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Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.

We aimed to identify risk factors and develop a predictive risk-scoring model for immediate post-polypectomy bleeding (IPPB) after cold snare polypectomy (CSP). This multicenter prospective observational study included 161 polyps (4-9 mm in diameter) that were removed via CSP from 118 patients between June and September 2019. IPPB was defined as post-polypectomy bleeding within 24 h or grade 3/4 intraprocedural bleeding requiring endoscopic hemostasis. IPPB incidences according to grade were 13.0% (21/161) (grade 3) and 0% (grade 4). Univariate analysis showed that polyp size, morphology, and iatrogenic ulcer size and shape were significantly associated with IPPB. Multivariate analysis showed that polyp size [6-9 mm vs. 4-5 mm, odds ratio (OR) 3.72, 95% confidence interval (CI) 1.28-10.79], polyp morphology (polypoid vs. non-polypoid, OR: 3.93, 95% CI: 1.22-12.64), and iatrogenic ulcer size (≥ 10 vs. ≤ 9 mm, OR: 3.12, 95% CI: 1.04-9.38) were significantly associated with IPPB. We created a four-marker risk-scoring model to predict IPPB after CSP; we summed the points assigned for the four factors. At a cut-off of 2, the sensitivity was 85.7% and the specificity was 65.0%; at a cut-off of 3, the sensitivity was 65% and the specificity was 90.0%. The four-marker risk-scoring model appears to effectively predict IPPB after CSP.

Background and AimsCrohn’s disease (CD) has a complex polygenic etiology with high heritability. We keep putting an effort to identify novel variants associated with susceptibility to CD through a genome-wide association study (GWAS) in large Korean populations.MethodsGenome-wide variant data from 902 Korean patients with CD and 72,179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1,621 patients with CD and 4,419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term.ResultsWe identified two novel genetic associations with the risk of CD nearZBTB38and within the leukocyte immunoglobulin-like receptor (LILR) gene cluster (P−8), with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci (QTL) for multiple LILR genes, of whichLILRB2directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants forTAP2involved in the antigen presentation of MHC class I molecules (P=4.11×10−4), showing higher CD-risk effects of theTAP2variant in individuals carrying more risk alleles of the LILR lead variant (OR=0.941,P=0.686 in non-carriers; OR=1.45,P=2.51×10−4in single-copy carriers; OR=2.38,P=2.76×10−6in two-copy carriers).ConclusionsThis study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR andTAP2loci confer risk of CD.

To identify the incidence, associated factors, and impact of hospital-acquired Clostridium difficile infection (CDI) among patients who have undergone orthopedic surgery.We retrospectively reviewed the charts of all adults patients who underwent orthopedic surgery from January 2016 through December 2017 at a tertiary hospital.Of 7,363 patients who underwent orthopedic surgical procedures, 52 (0.7%) developed hospital-acquired CDI. The independent factors associated with CDI were age ≥65 years (adjusted odds ratio [aOR], 3.4; P.001), preoperative hospital stay ≥3 days (aOR, 3.7; P.001), operating time ≥3 hours (aOR, 2.5; P.005), and antibiotic use for infection treatment (aOR, 4.3; P.001). After adjusting for the timing of CDI using a multistate model, the mean excess LOS attributable to CDI was 2.8 days (95% confidence interval [CI], 0.4-5.3). The impact of CDI on excess LOS was more evident among patients aged ≥65 years (4.4 days; 95% CI, 1.8-7.0) and those with any comorbidity (5.6 days; 95% CI, 3.0-8.1).The overall incidence of CDI after orthopedic surgery was 0.7%. The occurrence of CDI after orthopedic surgery contributes to increased LOS. The greatest impact of CDI on LOS occurs among elderly patients and patients with comorbidities.

Infliximab, a chimeric monoclonal antibody against anti-tumor necrosis factor-α (TNF-α), has revolutionized the management of inflammatory bowel disease. However, a recent nested case-control study showed that anti-TNF-α therapy exposure in patients with autoimmune diseases is associated with an increased risk of inflammatory central nervous system (CNS) events. A 27-year-old man diagnosed with Crohn’s disease at 17 years of age was referred to our clinic for suffering with Wernicke’s aphasia and the right-hand weakness over two weeks. Nine years of treatment for Crohn’s disease with infliximab anti-TNF-α therapy was well tolerated. An initial MRI revealed diffuse leptomeningeal enhancement along the bilateral cerebral sulci without any parenchymal abnormalities. Cerebrospinal fluid (CSF) and serum N-methyl-D-aspartate receptor (NMDAR) antibody testing yielded positive results. Anti-NMDAR encephalitis was diagnosed, and the patient was treated with rituximab. A follow-up brain MRI showed new multiple cerebral lesions in the left insular cortex and subcortical white matter of the left frontal and temporal gyri. Approximately 8 months after symptom onset, the CSF and serum NMDAR antibody converted to negative. Twelve months later, the patient fully recovered from anti-NMDAR encephalitis without any neurological deficits and is currently being treated with the anti-interleukin 12/23 agent ustekinumab for Crohn’s disease. This is the first report of not only a patient with infliximab-associated anti-NMDAR encephalitis in Crohn’s disease but also of an inflammatory non-demyelinating CNS event during long-term suppression of TNF-α. Our case highlights the need for clinicians to recognize the possibility of a paradoxical autoimmune response occurring with novel biological therapies.

Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the feces of patients with inflammatory bowel disease (IBD-F) than in those of healthy control volunteers (HC-F). The Enterococcaceae and Lactobacillaceae populations were higher in the feces of IBD patients with depression (IBD/D+-F) vs. the feces of IBD patients without depression (IBD/D−-F). Therefore, we examined the effects of Klebsiella oxytoca, Escherichia coli, Cronobacter sakazakii, Enterococcus faecium, and Pediococcus acidolactici overpopulated in IBD/D+-F and their byproducts LPS and exopolysaccharide (EPS) on the occurrence of depression and colitis in mice. Oral gavages of Klebsiella oxytoca, Escherichia coli, and Cronobacter sakazakii belonging to Enterobacteriaceae, singly or together, caused dose-dependently colitis and depression-like behaviors in germ-free and specific-pathogen-free mice. Although Enterococcus faecium and Pediococcus acidolactici did not significantly cause colitis and depression-like behaviors, they significantly deteriorated Klebsiella oxytoca- or Escherichia coli-induced colitis, neuroinflammation, and anxiety/depression-like behaviors and increased blood LPS, corticosterone, and IL-6 levels. The EPSs from Enterococcus faecium and Pediococcus acidolactici also worsened Klebsiella oxytoca LPS-induced colitis, neuroinflammation, and depression-like behaviors in mice and increased the translocation of fluorescein isothiocyanate-conjugated LPS into the hippocampus. However, Bifidobacterium longum, which was lower in IBD/D+-F vs. IBD/D−-F, or its EPS suppressed them. In conclusion, Enterococcus faecium and Pediococcus acidolactici, known as a probiotic strain, and their EPSs may be a risk factor for the outbreak of depression and IBD.

Existing elastic analysis methods cannot be adhered to in order to assess the structural integrity of a reactor vessel and internals for a beyond design basis earthquake. Elasto-plastic analysis methods are required, and the factors that affect the elasto-plastic behavior of reactor materials should be taken into account. In this study, a material behavior model was developed that considers the irradiation embrittlement effect, which affects the elasto-plastic behavior of the reactor material. This was used to perform the elasto-plastic time history analyses of the reactor vessel and its internals for beyond design basis earthquake. For this investigation, appropriate beyond design basis earthquakes and reliable finite element models were used. Based on the analysis results, consideration was given to the load reduction effect and the margin change. These were transferred to the internals due to the plastic deformation of the reactor vessel.

Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB+Iba1+ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB+CD11c+ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.

Background/Aims: A considerable number of patients with Crohn’s disease still need intestinal resection surgery. Postoperative recurrence is an important issue in Crohn’s disease management, including the selection of high-risk patients. Eastern Asian patients showed several differences from Caucasian patients. Therefore, we investigated the postoperative surgical recurrence outcome and identified risk factors in Korean patients. Methods: Clinical data of 372 patients with Crohn’s disease who underwent first intestinal resection between January 2004 and August 2014 at 14 hospitals in Korea were retrospectively reviewed. Results: Over the follow-up period, 50 patients (17.1%) showed surgi cal recurrence. The cumulative surgical recurrence rate was 6.5% at 1 year and 15.4% at 7 years. Age under 16 (p=0.011; hazard ratio [HR], 5.136; 95% confidence interval [CI], 1.576 to 16.731), colonic involvement (p=0.023; HR , 2.011; 95% CI, 1.102 to 3.670), and the presence of perianal disease at surgery (p=0.008; HR, 2.239; 95% CI, 1.236 to 4.059) were independent risk factors associated with surgical recurrence. Postoperative thiopurine treatment (p=0.002; HR, 0.393; 95% CI, 0.218 to 0.710) was a protective factor for surgical recurrence. Conclusions: Among the disease characteristics at surgery, younger age, colonic location, and perianal le sions were independent risk factors for surgical recurrence. Postoperative thiopurine treatment significantly reduced the incidence of surgical recurrence. (Gut Liver 2020;14:331-337)

Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D−), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D−) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D− caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D−-F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D− caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D−-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.

Chronic enteropathy associated withFrom July 2018 to July 2021, we performed Sanger sequencing of theFourteen out of 46 patients (30.4%) had genetically confirmed CEAS, and twoThe clinical and genetic characteristics of Korean patients with confirmed CEAS were similar to those reported in the literature. CEAS should be considered in the differential diagnosis for patients with unexplained chronic nonspecific ulcers of the small intestine.

BACKGROUND AND AIM PBK-1701TC is a novel sulfate tablet-based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK-1701TC compared with OSS in bowel preparation for colonoscopy. METHODS This randomized, multicenter, phase 3 non-inferiority trial included adults aged 19 years or older with a body mass index of 19-30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel-cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview. RESULTS Overall, 235 participants were randomized, and 224 were included in the per-protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non-inferior to the OSS group (98.2%, 110/112) with a difference of -2.7% (one sided 97.5% confidence limit, -8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P

Background/Aims: Limited data are available regarding psychosocial distress at the time of diagnosis of ulcerative colitis (UC). We investigated the psychosocial burden and factors related to poor health-related quality of life (HRQL) among patients newly diagnosed with moderate-to-severe UC who were affiliated with the nationwide prospective cohort study. Methods: Within the first 4 weeks of UC diagnosis, all patients were assessed using the Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ), and 12-Item Short Form (SF-12) health survey. A multiple linear regression model was used to identify factors associated with HRQL. Results: Between August 2014 and February 2017, 355 patients completed questionnaires. Significant mood disorders requiring psychological interventions, defined by a HADS score ≥11, were identified in 16.7% (anxiety) and 20.6% (depression) of patients. Patients with severe disease were more likely to have presenteeism, loss of work productivity, and activity loss than those with moderate disease (all p

Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007–2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p p Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).

Anorexia is a relevant geriatric syndrome because it accounts for most malnutrition in older adults. Constipation has been suggested as a risk factor for anorexia. This study aimed to examine the association between anorexia and functional constipation in community-dwelling older adults. Data on 899 subjects aged 72–86 years were obtained from a follow-up survey of the Korean Frailty and Aging Cohort Study in 2018. Anorexia was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ), while functional constipation was diagnosed based on Rome IV criteria. Anorexia and functional constipation were present in 30.9% and 19.6% of the participants, respectively. Age, female sex, chewing problems, malnutrition, polypharmacy, low Mini-Mental Status Examination (MMSE) score, depressed mood, low serum albumin, and functional constipation were associated with anorexia in the univariate analysis. In the multivariate logistic regression, functional constipation was associated with anorexia (OR 1.478, 95% CI 1.038–2.104) after adjusting for age, female sex, and MMSE score. However, after further adjusting for depressed mood (OR 2.568) and chewing problems (OR 2.196), the relationship was no longer significant. This study showed that functional constipation is associated with anorexia in community-dwelling older adults, but this association is confounded by depressed mood and chewing problems.

Crohn's disease (CD) is a chronic destructive inflammatory bowel disease that affects young people and is associated with significant morbidity. The clinical spectrum and disease course of CD are heterogeneous and often difficult to predict based on the initial presentation. In this article, changes in the disease location, behavior, clinical course during long-term follow-up, and predictive factors are reviewed. Generally, four different patterns of clinical course are discussed: remission, stable disease, chronic relapsing disease, and chronic refractory disease. Understanding the long-term disease course of CD is mandatory to reveal the underlying pathophysiology of the disease and to move toward a more optimistic disease course, such as remission or stability, and less adverse outcomes or devastating sequelae.

Backgrounds No inception cohort study has ever evaluated the early course of moderate-to-severe ulcerative colitis (UC) within one year of diagnosis in the non-Caucasian population. We aimed to investigate the early clinical course of moderate-to-severe UC patients in terms of remission, relapse, UC-related hospitalizations, colectomy, mortality and overall use of medications. Methods In the MOSAIK inception cohort, which is an ongoing multi-center, prospective, hospital-based, observational cohort, 354 patients with moderate-to-severe UC were followed up for one year. Main outcomes of UC and predictive factors for medication use over the course of one year were evaluated. Result Among 354 patients, 276 (78.0%) patients were followed up for one year. The rates of remission, relapse, UC-related hospitalizations, and proximal disease extension were 95.3%, 39.6%, 15.2%, and 12.3%, respectively. Systemic corticosteroids, thiopurines, and biologics were administered to 61.2%, 30.4%, and 10.5% of patients, respectively, throughout one year. One year after, 58.2% patients experienced remission or mild endoscopic activity. Overall disease courses did not show much difference according to moderate or severe disease activity at baseline. In addition, no colectomy and mortality were observed for one year. Predictive factors for medication use included disease severity, disease extent, endoscopic severity, and presence of periappendiceal inflammation at baseline for corticosteroid, disease extent and initial corticosteroid use for thiopurine, and only initial corticosteroid use for biologics. Conclusion Korean patients with moderate-to-severe UC may have more favorable early outcomes than Western patients. However, outcomes of them need to be further looked into for a longer time.

The 1-L polyethylene glycol (PEG)-based bowel preparation agent NER1006 (Plenvu; Norgine, Harefield, UK) has shown high cleansing efficacy and tolerability in clinical trials in Europe and North America. However, no clinical trials have yet been reported in Asia. Therefore, the aim of this study was to evaluate the efficacy and safety of 1L PEG-based bowel preparation with Plenvu compared with 2L PEG plus ascorbate bowel preparation in a Korean population.In this multicenter, endoscopist-blinded, randomized study, patients at 9 hospitals in South Korea undergoing colonoscopy received either Plenvu or 2L PEG + ascorbate (2L PEG) with a split dose. The primary endpoint was overall bowel cleansing success (Boston Bowel Preparation Scale [BBPS] score ≥2 for all segments of the colon). Secondary endpoints were high-quality bowel cleansing success (overall, BBPS score = 9; segmental colon, BPPS score = 3), polyp detection rate (PDR), and adenoma detection rate (ADR).Of 360 included patients, cleansing efficacy was analyzed in 346 (Plenvu, 174; 2L PEG, 172). The Plenvu group showed noninferior bowel cleansing success rates compared with 2L PEG (93.10% vs 91.86%; difference, 1.24%; 1-sided 97.5% lower confidence limit, -4.31%; PPlenvu showed noninferior overall bowel cleansing success rates comparable with 2L PEG but greater high-quality bowel cleansing in overall and right-sided colon, which might help improve the PDR in the Asian population. (Clinical trial registration number: KCT0005894.).

BackgroundThe gut microbiota closely communicate with the brain through the microbiota-gut-brain axis. The interaction between gut microbiota may regulate the occurrence of neuropsychiatric disorders, including depression. Therefore, we transplanted the fecal microbiota of patients with inflammatory bowel disease (IBD) or their overpopulated gut bacteria into specific-pathogen-free or germ-free mice and examined their effects regarding the occurrence of colitis and anxiety/depression. ResultsFecal microbiota transplantations (FMTs) from patients with IBD with (/D+) or without depression (/D-) caused IBD-like colitis in the transplanted mice: they increased myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon. FMTs from patients with IBD/D+ caused anxiety-/depression-like behaviors and NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell population and decreased the BDNF+/NeuN+ cell population in the hippocampus. FMTs from patients with IBD/D- caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of microbiota in the feces of patients with IBD (IBD-F) were different from those of healthy-control feces (HC-F). The Enterobacteriaceae and Enterococcaceae populations and fecal lipopolysaccharide levels were higher in IBD-F vs. HC-F. Moreover, the Enterococcaceae population was higher in IBD/D+-F vs. IBD/D--F, while the Bifidobacteria population was lower in IBD/D+-F. FMT from HC alleviated the IBD/D+-F-induced anxiety-/depression-like behaviors and colitis in the transplanted mice. Furthermore, it suppressed IBD/D+-F-induced Enterococcus sp. population in the feces. Enterobacteriaceae Klebsiella oxytoca, Klebsiella pneumoniae, Escherichia coli, and Cronobacter sakazakii abundant in IBD-F, singly or together, caused depression with colitis in germ-free and specific-pathogen-free mice, while Enterococcus faecium abundant in IBD/D+-F did not cause not anxiety/depression and colitis. However, the combination of Enterobacteriaceae with Enterococcus faecium synergistically deteriorated depression and colitis, while its combination with Bifidobacterium longum attenuated them. ConclusionThe interaction between gut microbiota Enterobacteriaceae, Enterococci, and Bifidobacteria may regulate the outbreak of anxiety/depression and IBD through the modulation of NF-κB-involved BDNF expression and gut microbiota. Enterococcus faecium, a probiotic strain, is a risk factor for the outbreak of anxiety/depression in patients with IBD.

Background We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. Methods Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn’s Disease Activity Index score Results Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. Conclusions Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

Backgrounds and Aims We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease. Methods Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30. Results After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death. Conclusions BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.

BACKGROUND AND AIM Despite the frequent loss of Ras association domain family 1 isoform A (RASSF1A) expression in various cancers, the precise mechanism underlying its tumor-suppressive effect is not fully understood. To elucidate the growth-inhibitory role for RASSF1A in colorectal tumorigenesis, this study investigated the RASSF1A regulation of the p53-p21WAF1 pathway. METHODS Ras association domain family 1 isoform A effect on cellular growth was tested in three human colon cancer cell lines by flow cytometry, cell counting, and [3 H]-thymidine incorporation assay. HCT116 p53+/+ and p53-/- isogenic sublines were utilized to determine the p53 dependence of RASSF1A effect on p21WAF1 . Cycloheximide chase experiment and immunoprecipitation assay were carried out to define RASSF1A effect on p53 stability and mouse double minute 2 (MDM2) homolog ubiquitination. RESULTS Ras association domain family 1 isoform A expression inhibits colonic cell proliferation by preventing the G1 to S phase transition of the cell cycle. The RASSF1A-induced G1 cell cycle arrest is accompanied by the increase in the level of p21WAF1 mRNA expression. The p21WAF -inducing activity of RASSF1A was substantially higher in HCT116 p53+/+ cell compared with isogenic p53-/- cells. The cycloheximide chase assay revealed that RASSF1A expression leads to p53 stabilization and MDM2 homolog degradation. Using p53-/- and p21WAF1-/- subline cells, this study finally validated a crucial role of the p53-p21WAF1 axis in RASSF1A-mediated growth inhibition. CONCLUSIONS RASSF1A suppresses colonic tumor growth through the activation of the p53-p21WAF1 pathway. This finding supports that RASSF1A could be a valuable marker for the assessment of colorectal cancer development and progression.

Background and Aims Data regarding healthcare costs and utilization for IBD at the population level are limited in Asia. We aimed to investigate the nationwide prevalence, and healthcare cost and utilization of IBD in Korea. Methods We tracked the IBD-attributable healthcare costs and utilization from 2010 to 2014 using the public dataset obtained from Korean National Health Insurance Service claims. We estimated the nationwide prevalence of IBD using population census data from Statistics Korea during the same period. Results In total, 236,106 IBD patients were analyzed. The estimated IBD prevalence significantly increased from 85.1/100,000 in 2010 to 106/100,000 in 2014. The overall annual healthcare costs for IBD increased from $23.2 million (US dollars) in 2010 to $49.7 million in 2014 (P

Background We investigated the real-life effectiveness and safety of vedolizumab maintenance treatment among Korean patients with Crohn’s disease (CD) or ulcerative colitis (UC) who previously failed anti-tumour necrosis factor (anti-TNF) therapy. Methods Adult patients with CD or UC who have previously failed anti-TNF therapy and received vedolizumab were prospectively enrolled from 16 hospitals in Korea. The primary outcome was clinical remission at week 54. Clinical remission was defined as a Crohn’s disease activity index (CDAI) Results Between August 2017 to July 2020, a total of 165 patients (81 with CD and 84 with UC) received vedolizumab therapy, of whom 154 patients (93.3%) (75 with CD and 79 with UC) received vedolizumab maintenance therapy (Table 1). Clinical remission and response rates at week 54 were 22.2% and 24.1% among patients with CD and 41.4% and 45.7% among patients with UC, respectively (Figure 1A and 1B). Among 70 patients with UC with baseline Mayo endoscopic subscore ≥2, endoscopic remission (Mayo endoscopic subscore ≤1) at week 54 was observed in 19 patients (27.1%). Out of 50 patients with CD with ulcers in baseline endoscopy, 2 patients (4%) showed a disappearance of ulcers at week 54 (Figure 1C). In the multivariable analysis, age at baseline (adjusted odds ration [aOR] 1.065, 95% confidence interval [CI] 1.003–1.131, P=0.041) and Mayo endoscopic subscore at baseline (aOR 0.141, 95% CI 0.026–0.746, P=0.021) were significantly associated with clinical remission at week 54 among patients with UC (Table 2). No factors were found to be associated with clinical remission at week 54 among patients with CD. Among patients who experienced one or more adverse events (n=134, 81.2%), serious adverse events occurred in 82 patients (49.7%) (Table 3). Disease exacerbation was the most common adverse events (n=89, 53.9%). Conclusion The real-life effectiveness of vedolizumab maintenance treatment for Korean patients with UC who failed anti-TNF therapy was generally similar with the outcomes reported from the previous Western studies. A substantial proportion of patients with CD experienced a loss of response during the first year of treatment. Less severe disease at baseline was associated with clinical remission at 1 year of vedolizumab therapy among patients with UC.

Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy.The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3).The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93-75.01, p .001), alcohol consumption (HR 3.84, 95% C.I. 1.99-7.39, p .001), and older age (HR 1.06, 95% C.I. 1.01-1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314).LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.

PURPOSE Fecal tests remain a mainstay of population-based colorectal cancer (CRC) screening programs worldwide. However, data on interval CRC (iCRC) arising after follow-up colonoscopy of a positive fecal test are scarce. We conducted a nationwide population-based study to reveal the risk and characteristics of iCRC in this setting. MATERIALS AND METHODS We searched the National Cancer Screening Program for CRC database in Korea (2005-2010). Incidence of iCRC within the program was estimated, then Cox proportional-hazards regression analysis was performed to determine the independent predictors of iCRC. The clinical characteristics of iCRC were compared with screen-detected CRC (sCRC). RESULTS We identified 280 iCRC among 150,660 negative colonoscopies as a follow-up exam to a positive fecal immunochemical test (FIT), and 2,427 sCRC. The overall incidence of iCRC was 0.49/1,000 person-years (95% confidence interval [CI], 0.48 to 0.51). iCRC was more likely to occur in men (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.39 to 2.30) and elderly patients (aHR, 1.77; 95% CI, 1.38 to 2.28 in 65-74 years; aHR, 3.13, 95% CI, 2.13 to 4.60 in ≥ 75 years). The National Quality Improvement Program for colonoscopy reduced a short-term risk of iCRC (aHR, 0.48; 95% CI, 0.27 to 0.87). Compared with sCRC, iCRC was more likely to occur in the proximal colon, be diagnosed at the localized stage, and have a lower CRC mortality (32.7 vs. 17.4%, 56.8 vs. 34.1%, and 12.5 vs. 17.7%, respectively; all p < 0.05). CONCLUSION In a population-based CRC screening program with FIT, the burden of iCRC after follow-up colonoscopy was substantial. Men and elderly patients possess a significantly higher risk of iCRC.