Introduction

Digestive diseases constitute a major component of healthcare utilization in Korea. However, up-to-date data on long-term trends in their epidemiologic and economic burden are scarce. This study aimed to assess nationwide changes in prevalence, healthcare utilization, and direct medical costs related to digestive diseases over the past decade.

Aims & Methods

Aims: Digestive diseases constitute a major and rising component of Korea’s healthcare demand. We therefore quantified longitudinal changes in their epidemiologic and economic burden by comparing nationwide data from 2010 to 2020.
Methods: We analysed the National Patient Sample from the Health Insurance Review and Assessment Service (HIRA), which is representative of the entire Korean population. Medical utilization was analyzed based on principled estimates defined as primary diagnosis and extensive estimates defined as primary diagnosis and 1st listed secondary diagnosis. Patient numbers, hospitalizations, emergency‑department (ED) visits, outpatient encounters and inflation‑adjusted direct expenditures and derived compound annual growth rates (CAGR) were calculated.

Results

On the principal estimate, the number of patients with digestive diseases rose from 17.3 million in 2010 to 18.5 million in 2020, while total expenditures escalated from US $4.2 billion to US $8.5 billion, effectively doubling per‑patient costs. Intestinal infectious diseases remained the leading cause of hospitalization and emergency‑department visits in both years. In the outpatient setting, the most frequent diagnosis shifted from gastritis/duodenitis in 2010 to gastro‑esophageal reflux disease in 2020. The fastest‑growing categories were gallbladder disorders (CAGR 19.5 %), pancreatic disorders (CAGR 12.0 %) and benign colonic neoplasms (CAGR 9.1 %), all exceeding the overall mean growth of 7.0%.

Conclusion

From 2010 to 2020, digestive diseases rose by 7 %, but related healthcare costs doubled, sharply raising per‑patient spending. Rapid surges in gallbladder and pancreatic disorders and benign colonic neoplasms call for intensified prevention, early screening, and stronger primary‑care management.

Introduction

Dutch society has witnessed significant societal and demographic changes over the decades. With 28% of the Dutch population having a migration background in 2023, understanding diversity within the gastroenterology workforce is imperative. This study examines the evolution of sex, ethnic, and socio-economic diversity among Dutch gastroenterologists from 2005-2023.

Aims & Methods

This repeated cross-sectional study utilized pseudonymized data from the BIG-register, paired with demographic variables from Statistics Netherlands (CBS), covering the years 2005, 2010, 2015, 2020, and 2023. The total population sample in each year consisted of all individuals registered as gastroenterologists for at least one day in a respective year. Variables such as sex, migration background, year of birth, and parental socio-economic status indicators were analyzed to assess trends and identify factors associated with being a
gastroenterologist. Descriptive and logistic regression analyses were employed to explore these trends and compare generational differences.

Results

The study revealed a narrowing sex gap with an increase in female gastroenterologists (28% to 43% from 2005-2023), particularly among the younger cohort (60% female). However, ethnic diversity has not kept pace, with a decline in the representation of gastroenterologists from migration backgrounds among younger professionals (27% to 18% for gastroenterologists < 1979 and ≥ 1980, respectively). Socio-economic analysis indicated that approximately 75% of gastroenterologists have parents from top-20% assets category.

Conclusion

The gastroenterology field in the Netherlands shows significant advancements in gender diversity, but lags in ethnic and socio-economic diversity. The increasing trend of gastroenterologists from medical families highlights the need for policy adjustments, to ensure access to candidates from more diverse socio-economic backgrounds. Policies should focus much more on promoting comprehensive diversity to enhance healthcare outcomes and reflect the demographic changes within society.

References

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Disclosure

OKB, ABB, PK and LM have no conflict of interests, CJJM is consultant for Douglas (New Zealand) and HLW (The Netherlands). All outside submitted work.

Introduction

The Pisa EoE Adaptation Questionnaire (PiEAQ) on adaptive behaviors at mealtime significantly improves the correlation between dysphagia scores and histological disease activity (HDA) in eosinophilic esophagitis (EoE) [Reference 1].

Aims & Methods

Whether longitudinal variations of PiEAQ scores (∆PiEAQ) can capture HDA trends following pharmacological treatment of EoE has not been investigated. Consecutive adults (>18 years) with histologically active EoE (i.e., ≥15 eos/high-power field) were prospectively enrolled. Clinical characteristics, HDA, a recall-modified dysphagia symptom questionnaire (mDSQ), esophageal hypervigilance and anxiety scale (EHAS), and PiEAQ (drinking water to push the bolus, lubricating food, chewing for long, and blending food) were recorded longitudinally at baseline (T0) and 12 weeks post-treatment using a 30-day recall period (T1). ROC curve analysis with DeLong test was used to calculate the diagnostic accuracy (AUC) of clinical scores for predicting HDA following treatment. Significance threshold was p<0.05.

Results

Thirty-seven histologically active EoE patients were included (Table 1). The mDSQ, PiEAQ, and EHAS score at baseline were 2.97 (IQR, 2-5), 2.00 (IQR, 1-3), and 21 (IQR, 14– 25), respectively. Following treatment with budesonide orodispersible tablets (72.2%), PPIs (19.6%), dupilumab (5.5%), or milk-free diet (2.7%), histological remission was achieved in 78.4% of patients, while 21.6% remained histologically active. Post-treatment (T1), mDSQ, PiEAQ, and EHAS scores decreased significantly only in patients who achieved histological remission (Table 2 and Figure1). ROC curve analysis showed that a post-treatment reduction of at least 2 adaptive behaviors compared to baseline (∆PiEAQ=-2) had AUC of 85.0%, with 100% specificity and 64% sensitivity for the identification of patients achieving histological remission following treatment. Similarly, a post-treatment reduction of at least 3 points in mDSQ scores compared to baseline (∆mDSQ=-3) had AUC of 81.1% with 100% specificity and 57.7% sensitivity. The non-inferiority analysis showed that the ∆PiEAQ had similar performance to ∆DSQ (DeLong p-value= 0.46). A combined score integrating both ∆PiEAQ and ∆DSQ scores increased the AUC of clinical scores for capturing variations of HDA post-treatment to 90%, with 100% specificity and 73.1% sensitivity for detecting patients achieving histological remission post-treatment (Figure 2).

Conclusion

The PiEAQ is the first questionnaire investigating adaptive behaviors as a standalone domain in EoE. We demonstrated that longitudinal variations in PiEAQ scores are sensitive to HDA variations over time and can monitor histological disease activity trends after treatment. This study confirms that, similar to dysphagia, adaptive behaviors contribute to disease burden in EoE and improve with treatment.

References

1. Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

EoE is a debilitating disease with physical, behavioral, and psychosocial impacts, resulting in substantial impairment in quality of life for patients and caregivers. Children with EoE can present with nonspecific symptoms such as food refusal or feeding difficulties, gastroesophageal reflux disease (GERD), nausea, and vomiting. Dupilumab is approved in the USA and EU for patients with EoE aged ≥1 year, weighing ≥15 kg. In the phase 3 randomized placebo-controlled EoE KIDS study (NCT04394351), in children aged 1 to 11 years, dupilumab significantly improved symptoms of EoE vs placebo, as measured by the Pediatric Eosinophilic Esophagitis Symptom Score version 2.0 (caregiver version; PEESSv2.0) after 16 weeks of treatment.

Aims & Methods

In this post-hoc analysis of the EoE KIDS study, we evaluated the effects of long-term dupilumab treatment on PEESSv2.0 scores during the Part C open-label extension. PEESSv2.0 is a validated observer-reported outcome measure that assesses the frequency and severity of EoE symptoms and adaptive behaviors, divided into four domains: GERD, dysphagia, pain, and nausea; each is scored 0–100, with higher scores indicating a greater symptom domain severity. Patients who completed Week 52 in Part B of EoE KIDS were eligible for Part C, where all patients received open-label dupilumab, using the weight-tiered regimen later approved by the FDA (similar to the Part A and B higher-exposure regimen). In patients who received placebo or dupilumab higher exposure during Parts A and B, changes from baseline of the EoE KIDS study (Part A baseline) in the PEESSv2.0 total, frequency, severity, and domain scores were assessed at Week 52 (Part C baseline), Week 76, and Week 100.

Results

At Week 52, the mean change from baseline (95% confidence interval) in PEESSv2.0 total score was –23.8 (–32.1, –15.6; Table), with further reductions observed at Week 100 (–31.5 [–41.5, –21.4]). Mean changes from baseline in PEESSv2.0 frequency and severity scores were further reduced from Week 52 (–25.1 [–34.2, –16.1] and –22.2 [–30.3, –14.1], respectively), to Week 100 (–33.8 [–44.9, –22.7] and –28.6 [–38.3, –19.0]). Similar patterns of reduction were observed for individual primary domain scores, namely, GERD, dysphagia, pain, and nausea. During the Part C open-label extension, dupilumab safety was consistent with the known dupilumab safety profile.

Conclusion

Children with EoE, treated with long-term dupilumab, experienced sustained improvements in the frequency and severity of symptoms of EoE up to Week 100, assessed by the PEESSv2.0. Reductions in GERD, dysphagia, pain, and nausea domain scores were also maintained or in some cases further improved, although interpretation of Part C symptom data is limited due to the open-label study design. Future studies should consider the correlation of symptoms with trends in both endoscopic and histologic outcomes.

Disclosure

Oliva S: Celgene/Receptos/Bristol Myers Squibb, Medtronic, Ocean Pharma, Sanofi/Regeneron Pharmaceuticals Inc – advisory board/consulting fees. Medtronic, Sanofi/Regeneron Pharmaceuticals Inc. – speaker fees.
Gold B: Diasorin Molecular, IQVIA/AstraZeneca, Ironwood Pharmaceuticals, Johnson&Johnson, Mead Johnson/Reckitt, Nutricia, Pfizer Inc, Sanofi/Regeneron Pharmaceuticals – advisory board/consultancy fees.
Ashok D: Alexion Pharma, LaunchitDTx, Mirum Pharma – advisory board/consulting fees. Sanofi – speaker fees.
Parrish C: Sanofi/Regeneron, Takeda – advisory board/consulting. Regeneron Pharmaceuticals Inc., Sanofi – speaker fees. DBV technologies, NIH/NIAID – research support.
Xia C, Raphael BP, Radwan A, Thomas RB: Regeneron Pharmaceuticals Inc. – employees and may hold stock or shares.
Cazeau C, Almansa C, Tilton ST: Sanofi – employees and may hold stock or shares.

Introduction

The correlation between fecal calprotectin (FC) levels and small bowel (SB) inflammation in patients with Crohn's Disease (CD) remains a subject of debate.

Aims & Methods

This study aims to investigate the relationship between FC levels and SB inflammatory activity in patients diagnosed with SB CD.
We conducted a retrospective cohort study involving patients with SB CD who underwent small bowel capsule endoscopy (SBCE) and FC testing. Patients with colon inflammation were excluded. Participants were categorized into four groups based on their SB inflammatory status: no inflammation (all three SB tertiles showed Lewis Score (LS) <135); proximal SB inflammation (first and/or second SB tertiles had LS ≥ 135, with no inflammation in the third SB tertile); distal SB inflammation (third SB tertile had LS ≥ 135, with no inflammation in the proximal SB); pan-SB inflammation (both proximal and distal SB with inflammation).

Results

A total of 87 patients were included in the study, with a median age of 35 years, 75.9% being female. The distribution of inflammation among the patients was as follows: no inflammation in 21.8%; proximal inflammation in 4.6%; distal inflammation in 33.3%; pan-SB inflammation in 40.4%.
FC median values exhibited an ascending trend along the SB axis: no inflammation 58 µg/g (33-180); proximal SB inflammation 65 µg/g (30-128); distal SB inflammation 122 µg/g (42-507); pan-SB inflammation 400 µg/g (205-852).
Statistically significant differences in FC levels were observed between pan-SB inflammation vs. isolated proximal inflammation (p = 0.014), and isolated distal inflammation (p = 0.012).
Additionally, FC showed a positive correlation with LS in the second (r = 0.464, p<0.001) and third tertiles (r = 0.435, p<0.001), but no correlation was noted in the first tertile.
FC demonstrated good predictive capacity for identifying inflammation in the distal SB and pan-SB vs. no inflammation and proximal inflammation, with an area under the curve of 0.790 (p < 0.001) and an optimal cutoff value of 228 µg/g.

Conclusion

FC levels correlate positively with the presence of SB lesions in the second and third tertiles of the small bowel. However, it is not a reliable marker for detecting inflammation in the first tertile, highlighting the importance of conducting a SBCE in these patients.

Introduction

Linked Color Imaging (LCI) is an endoscopic system that emphasizes the red mucosal color to identify subtle areas of inflammation. Endoscopic imaging, including LCI classification and LCI index, has been reported as a predictor of histological healing (HH) in ulcerative colitis (UC). Endoscopic changes (LCI classification, LCI index) in vedolizumab treatment have not been reported to date.

Aims & Methods

This study aimed to evaluate endoscopic remission and HH using LCI endoscopy at week 22 of vedolizumab treatment in patients with moderate to severe UC. This was a phase 4, multicenter, open-label, single-arm, prospective study involving 12 patients with moderately to severely active UC receiving vedolizumab. Vedolizumab was administered for 54 weeks. Endoscopy and mucosal sampling from most inflamed sites or the patient’s rectum when all sites had equal endoscopic severity were performed at weeks 0, 22, and 54 to assess the LCI index, LCI classification, Mayo endoscopic score (MES), Nancy score (If MES = 0, it was collected from the rectum). This study was also evaluated a variety of possible factors such as fecal calprotectin, serum vedolizumab concentration and mucosal gene expression associated with changes induced by vedolizumab. LCI index was numerically evaluated for the redness of a 40-pixel square area within the LCI image. LCI classification was defined by assigning one of the three categories (A, no redness; B, redness with visible vessels; C, intense redness without visible vessels). HH was defined as a Nancy score ≤1, and clinical outcomes were compared between HH and non-HH groups. Correlation coefficients between LCI endoscopy and other clinical markers (MES, Nancy score, fecal calprotectin and vedolizumab concentration) were analyzed at weeks 0, 22, and 54. Gene expression analysis was performed on 374 genes, comparing HH (n=8) vs. non-HH (n=3) and LCI classification A (n=5) vs. LCI classification B and C (n=6) at week 22. Biomarkers common to HH and LCI-A were identified as LCI-Deep remission (L-DR) markers.
The study was registered with the Japan Clinical Trial Registry (Identifier: UMIN000042855).

Results

At week 22, 66.7% (8/12) achieved histological healing (HH), while 50.0% (6/12) met LCI classification A criteria. The LCI index change from baseline showed a statistically significant difference between HH and non-HH (week 22: p=0.021; week 54: p=0.011).Correlation analysis demonstrated that LCI index was significantly associated with: MES (week 22: ρ=0.729, week 54: ρ=0.789), Nancy score (week 22: ρ=0.695, week 54: ρ=0.725), fecal calprotectin (week 22: ρ=0.555, week 54: ρ=0.783), vedolizumab concentration (week 22: ρ=0.758, week 54: ρ=-0.418). Gene expression analysis identified IL1B, CXCL11, CD38, CSF2RB, PTPN6, CD86, NFKB2, IFNAR2, STAT1, GNAI2, FES and IRF9 as L-DR markers, as they were commonly associated with both HH and LCI classification A. There are genes involved in NF-κB signaling pathway and JAK-STAT signaling pathway associated with UC. HH and LCI endoscopy have been found to correlate well but do not perfectly align.
In this study, we proposed a definition of L-DR, which encompasses both HH and LCI endoscopic remission.

Conclusion

This study introduces L-DR as a novel definition for combined endoscopic (LCI-A) and HH (Nancy score ≤1) in UC patients receiving vedolizumab. Additionally, we identified candidate L-DR biomarkers that may serve as potential indicators of deep remission.

Disclosure

Tomohisa Takagi, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Mitsubishi Tanabe Pharma Corporation,
Collaborative research fund from PreMedica Inc.,
Lecture fees by Mochida Pharma. Co., Ltd., Yanssen Pharmaceutical K.K., EA Pharma. Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Towa Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc.
Kazuhiko Uchiyama, Male, ( Kyoto Prefectural University of Medicine, Kyoto, Japan):
Collaboration research fund from Janssen Pharma. K.K.
Lecture fee by Mitsubishi Tanabe Pharma. Co. Ltd. and Janssen Pharma. K.K.
Yuji Naito, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Taiyo Kagaku Co. Ltd., Morinaga Co. Ltd., Miyarisan Pharma Co. Ltd, Morishita-Jintan Co. Ltd., Fujikko Co. Ltd., Mizkan Co. Ltd., Mykinso Co. Ltd.
Collaboration research fund from Takeda Pharma. Co. Ltd. and Taiyo Kagaku Co., Ltd.
Lecture fees by Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., Biofermin. Co. Ltd., Otsuka Pharma. Co. Ltd., and Miyarisan Pharma. Co. Ltd.

Introduction

Tryptophan metabolism is severely disrupted in IBD. Pro-inflammatory cytokines activate the first rate-limiting enzyme IDO1 leading to tryptophan degradation through the kynurenine pathway. Although Trp degradation typically support de novo NAD synthesis via KP activation, evidence suggests a metabolic block at the downstream enzyme QPRT in IBD. STING has been described as inducing the secretion of type I interferons and other inflammatory cytokines, suggesting its important role in regulating intestinal homeostasis. Several studies have reported an association between STING-mediated IDO1 activity and its role in promoting tumour immune evasion. However, the relationship between STING pathway and tryptophan metabolism in intestine has not be understood. This study aims to investigate the effect of STING signalling on tryptophan degradation and explore how the metabolic blockage in tryptophan-NAD axis may influence STING-mediated immune response.

Aims & Methods

To investigate the STING pathway's role in tryptophan metabolism within the intestinal microenvironment, we utilized human colonic fibroblast cell line CCD-18co. Quantitative RT-PCR and Western blot were employed to measure mRNA and protein expression. Tryptophan metabolism was quantified via LC-MS. QPRT knockdown was achieved using siRNA transfection. Transcriptomic changes were analysed by RNA sequencing. Intracellular NAD level were assessed by NAD-Glo assay. Seahorse assay was conducted to evaluate mitochondrial function.

Results

We screened a range of established IDO1-inducing cytokines (IFNγ, TNFα, etc.) and compared their effects on IDO1 expression with STING agonists diABZI, dsDNA and 2'3'cGAMP. STING agonists induced significantly higher IDO1 expression than any of the cytokines tested. While cultivation of in presence of Anifrolumab (type I IFN receptor antagonist) and Tofacitinib (pan-JAK inhibitor) strongly inhibited STING-induced IDO1 upregulation. LC-MS showed upregulation of IDO1 drive tryptophan into kynurenine pathway, which was again inhibited by Anifrolumab and Tofacitinib.
To mimic the reduced QPRT expression in IBD, we performed QPRT knockdown followed by RNA sequencing. Loss of QPRT resulted in spontaneous activation of type I interferon signature, which was further amplified upon stimulation with STING agonists, leading to a pronounced inflammatory transcriptional response. Mechanistically, QPRT-deficient cells exhibited reduced intracellular NAD levels and signs of mitochondrial dysfunction, including opening of the mitochondrial permeability transition pore (mPTP), release of mitochondrial DNA and RNA into the cytosol, and subsequent activation of the cGAS-STING and RIG-I/MAVS pathways, respectively. These events collectively led to a pronounced induction of type I interferons and pro-inflammatory cytokines. Notably, supplementation with nicotinamide riboside (NR) restored intracellular NAD levels and significantly attenuated the heightened inflammatory response induced by QPRT knockdown.

Conclusion

Our findings reveal a novel mechanism by which STING activation in intestinal fibroblasts promotes tryptophan metabolism via kynurenine pathway. Furthermore, QPRT deficiency-induced metabolic disruption amplifies STING-mediated pro-inflammatory responses via the release of mitochondrial nucleic acids, a process that can be effectively attenuated by supplementation with NAD precursors.