Introduction

Coeliac disease (CeD) is an autoimmune enteropathy of the small intestine triggered by gluten. Some clinical studies comparing CeD patients to healthy controls have suggested that CeD is a cardiovascular risk factor. In this study, we aimed to investigate the cardiovascular effects of CeD in a humanized CeD mouse model, focusing on vascular inflammation, endothelial dysfunction, and oxidative stress (in relation to intestinal inflammation), which are known triggers for later cardiovascular diseases and their mechanistic causes.

Aims & Methods

NOD-human DQ8 transgenic mice with genetic deletion of the murine MHCII complex (NOD-DQ8 mice), genetically predisposed to CeD, were raised on a zein (corn)-protein-based, gluten-free diet. Gluten sensitization was performed by 3 oral gavages of pepsin-trypsin digested and TG2 deamidated gliadin (500 µg) and cholera toxin (25 µg), concomitant with the feeding of a gluten-containing diet (gliadin group) for 14 days. A control group continued the gluten-free diet during sensitization with zein. An additional group was returned to a gluten-free diet for another 14 days to assess the reversibility of CeD and cardiovascular effects. Small animal transthoracic echocardiography (TTE) as well as non-invasive blood pressure measurements were performed. Vascular function was tested by isometric tension recording. Aortic, cardiac, perivascular adipose (PVAT) and duodenal tissue were used for qRT-PCR, dot blotting, Flow Cytometry or IHC to determine the extent of vascular and intestinal inflammation as well as (nitro-)oxidative stress. Plasma proteomics was performed using Olink.

Results

As in human CeD, gluten-challenged NOD-DQ8 mice developed a duodenal and jejunal infiltration of intraepithelial T-lymphocytes (IELs) and a reduction in the villus/crypt ratio. Tail-cuff measurements showed increased blood pressure in these mice compared to the controls. Endothelium-dependent (ACh) and -independent (NTG) vascular relaxation was impaired, as tested by isometric tension measurements, and transcripts of pro-inflammatory genes (Il6, Infy, Tnfa, Cybb-Nox2, Nos2-iNos) were upregulated in the duodenum and aorta. Flow cytometry revealed increased CD11b+ myeloid cell infiltration into the aortic wall in gluten-challenged NOD-DQ8 mice. Additionally, oxidative stress parameters 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE) were elevated in the heart tissue, as demonstrated by dot-blot analysis. However, cardiac function remained unimpaired, as assessed by TTE. To investigate the inflammatory gut-vascular connection, plasma proteomics tests (Olink) were performed, which showed increased concentrations of IL-17A, confirmed by ELISA. The cardiovascular complications were reversible with the return to the gluten-free diet.

Conclusion

In our humanized CeD mouse model, active CeD increases blood pressure and impairs vascular function. We conclude that CeD increases cardiovascular risk through gut inflammation that is transferred to the cardiovascular system, leading to vascular inflammation/oxidative stress and impaired endothelial function. A possible mediator is IL-17A whose role in other autoimmune diseases like psoriasis has already been demonstrated.
With the present study, we demonstrate a mechanistic approach to explain the role of coeliac disease as a cardiovascular risk factor and provide evidence for a gut-to-cardiovascular inflammatory axis.

Introduction

Duodenogastroesophageal reflux (DGER), or bile reflux, has gained renewed interest due to the increasing number of bariatric surgeries (BS) performed. Anatomical modifications after BS may predispose patients to reflux. Revisional bariatric surgery (RBS) is indicated for inadequate weight loss or refractory symptoms.

Aims & Methods

This study aimed to evaluate the diagnostic accuracy of pH-impedance (pH-Z) monitoring in detecting DGER, using spectrophotometric bilirrubin (Bilitec2000) as the clinical reference standard. This prospective study included consecutive patients with a history of sleeve gastrectomy (SG) referred for preoperative evaluation prior to RBS between October 2023 and February 2025. All patients underwent simultaneous 24-hour pH-Z monitoring and Bilitec2000 monitoring while off proton pump inhibitors (PPIs). Patients followed a standardized white semiliquid diet. Gastroesophageal reflux disease (GERD) was diagnosed according to the Lyon 2 Consensus. Pathological bile reflux was defined as a total bilirubin absorbance ≥ 0.14 for ≥ 1.9% of the monitoring time.

Results

Fifty-three patients were enrolled [38 (71.7%) female, median age 48 years (IQR 43 – 55), median BMI 37.3 Kg/m² (IQR 34.1 – 41.3)]. Reason for RBS evaluation included
inadequate weight loss (39.6%) refractory reflux symptoms (32.1%), both (24.5%) and other indications (3.5%). GERD was diagnosed in 31 patients (58.5%) and 21 (39.6%) had pathological bile reflux. Erosive GERD according to Los Angeles classification was identified in 10 patients (19.6%). The area under the curve for non-acid reflux episodes detected by pH-z in diagnosing DGER was 0.61 (CI 95% 0.44 - 0.78), with an optimal cutoff of 85 episodes (sensitivity: 38.1% (CI 95% 20.8 – 59.1); specificity of 93.6% (CI95% 79.9 – 98.3). A moderate correlation was found between non-acid reflux and bile reflux (r = 0.38, p=0.005). However, GERD was not associated with increased bile exposure time (1.4% (IQR 0.3 – 9.5) vs 1.3% (IQR 0.0 – 4.8), p=0.262), nor was this association observed in those with erosive esophagitis (1.9%, IQR 0.4 – 9.5 vs 1.4% IQR 0.0 – 5.8; p=0.914).

Conclusion

Approximate 40% of SG patients undergoing RBS evaluation had pathological bile reflux, which was not linked to GERD or erosive esophagitis. Despite a moderate correlation between bile and non-acid reflux episodes, pH-z monitoring failed to reliably detect DGER and should not be considered a substitute for spectrophotometric bilirrubin concentration monitoring.

References

- Basnayake C, Geeraerts A, Pauwels A, et al. Systematic review: duodenogastroesophageal (biliary) reflux prevalence, symptoms, oesophageal lesions and treatment. Aliment Pharmacol Ther. 2021;54(6):755-778. doi:10.1111/apt.16533.
- Eldredge TA, Bills M, Myers JC, Bartholomeusz D, Kiroff GK, Shenfine J. HIDA and Seek: Challenges of Scintigraphy to Diagnose Bile Reflux Post-Bariatric Surgery. Obes Surg. 2020;30(5):2038-2045. doi:10.1007/s11695-020-04510-7

Introduction

The Ki-67 labeling index is a well-established marker of cellular proliferation and has been associated with worse disease-free and overall survival in gastrointestinal stromal tumors (GISTs). Recent evidence highlights its potential role in risk stratification, particularly when Ki-67 exceeds certain thresholds. However, current assessment relies on postoperative histopathology. Radiomics, by extracting quantitative features from computer tomography (CT) images, may offer a non-invasive method to predict Ki-67 expression preoperatively. This meta-analysis aimed to evaluate the diagnostic performance of CT-based radiomics for predicting Ki-67 status in GISTs.

Aims & Methods

A systematic review and meta-analysis were conducted according to PRISMA guidelines). Four electronic databases (PubMed, Scopus, Science Direct, Cochrane Library) were searched for relevant articles up to December 2024. Eligible studies assessed CT radiomics in predicting Ki-67 in histologically confirmed GISTs. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were performed based on cohort type, CT protocol, number of features, and Ki-67 cutoff values. Study quality was assessed using the QUADAS-2 tool.

Results

Six studies comprising 1,632 patients met the inclusion criteria. Pooled sensitivity and specificity were 0.71 (95% CI: 0.63–0.79) and 0.76 (95% CI: 0.73–0.78), respectively. The pooled AUC was 0.79 (95% CI: 0.74–0.84). Subgroup analyses showed consistent performance across imaging protocols and feature counts, while Ki-67 cutoffs (8% vs. 10%) significantly impacted diagnostic accuracy. Sensitivity analysis confirmed robustness of specificity estimates. Publication bias was detected for specificity (Egger’s test p = 0.006).

Conclusion

CT radiomics demonstrates moderate accuracy for non-invasively predicting Ki-67 expression in GISTs. Given Ki-67's prognostic significance, radiomics could support preoperative risk assessment and personalized treatment planning. Further prospective validation is warranted.

Disclosure

No Conflict of Interest ​

Clinical Case Summary

Case 1: A 38-year-old male with stricturing ileocolic Crohn’s disease on adalimumab underwent a colonoscopy, which revealed active disease (SES-CD: 8) where biopsies were taken. The procedure was uneventful. However, the following day, he developed severe right upper quadrant (RUQ) pain, prompting emergency evaluation. He was afebrile but exhibited RUQ tenderness. Blood tests revealed leukocytosis (21.0×10⁹/L) and elevated CRP (4.26mg/dL). CT scan revealed pericolic fat stranding at the hepatic flexure extending to the gallbladder. Due to diagnostic uncertainty, observation with antibiotics was initiated. Clinical deterioration and worsening inflammatory markers led to an ultrasound, which confirmed an acute cholecystitis. Patient underwent laparoscopic cholecystectomy, revealing gangrenous cholecystitis with perforation. He was discharged on postoperative day 3 with full recovery.
Case 2: A 63-year-old female with a history of stricturing ileocolic Crohn’s disease (ileocecal resection in 2001) and ascending colon adenocarcinoma (right hemicolectomy in 2009) underwent a colonoscopy, which was uneventful. The next day, she developed RUQ pain and vomiting, prompting emergency evaluation. She was febrile with RUQ tenderness. Laboratory results showed leucocytosis (10.6×10⁹/L) and elevated CRP (9.11mg/dL). Ultrasound confirmed acute cholecystitis. She underwent urgent laparoscopic cholecystectomy and was discharged two days later without complications.
Conclusions: We report two cases of acute cholecystitis occurring within 24 hours of colonoscopy. Sixteen similar cases exist in the literature, most presenting within 72 hours¹. Crohn's disease activity does not appear to be a contributing factor, as one patient had no active inflammation. Proposed mechanisms include dehydration, bacterial translocation, trauma and inflammatory response². Finally, given the high frequency of colonoscopy and the prevalence of cholecystitis, a coincidental association cannot be excluded.

References

1. Neubeck KM, Mwagiru D, Boseto EF Acute cholecystitis following elective colonoscopy BMJ Case Reports CP 2023;16:e257166.
2. Shaikh D H, Kumar K, Patel H, et al. (October 10, 2020) Acute Cholecystitis, A Rare Complication Following Routine Colonoscopy: Case Series and Literature Review. Cureus 12(10): e10877.

Introduction

In recent years, eosinophilic gastrointestinal disorders (EGIDs) have attracted attention due to an increase in their incidence. Although many reports have focused on eosinophilic esophagitis (EoE), there are relatively few reports of eosinophilic enteritis (EoN), which causes eosinophil infiltration of the small intestine. In addition, although the diagnostic criteria for EGID also specify that the number of eosinophils infiltrating the gastrointestinal tract other than the esophagus should be 20 or more, the small intestine has not been clearly defined. Furthermore, not even normal eosinophils have been clearly defined for the small intestine, it is necessary to establish the clinical features of EoN. using double-balloon Enteroscopy (DBE) to differentiate it from other small intestinal diseases such as IBD and IBS, which cause similar symptoms of EoN. Accordingly, we examined both the extent of eosinophilic infiltration in the small intestine using DBE and the associated clinical background in cases which EoN was suspected.

Aims & Methods

Patients who underwent DBE for examination of the small intestine at our hospital from January 2021 to December 2024 and had a biopsy from the small intestine were included. Biopsies were taken from 1 or more of the duodenum, upper jejunum, lower jejunum, upper ileum, lower ileum, or terminal ileum, and the number of eosinophils per 1HPF was counted. By using a × 40 objective and × 10 oculars the number of eosinophils per high power field (EOS / HPF) in up to two HPFs was counted in each biopsy specimens. Five patients who visited our hospital with abdominal symptoms, were suspected of EoN, and underwent DBE‑guided small‑intestinal biopsy revealing more than 50 eosinophils per high‑power field, after other diseases had been ruled out, were classified into the EoN group. (3 males and 2 females, mean age 58.3 years). The non-EoN group (7 males and 6 females, mean age 48.4 years) consisted of 14 patients who underwent small intestinal biopsy by DBE for other reasons during the study period, and the number of eosinophil infiltration in the small intestinal mucosa and clinical background were compared.

Results

All five patients in the EoN group presented to our hospital with a chief complaint of abdominal pain and diarrhea and four cases showed edema of the small intestine on CT. All five had an elevated peripheral blood eosinophil count (median 13%). In contrast, the non-EoN group showed no increase with a median of 2.4%. In total, 80 small intestine biopsy specimens were obtained from 18 patients using DBE, 25 specimens in the EoN group and 55 specimens in the non-EoN group. The median eosinophil count in the EoN group was 77 (15-213), which was elevated and significantly higher than the 23 (3-111) in the non-EoN group. (P < 0.01)(Table 1)(Figure 1)
Table 1. Characteristics of patients and biopsy specimens

Conclusion

Small intestinal biopsy using DBE may be useful for the diagnosis of EoN, as eosinophil counts are significantly increased in the small intestine in patients with suspected EoN.