Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

Hybrid immunity augments cross-variant protection against COVID-19 among immunocompromised individuals.

BACKGROUND: Immunity to SARS-CoV-2 vaccination and infection differs considerably among individuals. We investigate the critical pathways that influence vaccine-induced cross-variant serological immunity among individuals at high-risk of COVID-19 complications. METHODS: Neutralizing antibodies to the wild-type SARS-CoV-2 virus and its variants (Beta, Gamma, Delta and Omicron) were analyzed in patients with autoimmune diseases, chronic comorbidities (multimorbidity), and healthy controls. Antibody levels were assessed at baseline and at different intervals up to 12 months following primary and booster vaccination with either BNT162b2 or mRNA-1273. Immunity induced by vaccination with and without infection (hybrid immunity) was compared with that of unvaccinated individuals with recent SARS-CoV-2 infection. Plasma cytokines were analyzed to investigate variations in antibody production following vaccination. RESULTS: Patients with autoimmune diseases (n = 137) produced lesser antibodies to the wild-type SARS-CoV-2 virus and its variants compared with those in the multimorbidity (n = 153) and healthy groups (n = 229); antibody levels were significantly lower in patients with neuromyelitis optica and those on prednisolone, mycophenolate or rituximab treatment. Multivariate logistic regression analysis identified neuromyelitis optica (odds ratio 8.20, 95% CI 1.68-39.9) and mycophenolate (13.69, 3.78-49.5) as significant predictors of a poorer antibody response to vaccination (i.e, neutralizing antibody <40%). Infected participants exhibited antibody levels that were 28.7% higher (95% CI 24.7-32.7) compared to non-infected participants six months after receiving a booster vaccination. Individuals infected during the Delta outbreak generated cross-protective neutralizing antibodies against the Omicron variant in quantities comparable to those observed after infection with the Omicron variant itself. In contrast, unvaccinated individuals recently infected with the wild-type (n = 2390) consistently displayed lower levels of neutralizing antibodies against both the wild-type virus and other variants. Pathway analyses suggested an inverse relationship between baseline T cell subsets and antibody production following vaccination. CONCLUSION: Hybrid immunity confers a robust protection against COVID-19 among immunocompromised individuals.

Low prevalence of 'classical' microscopic colitis but evidence of microscopic inflammation in Asian irritable bowel syndrome patients with diarrhoea.

BACKGROUND: There is increasing evidence for the role of microscopic inflammation in patients with IBS. We aimed to examine the prevalence of microscopic colitis and inflammation in Malaysian IBS patients with diarrhoea (IBS-D). METHODS: Consecutive patients who met the Rome III criteria for IBS-D and asymptomatic controls were prospectively recruited. Colonoscopy was performed in all study subjects and systematic biopsies taken from all segments of the colon. The diagnosis of lymphocytic colitis and collagenous colitis was made using previously defined criteria. Patients with post infectious IBS were excluded. RESULTS: 120 subjects (74 IBS-D, 46 controls) were recruited during the study period. In the IBS-D group, the colonoscopic (macroscopic) findings were as follows; normal findings n = 58 (78.4%), diverticula disease n = 5 (6.8%), diminutive polyps n = 9 (12.2%) and haemorrhoids n = 2(2.7%). No subject under the age of 40 had any significant findings. Microscopically, there was only one case (1.3%) with histology consistent with collagenous colitis. However, the IBS-D patients had a higher prevalence of moderate microscopic inflammation (n = 11, 14.9%) compared to controls (n = 1, 2.2%) (p = 0.005). CONCLUSIONS: 'Classical' microscopic colitis is uncommon in Malaysian patients with IBS-D but a significant number of adults showed evidence of microscopic inflammation.

Addition of thiopurines can recapture response in patients with Crohn's disease who have lost response to anti-tumor necrosis factor monotherapy.

BACKGROUND AND AIM: Anti-tumor necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However, a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response. METHODS: Five patients (four males; aged 22-38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment. RESULTS: All patients experienced improved clinical symptoms within 2-6 months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated C-reactive protein at the time of thiopurine addition demonstrated a fall in C-reactive protein. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted. CONCLUSIONS: Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.

Dental trauma in endoscopy: A systematic review and experience of a tertiary endoscopy centre.

BACKGROUND: Dental injury is the leading cause of litigation in anaesthesia but an underrecognized preventable complication of endoscopy. AIM: To determine frequency and effects of dental injury in endoscopy, we present findings from an audit of outpatient endoscopy procedures conducted at a tertiary university hospital and a systematic review of literature. METHODS: Retrospective review of 11265 outpatient upper endoscopy procedures over the period of 1 June 2019 to 31 May 2021 identified dental related complications in 0.284% of procedures. Review of literature identified a similar rate of 0.33%. RESULTS: Pre-existing dental pathology or the presence of prostheses makes damage more likely but sound teeth may be affected. Pre-endoscopic history and tooth examination are key for risk stratification and may be conducted succinctly with limited time outlay. Tooth retrieval should be prioritized in the event of dental injury to minimize aspiration and be followed by prompt dental consultation for specific management. CONCLUSION: Dental complications occur in approximately 1 in 300 of upper endoscopy cases. These are easily preventable by pre-endoscopy screening. Protocols to mitigate dental injury are also suggested.

Oral Microbiome of Crohn's Disease Patients With and Without Oral Manifestations.

BACKGROUND AND AIMS: Microbiome dysbiosis is associated with inflammatory destruction in Crohn's disease [CD]. Although gut microbiome dysbiosis is well established in CD, the oral microbiome is comparatively under-studied. This study aims to characterize the oral microbiome of CD patients with/without oral manifestations. METHODS: Patients with CD were recruited with age-, gender- and race-matched controls. Potential confounders such as dental caries and periodontal condition were recorded. The oral microbiome was collected using saliva samples. Microbial DNA was extracted and sequenced using shotgun sequencing. Metagenomic taxonomic and functional profiles were generated and analysed. RESULTS: The study recruited 41 patients with CD and 24 healthy controls. Within the CD subjects, 39.0% had oral manifestations with the majority presenting with cobblestoning and/or oral ulcers. Principal coordinate analysis demonstrated distinct oral microbiome profiles between subjects with and without CD, with four key variables responsible for overall oral microbiome variance: [1] diagnosis of CD, [2] concomitant use of steroids, [3] concomitant use of azathioprine and 4] presence of oral ulcers. Thirty-two significant differentially abundant microbial species were identified, with the majority associated with the diagnosis of CD. A predictive model based on differences in the oral microbiome found that the oral microbiome has strong discriminatory function to distinguish subjects with and without CD [AUROC 0.84]. Functional analysis found that an increased representation of microbial enzymes [n = 5] in the butyrate pathway was positively associated with the presence of oral ulcers. CONCLUSIONS: The oral microbiome can aid in the diagnosis of CD and its composition was associated with oral manifestations.

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Validation of genetic variants associated with metabolic dysfunction-associated fatty liver disease in an ethnic Chinese population.

BACKGROUND: Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM: To study the association of single nucleotide polymorphisms (SNPs), previously identified in Western populations, with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors. METHODS: A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography, magnetic resonance imaging, or controlled attenuation parameter score. Subjects were recruited from two tertiary hospitals. Genetic alleles such as NCAN, GCKR, LYPLAL1, PNPLA3, PPP1R3B, FDFT1, COL13A1, EFCAB4B, PZP, and TM6SF2 were genotyped using the TaqMan® Predesigned SNP Genotyping Assay. RESULTS: Weight and body mass index (BMI) were 1.2-times higher in patients (70.6 kg, 95% confidence interval [CI]: 57.1-84.1 vs 60.8 kg, 95%CI: 48.5-73.1, P < 0.001 and 26.9 kg, 95%CI: 23-40.8 vs 23.3 kg 95%CI: 19-27.6, P < 0.001 respectively). The prevalence of diabetes mellitus in patients was 40.3% and 20.8% in controls (P = 0.011). Patients had higher mean triglycerides than controls (P < 0.001). PNPLA3 GG was more likely to be associated with MAFLD (43.4% CC vs 69.7% GG, P = 0.017, and 44.8% CG vs 69.7% GG, P = 0.022). In multivariable analysis, hypertriglyceridemia (odds ratio [OR]: 2.04 95%CI: 1.3-3.1, P = 0.001), BMI (OR: 1.2 95%CI: 1.1-1.4, P < 0.001) and PNPLA3 GG (OR: 3.4 95%CI: 1.3-9.2, P = 0.014) were associated with MAFLD (area under the receiver operating characteristic curve of 0.823). CONCLUSION: Among the Chinese population of Singapore, PNPLA3 homozygous GG allele is a strong predictor of MAFLD, whereas LYPLAL1, GCKR, FDFT1, COL13A1, PZP, and TM6SF2 are not significantly associated. Hypertriglyceridemia, high BMI, and PNPLA3 GG are independent predictors of MAFLD.

Optimal liver stiffness measurement values for the diagnosis of significant fibrosis and cirrhosis in chronic liver disease in Singapore.

INTRODUCTION: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD). METHODS: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4). A high-quality cohort was selected by excluding those with failed LSM and invalid LSM readings. RESULTS: Of the 481 patients recruited, 322 fulfilled the pre-defined quality criteria. CLD aetiology was chronic hepatitis B (CHB) in 49%, non-alcoholic steatohepatitis (NASH) in 16% and chronic hepatitis C (CHC) in 12%. Area under the receiver operating characteristic curve for LSM was 0.775 (95% confidence interval [CI] 0.724-0.826) for significant fibrosis and 0.810 (95% CI 0.738-0.882) for cirrhosis. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 13 kPa for cirrhosis in the general cohort. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 12 kPa for cirrhosis for both CHB and CHC, while the corresponding values for NASH were 11 kPa and 15 kPa. CONCLUSION: Optimal cut-off LSM values should be selected based on disease aetiology. In Singapore, the optimal cut-off LSM values for CHB and CHC are 9 kPa for significant fibrosis and 12 kPa for cirrhosis. Optimal cut-off values for NASH require further validation.

Stopping anti-tumour necrosis factor therapy in patients with perianal Crohn's disease.

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.

Liver cancer in Malaysia: epidemiology and clinical presentation in a multiracial Asian population.

OBJECTIVE: Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians. METHODS: Consecutive patients with HCC were prospectively studied from 2006 to 2009. HCC was diagnosed principally on multiphasic computed tomography and magnetic resonance imaging scans of the liver. The tumor was staged according to the Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Altogether, 348 patients were diagnosed with HCC. There were 239 (68.7%) Chinese patients, 71 (20.4%) Malays and 38 (10.9%) Indians, with the median age of 62.5 years and the male to female ratio of 3.4:1. The predominant etiology in Malay and Chinese patients was hepatitis B virus infection (>60%) and in Indian patients was alcohol intake (26.3%) and cryptogenic cause (29.0%). Hepatitis C was seen in 18.3% of Malays, but less than 10% in Chinese and Indians. BCLC staging was: Stage A, 120 (34.5%); Stage B, 75 (21.6%); Stage C, 84 (24.1%); and Stage D, 69 (19.8%). A larger proportion of Indian than Chinese and Malays patients (44.7%) presented with stage D disease. Portal vein invasion was noted in 124 patients (35.6%) and extrahepatic metastases in 68 (19.5%). Surgical resection and radiofrequency ablation with curative intent was carried out in >90% of stage A patients and transarterial chemoembolization in 49.3% and 21.4% of stages B and C patients, respectively. CONCLUSIONS: HCC is most common among Chinese, followed by Malays and Indians in Malaysia. The etiology of HCC shows a peculiar racial pattern.

Anxiety and depression in various functional gastrointestinal disorders: do differences exist?

OBJECTIVE: To examine the differences in the prevalence and severity of anxiety and depression in patients with functional dyspepsia (FD), nonerosive reflux disease (NERD), irritable bowel syndrome (IBS) and healthy controls. METHODS: Consecutive patients undergoing an index endoscopic examination for various symptoms were interviewed. All the three functional gastrointestinal disorders (FGIDs) were diagnosed according to the Rome III criteria. Anxiety and depression were diagnosed using a locally validated version of the hospital anxiety and depression scale. RESULTS: A total of 248 patients were recruited (62 in FD, NERD, IBS and control groups each) with no differences in the basic characteristics. There was a higher prevalence of anxiety and depression in FD, NERD and IBS groups than that in the control group (43.5%, 45.2% and 67.7% vs 14.5%, P<0.001; and 22.6%, 33.9% and 38.7% vs 6.5%, P<0.0001). Using the cut-off score (>8) for anxiety or depression, IBS patients had a higher rate of anxiety than FD (P=0.01) and NERD (P=0.02), while no significant differences in depression rates were observed among all three groups. CONCLUSION: [corrected] Anxiety is more common in patients with IBS than in those with FD and NERD, indicating a possible causal link in the former.

Negative perception in those at highest risk--potential challenges in colorectal cancer screening in an urban asian population.

INTRODUCTION: Colorectal carcinoma (CRC) is the second commonest malignancy in Malaysia, with the highest incidence seen in the Chinese. The aim of this study is to examine the knowledge of CRC and to identify potential barriers for screening, which has yet to be carried out on a nationwide scale. METHODS: Subjects were recruited consecutively from friends and relatives accompanying patients to the general medical clinic in a tertiary hospital in Kuala Lumpur. Interviews were carried out using a standardized questionnaire for the Asia Pacific CRC working group based on the Health Belief Model (HBM). RESULTS: 991 subjects were interviewed. From our study, 414 (41.8%), 500 (50.5%) and 646 (65.2%) could not identify any of the symptoms, risk factors and screening methods for CRC respectively. Only 384 (38.7%) were agreeable to undergo screening. Independent factors associated with willingness to undergo screening were as follows; Malay and Indian race compared to the Chinese [aOR 2.73 (1.87, 3.98) and 3.04 (2.02, 4.59) respectively], perceived susceptibility, perceived barriers to screening, doctor's recommendation and personal contact with CRC. CONCLUSIONS: Knowledge of CRC and CRC screening is low among the Malaysian population. The majority are not willing to undergo screening, the Chinese paradoxically being the least willing despite being at greatest risk.