Clinical Case Summary

A 35-year-old woman referred to the emergency department with vomiting, hyporexia, abdominal distension and worsening of her chronic diarrhea.
Laboratory tests revealed neutrophilic leukocytosis (20x10⁹/L), eosinophilia (8.00x10⁹/L) and increased PCR values. The patient was hospitalized and scheduled for further examination:

• CT scan showed intra-abdominal ascites with thickening of some loops of the jejunum.
• Stool tests revealed a C. Difficile infection, which was treated with vancomycin. Calprotectin was in the normal range.
• Esophagogastroduodenoscopy and pancolonoscopy with terminal ileoscopy were within normal limits.
• PET scan revealed an extensive intra-abdominal ascitic effusion with an intense uptake along the jejunum.
• Paracentesis showed an exudate rich in eosinophilic granulocytes and negative for neoplastic cells. Bacterial culture and BK research were negative.

Lastly, a bone marrow biopsy and an anterograde push enteroscopy with biopsies were performed.
The first one showed no signs of myeloproliferative disease, but a normal marrow with an important eosinophilia. On the other hand, the enteroscopy highlited a hyperemic jejunal mucosa without macroscopic lesions. (FIGURE A.)
The histological examination revealed a regular architecture with normal villo/crypt ratio and focally >30x100 intraepithelial enterocytes. (FIGURE B.)
Although not all diagnostic criteria were satisfied for the diagnosis of primary eosinophilic gastroenteritis (diagnostic cut-off limit is >50/HPF), multidisciplinary evaluation diagnosed an idiopathic hypereosinophilic syndrome with prevalent gastrointestinal involvement and steroid therapy (1mg/kg) was started. In just two days of therapy, the blood eosinophils were reduced to normal values and the symptoms were significantly improved.
She has currently tapered steroid therapy to start a treatment with the monoclonal antibody mepolizumab. At latest laboratory tests eosinophils amount to 0.09x10³/µL.

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

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.

Table 1. Agreement of the investigational microarray immunoassay with comparators
tTG: tissue transglutaminase. PPA: positive percent agreement. NPA: negative percent agreement. CI: confidence Interval.
	PPA			NPA
Measurand / Parameter	PPA value (%)	n/N	95% CI	NPA value (%)	n/N	95% CI
tTG IgA	100	61/61	94.1, 100	98.7	456/462	97.2, 99.5
DGP IGA	95.8	69/72	88.3, 99.1	96.5	439/455	94.4, 98
tTG IgG	100	25/25	86.3, 100	97.1	471/485	95.2, 98.4
DGP IgG	95.7	45/47	85.5, 99.5	95.3	448/470	93, 97
Total IgA	100	158/158	97.7, 100	87.5	35/40	73.2, 95.8

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.