Introduction

Endoscopic scoring systems like Mayo endoscopic score (MES) is the gold standard for the assessment of disease activity in patients with ulcerative colitis. Intestinal ultrasound (IUS) is an attractive tool for assessing Ulcerative colitis (UC) disease activity. A novel IUS Score for UC was proposed by us in 2019 using simple IUS parameters which correlated well with MES.

Aims & Methods

Aims: We aim to internally validate our Intestinal UltraSound – Colitis Severity Index (IUS-CSI) scoring system.
Methods: Consecutive patients with UC undergoing colonoscopy for diagnosis, screening, or flare of symptoms were included in the study. These patients were evaluated with IUS within 1 week of their colonoscopy. The colon was divided into segments – sigmoid, left, transverse, and right colon. Rectum was excluded from the study. Endoscopic disease activity was graded using MES for each colonic segment. IUS-CSI score was calculated for each colonic segment using Bowel wall thickness (BWT), Colour doppler signal score (CDS) and bowel wall stratification (BWS). The correlation of IUS-CSI with MES for that segment was studied.

Results

45 consecutive patients with UC who underwent colonoscopy were included in the study. IUS was performed in 42 patients; 3 patients could not be evaluated in view of thick abdominal wall. Total of 168 colonic segments were assessed both by colonoscopy and IUS. 32 colonic segments had MES 0, 28 segments had MES 1, 92 segments had MES 2 and 16 segments had MES 3.
Mean BWT for MES 0, 1, 2 and 3 were 2.1mm, 2.5mm, 3.4mm and 5.1mm respectively. Of all the IUS parameters, BWT and CDS had consistent correlation with MES (p=<0.001).
The IUS-CSI was calculated for each colonic segment and correlated with the MES for that segment. A linear positive correlation was seen between IUS-CSI & MES for each colonic segment using Pearson’s correlation coefficient (r) and is as follows: Sigmoid colon r= 0.88(0.79,0.93), left colon r= 0.85(0.74,0.92), transverse colon r=0.89(0.8,0.94) and right colon r=0.79(0.64,0.88). The IUS-CSI for sigmoid colon correlated with the overall MES (r =0.83; p = 0.0001).

Conclusion

IUS-CSI has an excellent correlation with MES. IUS-CSI assessment of the sigmoid colon correlates best with overall endoscopic activity.
IUS-CSI scoring system with intestinal ultrasound can be used to assess disease activity in UC non-invasively.

References

P Kakkadasam Ramaswamy, A Yelsangikar, K V Nagarajan, A Nagar, N Bhat, P154 Development of a novel ultrasound based score for assessing disease activity in ulcerative colitis: preliminary results, Journal of Crohn's and Colitis, Volume 13, Issue Supplement_1, March 2019, Page S166, https://doi.org/10.1093/ecco-jcc/jjy222.278

Clinical Case Summary

Introduction: Mastocytosis is an uncommon hematopoietic neoplasm characterized by clonal proliferation of atypical mast cells. The clinical manifestations of mastocytosis are heterogeneous,ranging from limited cutanous involvement to aggressive disease with various levels of extra cutanous multi-organ involvement. Most cases of mastocytosis are indolent, usually cutanous or indolent systemic mastocytosis (SM). Aggressive SM is a rare and often fatal disease. Gastrointestinal involvement in aggressive SM presents with non specific symptoms and the final diagnosis depends on the pathology. Herein, we present a special case of colonic mastocytosis
Clinical case: We report a case of 66 years old female patient who presented with chronic abdominal pain not responding to treatment. On physical examination showed abnormal abdominal pigmentation and reported that skin biopsy previously revealed urticaria pigmentosa. Laboratory investigations were unremarkable. Colonscopy was planned and showed diffuse reddish mottling of cecum and ascending colon. Multiple biopsies were taken and histopathological examination revealed focal crypt architectural distortion. The lamina showed moderate inflammatory cellular infiltrate. These are formed of lymphocytes and plasma cells with excess eosinophils > 100/HPF. Esinophilic cryptitis is seen. Subtle population of scattered ovoid cells with rounded ovoid nuclei are seen. Slide stained for CD117 revealed positive reaction highlighting frequent mast cells. Moderate diffuse colitis with frequent mast cells and excess eosinophils > 100/HPF. Picture is suggestive of mastocytosis involving colon. The patient started imatinib and prednisone and long term follow up showed complete relieve of abdominal pain.

Introduction

Transcriptomic analysis has potential to evaluate the molecular basis and pathophysiology of inflammatory bowel disease (IBD), discover therapeutic targets, and identify biomarkers. However, the value of this technology in clinical trials is limited by substantial methodological heterogeneity, which confounds interpretation, generalisability, and comparison of data across studies.

Aims & Methods

We conducted a 2-part study that aimed to develop recommendations for standardising transcriptomic analysis in multicentre IBD clinical trials. First, 3 public databases were searched from inception to May 2021 to identify clinical trials that included patients with IBD and transcriptomic analyses. Studies that collected blood or intestinal samples and utilised microarray, RNA sequencing, or other global RNA analysis methods were eligible. Data on study design and methodological approaches to transcriptomic research ranging from biopsy location to data analysis and reporting were extracted by 2 independent reviewers. The results of the systematic review (SR) informed the second part of the study, in which a panel of 16 IBD translational researchers participated in a modified Research and Development/University of California Los Angeles appropriateness methodology (RAM) process. A list of statements focused on topics with substantial methodological heterogeneity (Table) was developed based on the SR and panel opinion and formed the basis for creation of a formal survey. Panellists rated the appropriateness of survey statements in 2 rounds, with panel input and survey modification between rounds.

Table. Overview of RAM survey topics

Results

The SR identified 37 reports (22 abstracts; 15 manuscripts) of 22 clinical trials (13 ulcerative colitis [UC]; 6 Crohn’s disease [CD]; 3 UC and CD) that included transcriptomic analyses. The earliest report was published in 2009, with most (>75%) reports published between 2017 and 2021. Most (59%) analyses were conducted at phase 1b or 2 of clinical development. The appropriateness of 416 statements were rated by 15 panellists in the first survey. The final survey included 305 statements, of which 14 panellists rated 75% appropriate, 1% inappropriate, and 24% uncertain. In general, transcriptomic analysis for multiple research objectives using either mucosal biopsy or blood samples was considered appropriate at all phases of clinical development in patients with active disease. Validation of results with external datasets and/or orthogonal methods was considered appropriate, as was the complete reporting of individual patient metadata (ex, patient demographics, disease/treatment history, sample location, and local disease activity); the latter of which was viewed as a critical component for further analysis and utility of transcriptomic data.

Conclusion

Although inclusion of transcriptomic analysis in IBD clinical trials has increased over the past decade, persistence of existing methodologic heterogeneity will continue to limit the interpretation and generalisability of the results of this important research. This study provides an initial framework for expert recommendations to address and overcome these discrepancies and increase the value of this research in clinical development.

Disclosure

BL, EC, MIS, LS: employees of Alimentiv Inc
AS: research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Alimentiv Inc, Boehringer Ingelheim and Agomab (Origo Biopharma); consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Origo Biopharma, Thabor Therapeutics, Goodgut and Boxer Capital
BS: employee of Lilly
BV: research support from from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda; speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris; consulting fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris
DM: consulting fees from Prometheus Biosciences, Takeda, Pfizer and Prometheus Laboratories; owns stock in Prometheus Biosciences.
FR: consulting fees from Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena,Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, CDISC,Celsius, Cowen,Ferring,Galapagos,Galmed,Genentech,Gilead,Gossamer,Granite,Guidepoint,Helmsley,Horizon Therapeutics,Image Analysis Limited, Index Pharma, Landos,Jannsen, Koutif, Mestag,Metacrine,Mopac,Morphic,Organovo,Origo,Pfizer,Pliant,Prometheus Biosciences,Receptos, RedX,Roche,Samsung,Sanofi,Surmodics,Surrozen,Takeda,Techlab,Teva,Theravance,Thetis,UCB,Ysios,89Bio
KA: grant support from Janssen, consulting fees from Johnson & Johnson/Janssen, Lilly, Takeda
MA: speaker/consultation fees or grants from Abbvie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Genentech, Gilead, IQVIA, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, and Tillots
RA: speaker/consultation fees or grants from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion, Dr Falk Pharma, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa Pharmaceuticals, MSD Sharp & Dohme, Novartis, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda, and Tillotts Pharma
SS: scientific advisory board fees from Pfizer, Pandion, Celgene, Lilly, Takeda, Cosmo Pharmaceuticals, Merck, Sonoma Biotherapeutics, and EcoR1; grant support from Pfizer, Amgen Takeda, and Novartis; consulting fees from Amgen, Kyverna, BMS, Merck, Third Rock, 89bio, GentiBio and Apple Tree Life Sciences
TR: research grants and/or speaker/consultation fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Takeda, UCB and XAP therapeutics
BFG: grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltech, Genentech/Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts Pharma AG, and UCB Pharma; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport, Aptevo Therapeutics, AstraZeneca, Atlantic Pharmaceuticals, Avir Pharma, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GlaxoSmithKline, Inception IBD, Johnson & Johnson/Janssen, Kyowa Hakko Kirin, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharmaceuticals, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts Pharma AG, UCB Pharma, Vertex Pharmaceuticals, Vivelix Pharmaceuticals, VHsquared, and Zyngenia; speakers bureau fees from Abbott/AbbVie, Johnson&Johnson/Janssen, Lilly, Takeda, Tillotts Pharma AG, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, AstraZeneca, Atlantic Pharmaceuticals, Avaxia Biologics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, Johnson & Johnson/Janssen, Merck, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharmaceuticals, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; Senior Scientific Officer of Alimentiv.
VJ: consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx, and Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Shire, Takeda, and Fresenius Kabi.
NVC: grant from R-Biopharm; personal fees from AcelaBio, Alimentiv, Pfizer, ProciseDX, Ventyx.
DA, DC, FU, LM, MN, VA, YH: none

Introduction

Bacterial translocation exacerbates circulatory dysfunction present in patients with liver cirrhosis. Probiotics can reduce bacterial translocation and consequently improve the outcomes in this population.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in the cirrhotic patients. We performed a systematic review in PubMed, Embase and Cochrane Central database, searching for studies analyzing the effects of probiotics use in overt hepatic encephalopathy incidence in cirrhotic patients. A Bayesian network meta-analysis was conducted to estimate the relative effects between treatments using risk ratios (RR) and to rank each one according to the Surface Under the Cumulative Ranking Curve (SUCRA).

Results

We included eight studies, comprising 975 patients. The assessment of SUCRA values indicated that lactulose plus probiotics (0.95) emerged as the most effective prevention for overt hepatic encephalopathy. Moreover, lactulose plus probiotics demonstrated superior efficacy compared to lactulose (0.54), probiotics only (0.51), LOLA (0.48), placebo (0.24), and no therapy (0.21). The risk of overt hepatic encephalopathy was low for lactulose plus probiotics (0.000025; credible interval [CrI] 1.3x1016, 1.5), lactulose only (RR 0.64; CrI 0.09, 4.0), probiotics (RR 0.69; CrI 0.17, 2.9), LOLA (RR 0.64; CrI 0.04, 8.9) and no therapy (RR 1.1; CrI 0.22, 7.0).

Conclusion

In our network meta-analysis, the best results in the treatment of the patients with cirrhosis and hepatic encephalopathy was seen with the association of lactulose plus probiotics. Both drugs have good tolerability and are widely disponible, so we suggest considering this association.

Introduction

Overweight and obesity present global health challenges, often managed through lifestyle changes and medications like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which can cause gastrointestinal (GI) adverse events. However, research on their effects in non-diabetic populations is lacking.

Aims & Methods

This review addresses this gap by examining the impact of GLP-1 RAs on GI adverse events in non-diabetic overweight or obese individuals. We systematically reviewed the literature by conducting a search using PubMed and EMBASE, adhering to predefined inclusion and exclusion criteria, to assess GI adverse events linked with GLP-1 RAs in non-diabetic overweight or obese populations. We conducted a dose response meta-analysis to evaluate each adverse event associated with different GLP-1 RAs. The quality of the included studies was appraised utilizing the Cochrane Collaboration's assessment tool.

Results

Our systematic review and meta-analysis encompassed thirty-eight articles, incorporating data from a total cohort of 32,882 individuals. Predominant GI adverse effects observed included nausea, vomiting, diarrhea, constipation, and abdominal pain. Across all evaluated GLP-1 RAs, a notable elevation in nausea risk was noted, with orforglipron exhibiting the highest risk, succeeded by exenatide, tirzepatide, semaglutide, and liraglutide. Moreover, liraglutide, orforglipron, semaglutide, and tirzepatide were associated with heightened vomiting risk, while cagrilinitide and exenatide displayed no significant increase. Exenatide, cagrilinitide, and orforglipron demonstrated no significant association with diarrhea risk. Conversely, semaglutide and liraglutide correlated with an elevated risk of constipation, while cagrilinitide and exenatide did not exhibit a significant increase. Notably, certain GLP-1 RAs were linked to a heightened risk of abdominal pain, with liraglutide, semaglutide, and tirzepatide displaying significant increases, whereas orforglipron showed no significant elevation in abdominal pain risk.

Conclusion

In conclusion, GLP-1 RAs are associated with an increased risk of GI adverse effects, including nausea, vomiting, diarrhea, constipation, and abdominal pain. Importantly, distinct GLP-1 RAs exhibited varying degrees of risk for these adverse effects, underscoring the importance of tailored risk assessment and management strategies in clinical practice.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.