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Compliance of the patient preparation instructions for colonoscopy

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Compliance of the patient preparation instructions for colonoscopy

Viktor Brusic 1

1 University Hospital Centre Rijeka, Rijeka, Croatia

Event

UEG Week Vienna 2024

Topics

Nurses

Session

Abstracts II: Patient care and endoscopic techniques

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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GP perspective: How to diagnose, review lifestyle and diet

Jelena Rakic Matic 1

1 Health Care Center Zagreb West, ZAGREB, Croatia

Event

UEG Week Berlin 2025

Topics

Primary Care

Session

Bloating

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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MULTI-DIMENSIONAL IMMUNOPROFILING OF UNCONVENTIONAL T CELLS OF INFLAMMATORY BOWEL DISEASE PATIENTS: ASSOCIATION WITH CLINICAL PHENOTYPES, DISEASE ACTIVITY AND PROGNOSIS

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Introduction

Inflammatory bowel disease (IBD) is a chronic systemic condition of unknown etiology. Dysregulated T-cell responses play a fundamental role in perpetuating intestinal inflammation in IBD. Unconventional T cells are a diverse subset of T cells with innate and adaptive characteristics including: Gamma Delta T cells (GDT), mucosa-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. As new studies emerge, unconventional T cells’ role in IBD pathogenesis has been increasingly recognized, but their role in the pathogenesis and possible clinical application remains to be elucidated.

Aims & Methods

The aim of the study is to characterize the immune profile of IBD patients and controls in a large well-characterized cohort with focus on Unconventional T cells. We performed an in-depth, multidimensional flow cytometry analysis of unconventional T cells and plasma proteins from patinets´samples collected from the IBD biobank in Norway.
We used immunophenotyping from isolated PBMC to study both conventional T cells and unconventional T cells and evaluated their gut-homing -a4 and b7 expression-, activation and senescence markers. A 65-plex Luminex assay was used to quantify soluble plasma proteins. We studied the variations of T cell profiles within the different disease phenotypes and their correlation with disease activity. A subset of patients was followed-up clinically for 6 (+/-2) years to evaluate the association with disease outcomes.
Statistical analysis was performed using GraphPad Prism (San Diego, CA). Two-tailed Mann-Whitney U test was used to compare two independent groups and ROC analysis was used for diagnostic accuracy; p≤ 0.05 was considered statistically significant. Ethical approvals were obtained and all patients gave written informed consent.

Results

A total of 184 individuals (106 F) were included: 149 IBD (84 UC and 65 CD) and 25 healthy controls. We found important quantitative and phenotypical differences in unconventional T cells and plasma protein in IBD and between UC and CD patients. Patients with IBD had a significant reduction in MAIT cells, and increase in GDT VD3+ and CD8+ cells (p< 0.05). MAIT cells from IBD patients had lower a4+ and b7+ expression than controls. (p<0.05, p<0.001). Interestingly, Macrophage Migration Inhibitor Factor (MIF) was significantly reduced in patients with UC but not in CD (p<0.0001).
Patients with total colitis presented a significant increase in platelet count, MIG, IL-2R, and CD30 (p<0.001,p<0.01 and p<0.05,respectively). CD patients with colonic affection (L2) had a significant increase in TNF-b, FGF-2, G-CSF compared with patients with ileal (L1) or ileocolonic (L3) CD (p<0.01). Interestingly, MAIT cells were the only immune cells significantly reduced in patients with extraintestinal manifestations. The combination of 6 parameters: IL-4, IL-5, IL-8, MIG, CD30 and Eotaxin-3 showed a good diagnostic accuracy in ROC curves (CI:0.759-1.000; p=0.0005) to distinguish patients with mucosal healing vs those with biochemical and clinical remission alone. A decrease in GDT VD2 cells was found in UC patients with worse outcomes (p<0.01). CD patients with bad prognosis showed a significant increase in platelet counts and a decrease in: FABP2, CXCL10 and APRIL (p<0.05).

Conclusion

These results demonstrate the potential of the characterization of Unconventional T cells and soluble plasma proteins as biomarkers in IBD and as markers of disease progression. Further investigation is warranted to elucidate the use of Unconventional T cells in precision medicine and as potential therapeutic targets in IBD.

References

1. Catalan-Serra I, Sandvik AK, Bruland T et al. Gammadelta T Cells in Crohn's Disease: A New Player in the Disease Pathogenesis? J Crohns Colitis. 2017;11:1135-1145.
2. Hinks TSC, Zhang XW. MAIT Cell Activation and Functions. Front Immunol. 2020 May 27;11:1014. doi: 10.3389/fimmu.2020.01014.

Disclosure

MULTI-DIMENSIONAL IMMUNOPROFILING OF UNCONVENTIONAL T CELLS OF INFLAMMATORY BOWEL DISEASE PATIENTS: ASSOCIATION WITH CLINICAL PHENOTYPES, DISEASE ACTIVITY AND PROGNOSIS

Ignacio Catalan-Serra 1, Weili Xu 2, Torunn Bruland 3, Arne K. Sandvik 4, Anis Larbi 2

1 Levanger Hospital. Norwegian University of Science and Technology. Centre for Molecular Inflammation, Levanger, Norway

2 Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Singapore, Singapore

3 Department of Clinical and Molecular Medicine (IKOM), NTNU - Norwegian University of Science and Technology, Trondheim, Norway., Trondheim, Norway|||Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondhe

4 Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav’s University Hospital, Trondheim, Norway, Trondheim, Norway|||Department of Clinical and Molecular Medicine (IKOM), NTNU - Norwegian University of Science and Technology, Trondhei

Event

UEG Week Vienna 2024

Topics

Gut Microbiota IBD Immunology

Submission format

Abstract

Session

Understanding disease primers of IBD: Part 2

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Poster

Standard Poster

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Clinical Case Summary

CD55 deficiency with Complement Hyperactivation, Angiopathic thrombosis and Protein Losing Enteropathy (CHAPLE) is a rare hereditary immune disease, driven by an overactivation of the complement system, caused by loss-of-function variants of CD55.¹ With fewer than 100 patients diagnosed with CHAPLE worldwide, providing evidence-based care can be complex. Previous studies showed that eculizumab, a complement C5 inhibitor, was broadly effective in patients with CHAPLE disease.² Recently, the FDA approved pozelimab, an anti-C5 antibody, as the first treatment for CHAPLE. This clinical case describes two sisters affected by CHAPLE disease highlighting the diagnostic process as well as their recent treatment with pozelimab, considering both clinical and immunological aspects.

In a Moroccan pedigree, two sisters were diagnosed with Crohn’s Disease (CD) at the ages of 12, and 27. Both sisters’ symptoms included recurrent edemas, abdominal pain, (bloody) diarrhea, nausea and vomiting, and abnormally low serum albumin levels. Treatment with diets, antibiotics, corticosteroids, immunomodulators and biologicals over multiple years had little effect. When a low IgG level was found in the younger sister, we initiated whole exome sequencing. This led to the diagnosis of CHAPLE disease in both sisters. Flow cytometry showed total absence of CD55 antigen on both patients’ blood cells and reduced expression of CD55 on the mother’s blood cells compared to a healthy control. A brother diagnosed with irritable bowel syndrome was genetically affected without clinical CD, demonstrating a highly variable penetrance.

Subcutaneous weekly pozelimab was started and allowed discontinuation of all immunosuppressive medication within 3 months in both sisters. Within a month of treatment, their symptoms resolved and inflammatory markers including fecal calprotectin and plasma albumin, as well as IgG levels, normalized. They have sustained remission since and reported no related adverse events.

References

Ozen A, Comrie WA, Ardy RC, et al. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med. 2017;377(1):52-61. doi:10.1056/NEJMoa1615887
Ozen A, Kasap N, Vujkovic-Cvijin I, et al. Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease. Nat Immunol. 2021;22(2):128-139. doi:10.1038/s41590-020-00830-z

COMPLEMENT REGULATOR CD55 DEFICIENT PROTEIN-LOSING ENTEROPATHY (CHAPLE DISEASE): SUCCESSFUL TREATMENT WITH POZELIMAB IN TWO SISTERS

Nikki van der Kruk 1, Esther C. W. de Boer 2, Richard B. Pouw 3, Taco W. Kuijpers 4, Johan E. van Limbergen 1

1 Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands|||Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endoc

2 Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands|||Amsterdam institute for Immunology and Infectious Diseases, Inflammatory diseases, Amsterdam, Netherlands|||Department of Pediatric Immunology,

3 Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands|||Amsterdam institute for Immunology and Infectious Diseases, Inflammatory diseases, Amsterdam, Netherlands|||Sanquin Diagnostic Services, Amsterd

4 Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands|||Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amst

Conference

UEG Week Vienna 2024

Topics

Colorectal

Submission format

Clinical Case

Session

Clinical Cases (Posters)

Published

2024

UEG Presentation

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Bugs and germs in GI-disease: Late-breaking abstracts (Complete Session)

Event

UEG Week Vienna 2024

Topics

Gut Microbiota IBD Mechanisms & Personalised Medicine

Session

Bugs and germs in GI-disease: Late-breaking abstracts

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART) PEPTIDE MEDIATES INTRACELLULAR CA2+ RELEASE IN SENSORY NEURONS AND INDUCES FIRING OF THE COLON-INNERVATING LUMBAR SPLANCHNIC NERVE

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Introduction

Inflammatory bowel disease (IBD) is characterised by inflammatory flares with excruciating pain, for which effective analgesics are lacking. Cocaine- and amphetamine-regulated transcript (CART) peptide regulates peripheral pain in mice.¹ However, its role in visceral nociception as well as the underlying molecular signalling mechanism in primary sensory neurons remains elusive. CART is highly expressed in TRPV1-positive colon-projecting sensory neurons.² In addition, the enzyme prohormone convertase 1/3, which is involved in processing CART into its bioactive fragment 55-102, is upregulated in colonic biopsies of IBD patients (internal data), suggesting a potential role for the peptide in colonic pain.

Aims & Methods

Here, we aimed to test if CART would affect firing of the colon-innervating lumbar splanchnic nerve (LSN) as model of visceral nociception and characterise its effect and signalling pathway in sensory neurons innervating the colon. Studies were performed using tissue from male and female C57BL/6J mice euthanised by cervical dislocation and exsanguination in accordance with Schedule 1 of the Animals (Scientific Procedures) Act 1986. Thoracolumbar dorsal root ganglia (DRG) neurons were dissociated and cultured overnight for Ca²⁺ imaging using Fluo-4 AM as previously described.³ Cells were perfused with extracellular solution (ECS) alone or supplemented with either rat CART 55-102, (20-300nM, ECS), thapsigargin (10mM, DMSO), xestospongin C (1mM, ECS), edelfosine (10mM, ECS), capsaicin (10mM, ethanol) or KCl solution (60mM, ddH₂O) for respective challenge or pre-treatment. All conditions were blinded and randomised. Colorectum with attached lumbar splanchnic nerve was carefully removed and mounted on a tissue bath superfused with Krebs buffer as previously described.³ Rat CART 55-102 was superfused at 5ml/min, resulting in a final concentration of 200nM. Statistical analysis was performed using Student´s t test or ANOVA and Dunnett´s multiple comparisons test. Data is displayed as mean ± SEM.

Results

CART elicited a concentration-dependent increase in intracellular Ca²⁺ in DRG neurons, which at the highest concentration tested (300nM) induced a significant increase in intracellular Ca²⁺ in 29.2 ± 2.98% of DRG neurons relative to 8.35 ± 1.25% of vehicle responders (p < 0.0001). 55.05% of CART-responsive neurons were putative nociceptors due to co-sensitivity to capsaicin. Further investigation revealed a statistically significant reduction in the proportion of CART-sensitive neurons compared to CART (300nM) alone following pre-treatment with edelfosine, a phospholipase C inhibitor (10.5 ± 3.88%, p = 0.006), thapsigargin, a SERCA pump inhibitor (7.25 ± 1.78%, p = 0.001), or xestospongin C, an inositol triphosphate receptor inhibitor (6.74± 1.87%, p = 0.006). Furthermore, tissue bath application of CART (200nM) elicited a marked transient increase in ongoing LSN discharge, which increased from a baseline of 12.8 ± 3.9 (spikes/s) to a peak firing of 19.7 ± 6.1 spikes/s (p = 0.0385).

Conclusion

CART stimulates intracellular Ca²⁺ release in capsaicin-sensitive neurons consistent with a role in pain processing. This response was mediated by the release of Ca²⁺ from intracellular stores such as the endoplasmic reticulum and attenuated by inhibitors of the G_q pathway, suggesting activation of a G_q-coupled GPCR. The pronociceptive activity of CART on nerve firing suggests a potential role in colonic pain. Further research is necessary to identify the role of CART in IBD.

References

1. Ohsawa M, Dun SL, Tseng LF, Chang J, Dun NJ. Decrease of hindpaw withdrawal latency by cocaine- and amphetamine-regulated transcript peptide to the mouse spinal cord. Eur J Pharmacol. Jul 7 2000;399(2-3):165-9. doi:10.1016/s0014-2999(00)00374-5
2. McGuire C, Boundouki G, Hockley JRF, et al. Ex vivo study of human visceral nociceptors. Gut. Jan 2018;67(1):86-96. doi:10.1136/gutjnl-2016-311629
3. Higham JP, Bhebhe CN, Gupta RA, et al. Transcriptomic profiling reveals a pronociceptive role for angiotensin II in inflammatory bowel disease. Pain. Jan 29 2024;doi:10.1097/j.pain.0000000000003159

Disclosure

The PhD research is partially funded by Metrion Biosciences.

COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART) PEPTIDE MEDIATES INTRACELLULAR CA2+ RELEASE IN SENSORY NEURONS AND INDUCES FIRING OF THE COLON-INNERVATING LUMBAR SPLANCHNIC NERVE

Nicole Rudi 1, Remigijus Lape 2, Edward Stevens 2, David Bulmer 1

1 University of Cambridge, Cambridge, United Kingdom

2 Metrion Biosciences, Cambridge, United Kingdom

Event

UEG Week Berlin 2025

Topics

Gut Microbiota Neurogastroenterology & Motility Small Intestine & Nutrition IBD

Submission format

Abstract

Session

Lower GI motility II

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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COMPARISON OF THE EFFICACY AND TOLERABILITY OF ELOBIXIBAT PLUS SODIUM PICOSULFATE WITH MAGNESIUM CITRATE AND SPLIT-DOSE 2-L POLYETHYLENE GLYCOL WITH ASCORBIC ACID FOR BOWEL PREPARATION BEFORE OUTPATIENT COLONOSCOPY: RESULTS OF MULTICENTER, RANDOMIZED, CON

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Introduction

Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. The standard formulation for bowel preparation is PEG; however, it requires a large dose and has a distinctive taste that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical studies have shown that SP/MC is superior to PEG in terms of acceptability.

Aims & Methods

Our aim was to compare the novel bowel cleansing method (test group) consisting of SP/MC with elobixibat hydrate and the standard bowel cleansing method consisting of PEG plus ascorbic acid (standard group) in patients preparing for outpatient colonoscopy. This was a multicenter, single-blind, non-inferiority, randomized controlled trial. Patients 40-69 years of age scheduled for outpatient colonoscopy were enrolled. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction were excluded. The target number of study participants was 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint was bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥6). Secondary endpoints were patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to BBPS (BBPS score ≥8), degree of bowel cleansing according to Aronchik scale, and bowel cleansing time. The non-inferiority margin for the primary endpoint was 10%. A study protocol of the present study has already been published in a peer-reviewed journal.

Results

Of 540 participants enrolled, efficacy was analyzed in 524 participants (test group, n=263; standard group, n=261) in the full analysis set. Non-inferiority of the test group was demonstrated for the primary endpoint (BBPS ≥6): 96.2% vs. 97.7% for test and standard group, respectively difference was -1.5%, [95%confidence interval (CI), -4.8 to 1.6%] with P<0.001 for non-inferiority. For the secondary endpoint BBPS≥8 was lower in test group (79.5% vs 91.2%: difference -11.7% [95% CI, -17.8 to -5.8%]). Patient acceptability was superior in the test group in the key questions (1. Was the bowel preparation medication easy to use? 2. Were all bowel preparation medications administered internally? 3. What is your overall impression of the bowel preparation? 4. How did the bowel preparation medicine taste? 5. Would you like to use the same bowel preparation medicine for your next colonoscopy?) Adverse events were similar in both groups.

Conclusion

A new regimen of elobixibat plus sodium picosulfate with magnesium citrate was non-inferior in bowel cleansing and superior in patient’s acceptability compared to split-dose 2-L polyethylene glycol with ascorbic acid.

References

1) Hotta K, Otake Y, Yamaguchi D, et al. Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split‑dose 2‑L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E‑PLUS trial. BMC Gastroenterol 2024 Feb 3;24(1):61.doi: 10.1186/s12876-024-03146-6.

Disclosure

The primary investigator (Kinichi Hotta) had received research funding from Nippon Chemiphar Co. Ltd.

COMPARISON OF THE EFFICACY AND TOLERABILITY OF ELOBIXIBAT PLUS SODIUM PICOSULFATE WITH MAGNESIUM CITRATE AND SPLIT-DOSE 2-L POLYETHYLENE GLYCOL WITH ASCORBIC ACID FOR BOWEL PREPARATION BEFORE OUTPATIENT COLONOSCOPY: RESULTS OF MULTICENTER, RANDOMIZED, CON

Hiroyuki Takamaru 1, Kinichi Hotta 2, Yosuke Otake 3, Daisuke Yamaguchi 4, Yuichi Shimodate 5, Norihiro Hanabata 6, Hiroaki Ikematsu 7, Yohei Yabuuchi 8, Yasushi Sano 9, Ryo Shimoda 10, Shinya Sugimoto 11, Mari Oba 12, Takumi Kanata 12, Kouichiro Kimura 3, Yoshihiro Kishida 2, Kazunori Takada 2, Sayo Ito 2, Kenichiro Imai 2, Kazuya Hosotani 8, Tatsuro Murano 7, Masayoshi Yamada 1, Kensuke Shinmura 7, Rio Takezawa 5, Michito Tomonaga 10, Yutaka Saito 1

1 National Cancer Center Hospital, Tokyo, Japan

2 Shizuoka Cancer Center, Sunto, Japan

3 Subaru Health Insurance Society Ota Memorial Hospital, Ota, Japan

4 National Hospital Organization Ureshino Medical Center, Ureshino, Japan

5 Kurashiki Central Hospital, Kurashiki, Japan

6 Aomori Prefectural Central Hospital, Aomori, Japan

7 National Cancer Center Hospital East, Kashiwa, Japan

8 Kobe City Medical Center General Hospital, Kobe, Japan

9 Sano Hospital, Kobe, Japan

10 Saga University Hospital, Saga, Japan

11 Japanese Red Cross Ise Hospital, Ise, Japan

12 National Center of Neurology and Psychiatry, Tokyo, Japan

Event

UEG Week Vienna 2024

Topics

Colorectal Endoscopy

Submission format

Abstract

Session

Optimising safety and efficacy of polyp treatment

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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