Dataset Information

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

ABSTRACT:

Background and aims

Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients.

Methods

MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score].

Results

In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis.

Conclusions

MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

SUBMITTER: Li XH

PROVIDER: S-EPMC8427713 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

Li Xue-Hua XH Feng Shi-Ting ST Cao Qing-Hua QH Coffey J Calvin JC Baker Mark E ME Huang Li L Fang Zhuang-Nian ZN Qiu Yun Y Lu Bao-Lan BL Chen Zhi-Hui ZH Li Yi Y Bettenworth Dominik D Iacucci Marietta M Sun Can-Hui CH Ghosh Subrata S Rieder Florian F Chen Min-Hu MH Li Zi-Ping ZP Mao Ren R

Journal of Crohn's & colitis 20210701 7

<h4>Background and aims</h4>Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients.<h4>Methods</h4>MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and va ...[more]

PMID: 33411893

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Project description:Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.

Project description:BackgroundTransmural healing (TH) is a potential therapeutic goal of Crohn's disease (CD) and is associated with better clinical outcomes. However, few studies have described early TH and its predictors.ObjectivesWe aimed to evaluate early TH and its predictors using magnetic resonance enterography (MRE) in patients with CD receiving ustekinumab (UST).DesignThis was a retrospective observational study.MethodsPatients with active CD treated with UST and their intestinal segments with bowel wall thickness (BWT) ⩽ 3 mm at baseline were included. Clinical characteristics, laboratory indicators, endoscopic manifestations, and MRE indices were evaluated at baseline and week 26 (W26) of the therapy. The following MRE parameters were assessed: BWT, edema, apparent diffusion coefficient (ADC), Clermont score, Magnetic Resonance Index of Activity score, fat stranding, comb sign, and stricture. TH was defined as BWT ⩽ 3 mm without any signs of inflammation (i.e., ulceration, edema, diffusion-weighted hyperintensity, and increased contrast enhancement) at W26.ResultsThe study included 37 patients with 106 intestinal segments (including 15 proximal small intestines, 33 terminal ilea, and 58 colons). Clinical features, laboratory indicators, endoscopic results, and MRE parameters at W26 were significantly improved after UST treatment in both patient-based and intestinal segment-based analysis. Seven (18.9%) patients and 26 (24.5%) intestinal segments achieved TH at W26. Baseline BWT [odds ratio (OR) = 0.287, 95% confidence interval (CI), 0.090-0.918, p = 0.035] and ADC (OR = 2.997, 95% CI, 1.009-8.908, p = 0.048) predict TH of patients at W26. Baseline ADC (OR = 2.857, 95% CI, 1.285-6.349, p = 0.010) and presence of stenosis (OR = 0.196, 95% CI, 0.052-0.735, p = 0.016) were associated with TH of segments at W26.ConclusionEarly TH assessed by MRE was observed in nearly one-fifth of patients with CD and intestinal segments after UST treatment for 26 weeks. Baseline MRE indices such as BWT and presence of stenosis might negatively predict TH, while ADC might positively predict early TH.

Project description:BackgroundCrohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue-derived stem cells (ADSCs) can regulate their adjacent cells. However, the regulating roles of ADSC-EVs in CrF (CrF-EVs) in CD, especially in modulating lymphatic function and mitigating the progression of mesenteritis and colitis, remains elusive.MethodsTo evaluate the regulative roles of CrF-EVs on lymphatic functions, in vitro assays were performed using human lymphatic endothelial cells (HLECs). Next, Interleukin 10 knock-out (Il-10-/-) mice were used to assess the biological functions of CrF-EVs in spontaneous mesenteritis and colitis. Moreover, tissue and serum from various cohorts of CD patients were used to determine the prognostic value of miR-132-3p.ResultsCrF-EVs significantly attenuated spontaneous mesenteritis and colitis in Il-10-/- mice via promoting lymphangiogenesis and lymphatic drainage. Using high-throughput sequencing, we demonstrated that CrF-EVs significantly increased HLEC proliferation, migration, tube formation and CCL-21 production in a miR-132-3p/RASA1/ERK1/2 axis-dependent manner. Accordingly, upregulated miR-132-3p was observed in patient CrF, positively correlated with lymphangiogenesis while negatively correlated with inflammatory factors (tumour necrosis factor-α and IL-6) level. Moreover, serum miR-132-3p demonstrated a positive correlation with disease activity.ConclusionsEVs derived from CrF ADSCs, containing elevated levels of miR-132-3p, could promote lymphatic function and restrain inflammation of CD. Our results provide a novel insight into the role of mesenteric lymphatics in CD progression and reveal a new potential therapeutic.Key pointsExtracellular vesicles (EVs) of creeping fat (CrF) derived adipose stem cells effectively attenuate chronic mesenteritis and colitis in Crohn's disease (CD). The lymphatic vessels play an important role in disease development of CD and their functions are improved by CrF-EV-miR-132-3p through RASA1/ERK1/2 signaling. MiR-132-3p expression is upregulated in CrF and serum of CD patients, and tightly linked with inflammation and disease activity.

Project description:Background:The treatment goal of Crohn's disease (CD) has moved towards achieving mucosal healing, resolution of transmural inflammation, and normalization of biomarkers. The purpose of this study was to evaluate how well computed tomography enterography (CTE) and fecal calprotectin (FC) correlated with endoscopic activity in newly diagnosed patients with CD and after 1 year of therapy. Methods:Consecutive patients with newly diagnosed CD were evaluated by endoscopy, CTE, and FC at diagnosis and 12 months after beginning immunosuppression. Endoscopic severity was assessed using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). Biomarkers, clinical indexes, and FC were recorded on the day of ileocolonoscopy at diagnosis and 1 year after diagnosis. We adapted a CTE score for disease activity based on radiological signs of inflammation (i.e. mural thickness, mural hyperenhancement, mesenteric fat proliferation, mesenteric fat densification, comb sign, presence of strictures, fistulas, abscesses, ascites, and lymphadenopathy). Correlations between endoscopy, CTE, and FC were assessed using Spearman's rank correlation. Results:A total of 29 patients (48% women; median age 30 (24.5-35.5) years) were included in this prospective cohort. CTE findings significantly correlated with endoscopic findings. Endoscopic remission (ER) at 1-year follow up significantly correlated with improvement in mural hyperenhancement (p = 0.004), mesenteric fat densification (p = 0.001), comb sign (p = 0.004), and strictures (p = 0.008) in CTE. None of the CTE findings improved in patients without ER. FC correlated with SES-CD (rs = 0.696, p < 0.001) and with CTE features of inflammation (rs = 0.596, p < 0.001). A cut-off of 100 µg/g predicted ER with 92% sensitivity, 65% specificity, and 83% accuracy (area under curve 0.878, p < 0.001). Conclusions:CTE findings and FC levels correlated with endoscopic activity in CD both at diagnosis and at 1-year follow up. These two noninvasive markers of disease activity may be used as an alternative to endoscopy to monitor disease response to therapy.

Dataset Information

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

Background and aims

Methods

Results

Conclusions

Publications

Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index.

Similar Datasets

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