scholarly journals Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis—An Exploratory Study to Define Deep Remission

2021 ◽  
Author(s):  
Marietta Iacucci ◽  
Louisa Jeffery ◽  
Animesh Acharjee ◽  
Olga Maria Nardone ◽  
Davide Zardo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Markers ◽  
Partial Least Square ◽  
Least Square ◽  
High Magnification ◽  
Gene Expressions ◽  
Endoscopic Score ◽  
Histological Remission ◽  
Cell Adhesion Molecule 1 ◽  
Culture Supernatants

Abstract Background Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores. Methods Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI). Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways. Results Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51–0.98) and NHI (r = 0.86; 95% CI, 0.42–0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27–0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa. Conclusions Endocytoscopy represents an interesting tool that may sit between endoscopy and histology—but closer to the latter—identifying gene expression markers and pathways that are also identified by histology.

scholarly journals DOP14 Ultra-high magnification endocytoscopy and molecular markers for defining endoscopic and histologic remission in Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S052-S054
Author(s):  
M Iacucci ◽  
O M Nardone ◽  
L Jeffery ◽  
A Acharjee ◽  
D Zardo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Molecular Markers ◽  
Cell Function ◽  
Enrichment Analysis ◽  
Partial Least Square ◽  
Least Square ◽  
Tumour Suppressor Genes ◽  
High Magnification ◽  
Histological Remission

Abstract Background Endoscopic and histological remission are important goals to achieve in patients with ulcerative colitis (UC). We aimed to define deep remission by assessing cellular architecture, expression of molecular markers and their correlation with endoscopic scores by using ultra-high-magnification endocytoscopy and histological indices Methods We conducted a prospective study enrolling 29 UC patients (18 males, mean age 41y) referred at a tertiary academic centre for assessing endoscopic remission (ER). All patients underwent colonoscopies with 520-fold magnification endocytoscope. The inflammatory activity was scored using the Mayo Endoscopic Score (MES). ER was defined as MES 0. To assess the grade of inflammation using ECS we set an ECS score (ECSS), whose parameters were summarized in table 1. Biopsies were taken targeting either the worst affected area of inflammation or the most representive area of ER and scored according to Nancy Histopatological Index (NHI) and Robarts Histopatological Index (RHI). Histological remission (HR) is defined as NHI≤1, and RHI≤3 without neutrophils in the epithelium and lamina propria.The correlation between ECSS and MES and with histological scores were determined. Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using Procartaplex Luminex assays and studied by Partial Least Square Discriminant Analysis (PLS-DA) and logistic model. Mucosal RNA sequencing and gene enrichment analysis (GO, KEGG) were performed to define differentially expressed genes/pathways. Results ECSS correlated strongly with RHI (r=0.89 [95%CI 0.51–0.98] and NHI (r=0.86 [95%CI 0.42–0.98] but poorly with MES (r=0.28 [95%CI-0.27–0.70]). We identified that BDNF, MIP-1α and sVCAM-1 predicted HR. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified genes expressed in colonic biopsies that discriminated between healed and non-healed mucosa and overlapped gene expression shared between ECSS, RHI or NHI defined healing. Based on PLS-DA, for healing vs. non healing comparison as defined by RHI, Nancy, Mayo and ECCS we found 32, 83, 127 and 60 differentially genes respectively. These included genes relevant to TGF-b signaling, macrophage recruitment into tissues, neutrophil and plasma cell function and tumour suppressor genes (Fig.1) A number of those identified were shared by MES and ECSS defined healing as well as histological criteria defined healing. Conclusion ECS may sit between endoscopy and histology but closer to the latter and identifies gene expression markers and pathways that are also detected by histology. *OMN,LJ,AA equal authors

scholarly journals Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology?

2021 ◽  
Vol 10 (23) ◽  
pp. 5551
Author(s):  
Panu Wetwittayakhlang ◽  
Livia Lontai ◽  
Lorant Gonczi ◽  
Petra A. Golovics ◽  
Gustavo Drügg Hahn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Current Evidence ◽  
Treat To Target ◽  
Therapeutic Goal ◽  
Treatment Targets ◽  
Patient Reported ◽  
Clinical Biomarker ◽  
Endoscopic Score ◽  
Histological Remission

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.

scholarly journals P545 Calprotectin at week 12 is a predictor for histological remission in ulcerative colitis patients treated with Vedolizumab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S515-S516
Author(s):  
D Rubstov ◽  
P Kakkadasam Ramaswamy ◽  
J Edwards ◽  
D Shukla ◽  
L Willmann ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Real World Setting ◽  
Endoscopic Remission ◽  
Endoscopic Score ◽  
Histological Activity ◽  
Maintenance Of Remission ◽  
Histological Remission ◽  
Endoscopic Assessment

Abstract Background Vedolizumab (VDZ) is a gut-specific α4β7 integrin antagonist that has demonstrated efficacy for induction and maintenance of remission in moderate to severe ulcerative colitis (UC). The aim of this study was to assess the rates of histological remission (HR) in a real-world setting and to identify predictors for histological remission. Methods Retrospective cohort study of all UC patients (≥18 years) initiated on VDZ from 2016 to 2020 was completed. Clinical, biochemical, endoscopic and histologic data were collected. All patients received standard induction therapy with VDZ 300 mg IV at Weeks 0, 2, and 6 and maintained on an 8-weekly regimen. Dose was escalated to a every 4-weekly regimen as per physician’s discretion. A 52-week follow-up was completed on all patients. Endoscopic assessment was carried out between 24 and 52 weeks after commencing VDZ. Histological activity was graded as per Nancy index and histological remission was defined as Nancy grade 0. Endoscopic remission was defined as Mayo endoscopic score = 0. Clinical remission was defined as SCCAI ≤ 5. Results A total of 51 patients [55% female, median age 48 years (IQR 35–60)] were included. 16/51 (34%) were anti-TNF exposed. In 30/51 (59%) patients VDZ was combined with steroids at induction and by week 12 steroids were completely tapered in 14/30 (46.7%) patients. At weeks 12, 24 and 52, 89.6%, 87% and 97.5% of patients, respectively, were in clinical remission. 19/37 (51.3%) patients were in endoscopic remission at end of follow up. Median Nancy score prior to commencing VDZ was 3 (IQR: 2–4) and the median Nancy score at end of follow up was 1 (IQR: 0–2). 19/37 (51.3%) patients achieved HR; 3 patients who were in HR at the time of commencement of VDZ remained in HR at the end of follow up. Median baseline faeces calprotectin (FC) was 320 mcg/g (IQR 45–1000) and was similar in patients who achieved HR and those who did not. Median FC at 12 weeks was 155 mcg/g (45–720) and was significantly lower in patients who achieved HR when compared to patients who did not achieve histological remission (45 vs 420, p 0.028). FC at week 12 predicted histological remission (AUC =0.8667). FC ≥ 200mcg/g at week 12 predicted failure to achieve HR with sensitivity 70%, specificity 100%, PPV 100%, NPV 75%, accuracy 84%. Conclusion Vedolizumab is effective in achieving histological remission and FC ≥ 200 mcg/g at week 12 accurately predicts failure to achieve HR in patients treated with VDZ.

Fecal Calprotectin Thresholds to Predict Endoscopic Remission Using Advanced Optical Enhancement Techniques and Histological Remission in IBD Patients

2020 ◽  
Author(s):  
Rosanna Cannatelli ◽  
Alina Bazarova ◽  
Davide Zardo ◽  
Olga Maria Nardone ◽  
Uday Shivaji ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Cross Sectional Study ◽  
Mucosal Healing ◽  
Cross Sectional ◽  
Endoscopic Techniques ◽  
Endoscopic Remission ◽  
Endoscopic Score ◽  
Histological Remission

Abstract Background Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn’s disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques. Patients and Methods In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients. Receiver operating characteristic curves were created to evaluate the optimum cut-off of FC to predict ER evaluated by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified PICaSSO (Paddington International Virtual Chromoendoscopy Score) for UC patients and Simple Endoscopic Score (SES-CD) in CD patients; and HR was scored by the Robarts Histology Index (RHI) and Nancy Index for UC and modified Riley for CD. Results In UC patients, the best thresholds of FC to identify ER calculated with MES, UCEIS, and modified PICaSSO were 112, 148, and 161 mcg/g with accuracy of 86.9% 86.8%, and 81.6%, respectively. The best value of FC to predict HR was 112 mcg/g and 172 mcg/g with accuracy of 84.2% and 81.6% for RHI and Nancy Index, respectively. In CD patients, the best cut-off of FC to predict ER was 96 mcg/g with accuracy of 82.9%. The HR was best predicted by an FC value of 225 mcg/g with accuracy of 75.6%. Conclusions The FC value threshold between 112 and 172 mcg/g could identify ER and HR in UC patients, whereas a value under 225 mcg/g should be considered for CD patients.

Endocytoscopy can be used to assess histological healing in ulcerative colitis

Endoscopy ◽  
2017 ◽  
Vol 49 (06) ◽  
pp. 560-563 ◽  
Author(s):  
Yoshihiro Nakazato ◽  
Makoto Naganuma ◽  
Shinya Sugimoto ◽  
Rieko Bessho ◽  
Mari Arai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Diagnostic Accuracy ◽  
White Light ◽  
High Accuracy ◽  
Biopsy Specimens ◽  
Endoscopic Remission ◽  
Endoscopic Score ◽  
Histological Remission ◽  
Microscopic Inspection

Abstract Background and study aim Endocytoscopy (ECS) is used in the in vivo microscopic inspection of microstructural mucosal features and enables endoscopists to assess the histological severity of ulcerative colitis (UC). The aim of this study was to assess histological healing in UC patients by using ECS. Patients and methods A total of 64 patients in clinical and endoscopic remission who underwent ECS were selected. The correlation between the ECS score and Geboes score at the rectum was evaluated in patients with a Mayo endoscopic score (MES) of 0. The diagnostic accuracy of the ECS score for histological remission (Geboes score ≤ 2) was also assessed. Results The ECS score ranged from 0 to 5 in patients with endoscopic remission on conventional white-light images (MES of 0). The agreement between histological remission regarding the ECS score and the Geboes score had a κ value of 0.72, and the ECS score showed high accuracy for histological remission, with a sensitivity of 0.77, a specificity of 0.97, and a diagnostic accuracy of 0.86. Conclusion ECS can be used to assess histological healing in patients with UC without the need for biopsy specimens.

scholarly journals P297 Novel serum soluble markers of histological healing in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S302-S302
Author(s):  
O M Nardone ◽  
L Jeffery ◽  
A Bazarova ◽  
A Acharjee ◽  
G Gkoutos ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Operating Characteristic ◽  
Demographic Data ◽  
Characteristic Curve ◽  
Standard Of Care ◽  
Inflammatory Proteins ◽  
Histological Remission ◽  
Cell Adhesion Molecule 1 ◽  
Enhancement Technologies

Abstract Background The recent introduction of a commercial panel of soluble biomarkers, that can predict endoscopic healing, may support the monitoring and management of Crohn’s disease reducing the need of repeated endoscopy.1 Achieving histological remission (HR) is currently considered to be an important target in ulcerative colitis (UC).2 The aim of this study was to identify serological markers of HR in patients with UC and determine their diagnostic accuracy individually and in combination to predict HR. Methods We enrolled 40 UC patients referred to a tertiary academic centre for colonoscopy as part of standard of care. Demographic data and histologic data (RHI, Nancy) were collected. Concentrations of these biomarkers were compared with the histology at the time that the patients underwent colonoscopy with advanced enhancement technologies and targeted biopsies. Histological healing was defined as Nancy ≤1 and RHI ≤3. A total of 55 soluble analytes, relevant to inflammation or shown to be altered in IBD, were measured in serum using Procartaplex luminex assays (ThermoFisher). Finally, 24 analytes that were detected in more than 40% of patients were selected in downstream modelling and used to train a logistic regression model. Results We identified Brain-Derived Neurotrophic Factor (BDNF) and Macrophage Inflammatory Proteins (MIP-1 α) that, when combined together, showed the highest predictive power for predicting RHI≤3 and Nancy ≤ 1 with an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% CI: 0.69–0.97). When we investigated analytes separately for predicting the same outcome, univariate logistic regression was significant for two other markers: Leukemia Inhibitory Factor (LIF) and Vascular Cell Adhesion Molecule 1 (sVCAM1) showing higher values associated with the lack of healing. The AUROC was 0.74 for LIF (95% CI: 0.591–0.89) and 0.72 for sVCAM1 (95% CI: 0.53–0.90). Conclusion BDNF, MIP-1α, LIF and sVCAM may be promising markers to assess histological healing in UC patients. Replication in larger cohorts of patients is now required. *OMN and LJ contributed equally. References

MOTIVASI MEMEDIASI PENGARUH PELATIHAN DAN LINGKUNGAN KERJA TERHADAP KINERJA KARYAWAN PT. TELKOM WITEL YOGYAKARTA

2020 ◽  
Vol 28 (1) ◽  
pp. 71-88
Author(s):  
Tyas Tunjung Sari ◽  
Pandu Nuansa Luhur
Keyword(s):  
Work Environment ◽  
Significant Influence ◽  
Structural Equation ◽  
Employee Performance ◽  
Partial Least Square ◽  
Least Square ◽  
Primary Data ◽  
Version 2.0 ◽  
Analyze Data

This study aims to determine the motivation of work to mediate the effect of training and work environment on employee performance at PT. Telkom Witel Yogyakarta Yogyakarta. The purpose of this study is to determine and analyze 1) the effect of training on employee performance at PT. Telkom Witel Yogyakarta 2) the effect of training on employee performance through motivation at PT. Telkom Witel Yogyakarta 3) the influence of the work environment on employee performance at PT. Telkom Witel Yogyakarta 4) the influence of the work environment on employee performance through motivation at PT. Telkom Witel Yogyakarta. This study uses primary data through research on 62 respondents. Structural Equation is used to analyze data, using PLS (Partial Least Square) version 2.0. The results of this study indicate that there are 1) positive and significant influence of training on employee performance 2) positive and significant influence of work environment on employee performance 3) positive and significant effect of training on employee performance through motivation 4) positive and significant influence of work environment on employee performance through motivation.

Locus Of Control Sebagai Varibel Moderasi Hubungan Kompleksitas Tugas Dan Kinerja Auiditor

2018 ◽  
Vol 16 (2) ◽  
pp. 113
Author(s):  
Sri Hastuti ◽  
Siti Sundari
Keyword(s):  
Locus Of Control ◽  
Big Five ◽  
Partial Least Square ◽  
Least Square

Research Objectives to prove the influence of the complexity of the tasks faced by the Auditor on performance in carrying out duties as an Auditor. The complexity of tasks related to various problems in the company requires locus of control from internal and external to maintain independence and competence.The first auditor performance case occurred in 2002 with the disclosure of the Enron case involving the KAP in the big five, Athur Anderson. In 2008 the Telkom case affected the closure of KAP Edy Priyanto, and there were still many other cases which were violations of the accountant's code of ethics.This research is in the form of quantitative, with proof of the complexity of the task and locus of control on the performance of the auditor. Sample 46 Junior auditors from several KAPs in Surabaya, using the Partial Least Square test, the result that the complexity of the task affects the performance of the Auditor and the interaction of the complexity of the task with locus of control does not affect the performance of the Auditor.

ANALYSIS THE IMPACT OF THE IMPLEMENTATION OF QUALITY MANAGEMENT SYSTEM (QMS) AND SAFETY AND HEALTHY AT WORK MANAGEMENT SYSTEM (SHWMS / SMK3) ON THE JOB PERFORMANCE OF EMPLOYEES

2018 ◽  
Vol 3 (01) ◽  
pp. 45
Author(s):  
Nur Hidayat ◽  
Indah Kusuma Hayati
Keyword(s):  
Quality Management ◽  
Job Performance ◽  
Latent Variables ◽  
Management System ◽  
Quality Management System ◽  
Partial Least Square ◽  
Least Square ◽  
Global Challenges ◽  
The Impact ◽  
Work Management

Recently, the evolvement of globalization era has been the global challenges that cannot be avoided either by private or government sectors, and they are requested to be survived encountering such the condition. The implementation of Quality Management System (QMS) in the operational company is the way how to guarantee the quality of products or services offered to the people. One of the purposes of QMS implementation is to provide a prime satisfaction to the customers. The impact of QMS implementation is expected to increase job performance of the employees. Besides the implementation of Quality Management System (QMS), the impact of global challenges has been increasing the competitive efforts to execute more effective production process. However, it has required manpower protection accordingly. This research aims to find out whether the implementation of quality management system and safety and healthy at work management system have impacted on the job performance of employees. Objects of this research are the employees in the production department at PT Guna Senaputra Sejahtera Plant 1 Bogor. Data analysis technique of this research has applied software Smart PLS (Partial Least Square). PLS has estimated a model of correlation among the latent variables and correlation between latent variables and its indicators. Result of data processing has indicated that the implementation of Quality Management System (QMS) and system of safety and healthy at work have positively and significantly impacted job performance of employees.Keywords : Quality Management System (QMS), Safety and Healthy at Work System ( SHWS / SMK3), and Job Performance of Employees

A Consuequence of Statisfaction and Loyalty: How Brand nd Purchase Intention Affect Its (An empirical study of Bengkulu)

2020 ◽  
Vol 7 (2) ◽  
pp. 61-70
Author(s):  
Fachri Eka Saputra ◽  
Fedyah Anggriani
Keyword(s):  
Customer Satisfaction ◽  
Customer Loyalty ◽  
Purchase Intention ◽  
Partial Least Square ◽  
Least Square ◽  
Primary Data ◽  
Price Fairness ◽  
Online Questionnaire ◽  
Positive Effect ◽  
Descriptive Method

The purpose of this study as to determine how the effect of waterpark image and price fairness on customer satisfaction and its implications for customer loyalty at Waterpark Wahana Surya Bengkulu. The measurement of this study uses 14 indicator items which are distributed using an online questionnaire. The number of samples in this study were 136 respondents and the data were analyzed using SEM PLS (Partial Least Square). Date were collected using a questionnaire using a Likert scale. This research used descriptive method with a quantitative approach. The type of data used in this study is primary data. The results of this study prove that 1. waterpark image has a positive effect on price fairness, 2. Waterpark image has a positive effect on customer satisfaction, 3. Fairness of price has a positive effect on customer satisfaction, 4. Waterpark image has a positive effect on customer loyalty, 5. Fairness of price has a positive effect on customer loyalty, 6. Customer satisfaction has no effect on customer loyalty.

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