Introduction

Some patients with inflammatory bowel disease require subtotal colectomy with ileostomy electively or in emergency as the first step of surgical treatment. Secondary proctectomy with ileal pouch anal anastomosis or ileorectal anastomosis can be considered for bowel continuity restoration. However, recent literature reports a significant number of patients who do not undergo subsequent surgery and are resigned to live with a definitive end ileostomy.

Aims & Methods

Assess the rate and cumulative incidence of secondary reconstructive surgery after subtotal colectomy for inflammatory bowel disease and identify the risk factors associated with the absence of a completion procedure in a large national cohort study.
A national retrospective study from 2013 and 2021 was conducted on prospective collected data from the French Medical Information System Database (PMSI). All patients undergoing subtotal colectomy in France for inflammatory bowel disease were included. Cumulative incidence of reconstruction surgery either with proctectomy and ileal pouch anal anastomosis or with ileorectal anastomosis was calculated by means of a Kaplan-Meier survival curve. The association between the absence of a subsequent intervention and potential risk factors was studied using univariate and multivariate analyses.

Results

1860 patients were included (45 +/-19 years old), with a median follow-up of 30­ months. 77% (n=1442) presented an ulcerative colitis and 23% (n=418) a Crohn’s disease. Mortality and morbidity at 90 days after subtotal colectomy were 5% (n=100) and 47% (n=868). Reconstructive surgery was identified in 1255 patients (67%) with a mean time of 7 months. 74% (n=932) underwent a completion proctectomy with ileal pouch anal anastomosis and 26% (n=323) an ileorectal anastomosis. Among patients with a permanent ileostomy who did not have bowel continuity restorative surgery (33%, n=605), 19% (n=114) had an abdominoperineal resection and 81% (n=491) did not had any further surgical procedure after subtotal colectomy. Independent risk factors for definitive end ileostomy identified in multivariate analysis were older age, Crohn’s disease, colic neoplasia, postoperative complication after subtotal colectomy, laparotomy, and low volume centre.

Conclusion

In this large national cohort study, 67% of patients undergoing subtotal colectomy with ileostomy for inflammatory bowel disease were treated with reconstructive surgery. This rate is higher than previously reported in other population-based studies. Absence of reconstructive surgery is associated with age, Crohn’s disease, colic neoplasia, post-operative morbidity, laparotomy, and low volume centre.

Introduction

Food-induced mucosal reactions have been visualised in the duodenum of patients with irritable bowel syndrome (IBS) using confocal laser endomicroscopy (CLE). The mechanisms underlying these alterations remain elusive but uncontrolled studies have reported symptomatic improvement in patients on a diet excluding foods that triggered acute alterations.

Aims & Methods

Aim: 1/ elucidate mechanisms underlying food-induced, acute mucosal alterations and 2/ assess whether a diet based on CLE results improves symptoms in patients with IBS.
Methods: Randomised, double-blind, controlled, cross-over study. Patients with ROME IV IBS (non-C), underwent CLE with sequential administration of foods (wheat, soy, milk, egg white, fish mix, and nut mix) in a randomised order ≥2 weeks after index gastroscopy. CLE was terminated after acute reactions or after administration of all foods. In case less than three foods were administered, a second exam was scheduled. Biological measures were compared between index endoscopy and CLE with food administration. Patients excluded food(s) that did (=real diet) and food(s) that did not (=sham diet) cause alterations for 4 weeks each in a blinded, cross-over diet intervention. Clinical response rate (=improvement of ≥50 points IBS-SSS) between real and sham diet was compared. Missing data was replaced using an extreme case approach (missing data on the primary endpoint was considered non-response). Healthy controls underwent CLE to assess disease specificity of observed alterations.

Results

Thirty-three patients were included, of which 21 underwent a second CLE. Alterations were observed in all 54 exams (100%) either at baseline (6/54, 11%) or after administration of food. Acute alterations were not associated with altered permeability (transepithelial electrical resistance 25.6 Ωxcm² after CLE vs 24.6 Ωxcm² at baseline; p = 0.6) nor with tryptase release from duodenal biopsies (1.1 µg/mg tissue vs 0.62 µg/mg tissue; p =0.15) . Two patients dropped out during the diet phase (one due to maladherence to study protocol, one due to acute increase of IBS symptoms during washout). Thirty-one patients completed the diet phase: 13 were clinical responders to the real diet (42%) versus 11 responders to sham (36%). The odds ratio (OR) for clinical response to the real diet was 1.33 (95% confidence interval: 0.46-3.84). The trial was terminated prematurely for futility (predetermined futility threshold OR <1.5). There was no difference in symptom evolution between real and sham diet (median change in IBS-SSS real diet: -30 points, median change sham diet: -20 points ; p = 0.7). No differences were observed between real and sham diet regarding change in pain duration (-0.1 vs +0.1, p =0.5) , in pain severity (-0.1 vs -0.1, p = 0.9), in bloating severity (-0.1 vs -0.4, p=0.6) or in flatulence severity (± 0.0 vs -0.2 p=0.5) based on 10cm VAS scales in symptom diaries. Fifteen healthy volunteers underwent CLE with alterations in all 15 (100%) exams at baseline (2/15, 13%) or after food administration. Distribution of alterations among different foods was similar to that in patients.

Conclusion

In this double-blind controlled cross-over trial, trigger foods identified based on CLE responses were not associated with superior clinical improvement following a targeted exclusion diet compared to a sham diet. Acute alterations in healthy controls suggest these alterations are not specific for IBS. The underling physiological or pathophysiological mechanism requires further studies.

Introduction

The low-FODMAP diet (LFD) is the most well-documented diet intervention for significantly improving irritable bowel syndrome (IBS) symptoms. The Mediterranean diet (MED), with plant-based foods, olive oil, fruits, herbs, wine, and lean proteins, has antioxidant properties that might ameliorate the low-grade inflammation characterizing the syndrome. The efficacy of the two diets combined in IBS is unknown.

Aims & Methods

Our primary aim was to examine the efficacy of combining LFD with MED diet components (MED-LFD) compared to the nutritional recommendations of the British National Institute for Health and Care Excellence (NICE) for managing non-constipation IBS.
Single-center, randomized, parallel groups design, single-masked, controlled study with six months of follow-up. We enrolled patients fulfilling Rome IV criteria with Bristol Stool Form Scale 3-7, IBS-SSS > 175, normal TSH, negative tTg-IgA/IgG, without either chronic systemic disorder or probiotic and/or antibiotic administration within a month before enrolment. Patients were randomized to either MED-LFD that included swapping high FODMAP for low FODMAP alternatives (1st phase), gradual introduction of foods rich in FODMAPs to test tolerance (2nd phase), and individualized diet based on personal tolerance (3rd phase) or a diet according to their energy needs adjusted to NICE recommendation for IBS. Patients were evaluated at baseline and follow-ups (1stFU: 4 weeks after initiation of intervention for NICE and at the end of phase 2 for MED-LFD, 2ndFU: at six 6 months) with: IBS-SSS (intervention responder: drop of >50 points), IBS-QOL, SF-12, modified for lower GI symptoms burden GSRS, and HADS.

Results

From July 2019 to April 2023, 108 patients (77.8% females, 40±11 yrs) were randomized (1:1) to MED-LFD or NICE diet groups. 92 (85.2%) patients completed the study. Primary endpoints: 1. Responders' rate was significantly higher in the MED-LFD group in the ITT and PP analysis at the 1st (81.5% vs. 57.4%, p=0.007 and 84.6% vs. 60.8%, p=0.007) and 2nd (68.5% vs. 40.7%, p=0.004 and 80.4% vs. 51.2%, p=0.004) FUs, respectively. 2. At both FUs, the MED-LFD group showed significantly greater improvement in symptom severity (IBS-SSS: 159±80 vs. 253±94 and 168±117 vs. 245±98). For all secondary endpoints (Table 1), patients in the MED-LFD group showed significantly higher improvement than the NICE group at each FU. Adherence rate was significantly higher in the MED-LFD group at both FUs (75% vs. 41% and 45% vs. 7%). No patient discontinued the intervention due to an adverse event. Eighteen (10 and eight in the MED-LFD and NICE groups, respectively) patients reported the use of rescue medication 26 times (12 and 14 in MED-LFD and NICE groups, respectively) during the intervention, including paracetamol (n=10), loperamide (n=14) and a combination of the two medications in two cases.

Table 1. Secondary endpoints: * denotes significant difference over baseline score at the different time points; $ denotes significant difference over comparator score at the FU.

Conclusion

Low-FODMAP diet combined with Mediterranean diet components is superior to the NICE nutritional recommendations for amelioration of IBS symptoms and improvement of quality of life of non-constipated IBS patients. The results are sustainable for six months

References

ClinicalTrials.gov identifier: NCT03997708

Introduction

Inflammatory bowel disease (IBD) is a chronic systemic condition of unknown etiology. Dysregulated T-cell responses play a fundamental role in perpetuating intestinal inflammation in IBD. Unconventional T cells are a diverse subset of T cells with innate and adaptive characteristics including: Gamma Delta T cells (GDT), mucosa-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. As new studies emerge, unconventional T cells’ role in IBD pathogenesis has been increasingly recognized, but their role in the pathogenesis and possible clinical application remains to be elucidated.

Aims & Methods

The aim of the study is to characterize the immune profile of IBD patients and controls in a large well-characterized cohort with focus on Unconventional T cells. We performed an in-depth, multidimensional flow cytometry analysis of unconventional T cells and plasma proteins from patinets´samples collected from the IBD biobank in Norway.
We used immunophenotyping from isolated PBMC to study both conventional T cells and unconventional T cells and evaluated their gut-homing -a4 and b7 expression-, activation and senescence markers. A 65-plex Luminex assay was used to quantify soluble plasma proteins. We studied the variations of T cell profiles within the different disease phenotypes and their correlation with disease activity. A subset of patients was followed-up clinically for 6 (+/-2) years to evaluate the association with disease outcomes.
Statistical analysis was performed using GraphPad Prism (San Diego, CA). Two-tailed Mann-Whitney U test was used to compare two independent groups and ROC analysis was used for diagnostic accuracy; p≤ 0.05 was considered statistically significant. Ethical approvals were obtained and all patients gave written informed consent.

Results

A total of 184 individuals (106 F) were included: 149 IBD (84 UC and 65 CD) and 25 healthy controls. We found important quantitative and phenotypical differences in unconventional T cells and plasma protein in IBD and between UC and CD patients. Patients with IBD had a significant reduction in MAIT cells, and increase in GDT VD3+ and CD8+ cells (p< 0.05). MAIT cells from IBD patients had lower a4+ and b7+ expression than controls. (p<0.05, p<0.001). Interestingly, Macrophage Migration Inhibitor Factor (MIF) was significantly reduced in patients with UC but not in CD (p<0.0001).
Patients with total colitis presented a significant increase in platelet count, MIG, IL-2R, and CD30 (p<0.001,p<0.01 and p<0.05,respectively). CD patients with colonic affection (L2) had a significant increase in TNF-b, FGF-2, G-CSF compared with patients with ileal (L1) or ileocolonic (L3) CD (p<0.01). Interestingly, MAIT cells were the only immune cells significantly reduced in patients with extraintestinal manifestations. The combination of 6 parameters: IL-4, IL-5, IL-8, MIG, CD30 and Eotaxin-3 showed a good diagnostic accuracy in ROC curves (CI:0.759-1.000; p=0.0005) to distinguish patients with mucosal healing vs those with biochemical and clinical remission alone. A decrease in GDT VD2 cells was found in UC patients with worse outcomes (p<0.01). CD patients with bad prognosis showed a significant increase in platelet counts and a decrease in: FABP2, CXCL10 and APRIL (p<0.05).

Conclusion

These results demonstrate the potential of the characterization of Unconventional T cells and soluble plasma proteins as biomarkers in IBD and as markers of disease progression. Further investigation is warranted to elucidate the use of Unconventional T cells in precision medicine and as potential therapeutic targets in IBD.

References

1. Catalan-Serra I, Sandvik AK, Bruland T et al. Gammadelta T Cells in Crohn's Disease: A New Player in the Disease Pathogenesis? J Crohns Colitis. 2017;11:1135-1145.
2. Hinks TSC, Zhang XW. MAIT Cell Activation and Functions. Front Immunol. 2020 May 27;11:1014. doi: 10.3389/fimmu.2020.01014.

Disclosure

No