Introduction

Low-volume bowel preparation solutions, including 1 L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability because of the low tolerability of high-volume polyethylene glycol agents. However, 1 L PEG-A still has its typical odor that is not pleasant for most patients. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. OST may have the better tolerability because of little odor due to its tablet formula.

Aims & Methods

We aimed to investigate the efficacy, safety, and tolerability of OST compared to 1 L PEG-A. We randomized patients aged 18 years or older who underwent colonoscopy into the OST (group A) and 1 L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston bowel preparation scale (BBPS) and bubble scale. Bowel preparation success was defined as BBPS score ≥ 6. The bubble scores ranged from 0 to 3 per segment (total from 0 to 9), with a lower score indicating lower bubbles in the colonic lumen. Safety and tolerability were evaluated using a systematized questionnaire.

Results

A total of 171 patients (group A: 87, group B: 84) were included in the final analyses. The average BBPS score of group A was 8.0±1.3, which was similar to that of group B (7.7±1.4) (p=0.215). The proportion of patients showing bowel preparation success was 95.4% in the group A whereas that in the group B was 96.4% (p=0.736). The adenoma detection rate was also similar between groups A (59.6%) and B (41.9%) (p=0.087). The bubble scale in the group A was 0.2±0.9, which was significantly better that that of the group B (1.9±1.7) (p<0.001). All adverse events were mild in both groups. The group A showed lower frequency of nausea compared to the group B (14.9% vs. 38.1%, p=0.001). Overall satisfaction was better in the group A (8.1 ± 2.1 vs. 6.4 ± 2.8, p<0.001).

Conclusion

Although both OST and 1 L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy, the OST showed fewer bubbles and slightly better tolerability.

Introduction

Colonic diverticular bleeding (CDB) is the most common cause of acute lower gastrointestinal bleeding (ALGIB). In a recent Japanese multicenter retrospective cohort study, 63.6% of patients with ALGIB were ultimately diagnosed with CDB [1]. It has also been reported that CDB in ALGIB is reportedly more severe than in other entities [2, 3]. However, few reports have demonstrated the efficacy and safety of bowel preparation for patients undergoing urgent colonoscopy.

Aims & Methods

We aim to clarify choice a of bowel preparation for urgent colonoscopy in patients with colonic diverticular bleeding. In a multicenter retrospective cohort study at 10 institutions, we analyzed the endoscopic findings and clinical course of patients diagnosed with CDB who underwent urgent colonoscopy within 24 hours after admission. Bowel preparation consisted of oral consumption of 1 to 2 L of polyethylene glycol lavage (PEL); enemas were not used. We compared those CDB patients who underwent PEL (PEL group) with a control group who did not undergo PEL (non-PEL group) before and after propensity score matching. For the matching, we selected variables known at the time of hospital admission (i.e. age, sex, comorbidities, medications, performance status, and laboratory data). The primary endpoint of the study was length of hospital stay, and secondary endpoints included blood transfusion requirements, rebleeding rates, endoscopic findings, and complications.

Results

242 patients were enrolled in this study. The median age was 76 years, and 60.7% of patients were men (n = 147). Approximately half of the patients underwent bowel preparation with PEL prior to urgent colonoscopy (n = 129). We compared with clinical findings between the PEL and non-PEL groups. The length of hospital stay was shorter in the PEL group (8.0 ± 5.1 days vs 10.9 ± 5.8 days; mean ± SD; P < 0.001). Further, the PEL group was significantly younger (72.2 ± 12.1 vs 75.4 ± 13.1; mean ± SD; P = 0.036), had fewer patients with hypertension (62.0% vs 75.2%; P = 0.027) and malignant neoplasm (1.6% vs 10.6%; P = 0.002), and had better performance statuses (86.1% vs 76.1%; P = 0.047). Patients in the PEL group received fewer blood transfusions (25.6% vs 44.3%; P = 0.002), had a higher rate of cecal completion (88.3% vs 49.6%; P < 0.001), and shorter endoscopic observation times (20.8 ± 16.2 min vs 29.9 ± 24.8 min; mean ± SD; P = 0.006). After propensity score matching, there were 91 patients each in PEL group and in non-PEL group. PEL group had a significantly shorter hospital stay (7.9 ± 4.6 days vs 10.7 ± 5.8 days; mean ± SD; P < 0.001), a higher cecum completion rate (87.8% vs 48.3%; P < 0.001), and a shorter endoscopic observation time (20.7 ± 16.8 min vs 28.9 ± 24.1 min; mean ± SD; P = 0.031) than non-PEL group. There were no significant differences in blood transfusion requirements, rebleeding rates, identification of SRH, need for endoscopic hemostatic treatment, or complication rates.

Conclusion

In patients with CDB, urgent colonoscopy under PEL resulted in shorter hospital stays, higher cecal completion rates, and shorter endoscopic observation time in urgent colonoscopy. The safety of urgent colonoscopy with PEL was comparable to colonoscopy without PEL. These results suggest that PEL is preferrable for urgent colonoscopy in patients with CDB.

References

1. Nagata N, Kobayashi K, Yamauchi A, et al. Identifying bleeding etiologies by endoscopy affected outcomes in 10,342 cases with hematochezia: CODE BLUE-J study. Am J Gastroenterol 2021; 116: 2222-2234.
2. Aoki T, Nagata N, Shimbo T, et al. Development and validation of a risk scoring system for severe acute lower gastrointestinal bleeding. Clin Gastroenterol Hepatol 2016; 14: 1562-1570.e2.
3. Xavier SA, Machado FJ, Magalhães JT, et al. Acute lower gastrointestinal bleeding: are STRATE and BLEED scores valid in clinical practice? Colorectal Dis 2019; 21: 357-364.

Introduction

Motorized spiral enteroscopy (MSE) has shown to be safe and effective for deep small bowel enteroscopy in patients with and without prior abdominal surgery, including patients with Crohn’s disease.
This case series reports our first results regarding the feasibility and safety of the MSE with endoscopic balloon dilatation in patients with small bowel strictures due to Crohn’s disease.

Aims & Methods

Data were collected retrospectively on patients who underwent MSE for endoscopic balloon dilatation of small bowel strictures due to Crohn’s disease. Strictures were either postoperative (P.O.) or post-inflammatory (P.I.).

Results

A total of ten consecutive patients with Crohn’s disease underwent 13 procedures. Propofol sedation without endotracheal intubation was used in all procedures. Demographic and procedure related data are shown in the table. One patient underwent three procedures with 3–4 month intervals. During the third procedure triamcinolone acetonide was injected at four quadrants of the stricture. Fluorescence imaging was used during six procedures. The procedure was technically successful in 12/13 of procedures. In one case, dilatation was not performed because of a longer than anticipated and a sharply angulated stricture.
The number of treated strictures ranged from one to five per procedure. Dilatation of multiple strictures in two patients (4 and 5) was achieved within a relatively short procedure duration of 55 and 70 minutes. Two retained video capsules were retrieved.
Besides the anticipated mild abdominal discomfort and/or sore throat in three patients, no adverse events occurred.

Conclusion

These retrospective data show that MSE with CRE dilatation is feasible and safe in a cohort of patients with strictures due to Crohn’s disease, postoperatively as well as post-inflammatory. The fact that the distal 16 cm of the endoscope are not covered by the spiral overtube makes cautious introduction of the endoscope beyond a recently dilated stricture feasible and safe. Therefore, dilatation of multiple strictures in one session is possible, provided that they are at a short distance from each other. Fluorescence imaging guidance may be helpful in severe stenosis, multiple strictures, or sharp angulations.

Introduction

Bowel urgency is increasingly being recognized as an impactful symptom in patients with ulcerative colitis (UC)¹. However, limited information is available regarding its potential association with other patient reported outcomes. We assessed the association of bowel urgency clinically meaningful improvement (CMI) or bowel urgency remission with Inflammatory Bowel Disease Questionnaire (IBDQ) scores whilst adjusting for the potential confounding effects of stool frequency (SF) and rectal bleeding (RB) remission using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Aims & Methods

Bowel urgency severity was assessed by the Urgency Numeric Rating Scale (UNRS) (0=no urgency to 10=worst possible urgency). Bowel urgency CMI was defined as ≥3-point decrease in UNRS compared to baseline and bowel urgency remission was defined as UNRS of 0 or 1.² IBDQ scores (range: 32–224) were calculated; higher scores indicate better quality of life. Mediation analyses were performed to examine the relative association between direct effects of bowel urgency CMI and bowel urgency remission (separate predictors) and IBDQ scores while adjusting for the potential confounding effects of SF remission and RB remission (mediators). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials at Week (W) 12 and 40 (W52 of continuous treatment).

Results

At W12 and W52, bowel urgency remission directly accounted for 44.8% and 32.5% improvement in IBDQ total score, respectively; 22.7% and 39.1% of improvement was mediated by RB remission and 32.5% and 28.4% by SF remission, respectively. At W12, bowel urgency remission resulted in the largest proportion of improvement in each of the IBDQ domain subscores, whereas at W52, RB remission had a greater confounding effect. At W12 and W52, bowel urgency CMI accounted for 70% and 57.3% improvement in IBDQ total score, respectively; 12.8% and 25.6% of effects were mediated by RB remission and 17.2% and 17.1% by SF remission, respectively. Bowel urgency CMI accounted for the largest proportion of association with improvement in each of the IBDQ domain subscores at both W12 and W52.

Conclusion

​Improvements in IBDQ scores were primarily ascribed to bowel urgency remission and bowel urgency CMI relative to RB remission and SF remission, particularly at W12, in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ quality of life.

References

¹Dubinsky MC, et al. J Patient Rep Outcomes. 2022;6(1):31.
²Dubinsky MC, et al., J Patient Rep Outcomes. 2022;6(1):114.

Disclosure

Alessandro Armuzzi: Consulting/advisory board fees: AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer-Ingelheim, BMS, Celgene, Celltrion, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker’s fees: AbbVie, Amgen, Arena, Biogen, BMS, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix; research grants: MSD, Takeda, Pfizer, Biogen. Brian Feagan: Consultant: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Avir, Azora Therapeutics, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boston Pharma, Boxer, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Everest Clinical Research Corp., Lilly, Equillium, Ermium, Ferring, First Wave, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Glenmark, Gossamer Pharma, GSK, Hoffmann-LaRoche, Hot Spot Therapeutics, Index Pharma, Imhotex, ImmunExt, Immunic Therapeutics, Intact Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, LifeSci Capital, Lument AB, Millennium, MiroBio, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Otsuka, Pandion Therapeutics, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, RedHill, Biopharma, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Theravance, Tigenix, Tillotts, UCB Pharma, VHSquared Ltd., Viatris, Ysios, Ysopia, Zealand Pharma; speakers bureau: AbbVie, Janssen, Takeda; scientific advisory board member: AbbVie, Amgen, Boehringer-Ingelheim, Celgene/BMS Genentech/Roche, Janssen, Novartis, Origo BioPharma, Pfizer, Prometheus, Takeda, Tillotts Pharma, Teva, Progenity, Index, Ecor1Capital, Morphic, GSK; stock shareholder: Gossamer Pharma; employment: Western University, Alimentiv Inc. Bruce Sands: Consultant: Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer-Ingelheim, Boston Pharmaceuticals, Calibr, Celltrion Healthcare, ClostraBio, Entera, Evommune, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Inotrem, Innovation Therapeutics, Ironwood Pharmaceuticals, Kaleido, Kallyope, Lilly, Miro Bio, Morphic Therapeutics, MRM Health, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Surrozen, Teva, TLL Pharmaceutical, USWM Enterprises, VielaBio; consultant, speaker, research funding: Bristol Myers Squibb; consultant, speaker, grant/research support: Janssen; consultant, speaker: Abivax, Pfizer, Takeda. Stefan Schreiber: Consultancy and personal fees: AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Takeda, and Theravance. Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, BMS, Celltrion, 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, Vividion; speaker’s fees: Abbvie, Ferring, BMS, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi. Anthony Keohane: Employment: Eli Lilly and Company. Kristina A Traxler: Employment: Eli Lilly and Company. Theresa Hunter Gibble: Employment: Eli Lilly and Company
William J Eastman: Employment: Eli Lilly and Company

Introduction

Postoperative ileus, is one of the most common causes of prolonged hospital stays after abdominal surgery which cause from physiologic hypomotility of the gastrointestinal tract occurring immediately after abdominal surgery. Multi-modal approach to the resolution of postoperative ileus includes ERAS protocol such as opioid minimization, early ambulation, intake of prokinetic drug. Mosapride citrate (mosapride) is known to promote gastrointestinal motility. The objective of this study is to evaluate the effects of mosapride on postoperative ileus and postoperative gastrointestinal motility in patients undergoing elective open and laparoscopic colorectal surgery.

Aims & Methods

The study was approved by ethics committee of the Faculty of Medicine Ramathibodi Hospital Mahidol University (Ref. Number COA.MURA2021/328,ClinicalTrials.gov Identifier: NCT04905147). Forty-four colorectal cancer patients, undergoing open and laparoscopic colorectal surgery in Ramathibodi Hospital during July 2021-August 2022, were randomly assigned to a mosapride group or control group. The mosapride group received 15 mg of mosapride by enteric route with 50 ml of water three times a day, starting on postoperative day 1. The control group received 15 mg of placebo drug with 50 ml of water at the same time. Postoperative time to the first passage of flatus and the first bowel movement were evaluated by one investigator with triple blind study. Time to step diet, length of postoperative hospital stays, and adverse effects were also evaluated in secondary outcomes.

Results

All forty four patients were include, twenty-three in control group and twenty-one in mosapride group. There were no statistically significance differences between mean age and type of surgery (laparoscopic or open) in two group (P>0.05). Time to first bowel movement and time to passage of flatus after operation were significantly shorter in the mosapride group than the control group (26 vs 50 hours, P=0.004 and 40 vs 70 hours, P=0.003, respectively). Time to step diet (soft diet) was also shorter in the mosapride group (90 vs 132 hours, P=0.004). Time to defecate was less in mosapride group than control group (80 vs 120 hours, P <0.001). Length of hospital stay was significantly shorter in patients receiving mosapride (7 vs 10 days, P=0.004).

Conclusion

This study demonstrated the efficacy of mosapride when administered to patients who underwent elective colorectal surgery. Mosapride significantly enhance recovery of gastrointestinal motility and shorter length of hospital stay with no significant adverse effects.

References

1. Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery. Ann Surg 1999;230:251–9
2. Vather R, O'Grady G, Bissett IP, Dinning PG. Postoperative ileus: mechanisms and future directions for research. Clin Exp Pharmacol Physiol. 2014;41(5):358-370.
3. Goldstein JL, Matuszewski KA, Delaney C, Senagore A, Chiao E, Shah M, et al. Inpatient economic burden of postoperative ileus associated with abdominal surgery in the United States. P AND T.2007;32(2):82.
4. Venara A, Neunlist M, Slim K, Barbieux J, Colas PA, Hamy A, et al. Postoperative ileus: Pathophysiology, incidence, and prevention. J Visc Surg 2016;153:439-46.
5. Luckey A, Livingston E, Taché Y. Mechanisms and Treatment of Postoperative Ileus. Arch Surg. 2003;138(2):206–214.
6. Georgiadis, G & Markantonis, Sophia & Triantafillidis, John. (2000). Prokinetic agents: Current aspects with focus on cisapride. Annals of Gastroenterology. 13.
7. Reynolds, J.C. & Putman, P.E. (1992) Prokinetic Agents, Gastroenterol Clin of North Am, Vol.21, pp.567-596.
8. Taniyama, K., Makimoto, N., Furuichi, A. et al. Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine₄ receptor, in gastrointestinal motility. J Gastroenterol 35, 575–582 (2000).

Introduction

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are non-infectious chronic inflammatory disorders of the gastro-intestinal tract. The continuous presence of inflammatory stimuli, such as increased circulation of cytokines and danger-associated molecular patterns (DAMPs), leads to an enhanced immune response in these patients that could explain some types of disease relapse. An important receptor for DAMPS and pathogen-associated molecular patterns (PAMPs) is NLRP3, a cytosolic pattern recognition receptor. The NLRP3 inflammasome is exclusively activated by inflammatory stimuli, like DAMPs and PAMPs, and therefore not expressed without inflammation. It is thought that NLRP3 associates with ASC to recruit pro-Caspase 1 to the NLRP3 inflammasome and cleave it to its active form. In turn, Caspase 1 cleaves pro-interleukin 1 beta (IL-1β) and pro-interleukin 18 (IL-18) to their mature forms. IL-1β is a known elevated pro-inflammatory cytokine in IBD, promoting intestinal inflammation and immune cell recruitment. We hypothesized that the NLRP3 inflammasome pathway is therefore upregulated in IBD patients.

Aims & Methods

We first set out to systematically analyze gene expression of NLRP3 and IL1B in IBD patients by performing a systematic literature review and subsequent meta-analysis according to the PRISMA guidelines and Cochrane Collaboration methods. Subsequently, an observational cohort of 70 active and quiescent patients with CD or UC was sampled for whole blood, to study NLRP3 inflammasome gene regulation, protein production, assembly and secretion. We performed ex vivo LPS and ATP challenges of whole blood, with and without NLRP3 inflammasome formation inhibitor MCC950.

Results

Across thirty studies with publicly available mRNA expression data, we found NLRP3 and IL1B expression to be significantly higher in IBD patients than in non-IBD controls. In fresh IBD patient-derived whole blood, LPS and ATP stimulation activated the NLRP3-related genes, protein production and subsequent cytokine secretion. No IL-1β and IL-18 were secreted upon incubation with MCC950, suggesting a crucial role for NLRP3 inflammasome assembly in IL-1β and IL-18 production in immune cells. In patients with active IBD, the inflammasome was transcribed at a higher level than in patients in remission. However, this effect was lost on the protein level. We found a large spread in IL-1β and IL-18 production, suggesting a variation in activation of the NLRP3 inflammasome between individuals which was not related to disease activity.

Conclusion

NLRP3 and IL1B mRNA transcription is significantly increased in IBD patients compared to non-IBD controls, and significantly higher in patients with active disease than in patients in remission. While this fits the inflammatory state of active IBD, we found that the level of IL-1β and IL-18 production by the NLRP3 inflammasome is not significantly different between disease states. This suggests a variance in individual immune response to challenges, that could help identify a subset of IBD patients that would benefit from additional therapies directed at NLRP3 and IL-1β.

Introduction

Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial aetiology, which is still not completely understood. OCTN1, an organic cation transporter could have a role in modulating the inflammatory response, whose genetic polymorphisms were associated to increased risk of inflammatory bowel diseases. Up to now, limited information exists on its role in predicting/modulating response to therapies.

Aims & Methods

The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and immune composition to Infliximab therapy in murine colitis. Dextran sodium sulphate model of colitis on C57BL/6 mice and ocnt1 gene knockout mice was used to assess clinical efficacy of infliximab administered intravenously. Stool, colon and mesenteric lymph node samples were collected to assess differences in gut microbiota composition, histology for Rachmilewitz score and T cell populations respectively.

Results

Octn1^-/-influences microbiota profile and is associated with a worse dysbiosis in colitis mice. Infliximab treatment attenuates colitis-associated dysbiosis with increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1^-/- mice have a higher baseline percentage of Treg, Tmemory, Th2 and Th17.

Conclusion

Our data support murine model to study OCTN1 genetic asset in inflammatory bowel diseases. This could be the first step to consider this membrane transporter as a biomarker in inflammatory conditions and as a predictor of response to therapies.