Introduction

High resolution manometry (HRM) currently has a marginal role in the diagnosis of gastroesophageal reflux disease (GERD) except for the correct placement of pH-impedance (MII-pH) probes. However, a Manometric Score for Gerd Probability (i.e., the Milan Score) has been recently developed to predict a diagnosis of GERD based on HRM findings prior to pH monitoring studies.

Aims & Methods

In this study, we performed the external validation of the Milan Score in a high-volume tertiary referral center. HRM and MII-pH tracings of consecutive patients reporting GERD symptoms between 2019-2022 were retrospectively reviewed. Clinical, MII-pH, and HRM data were recorded for all patients. Patients with achalasia, body mass index>35 Kg/m^2, previous esophageal surgery, paraesophageal hiatal hernia, eosinophilic esophagitis and scleroderma were excluded. To calculate the Milan Score score, data on diagnosis of ineffective esophageal motility (IEM) according to Chicago Classification v4.0, esophagogastric junction contractile integral (EGJ-CI), EGJ morphology (i.e., type I, II or III), intraesophageal pressure (IEP) during reference ID and straight-leg raise (SLR) pressures were collected. A SLR maneuver was considered positive if >11mmHg. The Milan Score was calculated using the nomogram published in the Milan Score paper (United European Gastroenterology Journal 2024 [1]). Wilcoxon rank sum test, Pearson's chi-squared test and Fisher's exact test were used for comparison. ROC curve analysis was used to calculate the diagnostic accuracy (AUC) of the MSGP score.

Results

Of the 86 included patients, 36 (41.8%) had conclusive GERD based on acid exposure time (AET) > 6%, while 50 (58.2%) had AET<6%. Patients with AET>6% and AET< 6% were comparable in terms of age, weight, regurgitation, chest pain, dysphagia, erosive esophagitis, and HRM diagnosis. Patients with AET>6% more frequently had heartburn (p=0.009), EGJ type 3, MNBI < 1500 Ohms (p< 0.001) and positive symptoms index and symptoms association probability (p=0.007). The median Milan Score was 78 (IQR, 54-132) in patients with AET<6% and 164 (IQR, 125-198) in patients with AET>6% group. Based on ROC curve analysis, a Milan Score higher than 103 was associated with a diagnosis of conclusive GERD (i.e., AET>6%) with AUC of 0.78, with 70% specificity and 80% sensitivity.

Conclusion

The Milan Score has good performance in the diagnosis of GERD upon HRM recording, prior to MII-pH in patients reporting GERD symptoms. The Milan Score proved external validity and can be used as a screening test for GERD in patients undergoing HRM.

Characteristic	AET ≤6%, n = 50 (58%)​	AET>6%, n = 36 (42%)	p-value​​​​​
Ineffective esophageal motility	5 / 50 (10%)	5 / 35 (14%)	0.24
SLR >11mmHg	13/50 (26.0%)	26/36 (72.2%)	<0.001
EGJ-Contractile Index (CI)	42 (28, 55)	27 (13, 42)	0.015
Positive SI/SAP	2 / 50 (4.0%)	9 / 36 (25%)
EGJ type			0.005
1	26 / 50 (52%)	14 / 36 (39%)
2	20 / 50 (40%)	9 / 36 (25%)
3	4 / 50 (8.0%)	13 / 36 (36%)
Total Milan Score​​​​​	78 (54, 132)	164 (125, 198)	<0.001

References

[1] Siboni, S., Sozzi, M., Kristo, I., Boveri, S., Rogers, B. D., De Bortoli, N., Hobson, A., Louie, B. E., Lee, Y. Y., Tolone, S., Marabotto, E., Visaggi, P., Haworth, J., Ivy, M. L., Greenan, G., Masuda, T., Penagini, R., Barcella, B., Coletta, M., Theodorou, D., … Gyawali, C. P. (2024). The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease. United European gastroenterology journal, 10.1002/ueg2.12565. Advance online publication. https://doi.org/10.1002/ueg2.12565

Introduction

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for Irritable Bowel Syndrome (IBS), demonstrating long-term improvements in symptoms and quality of life (QOL). However, its implementation is hindered by the complexity of treatment protocols, high time and financial costs, and limited accessibility in Japan.

Aims & Methods

This study aimed to develop a smartphone-based CBT application and evaluate its effectiveness in alleviating IBS symptoms.
Adults aged 18 or older who met the Rome IV criteria for IBS and scored ≥110 on the Japanese version of the IBS Symptom Severity Index (IBSSI-J) were enrolled. Twenty-six participants were randomly assigned to either the intervention group (n = 14) or the waiting-list control group (n = 12). Outcome measures included the IBSSI-J, Japanese versions of the IBS-QOL (IBS-QOL-J), Pain Catastrophizing Scale (PCS-J), and Visceral Sensitivity Index (VSI-J). A two-way ANOVA was conducted with group (intervention vs. control) and time (pre, mid, post, follow-up 1) as independent variables.
The intervention group used the app for 5–10 minutes daily over two months. The app included three components: psychoeducation, cognitive restructuring, and exposure. Psychoeducation consisted of educational materials and follow-up quizzes. Cognitive restructuring used gamified multiple-choice content (135 items), replacing conventional thought records. Exposure involved users creating individual anxiety hierarchies and recording their thoughts before and after exercises. The app visualized anxiety changes and progress via graphs.

Table 1.
Intervention module of the application

Week	Module	Content
1	Psychoeducation	Introduction to the vicious cycle of IBS symptom exacerbation.
2	Psychoeducation Cognitive-Restructuring	Understanding the link between cognition and symptoms; exploring alternative perspectives.
3	Psychoeducation Cognitive-Restructuring	Explanation of exposure therapy; preparing for symptom-related situations; continued cognitive restructuring.
4	Cognitive-Restructuring Anxiety Hierarchy	Identifying anxiety-provoking situations and planning exposure tasks.
5-8	Exposure	Gradual exposure to selected situations based on the individual anxiety hierarchy.
9	Psychoeducation Summarization	Post-intervention strategies and relapse prevention.

Results

Eleven participants in the intervention group and eight in the control group completed the program. Significant group × time interactions were observed for all outcome measures. For the IBSSI-J, the interaction was significant (F(3, 51) = 4.41, p < .001), with the intervention group showing greater improvement at mid-point (F(1, 17) = 5.54, p = .03, η² = .25). For the IBS-QOL-J, a significant interaction was found (F(3, 51) = 8.00, p < .001), with improvement evident at follow-up 1 (F(1, 17) = 6.65, p = .02, η² = .28). For the PCS-J, the interaction was significant (F(3, 51) = 3.83, p = .02), with improvements at post (F(1, 17) = 9.26, p = .01, η² = .35) and follow-up 1 (F(1, 17) = 5.83, p = .03, η² = .26). For the VSI-J, the interaction also reached significance (F(3, 51) = 3.32, p = .05).

Conclusion

The CBT-based app was effective in reducing IBS symptom severity. Its effects persisted after the intervention and extended to improvements in QOL, visceral anxiety, and pain catastrophizing—psychological factors associated with the maintenance and exacerbation of IBS. It is assumed that the cognitive restructuring component of the app facilitated cognitive diversification among participants. By empirically challenging the plausibility of these diversified cognitions through behavioral experiments in the form of exposure tasks, participants were able to further develop more adaptive thoughts. This process is considered to have contributed to the improvement of symptoms and enhancement of QOL. This digital approach may offer a viable solution to current barriers in CBT access.

Introduction

Cholesterol is a key lipid involved in maintaining intestinal epithelial cell membrane structure and function. Recent studies suggest that microbiome-derived cholesterol metabolites, like ursodeoxycholic acid (UDCA) and 7-ketolithocholic acid (7-keto-LCA) promote intestinal epithelial repair and enhance Wnt signalling, thereby facilitating the self-renewal of intestinal stem cells (Li et al., Cell Host & Microbes 2024).

Aims & Methods

This study aimed to evaluate the effects of cholesterol-derived microbial metabolites—specifically lithocholic acid (LCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), and 7-keto-LCA—on intestinal epithelial barrier integrity, inflammatory responses, and homeostasis. Primary screening was conducted in Caco-2 monolayers co-treated with pro-inflammatory cytokines IFN-γ and TNF-α for 24 hours to mimic an inflammatory environment. Metabolites were tested at the following concentrations: LCA (10 µM, 50 µM, 75 µM), DCA (10 µM, 100 µM, 200 µM), UDCA (100 µM, 250 µM, 500 µM), and 7-keto-LCA (5 µM, 10 µM, 50 µM, 100 µM). Selected compounds showing significant effects were further validated in 3D intestinal epithelial organoid cultures. Gene expression analysis of key markers—TNF-α, CXCL9 (inflammation), OCLN, TJP1 (barrier integrity), and FGF19, NR0B2 (homeostasis)—was performed using quantitative RT-PCR. Statistical significance was determined using Student’s t-test with a threshold of p ≤ 0.05.

Results

Primary screening on Caco-2 cells revealed that 7-keto-LCA (10µM, 50µM) and LCA (75µM) downregulated the expression of genes encoding inflammatory cytokines (TNF-a and/or CXCL9; p < 0.05) and upregulated the expression of tight junction proteins (OCLN and TPJ1; p < 0.05) and FXR downstream marker (FGF19, p < 0.05). The tested concentrations of DCA and UDCA did not reduce the expression of inflammatory cytokine coding genes and reinstate the expression of tight junction proteins coding genes. For further analysis in 3D intestinal organoid model we selected 7-keto-LCA (10µM). 7-keto-LCA significantly upregulated the expression of NR0B2 (p < 0.05) and showed a tendency to reduce the expression of TNF-α in intestinal organoids (p = 0.12).

Conclusion

7-keto-LCA showed a trend to reduce inflammation and restore homeostasis in intestinal organoid model.
Study has been funded by the Research Council of Lithuania (LMTLT, agreement No. S-MIP-23-101).

References

Li T, Ding N, Guo H, Hua R, Lin Z, Tian H, Yu Y, Fan D, Yuan Z, Gonzalez FJ, Wu Y. A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage. Cell Host Microbe. 2024 Feb 14;32(2):191-208.e9. doi: 10.1016/j.chom.2023.12.015.

Introduction

Recent evidence supports diagnosing coeliac disease without biopsy in patients with significantly elevated tissue transglutaminase (IgA-tTG) antibodies. However, the implementation of this no-biopsy approach relies on accurate and consistent serological testing across laboratories. In this nationwide survey, we aimed to evaluate the availability and variability of coeliac disease testing across the United Kingdom.

Aims & Methods

We conducted a cross-sectional telephone survey of biomedical scientists and laboratory managers from NHS trusts and health boards across England, Wales, Scotland, and Northern Ireland. Data collected included assay types, reporting methods, upper limit of normal (ULN) thresholds, turnaround times, total IgA testing, the availability of anti-endomysial antibodies (EMA),

Results

A total of 356 sites were approached, with a 96% response rate (n=342). Of responding sites, 177 performed coeliac serology tests in-house, while 165 transferred samples externally. Among sites performing tests, 12 different tTG assays were identified, with considerable variability in ULN thresholds ranging from 3 to 30 IU/mL, even within laboratories using the same assays. The median turnaround time for IgA-tTG results was 7 days (range 1–21 days). Only 43% of laboratories routinely measured total IgA when IgA-tTG was requested. EMA testing was available in 83% of laboratories.

Conclusion

Significant variability exists in coeliac serology testing across UK laboratories which poses a challenge for the implementation of the no-biopsy approach in clinical practice. Efforts to standardise serological testing are urgently needed. Until such standardisation is achieved, local assay validation remains critical.

Disclosure

MGS and HAP received speaker fees from Thermo Fisher.

Introduction

The aim of this study was to evaluate and to establish cut-off values for two new quantitative ultrasound (QUS) parameters, TSI (tissue scatter-distribution imaging) and TAI (tissue attenuation imaging) in early diagnosis of liver steatosis (LS), as compared to controlled attenuation parameter (CAP).

Aims & Methods

A prospective study was conducted in which LS was assessed in the same session by QUS (Samsung Medison RS85,CA1-7A probe) and CAP (FibroScan Compact M530, M/XL probes). Reliable measurements were defined for CAP the median value of 10 measurements with IQR/M<0.3, and for QUS, five consecutive measurements of TAI and TSI acquired by a color-coded map. TAI and TSI were automatically calculated and considered reliable when reliability index, R²>0.6. The CAP cut-off value used for the whole cohort for at least mild steatosis (S1) were 248 dB/m[1]; for ALD (alcoholic liver disease) cohort, 268 dB/mm[2]; for NAFLD(non-alcoholic liver disease) cohort 294dB/m[2]. Demographic and health related datas were recorded.

Results

A total of 285 patients, with a mean age of 56.1±12.4, 114 female and 171 male, were included in the study. According to aetiology, 164 (57.5%) patients had NAFLD, 61(21.4%) ALD, and 60 (21.1%) were other etiologies (viral, cardiac, autoimmune). The obtained TSI and TAI cut-off values for the diagnosis of at least mild steatosis (S1) are presented in Table 1.
Table 1. Cut-off values of TAI and TSI for S1

Variable		Overall	NAFLD	ALD
TSI	S1	>96.2 AUC=0.74,p<0.0001, Se=87.9%,Sp=53.0%;	>96.5 AUC=0.73, p<0.0001, Se=90.9%, Sp=47.9%;	>94.9 AUC=0.70, p=0.003 Se=72.9%,Sp=75.0%;
TAI	S1	>0.73 AUC=0.82,p<0.0001, Se=78.3%,Sp=71.6%;	>0.75 AUC=0.81, p<0.0001, Se=57.5%, Sp=90.8%;	>0.66 AUC=0.74, p<0.0001, Se=84.8%,Sp=57.1%;

There were no differences between the performance of TAI and TSI according to the DeLong test, p=0.18 and p=0.24. A strong direct correlation was observed between TAI and CAP r=0.701, moderate between TSI and CAP r=0.56 for the all cohort, but for NAFLD and ALD subgroups moderate correlations were found between TAI and CAP r=0.66, and r=0.66 respectively and TSI and CAP r=0.56 and 0.66, respectively.
In univariate regression analysis, the factors associated with TSI were hypertension, Diabettes mellitus(DM), and obesity, and all p-values were <0.0001, but in multivariate analysis, only hypertension(p=0.001) and obesity(p=0.0005) were associated. For TAI, in univariate analysis, the same factors: hypertension(p=0.004), obesity(p=0.0006) and DM (p=0.002) were associated, but in multivariate analysis, DM was the only factor associated, p=0.02. Age and gender were not correlated with any method, TSI or TAI.

Conclusion

TAI and TSI are feasible non-invasive methods for screening and diagnosis of liver steatosis, with good accuracy. Patients with NAFLD presented highest cut-off values, probably by the presence of DM and obesity, conditions independently associated with TAI and TSI values.

References

1.Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen Vet al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017 May;66(5):1022-1030. doi: 10.1016/j.jhep.2016.12.022. Epub 2016 Dec 28. PMID: 28039099.
2. Petroff D, Blank V, Newsome PN, Shalimar, Voican CS, Thiele M, et al. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol. 2021 Mar;6(3):185-198. doi: 10.1016/S2468-1253(20)30357-5. Epub 2021 Jan 16. PMID: 33460567.