Introduction

Diagnostics of enteropathy with membrane digestion disturbance (EMDD) is based on the evaluation of carbohydrase activity in duodenal mucosa (DM). There is no information about diagnostic value of ileum mucosa (IM) carbohydrases.
Study objective. Assess the diagnostic value of carbohydrases activity in mucous membrane of duodenum and distal ileum in patients with EMDD and irritable bowel syndrome (IBS).

Aims & Methods

The study includes 12 patients with EMDD, 16 patients with IBS and 12 relatively healthy persons (control group). Study design included analysis of food tolerance and evaluation of activity of sucrase (S), glucoamylase (GA), maltase (М) and lactase (L) in mucous membrane of duodenum and ileum based on the method of Dahlquist with N.I.Belostotsky modification. Microsoft Office Excel and STATISTICA 10.0 were used for statistical evaluation of material. Mann-Whitney criterion was used to evaluate the differences between quantitative parameters. The differences were considered to be significant at p <0.05. Control group was used for comparison.

Results

Ratio of carbohydrase activity in duodenum and ileum in control group and patients with IBS and EMDD.

In control group the carbohydrases activity in duodenum mucosa was not significantly statistically different from the one in ileum mucosa.
In patients with IBS glucoamylase and maltase activity parameters in IM were significantly different from activity in DM, which can be interpreted as functional inequality of enzyme activity of various departments of small intestine.
In patients with EMDD GA level in ileum mucosa is 5.2 times higher, maltase level is 3.8 times higher and sucrose level is 2 times higher than duodenum enzyme levels, which demonstrates the possibility of formation of compensatory reaction of adaptive shift type towards distal segments of small intestine, initially described by A.M. Ugolev et al. in 1985

Conclusion

Enzyme activity distribution along small intestine is an adaptor function of its segments. Our study confirmed the need and promising outlook of further investigations in terms of evaluation of proximo-distal gradients of enzyme activity to study compensatory reactions which can be fulfilled by distal segment of small intestine in case of duodenum damage.
The evaluation of carbohydrase activity in ileum mucosa provides additional opportunities for diagnostics of EMDD and its differentiation from IBS, which can be used to improve therapeutic approaches.

Introduction

Celiac disease is an autoimmune disorder where the intake of gluten (a protein found in wheat, barley, and rye) causes damage to the small intestine and impairs nutrient absorption. Studies have shown that individuals with celiac disease have reduced quality of life and higher levels of anxiety and depression. However, this has not been studied in the general population, among individuals with newly discovered, untreated celiac disease.

Aims & Methods

The aim of this study was to investigate anxiety, depression, mental health, and subjective well-being in individuals with newly diagnosed and untreated celiac disease, compared with the general population. This study used data from the fourth Trøndelag health study (HUNT4), conducted between 2017 and 2019 with over 56,000 adult participants from 20 years of age. Previously undiagnosed celiac disease was identified among the participants by analyses of blood samples from all participants and confirmed with endoscopy and duodenal biopsies. The participants in HUNT4 also answered questionnaires measuring levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), mental distress using the Cohort of Norway Medical Health Index (Conor-MHI), and subjective well-being using a three-part questionnaire. Differences in mental health among individuals with newly diagnosed celiac disease and the remaining HUNT4 participants were compared.

Results

Celiac disease was diagnosed in 454 HUNT4 participants by March 2022. The celiac group had a lower median age (53 vs. 56 years) compared to the remaining HUNT4 population. The celiac group had significantly lower mean scores on the HADS anxiety subscale (4.0 vs. 4.4), depression subscale (2.8 vs. 3.3), and total scale (6.8 vs. 7.7) compared to the reference population. On the CONOR-MHI scale, the celiac disease group had a lower total mean score (1.4 vs. 1.5) with lower scores in the categories of "secure and calm", "irritable", "happy and optimistic", "sad/depressed", and "lonely" compared to the reference population. Finally, the celiac disease group had a lower mean score on the question “Do you feel mostly strong and clear, or tired and fatigued?” (3.3 vs. 3.4) and a higher mean score on the question “How is your health now?” (3.0 vs. 2.9) compared to the reference population. No significant difference was observed in the HADS or CONOR-MHI scores by Marsh grades at diagnosis among the celiac disease group.

Conclusion

The study suggests that individuals with undiagnosed celiac disease have lower levels of anxiety, depression, and mental distress compared to the general population, while also reporting slightly better subjective well-being. These findings contradict other studies on psychological health in celiac disease.

Disclosure

No con

Introduction

Glucose breath test (GBT) is the most commonly used method for the diagnosis of small intestinal bacterial overgrowth (SIBO). SIBO is a common condition with very unspecific symptoms (bloating, abdominal pain, diarrhea or constipation). Recently, American and European recommandations have been published to standardize the indications and the conditions to perform these tests.^1,2 However, some discrepancies remain between the European and American recommandations, and many statements were supported by low quality of evidence.^1,2 Moreover, several counfounding factors related to the patient’s condition may impact the result of the test, leading to a difficult interpretation.

Aims & Methods

This study aimed to assess the factors that could impact the results of a GBT. Therefore, we retrospectively reviewed the results of the GBT performed in our physiology department from 2013 to 2023. The test was performed after ingestion of 75g of glucose, with breath samples collected every 15min during 2 hours. The result was considered positive for hydrogen (H₂) if a rise ≥ 20ppm was observed or positive for methane (CH4) if a rise ≥ 10ppm was observed. Demographic data were collected, such as symptoms and questionnaires during the exam including Rome questionnaire, and the Gastro-Intestinal Quality of Life Index (GIQLI). Severity of symptoms was based on the GIQLI questionnaire, where a higher score represents a better condition. Medical and surgery history, such as drug treatments were then retrospectively collected from medical records, using a computerized research.

Results

A total of 2373 tests from different patients were included. The mean age was 46.0 ± 15.8 years old, with 1727 females (73.7%). The number of positive GBT was 576 tests (24.3%), with 294 tests positive for H₂ only, 214 tests positive for CH₄ only, and 69 tests positive for both. In univariate analysis, a higher age, female sex, and a lower body mass index (BMI) were associated with a positive GBT (Table). A history of diabetes, and a previous gastric surgery (sleeve, or bypass) were associated with a positive test, while proton pump inhibitors (PPI) or opioids intake did not change the outcome (Table). Regarding the symptoms, more severe abdominal bloating and constipation were associated with a positive test (1.28 ± 1.0 vs 1.41 ± 1.1; p=0.02, and 2.67 ± 1.3 vs 2.82 ± 1.2; p=0.03), while abdominal pain and diarrhea were not statistically different (1.57 ± 1.1 vs 1.67 ± 1.1; p=0.07; and 2.23 ± 1.3 vs 2.33 vs 1.4; p=0.14). In multivariate analysis, age (Odds Ratio (OR) = 1.02 [1.01 – 1.03]; p<0.001), BMI (OR=0.93 [0.90 – 0.96]; p<0.001), a previous gastric surgery (OR=9.32 [3.74 – 24.86]; p<0.001) and more severe constipation (OR=0.88 [0.79 – 0.98]; p=0.02) were associated with a positive GBT.

	Negative GBT (n=1797)	Positive GBT (n=576)	p value
Age (years)	44.7 ± 15.5	50.0 ± 16.2	<0.001
Sex (female)	1280 (71.2%)	447 (77.6%)	0.005
BMI (kg/m²)	25.0 ± 5.5	23.9 ± 5.2	<0.001
Diabetes	62 (3.5%)	30 (5.2%)	0.02
Gastric sleeve	8 (0.4%)	14 (2.4%)	<0.001
PPI intake	361 (20.1%)	123 (21.4%)	0.50
Opioids intake	183 (10.2%)	57 (9.9%)	0.91
Irritable bowel syndrome	561 (31.2%)	148 (25.7%)	0.09
Functional dyspepsia	704 (39.2%)	190 (33.0%)	0.08

Conclusion

The result of GBT is more likely to be positive in patients with constipation. A previous gastric surgery is a cofounding factor, leading to a non-interpretable result of the test. A diagnosis of irritable bowel syndrome or functional dyspepsia did not change the result of the test, such as PPI or opioid intake.

References

1. Hammer HF, Fox MR, Keller J, et al. European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United European Gastroenterol J 2022;10:15-40.
2. Pimentel M, Saad RJ, Long MD, et al. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol 2020;115:165-178.

Introduction

The prevalence of functional dyspepsia (FD) and gastroparesis in diabetic patients remains unknown. A high prevalence of gastroparesis has been reported in diabetic patients reaching up to 5%.¹ However, recent consensus specified the symptom pattern for gastroparesis, with nausea and/or vomiting as predominant symptoms, now defined as “gastroparesis-like symptoms” (GPLS).² The global prevalence of GPLS has been estimated to reach only 1.2% in diabetic patients, but type 1 and type 2 diabetes were not assessed separately.²

Aims & Methods

We aimed to assess the prevalence and burden of FD and GPLS in primary care patients with diabetes, comparing patients with type 1 and type 2 diabetes. An online survey was addressed to diabetic patients through general practitioners and diabetic patient associations. The survey included the Rome IV questionnaire and the Patient Assessment of Gastro-Intestinal Disorders-Symptom Severity Index (PAGI-SYM) for upper gastro-intestinal symptoms. Anxiety, depression, somatization, and quality of life were also assessed by specific questionnaires (Generalized Anxiety Disorder GAD-7, Patient Health Questionnaire PHQ-9, PHQ-15, and PAGI-QoL questionnaires respectively).

Results

A total of 216 patients completed the questionnaires, among which 146 had type 1 diabetes, and 68 had type 2 diabetes, (2 patients did not know their type of diabetes). The median age of the population was 56 (50-61) years old, with 134 female patients (61.8%). The prevalence of FD was 13.0% with no difference between the 2 groups. The prevalence of GPLS reached 4.2% and was significantly higher in patients with type 2 diabetes (8.9% vs 2.1%; p=0.03). The burden of upper gastro-intestinal symptoms and their impact on quality of life was higher in type 2 diabetes patients with higher PAGI-SYM and PAGI-QoL scores while anxiety and somatization were not different between type 1 and type 2 diabetes patients (see Table). Overall, patients with GPLS had higher anxiety (9 vs 3; p=0.003), depression (12 vs 3; p=0.001) and somatization scores (16 vs 6; p<0.001) than patients without. Compared to patients with FD without GPLS, GPLS patients had numerically higher but not statistically different scores for symptom severity (51 vs 28; p=0.46), anxiety (9 vs 7; p=0.29), depression (12 vs 7; p=0.07), somatization (16 vs 11.5; p=0.16) and quality of life scores (52 vs 24; p=0.16).

	Type 1 diabetes (n=146)	Type 2 diabetes (n=68)	p value
Age	39 (29–51)	60 (50–67)	<0.001
Sex (female)	99 (67.8%)	35 (51.4%)	0.02
Functional dyspepsia PDS EPS	18 (12.3%) 17 (11.6%) 3 (2.1%)	10 (14.7%) 10 (14.7%) 3 (4.4%)	0.66 0.52 0.38
Gastroparesis-like symptoms	3 (2.1%)	6 (8.9%)	0.03
GAD-7 (Anxiety)	4 (1–6)	3 (0–7)	0.80
PHQ-9 (Depression)	3 (1–7)	3 (1–10)	0.05
PHQ-15 (Somatization)	7 (3.3–10)	8 (4–13)	0.10
PAGI-SYM	6.5 (1–8.8)	9.5 (2–35.5)	0.009
PAGI-QoL	6 (0–15.3)	10 (3–38)	0.003

Conclusion

This study confirms that the prevalence of GPLS seems to be higher in diabetic patients compared to available population data, especially in patients with type 2 diabetes. The impact of the symptoms was similar to the impact of FD in this population. Further studies are required to assess the prevalence of delayed gastric emptying in diabetic type 1 and 2 patients with GPLS.

References

1. Choung RS, Locke GR, Schleck CD, et al. Risk of Gastroparesis in Subjects with Type 1 and 2 Diabetes in the General Population. Am J Gastroenterol 2012;107:82-88.
2. Huang I-H, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J 2022;10:888-897.

Introduction

Infliximab (IFX) is a mainstay in the treatment of Crohn´s disease (CD) and ulcerative colitis (UC)^1,2. However, some patients do not respond to IFX; others develop antibodies to IFX (ATI), resulting in loss of response (LOR) over time^3,4. As second-line treatments for adults are not approved in pediatrics, current ECCO/ESPGHAN guidelines recommend combination therapy with an immunomodulator (IM) to improve response and prevent ATI development.^2,5 Recent studies suggested that combination therapy is not superior to IFX monotherapy if proactive therapeutic drug monitoring (TDM) is performed⁶.

Aims & Methods

We investigated whether recommended early combination therapy has an additional benefit in a proactively managed pediatric IBD cohort. Medical records from 01/2013 to 12/2022 were retrospectively reviewed and children (3-18 years) with at least four doses of IFX, 3-60 months (m) follow-up and proactive TDM were included. Patients were grouped in either early (IM^e: ≤3m since IFX start and duration of IM therapy >6m or until the end of observation) or late/never IM treatment (IM^l/n: >3m since IFX start/no IM combination therapy). Kaplan-Meier analysis and log-rank test (significance level p<0.05) were used to analyze time to LOR with IFX discontinuation or time to ATI development. Hazard ratio (HR) applying Cox regression represents the relative risk of LOR occurring in IM^l/n compared to IM^e.

Results

Of 315 reviewed IBD children, 127 patients were included (43% girls, median age at IFX start: 14 years, 77 CD, 50 UC including 5 IBD-u) and IFX treatment of 2855 visits was analysed. Sixty patients received IM^e (41 CD, 19 UC), 20 patients started IM >3m after IFX (13 CD, 7 UC) and 47 patients had IFX monotherapy (23 CD, 24 UC). Patient characteristics, previous therapies, IFX dosage and intervals were comparable between IM^e and IM^l/n groups (except E2 in UC). Proactive TDM was comparable in both IM^e and IM^l/n, i.e., duration from IFX start to first TL measurement (median of 6 weeks, p=0.9), median number of 4 TL measurements per follow-up year (p=0.6), and median TL of 10 and 11 μg/mL (p=0.6), respectively. Most patients (84%) had a median TL >5µg/ml over time. The median follow-up time was 29.6m for IM^e and 25.5m for IM^l/n.
IFX treatment persistence was 68% after 60m in the total cohort. LOR with IFX discontinuation was observed in 7 IM^e and 15 IM^l/n patients (p=0.2). Combining IFX infusions with IM^e significantly delayed the occurrence of LOR with IFX discontinuation (median LOR free interval IM^e 29.4m, IM^l/n 8.6m, p=0.01). The IM^l/n group was more likely to experience LOR than IM^e after 1, 2, 3, 4, and 5 years (HR₁=10.3, p₁=0.01; HR₂=4.1, p₂=0.02; HR₃=2.9, p₃=0.03; HR₄=2.9, p₄=0.03; HR₅=2.1, p₅=0.09). IM^l/n instead of IM^e increased the risk for LOR, especially in UC patients (HR 7.5, p=0.04).
Low ATI >10AU/ml were found in 76/106 IFX-treated patients, while high ATI >100AU/ml were detected in 10/52 IM^e and 15/54 IM^l/n patients, p=0.2. There was no significant difference regarding median ATI level (both 12AU/ml, p=0.7) and ATI-free interval (9m vs 8m, p=0.65) in the groups. Only in CD patients, IM^l/n showed a significantly higher risk of developing high ATI (HR 4.1, p=0.046) compared to IM^e.

Conclusion

Proactive TDM resulted in high IFX treatment persistence in pediatric IBD. Early combination therapy of IM with IFX showed a significant benefit with improved IFX treatment persistence during the first four years of therapy. This effect was partly explained by preventing high-titer ATI in CD patients.

References

1. van Rheenen, P. F. et al. The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update. J. Crohns Colitis 15, 171–194 (2021).
2. Turner, D. et al. Management of Paediatric Ulcerative Colitis, Part 1 and 2: Ambulatory Care-An Evidence-based Guideline from European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 67, 257–291 (2018).
3. Adedokun, O. J. et al. Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase study. Inflamm. Bowel Dis. 19, 2753–2762 (2013).
4. Vande Casteele, N. et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am. J. Gastroenterol. 108, 962–971 (2013).
5. van Rheenen, P. F. et al. The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update. J Crohns Colitis (2020) doi:10.1093/ecco-jcc/jjaa161.
6. Sandborn, W. J. et al. Treating beyond symptoms with a view to improving patient outcomes in inflammatory bowel diseases. J. Crohns Colitis 8, 927–935 (2014).

Introduction

Fatigue, defined as “an overwhelming sense of tiredness, lack of energy and feeling of exhaustion” [1] is a frequent complaint in celiac disease. A strict, lifelong gluten free diet is the only established treatment for celiac disease, however its long-term effect on fatigue is unknown.

Aims & Methods

Our aims were to investigate the course of fatigue severity and prevalence in celiac patients from diagnosis to five to seven years on a gluten free diet, and to investigate whether diet adherence, disease activity and selected biochemical markers are associated with fatigue.
We conducted a single-center prospective study in 45 patients with newly diagnosed celiac disease. The primary endpoints were fatigue severity, as measured by the Fatigue Severity Scale (FSS) [2], the fatigue Visual Analog Scale (fVAS) [3], and the Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs) [4]. SF-36vs scores were inverted (100 – SF-36vs = inverted SF-36vs) to ease comparison between the other scales, so that higher scores indicate more fatigue. Clinically relevant fatigue was defined by an FSS score of ≥4, a fVAS score of ≥50, and an inverted SF-36vs score of ≥65. Study visits were performed at the time of diagnosis (Visit 1), after adhering to a gluten free diet for one year (Visit 2) and for five to seven years (Visit 3). Diet adherence was evaluated through urinary gluten immunogenic peptides (GIP) and the Celiac Diet Adherence test (CDAT) [5]. Disease activity was assessed through Celiac Symptom Index (CSI) [6], celiac autoantibodies (anti tissue transglutaminase IgA and deamidated gliadin peptide IgG) and histologic evaluation (Marsh score). Nutritional status was assessed through BMI, hemoglobin, 25-hydroxy vitamin D, cobalamin, ferritin and folic acid levels.

Results

Fatigue severity was significantly reduced from time of diagnosis, for all three instruments (Table 1). Fatigue prevalence rates were significantly decreased from Visit 1 (40-53%) to Visit 3 (27-31%). Fatigue was significantly lower in patients with good adherence compared to patients with poor adherence according to CDAT scores (For FSS p=0.022, fVAS p=0.017, and for inverted SF-36vs p=0.033). There was however no difference in fatigue severity between adherent and nonadherent patients when evaluating adherence through urinary GIP. Fatigue was lower in patients in clinical remission according to CSI scores (for FSS p=0.002, fVAS p=0.004, and for inverted SF-36vs p=0.002), but not associated with autoantibodies or nutritional status. In multiple linear regression analysis, depression was the only independent variable significantly associated with all three fatigue measures at Visit 3, whereas pain was positively associated with inverted SF-36vs scores.

Table 1.

Fatigue instrument	Visit 1	Visit 2	Visit 3	Change from Visit 1 to Visit 3 (95% CI)	P-value Visit 1 vs. Visit 3	P-values across three time points (Visit 1, 2 and 3)
FSS	3.7 (2.2-5.0)	1.9 (1.5 - 3.3)	2.3 (1.3 - 4.2)	-0.5 (-1.2 – -0.2	0.012	<0.001
fVAS	45 (16.5-68.5)	15 (9.0 - 41.0)	21 (4.0 - 56.0)	-10 (-23.0 – -3.0)	0.003	0.001
SF-36vs (inverted)	65.0 (40.0-77.5)	30.0 (25.0 - 47.5)	45.0 (30.0 - 70.0)	-5.0 (-10 – 0)	0.006	<0.001

Conclusion

Fatigue remains a frequent complaint in celiac disease even after five to seven years on a gluten free diet. However, fatigue severity is reduced from time of diagnosis. Fatigue was associated with dietary adherence as assessed by CDAT. Disease activity according to CSI was associated with fatigue, whereas nutritional status, autoantibodies and histologic changes were not.

References

1. Krupp, L.B. and D.A. Pollina, Mechanisms and management of fatigue in progressive neurological disorders. Curr Opin Neurol, 1996. 9(6): p. 456-60.
2. Krupp, L.B., et al., The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol, 1989. 46(10): p. 1121-3.
3. Wolfe, F., Michaud K, Pincus T, Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis. J Rheumatol, 2005. 32(7): p. 1261-6.
4. Ware, J.E., Jr. and C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83.
5. Leffler, D.A., et al., A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(5): p. 530-6, 536.e1-2.
6. Leffler, D.A., et al., A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol, 2009. 7(12): p. 1328-34, 1334.e1-3.

Disclosure

Berit Mære Skjellerudsveen: Received lecture honoraria from Takeda for lectures on IBD and pregnancy. This study is partly funded by a grant from the patient organization “The Norwegian Coeliac Society”.