Introduction

Inflammatory bowel disease (IBD) shares many features with other chronic inflammatory diseases (CIDs), such as rheumatoid arthritis and psoriasis, which are characterized by dysregulated immune responses and systemic manifestations. While IBD is primarily associated with inflammation in the gut, it can also lead to extra-intestinal symptoms, including joint pain and skin lesions, which are commonly observed in these other diseases. Understanding commonalities and differences among these chronic inflammatory conditions is important for developing more effective therapies that can target the underlying immune dysregulation and improve patients' overall quality of life.

Aims & Methods

We aim to identify both the common disease signatures shared between IBD and other CIDs, as well as the disease-specific signatures unique to each condition. A cross-sectional cohort of 650 patients with CIDs, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, psoriasis, and systemic lupus erythematosus (SLE), were recruited from the University Hospital Kiel. Peripheral blood samples were collected from this cohort, along with samples from 202 healthy controls, and subjected to RNA sequencing and methylation profiling. At the time of sample collection, the patients in the cohort underwent detailed clinical phenotyping including assessments of disease activity and symptoms. Additionally, these patients were followed up for up to 5 years to record any potential future complications that may arise.

Results

We performed differential expression and methylation analysis between each CID diagnosis and the healthy control group to identify shared molecular signatures. Our analysis showed that IBD shared the most differential signatures with rheumatoid arthritis, indicating common pathways in their pathogenesis. Psoriatic diseases also shared a significant proportion of differentially expressed and methylated patterns, while SLE had the least in common with other CIDs, suggesting distinct molecular pathways driving its pathogenesis. Interestingly, we were able to identify core transcriptomic changes that persisted even during inactive disease by separating the analysis by disease activity. These signatures were shared across different CIDs and were correlated with DNA methylation changes, reflecting the molecular mechanism of chronicity. Commonly upregulated genes across all CIDs were enriched in pathways related to inflammatory response, cytokine signaling, neutrophil chemotaxis, and humoral immune response. Disease-specific pathways included interferon-beta production in SLE, several metabolic processes in psoriasis, and complement activation in ulcerative colitis. Disease-specific methylation signatures were mainly located in CpG islands, while methylation signatures in enhancers were shared among most diseases. Our large cohort design enabled us to identify subgroup of patients across CIDs that share molecular characteristics, including a cluster of genes related to interleukin and interferon signaling upregulated in 71 samples belonging to different CIDs.

Conclusion

In conclusion, our study identified common and disease-specific molecular signatures in CIDs. Our findings suggest shared immune dysregulation pathways underlying the pathogenesis of IBD and rheumatoid arthritis, as well as potential commonalities between psoriatic diseases. We show the clear presence of core signatures of disease regardless of disease activity, which could represent insights into actionable targets for causative treatments and better disease control of CIDs.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

The global burden of overweight and obesity-related diseases has been a growing public health concern over the past few decades. These conditions contribute significantly to morbidity and mortality worldwide and are associated with a wide range of chronic diseases. Understanding the trends and sex differences in disease burden attributable to overweight and obesity is essential for developing effective prevention and intervention strategies. This study aims to assess the burden of overweight and obesity-related diseases in males and females.

Aims & Methods

We analyzed data from the Global Burden of Diseases (GBD) study, covering overweight and obesity-related disease burdens in 26 diseases across 204 countries and territories. Key disease burden indicators, including mortality and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change.

Results

In 2019, the global burden of overweight and obesity-related diseases reached 160.2 million DALYs, and the number of deaths associated with these conditions was approximately 5.02 million in males and females. The age-standardized death rates in males showed an increase from 58.19 per 100,000 person-years in 1990 to 66.55 per 100,000 person-years in 2019 (APC =0.36%, 95% CI 0.30% to 0.42%, P <.001), while in females it decreased from 59.31 per 100,000 person-years in 1990 to 58.14 per 100,000 person-years in 2019 (APC =-0.22%, 95% CI -0.29% to -0.14%, P <.001). There was a higher increase in age-standardized DALY rates in males, from 1632.5 per 100,000 years in 1990 to 2070.34 per 100,000 years in 2019 (APC =0.74%, 95% CI 0.70% to 0.78%, P <.001), while females experienced a smaller increase from 1618.26 per 100,000 years in 1990 to 1789.67 per 100,000 years in 2019 (APC =0.24%, 95% CI 0.19% to 0.29%, P <.001). These trends resulted in a higher male-to-female rate ratio in deaths and DALYs in 2019, which did not exist in 1990. The higher male-to-female rate ratio in deaths and DALYs were found in more than half of countries and territories. A large proportion of the higher burden in males compared to females can be explained by an increase in development.

Table. Comparison of age-standardized mortality and disability-adjusted life years (DALYs) rates between males and females, 1990-2019
Metric	1990	2000	2010	2019	Annual percentage change (95% CI)	P-value
Mortality Rate (per 100,000 person-year)
Male	58.2	62.5	64.0	66.6	0.36% (0.30% to 0.42%)	<0.001
Female	59.3	61.0	58.3	58.1	-0.22% (-0.29% to -0.14%)	<0.001
Male to Female Ratio	0.98	1.02	1.10	1.14	0.58% (0.55% to 0.61%)	<0.001
DALYs Rate (per 100,000 year)
Male	1633	1798	1927	2070	0.74% (0.70% to 0.78%)	<0.001
Female	1618	1704	1719	1790	0.24% (0.19% to 0.29%)	<0.001
Male to Female Ratio	1.01	1.06	1.12	1.16	0.50% (0.48% to 0.52%)	<0.001

Conclusion

The study uncovers a significant increase in the burden of overweight and obesity-related diseases, with a marked disparity between males and females. These findings underscore the need for further research to investigate the underlying causes of this gender difference in overweight and obesity-related deaths and DALYs. Identifying the contributing factors will facilitate the development of targeted interventions and public health policies to address and resolve these disparities. It is crucial to ensure that both genders benefit equitably from efforts to combat the global burden of overweight and obesity-related diseases.

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed with inflammatory bowel disease (IBD) in 2010 and 2011 according to Copenhagen criteria. Of these, 482 were diagnosed with Crohn’s Disease (CD), 817 with ulcerative colitis (UC) and 91 with IBD unclassified (IBDU). The Epi-IBD cohort was established to examine differences in incidence, treatment strategies, disease course and prognosis among IBD patients in Eastern and Western Europe.

Aims & Methods

This study aims to describe the use of biological therapy as well as the treatment prior to biological therapy. IBD patients were followed prospectively from the time of diagnosis until the 31^st December 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org.

Results

During a median follow-up period of 10.7 (interquartile range (IQR), 10.0-11.4) years, 34% (N=165/482) of CD and 15% (N=122/817) of UC patients were started on biological therapy. Biological therapy was initiated within the first year after diagnosis in 16.8% (N=81/482) of all CD and 3.8% (N=31/817) of all UC patients. In median biological therapy was started at 1.0 year (IQR, 0.3-3.1) and 2.7 years (IQR, 1.6-4.0) after CD and UC diagnosis, respectively. First-line biological therapy was infliximab in 74% (N=213/287) and adalimumab in 22% (N=64/287) of the patients. The remaing (N=10/287) received either Golimumab, Vedolizumab, Ustekinumab or were part of a trial/unknown. The sequences of biological therapies are displayed in Sankey diagrams, Figures 1 and 2. Herein illustrated is that 34% (N=56/165) CD and 34% (N=41/122) UC received at least two different biological drugs. Immunomodulators were initiated simultaneously to the first biological therapy in 19% (N=31/165) of CD patients and in 9% (N=11/122) of UC patients. Overall 63% (N=104/165) CD and 51% (N=62/122) UC patients were receiving concomittant immunomodulators with the first biological therapy.
The sequences of therapy leading up to biological therapy are displayed in Sankey diagrams, Figures 3 and 4. Herein illustrated is that the most common sequence of treatment before the first biological therapy for CD was 1) Steroids, 2) Immunomodulators (21%, N=34/165), and for UC was 1) 5-aminosalicylic-acid (5ASA), 2) Steroids, 3) Immunomodulators (39%, N=48/122). Prior to the first biological therapy one, two and three or more courses of systemic steroid were used in 41%, 28% and 17% (N=67, 47 and 28) of CD patients and 43%, 24% and 26% (N=52, 29 and 32) of UC patients. In 14% (N=23/165) and 7% (N=9/122) of CD and UC patients, systemic steroids were not used prior to first biological therapy. In patients having immunomodulators prior to biological therapy, these were administered for a median of 0.5 (IQR, 0.1-1.9) years and 1.1 (IQR, 0.2-3,2) years in CD and UC, respectively. For 5ASA this was 0.8 (IQR, 0.2-1.5) years for CD and 2.2 (IQR, 0.8-4.3) years for UC.

Conclusion

In this multicenter European population-based cohort, different prescribing patterns for biologics emerge: 34% of CD and 15% of UC patients received biologics within 10 years after diagnosis. Infliximab was the most common first-line biological therapy. Only about half of the patients received concomitant immunomodulators. Prior to the first biological therapy, most patients were exposed to systemic steroids and many to repeated courses.

Introduction

Pancreatic cysts are a common finding in imaging studies, and, considering the different malignant potentials of mucinous and non-mucinous cysts, it is necessary to develop accurate methods and algorithms to differentiate between them. We conducted this study to compare the diagnostic performance of glucose levels and CEA levels in the diagnosis of mucinous pancreatic cysts.

Aims & Methods

We conducted a retrospective study of patients who underwent EUS-FNA of pancreatic cystic lesions between September 2020 and March 2023 at a tertiary referral center. We included patients whose glucose and CEA levels had been measured. Indicators of mucinous cysts include glucose levels less than 2.7 mmol/l and CEA levels greater than 192 ng/ml. It was compared to the final pathology (obtained after surgery or by EUS-FNB) result to determine their accuracy.

Results

	Non-mucinous	Mucinous
Gender (%male)	47.3%	33.3%
Age ( Median)	50.2	58.3
Cyst location
head	9	3
body	2	5
tail	8	4

A total of 31 patients were included in the study, 13 males and 18 females. The mean age was 55.7 years. Of the 31 patients, 12 (38.7%) were diagnosed with mucinous cysts (6 mucinous cystic neoplasms, 6 intraductal papillary mucinous neoplasms), and 19 (61.2%) were diagnosed with non-mucinous cysts (9 serous cystic neoplasm, 8 pseudocysts, 1 solid pseudopapillary neoplasm, and 1 lymphoepithelial cyst). There was a female prevalence in patients with mucinous cysts (8 females and 4 males) with a mean age of 59,6 years. From the cyst fluid analysis, the sensitivity, specificity, and accuracy of glucose in diagnosing mucinous cysts were 91.7%, 89.5%, and 90.3%, respectively. CEA’s sensitivity, specificity, and accuracy were 81.8%, 85.0%, and 83.9%, respectively.

Conclusion

In the diagnosis of pancreatic cystic lesions, glucose levels have high diagnostic performance with high sensitivity and accuracy. In contrast, CEA levels have a lower diagnostic performance. The findings of our study support the use of EUS-FNA and glucose levels in the diagnosis of pancreatic cystic lesions, as well as EUS-FNB to obtain histological specimens for a more accurate diagnosis of pancreatic cysts. Further studies are needed to validate these findings and explore the potential of other biomarkers in diagnosing and managing pancreatic cystic lesions.

Introduction

According to updated guidelines, non-pedunculated polyps of small size are resected with a cold snare in air dilated intestinal lumen(Conventional Cold Snare Polypectomy-CCSP) [1]. R0 resection rate(R0-RR) using CCSP ranges from 32.9% to 96.6%[2-5] while meta-analyses showed that the incomplete resection rate (IRR) after CCSP was 17.3% [6], highlighting the need for further research regarding the most suitable polypectomy method for small polyps. Recently, several studies have described the benefits of water-aided colonoscopy, as well as safety and efficacy of underwater polypectomy in large colon polyps. However, data on small polyps which are the most commonly diagnosed, are insufficient. In response to this gap in the literature, we conducted the first randomized, double-blind, controlled trial to compare underwater cold snare polypectomy(UCSP) to CCSP for non-pedunculated colon polyps of size 5-10mm.

Aims & Methods

The CCSP procedure involved: opening of the intestinal lumen using air/CO2, snaring of the lesion and surrounding healthy tissue, and excision. On the other, UCSP involved three more steps before snaring of the polyp: complete suction of air, partial opening of the intestinal lumen using sterile water, complete immersion of the lesion in water. In order to determine the IRR, additional biopsies were taken from the horizontal margins of the resection site. All polypectomy–related complications were recorded. The objective of the study was to compare the safety and efficacy between UCSP and CCSP regarding resection of non-pedunculated colon polyps with size 5-10mm. Primary outcome was the investigation of the difference in the rate of area containing muscularis mucosa between the two polypectomy techniques. The secondary outcomes focused on differences in R0-RR, IRR, en-bloc resection, and complications. Patients were allocated with a 1:1 ration to UCSP or CCSP group.If more than one polyp was diagnosed in a patient, then all were resected by the same method. The randomization process was done by using the random numbers method of Microsoft Excel 2016. Both pathologists and patients were blinded.

Results

Between March 2021 and December 2022, a total of 229 patients were enrolled in the study, with 397 polyps(UCSP:198, CCSP:199) included in the per protocol analysis. Results demonstrated that UCSP was superior to CCSP in terms of both muscularis mucosa resection rate (81.72% vs. 72.33%, p=0.003) and IRR (8.5% vs. 3.5%, p=0.05). However, the R0-RR did not differ significantly between the two groups (UCSP: 93.9%, CCSP: 90%, p=0.29). UCSP also achieved a higher rate of en bloc resections than CCSP(98% vs 93.5%, p=0.04). The only complication observed was non-severe intraprocedural bleeding, which was successfully managed during endoscopy(UCSP 0.5%, CCSP 2%, p=0.37). Expert endoscopists in CCSP achieved a higher R0-RR than non-experts (93% vs. 84%, p=0.05), whereas no significant difference in R0 resection rate was observed among different levels of expertise in UCSP. Polyp histology and size were found to affect R0 resection rates in both groups, with serrated histology and sizes of 8-10mm linked to lower R0 resection rates.

Conclusion

UCSP is a safe technique that achieves better results in the resection of muscularis mucosa and is associated with a lower IRR than CCSP, thus reducing the risk of residual or recurrent lesions. Furthermore, the efficacy of UCSP does not depend on the endoscopist's expertise and thus could be the optimal approach for young or inexperienced gastroenterologists.

References

1. Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2017;49:270–97.
2 Maruoka D, Arai M, Akizue N, Ishikawa K, Kasamatsu S, Taida T, Ishigami H, Okimoto K, Saito K, Matsumura T, Nakagawa T, Katsuno T, Kato N. Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study. Endoscopy. 2018 Jul;50(7):693-700. doi: 10.1055/s-0043-124869. Epub 2018 Feb 7. PMID: 29415287. 3
3. Zhang Q, Gao P, Han B, et al. Polypectomy for complete endoscopic resection of small colorectal polyps. GastrointestEndosc 2018;87:733–40
4. Kawamura T, Takeuchi Y, Asai S, et al. A comparison of the resection rate for coldand hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study). Gut 2018;67:1950–7.
5. Papastergiou V, Paraskeva KD, Fragaki M, et al. Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial. Endoscopy 2018;50:403–11.
6. Djinbachian R, Iratni R, Durand M, Marques P, von Renteln D. Rates of Incomplete Resection of 1- to 20-mm Colorectal Polyps: A Systematic Review and Meta-Analysis. Gastroenterology. 2020;159(3):904-914.e12. doi:10.1053/j.gastro.2020.05.018

Introduction

Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis (UC) but head-to-head trials are lacking. We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-TNF failure in UC patients.

Aims & Methods

All consecutive patients with UC treated with ustekinumab or vedolizumab after being exposed to at least one anti-TNF in 10 French centers between January 2019 and August 2022 were included retrospectively. The primary endpoint was clinical remission (Mayo score partial ≤ 2) without corticosteroid (SFCR) at week 16 (W16). Secondary endpoints were endoscopic remission (SFCR and endoscopic Mayo score ≤ 1 or fecal calprotectin < 150 µg/g), and histological healing (endoscopic remission and histological (Nancy index ≤ 1)). All the comparisons were performed using propensity score analyses (inverse probability of treatment weighting) adjusted for age, gender, smoking status, disease duration and extension, number of prior biologics or prior primary failure to biologics, the co-prescription of 5-ASA, corticosteroids or immunosuppressants, and disease severity.

Results

Among a total of 316 patients included, 165 and 151 received ustekinumab and vedolizumab, respectively. Baseline characteristics (gender, age, disease location, co-prescription of 5-ASA or corticosteroids) were similar between the two groups except for disease duration (ustekinumab, 9.3 vs vedolizumab 7.2 year; p=0.003), co-immunosuppressants (5.4% vs 20.5%, <0.001), and prior exposition to > 2 biologics (46.6% vs 5.9%, p<0.001). At W16, SFCR was respectively 40.3% and by 37.9% in the ustekinumab and vedolizumab groups (aOR = 1.10 [0.39-3.12], p=0.085). SFCR rates were 62.2% vs 53.2% (p=0.52) after one failure, 33.7% vs 44.3% (p=0.52) after two biologics and 19.1% vs 2.6% (p=0.03) after 3 biologics failure, in the ustekinumab and vedolizumab groups, respectively.
Endoscopic remission and histologic healing rates at week 16 were respectively of 17.5% vs 5.3% (aOR = 3.77 [1.25-11.36], p=0.018) and 11.1% vs 2.1% (aOR = 5.85 [1.47-23.30], p=0.012) in the groups ustekinumab and vedolizumab.

Conclusion

While no difference in terms of clinical remission was observed, ustekinumab appears to be more effective than vedolizumab to induce endoscopic and histological remission after failure of anti-TNFs in UC.

Disclosure

AbbVie, Ferring, Janssen, MSD, Takeda, Pfizer, Celgene, Biogen, Amgen, Boehringer Ingelheim, Hospira et Celltrion