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This article discusses the discovery of a novel variant of the thiopurine S-methyltransferase (TPMT) gene in a Malay individual. The TPMT gene is important for the metabolism of thiopurine drugs used in the treatment of various conditions. The variant, which involves an in-frame deletion and insertion event, was found to be specific to the Malay population and was not present in major genomic databases. The study highlights the importance of genetic testing in optimizing drug therapy and calls for further investigation into the variant's clinical implications. [Extracted from the article]

Background and Aims: Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. Methods: Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid‐free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. Results: Forty‐two patients (34 CD and 8 UC) underwent UST DI to either 6‐weekly (n = 19, 45.2%) or 4‐weekly (n = 23, 35.9%) and the median time to intensification was 31.1 weeks (17.8–65.7). Presence of perianal disease in CD (HR 4.9; 1.47–16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1 year and 2 years were 75.7% (95% CI 62.9–84.6) and 63.5% (95% CI 49.9–74.3), respectively. Conclusion: Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose‐intensified patients achieved remission by week 52. [ABSTRACT FROM AUTHOR]

Introduction Immune-modifying agents are the treatment of choice for different chronic inflammatory diseases of autoimmune origin. Antimetabolites (azathioprine and methotrexate) or biologics, such as TNF inhibitors (adalimumab and infliximab), anti-p40 [...], BACKGROUND. Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses. METHODS. We longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination. RESULTS. We demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile. CONCLUSION. Despite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection. FUNDING. This study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

Introduction: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.Methods: Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI.Results: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).Conclusion: First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD.Methods: We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed.Results: A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy.Conclusion: Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19. Methods: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24thApril 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model. Results: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I2 = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I2 = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I2 = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I² = 71%) were higher subjects in critical COVID-19. Conclusion: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID- 19-associated liver injury. [ABSTRACT FROM AUTHOR]