Assessment Of Disease Activity Research Articles

Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina

BackgroundThe frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. AimTo describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. Materials and methodsA multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. ResultsA total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. ConclusionsA significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.

Advancing Rheumatology Care Through Machine Learning.

Rheumatologic diseases are marked by their complexity, involving immune-, metabolic- and mechanically mediated processes which can affect different organ systems. Despite a growing arsenal of targeted medications, many rheumatology patients fail to achieve full remission. Assessing disease activity remains challenging, as patients prioritize different symptoms and disease phenotypes vary. This is also reflected in clinical trials where the efficacy of drugs is not necessarily measured in an optimal way with the traditional outcome assessment. The recent COVID-19 pandemic has catalyzed a digital transformation in healthcare, embracing telemonitoring and patient-reported data via apps and wearables. As a further driver of digital medicine, electronic medical record (EMR) providers are actively engaged in developing algorithms for clinical decision support, heralding a shift towards patient-centered, decentralized care. Machine learning algorithms have emerged as valuable tools for handling the increasing volume of patient data, promising to enhance treatment quality and patient well-being. Convolutional neural networks (CNN) are particularly promising for radiological image analysis, aiding in the detection of specific lesions such as erosions, sacroiliitis, or osteoarthritis, with several FDA-approved applications. Clinical predictions, including numerical disease activity forecasts and medication choices, offer the potential to optimize treatment strategies. Numeric predictions can be integrated into clinical workflows, allowing for shared decision making with patients. Clustering patients based on disease characteristics provides a personalized care approach. Digital biomarkers, such as patient-reported outcomes and wearables data, offer insights into disease progression and therapy response more flexibly and outside patient consultations. In association with patient-reported outcomes, disease-specific digital biomarkers via image recognition or single-camera motion capture enables more efficient remote patient monitoring.Digital biomarkers may also play a major role in clinical trials in the future as continuous, disease-specific outcome measurement facilitating decentralized studies. Prediction models can help with patient selection in clinical trials, such as by predicting high disease activity.Efforts are underway to integrate these advancements into clinical workflows using digital pathways and remote patient monitoring platforms.In summary, machine learning, digital biomarkers, and advanced imaging technologies hold immense promise for enhancing clinical decision support and clinical trials in rheumatology. Effective integration will require a multidisciplinary approach and continued validation through prospective studies.

Enhancing Calprotectin's Predictive Power as a Biomarker of Endoscopic Activity in Ulcerative Colitis: A Machine Learning Use Case.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of exacerbation and remission, making disease monitoring and management challenging. Endoscopy, the gold standard for assessing disease activity and severity, involves invasive procedures and is associated with patient discomfort and risks. Using machine learning (ML) to combine fecal calprotectin with other clinical or biological tests can significantly enhance the non-invasive prediction of endoscopic disease activity (EDA) in UC. Aim: To prove that by fusing fecal calprotectin with other clinical data into an ML model, the performance of the non-invasive prediction of EDA can be significantly improved. Methods: We conducted a prospective, observational, single-center study encompassing 103 patients diagnosed with UC. We employed multilayer perceptron models as the core ML algorithm for predicting EDA. For the constructed models, we utilized the varImp function from the caret library in R to assess the significance of each variable in predicting the outcome. Results: Calprotectin as a sole predictor obtained an accuracy of 70% and an area under the curve (AUC) of 0.68. Combining calprotectin with the list of selected predictors that were fed to the MLP models improved accuracy and the AUC. The accuracy of the algorithm on the test set was 85%. Similarly, the AUC increased to 0.93. This is the first study to propose the use of calprotectin as a predictor in an ML model to estimate UC endoscopic disease activity. Conclusion: The deployment of this ML model can furnish doctors and patients with valuable evaluation of endoscopic disease activity which can be highly beneficial for individuals with UC who need long-term treatment.

How to Monitor Disease Activity of Axial Spondyloarthritis in Clinical Practice.

Treatment guided by periodic and quantitative data assessment results in better outcomes compared to using clinical gestalt. While validated generic as well as specific disease activity measures for axial spondyloarthritis (axSpA) are available, there is vast scope to improve their actual utilization in routine clinical practice. In this review, we discuss available disease activity measures for axSpA, describe results from the survey conducted among general rheumatologists as well as Spondyloarthritis Research and Treatment Network (SPARTAN) members about disease activity measurement in daily practice, and discuss ways to improve axSpA disease activity using technological advances. We also discuss the definitions of active disease and target for the treatment of axSpA. The 2019 American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) axSpA treatment guidelines conditionally recommend the regular monitoring of disease activity using a validated measure such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or Ankylosing Spondylitis Disease Severity Index (ASDAS). Assessment of Spondyloarthritis International Society (ASAS)-European Alliance of Associations for Rheumatology (EULAR) guidelines recommend ASDAS as the most appropriate instrument for the assessment of disease activity, preferably calculated using C-reactive protein (CRP). ASAS has selected a core set of variables which were updated recently and have been endorsed by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group in order to bring homogeneity in assessment of axSpA. In a recent study, Patient-Reported Outcomes Measurement Information System (PROMIS®) measures were able to discriminate inactive, moderate, and high-very high ASDAS activity groups. A newly developed semi-objective index P4 (pain, physical function, patient global, and physician global) correlates well with BASDAI and ASDAS in axSpA and can also be used for other rheumatic diseases in busy clinical practices. Regular disease activity monitoring is critical for long-term management of axSpA and shared decision-making. The integration of electronic health records and smart devices provides a great opportunity to capture patient-reported data. Automated capture of electronic patient-reported outcome measures (ePROMs) is a highly efficient way and results in consistent regular monitoring and may improve the long-term outcomes. While currently used measures focus only on musculoskeletal symptoms of axSpA, a composite disease activity measure that can also incorporate extra-articular manifestations may provide a better assessment of disease activity.

Predictive value of individual serum neurofilament light chain levels in short-term disease activity in relapsing multiple sclerosis.

The assessment of serum neurofilament light chain (sNFL) has emerged as a diagnostic and prognostic tool in monitoring multiple sclerosis (MS). However, the application of periodic measurement in daily practice remains unclear. To evaluate the predictive value of individual sNFL levels in determining disease activity in patients with relapsing MS (RMS). In this two-year prospective study, 129 RMS patients underwent quarterly sNFL assessments and annual MRI scans. The study analyzed the correlation between individual NFL levels and past, current, and future disease activity. Group-level Z-scores were employed as a comparative measure. Among the 37 participants, a total of 61 episodes of disease activity were observed. sNFL levels proved valuable in distinct ways; they were confirmatory of previous and current clinical and/or radiological activity and demonstrated a high negative predictive value for future 90 days activity. Interestingly, Z-scores marginally outperformed sNFL levels in terms of predictive accuracy, indicating the potential for alternative approaches in disease activity assessment. In our cohort, sNFL cut-offs of 10.8 pg./mL (sensitivity 27%, specificity 90%) and 14.3 pg./mL (sensitivity 15%, specificity 95%) correctly identified 7 and 4 out of 26 cases of radiological activity within 90 days, respectively, with 14 and 15% false negatives. When using lower cut-off values, individuals with sNFL levels below 5 pg/mL (with a sensitivity of 92%, specificity of 25%, and negative predictive value of 94%) were less likely to experience radiological activity within the next 3 months. Individual sNFL levels may potentially confirm prior or current disease activity and predict short-term future radiological activity in RMS. These findings underscore its periodic measurement as a valuable tool in RMS management and decision-making, enhancing the precision of clinical evaluation in routine practice.

Development of a novel clinimetric tool: PAtient Reported Disease Activity Index in Rheumatoid Arthritis (PARDAI-RA) by PANLAR, for the assessment of patients living with rheumatoid arthritis.

Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care.

A225 ASSESSMENT OF BEDSIDE INTESTINAL ULTRASOUND IN MONITORING CROHN’S DISEASE ACTIVITY

Abstract Background Bedside intestinal ultrasound (IUS) is an evolving modality in monitoring disease activity and assessing complications in inflammatory bowel disease (IBD). The easy-tolerability and immediate accessibility to results for expedited clinical decision-making contribute to the growing global attraction of IUS integration into IBD care. Fecal calprotectin (FC) is a known, non-invasive tool to assess disease activity in IBD. However, it comes with limitations. Aims To assess the efficacy of IUS in monitoring Crohn’s Disease (CD) compared to FC level. Methods We conducted a retrospective observational study in patients with confirmed CD at a certified IUS gastroenterologist’s outpatient clinic in Saskatoon. Patients’ charts undergoing IUS between February 2022 and April 2023 were reviewed. Patients with CD and available FC results within a month of IUS performance were identified. Age, gender, disease character, clinical symptoms (Harvey-Bradshaw Index (HBI)), FC levels, and IUS bowel wall thickening (BWT) were collected. The cut-off for FC levels and BWT for disease activity were ampersand:003E250 μg/g and ampersand:003E3 mm, respectively. The correlation between IUS BWT and FC levels was analyzed based on the Pearson correlation. Results Among a total of 178 chart reviews, 71 patients were identified. The median age was 49 years, 52.1% were males and 47.8% were females. 35 (49.3%) ileal CD, 35 (49.3%) ileocolonic and 1 (1.4%) colonic CD were identified. The HBI score verified 67.6% mild disease, 19.7% moderate, 11.2% in remission, and 1.4% severe disease. The Pearson correlation coefficient (r) between FC levels and BWT findings on IUS was r = 0.29 (P ampersand:003C0.0001), indicating a weak positive correlation. Conclusions A positive but weak correlation exists between bowel wall thickening in IUS and FC level in monitoring CD. Recognizing FC limitations, future multi-center, larger cohort studies need to be done to investigate this correlation further. Funding Agencies None

The Concordance of Patient-Reported Symptoms, Physical Examination and Ultrasound-Detected Synovitis, in Active Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint synovitis and systemic inflammation, with joint swelling and tenderness as common clinical manifestations. Accurate assessment of disease activity is crucial for effective management and treatment planning. While ultrasound (US) has emerged as a sensitive tool for detecting synovitis, its concordance with clinical examination findings remains a subject of ongoing research. Objective: The objective of this study was to evaluate the concordance between clinical examination findings and ultrasound-detected synovitis in RA patients, with an emphasis on the diagnostic value of joint swelling and tenderness. Methods: This observational, cross-sectional study involved 40 RA patients with moderate to severe disease activity, assessed at a single center. Following ethical approval and informed consent, patients were evaluated for joint swelling, tenderness, and patient-reported symptoms. Ultrasound examinations were conducted to detect synovitis, employing gray scale (GS) and power Doppler (PD) modalities. Concordance between clinical findings and US-detected synovitis was analyzed using Cohen's kappa statistic. Disease activity was categorized using the DAS28 score, with subgroup analyses across different disease activity states. Results: Joint swelling demonstrated the highest concordance with US-detected synovitis (kappa = 0.44), while joint tenderness showed lower concordance (kappa = 0.23). Analysis across disease activity states revealed consistent concordance for joint swelling (kappa values ranging from 0.38 to 0.41), regardless of disease severity. Patient-reported symptoms and the use of specific treatments (methotrexate and biologics) were also analyzed, with 90% of patients on methotrexate and 10% on biologics. The study population was predominantly female (86%) and middle-aged (20 to 40 years: 66%). Conclusion: Our findings indicate that joint swelling is a more reliable clinical indicator of synovitis in RA patients compared to joint tenderness. This suggests that disease activity scoring systems in RA might benefit from placing greater emphasis on swelling and patient-reported symptoms. Future research should explore the integration of these parameters to enhance the accuracy and efficiency of RA management.

Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review

BackgroundIn anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers...

Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132

BackgroundCirculating, extracellular RNA is the primary trigger of type I interferon in systemic lupus erythematosus (SLE), and interferon is known to play a central pathogenic role in the disease. RSLV-132...

Diagnostic accuracy of bowel ultrasonography in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Bowel ultrasonography (BUS) is emerging as a promising noninvasive tool for assessing disease activity in inflammatory bowel disease (IBD) patients. We evaluated the diagnostic accuracy of BUS in IBD patients against the gold standard diagnostic method, standard colonoscopy. Major databases were searched from inception to May 2023 for studies on BUS diagnostic accuracy in IBD. Outcomes of interest were pooled sensitivity, specificity, positive (PPV), and negative (NPV) predictive values. Endoscopic confirmation served as ground truth. Standard meta-analysis methods with a random-effects model and I2 statistics were applied. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Twenty studies (1094 patients) were included in the final analysis. The majority (75%) of studies considered bowel wall thickness >3 mm as abnormal. Endoscopic evaluation was performed between days 3 and 180. The pooled diagnostic accuracy of BUS in IBD was 66% (95% confidence interval [CI] 58-72%; I2=78%), sensitivity was 88.6% (95%CI 85-91%; I2=77%), and specificity 86% (95%CI 81-90%; I2=95%). PPV and NPV were 94% (95%CI 93-96%; I2=25%) and 74% (95%CI 66-80%; I2=95%), respectively. On subgroup analysis, small-intestine contrast-enhanced ultrasonography (SICUS) demonstrated high sensitivity (97%, 95%CI 91-99%; I2=83%), whereas BUS exhibited high specificity (94%, 95%CI 92-96%; I2=0%) and NPV (76%, 95%CI 68-83%; I2=80.9%). Meta-regression revealed a significant relation between side-to-side anastomosis and BUS specificity (P=0.02) and NPV (P=0.004). The high diagnostic accuracy of BUS in detecting bowel wall inflammation suggests utilizing regular BUS as the primary modality, with subsequent consideration of SICUS if clinically warranted.

Association of disease activity with depression and anxiety in systemic lupus erythematosus: A comparison of SLEDAI-2K and SLE-DAS.

To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), with depression and anxiety in patients with systemic lupus erythematosus (SLE). A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patients (Spearman's r = 0.764, 95% confidence interval (CI) 0.655-0.842; p< 0.001) and those with moderate-to-high disease activity (Spearman's r = 0.792, 95%CI 0.616-0.892; p< 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; p= 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (OR = 4.472, 95%CI 1.035-19.328, p= 0.045) and anxiety (OR = 3.978, 95%CI 1.051-15.049, p= 0.042). The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

Clinical and Demographic Profiling of Patients with Spondyloarthritis and Its Association with Disease Activity in a Tertiary Hospital in Surabaya, Indonesia

Introduction: The assessment of disease activity is crucial for effectively managing chronic diseases like spondyloarthritis (SpA). Establishing the relationship between disease activity, demographic, and clinical factors is essential for better disease management. This study aimed to delve into the demographic and clinical characteristics of patients at Dr. Soetomo General Academic Hospital, a tertiary hospital in Surabaya, Indonesia, contributing to a comprehensive understanding of SpA occurrences in Surabaya.Methods: Data were obtained from 38 SpA patients’ data classified using ASAS 2009 criteria at Dr. Soetomo General Academic Hospital, excluding individuals with SLE, gout, RA, and septic arthritis. Disease activity was measured using ASDAS-CRP. Association analysis between disease activity, clinical parameters, and demographics was conducted using Mann-Withney U test and Spearman correlation test.Results: Results indicated a male-to-female ratio of 8:30, with patients having a median age of 48 (95% CI: 41-53) and most of the patients had a senior high school education (42.11%). The patients exhibited a mean BMI of 25.19 ± 3.77, a median disease duration of 8.5 (95% CI: 5-10) years, and a median CRP value of 0.2 (95% CI: 0.1-0.5) mg/dL. The majority displayed moderate disease activity, with a median ASDAS-CRP score of 2 (95% CI: 1.5-2.7). Interestingly, no significant correlation was found between disease activity using ASDAS-CRP and the demographic or clinical parameters studied.Conclusion: Disease activities were found not to have correlations with the demography and clinical parameters of patients with SpA from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. This emphasizes the necessity for further research to comprehend the intricate relationship between disease activity and diverse influencing factors.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis

BackgroundImaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). ObjectivesThis study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. MethodsA total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR−), presence/absence of 18F-FDG (PET+/PET−), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(−), MR(−)PET(+)FOCAL, MR(−)PET(+)DIFFUSE, MR(−)PET(−). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/−)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. ResultsPatients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. ConclusionsHybrid MR/PET image–based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image–based classification may have use in prognostication and treatment management in CS.

Dysregulation of long non-coding RNAs in Takayasu arteritis: A proof-of-concept study.

Takayasu arteritis (TAK) is a rare systemic vasculitis primarily affecting the aorta and its major branches. Early diagnosis is critical to prevent severe vascular complications, yet current biomarkers are insufficient. This proof-of-concept study explores the potential of long non-coding RNAs (lncRNAs) in TAK, an area largely unexplored. In this cross-sectional study, 53 TAK patients, 53 healthy controls, and 10 rheumatoid arthritis (RA) patients were enrolled. Clinical evaluations, disease activity assessments, and lncRNA expression levels were analyzed. TAK patients exhibited significant dysregulation in several lncRNAs, including THRIL (19.4, 11.1-48.8 vs. 62.5, 48.6-91.4 arbitrary units [a.u.]; p < 0.0001), HIF1A-AS1 (4.5, 1.8-16.6 vs. 26.5, 19.8-33.7 a.u.; p < 0.0001), MALAT-1 (26.9, 13.8-52.5 vs. 92.1, 58.5-92.1 a.u.; p < 0.0001), and HOTAIR (8.0, 2.5-24.5 vs. 36.0, 30.0-43.8 a.u.; p < 0.0001), compared to healthy controls. Notably, HOTAIR (area under the ROC curve [AUC] = 0.825), HIF1A-AS1 (AUC = 0.820), and THRIL (AUC = 0.781) demonstrated high diagnostic potential with superior specificity (approximately 95%). While lncRNAs showed diagnostic promise, no significant correlations with TAK activity were observed. Comparative analysis with RA patients revealed distinct lncRNA expression patterns. This study unveils significant dysregulation of lncRNAs THRIL, HIF1A-AS1, and HOTAIR in TAK patients, underscoring their potential as biomarkers and opening avenues for further research into the mechanistic roles of these lncRNAs in TAK pathogenesis.

DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.

Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.

NON-INVASIVE DETERMINATION OF DISEASE ACTIVITY IN CROHN’S DISEASE BY SERUM LUMINEX PROFILING

Abstract BACKGROUND &amp; AIMS Crohn’s disease (CD) is a chronic inflammatory disease with a complex pathogenesis; treatment and management largely depend on disease activity assessment, which can be challenging and invasive. The aim of this study was to assess the ability of multiplex Luminex technology to identify serum cytokine and/or chemokine markers of disease activity. METHODS Serum samples were prospectively obtained from 103 CD and 40 healthy controls undergoing colonoscopy. CD activity was determined by histologic assessment of colonoscopic biopsies. The Simple Endoscopic Score for Crohn’s Disease (SES) was available for 94 CD patients. We determined if the SES score was predictive of histologic activity (normal, quiescent, mild, moderate, or severe). Patient demographics and clinical history were obtained by chart review. Serum cytokines and chemokines were measured by a 47-plex Luminex assay. Analytes that had more than 70% of values below the lower limit of detection were excluded (GMCSF, IL3, IL17A, IL22, and TNFβ). Analyte profiles in controls v. CD patients were compared using the Mann-Whitney U test with Benjamini-Hochberg (BH) adjustment given multiple comparisons, and by disease activity (control v. inactive v. active) using the Kruskal-Wallis test, with post-hoc Dunn’s test with BH adjustment. RESULTS 34 CD patients were inactive (normal, quiescent) and 69 CD patients had active disease (mild, moderate, severe) on histology. Use of steroids, immunomodulators, and biologics did not differ significantly between the active and inactive CD groups. There was a strong positive correlation between SES score and histologic disease severity (Spearman’s r = 0.58, p&amp;lt;0.001). After BH adjustment, 16 analytes were significantly increased in CD v. controls: Fractalkine, GROα, IFNα2, IL1β, IL4, IL6, IL10, IL13, IL25, IL17F, IL18, MCP3, MCSF, PDGFAA, PDGFABBB, and TGFα. As shown in Table 1, when categorized by disease activity, 4 analytes were significantly increased and one analyte was significantly decreased in inactive disease v. control; 18 analytes were significantly increased in active v. control; and one analyte, CXCL9, which attracts effector T cells to sites of inflammation, was significantly increased in active v. inactive disease. CONCLUSIONS In CD patients, 16 of 42 serum cytokines and chemokines detectable by Luminex assay were increased v. healthy controls. When stratified by histologic disease activity, multiple analytes were found to be increased in inactive or active CD v. controls. Thus, CD is associated with alterations in serum cytokines and chemokines, which was much more frequent in CD patients with histologically active disease. Serum cytokine/chemokine profiling may be a non-invasive strategy to reduce the need for frequent colonoscopy in CD to assess disease activity. Table 1 Serum analyte profiles compared by disease activity (control v. inactive v. active). Data are shown in pg/mL as mean ± SD. p-values are calculated using Kruskal-Wallis test with post-hoc Dunn’s test with BH adjustment for multiple comparisons where 0.05 was considered significant. *p

P432 Real-time automated assessment of histological disease activity in patients with ulcerative colitis using single wavelength endoscopy technology

Abstract Background Assessment of mucosal healing as a key denominator in the treat-to-target strategy for managing ulcerative colitis remains challenging. To address this, objective evaluation of histological disease activity holds promise. Recent offline research shows encouraging results using a new deep-learning convolutional neural network based on single wavelength endoscopy technology (SWE-CAD) (Fujifilm Co, Japan). We aimed to validate the real-time performance of a new bedside prototype SWE-CAD model during standard colonoscopy. Methods A bedside module for real-time use was integrated in the endoscopy room to evaluate histological disease activity in patients with ulcerative colitis with Mayo Endoscopic Scoring (MES) ranging between 0 and 3. Imaging was performed in rectum and sigmoid following a standardized protocol based on white light and SWE (i.e. monochromatic light of 410nm). Biopsies were taken as reference at the center of the imaged region and were scored for the Geboes score (GBS). The SWE-CAD output was displayed on the separate monitor of the bedside module as a blue or red-colored indication, corresponding to histological remission or non-remission, respectively. Each region (2 in rectum and 2 in sigmoid) was simultaneously scored for MES by the endoscopist. Results In a total of 36 patients histological disease activity was automatically scored using the SWE-CAD. On a section level this CAD-system showed an accuracy of 96.4%, corresponding sensitivity was 99.3% and specificity was 85.5%. When differentiating for disease activity as mild, moderate and severe, accuracy was 97.7%, 62.8% and 95.0%, respectively. On a per-patient level, overall diagnostic accuracy remained high with 94.4%, with only 2/36 underestimations when compared to GBS. Conclusion In this pilot trial, we successfully tested a novel CAD-system, utilizing SWE technology, for real-time assessment of histological disease activity in patients with UC. The system demonstrated exceptional clinical accuracy at 94.4% per-patient level, potentially aiding physicians in interpreting subtle endoscopic abnormalities, leading to cost-effective and individualized patient management.

P357 Automated assessment of histological disease activity in Ulcerative Colitis using a deep learning algorithm

Abstract Background Assessment of histological disease activity in patients with ulcerative colitis (UC) is becoming more important. Therefore, the DCA score was developed for use in clinical practice. Distribution (D), chronicity (C) and activity (A) are each scored on a three-point scale with distribution being dependent on the percentage of biopsy area affected by inflammatory changes. A major problem for implementation of any score is interobserver heterogeneity. To overcome this hurdle, we developed a deep learning algorithm to automatically compute the DCA score. Methods A retrospective cohort was created consisting of 117 adult patients with ulcerative colitis from which biopsies were taken during a colonoscopy performed in the setting of routine clinical evaluation (training set of 537 slides). From 75 cohort patients, an additional set of biopsies was available (test set of 299 slides). An expert gastrointestinal pathologist performed the DCA score. The model was trained on H&amp;E-stained whole slide images scanned at 40x (0.243-μm pixel) resolution. Training was performed in a weakly supervised multiple-instance learning setup, using slide-level labels without region of interest annotations. The features from the convolutional neural network-based model trained at 2.5x, 5x, and 10x magnification were incorporated using a random forest classifier for final prediction. Model accuracy was evaluated using the test set. Results The algorithm differentiates between normal and inflamed with an accuracy of 90.9% (Table 1). Model performance from features aggregated across all magnification levels (i.e., 2.5x, 5x, and 10x) was superior to features from individual levels. This can be explained with the help of GradCam heatmaps (Figure 1), where we show that features learned at different magnification levels correspond to different aspects of histological changes in UC. The multiple instance approach did not appear to detect crypt abscesses, which may have resulted in a relatively poor performance in differentiating A1 from A2. The model accuracy for the 9-class DCA was 64.8%. Conclusion The algorithm first appears to assess architectural distortions at lower magnification and then the presence of cellular elements like neutrophils at higher magnification. This closely mirrors the approach of pathologists. The present model automates the scoring process and by supporting the daily diagnostic practice highlights the potential of deep learning technologies in assessment of histological disease activity in UC.

P713 The introduction of an intestinal ultrasound service significantly reduces diagnostic endoscopy usage in an Inflammatory Bowel Disease service – The SCOPELESS Study

Abstract Background Endoscopic assessment is the gold standard for monitoring of inflammatory bowel disease (IBD) activity. Intestinal ultrasound (IUS) is increasingly utilised as a non-invasive, alternative disease monitoring strategy. Our study aim was to quantify and compare endoscopy usage for evaluation of IBD disease activity before and after the introduction of an IUS service. Methods A retrospective single-centre study was performed. Total numbers of lower GI endoscopies (ileocolonoscopy or flexible sigmoidoscopy) performed for luminal Crohn’s disease (CD) or ulcerative colitis (UC) disease evaluation were collected across two 5-year time periods: the pre-IUS era (2010-2014) and the IUS era (2015-2019). Endoscopies for dysplasia surveillance were excluded. The primary endpoint was a comparison of the cumulative number of endoscopies for IBD disease activity evaluation annually relative to the annual number of patients seen in clinic in the pre-IUS and IUS eras. Secondary endpoints included evaluating the number of endoscopies by individual year within each time period, endoscopies according to diagnosis (CD vs. UC), and the number of IUS performed within the IUS era. Categorical variables were compared using a Chi-squared test. A p value &amp;lt;0.05 was considered statistically significant. Results The number of endoscopies performed for IBD disease evaluation decreased from 576 in the pre-IUS era to 474 in the IUS era despite an increase in cumulative annual patient reviews (1985 vs. 3337 patient reviews, respectively). The annual number of endoscopies for disease evaluation per patient in the pre-IUS and IUS eras is illustrated in Figure 1. The proportion of cumulative annual endoscopies relative to patients reviewed across the 5-years reduced from 29 per 100 patients in the pre-IUS era to 14 per 100 patients in the IUS era (OR 2.47, 95% CI 2.15-2.84; p &amp;lt; 0.001). There was a reduction in total endoscopies for CD evaluation from 325 to 264 and UC evaluation from 251 to 210. The proportion of endoscopies performed for CD vs. UC was unchanged between the two eras (56.4% vs. 55.7%; p = 0.81). In the IUS era, a total of 3319 IUS were performed (2673 CD, 646 UC). This included 1467 IUS for assessment of suspected activity (44 per 100 patients/year) and 1852 IUS for objective confirmation of clinical remission (55 per 100 patients/year). Conclusion In the 5 years following introduction of an IUS service, the number of endoscopies performed for evaluation of IBD activity per patient was halved. IUS was performed for both assessment of disease activity and objective confirmation of clinical remission. The potential workflow and cost savings of reduced endoscopies for IBD disease activity evaluation are significant.