Introduction

Crohn's disease (CD) is generally confined to the ileocecal tract. Upper gastrointestinal tract (UGIT) involvement is estimated to be between 0.5 and 4% of adult patients with CD.

Aims & Methods

The aim of our study was to describe the epidemioclinical and evolutionary profiles of patients with UGIT involvement in CD.
A retrospective, descriptive and comparative study including all patients followed for CD in our department during the period from January 2011 to December 2020 was conducted. Patients with UGIT involvement were identified. Data were entered and analyzed via the software SPSS 26.

Results

Among 341 patients followed for CD, we included 49 with UGIT involvement (14.3%), with a sex ratio of M/F=1,1. The mean age at diagnosis was 29.27 ± 11.8 years. Fifteen patients were smokers. A family history of chronic inflammatory bowel disease was statistically more present in patients with UGIT disease (p=0.031). The mean duration of disease progression since diagnosis was 9.43 years. Only one patient had exclusive upper GI involvement; in the other cases, it was associated with another luminal involvement represented mainly by ileal involvement in 59.3% of cases, with a significant association (p=0.019). The CD behaviour was mainly fistulizing in 40.8%, stricturing in 36.7% and inflammatory in 22.5%. Extensive luminal disease, defined as damage exceeding 50 cm, was observed in 12 patients (24.48%) and was associated with UGIT involvement (p=0,001). Eight patients had complex anoperineal fistulas and one patient had an associated anal stenosis. Forty percent of the patients had an associated extra-intestinal manifestation. The mean body mass index at diagnosis was 20.41 kg/m² [13.7 - 32,4]. The mean albumin level at diagnosis was 31.94g/L. Histological severe activity was noted in 14 patients. Epithelioid and gigantocellular granuloma, found in 13 patients (26.5%), was associated with UGIT involvement (p=0.027). On the other hand, a history of severe acute colitis was associated with the absence of upper GI involvement (p=0.01). The median number of flares was 4 [1-16]. The median number of hospitalizations was 4 with a maximum of 13 hospitalizations and a mean duration of hospitalization of 21 days. The use of anti-TNF drugs was associated with UGIT involvement with p<0.001. Surgical treatment was required in 48,4% of the patients (n=24), mainly ileo-caecal resection, without any significant difference (p=0.05). We noted that the number of surgical interventions was significantly higher in the presence of granuloma on histology (p=0.043). However, the detection of granuloma or severe activity on histology was not associated with a greater use of anti-TNF drugs.

Conclusion

Upper gastrointestinal tract involvement in Crohn's disease is rare and is more likely to be associated with a severe disease course.

Introduction

Patients with metabolic-dysfunction associated steatohepatitis (NAFLD activity score ≥4) and significant fibrosis (≥F2) (fibrotic MASH) are at increased risk for disease progression and development of cirrhosis. Following the recent approval of the first agent for the management of noncirrhotic MASH, timely identification of these patients is of major importance. Fibroscan-aspartate aminotransferase (FAST^TM) score enables the noninvasive diagnosis of fibrotic MASH, and has been assessed in several studies.

Aims & Methods

To assess the overall performance of FAST^TM score for diagnosing fibrotic MASH. We searched Medline, Cochrane library, Web of science and Scopus up to January 2024. We included diagnostic accuracy studies assessing the performance of FAST^TM score for ruling out (FAST^TM score ≤0.35) and ruling in (FAST^TMscore ≥0.67) fibrotic MASH using liver biopsy as the reference standard. We calculated pooled diagnostic accuracy estimates using bivariate random-effects models, and assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Results

We included 16 studies with 8838 participants. Most studies (87.5%) were at high or unclear risk of bias due to concerns regarding patient selection, interpretation of FAST score without knowledge of biopsy results, and length of biopsy specimens for fibrotic MASH diagnosis. Across all participants, 54.8% were females and 31% had type 2 diabetes. Mean age and body mass index (BMI) were 52.4 years and 32.4 kg/m². Mean aspartate aminotransferase and alanine aminotransferase were 45.0 IU and 57.6 IU, respectively. The prevalence of fibrotic MASH across studies was 32.9% ranging from 14% to 55%. Using the rule out cut off (≤0.35), FAST^TM yielded a pooled sensitivity of 0.88 (95 % CI; 0.83, 0.91), specificity 0.52 (0.45, 0.60), positive likelihood ratio (LRp) 1.8 (1.6, 2.1) and negative likelihood ratio (LRn) 0.23 (0.18, 0.30). By applying the rule in cut off (≥0.67), pooled sensitivity, specificity, LRp, and LRn were 0.45 (0.39, 0.52), 0.87 (0.82, 0.90), 3.4 (2.8, 4.1) and 0.63 (0.58, 0.69) respectively. Assuming a pre-test probability (prevalence) of 30% for fibrotic MASH, a FAST^TM score ≥0.67 resulted in a positive predictive value of 60%, while with a FAST^TM score ≤0.35 the negative predictive value was 91%.

Conclusion

FAST^MT score has acceptable accuracy for the diagnosis of fibrotic MASH. Proposed thresholds of ≤0.35 and ≥0.67 might be useful for ruling out/in fibrotic MASH respectively.

Introduction

Preterm birth complications such as sepsis and necrotizing enterocolitis (NEC), are the leading cause of death among neonates. (1) Preterm birth is likely associated with dysbalanced microbial colonization and immature intestinal epithelium at birth, which impacts functionality, and barrier function of epithelia once microbial colonization occurs. Both structural and functional maturation of the intestinal epithelium are required for sufficient digestion and absorption of nutrients. (2) Breastmilk (BM) has been shown to significantly reduce the risk of developing NEC in preterms, in contrast to infant formula (IF). (3) We hypothesize that this is partly explained by the fact that BM contains a unique fat component, the milk fat globule membrane (MFGM), absent in IF. MFGM comprises a triple membrane of polar lipids, embedding bioactive components such as proteins, phospholipids and gangliosides. MFGM has shown to induce elevated epithelial cell differentiation and enhanced barrier integrity in an allergic mouse model and an early life rat model. (4, 5) However, the effects of MFGM on human intestinal maturation are unknown. We studied the effects of MFGM on human intestinal maturation using in vitro human neonatal small intestinal organoids.

Aims & Methods

Primary human neonatal organoids were derived from ileal tissue collected during neonatal surgeries (age 5 weeks - 4 months). Three-dimensional organoids were exposed continuously for 7 days to either 0.25wt% MFGM-enriched whey or 0.25wt% whey protein isolate (WPI; whey protein control not containing MFGM). Differences in growth and morphology were assessed by brightfield microscopy. Organoid growth was assessed by quantification through ImageJ analyses. Epithelial maturation was defined by longitudinal expression of brush border enzymes sucrase isomaltase (Sis), lactase (Lct) and intestinal alkaline phosphatase (ALPI), epithelial differentiation into secretory Paneth cells (Lysozyme; Lyz) and Goblet cells (Mucin-2; Muc2), and decreased stemness (Lgr5). Epithelial maturation was assessed by immunohistochemical (IHC) staining and qPCR.

Results

Neonatal organoids stimulated with MFGM displayed slower growth rate and decreased Lgr5 expression compared to WPI and medium control. This was accompanied with a 15-fold increase in gene expression of ALPI and 18-fold increase in Sis, two brush border enzymes associated with epithelial maturation. Expression of Muc2 was increased in MFGM stimulated conditions compared to medium control. Additionally, IHC stainings showed higher expression of Lyz in MFGM stimulated organoids compared to control and WPI. This suggest that MFGM stimulation enhances maturation by increasing expression of brush border enzymes and epithelial differentiation, while reducing stemness.

Conclusion

Our data suggest that MFGM enhances epithelial maturation by enhancing expression of brush border enzymes and cell differentiation in a human primary neonatal organoid model.

References

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5. Gong H, Li T, Liang D, Gao J, Liu X, Mao X. Milk fat globule membrane supplementation protects against β-lactoglobulin-induced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner. Food Science and Human Wellness. 2024;13(1):124-36.