Gut microbiota develops to an adult-like mode in early life and stays comparatively stable since then. There are 3 stages in early life: delivery, breastfeeding, and post-weaning nutrition period. In our study, we ascertained the forming of adult-like microbiota pattern in early life time by establishing antibiotic-treated mice model and analyzed the residential microorganism of whole gastrointestinal tract using 16S rRNA sequencing. The antibiotic-treated mouse model showed antibiotics could influence gut bacterial development and breastfeeding is the critical period for gastric and ileal microbiota development. In this study, we were the first to investigate the residential bacteria in the whole gastrointestinal tract in early life time. With our approach of exploration of gut microbiota evolution, we hope to provide a better view of how residential microflora develop in early life and influence the future gut microbial system, which help us better understand gut microbiota and related diseases.
Background:Patients with small-bowel stricturing Crohn's disease (sbsCD) usually have a higher risk of intestinal surgical resection. We aimed to develop a machine-learning model for predicting the 1-year surgery risk in these patients. Methods:This study included 520 retrospectively enrolled patients with sbsCD (training cohort, n = 416; testing cohort, n = 104) from January 2018 to May 2021 and 126 prospectively enrolled patients in the validation cohort from July 2021 to December 2023 across four centers for inflammatory bowel disease in China. Clinical and radiological features were assessed by using logistic regression analyses to identify independent surgery risk factors. Six predictive machine-learning models for 1-year surgical risk were developed and the model performance was comprehensively evaluated by constructing receiver-operating characteristic (ROC) curves and comparing area under the curve (AUC) values. Four simplified Bayesian network (BN)-based risk matrices were constructed for clinical practice. Results:There were 158 (24.4%) Crohn's disease (CD)-related surgeries during the 1-year follow-up. Eight selected predictors of surgery included penetrating lesions, nonuse of biologics, nonuse of corticosteroids, a CD obstructive score of ≥3, endoscopic strictures, anemia, radiologic luminal narrowing, and prestenotic dilation. Among the six models evaluated, the Tree-Augmented Naïve Bayes (TAN) model demonstrated optimal performance, with a mean AUC of 0.878. A further prospective validation cohort verified the efficacy of the model, with 87.5% specificity, 76.7% sensitivity, and 84.9% accuracy for predicting 1-year surgery. Four simplified BN-based risk matrices were constructed for practical use. An online prediction tool is available at http://prebn.site/. Conclusion:We developed and validated a TAN-based BN model incorporating clinical and radiological features to accurately predict the 1-year surgical risk for clinical application in patients with sbsCD, thereby providing a promising tool for decision-making.
Aim: Adalimumab (ADA) is an effective treatment for Crohn's disease (CD); however, some patients still experience adverse reactions and nonresponse. This study aimed to explore the risk factors associated with ADA poor efficacy through machine learning algorithms, which provide promising guidance for the management of ADA in clinical practice.Methods: This single-center investigation included 114 CD patients treated with ADA in the Department of Gastroenterology from January 2020 to January 2023. Risk factors associated with each poor efficacy event were explored using logistic regression and machine learning algorithms. Shapley additive explanations (SHAP) and partial dependence plot methods were used to analyze the risk factors of each event.Results: The results showed 8 of these patients experienced primary non-response (PNR), 35 patients developed secondary loss of response (LOR), and 27.2% (31/114) of patients experienced at least one adverse events (AEs). After comparing the fit of the models established by 10 algorithms, the risk factors associated with PNR, LOR, and AEs were analyzed using the logistic regression algorithm, KNN algorithm, and Extra Tree algorithm, respectively. The most important variables related to the PNR, LOR, and AEs events were the history of corticosteroid use, baseline CDAI, and uric acid, respectively.Conclusions: This study confirmed the efficacy of ADA for clinical practice in the Chinese CD population, and that patients with a history of corticosteroid use, high levels of disease activity, and high inflammatory state before ADA treatment were associated with increased risks of poor efficacy.
Background Ustekinumab (UST) was approved in China for moderate-to-severe Crohn’s disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. Methods A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. Results Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. Conclusions UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.
Crohn′s disease (CD) is a chronic, progressive and destructive inflammatory disease affecting the entire digestive tract. Changes in the intestinal microbiota, particularly a decrease in gut microbiome diversity, are thought to be associated with chronic intestinal inflammation of CD. As for the mechanism of antibiotics in CD treatment, some scholars believe that antibiotics can affect the course of disease by reducing the concentration of intestinal bacteria and changing the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole and rifaximin, have been proved to have certain therapeutic effect on some patients with CD in clinical practice, but there are still limitations in the use of antibiotics.In this review, the relationship between intestinal flora and the incidence of CD and the application of antibiotics in CD were reviewed, providing reference and help for the standardized application of antibiotics in CD.
Background:Endoscopic disease activity monitoring is important for the long-term management of patients with ulcerative colitis (UC), there is currently no widely accepted non-invasive method that can effectively predict endoscopic disease activity. We aimed to develop and validate machine learning (ML) models for predicting it, which are desired to reduce the frequency of endoscopic examinations and related costs.Methods:The patients with a diagnosis of UC in two hospitals from January 2016 to January 2021 were enrolled in this study. Thirty nine clinical and laboratory variables were collected. All patients were divided into four groups based on MES or UCEIS scores. Logistic regression (LR) and four ML algorithms were applied to construct the prediction models. The performance of models was evaluated in terms of accuracy, sensitivity, precision, F1 score, and area under the receiver-operating characteristic curve (AUC). Then Shapley additive explanations (SHAP) was applied to determine the importance of the selected variables and interpret the ML models.Results:A total of 420 patients were entered into the study. Twenty four variables showed statistical differences among the groups. After synthetic minority oversampling technique (SMOTE) oversampling and RFE variables selection, the random forests (RF) model with 23 variables in MES and the extreme gradient boosting (XGBoost) model with 21 variables in USEIS, had the greatest discriminatory ability (AUC = 0.8192 in MES and 0.8006 in UCEIS in the test set). The results obtained from SHAP showed that albumin, rectal bleeding, and CRP/ALB contributed the most to the overall model. In addition, the above three variables had a more balanced contribution to each classification under the MES than the UCEIS according to the SHAP values.Conclusion:This proof-of-concept study demonstrated that the ML model could serve as an effective non-invasive approach to predicting endoscopic disease activity for patients with UC. RF and XGBoost, which were first introduced into data-based endoscopic disease activity prediction, are suitable for the present prediction modeling.
Objective:To investigate the incidence, clinical characteristics and risk factors of growth retardation in pediatric onset IBD patients.Methods:A cross-sectional study was conducted. IBD patients with the age at diagnosis younger than 18 years old were recruited and screened in the Wechat group of patients in 8 IBD medical centers across the country. Demographic, clinical and growth-related data were collected through questionnaire survey, and the incidences of growth retardation at the time of diagnosis and investigation were calculated. According to whether there was growth retardation at the time of investigation, the patients were divided into growth retardation group and non-growth retardation group. The influencing factors of growth retardation were analyzed by the univariate analysis and multivariate Logistic regression analysis.Results:A total of 97 patients were involved including 8 ulcerative colitis (UC) and 89 Crohn′s disease (CD). There was no growth retardation in UC patients. Among 89 patients with CD, there were 48 males and 41 females, and the age was 15.5 (1.0, 21.0) years old. At the time of investigation, 14 patients (15.7%) with growth retardation were set as the growth retardation group, and 75 without growth retardation were set as the non-growth retardation group. The incidence of growth retardation was 19.0% (16/84) at the time of diagnosis. Univariate analysis results showed that compared with non-growth retardation group, patients in growth retardation group had lower diagnostic age [5.0 (1.0, 13.8) years old vs. 14.0 (12.0, 16.0) years old, P = 0.003], severer disease activity ( P = 0.006), higher proportion of acute gastrointestinal perforation [28.6% (4/14) vs. 2.7% (2/75), P = 0.005], higher proportion of patients in using glucocorticoids [64.3% (9/14) vs. 33.3% (25/75), P = 0.029), and longer time of using glucocorticoids [1.5 (0, 6.5) months vs. 0 (0, 3.0) months, P = 0.040], while the proportion of patients using biological agents was lower [42.9% (6/14) vs. 80.0% (60/75), P = 0.010], and the time of using biological agents was shorter [0 (0, 6.3) months vs. 7.0 (1.0, 12.0) months, P = 0.006]. Logistic regression analysis revealed that the age at diagnosis of CD was still a risk factor for growth retardation after correcting other factors ( OR = 6.909, 95% CI: 1.250-38.195, P = 0.027) . Conclusion:The pediatric onset IBD patients with low diagnostic age are prone to growth retardation, which should be paid attention to.
Background Inflammatory bowel disease (IBD) is rising in China, and the tendency for lifelong recurrence decreases patients' quality of life. However, no studies on treatment decision-making in Chinese patients with IBD exist. Thus, this study aimed to determine the actual and ideal decision-making, as well as factors affecting decision-making in Chinese IBD patients. Methods A multicenter online questionnaire was distributed among patients diagnosed with IBD. To assess factors that influence treatment decision-making, univariate and multivariate logistic regression analyses were performed. Results From March 20, 2018, to May 20, 2018, a total of 866 patients completed the questionnaires, including 222 patients with ulcerative colitis, 588 patients with Crohn's disease, and 56 patients with unclassified IBD. There was a significant difference between ideal and actual decision-making in Chinese IBD patients (P < .005). The factors affecting ideal decision-making included income, education, illness severity, religiosity, the importance of the treatment decision, the employment situation, and occupation area. The factors affecting actual decision-making included age, illness severity, religiosity, the employment situation, economic anxiety, concern about the side effects, and the importance of the treatment decision. Conclusions There is a significant difference between ideal and actual decision-making in IBD patients in China. That is, the economy, religiosity, illness severity, and concern about the side effects of treatment are the most important factors affecting treatment decisions in Chinese IBD patients.
回顾性分析在中南大学湘雅二医院接受阿达木单抗治疗的93例克罗恩病患者的临床和影像学资料,阿达木单抗治疗3个月和1年的总体临床缓解(克罗恩病疾病活动指数<150)率分别为76.3%(71/93)、73.9%(65/88),1年内镜缓解[克罗恩病内镜严重程度指数(CDEIS)<3]率为31.3%(21/67)。9例单纯小肠型患者中影像学缓解(小肠CT造影肠壁厚度<3 mm且强化基本消退)2例。不良反应发生率为41.9%(39/93),大部分不良反应轻微可耐受。阿达木单抗治疗3个月实现临床缓解是1年内镜缓解的促成因素[ OR(95%置信区间) 50.220(2.054~1 227.725), P=0.016],小肠+结肠型克罗恩病是1年内镜缓解的促成因素[ OR(95%置信区间) 61.999(1.491~2 578.761), P=0.030];基线CDEIS≥5是1年内镜缓解的不利因素[ OR(95%置信区间) 0.008(0.001~0.123), P=0.001]。以上研究结果提示阿达木单抗治疗可有效诱导维持克罗恩病患者临床和内镜缓解,且患者耐受性良好。
Crohn′s disease (CD) is a chronic transmural inflammation disease which may affect the whole gastrointestinal tract. It is known that ileal and colonic involvement of CD is common. Capsule endoscopy (CE) is widely used for CD because of its noninvasiveness and convenience, especially for diagnosis of early-onset and atypical small bowel CD. CE also plays an important role in improving and modifying disease extent and assessment of disease activity. However, CE has its limitations. We mainly summarize the efficacy of CE for early-onset diagnosis and evaluation of extent and activity in small bowel CD. The retention risks are also reviewed to give some references for clinical practice.
Abstract Background Malnutrition is prevalent among patients with inflammatory bowel disease (IBD). Nutritional profiles among Asian patients with IBD have seldom been investigated. We assessed the prevalence of and risk factors for malnutrition, use of nutrition support, and sociopsychological status associated with malnutrition among patients with IBD in China. Methods Patients with ulcerative colitis and Crohn’s disease (CD) recruited from 43 tertiary referral hospitals were screened for malnutrition and nutrient deficiencies in this cross-sectional study. The use of nutrition support was recorded. The sociopsychological status was assessed by subjective questionnaires. Factors associated with malnutrition were analyzed, and multivariate regression was used to determine independent predictors for malnutrition. Results We recruited 1013 patients with a median age of 35.0 years, 58.5% of them had CD, and 61.4% of all patients were male. Overall, 49.5% (n = 501) of patients were diagnosed with malnutrition, including 57.0% of patients with CD, 38.8% of patients with ulcerative colitis, and 44.1% of patients with quiescent or mildly active disease. Nutrient deficiencies were prevalent despite the absence of malnutrition. Malnutrition was associated with adverse sociopsychological status, including decreased social support, higher perceived stress, and impaired quality of life. Moderate to severe disease activity and extensive disease were 2 independent risk factors for malnutrition. In total, 41.6% of patients received nutrition support, and patients with risk factors were more likely to receive nutrition support. Conclusions Malnutrition was highly prevalent and associated with adverse consequences in Chinese patients with IBD. Malnutrition screening and early initiation of nutrition support are essential components in IBD care.
Early-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases. IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.
肠易激综合征(IBS)是一种功能性肠病,发病机制尚未明确,多以腹痛、腹胀或腹部不适为主要症状,与排便相关或伴随排便习惯如频率和(或)粪便性状的改变.在消化科门诊病人中,有相当一部分患者都有共同的症状表述:一旦食用生冷食物或者辛辣食物就会立刻出现腹痛,排便急迫感,大便不成形,排便后症状可以缓解,不影响食欲,不影响体重,常伴有睡眠不佳;有的病人或是反复便秘,或者一会儿腹泻,一会儿便秘.这样的患者往往做了很多检查都没有阳性发现,病人却常常担心有隐性疾病而辗转多家医院重复检查,药物治疗效果欠佳或持续时间短.这时候我们会给病人下IBS的诊断.
Crohn′s disease (CD) that affects the gastrointestinal tract is a chronic, non-specific transmural inflammatory disease, and its pathogenesis is not clear at present. Traditional drug therapy includes glucocorticoids and immunosuppressive agents and so on. In nearly two decades, biological agents represented by anti-tumor necrosis factor (TNF) -α monoclonal antibodies have greatly changed the prognosis of CD. However, its clinical application still faces challenges, such as primary non-response or secondary non-response. With the in-depth study of the pathophysiology of CD, novel therapeutic targets drugs are emerging continuously. This article summarizes and discusses the research progress of these novel drugs to provide references for clinical treatment.
CD是一种以复发与缓解交替为特点的慢性胃肠道炎性疾病。肛周病变是CD的常见临床表现,但CD肛瘘相关性肛管癌罕见。大部分CD肛瘘相关性肛管癌患者确诊时已为晚期,失去手术机会,预后极差,目前对于此类患者的诊断,以及对高危患者是否需要监测尚无共识意见和指南。现对CD肛瘘相关性肛管癌的发病率、危险因素、诊断、预后和监测进行综述,以期为临床实践提供参考。
RATIONALE:Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (LPD) usually occurs in children and young adults. Gastrointestinal involvement is rare. EBV-associated T-cell lymphoproliferative disorder manifesting as intestinal ulcers poses diagnostic challenges clinically and pathologically because of the atypical manifestations. We concluded that some indicators according to our case and literatures, which might be helpful to the diagnosis of EBV-associated LPD manifested as intestinal ulcers.PATIENT CONCERNS:Here we present a 26-year-old man with complaints of diarrhea and abdominal pain that had persisted for 1 year. Multiform and multifocal deep ulcers were discovered in the colonoscopy. Cell atypia was not obvious but colitis with crypt distortion was found in pathology.DIAGNOSES:According to the symptoms, laboratory examinations, colonoscopy and pathology results, Crohn Disease was diagnosed.INTERVENTIONS:Infliximab therapy was initiated based on the diagnosis of Crohn Disease.OUTCOMES:After the fifth course of therapy, intermittent fever and hematochezia occurred. Physical examination revealed swollen tonsils and ulcers, and purulent exudate from the right tonsil and palatoglossal arch were observed. Biopsies obtained through colonoscopy and nasopharyngoscopy demonstrated EBV-associated T-cell proliferation disease (level 3). After that, the tissue sample from the first colonoscopy was reexamined immunohistochemically. The result suggested EBV-associated T-cell proliferation disease (level 1).LESSONS:When we confront with patients with multiform and multifocal deep intestinal ulcers, not only the common diseases such as Crohn Disease and intestinal tuberculosis should be considered, EBV-associated T-cell proliferation disease should be considered as well. Repeated multiple biopsy, gene rearrangement, EBV DNA quantitative analysis result, EBV-encoded RNA(EBER) and experienced pathologists might be helpful to the diagnosis.
十二指肠与腹腔内其他脏器如胆囊、胰腺等紧密毗邻,极少情况下当胆囊、胰腺病变累及十二指肠时也可造成上消化道大出血,早期内镜下表现并不明显,可能被忽视或误诊。本文报道了1例少见胆囊多发结石压迫十二指肠球部导致上消化道大出血并死亡的病例,希望能提供一些诊断和治疗方面的经验及教训。
This article summarizes the disease characteristics and current treatment status for ulcerative colitis,and suggests to choose appropriate patients for anti-TNF biologics top-down strategy.
BACKGROUND:We assessed the frequency of epigenetic lesions, including lymphoid-specific helicase (LSH), 5-hydroxymethylcytosine (5-hmC) and E2F1, and the possible correlations among molecular findings, phenotype, clinical features, and outcome. METHODS:We investigated 181 paraffin-embedded B-cell lymphoma samples using immunohistochemistry and in situ hybridization. RESULTS:The levels of Ki67, LSH, 5-hmC, and E2F1 were all increased in germinal center B-cell lymphomas when compared with those in normal lymph nodes, and LSH was highly expressed in diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphomas (BLs) that were positive for Epstein-Barr virus (EBV) infection, indicating that LSH is linked to EBV infection in DLBCL and BL. Interestingly, LSH was mainly localized in the germinal centers of lymph nodes whereas 5-hmC staining localized to areas surrounding the germinal centers. CONCLUSIONS:These findings indicate a critical role for LSH as a biomarker and therapeutic target in follicular germinal center B-cell lymphoma.