OBJECTIVES:The Ghent Stool Bank (GSB) was founded in 2018 at Ghent University Hospital to provide safe, ready-to-use fecal suspensions for fecal microbiota transplantation (FMT), primarily targeting recurrent Clostridioides difficile infection (rCDI) and supporting clinical trials. METHODS:This retrospective cohort study explores the relationship between donor characteristics and rCDI treatment outcomes following FMT. RESULTS:Between 2018 and 2024, 12.0% of screened candidates qualified as donors after rigorous evaluation, resulting in 159 approved donations. Forty-four FMT procedures were carried out in forty rCDI patients, achieving a primary cure rate of 77.1%, which increased to 85.7% following a second treatment. Donor microbiome diversity did not show association with treatment outcomes, and no statistically significant differences in taxa abundance were observed. Notably, fecal suspensions stored for up to five years were as effective as those stored for shorter periods. Additionally higher donor age did not appear to negatively impact treatment success in rCDI patients. CONCLUSION:These findings support the role of stool banks like the GSB in ensuring safe FMT procedures. Allowing higher donor age and longer storage periods may help sustain sufficient high‑quality donor availability. Future efforts should focus on improving safety, enhancing donor-recipient compatibility through microbiome profiling and increasing public awareness.
BACKGROUND & AIMS:Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS:An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia. RESULTS:The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION:This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD.
Background Dysregulation of the gut microbiome has been implicated in Parkinson ' s disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with earlystage PD. Methods The GUT-PARFECT trial, a single -centre randomised, double-blind, placebo -controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50 - 65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer -generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society -Uni fi ed Parkinson ' s Disease Rating Scale (MDSUPDRS) motor score obtained during off -medication evaluations. Intention -to -treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389). Findings Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score signi fi cantly improved by a mean of 5.8 points (95% CI - 11.4 to - 0.2) in the healthy donor group and by 2.7 points ( - 8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort. Interpretation Our fi ndings suggested a single FMT induced mild, but long-lasting bene fi cial effects on motor symptoms in patients with early -stage PD. These fi ndings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages. Funding Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.
In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy and disease esophageal tissue sample were included. In total, this comprehensive dataset consists of 102 sequenced libraries from 51 samples. Based on this data, 119 expression profiles are available for three biotypes, including miRNA (51), mRNA (51) and circRNA (17). This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations, fusion genes, and circular RNAs.
Background and Aims: The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control. Methods: In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13–16), problematic (9–12) or inadequate (0–8). QoL was dichotomized into “no problems” (EQ-5D level 1) or “problems” (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney U ) analyses and Spearman correlations were performed. Results: A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM ( p = 0.6) with similar proportions of sufficient (60 vs. 68%, p = 0.4), problematic (34 vs. 26%, p = 0.3) and inadequate HL (both 6%, p = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, p =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, p = 0.06). HL and QoL correlated in CD ( r = 0.6, p < 0.001) and DM patients ( r = 0.6, p < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, p = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], p = 0.04) compared to those without. Conclusions: Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.
Background: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10.64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0.3%) unaccounted for. Adjusted to population size, 0.257 per 100,000 population received FMT for CDI and 0-189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-8,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. (C) 2021 The Authors. Published by Elsevier Ltd.
Introduction Colonoscopy prevents colorectal cancer via the detection and resection of premalignant polyps. This effect may be attenuated by variations in polypectomy, with multiple techniques available and a wide range of experience amongst endoscopists. We assessed current practice against the best available contemporary evidence. Methods An online survey was distributed to members of the gastroenterological and surgical societies of seven countries during July 2017. Images of colorectal polyps were presented and respondents requested to provide the polypectomy technique they would employ in their daily practice. Responses were compared to the evidence-based techniques in the 2017 ESGE Colorectal Polypectomy Guideline. Results In total, 707 endoscopists (627 physicians, 71 surgeons, 9 nurse endoscopists, median practice duration 18 years) completed the survey. Of these, 3.1 % selected hot biopsy forceps and 5.2 % hot snare polypectomy (without submucosal lifting) to remove a 3 mm ascending colon polyp. Only 43.3 % selected cold snare polypectomy (CSP) to remove an 8 mm ascending colon polyp. Surgical referral was selected by 16.7 % of respondents for a 45 mm transverse colon polyp without endoscopic evidence of submucosal invasive cancer (SMIC). Endoscopic resection was selected by 12.0 % for an 80 mm sigmoid polyp with imaging consistent with deep SMIC, and a further 26.4 % selected tertiary endoscopist referral, suggesting they had not appreciated that it was endoscopically unresectable. Conclusion CSP is underutilized for small polyp resection despite its favorable safety and efficacy. Benign polyps are commonly referred for surgery and overt SMIC is underappreciated using endoscopic imaging. Addressing these issues may reduce diathermy-related adverse events, surgery, and unnecessary colonoscopic procedures for patients and reduce rates of post-colonoscopy colorectal cancer.
To the Editor: Considering the surgical excisional treatment of symptomatic prolapsing hemorrhoids, a recent network metaanalysis performed by Simillis et al1 showed benefits using the bipolar vessel–sealing instrument LigaSure (Valleylab, Boulder, CO) or the ultrasound Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH) in terms of reduction in complications and improved efficiency in comparison with the classical hemorrhoidectomy. However, no improved efficacy was noted. Thunderbeat (Olympus, Tokyo, Japan) is a novel instrument that combines bipolar energy, assuring reliable vessel sealing, and ultrasound energy, providing fast and precise cutting and dissection of tissue, thereby making sealing and cutting tissue possible in a single step. In a small pilot trial of 36 patients (mean age = 51.4 years), we investigated the feasibility, safety, and efficacy of this instrument for excisional hemorrhoidectomy. Outcomes were evaluated during 2 follow-up visits, respectively, at a mean of 34 days and 81 days after surgery, and by means of a questionnaire, of which the mean follow-up time was 20 months. Patients’ baseline status and follow-up outcomes are summarized in Table 1. Twenty-five (69%) patients had undergone prior day-case treatments and 5 (14%) an operation, of which 2 patients received a hemorrhoid artery ligation procedure, 2 a hemorrhoidectomy, and one a hemorrhoidopexy. Ten (27.8%) patients had anemia preoperatively. Median operating time of complete pedunculated, excisional hemorrhoidectomy was 20 minutes, and during 12 (33.3%) interventions, additional hemostasis was needed. No immediate postoperative urinary retention developed in any patient, nor did any single patient present with severe 14 days 908381 SRIXXX10.1177/1553350620908381Surgical InnovationHeyerick et al letter2020
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS: Patients with refractory IBS, defined as failure of >= 3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment.
Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular and anatomical compartments with that of plasma viruses sampled during analytical treatment interruption. We found a remarkably heterogeneous source of viral rebound. In addition, irrespective of the compartment or cell subset, genetically identical viral expansions played a significant role in viral rebound. Our study suggests that although there does not seem to be a primary source for rebound HIV, cellular proliferation is an important driver of HIV persistence and should therefore be considered in future curative strategies.
was a randomized, double-blind, placebo-controlled phase 2a study.Patients were randomized in a 2:1 ratio to receive 8 mg/kg of AMG 714 or matching placebo (7 intravenous doses over 10 weeks).Upper endoscopy and biopsy were performed before and after treatment (Week 12).Results: A total of 28 patients were included, with 19 patients meeting the ad-hoc criteria for "Pure" RCD-II/Pre-EATL (T cell receptor monoclonality).While the primary endpoint of reduction in intestinal aberrant IEL was not statistically significant, AMG 714 was associated with an interruption in the progression of the disease and with benefit across a range of endpoints.In the Per Protocol (PP) population there was a numeric reduction in the percentage of small-bowel aberrant IELs with AMG 714 (2.45% increase from baseline) as compared to placebo (7.3% increase).This reduction was also seen in the Pure RCD-II population, with a 14% increase on placebo and no increase on AMG 714.There was a benefit in villous atrophy, with 27% improvement in the Pure RCD-II population vs no improvement in placebo, and 26.4% vs 15.7% in AMG 714 vs placebo in the PP population.Clear benefit was observed at the molecular and symptom level.While no patient increased TcR clonality on AMG 714, 33% and 50% of placebo patients in PP and Pure RCD-II populations did, respectively (p=0.03 and 0.02 respectively; all p values nominal, as multiplicity was not adjusted in this exploratory study).The symptom reduction was seen in the Bristol Stool Form Scale, where the placebo arm experienced an increase in weeks with diarrhea, while the AMG 714 arm experienced a decrease (p<0.01 in the PP and Pure RCD-II populations).The safety profile was acceptable for this very sick population, with 6 serious adverse events (5 on AMG 714 and 1 on placebo).Mild nasopharyngitis was the most common adverse reaction in the AMG 714 arm.There was no immunogenicity nor NK cell decrease.Conclusion: AMG 714 demonstrated proof-of-mechanism and proofof-concept for halting the progression of RCD-II/Pre-EATL, with an acceptable safety profile.
Multiple evidence-based guidelines have been produced recently to address the question of how best to perform colonoscopic polypectomy. We aimed to assess the adherence to these guidelines in 7 countries using an online survey, comparing responses to the standards presented in the 2017 ESGE Colorectal polypectomy guideline1.
Background: Ambulatory surgery for anorectal procedures has become widely accepted. Recent reviews recommend a multimodal approach to pain management. However, these recommendations are largely based on single intervention studies. Our goal was to evaluate post-operative pain in patients receiving a multimodal analgesic regimen. Methods: All patients undergoing an ambulatory anorectal procedure between December 2015 and September 2016 received a pain diary. Mean pain throughout the day and pain during defecation where recorded on day 0-14 and day 21 postoperatively using a numeric rating scale-11. Use of oral analgesics was also recorded. Results: Forty-two patients completed the pain diary. The use of local anesthetic infiltration did not result in a significant difference in pain scores in this study. Patients who received written information on postoperative pain management and hygienic measures had higher intake of oral analgesics. Despite receiving multimodal analgesic treatment, patients undergoing surgery for hemorrhoids or anal fissures reported pain scores ≥4 and used analgesics longer. Conclusion: A multimodal analgesic approach consisting of local anesthetic infiltration, multiple oral analgesics and written information seems to be insufficient for certain patient groups after ambulatory anorectal surgery. Especially patients undergoing surgery for hemorrhoids or an anal fissure should receive adequate analgesia. Pain during defecation is problematic and finding a solution for this problem remains challenging. Further research into the combined use of different analgesic modalities is recommended.
BACKGROUND:Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS:Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS:684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS:Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.
Gastrointestinal bleeding originating from the small bowel (SB) poses a challenge to the treating gastroenterologist. Once diagnosed, management is not a walk in the park either. This review intends to summarize the current state-of-the-art evidence in a complete way with special attention for vascular and ulcerative lesions, to provide the reader with a clinical guide and flow chart towards SB bleeding.
Cystic fibrosis (CF) is a life-limiting disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). This defective chloride channel, present in different organ systems such as respiratory system, gastrointestinal tract, reproductive system and sweat glands, disturbs the ion and water transport over the membranes leading to the well known CF symptoms. CF has outgrown paediatric care, as half of CF patients are currently adults. The CF gastrointestinal tract has its own particularities. Some gastrointestinal manifestations are the direct consequence of the CFTR defect whilst others are secondary to treatment. The gastrointestinal diseases are classified according to the way they usually present in symptoms at diagnosis, acute and chronic abdominal pain and silently evolving conditions. (Acta gastroenterol. belg., 2016, 79, 481-486).
We read with interest the work by Halmos et al 1 in which they describe the effects of dietary FODMAP (Fermentable Oligo-, Di- and Mono- saccharides And Polyols) restriction in patients with IBS on the intestinal microbiota. They showed that low FODMAP intake was associated with reduced total bacterial and lower relative abundance of butyrate-producing Clostridium cluster XIVa, changes that are generally considered unfavourable.2 Therefore, they discourage long-term dietary FODMAP restriction, a suggestion also supported by the recent work of McIntosh and colleagues who noticed unfavourable changes in both microbiota and metabolome of patients with IBS who were on a low FODMAP diet.3 Although low FODMAP intake reduces GI symptoms in almost 75% of patients with IBS, the effects of this diet on the intestinal microbiota might be disadvantageous in the long run. Combining these observations with the important role for the intestinal microbiota in IBS pathogenesis,4 we report here faecal microbiota transplantation (FMT) as an alternative to FODMAP restriction in patients with IBS. We applied FMT in 12 refractory IBS patients (Rome III criteria) with intermittent diarrhoea and severe bloating, …