Introduction

Vitamin D levels are associated with important clinical parameters and outcomes in patients with IBD. However, the complex interplay of inflammation with vitamin D (vitD) and its metabolites poses a vicious circle in which cause and effect are unclear. We previously showed that all vitD metabolites, including 1,25OH2D, 24,25OH2D, free and bioavailable 25OHD and VDBP, but not total 25OHD, were influenced by at least one inflammatory marker.

Aims & Methods

In this study, we aimed to assess effects of vitD supplementation on serum levels of vitD metabolites and VDBP in patients with IBD with and without inflammation. A comparative, cross-sectional retrospective study was conducted using medical records and routine samples of IBD patients and controls. Blood count, serum albumin, transferrin, ESR, hsCRP and faecal calprotectin (FC) concentrations were analysed. Inflammatory disease activity was defined as hsCRP ≥5mg/dL and/or FC ≥250μg/g. Serum total 25OHD and 24,25OH2D levels were measured using ImmuTube® VitD duo LC-MS/MS (Immundiagnostik AG, Bensheim, Germany). Concentrations of 1,25OH2D and VDBP were detected with direct competitive ELISA using the IDK® human VDBP immunoassay kit (Immundiagnostik AG). Free and bioavailable 25OHD were calculated according to Bikle et al. Subjects were treated with 20,000 IU cholecalciferol p.o. in different frequencies based on severity of vitD insufficiency/deficiency: Patients with 25OHD levels of 21-29ng/mL 1x/wk for 2 weeks; those with 25OHD levels 11-20ng/mL 2x/wk for 2 weeks; those with 25OHD levels ≤10ng/mL 3x/wk for 1 week and 2x/wk for 2 weeks. In each case, therapy was followed by 2 therapy-free weeks. Statistical data were collected in Microsoft Excel 2016 and analyzed with IBM SPSS Statistics 25, p<0.05 was taken to be statistically significant.

Results

Overall, 265 subjects were included, 68 in the control group (27m/41f; age range 18-65y; mean age (±SD) 42.9±15.6y) and 197 patients with IBD (96m/101f; 18-65y; 42.3±13.0y; 115 Crohn’s disease, 82 ulcerative colitis). Inflammatory disease activity was seen in 96/197 (49%). No significant difference was found for season of blood sampling (with vs. without inflammation: p=0.468, IBD pats vs. controls: p=0.613; chi-square test for all results). As expected, vitD supplementation resulted in a significantly increased serum 25OHD, 24,25OH2D, free 25OHD and bioavailable 25OHD. Interestingly, vitD supplementation did not affect levels of VDBP or 1,25OH2D. After correlation coefficients were calculated, neither specific correlation nor statistical significance was observed between vitD parameters and ESR or FC. Also, no correlation was seen between hsCRP and serum 25OHD, 1,25OH2D, and 24,25OH2D regardless of vitD supplementation. However, for both supplemented (r=0.481, p<0.001) and non-supplemented groups (r=0.421, p<0.001), a significant moderate positive correlation was found for VDBP with hsCRP. Serum free 25OHD (r=-0.496, p<0.001; r=-0.450, p<0.001 respectively in supplemented and non-supplemented groups) and bioavailable 25OHD (r=-0.532, p<0.001; r=-0.497, p <0.001, respectively) showed a significant moderate negative correlation with hsCRP in both groups.

Conclusion

The vitD parameters VDBP, free vitD and 25OHD were primarily influenced by the presence of inflammation. The significant increase in VDBP observed in the presence of inflammation was uninfluenced by vitD supplementation. Since hsCRP and VDBP positively correlated, VDBP may have potential as a biomarker for inflammatory processes.

Disclosure

Julia Stötzel and Lea Tessmer have nothing to disclose.
Aysegül Aksan is an employee of Immundiagnostik AG, Bensheim, Germany.
Oliver Schröder: Lecturing fees: Abbvie, Falk, Janssen, Takeda, Norgine and Pfizer. Congress expenses: Falk, Pfizer.
Jürgen Stein: Consulting: Abbvie, Bristol Myers Squibb, Dr Schär, Falk, Ferring, Fresenius Kabi, Immundiagnostik, Janssen, Medice, MSD, Pfizer, Pharmacosmos, Shire, Takeda, Thermofisher, Vifor. Board member: Abbvie, Bristol Myers Squibb, Dr Schär, Ferring, Fresenius Kabi, Immundiagnostik, Janssen, MSD, NPS, Pharmacosmos, Takeda, Vifor and Shield. Lecturing fees: Vifor Pharma

Introduction

Chronic mesenteric ischemia (CMI) is a condition in which the mesenteric blood flow fails to meet the increased metabolic demands (1), mostly caused by atherosclerotic stenosis of the mesenteric arteries. This leads to severe postprandial abdominal pain, resulting in fear of eating and subsequent weight loss. According to the European Guidelines(2), a significant stenosis is defined as a luminal diameter reduction of ≥50% in multivessel disease and ≥70% in single-vessel disease. In the absence of a gold standard diagnostic test, treatment decisions rely on multidisciplinary consensus, which is reached based on the patient’s clinical history, presence of a significant stenosis on computed tomography angiography (CTA) and in case of single-vessel disease a functional test. The definitive diagnosis CMI is confirmed after revascularization by patient reported symptom reduction. However, prior research report clinical improvement in only 69-73%(3), suggesting possible overtreatment. Currently, radiologists manually grade a stenosis by measuring the luminal diameter reduction on cross-sectional slices. Yet, other morphological features, such as stenosis length and shape(4-6), also influence blood flow. Three-dimensional (3D) analysis of mesenteric stenosis may better reflect the hemodynamic and clinical relevance of a mesenteric artery stenosis. 3D-analysis using semi-automated segmentation tools, such as 3D Slicer, allows for more comprehensive evaluation, including cross-sectional area reduction. This study aims to compare the positive predictive value (PPV) and negative predictive value (NPV) of diagnosing definitive CMI by using semi-automated 3D segmentation based on area reduction versus the conventional luminal diameter reduction-based grading performed by radiologists.

Aims & Methods

This multicenter, retrospective study analyzed baseline CTA scans from 94 patients (CoBaGI trial 2015-2019) with a consensus diagnosis of atherosclerotic CMI who underwent endovascular treatment. The CoBaGI trial(7) was a randomized controlled trial comparing the patency of bare-metal and covered stents. Of this cohort, 72 patients had a definitive diagnosis CMI compared to 22 non-CMI patients. CTA scans were excluded if there was no arterial phase, low image quality or if centerline extraction failed. Stenoses were segmented semi-automatically by using 3D Slicer. The centerline curves of the celiac artery (CA) and superior mesenteric artery (SMA) were extracted, and minimum and maximum diameters and cross-sectional areas were measured. Diameter reduction and area reduction were calculated and used to compute the PPV and NPV for the definitive diagnosis CMI for each grading method.

Results

Of the 94 baseline CTA scans, 53 CTA scans were eligible for analysis (36 definitive CMI patients, 17 non-CMI patients). The PPV for diameter reduction graded by radiologists was 0.72 (95% CI 0.56 - 0.82), compared to 0.78 (95% CI 0.63 - 0.89) for 3D segmentation. The NPV was 0.50 (95% CI 0.24 - 0.76) for diameter reduction graded by radiologists compared to 0.56 (95% CI 0.33 - 0.77) for 3D segmentation. When applying a threshold of 75% area reduction, the PPV improved to 0.79 (95% CI 0.65 - 0.89), and the NPV to 0.80 (95% CI 0.49 - 0.94).

Conclusion

Grading a mesenteric artery stenosis by using 3D-segmentation with area reduction provides a higher PPV and NPV for diagnosing definitive CMI compared to the conventional diameter reduction based grading. These findings suggest that incorporating 3D-segmentatons could improve patient selection for revascularization and reduce unnecessary procedures.

References

1. Moawad J, Gewertz BL. Chronic mesenteric ischemia. Clinical presentation and diagnosis. Surg Clin North Am. 1997;77(2):357-69.
2. Terlouw LG, Moelker A, Abrahamsen J, Acosta S, Bakker OJ, Baumgartner I, et al. European guidelines on chronic mesenteric ischaemia - joint UEG, EAGEN, ESGAR, NVMDL, HSG, CIRSE and DMIS clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia. United European Gastroenterol J. 2020;8(4):371-95.
3. van Dijk LJD, Moons LMG, van Noord D, Moelker A, Verhagen HJM, Bruno MJ, Rouwet EV. Persistent symptom relief after revascularization in patients with single-artery chronic mesenteric ischemia. J Vasc Surg. 2018;68(3):779-85.
4. Mustapha N, Mandal P, Johnston P, Norsarahaida A. A numerical simulation of unsteady blood flow through multi-irregular arterial stenosis. Applied Mathematical Modelling, 34, pp 1559-1573. 2010;34.
5. Sriyab S. The Effect of Stenotic Geometry and Non-newtonian Property of Blood Flow through Arterial Stenosis. Cardiovasc Hematol Disord Drug Targets. 2020;20(1):16-30.
6. Kamangar S, Badruddin I, Ahammad N, Kalimuthu G, Nik Ghazali NN, N.J S, et al. The Influence of Geometrical Shapes of Stenosis on the Blood Flow in Stenosed Artery. Sains Malaysiana. 2017;46:1923-33.

Introduction

Autoantibody detection is a cornerstone in the evaluation of Celiac Disease (CD); however, there is a limited offer of multiplexed testing devices.

Aims & Methods

We assessed the analytical performance of a novel, single-use, multiplexed microarray immunoassay (MosaiQ AiPlex^® CD microarray. AliveDx, Switzerland), used with its fully automated high-throughput proprietary system, for the qualitative detection of total IgA and semiquantitative detection of autoantibodies (IgA and IgG isotypes) against tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP), compared with selected devices. The study was conducted at two sites. Site 1: North East Innovation Lab (The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK), Site 2: AliveDx (Eysins, Switzerland). Included human serum samples were banked, de-identified and tested using the investigational device after characterization as reactive or non-reactive to the respective measurand by Phadia AB assays: tTG IgA (EliA Celikey tTG IgA), tTG IgG (EliA Celikey tTG IgG), DGP IgA (EliA Gliadin^DP IgA) and DGP IgG (EliA Gliadin^DP IgG). Comparator for total IgA was Tina-quant IgA Gen.2 (Roche Diagnostics Gmbh). Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. Double-sided 95% Confidence Interval (CI) were calculated using Clopper-Pearson Exact Method.

Results

Compared with the respective devices (equivocal results excluded), the investigational microarray showed PPA ranging from 95.7% to 100% and NPA ranging from 87.5 to 98.7%. Table 1 shows the performance of the individual measurands.

Conclusion

The investigational microarray immunoassay showed high level of agreement with the compared singleplex devices, providing laboratorians and clinicians with unified results coming from one multiplexed device. This platform has the potential to assist in the simplification of CD evaluation by simultaneously and automatically analyzing key serological markers.

Disclosure

This study was funded by AliveDx Suisse SA, Eysins, Switzerland. Gerber Gomez, Jose Santiago, Ewa Garyga, Rocio Pasion-Galvan, Helen Laird, Mark Hooper, Susan Seaton, Anthony Yau, Christian Fischer are AliveDx employees.

Introduction

Celiac disease is a chronic disease that requires lifelong treatment with a strict diet, which has an impact on the health-related quality of life of the patients.

Aims & Methods

To analyse the quality of life in patients with celiac disease that are followed in our centre.
A single-center, prospective, observational study based in the Spanish version of Celiac Disease Quality of Life Survey (CD-QOL), a validated questionnaire.

Results

53 patients agreed to complete the questionnaire. Mean age of the patients at the moment of the consultation was 39.15 years, while mean age at diagnosis of the patients who agreed to participate was 33.20 years. Of them, 35.8% had university degree, 28.3% completed professional training and 35.8% only had compulsory basic education.
Of these patients, 69.2% didn’t have any relative diagnosed with celiac disease, and only the 13.2% used to live with another celiac patient. Just 9.4% of the patients who filled in the questionnaire were members of a celiac patient society.
75.5% of the patients claimed that celiac disease affects their social life, 84.9% declared that they comply properly with the gluten-free diet, although for the 32.7% the adherence to the dietary treatment is difficult.
Of the patients who participated, 33.9% declared that they feel quite / a lot limited by the disease, 27.4% feel quite / much stigmatized because of the illness, 22.7% have quite / a lot of problems in their social life, 32.2% have quite / a lot difficulties travelling, and 22.7% of patients declared that they have quite / a lot the impression to not have a normal life.

Conclusion

1. Celiac disease may be quite burdensome even in asymptomatic patients who are not supposed to have small bowel damage in their follow-up. According to our series, up to 75.5% of patients have problems in their social life.
2. Health education during the follow-up providing greater knowledge of the disease, support from specialized nurses, and the recommendation to join patients support groups (patient societies) could be tools that may empower celiac patients to help manage their disease and enjoy a normal life.

References

1. Al-Toma A, Volta U, Auricchio R, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J 2019;7(5):583-613.
2. Casellas F, Rodrigo L, Molina-Infante J, et al. Transcultural adaptation and validation of the Celiac Disease Quality of Life (CD-QOL) Survey, a specific questionnaire to measure quality of life in patients with celiac disease. Rev Esp Enferm Dig 2013; 105(10):585-93.

Introduction

Detection of autoantibodies directed to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) is important in the assessment of individuals under clinical suspicion of celiac disease (CD).

Aims & Methods

In this study, we compared the analytical performance for the detection of autoantibodies to tTG (IgA isotype), of the MosaiQ AiPlex^® CD microarray (AiPlex CD. AliveDx, Switzerland), a CE-marked, novel, single-use, fully automated, multiplexed microarray immunoassay and routine methods. De-identified serum samples, characterized as reactive or non-reactive for tTG IgA as per the routine practice method of the evaluation site (EliA™ Celikey^® IgA, Phadia AB, Sweden), were tested with the evaluated device. Although AiPlex CD features the semi-quantitative measurement of both tTG IgA and IgG and anti-deamidated gliadin peptide (DGP) IgA and IgG antibodies, and qualitative measurement of total IgA in serum; this comparison was limited to tTG IgA as no samples characterized for other CD autoantibodies were available. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated. Double-sided 95% Confidence Intervals (CI) were calculated using Clopper-Pearson Exact Method.

Results

77 samples characterized as reactive for tTG IgA by the routine method and 90 samples characterized as non-reactive for this marker were included in the analysis. The evaluated device identified 73 out of 77 samples characterized as reactive by the routine method, for a PPA of 95% (95% CI: 87.2, 98.5). Out of the four discordant samples, one also yielded a non-reactive result for tTG IgG and reactive results for both DGP IgA and IgG in the evaluated device and negative anti-endomysial antibodies (EMA) by immunofluorescence; two samples were reactive to DGP IgA or DGP IgG by the evaluated device and one sample was non-reactive to all four markers and was negative to EMA. Regarding the samples characterized as non-reactive by the routine method, the evaluated device identified 86 out of 90, for an NPA of 96% (95% CI: 89.0, 98.7). For the four samples with discordant results, the evaluated device also yielded reactive results for at least one additional CD antibody (tTG IgG, DGP IgA, DGP IgG).

Conclusion

In this study, the evaluated microarray immunoassay showed high concordance with the compared routine method for the serological assessment of tTG IgA, a key marker in the evaluation of CD.

Disclosure

This study was funded by AliveDx Suisse SA, Eysins, Switzerland. Gerber Gomez and Christian Fischer are AliveDx employees.

Introduction

Vit D is a known immunomodulator and is essential in maintaining immune balance as well as controlling processes observed in inflammatory disorders like ulcerative colitis (UC) [1,2].

Aims & Methods

Aim: We previously completed a study looking at the effect of vitamin-D on Crohn's disease activity and noted a marginal beneficial effect. In this study, we sought to investigate the association between Vitamin D (VitD) levels and Ulcerative Colitis (UC) activity in the Emirati patient population of the United Arab Emirates (UAE).
Methods: We designed a retrospective cohort study using a sample population of patients (16-85 years) with UC, who were followed for at least one year in the Division of Gastroenterology at our tertiary care center in Abu Dhabi, between January 2021 and October 2023. Demographics were collected on patients retrospectively identified in the EMR. Eligibility criteria were applied that included patients who had their VitD levels recorded at baseline and whose disease outcomes were measured between 1-12 months post-baseline visit. VitD was documented as a continuous variable and dichotomized into low vs. adequate level categories. The primary outcome was clinical disease activity measured dichotomously. Summary statistics were calculated. Unadjusted logistic regression analysis was employed to examine the association between VitD level as a continuous variable and when categorized into low vs. adequate levels on clinical disease activity in UC. Multivariable logistic regression looked at the independent effect of VitD levels by adjusting for covariates of effect size >20%. Statistical analysis was performed using R (version 4.0.2) and a p-value of <0.05 was considered statistically significant. IRB approval was in place for this study.

Results

We identified 89 patients with UC. Of these, 75 met our eligibility criteria, out of which 47 had their Vit D levels recorded at baseline, and 18 were noted to be deficient. 34 (45%) were women. The mean age of the cohort was 36 years. Detailed summary statistics were done. Unadjusted logistic regression analysis revealed that VitD did not appear to impact disease activity. However, in the multivariable logistic regression analysis, when the model was adjusted for variables with an effect size of greater than 20% (age, BMI, duration of disease, steroid use), a marginal association between VitD as a continuous variable and active clinical disease was observed (OR 0.96 95%CI 0.93-0.99 P=0.039).

Conclusion

This is the first study looking at the impact of VitD on Emirati patients with UC. While there are previous studies in other cohorts that have suggested an association between VitD level and disease activity in UC, it appears that having adequate VitD levels, similar to our experience with Emirati patients with CD has a positive effect. The results of this study highlight the need for IBD practices in the UAE to consider VitD level sampling at baseline and replacement when necessary but discourage the frequent use or overuse of VitD testing in the UC population in the UAE.

References

1.Gubatan, J., Mitsuhashi, S., Longhi, M. S., Zenlea, T., Rosenberg, L., Robson, S., & Moss, A. C. (2018). Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis. Cytokine, 103, 38–45. https://doi.org/10.1016/j.cyto.2017.12.023
2.Dash, K. R., Panda, C., Das, H. S., Mishra, D., Behera, S. K., Parida, P. K., & Mohapatra, D. (2021). Association of Vitamin D Level With Disease Severity and Quality of Life in Newly Diagnosed Patients of Ulcerative Colitis: A Cross-Sectional Analysis. Cureus, 13(7), e16481. https://doi.org/10.7759/cureus.16481