关键词： Anti-TNF alpha   Biosimilars   Crohn's disease   Inflammatory bowel disease   Tumor necrosis factor alpha   Ulcerative colitis  

摘要： The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： Morinda citrifolia   Noni   Polysaccharide   Intestinal mucosal barrier   Tight junction proteins   Mucus  

摘要： Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, has gradually emerged as a public health challenge worldwide. Morinda citrifolia (noni) has been used to treat various ailments by Pacific Islanders for centuries. In this work, noni fruit polysaccharide (NFP) was obtained by hot water extraction, and its structure was initially explored. The molecular weight of NFP was approximately 456 kDa, and its monosaccharide components predominantly consisted of Gala (58.44%), Gal (4.44%), Glu (21.13%), Rha (4.84%), and Ara (2.16%) to form galacturonic acid, rhamnogalacturonan-I, arabinogalactan, and arabinan. The protective effect of NFP on the intestinal mucosal barrier was then investigated using DSS-induced IBD model mice. Whereas DSS treatment inhibited intestinal mucosal expression and destroyed the tight junction of epithelial cells, by contrast, NFP promoted mucosal and tight junction protein (zonula occludens-1 and occludin) expression. In conclusion, NFP improved the clinical diagnosis of acute colitis in IBD mice and may present a potential source of IBD treatment.

关键词： very early-onset inflammatory bowel disease   whole-exome sequencing   immunodeficiency  

摘要： Purpose of Review Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. However, a subset of patients with IBD diagnosed <6 years of age, known as very early-onset (VEO)-IBD, can be phenotypically and genetically distinct from older onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to the underlying genomic and immunologic drivers of disease, and the significant impact on our therapeutic decisions. Recent Findings VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression, and poor response to most conventional therapies. This article will review some of the genetic findings in this population and the subsequent impact on therapy, with targeted approaches. Summary Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. An integrated approach combining genetics, immunology, and traditional IBD evaluations can lead to the identification of causal defects that directly impact management. These strategies can also be employed in older onset refractory IBD.

关键词： Inflammatory bowel disease   Epstein Barr-virus   Haemophagocytic lymphohistiocytosis   EBV-associated mucocutaneous ulcer  

摘要： Background and aimEpstein-Barr virus (EBV) is a proposed trigger in the etiopathogenesis of inflammatory bowel disease (IBD) and is associated with lymphoproliferative diseases. Nevertheless, testing for EBV DNA in the intestinal mucosa and screening for EBV infection before initiation of a drug therapy are not routinely performed. The aim of this article is to increase awareness of the relevance of EBV infection in specific clinical *** this short communication, we describe the disease course of three IBD patients with EBV infection, varying from EBV reactivation during disease flare up to a trigger of EBV-related mucocutaneous ulcer (EBV-MCU) and haemophagocytic lymphohistiocytosis (HLH).ResultsOur first patient was diagnosed with EBV reactivation-associated severe colitis and showed a rapid clinical improvement after induction therapy with infliximab and azathioprine. Without antiviral treatment, the patient remained in complete remission and no complications of EBV were seen. After diagnosing EBV-MCU in the second patient, immunosuppressive medication was discontinued and four infusions of rituximab resulted in a rapid clinical recovery and eventually complete response. After discontinuation of the immunosuppression in our last patient with haemophagocytic lymphohistiocytosis, treatment with a combination of corticosteroid and antiviral therapy resulted in a complete recovery over a time span of several *** infection has a wide variety of potentially life-threatening clinical manifestations in IBD patients. Testing for EBV in case of a flare up and screening for EBV before the start of immunosuppressive therapy will create awareness for EBV-related symptoms or complications during follow-up.

关键词： Crohn disease   EndoPAT   microvascular function   reactive hyperemia index   ulcerative colitis   vascular disease  

摘要： Background and Aims: Altered vascular flow is known to both play a role in the pathogenesis and influence the severity of inflammatory bowel disease (IBD). This phenomenon has been described in other systemic conditions and contributes to disease progression by facilitating inflammation and thrombosis. Microvascular dysfunction may represent an early sign of generalized vascular disease (VD). It manifests by failure to achieve a normal response of vasodilation and increased blood flow following a period of vaso-occlusion. Although thromboembolic complications are well described in IBD, their pathogenesis is not fully understood. This study sought to assess microvascular responsiveness in pediatric subjects with IBD, by recording postocclusion peripheral arterial pulsatile volume changes. Patients and Methods: A total of 32 pediatric subjects were studied, including 16 with IBD and 16 age-matched controls. All patients with IBD were in clinical remission, and none had known VD. Vascular reactivity was evaluated using the Itamar Medical EndoPAT2000, a noninvasive device utilizing plethysmography to measure microvascular flow. Results were reported as the reactive hyperemia index (RHI), indicating post- to preocclusion pulsatile volume changes. Results: Baseline characteristics, including body mass index, plasma lipid levels, hemoglobin, and serum albumin, were similar in both study groups. All patients with IBD were in clinical remission, assessed by standard disease activity scoring methods. Measurements of microvascular function indicated patients with IBD exhibited a mean RHI both within the range associated with VD risk in adults (<=1.67) and significantly lower than that in controls (IBD vs control = 1.66 vs 2.02, P = 0.036). Conclusions: Microvascular plethysmography is a safe and noninvasive method for assessing microvascular function in children with IBD. Patients with IBD in clinical remission demonstrate an attenuated, postocclusion microvascular hy

关键词： Bowel   Children   Gadolinium-based contrast agent   Inflammatory bowel disease   Magnetic resonance enterography  

摘要： BackgroundPediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their *** determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected *** and methodsWe conducted a retrospective study of 77 patients (7-18years;68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (), Fleiss kappa, ((F)), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard).ResultsThe pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%;0.713, P<0.001;P-value 0.549). Compared to combined endoscopy/histopathology, pre- vs. pre-/post-contrast sensitivity (67%, confidence interval [CI] 0.53-0.79 vs. 67%, CI 0.53-0.79) and specificity (80%, CI 0.59-0.92 vs. 68%, CI 0.46-0.84) varied little ( 0.42, P<0.001 and 0.32, P=0.003, respectively). The three readers had moderate agreement (85.2%;0.695, P=0.001;P-value 0.625). More penetrating complications were identified following contrast administration (P-value 0.04).ConclusionUse of a contrast agent does not improve the detection of active inflammation in the terminal ileum and colon compared to non-contrast MRE, although use of a contrast agent does aid in the detection of penetrating disease.

关键词： canine   histopathologic   gastrointestinal   endoscopy   disease activity  

摘要： Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant (P < .05) for duodenum (r = 0.42) and colon (r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant (P < .05) correlations were observed for crypt dilation (r = 0.42), lamina propria (LP) lymphocytes (r = 0.40), LP neutrophils (r = 0.45), mucosal fibrosis (r = 0.47), lacteal dilation (r = 0.39), and villus stunting (r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.

关键词： inflammatory bowel disease   venous thromboembolism   D-dimer   predictor   Caprini risk assessment model   Padua prediction score  

摘要： Background and Aim Venous thromboembolism (VTE) is a common complication of inflammatory bowel disease (IBD). The aim of the present study was to identify predictors of VTE in hospitalized patients with IBD. Methods Patients with IBD who were hospitalized from February 2015 to March 2016 at the Chiba University Hospital were included. VTE was detected using enhanced computed tomography, and VTE onset within 2 months after admission was assessed. Predictors of VTE onset were investigated with clinical factors during hospitalization. Availability of the Caprini risk assessment model and Padua prediction score at the time of admission was also assessed. Results Seventy-two patients with IBD were hospitalized, and central venous catheters were placed in 43 of the 72 patients. During the observation period, VTE occurred in six patients (8.3%);however, none died as a result of the condition. Cox proportional hazards regression analysis identified D-dimer values on admission as a risk factor that was highly associated with VTE onset (hazard ratio = 1.590;95% confidence interval, 1.132-2.233;P = 0.007) and significantly predicted the occurrence of VTE using the receiver operating characteristic curve (P = 0.005, area under the curve = 0.893). However, Caprini risk assessment model and Padua prediction scores were not useful tools for predicting VTE onset in patients with IBD. Conclusion In hospitalized patients with IBD, D-dimer values were highly associated with VTE onset. Therefore, measurement of D-dimer values on admission is critical for the management of thromboembolic complications in patients with IBD.

关键词： epidemiology   hospitalisation   treatment outcome   Crohn disease   ulcerative colitis  

摘要： Background High inflammatory bowel disease (IBD) rates have been reported in Australasia, but no state-wide studies have yet been performed. Aim This study estimates the 1-year incidence and point prevalence of IBD in the state of Tasmania, Australia. It also reports clinical outcomes after 12 months of diagnosis in an incident cohort. Methods A prospective, population-based study was performed collecting prevalent and incident state-wide cases from 1 June 2013 to 31 May 2014. Case data were identified from specialist doctors, pathology databases and hospital records. Age-standardised rates (ASR) were calculated based on World Health Organization 2000 standard population characteristics. Incident cases were followed up 12 months after diagnosis. Results There were 1719 prevalent cases: ASR for IBD, Crohn disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU) prevalence rates were 303.9, 165.5, 131.4 and 6.9 per 100 000 respectively. Prevalent CD cases were younger, with greater immunomodulator/biological use and bowel resections. There were 149 incident cases: ASR for IBD, CD, UC and IBDU incidence were 29.5, 15.4, 12.4 and 1.7 per 100 000 respectively. Incident CD cases were more likely than UC or IBDU to require escalation of medical therapy, hospitalisation and bowel resection, especially among those with penetrating or stricturing disease. They had a longer duration of symptoms prior to diagnosis. Conclusion IBD prevalence and incidence rates are high in Tasmania, comparable to data from other Australasian studies and those from Northern Europe and America. Poorer 12-month clinical outcomes occurred in complicated CD, with greater use of healthcare resources.

关键词： Child   Adolescent   Pediatric   Magnetic resonance imaging   Inflammatory bowel disease (IBD)   Crohn disease (CD)   Ulcerative colitis (UC)  

摘要： Inflammatory bowel disease (IBD) is an important cause of abdominal pain in the pediatric population. Magnetic resonance enterography (MRE) plays a crucial role in assessment of disease severity, location, extent of disease, and assessment for associated complications. As MR imaging technology has advanced, new techniques have been brought into clinical practice. Recent research has expanded our understanding of how the inflammatory processes in IBD manifest on MRE and improved radiology's ability to accurately assess the disease and its associated complications. This article discusses up-to-date MR imaging techniques and imaging manifestations of IBD in pediatric patients.