Role of Calprotectin, IL-6, and CRP in Distinguishing Between Inflammatory Bowel Disease and Diarrhea Predominant Irritable Bowel Syndrome.

Background: The early establishment of prophylaxis and immediate administration of anticoagulant therapy upon the diagnosis of venous thromboembolism should be the treatment objectives in these patients. Objective: The study aimed to determine the optimal cut-off point of Calprotectin, IL-6 (interleukin-6), CRP (C reactive protein) to differentiate UC, IBS-D. Methods: A cross-sectional descriptive study of 335 individuals ≥15 years old was performed, including 31 healthy controls, 215 with IBS-D, 71 diagnosed with UC, and 18 diagnosed with CD. Receiver Operating Characteristics (ROC), sensitivity, specificity, and area under curve (AUC) were computed. Results: The results showed that the median value of calprotectin (IQR) in healthy participants was 20.0 (6.0 - 34.0) µg/g; 17,7 (8,7-38,9) µg/g in IBS-D group; 1710.0 (588 - 4260,0) µg/g in UC group; and 560.5 (177.8 - 1210.0) µg/g in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of CRP (range IQR) was 1,3 (0,9 - 2,3) mg/L in IBS-D group; 7.0 (2.4 -16.6) mg/L in UC group; and 10.1 (2.2 - 42.5) mg/L in CD group. CRP concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of IL-6 (range IQR) was 2.3 (1.6 - 5.7) pg/mL in IBS-D group; 16.8 (9.4 - 47.0) pg/mL in UC group; and 9.4 (7.9 - 11.0) pg/mL in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The optimal cut-off point of calprotectin that differentiated IBS-D from IBD was 110.5 µg/g, with sensitivity and specificity of 93.3% and 91.4%, respectively; of IL-6 was 7.2 pg/mL with sensitivity and specificity of 92.0% and 78.0%, respectively; of CRP of 2.4 mg/L had specific sensitivities of 83.3% and 86.0%, respectively. Conclusion: The Calprotectin immunoassay has the best value in discriminating between IBD and IBS-D.

Identification and surgical management of acute severe ulcerative colitis: A guide for general practitioners.

BACKGROUND: Approximately 25% of patients with ulcerative colitis (UC) develop acute severe UC (ASUC), necessitating urgent care. General practitioners (GPs), whether based in rural or urban settings, are instrumental in detecting early warning signs, expediting emergency interventions, coordinating with medical teams, educating patients and overseeing outpatient care. This involvement ensures timely, appropriate surgical responses, especially if complications arise or medical treatments prove ineffective. OBJECTIVE: This review provides GPs with an understanding of ASUC evaluation and risk assessment, emphasising surgical management and complementing existing medical methods. The objective is to equip GPs, whether in rural or urban environments, with the knowledge and confidence to play an integral role in the treatment team. DISCUSSION: Identifying and diagnosing ASUC is crucial for timely emergency care. Moreover, effective ASUC management demands appropriate preoperative work-up. GPs should be adept at monitoring treatment efficacy and guiding patients through surgical aftercare. Thus, GPs should be well versed in diagnostic criteria and surgical approaches for ASUC, as well as their important role within a multidisciplinary team.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Inflammatory Bowel Disease in Adults - Experience and Challenges in Gastroenterology Practices in Calabar, South-South Nigeria.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is reported to be rare in Africans. The objective of this study is to share the experience of our Gastroenterology practice in Calabar, Cross River State on IBD. METHODS: This is a ten-year review of the records of patients visiting the Gastroenterology clinic of the University of Calabar Teaching Hospital and two private gastroenterology clinics in Calabar Municipality. The diagnosis of IBD was made based on clinical, laboratory, endoscopic, and histological data obtained. RESULTS: Eight patients presented with features consistent with IBD. Six had ulcerative colitis while 2 had Crohn's disease. Seven patients had moderate disease with the main clinical features being recurrent mucoid bloody diarrhoea. All the patients had treatments with either sulphasalazine or mesalazine as well as azathioprine, steroids and antibiotics with variable response. One patient had strictures requiring a colostomy, while another developed colorectal cancer as complications of IBD. CONCLUSION: Although IBD is uncommon in Nigeria, a high index of suspicion is important, especially in patients presenting with the recurrent passage of mucoid bloody stools. Hence, the role of colonoscopy and histology are invaluable in establishing the diagnosis.

FONDEMENT: La maladie inflammatoire de l'intestin (MII) est un trouble inflammatoire chronique du tractus gastro-intestinal qui est rapporté comme étant rare chez les Africains. L'objectif de cette étude est de partager l'expérience de notre pratique en gastroentérologie à Calabar, dans l'État de Cross River, sur la MII. MÉTHODES: Il s'agit d'une revue de dix ans des dossiers des patients fréquentant la clinique de gastro-entérologie de l'Hôpital universitaire de Calabar et de deux cliniques privées de gastroentérologie dans la municipalité de Calabar. Le diagnostic de MII a été posé sur la base de données cliniques, biologiques, endoscopiques et histologiques obtenues. RÉSULTATS: Huit patients présentaient des caractéristiques compatibles avec la MII. Six présentaient une colite ulcéreuse tandis que 2 présentaient une maladie de Crohn. Sept patients avaient une maladie modérée avec comme principale caractéristique clinique des diarrhées muqueuses sanglantes récurrentes. Tous les patients ont été traités soit avec de la sulfasalazine soit avec de la mésalazine ainsi que de l'azathioprine, des stéroïdes et des antibiotiques avec une réponse variable. Un patient avait des sténoses nécessitant une colostomie, tandis qu'un autre développait un cancer colorectal comme complications de la MII. CONCLUSION: Bien que la MII soit rare au Nigeria, un indice de suspicion élevé est important, surtout chez les patients présentant un passage récurrent de selles muqueuses sanglantes. Ainsi, le rôle de la coloscopie et de l'histologie est inestimable pour établir le diagnostic. MOTS-CLÉS: Adultes, Maladie de Crohn, Maladie inflammatoire de l'intestin, Colite ulcéreuse.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

BACKGROUND: Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. AIM: To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. METHODS: We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. RESULTS: The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. CONCLUSION: TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Disease clearance in ulcerative colitis: A new therapeutic target for the future.

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.

Infantile inflammatory bowel disease in three Syrian infants: a case series.

BACKGROUND: Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis, are chronic bowel relapsing inflammatory disorders. Inflammatory bowel diseases begin rarely in infants. Approximately 25% of patients with inflammatory bowel diseases present before the age of 20 years. Very early-onset inflammatory bowel disease occurs before the age of 6 years; infantile inflammatory bowel diseases occurs before the age of 2 years, and is extremely rare in infants under 1 year of age. CASE PRESENTATION: Herein, we report a case series of 7-month-, 11-month-, and 12-month-old Syrian infants that presented with diarrhea, hematochezia, and pale appearance and were finally diagnosed with infantile inflammatory bowel disease and treated. CONCLUSIONS: Early diagnosis and ruling out infantile inflammatory bowel diseases despite its rarity are recommended. Over and above that, new drugs such as vedolizumab, golimumab, and less invasive treatment methods should also be taken into consideration for better response and adequate remission with improved quality of life.

Diagnosis change in pediatric inflammatory bowel disease.

OBJECTIVES: This study aims to characterize pediatric inflammatory bowel disease (IBD) patients who change diagnosis and describe the characteristics of that change. METHODS: A retrospective study was conducted on pediatric IBD patients from the ImproveCareNow (ICN) multicenter international cohort from 2007 to January 2019. Primary outcome was change in diagnosis after the first four visits. Other variables included demographics, diagnostics, disease characteristics, and timing. RESULTS: 6.1% of 18,055 patients aged 1-20 years changed diagnosis. Median time between the baseline visit and first diagnosis change was 0.9 years. Change in diagnosis occurred in 257/12,178 (2.1%) patients with Crohn's disease (CD), 347/4758 (7.3%) patients with ulcerative colitis (UC), and 495/1119 (44.2%) patients with IBD-Unclassified (IBD-U). In multivariable analysis, initial diagnosis of IBD-U and longer follow-up times were associated with greater odds of a diagnosis change. CONCLUSION: IBD-U initial diagnosis and longer follow-up were associated with increased diagnosis change risk. The most common change was reclassification to CD. Disease activity, moderate malnutrition, and presence of EIMs were not associated with change in diagnosis.

A comparison of Bayesian and frequentist approaches to incorporating clinical and biological information for the prediction of response to standardized pediatric colitis therapy.

BACKGROUND: The prospective cohort study PROTECT is the largest study in pediatric ulcerative colitis (UC) with standardized treatments, providing valuable data for predicting clinical outcomes. PROTECT and previous studies have identified characteristics associated with clinical outcomes. In this study, we aimed to compare predictive modeling between Bayesian analysis including machine learning and frequentist analysis. METHODS: The key outcomes for this analysis were week 4, 12 and 52 corticosteroid (CS)-free remission following standardized treatment from diagnosis. We developed predictive modeling with multivariable Bayesian logistic regression (BLR), Bayesian additive regression trees (BART) and frequentist logistic regression (FLR). The effect estimate of each risk factor was estimated and compared between the BLR and FLR models. The predictive performance of the models was assessed including area under curve (AUC) of the receiver operating characteristic (ROC) curve. Ten-fold cross-validation was performed for internal validation of the models. The estimation contained 95% credible (or confidence) interval (CI). RESULTS: The statistically significant associations between the risk factors and early or late outcomes were consistent between all BLR and FLR models. The model performance was similar while BLR and BART models had narrower credible intervals of AUCs. To predict week 4 CS-free remission, the BLR model had AUC of 0.69 (95% CI 0.67-0.70), the BART model had AUC of 0.70 (0.67-0.72), and the FLR had AUC of 0.70 (0.65-0.76). To predict week 12 CS-free remission, the BLR model had AUC of 0.78 (0.77-0.79), the BART model had AUC of 0.78 (0.77-0.79), and the FLR model had AUC of 0.79 (0.74-0.83). To predict week 52 CS-free remission, the BLR model had AUC of 0.69 (0.68-0.70), the BART model had AUC of 0.69 (0.67-0.70), and the FLR model had AUC of 0.69 (0.64-0.74). The BART model identified nonlinear associations. CONCLUSIONS: BLR and BART models had intuitive interpretation on interval estimation, better precision in estimating the AUC and can be alternatives for predicting clinical outcomes in pediatric patients with UC. BART model can estimate nonlinear nonparametric association.

Identified S100A9 as a target for diagnosis and treatment of ulcerative colitis by bioinformatics analysis.

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease. UC confronts with severe challenges including the unclear pathogenesis and lack of specific diagnostic markers, demanding for identifying predictive biomarkers for UC diagnosis and treatment. We perform immune infiltration and weighted gene co-expression network analysis on gene expression profiles of active UC, inactive UC, and normal controls to identify UC related immune cell and hub genes. Neutrophils, M1 macrophages, activated dendritic cells, and activated mast cells are significantly enriched in active UC. MMP-9, CHI3L1, CXCL9, CXCL10, CXCR2 and S100A9 are identified as hub genes in active UC. Specifically, S100A9 is significantly overexpressed in mice with colitis. The receiver operating characteristic curve demonstrates the excellent performance of S100A9 expression in diagnosing active UC. Inhibition of S100A9 expression reduces DSS-induced colonic inflammation. These identified biomarkers associated with activity in UC patients enlighten the new insights of UC diagnosis and treatment.

Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Comparative maintenance performance of all biologic agents and small molecules in ulcerative colitis: a network meta-analysis.

BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30 mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2 mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10 mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10 mg/day and infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.

Gut Microbiota and Inflammation Modulation in a Rat Model for Ulcerative Colitis after the Intraperitoneal Administration of Apigenin, Luteolin, and Xanthohumol.

Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colon, with symptomatology influenced by factors including environmental, genomic, microbial, and immunological interactions. Gut microbiota dysbiosis, characterized by bacterial population alterations, contributes to intestinal homeostasis disruption and aberrant immune system activation, thereby exacerbating the inflammatory state. This study assesses the therapeutic efficacy of intraperitoneal (IP) injected flavonoids (apigenin, luteolin, and xanthohumol) in the reduction of inflammatory parameters and the modulation of the gut microbiota in a murine model of ulcerative colitis. Flavonoids interact with gut microbiota by modulating their composition and serving as substrates for the fermentation into other anti-inflammatory bioactive compounds. Our results demonstrate the effectiveness of luteolin and xanthohumol treatment in enhancing the relative abundance of anti-inflammatory microorganisms, thereby attenuating pro-inflammatory species. Moreover, all three flavonoids exhibit efficacy in the reduction of pro-inflammatory cytokine levels, with luteolin strongly demonstrating utility in alleviating associated physical UC symptoms. This suggests that this molecule is a potential alternative or co-therapy to conventional pharmacological interventions, potentially mitigating their adverse effects. A limited impact on microbiota is observed with apigenin, and this is attributed to its solubility constraints via the chosen administration route, resulting in its accumulation in the mesentery.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach.

Background: Understanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease. Methods: To obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques. Results: We analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn's disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment. Conclusion: Our findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.

The diagnostic performance of serum αvß6 autoantibodies for ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Currently, there is no single golden standard for diagnosing ulcerative colitis (UC). Now serum αvß6 autoantibodies have shown promise as a diagnostic tool for UC. Here the aim was to determine the diagnostic performance of serum αvß6 autoantibodies for UC. METHODS: PubMed, the Cochrane Library, the Embase, and the Web of Science were searched comprehensively. STATA software was utilized to analyze the relevant data. RESULTS: 9 studies from 6 articles with 1827 subjects were eligible. The summary sensitivity and specificity of serum αvß6 autoantibodies to diagnose UC were 0.82 (95 % confidence interval (CI): 0.65-0.92) and 0.94 (95 % CI: 0.90-0.97) with an area under the summary receiver operating characteristic curve of 0.96 (95 % CI: 0.94-0.97). Subgroup analysis was conducted owning to substantial heterogeneity between studies (I2 = 97 % and P < 0.001). The aggregate sensitivity and specificity to diagnose UC in adults were 0.75 (95 % CI: 0.61-0.86) and 0.95 (95 % CI: 0.90-0.97), and when using a threshold of mean control+3SD, 0.80 (95 % CI: 0.60-0.91) and 0.96 (95 % CI: 0.90-0.99), respectively. Additionally, to differentiate UC from healthy participants, non-inflammatory bowel disease, and Crohn's disease, the overall specificity was 0.96, 0.88, and 0.80, respectively. CONCLUSIONS: serum αvß6 autoantibodies, as a non-invasive tool, demonstrated good diagnostic accuracy for UC. However, their application may be limited in some immune-related disorders, and further studies are needed for validation.

Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.