P113 Serum adipokines as non-invasive biomarker in Crohn’s disease

Abstract Background Adipose tissue wrapping the gastrointestinal tract is a risk factor for disease activity in Crohn’s disease (CD). Indeed, adipokines associated to lipid metabolism can modulate local immune responses. However, few studies have investigated the possible association between adipokines and CD. Here, we aimed to evaluate the role of serum adipokines as possible biomarkers in CD. Methods Serum samples were obtained from 18 patients with endoscopically active CD (aCD), 22 patients with endoscopically quiescent CD (qCD) and 36 non-inflamed healthy controls (HC). Serum leptin, ghrelin, resistin and adiponectin were analysed by Multiplex (Bio-Rad, Hercules, CA) in a Luminex 200 system technology. Adipokines means for each group of patients were compared and adjusted by Bonferroni or Wilcoxon tests. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were carried on to evaluate the discriminatory capacity of the adipokines levels between patients groups. Furthermore, for those adipokines that showed an AUC > 0.7, a binary logistic regression adjusted by possible confounders (i.e. sex, age and BMI) was performed in order to test their possible association with CD. Results No differences were found in age, sex or BMI among aCD, qCD and HC; there was no correlation either among the adipokines analysed. Means distribution for serum resistin was different among aCD, qCD and HC (p = 0.006). However, only comparisons between HC and aCD groups showed significant differences (p = 0.02) in the post hoc test. Serum leptin, ghrelin and adiponectin did not show differences between means. ROC curve for resistin showed an AUC of 0.78, with a standard error (SE) of 0.067 when HC and aCD groups were analysed (Figure 1). Furthermore, in this case, as sensitivity and specificity for Youden index correspond to the resistin median concentration, this value was selected as a cut-off for the binary logistic regression analysis; thus, odds ratio (OR) along with their 95% confidence interval (CI) analysis of high relative resistin levels (values higher than their median) adjusted by age, sex and BMI yielded a value of 5.46 (1.34–22.14) when aCD group was compared with HC group. Comparison between qCD and aCD showed an AUC of 0.70 with an SE of 0.089. However, ROC curve did not show a good accuracy when HC and qCD groups were analysed (AUC = 0.58; SE = 0.08). ROC curves analysis for leptin, ghrelin and adiponectin did not show enough accuracy to discriminate between groups. Conclusion Resistin may modulate the inflammation state in CD and it is probably associated to activity, being this association independent of sex, age or BMI.

Download Full-text

Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD)

Gut ◽

10.1136/gutjnl-2020-323799 ◽

2021 ◽

pp. gutjnl-2020-323799

Author(s):

Neeraj Narula ◽

Emily C L Wong ◽

Jean-Frederic Colombel ◽

William J Sandborn ◽

John Kenneth Marshall ◽

...

Keyword(s):

Logistic Regression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Assessment Tool ◽

Training Dataset ◽

Mucosal Inflammation ◽

Youden Index ◽

Active Therapy ◽

Testing Dataset ◽

Endoscopic Remission

Background and aimsThe Simple Endoscopic Score for Crohn’s disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter’s prognostic value for achieving endoscopic remission (ER) while on active therapy.MethodsIn this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort.ResultsBaseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER.ConclusionsWe developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.

Download Full-text

Ustekinumab serum concentrations are associated with clinical outcomes in Crohn’s disease – a regional multi-center pilot study

Zeitschrift für Gastroenterologie ◽

10.1055/a-1088-1461 ◽

2020 ◽

Vol 58 (05) ◽

pp. 439-444 ◽

Cited By ~ 2

Author(s):

Anne Kerstin Thomann ◽

Lucas-Alexander Schulte ◽

Anna-Maria Globig ◽

Peter Hoffmann ◽

Thomas Klag ◽

...

Keyword(s):

Crohn’S Disease ◽

Pilot Study ◽

Crohn's Disease ◽

Clinical Response ◽

Roc Curve ◽

Response To Therapy ◽

Therapeutic Drug ◽

Serum Concentrations ◽

Serum Samples ◽

Area Under Roc Curve

Abstract Background and aim The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn’s disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16. Methods Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration. Results Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001). Conclusion Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation.

Download Full-text

Serum adipokines as non-invasive biomarkers in Crohn’s disease

Scientific Reports ◽

10.1038/s41598-020-74999-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lorena Ortega Moreno ◽

Ancor Sanz-Garcia ◽

Marina J. Fernández de la Fuente ◽

Ricardo Arroyo Solera ◽

Samuel Fernández-Tomé ◽

...

Keyword(s):

Logistic Regression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Area Under The Curve ◽

Healthy Controls ◽

High Concentration ◽

Serum Samples ◽

Receiver Operating Characteristic Curves ◽

Non Invasive ◽

Healthy Control

Abstract Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.

Download Full-text

Clinical Factors Associated With Response to Fecal Diversion in Crohn’s Disease

The American Surgeon ◽

10.1177/0003134820964223 ◽

2020 ◽

Vol 86 (10) ◽

pp. 1277-1280

Author(s):

Hassan Buhulaigah ◽

Adam Truong ◽

Karen Zaghiyan ◽

Phillip Fleshner

Keyword(s):

Logistic Regression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Disease Duration ◽

Binary Logistic Regression ◽

Fecal Diversion ◽

Age At Diagnosis ◽

Perianal Disease ◽

Perineal Pain

Up to 80% of Crohn’s disease (CD) patients require surgery. Fecal diversion is used selectively in CD proctocolitis refractory to medical treatment or advanced perianal disease. This study examines associations between clinical features in predicting clinical response (CR) to fecal diversion in CD. Charts of CD patients undergoing fecal diversion for medically refractory disease or perianal disease were reviewed. Clinical response was assessed focusing on improvements in urgency, abdominal and perineal pain, decreased anal fistula drainage, and weight gain. Univariate binary logistic regression and multivariate forward-stepwise modeling analysis were used to determine associations with CR. The study cohort comprised 79 patients. After a median follow-up of 36 (3-192) months, 40 (51%) patients achieved a CR. Binary logistic regression analysis revealed both age at diagnosis (hazard ratio [HR] 1.05; confidence interval [CI] 1.01-1.09; P = .007) and disease duration (HR .91; CI .86-.96; P = .001) to be significantly associated with CR. Later age of onset (HR 1.05; CI 1.01-1.10; P = .002) and shorter disease duration (HR .91; CI .86-.97; P = .02) remained significant on multivariate analysis. This largest reported series of fecal diversion for refractory CD in the biologic drug era revealed that young age at diagnosis and long disease duration are associated with a lower CR.

Download Full-text

Binary Logistic Regression Analysis of Foramen Magnum Dimensions for Sex Determination

Anatomy Research International ◽

10.1155/2015/459428 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Venkatesh Gokuldas Kamath ◽

Muhammed Asif ◽

Radhakrishna Shetty ◽

Ramakrishna Avadhani

Keyword(s):

Logistic Regression ◽

Sex Determination ◽

Roc Curve ◽

Structural Integrity ◽

Binary Logistic Regression ◽

Foramen Magnum ◽

Binary Logistic Regression Analysis ◽

Transverse Diameter ◽

South Indian Population ◽

South Indian

Purpose. The structural integrity of foramen magnum is usually preserved in fire accidents and explosions due to its resistant nature and secluded anatomical position and this study attempts to determine its sexing potential. Methods. The sagittal and transverse diameters and area of foramen magnum of seventy-two skulls (41 male and 31 female) from south Indian population were measured. The analysis was done using Student’s t-test, linear correlation, histogram, Q-Q plot, and Binary Logistic Regression (BLR) to obtain a model for sex determination. The predicted probabilities of BLR were analysed using Receiver Operating Characteristic (ROC) curve. Result. BLR analysis and ROC curve revealed that the predictability of the dimensions in sexing the crania was 69.6% for sagittal diameter, 66.4% for transverse diameter, and 70.3% for area of foramen. Conclusion. The sexual dimorphism of foramen magnum dimensions is established. However, due to considerable overlapping of male and female values, it is unwise to singularly rely on the foramen measurements. However, considering the high sex predictability percentage of its dimensions in the present study and the studies preceding it, the foramen measurements can be used to supplement other sexing evidence available so as to precisely ascertain the sex of the skeleton.

Download Full-text

Postoperative Ratio of C-Reactive Protein to Albumin as a Predictive Marker in Patients with Crohn’s Disease Undergoing Bowel Resection

Gastroenterology Research and Practice ◽

10.1155/2021/6629608 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hangfen Zhao ◽

Huaying Liu ◽

Weilin Qi ◽

Wei Liu ◽

Lingna Ye ◽

...

Keyword(s):

Crohn’S Disease ◽

Postoperative Complications ◽

Crohn's Disease ◽

Surgical Site Infections ◽

Predictive Marker ◽

Roc Curves ◽

Youden Index ◽

C Reactive Protein ◽

Reactive Protein ◽

Significant Independent Risk Factor

Background. The ratio of C-reactive protein (CRP) to albumin (CAR) has a significant correlation with postoperative complications and acts as a predictor in patients with pancreatic cancer and colorectal cancer. However, whether the CAR can be used to predict complications in Crohn’s disease (CD) patients after surgery has not yet been reported. Methods. A total of 534 CD patients undergoing surgery between 2016 and 2020 were enrolled. The risk factors of postoperative complications were assessed by univariate and multivariate analyses. The cutoff values and the accuracy of diagnosis for the CAR and postoperative CRP levels were examined with receiver operating characteristic (ROC) curves. Results. The rate of postoperative complications was 32.2%. The postoperative CAR (OR 13.200; 95% CI 6.501-26.803; P < 0.001 ) was a significant independent risk factor for complications. Compared with the CRP level on postoperative day 3, the CAR more accurately indicated postoperative complications in CD patients (AUC: 0.699 vs. 0.771; Youden index: 0.361 vs. 0.599). ROC curves showed that the cutoff value for the CAR was 3.25. Patients with a CAR ≥ 3.25 had more complications ( P < 0.001 ), a longer postoperative stay ( 15.5 ± 0.6 d vs. 9.0 ± 0.2 d, P < 0.001 ), and more surgical site infections (48.2% vs. 5.7%, P < 0.001 ) than those with a CAR < 3.25 . Conclusions. Compared to the CRP level, the CAR can more accurately predict postoperative complications and can act as a predictive marker in CD patients after surgery.

Download Full-text

Establishing a diagnostic scale of subacute thyroiditis without radioisotope scanning

10.21203/rs.3.rs-17946/v2 ◽

2020 ◽

Author(s):

Zhouyi Xiong ◽

Chunying Luo ◽

Li Wang ◽

Bin Xiong ◽

Jianneng Wu

Keyword(s):

Logistic Regression ◽

Regression Model ◽

Roc Curve ◽

Logistic Regression Model ◽

Univariate Analysis ◽

Binary Logistic Regression ◽

Subacute Thyroiditis ◽

Youden Index ◽

Control Group ◽

Radioisotope Scanning

Abstract Background: Radioisotope scanning is important to diagnose subacute thyroiditis(SAT), but it’s not always available. So we aim to establish a diagnostic scale for SAT without radioisotope scanning.Methods: The suspected SAT patients hospitalized in Yuebei people's Hospital from January 2012 to December 2016 were selected and divided into study group and control group according to whether they were diagnosed as SAT. The clinical indexes of two groups were collected and the diagnostic scale of SAT was established by using binary logistic regression analysis. The effectiveness of the scale was evaluated by ROC curve. Results: Of 309 patients, 58.25% of patients were confirmed with SAT and the remaining 41.75% of patients were not diagnosed with SAT. After univariate analysis, variables which were considered statistically different(P<0. 05) between the two groups were selected as independent variables and the diagnosis of SAT was taken as dependent variable in the binary logistic regression model. The logistic regression model consisted of 4 variables, each was thyroid tenderness, firm on palpation, increased ESR and elevated thyroid hormone level. The P value of Omnibus tests was≤0. 001 and the Nagelkerke R Square was 0. 915. The diagnostic scoring scale was established with these four variables according to their regression coeffient. The area under the ROC curve for this diagnostic scale was 0. 991(95% confidence interval, 0. 982-0.999). The highest Youden index was 0. 912, the corresponding cut-off point was 7. Internally validation shows a sensitivity of 92. 78% and a specificity of 98.45% of our scale. Conclusions: We established and validated a diagnostic scale for SAT without the need for radioisotope scanning for the first time. It has good application in institutions that do not have radioisotope machines or among pregnant and lactating women.

Download Full-text

Establishing a diagnostic scale of subacute thyroiditis without radioisotope scanning

10.21203/rs.3.rs-17946/v1 ◽

2020 ◽

Author(s):

Zhouyi Xiong ◽

Chunying Luo ◽

Li Wang ◽

Bin Xiong ◽

Jianneng Wu

Keyword(s):

Logistic Regression ◽

Regression Model ◽

Roc Curve ◽

Logistic Regression Model ◽

Univariate Analysis ◽

Binary Logistic Regression ◽

Subacute Thyroiditis ◽

Youden Index ◽

Control Group ◽

Radioisotope Scanning

Abstract Background: Radioisotope scanning is important to diagnose subacute thyroiditis(SAT),but it’s not always available.So we aim to establish a diagnostic scale for SAT without radioisotope scanning. Methods: The suspected SAT patients hospitalized in Yuebei people's Hospital from January 2012 to December 2016 were selected and divided into study group and control group according to whether they were diagnosed as SAT. The clinical indexes of two groups were collected and the diagnostic scale of SAT was established by using binary logistic regression analysis.The effectiveness of the scale was evaluated by ROC curve. Results: Of 261 patients,69% of patients were confirmed with SAT and the remaining 31% of patients were not diagnosed with SAT. After univariate analysis,variables which were considered statistically different( P <0.05) between the two groups were selected as independent variables and the diagnosis of SAT was taken as dependent variable in the binary logistic regression model. The logistic regression model consisted of 4 variables, each was thyroid tenderness,firm on palpation, increased ESR and hyperthyroidism.The P value of Omnibus tests was ≤0.001 and the Nagelkerke R Square was 0.894. The diagnostic scoring scale was established with these four variables according to their regression coeffient.The area under the ROC curve for this diagnostic scale was 0.989(95% confidence interval, 0.978-1.0).The highest Youden index was 0.908,the corresponding cut-off point was 5.5.Internally validation shows a sensitivity of 93.33% and a specificity of 97.53% of our scale. Conclusions: We established and validated a diagnostic scale for SAT without the need for radioisotope scanning for the first time.It has good application in institutions that do not have radioisotope machines or among pregnant and lactating women.

Download Full-text

Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease

Molecules ◽

10.3390/molecules24030449 ◽

2019 ◽

Vol 24 (3) ◽

pp. 449 ◽

Cited By ~ 12

Author(s):

Yunjia Lai ◽

Jingchuan Xue ◽

Chih-Wei Liu ◽

Bei Gao ◽

Liang Chi ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

High Resolution Mass Spectrometry ◽

Signaling Cascades ◽

Compound Identification ◽

Serum Samples ◽

Therapy Assessment ◽

Integral Role ◽

Important Pathway ◽

Biomarker Research

: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.

Download Full-text

Predicting Burn Mortality Using a Simple Novel Prediction Model

Indian Journal of Plastic Surgery ◽

10.1055/s-0040-1721867 ◽

2021 ◽

Author(s):

Sneha Sharma ◽

Raman Tandon

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Prediction Model ◽

Receiver Operating Characteristic ◽

Logistic Regression Analysis ◽

Operating Characteristic ◽

Binary Logistic Regression ◽

Apache Ii ◽

Apache Ii Score ◽

Binary Logistic Regression Analysis

Abstract Background Prediction of outcome for burn patients allows appropriate allocation of resources and prognostication. There is a paucity of simple to use burn-specific mortality prediction models which consider both endogenous and exogenous factors. Our objective was to create such a model. Methods A prospective observational study was performed on consecutive eligible consenting burns patients. Demographic data, total burn surface area (TBSA), results of complete blood count, kidney function test, and arterial blood gas analysis were collected. The quantitative variables were compared using the unpaired student t-test/nonparametric Mann Whitney U-test. Qualitative variables were compared using the ⊠2-test/Fischer exact test. Binary logistic regression analysis was done and a logit score was derived and simplified. The discrimination of these models was tested using the receiver operating characteristic curve; calibration was checked using the Hosmer—Lemeshow goodness of fit statistic, and the probability of death calculated. Validation was done using the bootstrapping technique in 5,000 samples. A p-value of <0.05 was considered significant. Results On univariate analysis TBSA (p <0.001) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p = 0.004) were found to be independent predictors of mortality. TBSA (odds ratio [OR] 1.094, 95% confidence interval [CI] 1.037–1.155, p = 0.001) and APACHE II (OR 1.166, 95% CI 1.034–1.313, p = 0.012) retained significance on binary logistic regression analysis. The prediction model devised performed well (area under the receiver operating characteristic 0.778, 95% CI 0.681–0.875). Conclusion The prediction of mortality can be done accurately at the bedside using TBSA and APACHE II score.

Download Full-text