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

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

Migraine is associated with the development of adult patients with inflammatory bowel disease: a nationwide, population-based study.

It has been reported that migraine is more common in patients with inflammatory bowel disease (IBD) than in general. However, the impact of migraine on the development of IBD has not yet been elucidated. The aim of this study was to determine the association between migraine and the development of IBD. This nationwide population-based cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 10,628,070 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 divided into two groups according to the presence or absence of migraine. We analyzed the incidence of newly developed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period. The incidence of IBD was significantly higher in patients with migraine (adjusted hazard ratio [aHR] with 95% confidence interval [95%CI] of 1.31 [1.173-1.468], p < 0.001), CD (aHR with 95%CI of 1.58 [1.237-2.013], p < 0.001) and UC (aHR with 95%CI of 1.26 [1.106-1.424], p < 0.001) than in those without migraine. After 5 years of follow-up, those with migraine showed curves implying cumulative incidences of IBD with a steep increase, especially for CD. In subgroup analysis, migraine was associated with the risk of UC in males (aHR, 1.431 vs. 1.117; interaction p = 0.042). Migraine is significantly associated with the development of IBD. Patients with migraine should be monitored carefully for the development of IBD.

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Regulation of psoriasis, colitis, and the intestinal microbiota by clusterin.

Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the so-called "gut-skin axis." Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (clusterin-/-) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in clusterin-/- mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated clusterin-/- and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model.

Infectious complications in patients with inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 8th Asian Organization for Crohn's and Colitis meeting.

BACKGROUND/AIMS: Infectious complications are major concerns when treating patients with inflammatory bowel disease (IBD). This study evaluated clinical differences across countries/regions in the management of infectious diseases in patients with IBD. METHODS: A multinational online questionnaire survey was administered to participants at the 8th meeting of the Asian Organization for Crohn's and Colitis. The questionnaire included questions regarding surveillance, diagnosis, management, and prevention of infection in patients with IBD. RESULTS: A total of 384 physicians responded to the questionnaire. The majority of Korean (n=70, 63.6%) and Chinese (n=51, 51.5%) physicians preferred vancomycin to metronidazole in the treatment of Clostridium difficile infection, whereas more than half of the Japanese physicians (n=62, 66.7%) preferred metronidazole. Physicians in Korea (n=88, 80.0%) and China (n=46, 46.5%) preferred a 3-month course of isoniazid and rifampin to treat latent tuberculosis infection, whereas most physicians in Japan (n=71, 76.3%) favored a 9-month course of isoniazid. Most Korean physicians (n=89, 80.9%) recommended hepatitis B virus (HBV) vaccination in patients lacking HBV surface antigen, whereas more than half of Japanese physicians (n=53, 57.0%) did not consider vaccination. CONCLUSIONS: Differences in the diagnosis, prevention, and management of infections in patients with IBD across countries/regions reflect different prevalence rates of infectious diseases. This survey may broaden understanding of the real-world clinical settings across Asian countries/regions and provide information for establishing practical guidelines to manage patients with IBD.

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Atopic dermatitis is associated with the clinical course of inflammatory bowel disease.

OBJECTIVES: There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It is implied that both diseases have common pathophysiologic mechanisms and can affect each other. However, little information is available on the effect of AD on the clinical course of patients with IBD. METHODS: This is a multi-center, retrospective, observational study. We define AD as a chronic eczematoid dermatosis diagnosed by dermatologists. Patients with concurrent IBD and AD were defined as a case group. Age, gender, and IBD subtype-matched patients without AD were included as a reference group. RESULTS: The numbers of patients in the case and reference groups were 61 and 122 respectively. There was a significantly shorter biologics-free survival in the case group than that in the reference group according to the multivariable-adjusted Cox regression analysis with the onset age, disease duration, smoking status, use of steroid, use of immunomodulator, initial C-reactive protein, initial erythrocyte sedimentation rate, presence of other allergic diseases and initial disease severity [hazard ratio (HR) 1.828, 95% confidence interval (CI) 1.022-3.271, p = .042]. The trend was consistent in the subgroup analysis with ulcerative colitis (HR 3.498, 95% CI 1.066-11.481, p = .039), but not with Crohn's disease (HR 1.542, 95% CI 0.720-3.301, p = .265). CONCLUSIONS: AD showed a significant effect on the biologics-free survival of patients with IBD and especially the UC subtype. Further mechanistic research is required to elucidate the pathogenesis of AD on the clinical course of IBD.

Depression and anxiety are associated with poor outcomes in patients with inflammatory bowel disease: A nationwide population-based cohort study in South Korea.

BACKGROUND: Prevalence of depression and anxiety are known to be increased in patients with inflammatory bowel disease (IBD), but it is unclear whether such elevations adversely affect IBD outcomes. OBJECTIVE: We aimed to investigate the association between depression or anxiety and clinical outcomes of IBD. METHOD: Using claims data from the South Korean National Health Insurance Service (NHIS), patients with IBD were identified by codes of the International Classification of Disease, 10th Revision (ICD-10) and the Rare/Intractable Disease (RID) registration program for years 2010 to 2017. ICD-10 codes were also used to identify depression and anxiety in this population. Primary study endpoints were IBD-related outcomes, including emergency room (ER) visits, hospitalizations, and surgeries during the follow-up period. RESULTS: Our cohort included 32,867 patients with IBD, of whom 3794 (11.5%) experienced depression and anxiety during the 6-year median follow-up period. In multivariate analysis, comorbid depression and anxiety were associated with increased risks of ER visits (hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.19-1.51) and hospitalizations (HR = 1.24, 95% CI: 1.12-1.37), whereas surgical risk was not different for IBD patients with and without depression and anxiety. There was no differential effect of depression and anxiety on outcomes in IBD patients, but depression was more closely associated with outcomes in CD patients and anxiety in UC patients. CONCLUSION: In patients with IBD, comorbid depression and anxiety are associated with increased risks of ER visits and hospitalizations, but not surgery. These associations are more pronounced for depression in CD patients and for anxiety in UC patients.

Positive Results from the Fecal Immunochemical Test Can Be Related to Dementia: A Nationwide Population-Based Study in South Korea.

BACKGROUND: The fecal immunochemical test (FIT) is widely used in screening for colorectal cancer (CRC), but FIT results can be positive for diseases other than CRC. OBJECTIVE: We investigated the association between positive results of FIT and the incidence of dementia using a nationwide database. METHODS: FIT-positive participants were collected from a database provided by the Korean National Health Insurance Service. RESULTS: The incidence of all kinds of dementia was higher in FIT-positive than FIT-negative subjects (p < 0.0001). FIT-positive participants had a higher risk of Alzheimer's disease (AD) (p < 0.0001) and vascular dementia (p = 0.0002), compared to participants with FIT negativity. The risk of all kinds of dementia or AD in FIT-positive participants was higher in younger (age < 65 years) than older participants (p < 0.0001 for all kinds of dementia; p = 0.0002 for AD). CONCLUSION: FIT positivity was correlated with an increased risk of dementia, especially in participants under 65 years of age. The study suggests that clinicians can consider dementia when FIT-positive participants fail to show any malignancies.

Impact of Crohn's Disease on the Survival of Patients with Small-Bowel Adenocarcinoma in Korea: A Bicenter Cohort Study.

Background/Aims: Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn's disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. Methods: In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. Results: Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p<0.05). In survival analysis, overall survival showed no statistical difference between the sporadic SBA and CD-associated SBA groups (p=0.370). However, when stratified by stage, the adjusted overall survival of the CD-associated SBA group was lower in patients with an advanced disease stage (p=0.029). Disease-free survival showed the same tendency, albeit without clinical significance (p=0.097). CD (hazard ratio [HR], 2.308; p=0.047), older age (≥65 yr) at SBA diagnosis (HR, 2.766; p=0.001), and stage III/IV disease (HR, 3.151; p<0.001) were factors associated with mortality. Conclusions: The overall survival of patients with CD-associated SBA did not differ from that of patients with sporadic SBA. However, as CD is an independent risk factor for mortality, vigilant surveillance in high-risk patients may be crucial.

Concomitant ankylosing spondylitis can increase the risk of biologics or small molecule therapies to control inflammatory bowel disease.

BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes. METHODS: Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients' electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised. RESULTS: The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863-9.021; P< 0.001) and Crohn's disease (odds ratio, 3.552; 95% confidence interval, 1.590-7.934; P= 0.002). CONCLUSIONS: Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.

Association between severe hepatic steatosis examined by Fibroscan and the risk of high-risk colorectal neoplasia.

The prevalence of colorectal neoplasm in patients with non-alcoholic fatty liver disease has increased twice as high as that in the general population. FibroScan is a new modality for evaluating hepatic steatosis. This study aimed to investigate the relationship between the risk of high-risk colorectal neoplasia and hepatic steatosis examined using FibroScan. This was a cross sectional study of prospectively enrolled subjects who were scheduled to undergo index colonoscopy as a health screening between March 2018 and February 2019. The severity of steatosis was graded as normal, mild, moderate, or severe using FibroScan. A total of 140 consecutive subjects were enrolled and sequentially examined using FibroScan and colonoscopy. Subjects with hepatic steatosis had more high-risk colorectal neoplasia than those without hepatic steatosis. In addition, tumor size was larger in subjects with hepatic steatosis. In multivariable analysis, severe hepatic steatosis was an independent risk factor for high-risk colorectal neoplasia (adjusted odds ratio: 3.309, confidence interval: 1.043-10.498, p = 0.042). Alcohol consumption was also identified as a risk factor for high-risk colorectal neoplasia. In conclusion, severe hepatic steatosis on FibroScan is associated with the development of high-risk colorectal neoplasia. Thus, physicians should be aware of the association between colorectal neoplasia and hepatic steatosis assessed by FibroScan and its clinical implications.

Clinical Characteristics of Korean Patients with Elderly-Onset Crohn's Disease: Results from the Prospective CONNECT Study.

The clinical course and prognosis of patients with elderly-onset Crohn's disease (CD) remain unclear. This study aimed to analyze the clinical characteristics and outcomes of elderly-onset CD patients from the prospective CONNECT study cohort, a nationwide, multicenter cohort study of patients with CD in Korea. Among a total of 1,175 patients in the prospective CONNECT study cohort, 94 patients (Montreal age A3) were included and divided into two groups according to their age at diagnosis: the elderly-onset group (diagnosed with CD after 60 years of age, n=26, 67.54±6.7 years) and late adult-onset group (diagnosed as CD at age 41 to 59 years, n=68, 48.06±5.1 years). The elderly-onset group was characterized by a lower Crohn's disease activity index at diagnosis (124.89±101.9 vs 189.55±128.6, p=0.023) and higher rates of previous anti-tuberculosis treatment (34.6% vs 4.4%, p<0.001) than the late adult-onset group. Compared with the late adult-onset group, the elderly-onset group showed a significantly less use of thiopurines (p=0.003), as well as anti-tumor necrosis factor-alpha agents (p=0.047). Additionally, the elderly-onset group was less likely to require bowel resection than the late adult-onset group (p=0.067), suggesting that elderly-onset CD patients in Korea appear to have more favorable clinical outcomes than late adult-onset CD patients.

Depression in patients with inflammatory bowel disease is associated with increased risk of dementia and Parkinson's disease: A nationwide, population-based study.

Background: Inflammatory bowel disease (IBD) may be associated with depression which is considered an important cause of dementia and Parkinson's disease (PD). In the present study, the effects of depression on the development of dementia and/or PD in patients with IBD were evaluated. Materials and methods: A nationwide population-based cohort study was conducted using claims data from the Health Insurance Review and Assessment Service in Korea. The incidence of dementia and PD were analyzed based on the presence of depression in patients with IBD. Results: During a mean follow-up of 8 years, IBD patients with depression experienced dementia (6.7 vs. 2.0%; p < 0.001) and PD (1.1 vs. 0.3%; p < 0.001) significantly more than IBD patients without depression. Compared with IBD patients without depression, the risk of developing dementia was significantly higher in IBD patients with depression [adjusted hazard ratio (aHR) for IBD, Crohn's disease (CD), and ulcerative colitis (UC), 2.03, p < 0.001; 1.68, p = 0.033; 2.13, p < 0.001, respectively]. Compared with IBD patients without depression, the risk of developing PD was significantly higher in IBD patients with depression (aHR for IBD, CD, and UC, 2.54, p < 0.001; 1.93, p = 0.470; 2.75, p < 0.001, respectively). The cumulative incidence of dementia and PD in IBD patients with depression was significantly higher than in IBD patients without depression and showed a steady increase after a diagnosis of depression. Conclusion: The risk of dementia and/or PD increased after a diagnosis of depression in patients with IBD.

Additive effect of probiotics (Mutaflor) on 5-aminosalicylic acid therapy in patients with ulcerative colitis.

BACKGROUND/AIMS: In ulcerative colitis (UC) patients, Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, evidence of the ability of EcN to increase health-related quality of life or induce remission remains scarce. We investigated the efficacy of EcN as an add-on therapy for UC. METHODS: In this multicentre, double-blind, randomised, placebo-controlled study, a total of 133 UC patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks. Inflammatory bowel disease questionnaire (IBDQ) scores (primary endpoint) and clinical remission and response rates (secondary endpoints) were compared (Clinical trial registration number: NCT04969679). RESULTS: In total, 118 patients (EcN, 58; placebo, 60) completed the study. The number of patients reaching the primary endpoint did not differ between the EcN and placebo groups (30 [51.7%] vs. 31 [51.7%]; per-protocol analysis, p = 1.0; intention-to-treat analysis, p = 0.86). However, significantly fewer patients in the EcN group exhibited a decreased IBDQ score (1 [1.7%] vs. 8 [13.3%]; per-protocol analysis, p = 0.03; intention- to-treat analysis, p = 0.02). Moreover, a significantly higher number of patients in the EcN group displayed clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], p = 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], p = 0.03). CONCLUSION: Although the number of patients reaching the primary endpoint did not differ between the EcN and placebo groups, EcN was found to be safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remission in patients with mild-to-moderate UC.

Preventive Effect of Vitamin C on Dextran Sulfate Sodium (DSS)-Induced Colitis via the Regulation of IL-22 and IL-6 Production in Gulo(-/-) Mice.

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C's influence on the development and progression of IBD in Gulo(-/-) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ-lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(-/-) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(-/-) mice to vitamin C-sufficient Gulo(-/-) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.

Silver-Reduced Poly(Ethylene Glycol) Diacrylate Composites with Microline Arrays for Directional Bending Sensors.

Herein, a soft and flexible polymer composite sensor with a surface structure is manufactured that is sensitive to a wide range of mechanical stimuli, including small actions and large motions. A polymer sensor performing with a piezoresistive mechanism is proposed by synthesizing a new conductive polymer composite to fabricate a microline structure by itself, named Ag-reduced poly(ethylene glycol) diacrylate (PEGDA) composite directional bending sensor (ACBS). A simple but effective process of forming nanoparticles (NPs) and surface structures is a notable characteristic. High sensitivity to a small stimulus was achieved by forming Ag NPs within PEGDA, particularly concentrating on the surface and applying the microline structure. With the structural characteristics of a line structure, the ACBS achieved anisotropic sensitivity to bulk motion along the arranged line direction. The excellent sensitivity of this polymer sensor was experimentally demonstrated via water droplets, blowing, and breathing. Combining the advantages of a simple synthetic and simple fabrication process along with the fabrication ability of the microsurface structure with the material itself and the conductive Ag/PEGDA integrated layer, this ACBS is outstanding as a soft and flexible polymer composite sensor and has potential application in physical devices such as wearable devices and biosensors.

Composite scoring system and optimal tumor budding cut-off number for estimating lymph node metastasis in submucosal colorectal cancer.

BACKGROUND: Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. METHODS: In total, 395 patients with histologically confirmed T1N0-2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. RESULTS: The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80-36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91-11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21-7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. CONCLUSIONS: For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

The Common and Unique Pattern of Microbiome Profiles among Saliva, Tissue, and Stool Samples in Patients with Crohn's Disease.

This study aimed to elucidate common and unique microbiome patterns in saliva, intestinal tissue biopsy, and stool samples from patients with Crohn's disease (CD). Saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. A total of 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus, Pantoea, and Actinomyces from the saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus, which are commonly observed in saliva, stool, and tissue, can be considered a potential biomarker related to the diagnosis or prognosis of CD.