Introduction

Coeliac disease-associated symptoms recover usually on a gluten-free diet (GFD) while its effect on the quality of life is not as straightforward. Some patients experience the diet burdensome and socially resctritive, which predispose them to negative experiences. Deciphering factors associated with reduced quality of life at coeliac disease diagnosis and significant improvement on GFD would be important for optimal treatment outcomes. We studied these issues in a prospective patient cohort.

Aims & Methods

Medical data on 178 adult coeliac disease patients were gathered at diagnosis and after one year on a strict GFD via structured interviews including Psychological General Well-Being (PGWB) and Gastrointestial Symptom Rating Scale questionnaires. Data were supplemented with available medical records. Decreased quality of life was defined as PGWB total score below the 25^th percentile and significant improvement as a change in PGWB total score above the 75^th percentile of the whole cohort. Logistic regression model was used to discover the factors associated with reduced quality of life and significant improvement on GFD.

Results

Decreased quality of life at diagnosis was associated with female sex (odds ratio 2.83, 95% confidence interval 1.15-6.97), severe gastrointestinal symptoms (4.02 [1.84-8.77]), presence of psychiatric comorbidities (17.7 [1.99-156]) and clinically vs. screen-detected presentation (2.54 [1.17-5.50]). Same factors increased risk for decreased quality of life on a GFD. Significant improvement in the quality of life was associated with reduced quality of life (5.98, [2.67-13.4]) and severe gastrointestinal symptoms (4.92 [2.24-10.8]) at diagnosis, autoimmune comorbidities (2.65 [1.12-6.31]), and clinically vs. screen-detected presentation (4.54 [1.98-10.5]).

Conclusion

Female sex, psychiatric comorbidities and severe gastrointestinal symptoms were associated with reduced quality of life both at coeliac disease diagnosis and on GFD. These patients may need additional support in health care, and good response to GFD should be documented. On the other hand, especially patients with severe symptoms and decreased quality of life at diagnosis as well as those with autoimmune comorbidities seemed to benefit from GFD.

Introduction

Patients with coeliac disease have well-known increased risks of non-Hodgkin’s lymphoma and small bowel cancer but risks of other digestive cancers remain controversial. The objective of this study was to assess the risks of gastrointestinal cancers in coeliac patients and possible favoring conditions.

Aims & Methods

We performed an exposed-non-exposed cohort study comparing coeliac patients with non-exposed control individuals (with a diagnosis of cutaneous superficial burn or sprained ankle) for risk of malignant gastrointestinal diseases using the French nationwide hospitalization database covering all the inpatient admissions during a 9-years follow-up (2011-2019).

Results

27244 patients with coeliac disease were compared to the same number of non-exposed age and sex matched patients. 104 cases of Enteropathy Associated T cell Lymphoma were recorded in the group of coeliac patients and none in control group. In addition to non-Hodgkin’s lymphoma (OR=4.1 [95% CI 2.8; 6.2]) and small bowel cancer (OR=13.9 [95% CI 7.5; 29.6]), coeliac patients had increased risk of pancreatic cancer (OR=2.4 [95% CI 1.8; 3.3], esophageal cancer (OR=1.7 [95% CI 1.1; 2.8]), gastric cancer (OR=1.5 [95% CI 1.1; 2.2]) and colonic cancer (OR=1.7 [95% CI 1.4; 2.1]) but neither of rectal cancer (OR=1.1 [95% CI 0.8; 1.4]) nor of hepatocellular carcinoma (OR=0.8 [95% CI 0.54; 1.21]). Regarding possible favoring conditions, we also noted an increased risk of pernicious anaemia (OR=11.3 [95%CI 7.3; 18.4]), Crohn’s disease (OR=4.2 [95%CI 3.4; 5.1]), ulcerative colitis (OR=3.3 95%CI 2.7; 4.0]), microscopic colitis (OR=4.5 [95%CI 4.1; 5]) and non-alcoholic chronic pancreatitis (OR=1.7 [95% CI 1.2; 2.3]) in coeliac group. Coeliac patients with non-alcoholic chronic pancreatitis, pernicious anaemia and microscopic colitis had a more increased risk of pancreatic (OR=5.9 [95%CI 1.4;15.9]; p=0.003), gastric ((OR=9 [95%CI 3.1;20.4]; p<0.001) and colonic cancers (OR=1.8 [95%CI 1.3;2.6]; p<0.001), respectively.

Conclusion

In addition to small bowel cancer and lymphoma, coeliac patients have increased risk of pancreatic, gastric and colonic cancers. Coeliac patients have also increased risks of inflammatory and/or autoimmune gastrointestinal diseases which major risks of corresponding digestive cancers. These results argue for an early and regular screening of digestive cancers and inflammatory/autoimmune digestive diseases in coeliac patients.

Disclosure

none

Introduction

Nearly 25% of patients are diagnosed with Inflammatory Bowel Disease (IBD) under 18 years old of age. To date, there are no transition models established and recommended in IBD setting, so each center tends to develop a transition model based on its own needs and experience.

Aims & Methods

To compare the effectiveness on transition readiness and quality of life of two different modes of transition, one based on sending the subject to a first gastroenterological visit in the clinic with the support of a clinical report prepared by the pediatrician (letter-based transition) and the other one characterized by combined visits in the presence of both the pediatrician and adult gastroenterologist (combined-visit- based transition).
From 2018 to 2021, patients diagnosed with IBD, aged between 16 and 19 years, and followed at the Paediatric Gastroenterology and Hepatology Unit of the Azienda Ospedale Università Padova, were randomized to the letter-based transition or the combined- visits-based transition. The transition readiness was verified using the Transition Readiness Assessment Questionnaire (TRAQ), whilst the quality of life was analysed using the Pediatric Quality of Life Inventory TM at the start of the study, at six months and after one year.

Results

The final sample analyzed consisted of 40 patients, 22 assigned to the letter-based group (10 males, mean age 18.6 ± 0.4) and 18 to the combined-visits groups (10 males, mean age 18.6 ± 0.5) with similar age and sex distribution. Twenty-one and 18 reached T2, respectively, and 17 in both groups reached T3. The clinical activity and calprotectin value did not change along the study in both groups (p >0.05). Three azathioprine and 4 anti-TNF therapy were stopped after transition. The TRAQ questionnaire improved significantly during the study both in the letter-based group (from 72.1 ± 12.46 to 82.35 ± 5.88, p 0.002) and in the combined-visits group (from 66.52 ± 15.06 to 76.0 ± 12.83, p 0.008). No significant change was observed in patients' perceived quality of life along the study in the letter-based group (from 83.9±8 to 86.2 ± 9.54, p = 0.17) while it improved in the combined-visits group (from 82.5 ± 8.23 to 89.1 ± 7.63, p <0.05).

Conclusion

Our data suggest that both transition models are able to obtain a marked improvement in transition readiness, while the quality of life improves only in the combined-visits transition. Therefore, despite the letter-based transition approach is a good option interms of costs and time sparing, the combined-visits process should be preferable when possible to improve both transition readiness and quality of life.

Introduction

Intestinal ultrasound (IUS), in particular bowel wall thickness (BWT), is accurate in determining endoscopic disease activity in ulcerative colitis (UC). Reduction of BWT six weeks into advanced anti-inflammatory treatment predicted endoscopic response and clinical remission. Filgotinib is a preferential JAK1-inhibitor effective in UC. Currently, there is no data on IUS-kinetics or early prediction of treatment response with filgotinib.

Aims & Methods

In this study, we aimed to identify early IUS predictors of treatment response to filgotinib in patients with moderate to severe UC. This prospective observational study included UC patients with active endoscopic disease (i.e. endoscopic MAYO score (EMS) ≥2) starting with filgotinib. Clinical scores (UCEIS, Lichtiger), biochemical parameters and IUS parameters of the sigmoid were assessed at baseline, after 4 weeks (W4) and at the time of the second endoscopy (between W8 and W23). Endoscopic remission (i.e. EMS=0), endoscopic response (i.e. decrease in EMS ≥1 compared to baseline) and clinical remission (SCCAI ≤2 or Lichtiger score ≤3) were assessed. IUS response (i.e. defined as a reduction in BWT of >25% or >2.0 mm, or >1.0 mm and one colour Doppler signal) was assessed at week 4. All normally distributed data were reported in mean ± standard deviation [SD] and non-normally distributed in median and interquartile range [IQR]. Mann–Whitney U tests were used to compare continuous non-parametric variables, chi square tests for dichotomous variables.

Results

A total of 20 patients were included. 13 patients underwent second endoscopy, 2 refused a follow-up endoscopy and 5 patients were still in follow-up. At baseline, 9 patients (9/20, 45%) had received ≥2 biologicals, 16 patients (16/20, 80%) had previous anti-TNF exposure, and no patients were exposed to other JAK-inhibitors. 8 patients (8/20, 40%) had severe endoscopic disease at baseline (i.e. EMS=3). 5 patients (5/13, 38%) were endoscopic responders at W8-23, and no patient reached endoscopic remission. BWT was significantly lower in the sigmoid colon from W4 onwards for patients reaching endoscopic response (Table 1). Decrease in BWT compared to baseline was statistically greater in endoscopic responders from W4 onwards (Table 1). IUS response was seen at W4 in 6 patients, of which 5 were endoscopic responders (83%, p=0.002). Decrease in BWT from W4 onwards was statistically greater in patients reaching clinical remission at W8-23 (-45% (-55% to -36.6%) vs -9% (-25% to +8%), p=0.014).

Conclusion

On IUS, UC patients treated with filgotinib have significantly lower BWT from week 4 onwards compared to baseline, which could predict endoscopic response.

Disclosure

MP received speakers fees from Janssen and Tillotts
CT received speakers fees from Tillotts
FV received speaker or honoraria fees from AbbVie, Janssen and Tillotts
ML received consultancy/lecturefees from Abbvie, Bristol Myers Squibb , Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda and Tillotts.
RG Received speakers fee from Janssen and Tillotts
GD has served as a consultant and/or received speaker’s fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences.
KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Abbvie, Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Introduction

Many individuals rapidly regain excess weight once they stop dieting. This phenomenon, which is commonly called yoyo-dieting, is a pattern of losing weight and then regaining it, placing individuals at greater risk for metabolic complications and obesity. There is some evidence that yoyo-dieting-induced obesity causes long-term alterations in the gut microbiome composition. There is also increasing evidence suggesting that diets high in resistant starch (RS) may positively improve gut health and metabolism.

Aims & Methods

This study aimed to investigate how yoyo-dieting affects gut health and whether supplementation with resistant starch could be a promising and effective weight management strategy.
Male and female C57BL/6 mice (n=48/sex, n=8/group) were allocated to six different diets for 20 weeks [control, high-fat (HFD), yoyo-diet (HFD interspaced with control every 5 weeks), control with RS, HFD with RS, and yoyo-diet with RS]. Metabolic measurements were performed, including body weight, glucose and insulin tolerance tests, adipose tissue, and organ weight. Liver and intestines were collected for structural changes assessed by histology. Epithelial barrier integrity was assessed in Ussing chambers. Faecal samples were collected for microbial profiling using 16S ribosomal RNA sequencing.

Results

Male mice fed a HFD with RS had significantly lower weight gain, liver mass, adipose tissue, and insulin tolerance compared to mice fed a HFD alone, while no significant differences were observed in females. No significant differences in glucose tolerance and intestinal permeability were observed across all diets and between sexes. Male mice had significantly higher alpha diversity and a different microbiota profile compared to female mice. Mice fed diets supplemented with RS had significantly lower alpha diversity and a different microbiota profile compared to mice fed without RS. Male and female mice have different microbiota profiles. Mice fed a HFD with RS have a similar microbiota profile to mice fed the control diet with RS. After changing diets (switching from diets high in fat to the control diet – yoyo groups), no change in microbiome profile was observed in female mice previously fed HFD with RS, while male mice previously fed a HFD supplemented with RS had a similar microbiome profile to control mice.

Conclusion

Different microbiome signatures and metabolic measurements were observed in male and female mice. In male mice consuming a HFD, RS lowered weight gain and shifted the microbiota profile to one similar to mice fed a control diet with RS. In males consuming a HFD diet interspaced with the control diet (yoyo-diet), RS shifted the microbiota profile of mice to a similar signature seen in control animals. No significant differences were observed in females.

Disclosure

No conflict of interest

Introduction

Segmental colitis associated with diverticulosis (SCAD) is an increasingly recognized clinical and pathological disorder, characterized by a chronic inflammatory response involving the inter-diverticular mucosa of a colonic segment, sparing the rectum and the right colon. However, its prevalence and outcome in the setting of colorectal cancer (CRC) screening is unknown.

Aims & Methods

Aims: to assess the prevalence of SCAD in the setting of a CRC screening program and to evaluate the differences in terms of oncological outcomes between SCAD and "simple" diverticulosis. We performed a retrospective analysis from a prospectively-maintained database including all subjects undergoing first screening colonoscopy according to regional CRC program from 2019 to 2022. Patients with incomplete colonoscopy, inadequate bowel preparation or known diagnosis of SCAD or CRC were excluded. Endoscopic signs of SCAD were registered as “crescentic fold disease”, “mild-to-moderate UC-like”, “Crohn’s disease-like” and “Severe UC-like”. The number of adenomas (ADR) and cancers was also recorded. Statistical analysis included chi-square, Student’s t-test and odds ratio (OR) with 95% confidence interval (CI) when indicated.

Results

a total of 1518 patients were included (males 51.8%, mean age 63.48±6.39). Adenomas were detected in 638 patients (ADR 42%), while CRC was diagnosed in 86 cases (5.7%). Diverticulosis was described in 570/1518 patients (37.5%), while SCAD was endoscopically diagnosed in 69 patients (4.5%). Among them, 48 (69.6%) presented a crescentic fold disease, 14 (20.3%) a mild-to-moderate UC-like pattern, 6 (8.7%) a CD-like pattern and 1 (1.4%) had a severe UC-like pattern. When SCAD patients were compared to subjects with simple diverticulosis (501 patients), we found no differences in terms of gender (males 55.1% vs 50.7%, p=0.46) or age (63.86±6.45 vs 64.45±6.38, p=0.47). Interestingly, the use of anticoagulant/antiplatelet (28.9% vs 30.1%, p=0.79), anti-hypertensive (46.4% vs 48.1%, p=0.89) or anti-hyperglycemic drugs (36.2% vs 41.1%, p=0.52) had no effect on SCAD onset as compared with patients with diverticulosis. However, patients with SCAD had significant lower rate of adenomas (ADR 31.9% vs 47.3%, p=0.018, OR 0.52, 95%CI 0.31-0.89), and lower –but not significant– rate of CRC (1.4% vs 6.2%, p=0.14, OR 0.22, 95%CI 0.02-1.66). Most patients were successfully treated with 5-ASA and none needed surgery for SCAD.

Conclusion

SCAD can be diagnosed in about 5% of population undergoing screening colonoscopy and in about 12% of those with diverticulosis. SCAD seems to be associated with a reduced rate of adenomas or CRC as compared with diverticulosis.

Introduction

Gluten free diet (GFD) is the one therapy for patients affected by celiac disease (CD). Dietary products are considered safe (“without” gluten) when containing less of 20 ppm (20 mg/kg). CD diagnosis is quite simple in most cases, however some patients start GFD before the serological and histological approach, so significantly complicating the CD diagnostic work-up. In these cases, the Oslo guidelines for CD suggest a 14-day gluten intake > 3 gr (about 2 slices of bread/day) to induce serological and histological changes in most CD patients; though, many subjects refuse this method being fearful for symptoms reviving (1). In 2007, Catassi showed that the intake of a daily dose of 50 mg/day of gluten for 3 months was able to determine villous atrophy and serological positivity in most CD patients (2).

Aims & Methods

Aims: Starting from these considerations, we performed a pilot dietary study administering a daily low-dose of gluten in form of a package of “crackers” (2-4 crackers/day; about 60-120 mg of gluten/day) for 3 months, in order to detect serological/histological activation in subjects with doubt CD already on “self-prescribed” GFD.
Methods: From May 2019 to September 2022, all DQ2/DQ8+ adult patients with a doubt of CD who had started a self-prescribed GFD before the diagnostic work-up and that had refused the traditional gluten challenge. All patients were recruited at Gastroenterology Unit of University of Naples and Salerno. All subjects were invited to continue their GFD by adding a half (or full) package of crackers containing gluten for a 3-months period. At the end of 3 months, all patients were analysed for the presence of Ab anti-transglutaminases (a-tTG), anti-endomisyal antibodies (EMA) and deamidated gluten peptited (DGP). All patients with positive serology underwent endoscopic/histological evaluation. The diagnosis of CD was made by histology in accordance with Marsh-Oberhuber classification. Furthermore, the grade of satisfaction for this kind of challenge diet and the possible onset of adverse events were recorded. Patient’s satisfaction about this kind of challenge was evaluated by a simple VAS (1-10).

Results

At the end, we enrolled 120 patients (M/F 42/78; mean age 38 years). All patients could terminate the study without relevant adverse events. Serological positivity/activation was detected in 54 patients (45%): positive a-tTG: 51 patients; EMA (slight/full) positivity: 49 patients; DGP positivity: 48 patients. At histology, 47 (88%) were atrophic, while 7 subjects showed a Marsh 1-2 grade. The remaining 66 patients continued the trial for further 3 months without substantial serological modifications and, finally, were considered as not CD patients. Regarding patient’s satisfaction, 99 patients (83%) resulted to be satisfied and reassured by this dietary approach. About adverse events, 15 patients (12%) recorded bloating, 12 (10%) mild pain and 8 (6%) mild diarrhoea.

Conclusion

Low-dose gluten diet by using “crackers” could be a very simple, useful, and safe diagnostic approach in subject with doubt of CD who had start a GFD before the regular diagnostic work-up for CD.

References

1) Ludvigsson JF et. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014;63:1210-28.
2) Catassi C et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007 Jan;85(1):160-6.