Introduction

Balanced propofol sedation administered by adequately trained non-anesthesiologist personnel has gained popularity in GI endoscopy because of its shorter procedure and recovery time, high patient satisfaction, and low rate of adverse events (AEs), even if it's still considered controversial. We reported data from a retrospective audit of Endoscopist directed nurse administered sedation (ED-NAAS) over a 2-year period in an Italian referral hospital.

Aims & Methods

Consecutive endoscopic procedures performed between October 2020 and October 2022 were considered. Under the guidance of the endoscopist, the nurse administered 1 to 2mg of midazolam, followed by a progressive top-up dosages of 10-20mg bolus of propofol to achieve moderate to deep sedation. Fentanyl was administred based on the patient's weight if indicated. Endoscopists and nurses were all certified in our hospital with a continuous and scheduled training from 2006. The patients' characteristics, dosage of administered drugs, AEs during and after the examination, were all investigated. The following AEs were deemed minor but significant: bradycardia (≤50 beats/min ≥10 seconds), hypoxia (SaO2 ≤ 90% ≥10 seconds) and hypotension (systolic BP ≤100 mmHg with a drop ≥ 20 mmHg). Major consequences included death, a persistently low state of awareness, permanent harm, the need for an emergency anaesthetist evaluation, the need for hospitalization or endotracheal intubation. To increase the sensitivity of AEs detection, reports were reviewed in these cases: (1)AEs declared in the report, (2)search by string "desaturation" "hypotension" "bradycardia" "apnoea” “hypoxia" in the report, (3)oxygen saturation level, systolic BP and heart rate ≤50 bpm annotated during the intra-procedural monitoring compared to parameters measured before sedation, (4)patients administered flumazenil, naloxone, etilephrine, atropine.

Results

A total of 19407 examinations (7803 EGDS, 10439 colonoscopies, 77 PEG, 697 EUS and 365 ERCP) and 14415 patients were enrolled. 29.4% of patients were classified as ASA I, 66.5% as ASA II and 5.1% as ASA III. Balanced sedation with propofol was administered in 86% of EGDS, 94% of colonoscopies, 92% of EUS, 94% of ERCP and in 72% of PEG. Hypotension was recorded in 1293 (6%) examination, which required fluid infusion in 330 cases (26%) and in 8 cases etilephrine to restore blood pressure. Bradycardia was recorded in 176 (0.9%) patients, which required atropine in 134 (72.8%) cases. 11 patients (0.06 %) had a minor respiratory adverse event. The mean age of patients of hypotension, bradycardia and respiratory adverse event was respectively 61.1±15 years, 64.3±15.3 and 55.6±16.2. ASA III patients were respectively 4.1%, 2.8% and 27.2% in the three groups of AEs. The mean SD/median (25^th-75^th percentil) dosage of medications were respectively 2.0±0.7mg, 2.0±0.7mg, 1.8±0.3mg of midazolam, 71.0±34.5mcg, 68.0±31.0mcg and 62.5±9.5mcg of fentanyl, 94.0±74.3mg, 77.0±61.7mg and 120 (70-190)mg of propofol. BMI and Mallampati score of II were respectively 23.0±4.5 and 72.8% in patients with respiratory AEs. 1 patient (0.001%) had a major AE, needing oro-tracheal intubation. He was 63 years old with unknown diagnosis of amyotrophic lateral sclerosis, with normal BMI, Mallampati score I, sedated with 2mg of midazolam + 80mg of propofol. Limits of the study include recall bias (missed cases of AEs not caused by sedation but because of examination itself, e.g., bradycardia or laryngospasm).

Conclusion

Balanced propofol ED-NAAS is safe in low-risk patients. Major adverse events occurred in 0.001% procedures.

Introduction

The PROFILE trial in patients with newly-diagnosed Crohn’s disease demonstrated that “top-down” therapy, with combination infliximab and immunomodulator from diagnosis, provided superior efficacy and a better safety profile over a one-year follow-up period compared to a conventional “accelerated step-up” management approach.

Aims & Methods

The current study aimed to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication (intravenous infliximab, subcutaneous infliximab, subcutaneous adalimumab) as soon as possible after diagnosis. A de novo Markov model was developed to model the cost-effectiveness of using a “top-down” compared to “accelerated step-up” strategy in adults newly-diagnosed with active Crohn’s disease (HBI score >7, elevated CRP and/or faecal calprotectin >200ug/g and endoscopic evidence of disease activity with simple endoscopic score of Crohn’s disease activity of >6 [>4 if ileal-only disease]). Parameters were informed by individual patient data from PROFILE and data from the published literature. Use of intravenous infliximab, or subcutaneous infliximab, or subcutaneous adalimumab from diagnosis were modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 18 PROFILE trial sites in 2024. Key model outcomes included healthcare costs (drug acquisition, drug administration, disease management, hospitalisation, surgery) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results

The base case cost-effectiveness analysis indicated that a “top-down” strategy dominated over an “accelerated step-up” approach. Initiating intravenous infliximab from diagnosis yielded greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and was less costly, saving £1,681 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of SC infliximab and adalimumab. The greatest cost savings were with adalimumab, totalling £10,059 per patient over 5 years. Sensitivity analyses further supported the robustness of the results for “top-down” therapy, showing it to be the most cost-effective option in 98.7% of model simulations.

Conclusion

This health economic analysis demonstrates that early effective “top-down” treatment with anti-TNF therapy from diagnosis results in lower healthcare resource use compared to an “accelerated step-up” strategy. The economic benefits align with improved clinical outcomes, as early, effective treatment better controls inflammation. Patients experience longer periods in remission, fewer disease-related flares, and enhanced quality of life. These findings were demonstrated for intravenous infliximab, subcutaneous infliximab and subcutaneous adalimumab. In newly-diagnosed patients with active Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-effective than “accelerated step-up” based treatment strategies.

References

Noor NM, Lee JC, Bond S et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427.

Disclosure

NMN declares educational/travel grants and/or speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda and Tillotts Pharma AG.

Introduction

Duodenal stump fistula (DSF) represents a significant complication that can arise following gastrectomy, with a prevalence ranging from 1.0% to 2.5%. This condition is characterised by a high mortality risk (12.5% to 28%) and a high morbidity rate (75%). In instances where conservative management has proven ineffective, percutaneous transhepatic biliary drainage (PTBD) emerges as a valuable intervention. This procedure involves the aspiration of bile, thereby reducing duodenal pressure and diminishing fistula output. However, it is important to note that PTBD does necessitate a prolonged healing period and frequently requires subsequent treatments, such as percutaneous or endoscopic injection of glue. The prolonged hospitalization is also to be considered in these patients, in which the resolution of the fistula generally requires a period of between 60 and 240 days.
The objective of this study was to ascertain the viability and effectiveness of a pioneering technique involving percutaneous DFS embolization with ethylene vinyl alcohol copolymer (EVOH) in combination with an occlusion balloon, utilised in the management of DSF following gastrectomy for malignant or benign indications.

Aims & Methods

The present study encompassed patients with a diagnosis of DSF, as determined by the presence of duodenal juice in the surgical drainage or its leakage through the abdominal wall. This diagnosis was confirmed through surgical approach and/or a computerised tomography (CT) scan. A retrospective analysis was conducted on 15 consecutive patients who underwent PTB-A embolization with Ethylene-Vinyl Alcohol Copolymer (EVOH) as a treatment for DSF, following the failure of medical, surgical, or endoscopic interventions.
An analysis was conducted of clinical and technical success, morbidity and mortality.

Results

The population under scrutiny comprised 10 female and 5 male subjects. Furthermore, it is noteworthy that 74% of patients underwent surgery for a malignant lesion. In the present study, a total of 13 patients underwent subtotal gastrectomy. In all cases, technical success was achieved. A positive outcome was achieved in 11 out of 15 patients following a single treatment. In 4 cases, patients required further treatment to achieve complete fistula healing. In the course of treatment, it was observed that a single patient required four treatment sessions to achieve complete healing. No procedure-related complications or mortalities were recorded. No recurrence of the fistula was observed in the population under study. Radiological follow-up was conducted at one or three months following the procedure for a total of 11 patients. 2 patients expired prior to the scheduled follow-up due to unrelated causes, while 2 patients failed to attend the control appointment.

Conclusion

PTB-A embolization with EVOH of duodenal stump fistula seems to be an effective treatment for DSF, with prompt recovery, no mortality and short hospitalization after the procedure.

References

1. Orsenigo E,et al. Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience. Gastric Cancer. 2014 Oct;17(4):733-44. doi: 10.1007/s10120-013-0327-x.

2. Paik HJ, et al. Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management. Ann Surg Treat Res. 2016 Mar;90(3):157-63. doi: 10.4174/astr.2016.90.3.157.

3. Gu L, et al. Risk Factors for Duodenal Stump Leakage after Laparoscopic Gastrectomy for Gastric Cancer. J Gastric Cancer. 2020 Mar;20(1):81-94. doi: 10.5230/jgc.2020.20.e4.

4. Naito R, et al. Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report. Surg Case Rep. 2024 Feb 18;10(1):44. doi: 10.1186/s40792-024-01842-9.

5. Aurello P, et al. Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review. World J Gastroenterol. 2015 Jun 28;21(24):7571-6. doi: 10.3748/wjg.v21.i24.7571.

6. Zizzo M, et al. Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature. BMC Surg. 2019 May 28;19(1):55. doi: 10.1186/s12893-019-0520-x.

7. Cozzaglio L, et al. Percutaneous transhepatic biliary drainage and occlusion balloon in the management of duodenal stump fistula. J Gastrointest Surg. 2011 Nov;15(11):1977-81. doi: 10.1007/s11605-011-1668-6.

Introduction

H. pylori eradication therapy induces significant alterations in the gut microbiome. While probiotics have been extensively studied as a potential strategy to mitigate microbiota-related consequences of antibiotics, their efficacy remains a subject of debate.

Aims & Methods

The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (including gut microbiota taxonomic composition, functional potential, and gut resistome) induced by H.pylori eradication therapy. A total of 22 H. pylori-positive patients aged 19 to 64 years were enrolled in the study. Patients were randomized into two H. pylori eradication regimens: 1) ECAB-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, orally, for 14 days. 2) ECAB-Z-14: esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk) supplementation (two tablets daily, each containing 250 mg of butyric acid and 250 mg of inulin), orally, for 14 days. Stool samples were collected from each subject at three time points: prior to eradication therapy (I), after therapy completion (II), and one month post-therapy (III). Total DNA from fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform.

Results

Gut Microbiota Alpha Diversity (Shannon Index): Immediately after eradication therapy, both the ECAB-14 and ECAB-Z-14 groups experienced a significant decrease in gut microbiota alpha diversity compared to the initial level: (2.46 ± 1.06) vs. (3.75 ± 0.342), p = 0.0029, and (3.22 ± 0.73) vs. (3.82 ± 0.30), p = 0.037, respectively. After one month, the Shannon index was restored to the baseline level in the ECAB-Z-14 treatment group: no statistically significant differences were identified between time points III and I [(3.71 ± 0.33) vs. (3.82 ± 0.30), p = 0.206]. However, even a month after therapy, the ECAB-14 treatment group still exhibited a lower Shannon index than the baseline level [(3.27 ± 0.39) vs. (3.75 ± 0.342), p = 0.019].
Functional Potential Alterations: In the ECAB-Z-14 treatment group, less pronounced alterations in gut microbiota functional potential were observed. Specifically, 72 metabolic pathways changed immediately after eradication therapy. In contrast, the ECAB-14 group showed impact on 112 signaling pathways.
Butyrate Production Genes: The abundance of genes associated with butyrate production decreased only in the ECAB-14 treatment group. However, in the ECAB-Z-14 treatment group, the abundance of genes responsible for butyrate production remained stable.
Antibiotic Resistance Genes: The prevalence of gut microbiota antibiotic resistance genes increased significantly in both treatment groups immediately after eradication. Notably, more severe alterations were observed in the ECAB-14 treatment group, where the abundance of 73 antibiotic resistance genes significantly increased. Meanwhile, the ECAB-Z-14 group showed an increase in only 50 antibiotic resistance genes immediately after eradication therapy.

Conclusion

H. pylori eradication therapy significantly affects gut microbiota composition, functional potential, and increases the abundance of antibiotic resistance genes. However, the addition of butyric acid+inulin supplements to the H. pylori eradication regime may mitigate these effects.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/

Introduction

The pathophysiology of irritable bowel syndrome (IBS) includes alterations in gut-brain communication, gastrointestinal (GI) physiology and gut microbiota. The essential amino acid tryptophan (Trp) is metabolized in the gut to different classes of metabolites, including serotonin, kynurenine and indoles which have been implicated in the modulation of intestinal motility, immune function and pain sensation. Balanced Trp metabolism requires a complex host-microbiota interplay, which might be dysregulated in IBS. However, Trp metabolism is incompletely understood, and studies are needed to clarify its link with IBS and gastrointestinal physiology.

Aims & Methods

Aim: To profile fecal and circulating levels of Trp metabolites in IBS and explore relationships with oro-anal transit time (OATT) and symptoms.
Methods: We combined targeted and untargeted metabolomics to determine fecal and serum Trp metabolites in a cohort of healthy controls (HC; n=29) and IBS patients with predominant constipation (IBS-C; n=59), diarrhea (IBS-D; n=53) or mixed bowel habits (IBS-M; n=55). OATT was measured using radiopaque markers and participants completed questionnaires to assess GI symptom severity (GSRS-IBS), stool frequency and consistency (Bristol Stool Form Scale), non-GI somatic symptoms (PHQ-12), and symptoms of anxiety and depression (HAD). For correlation analyses, Spearman’s rho (r) was used.

Results

Levels of Trp did not differ significantly between HC and IBS subtypes. The Trp metabolite kynurenine, the microbially produced indole propionic acid (IPA) and the serotonin degradation metabolite 5-hydroxyindoleacetic acid (5-HIAA) were lower in IBS-C compared to HC and IBS-D. There were inverse correlations between OATT and both fecal (p<0.0001; r= -0.40) and circulating (p= 0.021; r= -0.17) Trp levels. Similarly, stool kynurenine and indoles were negatively correlated with OATT. Fecal but not circulating serotonin was positively correlated with OATT (p= 0.041; r= 0.14) while 5-HIAA showed a negative correlation (p<0.0001; r= -0.29), suggesting potential serotonin accumulation due to deficient degradation. In IBS patients, fecal Trp, 5-HIAA, IPA and kynurenine, correlated negatively with the proportion of hard stools (BSF1-2) and positively with the proportion of loose stools (BSF6-7). Finally, serotonin catabolites and IPA were negatively correlated with the severity of constipation and positively correlated with diarrhea. No statistically significant correlations were noted between these metabolites and abdominal pain, abdominal distension, early satiety, or postprandial fullness while bloating was positively correlated with circulating IPA (p= 0.018; r= 0.18). Additionally, we report a negative correlation between circulating serotonin with symptoms of depression and anxiety, which was not found for fecal serotonin. No significant correlations were noted with non-GI somatic symptoms.

Conclusion

Our results suggest that slower transit time may favour increased intestinal catabolism of Trp, directly or indirectly through its effects on the gut environment and the microbiota. In addition, we report an association of fecal Trp metabolites with bowel habits, in line with their relations to OATT. On the other hand, these same fecal metabolites did not correlate with other GI (i.e., pain and bloating) or non- GI symptoms. This study underscores the link between intestinal transit time and the regulation of host and microbial metabolites important for intestinal homeostasis.

Introduction

The subcutaneous (SC) formulation of infliximab offers a patient-centered alternative to the intravenous (IV) route, with the potential to improve treatment adherence, quality of life, and reduce the burden of care in patients with inflammatory bowel disease.

Aims & Methods

Aim of our study was to evaluate the clinical impact, safety, and patients’ outcomes associated with the switch from IV to SC infliximab in routine care. This was a single-center observational study incorporating both prospective and retrospective data collection. Patients with confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) who received at least two infusions of IV infliximab and subsequently transitioned to SC infliximab 120 mg every other week were eligible for inclusion. The primary endpoint was the impact of switching from IV to SC infliximab on patients' quality of life and work productivity measured through the SF-36 and WPAI-GH questionnaires administered at baseline and at week 52. Secondary endpoints included safety profile and clinical effectiveness, defined as clinical remission or improvement at weeks 8, 24 and 52 following the switch to SC infliximab.

Results

A total of 109 adult patients (72 UC (66,1%), 64 male (58.7%)) were enrolled. Median age was 41.6 ± 12.2 years. The switch from IV to SC infliximab was associated with an improvement in work productivity in both UC and CD at week 52 in terms of absenteeism (p = 0.04; η² = 0.18; 95% CI: 0.03–1.00 in CD and p < 0.001; η² = 0.25 in UC) and productivity loss (p < 0.001; η² = 0.47; 95% CI: 0.34–1.00 in CD and p < 0.001; η² = 0.30 in UC) . No significant differences were found in activity impairment, presenteeism, or across SF-36 domains in either CD or UC cohorts (all p > 0.05). Transitioning from IV to SC infliximab did not affect patients’ perceived quality of life as assessed by physical, mental, or social functioning scores. At week 52, 51 out of 55 (93%) patients with UC and 20 out of 27 (74%) patients with CD were in clinical remission. Switching from IV to SC infliximab was significantly associated with achievement of clinical remission over time in UC (χ² = 8.83, p = 0.03 with Cramér’s V = 0.16). In patients with CD, switching from IV to SC infliximab did not show a statistically significant association with the achievement or maintenance of clinical remission at months 12 (χ² = 1.02, p = 0.80 with Cramér’s V = 0.00; 95% CI: 0.00–0.13). The switch was well tolerated with no new safety issues. In total, 6 patients experienced mild adverse events (erythema in the injection site in 3 patients, urinary tract infection in 1 patient, allergic reaction in 1 patient, and skin rash in 1 patient), leading to treatment discontinuation in 3 cases. No patient suffered from severe adverse events.

Conclusion

Switching from IV to SC infliximab is associated with significant improvements in work productivity at week 52 in both UC and CD. No new safety issues were found. These findings support the SC formulation of infliximab as a safe and effective option in the management of inflammatory bowel disease.

Disclosure

G Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. LPeyrin‐Biroulet declares personal fees from Galapagos, AbbVie,Janssen,Genentech,Ferring,Tillots,Celltrion,Takeda,Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS,Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, PandionTherapeutics,GossamerBio,Viatris, ThermoFisher.Grants fromAbbvie,MSD, Takeda, FreseniusKabi. Stockoptions:CTMA. S Danese has served as a speaker, consultant and advisory board member for Schering‐Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, MilleniumTakeda, Nycomed, Pharma cosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, NovoNordisk, Cosmo Pharmaceuticals, Vifor and Johnson&Johnson, NikkisoEuropeGMBH, Theravance