Journal of Clinical Medicine

Research

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19 pages, 1277 KiB

Open AccessArticle

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

by Shahed Kamal, Nikita Parkash, William Beattie, Britt Christensen and Jonathan P. Segal

J. Clin. Med. 2023, 12(18), 5786; https://doi.org/10.3390/jcm12185786 - 5 Sep 2023

Cited by 1 | Viewed by 1791

Abstract

Crohn’s disease (CD) is a type of inflammatory bowel disease. The number of IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment. The classical description [...] Read more.

Crohn’s disease (CD) is a type of inflammatory bowel disease. The number of IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment. The classical description of CD involves transmural inflammation with skip lesions anywhere along the entire gastrointestinal tract. The complexity and heterogeneity of Crohn’s disease is not currently reflected in the conventional classification system. Though the knowledge of Crohn’s pathophysiology remains far from understood, the established complex interplay of the omics—genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics and immunophenomics—provides numerous targets for potential molecular markers of disease. Advancing technology has enabled identification of small molecules within these omics, which can be extrapolated to differentiate types of Crohn’s disease. The multi-omic future of Crohn’s disease is promising, with potential for advancements in understanding of its pathogenesis and implementation of personalised medicine. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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8 pages, 804 KiB

Open AccessArticle

Radiation Exposure among Patients with Inflammatory Bowel Disease: A Single-Medical-Center Retrospective Analysis in Taiwan

by Chen-Ta Yang, Hsu-Heng Yen, Yang-Yuan Chen, Pei-Yuan Su and Siou-Ping Huang

J. Clin. Med. 2022, 11(17), 5050; https://doi.org/10.3390/jcm11175050 - 28 Aug 2022

Cited by 2 | Viewed by 1418

Abstract

Inflammatory bowel disease (IBD) is a chronic and relapsing disease that can be complicated by abscesses, fistulas, or strictures of the damaged bowel. Endoscopy or imaging studies are required to diagnose and monitor the treatment response or complications of the disease. Due to [...] Read more.

Inflammatory bowel disease (IBD) is a chronic and relapsing disease that can be complicated by abscesses, fistulas, or strictures of the damaged bowel. Endoscopy or imaging studies are required to diagnose and monitor the treatment response or complications of the disease. Due to the low incidence of the disease in Taiwan, the pattern of radiation exposure from medical imaging has not been well studied previously. This retrospective study aimed to evaluate the pattern of radiation exposure in 134 Taiwanese IBD patients (45 CD and 89 UC) diagnosed and followed at Changhua Christian Hospital from January 2010 to December 2020. We reviewed the patient demographic data and radiation-containing image studies performed during the follow-up. The cumulative effective dose (CED) was calculated for each patient. During a median follow-up of 4 years, the median CED was higher for patients with CD (median CED 21.2, IQR 12.1–32.8) compared to patients with UC (median CED 2.1, IQR 0–5.6) (p < 0.001). In addition, the CD patients had a trend of a higher rate of cumulative ≥50 mSv compared with the UC patients (6.7% vs. 1.1%, p = 0.110). In conclusion, our study found a higher radiation exposure among CD patients compared to patients with UC, representing the complicated nature of the disease. Therefore, increasing the use of radiation-free medical imaging such as intestinal ultrasound or magnetic resonance imaging should be advocated in daily practice to decrease the risk of excessive radiation exposure in these patients. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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Review

Jump to: Research

0 pages, 263 KiB

Open AccessReview

Ustekinumab or Vedolizumab after Failure of Anti-TNF Agents in Crohn’s Disease: A Review of Comparative Effectiveness Studies

by Mohmmed Tauseef Sharip, Nilanga Nishad, Lushen Pillay, Nilkantsingh Goordyal, Samuel Goerge and Sreedhar Subramanian

J. Clin. Med. 2024, 13(8), 2187; https://doi.org/10.3390/jcm13082187 - 10 Apr 2024

Viewed by 679

Abstract

Background: Anti-tumour necrosis factor (TNF) agents are effective in Crohn’s disease (CD), but some patients lose responsiveness and require alternative biologic therapy. Until recently, ustekinumab and vedolizumab were the only other biological agents approved for use in CD. There are no randomised trials [...] Read more.

Background: Anti-tumour necrosis factor (TNF) agents are effective in Crohn’s disease (CD), but some patients lose responsiveness and require alternative biologic therapy. Until recently, ustekinumab and vedolizumab were the only other biological agents approved for use in CD. There are no randomised trials which compare the efficacy of these two agents in patients with anti-TNF refractory disease, but several retrospective cohort studies have compared their effectiveness in this setting. Aim: To review the effectiveness of ustekinumab and vedolizumab in anti-TNF refractory patients with CD. Methods: We included studies that compared the effectiveness of ustekinumab and vedolizumab in treating patients with anti-TNF refractory CD. We recorded the sample size, primary and secondary outcome measures and whether the studies employed adjustments for appropriate confounders. Results: Fourteen studies were included with a total sample size of 5651, of whom 2181 (38.6%) were treated with vedolizumab and the rest were treated with ustekinumab (61.4%). Of the fourteen studies included, eight found ustekinumab to be more effective in achieving clinical remission/steroid-free remission in the induction phase or during maintenance therapy (at least 1-year post-treatment) or that treatment persistence rates with ustekinumab were higher than with vedolizumab. Only one study reported vedolizumab to be superior during the maintenance phase in terms of clinical remission or treatment persistence rates. Biochemical outcomes were reported in five studies, two of which showed superiority for ustekinumab at 14 weeks and the other at 52 weeks. Only two studies reported endoscopic and/or radiologic outcomes; of these, one study showed ustekinumab to be significantly better at achieving endoscopic and radiologic responses. Adverse outcomes were broadly comparable, barring a single study which reported a lower hospitalisation rate for severe infection with ustekinumab. Conclusions: Most studies found ustekinumab to be more effective or non-inferior to vedolizumab in treating patients with anti-TNF refractory CD. Although many studies adjusted appropriately for confounders, the possibility of residual confounding remains and further data from prospective studies are warranted to confirm these findings. Further studies are required to compare these two therapies to other emerging therapies, such as Janus-kinase inhibitors. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

17 pages, 1486 KiB

Open AccessReview

Where Are We and Where to Next?—The Future of Perianal Crohn’s Disease Management

by Sulak Anandabaskaran, Luke Hanna, Nusrat Iqbal, Laura Constable, Phil Tozer and Ailsa Hart

J. Clin. Med. 2023, 12(19), 6379; https://doi.org/10.3390/jcm12196379 - 6 Oct 2023

Viewed by 1549

Abstract

Perianal fistulizing Crohn’s Disease (pCD) affects about 25% of patients with Crohn’s Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an [...] Read more.

Perianal fistulizing Crohn’s Disease (pCD) affects about 25% of patients with Crohn’s Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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21 pages, 2290 KiB

Open AccessReview

Unmet Challenges in Patients with Crohn’s Disease

by Katharina M Scheurlen, Mary A Parks, Anne Macleod and Susan Galandiuk

J. Clin. Med. 2023, 12(17), 5595; https://doi.org/10.3390/jcm12175595 - 27 Aug 2023

Cited by 2 | Viewed by 2062

Abstract

Patients with Crohn’s disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based [...] Read more.

Patients with Crohn’s disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn’s disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn’s disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn’s, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn’s disease. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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13 pages, 1507 KiB

Open AccessFeature PaperReview

The Promise of Single-Cell RNA Sequencing to Redefine the Understanding of Crohn’s Disease Fibrosis Mechanisms

by Iona Campbell, Michael Glinka, Fadlo Shaban, Kathryn J. Kirkwood, Francesca Nadalin, David Adams, Irene Papatheodorou, Albert Burger, Richard A. Baldock, Mark J. Arends and Shahida Din

J. Clin. Med. 2023, 12(12), 3884; https://doi.org/10.3390/jcm12123884 - 7 Jun 2023

Viewed by 2522

Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a high prevalence throughout the world. The development of Crohn’s-related fibrosis, which leads to strictures in the gastrointestinal tract, presents a particular challenge and is associated with significant morbidity. There are currently no [...] Read more.

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a high prevalence throughout the world. The development of Crohn’s-related fibrosis, which leads to strictures in the gastrointestinal tract, presents a particular challenge and is associated with significant morbidity. There are currently no specific anti-fibrotic therapies available, and so treatment is aimed at managing the stricturing complications of fibrosis once it is established. This often requires invasive and repeated endoscopic or surgical intervention. The advent of single-cell sequencing has led to significant advances in our understanding of CD at a cellular level, and this has presented opportunities to develop new therapeutic agents with the aim of preventing or reversing fibrosis. In this paper, we discuss the current understanding of CD fibrosis pathogenesis, summarise current management strategies, and present the promise of single-cell sequencing as a tool for the development of effective anti-fibrotic therapies. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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Graphical abstract

12 pages, 520 KiB

Open AccessReview

Obstetric Considerations in Pregnant Women with Crohn’s Disease

by Konstantina Rosiou and Christian P. Selinger

J. Clin. Med. 2023, 12(2), 684; https://doi.org/10.3390/jcm12020684 - 15 Jan 2023

Cited by 1 | Viewed by 3538

Abstract

Crohn’s disease affects many women of childbearing age. Fecundity rates are often lower than in the general population due to reduced fertility during active inflammation, effects of pelvic surgery or voluntary childlessness. Many women have concerns regarding the effects of pregnancy on their [...] Read more.

Crohn’s disease affects many women of childbearing age. Fecundity rates are often lower than in the general population due to reduced fertility during active inflammation, effects of pelvic surgery or voluntary childlessness. Many women have concerns regarding the effects of pregnancy on their Crohn’s, any potential effect of medication on the fetus, and passing on Crohn’s disease to the offspring. International guidelines on reproduction for women with Crohn’s disease provide evidence-based advice to patients and health care professionals. There is an increasing literature on the safety of advanced medication for Crohn’s disease during pregnancy. This review article therefore focuses on obstetric considerations beyond medication safety. We provide information on fertility, factors affecting pregnancy and fetal outcomes, obstetric complications, factors influencing mode of delivery, management of intestinal stomas during pregnancy and general considerations around breast feeding. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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18 pages, 1350 KiB

Open AccessReview

Frailty and Inflammatory Bowel Disease: A Scoping Review of Current Evidence

by Anne Fons, Kees Kalisvaart and Jeroen Maljaars

J. Clin. Med. 2023, 12(2), 533; https://doi.org/10.3390/jcm12020533 - 9 Jan 2023

Cited by 6 | Viewed by 2051

Abstract

Frailty is increasingly recognized as an important concept in patients with Inflammatory Bowel Disease (IBD). The aim of this scoping review is to summarize the current literature on frailty in IBD. We will discuss the definition of frailty, frailty assessment methods, the prevalence [...] Read more.

Frailty is increasingly recognized as an important concept in patients with Inflammatory Bowel Disease (IBD). The aim of this scoping review is to summarize the current literature on frailty in IBD. We will discuss the definition of frailty, frailty assessment methods, the prevalence of frailty, risk factors for frailty and the prognostic value of frailty in IBD. A scoping literature search was performed using the PubMed database. Frailty prevalence varied from 6% to 53.9%, depending on the population and frailty assessment method. Frailty was associated with a range of adverse outcomes, including an increased risk for all-cause hospitalization and readmission, mortality in non-surgical setting, IBD-related hospitalization and readmission. Therefore, frailty assessment should become integrated as part of routine clinical care for older patients with IBD. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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Graphical abstract

14 pages, 1287 KiB

Open AccessReview

Crohn’s Disease-Associated and Cryptoglandular Fistulas: Differences and Similarities

by Zhou Zhou, Laura F. Ouboter, Koen C. M. J. Peeters, Lukas J. A. C. Hawinkels, Fabian Holman, Maria F. Pascutti, Marieke C. Barnhoorn and Andrea E. van der Meulen-de Jong

J. Clin. Med. 2023, 12(2), 466; https://doi.org/10.3390/jcm12020466 - 6 Jan 2023

Cited by 2 | Viewed by 3965

Abstract

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn’s disease (CD), [...] Read more.

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn’s disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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9 pages, 14055 KiB

Open AccessReview

The Effects of the COVID Pandemic on Patients with IBD: Lessons Learned and Future Directions

by Eva Zhang, Britt Christensen, Finlay Alistair Macrae and Rupert Leong

J. Clin. Med. 2022, 11(23), 7002; https://doi.org/10.3390/jcm11237002 - 27 Nov 2022

Cited by 3 | Viewed by 1266

Abstract

The COVID-19 pandemic has caused extended global disruption and changed healthcare behaviour and delivery in patients with inflammatory bowel disease, many of whom take immune modifying treatment. Although there were fears about the vulnerability of IBD patients to SARS-CoV-2 infection, we have learnt [...] Read more.

The COVID-19 pandemic has caused extended global disruption and changed healthcare behaviour and delivery in patients with inflammatory bowel disease, many of whom take immune modifying treatment. Although there were fears about the vulnerability of IBD patients to SARS-CoV-2 infection, we have learnt that overall IBD patients are equivalent to the general population in both viral acquisition and infection outcomes. Overall IBD patients obtain effective vaccine-induced immune responses, although in some groups an additional vaccine dose is required to constitute a primary course. The pandemic has led to significant changes in healthcare delivery, some of which will be enduring. As we grapple with the challenges of recovery, the lessons learnt will continue to be important in optimising outcomes in future outbreaks. Full article

(This article belongs to the Special Issue Current Status, Challenges and Future Directions in Crohn's Disease)

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