Introduction

Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interactions characterised by pain and altered bowel habits¹. The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet is efficacious for improving symptoms and quality of life (QoL)², however not all individuals will have a therapeutic response resulting in adequate symptom relief³. Behavioural, emotional and cognitive predictors of response have been explored in psychological therapies, but not in dietary treatments of IBS⁴.

Aims & Methods

The aim of this study was to identify psychological predictors of treatment response to the low FODMAP diet. Participants underwent a three-phase dietitian-led low FODMAP diet between August 2018 and July 2021. Participants completed questionnaires to obtain scores for psychological factors and symptoms (predictor variables). Data on depression, anxiety, gastrointestinal (GI) specific anxiety, somatic symptoms, illness perceptions, behavioural avoidance, treatment beliefs and expectations, symptom severity and QoL was collected at five time points; pre dietitian (week 0), post dietitian (week 1), post FODMAP restriction (week 5), post FODMAP reintroduction (week 13) and personalisation (week 25). Linear mixed models (LMM) were used to test the effect of baseline psychological scores on IBS symptoms and QoL over time. Cross lag panel models (CLPM) were used to identify directional relationships between predictor variables on the one hand, and IBS symptoms and QoL on the other.

Results

112 participants, (89% female, median age 30 ± 17 years) were included. LMM showed that higher treatment beliefs predicted a stronger initial symptom response (effect on linear slope p=0.036). Of the illness perceptions, lower emotional representations predicted a stronger initial and later QoL response (effect on linear (p=0.006) and quadratic (p=0.049) slopes). Increased cyclical time beliefs predicted poorer initial and later QoL response (effect on linear (p=0.015) and quadratic (p=0.029) slopes). CLPM showed that lower GI specific anxiety predicted a stronger reduction in symptoms from week 0 to 25. Of the illness perceptions, positive perceptions relating to higher personal and treatment control predicted a stronger reduction in symptoms from week 0 to week 25. Increased QoL predicted reductions in GI specific anxiety and stress from week 0 to week 25 and week 1 to week 25, respectively. Increased personal and treatment control predicted improved QoL across all time points.

Conclusion

Negative illness perceptions were associated with poorer symptom and QoL response, whereas positive illness perceptions and treatment beliefs predicted better QoL and symptom responses to the low FODMAP diet in adults with IBS. Illness perceptions and treatment beliefs can be easily assessed in clinical practice and should be considered when determining if the low FODMAP diet is a suitable treatment, and may serve as targets to enhance treatment response.

References

¹Camileri, M & Dilmaghani, S. (2023). Update on treatment of abdominal pain in irritable bowel syndrome: a narrative review. Pharmacology and therapeutics, 245, 108400-108400. http://doi.org/10.1016/j.pharmthera.2023.108400
²van Lanen, A.S., de Bree, A & Greyling, A. (2021). Efficacy of a low FODMAP diet in adult irritable bowel syndrome: a systematic review and meta-analysis. Eur J Nutr, 60(6), 3505-3522. doi:10.1007/s00394-020-02437-0
³Wilson, B., Cox, S.R. & Whelan, K. (2021). Challenges of the low FODMAP diet for managing irritable bowel syndrome and approaches to their minimisation and mitigation. Proc Nutr Soc, 80(1), 19-8. doi:10.1017/s0029665120006990
⁴ Radu, M., Moldovan, R., Pintea, S., Baban, A & Dumitrascu. (2018). Predictors of outcome in cognitive and behavioural interventions for irritable bowel syndrome. A meta-analysis. Journal of Gastrointestinal and Liver Diseases, 27(3), 257-263. http://dx.doi.org/10.15403/jgld.2014.1121.273.bab

Introduction

A transmural oxidative imbalance, mainly affecting longitudinal muscle, has been reported in the different clinical phenotypes of Diverticular Disease (DD) (Pallotta L,2022; Cappelletti M,2022) but the genesis of the oxidative stress remains to be defined. Since the central role of the mitochondria for the cell metabolism and radicals production, aim of the study is to elucidate the involvement of mitochondria alterations in the different DD clinical phenotypes in order to improve the knowledge of the DD natural history and management.

Aims & Methods

Longitudinal smooth muscle tissues and cells were isolated separately from surgical specimens of complicated stenotic DD (cDD n=5), up-stream non-occlusive colon cancer with diverticula (DIV n=5) and without diverticula (controls n=5). Oxidized proteins, thioredoxin and, succinate deidrogenase (complex II) and complex IV (cytochrome c oxidase) of mitochondrial respiratory chain were evaluated on tissues by Western Blot. Mitochondrial mass, mitochondrial ROS, mitochondrial membrane potential and glutathione (GSH) were evaluated in cells by FACS. Functional cells activity was tested by image micrometry assessing maximal contraction to acetylcholine and relaxation to VIP, before and after 24h-incubation with 14mM polyphenols (Phenolea Active Complex L). Data (mean±SE) were expressed as fold variations or % decrease from controls, *p value<0.05 considered significant.

Results

In respect to control, oxidized proteins content in longitudinal muscle was increased both in DIV (5.0*±1.1) and cDD (2.6±0.6), associated to a progressive loss of the antioxidant thioredoxin molecule (DIV:70.9%±9.2;cDD:83.3%±3.4). The oxidative status resulted associated to a loss of the mitochondrial complex II succinate deidrogenase codified by nuclear DNA (DIV:43.4%±19.7;cDD:67.9%±10.3) suggestive of the electron respiratory chain impairement. Compensatory stress mechanisms likely occurred with an increase of the complex IV cytochrome c oxidase codified by mitochondrial DNA in muscle tissue (DIV:1.1±0.77;cDD:2.3±1.7) and mitochondrial mass increase (DIV:2.4±1.2;cDD:3.7*±1.3) in cells. Radicals over production was observed mainly in cDD with a cellular increase in mitochondrial ROS (cDD:1.50±0.57) and mitochondrial membrane potential (cDD:1.4±0.3). Antioxidant GSH cellular content progressively decreased from DIV (51.9%*±9.5) to cDD (72.2%*±1.5). These oxidative alterations were associated to an impairment of functional cellular activity with a reduction of contraction (DIV:51.3%*±4.5;cDD:52.5%*±8.5) and relaxation (DIV:34.9%*±14.3;cDD:37.6%*±10.6). The prominent role of oxidative stress in these functional alterations was confirmed by the ability of a 24/h polyphenols treatment to restore GSH content (DIV:1.1±0.06;cDD:1.4±0.3) and relaxation, in both DD phenotypes.

Conclusion

Oxidative stress-driven alterations are present in longitudinal muscle in DD, independently from the clinical stage. In accordance to the severity of the pathology, mitochondrial imbalance resulted more prevalent in complicated diverticular disease. The beneficial effects of the antioxidant treatment could open new tailored-therapeutic and prevention strategies still not tested in this disease.

Disclosure

No disclosure

Introduction

​The clinical scenarios in which probiotics (PB) are useful as adjuvants to Helicobacter pylori eradication therapy have not been well established.

Aims & Methods

Aims: To determine the use and factors associated with the prescription of PB adjuvants to H pylori eradication regimens, by European gastroenterologists in clinical practice.
Methods: Prospective, multicentre, non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Data were collected in an AEG-REDCap e-CRD from 2013 to 2022. All data from countries with at least 30 cases undergoing eradication therapy and at least 1 case with associated PB were included, using patients without PB as controls. Analysis was performed by geographic area.

Results

A total of 36,699 patients were included, 8,233 (22%) with PB. Multiple PB formulations were used, including 9 genera and 32 species, the most frequent being Saccharomyces boulardii (2,315), Lactobacillus rhamnosus (1,897), Bifidobacterium breve (1,765), Lactobacillus reuteri (1,732) and Lactobacillus acidophilus (1,447). Forty-one percent of the formulations were multi-genus, 34% were symbiotic and 11% were combined with other products.
As factors associated with prescribing, there was a higher rate of females in the PB group (64% vs 60%; p<0.0001), with similar age (49 vs 51). Patients in the PB group had a higher rate of resistance to clarithromycin (11.4 vs 1.4), metronidazole (10.7 vs 1.4) and dual (10.7 vs 1.4). In terms of line of eradication therapy, PB use was more frequent (p<0.0001) in patients in 5th (28%) and 6th line (46%) compared to 1st (22%), 2nd (23%), 3rd (24%) and 4th (24%).
The rate of PB use varied between the different eradication regimens, being most frequent in sequential (74%), followed by hybrid (38%) and dual (33%). In contrast, the rate was lower in classic bismuth quadruple (24%), or the same in single capsule (21%), triple (17%) and non-bismuth quadruple (15%).
The percentage of PB use per country ranged from 95% in Serbia to 0.2% in Slovenia. The central geographical area had by far the highest prescription rate (83%). The rates in the rest were 38% in the east, 9% in the southeast, 7% in the southwest and 1% in the north. We observed that the rate of adverse effects in the non-PB group was higher in the central area than in the other areas (38% vs. 28%; p<0.0001), suggesting that in areas with less PB use there may be a prescription of PBs driven by the expectation of adverse effects.

Conclusion

The prescription of PB adjuvant to eradication therapy is very heterogeneous. There is greater use of PB associated with sequential, dual and hybrid therapies, patients with antibiotic resistance, advanced lines of treatment and women. In areas with lower PB use, there seems to be a prescription bias towards patients with a higher expected risk of adverse effects.

Introduction

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc.

Aims & Methods

The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the high resolution manometry with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total Warrick score≥7 was considered predictive of ILD, while a score≥10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement.

Results

Forty-two patients were included. We found a score≥7 in 11 patients with aperistalsis, in 6 subjects with ineffective esophageal motility and in 6 patients with a normal manometry. Otherwise, a Warrick score<7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with ineffective esophageal motility disorder and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline pressure of lower esophageal sphincter and greater HrCT scores at follow-up evaluation were significantly associated.

Conclusion

This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Crohn’s disease (CD) clinical trials have evolved from evaluating symptoms to including endoscopic outcomes as coprimary endpoints, as was done in clinical trials of upadacitinib (UPA), an oral, reversible Janus kinase inhibitor, and ustekinumab (UST), an anti-interleukin 12/23. Endoscopic healing has been recommended as a long-term treatment target by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative.

Aims & Methods

The objective of this study is to conduct a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) of endoscopic outcomes between UPA and UST among patients with moderately to severely active CD. Data from phase 3 UPA trials (NCT: 03105128, 03104413, 03105102) and an UST endoscopy substudy (NCT: 01369329, 01369342, 01369355) from the phase 3 UNITI/IM-UNITI program were used. For induction, patients (pts) received UPA 45mg once daily (QD) for 12 weeks (wks), UST 6mg/kg intravenously, or PBO. For maintenance, pts received UPA 15mg or 30mg QD, subcutaneous UST 90mg every 8 (Q8W) or 12 wks (Q12W), or PBO. Individual pt level data from the UPA trials included pts with baseline (BL) CD Activity Index between 220-450 and excluded pts with prior UST or vedolizumab exposure or missing data due to COVID. Induction BL characteristics identified as treatment-effect modifiers, including disease duration, location, and phenotype, median c-reactive protein, prior biologic failure, and mean Simple Endoscopic Score for CD (SES-CD), were weighted to match those reported in the UST endoscopy substudy for both induction and maintenance. Endoscopic outcomes were evaluated after induction (Wk 12 UPA, Wk 8 UST) and maintenance (Wk 52 UPA, Wk 44 UST). Endoscopic outcomes included endoscopic response (reduction of ≥50% from induction BL in SES-CD) and remission (total SES-CD ≤2), mucosal healing (present with ulceration in at least 1 ileocolonic segment at induction BL) and change in SES-CD score from induction BL.

Results

The effective sample sizes for induction MAICs were 207 UPA and 155 UST pts and ranged from 16–53 (UPA) and 17–46 (UST) for maintenance MAICs. A significantly (P<0.05) greater proportion of UPA vs UST pts achieved endoscopic response and remission, mucosal healing, and had a larger reduction from BL in mean SES-CD score at the end of induction; PBO-adjusted treatment differences were 26.3%, 9.9%, 13.0%, and –3.7 points, respectively. Endoscopic remission rates at the end of maintenance were numerically higher for UPA 30mg vs UST 90mg (Q8W+Q12W). PBO-adjusted rate differences in endoscopic response and mucosal healing between UPA 30mg and UST Q12W were significant (35.5% and 39.0%, respectively; p<0.05); other outcomes (UPA 15mg vs UST) were comparable.

Conclusion

Greater proportions of pts on UPA vs UST achieved endoscopic outcomes at the end of induction for pts with moderately to severely active CD. Although sample sizes during maintenance were limited, these MAICs show endoscopic outcomes are achieved in a numerically higher proportion of pts treated with UPA 30mg vs. UST, while outcomes are comparable with UPA 15mg vs UST.

Disclosure

C Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Tillotts; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; research support from Ferring, Pfizer.
MC Dubinsky has received consulting fees from AbbVie, Abivax, Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Prometheus Biosciences, Prometheus Labs, Takeda
JE Axelrad reports receiving research grants from BioFire Diagnostics; consultancy fees or honorarium from BioFire Diagnostics, Janssen, Pfizer, Abbvie, and BMS; and holds US Patent 2012/0052124A1 and no other conflicts of interest.
J Griffith, S Anyanwu, and N Joshi are employees of AbbVie and may own stock.
J Tran is a funded PhD student at the University of Washington and a contractor for AbbVie.

Introduction

Individuals with coeliac disease (CeD) commonly complain of persistent symptoms despite adhering to a gluten free diet (GFD). We analysed baseline data from the prospective pseudonymized German CeD Registry to identify factors associated with ongoing complaints.

Aims & Methods

​​​​​​After written informed consent, participants self-reported demographic, clinical and healthcare related information at baseline and yearly thereafter. Symptoms before diagnosis and during the four weeks prior to completing the baseline questionnaire were retrospectively assessed. Factors associated with symptoms after at least one year of gluten-free diet (GFD) were evaluated by multivariate logistic regression.

Results

From 11/2019 to 10/2021, 2164 participants provided baseline data: 78% were female, median age 36 years (range 1.1 to 93.2), median time since diagnosis 6.3 years (0 to 58.7), and median diagnostic delay (time from first symptom to diagnosis) 2.2 years (0 to 64.8). Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Individuals diagnosed in adulthood were more symptomatic compared to paediatric patients. Although 93.4% of participants reported improvement after diagnosis, a substantial proportion of those keeping a GFD >1year (n=1861, 86% of cohort) had ongoing symptoms. Factors associated with regularly experiencing above symptoms included female gender, having the same symptom before diagnosis, feeling insufficiently informed by their physician about CeD and implications for their daily life, and age at diagnosis (per decade), but not time since diagnosis (table).

Conclusion

Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care. In this large cohort of patients with CeD we identified factors associated with persistence of symptoms despite keeping a GFD for at least one years. Early diagnosis, providing comprehensive education after confirmed diagnosis, and ensuring strict dietary adherence are pivotal for symptom resolution. A population-based mass-screening for CeD in childhood should be further explored. Implementing a multifaceted approach will enhance care for individuals with CeD and ultimately improve long-term health and well-being.