摘要： A female with very early onset inflammatory bowel disease (VEO‐IBD) was shown to carry two compound heterozygous missense variants in Nuclear Factor of Activated T cells 5 and have impaired induction of iTregs. The variants in NFAT5 may be the cause of lack of iTregs and consequently the development VEO‐IBD.

关键词： inflammatory bowel disease   dysplasia   decision‐   making  

摘要： Aim In cases of prognostic uncertainty and equipoise as to the best management (prophylactic colectomy vs. surveillance) for dysplasia in inflammatory bowel disease (IBD), individualized discussion with the patient is required. Further understanding of patients' preferences is needed. Methods A nationwide cross-sectional survey was distributed to adult IBD patients who had never been diagnosed with dysplasia (dysplasia-naive) and those who had (dysplasia-experienced). Risk perceptions and factors that influence management choices were explored. Results There were 123 respondents. A substantial proportion (29%) of the dysplasia-experienced respondents did not feel well informed about the associated cancer risk and/or its management by their clinical team. Contributing themes included contradictory advice and lack of personalized information regarding their cancer risk, alternative management options and impact on long-term quality of life. Decisional regret and health-related quality of life amongst those who chose either surveillance or surgery were comparable, but cancer-related worry scores were elevated in the surveillance group. The dysplasia-naive respondents reported that they would only consider having a prophylactic colectomy if they had on average a 50% or even higher risk of developing cancer. On multivariable logistic regression analyses, predictors of colectomy or surveillance preference included ethnicity, personality traits such as health locus of control (whether health status is influenced by luck) and differences in perception of what a low risk of cancer is. Conclusions This study identifies predictive factors that can influence decision-making and satisfaction with the counselling process when IBD dysplasia is diagnosed. Further qualitative exploration of cultural themes would be informative.

关键词： bioelectric medicine   celiac plexus   Crohn&apos   s disease   dextran sulfate sodium   IBD   medical device   peripheral ganglion   superior mesenteric plexus   ulcerative colitis  

摘要： New Findings What is the central question of this study? Does peripheral non-invasive focused ultrasound targeted to the celiac plexus improve inflammatory bowel disease? What is the main finding and its importance? Peripheral non-invasive focused ultrasound targeted to the celiac plexus in a rat model of ulcerative colitis improved stool consistency and reduced stool bloodiness, which coincided with a longer and healthier colon than in animals without focused ultrasound treatment. The findings suggest that this novel neuromodulatory technology could serve as a plausible therapeutic approach for improving symptoms of inflammatory bowel disease. Individuals suffering from inflammatory bowel disease (IBD) experience significantly diminished quality of life. Here, we aim to stimulate the celiac plexus with non-invasive peripheral focused ultrasound (FUS) to modulate the enteric cholinergic anti-inflammatory pathway. This approach may have clinical utility as an efficacious IBD treatment given the non-invasive and targeted nature of this therapy. We employed the dextran sodium sulfate (DSS) model of colitis, administering lower (5%) and higher (7%) doses to rats in drinking water. FUS on the celiac plexus administered twice a day for 12 consecutive days to rats with severe IBD improved stool consistency scores from 2.2 +/- 1 to 1.0 +/- 0.0 with peak efficacy on day 5 and maximum reduction in gross bleeding scores from 1.8 +/- 0.8 to 0.8 +/- 0.8 on day 6. Similar improvements were seen in animals in the low dose DSS group, who received FUS only once daily for 12 days. Moreover, animals in the high dose DSS group receiving FUS twice daily maintained colon length (17.7 +/- 2.5 cm), while rats drinking DSS without FUS exhibited marked damage and shortening of the colon (13.8 +/- 0.6 cm) as expected. Inflammatory cytokines such as interleukin (IL)-1 beta, IL-6, IL-17, tumour necrosis factor-alpha and interferon-gamma were reduced with DSS but coincided with control levels af

关键词： Integrin Inhibitor   Interleukin   Anti-IL12-23   CD   UC  

摘要： BACKGROUND & AIMS: There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy. METHODS: In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84;95% CI, 0.68-1.05;I2 = 13.9%;Q test P = .17) or ustekinumab (15 studies: OR, 1.1;95% CI, 0.87-1.38;I2 = 11%;Q test P = .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13;95% CI, 0.48-2.68;I2 = 0;Q test P = .96) or ustekinumab (2 studies: OR, 0.58;95% CI, 0.21-1.16;I2 = 47%;Q test P = .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17;95% CI, 0.75-1.84;I2 = 0;Q test P = .110). CONCLUSIONS: In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab w

关键词： CX3CR1   Macrophage   Inflammatory bowel disease   IBD classification   Precision therapy  

摘要： Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), is featured by overactive immune response and enduring course of unrestrained colitis. Genetic predisposition and environmental factors are fundamental in disease progression. Notably, microbiota dysregulation and its interaction with host mucosal barrier perplex disease phenotype. Under experimental setting, distinct mouse models are established to mimic human colitis process, including infection induced dysbiosis, dextran sulfate sodium (DSS) etc. induced barrier destruction, anti-CD40 L induced innate immunity dominant colitis and T cell transfer colitis model. Thus, from a more detailed aspect, IBD is heterogeneous and can be further classified into different subtypes based on the specific etiological pathways. As a typical inflammatory disorder, various immune cell types are involved in IBD pathogenesis. Among them, macrophages are believed to play a pivotal role. CX3CR1(+) macrophages, deriving from peripheral patrolling CD14(+) Ly6C(hi) monocytes, are specified cell population dwelling in the gut. Accumulating evidence suggests that CX3CR1(+) macrophages are critical for mucosal homeostasis and IBD pathogenesis, while some conflicts exist in current studies with both protective and harmful effects being revealed. Herein, we reviewed published literatures and found that the observed discrepancies stem from many aspects: the expression level of CX3CR1, the confounding dendritic cell subsets and most importantly, the different colitis stages and subtypes. Overall, CX3CR1 targeting strategy could be powerful weapon in fighting against colitis, but at the same time, the precise etiological and pathological mechanisms should be cautiously examined concerning the appropriate usage of CX3CR1 targeted therapy.

关键词： Crohn disease   Ulcerative colitis   Height   Weight   Puberty   Bone mass  

摘要： Growth delay with height and weight impairment is a common feature of pediatric inflammatory bowel diseases (PIBD). Up to 2/3 of Crohn Disease patients have impaired weight at diagnosis, and up to 1/3 have impaired height. Ulcerative colitis usually manifests earlier with less impaired growth, though patients can be affected. Ultimately, growth delay, if not corrected, can reduce final adult height. Weight loss, reduced bone mass, and pubertal delay are also concerns associated with growth delay in newly diagnosed PIBD patients. The mechanisms for growth delay in IBD are multifactorial and include reduced nutrient intake, poor absorption, increased fecal losses, as well as direct effects from inflammation and treatment modalities. Management of growth delay requires optimal disease control. Exclusive enteral nutrition (EEN), biologic therapy, and corticosteroids are the primary induction strategies used in PIBD, and both EEN and biologics positively impact growth and bone development. Beyond adequate disease control, growth delay and pubertal delay require a multidisciplinary approach, dependent on diligent monitoring and identification, nutritional rehabilitation, and involvement of endocrinology and psychiatry services as needed. Pitfalls that clinicians may encounter when managing growth delay include refeeding syndrome, obesity (even in the setting of malnutrition), and restrictive diets. Although treatment of PIBD has improved substantially in the last several decades with the era of biologic therapies and EEN, there is still much to be learned about growth delay in PIBD in order to improve outcomes.

关键词： Inflammatory bowel disease   Gastrointestinal tract cancer   Meta-analysis  

摘要： Purpose The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. Methods We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. Results Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. Conclusions IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

关键词： anti‐   TNF   biologicals   IBD   patient reporting   PRO  

摘要： Purpose To assess the agreement between patient-reported and health care provider-reported medical information in inflammatory bowel disease (IBD). Methods This multicentre, prospective, event monitoring study enrolled adult Crohn's disease (CD) and ulcerative colitis (UC) patients treated with a biological in four medical centers in the Netherlands. At two-monthly intervals, patients completed questionnaires on biological use, combination therapy and indication. The patient-reported information was compared with their electronic health records (EHRs) and analysed for percentage agreement and Cohen's kappa. A reference population from a prospective IBD registry was used to assess the representativeness of the study population. Results In total, 182 patients (female 50.5%, mean age 42.2 years, CD 76.9%) were included in the analysis. At baseline, 51.0% of the patients were prescribed an immunomodulator (43.9% thiopurines, 7.1% methotrexate), and patients were prescribed biologicals as follows: 59.3% infliximab, 30.2% adalimumab, 9.3% vedolizumab, and 1.1% ustekinumab. Agreement on patient-reported indication and biological use was almost perfect (kappa = 0.878 and kappa = 1.000, respectively);substantial for combination therapy (kappa = 0.672). Gender, age, type of IBD, biological use and combination therapy were comparable with the reference population. Conclusion Systematic patient-reporting by questionnaires was reliable in retrieving indication and treatment specific information from IBD patients. These results indicate that the use of patient-reporting outcomes in daily IBD practice can ensure reliable information collection.