Efficacy of probiotics, prebiotics and synbiotics in irritable bowel syndrome: a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.

Introduction. Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that affects the quality of life of numerous people worldwide.Gap statement. The therapeutic role of gut microbiota modulation in IBS remains controversial.Aim. We aimed to assess the efficacy of probiotics, prebiotics or synbiotics in patients with IBS.Methodology. We searched MEDLINE and EMBASE up to 1 August 2023, to identify the randomized, double-blind, placebo-controlled trials investigating the effectiveness of probiotics, prebiotics or synbiotics among patients with IBS. Pooled analyses of the effects of probiotics in relieving IBS symptoms were calculated using a random-effects model. Further subgroup analyses were performed by different genera, doses and duration of treatment.Results. Our final analysis included 52 trials involving 6289 IBS patients. Probiotics significantly increased the overall response rate (RR:1.64; P<0.00001), subjective relief rate (RR:1.50; P=0.0002) and abdominal pain relief rate (RR:1.69; P<0.00001). As for specific genera, mixed probiotics (RR:1.41; P=0.0001), Bifidobacterium (RR:1.76; P<0.00001), Lactobacillus (RR:1.97; P=0.0004) and Saccharomyces (RR:1.31; P=0.0004) markedly relieved IBS symptoms. Mixed probiotics (RR:1.31; P=0.005), Lactobacillus (RR:2.22; P=0.04) and Bifidobacterium (RR:1.62; P<0.0001) elevated patients' subjective relief rate. Besides, probiotics effectively relieved the abdominal pain in IBS patients (RR:1.69; P<0.00001). Probiotics appeared to show a remarkable beneficial role at a dose of 109 c.f.u./day or above (RR:1.662; P<0.0001) and started to work at 4 weeks (RR 1.72; P<0.00001). Efficacy of prebiotics and synbiotics in IBS remained uncertain, due to the deficiency of available RCTs.Conclusions. Probiotics have a therapeutic role in IBS. However, the effect of different probiotics varies. The minimal effective dose of probiotics may be 109 c.f.u./day. With appropriate probiotic formula, the therapeutic effect can occur at 4 weeks. These data provide a basis for further research on the optimal probiotic therapy in IBS.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors.

BACKGROUND: Colorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable. AIM: To investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs. METHODS: The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 µm) were determined using multivariate logistic regression. RESULTS: A total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI. CONCLUSION: Because of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Endoscopic submucosal dissection for colorectal laterally spreading tumors: Clinical outcomes and predictors of technical difficulty.

OBJECTIVE: We aimed to investigate the clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of colorectal laterally spreading tumors (LSTs) and the factors related to technical difficulty. METHODS: Consecutive patients who underwent ESD for colorectal LSTs between June 2013 and January 2019 were retrospectively included. Factors associated with difficult ESD procedures (defined as conversion to piecemeal resection or discontinuation of endoscopic procedure), and dissection with a slow speed (<8 mm2 /min), were determined using the logistic regression analysis. RESULTS: A total of 325 patients with 342 colorectal LSTs (median size 20.0 mm) were enrolled. The proportions of granular (LST-G) and non-granular LST (LST-NG) were 62.9% and 37.1%, respectively. The overall en bloc and complete resection rates were 89.8% and 81.9%, respectively. The endoscopic procedure was discontinued in four lesions (1.2%), and 31 (9.1%) converted to piecemeal resection because of technical difficulty. Using multivariate analysis, positive non-lifting sign (odds ratio [OR] 19.9, P < 0.001), tumor size ≥20 mm (OR 10.0, P < 0.001), and less experienced endoscopists (OR 3.7, P = 0.005) were independent factors for technically difficult procedure. Positive non-lifting sign (OR 3.7, P = 0.004), lesion size <20 mm (OR 3.7, P < 0.001), LST-NG type (OR 1.8, P = 0.034), and less colorectal ESD experience (OR 1.9, P = 0.016) were independent factors of slow-speed dissection. CONCLUSIONS: ESD was feasible and safe for treating colorectal LSTs. Positive non-lifting sign and tumor ≥20 mm indicated difficult ESD procedures. Technical failure was more likely to occur in lesions resected by less-experienced endoscopists. Dissection speed might be improved with more experienced operators.

Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies.

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.

Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders. Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT. Conclusion: Serum LTA4H may be a potential biomarker for early prediction of an effective AIT.

Investigation of self-reported chronic urticaria among adults in grasslands of northern China.

The clinical epidemiological characteristics of chronic urticaria (CU) in different populations were not completely consistent, and the epidemiological characteristics of CU were very complex. At present, there were some patient-based studies on CU, but few natural population-based studied in the world.This study aimed to analysis the prevalence of self-reported CU among adults in grasslands of northern China and its closely related factors.A multistage and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.A total of 3406 subjects completed the study. The prevalence of self-reported CU was 5.61% (n = 191), which was higher in women than that of men (6.91% vs 4.08%, X = 12.785, P < .001). Seasonal or seasonal aggravation CU accounted for 110 (57.59%) patients. Pollen dispersal season was basically consistent with the peak season of CU, but there was no significant difference in the positive rate of pollen SPT between CU with seasonal or seasonal aggravation symptom and CU with free of symptom (X = 0.425, P = .51), as well as between CU with seasonal or seasonal aggravation symptom and perennial CU (X = 0.439, P = .51). Eczema (odds ratio [OR] = 2.807, P < .001), chronic diarrhea (OR = 2.486, P < .01), food allergy history (OR = 1.890, P < .01), history of family allergy (OR = 1.800, P < .001), and conjunctivitis (OR = 1.749, P < .01) were closely related to CU.This investigation provided the factors closely related to CU, and provided certain ideas for further research on the etiology and prevention of CU.

Clinical Efficacy Evaluation of 1-Year Subcutaneous Immunotherapy for Artemisia sieversiana Pollen Allergic Rhinitis by Serum Metabolomics.

Subcutaneous immunotherapy is the only treatment that improves the natural progression of allergic rhinitis and maintains long-term outcomes after discontinuation of the drug. Metabolomics is increasingly applied in the study of allergic diseases, including allergic rhinitis. However, little is known about the discovery of metabolites that can evaluate clinical efficacy and possible mechanisms of Artemisia sieversiana pollen subcutaneous immunotherapy. Thirty-three patients with Artemisia sieversiana pollen allergic rhinitis significantly improved after 1-year subcutaneous immunotherapy treatment, while ten patients were ineffective. Pre- and post-treatment serum samples from these patients were analyzed by metabolomics based on the combined detection of liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. As a result, L-Tyrosine can be a potential biomarker because of its opposite trend in effective patients and ineffective patients. And mechanism of immunotherapy may be closely related to NO and nitric oxide synthase. The discovery of potential biomarkers and metabolic pathways has contributed to the in-depth study of mechanisms of subcutaneous immunotherapy treatment of Artemisia sieversiana pollen allergic rhinitis.

The state of the art on treatment of Crohn's disease.

Crohn's disease (CD) is a chronic, progressive, and destructive disease of the gastrointestinal tract. Although its incidence appears to be stable or decreasing in most countries in the North America and Europe, the incidence is rising rapidly in Asian countries. Immunomodulators and biologics are increasingly used to avoid long-term bowel damage and subsequent disability. Therapeutic drug monitoring facilitates optimizing thiopurines and anti-TNFs use. New biologic agents targeting various pathological pathways of CD are blooming in recent years, and the high cost of biologics and expiration of patents for several biologic agents have driven the utility of biosimilars for CD treatment. Here, the literature regarding the efficacy, safety, and withdrawal of the drugs, as well as the evolution of therapeutic targets will be reviewed.

Ethnicity Influences Phenotype and Outcomes in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Population-based Studies.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) (Crohn's disease [CD], ulcerative colitis) are global diseases. Similarities and differences in disease presentation and outcomes across different geographic regions and ethnic groups have not been compared previously. METHODS: We performed a systematic review and meta-analysis of population-based cohort studies examining the phenotype and outcome of IBD across ethnic groups categorized as Whites, Blacks, Hispanics, and Asians. Further stratification was performed by migration status (native or immigrant). Pooled proportions of disease location, behavior, medication, and surgery use were calculated by using a random-effects model and compared statistically. RESULTS: Our final analysis included 198 unique studies reporting outcomes on 525,425 IBD patients (Caucasian, 65%; Asian, 30%; Hispanic, 2%; and Black, 1%). CD in Asians but not other ethnicities demonstrated a strong male predominance. Family history of IBD was infrequent in Asian patients. Both Black and Asian CD patients demonstrated perianal involvement more frequently. Surgery for both CD and UC was less common in Asians than Caucasians. Compared with native residents, a family history of IBD was reported more often among immigrant IBD patients, but no significant differences were noted in phenotype. CONCLUSIONS: We demonstrate significant variation in the demographic distribution, familial predisposition, phenotype, and outcomes of IBD between Caucasians, Blacks, Hispanics, and Asians. There is need for further study to understand the biology behind this variation.

Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.

BACKGROUND: Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. METHODS: We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI. FINDINGS: We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8-17·8] and APC for ulcerative colitis +14·9% [10·4-19·6]) and Taiwan (APC for Crohn's disease +4·0% [1·0-7·1] and APC for ulcerative colitis +4·8% [1·8-8·0]). INTERPRETATION: At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease. FUNDING: None.

Accuracy of Faecal Immunochemical Test to Predict Endoscopic and Histological Healing in Ulcerative Colitis: A Prospective Study Based on Validated Histological Scores.

BACKGROUND AND AIMS: Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. METHODS: We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade ≤ 1]. The predictive abilities of FIT were compared with those of FC. RESULTS: FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 µg/g achieved histological healing. CONCLUSIONS: FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC.

A prospective study on second-generation colon capsule endoscopy to detect mucosal lesions and disease activity in ulcerative colitis (with video).

BACKGROUND AND AIMS: Mucosal healing is the goal for ulcerative colitis (UC) therapy, but it needs to be confirmed via colonoscopy. Colon capsule endoscopy (CCE) is a noninvasive technique for colon investigation. Our study investigated the accuracy of second-generation CCE (CCE-2) in assessing mucosal lesions and disease activity in UC. METHODS: In this prospective study, CCE-2 and conventional colonoscopy were performed on the same day. CCE-2 reviewers and colonoscopists used the Mayo endoscopic subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) to assess disease activity, and they were blinded to each other's findings. Diagnostic parameters of CCE-2 for identifying mucosal lesions were evaluated by using colonoscopy as the reference. RESULTS: A total of 150 patients were enrolled. Of the 150 patients, 108 were included for per-patient analysis. CCE-2 and colonoscopy showed substantial agreement in measuring MES (intraclass correlation coefficient [ICC] 0.69; 95% confidence interval [CI], 0.46-0.81; P < .001) and UCEIS (ICC 0.64; 95% CI, 0.38-0.78; P < .001). CCE-2 had a sensitivity of 97% and 94% to detect mucosal inflammation (MES >0) and moderate to severe inflammation (MES >1), respectively. In per-segment analysis, the negative predictive values of CCE-2 to detect mucosal inflammation, including vascular pattern loss, bleeding, and erosions reached 94% to 95%. Interobserver agreement between 2 independent CCE-2 readers for both scoring systems was good (ICC > .80). The sensitivity and specificity of CCE-2 in detecting postinflammatory polyps were 100% and 91%, respectively. CCE-2 was better tolerated and preferred by patients than was colonoscopy. CONCLUSIONS: CCE-2 yields high accuracy in detecting mucosal lesions and determining disease severity in UC. It represents a well-tolerated and reliable tool for disease monitoring in UC. (Clinical trial registration number: NCT02469103.).

Epidemiology of Inflammatory Bowel Disease from 1981 to 2014: Results from a Territory-Wide Population-Based Registry in Hong Kong.

BACKGROUND: Incidence of inflammatory bowel disease (IBD) is increasing in Asia, but population-based prevalence data are limited. This study examined IBD incidence and prevalence based on results of a territory-wide IBD registry in Hong Kong. METHODS: We collected data on 2575 patients with IBD (1541 ulcerative colitis [UC], 983 Crohn's disease [CD], 51 IBD unclassified) from 1981 to 2014 using hospital and territory-wide administrative coding system. Prevalence and incidence, disease phenotype, surgery, and mortality were analyzed. RESULTS: Adjusted prevalence of IBD, UC, CD, and IBD unclassified per 100,000 individuals in 2014 were 44.0, 24.5, 18.6, and 0.9, respectively. Age-adjusted incidence of IBD per 100,000 individuals increased from 0.10 (95% confidence interval, 0.06-0.16) in 1985 to 3.12 (95% confidence interval, 2.88-3.38) in 2014. UC:CD incidence ratio reduced from 8.9 to 1.0 over 30 years (P < 0.001). A family history of IBD was reported in 3.0% of patients. Stricturing or penetrating disease was found in 41% and perianal disease in 25% of patients with CD. 5-aminosalicylate use was common in UC (96%) and CD (89%). Cumulative rates of surgery for CD were 20.3% at 1 year and 25.7% at 5 years, and the corresponding rates for UC were 1.8% and 2.1%, respectively. Mortality for CD and UC was not significantly different from the general population. CONCLUSIONS: In a population-based study in Hong Kong, prevalence of IBD is lower than in the west although comparable to that of other East Asian countries. Complicated CD is common. Overall mortality remains low in Asians with IBD.

Low-dose azathioprine is effective in maintaining remission in steroid-dependent ulcerative colitis: results from a territory-wide Chinese population-based IBD registry.

BACKGROUND: Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC. METHODS: We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test. RESULTS: Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1-100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001]. CONCLUSIONS: In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.

Systematic Review and Meta-analysis: Phenotype and Clinical Outcomes of Older-onset Inflammatory Bowel Disease.

BACKGROUND: Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects. METHODS: A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age ≥ 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated. RESULTS: We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57]. CONCLUSIONS: Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly.

Natural History of Elderly-onset Ulcerative Colitis: Results from a Territory-wide Inflammatory Bowel Disease Registry.

BACKGROUND AND AIMS: Data on the natural history of elderly-onset ulcerative colitis [UC] are limited. We aimed to investigate clinical features and outcomes of patients with elderly-onset UC. METHODS: Patients with a confirmed diagnosis of UC between 1981 and 2013, from 13 hospitals within a territory-wide Hong Kong Inflammatory Bowel Disease Registry, were included. Clinical features and outcomes of elderly-onset patients, defined as age ≥ 60 years at diagnosis, were compared with those of non-elderly-onset disease [< 60 years at diagnosis]. RESULTS: We identified 1225 patients, of whom 12.8% [157/1225; 56.1% male] had elderly-onset UC. Median duration of follow-up was 11 years [interquartile range, 6-16 years]. Age-specific incidence of elderly-onset UC increased from 0.1 per 100000 persons before 1991 to 1.3 per 100000 persons after 2010. There were more ex-smokers [32.2% vs. 12.2%, p < 0.001] and higher proportion of comorbidities [p < 0.001] in elderly-onset than non-elderly-onset patients. Disease extent, corticosteroids, immunosuppressants use, and colectomy rates were similar between the two groups. Elderly-onset disease was an independent risk factor for cytomegalovirus infection [odds ratio 2.9, 95% confidence interval 1.6-5.2, p < 0.001]. More elderly-onset patients had Clostridium difficile infection [11.0% vs. 5.4%, p = 0.007], hospitalisation for UC exacerbation [50.6% vs. 41.8%, p = 0.037], colorectal cancer [3.2% vs. 0.9%, p = 0.033], all-cause mortality [7.0% vs. 1.0%, p < 0.001], and UC-related mortality [1.9% vs. 0.2%, p = 0.017] than non-elderly-onset patients. CONCLUSIONS: Elderly-onset UC patients are increasing in number. These patients have higher risk of opportunistic infections, hospitalisation, colorectal cancer, and mortality than non-elderly-onset patients. Management and therapeutic strategies in this special group need careful attention.

Factors associated with mucosal healing in patients with ulcerative colitis in clinical remission.

BACKGROUND: Mucosal healing (MH) has been associated with improved outcomes in ulcerative colitis but factors associated with MH are not well defined. METHODS: Consecutive patients with ulcerative colitis in clinical remission (Mayo symptomatic subscore = 0) who had at least 1 colonoscopy since diagnosis from 6 centers were included. For patients who had at least 2 colonoscopies during follow-up, each colonoscopy was reviewed to define whether they had early MH (Mayo endoscopic subscore reduced to 0 within 3 yr of clinical remission). Factors associated with MH and early MH were determined using logistic regression. RESULTS: Two hundred thirty-seven patients with ulcerative colitis (mean age 50.39 ± 14.10 yr; 56.5% male) were included. Independent factors for MH were clinical remission >3 years (odds ratio [OR] 4.0; 95% confidence interval [CI], 1.2-13.1), mild/moderate mucosal inflammation (OR 3.3; 95% CI, 1.3-8.5), and immunosuppressant use (OR 4.6; 95% CI, 1.5-14.6). Among patients who had ≥2 of above factors, 74% achieved MH, whereas only 39% with <2 factors achieved MH (P < 0.001). Of patients in clinical remission <1 year, 1 to 3 years and >3 years, 30%, 45.9%, and 62.9% achieved MH, respectively. Immunosuppressant therapy was associated with early MH (P = 0.025). In multivariate analysis, patients with previous mild inflammation were more likely to achieve early MH than those with moderate/severe inflammation (OR 2.8; 95% CI, 1.2-6.2). CONCLUSIONS: A longer disease remission, previous less severe mucosal inflammation, and immunosuppressant use are associated with MH. Severity of mucosal inflammation and use of immunosuppressant are also associated with early MH.

The role of capsule endoscopy in assessing mucosal inflammation in ulcerative colitis.

Assessment of mucosal inflammation is important in the management of patients with ulcerative colitis (UC). Colon capsule endoscopy (CCE) has recently been shown to be effective in colorectal polyp detection. However, its role in the evaluation of mucosal inflammation in UC is unclear. This systematic review aims to clarify the state of the art with an evidence-based summary of current studies on the utility of CCE in UC. The overall results show that the accuracy of CCE for assessment of mucosal inflammation in UC appeared to be comparable with that of colonoscopy. Long-term follow-up studies with larger sample size are needed to further validate the utility of CCE in the management of UC subjects in clinical practice.