Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

Background/Aims: : A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusions: : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.

Background: Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.

Differences in treatment efficacy between thiopurine and methotrexate in patients with Crohn's disease who were not treated with biologics Immunomodulators (IMMs) used in the treatment of Crohn's disease (CD) include medications such as thiopurine and methotrexate (MTX). Although IMMs are widely prescribed for patients with CD, it remains unclear whether treatment outcomes differ according to the specific types and dosages of IMMs and administration routes of MTX. In this study, we investigated the risk of treatment failure between thiopurines and MTX in CD patients not undergoing biologic treatment. Patients treated with MTX had a higher risk of maintenance failure than those treated with thiopurines. There was no difference in the risk of treatment failure according to the dosage of thiopurine. However, the risk of maintenance failure was higher in patients receiving standard-dose MTX than in those receiving low-dose MTX. There was no difference in the risk of maintenance failure according to the administration route of MTX. Our study enriches the knowledge regarding the treatment efficacy of thiopurines and MTX for patients with CD and may help clinicians develop appropriate treatment plans.

The Effect of Clostridium butyricum on Gut Microbial Changes and Functional Profiles of Metabolism in High-fat Diet-fed Rats Depending on Age and Sex.

Background/Aims: A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. Methods: Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. Results: A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1ß (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). Conclusion: The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.

Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis.

Background/Aims: : The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: : Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor ß (TGF-ß), interleukin (IL)-1ß, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: : The messenger RNA expressions of TGF-ß, IL-1ß, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-ß, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-ß, IL-1ß, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions: : Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions (ClinicalTrials.gov, NCT05653011).

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients.

Background/Aims: Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. Methods: A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. Results: The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. Conclusions: SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).

Sex Difference of Colon Adenoma Pathway and Colorectal Carcinogenesis.

Colorectal cancer (CRC) is one of the most common causes of cancer morbidity in both sexes but shows sex differences. First, sex-specific differences in tumor recurrence and survival rates have been reported. For example, the development of CRC is found about 1.5 times higher and 4-8 years earlier in males compared to females, suggesting the protective role of estrogen in the disease. Furthermore, female patients have a higher risk of developing right-sided (proximal) colon cancer than male patients, which is known to have more aggressive clinical character compared to left-sided (distal) colon cancer. That is, left and right CRCs show differences in carcinogenic mechanism, that the chromosomal instability pathway is more common in left colon cancer while the microsatellite instability and serrated pathways are more common in right colon cancer. It is thought that there are sex-based differences on the background of carcinogenesis of CRC. Sex differences of CRC have two aspects, sexual dimorphism (biological differences in hormones and genes) and gender differences (non-biological differences in societal attitudes and behavior). Recently, sex difference of colon adenoma pathway and sexual dimorphism in the biology of gene and protein expression, and in endocrine cellular signaling in the CRC carcinogenesis have been accumulated. In addition, behavioral patterns can lead to differences in exposure to risk factors such as drinking or smoking, diet and physical activity. Therefore, understanding sex/gender-related biological and sociocultural differences in CRC risk will help in providing strategies for screening, treatment and prevention protocols to reduce the mortality and improve the quality of life. In this review, sex/gender differences in colon adenoma pathway and various aspects such as clinicopathological, biological, molecular, and socio-cultural aspects of CRC were described.

Evaluation of Bacterial and Fungal Biomarkers for Differentiation and Prognosis of Patients with Inflammatory Bowel Disease.

This study aimed to evaluate bacterial and fungal biomarkers to differentiate patients with inflammatory bowel disease (IBD), predict the IBD prognosis, and determine the relationship of these biomarkers with IBD pathogenesis. The composition and function of bacteria and fungi in stool from 100 IBD patients and 97 controls were profiled using next-generation sequencing. We evaluated the cumulative risk of relapse according to bacterial and fungal enterotypes. The microbiome and mycobiome alpha diversity in IBD patients were significantly lower and higher than in the controls, respectively; the micro/mycobiome beta diversity differed significantly between IBD patients and the controls. Ruminococcus gnavus, Cyberlindnera jadinii, and Candida tropicalis increased in IBD patients. Combining functional and species analyses revealed that lower sugar import and higher modified polysaccharide production were associated with IBD pathogenesis. Tricarboxylic acid cycling consuming acetyl CoA was higher in IBD patients than the controls, leading to lower short-chain fatty acid (SCFA) fermentation. Bacterial and fungal enterotypes were not associated with IBD relapse. We found differences in bacterial and fungal species between IBD patients and controls. A working model for the role of gut bacteria in IBD pathogenesis is proposed, wherein bacterial species increase modified N-glycan production and decrease SCFA fermentation.

Intelligent Complementary Multi-Modal Fusion for Anomaly Surveillance and Security System.

Recently, security monitoring facilities have mainly adopted artificial intelligence (AI) technology to provide both increased security and improved performance. However, there are technical challenges in the pursuit of elevating system performance, automation, and security efficiency. In this paper, we proposed intelligent anomaly detection and classification based on deep learning (DL) using multi-modal fusion. To verify the method, we combined two DL-based schemes, such as (i) the 3D Convolutional AutoEncoder (3D-AE) for anomaly detection and (ii) the SlowFast neural network for anomaly classification. The 3D-AE can detect occurrence points of abnormal events and generate regions of interest (ROI) by the points. The SlowFast model can classify abnormal events using the ROI. These multi-modal approaches can complement weaknesses and leverage strengths in the existing security system. To enhance anomaly learning effectiveness, we also attempted to create a new dataset using the virtual environment in Grand Theft Auto 5 (GTA5). The dataset consists of 400 abnormal-state data and 78 normal-state data with clip sizes in the 8-20 s range. Virtual data collection can also supplement the original dataset, as replicating abnormal states in the real world is challenging. Consequently, the proposed method can achieve a classification accuracy of 85%, which is higher compared to the 77.5% accuracy achieved when only employing the single classification model. Furthermore, we validated the trained model with the GTA dataset by using a real-world assault class dataset, consisting of 1300 instances that we reproduced. As a result, 1100 data as the assault were classified and achieved 83.5% accuracy. This also shows that the proposed method can provide high performance in real-world environments.

The Possible Preventative Role of Lactate- and Butyrate-Producing Bacteria in Colorectal Carcinogenesis.

Background/Aims: : The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. Methods: : Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. Results: : In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. Conclusions: : The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

10 years of biologic use patterns in patients with inflammatory bowel disease: treatment persistence, switching and dose intensification - a nationwide population-based study.

Background: Treatments for inflammatory bowel diseases (IBD) have evolved in the era of biologics. However, the real-world data on their usage patterns and sequencing are still limited. Objectives: We aimed to investigate treatment persistence and dose intensification of first- and second-line biologics in patients with IBD. Design: In this retrospective, cohort study using nationwide claims data, 13,087 patients with IBD initiating biologic therapy between 2010 and 2020 were identified. Methods: Treatment persistence and dose intensification during the first 2 years and switching patterns of biologics were analysed while identifying predictors of non-persistence. Results: As a first-line treatment of Crohn's disease (CD), ustekinumab had a lower risk for non-persistence compared to infliximab [adjusted hazard ratio (aHR), 0.69, p = 0.048]. Second-line ustekinumab and vedolizumab showed the highest and lowest persistence (79.2% and 54.9%), respectively. As a first-line treatment of ulcerative colitis (UC), golimumab had a higher risk for non-persistence compared to infliximab (aHR, 1.68, p < 0.001). Second-line golimumab also showed a significantly lower persistence rate than adalimumab and vedolizumab. The risk of non-persistence was higher in UC than in CD (first line: aHR, 1.97; second line: aHR, 1.39; p < 0.001), and in the second-line treatment than in the first-line treatment for CD (aHR, 1.55; p < 0.001). The cumulative rate of dose intensification was highest with ustekinumab for CD (first line, 43.3%, second line, 69.1%) and adalimumab for second-line UC (40.7%). It was significantly increased in second-line therapy in CD, but not in UC. Among switchers of first-line anti-tumour necrosis factor-α inhibitor therapy, after all biologics were approved, 69% of CD patients and 78.4% of UC patients switched to other classes of second-line treatment. Conclusion: Ustekinumab had higher persistence in the first-line treatment of CD, while golimumab had lower persistence for first- and second-line treatments of UC. Dose intensification rates varied, with the highest cumulative rates observed for ustekinumab in CD and adalimumab in second-line UC.

Staging Chest CT in Patients With Early-Stage Colon Cancer: Analysis of Impact on Survival Using Inverse Probability Weighting and Causal Diagram.

BACKGROUND. Staging chest CT has been shown to have negligible diagnostic yield for detecting lung metastases in patients with early-stage colon cancer. Nonetheless, staging chest CT may have potential survival benefits, including opportunistic screening of comorbidity and provision of a baseline examination for future comparisons. Evidence is lacking regarding the impact of staging chest CT on survival in patients with early-stage colon cancer. OBJECTIVE. The purpose of this study was to determine whether the performance of staging chest CT affects survival in patients with early-stage colon cancer. METHODS. This retrospective study included patients with early-stage colon cancer (defined as clinical stage 0 or I on staging abdominal CT) at a single tertiary hospital between January 2009 and December 2015. Patients were divided into two groups according to the presence of a staging chest CT examination. To ensure comparability between the two groups, inverse probability weighting was applied to adjust for the confounders derived from a causal diagram. The between-group differences in adjusted restricted mean survival time at 5 years were measured for overall survival, relapse-free survival, and thoracic metastasis-free survival. Sensitivity analyses were performed. RESULTS. A total of 991 patients (618 men and 373 women; median age, 64 years [IQR, 55-71 years]) were included: 606 patients (61.2%) had staging chest CT. For overall survival, the difference between groups in restricted mean survival time at 5 years was not significant (0.4 months [95% CI, -0.8 to 2.1 months]). The differences between groups in restricted mean survival at 5 years were also not significant for relapse-free survival (0.4 months [95% CI, -1.1 to 2.3 months]) and for thoracic metastasis-free survival (0.6 months [95% CI, -0.8 to 2.4 months]). Similar results were observed in sensitivity analyses that tested 3- and 10-year RMST differences, excluded patients who underwent FDG PET/CT during staging workup, and added treatment decision (surgery vs no surgery) to the causal diagram. CONCLUSION. The use of staging chest CT did not affect survival in patients with early-stage colon cancer. CLINICAL IMPACT. Staging chest CT may be omitted from the staging workup for patients with colon cancer of clinical stage 0 or I.

Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months.

BACKGROUND: The association between Helicobacter pylori (HP) infection and coronary heart disease (CHD) is controversial. This study aimed to investigate the effect of H. pylori eradication on CHD, especially in terms of age and sex. MATERIALS AND METHODS: From May 2003 to March 2022, 4765 subjects with H. pylori infection and without CHD (median follow-up: 51 months) were prospectively enrolled. The participants were categorized into two groups: H. pylori eradication and H. pylori non-eradication. After propensity-score matching (PSM), the effect of H. pylori eradication on CHD was analyzed using Cox proportional hazards. RESULTS: There were no significant differences in age, sex, alcohol consumption, smoking habits, history of diabetes, hypertension, and dyslipidemia, and aspirin intake between the eradication and non-eradication groups (3783 vs. 982) before and after PSM. Multivariate analysis after PSM showed that H. pylori eradication (HR: 0.489, CI: 0.314-0.761, p = .002), age (HR: 1.027, CI: 1.007-1.047, p = .007), hypertension (HR: 2.133, CI: 1.337-3.404, p = 001), dyslipidemia (HR: 1.758, CI: 1.086-2.848, p = .022), and aspirin intake (HR: 2.508, CI: 1.566-4.017, p < .001) were associated with CHD development. H. pylori eradication prevented CHD in males ≤65 years (HR: 0.133, CI: 0.039-0.455, p = .001), but not in those aged >65 years (p = .078) (p for interaction = .022). In contrast, females aged >65 years (HR: 0.260, CI: 0.110-0.615, p = .002) were protected by H. pylori eradication and not those ≤65 years (p = .485) (p for interaction = .003). This preventive effect increased more after PSM, particularly in males ≤65 years and females >65 years. CONCLUSIONS: H. pylori eradication prevented CHD and this effect was different depending on age and sex.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

The Clinicopathological Features of Mixed Carcinoma in 7,215 Patients with Gastric Cancer in a Tertiary Hospital in South Korea.

Background/Aims: There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. Methods: A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (well-moderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. Results: The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. Conclusions: Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).

Impact of Body Mass Index on Survival Depending on Sex in 14,688 Patients with Gastric Cancer in a Tertiary Hospital in South Korea.

Background/Aims: The incidence and prognosis of gastric cancer (GC) shows sex difference. This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex. Methods: The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital. Results: Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%). However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p<0.001). Both sexes had the worst prognosis in the underweight group (p<0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group. Conclusions: GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).

Long-term Effects of the Eradication of Helicobacter pylori on Metabolic Parameters, Depending on Sex, in South Korea.

Background/Aims: Helicobacter pylori (HP) infection is positively associated with metabolic syndrome (MS). However, the long-term effects of eradication therapy on MS and sex differences have not been thoroughly studied. We aimed to investigate the long-term effects of HP eradication on MS and sex differences. Methods: This study included 2,267 subjects who visited a tertiary referral center between May 2003 and May 2019. HP was diagnosed by histology, a Campylobacter-like organism test, and culture, and the subjects were prospectively followed up. The participants were categorized into three groups: HP uninfected, HP infected but non-eradicated, and HP eradicated. The baseline characteristics and changes in metabolic parameters after HP eradication were compared over a 5-year follow-up period. Results: Among 1,521 subjects, there was no difference in baseline metabolic parameters between the HP-uninfected (n=509) and HP-infected (n=1,012) groups, regardless of sex. Analysis of the metabolic parameters during follow-up among HP-uninfected (n=509), HP-non-eradicated (n=346), and HP-eradicated (n=666) groups showed that high-density lipoprotein (HDL) and the body mass index (BMI) increased after eradication, with a significant difference at 1-year of follow-up. In females, HDL increased after eradication (p=0.023), and the BMI increased after eradication in male subjects (p=0.010). After propensity score matching, the HDL change in female remained significant, but the statistical significance of the change in BMI in the male group became marginally significant (p=0.089). Conclusions: HP eradication affected metabolic parameters differently depending on sex. HDL significantly increased only in females over time, especially at 1-year of follow-up. In contrast, BMI showed an increasing tendency over time in males, especially at the 1-year follow-up.

Effects of Aging and Gender on the Anorectal Function of Healthy Subjects Assessed with Conventional Anorectal Manometry.

Background/Aims: Anorectal functions are influenced by gender and age. This study sought to define the normal anorectal pressure values measured with conventional anorectal manometry (ARM) and to evaluate the effects of age and gender on anorectal function in asymptomatic subjects. Methods: Conventional ARM was used to measure the anorectal pressures of 164 asymptomatic healthy subjects, including 86 males and 76 females. Results: The resting anal pressures of males and females aged >60 years were significantly lower than those ≤60 years (males, 44.09±14.22 vs. 57.45±17.69, p<0.001; females, 44.09±14.22 vs. 57.45±17.69, p<0.001). The anal high-pressure zone was significantly lower in older males than in younger males (2.42±0.93 vs. 2.82±0.739, p=0.048). In both age groups (<60 and ≥60 years), the anal squeezing pressures of males were significantly higher than those of females (<60 years old, 168.40±75.94 vs. 119.15±57.53, p=0.001; ≥60 years, 149.61±64.68 vs. 101.3±54.92, p=0.006). Conclusions: The normal anorectal pressure values measured with ARM in males and females were different. Older males and females had lower anal resting pressures than those of the younger subjects, but squeezing pressure was not affected by age.