [CI], 1.5-9.9; UC, OR 3.0; 95% CI, 1.2-7.4). Gender inequities in misdiagnosis were found at all levels of the health system (emergency department, OR 2.4; 95% CI, 1.1-5.1; primary care, OR 2.5; 95% CI, 1.3-4.7; gastroenterology secondary care, OR 3.2; 95% CI, 1.2-8.4; and hospital admission, OR 4.3; 95% CI, 1.1-16.9)., Conclusions: There is a longer diagnostic delay in women than in men for both CD and UC due to a drawn-out evaluation of women, with a higher number of misdiagnoses at all levels of the health care system., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

The disease activity of axSpA after initiating anti-TNF agents for inflammatory bowel diseases (IBD) is poorly understood. We sought to examine the disease activity of axial spondyloarthritis (axSpA) after initiation of anti-tumor necrosis factor (TNF) agents among patients with IBD. This retrospective cohort study included adults with IBD and axSpA who initiated anti-TNF agents between 1/1/2012-10/1/2021 at a large academic center. The primary outcome was symptom resolution (SR) of axSpA at 12 months ("0/10 pain" or "no pain" or "controlled pain" with no morning stiffness and no use of daily NSAIDs). The secondary outcome was clinical remission (CR) of IBD at 12 months (simple clinical colitis activity index <3, Harvey-Bradshaw Index <5, or provider assessment with no use of oral/IV steroids for 30 days). Associations between baseline characteristics and SR of axSpA were examined using logistic regression. 82 patients with axSpA and IBD initiated anti-TNF agents. At 12 months, 52% and 74% achieved SR of axSpA and CR of IBD, respectively. IBD duration <5 years (OR 3.0, 95% CI 1.2-7.5) and adalimumab use (reference: all other anti-TNFs; OR 2.7, 95% CI 1.002-7.1) were associated with SR of axSpA at 12 months. 52% of patients with axSpA and IBD achieved SR of axSpA at 12 months after initiating anti-TNF therapy. Shorter disease duration and adalimumab use may be associated with higher odds of SR. Larger studies are needed to confirm these findings, examine additional clinical predictors of SR, and identify more effective therapeutics for this population., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: The consensus guidelines of the European Crohn's and Colitis Organization (ECCO) for the diagnosis and treatment of iron deficiency anemia (IDA) were published in 2015. We examined the management practices of both adult gastroenterologists (AGs) and pediatric gastroenterologists (PGs) in Israel in treating ID among patients with inflammatory bowel disease (IBD)., Methods: An 18-question multiple-choice anonymous questionnaire was electronically delivered to AGs and PGs. Questions explored 3 areas of interest: physician demographics, adherence to ECCO guidelines, and management practices of IDA in patients with IBD., Results: Completed questionnaires were returned by 72 AGs and 89 PGs. Practice setting and years of practice were similar. A large majority of AGs and PGs (89% and 92%, respectively) measure complete blood count (CBC) and serum ferritin (S-Fr) at least every 3 months in outpatients with active IBD, as recommended by the ECCO guidelines. In contrast, in IBD patients in remission, only 53% and 26% of AGs and PGs, respectively ( P < 0.001), reported adherence to ECCO guidelines, measuring CBC and S-Fr every 6 months. The ECCO treatment guidelines recommend that intravenous (IV) iron should be considered the first-line treatment in patients with clinically active IBD, with previous oral iron intolerance and those with a hemoglobin level <10 g/dL. Study results indicate that only 43% of AGs recommend IV iron for these indications, compared to 54% of PGs ( P > 0.1)., Conclusions: In this study we have demonstrated a relatively low level of adherence to ECCO guideline recommendations among both AGs and PGs, regarding the management of IDA in patients with IBD., Competing Interests: Dr Zittan has received research support and consulting fees from Janssen, AbbVie, Takeda, Neopharm, Celgene, and Pfizer. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view., Methods: A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <-2.0. Non-fatigued children had a z score ≥-2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated., Results: Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008)., Conclusion: Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life., Competing Interests: Dr Pierik reports grants and nonfinancial support from Falk Pharma, grants from European commission, grants from ZONMW (Dutch national research fund), grants and nonfinancial support from Takeda, grants and nonfinancial support from Johnson and Johnson, grants and nonfinancial support from AbbVie, nonfinancial support from Ferring, nonfinancial support from Immunodiagnostics, and nonfinancial support from MSD, all outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: This is an overview of the effects of COVID-19 in the gastrointestinal tract in children, and current evidence of the impact of COVID-19 in pediatric patients with chronic gastrointestinal conditions, including inflammatory bowel disease (IBD), chronic liver disease, and disorders of the gut-brain interaction., Recent Findings: Children with COVID-19 have a milder course and more favorable outcomes than adults, even in those with immunosuppression due to IBD or liver transplantation. Children with chronic gastrointestinal conditions do not have worse clinical outcomes than healthy children and infection itself has not been linked to an increased incidence of conditions such as IBD and celiac disease, but results regarding post-infectious irritable bowel syndrome are mixed., Summary: Research specific to pediatrics is needed, particularly in post-infectious disorders of the gut-brain interaction (PI-DGBIs) and long COVID-19. Data extrapolated from adult trials may not apply to children, as their clinical course is different. PI-DGBIs and long COVID-19 require special attention, as they represent a major morbidity burden in children., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: One of the greatest challenges in the current IBD clinical trial landscape is, perhaps, the recruitment and retention of eligible participants. Seamless testing of promising investigational compounds is paramount to address unmet needs, but this is hindered by a number of barriers, particularly patient concerns of placebo assignment., Aims: To review the use of novel trial designs leveraging externally derived data to synthetically create control groups or augment existing ones, and to summarise the regulatory position on the use of external controls for market authorisation., Methods: We conducted a PubMed literature search without restriction using search terms such as 'external controls' and 'historical controls' to identify relevant articles., Results: External controls are increasingly being used outside the context of cancer and rare diseases, including IBD, and increasingly recognised by regulatory bodies. Such designs, particularly in earlier phase trials, can inform key nodes in drug development and permit evaluating efficacy of interventions without combating the ethical and numerical enrolment challenges described. However, the lack of randomisation and blinding subjects them to significant bias. Groups require robust statistical and computational approaches to ensure patient-level data across groups are adequately balanced., Conclusions: While this approach has several pitfalls, and is not robust enough to replace traditional randomised, placebo-controlled trials, it may offer a compromise to address key research questions at a more rapid pace, with fewer patients, and lower cost., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: Outpatient inflammatory bowel disease (IBD) care shifted from office visits (OVs) to a model with integrated telemedicine during the 2020 COVID-19 pandemic. We describe the impact of this shift on delivery of pediatric IBD care., Methods: We collected electronic medical record data from office and telemedicine visits for pediatric patients with IBD at a single center from April 2019 to December 2020. We compared visit volume, duration, and test ordering between 2019 and 2020, and between OV and telemedicine, and assessed for differences in telemedicine adoption by sociodemographic factors., Results: Visit volume was maintained between 2019 and 2020. Median overall appointment time was shorter for telemedicine versus OV [46 (interquartile range, IQR 35-72) vs 62 (IQR 51-80) minutes; P < 0.001] with no significant difference in time spent with provider [28 (IQR 21-41) vs OV 30 (IQR 24-39) minutes; P = 0.08]. Accounting for drive time, telemedicine visits were 2.6 times shorter than office visits in 2020 ( P < 0.001). In univariate analyses, there was no difference in telemedicine utilization by race or gender. Variables significantly associated with telemedicine were older age, English as primary language, being non-Hispanic, commercial insurance, living in an area of very high opportunity, and having a longer drive time to the office ( P < 0.05 for all comparisons). In multivariate analyses, visits among patients with commercial insurance were significantly more likely to be conducted via telemedicine ( P = 0.02). Among those with a telemedicine visit, multivariate analyses demonstrated multiracial patients were significantly more likely to have video visits (vs audio-only; P = 0.02), while patients with public insurance, no or missing insurance, and whose primary language was Arabic were significantly less likely to have video visits ( P < 0.05 for all comparisons)., Conclusions: Integrated telemedicine allowed for continued delivery of pediatric IBD care and significantly decreased appointment time. While telemedicine may improve access for those who live further from the office, concerns remain about the introduction of disparities., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Several new classes of drugs have recently been developed for the management of Inflammatory Bowel Disease (IBD). In response, updated international guidelines have been published providing recommendations on how to incorporate these agents into existing treatment algorithms. Recent approval of these new therapies in South Africa has however raised many questions on how they should best be used in a local setting. Since no formal guidance is available, the South African Gastroenterology Society (SAGES) has put forward, in the present position paper, guidance on the best use of both existing and novel drug therapies in the management of IBD in the South African setting. [ABSTRACT FROM AUTHOR]

Very early onset inflammatory bowel disease (VEO-IBD) is diagnosed in children < 6 years of age, and in rare cases may be due to an identifiable monogenic cause. Recent advances in genetic testing have allowed for more accurate diagnosis, with as many as 100 genes now known to be associated with monogenic inflammatory bowel disease. These genes are involved in many immune pathways and thus may represent potential avenues for targeted precision medicine with pharmacologic treatments aimed at these. This review describes the broad classifications of monogenic disorders known to cause VEO-IBD, as well as empiric and disease-specific medical therapies. These include immune-modulating or immunosuppressant medications, nutritional therapy, surgery, and hematopoietic stem cell transplantation. We aim to provide an overview of the current state of targeted therapy for VEO-IBD., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)