Introduction

Gut-liver axis has been implicated in the pathophysiology of cirrhosis due to metabolic dysfunction-associated steatotic liver disease (MASLD), however an in vitro model for studying epithelial gut dysfunction in MASLD is lacking.

Aims & Methods

In this study we aimed to characterize intestinal organoids derived from subjects with MASLD. Intestinal organoids were obtained from duodenal samples of individuals with non-fibrotic MASLD and with MASLD-cirrhosis. After 7-10 days of culture, RNA extraction, transcriptomic analysis and Real-time PCR were performed. Energetic and redox status of organoids were assessed by chromatographic analysis.

Results

Microarray analysis showed approximately 600 dysregulated transcripts in organoids isolated from patients with MASLD-cirrhosis compared to non-fibrotic MASLD. Bioinformatic analysis indicated that dysregulated transcripts were involved in pathways related to regeneration and pluripotency of stem cells and regulating mitochondrial metabolism and hypoxia. Overall, chromatographic analysis demonstrated that energetic status was remarkably impaired in both differentiated and undifferentiated organoids from cirrhotic patients compared to steatotic subjects. In either undifferentiated or differentiated organoids from cirrhotic subjects, the triphosphate sum, the ATP/ADP and NAD+/NADH ratios were lower in MASLD-cirrhosis, indicating a decline in the phosphorylating capacity and a mitochondrial derangement of duodenal cells. In addition, we found lower levels of reduced glutathione, NADPH and UDP-glucuronic acid in undifferentiated and differentiated cells from cirrhotics indicating impairment of antioxidant defense and of response to xenobiotics.

Conclusion

Our study provides a comprehensive view of intestinal epithelial dysfunction in MASLD-cirrhosis, characterized by a cluster of regenerative and metabolic disturbances.

Introduction

Burnout is an increasingly recognised occupational hazard that negatively affects clinicians' well-being, patient safety and the sustainability of healthcare systems. It is characterised by emotional exhaustion, depersonalisation, and a sense of low personal accomplishment. In this systematic review and meta-analysis, we aimed to estimate the global prevalence of burnout in gastroenterology, hepatology and endoscopy.

Aims & Methods

We searched MEDLINE, Embase, Scopus and PsycINFO, from their inception to November 2024, for studies reporting the prevalence of burnout among gastroenterologists, hepatologists and endoscopists. The primary outcome was the pooled prevalence of burnout. The secondary outcomes included the prevalence of emotional exhaustion, depersonalisation, the sense of low personal accomplishment, and gender-related differences in burnout.

Results

A total of 22 studies comprising 8,124 participants were included. The pooled prevalence of burnout was 45% (95% CI, 37% - 54%), with significant variability observed across different geographical regions, assessment tools and definitions of burnout. The pooled prevalence of emotional exhaustion was 31% (95% CI, 22% - 40%), depersonalisation was 23% (95% CI, 16% - 31%), and low sense of personal accomplishment was 25% (95% CI, 10% - 40%). Female gastroenterologists were more likely to experience burnout than males (OR 1.53; 95% CI, 1.16 – 2.01; p<0.001).

Conclusion

Almost half of gastroenterologists and endoscopists experience burnout, with females being disproportionately affected. These findings highlight the need for urgent actions to address burnout and its contributing factors, including gender disparities.

Introduction

It is a common practice to have nasogastric or nasojejunal tubes(NG or NJ) decompression after gastrectomy. It is believed that it can help to rest the bowel, prevent abdominal distension, decrease nausea and vomiting, and possibly protect the anastomosis. However, evidence from many "Enhanced Recovery After Surgery" programs shows NG and NJ tubes are associated with discomfort, decreased coughing effect and impaired mobilization. Patients without these tubes may have less throat discomfort and less pulmonary complications.

Aims & Methods

The aim of our study is to investigate the need of the use of NG and NJ tubes after gastrectomy for cancer in a randomized controlled trial setting. If the non-necessity can be proved, the practice can be applied to "Enhanced Recovery After Surgery" programs. The patients may have less discomfort and earlier discharge without compromise in complication and mortality.
This is an open labelled randomized controlled trial conducted in Department of Surgery, Tuen Mun Hospital, Hong Kong. It is approved by the ethics and research committee. Inclusion criteria include patients undergoing elective operations for gastric cancer, patents with age>18, and patients mentally fit. Exclusion criteria include gastric outlet obstruction, intestinal obstruction, unresectability, ASA>2. Randomization is made at pre-anaesthetic clinic by generation of random number. In Group A, NG or NJ tubes are inserted in operation room and removed at the end of operation. In Group B, NG or NJ tubes are inserted in operation room and kept at the end of operation. Primary end points include pulmonary and overall complications rate, degree of throat discomfort(0 to 4), length of hospital stay. Secondary endpoints include anastomotic leakage rate, reoperation and mortality. Sample size is calculated assuming a difference of 5% in pulmonary complication rate, alpha=0.5, beta=0.8, thus requiring 70 patients in each arm. Analysis is based on intention-to-treat basis. Chi-square or Fisher exact tests are used to compare categorical variables. Student t-test or Mann-Whitney test are used to compare continuous variables. P values are 2-sided and values less than 0.05 will be considered significant.

Results

From 2013 to 2021, 160 patients were recruited. 80 patients were randomized to group A and 80 to group B. The overall crossover rate was 13.1%. In group A, the mean age was 64.1. In group B, the mean age was 64. Concerning throat discomfort score on postoperative day 1, the mean score for group A and group B were 0.45 and 1.01 respectively(p<0.005). The mean score on day 3 were 0.31 and 0.40. The mean score on day 7 were 0.03 and 0.23(P>0.05).The pulmonary complication rate for group A and Group B was 17.5% and 21.3%(no significant difference). The non-pulmonary complication rate for group A and B was 20% and 21.3%(no significant difference). The mean time for patients to pass flatus for group A and B was 3.5 and 3.9(no significant difference). The mean length of stay for group A and B was 15.11 and 15.7(no significant difference). There was no hospital mortality.

Conclusion

This randomized controlled trial showed similar postoperative recovery for patients with and without NG or NJ tubes after gastrectomy for cancer. The was a trend for less throat discomfort, postoperative complications, time to pass flatus and shorter length of stay for the group without tubes. However, it only reached statistical significance in early postoperative throat discomfort score.
Performing gastrectomy for cancer without NG and NJ tubes is safe. It also causes less throat discomfort for the patients. It should be part of the "Enhanced Recovery After Surgery" program.

References

1. The future of fast-track surgery--British Journal of Surgery 2012;99: 1025-1026
2. Efficacy and necessity of nasojejunal tubes after gastrectomy--Intenrational Journal of Surgery 2011;9: 233-236
3. Nasojejunal tube placement after total gastrectomy: a multicenter prospective randomized trial--Arch Surg 2004;139(12): 1309-13
4. Enhanced Recovery after Surgery for gastric cancer patients improves clinical outcomes at a US Cancer Centre--J Gastric Cancer 2018;18(3): 230-241
5. Omitting nasogastric tube placement after gastrectomy does not enhance postoperative recovery:a propensity score matched analysis--Langenbeck's Archives of Surgery 2022;407:113-122
6.The application of enhanced recovery after surgery in total gastrectomy: a propensity score-matched analysis--World Journal of Surgical Oncology 2023;21:148

Disclosure

Nothing to declare.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, an influx of eosinophils and esophageal remodeling. Therapy for EoE includes proton-pump inhibitors, swallowed topical corticosteroids, dupilumab, and dietary elimination, but these are not always effective and have potential side effects.
EP-104GI is a long-acting fluticasone propionate (FP) injectable suspension being developed as a first-in-class treatment for EoE. EP-104GI consists of coated FP crystals that release at a pre-defined rate via diffusion at the injection site. Steady-state diffusion reduces peak concentrations while prolonging the therapeutic window.
RESOLVE (NCT05608681) is a Phase 1b/2a, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, feasibility, pharmacokinetics, and efficacy of EP-104GI in adults with symptomatic and histologically confirmed active eosinophilic esophagitis.

Aims & Methods

In this study, EP-104GI is injected at multiple sites in alternating quadrants at 2 cm intervals in the esophagus. Dose escalations increase the dose per injection site and/or number of sites, with the 6th cohort receiving 4 mg at 16 sites (64 mg total dose). After a single administration of EP-104GI, participants are followed for 24 weeks (cohorts 1-4) or 52 weeks (cohorts 5+). Safety assessments include adverse events and laboratory tests. Efficacy assessments include histological endpoints and patient-reported symptom outcomes, including the Straumann Dysphagia Index (SDI) and EoE Histologic Scoring System (EoEHSS). Esophageal biopsies are collected at baseline, Weeks 4, 12, and 36.

Results

Previously reported data from cohorts 3-5 (total doses 20-48 mg) showed symptom (SDI) reductions at Week 12 for 8/9 patients, the majority maintained to Week 24. Mean peak eosinophil count declined for 7/9 participants at Week 12, including one patient who achieved <6 eosinophils/hpf at all sites assessed, representing complete histological remission.
In Cohort 6, all three participants experienced a significant reduction in peak eosinophil count compared to baseline, ranging from 59 to 91% by Week 12. Symptoms (SDI) decreased for all 3 participants to Week 12, with a peak reduction of up to 6 points (0-9 scale). Histology scores have shown a progressively greater decrease from baseline with increasing EP-104GI dose. In Cohort 6 at Week 12, mean EoEHSS stage reduction was 66% or 0.40 points (composite score of 0-1) and mean EoEHSS grade reduction was 65% or 0.38 points (Table 1).
Plasma FP levels increased with dose and in Cohort 6 were stable at <25 pg/mL after the initial peak. Treatment-emergent adverse events were mild to moderate, most unlikely related to EP-104GI. Serum glucose and cortisol were stable post-dose with no adverse events such as candidiasis or adrenal suppression.

Table 1: Change from Baseline in EoEHSS, SDI, PEC, and mean plasma FP after a single dose of EP-104GI

Conclusion

These data support that local delivery of FP via EP-104GI has been feasible and safe in the ongoing study. Higher doses yield improved patient responses such as histological remission, enhanced patient-reported symptom scores, and favorable histology results, without the occurrence of corticosteroids-related side effects.

Disclosure

AM, JH, MMK, CD, VP: Employees of Eupraxia Pharmaceuticals. HHK, GH: Nothing to declare. WA: Speaker, advisory board member, and a clinical investigator for Abbvie, Amgen, Avir Pharma, Eli-Lilly, Eupraxia, Janssen, JAMP Pharma, Merck, Pfizer, Roche, Sandoz, Sanofi, Takeda. GH: TBD. ESD: Research funding: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Sanfoi, Shire/Takeda, Uniquity; Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apogee, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Third Harmonic Bio, Upstream Bio Educational grant: Allakos, Aqilion, Holoclara, Invea. AJB: Research funding: Nutricia, Thelial, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Reckitt and AstraZeneca.