Introduction

There are limited studies that examined the risk factors of childhood Irritable Bowel Syndrome (IBS). Studies on the risk factors for adult IBS frequently indicate that early life periods play a significant role in the development of IBS. However, the majority of these studies are retrospective and prone to confirmation bias. To address this limitation, we conducted the first prospective mother-offspring cohort study (Growing Up in Singapore Towards healthy Outcomes (GUSTO)) to investigate the early life risk factors associated with the development of childhood IBS.

Aims & Methods

Under the GUSTO study, we conducted a prospective population-based mother-child birth cohort study of 1176 children born in Singapore from November 2009 to May 2011. We analysed data from 827 mother-child pairs with complete follow-up at Year 11 and without an initial diagnosis of organic gastrointestinal disease. Incident cases of IBS were defined according to the Rome IV Criteria in Years 9, 10, and 11 of the study. Perinatal, childhood and parental data were collected (see table) at different intervals since birth. Factors significant on univariate analysis (* in table) were analyzed using multivariable binomial regression to determine association with IBS.

Results

Our participants were predominantly males (n=431, 52.1%) of ethnic Chinese descent (n=475, 57.4%) and were delivered vaginally (n=574, 69.4%). By the 11th year of the study, 40 (4.8%) of our participants were diagnosed with IBS. Perinatal factors significantly associated with IBS include emergency intervention† (AOR: 2.74, 1.11-6.75, p<0.001), female child gender (AOR: 3.69, 1.68-8.06, p=0.001), higher birth weight (AOR: 2.47, 1.12-5.44, p=0.025) and maternal depression (AOR: 1.12, 1.04-1.20, p=0.004). Childhood factors significantly associated with IBS include child generalized anxiety (AOR: 1.61, 1.09-2.36, p=0.016), maternal anxiety (AOR: 1.06, 1.01-1.10, p=0.008) and authoritarian parenting style (AOR: 8.75, 1.30-59.13, p=0.034).

† Emergency intervention was defined as assisted vaginal delivery or emergency Caesarean-section

Conclusion

In conclusion, this study provides important insights into the risk factors associated with childhood IBS. The findings suggest that early life periods, including perinatal, childhood, and parental factors, play a significant role in the development of IBS. This has significant clinical implications for identifying at-risk children and implementing targeted interventions to prevent the development of IBS. Further research is needed to validate these findings and explore potential mechanisms underlying these associations.

References

Soh, S. E., Tint, M. T., Gluckman, P. D., Godfrey, K. M., Rifkin-Graboi, A., Chan, Y. H., Stünkel, W., Holbrook, J. D., Kwek, K., Chong, Y. S., Saw, S. M., & GUSTO Study Group (2014). Cohort profile: Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. International journal of epidemiology, 43(5), 1401–1409. https://doi.org/10.1093/ije/dyt125

Introduction

Irritable bowel syndrome (IBS) has a worldwide prevalence of ~11%, and thus has a considerable negative impact on both society and millions of individuals. The pathophysiology of IBS is multifactorial and incompletely understood, involving low-grade inflammation in the gut, visceral hypersensitivity, increased epithelial barrier permeability, altered gut-brain interactions, and an unfavourable composition of gut microbiota. Although we currently have no cure for IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has shown to give ~70% of patients clinically significant symptom relief.

Aims & Methods

In this study, we seek to uncover how 12 weeks of strict low-FODMAP diet affect the intestinal immune system, visceral hypersensitivity, and gut integrity in patients with IBS. We will use highly multiplexed Hyperion imaging mass cytometry to investigate the cellular microenvironments in duodenal biopsies from n = 48 patients and n = 21 healthy controls at baseline and n = 21 patients at 12-week follow-up.

Results

With basis in known literature on relevant markers in IBS, we have developed an antibody panel for use on formalin-fixed, paraffin-embedded (FFPE) duodenal tissue with Hyperion imaging mass cytometry. The panel includes 35 markers for comprehensive spatial analyses of the gut mucosa in IBS before and after diet intervention. It comprises several immune cell markers for a broad immunologic mapping, in addition to markers for gut integrity and neuro-immune communication. The panel was tested on duodenal FFPE tissue with Hyperion, and resulting images were segmented with the Steinbock framework. Downstream single-cell analysis was performed in R with the imcRtools R/Bioconductor and cytomapper packages. Different cell types, including CD4 and CD8 T cells, were identified in duodenal tissue by means of cell segmentation and unsupervised clustering.

Conclusion

Through multimodal integration of tissue analyses and clinical symptom scores before and after treatment, we aim to provide clinically meaningful intestinal biomarkers in order to improve treatment strategies for patients with IBS.

Introduction

Irritable bowel syndrome (IBS) is a common disorder of gut brain interaction (DGBI) characterized by abdominal pain associated with altered bowel habits – symptoms are often related to food intake. Confocal laser endomicroscopy (CLE) has shown acute food-triggered disruption of the epithelial barrier in the duodenum of IBS patients. While this technique promises new insights into the pathophysiology of IBS, image interpretation is subjective and interobserver agreement rates have not been assessed.

Aims & Methods

Aim: To assess the agreement rate between assessors regarding acute food induced mucosal changes visualized by CLE.
Methods: In Rome IV IBS (non-constipated) patients, allergic sensitization to nutrients was excluded by specific serum Immunoglobulin E tests. CLE was performed during upper GI endoscopy: duodenal mucosa was visualized before and after sequential application of 10mL dissolved aliquots of lyophilized fish, nuts, egg white, soy, milk and wheat. Two investigators (experience of ≥20 exams each) assessed separately recorded sequences for the presence or absence of acute mucosal alterations defined as fluorescence leakage and cell shedding visualized on ≥3 different mucosal spots. Assessors were blinded for patient characteristics, and for the timepoint of recordings (i.e. baseline or after food administration). Agreement rates are reported in percent and using Cohen’s Kappa computed with Rstudio.

Results

A total of 75 video sequences from 22 procedures in 13 patients were interpreted. Regarding presence or absence of mucosal alterations, assessors agreed in 81% (61/75) of assessed sequences resulting in a Cohen’s Kappa of 0.63.
Overall, 52% (32/61) of sequences with agreement were judged by both assessors to present leakiness and cell shedding whereas 48% (29/61) were considered normal.

Conclusion

When assessed in a blinded manner, mucosal leakiness is visualized on CLE recordings with a high agreement rate between assessors and substantial agreement when accounting for random chance agreement. Further increasing agreement rates by possibly modifying criteria might increase the validity of this technique.

Introduction

Early-onset gastric cancer (eoGC), defined as GC before 50, accounts for about 5% of GC and 3% are part of a hereditary syndrome. Its incidence is rising. eoGC was reported to present at an advanced stage at diagnosis, with a poor differentiation and a worse prognosis than in the elderly (late-onset GC, loGC), even though eoGC risk factors and characteristics remain unclear.

Aims & Methods

Therefore, we compared eoGCs with loGCs in terms of clinicopathological characteristics and risk factors. We conducted a retrospective case-case study of patients with eoGC and loGC diagnosed from 2015 to December 2022 at IRCCS San Raffaele Scientific Institute (Milan, Italy). We collected clinical data, tumor characteristics (including Helicobacter Pylori status, HP), family history of GC, smoking habit, alcohol intake, and BMI. We performed multi-gene panel testing on all eoGC.

Results

58 eoGC (51.7%M, 48.3%F; median age at diagnosis [IQR] 44.5y [39.00, 47.75]) and 290 loGCs (63.8%M, 36.2%F; median age at diagnosis [IQR] 70.33y [63.90, 75.00]) were enrolled. 19.2% eoGCs carried a germline pathogenic variant (4 CDH1; 2 TP53; 1 MMR; 1 ATM; 1 PTEN; 1 heterozygous MUTYH). Having a second-degree relative (SDR) with GC was significantly associated with eoGC (15.8% eoGCs vs. 4.6% loGCs, p = 0.015). eoGCs reported lower BMI (median 22 eoGC vs 24 loGC, p=0.016). We also found a statistically significant difference between groups in alcohol consumption (P = 0.042) and smoking status (P = 0.023). While eoGCs were mainly at the cardia (29.3% eoGCs vs. 1.7 % loGCs; p<0.001), loGCs were mostly at the antrum (19% eoGC vs. 36.9% oGCs; p=0.009). eoGCs reported more dysphagia (30.9% eoGCs, compared to 4.9% loGCs, p < 0.001), while most patients in the loGC cohort had anemia (25.3% loGCs vs 7.3% eoGCs, p = 0.002) and asthenia (9.1% loGCs vs 0% eoGCs, p = 0.012). 48.3% eoGCs were diffuse-type adenocarcinoma (p=0.014), while 51% loGCs were intestinal-type (p<0.001). No significant differences were observed in terms of T and N status, while more eoGC were M1 (26.3% eoGCs vs. 9.7% loGCs, p=0.001) and presented at stage III-IV (56.9% eoGCs vs. 41.7% loGCs, p=0.042) at diagnosis.

Conclusion

19.2% patients with eoGC carry a germline pathogenic variant, suggesting that patients with eoGC should be evaluated for germline testing at diagnosis. eoGC more often is localized at the cardia with dysphagia and presents as diffuse-type adenocarcinoma at an advanced stage (III-IV) ad diagnosis. However, 35.6% patients with eoGC presents with early gastric cancer T1 (vs 24.1% loGCs), possibly implying that younger age does not entail worse outcomes.

Introduction

Esophageal variceal bleeding (EVB) is a severe complication of liver cirrhosis. An effective prophylactic intervention and treatment option in EVB is endoscopic band ligation (EBL). An average post-banding bleeding (PBB) rate of approximately 3.5% within two weeks post-intervention has been reported¹. This study aims to assess the risk of bleeding after EBL of esophageal varices and to identify patient-specific and procedure-related risk factors for PBB.

Aims & Methods

For risk stratification, a retrospective analysis was conducted on 233 patients who underwent ligation therapy for esophageal varices at a tertiary care centre between January 2019 and February 2023. In total, 616 ligation therapies were analysed with regard to the occurrence of PBB within 21 days post-intervention. Data collected included laboratory parameters, type and severity of underlying liver disease, recent alcohol consumption, anticoagulant use, and procedural details such as the number of bands applied and intra-procedural bleeding. Data was analysed using R and SPSS statistical software.

Results

In our study, PBB occurred in 30 of 616 EBL procedure (4.9%). Importantly, for interventions to treat acute variceal bleedings, the PBB rate was 20.8% (16/77 cases), whereas ligature in patients without acute bleeding had a low PBB rate of only 2.6% (14/539 cases, p<0.001). Additionally, recent alcohol abuse within 28 days prior to the procedure was reported in 50% (15/30) of interventions with PBB, whereas alcohol abuse was observed in only 20.3% (119/586) of non-PBB cases (p < 0.001). Furthermore, impaired liver function assessed by Child-Pugh and MELD scores was associated with an increased risk of PBB (p < 0.001). Conversely, low platelet counts below 50 G/L or even below 30 G/L did not show a significant increase in the occurrence of PBB in our patient cohort, suggesting that EBL can be safely performed in patients with platelet counts < 50 G/L². Additionally, the use of acetyl salicylic acid (ASA) was not associated with a significantly higher incidence of PBB in this cohort.

Conclusion

While the overall risk of PBB following EBL is relatively low, we could identify several risk factors that increased the likelihood of esophageal variceal bleeding following EBL. Relevant risk factors were ligature for acute EVB, impaired liver function, and active alcohol abuse. In contrast, patients with low platelet counts (<50 G/L) or those taking ASA medication did not show an increased risk of PBB in our cohort. These findings allow for a more precise risk stratification for PBB and will be useful to assess which patients require extended in-hospital observation after EBL and who can be safely discharged shortly after the procedure.

References

1. Vanbiervliet G, Giudicelli-Bornard S, Piche T, et al. Predictive factors of bleeding related to post banding ulcer following endoscopic variceal ligation in cirrhotic patients: a case-control study. Aliment Pharmacol Ther. 2010;32(2):225-232
2. Katsumi, T. and Y. Ueno, Prospects for treatment of esophageal varices considering the safety of endoscopic band ligation. Hepatology International, 2023. 17(5): p. 1079-1081

Introduction

The severity of bleeding and the time-to-endoscopy are generally recognised as risk factors for mortality in patients with GI bleeding. However, how to grade the bleeding severity (BS) is not clearly defined and it is not clear its relationship with the time-to-endoscopy. We found that the bleeding severity correlates with 5 clinical items: altered mental status, systolic blood pressure ≤100 mmHg, blood ureic nitrogen ≥130 mg/dl, haemoglobin ≤8 gr/dl and clinical presentation with hematemesis.

Aims & Methods

The aim of the study is to evaluate if the interaction between bleeding severity and timing-to-endoscopy could impact on the death risk. A prospective multicentre cohort study, including all consecutive patients with upper gastrointestinal bleeding admitted to 50 Italian hospitals was conducted. Charlson's comorbidity index and ASA scores were used to define the patients’ performance status. According to the previously cited clinical items, we defined bleeding severity (BS) and graded it in low, intermediate, and high-risk classes depending on the presence and the number of items at the time of admission. Timing to endoscopy was defined according to ESGE* guidelines and was divided into 4 time-frames (<6h; 6/12h; 12/24h; >24h).

Results

2,525 patients were included (mean age 68 [±15.8], male 67.3%); the bleeding was non-variceal in 82.3%. Overall, 176 patients died (6.9%); 28 (1.9%) in the low BS group (1,463 patients), 28 (8.6%) in the intermediate BS group (606 pts) and 96 (21%) in the high BS group (p<0.000). In our population, the 4-time frames do not impact on the mortality in the low and intermediate classes of risk. In the high BS class, there is an interaction between the time to endoscopy and the mortality, with the lower mortality observed in the 6/12 hrs frame.

Conclusion

In our population, the death risk gradually rises as the bleeding severity increases. Bleeding severity identifies 3 different classes of death risk and the time to endoscopy seems unrelated to mortality in low and intermediate BS classes. In the high BS patients, the lower mortality was observed in the timing to endoscopy 6-12 hrs.

References

* Ian M. Gralnek et al. Endoscopy 2021; 53: 300–332

Disclosure

nothing to disclose