Introduction

Approximately 50% of patients with Ulcerative Colitis (UC) suffer from daily symptoms of faecal urgency, significantly impacting their quality of life¹. Treatment in quiescent disease is challenging and the first line treatment, loperamide, is often used with caution due to the side effect of constipation.
Enterosorbents such as Enterosgel provide a potential alternative treatment. Enterosgel is thought to work through the adsorption of small molecules in the gastrointestinal (GI) tract, with minimal or no systemic absorption and metabolism², without causing constipation. Enterosgel has shown clinical effectiveness in reducing urgency in patients with diarrhoea predominant irritable bowel syndrome (IBS-D), suggesting potential therapeutic value in patients with UC³, however the mechanism by which this may occur is unknown.

Aims & Methods

This study aimed to evaluate the in vitro adsorption capacity of Enterosgel for three key inflammatory mediators implicated in UC pathogenesis (IL-1β, MMP9 and TNF-α) to explore its potential as a therapeutic option in this patient group.
Three experimental paradigms were performed by diluting recombinant cytokines and enzymes in water-based Enterosgel solutions. After incubation, gel-free supernatants were harvested to analyse residual levels of metabolite via ELISA to identify the quantity of adsorption by Enterosgel. Conditions were conducted with different:

1. Incubation times (15,30,60,120 min)
2. Metabolite concentrations (5 concentrations ranging from 0 - 3000pg/mL)
3. Gel concentrations (0.056, 0.1125, 0.225g/mL)

Results

Enterosgel demonstrated measurable concentration-dependent adsorption of IL-1β, MMP9 and TNF-α with higher analyte input concentrations resulting in greater absolute adsorption. However for TNF-α adsorption saturated at 1000pg/mL, indicating that Enterosgel may not fully adsorb analytes at levels simulating extreme luminal inflammation. Charcoal consistently resulted in lower residual concentrations, although this did not reach statistical significance on permutation testing (p = 0.14).
In time dependent analysis, Enterosgel induced a rapid initial reduction in cytokine levels within 15 minutes, (IL-1β: 98.7%, MMP9: 99.4%, TNF-α: 95.8% adsorbed) with a plateau by 120 minutes (IL-1β: r²=0.74, MMP9: r²=0.64, TNF-α: r²=0.45). In contrast, charcoal demonstrated a near-linear monotonic decline with a slightly greater concentration adsorbed by 120 minutes (IL-1β: 99.9% vs. 99.8%; MMP9: 99.9% vs. 99.1%; TNF-α: 97.2 vs. 96.3%). Increasing gel concentrations improved adsorption efficiency; however, at the highest gel concentration small amounts of residual cytokines remained (IL-1β: 0.25%, MMP9: 0.28%, TNF-α: 3.5%). Doubling of gel concentration led to an average 30% decrease in residual cytokines.

Conclusion

Our findings suggest that Enterosgel demonstrates excellent adsorption of three key pro-inflammatory cytokines relevant to UC, with the greatest reduction at 1 hour and the highest gel concentration—though less than that achieved by charcoal. Evidence of saturation at high analyte levels suggests a limit to Enterosgel’s binding capacity under conditions simulating severe inflammation. These results highlight Enterosgel's clinical potential, however further validation with biological replicates and clinical studies assessing urgency in treated UC is required.

References

(1) Theresa Hunter Gibble, April N. Naegeli, Michael Grabner, Keith Isenberg, Mingyang Shan, et al. Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn’s disease and ulcerative colitis in the United States. 2023; 63 (23): 10.1186/s12876-023-02675-w.
(2) Howell CA, Mikhalovsky SV, Markaryan EN, Khovanov AV. Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs. Scientific Reports. 2019; 9 (1): 10.1038/s41598-019-42176-z.
(3) Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, Mclaughlin J, et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). BMJ; 2022.
(4) Shane O'Sullivan, John F Gilmer, Carols Medina. Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update. Mediators of Inflammation. 2015; 2015 (1): 10.1155/2015/964131.
(5) Qingdong Guan JZ. Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease. Mediators of Inflammation. 2017; 2017 (1): 10.1155/2017/4810258.

Introduction

The integrity of the intestinal barrier is crucial in preventing bacterial translocation and systemic inflammation, both of which contribute to the progression of advanced chronic liver disease (ACLD). While surrogate biomarkers exist, direct real-time assessment of intestinal barrier function has been challenging. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that allows direct visualization of mucosal integrity during endoscopy.

Aims & Methods

The present study aims to determine the prevalence of CLE-detectable barrier dysfunction in ACLD patients, to explore its association with disease severity, and to assess its prognostic significance. In our prospective study, 48 ACLD patients who underwent routine upper gastrointestinal endoscopy between 11/2022 and 04/2024 were examined using CLE (Cellvizio®) in the duodenum following intravenous fluorescein injection (2.5–5 mg). The presence or absence of fluorescein leakage into the intestinal lumen was determined. The presence of leakage in more than three different locations in the duodenum was indicative of intestinal barrier dysfunction. Clinical data including Child-Turcotte-Pugh (CTP) score, MELD score, hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and biomarkers of liver function were recorded. Patients were followed for a median of 13.2 months, with liver-related events (LRE) including first or further decompensation, acute-on-chronic liver failure (ACLF), and liver-related death as endpoints.

Results

Intestinal barrier dysfunction was detected in 52% of patients and was found to be significantly more prevalent in decompensated ACLD compared to compensated ACLD (73% vs. 25%, p=0.021). CLE-based barrier dysfunction correlated with bilirubin (p=0.033) and albumin (p=0.010), but not with HVPG (p=0.314), LSM (p=0.482), or C-reactive protein (p=0.457). Patients exhibiting intestinal barrier dysfunction demonstrated a significantly higher risk of LRE during follow-up (25% vs. 5% at 12 months, 43% vs. 5% at 18 months, log-rank p=0.005). In univariable Cox regression analysis, intestinal barrier dysfunction remained independently associated with LRE (hazard ratio: 2.36, 95% confidence interval: 1.34–84.0, p=0.025). Importantly, the prognostic impact of CLE findings aligned with established risk markers such as MELD and albumin.

Conclusion

CLE provides real-time, high-resolution insight into intestinal barrier integrity in ACLD patients. The strong correlation between CLE-detected barrier dysfunction and adverse clinical outcomes suggests that CLE has the potential to serve as a prognostic instrument for risk stratification. As CLE can be integrated into standard endoscopic procedures, it may provide an accessible and clinically relevant means of assessing intestinal barrier function in routine practice in patients with liver cirrhosis. Further studies in larger cohorts are needed to validate CLE for routine clinical use and to explore therapeutic interventions targeting intestinal barrier dysfunction.

Disclosure

NO CoI to declare

Clinical Case Summary

A 27-year-old male with diarrhea and rectal bleeding was diagnosed with moderate ulcerative colitis (UC) (Montreal: E3, Mayo endoscopic subscore: 2). He was started on mesalazine 4 g/day and oral prednisolone 40 mg/day, with clinical remission after 2 weeks. Prednisolone was successfully tapered off over the course of 8 weeks. He was not taking other medications. After starting therapy, the patient reported intermittent red urine discoloration, without other symptoms or association with respiratory tract infections.
Extensive investigation of hematuria was negative, including ANA, ANCA, anti-dsDNA and anti-GBM antibodies and imaging studies. Urine samples were macroscopically normal, with no red blood cells, casts or crystals. Urethrocystoscopy and urine cytology were unremarkable. Renal biopsy was considered.
The patient remained on mesalazine, with clinical, analytical and endoscopic response. During one episode, he noticed that the urine only became reddish after contact with toilet water disinfected with bleach. After stopping bleach toilet disinfection, there was no recurrence. He was diagnosed with mesalazine induced pseudohematuria and did not undergo further investigation.
Mesalazine is the first-line treatment for mild-to-moderate UC. Although uncommon, nephrotoxicity has been described and may result in urine discoloration or hematuria. Mesalazine is excreted in the urine and, when in contact with sodium hypochlorite (the active component of household bleach), oxidises, resulting in red-brown urine discoloration. Rare cases of patients reporting similar situations have been described in the literature. The role of gastroenterologists in recognizing this phenomenon is crucial, since mesalazine is a widespread efficient drug with an otherwise favorable safety profile. As our case illustrates, knowledge of this harmless reaction is desirable to avoid additional tests and potentially harmful unnecessary interventions, such as renal biopsy.

References

Figure 1 - Reaction between the urine of a patient taking mesalazine and the sodium hypochlorite present in household bleach (1A - before addition of bleach; 1B - after addition of bleach).

Disclosure

No conflict of interest to declare.

Introduction

Endoscopists with baseline adenoma detection rates (ADRs) ≤26% who improve their ADRs significantly reduce their patients’ risk of post-colonoscopy colorectal cancer (PCCRC)¹. The recommended withdrawal time (WT) of 8–9 minutes is associated with higher ADRs; however, it includes time spent on therapeutic interventions, which may overestimate actual inspection time and limit its accuracy as a performance metric².

Aims & Methods

We aimed to determine the corrected withdrawal time (cWT)—defined as WT minus intervention time—required for low-performing endoscopists to achieve ADR thresholds of ≥26 and ≥35.
We prospectively analyzed 1,165 the recorded videos of elective colonoscopies performed by 17 endoscopists at Montreal University Hospital Center (IRB; CER22.013/ CER25.12283). Eligible cases were consecutive adults (≥18 years) undergoing elective colonoscopy. Exclusions were complex resections, sigmoidoscopies, incomplete exams, failed recordings, and procedures by endoscopists with <10 prior cases. A research assistant was present during each procedure and documented all periprocedural metrics in real-time. Endoscopists were stratified as low (ADR ≤25%) or high performers (ADR >25%). The primary outcome was the mean cWT required for low performers to achieve an ADR ≥26%. Secondary outcomes included the cWT needed to reach ADR ≥35% and the incremental impact of each additional minute of cWT on detection metrics. Multivariable generalized estimating equation (GEE) models adjusted for patient demographics, bowel preparation, indication of colonoscopy, time of day/month, CADe use, and endoscopist effect.

Results

Low performers required a mean cWT of 10′58″ to achieve an ADR ≥26%, and 13′51″ to reach ≥35% compared to 4′01″ for high performers. Each additional minute of cWT increased ADR odds by 15.3% for low performers and 5.0% for high performers (P < .001). Similar improvements were observed across all detection metrics (Table 1). For every additional cWT minute, the odds of detecting advanced adenomas increased by 10.1%, sessile serrated lesions (SSLs) by 10.1%, and polyps by 16.5% (all P <  .001). Adenoma and polyp counts increased by 7.5% and 7.9%, respectively. Absolute gains per minute were greater in low performers, with ADR increases exceeding 3% beyond 12 minutes of cWT. After adjusting for covariates, each additional cWT minute was associated with a significant increase in the odds of detection: an increase of 6.5% (P = .002) for adenomas, 9.2% (P < .001) for advanced adenomas, 11.5% (P < .001) for SSLs, and 14.9% (P < 0.01) for polyps. With each additional cWT minute, the adenoma count increased by 7.3% and the polyp count increased by 7.8% (P < .001) (results not shown).

Table 1. Mean Detection Metrics and Their Incremental Increase Per Additional Minute of Corrected Withdrawal Time, Overall and Stratified by High vs Low Performers.

Conclusion

Longer cWT enhanced detection across all metrics, particularly for low performes. These findings support personalized cWT targets based on individual performance rather than uniform WT recommendations.

References

1. Pilonis ND, Spychalski P, Kalager M, et al. Adenoma detection rates by physicians and subsequent colorectal cancer risk. JAMA 2025;333:400–407.
2. Rex DK, Anderson JC, Butterly LF, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2024;100:352–381.

Disclosure

Daniel von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax, and has received consultant or speaker fees from Boston Scientific Inc., ERBE Elektromedizin GmbH, and Pendopharm. Roupen Djinbachian has received speaker fees from Fujifilm. The remaining authors declare that they have no conflict of interest.

Clinical Case Summary

Introduction: Intra-abdominal sepsis from colonic perforation is a surgical emergency with high mortality. While diverticulitis is a common cause in older adults, its presence in young, healthy individuals suggests additional etiologies. Parasitic infestations such as Ascaris lumbricoides, though rare in developed regions, can complicate outcomes.
Case presentation: A 35-year-old previously healthy male presented with 3 days of severe abdominal pain and vomiting. CT scan revealed pneumoperitoneum. Emergency laparotomy showed perforated sigmoid diverticulitis with fecal peritonitis. A Hartmann’s procedure was performed with an open abdomen due to gross contamination. Despite surgery, the patient developed persistent sepsis, requiring seven relook laparotomies. During the fourth, live Ascaris worms were seen emerging from the bowel during ileostomy creation, prompting Albendazole treatment. Histopathology confirmed diverticulitis with perforation. Recovery was complicated by multidrug-resistant infections, anemia, malnutrition, and thrombotic events, prolonging ICU stay.
Discussion: This case highlights how unrecognized parasitic infestation can worsen intra-abdominal sepsis. Ascaris may contribute to mucosal damage, obstruction, and inflammation, exacerbating outcomes. Early hypoalbuminemia might have reflected chronic enteric loss or parasite burden.
Conclusion: In endemic areas, chronic helminthic infections should be considered in young patients with unusual presentations or poor postoperative progress. Timely recognition may impact treatment and recovery.

References

Figure 1: CT Abdomen with Contrast showing Moderate Pneumoperitoneum
Figure 2: Worm coming out of iliostomy
Figure 3: acsaris
Figure 4 : CT Chest showing bilateral moderate pleural effusion more on the right side with underlying lung consolidation collapse.
Figure 5 : US Neck showing Left internal jugular vein central line with echogenic thrombus not completely occluding the lumen.