Dataset Information

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

ABSTRACT:

Background

Data on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, endoscopic, and/or pathology findings to differentiate CD from ITB.

Methods

Data from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Limsrivilai, et al. model.

Results

Five hundred and thirty patients (383 CD, 147 ITB) with clinical and endoscopic data were included. The area under the receiver operating characteristic curve (AUROC) of Limsrivilai's clinical-endoscopy (CE) model was 0.853, which was comparable to the value of 0.862 in Jung's model (p = 0.52). Both models performed significantly better than Lee's endoscopy model (AUROC: 0.713, p<0.01). Pathology was available for review in 199 patients (116 CD, 83 ITB). When 3 modalities were combined, Limsrivilai's clinical-endoscopy-pathology (CEP) model performed significantly better (AUROC: 0.887) than Limsrivilai's CE model (AUROC: 0.824, p = 0.01), Jung's model (AUROC: 0.798, p = 0.005) and Makharia's model (AUROC: 0.637, p<0.01). In 83 ITB patients, the rate of misdiagnosis with CD when used the proposed cutoff values in each original study was 9.6% for Limsrivilai's CEP, 15.7% for Jung's, and 66.3% for Makharia's model.

Conclusions

Scoring systems with more parameters and diagnostic modalities performed better; however, application to clinical practice is still limited owing to high rate of misdiagnosis of ITB as CD. Models integrating more modalities such as imaging and serological tests are needed.

SUBMITTER: Limsrivilai J

PROVIDER: S-EPMC7703980 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

Limsrivilai Julajak J Lee Choon Kin CK Prueksapanich Piyapan P Harinwan Kamin K Sudcharoen Asawin A Cheewasereechon Natcha N Aniwan Satimai S Sripongpan Pimsiri P Wetwittayakhlang Panu P Pongpaibul Ananya A Sanpavat Anapat A Pausawasdi Nonthalee N Charatcharoenwitthaya Phunchai P Higgins Peter D R PDR Ng Siew Chien SC

PloS one 20201130 11

<h4>Background</h4>Data on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, endoscopic, and/or pathology findings to differentiate CD from ITB.<h4>Methods</h4>Data from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Lim ...[more]

PMID: 33253239

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Project description:AimTo explore the diagnostic models of Crohn's disease (CD), Intestinal tuberculosis (ITB) and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles.MethodsSerum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs) were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05). Genetic algorithm combining with support vector machine (SVM) was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO) cross validation method.ResultsThere were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05) to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900) can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541) can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80.0% respectively. Among the eleven protein peaks from the diagnostic models and differential diagnostic model, two have been successfully purified and identified, Those two peaks were M/Z 2900 from the diagnostic model between CD and HCs and M/Z 1541 from the differential diagnostic model between CD and ITB. M/Z 2900 was identified as appetite peptide, M/Z 1541 was identified as Lysyl oxidase-like 2 (LOXL-2).ConclusionThe differently expressed protein peaks analyzed by serum proteome with weak cationic magnetic beads combined MALDI-TOF-MS technique can effectively distinguish CD patients and HCs, ITB patients and HCs, CD patients and ITB patients. The diagnostic model between CD patients and HCs consisting of four protein peaks (M/Z 4964, 3029, 2833, 2900), the diagnostic model between ITB patients and HCs comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) and the differential diagnostic model between CD patients and ITB patients comprising three protein peaks (M/Z 4267, 4223, 1541) had high specificity and sensitivity and can contribute to diagnoses of CD, ITB and the differential diagnosis between CD and ITB. Two proteins from the diagnostic model of CD and the differential diagnostic model between CD and ITB were identified. Further experiments are required using a larger cohort of samples.

Project description:Background and aimsCrohn's disease (CD) and intestinal tuberculosis (ITB) are both chronic granulomatous conditions with similar phenotypic presentations. Hence, there is need for a biomarker to differentiate between both these two diseases. This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls. To evaluate the role of T regulatory cells, forkhead box P3 (FOXP3) mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls.MethodsPaired samples, including serum and colonic biopsies, were taken from 33 study subjects (CD, ITB and controls), and total RNA was extracted. Human whole genome gene expression microarray analysis was performed using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three groups in duplicates. Real-time PCR for FOXP3 mRNA expression was analyzed in serum samples and colonic biopsy samples (4-CD, 5-ITB, 4-controls).ResultsIn CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold downregulation of 91 and 256 genes, respectively. Peroxisome proliferators via the PPARγ pathway were most significantly downregulated (P < 0.005) in CD. Additionally, the IL4/5/6 signaling pathways and Toll-like receptor signaling pathway were identified as significantly differentially regulated (P < 0.005) at > 2-fold change. In ITB, the complement activation pathway, specifically the classical pathway, was the most significantly upregulated. FOXP3 mRNA expression was significantly elevated in colonic biopsies obtained from ITB patients as compared with CD cases (4.70 ± 2.21 vs 1.48 ± 0.31, P = 0.016).ConclusionsFOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between ITB and CD. Upregulation of the complement activation pathway in ITB suggests that pathogenetic mechanisms for ITB are similar to those of pulmonary tuberculosis. In CD, downregulation of PPARγ was seen in colonic tissue, suggesting that restoration of PPARγ-dependent anti-microbial barrier function may be a therapeutic target.

Project description:ObjectivesDistinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD.MethodsA systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I2<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability.ResultsThirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively.ConclusionsA Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.

Dataset Information

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

Background

Methods

Results

Conclusions

Publications

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

Similar Datasets

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