The selective cyclooxygenase-2 inhibitor DFU does not suppress prostaglandin E2 formation in colonic mucosa of patients with active Crohn's disease

Background and Aims: Mucosal healing (MH) is associated with a stable course of Crohn’s disease (CD) which can be assessed by confocal laser endomicroscopy (CLE). To minimize the operator’s errors and automate assessment of CLE images, we used a deep learning (DL) model for image analysis. We hypothesized that DL combined with convolutional neural networks (CNNs) and long short-term memory (LSTM) can distinguish between normal and inflamed colonic mucosa from CLE images. Methods: The study included 54 patients, 32 with known active CD, and 22 control patients (18 CD patients with MH and four normal mucosa patients with no history of inflammatory bowel diseases). We designed and trained a deep convolutional neural network to detect active CD using 6,205 endomicroscopy images classified as active CD inflammation (3,672 images) and control mucosal healing or no inflammation (2,533 images). CLE imaging was performed on four colorectal areas and the terminal ileum. Gold standard was represented by the histopathological evaluation. The dataset was randomly split in two distinct training and testing datasets: 80% data from each patient were used for training and the remaining 20% for testing. The training dataset consists of 2,892 images with inflammation and 2,189 control images. The testing dataset consists of 780 images with inflammation and 344 control images of the colon. We used a CNN-LSTM model with four convolution layers and one LSTM layer for automatic detection of MH and CD diagnosis from CLE images. Results: CLE investigation reveals normal colonic mucosa with round crypts and inflamed mucosa with irregular crypts and tortuous and dilated blood vessels. Our method obtained a 95.3% test accuracy with a specificity of 92.78% and a sensitivity of 94.6%, with an area under each receiver operating characteristic curves of 0.98. Conclusions: Using machine learning algorithms on CLE images can successfully differentiate between inflammation and normal ileocolonic mucosa and can be used as a computer aided diagnosis for CD. Future clinical studies with a larger patient spectrum will validate our results and improve the CNN-SSTM model.

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Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis.

Gut ◽

10.1136/gut.35.11.1593 ◽

1994 ◽

Vol 35 (11) ◽

pp. 1593-1598 ◽

Cited By ~ 73

Author(s):

T Minami ◽

H Tojo ◽

Y Shinomura ◽

Y Matsuzawa ◽

M Okamoto

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Phospholipase A2 ◽

Colonic Mucosa ◽

Group Ii

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29 HUMAN BONE MARROW DERIVED MESENCHYMAL STEM CELLS MEDIATE IMMUNOSUPPRESSION IN EXPERIMENTAL CROHN’S DISEASE BY SECRETING PROSTAGLANDIN E2 AND REPROGRAMMING MACROPHAGES TO AN ANTI-INFLAMMATORY PHENOTYPE

Gastroenterology ◽

10.1053/j.gastro.2019.01.208 ◽

2019 ◽

Vol 156 (3) ◽

pp. S89-S90

Author(s):

Maneesh Dave ◽

Nan Zhao ◽

Ganapati Mahabaleshwar ◽

Rodrigues Somosa ◽

Jonathan Kenyon ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Prostaglandin E2 ◽

Human Bone ◽

Human Bone Marrow ◽

Inflammatory Phenotype ◽

Anti Inflammatory

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Proteome analysis of the macroscopically affected colonic mucosa of Crohn’s disease and intestinal tuberculosis

Scientific Reports ◽

10.1038/srep23162 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 7

Author(s):

Lokesh A. Rukmangadachar ◽

Govind K. Makharia ◽

Asha Mishra ◽

Prasenjit Das ◽

Gururao Hariprasad ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Colonic Mucosa ◽

Intestinal Tuberculosis ◽

Proteome Analysis

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INTERLEUKIN 1B PRODUCTION BY COLONIC MUCOSA CHILDREN WITH CROHN'S DISEASE

Pediatric Research ◽

10.1203/00006450-198909000-00072 ◽

1989 ◽

Vol 26 (3) ◽

pp. 275-275

Author(s):

S Hill ◽

P J Milla ◽

R Mirakian

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Colonic Mucosa

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Replication of Colonic Crohn's Disease Mucosal Escherichia coli Isolates within Macrophages and Their Susceptibility to Antibiotics

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00375-07 ◽

2007 ◽

Vol 52 (2) ◽

pp. 427-434 ◽

Cited By ~ 61

Author(s):

Sreedhar Subramanian ◽

Carol L. Roberts ◽

C. Anthony Hart ◽

Helen M. Martin ◽

Steve W. Edwards ◽

...

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Colonic Mucosa ◽

Human Monocyte ◽

Fold Increase ◽

Serum Concentrations ◽

Similar Extent ◽

E Coli ◽

K 12

ABSTRACT There is increasing evidence that Escherichia coli organisms are important in Crohn's disease (CD) pathogenesis. In CD tissue they are found within macrophages, and the adherent-invasive CD ileal E. coli isolate LF82 can replicate inside macrophage phagolysosomes. This study investigates replication and antibiotic susceptibility of CD colonic E. coli isolates inside macrophages. Replication of CD colonic E. coli within J774-A1 murine macrophages and human monocyte-derived macrophages (HMDM) was assessed by culture and lysis after gentamicin killing of noninternalized bacteria and verified by electron microscopy (EM). All seven CD colonic isolates tested replicated within J774-A1 macrophages by 3 h (6.36-fold ± 0.7-fold increase; n = 7 isolates) to a similar extent to CD ileal E. coli LF82 (6.8-fold ± 0.8-fold) but significantly more than control patient isolates (5.2-fold ± 0.25-fold; n = 6; P = 0.006) and E. coli K-12 (1.0-fold ± 0.1-fold; P < 0.0001). Replication of CD E. coli HM605 within HMDM (3.9-fold ± 0.7-fold) exceeded that for K-12 (1.4-fold ± 0.2-fold; P = 0.03). EM showed replicating E. coli within macrophage vacuoles. Killing of HM605 within J774-A1 macrophages following a 3-h incubation with antibiotics at published peak serum concentrations (C max) was as follows: for ciprofloxacin, 99.5% ± 0.2%; rifampin, 85.1% ± 6.6%; tetracycline, 62.8% ± 6.1%; clarithromycin, 62.1% ± 5.6% (all P < 0.0001); sulfamethoxazole, 61.3% ± 7.0% (P = 0.0007); trimethoprim, 56.3% ± 3.4% (P < 0.0001); and azithromycin, 41.0% ± 10.5% (P = 0.03). Ampicillin was not effective against intracellular E. coli. Triple antibiotic combinations were assessed at 10% C max, with ciprofloxacin, tetracycline, and trimethoprim causing 97% ± 0.0% killing versus 86% ± 2.0% for ciprofloxacin alone. Colonic mucosa-associated E. coli, particularly CD isolates, replicate within macrophages. Clinical trials are indicated to assess the efficacy of a combination antibiotic therapy targeting intramacrophage E. coli.

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