scholarly journals Multi-“-Omics” Profiling in Patients With Quiescent Inflammatory Bowel Disease Identifies Biomarkers Predicting Relapse

2020 ◽  
Vol 26 (10) ◽  
pp. 1524-1532
Author(s):  
Nienke Z Borren ◽  
Damian Plichta ◽  
Amit D Joshi ◽  
Gracia Bonilla ◽  
Ruslan Sadreyev ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Confidence Interval ◽  
Risk Score ◽  
Crohn Disease ◽  
Odds Ratio ◽  
Risk Scores ◽  
Clinical Relapse ◽  
Cell Surface Glycoprotein ◽  
Microbial Biomarkers ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease. Methods This prospective study enrolled patients with quiescent Crohn disease and ulcerative colitis, defined as the absence of clinical symptoms (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) and endoscopic remission within the prior year. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy or IBD-related hospitalization or surgery. Biomarkers were tested in a derivation cohort, and their performance was examined in an independent validation cohort. Results Our prospective cohort study included 164 patients with IBD (108 with Crohn disease, 56 with ulcerative colitis). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (interleukin-10, glial cell line–derived neurotrophic factor, and T-cell surface glycoprotein CD8 alpha chain) and 4 metabolomic markers (propionyl-L-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models. Proteomic and metabolomic risk scores independently predicted relapse with a combined area under the curve of 0.83. A high proteomic risk score (odds ratio = 9.11; 95% confidence interval, 1.90-43.61) or metabolomic risk score (odds ratio = 5.79; 95% confidence interval, 1.24-27.11) independently predicted a higher risk of relapse over 2 years. Fecal metagenomics showed an increased abundance of Proteobacteria (P = 0.0019, q = 0.019) and Fusobacteria (P = 0.0040, q = 0.020) and at the species level Lachnospiraceae_bacterium_2_1_58FAA (P = 0.000008, q = 0.0009) among the relapses. Conclusions Proteomic, metabolomic, and microbial biomarkers identify a proinflammatory state in quiescent IBD that predisposes to clinical relapse.

scholarly journals DOP30 Multi-‘omics profiling in patients with quiescent inflammatory bowel disease identifies biomarkers predicting relapse

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S069-S070
Author(s):  
N Borren ◽  
D Plichta ◽  
A joshi ◽  
G Bonilla ◽  
R Sadreyev ◽  
...  
Keyword(s):  
Risk Score ◽  
Validation Cohort ◽  
Clinical Symptoms ◽  
Risk Scores ◽  
Clinical Relapse ◽  
Metagenomic Sequencing ◽  
Illumina Hiseq ◽  
Derivation Cohort ◽  
Microbial Biomarkers ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases (IBD) are characterised by intermittent relapses and their course is heterogeneous and often unpredictable. The ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease is unknown. Methods This prospective study enrolled patients with quiescent Crohn’s disease (CD) and Ulcerative colitis (UC) defined as absence of clinical symptoms (HBI < 4, SCCAI < 2) and a colonoscopy within the 1 year prior with endoscopic remission. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy, or IBD-related hospitalisation or surgery. Metabolomic and proteomic profiling was performed on serum samples and stool samples underwent shotgun metagenomic sequencing on Illumina HiSeq platform. Biomarkers were tested in a derivation cohort and their performance examined in an independent validation cohort. Results Our prospective cohort study included 164 patients with IBD (108 CD, 56 UC). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (IL-10, GDNF, and CD8A) and four metabolomic markers (propionyl-l-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models at p < 0.05. Proteomic and metabolomic risk scores, defined as the tertile sum of the serum levels of these biomarkers independent predicted relapse with a combined AUC of 0.83. This risk score clearly differentiated relapsers from those who remained in remission in both the derivation and validation cohort (Figure 2). A high proteomic risk score (OR 9.11, 95% CI 1.90–43.61) or metabolomic risk score (OR 5.79, 95% CI 1.24–27.11) independently predicted higher risk of relapse over 2 years. Faecal metagenomics from 85 patients demonstrated increased abundance of Proteobacteria (p = 0.0019, q = 0.019) and Fusobacteria (p = 0.0040, q=0.020) and at the species-level Lachnospiraceae_bacterium_2_1_58FAA (p = 0.000008, q = 0.0009) among relapses. Proinflammatory changes in the microbiome correlated with the metabolomic and proteomic perturbations associated with relapse. Conclusion Proteomic, metabolomic, and microbial biomarkers identify a pro-inflammatory state in quiescent IBD that predisposes to clinical relapse.

scholarly journals Predictors of mortality in inflammatory bowel disease patients treated for pneumonia

2020 ◽  
Vol 13 ◽  
pp. 175628482093945
Author(s):  
Offir Ukashi ◽  
Yifatch Barash ◽  
Michael J. Segel ◽  
Bella Ungar ◽  
Shelly Soffer ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Confidence Interval ◽  
Bowel Disease ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Predictors Of Mortality ◽  
Inflammatory Bowel

Background: Community-acquired pneumonia is among the most common infections affecting ulcerative colitis and Crohn’s disease patients. Data regarding epidemiology and outcomes of pneumonia in inflammatory bowel disease patients is lacking. We aimed to identify predictors of adverse outcomes among inflammatory bowel disease patients treated for pneumonia. Methods: This was a retrospective cohort study that included adult patients admitted to Sheba Medical Center for pneumonia between 2012 and 2018. Data was collected from an electronic repository of all emergency department admissions and included tabular demographic and clinical variables and free-text physician records. Pneumonia cases were extracted using the International Classification of Diseases (ICD-10) coding. Results: Of 16,732 admissions with pneumonia, 97 were inflammatory bowel disease patients (45 Crohn’s disease; 52 ulcerative colitis). We found a similar rate of 30-day mortality among inflammatory bowel disease and non-inflammatory bowel disease patients (12.1% versus 11.3%, p = 0.824) and between Crohn’s disease and ulcerative colitis patients (11.1% versus 11.5%, p = 0.947). There was an increased hospitalization rate among inflammatory bowel disease patients (92.8% versus 85.6%, p = 0.045), but similar hospitalization duration (4 versus 4 days, p = 0.384). Crohn’s disease patients had a shorter hospitalization duration compared with ulcerative colitis patients (3 versus 5.5 days, p = 0.029). Bronchiectasis (adjusted odds ratio 60.95, 95% confidence interval 2.72–1364.39, p = 0.01) and opioids use (adjusted odds ratio 13.21, 95% confidence interval 1.29–135.18, p = 0.03) were associated with an increased 30-day mortality rate in inflammatory bowel disease patients. Conclusion: This is the first study to identify predictors of mortality in inflammatory bowel disease patients with pneumonia. The rate of mortality and hospitalization duration of stay were similar among inflammatory bowel disease and non-inflammatory bowel disease patients. Use of opioids and presence of bronchiectasis were associated with a higher risk of mortality in inflammatory bowel disease patients with pneumonia.

scholarly journals Is Isotretinoin Innocent from Causing Inflammatory Bowel Disease?

2016 ◽  
Vol 6 (2) ◽  
pp. 21-33
Author(s):  
Saad M. Alrajhi
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Confidence Interval ◽  
Bowel Disease ◽  
Odds Ratio ◽  
Random Model ◽  
P Value ◽  
Inflammatory Bowel

Objectives: Multiple case reports suggesting isotretinoin causes inflammatory bowel disease leading to compensations reaching millions of dollars. New larger studies question this effect. This is a meta-analysis to study the association. Methods: We searched PubMed, Cochrane, Google Scholar, and WorldCat. We extracted six articles measuring drug exposure and disease incidence. We measured the effects of isotretinoin on inflammatory bowel disease, Crohn’s disease and ulcerative colitis, using pooled odds ratio. The effect can be measured using the fixed or the random model. The fixed effect assumes studies have the same effect in the same population, while the random assumes heterogeneity. The correct model is chosen based on a Q-heterogeneity test. Results: Sample size was 9723864. Inflammatory bowel disease in isotretinoin exposed had an odds ratio of {1.075, 95% confidence interval (0.78, 1.49)}, Crohn’s disease{0.97, 95% confidence interval (0.65, 1.43)} and ulcerative colitis {1.28, 95% confidence interval (0.88, 1.86)}. All odds ratios had a p-value > 0.05 using the random-model which was chosen due to significant Q and I-squared score p value < 0.05. There was significant heterogeneity of the six studies, which lack consistency in adjusting for important co-variables (dose, family history, smoking, etc.)    

Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy

2020 ◽  
Author(s):  
Motasem Alkhayyat ◽  
Mohammad Abureesh ◽  
Arshpal Gill ◽  
George Khoudari ◽  
Mohannad Abou Saleh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Multivariate Analysis ◽  
Tumor Necrosis Factor ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Tumor Necrosis ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Abstract Background Chronic inflammation is a key factor for the development of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD). Despite the increased use of biologic agents in patients with IBD, their impact on colorectal carcinogenesis remains unclear. With the use of a large database, we sought to describe the effect of biologics on CRC among patients with IBD. Methods We evaluated a multicenter database (Explorys) consisting of electronic medical records from several U.S. hospitals between 1999 and 2020. A cohort of patients with a diagnosis of IBD was identified. We performed a multivariate analysis to adjust for multiple factors including medical and surgical therapies. Results There were a total of 62,007,510 patients in the database between 1999 and 2020. Amongst those, 225,090 (0.36%) individuals had Crohn’s disease and 188,420 (0.30%) had ulcerative colitis. After adjusting for confounding factors using multivariate analysis, patients with IBD were more likely to develop CRC. Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn’s disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P &lt; 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P &lt; 0.0001. Conclusions Patients with IBD who were treated with anti-tumor necrosis factor agents were less likely to develop CRC. Prospective studies are needed to evaluate whether anti-tumor necrosis factor drugs provide a chemoprotective effect in patients with IBD by inflammation control and mucosal healing.

scholarly journals Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao-Fu Chen ◽  
Yuan Zhao ◽  
Yu Guo ◽  
Zhi-Ming Huang ◽  
Xie-Lin Huang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Confidence Interval ◽  
Disease Activity ◽  
Bowel Disease ◽  
Odds Ratio ◽  
Activity Index ◽  
Characteristic Curve ◽  
Disease Activity Index ◽  
Mayo Score ◽  
Inflammatory Bowel

Abstract Background We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). Methods The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn’ s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. Results The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428–3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433–3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751–0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839–0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. Conclusions Fibrinogen is a convenient and practical biomarker to identify active IBD.

Pathophysiology and Diagnosis of Ulcerative Colitis and Crohn Disease

2017 ◽  
Author(s):  
Julia B. Greer ◽  
Miguel D. Regueiro
Keyword(s):  
Computed Tomography ◽  
Ulcerative Colitis ◽  
Crohn Disease ◽  
Extraintestinal Manifestations ◽  
Infectious Colitis ◽  
Computed Tomographic ◽  
Computed Tomography Images ◽  
Computed Tomographic Scan ◽  
Inflammatory Bowel ◽  
Toxic Colitis

Inflammatory bowel disease (IBD) encompasses both ulcerative colitis and Crohn disease, and is characterized by recurrent bouts of inflammation of the gastrointestinal tract. IBD affects approximately 4 million people worldwide, and rates are gradually increasing. This review covers the etiology, epidemiology, definition and pathophysiology, extraintestinal manifestations, and other disease-related complications of IBD. Figures show the distribution of ulcerative colitis and Crohn disease by location, several colonoscopic photographs of patients with ulcerative colitis as well as those with Crohn disease, computed tomography images of patients with Crohn disease, small bowel follow-through and fluoroscopic spot images of a patient with chronic structuring Crohn disease, and a computed tomographic scan showing extraenteric manifestations of Crohn disease. Tables list the differential diagnosis of ulcerative colitis, types of infectious colitis, complications of IBD, diagnostic criteria of toxic colitis, physical signs of Crohn disease, differences between Crohn disease and ulcerative colitis, and common extraintestinal manifestations of IBD. This review contains 11 highly rendered figures, 7 tables, and 63 references.

Clinical Features and Differential Diagnosis of Ulcerative Colitis and Crohn Disease

2015 ◽  
Author(s):  
Edward L. Barnes ◽  
Jonathan S. Levine
Keyword(s):  
Ulcerative Colitis ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Crohn Disease ◽  
Clinical Utility ◽  
Fecal Calprotectin ◽  
Position Emission Tomography ◽  
Extraintestinal Manifestations ◽  
Pet Ct ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is composed of two major subtypes, ulcerative colitis (UC) and Crohn disease (CD). These chronic disorders, characterized by inflammation of the gastrointestinal tract, demonstrate a variety of clinical features, including intestinal and extraintestinal manifestations during periods of relapse and remission over many years. This review examines the clinical features of IBD, including the extraintestinal manifestations and diagnosis. Figures include examples of images conducted via computed tomography (CT), magnetic resonance imaging, and position emission tomography (PET)/CT. Tables list the location frequencies of UC and CD at the time of diagnosis, extraintestinal manifestations of IBD, differential diagnosis of UC and CD, and clinical utility of fecal calprotectin in the evaluation and management of IBD. This review contains 4 highly rendered figures, 5 tables, and 48 references. 

scholarly journals News and controversy in inflammatory bowel disease treatment

2013 ◽  
pp. 179-186
Author(s):  
Giulia Straforini ◽  
Ramona Brugnera ◽  
Rosy Tambasco ◽  
Fernando Rizzello ◽  
Paolo Gionchetti ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn Disease ◽  
Bowel Disease ◽  
Topical Treatment ◽  
Preventive Treatment ◽  
High Dose ◽  
First Choice ◽  
Oral Steroids ◽  
Inflammatory Bowel

Background: The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. Discussion: In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti- TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.

scholarly journals P536 Early prediction of intravenous corticosteroid therapy failure in moderate–severe ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S458-S458
Author(s):  
A Croft ◽  
A Lord ◽  
G Radford-Smith
Keyword(s):  
Ulcerative Colitis ◽  
High Risk ◽  
Clinical Outcomes ◽  
Corticosteroid Therapy ◽  
Risk Score ◽  
Risk Scores ◽  
Albumin Concentration ◽  
Therapy Failure ◽  
Severe Ulcerative Colitis ◽  
Intravenous Corticosteroid

Abstract Background An episode of acute severe ulcerative colitis (UC) is a watershed event during the disease course with a heightened risk of colectomy during and following these episodes.1 The prompt identification of these events followed by the early implementation of appropriate treatment is essential to obtaining the best clinical outcomes for these unwell patients. The majority of published risk scores predicting the important clinical outcomes of intravenous corticosteroid therapy failure and colectomy-by-discharge rely on clinical data from days 1–3 of therapy.2 There is a paucity of tools that allow for a simple and individualised prediction of risk of corticosteroid therapy failure during the earliest stages of admission. Methods Data were prospectively obtained from 349 presentations of moderate–severe UC requiring hospital admission to a tertiary referral hospital. The failure of intravenous corticosteroid therapy was strictly defined by the (Oxford) Day 3 and Day 7 criteria.3 Seventeen clinical, laboratory and endoscopic variables all available within 24 h of hospital presentation were assessed for their ability to differentiate intravenous corticosteroid therapy responders from non-responders. A stepwise generalised linear model was formulated based on the results of the initial univariate analyses. Results Intravenous corticosteroid therapy failure occurred in 208/349 (60%) of presentations. The formulated risk score included the variables of oral corticosteroid therapy failure, bowel frequency and serum albumin concentration with or without the Mayo endoscopic subscore (MES). With the addition of the MES, the area under the curve (AUC) of the risk score was 0.758. When the positive predictive value of the score (threshold) for correctly predicting intravenous corticosteroid therapy failure was set at 85%, 105/275 (38%) of presentations with available data were identified as high risk for corticosteroid therapy failure (Figure 1). Conclusion This practical risk assessment tool provides clinicians with a personalised prediction of the likelihood of success of a course of intravenous corticosteroid therapy in moderate–severe UC. It enables the identification of individuals at high risk of treatment failure who may be suitable for consideration of early treatment escalation or screening for appropriate clinical trials. References

scholarly journals Systematic Review with Meta-Analysis: Fecal Calprotectin as a Surrogate Marker for Predicting Relapse in Adults with Ulcerative Colitis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jiajia Li ◽  
Xiaojing Zhao ◽  
Xueting Li ◽  
Meijiao Lu ◽  
Hongjie Zhang
Keyword(s):  
Ulcerative Colitis ◽  
Receiver Operating Characteristic ◽  
Likelihood Ratio ◽  
Odds Ratio ◽  
Operating Characteristic ◽  
Diagnostic Odds Ratio ◽  
Fecal Calprotectin ◽  
Clinical Relapse ◽  
Sensitivity Specificity ◽  
Receiver Operating

The clinical course of ulcerative colitis (UC) is featured by remission and relapse, which remains unpredictable. Recent studies revealed that fecal calprotectin (FC) could predict clinical relapse for UC patients in remission, which has not yet been well accepted. To detect the predictive value of FC for clinical relapse in adult UC patients based on updated literature, we carried out a comprehensive electronic search of PubMed, Web of Science, Embase, and the Cochrane Library to identify all eligible studies. Diagnostic accuracy including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and pooled area under the receiver operating characteristic (AUROC) was calculated using a random effects model. Heterogeneity across studies was assessed by the I2 metric. Sources of heterogeneity were detected using subgroup analysis. Metaregression was used to test potential factors correlated to DOR. Publication bias was assessed using Deek’s funnel plots. In our study, 14 articles enrolling a total of 1110 participants were finally included, and all articles underwent a quality assessment. Pooled sensitivity, specificity, PLR, and NLR with 95% confidence intervals (CIs) were 0.75 (95% CI: 0.70–0.79), 0.77 (95% CI: 0.74–0.80), 3.45 (95% CI: 2.31–5.14), and 0.37 (95% CI: 0.28–0.49) respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.82, and the diagnostic odds ratio was 10.54 (95% CI: 6.16–18.02). Our study suggested that FC is useful in predicting clinical relapse for adult UC patients in remission as a simple and noninvasive marker.

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