Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia.

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

The Future of IBD Therapy: Where Are We and Where Should We Go Next?

BACKGROUND: The advent of biologic agents opens up a new era for the treatment of inflammatory bowel disease (IBD). In this era, the treatment goal has evolved from the traditional goal of clinical remission to a combination of clinical remission, laboratory normalization and mucosal healing, designated as 'complete deep remission'. Such complete deep remission comprises a more ambitious disease control strategy that is believed to probably modify the natural course of IBD. KEY MESSAGES: To achieve this goal, optimization of current strategy and introduction of novel therapies have gained significant interest. In this concise review, we aim to provide an overview of the current status and future direction of IBD treatment. Specifically, we will describe the application of personalized therapy, development of new biologics, intestinal microbiome manipulation and out-of-the-box agents for IBD. CONCLUSIONS: More evidence is still desirable to better optimize the current treatment and apply novel biologics. Personalized medicine has the potential to optimize efficacy, decrease the risk of adverse events and minimize costs and should be proposed as a standard of care for the management of IBD.

Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn's and Colitis Epidemiology Study aimed to determine the incidence and phenotype of IBD in 8 countries across Asia and in Australia. METHODS: We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. RESULTS: We identified 419 new cases of IBD (232 of ulcerative colitis [UC], 166 of Crohn's disease [CD], and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25-1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46-29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4-15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P < .001). CONCLUSIONS: We performed a large-scale population-based study and found that although the incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations.

[The prevalence and characteristics of anemia in Crohn's disease in the Chinese].

OBJECTIVE: To investigate the prevalence and characteristics of anemia among patients with Crohn's disease (CD) in Chinese population and identify the possible risk factors. METHODS: A cross-sectional study was performed in 441 patients with CD enrolled from the First Affiliated Hospital of Sun Yat-Sen University between January 2003 and May 2012. The prevalence, severity, type of anemia in these patients was assessed when diagnosis was confirmed. A multivariate logistic regression including 122 patients was performed to screen risk factors of anemia. RESULT: The prevalence of anemia was 64.4% (284/441) with 69.0% (196/284) mild anemia, 28.9% (82/284) moderate anemia and 2.1% (6/284) severe anemia. The most common morphological classification was hypochromic microcytic anemia (43.7%, 124/284). Multivariate logistic regression showed the predictive factors for anemia were higher levels of modified Crohn's disease activity index (CDAI) (OR = 1.007, 95% CI 1.002-1.013), platelet count (OR = 1.007, 95% CI 1.001-1.012), erythrocyte sedimentation rate (OR = 1.024, 95% CI 1.000-1.048), penetrating behavior (OR = 16.952, 95% CI 2.626-108.626), structuring behavior (OR = 6.717, 95% CI 1.583-28.507), older age at diagnosis (OR = 1.065, 95% CI 1.012-1.121),and lower body mass index (BMI) (OR = 0.769, 95% CI 0.633-0.935). CONCLUSIONS: Anemia is a common complication in patients with CD among Chinese population. Activity of the underlying disease, older age at diagnosis, penetrating or structuring disease behavior and low BMI are the risk factors.

Clinical characteristics and risk factors of ovarian reserve decreases in women with Crohn's disease: a case-control study.

BACKGROUND: Crohn's disease (CD), often occurring in women of child-bearing age, can decline the fertility rate. However, whether it reduces ovarian reserve has been rarely reported. This study aimed to evaluate the ovarian reserve in women with CD from the perspective of anti-Müllerian hormone (AMH), and explore the factors that can decrease ovarian reserve. METHODS: A case-control retrospective study was designed. We analyzed the AMH levels in a total of 135 CD women and 878 healthy controls. Through propensity score matching, the subjects were assigned in a ratio of 1:3 to CD group (n = 121) and control group (n = 324). Both groups shared similar basic characteristics, like age, body mass index and smoking status. Serum AMH levels were measured by chemiluminescence. RESULTS: The AMH level in the CD group was significantly lower than that in the control group (2.17 ± 2.23 µg/L vs 3.95 ± 2.01 µg/L, 95%CI [1.34-2.21], P < 0.001). In both groups, the AMH levels decreased as age increased, but without between-group difference in the decreasing rate (P = 0.639). Multivariate analysis showed that age > 30 years (OR, 2.905; 95%CI [1.053-8.531], P = 0.017), disease activity (OR,4.314; 95%CI [1.561-12.910], P = 0.002) and thalidomide use (OR,12.628; 95%CI [4.351 -42.820], P < 0.001) were independent risk factors associated with decreased ovarian reserve (AMH<1.1µg/L). CONCLUSION: Ovarian reserve is lower in CD women than in healthy women. Age, CD activity and medication of thalidomide are risk factors that can aggravate the decline of ovarian reserve.

Comparison and development of machine learning for thalidomide-induced peripheral neuropathy prediction of refractory Crohn's disease in Chinese population.

BACKGROUND: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence. AIM: To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables. METHODS: A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score. RESULTS: The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [P = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, P = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 (P = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 (P = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 (P = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence. CONCLUSION: The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients.

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease.

BACKGROUND AND AIMS: To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohn's disease (CD) patients. METHODS: Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients--finished regular follow-up--were recruited for postoperative recurrence analysis. RESULTS: One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291-3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064-7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060-7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218-0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59-19.766, p = 0.007). CONCLUSIONS: The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.

High-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia.

BACKGROUND AND AIM: The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control. METHODS: Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24-h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual-channel 24-h pH test at the end of 4-week therapy. If the 24-h esophageal pH was still abnormal at the end of 4-week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24-h pH test was repeated at the end of the therapy. RESULTS: Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non-responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without. CONCLUSIONS: The standard-dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the "double-dose" esomeprazole therapy is required.

[The clinical and endoscopic efficacy of step-up and top-down infliximab therapy in Crohn's disease].

OBJECTIVE: To compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD). METHODS: A prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010. Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group. Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0, 2 and 6, followed by maintenance dosing every 8 weeks beginning at week 14. The clinical and endoscopic follow up lasted 30 weeks. Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30. RESULTS: Forty-one CD patients were enrolled, with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P = 0.006), combination therapy (P < 0.001) and severity of disease (P = 0.011) in baseline between step-up and top-down groups. At week 10 and 30 during treatment, the clinical remission rates in step-up group were 45.8% (11/24) and 58.3% (14/24) respectively; the mucosal healing rates in step-up group were 33.3% (8/24) and 54.2% (13/24) respectively; the clinical remission rates in top-down group were 70.6% (12/17) and 82.4% (14/17) respectively; and the mucosal healing rates in top-down group were 35.3% (6/17) and 52.9% (9/17) respectively. No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups. The prevalences of adverse events in step-up and top-down group were 41.7% (10/24) and 29.4% (5/17) respectively (P = 0.422). CONCLUSION: Both step-up and top-down infliximab therapy can induce remission in more than half of CD patients, while top-down therapy might be more beneficiary to symptom and endoscopic remission.

[Multi-centered stratified clinical studies for psychological and sleeping status in patients with chronic constipation in China].

OBJECTIVE: To survey the emotional and sleeping status of patients with chronic constipation (CC) and analyze the relationship between psychological status and constipated symptoms. METHODS: From January 2009 to April 2010, 5 centers and 25 stratified hospitals were selected as the representatives of different regions of mainland China. The CC questionnaires including constipated symptoms, emotional and sleeping status, previous treatments and self-reported impact of constipation on health status, etc. Questionnaires were completed by well-trained physicians or investigators during face-to-face interviews. CC was diagnosed in accordance with the Rome III criteria. RESULTS: A total of 909 valid questionnaires analyzed. There were 258 males and 651 females with a mean age of (49 ± 19) years. 41.5% (377 cases) reported "tense feelings" and 38.3% (348 cases) "felt downcast" over the past 3 months. The patients feeling tense and(or) downcast "frequently" and "most of time" were around 11.3% (103 cases) and 9.4% (85 cases). And 43.8% (398 cases) patients reported sleeping disorders over the past 3 months. Regional differences existed in the comorbidities of psychological and sleeping disorders in CC patients, especially in those from tertiary hospitals. And it was the highest in Beijing area for tense feelings and downcast. The sleeping disorders were the most common in the patients from secondary hospitals, of which 66.1% (37/56) and 65.0% (39/60) were from Wuhan and Xi'an respectively. They were higher than Beijing and Guangzhou (39.7% (23/58), 29.0% (9/31), all P = 0.001). The patients from rural primary clinics suffered more sleeping disorders than those from urban primary cares (P = 0.026). About 35.0% (318 cases) and 28.4% (258 cases) patients reported their constipation was related with emotional and sleeping disorders. The comorbidities of psychological and sleeping disorders were more common in severe constipated patients than mild and moderate counterparts and resulted in more hospital visits (both P = 0.000). CONCLUSIONS: The CC patients often have the comorbidities of psychological and sleeping disorders with regional differences. The patients from the hospitals at various levels may present different spectrums of comorbidities of psychological and sleeping disorders. And the severity of CC influences the moods, sleeps and hospital visits.

The efficacy and safety of thalidomide in the treatment of refractory Crohn's disease in adults: a double-center, double-blind, randomized-controlled trial.

Background: Thalidomide is applied in therapy for refractory Crohn's disease (CD) in adults, but systematic and rigorous clinical evidence is scant. The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults. Methods: A double-center, double-blind, placebo-controlled, randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China. In the double-blind trial, patients were randomly assigned to 100 mg of thalidomide or placebo daily for 8 weeks. The primary outcome was considered as the clinical remission rate calculated based on the Crohn's disease activity index at the eighth week following thalidomide or placebo treatment. In open label, non-response to placebo was additionally treated with 8 weeks of thalidomide; all responders were continuously treated with thalidomide until the 48th week. Results: Twenty-five patients were randomly assigned to each group. At the eighth week, the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group (68.0% [17/25] vs 16.0% [4/25]; relative risk, 4.2; 95% confidence interval, 1.8-10.9, P < 0.001). After a 48-week follow-up, the continuous treatment rate of thalidomide was 46.3% (19/41). Adverse events during the whole process were reported in 58.5% of patients, mainly involving drowsiness, rash, and peripheral neuropathy that were mild and tolerable. Conclusion: Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults. And it could be one of the treatment options for refractory CD.

DNA-Thioguanine Nucleotides as a Marker for Thiopurine Induced Late Leukopenia after Dose Optimizing by NUDT15 C415T in Chinese Patients with IBD.

Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6-thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells < 3.5 × 109 /L) were observed in 43 patients (14.0%), who had significantly higher DNA-TG concentration than those without leucopenia (P = 4.1 × 10-9 , 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/µg DNA). No difference in 6TGN concentrations between leucopenia and non-leucopenia was found. With a DNA-TG threshold of 340.1 fmol/µg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA-TG was an independent risk factor for late leucopenia. Quantification of DNA-TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD.

Clinical features and risk factors for primary surgery in 205 patients with Crohn's disease: analysis of a South China cohort.

BACKGROUND: The frequency of Crohn's disease in China is increasing, but few reports are available on clinical features, phenotypes according to the Montreal classification, or risk factors for surgery in mainland China. OBJECTIVE: This study aimed to assess clinical presentation, phenotypes according to the Montreal classification, and potential risk factors for initial surgery in patients with Crohn's disease in southern China. DESIGN: This was an observational study designed as a retrospective analysis of a historical cohort. SETTINGS: The study was conducted at a tertiary referral hospital, Guangzhou, China. PATIENTS: Medical records of 212 consecutive patients with Crohn's disease were reviewed; data from 205 patients who met inclusion criteria were analyzed. MAIN OUTCOME MEASURES: The value of age, location, and behavior of disease according to the Montreal system, smoking behavior, and other clinical variables as potential risk factors in predicting the requirement for initial surgery was assessed by use of Cox regression analysis. RESULTS: A total of 205 patients were studied. Abdominal pain (181 patients, 88.3%) was the most common clinical presentation. At the time of diagnosis, age was between 17 and 40 years in 145 patients (70.7%). The Montreal classification of disease location was L3 (ileocolonic) in 114 patients (55.6%), disease behavior was classified as inflammatory in 133 patients (64.9%). During the course of their disease (median, 4 years; range, 1-21 years), 79 patients (38.5%) required bowel resection. Kaplan-Meier analysis showed that the overall cumulative rate of primary bowel surgery was 17.6% at 1 year after onset of symptoms, 20.3% at 2 years, 35.2% at 5 years, and 58.3% at 10 years. In our final Cox model, stricturing (HR, 3.67; 95% CI, 2.14-6.29; P < .001), penetrating behavior (HR, 4.60; 95% CI, 2.58-8.22; P < .001), and smoking habit (HR, 2.02; 95% CI, 1.15-3.53; P = .014) were significantly associated with an increased risk for bowel resection. LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS: In Chinese patients with Crohn's disease, abdominal pain is the most common clinical presentation, and the most common phenotypes are age 17 to 40 years at diagnosis, ileocolonic disease location, and inflammatory disease behavior. More than one-third of patients require surgery at a median of 4 years after onset of symptoms. Stricturing, penetrating disease, and smoking are associated with an increased risk of requiring bowel resection.

The clinical analysis of 34 cases of intestinal tuberculosis in China's big city hospitals.

AIMS: Intestinal tuberculosis is not uncommon in developing countries. The diagnosis of this disease is quite difficult. The purpose of our research was to recall the clinical, colonoscopic, and histopathological features of this disease. METHODS: The clinical, colonoscopic, and histopathological findings were retrospectively analyzed in 34 patients with intestinal colonic tuberculosis in recent 5 years. RESULTS: The mean age of the patients was 34.7 ± 10.5 years. There were 18 males and 16 females in this group. Abdominal pain, fever, diarrhea, weight loss, and fatigue were the commonest symptoms. Extraintestinal tuberculosis was present in 14 patients. Colonoscopy revealed ulcers in 18 patients, nodules in 11, a deformed cecum and ileocecal valve in 17, strictures in five, polypoid lesions in four, and fibrous bands forming mucosal bridges in three. The cecum and ascending colon were the commonest sites involved. Segmental tuberculosis was seen in five of the 34 patients in whom full-length colonoscopy could be performed. Two or more sites were involved in 18 patients. Histopathology revealed well-formed granulomas in 23 patients. Fourteen of the above patients had caseation and 11 had confluence of the granulomas. Ill-formed granulomas were seen in seven patients and chronic inflammatory changes in 13. Both caseation granulomas and stain for acid-fast bacilli in the biopsies positive were from four patients. We divided the patients into groups I (definitive intestinal tuberculosis, 27 cases) and II (suspected intestinal tuberculosis, seven cases). Despite the various histopathological findings, all of the patients responded to antitubercular treatment and continued to remain asymptomatic during the follow-up period. CONCLUSIONS: Colonoscopy with biopsy is essential for diagnosing colonic tuberculosis. Even in the absence of the classic histopathological features, a therapeutic trial may be indicated in a given clinical and colonoscopic setting. Follow-up is important.

Six ulcerative colitis patients with refractory symptoms co-infective with Blastocystis hominis in China.

Blastocystis hominis is an enteric parasite which has long been considered as an innocuous commensal living in the intestinal tract. Our research was to explore the role of B. hominis in refractory ulcerative colitis. Our department admitted 122 cases of ulcerative colitis patients. In these patients, there were 73 cases of patients who were responsive to sulfasalazinec, mesalazine in a standard dosage, according to the symptoms change. There was one patient who was detected to have B. hominis infection through stool detection. There were 49 patients with relapse symptoms. In this group, there were six patients who were detected with B. hominis infection through stool detection. The six patients of refractory ulcerative colitis were treated with metronidazole for 10-14 days. They almost completely recovered 3 weeks later. Patients diagnosed with ulcerative colitis should always consider this parasite infection when the symptoms are refractory and cannot be released.

Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients.

Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6-mercaptopurine (6-MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine-induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6-MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu-like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu-like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine-induced toxicity.

Association of Serum Immunoglobulins Levels With Specific Disease Phenotypes of Crohn's Disease: A Multicenter Analysis in China.

Background and Aim: Serum immunoglobulins were reported to be associated with clinical characteristics of inflammatory bowel disease. However, whether a difference exists in the serum immunoglobulins levels in patients with Crohn's disease (CD) with different disease location and behavior phenotypes remains unclear. Therefore, this study aimed to explore the associations of serum immunoglobulins levels with specific CD phenotypes. Methods: Patients with CD having recorded serum immunoglobulins levels were recruited through multicenter collaborative efforts. The associations between serum immunoglobulins levels and distinct phenotypes of CD were evaluated using multiple logistic regression models. Results: A total of 608 patients with CD were included in the study. Elevated (above the upper limit of normal) serum immunoglobulin G (IgG), IgA, IgM, and IgG4 were identified in 24.5, 17.4, 2.1, and 8.2% of patients, respectively. Elevated serum IgG4 levels negatively correlated with complicated disease behavior [odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.92]. Elevated serum IgG was linked to isolated ileal disease with an OR of 0.37 (95% CI 0.23-0.61). The ORs of isolated ileal disease progressively reduced across increasing quartiles of IgG (P for trend < 0.001). The adjusted ORs of isolated ileal disease for increasing quartiles of IgM were 1.82 (1.07-3.1), 1.92 (1.14-3.24), 1.17 (0.69-1.98), and 1 (P for trend = 0.008). Besides, serum IgA and IgG levels significantly correlated with several disease activity indices. Conclusions: These results suggested that certain serum immunoglobulins were associated with specific disease phenotypes of CD. Further investigations to account for the associations are warranted.

Prevalence and symptom pattern of pathologic esophageal acid reflux in patients with functional dyspepsia based on the Rome III criteria.

OBJECTIVES: To determine the prevalence and symptom pattern of pathologic esophageal acid reflux (PEAR) in patients with functional dyspepsia (FD) using the Rome III criteria, and to explore the value of a proton pump inhibitor (PPI) test in distinguishing the patients with and those without PEAR among FD patients. METHODS: Consecutive FD patients who fulfilled the Rome III criteria without predominant typical reflux symptoms (i.e., heartburn or regurgitation) were enrolled. All patients underwent upper endoscopy and an ambulatory 24-h pH monitoring. PEAR was defined as the percentage total time for which a pH value <4 was >4.2% in the distal esophagus. Then, patients were treated with rabeprazole 10 mg twice daily for 28 days. The symptom scores were measured by the frequency score multiplied by the severity scores of the predominant symptom before and at the end of the treatment, and the "PPI test" was defined as positive if the overall scores of the predominant dyspeptic symptom in the fourth week decreased by >50% compared with those of the baseline. RESULTS: One hundred eighty-six FD patients were enrolled, with predominant symptoms of epigastric pain (n=68), epigastric burning (n=47), bothersome postprandial fullness (n=54), and early satiation (n=17). The prevalence of PEAR was 31.7%, with the highest percentage (48.9%) in patients with epigastric burning as their predominant symptom. The prevalence of PEAR in patients with postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were 36.6% (26/71) and 28.7% (33/115), respectively. Overall, 63.4% were positive for the "PPI test"; the rates were 51.5, 85.0, 66.7, and 41.1% in patients with epigastric pain, epigastric burning, bothersome postprandial fullness, and early satiation as their predominant symptoms, respectively (χ(2)=17.59, P=0.001). The positive rates were 65.5 and 60.6% in patients with PDS and EPS, respectively (χ(2)=0.41, P=0.522). The sensitivity and specificity of the "PPI test" in distinguishing FD patients with PEAR was 83.1 and 45.7%, respectively. CONCLUSIONS: PEAR is present in almost one third of FD patients; the prevalence is ∼50% in those with epigastric burning. The "PPI test" has a limited value in distinguishing the FD patients with and those without PEAR.