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The article focuses on the development of an ion trap and release dynamics (iTRD)-driven monolithic artificial tactile neuron (NeuroMAT) for tactile perception and memory consolidation, addressing the challenges of weak tactile memory and complex integration. Topics discussed include the mechanism of tactile-driven ion release and the integration of NeuroMAT with a robotic hand system to emulate memory-based human motion for reliable gripping.

Background: Recent studies have shown that men with diabetes have lower testosterone levels than healthy men. However, studies on the correlation between testosterone and diabetes are rare in Korea. We examined the relationship between testosterone deficiency and markers related to diabetes in adult Korean men. Methods: A total 464 men with diabetes who visited an outpatient clinic at Ajou University Hospital and had serum total testosterone and serum insulin levels measured between January 2000 and September 2013 were selected. Blood samples were collected after the subjects had fasted overnight. We divided the participants into testosterone deficient and normal groups. Testosterone deficiency was defined as having a serum total testosterone level <3.5 ng/mL. Results: Of 464 subjects, 34.9% had a testosterone deficiency. The mean levels of fasting plasma glucose (P=0.007) and glycat-ed hemoglobin (HbA1c; P=0.038) were significantly higher in the testosterone deficiency group than in the normal group. To clarify the relationship between serum total testosterone level and fasting plasma glucose or HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r=-0.142, P=0.002) and HbA1c values (r=-0.097, P=0.040) showed a significant negative correlation with serum testosterone levels in men with diabetes. Conclusion: Major markers of diabetes that are associated with testosterone deficiency are fasting plasma glucose and HbA1c values. Poor glycemic control appears to be associated with testosterone deficiency in Korean men with diabetes. [ABSTRACT FROM AUTHOR]

Mutation of the cj1461 predicted methyltransferase gene reduced the motility of Campylobacter jejuni 81-176. Electron microscopy revealed that the mutant strain had flagella but with aberrant structure. The {Delta}cj1461 mutant was sevenfold more adherent to but 50-fold less invasive of INT-407 human epithelial cells than the wild type. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni and Campylobacter coli are naturally competent, but limited information exists on the impact of environmental conditions on transformation. In this study, we investigated the impact of temperature and microaerobic versus aerobic atmosphere on transformation of C. coli to erythromycin and nalidixic acid resistance. Frequency of transformation was not significantly different between microaerobic (5 to 10% CO2) and aerobic conditions. However, C. coli was transformed to erythromycin resistance at a significantly higher frequency at 42°C than at 25°C (P < 0.05), and few or no transformants were obtained at 25°C. In contrast, transformation to nalidixic acid resistance was highly efficient at both 42°C and 25°C and was similar or, at the most, fourfold higher at 42°C than at 25°C. DNase I treatment experiments suggested that steps both prior and subsequent to internalization of DNA were influenced by temperature in the case of transformation of C. coli to erythromycin resistance. However, the moderately increased (fourfold) frequency of transformation to nalidixic acid resistance at 42°C compared to that at 25°C was exclusively associated with steps prior to DNA internalization. These findings suggest that transformation to erythromycin resistance may be significantly more frequent in the gastrointestinal tract of hosts such as poultry (at 42°C) than in other habitats characterized by lower temperatures, whereas transformation to nalidixic acid resistance may be highly efficient both within and outside the animal hosts. [ABSTRACT FROM AUTHOR]

Background: Although white light (WL) colonoscopy is a gold standard to detect colorectal polyps, substantial polyps are missed. Narrow band imaging (NBI) is a new technology that enables a more detailed visualization of the mucosal surface. The aim of the present study was to determine whether NBI can improve the detection of colorectal polyps. Methods: We prospectively enrolled 188 (M : F = 99:89, 21–80 years) subjects undergoing colonoscopy as a screening procedure in nine referral centers. After a careful WL examination of the whole colorectum, rectosigmoid colon (0–30 cm from the anal verge) was reobserved by NBI. Size, macroscopic morphology, and the histology of all the polyps detected during WL and NBI examination were analyzed. Results: WL examination detected 162 polyps in 188 subjects, of which 106 lesions were neoplastic, while NBI of rectosigmoid colon detected an additional 61 polyps of which eight lesions were neoplastic. Only 10 (6.2%) of 162 polyps discovered during WL examination were flat polyps compared to 10 (16.4%) of 61 newly detected polyps during NBI being flat type ( P = 0.002). The mean polyp size detected by NBI was smaller than that found by WL colonoscopy (2.8 ± 1.0 mm vs 6.5 ± 4.5 mm, P < 0.001). Conclusion: Many additional colorectal polyps, especially flat type, could be detected by NBI examination for normal-looking rectosigmoid mucosa. The role of NBI in colorectal neoplasm screening needs to be further investigated in future studies. [ABSTRACT FROM AUTHOR]

The examination of serration behavior has been made after the tensile deformation of the AA/PP/AA sandwich sheets as well as that of the 5182 aluminum skins. All sandwich sheets and the 5182 aluminum skin showed serration behavior on their flow curves. However, the magnitude of serration was significantly diminished in the sandwich sheet with high volume fraction of the polypropylene core. According to the results of the analysis of the surface roughness following the tensile test, Lüders band depth of the sandwich sheet evidently showed lower than that of the 5182 aluminum skin. The strain rate sensitivity, m-value, of the 5182 aluminum skin was -0.006. By attaching these skins to the polypropylene core, which has relatively large positive value of 0.050, m-value of the sandwich sheets changed to a positive value. The serration reduction of the sandwich sheets was quantitatively investigated with respect to the effect on polypropylene thickness variation, that on the strain rate sensitivity and that on the localized stress state. It was found that the serration reduction degree from the experimental results of the sandwich sheet was higher than from the calculated values by the rule of mixture based on the volume fraction of the skins and the core. [ABSTRACT FROM AUTHOR]

Erythromycin resistance in Campylobacter coli from meat animals is frequently encountered and could represent a substantial barrier to antibiotic treatment of human infections. Erythromycin resistance in this organism has been associated with a point mutation (A2075G) in the 23S rRNA gene. However, the mechanisms responsible for possible dissemination of erythromycin resistance in C. coli remain poorly understood. In this study, we investigated transformation-mediated acquisition of erythromycin resistance by genotypically diverse C. coli strains from turkeys and swine, with total genomic DNA from erythromycin-resistant C. coli of either turkey or swine origin used as a donor. Overall, transformation to erythromycin resistance was significantly more frequent in C. coli strains from turkeys than in swine-derived strains (P < 0.01). The frequency of transformation to erythromycin resistance was 10-5 to 10-6 for turkey-derived strains but 10-7 or less for C. coli from swine. Transformants harbored the point mutation A2075G in the 23S rRNA gene, as did the erythromycin-resistant strains used as DNA donors. Erythromycin resistance was stable in transformants following serial transfers in the absence of the antibiotic, and most transformants had high MICs (>256 μg/ml), as did the C. coli donor strains. In contrast to the results obtained with transformation, spontaneous mutants had relatively low erythromycin MICs (32 to 64 μg/ml) and lacked the A2075G mutation in the 23S rRNA gene. These findings suggest that natural transformation has the potential to contribute to the dissemination of high-level resistance to erythromycin among C. coli strains colonizing meat animals. [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori induces the expression of proinflammatory cytokines in vitro by activating nuclear factor-κB, a transcriptional regulator. However, it has not been clarified whether H. pylori-induced proinflammatory cytokines are also mediated through nuclear factor-κB in vivo. The aim of this study was to evaluate the role of nuclear factor-κB on the expressions of proinflammatory cytokines in H. pylori-infected mice. Materials and Methods. We evaluated nuclear factor-κB (p65) activation in the H. pylori-infected gastric mucosa of mice by immunofluorescent staining using antip65 polyclonal antibody, and the expressions of proinflammatory cytokines with inhibition of nuclear factor-κB pathway by using phosphorothioate antisense and sense oligonucleotide against the nuclear factor-κB (p65). Results. In the H. pylori-infected gastric mucosa of mice, immunofluorescent staining using antip65 polyclonal antibody showed nuclear factor-κB (p65) activation, which was particularly localized to epithelial cells. Tumor necrosis factor-α and interleukin-1β concentrations in gastric mucosa by enzyme-linked immunosorbent assay (ELISA) were elevated in the infected group versus the uninfected group. Pretreatment with nuclear factor-κB (p65) antisense oligonucleotide inhibited the activation of nuclear factor-κB and the expressions of tumor necrosis factor-α and interleukin-1β in H. pylori-infected gastric mucosa. Sense oligonucleotide did not influence on the expression of proinflammatory cytokines. Conclusions. H. pylori infection was found to activate the expressions of proinflammatory cytokines via nuclear factor-κB in vivo, and this may play an important role in the initiation of H. pylori-induced gastric inflammation. [ABSTRACT FROM AUTHOR]

The immunomodulatory and anti-inflammatory effects of thalidomide are associated with inhibition of TNF-α levels. However, the mechanism by which thalidomide reduces TNF-α production remains elusive. NF-κB is known to play a central role in regulating inflammatory responses in patients with inflammatory bowel disease (IBD). We tested whether thalidomide acts through inhibiting NF-κB activity. HT-29 cells were stimulated with LPS (1 ug/ml) alone, or after pretreatment with thalidomide (100 pg/ml), and NF-κB activity was determined by gel mobility shift assays. RT-PCR was used to measure expression of the proinflammatory cytokine genes TNF-α, IL-ip and IL-8. The level of TNF-α mRNA was also analyzed by real-time quantitative RT-PCR, and TNF-α protein was measured by ELISA. Thalidomide pretreatment did not affect NF-κB activity in HT-29 cells stimulated with LPS but production of TNF-α was depressed. Thalidomide was found to accelerate the degradation of TNF-α mRNA, but had little effect on IL-1β or IL-8. These observations suggest that the immunomodulatory effect of thalidomide in colonic epithelial cells is associated with inhibition of TNF-α. However, it does not act by inhibiting NF-κB but rather by inducing degradation of TNF-α mRNA. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection induces apoptosis and inducible nitric oxide synthase (iNOS) expression in gastric epithelial cells. In this study, we investigated the effects of NF-κB activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-κB significantly increased caspase-3 activity and apoptosis in H. pylori-infected MKN-45 and Hs746T gastric epithelial cell lines as well as primary gastric epithelial cells. An NF-κB signaling pathway via NF-κB-inducing kinase and IκB kinase-β activation was found to be involved in the inhibition of apoptosis in H. pylori-infected gastric epithelial cells. In gastric epithelial cells transfected with retrovirus containing IκBα superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-κB. Moreover, a NO donor, S-nitroso-Nacetylpenicillamine (100 µM), decreased caspase-3 activity and apoptosis in NF-κB-suppressed cells infected with H. pylori. These results suggest that NF-κB activation may play a role in protecting gastric epithelial cells from H. pyloriinduced apoptosis by upregulating endogenous iNOS. [ABSTRACT FROM AUTHOR]

Helicobacter pylori stimulates nuclear factor-kappa B (NF-κB) activation and chemokine interleukin-8 (IL-8) expression in gastric epithelial cells. Ecabet sodium (ecabet), a locally acting antiulcer drug, is known to have anti- H. pylori activity. However, there is little understanding of how ecabet induces anti-inflammatory activity in gastric epithelial cells infected with H. pylori. The aim of this study was to investigate the effects of ecabet on IL-8 gene expression and NF-κB activation in human gastric epithelial cells infected with H. pylori. After Hs746T, MKN-45, or SNU-5 gastric epithelial cell lines had been infected with cagA+cytotoxin+ H. pylori in the presence of ecabet, IL-8 mRNA expression was assessed by quantitative reverse transcription–polymerase chain reaction, and IL-8 secretion was measured by enzyme-linked immunosorbent assay. NF-κB and inhibitory kappa B-alpha (IκBα) signals were assayed by electrophoretic mobility shift assay and Western blot, respectively. The activation of NF-κB and IL-8 reporter genes was determined by luciferase assay. Ecabet showed no antimicrobial activiy against Gram-positive or -negative bacteria. However, ecabet inhibited transcription of the IL-8 gene and secretion of IL-8 by gastric epithelial cells infected with H. pylori at a concentration of 5 µg/ml. Moreover, ecabet inhibited the activation of NF-κB and the degradation of IκBα in gastric epithelial cells in response to H. pylori infection. In addition, the NF-κB signal inhibited by ecabet was comprised predominantly of heterodimers of p65/p50. Ecabet inhibited H. pylori-induced IL-8 gene transcription and secretion by suppressing the NF-κB signal. This inhibition might be one pathway by which ecabet exerts its anti-inflammatory effect on H. pylori-induced gastric inflammation. [ABSTRACT FROM AUTHOR]

Discusses a study which examined the outcome of patients with low-grade gastric mucosa-associated lymphoid tissue lymphoma. Patients and methods; Results; Conclusions.

Background/Aims: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. Methods: This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. Results: During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. Conclusions: PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients. [ABSTRACT FROM AUTHOR]

Presents the study on the arylation of malonates with diaryliodonium salts. Reaction of diethyl methylmalonate with diphenyliodonium tetrafluoroborate; Effect of the palladium catalyst in the desired arylation; Preparation of (2,4,6-trimethoxyphenyl)phenyliodonium salt and its reaction with various enolates.

A response from the author of the article "Long-term outcomes of cytomegalovirus reactivation in patients with moderate to severe ulcerative colitis" that was published in the previous issue, is presented.

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

This study investigated the effects of enzyme application on biofilms of bacterial isolates from a cafeteria kitchen and foodborne pathogens and the susceptibility of Salmonella biofilms to proteinase K combined with chlorine treatment. For four isolates from a cafeteria kitchen (Acinetobacter, Enterobacter, and Kocuria) and six strains of foodborne pathogens (Salmonella enterica, Staphylococcus aureus, and Vibrio parahaemolyticus), the inhibitory effect of enzymes on biofilm formation at 25°C for 24 h or the degradative efficacy of enzymes on 24-h mature biofilm at 37°C for 1 h in tryptic soy broth (TSB) was examined in a polystyrene microtiter plate. The effect of enzymes was also evaluated on a subset of these strains in 20 times diluted TSB (1/20 TSB) at 25°C. The working concentrations of five enzymes were 1 U/100 μL for α-amylase, amyloglucosidase, cellulase, and DNase and 1 milli-Anson unit/100 μL for proteinase K. In addition, 24-h mature Salmonella Typhimurium biofilm on a stainless steel coupon was treated with proteinase K for 1 h at 25°C followed by 20 ppm of chlorine for 1 min at 25°C. The results showed that certain enzymes inhibited biofilm formation by the kitchen-originated bacteria; however, the enzymatic effect was diminished on the mature biofilms. Biofilm formation of V. parahaemolyticus was suppressed by all tested enzymes, whereas the mature biofilm was degraded by α-amylase, DNase I, and proteinase K. Proteinase K was effective in controlling Salmonella biofilms, whereas a strain-dependent variation was observed in S. aureus biofilms. In 1/20 TSB, Enterobacter cancerogenus and Kocuria varians were more susceptible to certain enzymes during biofilm formation than those in TSB, whereas the enzymatic effect was much decreased on 24-h mature biofilms, regardless of nutrient conditions. Furthermore, synergistic inactivation of Salmonella Typhimurium in biofilms was observed in the combined treatment of proteinase K followed by chlorine. Live/Dead assays also revealed a decrease in density and loss of membrane integrity in Salmonella Typhimurium biofilms exposed to the combined treatment. Therefore, certain enzymes can control biofilms of isolates residing in a cafeteria kitchen and foodborne pathogens. This study demonstrates the potential of enzymes for the sanitation of food processing environments and of proteinase K combined with chlorine to control Salmonella biofilms on food contact surfaces. [ABSTRACT FROM AUTHOR]

The author discusses the effectiveness of germinated barley foodstuff (GBF) in colitis-associated colon cancer prevention and treatment. The author denotes how the inflammatory bowel disease (IBD) can aggravate the risk of acquiring such cancer. The author notes the fermentation of the GBF through gut microbiota and it provokes the growth of prebiotics such as Bifidobacterium, Eubacterium, and Lactobacillus species which can prevent colitis as well as colon cancer.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims Balloon expulsion test (BET) is regarded as a screening tool of dyssynergic defecation (DD). However, some patients with normal BET results may be treated effectively by biofeedback training. This study aims to validate BET as a single screening test. Methods Two hundred and thirty-two patients who were diagnosed with functional constipation or irritable bowel syndrome with constipation who underwent anorectal manometry (ARM) and BET at Seoul National University Hospital were enrolled. We evaluated the validity of BET based on ARM and electromyography (EMG) during biofeedback training. Results If BET ≤ 1 minute was defined as normal, sensitivity and negative predictive value (NPV) of BET in predicting paradoxical contraction based on ARM findings were 71.4% and 13.9%. If BET ≤ 3 minutes was defined as normal, sensitivity and NPV were 35.2% and 6.6%. Specificity and positive predictive value (PPV) of BET ≤ 3 minutes criteria were 84.8% and 93.3%. Same analysis was conducted in 107 patients who underwent EMG during biofeedback training. With 1-minute criteria, sensitivity and NPV of BET were 70.3% and 14.3%. With 3 minutes criteria, sensitivity and NPV of BET was 38.6% and 8.8%. Specificity and positive predictive values were both 100.0%. Conclusions Based on either ARM or EMG during biofeedback training, sensitivity was at most 71.4% and NPV was less than 15.0% irrespective of whether BET was within 1minute or within 3 minutes. BET seems to have a limitation as both a screening test for dyssynergic defecation and a simple assessment to rule out the necessity of biofeedback training. [ABSTRACT FROM AUTHOR]

Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to compare the diagnostic capabilities of narrow band imaging (NBI) colonoscopy with and without optical magnification in differentiating neoplastic from nonneoplastic colorectal polyps. Methods: Between April 2012 and March 2013, 122 patients with colorectal polyps detected by using diagnostic conventional colonoscopy were prospectively enrolled. A total of 236 polyps were evaluated with NBI, in vivo in real time during therapeutic colonoscopy, by one experienced endoscopist. Whether magnification was used or not was determined by randomization. After an in vivo real-time endoscopic prediction of histology, all lesions were endoscopically excised. Surgical pathologic reports were used as the criterion standards. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of identifying neoplastic polyps were calculated. Results: A total of 236 lesions with an average size of 5.6 mm in 122 patients were assessed (159 neoplastic, 77 nonneoplastic). The Sn, Sp, PPV, and NPV in differentiating neoplastic from nonneoplastic lesions with the magnified NBI were 97.5%, 83.3%, 94.0%, and 92.6%, respectively, whereas those of the nonmagnified NBI group were 97.5%, 85.1%, 91.7%, and 95.2%, respectively. Conclusions: Nonmagnified NBI colonoscopy distinguishes neoplastic from nonneoplastic colorectal polyps as accurately as does magnified NBI colonoscopy. [ABSTRACT FROM AUTHOR]

Background/Aims: Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods: A multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results: In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period. Conclusions: Optimally controlled disease status improves HRQL in patients with moderate-to-severe UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives. [ABSTRACT FROM AUTHOR]

Background/Aims: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the longterm outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. Methods: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. Results: The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. Conclusions: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation. [ABSTRACT FROM AUTHOR]

Background/Aims: The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. Methods: A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. Results: A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). Conclusions: Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma. [ABSTRACT FROM AUTHOR]

Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography (EUS) has been a useful method for the accurate staging of esophageal cancer. This study aimed to compare the diagnostic performance of EUS, positron emission tomography (PET), and computed tomography (CT) in the locoregional staging of resectable esophageal cancer. A total of 109 patients with resectable esophageal cancer were prospectively enrolled and retrospectively reviewed for evaluation of preoperative EUS, PET, and CT. The sensitivity, specificity, and accuracy of tumor depth (T) staging and regional lymph nodal (N) staging for each test were compared with the postoperative histopathologic stage as the gold standard. The overall accuracy of EUS for T staging was 72%, and it was the only method for delineating the layers of the esophageal wall. The sensitivities for N staging were 42% for EUS, 49% for PET, and 35% for CT, and their specificities were, respectively, 91, 87, and 93%. The accuracy for N staging was 66% for EUS, 68% for PET, and 63% for CT, and it did not differ significantly across the three tests. Preoperative EUS for the locoregional staging of esophageal cancer provides excellent T staging accuracy and similar accuracy for N staging compared with PET and CT. Especially in T staging, EUS could play an important role in the choice of candidates for esophageal cancer surgery. [ABSTRACT FROM AUTHOR]

Early gastric cancer (EGC) with undifferentiated histology has not been generally accepted as an indication for endoscopic treatment. This study was designed to evaluate the outcomes and clinicopathological factors associated with the complete resection of undifferentiated EGC using endoscopic submucosal dissection (ESD). A retrospective analysis of prospectively collected data was performed on consecutive patients who underwent ESD. Among the 456 EGCs treated using ESD at the Seoul National University Hospital, Seoul, Korea, between April 2005 and June 2008, 60 lesions (13.2%) were diagnosed as undifferentiated gastric cancer (poorly differentiated adenocarcinoma or signet ring cell carcinoma). En bloc resection was performed in all lesions without significant complications. The size discrepancy between the pretreatment endoscopy and the resected specimen was significantly higher in undifferentiated EGCs than differentiated EGCs ( p = 0.002). The complete resection rate was significantly lower for undifferentiated EGC (55%) cases than differentiated EGC cases (84.1%; p < 0.001). Independent risk factors for incomplete resection of undifferentiated EGC included tumor size >20 mm, submucosal invasion, and presence of ulceration. During a mean observation time of 16 months, no recurrence developed in any of the patients with undifferentiated EGCs thought to be completely resected by ESD. ESD might be considered an alternative treatment modality in carefully selected cases of undifferentiated EGC. [ABSTRACT FROM AUTHOR]

Depressed-type early gastric cancer (EGC) is known to repeat improvement and exacerbation of ulceration during its natural course, forming a “malignant cycle.” However, it is difficult to observe the malignant cycle of EGC in clinical practice, and little is known about the clinicopathologic factors associated with this cycle. This study aimed to evaluate the malignant cycle of EGC and to determine the clinicopathologic factors associated with the time-dependent morphologic change of EGC. The medical records of EGC patients treated at the Seoul National University Hospital were retrospectively reviewed with two or more comparable endoscopic photos taken between March 1999 and December 2005. The ulcer stages in EGC were classified by the gastric ulcer stage system and evaluated for time-dependent morphologic changes according to the relevant factors. In this study, 231 cases of depressed-type EGC were evaluated. At the follow-up endoscopy after a median interval of 23 days, a change in ulcer stage was observed in 66 patients (29%), with improvement in 45 patients (20%) and exacerbation in 21 patients (9%). Of the 177 patients who demonstrated an active or healing stage, 45 (25%) showed improvement and 10 (6%) exhibited exacerbation. The multivariate analysis showed that the usage of antisecretory medications, mucosal cancer, and a longer interval between the two endoscopic examinations were the factors that had a significant association with improvement of the ulcer stage. The malignant cycle was frequently observed in depressed-type EGC. The improvement of ulceration in EGC was time dependent and associated with the usage of antisecretory medication and the depth of invasion. [ABSTRACT FROM AUTHOR]

Background and Aim: The number of patients with ulcerative colitis (UC) in Korea has increased. In addition, the number of patients with colorectal cancer (CRC) associated with UC has also increased. Therefore, this population-based nationwide study was conducted to investigate the incidence of CRC in patients with UC in Korea and compare these results to those of studies conducted in other countries. Methods: The Korean Association for the Study of Intestinal Diseases (KASID) reviewed 7061 cases of UC that occurred between 1970 and 2005 and found a total of 26 cases of CRC. Results: The overall prevalence of CRC in patients with UC was 0.37%. In addition, the estimated cumulative risk of UC-associated CRCs was 0.7% for patients that had UC for 10 years, 7.9% for patients that had UC for 20 years, and 33.2% for patients that had UC for 30 years. The mean age at the time of diagnosis with CRC was 49.6 years, and the mean duration of UC prior to the development of CRC was 11.5 years. Most UC-associated CRCs were diagnosed after they were already in advanced stages; however, the stage at diagnosis was lower in patients that had good compliance with medical treatment. Conclusion: The cumulative incidence of UC-associated CRCs in Korea was found to be comparable to that of western countries. The overall occurrence of UC-associated CRC in Korea may be growing, therefore, intensive surveillance colonoscopy and constructive chemoprevention should be encouraged to enable early detection and treatment of UC-associated CRCs in Korea. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a well-established population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions: In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims: Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods: A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I2 statistics. Results: We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions: Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG. [ABSTRACT FROM AUTHOR]

Background/Aims: Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. Methods: The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels. Results: In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. Conclusions: Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication. [ABSTRACT FROM AUTHOR]

A 59-year-old man underwent endoscopic mucosal resection (EMR) for gastric adenoma. He had suffered from end-stage renal disease for several years and had received renal transplantation some 5 months before EMR. Subsequently, he took immunosuppressive agents. Follow-up gastrofiberscopy 6 months after EMR showed a sessile polyp at the resection site twice as large as the original adenoma; biopsy specimens revealed a hyperplastic nature. At the time of writing, this hyperplastic polyp has neither increased in size nor developed adenomatous or carcinomatous changes by histological examinations over the past 5 years. Therefore, this is a case of hyperplastic polyp occurring at the gastric adenoma resection site, and suggests the possible effect of immunosuppressive therapy on the post-EMR healing process and hyperplastic polyp development. [ABSTRACT FROM AUTHOR]

Background/Aims: Little is known about the national colonoscopy volume in Asian countries. This study aimed to assess the national colonoscopy volume in Korea over a 12- year period on the basis of a nationwide population-based database. Methods: We conducted a population-based study for colonoscopy claims (14,511,158 colonoscopies performed on 13,219,781 patients) on the basis of the Korean National Health Insurance Service database from 2002 to 2013. The 12-year national colonoscopy burden was analyzed according to patient age, patient sex, and healthcare facility type. Results: The overall volume of colonoscopy increased 8-fold over the 12-year period. The annual colonoscopic polypectomy rate significantly increased in all patient sex and age groups over the 12-years period (all p<0.001). The yearly colonoscopic polypectomy rate for men was significantly increased compared with that for women (2.3% vs 1.7%, p<0.001) and for the screening-age group compared with that for the young-age group (2.0% vs 1.6%, p<0.001). The yearly colonoscopic polypectomy rate relative to the total colonoscopy volume significantly increased in primary, secondary, and tertiary facilities by 2.4%, 1.9%, and 1.4% during the 12-year period (all p<0.001). In addition, the annual colonoscopy volume covered by high-volume facilities significantly increased by 1.8% in primary healthcare facilities over the 12-year period (p<0.001). Conclusions: Healthcare resources should be prioritized to allow adequate colonoscopic capacity, especially for men, individuals in the screeningage group, and at primary healthcare facilities. Cost-effective strategies to improve the quality of colonoscopy may focus on primary healthcare facilities and high-volume facilities in Korea. [ABSTRACT FROM AUTHOR]

Crohn's disease is associated with altered body composition, such as low muscle mass, which can affect clinical outcomes. However, there are few studies regarding the effect of sarcopenia on prognosis of Crohn's disease. In this study, we evaluated the body composition at the initial diagnosis of Crohn's disease and analyzed the clinical meaning of sarcopenia. Methods: We conducted a retrospective review of medical records of patients who were diagnosed as Crohn's disease and underwent computed tomography within 3 months after diagnosis. Sarcopenia was defined as an L3 skeletal muscle index (SMI) of < 49 cm2/m2 for men and < 31 cm2/m2 for women. Outcomes such as need for hospitalization, surgery, use of steroids, immunomodulators and biologics were analyzed. Results: A total of 79 patients (male, 73.4%; mean age, 29.9 years) were included and 40 patients (51%) were diagnosed as sarcopenia. C-reactive protein (CRP) level was correlated with sarcopenia (P= 0.044). Erythrocyte sedimentation rate (ESR) showed a tendency to decrease inversely with SMI (r = -0.320, P= 0.008) and hemoglobin and albumin tended to increase in proportion to SMI (hemoglobin: r = 0.271, P= 0.016 and albumin: r = 0.350, P= 0.002). However, there was no statistically significance in time-to-first-event analysis in aspects of sarcopenia. Conclusions: Approximately 50% of patients with newly diagnosed as Crohn's disease had sarcopenia. CRP levels were higher in the sarcopenia group and SMI correlated with ESR, hemoglobin, and albumin. However, none of prognostic values were demonstrated. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sexmatched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis. [ABSTRACT FROM AUTHOR]

Background: The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia has been suggested. We investigated the association between sarcopenia and NAFLD independent of visceral adiposity and searched for the clinical characteristics that affect this association. Methods: We performed a retrospective study including of 5,989 subjects (mean age, 53.2 years; men, 57.3%) who underwent bioelectrical impedance analysis (BIA) and abdominal ultrasonography in 2012. The appendicular skeletal muscle mass (ASM) was assessed by BIA method. Sarcopenia was defined as ASM/weight (ASM%) <2 standard deviation of the mean for healthy young reference population. NAFLD was diagnosed by ultrasonography. Results: The prevalence of sarcopenia was 5.3%. The prevalence of NAFLD was significantly higher in subjects with sarcopenia than in those without (69.5% vs. 36.5%, P<0.001). After adjusting with age, sex, visceral fat area, hypertension, diabetes, total and low-density lipoprotein cholesterol, subjects with sarcopenia showed significantly high odds of NAFLD (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84; P=0.036). Subjects with sarcopenia have more likely severe grade of NAFLD compared to non-sarcopenic group (OR, 1.58; 95% CI, 1.25-2.00; P<0.001). There was significant interaction for effect modification in the association between sarcopenia and NAFLD by age (P of interaction for effect modification, 0.007). Conclusion: Sarcopenia was significantly associated with the presence and the severity of ultrasonographygraded NAFLD in our study population independent of visceral fatness and other metabolic confounder. Younger age showed greater magnitude of association between sarcopenia and NAFLD. [ABSTRACT FROM AUTHOR]

Background/Aims: The risk of herpes zoster (HZ) among patients with inflammatory bowel disease (IBD) remains un-clear in terms of age and metabolic comorbidities, including diabetes mellitus, hypertension, or dyslipidemia. We con-ducted a nationwide population based study to investigate the risk of HZ in patients with IBD. Methods: From 2010 to 2013, a retrospective study was performed using claims data in Korea. We compared the incidence of HZ between 30,100 IBD patients (10,517 Crohn's disease [CD] and 19,583 ul-cerative colitis [UC] patients) and 150,500 non-IBD controls matched by age and sex. Results: During a mean follow-up of 5.0 years, incidence rates of HZ (per 1,000 person-years) were 13.60, 14.99, and 9.19 in the CD, UC, and control groups, respectively. The risk of HZ was significantly higher in patients with CD (adjusted hazard ratio [HR], 2.13; p<0.001) and UC (adjusted HR, 1.40; p<0.001) than in the controls. The impact of CD on developing HZ was significantly more prominent in younger patients (adjusted HR, 2.61 for age <15, whereas 1.39 for age ≥60; interaction p=0.001) and in patients without metabolic comorbidities (adjusted HR, 2.24, whereas 1.59 in those with metabolic comorbidities; interac-tion p=0.015). Moreover, the impact of UC on developing HZ significantly increased in younger patients (adjusted HR, 2.51 in age <15, whereas 1.22 in age ≥60; interaction p=0.014) and patients without metabolic comorbidities (adjusted HR, 1.49 whereas 1.16 in those with metabolic comorbidities; interaction p<0.001). Conclusions: IBD was associated with an increased risk of HZ, especially in younger patients without metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Purpose This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. Materials and Methods AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. Results Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-B (NF-B) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-B and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. Conclusion The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation. [ABSTRACT FROM AUTHOR]

Background/Aims: The exact relationship between vitamin D deficiency and inflammatory bowel disease (IBD) remains unclear. We evaluated the effect of vitamin D3 administration on inflammatory responses and disease severity in patients with IBD. Methods: We investigated the serum 25-hydroxyvitamin D3 [25-(OH)D], C-reactive protein (CRP) levels and the partial Mayo score (PMS) in patients with IBD. Vitamin D3 was administered in patients with either vitamin D deficiency or insuffi- ciency and CRP, serum vitamin D levels and PMS were re-examined at 6 months of administration. Results: In 88 patients with Crohn's disease (CD), a negative correlation was found between serum vitamin D and CRP. In 178 patients with ulcerative colitis (UC), serum vitamin D showed no association with CRP or PMS. Serum vitamin D increased from 11.08 ± 3.63 to 22.69 ± 6.11 ng/mL in 29 patients with CD and from 11.45 ± 4.10 to 24.20 ± 6.61 ng/mL in 41 patients with UC who received vitamin D3 treatment (P< 0.001 and P< 0.001, respectively). In patients with CD, median ΔCRP was -0.24 in the normalized vitamin D group and -0.11 in the non-normalized group (P= 0.308). In patients with UC, median ΔCRP was -0.01 in the normalized vitamin D group and 0.06 in the non-normalized group (P= 0.359). Conclusions: Although a negative correlation was found between serum vitamin D and CRP levels in patients with CD, administration of vitamin D did not improve the CRP level in patients with CD. In patients with UC, serum vitamin D level was unrelated to CRP or PMS. [ABSTRACT FROM AUTHOR]

Background/Aims: Spontaneous intramural small bowel hematoma (SISBH) is an extremely rare complication of anticoagulant or antiplatelet therapy. We assessed the clinical characteristics and outcomes of patients with SISBH according to the anatomical location of the hematoma. Methods: From January 2003 to February 2016, medical records for all patients hospitalized for SISBH at 2 tertiary referral hospitals were retrospectively reviewed. The primary outcome was requirement for surgery. Results: A total of 37 patients were enrolled. The mean age was 74.1 years. Among them, 33 patients (89.2%) were taking anticoagulant and/or antiplatelet agents. Duodenal intramural hematoma was detected in 4 patients (10.8%), jejunal in 16 (43.2%), and ileal in 17 (45.9%). Compared to jejunal and ileal involvement, duodenal intramural hematoma was significantly associated with high Charlson comorbidity index and low levels of white blood cells, hemoglobin, and platelets in the blood. SISBH in the duodenum was related to thrombocytopenia in 3 patients following systemic chemotherapy for malignancy. All patients with SISBH showed clinical improvement with conservative therapy. Mean length of hospital stay was 9.35 days. Independent predictors of a hospital stay of more than 7 days were body weight less than 60 kg (odds ratio [OR], 12.213; 95% confidence interval [CI], 1.755-84.998; P =0.011) and a history of cerebrovascular accidents (OR, 6.667; 95% CI, 1.121-39.650; P =0.037). Conclusions: Compared to jejunal and ileal involvement, thrombocytopenia may result in spontaneous duodenal intramural hematoma among patients who are treated with systemic chemotherapy for malignancies. Patients with SISBH have excellent clinical outcomes with conservative therapy regardless of the anatomical location of the hematoma. [ABSTRACT FROM AUTHOR]

Background/Aims To evaluate the efficacy and safety of Aloe vera (AV) in patients with irritable bowel syndrome (IBS). Methods We searched the MEDLINE, EMBASE, and Cochrane databases for studies dated between 1st January 1960 and 30th December 2017. Eligible randomized controlled trials (RCTs) compared AV to placebo in patients with IBS. The primary outcome was standardized mean difference of the change in severity of IBS symptoms as measured by patient-rated scales. Secondary outcomes included response rate of IBS symptoms and adverse events. Heterogeneity among studies was assessed using Cochrane's Q and I 2 statistics. Results Three RCTs with a total of 151 patients with IBS were included. The meta-analysis showed a significant difference for patients with AV compared to those with placebo regarding improvement in IBS symptom score (standardized mean difference, 0.41; 95% CI, 0.07-0.75; P = 0.020). Using intention-to-treat analysis, the AV patients showed significantly better response rates of IBS symptoms compared to placebo (pooled risk ratio, 1.69; 95% CI, 1.05-2.73; P = 0.030). No adverse events related with AV were found in included studies. There was no significant heterogeneity of effects across studies (P = 0.900; I 2 = 0%). Conclusion AV is effective and safe for the treatment of patients with IBS compared to placebo. [ABSTRACT FROM AUTHOR]

Background/Aims: The disease course and factors associated with poor prognosis in Korean patients with Crohn's disease (CD) have not been fully determined. The aim of this study was to explore potential associations between the clinical characteristics and long-term outcomes of CD and perianal fistulas in a Korean population. Methods: The retrospective Crohn's Disease Clinical Network and Cohort (CONNECT) study enrolled patients diagnosed with CD between July 1982 and December 2008 from 32 hospitals. Those followed for <12 months were excluded. Clinical outcomes were CD-related surgery and complications, including nonperianal fistulas, strictures, and intra-abdominal abscesses. Results: The mean follow-up period was 8.77 years (range, 1.0 to 25.8 years). A total of 1,193 CD patients were enrolled, of whom 465 (39.0%) experienced perianal fistulas. Perianal fistulizing CD was significantly associated with younger age, male gender, CD diagnosed at primary care clinics, and ileocolonic involvement. Both nonperianal fistulas (p=0.034) and intra-abdominal abscesses (p=0.020) were significantly more common in CD patients with perianal fistulas than in those without perianal fistulas. The rates of complicated strictures and CD-related surgery were similar between the groups. Independently associated factors of nonperianal fistulas were perianal fistulas (p=0.015), female gender (p=0.048), CD diagnosed at referral hospital (p=0.003), and upper gastrointestinal (UGI) involvement (p=0.001). Furthermore, perianal fistulas (p=0.048) and UGI involvement (p=0.012) were independently associated with the risk of intra-abdominal abscesses. Conclusions: Perianal fistulas predicted the development of nonperianal fistulas and intra-abdominal abscesses in Korean CD patients. Therefore, patients with perianal fistulizing CD should be carefully monitored for complicated fistulas or abscesses. [ABSTRACT FROM AUTHOR]

Background/Aims: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. Methods: We performed a genomewide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. Results: After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p<8.56×10-8) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p<8.56×10-8). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p<2.0×10-10 in the discovery set and p<2.0×10-6 in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p<2.0×10-10 in the discovery set and p<2.0×10-6 in the validation set). Conclusions: We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]