Introduction

Based on the Chicago classification, HREM diagnosis is classically based on metrics obtained with wet swallows carried out in the supine position. However, both patients and physicians often feel that this is not a physiological position to conduct the test as it may not translate to the real world experience. With the patient in the upright/sitting position, the test would more closely simulate real-life behaviour and may be safer for elderly patients at risk of aspiration.

Aims & Methods

In an Asian tertiary centre, a total of 104 patients had undergone high resolution esophageal manometry (HREM) with retrospective data analysis comparing both conventional supine position with the upright position. The latter is generally favoured by all patients as this represents the physiological posture during meals.

Results

Using 2-tailed paired sample T-test, comparison across all cases showed a consistently lower median Integrated Relaxation Pressure (IRP) [6.0 mmHg vs to 8.7 mmHg; p <0.01] and lower mean Distal Contractile Integral (DCI) [1463 mmHg/cm/sec vs 1864 mmHg/cm/sec; p =0.014] in the upright posture compared to supine position although the mean Distal Latency (DL) difference was not significant [6.21secs vs 6.27 secs; p =0.491]. During upright and supine position comparison respectively, subgroup analysis on subjects with normal HREM diagnosis showed even lower median IRP [4.9 mmHg vs 7.5 mmHg; p <0.01] and lower mean DCI results [1436 mmHg/cm/sec vs 1695 mmHg/cm/sec; p <0.01] with mean DL in this subgroup showing no significant statistical difference [6.29 secs vs 6.38secs; p=0.545]. The final HREM diagnosis in upright position is concordant with the conventional supine position up to 81.7% and showed an even higher concordance in terms of management similarity up to 98.1%. Only 2 cases (2/104) showed a significant discordance between supine and upright HREM diagnosis [normal HREM vs esophagogastric juntion –outflow obstruction(EGJ-OO) and hypercontractile esophagus vs normal HREM]. Minor diagnostic discordance [normal HREM vs ineffective esophageal motility (IEM)] was noted in 17/104 cases which had no major clinical impact on patients and may be overcome by adopting a lower cut-off for mean DCI for upright group.

Conclusion

In patients who are unable to perform HREM in supine position, adopting the upright position shows a high clinical concordance and may be considered a more physiological approach in the HREM protocol.

References

Riva CG, Siboni S, Ferrari D, Sozzi M, Capuzzo M, Asti E, Ogliari C, Bonavina L. Effect of Body Position on High-resolution Esophageal Manometry Variables and Final Manometric Diagnosis. J Neurogastroenterol Motil. 2020 Jul 30;26(3):335-343. doi: 10.5056/jnm20010. PMID: 32606256; PMCID: PMC7329148.

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.

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

While wide-scale screening for celiac disease (CeD) is increasingly being considered, its overall benefits are not well established.

Aims & Methods

We investigated the general health at diagnosis and long-term outcomes in CeD patients identified through screening in a population-representative cohort. Comprehensive health data from individuals participating in the nationally representative Health 2000 survey (N=6,376) were analyzed using registry data and interviews. Additionally, blood was collected to measure tissue transglutaminase antibodies (TGA) and endomysial antibodies (EmA) if TGA was positive, as well as other laboratory parameters. Altogether, 3254 subjects participated in a follow-up study in 2011. Mortality among subjects in the Health 2000 cohort was evaluated at the 17-year follow-up using the national statistics registry.

Results

Ninety CeD patients were identified in 2000, of whom 54 participated in the follow-up in 2011 while on a gluten-free diet. At diagnosis, patients more often had pre-eclampsia (13% vs. 5%, p=0.016), and lower levels of hemoglobin (median 140 vs 143 g/L, p=0.046), ferritin (29 vs 68 ng/mL, p<0.001), total cholesterol (5.4 vs 5.9 mmol/L, p<0.001), apolipoprotein A1 (1.40 vs 1.57 g/L, p<0.001) and apolipoprotein B (1.16 vs 1.21 g/L, p=0.009) compared to seronegative population. The groups did not differ in age (48 vs 51 years, p=0.159), sex (females 62% vs 56%, p=0.205), BMI (26 vs 26, p=0.567), blood pressure (131/81 mmHg vs 132/82 mmHg, p=0.230), or the presence of other gastrointestinal diseases, cardiovascular and psychiatric diseases, osteoporosis, malignancies, or smoking and alcohol consumption. No significant changes in cholesterol or apolipoprotein levels, mental health, or health care utilization were observed among CeD patients during the 11-year follow-up. The patients had a lower mortality rate compared to non-CeD individuals after 17 years with borderline significance (14.1% vs. 25.6%, p=0.059).

Conclusion

Population-representative individuals with screen-detected celiac disease exhibit a more favorable metabolic profile, but have lower hemoglobin and iron levels and a higher prevalence of pre-eclampsia at diagnosis. Gluten-free diet does not appear to cause adverse effects. Screen-detected patients may also have a reduced long-term mortality, although further research is needed.

Introduction

Celiac disease, a chronic autoimmune enteropathy caused by exposure to gluten in genetically predisposed individuals, is characterized by a broad clinical spectrum often with multisystem involvement. Symptoms related to the reproductive system include delayed menarche, early menopause, fertility disorders, miscarriages, and prematurity.

Aims & Methods

To study the impact of celiac disease on fertility in a female Greek population. A retrospective review of all patient records from the celiac disease outpatient clinic at our hospital.

Results

Medical histories of 231 female patients were reviewed (69% of the total patient population) with a mean age of 44.3 years and a mean age at diagnosis of 35.3 years. The mean age of menarche was 12.7 years. Menstrual irregularities were reported in 27% (20% instability, 7% dysmenorrhea). A total of 28% (65/231) were in menopause, with an average age of menopause onset at 50.7 years. A history of miscarriages was recorded in 15% of all women (35/231), but in 29% of women in menopause (19/65). 82% (53/65) of women in menopause had children, with 98% (52/53) having been pregnant before the diagnosis of the disease. Among all women who gave birth, only 12/113 (11%) had been diagnosed before pregnancy. 56% (63/113) and 44% (50/113) had a vaginal delivery and cesarean section, respectively. Pregnancy complications were recorded in 24 women (18 preterm births, 15 low birth weight infants, 1 intrauterine death).

Conclusion

Women with celiac disease tend to have relatively late menarche and an increased rate of miscarriages. However, the disease does not seem to significantly affect fertility.

References

1.Ehud Galron MD, Rayna Boyarsky MD,Ido Sold MD, Chen Ben David MD,and Eyal Gal MD,Interactions between celiac disease and pregnancy:A literature review, Isr Med Assoc J.2023 Dec;25(12):830-835
2.Giovanni Casella et. Al. Celiac disease and obstetrical-gynecological contribution, Gastroenterol Hepatol Bed Bench. 2016 Autumn; 9(4): 241–249.
3.Stephanie M. Moleski et. Al., Increased rates of pregnancy complications in women with celiac disease, Annals of Gastroenterology (2015) 28, 236-240
4.Nafeesa N. Dhalwani et Al., Women With Celiac Disease Present With Fertility ProblemsNo More Often Than Women in the General Population, Gastroenterology 2014;147:1267–1274

Introduction

Anti-tissue transglutaminase IgA antibodies (tTG) are used in the follow-up of celiac disease (CD) to assess adherence to a gluten-free diet (GFD). Persistent positivity may indicate the need for histological reassessment. There is limited information about the rate of complete normalization of tTG and associated factors. Our objective was to evaluate the percentage, kinetics, and factors related to tTG normalization.

Aims & Methods

This was a retrospective observational study including patients with tTG testing at diagnosis and follow-up monitoring of these antibodies from 1991 to 2023 in a specialized unit dedicated to patients with CD. Inclusion criteria were: patients over 16 years of age at diagnosis, initially elevated tTG titres, and at least one serological follow-up after starting a GFD. Time to tTG normalization was estimated using the Kaplan-Meier method. Comparisons between groups were performed using the log-rank test. The association between demographic and clinicopathological characteristics at diagnosis and time to tTG normalization was assessed using Cox regression analysis.

Results

A total of 179 patients were included (75% female, mean age 40 ± 16 years). Duodenal atrophy was present in 81%, and 79% had symptoms. 83% strictly adhered to a GFD. Median follow-up was 3 years. The incidence rate of tTG normalization was 35% per patient-year. The cumulative tTG normalization rate was 38% (95% CI: 30-45) at 1 year, 61% (53-69) at 2 years, 70% (63-77) at 3 years, 80% (73-87) at 4 years, 81% (74-89) at 5 years, and 95% (88-100) at 10 years. The median time to tTG normalization was 24 months (95% CI: 20–28). Table 1 shows Kaplan–Meier estimates expressed as percentages of tTG normalization by adherece to GFD and baseline tTG. In the multivariable analysis, two factors were found to be significantly associated with the normalization of tTG: lower baseline tTG and good adherence to a GFD. Regarding baseline tTG level, patients with titres ≤ 286 U/ml (median) had 2.46 times higher likelihood of antibody normalization compared to those with higher titres (HR: 2.46; 95% CI: 1.69–3.56; p < 0.001). Regarding adherence to a GFD, patients who followed a strict GFD had 5.38 times higher likelihood of tTG normalization (HR: 5.38; 95% CI: 2.79–10.36; p < 0.001).

Table 1. Kaplan–Meier estimates expressed as percentages of normalization (with 95% CIs) after CD diagnosis, by adherece to GFD and baseline tGA titres.

Conclusion

1. The incidence rate of tTG normalization in CD patients after initiating a GFD was 35% per patient-year of follow-up.
2. In the long-term (10 years), 95% of CD patients achieved tTG normalization.
3. Lower tTG titres at diagnosis and good adherence to the GFD were predictive factors for tTG normalization.
4. Understanding the kinetics of tTG normalization according to various factors is essential before considering histological reassessment for suspected poor disease progression.

Introduction

Nanoparticles containing gliadin (TAK-101) are under development to induce gliadin tolerance in patients with celiac disease (CeD). We assessed the immunomodulatory signature induced by TAK-101 treatment in a mouse model of CeD.

Aims & Methods

Human leukocyte antigen (HLA)-DQ8 transgenic mice were intravenously pretreated on Days −11 and −3 with 2.5 mg TAK-101 or were not pretreated (‘gliadin immunization-only’). Animals were then immunized with gliadin on Day 0 and boosted on Day 14. Mice from both groups were sacrificed after 1month. After sacrifice, spleen cells were cultured for 3 days with gliadin, and supernatant cytokine and antigliadin IgG2c antibody levels assessed. Single cell RNA-Seq was performed on cultured spleen cell samples from both groups (n=4).

Results

Production of complement-fixing anti-gliadin IgG2c and pro-inflammatory cytokines, including interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor α (TNFα), IL-17, IL-6 and IL-22 was reduced in splenic cells of TAK-101-treated relative to gliadin immunization-only mice. Differential expression of 1380 genes was demonstrated in B cells following TAK-101 treatment relative to gliadin immunization-only, confirming earlier results from bulk RNA-Seq, including of fractionated B cells. Transcriptomic changes in B cell activation, signaling, proliferation and apoptosis pathways (Gene Ontology) were significantly associated with TAK-101 treatment, while manually curated pathways for B cell anergy and regulatory B cells also matched the identified gene signature.

Conclusion

B cells appear to be important for the immunomodulation of the adaptive gliadin immune response by TAK-101.