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Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls. A total of 942 subjects with IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), unclassified IBS (IBS-U), and 942 non-IBS controls were included. We compared taxonomic and functional composition of gut microbiota based on 16S sequencing data and linked them with clinical characteristics and dietary factors. Subjects with IBS-D or IBS-U but not IBS-C showed significantly reduced bacterial diversity (Shannon; p .01). Distinct bacterial signatures were associated with different IBS subtypes, and the related functional changes were related to IBS pathogenesis, such as the increased hydrogen sulfide production pathway in IBS-D and the increased palmitoleate biosynthesis pathway in IBS-C. IBS subjects with depression showed lower abundance of

Surveillance of C. difficile infections suggests correlation of incidence to antibiotic stewardship programs., We conducted a territorywide survey to investigate the epidemiology, risk factors, and clinical outcomes of Clostridioides difficile infection (CDI) among hospitalized patients in Hong Kong. A total of 17,105 cases of CDI were identified, of which 15,717 (91.9%) were healthcare-associated and 1,025 (6.0%) were community-associated. Although CDI incidence increased substantially from 2006 to 2017, it plateaued in 2018 and 2019. The 30-day mortality rates decreased from 20.1% in 2015 to 16.8% in 2019, whereas the 60-day recurrence rates remained constant at ≈11% during the study period. Cross-correlation statistic showed significant correlations between incidence trend and overall antimicrobial drug use (r = 0.865, p

Inflammatory bowel disease (IBD) is increasing in prevalence in resource-limited settings in Asia. Although the prevalence of IBD is lower in these settings than in high-income countries, the high disease burden due to large population size is projected to overtake that of high-income countries in the near future. Unique challenges exist for diagnosing and managing IBD in Asia. On one hand, the inadequate disease awareness in physicians and the general population, the scarcity of diagnostic services, the infectious mimics of IBD (specifically intestinal tuberculosis), and the widespread use of empirical antibiotics and antitubercular therapy pose diagnostic challenges. On the other hand, the absence of a centralised health-care delivery system or universal health insurance, the high cost of therapy, limited access to biologics, and the high risk of opportunistic infections with immunosuppressive therapy present therapeutic challenges. The high probability of tuberculosis reactivation often precludes biological therapy because Asia is highly endemic for tuberculosis and has a high prevalence of latent tuberculosis. Current screening strategies are often ineffective in ruling out latent tuberculosis. Hence, management strategies are often modified according to these challenges. This Series paper discusses the challenges in the diagnosis and management of IBD in resource-limited settings in Asia.

Endoscopy is an essential component in the management of inflammatory bowel disease [IBD]. There is a risk of SARS-CoV-2 transmission during endoscopic procedures. The International Organization for the study of IBD [IOIBD] has developed 11 position statements, based on an online survey, that focus on how to prioritise endoscopies in IBD patients during the COVID-19 pandemic, alternative modes for disease monitoring, and ways to triage the high number of postponed endoscopies after the pandemic. We propose to pre-screen patients for suspected or confirmed COVID-19 and test for SARS-CoV-2 before endoscopy if available. High priority endoscopies during pandemic include acute gastrointestinal bleed, acute severe ulcerative colitis, new IBD diagnosis, cholangitis in primary sclerosing cholangitis, and partial bowel obstruction. Alternative modes of monitoring using clinical symptoms, serum inflammatory markers, and faecal calprotectin should be considered during the pandemic. Prioritising access to endoscopy in the post-pandemic period should be guided by control of COVID-19 in the local community and availability of manpower and personal protective equipment. Endoscopy should be considered within 3 months after the pandemic for patients with a past history of dysplasia and endoscopic resection for dysplastic lesion. Endoscopy should be considered 3–6 months after the pandemic for assessment of postoperative recurrence or new biologic initiation. Endoscopy can be postponed until after 6 months of pandemic for routine IBD surveillance and assessment of mucosal healing.

IntroductionOver-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders.MethodsThis was a multicentre international randomised controlled trial from July 2017 to October 2020. All patients with Forest IIa or above peptic ulcers of ≥1.5 cm were included. Primary outcome was 30-day clinical rebleeding. Secondary endpoints include 3-day all-cause mortality, transfusion requirement, hospital stay, technical and clinical success, and further interventions. 100 patients are needed to yield a power of 80% to detect a difference of −0.15 at the 0.05 significance level (alpha) using a two-sided Z-test (pooled).Results100 patients were recruited. Success in achieving primary haemostasis was achieved in 46/50 (92%) and 48/50 (96%) in the OTSC and conventional arm, respectively. Among patients who had success in primary haemostasis, 2/46 (4.35%) patients in the OTSC arm and 9/48 (18.75%) patients in the conventional arm developed 30-day rebleeding (p=0.03). However, in an intention-to-treat analysis, there was no difference in rebleeding within 30 days (5/50 (10%) OTSC vs 9/50 (18%) standard, p=0.23) or all-cause mortality (2/50 (4%) OTSC vs 4/50 (8%) standard, p=0.68; OR=2.09, 95% CI 0.37 to 11.95). There was also no difference in transfusion requirement, hospital stay, intensive care unit admission and further interventions.ConclusionThe routine use of OTSC as primary haemostasis in large bleeding peptic ulcers was not associated with a significant decrease in 30-day rebleeding.Trial registration numberNCT03160911.

Background Elderly-onset inflammatory bowel disease [IBD], defined as age ≥60 at diagnosis, is increasing worldwide. We aimed to compare clinical characteristics and natural history of elderly-onset IBD patients with those of adult-onset IBD patients. Methods Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features, and outcomes of elderly-onset IBD patients were compared with those of adult-onset IBD patients. Results A total of 2413 patients were identified, of whom 270 [11.2%] had elderly-onset IBD. Median follow-up duration was 111 months (interquartile range [IQR]: 68–165 months). Ratio of ulcerative colitis [UC]: Crohn’s disease [CD] was higher in elderly-onset IBD than in adult-onset IBD patients [3.82:1 vs 1.39:1; p Conclusions Elderly-onset IBD was associated with increased risk of infections and cancer development, and increased infection- and IBD-related hospitalisations. Specific therapeutic strategies to target this special population are needed.

Inflammatory bowel disease (IBD) is a major intestinal disease. Excessive inflammation and increased endoplasmic reticulum (ER) stress are the key events in the development of IBD. Search of a genome-wide association study database identified a remarkable correlation between a TM9SF4 single-nucleotide polymorphism and IBD. Here, we aimed to resolve its underlying mechanism.The role of TM9SF4 was determined with experimental mouse models of IBD. ER stress cascades, barrier functions, and macrophage polarization in colonic tissues and cells were assessed in vivo and in vitro. The expression of TM9SF4 was compared between inflamed regions of ulcerative colitis patients and normal colon samples.In mouse models of IBD, genetic knockout of the TM9SF4 gene aggravated the disease symptoms. In colonic epithelial cells, short hairpin RNA-mediated knockdown of TM9SF4 expression promoted inflammation and increased ER stress. In macrophages, TM9SF4 knockdown promoted M1 macrophage polarization but suppressed M2 macrophage polarization. Genetic knockout/knockdown of TM9SF4 also disrupted epithelial barrier function. Mechanistically, TM9SF4 deficiency may act through CaOur study identified a novel IBD-associated protein, TM9SF4, the reduced expression of which can aggravate intestinal inflammation. Deficiency of TM9SF4 increases ER stress, promotes inflammation, and impairs the intestinal epithelial barrier to aggravate IBD.

Background Evidence regarding the use of proton-pump inhibitors (PPIs) in COVID-19 patients remains elusive. We examined the impact of PPI use on clinical outcomes of COVID-19 patients in a territory-wide cohort. Methods We performed a retrospective cohort study using data from an electronic healthcare database managed by the Hospital Authority, Hong Kong. COVID-19 patients diagnosed virologically between 23 January 2020 and 1 January 2021 in Hong Kong were identified. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI user was identified by PPI use within 12 months before the diagnosis of COVID-19. In subgroup analysis, current PPI users were defined as patients who used PPIs within 1 month before the diagnosis of COVID-19;past PPI users were defined as patients who used PPIs 1 to 12 months before COVID-19 diagnosis. We performed sensitivity analysis after excluding patients with short-term new NSAID use within 1 month before COVID-19 diagnosis to minimize reverse causation bias. Results We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all the reported cases in Hong Kong);579 (6.7%) patients had used PPI. PPI users were older, more likely to have comorbidities, concomitant medications and unfavorable laboratory parameters than non-users. Of 8,675 COVID-19 patients, 500 (5.8%) developed the primary endpoint. After propensity score (PS) balancing for patients' demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not associated with the development of primary endpoint in PS weighting (weighted hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.83-1.47, P=0.482) (IDDF2021-ABS- 0122 Figure 1. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton- pump inhibitor (PPI) users after propensity score (PS) weighting in a single multiple imputation data set.), and PS matching analysis (weighted HR 0.81, 95%CI 0.57-1.14, P=0.228) (IDDF2021-ABS-0122 Figure 2. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton-pump inhibitor (PPI) users after propensity score (PS) matching in a single multiple imputation data set). Consistent non-association was observed after multivariable adjustment (adjusted HR 0.84, 95%CI 0.66- 1.07, P=0.151), in subgroups of current and past PPI users, and in sensitivity analysis after excluding short-term new NSAID users. Conclusions PPI use is not associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, multivariable adjustment, and subgroup analyses.

BackgroundLong-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.ObjectiveTo investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus.MethodsWe conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months.ResultsAt 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all pBifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months.ConclusionThese findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.

Probiotics, as live microorganisms that improve intestinal microbial balance, have been implicated in the modulation of neurodegenerative diseases via the microbiome-gut-brain axis by improving gut dysbiosis. This review examines the association between probiotics and neurocognitive function in age-related dementia.We searched MEDLINE, Embase, Scopus, Web of Science and Cochrane library for in vivo studies using equivalent combinations of "probiotics" and "dementia" as per PRISMA. From the 52 in vivo studies identified, 5 human and 22 animal studies with comparable quantitative outcomes on neurocognitive/behavioural function were meta-analysed by forest plots, subgroup analysis and meta-regression. The analysis of biomarkers, risk of bias and publication bias were also performed.In elderly humans, probiotics correlates with a non-significant difference of neurocognitive function in Mini-Mental State Examination, but with significant improvement only in those diagnosed with Alzheimer's disease. In animals, probiotics significantly improved neurocognitive function as measured by Morris Water Maze, Y-Maze, and Passive Avoidance. Further analysis by subgrouping and meta-regression found that the probiotics-neurodegeneration association is age dependent in humans but is neither dose dependent nor duration dependent in animals or humans. Analysis of biomarkers suggested that the neurocognitive effect of probiotics is associated with an altered gut microbiome profile, downregulated proteinopathic, inflammatory and autophagic pathways, and upregulated anti-oxidative, neurotrophic, and cholinergic pathways.Overall, we report promising results in animal studies but limited evidence of probiotics leading to neurocognitive improvement in humans. More research into probiotics should be conducted, especially on live biotherapeutic products for targeted treatment of gut dysbiosis and age-related dementia.

Background Incidence of elderly-onset inflammatory bowel disease (IBD), defined as age ≥ 60 at diagnosis, is increasing rapidly worldwide. We aimed to compare the clinical characteristics and natural history of elderly onset IBD patients to non-elderly onset IBD patients. Methods Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features and outcomes of elderly-onset IBD patients were compared with non-elderly onset IBD patients. Results Total 2413 patients were identified, of whom 270 (11.2%) had elderly-onset IBD during 21805 person-years follow-up. Median follow-up duration was 111 months (Interquartile range [IQR]: 68–165 months). The ratio of ulcerative colitis (UC): Crohn’s disease (CD) was higher in elderly-onset IBD than non-elderly onset IBD patients. (3.82:1 vs. 1.39:1; p < 0.001). Elderly-onset Crohn’s disease (CD) had less perianal involvement (5.4% vs. 25.4%; p < .001) but more stricturing phenotype (32.1% vs. 20.5%; p = 0.04) than non-elderly onset. There was no difference in the rate of cumulative use of biologics (p = 0.49), but significantly lower use of immunosuppressants in elderly-onset IBD patients (p = 0.001). Cumulative risk of IBD-related surgeries was similar (p = 0.89). Elderly-onset IBD was associated with higher risks of cytomegalovirus colitis (Odds ratio [OR]: 3.07; 95% Confidence Interval (CI) 1.92–4.89; p < 0.001); herpes zoster infections (OR: 2.42; 95% CI: 1.22–4.80; p = 0.12) and all cancer development (Hazard ratio: 2.97; 95% CI: 1.84–4.79; p < 0.001). Elderly-onset IBD was also associated with increased number of overall hospitalisation (OR: 1.14; 95% CI 1.09–1.20; p < 0.001), increased number of infections-related hospitalisation (OR: 1.87; 95% CI 1.47–2.38; p < 0.001) and longer hospitalisation (OR: 1.004; 95% CI: 1.001- 1.007; p = 0.007) compared with non-elderly onset IBD. Conclusion Elderly-onset IBD has less perianal CD. However, they have significantly more comorbidities and are associated with increased risk of infections, cancer development and increased and prolonged hospitalisations. Specific therapeutic strategies are needed in this special group of patients.

ObjectiveThe impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).DesignIn this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.ResultsProportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (pBifidobacterium and Lactobacillus compared with FMT alone (pConclusionRepeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.Trial registration numberNCT03127696.

Background Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms supporting the effect remain unclear. Aim To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs. Methods We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated. Results We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were Lactobacillus followed by Bifidobacterium and Lactococcus. In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity. Conclusion Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs. Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02519-x.

Background Prebiotics, as non-digestible substances that stimulate the growth and activity of beneficial bacteria, is hypothesized to improve neurocognitive function through the Gut-Brain axis. This review therefore, investigates whether the administration of prebiotics is efficacious in attenuating age-related neurodegeneration. Methods 2675 studies from MEDLINE, Embase, Scopus, Web of Science and Cochrane library were searched for in vivo studies using equivalent combinations of ‘prebiotics’ and ‘age-related neurodegeneration’ in concordance with PRISMA guidelines. Quantitative outcomes such as Morris Water Maze (MWM), a cognitive-behavioural task, were examined and pooled with Forest Plots for overall effect (95% CI) and heterogeneity (I2). Weighted meta-regression of the prebiotic-neurodegeneration association with other continuous parameters such as treatment duration, study sample size and year of publication were assessed for potential confounding associations. Risk of Bias (RoB) for animal studies was assessed by the SYRCLE tool. Publication bias was analysed by the Begg-Mazumdar funnel plot. The potential conflict of interest in the source of funding was examined by subgroup analysis. Results 5 human studies on aged healthy volunteers were found. 23 animal studies were identified, with 9 animal studies having comparable quantitative results (149 subjects). Overall results in figure 1 demonstrate a 17.69 sec (11.71–23.67; I2: 96.8) improvement in MWM Escape Latency, suggesting an improvement in neurocognitive function in animal models. Meta-regression revealed that prebiotic-neurodegeneration association is independent from duration of treatment (p=0.202), year of publication (p=0.184); and sample size (p=0.0685). RoB analysis of animal studies on prebiotics shows that there is a risk for bias in terms of study personnel blinding and random housing and outcome assessment of subjects. An asymmetric distribution that is largely beyond the 95% CIs was observed in the Begg-Mazumdar funnel plot. 4 privately-funded studies had significantly weaker association of 12.67s (3.18–22.17) than 5 government-funded studies 21.61s (15.26–27.97). Conclusions Weak evidence suggests that prebiotic supplementation is useful in attenuating age-related neurocognitive decline, thus requiring more clinical trials to evidence its true efficacy.

Background Probiotics have been shown to improve neurocognitive behaviour in animal models via the gut-brain-axis. This meta-analysis aims to evaluate the evidence in human studies on the potential of probiotics as a treatment for age-related neurodegeneration such as Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Methods A PRISMA meta-analysis was conducted by screening through MEDLINE, Embase, Scopus, Web of Science and Cochrane library for human studies using equivalent combinations of ‘probiotics’, ‘age-related neurodegeneration’, ‘MCI’ and ‘AD’. Studies with Mini-mental State Examination (MMSE), a test for cognitive function with comparable quantitative outcome were meta-analysed using RStudio. The analysis for overall effect (95% CI) and heterogeneity (I2) was performed by Forest Plots and subgroup analysis. We further assessed whether the results varied with age,%female, BMI, dosage and sample size with weighted meta-regression. Probiotic amelioration of neurodegeneration was also evaluated through biomarker analysis. Results 9 human studies were identified, where 5 studies had quantitative results. Meta-analysis demonstrates that there is a 0.9 mark (0.1 to 1.9) improvement in MMSE scores in human RCTs, though the results are quite heterogeneous (I2 = 94%) (figure 1). Subgroup analysis of MCI and AD models were divergent with a difference of -0.1 (-0.3 to 0.2) versus a 1.7 (0.9 to 2.5) difference in MMSE score between the two groups. Studies also report improvement in other cognitive tests, such as CERAD and RBANS. Meta-regression revealed that the improvement in MMSE scores is age-dependent (p Conclusions Human study evidence generally shows an association between probiotic supplementation and improved neurocognitive function, although confounded by age and severity of neurodegeneration. Caution should be applied in the use of probiotics as an intervention for cognitive decline.

Background and Aim It is unsure whether inflammatory bowel disease (IBD) is a risk factor for novel coronavirus infection (COVID‐19). Methods IBD patients were identified from population‐based databases in Hong Kong and Taiwan from January 21, 2020, until April 15, 2020. Results Total 2954 and 2554 IBD patients were identified in Hong Kong and Taiwan, respectively. None had COVID‐19. Pooled analysis showed that 65.3%, 39.1%, 4.3%, and 12.8% IBD patients in Hong Kong and 75.8 %, 51.4 %, 26.1%, and 52.3 % in Taiwan were on 5‐aminosalicylates, immunomodulators, corticosteroids, and biologics, respectively. Conclusion There were no reported cases of COVID‐19 infection amongst IBD patients in Hong Kong and Taiwan. IBD patients should continue their usual medications during the COVID‐19 pandemic.

Objectives Patients with rheumatologic diseases might be more susceptible to COVID-19 and carry a poorer prognosis. The aim of this study is to examine the incidence and outcomes of all COVID-19 patients with rheumatologic conditions in Hong Kong. Methods This is a population-based retrospective study. All patients tested positive for SARS-CoV-2 by PCR with a previous diagnosis of rheumatologic diseases were reviewed. The incidence of COVID-19 in patients with rheumatologic conditions was calculated and compared to the general population in Hong Kong. Descriptive data of those rheumatologic patients with COVID-19 and the clinical course of the index infection were presented. Results Up till 27 May 2020, there were 1067 cases of COVID-19 diagnosed in Hong Kong which had a population of 7.5 million. Out of the 39,835 patients with underlying rheumatologic diseases, we identified 5 PCR confirmed COVID-19 cases. The estimated incidence of COVID-19 was 0.0126% patients with rheumatologic diseases, compared to 0.0142% in the general population. All 5 patients had inflammatory arthropathies. One patient was on hydroxychloroquine and sulphasalazine, and one was on methotrexate. None of the 3534 patients on b/tsDMARDs was infected. Four patients had leucopenia/lymphopenia and stool viral PCR was positive in 3 patients. All patients made uneventful recovery without complications or flare of underlying diseases. Conclusions We found no alarming signals of increased frequency or severity of COVID-19 in patients with rheumatologic diseases, although extrapolation of the results to other populations with different infection control strategies should be made with caution.

Background & Aims Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. Methods Proteus spp abundance was assessed by ure gene–specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. Results Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. Conclusions P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined.To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization.A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval [CI], -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.).

Background and aim: Role of 5-aminosalicylic acid (5-ASA), statin and aspirin in reducing cancer risks in inflammatory bowel disease (IBD) remains controversial. We aimed to examine chemo-preventive effects of these drugs in all cancers in IBD in population-based setting. Methods: IBD patients diagnosed between 2000 and 2016 were identified from the Hong Kong IBD Registry and followed from IBD diagnosis until first cancer occurrence. Primary outcome was cancer development ≥6 months after IBD diagnosis. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated with Cox proportional hazards model. Additional effects of statin and aspirin on chemoprevention were also assessed. Results: Amongst 2103 IBD patients (857 Crohn’s disease, 1246 ulcerative colitis; mean age 40.0 ± 15.6; 60.3% male) with 16,856 person-years follow-up, 48 patients (2.3%) developed cancer. The 5-r, 10-r and 15-year (95% CI) cumulative incidence of cancer were 1% (0.6 − 1.5%), 2.8 (2.0 − 3.9%) and 4.8 (3.4 − 6.5%), respectively. Total 1891 (89.9%) and 222 (10.6%) patients have received one or more prescriptions of 5-ASA and statin respectively. In multivariable analysis adjusted for age, gender, smoking status, IBD type and use of other medications, use of 5-ASA or statin was not associated with a reduced risk of cancer development (5-ASA: aHR 1.22, 95% CI: 0.60–2.48, p = .593; statin: aHR 0.48, 95% CI: 0.14–1.59, p = .227). Adding aspirin was not associated with a lowered cancer risk (aHR 1.18, 95% CI: 0.32–4.35, p = .799). Conclusion: Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.Key summaryInflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis are associated with increased risk of both intestinal and extra- intestinal cancers.Various medications including 5-aminosalicylate acid (5-ASA), statins and aspirin have been studied for their chemoprevention effects. However, most studies focused on colorectal cancer only and showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD.The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6–1.5%), 2.8 (2.0–3.9%) and 4.8 (3.4–6.5%), respectively.Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit. Inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis are associated with increased risk of both intestinal and extra- intestinal cancers. Various medications including 5-aminosalicylate acid (5-ASA), statins and aspirin have been studied for their chemoprevention effects. However, most studies focused on colorectal cancer only and showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD. The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6–1.5%), 2.8 (2.0–3.9%) and 4.8 (3.4–6.5%), respectively. Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.

Fibrostenosis occurs in both Crohn's disease (CD) and ulcerative colitis (UC). Up to 21% of patients with CD present with strictures at diagnosis, while the rate of stenosis varies from 1% to 11% in UC. Despite the increasing use of immunomodulators and biologics in treatment, there has been no decrease in the rate of progression from inflammatory to complicated disease phenotypes (either stricturing or penetrating). The presence of stenosis is an independent risk factor for surgery in patients with CD, who are at a risk of postoperative recurrence at a rate of up to 55% at 10 years after surgery. Patients with inflammatory bowel disease (IBD) strictures are at risk of malignant transformation. Thus, surveillance colonoscopy should be offered to this group of patients. Several risk factors for the development of stricture have been identified. In CD, patients aged less than 40-years old, with perianal disease at diagnosis, who need steroids at the first flare up or have ileal disease are at the risk of developing strictures; while in UC, patients with extensive colitis and long-standing disease are at risk. Recently, microbiota signatures have also been identified as markers for stricture development. The presence of Ruminococcus spp. is associated with the development of stricture in pediatric patients with CD. In this review, we highlight the epidemiology, risk factors and natural history of fibrostenosing IBD.

Over the 21st century, inflammatory bowel disease (IBD) has become a global disease with increasing prevalence reported in the Asian subcontinent as a result of rapid urbanisation, industrialisation, and westernisation of lifestyles. Although rates of surgery have shown a temporal decrease globally because of the increasing availability of new drugs and early initiation of effective therapy, health-care costs associated with IBD have continued to rise. The increase in IBD prevalence in resource-limited countries poses a substantial health-care burden. Drugs are not universally accessible or available. An optimised and practical management strategy of IBD in resource-limited countries in Asia is urgently needed. Special consideration should be made to balance the risk of undertreatment (and suboptimal disease control) because of financial constraints with the risk of overtreatment, which is associated with side-effects and costly therapeutics. In this Series paper, we summarise the current approach in optimising conventional therapies, use of other therapies, and de-escalation of biologics in low-resource settings in Asia. The long-term objective is to strive for more effective and affordable therapies with sustained durability of benefit.

Background Psychiatric co-morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD. Aim To review the literature on microbiota-brain-gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co-morbidities in IBD. Methods A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota. Results Gut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety- and depression-like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity. Conclusion Both IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co-morbidities in IBD.

Although there are international guidelines on the management of antithrombotic therapy in patients undergoing colonoscopic polypectomy, whether clinicians and patients follow these recommendations are largely unknown. We aimed to evaluate clinician adherence and patient compliance to periendoscopic management of antithrombotic therapy and their impact on clinical outcomes.Consecutive patients on antithrombotic therapy scheduled for elective colonoscopy in a tertiary referral center were recruited prospectively. Demographic data, indications and periprocedural management of antithrombotic drugs, colonoscopy findings, postpolypectomy bleeding, and serious cardiovascular events were collected systematically. We used Joint Asian Pacific Association of Gastroenterology-Asian Pacific Society for Digestive Endoscopy Practice Guidelines 2018 and assumed clinicians should hold antithrombotics for polypectomy in all colonoscopy patients. Patient compliance was assessed by checking whether discontinuation and resumption of antithrombotic drugs were in accordance with clinician advice.Between December 2017 and October 2019, there were 602 patients recruited who were on antithrombotic drugs undergoing colonoscopy with polypectomy. A total of 98.4%, 41.2%, and 40.0% of clinicians adhered to the guidelines for aspirin alone, clopidogrel alone, and dual-antiplatelet therapy, respectively. Adherence rates were 8.5% for warfarin and 5.2% for direct oral anticoagulants. Compliance to instructions for aspirin alone, clopidogrel alone, dual-antiplatelet therapy, warfarin, and direct oral anticoagulants were achieved in 74.8%, 41.2%, 0%, 36.2%, and 17.5% of patients, respectively. Clinician nonadherence to guidelines was a risk factor for delayed postpolypectomy bleeding (adjusted hazard ratio, 3.54; 95% CI, 1.46-8.58; P = .005), and serious cardiovascular events (hazard ratio, 15.63; 95% CI, 1.83-133.80; P = .012).Physician adherence to the guideline and patient compliance, with the exception of aspirin, were poor and contributed to adverse clinical outcomes. ClinicalTrials.gov number: NCT03363061.

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States.1 Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19.2 Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access.3 Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities.

ObjectiveWhile it is recommended that patients presenting with acute upper gastrointestinal bleeding (AUGIB) should receive endoscopic intervention within 24 hours, the optimal timing is still uncertain. We aimed to assess whether endoscopy timing postadmission would affect outcomes.DesignWe conducted a retrospective, territory-wide, cohort study with healthcare data from all public hospitals in Hong Kong. Adult patients (age ≥18) that presented with AUGIB between 2013 and 2019 and received therapeutic endoscopy within 48 hours (n=6474) were recruited. Patients were classified based on endoscopic timing postadmission: urgent (t≤6), early (6ResultsResults showed that urgent timing (n=1008) had worse outcomes compared with early endoscopy (n=3865), with higher 30-day all-cause mortality (pConclusionCompared with urgent and late endoscopy among patients who have received therapeutic endoscopies, early endoscopy was associated with superior outcomes especially among patients with non-variceal bleeding. This supports the notion that non-variceal AUGIB patients should receive endoscopy within 24 hours, but also emphasises the importance of prior resuscitation and pharmacotherapy.

Background Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy. Aim To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy. Methods Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method. Results After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months. Conclusions More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.

We read with interest the report by Favalli, et al on the incidence of the coronavirus disease 2019 (COVID-19) in Italian patients with connective tissue diseases1 None of the 61 patients with systemic lupus erythematosus (SLE) surveyed was confirmed to have COVID-19. This is in contrast to the initial analysis of the COVID-19 Global Rheumatology Alliance registry, which shows an overrepresentation of SLE in patients with rheumatic diseases who have been diagnosed with COVID-192.