Search

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

The rate of pediatric inflammatory bowel disease (IBD) has been increasing over the last decade and this increase has occurred most rapidly in the youngest children diagnosed

The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.

The role of gut microbiota in early life and its impact on gut health and subsequent diseases remain unclear. There is a lack of research and awareness in this area, especially in the Asia-Pacific region, including Malaysia. This paper reports the position of a Malaysian Working Group on some key issues surrounding gut microbiota in early life and its role in gut health and diseases, as well as experts' stand on probiotics and prebiotics. The group reached a consensus that certain factors, including elective caesarean; premature deliveries; complementary feeding; use of antibiotics, prebiotics and/or probiotics; and exposure to the external environmental, have an impact on gut microbiota in early life. However, as evidence is lacking, especially from the Asia-Pacific region, further studies are needed to understand how gut microbiota in early life affects subsequent diseases, including allergy, inflammatory bowel disease, obesity and infantile colic. Lastly, although beneficial in acute diarrhoeal disease and probably allergic eczema, probiotics (and/or prebiotics) should be used cautiously in other gut dysbiotic conditions until more data are available.

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1–8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn’s and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

Article first published online 29 September 2015. Supplemental Digital Content is Available in the Text., Biologic therapy with anti–tumor necrosis factor (TNF)-α antibody medications has become part of the standard of care for medical therapy for patients with inflammatory bowel disease and may help to avoid surgery in some. However, many of these patients will still require surgical intervention in the form of bowel resection and anastomosis or ostomy formation for the treatment of their disease. Postsurgical studies suggest up to 30% of patients with inflammatory bowel disease may be on or have used anti–TNF-α antibody medications for disease management preoperatively. Significant controversy exists regarding the potential deleterious impact of these medications on the outcomes of surgery, specifically overall and/or infectious complications. In this position statement, we systematically reviewed the literature regarding the potential risk of anti–TNF-α antibody use in the perioperative period, offer recommendations based both on the best-available evidence and expert opinion on the use and timing of anti–TNF-α antibody therapy in the perioperative period, and discuss whether or not the presence of these medications should lead to an alteration in surgical technique such as temporary stoma formation.

BACKGROUND AND AIMS: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients. METHODS: A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature. RESULTS: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; macronutrients needs; trace elements, minerals, and vitamins; nutrition as a primary therapy of pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and dietary compounds and the risk of IBD. CONCLUSIONS: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial. Various causes include iron deficiency, anemia of inflammation and chronic disease, vitamin deficiencies, hemolysis, or myelosuppressive effect of drugs. Anemia and iron deficiency in these patients may be underestimated because of their insidious onset, lack of standardized screening practices, and possibly underappreciation that treatment of anemia is also required when treating IBD. Practitioners may hesitate to use oral preparations because of their intolerance whereas intravenous preparations are underutilized because of fear of adverse events, availability, and cost. Several publications in recent years have documented the safety and comparative efficacy of various intravenous preparations. This article reviews management of anemia in children with IBD, including diagnosis, etiopathogenesis, evaluation of a patient, protocol to screen and monitor patients for early detection and response to therapy, treatment including parenteral iron therapy, and newer approaches in management of anemia of chronic disease. This report has been compiled by a group of pediatric gastroenterologists serving on the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) IBD committee, in collaboration with a pediatric hematologist, pharmacist, and a registered dietician who specializes in pediatric IBD (IBD Anemia Working Group), after an extensive review of the current literature. The purpose of this review is to raise awareness of under-diagnosis of anemia in children with IBD and make recommendations for screening, testing, and treatment in this population.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Biological agents are widely used in rheumatology, dermatology and inflammatory bowel disease. Evidence about their efficacy and safety has been strengthened for all those therapeutic indications over the last decade. Biosimilar agents are monoclonal antibodies similar to previously approved biologics. In the European Union, they have been approved for all the indications in the management of immune-mediated inflammatory diseases (IMIDs), although data only in rheumatoid arthritis and ankylosing spondylitis are currently available. Direct evidence on efficacy, safety, and immunogenicity of biosimilars is mandatory in psoriasis, psoriatic arthritis, and inflammatory bowel disease, as well as in children. Based on the current evidence in the literature, we present the joint official position of the Italian Societies of Rheumatology, Dermatology and Inflammatory Bowel Disease on the use of biosimilars in IMIDs.

Objective Although paediatric-onset IBD is becoming more common, few medications have a registered paediatric indication. There are multiple hurdles to performing clinical trials in children, emphasising the importance of choosing an appropriate outcome measure, which can facilitate enrolment, and thereby also drug approval. The aim of this consensus statement is to highlight paediatric specific issues and key factors critical for the optimal conduct of paediatric IBD trials. Design The Paediatric European Crohn9s and Colitis Organisation (ECCO) committee has established an international expert panel to determine the best outcome measures in paediatric IBD, following a literature search and a modified Delphi process. All recommendations were endorsed by at least 80% agreement. Results Recognising the importance of mucosal healing (MH), the panel defined steroid-free MH as primary outcome measure for all drugs of new category with one or two postintervention endoscopies per trial (at 8–12 weeks and/or 54 weeks). Since endoscopic evaluation is a barrier for recruitment in children, trials with medications already shown to induce MH in children or adults, could use paediatric-specific disease activity scores as primary outcome, including a modified Paediatric Crohn9s Disease Activity Index in Crohn9s disease and the Paediatric Ulcerative Colitis Activity Index in UC. Secondary outcomes should include safety issues, MR enterography-based damage and inflammatory scores (in Crohn9s disease), faecal calprotectin, quality of life scales, and a patient-reported outcome. Conclusions It is crucial to perform paediatric trials early in the development of new drugs in order to reduce off-label use of IBD medication in children. The thoughtful choice of feasible and standardised outcome measures can help move us towards this goal.

Background: The importance of a holistic approach with a comprehensive multidisciplinary team, including nutritional and psychosocial support, is becoming well recognised as a key contributor to optimal care in paediatric inflammatory bowel disease [IBD]. The Paediatric committee of ECCO [P-ECCO] aimed to determine important components that would contribute to quality of care in a paediatric IBD centre [henceforth 'quality items']. Methods: First, a list of items has been generated by a Delphi group of 111 international paediatric IBD experts. Through an iterative process, the group graded and ranked the items according to their perceived relative contribution to quality care. We then surveyed 101 paediatric IBD centres affiliated with the Porto and Interest groups of ESPGHAN in Europe and with the ImproveCareNow registry in North America, exploring the availability of the retained items in their centres. Results: A total of 68 items were generated and reduced to a list of 60 ranked order items, grouped in six domains: Facility, Personnel, Management, Supportive Services, Patient Support and Accessibility, and Academia and Communications. Of the retained items, 52 [88%] were present in most of the 101 high-performing paediatric IBD centres, and there was a trend for increased availability with increased patient volume at the centres. Conclusion: In this P-ECCO study, we attempted to tabulate, for the first time in paediatrics, 60 quality items that paediatric IBD referral centres may wish to include.

Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic, relapsing conditions resulting from uncontrolled inflammation of the intestinal mucosa. Both conditions are associated with significant disability and patients with CD face higher mortality rates compared to the general population. The increasing understanding of the immunological basis of the disease led to the introduction of biologic therapies targeting key pathways of the natural and adaptive immune response such as Tumor Necrosis Factor alpha (TNF-alpha) inhibitors and, more recently, integrin-receptor antagonists. Treatment with TNF-alpha inhibitors improved clinical and patient-reported outcomes for many patients who did not benefit from conventional therapy. However, a sizeable share of patients still face suboptimal outcomes due to primary or secondary therapy failure. With the introduction of VDZ, a biologic treatment targeting novel IBD-relevant biologic pathways, it is crucial to understand how to integrate such innovations into current clinical practice. To this end, a panel of 14 Italian experts in the management of IBD met for a roundtable discussion. Recommendations concerning the management of moderate-to-severe IBD based on experts' opinions and literature review are discussed in the present report. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) are a collection of chronic idiopathic inflammatory disorders of the intestine and/or colon. Although the pathophysiology of IBD is not known with certainty, a growing body of experimental and clinical data suggests that chronic gut inflammation may result from a dysregulated immune response to normal bacterial antigens. This uncontrolled immune system activation results in the sustained overproduction of reactive metabolites of oxygen and nitrogen. It is thought that some of the intestinal and/or colonic injury and dysfunction observed in IBD is due to elaboration of these reactive species. This review summarizes the current state-of-knowledge of the role of reactive oxygen species and nitric oxide in the pathophysiology of IBD.

An integrated model of care has been used effectively to manage chronic diseases; however, there is limited, yet encouraging evidence on its introduction in the management of inflammatory bowel disease (IBD), a chronic gastrointestinal condition. Here, the rationale for and implications of introducing an integrated model of care for patients with IBD are discussed, with a particular focus on psychology input, patient-centred care, efficiency as perceived by patients and doctors, financial implications and the possible means of model introduction. This is a discussion paper on the integrated model of care for IBD against a background of what has been learned from an integrated model of care established in other chronic conditions. Although limited, the emerging data on an integrated model of care in IBD are encouraging with respect to patient outcomes and savings in healthcare costs. In other conditions, the model has been well received by both patients and practitioners, although the loss of autonomy by doctors is listed among its drawbacks. The cost-effectiveness data are now sufficiently convincing to recommend the model's acceptance in principle. The model should be promoted at the policy level rather than by individual practitioners to facilitate equal access for patients with IBD on a larger scale than currently. Refereed/Peer-reviewed

orrigendum to “Expert consensus paper on the use of Vedolizumab or the management of patients with moderate-to-severe nflammatory Bowel Disease” [Dig. Liver Dis. 48 (2016) 360–370] lessandro Armuzzia, Paolo Gionchettib, Marco Dapernoc, Silvio Danesed, mbrogio Orlandoe, Maria Lia Scribanof, Maurizio Vecchig, Fernando Rizzellob,∗, on ehalf of the GIVI (Gruppo Italiano su Vedolizumab nelle IBD) Group1

BACKGROUND—Excessive mucosal generation of cytokines and eicosanoids has been reported in vitro in ulcerative colitis (UC) using traumatising biopsy techniques, and in vivo using time consuming rectal dialysis. AIMS—To validate a simple filter paper technique to profile rectal mucosal production of cytokines and eicosanoids in vivo in patients with UC compared with controls. PATIENTS—Forty one patients with UC (21 with active disease) and 16 controls were studied. METHODS—In vitro, recovery of known concentrations of cytokine or mediator applied to filter papers was measured by ELISA following incubation in buffer. In vivo, patients and controls had filter papers apposed to the rectal mucosa briefly through a rigid sigmoidoscope. Filter papers were then incubated prior to assay by ELISA. RESULTS—In vitro validation studies showed that the filter paper technique could be used to measure mucosal release of interleukin-1β (IL-1β), tumour necrosis factor α (TNF-α), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2), but not interferon γ (IFN-γ). Mucosal release of IL-1β, TNF-α, TXB2 and PGE2 were significantly increased in active UC (p=0.001) and correlated directly with disease activity (p=0.02). CONCLUSIONS—The filter paper technique confirmed increased rectal mucosal release of cytokines and eicosanoids in UC, in proportion to disease activity. The simplicity, safety and speed of the technique make it a practicable option for use in the outpatient clinic to study the pathogenesis of inflammatory bowel disease, and potentially its response to treatment. Keywords: cytokines; eicosanoids; ulcerative colitis; rectal dialysis

Introduction Self management in inflammatory bowel disease (IBD) has proven itself to be a safe and cost effective method of managing the more stable IBD patients. It is however not without its issues. In February 2012 we introduced our IBD-Supported, Self Help and Management Programme (IBD-SSHAMP) with specialist nursing and consultant support to try an avoid some of the issues inherent on relying on self management alone. We now have 3 years experience in running IBD-SSHAMP with regular virtual telephone clinics and personalised web-site supported management. Some of the outcomes seen in transferring patients from self management to a supported self management system are presented here. Method In total 425 of our more stable IBD patients are now managed in the community on IBD-SSHAMP. Using hospital coding data, Evolve (the hospital–s electronic record system), the National IBD Registry and HICSS (the endoscopy reporting software) we reviewed the following aspects;- number of flares, steroid courses, emergency outpatient clinics, and hospital admissions. By continuing to keep them under a close monitoring system we were interested to know if improvements would be seen in their compliance with prophylactic medication and their uptake on surveillance colonoscopy. Results In 3 years just 43 flares were experienced in this cohort, and most of these were successfully treated using mesalazines alone. Steroids were however required in 16 of these patients, most of which was directed by telephone consultation. In that 3 year period only 8 required urgent outpatient appointments (OPAs) were required and no patients needed hospital admission. Many patients on pure self management had been lost to follow up and had avoided surveillance colonoscopy. Unfortunately after bringing these patients back into a monitored and supported management system we have subsequently found 3 colorectal cancers (ascending, sigmoid and ano-rectal) within this group. Most of these patients were overdue their surveillance colonoscopy, but despite the known risks 114 still declined surveillance. Other cancers were also found amongst this cohort, including; 2 breast cancers, one prostrate cancer and one skin cancer. Most were happy with the new IBD- SSHAMP, but 3 patients chose to attend standard hospital based OPAs. Conclusion IBD-SSHAMP has been shown to be a highly efficient and cost effective method of keeping community based IBD patients under close specialist review. Reductions in flares, emergency OPAs and admissions have been seen. It has been well received by the patients who prefer to be supported rather than discharged and left alone to self manage. Disclosure of interest None Declared.

Dear Editor, We thank Drs. Selinger, Leong and McLaughlin for their interest and insightful comments on our work. Their previous study on patients’ understanding and preference on methods of conveying statistical information is truly a pioneering work on this topic in the area of inflammatory bowel disease. The study shows the preference of patients for relative risk reduction (RR) over optical illustrations such as Cates Plots (CP) …

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.

Paired related homeobox 1 (PRRX1) is a newly identified transcription factor that regulates the expression of various genes. We aimed to investigate the roles of PRRX1 and Matrix metalloproteinases (MMP)13 in dextran sulfate sodium (DSS)-induced inflammation and barrier dysfunction of NCM460 cells. PRRX1 expression in the mucosal tissues of patients with ulcerative colitis was analyzed using the GSE87466 microarray. PRRX1 and MMP13 expression was examined using Western blotting and RT-qPCR following the exposure of the NCM460 cells to DSS. The JASPAR database was used to predict the binding sites of PRRX1 to the MMP13 promoter, which was verified by luciferase reporter and chromatin immunoprecipitation assays. MMP13 expression was then detected following PRRX1 silencing or overexpression. The levels of inflammatory factors were determined using ELISA. Finally, the expression of intestinal barrier function-related proteins was evaluated using Western blotting and cellular permeability was detected by Transepithelial electrical resistance. PRRX1 was upregulated in the mucosal tissue samples of patients with UC. DSS induction upregulated PRRX1 and MMP13 expression. PRRX1 bound to the promoter of MMP13, which was further supported by the decreased expression of MMP13 observed following PRRX1 knockdown and its increased expression following PRRX1 overexpression. Furthermore, PRRX1 deletion decreased TNF-α, IL-1β and IL-6 levels in the DSS-challenged NCM460 cells, which were subjected to MMP13 overexpression. Moreover, PRRX1 silencing upregulated ZO-1, occludin and claudin-1 expression and elevated the TEER value, whereas MMP13 overexpression attenuated these effects. Collectively, PRRX1 activates MMP13, which in turn promotes the DSS-induced inflammation and barrier dysfunction of NCM460 cells.