Introduction

Sarcopenia is a progressive disorder characterized by reduced musculoskeletal mass leading to reduced strength and poor physical performance. Nutritional status is critical to therapeutic success in Crohn’s Disease (CD) and Ulcerative Colitis (UC) but it is clear how traditional weight and body mass index (BMI) scores are poorly representative of these.^[1,2] Sarcopenia could better reflect the degree of malnutrition.^[3] In inflammatory bowel disease (IBD) sarcopenia has been associated with refractory to medical treatment, prolonged hospitalization, increased rate of surgery and increased frequency of post-operative complications.^[4–6] Recently the measurement of the psoas muscle (PM) by ultrasound (US) has been proposed as a surrogate of sarcopenia obtaining an high concordance with the reference standard CT scan.^[7]

Aims & Methods

Our preliminary prospective study aims to identify correlations between US measurement of PM in a cohort of 57 patients with IBD and their clinical history and variables. The transverse area of the PM in cm² (US-TPA) and the same divided the square height in cm²/m2 (US-PMI) were measured in the right iliac fossa using a low frequency probe: General Electric Logiq P8 (Boston, USA) for outpatients whereas Esaote MyLab One/Touch (Genova, Italia) for inpatients.

Results

Normal weight patients have significantly higher US-TPA and US-PMI values (p=0.032 and 0.031) than underweight (BM<18.5 kg/m²) or overweight (BMI>25 kg/m²). CD patients have significantly lower US-TPA (p=0.03) than UC patients. Patients with history of fistulizing perianal disease or who have at least two surgeries have significantly lower US-TPA and US-PMI values than the rest of the population (p=0.02). Patients with severe disease activity (Mayo Partial 5 or Harvey-Brashaw Index>8) have lower US-TPA and US-PMI (p = 0.0003 and 0.0004) than those in clinical remission or mild-moderate activity. As well as for patients with disease activity of any degree (Mayo Partial >2 or HBI>5) compared to remission (p= 0.001 and 0.002). With due caution, we have empirically applied the US-PMI cut-offs proposed by Kobayashi^[8] in their cirrhotic cohort of 1.89 cm²/m² for males and 1.81 cm²/m² for females: 13 (23%) of our patients were found to be sarcopenic. Of these, 46% of patients were admitted at the time of inclusion, 50% clinically active and 77% clinically severe. The higher frequency of sarcopenia observed in these groups was statistically significant with OR 5.42 (IC 95% 1.4-21.8) and p=0.017, OR 5.4 (IC 95% 1.4-21.2) and p=0.02 and OR 19.3 (IC 95% 3.2-116) and p=0.0002 respectively. Underweight and overweight subjects (BMI <18.5 kg/m2 or >25 kg/m2) were more frequently sarcopenic according to the same cut-off than normal weighted with OR 3.97 (95% IC 1.08 - 14.53) and p=0.037.

Conclusion

US is a simple and reproducible method of measuring the PM as a surrogate for sarcopenia, an independent nutritional index that could affect therapeutic responses and outcome in IBD. Our study has found a correlation between the so quantified sarcopenia and the disease activity and clearly demonstrates how such a state of malnutrition is linked to both underweight and overweight. The widening of the population will allow us in future to emphasize associations and differences. The impact and predictive role of sarcopenia on IBD outcomes will be investigated. It will be necessary to identify PM US cut-off for IBD, validated and related by nutritional parameters or other quantitative or qualitative methods.

References

1 Bryant R V. et al. Systematic review: body composition in adults with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38: 213–225.
2 Dhaliwal A, Quinlan JI, Overthrow K, Greig C, Lord JM, Armstrong MJ, Cooper SC. Sarcopenia in Inflammatory Bowel Disease: A Narrative Overview. Nutrients 2021, Vol 13, Page 656 2021; 13: 656.
3 Adams DW et al. Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery. Inflamm Bowel Dis 2017; 23:1182–1186.
4 Sigurdsson GV et al. Altered body composition profiles in young adults with childhood-onset inflammatory bowel disease. 2020; 55: 169–177.
5 Bryant R V. et al.Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease.Aliment Pharmacol Ther 2015; 41: 895–906.
6 Pedersen M et al. Sarcopenia is a Predictor of Surgical Morbidity in Inflammatory Bowel Disease.Inflamm Bowel Dis 2017; 23: 1867–1872.
7 Takai Y. et al.Ultrasound method for estimating the cross-sectional area of the psoas major muscle. Med Sci Sports Exerc 2011; 43: 2000–2004.
8 Kobayashi K et al. Application of transcutaneous ultrasonography for the diagnosis of muscle mass loss in patients with liver cirrhosis. J Gastroenterol2018; 53: 652–659

Disclosure

Francesco Maria Stalla hosted to congresses: Giuliani s.p.a.

Introduction

Low grade dysplasia (LGD) is a key risk factor for development of high grade dysplasia (HGD) and colorectal cancer (CRC), in individuals with inflammatory bowel disease (IBD). Current clinical guidelines recommend that the detection of LGD should guide decision making, often leading to intensified surveillance or, in some cases, colectomy. As such, the detection of LGD in IBD imposes a considerable burden on both affected individuals and healthcare systems. The incidence, prevalence and treatment of IBD are continuously evolving. This may have influenced the incidence of IBD-related LGD and potentially its progression to HGD and CRC. Despite these developments, limited literature describes temporal trends in the incidence of IBD-related LGD, HGD and CRC, especially over the past decade, a period marked by the widespread use of biological therapies. Therefore, we aimed to utilize nationwide Danish health registers to describe trends over time in the incidence of IBD-related LGD, HGD and CRC.

Aims & Methods

We conducted a nationwide cohort study using data from Danish national health registers from 1990 to 2022. All Danish residents with a first-time diagnosis of either IBD, IBD-related LGD, HGD or CRC during this period were included. IBD-relation was established when a diagnosis of dysplasia or CRC was recorded within 180 days prior to, or at any time after, a first IBD diagnosis. HGD and/or CRC was defined as a composite endpoint, with the date assigned to the first occurring diagnosis if both were present. Incidence rates for IBD, IBD-related LGD, and HGD/CRC were calculated per 100,000 person years. Annual incidence rates and incidence rate ratios (IRRs) with 95 percent confidence intervals (CIs) were calculated using a Poisson approximation.

Results

During the study period, a total of 92,717 new cases of IBD, 8,406 cases of LGD, and 2,480 cases of HGD/CRC were identified.
The incidence of IBD per 100,000 person years increased markedly over time, rising from 30.36 in 1990 (95% CI: 28.89 to 31.91) to 59.71 in 2020 (95% CI: 57.76 to 61.73). A similar trend was observed for IBD-related LGD, with the incidence increasing from 0.33 (95% CI: 0.21 to 0.53) in 1990 to 10.41 (95% CI: 9.61 to 11.27) in 2020. For IBD-related HGD/CRC, the incidence rose from 0.12 (95% CI: 0.05 to 0.26) to 0.81 (95% CI: 0.61 to 1.07) in the same period. In the yearly incidence curves, the increase for both IBD and HGD/CRC appeared steady over time until a plateau was reached around 2008, whereas a distinct spike in LGD incidence was observed in 2014. This spike coincided with the introduction of a national CRC screening program in Denmark. Notably, the overall increase in IBD-related LGD far exceeded that of advanced dysplasia, with an IRR between 1990 and 2020 of 31.44 (95% CI: 28.01 to 35.28) for LGD, compared to 3.59 (95% CI: 3.35 to 3.85) for HGD/CRC.

Conclusion

The incidence of IBD, IBD related LGD, and IBD-related HGD/CRC has increased substantially in Denmark over the past 30 years. We observed a plateau in the incidence of IBD and IBD-related HGD/CRC within the last decade. Notably the overall increase in incidence was far more pronounced for IBD-related LGD, where we also observed a very notable spike in 2014, temporally aligned with the introduction of CRC screening in Denmark, this was not mirrored in the incidence of IBD-related HGD/CRC.

Introduction

Oesophageal food bolus impaction [OFBI] is a common presentation to emergency room [ER] and often requires endoscopic intervention. We aimed to describe the incidence of OFBI in Canterbury, New Zealand and examine factors predicting the need for endoscopic intervention and complications in the population-based cohort.

Aims & Methods

All ER presentations of OFBI in Canterbury between October 2018 and August 2023 were included. Population data for the Canterbury population was obtained from Statistics NZ. Ethnicity was defined according to hospital records based on patients’ self-identification. Endoscopic intervention was defined as the presence of bolus during the endoscopy requiring any endoscopic manoeuvre for clearance. Complications were defined as unsuccessful attempts requiring a repeat procedure or procedure-related injuries.

	Total (n = 187)
Age (years)	Mean 55 Median 54.9
Gender - Male (%) : Female (%)	113 (60.4) : 74 (39.6)
Ethnicity - European (%) : Non-European (%)	163 (87.2) : 24 (12.8)
Cause of oesophageal impaction (%)	EoE 42 (22.5) Stricture 43 (23)£ Other 15 (8)* Idiopathic/unknown 87 (46.5)¥
Food type (%)	Meat 141 (86.5) Non-meat 46 (24.5)
Spontaneous clearance of food bolus clinically, without endoscopy performed (inpatient or outpatient) (%)	42 (22.5)
Spontaneous clearance of food bolus diagnosed on endoscopy as an inpatient (%)	37 (19.8)
Inpatient endoscopic intervention required (%)	92 (49.2)
Total complications (%)	8 (4.3)

£ cause of impaction from Schatzi ring or benign esophageal stricture
* cause of impaction from severe reflux oesophagitis (Los Angeles Grade C or D), esophageal dysmotility, malignant stricture, or esophageal candidiasis
¥ no cause for impaction found; either no endoscopy performed as an inpatient or outpatient or no pathology found on endoscopy

Results

There were 187 ER presentations of OFBI between October 2018 and August 2023. Clinical characteristics of the population-based cohort are presented in Table 1.
The average annual incidence of ER presentations of OFBI in Canterbury region between 2019 – 2022 was 5.82 per 100,000 population (95% CI 3.96-7.68/100,000). The incidence of ER presentations of OFBI in Europeans and non-Europeans over the same period was 8 per 100,000 European population (95% CI 5.27-10.73/100,000) and 1.94 per 100,000 non-European population (95% CI 0.15-3.73/100,000).
A total of 92 cases (49%) required endoscopic intervention. Factors predicting the need for endoscopic intervention were meat bolus [p= 0.01], stricture [p<0.01], and early endoscopy performed <12hrs [p<0.01]. There were only 8 complications. Predictors with a trend associated with complications were after-hours presentation [p=0.06] and early endoscopy performed <6hrs [p=0.06].

Conclusion

Our population-based cohort showed a significantly higher incidence of ER presentations of OFBI in Europeans than in non-European ethnic groups. Factors predicting the need for endoscopic intervention were meat bolus, stricture and early endoscopy. After-hours presentation and early endoscopy <6hrs showed a trend towards a higher risk of complications. The results suggest that a delayed approach may be associated with a higher chance of spontaneous clearance and a lower risk of complications, although further study is needed.

Disclosure

Not applicable

Introduction

As many as 40% of IBD patients do not respond to targeted therapies¹. Enhancing the efficacy of these therapies is a key priority, and defective host-microbe interplay is often thought to underpin a proportion of mechanistic therapeutic failure. Interactions of macrophages with the microbial-derived SCFAs (Butyrate, Propionate and Acetate) in particular; may be critical for disease remission. Therefore, we examined the manner that macrophages interacted with, and changed their behaviour according to exposure to SCFAs in order to identify new therapeutic targets.

Aims & Methods

This study aimed to explore phenotypic changes of macrophages upon sensing of SCFAs in the context of IBD. We hypothesised that SCFAs would alter the inflammatory signature of macrophages, and that de-orphanized transmembrane G-protein receptor Free-fatty acid receptor 3 (FFA3) expressed by immune cells in GI tract would be critical for this process, and furthermore that effective sensing of SCFAs would be necessary for shaping macrophage phenotype. THP-1 and monocyte-derived macrophage models were developed for exploring inflammatory signatures in the presence of 1mM or 4mM of each SCFA (Butyrate/Propionate/Acetate). By using a pharmacological activator of FFA3 (AR420626) we aimed to identify whether this receptor play an important role in directing macrophage phenotype. Secretion of (type-I Interferon) IFN-I and pro-inflammatory cytokines were measured using ELISA. Expression of Interferon-stimulated genes (ISGs) was quantified using RT-PCR. Subsequent experiments aimed to validate our findings with a knock-down model of FFA3.

Results

We demonstrated that polarisation of macrophages with LPS & IFN-γ rapidly led to the induction of type-I interferon responses and release of pro-inflammatory cytokines. This heightened secretion of IFN-I was almost entirely muted in the presence of butyrate and propionate (1mM and 4mM). As IFN-I drives the expression of ISGs though activation of IFNAR1-JAK/STAT axis, we quantified expression of the ISGs MX1 and IFIT1 as an indirect measure of bioactive IFN. Induction of MX1 and IFIT1, were strongly repressed by butyrate and propionate. Based on these observations, we determined that these responses to both SCFAs were being mediated by FFA3. Intriguingly, our results were closely mimicked by pharmacological intervention with AR420626 in a dose-dependent manner (10 – 50 μM), suggesting that IFN-I secretion could be attenuated through activation of FFA3. Introducing a knock-down to our model, we validated our findings, and macrophages displayed impaired sensing of SCFA in the absence of FFA3.

Conclusion

We identified that macrophages reduce IFN-I release in the presence of butyrate and propionate, which is partly mediated through FFA3, and FFA3 ligands may be helpful for dampening inflammation in the gut mucosa in IBD.

References

(1). Ben-Horin, S., Kopylov, U. & Chowers, Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun. Rev. 13, 24–30 (2014).

Introduction

Human-computer interactions (HCI) can substantially influence the performance of Artificial Intelligence (AI). Studies indicate that although endoscopists, when assisted by AI, demonstrate significant improvements in assessing Barrett’s esophagus (BE), their performance does not reach the stand-alone level achieved by AI. A critical aspect of HCI is the impact of AI on the certainty and confidence exhibited by endoscopists. Indirectly, diagnostic confidence when utilizing AI may be associated with the trust and acceptance of AI. In a study focusing on BE videos, our objective was to examine the influence of AI on endoscopists' diagnostic confidence and explore potential correlations with diagnostic performance.

Aims & Methods

Twenty-two endoscopists from twelve centers, with varying levels of BE experience, reviewed ninety-six standardized endoscopy videos. The endoscopists were categorized as experts and non-experts and were randomly assigned to evaluate the videos with and without AI. Participants were divided into two arms: Arm A assessed videos initially without AI and then with AI, while Arm B followed the opposite order. Evaluators were tasked with identifying BE-related neoplasia and providing confidence ratings both with and without AI on a scale from 0 to 9. The study was followed up by a survey.

Results

In Arm A (without AI first, with AI second), the use of AI significantly increased confidence levels for both experts and non-experts (p<0.001). Notably, only non-experts experienced a significant improvement in sensitivity and specificity (p<0.001 bzw. p<0.05) with the assistance of AI. While experts exhibited higher confidence levels without AI compared to non-experts with AI, there was no significant difference in accuracy between these two groups. In Arm B both groups demonstrated a significant reduction in confidence (p<0.001), while maintaining consistent accuracy levels. In addition, in 9% of the choice changes with AI, the wrong choice was made despite correct indications made by AI.

Conclusion

AI significantly boosted confidence levels for both expert and non-expert endoscopists - an effect that was reversible in the study model. Furthermore, experts consistently displayed higher confidence levels, with or without AI, compared to non-experts with AI, despite comparable outcomes. It was further observed that in 9% of the choice changes the investigators ignored the AI in disadvantage of the patient. These findings highlight the potential role of AI in enhancing diagnostic confidence during endoscopic assessments.

Introduction

Alternate day oral iron therapy is better than daily oral iron therapy in Iron deficiency anemia (IDA) as it increases the fractional absorption of iron. In Ulcerative colitis (UC) with IDA increased fractional absorption of iron with alternate day iron may not only be better in improvement of anemia but also results in reduced unabsorbed iron delivery to distal bowel and may hence reduce adverse effects.

Aims & Methods

In a randomized, open label trial, from February 2023 to December 2024 patients of UC in remission (Mayo ≤2 OR partial Mayo ≤1 with fecal calprotectin <150mcg/gm for last 3 months) with IDA (ferritin <30mcg/l, transferrin saturation <20%, Hb 8-12 gm/dl) were randomized to every other day 132mg (EOD group) or daily 66mg (OD group) elemental oral iron given as ferrous fumarate for 8 weeks. Primary outcome was the difference in mean change in Hemoglobin (Hb) at 8 weeks. Secondary outcomes were the difference in mean change in RBC indices, iron indices and adverse events at 8 weeks.

Results

54 patients were randomized between both groups. One patient in EOD and 2 in OD group withdrew before treatment initiation. Eleven patients had disease flare on oral iron therapy (5 in EOD and 6 in OD group) p= 0.62 and two patients in EOD group had intolerance requiring oral iron stoppage. Thirty-eight patients completed treatment. The mean change in Hb at 8 weeks in EOD and OD groups was 2.08±1.0gm/dl and 2.09±1.11gm/dl respectively in per protocol analysis (p=0.797). The mean change in serum ferritin, serum iron, transferrin saturation and total iron binding capacity in both the groups is not significant. Disease flare within 6 months prior to oral iron therapy correlated with increased incidence of flare on oral iron therapy. (P=0.04)

Conclusion

Alternate day oral iron is not better than daily oral iron in improving Hb levels, iron indices and with similar incidence of adverse events in patients of UC in remission. A recent flare has increased chances of disease flare with oral iron therapy

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectalcancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC.
C57/BL6 wild-type (WT), Il33-/-, T1/St2-/- and Nt5e-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well asendoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33-/- and T1/St2-/-. qPCR analysis was done on isolated polyps from WT, Il33-/- and T1/St2-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well asIL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33-/- and T1/St2-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33-/- and T1/St2-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e-/-showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotestumorigenesis in colitis-associated CRC through the activation of CD73.Further studies are underway to determine mechanisms of action that support these findings.