Active Colitis Research Articles

The Nancy Histopathological Index has limited value in predicting clinical outcomes in newly diagnosed pediatric patients with ulcerative colitis.

The Nancy Histological Index (NHI) is used to score histologic disease activity in patients with ulcerative colitis (UC). Our goal was to assess the utility of NHI at diagnosis in predicting clinical outcomes in pediatric patients with UC, in comparison to clinical and endoscopic scores. We retrospectively reviewed data at diagnosis of 106 children with UC (59 [55.7%] females; median age 14.4 [11.2-15.9] years, median Pediatric Ulcerative Colitis Activity Index [PUCAI] 35 [25-55]). During a follow-up of 116 (55-171) weeks, 33 patients (31.1%) required azathioprine therapy, and 32 (30.2%) were escalated to anti-tumor necrosis factor alpha (anti-TNFa). The PUCAI and Mayo endoscopic scores at diagnosis were significantly associated with escalation to anti-TNFa (p = 0.036 and p = 0.02, respectively), but not with initiation of azathioprine or subsequent acute severe colitis (ASC) events. However, the NHI was not associated with subsequent immunomodulators or anti-TNFa therapy (p = 0.42 and p = 0.78, respectively), nor with future ASC events (p = 0.70). In conclusion, the NHI failed to predict clinical outcomes in newly diagnosed pediatric patients with UC.

Upadacitinib is associated with clinical response and steroid-free remission for children and adolescents with inflammatory bowel disease.

Upadacitinib, an oral Janus kinase inhibitor (JAKi), is approved for inflammatory bowel disease (IBD) in adults. As on-label use will face significant delay in pediatrics, a real-world understanding of safety and efficacy in children is critical. This is a single-center retrospective cohort of pediatric subjects (ages 9-20 years) with a diagnosis of IBD initiated on upadacitinib. The primary outcome was clinical response following induction (decrease of ≥20 points in the Pediatric Ulcerative Colitis Activity Index [PUCAI] or ≥12.5 points for the Pediatric Crohn's Disease Activity Index [PCDAI]). Secondary outcomes included steroid-free clinical remission (SF-CR) following induction and at Week 24 (PUCAI or PCDAI ≤10), post-induction mucosal response and remission (Mayo for ulcerative colitis [UC]/IBD-unclassified [IBD-U] and simple-endoscopic scoring for CD), and improvement in calprotectin and C-reactive protein (CRP) post-induction. Monitoring for adverse events was recorded. Twenty subjects (40% female with a median age of 16.3 years; 3 CD, 13 UC, 4 IBD-U) were initiated on upadacitinib. Clinical response at Week 8 (UC/IBD-U) and Week 12 (CD), was achieved in 90% (18/20). SF-CR was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy. In subjects with UC/IBD-U (17), PUCAI was significantly improved at Weeks 8 and 24. Calprotectin post-induction showed a significant downtrend, whereas CRP did not. Endoscopic response was noted in seven of the eight cases, with three achieving endoscopic remission. One patient underwent subtotal colectomy after 2 weeks of upadacitinib induction. Another patient stopped therapy following the creation of a diverting ileostomy secondary to rectal perforation experienced following manual dilation of a rectal stricture. No new safety signals were reported. Therapeutic options for children with IBD remain limited. In cases refractory to approved agents, our experience suggests that upadacitinib is effective with no new safety signals in a small subset of patients with IBD (ages 9-20 years) treated at a children's hospital.

Effect of Learning Package on Knowledge, Symptoms Severity and Quality of Life for Patients with Inflammatory Bowel Disease

Background: Inflammatory bowel disease (IBD), a chronic gastrointestinal condition, significantly impacts patients' quality of life, leading to severe symptoms and frequent hospitalizations. Patient education plays a crucial role in managing the disease, as improved overall well-being. Aim: Evaluate the effect of learning package on knowledge, symptoms severity and quality of life for patients with inflammatory bowel disease. Research design: A quasi-experimental research design (pre-posttest). Subjects and setting: 33 patients diagnosed with inflammatory bowel disease were recruited from Tropical Medicine and Gastroenterology department at Aswan University Hospital within 6 months. Tools: (I): Patient's assessment Questionnaire which contained Demographic, Medical history and Knowledge Assessment sheet, (II): Symptom Severity Scale: (Modified Harvey Bradshaw Index Assessment Scale (CD) and Partial Mayo scoring index assessment scale) and (III): Inflammatory Bowel Disease Questionnaire (IBDQ). Results: post-intervention of the learning package, patients' knowledge level increasing from 57.6% to 84.8% (0.028), a statistically significant improvement in the ulcerative colitis activity scoring index and reduced symptom severity (0.001), the overall quality of life also saw a marked improvement, as evidenced by an increase from 63.6% to 90.9% (0.017). Furthermore, significant correlations were found between knowledge and quality of life as well as between quality of life and symptom severity (0.004). Conclusion: The application of the educational package had a significant positive effect on improving knowledge, reducing symptom severity, and enhancing quality of life. Recommendation: The integration of comprehensive educational programs for those patients should be prioritized to improve self-management, and enhance overall patient outcomes.

Extended Monitoring for Transition to Oral Corticosteroids in Acute Severe Ulcerative Colitis May Be Unnecessarily Prolonging Length of Stay.

There is no guideline regarding whether patients treated with intravenous corticosteroids for acute severe ulcerative colitis (ASUC) should be monitored in the hospital after transitioning to oral steroids. Our study aimed to: (1) compare rates of oral steroid transition failure and 30-day readmission between ASUC hospitalizations with extended inpatient monitoring compared to accelerated inpatient monitoring, and (2) identify predictors of oral steroid transition failure. A retrospective cohort study of ulcerative colitis (UC) related admissions at UCSF from 2014 to 2022 was conducted comparing rates of steroid transition failures in extended inpatient monitoring (≥ 24h on oral steroids prior to discharge) to accelerated inpatient monitoring (< 24h on oral steroids). Steroid transition failure was defined as worsening colitis activity with the need to return to IV steroids or undergo colectomy. Data analysis incorporated demographics, disease features, and treatment history. Transition failures from intravenous to oral corticosteroids occurred in 8% of all UC-related admissions. There was a significant difference in transition failure observed between the extended and accelerated monitoring groups, 13 vs 3% (p = 0.03), respectively, with 83.3% of total transition failures occurring within the extended monitoring group. The 30-day readmission rate was 6% in each group (p = 0.93). No significant predictors of transition failures were identified. Transition failures from IV to oral steroids are uncommon in ASUC hospitalizations. Transition failures were more likely to occur with extended monitoring, suggesting potential predictors and/or patient selection bias within this group. Further studies are needed to investigate the parameters driving clinician decision-making regarding oral steroid transitioning.

Sexual dysfunctions in inflammatory bowel disease: role of Mediterranean diet and quality of life.

Dietary factors and chronic gastrointestinal diseases are frequent determinants of sexual dysfunctions (SD). Whether inflammatory bowel diseases (IBD) are associated with SD is not well known as well as the role of diet and quality of life (QoL). To evaluate the prevalence of SD in a cohort of IBD patients and assess the role of clinical-demographic variables, adherence to Mediterranean diet (MD) and QoL. This is a cross-sectional observational study involving 301 patients (134 females and 167 males); 119 had Crohn's Disease and 182 had ulcerative colitis. SD were assessed through the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Adherence to MD was evaluated by the MD Score. QoL was investigated by the 12-item Short-Form Health Survey (SF-12) which yields summary scores of physical (PCS) and mental (MCS) health. Multiple logistic regression was used to identify predictors of SD. Prevalence of SD in females was 61.9%, while 52.1% of males had erectile dysfunction. No differences in the prevalence of SD were found between CD and UC in both males and females. IBD activity, as defined by patient-reported outcomes, was significantly associated with SD in both sexes. In females, MD adherence score (OR 0.8, 95% CI 0.653-0.974, p=0.027), PCS (OR=0.936, CI 95%=0.891-0.983, p=0.008), and MCS (OR 0.9, 95% CI 0.906-0.985, p=0.008) were protective against SD, whereas in males a higher PCS was associated with a lower probability of SD (OR 0.9, 95% CI 0.891-0.978, p=0.004) DISCUSSION: IBD patients had a significant prevalence of SD which occurred more frequently in females than in males. Disease activity is associated with a higher likelihood of SD in both sexes, whereas dietary factors are differentially associated with SD in males and females. A better QoL is associated with a lower risk of SD. SD is prevalent among men and women with IBD. Adherence to MD, PCS and MCS in females as well as PCS in males were protective against SD. The assessment of sexual function in IBD patients could be relevant in order to reach an early diagnosis and a timely treatment.

Metabolic Transcriptional Activation in Ulcerative Colitis Identified Through scRNA-seq Analysis

Background: Ulcerative colitis is a chronic inflammatory disease affecting the colon. During chronic inflammation of epithelial cells, lipid metabolism via pro-inflammatory eicosanoids is known to modify the immune response. Methods: Starting from the Mammalian Metabolic Database, the expression of metabolic enzymes was investigated in two independent cohorts from transcriptome datasets GSE38713 and GSE11223, which analyzed ulcerative colitis tissue samples from the digestive tract. Results: In the first cohort, 145 differentially expressed enzymes were identified as significantly regulated between ulcerative colitis tissues and normal controls. Overexpressed enzymes were selected to tune an Elastic Net model in the second cohort. Using the best parameters, the model achieved a prediction accuracy for ulcerative colitis with an area under the curve (AUC) of 0.79. Twenty-two metabolic enzymes were found to be commonly overexpressed in both independent cohorts, with decreasing Elastic Net predictive coefficients as follows: LIPG (3.98), PSAT1 (3.69), PGM3 (2.74), CD38 (2.28), BLVRA (1.99), CBR3 (1.94), NT5DC2 (1.76), PHGDH (1.71), GPX7 (1.58), CASP1 (1.56), ASRGL1 (1.4), SOD3 (1.25), CHST2 (0.965), CHST11 (0.95), KYNU (0.94), PLAG2G7 (0.92), SRM (0.87), PTGS2 (0.80), LPIN1 (0.47), ME1 (0.31), PTGDS (0.14), and ADA (0.13). Functional enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the main implications of these enzymes in cysteine and methionine metabolism (adjusted p-value = 0.01), arachidonic acid and prostaglandin metabolism (adjusted p-value = 0.01), and carbon metabolism (adjusted p-value = 0.04). A metabolic score based on the transcriptional activation of the validated twenty-two enzymes was found to be significantly greater in Ulcerative colitis samples compared to healthy donor samples (p-value = 1.52 × 10−8). Conclusions: A metabolic expression score was established and reflects the implications of heterogeneous metabolic pathway deregulations in the digestive tract of patients with ulcerative colitis.

Long-Term Sequelae of SARS-CoV-2 Infection in Patients with Inflammatory Bowel Diseases Compared to Relatives with SARS-CoV-2 Infection without Inflammatory Bowel Disease and Inflammatory Bowel Disease Patients without SARS-CoV-2: Results of a Retrospective Case-Control Study

Introduction: Long-term sequelae following acute SARS-CoV-2 infection appear to be common in patients with inflammatory bowel diseases (IBDs). Methods: We examined the frequency and characteristics of post-COVID-symptoms in patients with IBD (IBD-COVID), comparing them to two control cohorts: infected household members of the IBD-COVID patients without IBD (CONT-COVID) and IBD patients without SARS-COV-2 infection (IBD-no-COVID). A questionnaire for the retrospective documentation of possible post-COVID-19 symptoms was distributed to patients and controls from eight referral centers. Results: The 319 IBD-COVID, 108 CONT-COVID, and the 221 IBD-no-COVID patients were similar in terms of sex, age, and comorbidities. The occurrence and duration of fatigue in the IBD-COVID cohort correlated with IBD activity. Other complaints such as reduced cognitive performance (p &lt; 0.05) and sleeping disorders (p &lt; 0.05) were even more common in IBD-COVID patients. Persistent hematochezia (p &lt; 0.001), abdominal pain (p &lt; 0.005), diarrhea (p &lt; 0.0001), and anal problems (p &lt; 0.01) were more often in the IBD-COVID patients than in the CONT-COVID cohort. Furthermore, typical IBD-associated symptoms persist for a longer period after an infection. Frequency of post-COVID complaints is higher in IBD patients compared to controls. After infection, the number of outpatient consultations increased in IBD-COVID patients (7.8% vs. 10.9%, p = 0.008). Conclusion: Fatigue, cognitive impairment, and sleep disturbances are more prevalent among IBD-COVID than CONT-COVID patients. Furthermore, typical IBD-associated symptoms persist for a longer period after an infection. Frequency of post-COVID complaints is higher in IBD patients compared to controls. Tight control of IBD activity could be a suitable tool to avoid post-COVID problems.

The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD. This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD. PD was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups. Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative "pro-inflammatory" microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory-axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Non-coding RNAs as a Critical Player in the Regulation of Inflammasome in Inflammatory Bowel Diseases; Emphasize on lncRNAs.

Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. A hyperactive inflammatory and immunological response in the gut has been shown to be one of the disease's long-term causes despite the complexity of the clinical pathology of IBD. The innate immune system activator known as human gut inflammasome is thought to be a significant underlying cause of pathology and is closely linked to the development of IBD. It is essential to comprehend the function of inflammasome activation in IBD to treat it effectively. Systemic inflammasome regulation may be a proper therapeutic and clinical strategy to manage IBD symptoms since inflammasomes may have a significant function in IBD. Non-coding RNAs (ncRNAs) are a type of RNA transcript that is incapable of encoding proteins or peptides. In IBD, inflammation develops and worsens as a result of its imbalance. Culminating evidence has been shown that ncRNAs, and particularly long non-coding RNAs (lncRNAs), may play a role in the regulation of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in IBD. The relationship between IBD and the gut inflammasome, as well as current developments in IBD research and treatment approaches, have been the main topics of this review. We have covered inflammasomes and their constituents, results from in vivo research, inflammasome inhibitors, and advancements in inflammasome-targeted therapeutics for IBD.

Impact of pain, fatigue and bowel incontinence on the quality of life of people living with inflammatory bowel disease: A UK cross-sectional survey.

People with inflammatory bowel disease (IBD) often experience pain, fatigue and bowel incontinence and are at an increased risk of anxiety and depression. Our aim was to assess the impact of these symptoms on health-related quality of life (QoL) in IBD. In the IBD-BOOST survey, over 26,000 people with IBD across the UK were approached; 8486 participant-completed surveys were returned. Participants' QoL was measured using the EQ-5D-5L questionnaire and their QoL was calculated on a scale ranging from 1 (perfect health) to -0.594 (worst health). Item non-response was imputed. Stages of linear regression models assessed the associations of symptoms with QoL controlling for IBD type, socio-demographic characteristics, co-morbidities and, in further analysis, for IBD activity and IBD control. The EQ-5D-5L questionnaire was fully completed by 8093 (95.4%) participants (mean age of 50years [SD 15]; 49% with Crohn's disease). The mean QoL was 0.76 (SD 0.23). From the three IBD-related symptoms, pain was associated with the largest QoL decrement (-0.159), followed by fatigue (-0.140) and bowel incontinence (-0.048). Co-occurrence of pain and fatigue further reduced QoL. Clear graded associations were observed between symptom severity and QoL decrements (all trend p<0.001). Depression and anxiety were also associated with significant QoL decrements (-0.102 and -0.110 for moderate-to-severe anxiety and moderately severe depression, respectively). Worse IBD control and higher IBD activity were associated with lower QoL. We report strong associations between symptoms of pain, fatigue, bowel incontinence, anxiety, depression, and their severity and reduced QoL in IBD. These estimates could inform future IBD management interventions.

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis

BackgroundThe gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear.Materials and methodsIn this study, we aimed to investigate “novel proteins” underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn’s disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes.ResultsPWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD.ConclusionThe two “novel proteins,” SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in pediatric Inflammatory Bowel Disease: clinical characteristics and outcomes.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in children with inflammatory bowel disease (IBD) has been reported only anecdotally. This study aimed at describing the clinical features and outcomes of children diagnosed with both IBD and HLH/MAS. Data on IBD and HLH/MAS characteristics, biochemical, microbiological and genetic assessments, treatments, and outcomes were collected from the Italian Pediatric IBD Registry and presented using descriptive statistics. Out of 4643 patients with IBD, 18 (0.4%) were diagnosed with HLH/MAS, including 12 with ulcerative colitis and 6 with Crohn disease. Among the 18 patients, 7 (39%) had early-onset IBD, but the median age at HLH/MAS diagnosis was 14.0years (IQR 11.9-16.0). Half of the patients had active IBD at HLH/MAS diagnosis, 11 (61%) patients were on thiopurines, and 6 (33%) were on anti-TNF biologics. An infectious trigger was identified in 15 (83%) patients. One (5%) patients was diagnosed with XIAP deficiency. All patients discontinued thiopurines and 5 (83.3%)discontinued anti-TNF biologics; 16 (80%) patients received steroids for HLH/MAS. Three (17%)patients had a relapse of HLH/MAS. No patient developed lymphoma or died during a median follow-up of 2.7years (IQR 0.8-4.4). Conclusions: HLH/MAS mainly affects children with early-onset IBD but primarily develops during adolescence, following an infection while on immunosuppressant treatment. Although the prognosis is generally favorable, it is crucial to investigate an underlying immune deficiency.

Histopathological Characteristics and Distinction of Immune Checkpoint Inhibitor-Related Colitis

Abstract Introduction/Objective Immune checkpoint inhibitors (ICPIs) represent a groundbreaking class of cancer immunotherapy for patients with various advanced-stage solid cancers. ICPIs have been associated with immune- related adverse events, with ICPI-related colitis being a prominent concern due to its potential for life-threatening clinical complications. Recognizing the histopathologic characteristics specific to ICPI-related colitis is crucial for pathologists to provide an accurate diagnosis. Here we have collected and analyzed colon biopsies from patients with ICPI-related colitis following treatment of ICPIs to identify its distinctive histopathologic features and differentiate it from other colitis. Methods/Case Report Colon biopsies are collected from patients with ICPI-related colitis after receiving CTLA-4 and PD-L1 inhibitors as treatment for advanced melanoma. Histopathological features, including epithelial mucin depletion, enterocyte apoptosis, basal lymphoplasmacytosis, cryptitis, glandular architectural distortion, and granuloma, are compared with those in other colitis including ulcerative colitis, Crohn’s disease, microscopic colitis, ischemic and infectious colitis. Immunohistochemistry is employed to analyze inflammatory cell populations and specific enterocyte subtypes. Results (if a Case Study enter NA) ICPI-related colitis, following treatment with Ipilimumab and Nivolumab, commonly presents as active colitis, either with or without chronic colitis. Less frequently, it manifests as microscopic colitis, infectious or ischemic colitis. The acute active form of ICPI-related colitis resembles acute colitis in infectious or ischemic colitis; however, prominent enterocyte apoptosis and intraluminal apoptotic debris are relatively unique features to ICPI-related colitis. The chronic active form of ICPI-related colitis resembles inflammatory bowel diseases, particularly Crohn’s disease, but ICPI-related colitis exhibits an inflammatory injury more affecting surface mucosa and less basal lymphoplasmacytosis. Notably, the most distinctive feature of ICPI-related colitis is the depletion of specific mucinous epithelium observed in our cohort. Conclusion Recognizing specific histopathologic features of ICPI-related colitis, such as mucinous epithelial depletion, enterocyte apoptosis, and surface-dominant inflammation, are essential for pathologists in accurately diagnosing and distinguishing this disease to ensure proper clinical management for patients receiving ICPI treatment.

Immunomodulatory effect of Dicrocoelium dendriticum ova on DSS-induced experimental colitis in C57BL/6 mouse

Inflammatory bowel disease (IBD) significantly diminishes an individual’s quality of life and increases the risk of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths may suppress the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory effects of Dicrocoelium eggs on experimentally induced colitis in C57BL/6 mice using dextran sulfate sodium (DSS). C57BL/6 mice received 3.5% DSS orally for 7 days to induce colitis, during which they were treated intraperitoneally with Dicrocoelium eggs. The severity of colitis was assessed through parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that Dicrocoelium eggs administration significantly reduced the severity of colitis and disease activity. Histopathological scores improved, correlating with downregulation of IFN-γ and upregulation of IL-4 expression. This findings suggest the therapeutic potential of Dicrocoelium eggs in treating colitis. Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD.

Comparative Value of CRP and FCP for Endoscopic and Histologic Remissions in Ulcerative Colitis.

Aim: We have previously shown that CRP < 2.9 mg/L is a better predictor of endoscopic remission (ER) than CRP < 5 mg/L in ulcerative colitis (UC). Here, we prospectively evaluate CRP and FCP cut-offs and compare them in predicting ER and histological remission (HR) in UC. Method: One hundred thirty-five steroid-free UC patients were evaluated prospectively. ER was defined as Mayo endoscopic sub-score 0-1. In colonoscopy, the colon was evaluated as seven segments: rectum, sigmoid, descending, proximal-transverse, distal-transverse, ascending colon, and cecum. Two biopsies of each segment were evaluated for histological inflammation and graded using the Nancy and Geboes scores. All segment biopsies with Nancy < 1 and Geboes < 2 were defined as HR. Results: The optimum cut-off values for FCP and CRP were 120 μg/g and 2.75 mg/L for ER, respectively. AUC values of FCP and CRP were similar for ER and Mayo-0 disease in ROC analysis. CRP and FCP also had similar performances with these cut-offs regarding ER. While CRP was a predictor to assess the extensiveness of active UC, FCP was not. ROC analysis showed no difference between CRP and FCP regarding HR. Cut-off values for HR were 2.1 mg/L and 55 μg/g for CRP and FCP, respectively. CRP and FCP, in combination with the mentioned cut-off values, detected ER and HR in nearly 2/3 and ½ of the patients, respectively, with high specificity. Conclusions: Reappraised CRP (ER: 2.75 mg/L, HR: 2.1 mg/L) has as much diagnostic contribution as relevant FCP in predicting ER and HR and contributes more to revealing the proximal extension in active colitis compared to FCP. Relevant CRP and FCP combinations may improve the prediction rates.

Pathologist-level diagnosis of ulcerative colitis inflammatory activity level using an automated histological grading method

Background and AimsInflammatory bowel disease (IBD) is a global disease that is evolving with increasing incidence. However, there are few works on computationally assisted diagnosis of IBD based on pathological images. Therefore, based on the UK and Chinese IBD diagnostic guidelines, our study established an artificial intelligence-assisted diagnostic system for histologic grading of inflammatory activity in ulcerative colitis (UC). MethodsWe proposed an efficient deep-learning (DL) method for grading inflammatory activity in whole-slide images (WSIs) of UC pathology. Our model was constructed using 603 UC WSIs from Nanjing Drum Tower Hospital for model train set and internal test set. We collected 212 UC WSIs from Zhujiang Hospital as an external test set. Initially, the pre-trained ResNet50 model on the ImageNet dataset was employed to extract image patch features from UC patients. Subsequently, a multi-instance learning (MIL) approach with embedded self-attention was utilized to aggregate tissue image patch features, representing the entire WSI. Finally, the model was trained based on the aggregated features and WSI annotations provided by senior gastrointestinal pathologists to predict the level of inflammatory activity in UC WSIs. ResultsIn the task of distinguishing the presence or absence of inflammatory activity, the Area Under Curve (AUC) value in the internal test set is 0.863 (95% confidence interval [CI] 0.829, 0.898), with a sensitivity of 0.913 (95% [CI] 0.866, 0.961), and specificity of 0.816 (95% [CI] 0.771, 0.861). The AUC in the external test set is 0.947 (95% confidence interval [CI] 0.939, 0.955), with a sensitivity of 0.889 (905% [CI] 0.837, 0.940), and specificity of 0.858 (95% [CI] 0.777, 0.939). For distinguishing different levels of inflammatory activity in UC, the average Macro-AUC in the internal test set and the external test set are 0.827 (95% [CI] 0.803, 0.850) and 0.908 (95% [CI] 0.882, 0.935). the average Micro-AUC in the internal test set and the external test set are 0.816 (95% [CI] 0.792, 0.840) and 0.898 (95% [CI] 0.869, 0.926). ConclusionsComparative analysis with diagnoses made by pathologists at different expertise levels revealed that the algorithm reached a proficiency comparable to the pathologist with 5 years of experience. Furthermore, our algorithm performed superior to other MIL algorithms.

Predicting Outcomes in Hospitalized Patients With Acute Severe Ulcerative Colitis in a Prospective Multicenter Cohort.

Acute severe ulcerative colitis (UC) (ASUC) requiring hospitalization affects up to 1 in 4 patients with UC. There is a paucity of prospective and multicenter clinical cohorts to study treatment trends and predictors of disease outcomes. Here, we conduct a US-based multicenter prospective clinical cohort of ASUC to study predictors of the need for medical rescue therapy and colectomy. A total of 94 patients hospitalized for ASUC were included across 5 academic centers from December 2018 to December 2021. Demographic, clinical, and laboratory data were collected throughout the hospitalization. Patients were followed up to 1-year post-hospitalization to identify predictors of the need for rescue therapy and colectomy. A total of 21 (22.3%) patients required colectomy within 1 year of admission with 11 (12%) requiring colectomy during the index admission. On multivariate analyses, a BMI < 21.5kg/m2 (OR = 6.16, P = .02), a simple clinical colitis activity index (SCCAI) greater than 8 (OR = 14.44, P = .01) and an albumin level at admission lower than 2.4g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease. In a prospective, multicenter cohort of patients hospitalized with ASUC, BMI, SCCAI, and albumin at admission were important determinants of colectomy risk during the index hospitalization and within 1 year of admission. Colectomy rates remain high-22.3% in this cohort across 5 academic, tertiary care centers-underscoring the need to identify the highest-risk patients, establish novel treatment and care paradigms, and examine opportunities to standardize care.

Evaluation of inhibitory potential of the flavonoid-rich fraction of Myrica esculenta Buch.-Ham. ex D. Don against DSS-induced colonic inflammation in mice

ObjectiveMyrica esculenta (family Myricaceae), a valuable plant species in China and India, has been traditionally used by many tribes and local communities to manage gut disorders. Scientific validation of its anti-ulcerative colitis activity was aimed. MethodsThe ethyl acetate fraction of Myrica esculenta (MeEa) was prepared and evaluated for its potency against DSS-induced ulcerative colitis (UC) in mice at 200 and 400 mg/kg BW oral dose. The effective dose of MeEa was determined through its effect on DSS-induced UC and was further analyzed through its effects on disease activity index (DAI), colon length, colon weight/length ratio, spleen weight, serum and colon tissue cytokine level, cell count and hemoglobin content. Further, the effect was determined through histopathology and FITC-dextran-induced membrane permeability assay. ResultsBetween the two doses, MeEa at 400 mg/kg BW was found to be the most effective dose in terms of reduced DAI scores, protected colon length from shortening, decreased colon weight/length ratio, reduced spleen weight, decreased pro-inflammatory cytokine level and stabilized the anti-inflammatory cytokine level in serum and colon tissue. MeEa 400 reduced cell counts and increased hemoglobin content and platelet count. MeEa 400 also prevented the colon by protecting epithelial cells and crypts. MeEa 400 provided significant protection from intestinal leakage and reduced FITC dextran level in serum. DiscussionMeEa 400 possesses significant anti-inflammatory potential and acts via attenuation of DSS-induced UC and inhibition of DAI scores. It reduces pro-inflammatory cytokines and stabilizes anti-inflammatory cytokine levels, reduces cell count, and protects epithelial tissue and crypts in the colon, as well as intestinal membrane leakage that occurred due to FITC-dextran administration in mice.

S1189 Serum Protein Capillary Electrophoresis as a Biomarker for Endoscopic Disease Activity in Inflammatory Bowel Disease: A Prospective Pilot Study

S1189 Serum Protein Capillary Electrophoresis as a Biomarker for Endoscopic Disease Activity in Inflammatory Bowel Disease: A Prospective Pilot Study

Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity: A systematic review and meta-analysis

Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (i) active IBD versus healthy controls; (ii) inactive IBD versus healthy controls; (iii) active CD versus inactive CD; and (iv) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids also emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD.