Histological Disease Activity Research Articles

Patient-reported Outcomes and Disability Are Associated with Histological Disease Activity in Patients with Ulcerative Colitis: Results from the APOLLO Study.

Treating beyond endoscopic remission, aiming for histological remission, is an emerging target in ulcerative colitis [UC]. Patient-reported outcome measurements [PROMs] become increasingly important, but their association with histology is unclear. Multiple PROMs were prospectively collected in UC patients undergoing colonoscopy. Mayo endoscopic sub-score [MES] and ulcerative colitis endoscopic index of severity [UCEIS] were determined, as well as the Nancy histological index [NHI] of the most affected area. Endoscopic remission was defined as MES and UCEIS 0, histological remission as NHI 0, and histo-endoscopic mucosal remission [HEMR] as a combination of both. A total of 109 assessments were collected in 80 patients with endoscopic and HEMR remission rates of 24.8% and 16.5%, respectively. Patients with HEMR had a significantly lower overall inflammatory bowel disease [IBD] disability [p <0.001] and disease activity score [p <0.001] as compared with patients without. In line, NHI correlated with the overall IBD-disk [r = 0.36, p <0.001] and simple clinical colitis activity index [SCCAI] score [r = 0.44, p <0.001]. Many individual components of both differed significantly between patients with and without HEMR. Although the overall accuracy of the IBD-disk [0.78] or SCCAI score [0.83] for HEMR is lower [p <0.005] than the MES or UCEIS [0.95], a cumulative IBD-disk score >35.5 and an SSCAI score >3.5 have a high negative predictive value [98.6% and 100.0%, respectively] to exclude HEMR. Histo-endoscopic inactive disease is associated with reduced IBD disability, but not with complete absence thereof. PROMs for disability and clinical disease activity cannot fully replace histo-endoscopic findings, and should be considered complementary in patient-centred endpoint discussions. Nevertheless, PROMs have a high negative predictive value to rule out HEMR.

MULTIPLE ENVIRONMENTAL AND SOCIAL DETERMINANTS OF HEALTH FACTORS WERE NOT ASSOCIATED WITH THE GASTROINTESTINAL SYMPTOMATIC BURDEN OF ULCERATIVE COLITIS WITH MUCOSAL HEALING

Abstract INTRODUCTION In a biopsychosocial interdisciplinary model, complex interactions between the hosts (individuals/patients), disease (e.g., ulcerative colitis [UC]), and environment (e.g., social determinants of health [SDOH]) may all contribute to the disease burden. Whether SDOH contributes to the symptomatic burden of UC in deep remission is unclear. METHODS We performed a secondary analysis on prospectively collected data from adults with UC enrolled in the biobank at a tertiary referral center in southern California from 2014-2021. Standardized clinical (unweighted two-item patient-reported outcome [PRO-2] for stool frequency [SF] and rectal bleeding [RB]; remission=SF0/RB0), endoscopic (Ulcerative Colitis Endoscopic Index of Severity [UCEIS]; remission UCEIS=0), and histologic (Geboes score; remission &amp;lt;2B.0) disease activity assessments were performed within 30 days of a colonoscopy (case) with segmental colonic biopsies. SDOH were assessed using the California Healthy Places Index (SDOH Index), a publicly available zip code-based system that ranks SDOH domain and subdomain scores from the least to most healthy (0-100 percentile) using weighted z-scores. Patients without SDOH scores (e.g., reside outside of California; n=88 cases) were excluded. We used χ2-square and Wilcoxon-Mann Whitney tests to investigate for associations between SDOH factors (non-parametric, independent variables dichotomized as below vs above the median) and cardinal GI symptoms (continuous unweighted PRO-2 symptomatic severity and dichotomized clinical remission/active disease), patient-, and disease-related factors. In adults with UC in endoscopic or endo-histologic remission, we used univariate logistic regression to assess the risk of health disadvantage (SDOH score below median) and the presence of GI symptoms. RESULTS Of the 166 UC cases, 46% (76/166), 38% (63/166), and 30% (49/166) were in clinical, endoscopic, and endo-histologic remission, respectively. Approximately one-fifth of cases (21%, 35/166) had SDOH scores below the state median. However, health disadvantage (below SDOH index median) was not associated with clinical, endoscopic, or endo-histologic disease activity; and neither were IBD duration; gender or race/ethnicity (all p&amp;gt;0.05) (Tab 1). Approximately one-third of cases had active GI symptoms despite endoscopic (32%, 20/63) and endo-histologic remission (29%, 14/49). However, none of the eight investigated SDOH domains were associated with increased risks for GI symptoms when UC had objective mucosal healing on colonoscopy (Tab 2) CONCLUSION Although one-third of adults with mucosal healing of UC report GI symptoms (diarrhea/rectal bleeding), there was no association with multiple social determinants of health factors (e.g., education, neighborhood, economic, social, and environmental) in this secondary analysis of a prospective cohort.

MACHINE LEARNING-BASED PREDICTION OF GEBOES SCORE AND HISTOLOGIC IMPROVEMENT AND REMISSION THRESHOLDS IN ULCERATIVE COLITIS

Abstract BACKGROUND Histology is emerging as a key therapeutic endpoint for ulcerative colitis driven by associations between histologic response and long-term outcomes. However, existing scoring systems are subjective and consequently have variable inter- and intra-reader variability. Geboes scoring is a well-established system for ulcerative colitis histologic assessment that has previously been used to define thresholds for histo-endoscopic mucosal improvement (Geboes Score ≤3.1, together with Mayo score 0 or 1) and histologic remission (Geboes Score &amp;lt;2). Here we report the first machine learning (ML)-based prediction of the Geboes Score, and Geboes Score-derived thresholds of histologic improvement and remission, directly from whole slide images (WSI) of hematoxylin and eosin (H&amp;E)-stained mucosal biopsies. METHODS 3,148 WSI were scored by three expert gastrointestinal pathologists and the median consensus score was used to determine the Geboes score for each slide as ground truth. ML models were trained on median consensus scores to predict the Geboes score and subscores for each slide. Model performance vs. pathologist median consensus score was measured using accuracy and the F1 score, which accounts for both false positive and false negative errors. RESULTS The ML-based model performance, measured against median consensus scores of three pathologists, showed strong performance at predicting overall Geboes Score, with a quadratic kappa of 0.89. The model was also able to predict both histologic improvement and histologic remission with high accuracy. For predicting histological improvement as defined by a Geboes Score of ≤3.1, the model showed accuracy of 0.92 and F1 score of 0.92 (Figure 1). For predicting histological remission as defined by a Geboes Score of &amp;lt; 2, the model showed accuracy of 0.91 and F1 score of 0.89 (Figure 2). CONCLUSIONS We report a ML-based approach for predicting Geboes score and Geboes score-based key thresholds of histologic improvement and histologic remission. Model predictions show high accuracy compared to median consensus pathologist scores. This approach may enable standardized, reproducible and accurate prediction of these clinically relevant thresholds to better measure histologic disease activity and treatment response in clinical trials.

Возможности использования электрических и вязкоупругих параметров эритроцитов для диагностики стеатогепатита у пациентов с жировой болезнью печени

Aim: to study the possibilities of using electrical and viscoelastic parameters of erythrocytes to differentiate steatohepatitis from liver steatosis. Patients and Methods: 84 men (48.9±2.5 years) with fatty liver disease diagnosed by abdominal ultrasound were examined. Liver fibrosis severity, which did not exceed grade 1, was determined by indirect elastometry on the FibroScan® 502 Echosens device (France), with confirmation using the FibroTest–ActiTest test system (BioPredictive, France). Patients were divided into 2 groups according to the severity of hepatic necroinflammatory activity, assessed using the same test system. Group 1 (n=44) included patients with hepatic steatosis with minimal histologic disease activity (A 0–1); group 2 (n=40) included patients with steatohepatitis with significant necro-inflammatory activity (A 2–3). The electrical and viscoelastic parameters of erythrocytes were determined by dielectrophoresis at 4 frequencies of an inhomogeneous alternating electric field. Results and Discussion: the most significant electrical and viscoelastic indicators allowing to differentiate steatohepatitis from fatty liver disease were reduced values of strain amplitude at a frequency of 1 MHz (p=0.0003), dipole moment (p=0.009), capacity (p=0.014) and cell polarizability at a frequency of 1 MHz (p=0.03) and more high summarized viscosity (p=0.006), rigidity (p=0.005) and electrical conductivity (p=0.008). Diagnostic panel, including a set of electrical and viscoelastic parameters of erythrocytes, for the differentiation of steatohepatitis from steatosis demonstrated the following: AUC 0.904, sensitivity 0.9, specificity 0.83. Correlations of erythrocyte parameters with indicators of cytolysis syndrome (transaminase activity, serum iron levels, direct bilirubin) and serum inflammatory markers (fibrinogen, C-reactive protein, ferritin) were established. Conclusion: the electrical and viscoelastic parameters of erythrocytes studied using the dielectrophoresis should be considered as a new promising method in determining the severity of fatty liver disease. KEYWORDS: fatty liver disease, steatohepatitis, steatosis, electrical and viscoelastic parameters, erythrocytes, dielectrophoresis, diagnostic model. FOR CITATION: Kruchinina M.V., Parulikova M.V., Belkovets A.V., Gromov A.A. Possibilities of using electrical and viscoelastic parameters of erythrocytes for the diagnosis of steatohepatitis in patients with fatty liver disease. Russian Medical Inquiry. 2023;7(5):249–257 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-2.

Prevalence and Correlations of Gastrointestinal Symptoms With Endoscopic and Histologic Mucosal Healing in Crohn's Disease.

To characterize the associations between clinical disease activity with endoscopic and histologic (endohistologic) mucosal healing in Crohn's disease, we performed a secondary analysis of prospectively collected data on 424 ileocolonoscopies from 258 unique adults at a tertiary referral center from 2014 to 2021. One-third of patients (34%, 25/73) in endoscopic-histologic remission reported gastrointestinal symptoms. The 2-item patient-reported outcome measure for abdominal pain and stool frequency correlated weakly with endoscopic (Simple Endoscopic Score for Crohn's Disease; r = 0.17, 95% CI 0.08-0.26, P = 0.0003) and histologic disease activity (Global Histologic Disease Activity Score; r = 0.14, 95% CI 0.03-0.24, P = 0.015). Overall, gastrointestinal symptoms correlate poorly with endohistologic disease activity.

Pretreating mesenchymal stem cells with IL-6 regulates the inflammatory response of DSS-induced ulcerative colitis in rats

The immunomodulatory properties of mesenchymal stem cells (MSCs) have been broadly investigated in research on inflammatory diseases including ulcerative colitis. Treating MSCs with an inflammatory stimulus before transplantation is an adaptive strategy that helps MSCs survive in areas of inflammation and promotes the regulation of local immune responses. This study aimed to examine the effects of pretreating bone marrow MSCs (BMSCs) with Interleukin-6 (IL-6) on attenuation of dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. Experimental ulcerative colitis was induced in Wistar rats by administering 2% DSS in their water for 7 days and normal water for the next 3 days. The experimental group received 1 × 106/0.4 ml of BMSCs that were treated with IL-6 for 24 h. Histological changes, colon length, and disease activity index were compared among groups, and the levels of TNF-α, IL-6, and IL-1β in homogenate supernatants were evaluated using ELISA. IL-6-pretreated BMSCs significantly reduced the colonic damage score. The colon length shortened by 6.1 ± 0.14 cm for the rats that received IL-6-pretreated BMSCs, whereas the control group rats' value was 3.8 ± 0.14 cm on the 14th day. The levels of pro-inflammatory cytokines were significantly decreased in the colons of the IL-6-pretreated BMSCs group compared with those of the control group (p < 0.05). This study revealed that IL-6-pretreated BMSCs ameliorated DSS-induced colitis via local anti-inflammatory action and suggested that IL-6-pretreated BMSCs are a promising therapeutic agent for ulcerative colitis treatment.

Interobserver Reliability of the Nancy Index for Ulcerative Colitis: An Assessment of the Practicability and Ease of Use in a Single-Centre Real-World Setting.

Histological disease severity assessment in ulcerative colitis [UC] has become a mainstay in the definition of clinical endpoints ['histological remission'] in clinical trials of UC. Several scores have been established in the microscopic assessment of disease activity, but the Nancy index [NI] stands out as being the histological index with the fewest scoring items. To what extent histological assessment using the NI is affected by interobserver reliability in a real-word setting is poorly understood. We therefore performed a single-centre retrospective analysis of NI assessment in patients with UC. We retrospectively evaluated the NI in two independent cohorts [total: 1085 biopsies, 547 UC patients] of clinically diagnosed UC patients, who underwent colonoscopy between 2007 and 2020. Cohort #1 consisted of 637 biopsies from 312 patients, while Cohort #2 consisted of 448 biopsies from 235 patients. Two blinded pathologists with different levels of expertise scored all biopsies from each cohort. A consensus conference was held for cases with discrepant scoring results. Finally, an overall consensus scoring was obtained from both cohorts. The interobserver agreement of the NI was substantial after the assessment of 1085 biopsy samples (κ = 0.796 [95% confidence interval, CI: 0.771-0.820]). An improvement of the interobserver agreement was found with increasing numbers of samples evaluated by both observers (Cohort #1: κ = 0.772 [95% CI: 0.739-0.805]; Cohort #2: κ = 0.829 [95% CI: 0.793-0.864]). Interobserver discordance was highest in NI grade 1 [observer 1: n = 128; observer 2: n = 236]. Interobserver discordance was lowest in NI grades 0 [observer 1: n = 504; observer 2: n = 479] and 3 [observer 1: n = 71; observer 2: n = 66]. The NI is an easy-to-use index with high interobserver reliability for assessment of the histological disease activity of UC patients in a real-world setting. While NI grades 0 and 3 had a high level of agreement between observers, NI grade 1 had a poorer level of agreement. This highlights the clinical need to specify histological characteristics leading to NI grade 1.

Intestinal Barrier Healing Is Superior to Endoscopic and Histologic Remission for Predicting Major Adverse Outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial

Endoscopic and histologic remission have emerged as key therapeutic goals in the management of inflammatory bowel diseases (IBD) that are associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of barrier healing with endoscopic and histologic remission for predicting long-term disease behavior in a large cohort of patients with IBD in clinical remission. At baseline, patients with IBD in clinical remission underwent ileocolonoscopy with assessment of intestinal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity, as well as barrier healing, was prospectively assessed along established scores. During subsequent follow-up, patients were closely monitored for clinical disease activity and the occurrence of major adverse outcomes (MAOs): disease flares, IBD-related hospitalization or surgery, and initiation or dose escalation of systemic steroids, immunosuppressants, small molecules, or biological therapy. The final analysis included 181 patients, 100 with Crohn's disease [CD] and 81 with ulcerative colitis (UC). During a mean follow-up of 35 (CD) and 25 (UC) months, 73% of patients with CD and 69% of patients with UC experienced at least 1 MAO. The probability of MAO-free survival was significantly higher in patients with IBD with endoscopic remission compared with endoscopically active disease. In addition, histologic remission predicted MAO-free survival in patients with UC but not CD. Barrier healing on endomicroscopy was superior to endoscopic and histologic remission for predicting MAO-free survival in both UC and CD. Barrier healing is associated with decreased risk of disease progression in patients with clinically remittent IBD, with superior predictive performance compared with endoscopic and histologic remission. Analysis of barrier function might be considered as a future treatment target in clinical trials. gov number, NCT05157750.

Biopsy and blood-based molecular biomarker of inflammation in IBD

ObjectiveIBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.DesignTranscriptome analysis on 712 endoscopically...

Self-supervised neural network improves tri-exponential intravoxel incoherent motion model fitting compared to least-squares fitting in non-alcoholic fatty liver disease.

Recent literature suggests that tri-exponential models may provide additional information and fit liver intravoxel incoherent motion (IVIM) data more accurately than conventional bi-exponential models. However, voxel-wise fitting of IVIM results in noisy and unreliable parameter maps. For bi-exponential IVIM, neural networks (NN) were able to produce superior parameter maps than conventional least-squares (LSQ) generated images. Hence, to improve parameter map quality of tri-exponential IVIM, we developed an unsupervised physics-informed deep neural network (IVIM3-NET). We assessed its performance in simulations and in patients with non-alcoholic fatty liver disease (NAFLD) and compared outcomes with bi-exponential LSQ and NN fits and tri-exponential LSQ fits. Scanning was performed using a 3.0T free-breathing multi-slice diffusion-weighted single-shot echo-planar imaging sequence with 18 b-values. Images were analysed for visual quality, comparing the bi- and tri-exponential IVIM models for LSQ fits and NN fits using parameter-map signal-to-noise ratios (SNR) and adjusted R 2. IVIM parameters were compared to histological fibrosis, disease activity and steatosis grades. Parameter map quality improved with bi- and tri-exponential NN approaches, with a significant increase in average parameter-map SNR from 3.38 to 5.59 and 2.45 to 4.01 for bi- and tri-exponential LSQ and NN models respectively. In 33 out of 36 patients, the tri-exponential model exhibited higher adjusted R 2 values than the bi-exponential model. Correlating IVIM data to liver histology showed that the bi- and tri-exponential NN outperformed both LSQ models for the majority of IVIM parameters (10 out of 15 significant correlations). Overall, our results support the use of a tri-exponential IVIM model in NAFLD. We show that the IVIM3-NET can be used to improve image quality compared to a tri-exponential LSQ fit and provides promising correlations with histopathology similar to the bi-exponential neural network fit, while generating potentially complementary additional parameters.

Ustekinumab Tissue and Serum Levels in Patients With Crohn's Disease Are Closely Correlated Though Not Consistently Associated With Objective Response After Induction.

Ustekinumab (UST), which targets p40/interleukin (IL)-23 and IL-12, is an effective treatment for Crohn's disease (CD). Therapeutic drug monitoring may optimize UST posology. The aim of this study was to investigate UST and IL-23 serum and tissue concentrations in relation to mucosal inflammation and treatment response at an early time point. CD patients starting UST between December 2016 and November 2018 were prospectively enrolled. Endoscopies were performed at baseline and week 16. UST and IL-23 serum and tissue concentrations were measured at week 16. Clinical and biochemical response were defined as decline of ≥3 points in Harvey-Bradshaw Index and reduction of ≥50% in fecal calprotectin levels. Endoscopic response was defined as a ≥50% decline in Simple Endoscopic Score or a decline of ≥1 points in Rutgeerts score. Histological remission was defined as Global Histologic Disease Activity Score ≤4. Of 56 included patients, 17 (30%) of 56 showed clinical response, 16 (30%) of 53 showed biochemical response, and 20 (36%) of 56 showed endoscopic response. UST, but not IL-23, concentration in biopsies was correlated to levels in corresponding sera (P < .0001). No correlation was found between UST tissue levels and treatment response. Patients achieving biochemical response showed significantly higher UST serum levels (3.12 µg/mL vs 1.41 µg/mL; P = .01). Tissue IL-23-to-UST ratio correlated with mucosal inflammation (P = .01). This is the first study to demonstrate a correlation between serum and tissue UST levels. While tissue IL-23-to-UST ratio correlated with mucosal inflammation, UST serum levels were more indicative for biochemical response. The role of UST levels for therapeutic drug monitoring in inflammatory bowel disease needs further research.

Increased Expression of Interleukin-13 Receptor in Ileum Associated With Nonresponse to Adalimumab in Ileal Crohn's Disease.

The terminal ileum poses a predilection for Crohn's disease (CD) but is less susceptible to undergo healing to treatment with biologics and small molecules. This study aimed to evaluate histologic features associated with endoscopic remission (ER). This is a post hoc analysis of patients with moderately to severely active CD, defined as Crohn's disease activity index 220 to 450, and terminal ileal ulceration treated with antitumor necrosis factor (TNF)-α inhibitor adalimumab from the EXTEND trial. We studied whether baseline total Global Histologic Disease Activity Scores (GHAS), any individual histologic element, and specific immunohistochemical (IHC) markers of chronic inflammation from biopsy specimens were associated with postinduction (week 12) and maintenance (week 52) ER, defined as Simple Endoscopic Score for Crohn's Disease of 0. Multivariable logistic regression models adjusted for confounders were used to assess the relationship between histologic markers and 1-year outcomes. Seventy-one adult patients with CD affecting the ileum were included in this analysis. Both baseline ileal GHAS scores and individual histologic components were not found to be associated with ER at weeks 12 or 52. Increased expression of interleukin-13 receptor (IL-13R) on IHC stains was associated with reduced likelihood of achieving 1-year ER (adjusted odds ratio, 0.06; 95% CI, 0.01-0.92; P = .044). No other biomarker assessed was associated with 1-year ER. Ileal histologic disease activity and IHC activation markers of chronic mucosal inflammation were not associated with 1-year ER. However, strong staining for IL-13 receptor in the ileum was associated with reduced odds of 1-year ER using adalimumab. Mucosal cellular disease profiles might pose an opportunity to guide treatment of CD.

Regulatory and Clinical Expert Perspective of the 2022 FDA Draft Guidance “Celiac Disease: Developing Drugs for Adjunctive Treatment to a Gluten-Free Diet”

Regulatory and Clinical Expert Perspective of the 2022 FDA Draft Guidance “Celiac Disease: Developing Drugs for Adjunctive Treatment to a Gluten-Free Diet”

Clinical application and diagnostic accuracy of artificial intelligence in colonoscopy for inflammatory bowel disease: systematic review

Background and aims Artificial intelligence (AI) technology is being evaluated for its potential to improve colonoscopic assessment of inflammatory bowel disease (IBD), particularly with computer-aided image classifiers. This review evaluates the clinical application and diagnostic test accuracy (DTA) of AI algorithms in colonoscopy for IBD. Methods A systematic review was performed on studies evaluating AI in colonoscopy of adult patients with IBD. MEDLINE, Embase, Emcare, PsycINFO, CINAHL, Cochrane Library and Clinicaltrials.gov databases were searched on 28 th April 2021 for English language articles published between January 1, 2000 and April 28, 2021. Risk of bias and applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Diagnostic accuracy was presented as median (interquartile range). Results Of 1029 records screened, nine studies with 7813 patients were included for review. AI was used to predict endoscopic and histologic disease activity in ulcerative colitis, and differentiation of Crohn’s disease from Behcet’s disease and intestinal tuberculosis. DTA of AI algorithms ranged between 52–91 %. The sensitivity and specificity for AI algorithms predicting endoscopic severity of disease were 78 % (range 72–83, interquartile range 5.5) and 91 % (range 86–96, interquartile range 5), respectively. Conclusions AI has been primarily used to assess disease activity in ulcerative colitis. The diagnostic performance is promising and suggests potential for other clinical application of AI in IBD colonoscopy such as dysplasia detection. However, current evidence is limited by retrospective data and models trained on still images only. Future prospective multicenter studies with full-motion videos are needed to replicate the real-world clinical setting.

FRI040 - Reliability of histologic disease activity measures in non-alcoholic fatty liver disease (NAFLD) and development of an expanded NAFLD activity score

FRI040 - Reliability of histologic disease activity measures in non-alcoholic fatty liver disease (NAFLD) and development of an expanded NAFLD activity score

Mucosal p-STAT1/3 correlates with histologic disease activity in Crohn’s disease and is responsive to filgotinib

ABSTRACT The validity and relevance of histologic disease activity in Crohn’s disease (CD) is unclear, owing to disconnects with endoscopic pathology. Here, we explore relationships between endoscopic, histologic, and molecular activity. This post hoc analysis of the Phase 2 FITZROY trial (NCT02048618) assessed baseline and week 10 (W10) inflammation across matched ileal and colonic segments in CD patients receiving filgotinib 200 mg (n = 42) vs placebo (n = 18). Macroscopic and microscopic disease were assessed by Simple Endoscopic Score for CD ulceration subscore (uSES-CD) and Global Histologic Activity Score activity subscore (aGHAS), respectively. Molecular activity was quantified by phosphorylated signal transducer and activator of transcription (pSTAT)1 and pSTAT3 in epithelium and nonepithelium. Segments were classified as “low” or “high” activity; correlations and concordance were calculated. Logistic regression identified W10 outcome predictors. Overall, 300 segments in 60 patients were assessed. Baseline uSES-CD and aGHAS correlations were 0.72 and 0.53 in colon and ileum, respectively. pSTAT levels had poor-to-moderate concordance with uSES-CD (κ range, 0.11–0.49) but moderate-to-good concordance with aGHAS (0.43–0.77). With filgotinib vs placebo, uSES-CD and aGHAS decreased in significantly more segments with high baseline uSES-CD and aGHAS, and significantly more segments with high baseline pSTAT improved at W10. pSTAT1 was more sensitive to change than uSES-CD and aGHAS. Low baseline pSTAT3 in colon nonepithelium predicted W10 low uSES-CD (P = .044). There was better concordance between histologic and molecular disease activity associated with higher sensitivity to change vs endoscopic severity in ileocolonic CD. Our results suggest histologic activity be included in the assessment of CD inflammatory burden.

Clinical Phenotyping and the Application of Precision Medicine in MAFLD.

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Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita.

Stress-induced heat shock protein 70 (Hsp70) is a key intra- and extracellular molecular chaperone implicated in autoimmune processes. Highly immunogenic extracellular Hsp70 can activate innate and acquired (adaptive) immune responses driving the generation of anti-Hsp70 autoantibodies that are frequently observed in inflammatory/autoimmune disorders. We recently described the direct pathological role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-mediated autoimmune blistering skin disease. Here, we determined the role of anti-Hsp70 autoantibodies in EBA. We observed that circulating anti-Hsp70 IgG autoantibodies were significantly elevated in EBA patients compared to healthy individuals and positively correlated with serum levels of pro-inflammatory interferon gamma (IFN-γ). The pathophysiological relevance of anti-Hsp70 IgG autoantibodies was demonstrated in an antibody transfer-induced EBA mouse model in which elevated serum levels of anti-Hsp70 IgG were found. In addition, anti-Hsp70 IgG-treated animals had a more intense clinical and histological disease activity, as well as upregulated nuclear factor kappa B (NF-κB) activation in skin biopsies compared to isotype-treated animals. Our results suggest that autoantibodies to Hsp70 may contribute to EBA development via enhanced neutrophil infiltration to the skin and activation of the NF-κB signaling pathway in an IFN-γ-associated manner.

Histological Indices and Risk of Recurrence in Crohn's Disease: A Retrospective Study of a Cohort of Patients in Endoscopic Remission.

Although histological healing is raising interest in ulcerative colitis to predict recurrence, its meaning in Crohn's disease (CD) remains unknown. We aimed to study the performances of different histological indices to predict recurrence of CD patients with mucosal healing. Crohn's disease patients with mucosal healing diagnosed between 2010 and 2018 were included if there was available clinical and endoscopical data. Nancy Histological index (NHI), Geboes score (GS), Robarts Histopathology index (RHI), Global Histological Disease Activity Score (GHAS), and Inflammatory Bowel Disease-Distribution Chronicity Activity score (IBD-DCA) were independently assessed by 3 pathologists. Eighty-eight patients were included, of which 28 relapsed (32%) within 30.5 months. All 4 histological indices were associated with recurrence, with significant relapse risk (NHI, odds ratio [OR], 1.67; GHAS, OR, 2.33; RHI, OR, 1.19; GS, OR, 2.09; and IBD-DCA, OR, 2.14). Microscopic activity was significantly associated with relapse only with the IBD-DCA score. Predicting performances of all these scores were poor. Calibration curves indicate that the GHAS and IBD-DCA are the closest to the ideal predicted probability curve and thus could better predict recurrence than the other scores. Interobserver agreement varied from poor for GHAS (k = .39) to good for RHI (k = .68). Histological scores are valuable indicators to predict recurrence. Histological assessment of activity seems insufficient to predict CD course with most of the score evaluated, highlighting the need for new indices or adaptation of actual scores to CD specificities.

Close follow-up is associated with fewer stricture formation and results in earlier detection of histological relapse in the long-term management of eosinophilic esophagitis.

Background and aimsNo recommendations exist regarding optimal follow‐up schedule in patients with eosinophilic esophagitis (EoE) under maintenance treatment.MethodsWe retrospectively evaluated a long‐term surveillance concept at the Swiss EoE clinic, where clinical, endoscopic and histological disease activity is assessed annually regardless of EoE symptoms. Data on 159 adult patients under maintenance steroid treatment with available follow‐up were analyzed. Patients were classified as having close (duration between visits <18 months) or non‐close follow‐up (≥18 months).ResultsWe analyzed a total of 309 follow‐up visits of 159 patients (123 males, age at diagnosis 38.9 ± 15.4 years). 157 (51%) visits were within a close follow‐up schedule (median duration between visits of 1.0 years (interquartile range (IQR) 0.9–1.2)), while 152 visits (49%) were not (median duration between visits 2.9 years (IQR 2.0–4.1)). There was no difference regarding ongoing clinical, endoscopic, and histological disease activity, and adherence to prescribed steroid treatment between the two groups. However, stricture formation was significantly less frequently observed at visits within a close follow‐up schedule (22.9 vs. 33.6%, p = 0.038). Absence of close follow‐up was a significant risk factor for stricture development in a multivariate regression model. Patients who achieved histological remission and were followed within a close‐follow‐up schedule had significantly earlier detection of histological relapse compared to patients not within such close follow‐up.ConclusionClose follow‐up is associated with fewer stricture formation and appears to result in earlier detection of histological relapse in patients with eosinophilic esophagitis. We advocate for regular assessment of disease activity (every 12–18 months) in order to detect relapsing disease as early as possible, and therefore potentially minimize the risk for EoE complications.