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New Proactive Approaches and Precision Medicine in Crohn's Disease
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New Proactive Approaches and Precision Medicine in Crohn's Disease

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 22538

Special Issue Editor

Prof. Dr. Uri Kopylov

E-Mail Website
Guest Editor
Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
Interests: inflammatory bowel disease; capsule endoscopy; biomarkers; machine learning; therapeutic drug monitoring
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, huge progress has been made in both the diagnosis and monitoring of Crohn’s disease. Non-invasive, patient-friendly, and remote monitoring techniques such as capsule endoscopy, intestinal ultrasound, and home-based fecal calprotectin are gaining increased acceptance, replacing more traditional and invasive monitoring techniques. The ongoing COVID-19 pandemic has caused significant restrictions on patient mobility and enhanced the need for friendly remote monitoring and telemedicine. Novel therapies with more ambitious treatment goals, such as transmural healing and histological healing, are being evaluated in clinical trials and observational studies. Although these treatment goals are not yet considered as major therapeutic goals, they are routinely included in clinical trials as secondary endpoints. Proactive treatment strategies and personalized monitoring approaches are also being increasingly evaluated.

The therapeutic armamentarium in IBD has been rapidly expanding during the last decade. In addition to monoclonal antibodies targeting novel mechanisms (leukocyte adhesion, JAK/STAT pathway, interleukin 12 and 23, and S1P agonists), biosimilar therapies are changing the biological therapy market, resulting in significant cost reductions for well-established molecules such as infliximab and adalimumab. In addition, there is increasing evidence to support subcutaneous use of previously IV-only medications (infliximab and vedolizumab), with this trend being particularly important during the COVID-19 era.

The current Special Issue will focus on personalized medicine in CD, including but not limited to novel biomarkers, remote monitoring of disease activity, novel drug combinations, predictors of response to treatment and disease course and therapeutic targets.

Prof. Dr. Uri Kopylov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • personalized medicine
  • machine learning
  • big data
  • omics
  • treat-to-target
  • transmural healing

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Published Papers (6 papers)

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Research

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13 pages, 1747 KiB  
Article
The Inflammatory Bowel Disease—Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version
by Anastasia Katsoula, Georgios Axiaris, Afroditi Mpitouli, Maria Palatianou, Angeliki Christidou, Nikolaos Dimitriadis, Andreas Nakos, Ploutarchos Pastras, Panagiotis Kourkoulis, Pantelis Karatzas, Miltiadis Moutzoukis, Charalampos Zlatinoudis, Athanasios Philippidis, Anastasia Kourikou, Georgios Kokkotis, Antonios Gklavas, Angeliki Machaira, Aikaterini Mantaka, Persefoni Talimtzi, Evaggelia Anagnostopoulou, Ioannis E. Koutroubakis, Ioannis Papaconstantinou, Georgios Bamias, Spilios Manolakopoulos, Nicoletta Mathou, Konstantina Paraskeva, Andreas Protopappas, Eftychia Tsironi, Konstantinos H. Katsanos, Dimitrios K. Christodoulou, Georgios Papatheodoridis, Georgios Michalopoulos, Georgios Theocharis, Christos Triantos, Ioannis Pachiadakis, Konstantinos Soufleris, Nikolaos Viazis, Gerassimos J. Mantzaris, Georgios Tribonias, Maria Tzouvala, Angeliki Theodoropoulou, Konstantinos Karmiris, Evanthia Zampeli, Spyridon Michopoulos, Anna-Bettina Haidich and Olga Gioulemeadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(8), 3023; https://doi.org/10.3390/jcm12083023 - 21 Apr 2023
Cited by 2 | Viewed by 2182
Abstract
Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. Methods: [...] Read more.
Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. Methods: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. Results: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86–0.91)]. Cronbach’s coefficient alpha for all items achieved 0.90 (95%CI 0.88–0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. Conclusions: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
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11 pages, 1023 KiB  
Article
A Novel Prediction Tool for Endoscopic Intervention in Patients with Acute Upper Gastro-Intestinal Bleeding
by Ido Veisman, Amit Oppenheim, Ronny Maman, Nadav Kofman, Ilan Edri, Lior Dar, Eyal Klang, Sigal Sina, Daniel Gabriely, Idan Levy, Dmitry Beylin, Ortal Beylin, Efrat Shekel, Nir Horesh and Uri Kopylov
J. Clin. Med. 2022, 11(19), 5893; https://doi.org/10.3390/jcm11195893 - 5 Oct 2022
Cited by 3 | Viewed by 2042
Abstract
(1) Background: Predicting which patients with upper gastro-intestinal bleeding (UGIB) will receive intervention during urgent endoscopy can allow for better triaging and resource utilization but remains sub-optimal. Using machine learning modelling we aimed to devise an improved endoscopic intervention predicting tool. (2) Methods: [...] Read more.
(1) Background: Predicting which patients with upper gastro-intestinal bleeding (UGIB) will receive intervention during urgent endoscopy can allow for better triaging and resource utilization but remains sub-optimal. Using machine learning modelling we aimed to devise an improved endoscopic intervention predicting tool. (2) Methods: A retrospective cohort study of adult patients diagnosed with UGIB between 2012–2018 who underwent esophagogastroduodenoscopy (EGD) during hospitalization. We assessed the correlation between various parameters with endoscopic intervention and examined the prediction performance of the Glasgow-Blatchford score (GBS) and the pre-endoscopic Rockall score for endoscopic intervention. We also trained and tested a new machine learning-based model for the prediction of endoscopic intervention. (3) Results: A total of 883 patients were included. Risk factors for endoscopic intervention included cirrhosis (9.0% vs. 3.8%, p = 0.01), syncope at presentation (19.3% vs. 5.4%, p < 0.01), early EGD (6.8 h vs. 17.0 h, p < 0.01), pre-endoscopic administration of tranexamic acid (TXA) (43.4% vs. 31.0%, p < 0.01) and erythromycin (17.2% vs. 5.6%, p < 0.01). Higher GBS (11 vs. 9, p < 0.01) and pre-endoscopy Rockall score (4.7 vs. 4.1, p < 0.01) were significantly associated with endoscopic intervention; however, the predictive performance of the scores was low (AUC of 0.54, and 0.56, respectively). A combined machine learning-developed model demonstrated improved predictive ability (AUC 0.68) using parameters not included in standard GBS. (4) Conclusions: The GBS and pre-endoscopic Rockall score performed poorly in endoscopic intervention prediction. An improved predictive tool has been proposed here. Further studies are needed to examine if predicting this important triaging decision can be further optimized. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
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Review

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14 pages, 1860 KiB  
Review
Recent Advances and Potential Multi-Omics Approaches in the Early Phases of Inflammatory Bowel Disease
by Iago Rodríguez-Lago, Jonathan Blackwell, Beatriz Mateos, Urko M. Marigorta, Manuel Barreiro-de Acosta and Richard Pollok
J. Clin. Med. 2023, 12(10), 3418; https://doi.org/10.3390/jcm12103418 - 11 May 2023
Cited by 1 | Viewed by 2619
Abstract
Inflammatory bowel disease leads to debilitating gastrointestinal symptoms and reduced quality of life, resulting in a significant burden on healthcare utilization and costs. Despite substantial advancements in diagnosis and treatment, there may still be considerable delays in diagnosing some patients. To reduce disease [...] Read more.
Inflammatory bowel disease leads to debilitating gastrointestinal symptoms and reduced quality of life, resulting in a significant burden on healthcare utilization and costs. Despite substantial advancements in diagnosis and treatment, there may still be considerable delays in diagnosing some patients. To reduce disease progression before the full disease spectrum appears and improve prognostic outcomes, several strategies have concentrated on early intervention and prevention. Recent evidence shows that initial immune response changes and endoscopic lesions may exist for years before diagnosis, implying the existence of a preclinical phase of inflammatory bowel disease comparable to findings in other immune-mediated disorders. In this review, we highlight the most relevant findings regarding preclinical inflammatory bowel disease and the prospective role of novel omics techniques in this field. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
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14 pages, 1794 KiB  
Review
Fibro-Stenosing Crohn’s Disease: What Is New and What Is Next?
by Virginia Solitano, Arianna Dal Buono, Roberto Gabbiadini, Marek Wozny, Alessandro Repici, Antonino Spinelli, Stefania Vetrano and Alessandro Armuzzi
J. Clin. Med. 2023, 12(9), 3052; https://doi.org/10.3390/jcm12093052 - 22 Apr 2023
Cited by 17 | Viewed by 4786
Abstract
Fibro-stenosing Crohn’s disease (CD) is a common disease presentation that leads to impaired quality of life and often requires endoscopic treatments or surgery. From a pathobiology perspective, the conventional view that intestinal fibro-stenosis is an irreversible condition has been disproved. Currently, there are [...] Read more.
Fibro-stenosing Crohn’s disease (CD) is a common disease presentation that leads to impaired quality of life and often requires endoscopic treatments or surgery. From a pathobiology perspective, the conventional view that intestinal fibro-stenosis is an irreversible condition has been disproved. Currently, there are no existing imaging techniques that can accurately quantify the amount of fibrosis within a stricture, and managing patients is challenging, requiring a multidisciplinary team. Novel therapies targeting different molecular components of the fibrotic pathways are increasing regarding other diseases outside the gut. However, a large gap between clinical need and the lack of anti-fibrotic agents in CD remains. This paper reviews the current state of pathobiology behind fibro-stenosing CD, provides an updated diagnostic and therapeutic approach, and finally, focuses on clinical trial endpoints and possible targets of anti-fibrotic therapies. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
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25 pages, 396 KiB  
Review
Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease
by Eleni Orfanoudaki, Kalliopi Foteinogiannopoulou, Eirini Theodoraki and Ioannis E. Koutroubakis
J. Clin. Med. 2023, 12(7), 2452; https://doi.org/10.3390/jcm12072452 - 23 Mar 2023
Cited by 4 | Viewed by 2794
Abstract
Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn’s disease and ulcerative colitis. However, this does not only secure [...] Read more.
Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn’s disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
16 pages, 1003 KiB  
Review
Contemporary Management of Postoperative Crohn’s Disease after Ileocolonic Resection
by Jurij Hanzel and David Drobne
J. Clin. Med. 2022, 11(22), 6746; https://doi.org/10.3390/jcm11226746 - 15 Nov 2022
Cited by 7 | Viewed by 7281
Abstract
Surgery remains an important treatment modality in the multidisciplinary management of patients with Crohn’s disease (CD). To illustrate the recent advances in the management of postoperative CD we outline the contemporary approach to treatment: diagnosing disease recurrence using endoscopy or noninvasive methods and [...] Read more.
Surgery remains an important treatment modality in the multidisciplinary management of patients with Crohn’s disease (CD). To illustrate the recent advances in the management of postoperative CD we outline the contemporary approach to treatment: diagnosing disease recurrence using endoscopy or noninvasive methods and risk stratification underlying decisions to institute treatment. Endoscopic scoring indices are being refined to guide treatment decisions by accurately estimating the risk of recurrence based on endoscopic appearance. The original Rutgeerts score has been modified to separate anastomotic lesions from lesions in the neoterminal ileum. Two further indices, the REMIND score and the POCER index, were recently developed with the same intention. Noninvasive monitoring for recurrence using a method with high negative predictive value has the potential to simplify management algorithms and only perform ileocolonoscopy in a subset of patients. Fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography are all being evaluated for this purpose. The use of infliximab for the prevention of postoperative recurrence is well supported by data, but management decisions are fraught with uncertainty for patients with previous exposure to biologics. Data on the use of ustekinumab and vedolizumab for postoperative CD are emerging, but controlled studies are lacking. Full article
(This article belongs to the Special Issue New Proactive Approaches and Precision Medicine in Crohn's Disease)
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