Optimal Treatment Approaches to Intestinal Behçet's Disease Complicated by Myelodysplastic Syndrome: The KASID and KSBD Multicenter Study.

PURPOSE: Studies on intestinal Behçet's disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy. MATERIALS AND METHODS: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated. RESULTS: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases. CONCLUSION: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS.

A Comprehensive Understanding of Post-Translational Modification of Sox2 via Acetylation and O-GlcNAcylation in Colorectal Cancer.

Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a. O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC.

Neither hepatic steatosis nor fibrosis is associated with clinical outcomes in patients with intestinal Behçet's disease.

BACKGROUND: Behçet's disease (BD) and nonalcoholic fatty liver disease (NAFLD) are chronic inflammatory diseases that share pathogenetic mechanisms. In this study, we investigated whether NAFLD influences the clinical outcomes in patients with intestinal BD. METHODS: Patients with intestinal BD and available hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) scores were recruited between 2005 and 2022. An HSI of ≥30 and FIB-4 of ≥1.45 were used to diagnose hepatic steatosis and significant liver fibrosis, respectively. The primary outcomes were intestinal BD-related hospitalization, surgery, emergency room visits, or the first use of corticosteroids, immunomodulators, or biologic agents for intestinal BD. RESULTS: A total of 780 patients with BD were selected. The prevalence of hepatic steatosis and significant liver fibrosis were 72.3% and 8.8%, respectively. Multivariate analysis showed that younger age, prior smoking history, concomitant skin lesions, higher white blood cell count, and lower serum albumin levels were independently associated with an increased risk of clinical relapse (all P < 0.05), whereas hepatic steatosis and significant liver fibrosis were not (hazard ratio [HR] = 1.164, 95% confidence interval [CI] 0.923-1.468; P = 0.199 for hepatic steatosis; HR = 0.982, 95% CI 0.672-1.436; P = 0.927 for significant liver fibrosis). CONCLUSION: Hepatic steatosis and liver fibrotic burden were not independently associated with clinical outcomes in patients with intestinal BD.

Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn's Disease: A Multicenter Observational Study.

BACKGROUND: Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn's disease (CD). METHODS: We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission. RESULTS: MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037). CONCLUSIONS: MTX combination therapy with biologics was effective and tolerable in patients with CD.

Risk factors for post-polypectomy bleeding in patients with end-stage renal disease undergoing colonoscopic polypectomy.

BACKGROUND AND AIMS: Little is known about the risk factors of bleeding after colonoscopic polypectomy in patients with end-stage renal disease (ESRD). This study investigated the incidence and risk factors of post-polypectomy bleeding (PPB), including immediate and delayed bleeding, in patients with ESRD. METHODS: Ninety-two patients with ESRD who underwent colonoscopic polypectomy between September 2005 and June 2020 at a single tertiary referral center were included. The patients' medical records were retrospectively reviewed. Patient- and polyp-related factors associated with immediate PPB (IPPB) were analyzed using logistic regression analysis. Additionally, the optimal cutoff polyp size related to a significant increase in the risk of IPPB was determined by performing receiver operating characteristic (ROC) analysis and calculating the area under the ROC curve (AUC). RESULTS: In total, 286 polyps were removed. IPPB occurred in 24 (26.1%) patients and 46 (16.1%) polyps and delayed PPB occurred in 2 (2.2%) patients. According to multivariate analysis, the polyp size (> 7 mm), old age (> 70), and endoscopic mucosal resection (EMR) as the polypectomy method (EMR versus non-EMR) were found to be independent risk factors for IPPB. According to the Youden index method, the optimal cutoff polyp size to identify high-risk polyps for IPPB was 7 mm (AUC = 0.755; sensitivity, 76.1%; specificity, 69.6%). CONCLUSIONS: Colonoscopic polypectomy should be performed with caution in patients with ESRD, especially in those with the following risk factors: advanced age (> 70 years), polyp size > 7 mm, and EMR as the polypectomy method.

Hepatic Steatosis but Not Fibrosis Is Independently Associated with Poor Outcomes in Patients with Inflammatory Bowel Disease.

Background/Aims: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. Methods: We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. Results: The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p<0.05). Conclusions: Hepatic steatosis was independently associated with increased risks of clinical relapse in patients with ulcerative colitis and Crohn's disease, whereas fibrotic burden in the liver was not. Future studies should investigate whether assessment and therapeutic intervention for NAFLD will improve the clinical outcomes of patients with IBD.

Impact of age at diagnosis on long-term prognosis in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long-term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long-term clinical outcomes of patients with intestinal BD according to age of disease onset. METHODS: Patients diagnosed with intestinal BD at < 18, 18-60, and > 60 years of age were classified into early-onset, adult-onset, and late-onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD-related intestinal surgery, hospitalization, and emergency room visits, was compared using the log-rank test in a large cohort of patients with intestinal BD. RESULTS: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early-onset, adult-onset, and late-onset groups, respectively. Patients in the early-onset group were more likely to require immunosuppressants than those in the adult-onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early-onset, adult-onset, and late-onset groups, respectively, underwent intestinal resection. The early-onset group exhibited a higher risk for intestinal resection than the late-onset (P = 0.043) and adult-onset (P = 0.030) groups. The late-onset group exhibited a higher risk for BD-related hospitalization than the adult-onset group (P = 0.023). CONCLUSIONS: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis.

Effectiveness and safety of adalimumab in patients with intestinal Behçet's disease: a real-world prospective observational study in South Korea.

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/ß-catenin pathways in hepatocellular carcinoma.

BACKGROUND: Sorafenib improves the overall survival in patients with advanced hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) is commonly overexpressed in HCC. In this study, we investigated whether the inhibition of DKK1 enhances the anti-tumor efficacy of sorafenib in HCC. METHODS: HCC cells were treated with sorafenib and WAY-262611, which is an inhibitor of DKK1. Transgenic mouse models were also developed using hydrodynamic tail vein injection. Mice were orally administered with sorafenib (32 mg/kg), WAY-262611 (16 mg/kg), or sorafenib + WAY-262611 for 10 days. Mechanisms of sorafenib and WAY-262611 were explored via western blotting, immunostaining, and RNA sequencing. RESULTS: DKK1 was significantly overexpressed in patients with HCC than in the healthy controls and patients with liver diseases except HCC (all P < 0.05). Compared with sorafenib alone, sorafenib + WAY-262611 significantly inhibited the cell viability, invasion, migration, and colony formation by promoting apoptosis and altering the cell cycles in HCC cells (all P < 0.05). Moreover, sorafenib + WAY-262611 decreased the p110α, phospho-Akt (all P < 0.05), active ß-catenin (all P < 0.05) and phospho-GSK-3ß (Ser9) expression levels, while increasing the phospho-GSK-3ß (Tyr216) expression levels compared with those in the sorafenib alone in vitro and in vivo. In addition, sorafenib + WAY-262611 inhibited tumor progression by regulating cell proliferation and apoptosis, significantly better than sorafenib alone in mouse models. CONCLUSIONS: Our results indicate that DKK1 inhibition significantly enhances the anti-tumor efficacy of sorafenib by inhibiting the PI3K/Akt and Wnt/ß-catenin pathways via regulation of GSK3ß activity, suggesting a novel therapeutic strategy for HCC. Video Abstract.

Characteristics and Treatment Outcomes of Transition among Patients with Inflammatory Bowel Disease.

PURPOSE: This study aimed to assess disease characteristics and outcomes of transition in patient care among adolescent patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: Data from patients younger than 18 years who were diagnosed with IBD (Crohn's disease, ulcerative colitis, or intestinal Behçet's disease) were investigated. We categorized the patients into two groups: transition IBD group (Group A, diagnosed in pediatric care followed by transfer to/attendance in adult IBD care) and non-transition group (Group B, diagnosed and followed up in pediatric care or adult IBD care without transfer). RESULTS: Data from a total of 242 patients [Group A (n=29, 12.0%), Group B (n=213, 88.0%)] were analyzed. A significantly higher number of patients was diagnosed at an earlier age in Group A than in Group B (p<0.001). Group A patients had more severe disease in terms of number of disease flare ups (p=0.011) and frequency of bowel-related complications (p<0.001). Multiple linear regression analysis showed that Group B patients had more medical non-compliance than Group A patients (ß=2.31, p=0.018). After transition, IBD-related admission frequency, emergency admission frequency, disease flare frequency, and medical non-compliance were significantly improved. CONCLUSION: The transition IBD group had more severe disease. Medical non-compliance was lower in the transition IBD group. Clinical outcomes improved after transition.

Clinical characteristics and risk factors related to polyposis recurrence and advanced neoplasm development among patients with non-hereditary colorectal polyposis.

BACKGROUND/AIMS: Patients with more than 10 cumulative polyps might involve a greater genetic risk of colorectal neoplasia development. However, few studies have investigated the risk factors of polyposis recurrence and development of advanced neoplasms among patients with non-hereditary colorectal polyposis. METHODS: This study included patients (n=855) with 10 or more cumulative polyps diagnosed at Severance Hospital from January 2012 to September 2021. Patients with known genetic mutations related to polyposis, known hereditary polyposis syndromes, insufficient information, total colectomy, and less than 3 years of follow-up were excluded. Finally, 169 patients were included for analysis. We collected clinical data, including colonoscopy surveillance results, and performed Cox regression analyses of risk factors for polyposis recurrence and advanced neoplasm development. RESULTS: The 169 patients were predominantly male (84.02%), with a mean age of 64.19±9.92 years. The mean number of adenomas on index colonoscopy was 15.33±8.47. Multivariable analysis revealed history of cancer except colon cancer (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.23-4.01), current smoking (HR, 2.39; 95% CI, 1.17-4.87), and detection of many polyps (≥15) on index colonoscopy (HR, 2.05; 95% CI, 1.21-3.50) were significant risk factors for recurrence of polyposis. We found no statistically significant risk factors for advanced neoplasm development during surveillance among our cohort. CONCLUSIONS: The presence of many polyps (≥15) on index colonoscopy, history of cancer except colon cancer, and current smoking state were significant risk factors for polyposis recurrence among patients with non-hereditary colorectal polyposis.

Interplay between chronic inflammation and clonal haematopoiesis of indeterminate potential in Behçet's disease.

BACKGROUND: Clonal haematopoiesis of indeterminate potential (CHIP) is a predisposition to haematological malignancy whose relationship with chronic inflammatory diseases, such as cardiovascular diseases, has been highlighted. Here, we aimed to investigate the CHIP emergence rate and its association with inflammatory markers in Behçet's disease (BD). METHODS: We performed targeted next-generation sequencing to detect the presence of CHIP using peripheral blood cells from 117 BD patients and 5004 healthy controls between March 2009 and September 2021 and analysed the association between CHIP and inflammatory markers. RESULTS: CHIP was detected in 13.9% of patients in the control group and 11.1% of patients in the BD group, indicating no significant intergroup difference. Among the BD patients of our cohort, five variants (DNMT3A, TET2, ASXL1, STAG2, and IDH2) were detected. DNMT3A mutations were the most common, followed by TET2 mutations. CHIP carriers with BD had a higher serum platelet count, erythrocyte sedimentation rate, and C-reactive protein level; older age; and lower serum albumin level at diagnosis than non-CHIP carriers with BD. However, the significant association between inflammatory markers and CHIP disappeared after the adjustment for various variables, including age. Moreover, CHIP was not an independent risk factor for poor clinical outcomes in patients with BD. CONCLUSIONS: Although BD patients did not have higher CHIP emergence rates than the general population, older age and degree of inflammation in BD were associated with CHIP emergence.

Validation of the simplified magnetic resonance index of activity by using DWI without gadolinium enhancement to evaluate bowel inflammation in Crohn's disease.

OBJECTIVES: To validate the modified simplified magnetic resonance index of activity (sMARIA) score using DWI on non-contrast magnetic resonance enterography (MRE) to evaluate active inflammation in patients with Crohn's disease (CD), compared to the original sMARIA scoring system, with and without contrast enhancement. METHODS: This retrospective study included 275 bowel segments from 55 CD patients who underwent ileocolonoscopy and MRE within a 2-week period. Two blinded radiologists evaluated original sMARIA on both conventional MRE (CE-sMARIA) and non-contrast MRE (T2-sMARIA). Modified sMARIA was then evaluated using non-contrast MRE, replacing ulcerations with DWI grades. Three scoring systems were compared for diagnostic accuracy of active inflammation, correlation with simple endoscopic score (SES)-CD, and interobserver reproducibility. RESULTS: The AUC of modified sMARIA for detecting active inflammation (0.863, 95% confidence interval [0.803-0.923]) was significantly higher than T2-sMARIA (0.827 [0.773-0.881], p = 0.017), and comparable to CE-sMARIA (0.908 [0.857-0.959], p = 0.122). CE-sMARIA, T2-sMARIA, and modified sMARIA all showed moderate correlation with SES-CD (r = 0.795, 0.722, and 0.777, respectively). Interobserver reproducibility of diffusion restriction (κ, 0.686 [0.602-0.770]) was significantly better than ulcers on conventional MRE (κ, 0.382 [0.212-0.552]; p = 0.001) and T2-weighted image (κ, 0.312 [0.034-0.590]; p = 0.012). CONCLUSIONS: Modified sMARIA using DWI can improve the diagnostic performance of sMARIA on non-contrast MRE, showing comparable performance to sMARIA using contrast-enhanced MRE. KEY POINTS: • DWI can improve the diagnostic performance of non-contrast magnetic resonance enterography (MRE) for assessing active inflammation in patients with Crohn's disease. • Modified simplified magnetic resonance index of activity (sMARIA) using DWI grades in place of ulcers showed comparable diagnostic performance to sMARIA using conventional MRE with contrast-enhanced sequences.

Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn's Disease.

Background/Aims: Crohn's disease (CD) with recurrent inflammation can cause intestinal fibrostenosis due to dysregulated deposition of extracellular matrix. However, little is known about the pathogenesis of fibrostenosis. Here, we performed a differential proteomic analysis between normal, inflamed, and fibrostenotic specimens of patients with CD and investigated the roles of the candidate proteins in myofibroblast activation and fibrosis. Methods: We performed two-dimensional difference gel electrophoresis and identified candidate proteins using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and orbitrap liquid chromatography-mass spectrometry. We also verified the levels of candidate proteins in clinical specimens and examined their effects on 18Co myofibroblasts and Caco-2 intestinal epithelial cells. Results: We identified five of 30 proteins (HSP72, HSPA5, KRT8, PEPCK-M, and FABP6) differentially expressed in fibrostenotic CD. Among these proteins, the knockdown of heat shock protein 72 (HSP72) promoted the activation and wound healing of myofibroblasts. Moreover, knockdown of HSP72 induced the epithelial-mesenchymal transition of intestinal epithelial cells by reducing E-cadherin and inducing fibronectin and α-smooth muscle actin, which contribute to fibrosis. Conclusions: HSP72 is an important mediator that regulates myofibroblasts and epithelial-mesenchymal transition in fibrosis of CD, suggesting that HSP72 can serve as a target for antifibrotic therapy.

Risk Factors for Surgery in Patients with Intestinal Behçet's Disease During Anti-Tumor Necrosis Factor-Alpha Therapy.

PURPOSE: Behçet's disease (BD) is a chronic inflammatory immune-mediated disease involving multiorgan systems. Gastrointestinal (GI) manifestations of BD include abdominal pain, vomiting, GI bleeding, fistula formation, obstruction, and perforation that might require surgery. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) therapy has been shown to have favorable outcomes in patients with intestinal BD who are refractory to conventional therapy. This study sought to figure out the risk factors for undergoing surgery during anti-TNF-α therapy in patients with intestinal BD. MATERIALS AND METHODS: In this retrospective analysis of intestinal BD patients who were treated with anti-TNF-α, we collected the baseline patient data including comorbidities, clinical, endoscopic, and radiologic characteristics, and the Disease Activity Index for Intestinal Behçet's Disease at the time of anti-TNF-α initiation. Each potential risk factor was compared. For multivariate analysis, Cox regression was used. RESULTS: A total of 62 patients were considered eligible for analysis, and 15 of them (24.1%) underwent surgery. In univariate analysis, the presence of extraintestinal manifestation, such as joint symptoms and erythrocyte sedimentation rate (ESR), were significantly associated with surgery during therapy. In multivariate analysis, drug response within 4 weeks [hazard ratio (HR), 64.59], skin and joint manifestation (HR, 10.23 and HR, 6.22), geographic ulcer (HR, 743.97), and ESR >42.5 mm/h (HR, 9.16) were found to be factors predictive of undergoing surgery during anti-TNF-α therapy. CONCLUSION: We found five risk factors predictive of surgery in patients with intestinal BD receiving anti-TNF-α therapy, which can guide physicians in selecting appropriate patients between anti-TNF-α therapy and early surgery.

COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis.

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.

Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer.

Development of colorectal cancer (CRC) is regulated by a series of genetic and microenvironmental alterations. Olfactomedin 4 (OLFM4) is a secreted glycoprotein that is highly expressed in the gastrointestinal tract and modulates inflammation. However, the role of OLFM4 in CRC is uncertain. Here we aimed to explore the function of OLFM4 in CRC in vivo and in vitro. The mRNA expression of OLFM4 was up-regulated in precursor lesions with dysplasia or ulcerative colitis but was reduced in CRC. OLFM4 neutralizing antibody suppressed inflammation-mediated early-stage CRC formation in an AOM/DSS colitis-associated cancer model. OLFM4 knockdown cells exhibited increased cell proliferation and motility in vitro and in vivo. Ablation of OLFM4 increased tumor growth and metastasis in xenograft experiments. In addition, OLFM4 knockdown cells showed elevated expression of colon cancer stem cell markers including CD133, resulting in increased metastasis via epithelial-mesenchymal transition signaling. This study demonstrated that OLFM4 regulates inflammation and cancer progression differently; ablation of OLFM4 promotes cancer metastasis via stemness and epithelial-mesenchymal transition. These results suggest a new route for controlling cancer progression and metastasis.

Efficacy and Safety of Infliximab in Intestinal Behçet's Disease: A Multicenter, Phase 3 Study (BEGIN).

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).

Feasibility of a Clinical Decision Support Tool for Ustekinumab to Predict Clinical Remission and Relapse in Patients With Crohn's Disease: A Multicenter Observational Study.

BACKGROUND: Ustekinumab was recently approved for the treatment of moderate to severe Crohn's disease (CD). Although the ustekinumab Clinical Decision Support Tool (UST-CDST) was able to predict ustekinumab responsiveness in a clinical trial, it is not clear whether UST-CDST can also predict a future clinical relapse following ustekinumab therapy in the real-life setting. METHODS: We enrolled patients with moderate to severe CD who were refractory to conventional therapies and who showed a clinical response after induction therapy with ustekinumab and monitored them until the relapse. We performed a Cox proportional hazard analysis to investigate the predictive capability of UST-CDST for a clinical disease relapse. RESULTS: Clinical remission rates at week 20 were 25.0% for low-probability responders, 66.7% for intermediate-probability responders, and 75.0% for high-probability responders. The high-probability responders were more likely to achieve clinical remission at week 20 compared with the low-probability responders. Among 99 patients with moderate to severe CD, 37 (37.4%) experienced a clinical relapse during the median follow-up period of 18.0 months of ustekinumab treatment. The cumulative relapse rates were 70.0% in the low-probability responders, 35.9% in the intermediate-probability responders, and 22.5% in the high-probability responders (P = .001). In a multivariable Cox proportional hazard analysis, the high-probability responders and intermediate-probability responders had a lower risk of clinical relapse than the low-probability responders. Receiver operating characteristic analysis using UST-CDST to predict relapse revealed an area under the curve of 0.698. CONCLUSIONS: The UST-CDST can predict clinical relapse in patients with moderate to severe CD subjected to ustekinumab therapy.

Clinical decision tools are useful in stratifying patients for optimal treatment. Here, we validate the capacity of Ustekinumab Clinical Decision Support Tool to predict clinical remission and relapse in Korean patients with moderate to severe Crohn's disease.

Long-term clinical outcomes of intestinal Behçet's disease: A 30-year cohort study at a tertiary hospital in South Korea.

BACKGROUND AND AIM: We aimed to identify the long-term clinical outcomes of and prognostic factors for intestinal Behçet's disease (BD). METHODS: A cohort of 780 patients with intestinal BD between 1997 and 2021 was investigated to determine long-term clinical outcomes and prognostic factors at an inflammatory bowel disease clinic at Severance Hospital, Seoul, Korea. RESULTS: During the median follow-up period of 12.7 ± 7.2 years, 5-aminosalicylic acids, corticosteroids, immunomodulators, and anti-tumor necrosis factor-alpha (TNF-α) agents were required in 94.9%, 67.2%, 43.8%, and 14.6% of the patients, respectively. The cumulative rates of anti-TNF-α use were 3.7%, 7.5%, 8.5%, 12.1%, 17.6%, and 24.0%, and those for abdominal surgery were 5.7%, 10.9%, 12.6%, 16.5%, 21.6%, and 28.3%, at 1, 3, 5, 10, 20, and 30 years, respectively, after initial diagnosis of intestinal BD. The cumulative rates of hospitalization were 11.8%, 21.9%, 27.9%, 38.8%, 54.4%, and 74.8%, and those of emergency room visits were 10.0%, 19.8%, 22.7%, 31.6%, 50.0%, and 65.0% at 1, 3, 5, 10, 20, and 30 years. Older age at primary diagnosis, previous appendectomy history, higher disease activity index for intestinal Behçet's disease score, systemic BD, multiple intestinal ulcers, deep intestinal ulcers, higher C-reactive protein, lower hemoglobin, and lower albumin levels were associated with poor prognosis. Married status, higher body mass index, oral ulceration, and arthritis were negatively associated with poor prognosis. CONCLUSIONS: Data on the long-term clinical outcomes of intestinal BD and their prognostic factors could guide physicians in patient monitoring and in optimizing individualized treatment.