Exploring the association between cardiovascular health and bowel health.

Chronic constipation, diarrhea, and fecal incontinence have high incidence, potential disability, and socioeconomic impact, imposing a heavy burden on the quality of life. We aim to explore the association between cardiovascular health (CVH) and bowel health from National Health and Nutrition Survey 2005-2010. CVH is assessed using Life's Essential 8 (LE8). Chronic constipation, chronic diarrhea, and fecal incontinence are assessed based on Bristol Stool Form Scale classification, bowel movements, and bowel leakage. Better health behaviors (odds ratio [OR]: 0.71, 95% confidence interval [CI] 0.53-0.94, p = 0.02) and worse health factors (OR: 1.45, CI 1.03-2.04, p = 0.04) were associated with less chronic constipation. Less chronic diarrhea is correlated with better CVH (OR: 0.53, 95% CI 0.35-0.79, p = 0.003) and health factors (OR: 0.61, CI 0.46-0.81, p = 0.001). Meanwhile, the proportion of chronic diarrhea significantly decreases when the health behaviors score exceeds 59.42. Lower fecal incontinence was associated with better health behaviors (OR: 0.63, CI 0.44-0.90, p = 0.01) CVH. Better CVH and health behaviors are both linked to lower all-cause mortality in participants with chronic constipation and chronic diarrhea. A higher health behaviors score is also associated with less all-cause mortality in patients with fecal incontinence. Maintaining CVH at the population level contributes to intestinal health, achieving the dual management of both while saving on healthcare costs. However, further prospective research is needed to confirm these associations.

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Consistent efficacy outcomes between phase 2 and phase 3 trials in Crohn's disease or ulcerative colitis in adults: a meta-analysis.

INTRODUCTION: The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. METHODS: We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. RESULTS: We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). CONCLUSIONS: Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. REGISTRATION: PROSPERO (CRD42023407947).

Fragility index analysis for randomized controlled trials of approved biologicals and small molecule drugs in inflammatory bowel diseases.

INTRODUCTION: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated. METHODS: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated. RESULTS: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ. CONCLUSION: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse. AIM: To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up. METHODS: This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS). RESULTS: EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003). CONCLUSION: In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

The influence of sleep factors and dietary habits on the disease pattern of ulcerative colitis patients with long and short disease courses - a multicentre cross-sectional analysis.

BACKGROUND: Ulcerative colitis (UC) is a disease characterized by chronic relapsing-remitting inflammatory disorders and is associated with environmental changes. AIM: To explore the disease patterns of Chinese UC patients and to determine controllable related environmental factors. METHODS: This multicentre cross-sectional study was performed using a questionnaire survey. Data on clinical characteristics and environmental factors were collected. Patients with a disease course ≥5 years were defined as the long course group, and those with a disease course < 5 years were defined as the short course group. RESULTS: A total of 588 effective questionnaires were collected. The proportion of the chronic continuous pattern was the highest among patients with a long disease course (46.8%), and in patients with a short disease course, the proportion of the active to remission pattern was the highest (53.3%). In patients with a long disease course, a higher proportion of patients with adequate sleep was found in the active to remission pattern than in the chronic intermittent (72.1% vs. 43.3%, p = 0.008) and chronic continuous (72.1% vs. 52.4%, p = 0.016) patterns. In patients with a short disease course, the frequency of shellfish and shrimp was higher in the chronic continuous pattern group than in the active to remission pattern group (P = 0.001 and 0.017 respectively). CONCLUSIONS: For early diagnosis patients, dietary guidance should be actively carried out. With the prolongation of the disease course, attention should be given to the sleep quality of patients.

1.UC exhibits various disease patterns, which may be associated with differences in patient prognosis and treatment response.2.Environmental factors, especially sleep and dietary factors, correlated strongly with disease patterns, which varied in different disease courses.3.Early diagnosis patients should receive active dietary guidance, while patients with a prolonged disease course require attention to their sleep quality and appropriate drug interventions when necessary.

A Shortened Diagnostic Interval and Its Associated Clinical Factors and Related Outcomes in Inflammatory Bowel Disease Patients from a Cohort Study in China.

Aim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined. Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval. Results: A total of 516 and 848 patients were confirmed to have Crohn's disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P<0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51-60 years and 12.5 months in UC patients at the age of 41-50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay. Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.

Differences in the incidence and mortality of digestive cancer between Global Cancer Observatory 2020 and Global Burden of Disease 2019.

The burden of digestive cancers is increasing worldwide. The Global Cancer Observatory (GLOBOCAN) 2020 and the Global Burden of Disease (GBD) 2019 are two primary cancer databases, which have a significant impact on policy formulation and resource allocation. We aim to compare the incidence and mortality of digestive cancers between them. Digestive cancer (esophageal, stomach, colorectal, liver, gallbladder and pancreatic cancer) incidence was obtained from the Cancer Today and GBD 2019 result tool. The top five countries with the most or minor difference between GLOBOCAN 2020 and GBD 2019 in age-standardized incidence rates (ASIRs) of digestive cancers were identified. A systematic search on the incidence of specific digestive cancer in selected countries from PubMed and Embase was conducted, and 20 of 281 publications were included. The most significant differences in digestive cancers incidence were commonly found in Asian countries (70%), particularly Indonesia, Vietnam and Myanmar, located in Southeast Asia. The ASIRs for most digestive cancers, except liver cancer, in GLOBOCAN 2020 were higher than those in GBD 2019. Gallbladder cancer had the highest average ratio, followed by liver cancer. The most commonly used standard population was Segi's standard population, followed by the World Health Organization standard population. The data sources nor the processing methods of GLOBOCAN 2020 and GBD 2019 were not similar. Low- and middle-income countries without population-based cancer registries were more likely to have selection bias in data collection and amplify regional variations of etiological factors. Better judgments on the quality of cancer data can be made.

Ocular manifestations of mitochondrial neurogastrointestinal encephalomyopathy: A case report and literature review.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystem disorder that often presents with gastrointestinal and neurological symptoms. Here we report a 33-year-old male who presented with a 16-year history of diarrhea with black stool and progressive weight loss. He complained of progressive bilateral blurred vision, upper eyelids heaviness, ocular motility impairment, and color blindness. Peripheral neuropathy, bilateral sensorineural deafness, hyperlactatemia, diabetes mellitus, hepatic steatosis, blood coagulation dysfunction, and diffuse leukoencephalopathy were detected in the systemic evaluation. Based on the novel homozygous pathogenic variant in the TYMP gene (c.1159+1G>A), he was diagnosed with MNGIE. On ophthalmic examinations, the thickness of the inner retina and ganglion cell complex significantly decreased. ERG showed diffusely decreased amplitudes. The electronegative electroretinogram, which was first reported in MNGIE, indicated a more severe inner retina impairment. The bilateral papillomacular bundle defect and central vision loss in MNGIE are consistent with classical mitochondrial optic neuropathies' features. According to the literature, pigmentary retinopathy, optic neuropathy, and abnormal pupillary reflexes are uncommon ocular features of MNGIE. This study contributes to a better understanding of ocular manifestations in MNGIE and demonstrates that MNGIE may have dyschromatopsia and an electronegative electroretinogram.

Eosinophilic gastroenteritis: Pathogenesis, diagnosis, and treatment.

ABSTRACT: Eosinophilic gastroenteritis (EGE) is a gastrointestinal disorder of unclear etiology that is characterized by eosinophilic infiltration of the stomach and small intestine, and consists of mucosal, muscular, and serosal subtypes. Eosinophilic infiltration of the gastrointestinal tract is a fundamental histopathological characteristic of EGE and is driven by several T-helper type 2 (Th2)-dependent cytokines and induced by food allergy. Due to the lack of a diagnostic gold standard, EGE has a high rate of delayed diagnosis or misdiagnosis. However, several new diagnostic strategies have been developed, such as novel genetic biomarkers and imaging tests. Although dietary therapy and corticosteroids remain the common choices for EGE treatment, recent decades have seen the emergence of novel treatment alternatives, such as biologics that target particular molecules involved in the pathogenic process. Preliminary investigations and clinical trials have demonstrated the efficacy of biologics and provided additional insights for the era of refractory or corticosteroid-dependent EGE biologics.

Trend and Geographic Variation in Incidence and Prevalence of Inflammatory Bowel Disease in Regions Across China: A Nationwide Employee Study Between 2013 and 2016.

Background: Incidence and prevalence rates and trends of inflammatory bowel disease (IBD) in China remain largely unknown. Objective: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in China between 2013 and 2016. Methods: We conducted a population-based analysis using data from the National Urban Employee Basic Medical Insurance database. Patients with at least three claims of IBD diagnosis were identified. A Joinpoint regression model was used to analyze the annual percent change (APC) of the age-standardized incidence and prevalence. Results: The age-standardized prevalence of Crohn's disease (CD) increased from 1.59/100,000 in 2013 to 3.39/100,000 (p < 0.05) in 2016, and that of ulcerative colitis (UC) increased from 8.72/100,000 to 17.24/100,000 (p < 0.05) during the period, with a UC/CD ratio of 5.09 in 2016. The age-standardized incidence of CD varied between 0.82/100,000 and 0.97/100,000 (p = 0.9), whereas that of UC slightly increased from 4.54/100,000 to 4.85/100,000 (p = 0.7). The eastern region of China had the highest incidence and prevalence, and the western region had the lowest rates, in both UC and CD, showing an east-to-west gradient. Conclusion: The incidence and prevalence of IBD in most urban regions in China had an emerging trend over the study period, and an east-to-west gradient was observed, which indicated a greater burden in eastern China. Efforts to improve prevention strategies and promote awareness of IBD are needed, particularly in young men who are at higher risk for CD.

Challenges of senior 8-year-program medical students' scientific research in China: A multicenter questionnaire-based study.

ABSTRACT: Among the diverse medical education systems in China, the 8-year program is dedicated to cultivating physician scientists. Although the research ability of senior students in 8-year medical programs is a pivotal quality, it remains unclear. This study aimed to clarify the current status and challenges of students' research experience, abilities, and outputs.A multicenter cross-sectional study was conducted in 5 medical schools in northern China. Electronic questionnaires were sent to 235 randomly chosen fifth-grade or sixth-grade 8-year-program medical students. A total of 211 responses were collected and analyzed using SPSS 22.0.Only 13.3% of participants chose research as their future career goal. Students generally felt that conducting research was stressful and difficult. The greatest obstacle was a lack of time due to heavy workloads. The 2 major motivations for research were graduation and/or future employment (75.8%) and research interest (24.2%). More than half of the students (142, 67.3%) had research experience by the time of the survey, among whom 84 students already had research outputs. A higher proportion of students with outputs was motivated by the requirements for graduation or employment compared to students without outputs (71.4% vs 55.2%, P  =  .046).Senior 8-year-program medical students in China generally had high pressure to conduct research and devoted their efforts to overcome these challenges. More guidance and novel encouragement to enhance students' initiative and interest in research could be provided by medical schools and educators in the future.

Helicobacter pylori may participate in the development of inflammatory bowel disease by modulating the intestinal microbiota.

ABSTRACT: Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the gastrointestinal (GI) tract that is generally accepted to be closely related to intestinal dysbiosis in the host. GI infections contribute a key role in the pathogenesis of IBD; however, although the results of recent clinical studies have revealed an inverse correlation between Helicobacter pylori (H. pylori) infection and IBD, the exact mechanism underlying the development of IBD remains unclear. H. pylori, as a star microorganism, has been a focus for decades, and recent preclinical and real-world studies have demonstrated that H. pylori not only affects the changes in the gastric microbiota and microenvironment but also influences the intestinal microbiota, indicating a potential correlation with IBD. Detailed analysis revealed that H. pylori infection increased the diversity of the intestinal microbiota, reduced the abundance of Bacteroidetes, augmented the abundance of Firmicutes, and produced short-chain fatty acid-producing bacteria such as Akkermansia. All these factors may decrease vulnerability to IBD. Further studies investigating the H. pylori-intestinal microbiota metabolite axis should be performed to understand the mechanism underlying the development of IBD.

Tofacitinib for extraintestinal manifestations of inflammatory bowel disease: A literature review.

BACKGROUND AND AIMS: Extraintestinal manifestations (EIMs) are commonly seen in patients with inflammatory bowel disease (IBD); management of EIMs is difficult and increases the primary disease burden. Recently, tofacitinib (TOF) was reported to be a promising option for treatment of EIMs. We aimed to review published articles and report experience to date. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched to identify eligible studies. The inclusion criteria were as follows: confirmed diagnosis of IBD; definitive EIMs; treatment with TOF; human study and published in English. The Newcastle-Ottawa Scale score and Cochrane Collaboration's tool for assessing risk of bias were used to determine the quality of the selected studies. RESULTS: Twenty-three studies met the inclusion criteria and were included. For nonrandomized studies, 16 were low quality, 5 were moderate quality, and 1 was high quality. For the one randomized controlled trial, the overall bias risk was low. The most concerning EIMs were dermatological manifestations, rheumatologic manifestations, and others, such as primary sclerosing cholangitis, autoimmune hepatitis, uveitis, and Takayasu arteritis. After administering doses of 5-20 mg/d TOF, the included studies reported varying degrees of clinical remission for both the primary disease and EIMs, except for musculoskeletal EIMs. CONCLUSION: TOF might benefit EIMs in IBD, especially ulcerative colitis, and elevated dosages and longer treatment times may increase its effectiveness. Manifestation-specific results and large prospective studies are highly warranted.

The efficacy and safety of anti-tumor necrosis factor agents in the treatment of intestinal Behcet's disease, a systematic review and meta-analysis.

BACKGROUND AND AIM: Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of anti-tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease. METHODS: We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti-TNF agents was performed. RESULTS: Of the 828 studies initially identified, 13 were included finally, all of which were single-arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48-0.78), 0.51 (95%CI 0.40-0.66), 0.57 (95%CI 0.48-0.67), and 0.38 (95%CI 0.16-0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50-0.86), 0.82 (95%CI 0.48-0.98), 0.65 (95%CI 0.51-0.81), and 0.69 (95%CI 0.39-1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07-0.69). CONCLUSIONS: Anti-TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti-TNF agents used in the treatment of intestinal Behcet's disease was acceptable.

Long-term Disease Behavior and Surgical Intervention Analysis in Hospitalized Patients With Crohn's Disease in China: A Retrospective Cohort Study.

BACKGROUND: There is lack of real-world data for disease behavior and surgery of Crohn's disease (CD) from large-scale Chinese cohorts. METHODS: Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. RESULTS: Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. CONCLUSIONS: This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, immune-related adverse events (irAEs) in the gastrointestinal (GI) system commonly occur. In this study, data were obtained from the US Food and Drug Administration adverse event reporting system between July 2014 and December 2020. Colitis, hepatobiliary disorders, and pancreatitis were identified as irAEs in our study. Reporting odds ratio (ROR) with information components (IC) was adopted for disproportionate analysis. A total of 70,330 adverse events were reported during the selected period, 4,075 records of which were associated with ICIs. GI toxicities have been reportedly increased with ICI, with ROR025 of 17.2, 6.7, and 2.3 for colitis, hepatobiliary disorders, and pancreatitis, respectively. The risks of colitis, hepatobiliary disorders, and pancreatitis were higher with anti-CTLA-4 treatment than that with anti-PD-1 (ROR025 2.6, 1.3, and 1.1, respectively) or anti-PD-L1 treatment (ROR025 4.8, 1.3, and 1.3, respectively). Logistic analysis indicated that hepatobiliary disorders and pancreatitis more frequently occurred in female patients (adjusted odds ratio, 1.16 and 1.52; both p < 0.05). Consistently, polytherapy was a strong risk factor for colitis (adjusted odds ratio 2.52, p < 0.001), hepatobiliary disorders (adjusted odds ratio 2.50, p < 0.001), and pancreatitis (adjusted odds ratio 2.29, p < 0.001) according to multivariate logistic analysis. This pharmacovigilance analysis demonstrated an increased risk of all three GI irAEs associated with ICI therapies. The comparative analysis offered supportive insights on selecting GI irAEs for patients treated with ICIs.

Bowel ultrasound enhances predictive value based on clinical indicators: a scoring system for moderate-to-severe endoscopic activities in patients with ulcerative colitis.

BACKGROUND AND AIM: The aim was to assess non-invasive factors among clinical features, laboratory, and bowel ultrasound (BUS) characteristics and to develop a scoring system to predict endoscopic activities for ulcerative colitis (UC) patients. METHODS: We performed a retrospective study collecting UC patients between January 2015 to September 2020. Logistic regression was performed to predict moderate-to-severe endoscopic activities, defined as endoscopic Mayo score ⩾2. Model performance was described with discrimination and calibration ability and validated by internal and external methods. RESULTS: A total of 103 and 29 patients were enrolled in the modeling and validation groups, respectively. Stool frequency ⩾5 times/day, hematochezia, erythrocyte sedimentation rate (ESR), and colonic wall flow in BUS were included into two predictive models for endoscopic activities, both with good discrimination ability [Area under curve (AUC) 0.879 and 0.882, p < 0.001] and a sensitivity of 76.7% and specificity of 92.3%, which showed an adequate calibration ability by using the Hosmer-Lemeshow test (p = 0.14 and 0.07). The external validation displayed consistent results with the above mentioned. Nomograms were also established for these models. CONCLUSION: We developed predictive models for endoscopic disease activities by using noninvasive factors based on stool frequency, hematochezia, ESR, and colonic wall blood flow in BUS. These models performed well in the internal and external validation.

Artificial Neural Network Analysis-Based Immune-Related Signatures of Primary Non-Response to Infliximab in Patients With Ulcerative Colitis.

Infliximab (IFX) is an effective medication for ulcerative colitis (UC) patients. However, one-third of UC patients show primary non-response (PNR) to IFX. Our study analyzed three Gene Expression Omnibus (GEO) datasets and used the RobustRankAggreg (RRA) algorithm to assist in identifying differentially expressed genes (DEGs) between IFX responders and non-responders. Then, an artificial intelligence (AI) technology, artificial neural network (ANN) analysis, was applied to validate the predictive value of the selected genes. The results showed that the combination of CDX2, CHP2, HSD11B2, RANK, NOX4, and VDR is a good predictor of patients' response to IFX therapy. The range of repeated overall area under the receiver-operating characteristic curve (AUC) was 0.850 ± 0.103. Moreover, we used an independent GEO dataset to further verify the value of the six DEGs in predicting PNR to IFX, which has a range of overall AUC of 0.759 ± 0.065. Since protein detection did not require fresh tissue and can avoid multiple biopsies, our study tried to discover whether the key information, analyzed by RNA levels, is suitable for protein detection. Therefore, immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with IFX and a receiver-operating characteristic (ROC) analysis were used to further explore the clinical application value of the six DEGs at the protein level. The IHC staining of colon tissues from UC patients confirmed that VDR and RANK are significantly associated with IFX efficacy. Total IHC scores lower than 5 for VDR and lower than 7 for RANK had an AUC of 0.828 (95% CI: 0.665-0.991, p = 0.013) in predicting PNR to IFX. Collectively, we identified a predictive RNA model for PNR to IFX and explored an immune-related protein model based on the RNA model, including VDR and RANK, as a predictor of IFX non-response, and determined the cutoff value. The result showed a connection between the RNA and protein model, and both two models were available. However, the composite signature of VDR and RANK is more conducive to clinical application, which could be used to guide the preselection of patients who might benefit from pharmacological treatment in the future.