Introduction

Several studies have recently reported an increased risk of gastric cancer (GC) risk in both underweight and obese population in East Asia. However, the impact of underweight or obesity on the development of non-cardia GC is not fully established yet. In addition, GC is a male dominant cancer, and considering the phenotype differences in body composition between males and females, sex differences must be considered in evaluating the association between obesity and the risk of developing non-cardia GC.

Aims & Methods

Therefore, we aimed to evaluate associations between body mass index (BMI) and non-cardia GC risk with consideration of sex. This study was performed based on a retrospective cohort, which consists of Koreans randomly sampled from participants who underwent the National Health Screening programs and is termed National Health Insurance Service–Health Screening Cohort (NHIS-HEALS). The National Health Insurance system provides health checkups biennially for adults aged ≥20 years through the National Health Screening program. This program covers over 70% of total population in Korea, thus the NHIS-HEALS is a nationwide representative database in South Korea. This study includes a total of 341,999 subjects including 4,103 incident non-cardia GC cases identified during a median follow-up period of 10 years after exclusion of incident GC cases identified within 2 years from the follow-up start. We classified subjects into five groups according to BMI (<18.5, 18.5-22.9, 23.0-24.9, 25.0-29.9, ≥30.0kg/m²) and evaluated the association between BMI level and GC risk by calculating hazard ratio (HR) and corresponding 95% confidence interval (95% CI) based on the Cox proportional hazard regression.

Results

Table. Association between body mass index and non-cardia gastric cancer risk according to sex in Korea

Age1	Sex	Body mass index (kg/m2)
		<18.5	18.5-22.9	23.0-24.9	25.0-29.9	≥30.0
		HR (95% CI)	HR (95% CI)	HR (95% CI)	HR (95% CI)	HR (95% CI)
<50 years	Total	1.53 (0.74-3.16)	1.01 (0.77-1.32)	1.00	0.88 (0.66-1.17)	1.41 (0.77-2.58)
	Males	1.74 (0.75-4.02)	1.06 (0.77-1.46)	1.00	0.94 (0.69-1.30)	1.91 (1.03-3.55)
	Females	1.39 (0.17-11.02)	0.88 (0.38-2.02)	1.00	0.91 (0.34-2.44)	N/A
≥50 years	Total	1.06 (0.85-1.32)	1.01 (0.93-1.10)	1.00	1.13 (1.04-1.23)	1.17 (0.96-1.44)
	Males	1.09 (0.85-1.39)	0.96 (0.87-1.06)	1.00	1.08 (0.99-1.19)	1.33 (1.04-1.70)
	Females	0.97 (0.61-1.54)	1.17 (0.99-1.38)	1.00	1.30 (1.10-1.53)	0.98 (0.68-2.26)

Abbreviations: HR, Hazard ratio; CI, Confidence interval
1. Age at BMI measurement

Increased non-cardia GC risks were observed in severely obese (BMI ≥30.0 kg/m²) males and obese (BMI 25.0-29.9 kg/m²) females, respectively (HR, 1.40; 95% CI, 1.11-1.75 for severely obese males; HR, 1.25; 95% CI, 1.06-1.46 for obese females). In contrast, evidences supporting that underweight (BMI <18.5kg/m²) is associated with increased non-cardia GC risk was not found overall (HR, 1.08; 95% CI, 0.88-1.33). In males, the increased risk of non-cardiac GC in the severely obese group remained regardless of age at BMI measurement. However, the increased risk of non-cardia GC risk related to obesity was confirmed only in elderly females, and was not found in females under 50 years of age. In addition, increased non-cardia GC risk in the normal weight group (18.5-22.9 kg/m²) was found compared to that in overweight group among females over 50 years of age.

Conclusion

Results suggest that elevated risk of non-cardia GC development might be originated from obesity, especially in elderly populations in East Asia regardless of sex. However, this study proposes that being overweight, which is the pre-obesity stage, may rather have a lower risk of developing non-cardia GC than being normal weight in elderly females.

Introduction

Accurate assessment of disease activity and prediction of treatment response and prognosis are challenges in the management of chronic inflammatory bowel disease (IBD). Due to the invasiveness of colonoscopy, non-invasive methods are of high clinical relevance. Bowel ultrasonography (B-US) is establishing itself as a non-invasive, cost-effective method in daily clinical practice.

Aims & Methods

The aim of this study is to evaluate the correlation between B-US and endoscopy in relation to inflammatory activity and severity of IBD. Patients were retrospectively selected for comparison between B-US and endoscopy. A total of 473 patients were included, of whom (n=274) had Crohn's disease (CD) and (n=199) had ulcerative colitis (UC). The examination results were divided into four sections (terminal ileum, proximal colon, distal colon and rectum) and systematically analyzed. Inflammatory activity was classified according to intestinal wall thickness in mm: none (0): 0-2.9, mild (1): 3.0-4.9, moderate (2): 5.0-7.9, severe (3): >8.0. Endoscopic evaluation was performed according to simplified Mayo and SES-CD criteria.

Results

Based on endoscopy, patients were divided into groups with inflammatory activity (274 CD, 175 UC) and remission (34 CD, 24 UC). Comparison of B-US and endoscopy showed a significant correlation regarding inflammatory activity (r=0.44, p<0.001). The correlation was more significant in UC (r=0.5548, p<0.001) than in CD (r=0.3665), except in the ileum in UC (r=-0.1050, p<0.4822). The best correlation in MC was found in the ileum (r=0.4783, p<0.001) and in the distal colonic segments (r=0.5217, p<0.001), while in UC the best correlation was found in the proximal (r=0.5586, p<0.001) and in the distal colonic segments (r=0.6250, p<0.001). Localization of rectal inflammation was associated with lower diagnostic accuracy. Compared to endoscopy, B-US showed a sensitivity of 82.2%, a specificity of 51.7% and a positive predictive value of 92.4%.

Conclusion

B-US shows reliable diagnostic accuracy compared to endoscopy in assessing inflammatory activity in IBD patients and can be considered as a complementary non-invasive diagnostic tool.

Disclosure

AL recieved research funding from the European Regional Development Fund (Project ID: ZS/2018/11/95324) and the German Federal Ministry of Education and Research (BMBF) (FKZ 01GM2204A). AL has received speaker fees from Janssen, Ferring and Luvos.

Introduction

Mirikizumab is a humanized immunoglobulin G4 monoclonal antibody against the p19 subunit of interleukin-23, a key inflammatory mediator in ulcerative colitis (UC). Mirikizumab demonstrated an acceptable safety profile, clinical response, clinical remission, and endoscopic remission in the pediatric SHINE-1 study. Here we describe patient-reported outcomes in pediatric patients with moderate to severe UC from the phase 2 SHINE-1 study (NCT04004611) following 52 weeks of mirikizumab treatment.

Aims & Methods

Patients aged 2 to <18 years with active UC who had an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies, or had corticosteroid-dependent colitis, were included in the study. Patients weighing >40 kg received an induction dose of mirikizumab 300 mg via intravenous infusion; patients weighing ≤40 kg received mirikizumab 5 or 10 mg/kg via intravenous infusion at weeks 0, 4, and 8. At week 12, patients were assessed for clinical response using the Modified Mayo Score. Responders entered a maintenance period and received subcutaneous doses of mirikizumab at 200 mg (>40 kg), 100 mg (>20 kg to ≤40 kg), or 50 mg (≤20 kg) once every 4 weeks, with the last patient visit at week 52. Abdominal Pain Numeric Rating Scale (NRS), Urgency NRS, and Fatigue NRS scores were assessed through 52 weeks.

Results

Responders (69.2%, n=18/26) reported improvements in Abdominal Pain NRS, Urgency NRS, and Fatigue NRS scores through all age groups compared to baseline at week 52 (Table 1). A ≥30% improvement in the Abdominal Pain NRS was observed in 50% (n=7) of patients aged 12 to <18 years who scored ≥3 at baseline (N=14).

Table 1.

Conclusion

Mirikizumab demonstrated improvements in abdominal pain, bowel urgency, and fatigue following induction and maintenance treatment. These results provide supporting evidence for the pivotal phase 3 pediatric study SHINE-2 and suggest important improvements in quality of life.

Disclosure

M. Dubinsky has received honoraria as a consultant for: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Genentech, Gilead Sciences, Janssen, Pfizer, Prometheus Therapeutics and Diagnostics, Takeda, and UCB Pharma; has been contracted for research by: AbbVie, Janssen, Pfizer, and Prometheus Biosciences; has stock interest in: Trellus Health; and has received licensing fees from: Takeda; J. L. Kaplan has nothing to disclose; A. Bousvaros has received research support from: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, BUHLMANN Diagnostics, Eli Lilly and Company, Janssen, ProciseDx, and Takeda; was a consultant for: Best Doctors, Eli Lilly and Company, Fresenius Kabi, and Takeda; and has received honoraria and royalties from: Boston University and UptoDate; D. Turner has received consultation fees, research grants, royalties, and/or honoraria from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring Pharmaceuticals, Janssen, Pfizer, Prometheus Biosciences, Roche, Shaare Zedek Medical Center, Shire, Sorriso Pharmaceuticals, Takeda, The Hospital for Sick Children, and Thermo Fisher Scientific; T. Hunter Gibble, W. J. Komocsar, A. Larkin, J. Johns, X. Zhang, and W. Crandall are employees and shareholders of: Eli Lilly and Company; J. Hyams is on the advisory board for: Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, and Janssen; and was a consultant for: AbbVie, Pfizer, and Takeda.

Introduction

The incidental finding of terminal ileal inflammation during routine colonoscopy is not uncommon and is of unclear significance. It has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. There is limited data on long term follow-up and outcomes of such findings.(1)

Aims & Methods

This is a monocentric retrospective observational study spanning from 2018 to 2023, comparing two periods: the first period (P1) before the impact of the Covid-19 pandemic in 2020, and the second period (P2) starting 2020 reflecting the impact the pandemic left on colonoscopies. For each patient, variables were collected from medical records.

Results

Our initial database included 11200 colonoscopies, from which we randomly selected 2394 patients proportionally to the annual activity (mean of 1686/year before 2020 and 1189/year after 2020). Among indications of colonoscopy were screening and follow-up, change in bowel habits, anemia and bleeding. We excluded 287 patients (known history of inflammatory bowel disease and no ileum intubation). Then the sample was divided into P1 (681 patients) and P2 (1483 patients). Characteristics and findings are shown in Table 1. We noted better bowel preparation (77.1 vs 91.7%) and a higher ileum intubation in P2 (79.7 in P1 vs 93.8% in P2).
​

N=2164			P1 (N1=681)	P2 (N2= 1483)	p
Age (years)			57.5	56.9	NS
Overall endoscopic findings n(%)	Endoscopic aspect of ileitis		0 (0)	71 (5.8)	<0.001
	Abnormal ileal findings on histology		23 (3.4)	169 (11.4)	<0.001
	Diagnosis of Crohn's disease		0 (0)	19 (0.9)	<0.001
Overall histological findings n(%)	Active ileitis		19 (2.8)	147 (9.9)	<0.001
	Focal ileitis		10 (1.5)	89 (6)	<0.001
	Ulcerative ileitis		11 (1.6)	48 (3.2)	0.031
	Erosive ileitis		3 (0.4)	31 (2.1)	0.004
	Architectural distortion		1 (0.1)	16 (1.1)	0.023

Overall ileoscopy findings showed an increased aspect of ileitis on endoscopy (0% in P1 and 5.8% in P2, with p<0.001), correlating with a significant increase in the incidence of histological findings on ileal biopsies (3.4% in P1 vs 11.4% in P2; p<0.001). These histological findings included active, focal and ulcerative ileitis, with more architectural distortion. However, these results corresponded to a less severe ileitis (0.3 vs 2.3%; p=0.001). Nineteen of these patients with positive results of ileitis were diagnosed with Crohn’s disease.

Conclusion

This study showed an increase in endoscopic and histologic ileitis on colonoscopy following the Covid-19 era. This could be the result of the direct virologic effect that the virus has on intestinal inflammation, its indirect effect on immunity triggering the onset of enteritis, or the consequence of the mass vaccination campaign held to protect from the virus. Furthermore, histology showed granulomatous inflammation similar to Crohn’s disease, which may lead to misdiagnosis and probably overtreatment.

References

1. Agrawal M, Miranda MB, Walsh S, Narula N, Colombel JF, Ungaro RC. Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis. J Crohns Colitis. 2021 Feb 14;15(9):1455–63.

Introduction

Inflammatory bowel disease (IBD) is strongly associated with joint inflammation, as is highlighted by the high prevalence of spondyloarthritis (SpA) in patients with IBD (up to 13%) compared to the general population (0.2-1.6%) [1, 2]. IBD and SpA have many overlapping features, including genetic risk factors, changes in the gut microbiota, and therapies targeting TNF-α , IL-23, or JAK [3]. However, current therapies for both diseases are unable to break the cycle of chronic inflammation, and still a significant proportion of patients fail to respond. Disease heterogeneity likely plays a role in this [4, 5], underscoring the necessity to improve management and refine classification.

Aims & Methods

In this study, 92 inflammation-related proteins were quantified in serum of patients from one IBD and one SpA cohort using the novel Olink proteomics proximity extension assay. Fold changes (FC) in expression with |log₂FC| > 0.5 were considered meaningful, and false discovery rates (FDR) <0.05 were considered significant. The IBD cohort existed of 255 IBD patients with (n=155) and without (n=100) self-reported joint complaints [8]. From the patients with joint complaints, 58 fulfilled any of the SpA criteria. The SpA cohort, or SPACE cohort, consisted of 169 patients with chronic back pain (≥3 months, ≤2 years) of unknown origin [9]. After 2 years of follow-up, 85 patients had proven axSpA. Serum samples were taken at baseline, and 167/169 samples from the SPACE cohort and 241/255 samples from the IBD cohort passed quality control and were included in the analysis.

Results

Thirty-four proteins were differentially expressed between 95 IBD patients without joint complaints and 85 proven axial SpA (axSpA) patients from the SPACE cohort, of which 14 were higher in IBD patients (including 4E‑BP1, IFN‑γ, TNF, FGF‑21, CD8A, and CCL9), and 20 were higher in axSpA patients (including CASP‑8, SIRT2, STAMBP, FGF‑19, ST1A1, and EN‑RAGE). In addition, the immune profile of IBD patients with joint complaints differed from IBD patients without joint complaints: 4E‑BP1, CASP-8, STAMBP, SIRT2, AXIN1, and TNFSF14, were significantly upregulated in patients with joint complaints. Of note, if IBD patients without joint complaints were compared to the subgroup of 58 patients with joint complaints who met criteria for SpA, the same proteins showed significant upregulation, suggesting minimal difference between IBD patients with joint complaints who meet or who do not meet SpA criteria. Direct comparison of patients who met and who did not meet SpA criteria within the group of IBD patients with joint complaints indeed showed no noteworthy difference in serum immune profile. Within the SPACE cohort, comparison of patients with chronic back pain with and without axSpA diagnosis also showed no significant difference in serum protein expression.

Conclusion

This study shows that patients with axSpA versus patients with IBD without joint complaints have differing serum immune profiles. Within IBD patients with self-reported joint complaints and within patients with self-reported chronic back pain (from the SPACE cohort), no distinct difference in immune profile is observed, regardless of SpA diagnosis. The inflammation signatures of patients with chronic inflammatory diseases should be further investigated to provide insights for enhancing disease management in the future.

References

1. Karreman, M.C., et al., The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis, 2017. 11(5): p. 631-642.
2. Stolwijk, C., et al., Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res (Hoboken), 2016. 68(9): p. 1320-31.
3. Gracey, E., et al., Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis. Nat Rev Rheumatol, 2020. 16(8): p. 415-433.
4. van Unen, V., et al., Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets. Immunity, 2016. 44(5): p. 1227-39.
5. Gulino, G.R., M. Van Mechelen, and R. Lories, Cellular and molecular diversity in spondyloarthritis. Semin Immunol, 2021. 58: p. 101521.
6. van Erp, S.J., et al., Classifying Back Pain and Peripheral Joint Complaints in Inflammatory Bowel Disease Patients: A Prospective Longitudinal Follow-up Study. J Crohns Colitis, 2016. 10(2): p. 166-75.
7. Marques, M.L., et al., Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort. Ann Rheum Dis, 2024. 83(5): p. 589-598.

Disclosure

FAG: grants from Stichting vrienden van Sole Mio and Stichting ASAS, grants and/or consulting fees from Abbvie, ASAS, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB.
AEM: grants from Nestle, Norgine, Cablon, Galapagos, and ZonMW, ad boards/speaker fees from Tramedico, Janssen, Takeda, Galapagos, Vedanta, Ferring, AbbVie, and Dear Health.
PV: speaker fees from Takeda and Galapagos, advisory board: Takeda, Galapagos, Lilly, BMS, Janssen, and Abbvie

Introduction

The place that regular Physical Activity (PA) should occupy in managing patients with Inflammatory Bowel Diseases (IBD) is unclear. Unfortunately, there is little data on PA in patients with IBD, although it appears to be reduced compared to the general population. Nevertheless, PA may provide several multidimensional metabolic, anti-inflammatory, and sarcopenia benefits. Therefore, the World Health Organization recommends for each age group and patients with disabilities regular PA adapted to individual ability/tolerance. However, there are no precise guidelines on the best PA and the intensity to recommend for patients with IBD. Therefore, this study aims to assess PA levels and barriers to PA in a southern European Italian IBD population.

Aims & Methods

IBD patients with non-severe disease activity [assessed with partial Mayo score for Ulcerative Colitis (UC) and Harvey-Bradshaw index for Crohn's Disease (CD)] were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire (IPAQ) and to assess disease activity as Patient-Reported Outcomes 2 (PRO-2) and finally to assess habits, beliefs and barriers in conducting regular PA. Clinical, anthropometric and demographic data of patients were also collected. PA was expressed as continuous units of resting metabolic rate (Met) in minutes/week (Met min/wk). Three PA groups were identified: inactive (< 700 Met min/wk), sufficiently active (700-2500 Met min/wk) and Health Enhancing PA (i.e., HEPA active, > 2500 Met min/wk) patients.

Results

Included patients (219) showed overall PA levels of 834.5 Met min/wk, with a large proportion (94, 42.9%) classified as inactive while only a minority (9, 4.1%) as health-enhancing PA (see Table). Patients without dyslipidaemia (p < 0.0001) or on biologics therapy (p=0.022) showed better IPAQ scores in moderate activities. UC PRO-2 correlated negatively with IPAQ intense activities scores (τ= -0.156, p=0.038). PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity (AUC < 0.6). IBD activity did not differ between active and inactive patients (p > 0.05). Active patients expressed the need to discuss PA with their gastroenterologist. Some barriers (e.g., diagnosis of IBD and fear of flare-ups after PA) are significantly more reported by inactive patients.

PA variable	Crohn’s disease (N=92)	Ulcerative colitis (N=127)	P-value*
Intense activities (Met min/wk)	0 (0 – 192)	0 (0 – 240)	0.099
Moderate activities (Met min/wk)	208 (0 – 536)	140 (0 – 540)	0.590
Mild activities (Met min/wk)	293.75 (158.12 – 711.6)	350 (120 – 840)	0.940
Sitting time at work (min)	210 (113 – 292.5)	215 (125 – 292)	0.719
Sitting time at home (min)	174 (118.75 – 221.75)	177 (115 – 229)	0.855
Total score (Met min/wk)	828.25 (339.37 – 1343.5)	839 (390 – 1451)	0.678
PA level Inactive Sufficiently active HEPA active	39 (42.4%) 50 (54.3%) 3 (3.3%)	55 (43.3%) 66 (52%) 6 (4.7%)	0.995

HEPA: Health Enhancing Physical Activity. *The P-value was calculated by checking the difference in the distribution of different variables between the two identified groups (i.e., Crohn's disease and ulcerative colitis). Data are expressed for continuous variables as median (interquartile range) and, for categorical and ordinal variables, as numerosity (%).

Conclusion

There was a significant rate of physical inactivity in patients with IBD in this setting. Many IBD southern European patients are inactive and may be exposed to all the complications of not practising regular PA. This does not seem dependent on disease activity but is affected by patients' beliefs about PA's impact on baseline IBD. There is some patient interest in discussing PA with their gastroenterologist that should be used to inform them about the available evidence on PA and the risks of impact on IBD that they fear.

References

- Ananthakrishnan AN., Kaplan GG., Bernstein CN., Burke KE., Lochhead PJ., Sasson AN., et al. Lifestyle, behaviour, and environmental modification for the management of patients with inflammatory bowel diseases: an International Organization for Study of Inflammatory Bowel Diseases consensus. Lancet Gastroenterol Hepatol 2022;7(7):666–78.
- Mareschal J., Douissard J., Genton L. Physical activity in inflammatory bowel disease: benefits, challenges and perspectives. Curr Opin Clin Nutr Metab Care 2022;25(3):159–66. Kim B., Chae J., Kim EH., Yang HI., Cheon JH., Kim TI., et al. Physical activity and quality of life of patients with inflammatory bowel disease. Medicine (Baltimore) 2021;100(27):e26290.