Introduction

Inflammatory bowel disease (IBD) is associated with an increased risk of cerebrovascular disease (CVD) and coronary heart disease (CHD). It has been suggested that chronic inflammation may be the mechanism. Previous studies have primarily assessed IBD as a group and not ulcerative colitis (UC) or Crohn’s disease (CD) separately.

Aims & Methods

This study aims to determine the relationship between UC and CD and CVD and CHD risk factors/outcomes in a large UK population. General practice electronic medical records were sourced from the United Kingdom (UK) via The Health Improvement Network (THIN). UC and CD risk factors and disease outcomes were identified through Read codes.

Results

Factors	UC Prevalence, n (%) n=3,432	UC Odds Ratio, 95% CI	CD Prevalence, n (%) n=2,831	CD Odds Ratio, 95% CI
Female Sex	1,796 (52.3%)	1.16, 1.09-1.25	1,689 (59.7%)	2.71, 2.08-3.62
Age	43.95 ± 14.4	0.99, 0.99-0.99	45.7 ± 15.7	0.95, 0.94-0.96
Diabetes Type II	417 (12.2%)	1.50, 1.35-1.66	265 (9.4%)	1.12, 0.98-1.27
Dyslipidemia	176 (5.1%)	1.26, 1.08-1.47	112 (4.0%)	0.96, 0.79-1.16
Obesity	7 (0.2%)	0.99, 0.47-2.10	7 (0.3%)	1.21, 0.58-2.55
AMI	113 (3.3%)	1.57, 1.30-1.89	57 (2.0%)	0.95, 0.73-1.23
Ischemic Stroke	47 (1.4%)	1.46, 1.09-1.95	23 (0.8%)	0.86, 0.57-1.30
Intracranial Hemorrhage	15 (0.4%)	1.67, 1.01-2.78	10 (0.4%)	1.35, 0.72-2.51
COPD	31 (0.9%)	1.85, 1.30-2.64	24 (0.9%)	1.74, 1.16-2.59

A total of 1,062,022 unique adult patients were available for analysis. There were 3,432 UC (mean age: 43.95 years, SD=14.4 years; 52% female) and 2,831 CD cases (mean age: 40.9 years, SD=14.06 years; 60% female).

Ulcerative Colitis: Univariate analysis in Table 1. Multiple logistic regression (MLR) of CHD risk factors and outcomes (adjusted in all models for age, sex, diabetes, COPD, dyslipidaemia, obesity, and statins) revealed statistically significant independent CHD risk factors: female sex (OR: 1.19, 95%CI: 1.11-1.28), younger age (OR: 0.98, 95%CI: 0.98-0.99), type 2 diabetes (OR: 1.22, 95%CI: 1.09-1.37), and increased risk of acute myocardial infarction (AMI) (OR: 1.35, 95%CI: 1.11-1.64).
MLR of CVD risk factors and outcomes (adjusted as above plus thrombolytic agents) found statistically significant independent CVD risk factors: female sex (OR: 1.19, 95%CI: 1.10-1.27), younger age (OR: 0.99, 95%CI: 0.98-0.99), diabetes type 2 (OR: 1.20, 95%CI: 1.07-1.34), statin use (OR: 1.13, 95%CI: 1.03-1.25), and any anti-thrombolytic agents (OR: 1.37, 95%CI: 1.25-1.51).
Crohn’s Disease: Univariate analysis in Table 1. MLR of CHD risk factors and outcomes (adjusted) revealed statistically significant independent CHD risk factors: female sex (OR: 0.92, 95%CI: 0.85-0.99), younger age (OR: 0.98, 95%CI: 0.97-0.99), statin use (OR: 1.23, 95%CI: 1.11-1.36), and an increased likelihood of death (OR: 1.28, 95%CI: 1.12-1.47).
MLR of CVD risk factors and outcomes (adjusted) revealed statistically significant independent CVD risk factors: female sex (OR: 0.91, 95%CI: 0.84-0.98), younger age (OR: 0.97, 95%CI: 0.96-0.98), anti-thrombolytic agents (OR: 1.71, 95%CI: 1.55-1.90), and an increased likelihood of death (OR: 1.18, 95%CI: 1.03-1.35).

Conclusion

UC cases are more likely to be female, have diabetes, be taking statins, and anti-thrombolytic agents, and have an increased risk of AMI and death. CD cases are less likely to be female, but more likely to be taking statins, anti-thrombolytic agents, and more likely to die.

Disclosure

Guy D. Eslick and Michael P. Jones have nothing to disclose. Nicholas J. Talley Disclosures: GutSee Ltd (consulting microbiome, 2025), Brown University, Agency for Health Care Research and Quality (fiber and laxation) (2024), Rome Foundation (member gastroduodenal committee) (present) Biocodex (FD diagnostic tool) (present) Microba (consulting microbiome - commencing 2025) Comvita Manuka Honey (FD trial consulting) (2025), BluMaiden outside the submitted work. In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, ”Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Patent Application No. 63/537,725.
Boards: The Gut Foundation Board (2025-present), Asia Pacific Association of Medical Editors (APAME) Board (President 2023-2025), Doctors for the Environment (Chair 2024-present), Luminal Faculty GESA (Chair) (2023-2025)
Editorial: UptoDate (Section Editor), Mayo Clinic Proceeding Associate Editor (2023-present)
Financial support: Dr. Talley is supported by funding from the National Health and Medical Research Council (NHMRC) to the Centre for Research Excellence in Digestive Health and he holds an NHMRC Investigator grant.

Clinical Case Summary

A 24-year-old male presented with jaundice and mild vertigo after a 10-day prodrome (asthenia, nausea, headache, fever). Ibuprofen (1200 mg/d) was taken for these symptoms only during the first 5 days. Labs revealed acute hepatocellular injury and elevated cholestasis (AST 215, ALT 862, FA 134, GGT 126 IU/L), marked mixed hyperbilirubinemia (Total 13.5 mg/dL, Direct 7.58 mg/dL) and coagulopathy (INR 1.59). Ultrasound showed hepatosplenomegaly. Viral hepatitis (HAV/HBV/HCV/CMV) and autoimmune/metabolic causes were excluded. Epstein-Barr Virus (EBV) serology showed low-titer positive VCA IgM but negative VCA IgG, EBNA IgG, and serum EBV DNA PCR, indicating recent non-active infection. Given ibuprofen timing and high RUCAM score, drug-induced liver injury (DILI) with a hepatocellular pattern was suspected. Liver biopsy confirmed acute hepatitis with lymphomonocytic infiltrate, necrosis and canalicular cholestasis. Despite improving liver function tests post-ibuprofen cessation, he developed worsening vertigo, severe ataxia, nausea, vomiting, hypophonia, necessitating nasogastric feeding/bed confinement. Cerebrospinal fluid (CSF) showed mild mononuclear pleocytosis (16 cells/mm³); a multiplex PCR pathogen panel (including EBV) was negative. Brain MRI/EEG were normal. Post-infectious EBV acute cerebellar ataxia was diagnosed concurrently with DILI, based on timing post-recent EBV, exclusion of active neurological infection (negative CSF PCR, normal imaging), mild pleocytosis, and supported by later IgG seroconversion. IV methylprednisolone treatment, chosen for clinical severity, led to significant neurological improvement within days and eventual recovery after physiotherapy. This case highlights the significant challenges of diagnosis and management of concomitant DILI and recent EBV infection with neurological sequelae, requiring careful differentiation of liver damage patterns (hepatocellular DILI vs cholestatic EBV) and optimal management of neurological symptoms.

References

Illustrative Material References:
- Liver biopsy histology slides (highlighting lymphomonocytic infiltrate, necrosis, and canalicular cholestasis characteristic of DILI).
- Table/Graph showing serial Liver Function Tests (AST, ALT, Bilirubin) over time, depicting injury peak and recovery trend.
- Table summarizing sequential Epstein-Barr Virus (EBV) serology results (VCA IgM, VCA IgG, EBNA IgG) demonstrating seroconversion.
- Table summarizing Cerebrospinal fluid (CSF) analysis results (cell count, protein, glucose, negative multiplex PCR).
- Representative Brain MRI images (axial/sagittal views) confirming absence of structural lesions or encephalitis signs.

Introduction

Among immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs), gastrointestinal irAEs (GI-irAEs) are relatively rare, and their risk factors and prognostic implications remain unclear.

Aims & Methods

We retrospectively analyzed 1,104 patients who initiated ICI therapy at our institution between January 2016 and December 2022 and for whom survival data were available. GI-irAEs were defined as colitis with an increase of ≥3 bowel movements/day from baseline in the absence of other causes, or symptomatic gastritis confirmed histologically. Risk factors and prognostic impact of GI-irAEs were evaluated.

Results

The median duration of ICI therapy was 107 days. The cohort included 754 males (68%) with a median age of 69 years. The primary tumor types were lung cancer (32%), gastrointestinal cancers (19%), urothelial carcinoma (13%), head and neck cancer (13%), and melanoma (11%). The overall response rate was 27.8%, and the disease control rate was 49.0%. irAEs of any grade occurred in 310 patients (28%), and GI-irAEs were observed in 30 patients (2.7%). In univariate logistic regression analysis, use of anti-CTLA-4 antibody, combination ICI therapy, a prognostic nutritional index (PNI) ≥ 40, and platelet-to-lymphocyte ratio (PLR) ≥ 1.8 were associated with an increased risk of GI-irAEs. In multivariate analysis, only anti-CTLA-4 antibody use remained a significant risk factor (odds ratio: 9.2; 95% CI: 1.9–45). Kaplan–Meier analysis revealed that patients with GI-irAEs had significantly longer overall survival (OS) compared to those without irAEs in the overall cohort (median OS: 22.9 vs. 12.6 months, P < 0.0001). However, this difference was not observed in landmark analyses at 4 and 8 weeks post-treatment. Subgroup analysis based on PNI showed that in patients with PNI ≥ 40, those with GI-irAEs had significantly longer OS than those without irAEs (median not reached vs. 19.3 months, P = 0.0003). In contrast, in patients with PNI < 40, GI-irAE cases tended to have shorter OS than non-irAE cases (8.2 vs. 9.3 months). This trend was consistent in landmark analyses at 4 and 8 weeks.

Conclusion

The impact of GI-irAEs on prognosis appears to differ depending on the patient’s nutritional status. Particular caution is warranted for patients in poor general condition receiving ICIs, especially those involving anti-CTLA-4 antibodies, as GI-irAEs may serve as a poor prognostic factor in this population.

Introduction

Artificial intelligence (AI) characterization (CADx) systems for colonic polyps exhibit high diagnostic accuracy. However, they may only support, not replace, clinical decision-making and little is known of this human-AI interaction – even less so with trainee endoscopists. This issue is difficult to explore, but data from a study investigating CADx-supported trainee endoscopists compared to AI-blinded experts could give insight.

Aims & Methods

This analysis draws on data from a prospective observational study comparing the diagnostic performance of CADx-supported trainee endoscopists (using GI Genius®, Medtronic) to expert endoscopists blinded to AI support. Two key scenarios were explored: (a) instances in which the CADx system produced a ‘no prediction’ output, and (b) cases where trainees actively overruled AI-generated diagnoses. These were assessed to examine the impact of AI absence and human-AI discordance on diagnostic accuracy.

Results

The baseline cohort included 11 trainees performing 225 colonoscopies, mean age 63.8 years (SD 12.7), 48.9% male patients. Baseline ADR was 57.8%. Of 630 resected lesions (median size 3 mm, IQR 2;4), 40.0% were in the rectosigmoid, and 53.6% were non-adenomatous. CADx failed to provide a prediction in 19.2% (n=121) of cases. These ‘no prediction’ polyps were smaller (median 3 mm, p=0.048) and more often located in the right colon (72% vs. 58%, p=0.005. In the absence of AI support, trainee diagnostic accuracy declined significantly by 12.8% (63.6% vs. 76.4%, p=0.007). Interestingly, expert endoscopists—despite being blinded to AI—also performed worse on these polyps (64.7% vs. 73.9%, p=0.045), suggesting an inherent difficulty in classifying these lesions.
Trainees overruled AI suggestion leading to discordant diagnoses in 9.0% (57/630) of polyps, comprised of 20 (35.1%) non-adenomatous, and 37 (64.9%) adenomatous lesions. Trainees incorrectly overruled AI in 59.6% (34/57), which mostly consisted of downgrading lesions to NICE 1. Discordant polyps did not differ in size (3 mm vs. 3 mm, p=0.413), but were more often located proximally (77.2% vs. 58.1%, p=0.005). The difference in false negative rate (FNR) between trainees and AI was 62.16% (81.07% vs. 18.92%, p<0.0001), demonstrating a risk of missed adenomas when trainees override AI. Blinded expert endoscopists achieved identical overall diagnostic accuracy in those polyps as the AI system (59.6%). However, their error profiles differed – In this subset, blinded experts and AI performed equally in overall accuracy (59.6%), although with differing error profiles: AI showed a numerically lower FNR (18.9% vs. 35.1%, Δ16.2%, p=0.17), offset by a higher false positive rate (80.0% vs. 50.0%).

	´No prediction´ polyps (n=121)	Polyps with AI prediction (n=492)
Size mm, median (IQR)	3 (2;4)	3 (2;4)	p=0.0483
Location in right colon	72%	58%	p=0.005
Diagnostic accuracy, trainees, % (95%CI)	63.6% (0.55-0.72)	76.4% (0.73-0.80)	p=0.007
Diagnostic accuracy, experts, % (95%CI)	64.7% (0.53-0.72)	73.9% (0.69-0.78)	p=0.0454

Conclusion

CADx systems generate ‘no prediction’ outputs in a substantial proportion of polyps, significantly impairing trainee diagnostic performance. These cases may represent inherently more challenging lesions. Despite CADx’s high accuracy, trainees overrule AI in almost every tenth polyp, most often incorrectly downstaging polyps. Structured training on appropriate use of CADx, emphasizing both its capabilities and limitations, may enhance clinical effectiveness. Further research on human-AI interaction and trust is warranted, as these factors will be critical for successful integration of CADx into routine endoscopic practice.

Disclosure

The original study (AC-CADx) received technical support by Medtronic. Medtronic was not involved in the design of the study or analysis of the data, neither in the original study nor this exploratory analysis.

Clinical Case Summary

Background: Crohn’s disease (CD) is a chronic inflammatory condition frequently managed with biologic therapies. While venous thromboembolism (VTE) is a recognized complication in inflammatory bowel disease (IBD), certain biologics, including JAK2 inhibitors, have been linked to increased thrombotic events. This case report describes a rare instance of recurrent, unprovoked pulmonary embolism (PE) in a CD patient receiving Vedolizumab (VDZ).
Case presentation: A 45-year-old male with a long-standing history of CD experienced recurrent disease flares. His medical history included an ileo-colonic resection and anastomotic revision, after which he developed a provoked PE requiring long-term anticoagulation. Previous treatments, including infliximab, Adalimumab, Ustekinumab, Methotrexate, and 6-MP, had failed before he was started on VDZ monotherapy, which effectively controlled his colitis. Despite intensified anticoagulation, he had four hospitalizations for unprovoked PE within a year. A comprehensive hematologic evaluation, reviewed by a consultant haematologist, ruled out any underlying thrombophilic disorders. Given concerns about a potential association between VDZ and recurrent VTE, the medication was discontinued, and the patient was transitioned to Risankizumab. After four months, no further VTE episodes were reported.
Discussion & conclusion: Emerging evidence, including a study by Cross et al. (2017), suggests that patients treated with VDZ have a higher risk of thrombotic complications. This case highlights a potential, yet rare, association between Vedolizumab and recurrent PE in CD patients. Clinicians should remain vigilant when prescribing VDZ, particularly in patients with a history of thromboembolic events. Further research is needed to explore this association and guide clinical decision-making.

References

https://www.researchgate.net/publication/316370555_The_Incidence_of_Cardiovascular_Events_in_Patients_with_Crohn's_Disease_Treated_with_Vedolizumab_and_Anti-TNF_Therapies

Disclosure

No Conflict of Interest

Introduction

Inflammatory bowel diseases (IBD), comprising two main disorders, Crohn’s disease (CD) and ulcerative colitis (UC) are chronic conditions characterized by a fluctuating disease course. Symptoms vary depending on disease activity, localization, and behavior. The etiopathogenesis of IBD is complex and environmental factors play a key role in developing intestinal inflammation. We hypothesized that seasonal changes may influence the severity and frequency of exacerbations.

Aims & Methods

The goal of the study was to determine the impact of seasonal changes on the onset and clinical presentation of IBD. As the normal distribution was violated the Kruskall-Wallis test was utilized. Results are presented as median with interquartile range (IQR). p-values <0.05 were considered statistically significant. We retrospectively assessed cases of IBD exacerbations requiring hospitalization in the Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland between 2010 and 2025. A total of 563 patients were analyzed (207 with CD and 365 with UC). Additional data, such as age of onset, disease duration, and disease severity were extracted from the medical records where possible.

Results

The median age was 43 years (IQR: 35.00-55.00) for CD patients and 43.5 years (IQR: 34.50-62.50) for UC patients. Median age at diagnosis was 27 years (IQR: 20.00-41.00) for CD patients and 29 years (IQR: 22.00-45.00) for UC patients. Median disease duration was 5 years (IQR: 1.00-11.00) for CD and 3 years (IQR: 0.00-9.00) for UC. No statistically significant seasonal variation in exacerbation rates was observed for either CD or UC patients (p = 0.509). There were also no significant seasonal differences in age (CD: p = 0.866; UC: p = 0.340), age at diagnosis (CD: p = 0.576; UC: p = 0.571), disease duration (CD: p = 0.434; UC: p = 0.244), or disease severity (Total Mayo Score: p = 0.619; Partial Mayo Score: p = 0.790; Harvey-Bradshaw Index: p = 0.540).

		Median (IQR)
	Spring	Summer	Autumn	Winter
Age of CD diagnosis	26.00 (20.00 – 42.00)	30.50 (19.75 – 38.50)	27.00 (21.50 – 39.50)	26.50 (19.00 – 39.00)
Age of UC diagnosis	29.50 (20.50 – 45.50)	28.00 (20.00 - 46.00)	32.00 (24.00 – 49.00)	29.00 (22.00 – 40.00)
CD duration	6.00 (2.00 – 14.25)	4.00 (1.00 – 9.50)	4.00 (1.00 – 9.50)	5.00 (1.00 – 10.00)
UC duration	3.00 (0.00 – 8.00)	4.50 (0.00 – 11.00)	1.00 (0.00 – 9.00)	2.00 (0.00 – 7.00)
TMS	10.00 (9.00 – 11.00)	10.00 (8.00 – 11.00)	10.00 (9.00 - 11.00)	10.00 (8.00 – 11.00)
PMS	7.00 (6.00 - 8.00)	7.00 (6.00 – 8.00)	7.50 (6.00 – 8.00)	7.00 (5.00 – 8.00)
HBI	12.00 (9.00 – 15.00)	11.00 (8.00 – 14.50)	10.00 (7.00 – 13.00)	11.00 (8.00 – 14.00)

Conclusion

Despite anecdotal claims of seasonal patterns in IBD exacerbations, our 15-year retrospective analysis found no significant seasonal variation in hospitalization rates or clinical parameters. These findings challenge the presumed role of seasonal factors in IBD flare-ups. Further studies are warranted to validate these results in broader populations, including exacerbation managed in outpatient clinics.