Introduction

Crohn’s disease (CD) is a chronic disabling condition in which a consistent proportion of patients may develop stricturing complications. Despite the increasing availability of therapeutic options, to date no treatment exists for prevention or treatment of intestinal fibrosis in CD patients. Autophagy is a vital metabolic process by which the cell degrades, eliminates and recycles misfolded proteins and damaged organelles, and autophagy-related genes have been linked to CD occurrence, particularly in disease with fibrostricturing phenotype. In the intestinal mucosa, autophagy regulates oxidative stress and plays a role in controlling the inflammatory process by eliminating and degrading pathogenic bacteria and inhibiting the inflammasome complex. Increased levels of oxidized circulating biomarkers have been implicated in the pathogenesis of CD, particularly in the occurrence of tissue damage and fibrosis.

Aims & Methods

Aim of the study was to evaluate the potential role of defective autophagy in CD, and, in particular, we tested the novel hypothesis that autophagy/oxidative stress imbalance can be a relevant feature in CD patients with stenosing phenotype. We collected blood and bioptic samples from patients with CD (n=25) and in healthy controls (n=11). CD patients were divided into three groups based on their clinical history and colonoscopy findings: A) Inflammatory phenotype in remission (B1 according to Montreal Classification, with normal appearing mucosa); B) Inflammatory phenotype with active disease (B1, with endoscopic findings of inflamed mucosa); and C) stenosing (B2). We evaluated autophagy using the autophagosomal marker Lc3b-II, after extraction of total protein from bioptic samples and Western Blot analysis. Serum oxidative stress markers sNOX2-dp, H2O2, and serum hydrogen peroxide (H2O2) breakdown activity (HBA) were measured by means of ELISA method and HBA assay kit. Comparison between groups for continuous variables was carried out by ANOVA with Bonferroni correction.

Results

Lc3b-II levels are significantly reduced in samples with active inflammation (P<0.01) and stenotic phenotype (P<0.001). Remission samples have lower levels of autophagosomes (P<0.05) than healthy patients but higher than the stenotic phenotype. sNOX2-dp levels are significantly increased in groups with active inflammation (P<0.001), in remission (P<0.001), and in the stenotic group (P<0.0001). Moreover, H₂O₂ levels are significantly increased in groups with active inflammation (P<0.01) and stenosis (P<0.01) compared to the control group. Lastly, antioxidant power is significantly reduced in groups with active inflammation (P<0.001), in remission (P<0.01), and in the stenotic group (P<0.01).

Conclusion

Autophagic and redox homeostasis are impaired in CD patients, in particular in those with stenosing phenotype. Autophagy stimulation may represent an innovative pathway for the development of future anti-fibrotic therapies in CD patients and deserves further research.

Clinical Case Summary

Cryptosporidiosis is a gastrointestinal infection caused by the protozoan Cryptosporidium spp. It is typically self-limited in immunocompetent patients. However, in immunocompromised individuals, it can lead to moderate to severe diarrhea and significant morbidity and mortality.¹
We present the case of a 31-year-old woman with a history of Crohn’s disease in remission, who presented with a one-week history of diarrhea (up to 10 bowel movements daily), abdominal pain, and fever (38°C). Laboratory tests revealed an elevated C-reactive protein (CRP), and intestinal ultrasound showed bowel wall thickening, hyperemia and wall disruption, suggestive of an active flare. However, routine stool culture isolated Cryptosporidium, and based on her clinical background, oral paromomycin and azithromycin were initiated, resulting in complete clinical remission.
Cryptosporidiosis is a common parasitic cause of diarrhea, particularly affecting immunocompromised patients, such as those with HIV, cancer or solid organ transplants.²
Although few cases have been described in inflammatory bowel disease (IBD), the immunosuppressive state of these patients may increase the risk of infection. Diagnosing cryptosporidiosis in this population can be challenging, as stool tests detect only about 30% of cases, and the clinical presentation often mimics an IBD flare.³
Treatment is generally supportive and reserved for severe or refractory cases. Nitazoxanide is the drug of choice, and in non-responders, it can be combined with fluoroquinolones or azithromycin. In IBD patients, the decision to initiate specific antiparasitic treatment depends on the degree of immunosuppression and the clinical scenario.⁴
A clear association between IBD and cryptosporidiosis has not been established, but it is crucial to rule out opportunistic gastrointestinal infections in suspected flare-ups before starting specific therapies.
image "Bowel wall thickening, hyperemia, and disruption of the normal layer pattern."

References

(1) Janssen B, Snowden J. Cryptosporidiosis. 2023 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 28846353.
(2) Liu B, Schnider A, DeArmond M, Banach DB, Haubrich BA. Cryptosporidiosis in individuals with inflammatory bowel disease: a scoping review protocol. BMJ Open. 2024 Oct 15;14(10):e086529. doi: 10.1136/bmjopen-2024-086529. PMID: 39414295; PMCID: PMC11481120.
(3) Ferreira J, Baden R, Magge S, Cheifetz A. Cryptosporidiosis masquerading as a Crohn's flare. Inflamm Bowel Dis. 2011 Oct;17(10):E133-4. doi: 10.1002/ibd.21811. Epub 2011 Jul 7. PMID: 21739536.
(4) Manthey MW, Ross AB, Soergel KH. Cryptosporidiosis and inflammatory bowel disease. Dig Dis Sci 1997;42:1580–6.

Introduction

Crohn’s disease (CD) poses a clinical challenge due to its unpredictable post-operative recurrence and the necessity for effective therapeutic interventions. The molecular mechanisms governing recurrence are poorly understood, although oxidative stress (OS) has been implicated in CD pathogenesis. However, its specific role in recurrence remains elusive. This study aimed to analyze the gene expression signatures regarding OS and their implications for CD recurrence using transcriptomic analysis.

Aims & Methods

Ileal mucosa samples were obtained from the prospective mutlicentrique cohort of CD patients undergoing surgery. They were collected from ileal resection margins (n = 196) at the time of surgery (M0) and in the neo-terminal ileum (n = 121) 6 months after surgery (M6) while patients were classified as in remission (Rem) or recurrence (Rec) based on the Rutgeerts score. Endoscopic recurrence was defined as a Rutgeerts score ≥i2b. Gene data sets (Affymetrix microarrays) were issued on a princeps paper*. Pathway analysis was conducted to identify significant OS pathways using the Ensemble of Gene Set Enrichment Analyses (EGSEA) method and through unsupervised signature generation (Independent Component Analysis) from M0 and M6 genes dataset. Statistical analyses were carried out to assess differential gene expression and pathway enrichment between Rem and Rec patients at M0 and M6.

Results

No significant genes were differentially expressed between Rem and Rec groups at M6 and M0. However, using EGSEA at M6, of the 1766 significant pathways, 40 were related to OS and predominantly overexpressed in the Rec group, indicating a potential association between OS resolution and pressure relief. At M0, of the 2556 significant pathways, 40 were related to OS and equally distributed between the Rem and Rec groups, and therefore did not predict recurrence at M6. Applying unsupervised signature generation, 140 signatures were identified and 8 were annotated as OS pathways. Theses OS pathways were upregulated at M6 in the Rec group and at M0 in the Rem group.

Conclusion

The study highlights the role of OS in CD progression and post-operative relapse. The significant increase in OS pathways at M6 in relapsed patients and at M0 in patients who remain in remission suggests that resolution of OS is necessary to counteract CD relapse. Further research is needed to delineate the role of oxidative stress in CD recurrence and to identify new therapeutic targets tailored to individual patient profiles.

References

*Ngollo et al. Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease JCC 2022;16(8):1269-1280. doi: 10.1093/ecco-jcc/jjac021.

Disclosure

There is no conflict of interest regarding this abstract

Introduction

5-aminosalicylates (5-ASAs) are commonly used in patients with Crohn’s disease (CD), especially in mild-to-moderate disease. Over half of patients receive 5-ASA during their disease course, with up to 30% continuing long-term therapy for either active (induction of remission) or quiescent (maintenance of remission) disease. However, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs). In preparation for the results of the STATIC trial (NCT 03261206)¹, we conducted an umbrella review to consolidate existing knowledge by identifying, evaluating, and synthesizing findings from published SRs on the use of 5-ASA in patients with active or quiescent CD.

Aims & Methods

Following Cochrane guidelines for "Overviews of Reviews" and adhering to the Preferred Reporting Items for Overviews of Reviews (PRIOR), we systematically searched major databases for relevant SRs published in English until February 28, 2024, summarizing data on 5-ASA use in induction, maintenance, or withdrawal trials of CD. We excluded SRs focusing solely on post-surgical patients or studying the chemoprevention effects of 5-ASA. Two independent reviewers screened articles, extracted data, and assessed quality using AMSTAR 2.

Results

Of 795 screened references, 8 SRs met our inclusion criteria, with the number of included RCTs ranging from 2 to 22 (Table). Most SRs included RCTs of patients with mild-to-moderate ileo-colonic CD. Three SRs focused on induction of remission, two on maintenance of medically induced remission, and three included both, while none investigated withdrawal of therapy. Two SRs were network meta-analyses (NMA) comparing 5-ASAs with other active treatments or placebo; four were Cochrane systematic reviews comparing 5-ASAs with placebo, corticosteroids, or thiopurines (AZA or 6-MP). One SR, published in 2017,used the outdated Jadad scale to assess the risk of bias of RCTs; only Cochrane reviews assessed the level of certainty of evidence. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine was more effective than placebo, ranking higher than low-dose budesonide and sulfasalazine, though lower than systemic corticosteroid and high-dose budesonide. Conversely, the latest Cochrane review in 2016, including 12 RCTs for maintenance of remission, found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. No SRs performed subgroup analysis for duration of remission upon enrollment. Only the NMA conducted a sensitivity analysis to evaluate baseline disease activity, indicating that high-dose mesalamine was superior to placebo when restricted to RCTs with an enrollment CDAI between 150 to 450.

Conclusion

The results of this umbrella review of SRs suggest that high-dose mesalamine may be considered for inducing remission in mild-to-moderate CD. However, evidence does not support the role of 5-ASA for maintaining medically induced remission. Updating SRs with new evidence is imperative to provide guidance on patient subsets who may benefit from 5-ASA use and these results will be updated with the STATIC trial ¹.

References

1. NCT03261206. Stopping Aminosalicylate Therapy in Inactive Crohn's Disease (STATIC) https://classic.clinicaltrials.gov/ct2/show/NCT03261206

Introduction

Endoscopic scores are crucial for assessing Crohn's disease (CD) severity, guiding therapy, and monitoring progression. The Simplified Endoscopic Score for Crohn's Disease (SES-CD) is widely used for this purpose [1]. Accurate scoring is vital for patient care. Recently, artificial intelligence has demonstrated potential in medical image interpretation [2]. This study aims to evaluate ChatGPT's effectiveness in rating the SES-CD.

Aims & Methods

This retrospective study evaluated ChatGPT's accuracy in assessing CD endoscopic activity using the SES-CD. One representative still image was selected for each bowel segment, and stricture degrees were provided separately if present. ChatGPT scored the SES-CD based on these images. The IBD expert's ratings were validated by calculating the intra-class correlation coefficient (ICC) with clinical trial central readers. The ICC between the IBD expert and ChatGPT scores was calculated to determine ChatGPT's reliability in SES-CD scoring.

Results

Nine (mean age 32.0 ± 11.8 years, 77.8% male) were included, with 45 bowel segments. Three (33.4%), 5 (55.6%), and 1 (11.1%) had nonstricturing nonpenetrating, structuring, and penetrating disease, respectively. Four (44.4%) had ileal disease and 5 (55.6%) had ileocolonic disease. Five (55.6%) had previous IBD surgery.
The SES-CD scores of the participants, rated by IBD expert in the hospital, revealed the following mean and standard deviation for each segment of the bowel: 6.9 ± 2.3 in the ileum, 1.3 ± 2.6 in the right colon, 1.6 ± 2.4 in the transverse colon, 1.3 ± 2.6 in the left colon, and 1.3 ± 2.6 in the rectum. The total SES-CD score was 12.4 ± 10.9. The score reliability of the institute IBD expert was tested compared to the clinical trial central reader and an intraclass correlation coefficient was calculated and found to be 0.96 (95% CI, 0.84-0.99) which is considered extremely correlated.
The mean and standard deviation of ChatGPT score in each segment were: 6.4 ± 2.4 in the ileum, 2.4 ± 3.8 in the right colon, 0.9 ± 2.7 in the transverse colon, 0.3 ± 1.0 in the left colon, 0.6 ± 1.3 in the rectum, with total SES-CD score of 10.6 ± 6.8. The calculated ICC between the expert and ChatGPT obtained SES-CD scores was 0.80 (95% IC, 0.64- 0.89) which is considered highly correlated.

Conclusion

Despite being based on only one photo per segment, ChatGPT demonstrated satisfactory performance in estimating endoscopic activity in CD. The differences between the IBD expert obtained scores and ChatGPT scores were acceptable, suggesting that artificial intelligence has the potential to be a useful tool in clinical and research settings, providing an accurate estimation of disease severity based on limited visual data.

References

1- Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
2- Levartovsky A, Albshesh A, Grinman A, et al. Enhancing diagnostics: ChatGPT-4 performance in ulcerative colitis endoscopic assessment. Endosc Int Open. 2025;13:a25420943. Published 2025 Mar 14.