Introduction

Button battery ingestions (BBI) are increasingly common. The ESPGHAN position paper on BBI was published in 2021 outlining procedures for the diagnosis and management of BBI. Despite rising cases, the true global incidence of BBI is underreported.

Aims & Methods

An online survey was distributed via the monthly ESPGHAN newsletter between May and February 2023, requesting details about BBI cases managed the last 3
years.

Results

A total of 177 responses were received (82% paediatric gastroenterologists) with most practicing in Europe (64) or North America (69). The total number of BBI cases managed by respondents was 1830 with 28.6% of cases involving a large (>20mm) button battery (BB) and 21 reported deaths.
38% of responders reported increasing numbers of BBI cases. Honey for children > 12 months of age is recommended within 12 hours post ingestion for oesophageal impaction but was not used by 70% of doctors (Fig.1.A). Acetic acid irrigation immediately after removing the button battery was also not used by 76.5% of responders (Fig.1.B). Only 56% of responders reported placing a nasogastric tube after BB removal and 56.1% performed contrast study after 1-2 days. Significant variability was noted in timing of initiating oral feeds post-BB removal (44% reported starting oral feeds after 24 hours, 37% within the first 24 hours, 19% deferred starting until seeing a normal contrast study (Fig.1.C). Nearly half of the cases required admission <2 days: (43.7%). 1281 cases (70%) experienced full recovery without complications. However, the remaining 30% developed complications: strictures; dysphagia; fistulas (Fig.1.D). More than 80% of doctors were aware of the ESPGHAN BBI position paper, but their practice varies widely.

Conclusion

BBI cases are increasing, and children continue to die. We propose a pan-European prospective registry with global reach to better evaluate incidence and outcomes and further, inform management and prevention.

References

1. Mubarak A, Benninga MA, Broekaert I, Dolinsek J, Homan M, Mas E, Miele E, Pienar C, Thapar N, Thomson M, Tzivinikos C, de Ridder L. Diagnosis, Management, and Prevention of Button Battery Ingestion in Childhood: A European Society for Paediatric Gastroenterology Hepatology and Nutrition Position Paper. J Pediatr Gastroenterol Nutr. 2021 Jul 1;73(1):129-136.
2. Chandler MD, Ilyas K, Jatana KR, Smith GA, McKenzie LB, MacKay JM. Pediatric Battery-Related Emergency Department Visits in the United States: 2010-2019. Pediatrics. 2022 Sep 1;150(3):e2022056709

Disclosure

nil to disclose

Introduction

There is a need for more effective treatments for IBD, with advanced therapies having placebo-adjusted clinical remission rates of only 10 to 25%. The combined use of targeted biologic agents could break through this efficacy ceiling while avoiding the risks associated with broad immunosuppression. Towards this end, Spyre Therapeutics is developing half-life extended antibody drug candidates that can be administered in combination, inhibiting the clinically validated IBD targets α4β7 integrin (SPY001), TL1A (SPY002), and IL-23 (SPY003). The efficacy of combined inhibition of integrin β7 and TL1A, integrin β7 and IL-23, and TL1A and IL-23 was evaluated in proof-of-concept studies utilizing the TNBS-induced murine colitis model.

Aims & Methods

Mice were dosed intravenously with surrogate antibodies targeting mouse integrin β7 (25 mg/kg), mouse TL1A (25 mg/kg), mouse IL-23 (25 or 1 mg/kg), pairwise combinations of these three antibodies (integrin β7 + TL1A, integrin β7 + IL-23, TL1A + IL-23), an isotype control antibody, or vehicle on Day -1 and Day 2. TNBS was administered intrarectally (IR) on day 0 to induce colitis in all mice except the non-disease control group, which received IR vehicle. Body weight and disease activity score were recorded daily until the end of the study on Day 6. Colon weight and length were measured at the conclusion of the study. Colon histopathology was scored by a blinded pathologist.

Results

Monotherapy treatment with 25 mg/kg anti-β7 or 25 mg/kg anti-TL1A antibodies resulted in low magnitude, directional improvements in colitis outcome measurements, while treatment with 25 mg/kg anti-IL-23 antibody resulted in significant improvements relative to the vehicle and isotype control groups. Combinations of anti-β7 + anti-TL1A, anti-β7 + anti-IL-23, and anti-TL1A + anti-IL-23 resulted in superior efficacy compared to their constituent monotherapies based upon disease activity scoring. To further explore combination therapy benefit, a lower dose (1 mg/kg) of anti-IL-23 alone or in combination with anti-β7 or anti-TL1A was evaluated. Low dose anti-IL-23 showed minimal activity as a monotherapy, but low dose anti-IL-23 + anti-β7 maintained efficacy similar to the high dose combination. The combination of low dose anti-IL-23 + anti-TL1A was more effective than either monotherapy alone.

Conclusion

Combination therapy with anti-β7 + anti-TL1A, anti-β7 + anti-IL-23 or anti-TL1A + anti-IL-23 resulted in efficacy superior to their constituent monotherapies in the murine TNBS model of colitis. These data support and provide biologic rationale for the advancement of antibody combinations into human clinical trials for inflammatory bowel disease.

Disclosure

All authors are employees and shareholders in Spyre Therapeutics, Inc.

Clinical Case Summary

Colonoscopy is an essential tool in the diagnosis and management of various gastrointestinal disorders, yet it carries a risk of complications that can complicate patient care. Among these, post-colonoscopy appendicitis represents a rare but critical condition. The interplay between colonoscopy-induced inflammation and pre-existing appendiceal pathology may contribute to this phenomenon. A thorough understanding of the pathophysiology, clinical manifestations, and management strategies associated with post-colonoscopy appendicitis is vital for healthcare professionals to enhance early recognition and optimize patient outcomes.
A sixty-one-year-old female patient underwent esophagogastroduodenoscopy(EGD) and colonoscopy due to recurrent episodes of diffuse, non-radiating mild abdominal pain, as well as for colorectal cancer screening. The procedure was conducted without complications, but the bowel preparation was deemed inadequate (BBPS: 1-2-1). Twenty-four hours later, the patient presented to the emergency department, reporting severe diffuse non-radiating abdominal pain accompanied by multiple episodes of vomiting, nausea, and watery non-bloody diarrhea. Computed tomography of the abdomen was performed showing acute appendicitis. Subsequently, open appendectomy was performed with a course of intravenous antibiotics and patient then discharged home in good physical condition.
In conclusion, this case highlights the potential for post-colonoscopy appendicitis as a rare but significant complication that can arise following gastrointestinal procedures. It underscores the importance of maintaining a high index of suspicion for appendicitis in patients presenting with abdominal symptoms after colonoscopy, facilitating timely diagnosis and treatment.

References

• Ali,Mohammad MD¹; Patel, Jigar MD²; Katz, Douglas MD²; Friedel, David MD³. Post-Colonoscopy Appendicitis: A Rare but Concerning Entity: 1548. American Journal of Gastroenterology 113():p S891, October 2018
• ASGE review of adverse events in colonoscopyKothari, Shivangi T. et al.
  Gastrointestinal Endoscopy, Volume 90, Issue 6, 863 - 876.e3
  

Introduction

Microplastic particles (MPs) have previously been confirmed to be found in the human body and are suspected to lead to systemic health effects (1). One biological matrix in which MPs have been detected is human faeces (2). While there is growing evidence suggesting potential impacts on the gut microbiome from animal (3) and in-vitro/ex-vivo studies (4), studies investigating this relationship in the human are still lacking.

Aims & Methods

This pilot study aimed to investigate the impact of short-term plastic reduction on the gastrointestinal tract of healthy participants, focussing on MP presence and gut microbial composition.
Sixty healthy volunteers participated by providing two stool samples: one prior to and one after a seven-day intervention during which they actively minimized plastic exposure. To facilitate the reduction, participants were provided with plastic-free alternatives (e.g., glass water bottles, wooden kitchen utensils, plastic-free dental care products, tin lunch boxes), together with instructions on how to avoid plastic-packaged goods and find alternatives. Dietary habits and plastic contact were recorded using detailed questionnaires to assess behavioural changes and identify potential sources of exposure. Stool samples were analysed using 16S rRNA gene sequencing for changes in microbial diversity and potential differential taxa. Additionally the samples were frozen at –80°C for future MP quantification, where method development is ongoing.

Results

Fifty-five participants completed the study, with an average self-reported success rate of 76% in adhering to the intervention. Forty percent of participants fully avoided plastic packaging, while 56% achieved partial avoidance. Participants noted challenges, particularly in avoiding plastic in meat and dairy products and during restaurant visits. Despite these obstacles, 92.7% expressed a lasting commitment to reducing plastic use post-intervention, with many reporting intentions to continue purchasing fresh products, reduce fast food intake, and adopt sustainable household practices, especially replacing plastic utensils. Initial microbiome analysis revealed no significant changes in alpha or beta diversity following reduced plastic exposure; however, differential abundance analysis identified potential specific taxa shifts. One species each within the genera Clostridium, Ruminococcus, and Blautia showed reduced abundance post-intervention, while species from the genera Bacteroides and Anaerostipes were associated with increased abundance after plastic fasting.

Conclusion

A short-term reduction in plastic exposure is feasible and can effectively raise awareness and promote long-term behavioural change in plastic consumption habits. However, no significant changes in gut microbial diversity were observed within the study period, with only shifts in a limited number of species visible. Due to the stability of the gut microbial composition, longer changes in plastic exposure might be necessary to trigger stronger effects.

References

(1) Prata, J. C., da Costa, J. P., Lopes, I., Duarte, A. C., & Rocha-Santos, T. (2020). Environmental exposure to microplastics: An overview on possible human health effects. The Science of the total environment, 702, 134455. https://doi.org/10.1016/j.scitotenv.2019.134455
(2) Schwabl, P., Köppel, S., Königshofer, P., Bucsics, T., Trauner, M., Reiberger, T., & Liebmann, B. (2019). Detection of Various Microplastics in Human Stool: A Prospective Case Series. Annals of internal medicine, 171(7), 453–457. https://doi.org/10.7326/M19-0618
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Tamargo, A., Molinero, N., Reinosa, J. J., Alcolea-Rodriguez, V., Portela, R., Bañares, M. A., Fernández, J. F., & Moreno-Arribas, M. V. (2022). PET microplastics affect human gut microbiota communities during simulated gastrointestinal digestion, first evidence of plausible polymer biodegradation during human digestion. Scientific reports, 12(1), 528. https://doi.org/10.1038/s41598-021-04489-w