Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

BACKGROUND: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. OBJECTIVE: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. DESIGN: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136). SETTING: 6 sites in Taiwan, July 2018 through July 2020. PARTICIPANTS: Participants aged 40 years or older with polyps of 4 to 10 mm. INTERVENTION: CSP or HSP to remove polyps of 4 to 10 mm. MEASUREMENTS: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. RESULTS: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, -1.1% [95% CI, -1.7% to -0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, -0.3% [CI, -0.6% to -0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, -44.0 seconds [CI, -53.1 to -34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, -0.4% [CI, -0.8% to -0.04%]). LIMITATION: An open-label, single-blind trial. CONCLUSION: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. PRIMARY FUNDING SOURCE: Boston Scientific Corporation.

Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSIONS: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Impact of the COVID-19 pandemic on inflammatory bowel disease care in Taiwan: A multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on healthcare system and patients. This study aimed to evaluate the effect of the COVID-19 pandemic on the perceptions of patients with inflammatory bowel disease (IBD). METHODS: This prospective multicenter study was conducted between July 2021 and December 2021. Patients with IBD answered a structured questionnaire, and their degree of anxiety was assessed using a visual analogue scale (VAS) before and after reading educational materials. RESULTS: A total of 225 (47.67%) patients with Crohn's disease, 244 (51.69%) with ulcerative colitis and 3 (0.64%) with indeterminate colitis were enrolled. Common concerns were adverse events from vaccination (20.34%), and higher risks of developing severe COVID-19 (19.28%) and COVID-19 infection (16.31%) than the general population. Medications deemed by the patients to increase the risk of COVID-19 were immunomodulators (16.10%), anti-tumor necrosis factor-α antagonists (9.96%), and corticosteroids (9.32%). Thirty-five (7.42%) patients self-discontinued IBD medication, of whom 12 (34.28%) had worse symptoms. Older age (>50 years) (OR 1.10, 95% CI 1.01-1.19, p = 0.03), IBD-related complications (OR 1.16, 95% CI 1.04-1.28, p = 0.01), education status below senior high school (OR 1.22, 95% CI 1.08-1.37, p = 0.001), and residing in north-central Taiwan (OR 1.21, 95% CI 1.10-1.34, p < 0.001) were associated with more anxiety. None of the enrolled patients contracted COVID-19. The anxiety VAS score (mean ± SD) improved after reading the educational materials (3.84 ± 2.33 vs. 2.81 ± 1.96, p < 0.001). CONCLUSION: The medical behavior of IBD patients was influenced by the COVID-19 pandemic, and their anxiety could be mitigated after education.

A novel galactose electrochemical biosensor intended for point-of-care measurement of quantitative liver function using galactose single-point test.

Liver disease has emerged as a healthcare burden because of high hospitalization rates attributed both to steatohepatitis and to severe hepatic toxicity associated with changes of drug exposure. Early detection of hepatic insufficiency is critical to preventing long-term liver damage. The galactose single-point test is recommended by the US FDA as a sensitive means to quantify liver function, yet the conventional method used for quantitation of circulating galactose still relies on the standard colorimetric method, requiring time-consuming and labor-intensive processes, and is confined to the medical laboratory, thus limiting prevalence. To facilitate time- and cost-effective disease management particularly during a pandemic, a pocket-sized rapid quantitative device consisting of a biosensor and electrochemical detection has been developed. An in vitro validation study demonstrated that the coefficient of variation was less than 15% and deviations were between -4 and 14% in the range of 100-1500 µg/mL. The device presented good linear fit (correlation coefficient, r = 0.9750) over the range of 150-1150 µg/mL. Moreover, the device was found to be free from interference of common endogenous and exogenous substances, and deviated hematocrit, enabling a direct measurement of galactose in the whole blood without sample pre-treatment steps. The clinical validation comprising 118 subjects showed high concordance (r = 0.953) between the device and the conventional colorimetric assay. Thus, this novel miniaturized device is reliable and robust for routine assessment of quantitative liver function intended for follow-up of hepatectomy, drug dose adjustment, and screening for galactosemia, allowing timely and cost-effective clinical management of patients.

Efficacy and safety of gastric peroral endoscopic myotomy (G-POEM) for refractory gastroparesis: 3-year follow up results.

BACKGROUND/PURPOSE: Gastroparesis is a common but easily overlooked disease. Gastric peroral endoscopic myotomy (G-POEM) is one of the third-space endoscopy techniques to treat gastroparesis. In this study, we aimed to evaluate the efficacy and safety of G-POEM for patients with refractory gastroparesis. METHODS: Between December 2017 and 2020, we consecutively enrolled patients with gastroparesis who failed after the administration of several kinds of medication and repeated admission for nutritional support. All patients underwent gastric emptying scintigraphy and answered a questionnaire on Gastroparesis Cardinal Symptom Index (GCSI). Demographic data, endoscopic procedure, and post procedural outcome were analyzed. RESULTS: A total of 11 (9 women and 2 men) patients with refractory gastroparesis (nine with diabetes mellitus, one systemic lupus erythematosus, and one idiopathic) were enrolled. The mean (±standard deviation (SD)) procedure time was 61.82 (±18.99) min with technical and clinical success rates of 100% and 81.82%, respectively. A statistically significant improvement was observed in the clinical severity (mean GCSI score 36.00 vs. 14.73, p < 0.0001) and gastric emptying time (mean T1/2 341.92 vs. 65.92 min, p = 0.016) after G-POEM. Hospital stay was 7.18 (±4.49) days without mortality. Complications included 4 (36.36%) patients with self-limited postprocedural abdominal pain and 3 (27.27%) patients with intra-procedural pneumoperitoneum. During the mean follow-up period of 554.36 days, one (9.09%) patient had relapsed clinical symptoms after 6 months. CONCLUSION: G-POEM is an efficient and safe pylorus-directed endoscopic therapy for refractory gastroparesis with promising results.

Endoscopic management of strictures in patients with Crohn's disease - A multi-center experience in Taiwan.

BACKGROUND/PURPOSE: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn's disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan. METHODS: We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed. RESULTS: In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents. CONCLUSION: EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.

Early Initiation of Post-Pyloric Feeding in Patients with Major Burns: Experience in Taiwan Formosa Water Park Dust Explosion Disaster.

Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a "fortuitously controlled" study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.

Clinical characteristics and risk factors of active bleeding in colonic angiodysplasia among the Taiwanese.

BACKGROUND: Colonic angiodysplasia (AGD) is a common cause of gastrointestinal bleeding. However, information on the characteristics and prevalence of colonic AGD is limited. We determined the clinical features of and risk factors for active bleeding in colonic AGD in a Taiwanese population. METHODS: From February 2007 to December 2016, 13,047 patients undergoing 16,760 colonoscopies at the Tri-Service General Hospital were included in this study. Eighty-four patients were diagnosed with AGD. We conducted a retrospective study by analyzing the medical records of these patients. The clinical features and endoscopic findings were evaluated. Furthermore, we distinguished colonic AGD into bleeding and non-bleeding types and identified the risk factors for bleeding in colonic AGD. RESULTS: In our study, the prevalence of colonic AGD was 0.6% among all patients who received colonoscopy. Among patients with colonic AGD, we found that many were aged; in all, 58.3% of patients with colonic AGD were older than 65 years. More than half of the patients had hypertensive cardiovascular disease (53.6%) and the AGD lesions were predominantly located in the left-sided colon (41.7%). We analyzed several factors to identify those associated with bleeding colonic AGD. Our results indicated that age (p < 0.001), hypertension (p = 0.020), atrial fibrillation (p = 0.027), and in-patient status (p = 0.006) were significant factors associated with active bleeding lesions. On multivariate analysis, old age was the only significant risk factor. CONCLUSION: Angiodysplastic lesions in Taiwanese patients were predominantly identified in the left-sided colon. Old age was an independent risk factor associated with active bleeding in colonic angiodysplasia.

Is a bleeding scan prior to single-balloon enteroscopy necessary in patients with obscure gastrointestinal bleeding?

BACKGROUND/PURPOSE: To evaluate the efficacy and accuracy of bleeder localization in a pre-enteroscopic bleeding scan in patients with obscure gastrointestinal bleeding (OGIB). METHODS: From January 2009 to December 2014, 98 patients with OGIB undergoing single-balloon enteroscopy (SBE) were enrolled. These patients were classified based on their history of a previous bleeding scan; 56 patients had undergone a previous bleeding scan, whereas 42 had not. The clinical characteristics, endoscopic findings, and rebleeding rate were compared between these two groups. The ability of the bleeding scan to localize the bleeding site was analyzed. RESULTS: The mean age of patients was 56 ± 22 years; final diagnostic yield, 65.3%; and the most common etiology of OGIB, angiodysplasia (29.6%). There was no significant difference in demographic characteristics, OGIB etiologies, and final diagnostic yields (67.9% vs. 61.2%, bleeding scan vs. control group) between groups. In the bleeding scan group, the rate of positive detection was approximately 80.4%. However, only 26.7% patients with a positive bleeding scan showed correct localization of bleeding. Moreover, the bleeding scan delayed SBE (8.9 days vs. 3.0 days, p < 0.001). During the 24 months of follow-up, 15 patients (15.3%) exhibited rebleeding and needed to be hospitalized, but there was no significant difference between the groups. CONCLUSION: In our study, bleeding scans in patients with OGIB revealed poor localization of the bleeder and delay in performing SBE. Thus, a bleeding scan prior to SBE showed a limited role for patients with OGIB.

Identification of risk factors for neoplastic colonic polyps in young adults with bloody stool in comparison with those without symptom.

BACKGROUND AND AIMS: The incidence and disease burden of colorectal cancer (CRC) in young adults were increasing. However, there was a dearth of advice on how to identify young population at risk for neoplastic colonic polyps (NCPs) and CRC. We aimed to identify risk factors for NCPs and CRC in young adults presenting with bloody stool. METHODS: A total of 1496 subjects younger than 40 years old who underwent colonoscopy due to bloody stool from 2005 to 2014 were enrolled in this retrospective study as the study group, and 1481 age-matched and gender-matched asymptomatic subjects who underwent colonoscopy for health checkup from 2011 to 2016 were enrolled as the control group at a tertiary center hospital. RESULTS: Multivariate analysis results showed that increasing age (odds ratio [OR] = 1.11, 95% confidence interval [CI]: 1.07-1.15, P < 0.001), higher body mass index (BMI) (OR = 1.07, 95%CI: 1.03-1.12, P = 0.001), diabetes mellitus (OR = 2.80, 95%CI: 1.06-7.42, P = 0.038), and positive family history of CRC (OR = 13.28, 95%CI: 5.70-30.97, P < 0.001) were identified as independent risk factors for NCPs in study group. The best cut-off values by receiver operating characteristic curve for age and BMI were 32 years old and 24.8 kg/m2 , respectively. More risk factors were associated with the higher risk for NCPs (OR = 2.17 every increasing one risk factor, P < 0.001). In the control group, no independent risk factors were identified. CONCLUSIONS: Adults aged ≤ 40 years with bloody stool who had increasing age (> 32 years old), higher BMI (> 24.8 kg/m2 ), diabetes mellitus, and positive family history of CRC had a higher detection rate of NCPs and CRC.

Small bowel tumors: A digestive endoscopy society of Taiwan (DEST) multicenter enteroscopy-based epidemiologic study.

BACKGROUND/PURPOSE: Small bowel (SB) accounts for the majority of gastrointestinal tract but its tumors are rare and always overlooked. In this study, we aimed to evaluate the epidemiology of SB tumors. METHODS: This multicenter retrospective study utilized endoscopy database from 2006/11 to 2016/07. Baseline demographic characteristics, clinical, radiologic and endoscopic findings were collected. RESULTS: Totally 103 (34 benign, 69 malignant lesions) patients with SB tumors in 1070 enteroscopic examinations were enrolled. There were male preponderance (56.3% males, 43.7% females), both in benign (52.9%, 49.1%) and malignant (58.0%, 42.0%) lesions, except for subtype gastrointestinal stromal tumors (GISTs) (31.6%, 68.4%). The age (mean ± SD) at diagnosis in malignant SB tumors (62.2 ± 15.6) was older than those with benign tumors (50.7 ± 21.4) (p < 0.01). Bleeding (43.7%), abdominal pain (40.8%) and ileus (10.7%) were the most common clinical presentations. Hamartoma (32.4%) and adenoma (14.7%) were the most common benign histology. Four major malignant histological subtypes were lymphomas (29.0%), GISTs (27.5%), adenocarcinomas (26.1%) and metastatic cancers (14.5%). SB adenocarcinoma patients (>60-year-old, 77.8%) were older than lymphomas (60%) and GISTs (50%). Proximally location rates of lymphomas, GISTs, adenocarcinomas were 25.0% (5/20), 84.2% (16/19), and 88.9% (16/18), respectively. CONCLUSION: This endoscopy-based study revealed the most common histology of benign SB tumors were hamartoma and adenoma, and malignant ones were lymphomas, GISTs, adenocarcinomas and metastatic cancers. Most of them were male gender, except for GISTs, and with proximal location, except for lymphomas. Further large-scale investigation efforts are warranted to elucidate the epidemiology of SB tumors.

A Role for CHH Methylation in the Parent-of-Origin Effect on Altered Circadian Rhythms and Biomass Heterosis in Arabidopsis Intraspecific Hybrids.

Hybrid plants and animals often show increased levels of growth and fitness, a phenomenon known as hybrid vigor or heterosis. Circadian rhythms optimize physiology and metabolism in plants and animals. In plant hybrids and polyploids, expression changes of the genes within the circadian regulatory network, such as CIRCADIAN CLOCK ASSOCIATED1 (CCA1), lead to heterosis. However, the relationship between allelic CCA1 expression and heterosis has remained elusive. Here, we show a parent-of-origin effect on altered circadian rhythms and heterosis in Arabidopsis thaliana F1 hybrids. This parent-of-origin effect on biomass heterosis correlates with altered CCA1 expression amplitudes, which are associated with methylation levels of CHH (where H = A, T, or C) sites in the promoter region. The direction of rhythmic expression and hybrid vigor is reversed in reciprocal F1 crosses involving mutants that are defective in the RNA-directed DNA methylation pathway (argonaute4 and nuclear RNA polymerase D1a) but not in the maintenance methylation pathway (methyltransferase1 and decrease in DNA methylation1). This parent-of-origin effect on circadian regulation and heterosis is established during early embryogenesis and maintained throughout growth and development.

Outcome of nonsurgical intervention in patients with perforated peptic ulcers.

BACKGROUND: Although surgical intervention is the favorable treatment modality for perforated peptic ulcer, nonsurgical treatment is another option. The aim of this study is to analyze the results of conservative treatment for perforated peptic ulcer. METHODS: Between 2003 and 2014, 403 patients were admitted to our hospital for perforated peptic ulcer, and 383 patients underwent surgery, whereas 20 were allocated to conservative treatment. The results of nonsurgical intervention in these patients were analyzed retrospectively. RESULTS: The overall mortality rate of conservative treatment was 40%. Eleven patients remained hospitalized less than 2 weeks; among them, patients with a high (≥IV) American Society of Anesthesiologists class at admission had higher mortality than those with a low (

Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study.

AIMS: The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner. METHODS: We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively. RESULTS: The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22). CONCLUSIONS: MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.

Nuclear factor κB down-regulates human UDP-glucuronosyltransferase 1A1: a novel mechanism involved in inflammation-associated hyperbilirubinaemia.

Jaundice or hyperbilirubinaemia is a common complication of sepsis. UGT1A1 (UDP-glucuronosyltransferase 1A1) is a critical gene for bilirubin metabolism and irinotecan detoxification. However, the molecular pathogenesis of hyperbilirubinaemia during inflammation needs to be further clarified. Human hepatic UGT1A1 expression was analysed by RT (reverse transcription)-PCR, qRT-PCR (quantitative real-time PCR) and Western blotting in response to LPS (lipopolysaccharide) stimulation. Transcription regulatory elements in the upstream promoter region of the human UGT1A1 gene were determined using EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation). The important role of the transcription regulatory element was examined using a luciferase assay, and was determined by qRT-PCR using a transcription factor activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human hepatoma cell lines. A newly identified NF-κB (nuclear factor κB)-binding site was located on the upstream promoter region (-725/-716) of the human UGT1A1 gene. LPS-induced NF-κB activation and specific binding to the NF-κB-binding site can suppress human UGT1A1 promoter activity and human UGT1A1 expression. We demonstrated that LPS mediates the suppression of human UGT1A1 expression through specific binding of NF-κB to this newly identified NF-κB-binding site in the upstream promoter of the human UGT1A1 gene. The present study may partly explain the molecular pathogenesis of inflammation-associated hyperbilirubinaemia.

Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population­based cohort study.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn's disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions: Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

The NAT2 tag SNP rs1495741 correlates with the susceptibility of antituberculosis drug-induced hepatotoxicity.

BACKGROUND: Earlier studies have demonstrated an association between N-acetyltransferase 2 (NAT2) catalytic activity and the genotype of a recently published tag single nucleotide polymorphism (SNP), rs1495741. There have been no reports on the relationship between the rs1495741 genotype and antituberculosis drug-induced hepatotoxicity (ATDIH) to date. OBJECTIVE: The aim of the present study was to determine the frequency of the NAT2 tag SNP (rs1495741) in the Taiwanese and its relation to the incidence of ATDIH. MATERIALS AND METHODS: A total of 348 tuberculosis patients were enrolled to determine the frequency of NAT2 tag SNP rs1495741 and its relation to the incidence of ATDIH. The conventional NAT2 variants alleles have also been investigated. Furthermore, to evaluate the correlation of NAT2 activity and rs1495741 genotypes, a pharmacokinetic study of isoniazid was also conducted in healthy volunteers. RESULTS: Among the 348 tuberculosis patients, 20 (5.7%) were diagnosed with ATDIH. The frequencies of the three rs1495741 genotypes, viz., AA, AG, and GG, were 24.7, 52.3, and 23.0%, respectively. Significant differences among rs1495741 genotypes and susceptibility to hepatotoxicity were noted (odds ratio=14.068, P<0.05). Moreover, the rs1495741 genotypes showed an association with the isoniazid dosage required for induction of hepatotoxicity. In the pharmacokinetic study, NAT2 activity was strongly associated with genotype categories (P<0.001). CONCLUSION: The present study demonstrated that the three genotypes according to rs1495741 were in good accordance with conventional NAT2 alleles-inferred phenotypes and the tag SNP could be used as a proxy to determine the susceptibility to ATDIH.

Carbon dioxide insufflation does not reduce pain scores during colonoscope insertion in unsedated patients: a randomized, controlled trial.

BACKGROUND: CO(2) is rapidly absorbed from the colon and eliminated via the lung. Insufflation of CO(2) instead of air during colonoscopy can reduce distention-induced pain. OBJECTIVE: This study aimed to evaluate the effects of CO(2) insufflation on pain during intubation and extubation and to identify predictors of pain and discomfort during colonoscope insertion. DESIGN: Prospective, randomized, controlled trial. SETTING: Single tertiary medical center in Taiwan. PATIENTS: A total of 193 patients enrolled from September 2010 through June 2011. INTERVENTIONS: Colonoscope insertion with either air or CO(2) insufflation. CO(2) was used for extubation in both groups. MAIN OUTCOME MEASUREMENTS: The main outcome measurement was pain, recorded on a 10-point visual analog scale (VAS) for left-sided colonoscope insertion and right-sided colonoscope insertion and at 1, 3, 6, and 24 hours post-procedure. Colonoscope cecal intubation time and extubation time, completeness of intubation, and loop formation were also assessed. RESULTS: CO(2) insufflation during colonoscope intubation was used in 98 patients and air in 97 patients. The mean pain scores during intubation were low (2-3) for patients undergoing air insufflation and were not reduced further in patients receiving CO(2). A mean pain score of 0 was reported by both groups for all postprocedure time points. Multivariate analysis identified sex, loop formation of the sigmoid colon, time to reach the transverse colon, and requested sedation as factors that significantly affect VAS pain scores. LIMITATIONS: This study was limited in scope to a single medical center with experienced endoscopists. CONCLUSIONS: We detected no significant benefit to the use of CO(2) insufflation compared with air insufflation during intubation for colonoscopy performed by experienced colonoscopists. The absence of postprocedure pain in both groups supports previous observations that CO(2) insufflation during extubation is effective in reducing postprocedure pain. Female sex and loop formation were identified as key factors influencing pain scores on colonoscope insertion. ( CLINICAL TRIAL REGISTRATION NUMBER: TSGHIRB-099-05-081.).

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.