Gastric mucosal swab as an alternative to biopsy for Helicobacter pylori detection.

BACKGROUND AND AIMS: Gastric mucosal swab may be a more sensitive sampling method than a biopsy since Helicobacter pylori (H. pylori) resides within the mucus layer. We compared the diagnostic performance of the rapid urease test (RUT) and bacterial load of H. pylori between swabs and tissue biopsy. METHODS: Overall, 276 RUTs (138 swab-RUTs (S-RUT) and 138 tissue-RUTs (T-RUT)) were performed. To diagnose H. pylori infection, RUT, H. pylori PCR, and 16S ribosomal RNA gene sequencing of tissue and swab were used, and its infection was defined as at least two positives of the six test results. The diagnostic performances of RUTs and the H. pylori bacterial load using qPCR were compared between swab and biopsy. RESULTS: The positivity rates of S-RUT and T-RUT were 35.5% (49/138) and 25.4% (35/138), respectively. The sensitivity, specificity, and accuracy of S-RUT were 98.0%, 100.0%, and 99.2%, while those of T-RUT were 70.0%, 100%, and 89.1%, respectively. The sensitivity and accuracy were significantly higher for S-RUT than for T-RUT (p < 0.05). In the patients with atrophic gastritis and intestinal metaplasia, S-RUT showed significantly higher sensitivity than T-RUT. qPCR showed that the swab contained a significantly higher H. pylori bacterial load than tissue biopsy (22.92-fold and 31.61-fold in the antrum and body (p < 0.05), respectively). CONCLUSIONS: Gastric mucosal swabs showed higher RUT accuracy and H. pylori bacterial load than a tissue biopsy. This may be an alternative to a biopsy when diagnosing H. pylori infection during endoscopy is necessary. (ClinicalTrials.gov, NCT05349578).

Deep learning model for diagnosing gastric mucosal lesions using endoscopic images: development, validation, and method comparison.

BACKGROUND AND AIMS: Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection, differential diagnosis (AI-DDx), and invasion depth (AI-ID; pT1a vs pT1b among EGC) models. METHODS: This study included 1366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histologic diagnoses were set as the criterion standard. Performance of the AI-DDx (training/internal/external validation set, 1009/112/245) and AI-ID (training/internal/external validation set, 620/68/155) was compared with visual diagnoses by independent endoscopists (stratified by novice [<1 year of experience], intermediate [2-3 years of experience], and expert [>5 years of experience]) and EUS results, respectively. RESULTS: The AI-DDx showed good diagnostic performance for both internal (area under the receiver operating characteristic curve [AUROC] = .86) and external validation (AUROC = .86). The performance of the AI-DDx was better than that of novice (AUROC = .82, P = .01) and intermediate endoscopists (AUROC = .84, P = .02) but was comparable with experts (AUROC = .89, P = .12) in the external validation set. The AI-ID showed a fair performance in both internal (AUROC = .78) and external validation sets (AUROC = .73), which were significantly better than EUS results performed by experts (internal validation, AUROC = .62; external validation, AUROC = .56; both P < .001). CONCLUSIONS: The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesions. The AI-ID performed better than EUS for evaluation of invasion depth.

Occult Blood in Feces Is Associated with Increased Risk of Psoriasis.

BACKGROUND: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease. METHODS: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017. RESULTS: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results. CONCLUSION: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population.

Atopic Diseases Are Associated With Development of Inflammatory Bowel Diseases in Korea: A Nationwide Population-based Study.

BACKGROUND & AIMS: The association between atopic diseases and inflammatory bowel diseases (IBD) is unclear. We conducted a nationwide population-based study in Korea to investigate the effect of atopic diseases on the development of IBD. METHODS: A total of 9,923,521 participants, who received a medical check-up in 2009, were included and followed through 2017. The presence of any atopic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, was evaluated. Patients who developed IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified using claims data from National Health Insurance; the association between atopic diseases and the risk of IBD was evaluated using Cox proportional hazard models, and presented as adjusted hazard ratios (aHRs) with 95% CIs. RESULTS: During a mean follow-up period of 7.3 years, 1419 patients (0.014%) developed CD and 5897 patients (0.059%) developed UC. The incidences of CD (per 100,000 person-years) were 3.756, 2.248, and 2.346 in patients with AD, AR, or asthma, respectively. The incidences of UC were 11.952, 9.818, and 9.358 in patients with AD, AR, or asthma, respectively. Multivariable analysis revealed that the aHRs for incident CD in patients with AD, AR, or asthma were 2.02, 1.33, and 1.60 (95% CIs, 1.118-3.663, 1.149-1.529, and 1.193-2.136, respectively) compared with controls. The risks of incident UC in patients with AD, AR, or asthma were 1.51, 1.32, and 1.29 (95% CIs, 1.082-2.104, 1.229-1.410, and 1.115-1.491, respectively) compared with controls. Moreover, an increase in the number of atopic diseases gradually increased the risk for CD and UC; for 1 or 2 or more atopic diseases, the aHRs for CD were 1.35 and 1.65 (95% CIs, 1.171-1.560 and 1.146-2.376), and the aHRs for UC were 1.30 and 1.49 (95% CIs, 1.211-1.392 and 1.249-1.774), respectively. CONCLUSIONS: Based on a nationwide population-based study in Korea, patients with any atopic disease, including AD, AR, or asthma, have an increased risk for CD and UC. The risk for IBD increases with the increase in the number of atopic diseases.

Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.

BACKGROUND AND AIM: While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence. METHODS: Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA. RESULTS: During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm2 increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm2 increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA. CONCLUSION: Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.

Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited. OBJECTIVE: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD. METHODS: Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed. RESULTS: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results. CONCLUSIONS: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.

Increased risk of idiopathic pulmonary fibrosis in inflammatory bowel disease: A nationwide study.

BACKGROUND AND AIM: The relationship between inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the risk for developing IPF in patients with IBD using a nationwide population-based study. METHODS: Using claims data from the National Health Insurance service in Korea, patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were identified through both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease program codes from January 2010 to December 2013. We compared 38 921 IBD patients with age-matched and sex-matched individuals without IBD in a ratio of 1:3. Patients with newly diagnosed IPF were identified by both the 10th revision of the International Statistical Classification of Diseases and Related Health Problems and rare and intractable disease registration codes. RESULTS: During a mean 4.9-year follow-up, the incidence of IPF in patients with IBD was 33.21 per 100 000 person-years. The overall risk of IPF was significantly higher in IBD patients than in non-IBD controls (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.20-2.20; P = 0.003). In patients with CD, the incidence (per 100 000 person-years) of IPF was 26.04; in controls, the incidence was 9.15 (HR, 2.89; 95% CI, 1.46-5.72; P = 0.002). The incidence of IPF in patients with UC tended to be higher than in controls (36.66 vs 26.54 per 100 000 person-years; 95% CI, 0.99-1.99; HR, 1.41; P = 0.066). The risk of developing IPF in patients with IBD was higher in male patients than in female patients (P = 0.093 in CD; P = 0.147 in UC by interaction analysis). CONCLUSIONS: Patients with IBD, especially CD, have an increased risk of developing IPF.

Novel sulfate tablet PBK-1701TC versus oral sulfate solution for colon cleansing: A randomized phase 3 trial.

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 < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05). CONCLUSION: The novel sulfate tablet, PBK-1701TC, was non-inferior to OSS with respect to bowel-cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy.

Occult Blood in Feces Is Associated With an Increased Risk of Ischemic Stroke and Myocardial Infarction: A Nationwide Population Study.

Background Although occult hemoglobin in feces is universally valued as a screening tool for colorectal cancer (CRC), only few studies investigated the clinical meaning of fecal immunochemical test (FIT) in other diseases. We evaluated the clinical utility of FIT in patients with cardiovascular diseases (namely, ischemic stroke and myocardial infarction [MI]). Methods and Results Using the National Health Insurance database, participants (aged >50 years) with CRC screening records from 2009 to 2012 were screened and followed up. Subjects with a history of cardiovascular diseases and CRC were excluded. Ischemic stroke, MI, and other comorbidities were defined by International Classification of Diseases, Tenth Revision (ICD-10), codes. Age, sex, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and body mass index were adjusted in a multivariate analysis. A total of 6 277 446 subjects were eligible for analysis. During the mean 6.79 years of follow-up, 168 570 participants developed ischemic stroke, 105 983 developed MI, and 11 253 deaths were observed. A multivariate-adjusted model revealed that the risk of ischemic stroke was higher in the FIT-positive population (adjusted hazard ratio [HR], 1.09; 95% CI, 1.07-1.11). Similarly, FIT-positive subjects were at an increased risk of MI (adjusted HR, 1.09; 95% CI, 1.06-1.12). Moreover, increased all-cause mortality was observed in the FIT-positive population (adjusted HR, 1.15; 95% CI, 1.07-1.23). The increased risk remained consistent in the stratified analysis on anemia and CRC status. Conclusions Positive FIT findings were associated with ischemic stroke, MI, and mortality. Occult blood in feces may offer more clinical information than its well-known conventional role in CRC screening.

Risk of gastrointestinal cancer in patients with an elevated level of gamma-glutamyltransferase: A nationwide population-based study.

Emerging evidence that an elevated serum gamma-glutamyltransferase (GGT) level is associated with an increased risk of gastrointestinal cancer, but still controversial. The aim of this study to assess the relationship between GGT level and risk of gastrointestinal cancer, and the contribution of the interaction of hyperglycemia with elevated GGT level to the incidence of gastrointestinal cancer by the stratified analysis. A total of 8,120,665 Koreans who received medical checkups in 2009 were included. Subjects were classified according to the quartile of GGT level for women and men. The incidence rates of gastrointestinal cancer for each group were analyzed using Cox proportional hazards models. During follow-up, 129,853 cases of gastrointestinal cancer newly occurred (esophagus, 3,792; stomach, 57,932; and colorectal, 68,789 cases). The highest GGT quartile group showed an increased risk of gastrointestinal cancer (esophagus, hazard ratio = 2.408 [95% confidence interval, 2.184-2.654]; stomach, 1.121 [1.093-1.149]; and colorectal, 1.185 [1.158-1.211]). The risk increased significantly with the rise in GGT quartile level, regardless of the site of cancer. The stratified analysis according to glycemic status showed that the effect of elevated GGT was predominant in the risk of esophageal cancer. The effect of elevated GGT further increased the risk of stomach and colorectal cancers in diabetic patients. An elevated level of GGT was associated with an increased risk of gastrointestinal cancer, regardless of the site of cancer. The effect of the increase in GGT level on the risk of gastrointestinal cancer depended on the type of cancer and glycemic status.

Risk of Diabetes in Subjects with Positive Fecal Immunochemical Test: A Nationwide Population-Based Study.

BACKGROUND: Positive fecal immunochemical test (FIT) results have been recently suggested as a risk factor for systemic inflammation. Diabetes induces inflammation in the gastrointestinal tract via several ways. We investigated the association between FIT results and the incidence of diabetes. METHODS: A total of 7,946,393 individuals aged ≥50 years from the National Cancer Screening Program database who underwent FIT for colorectal cancer (CRC) screening from 2009 to 2012 were enrolled. The primary outcome was newly diagnosed diabetes based on the International Classification of Disease 10th revision codes and administration of anti-diabetic medication during the follow-up period. RESULTS: During a mean follow-up of 6.5 years, the incidence rates of diabetes were 11.97, 13.60, 14.53, and 16.82 per 1,000 personyears in the FIT negative, one-positive, two-positive, and three-positive groups, respectively. The hazard ratios (HRs) for the incidence of diabetes were 1.14 (95% confidence interval [CI], 1.12 to 1.16; HR, 1.21; 95% CI, 1.16 to 1.27; and HR, 1.40; 95% CI, 1.28 to 1.55) in the one-positive, two-positive, and three-positive FIT groups compared with the FIT negative group, respectively. The effect was consistent in individuals with normal fasting blood glucose (adjusted HR 1.55 vs. 1.14, P for interaction <0.001). CONCLUSION: Positive FIT results were associated with a significantly higher risk of diabetes, suggesting that the FIT can play a role not only as a CRC screening tool, but also as a surrogate marker of systemic inflammation; thus, increasing the diabetes risk.

Long-term outcomes of infliximab in a real-world multicenter cohort of patients with acute severe ulcerative colitis.

BACKGROUND/AIMS: Infliximab (IFX) has proven effective as rescue therapy in steroid-refractory acute severe ulcerative colitis (ASUC), however, the long-term real-world data are scarce. Our study aimed to assess the long-term treatment outcomes of IFX in a real-life cohort. METHODS: We established a multicenter retrospective cohort of hospitalized patients with ASUC, who met Truelove and Witt's criteria and received intravenous corticosteroid (IVCS) or IFX during index hospitalization between 2006 and 2016 in 5 university hospitals in Korea. The cohort was systematically followed up until colectomy, death or last follow-up visit. RESULTS: A total of 296 patients were followed up for a mean of 68.9 ± 44.0 months. During index hospitalization, 49 patients were treated with IFX; as rescue therapy for IVCS failure in 37 and as first-line medical therapy for ASUC in 12. All patients treated with IFX avoided colectomy during index hospitalization. The cumulative rates of rehospitalization and colectomy were 20.4% and 6.1% at 3 months and 39.6% and 18.8% at the end of follow-up, respectively. Patients treated with IFX presented with significantly shorter colectomy-free survival than IVCS responders (P= 0.04, log-rank test). Both cytomegalovirus colitis and Clostridioides difficile infection (CDI) were the significant predictors of colectomy in the overall study cohort (hazard ratios of 6.57 and 4.61, respectively). There were no fatalities. CONCLUSIONS: Our real-world cohort study demonstrated that IFX is an effective therapeutic option in Korean patients with ASUC, irrespective of IFX indication. Aggressive vigilance for cytomegalovirus colitis and CDI is warranted for hospitalized patients with ASUC.

Proteinuria Is Associated with the Development of Crohn's Disease: A Nationwide Population-Based Study.

BACKGROUND AND AIMS: The impact of proteinuria and its severity on the incidence of inflammatory bowel disease (IBD) has not yet been studied. We aimed to determine the association between proteinuria measured by urine dipstick tests and the development of IBD. METHODS: This nationwide population-based study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 9,917,400 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was classified into four groups-negative, trace, 1+, and ≥ 2+-according to the degree of proteinuria measured by the urine dipstick test. The primary endpoint was newly diagnosed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period. RESULTS: Compared with the dipstick-negative group, the incidence of CD significantly increased according to the degree of proteinuria (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.01 [0.703-1.451], 1.515 [1.058-2.162], and 2.053 [1.301-3.24] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.007). However, there was no significant difference in the incidence of UC according to the degree of proteinuria (aHR with 95% CI, 1.12 [0.949-1.323], 0.947 [0.764-1.174], and 1.009 [0.741-1.373] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.722). In the subgroup analysis, dipstick-positive proteinuria independently increased the incidence of CD regardless of the subgroup. However, dipstick-positive proteinuria was associated with the risk of UC in those with diabetes mellitus and not in those without diabetes mellitus (aHR, 1.527 vs. 0.846; interaction p-value 0.004). The risk of CD was increased or decreased according to proteinuria changes but not associated with the risk of UC. CONCLUSION: Proteinuria, measured by the dipstick test, is strongly associated with the development of CD.

Anemia is associated with the risk of Crohn's disease, not ulcerative colitis: A nationwide population-based cohort study.

Anemia is a common manifestation of inflammatory bowel disease (IBD), but it remains unclear whether anemia is associated with the development of IBD. We assessed the risk of developing IBD in anemic patients, and stratified the results with respect to their hemoglobin concentrations. A population-based study was conducted using the National Healthcare Insurance Service database in South Korea. We included individuals over 20 years' old who participated in the national health screening program in 2009 (n = 9,962,064). Anemia was defined as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. We compared the rate of newly diagnosed IBD in anemic patients and non-anemic individuals. Newly diagnosed IBD was identified using both the ICD-10 medical code and specialized V codes for rare intractable diseases in South Korea. During the mean follow-up period of 7.3 years, the incidences of CD and UC in anemic patients were 2.89 and 6.88 per 100,000 person-years, respectively. The risk of CD was significantly higher in anemic patients than in non-anemic individuals [adjusted hazard ratio (aHR), 2.084; 95% confidence interval (CI), 1.769-2.455]. The risk of CD development was inversely proportional to the hemoglobin concentration. A J-curve relationship was observed between age and the risk of CD in anemic patients. The risk of CD in male anemic patients was significantly higher than that in female anemic patients (aHR, 1.432 vs. 1.240, respectively). By contrast, there was no statistically significant difference in the risk of developing UC in anemic and non-anemic individuals (aHR, 0.972; 95% CI, 0.880-1.073). This work indicates that anemia is related to the development of CD, and this risk was inversely proportional to the hemoglobin concentration.

Soluble Siglec-9 alleviates intestinal inflammation through inhibition of the NF-κB pathway.

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models. METHODS: COLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined. RESULTS: sSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models. CONCLUSION: sSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease.

Toll-like receptor 4 regulates intestinal fibrosis via cytokine expression and epithelial-mesenchymal transition.

Intestinal fibrosis induced by chronic and recurrent colitis, which is exacerbated by bowel stenosis, stricture, and obstruction, is challenging to treat. Toll-like receptor 4 (TLR4) stimulates innate and acquired immunity in response to specific microbial components, but the role of TLR4 in intestinal fibrosis is largely unknown. We investigated its role in intestinal fibrosis using not only a murine fibrosis model but also human myofibroblasts and intestinal epithelial cells. Colon fibrosis was induced in TLR4-deficient (TLR4-/-) mice and its wild-type counterparts with 3% dextran sulfate sodium. Absence of TLR4 gene attenuated chronic inflammation and colonic macrophages infiltration; intestinal fibrosis and collagen deposition were suppressed. Also, the production of tumor necrosis factor-α, interleukin-12p40, and transforming growth factor-ß was reduced in TLR4-deficient peritoneal macrophages. TLR4 was silenced in CCD-18Co cells by small interfering RNA (siRNA), and matrix metalloproteinase-1, tissue inhibitor of metalloproteinase, and collagen α1 expression was evaluated. Role of TLR4 in epithelial-mesenchymal transition (EMT) was evaluated in HCT116 cells. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis.

Trends and risk factors of elderly-onset Crohn's disease: A nationwide cohort study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is increasing in Asia. Numerous risk factors associated with IBD development have been investigated. AIM: To investigate trends and environmental risk factors of Crohn's disease (CD) diagnosed in persons aged ≥ 40 years in South Korea. METHODS: Using the National Health Insurance Service database, a total of 14060821 persons aged > 40 years who underwent national health screening in 2009 were followed up until December 2017. Patients with newly diagnosed CD were enrolled and compared with non-CD cohort. CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database. The mean follow-up periods was 7.39 years. Age, sex, diabetes, hypertension, smoking, alcohol consumption, regular exercise, body mass index, anemia, chronic kidney disease (CKD) and dyslipidemia were adjusted for in the multivariate analysis model. RESULTS: During the follow-up, 1337 (1.33/100000) patients developed CD. Men in the middle-aged group (40-64 years) had a higher risk than women [adjusted hazard ratio (aHR) 1.46, 95% confidence interval (CI): 1.29-1.66]; however, this difference tended to disappear as the age of onset increases. In the middle-aged group, patients with a history of smoking [aHR 1.46, 95%CI: 1.19-1.79) and anemia (aHR 1.85, 95%CI: 1.55-2.20) had a significantly higher CD risk. In the elderly group (age, ≥ 65 years), ex-smoking and anemia also increased the CD risk (aHR 1.68, 95%CI: 1.22-2.30) and 1.84 (95%CI: 1.47-2.30, respectively). Especially in the middle-aged group, those with CKD had a statistically elevated CD risk (aHR 1.37, 95%CI: 1.05-1.79). Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups. [Middle-aged: aHR 0.77 (95%CI: 0.66-0.89) and aHR 0.73 (95%CI: 0.63-0.84), respectively] [Elderly-group: aHR 0.57 (95%CI: 0.42-0.78) and aHR 0.84 (95%CI 0.67-1.04), respectively]. For regular physical activity and dyslipidemia, negative correlation between CD incidences was proved only in the middle-aged group [aHR 0.88 (95%CI: 0.77-0.89) and aHR 0.81 (95%CI: 0.68-0.96), respectively]. CONCLUSION: History of cigarette smoking, anemia, underweight and CKD are possible risk factors for CD in Asians aged > 40 years.

Crohn's disease and ulcerative colitis are associated with different lipid profile disorders: a nationwide population-based study.

BACKGROUND: The relationships between lipid profiles and IBD remain elusive. AIM: To determine the association of IBD with serum lipid profiles. METHODS: A nationwide population-based study was performed using claims data from the Korean National Healthcare Insurance service. A total of 9 706 026 subjects undergoing medical check-ups in 2009 were enrolled and followed up until 2016. Individuals who developed Crohn's disease (CD) or ulcerative colitis (UC) were identified during follow-up. Adjusted hazard ratio (aHR) by age, sex, body mass index, cigarette smoking, alcohol drinking, exercise, income and underlying comorbidities was calculated to define the impact of serum lipid profiles on developing IBD. RESULTS: During a median follow-up of 7.3 years, IBD was detected in 7,058 (0.07%) individuals. Compared with the highest quartile of serum total cholesterol (TC) levels, lower TC levels were associated with higher incidence of CD (aHR: Q1, 2.52; Q2, 1.52; Q3, 1.27), but not UC. Lower serum LDL-C levels were associated with higher incidence of CD (aHR: Q1, 1.92; Q2, 1.47; Q3, 1.22), but not UC. Moreover, lower serum HDL-C levels were associated with higher incidence of CD (aHR: Q1, 2.49; Q2, 1.90; Q3, 1.43), but not UC. In contrast, lower serum triglyceride levels were associated with higher incidence of UC (aHR: Q1, 1.22; Q2, 1.19; Q3, 1.19), but not CD. CONCLUSIONS: Low serum TC, LDL-C and HDL-C levels were associated with CD. Low serum triglyceride levels were related to UC.

Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study.

BACKGROUND: Periodontitis is a chronic inflammation of periodontal tissues. The effect of periodontitis on the development of inflammatory bowel disease (IBD) remains unclear. AIM: To assessed the risk of IBD among patients with periodontitis, and the risk factors for IBD related to periodontitis. METHODS: A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service. In total, 9950548 individuals aged ≥ 20 years who underwent national health screening in 2009 were included. Newly diagnosed IBD [Crohn's disease (CD), ulcerative colitis (UC)] using the International Classification of Disease 10th revision and rare intractable disease codes, was compared between the periodontitis and non-periodontitis groups until 2017. RESULTS: A total of 1092825 individuals (11.0%) had periodontitis. Periodontitis was significantly associated with older age, male gender, higher body mass index, quitting smoking, not drinking alcohol, and regular exercise. The mean age was 51.4 ± 12.9 years in the periodontitis group and 46.6 ± 14.2 years in the non-periodontitis group (P < 0.01), respectively. The mean body mass index was 23.9 ± 3.1 and 23.7 ± 3.2 in the periodontitis and non-periodontitis groups, respectively (P < 0.01). Men were 604307 (55.3%) and 4844383 (54.7%) in the periodontitis and non-periodontitis groups, respectively. The mean follow-up duration was 7.26 years. Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis [adjusted hazard ratio: 1.091; 95% confidence interval (CI): 1.008-1.182], but not CD (adjusted hazard ratio: 0.879; 95% confidence interval: 0.731-1.057). The risks for UC were significant in the subgroups of age ≥ 65 years, male gender, alcohol drinker, current smoker, and reduced physical activity. Current smokers aged ≥ 65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged ≥ 65 years without periodontitis. CONCLUSION: Periodontitis was significantly associated with the risk of developing UC, but not CD, particularly in current smokers aged ≥ 65 years.

Child-Pugh B or C Cirrhosis Increases the Risk for Bleeding Following Colonoscopic Polypectomy.

Background/Aims: The risk for colonoscopic postpolypectomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, especially those with liver cirrhosis. Methods: We retrospectively reviewed the medical records of patients with CLD who underwent colonoscopic polypectomy at Seoul National University Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. Results: A total of 1,267 consecutive patients with CLD were included in the study. Immediate PPB occurred significantly more often in the Child- Pugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p<0.001). Moreover, the incidence of delayed PPB in the CP-B or C cirrhosis group (4.4%) was significantly higher than that in the CP-A (0.7%) and chronic hepatitis (0.2%) groups (p<0.001). The independent risk factors for immediate PPB were CP-B or C cirrhosis (p=0.011), a platelet count <50,000/µL (p<0.001), 3 or more polyps (p=0.017), endoscopic mucosal resection or submucosal dissection (p<0.001), and polypectomy performed by trainees (p<0.001). The independent risk factors for delayed PPB were CP-B or C cirrhosis (p=0.009), and polyps >10 mm in size (p=0.010). Conclusions: Patients with CP-B or C cirrhosis had an increased risk for bleeding following colonoscopic polypectomy.