Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN)

The microbiome and immune system of the digestive tract are highly important in both health and disease. Exclusive enteral nutrition (EEN) is a common anti-inflammatory treatment in children with Crohn’s disease in the European countries, and the mechanism is most likely linked to changes in the intestinal microbiome. In the present study, EEN was given in two treatment periods several months apart to a patient with very severe, disabling juvenile idiopathic arthritis (JIA), with a remarkable clinical response as the result. The aim of the present study was to study how the EEN treatment influenced the microbiome and metabolome of this patient. Fecal samples from before, during, and between treatments with EEN were studied. The microbiome was analyzed by sequencing of 16S rRNA amplicons using Illumina MiSeq, and the metabolome was analyzed using nuclear magnetic resonance. The microbiome changed markedly from treatment with EEN, with a strong reduction of the Bacteroidetes phylum. Metabolic profiles showed clear differences before, during, and between treatment with EEN, where butyrate, propionate, and acetate followed a cyclic pattern with the lowest levels at the end of each treatment period. This patient with JIA showed remarkable clinical improvement after EEN treatment, and we found corresponding changes in both the fecal microbiome and the metabolome. Further studies are needed to explore the pathophysiological role of the intestinal canal in children with JIA.     

Exclusive enteral feeding as primary therapy for Crohn's disease in Australian children and adolescents: a feasible and effective approach

BACKGROUND: Exclusive enteral feeding has been shown to be as efficacious as corticosteroids in inducing remission in children with Crohn's disease (CD), with additional nutritional benefits. The use of polymeric formulae provides superior palatability and acceptance over elemental feeds, but polymeric formulae have not been universally adopted. The present retrospective analysis of enteral feeding in children with Crohn's disease aims to demonstrate the short-term benefits of enteral feeding in children upon disease activity and nutrition parameters. METHODS: The case records of children with CD managed with exclusive enteral nutrition (EEN) by a multidisciplinary team over a 2-year period were reviewed. Data relating to therapy, background disease details, and outcome were collated. Primary outcome measures established were weight change and disease activity (Pediatric Crohn's Disease Activity Index: PCDAI). RESULTS: Twenty-seven children received EEN with polymeric formulae. Fifteen children had newly diagnosed CD and 12 had known long-standing CD. Twenty-four children completed the prescribed period of EEN. Twelve of 15 (80%) newly diagnosed CD and seven of 12 (58%) with long-standing disease entered remission. Children with newly diagnosed CD responding to EEN took all feeds orally and gained an average of 4.7+/-3.5 kg with mean PCDAI decreasing from 37.1+/-10.8 to 6.7+/-5.1 after 8 weeks. In addition, four children continued supplementary polymeric formula (without other medical therapies) and all have maintained remission during an average follow-up period of 15.2 months. CONCLUSION: Exclusive enteral feeds induced remission in 80% of children with newly diagnosed CD (on intention-to-treat basis) when used as sole initial therapy while also improving nutritional status. All newly diagnosed children treated with EEN, who were able to establish feeds, achieved remission. In addition, remission may be prolonged with oral supplementary formula as sole ongoing treatment. Further study of the role(s) of enteral feeds and of longer-term benefits of enteral feeding in children with CD is now required.     

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and ‘dysbiosis’ is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non‐IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High‐quality studies have shown that VSL#3 (a high‐potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.     

Longer-Term Outcomes of Nutritional Management of Crohn’s Disease in Children

Background

While the short-term benefits of exclusive enteral nutrition (EEN) for induction of remission in children with Crohn’s disease (CD) are well documented, the longer-term outcomes are less clear.

Aim

This retrospective study aimed to ascertain the outcomes for up to 24 months following EEN in a group of children with CD.

Methods

Children treated with EEN as initial therapy for newly diagnosed CD over a 5-year period were identified. Details of disease activity, growth, and drug requirements over the period of follow-up were noted. Outcomes in children managed with EEN were compared to a group of children initially treated with corticosteroids.

Results

Over this time period, 31 children were treated with EEN and 26 with corticosteroids. Twenty-six (84 %) of the 31 children treated with EEN entered remission. Children treated with EEN exhibited lower pediatric Crohn’s disease activity index (PCDAI) scores at 6 months (p = 0.02) and received lower cumulative doses of steroids over the study period (p < 0.0001) than the group treated with corticosteroids. Height increments over 24 months were greater in the EEN group (p = 0.01). Although the median times to relapse were the same, the EEN group had a lower incidence of relapse in each time interval and survival curve analysis showed lower risk of relapse (p = 0.008).

Conclusions

EEN lead to multiple benefits beyond the initial period of inducing remission for these children, with positive outcomes over 2 years from diagnosis. Of particular clinical relevance to growing children was the reduced exposure to corticosteroids.     

Use of exclusive enteral nutrition in adults with Crohn’s disease: A review

Exclusive enteral nutrition(EEN)is well-established as a first line therapy instead of corticosteroid(CS)therapy to treat active Crohn’s disease(CD)in children.It also has been shown to have benefits over and above induction of disease remission in paediatric populations.However,other than in Japanese populations,this intervention is not routinely utilised in adults.To investigate potential reasons for variation in response between adult studies of EEN and CS therapy.The Ovid database was searched over a 6-mo period.Articles directly comparing EEN and CS therapy in adults were included.Eleven articles were identified.EEN therapy remission rates varied considerably.Poor compliance with EEN therapy due to unpalatable formula was an issue in half of the studies.Remission rates of studies that only included patients with previously untreated/new CD were higher than studies including patients with both existing and new disease.There was limited evidence to determine if disease location,duration of disease or age of diagnosis affected EEN therapy outcomes.There is some evidence to support the use of EEN as a treatment option for a select group of adults,namely those motivated to adhere to an EEN regimen and possibly those newly diagnosed with CD.In addition,the use of more palatable formulas could improve treatment compliance.     

Exclusive enteral nutrition induces early clinical,mucosal and transmural remission in paediatric Crohn’s disease

Background and aims

Exclusive enteral nutrition (EEN) induces clinical and mucosal healing (MH) in Crohn’s disease (CD), with MH the best determinant of future outcome. We investigated efficacy of EEN for inducing early clinical, biochemical, mucosal and transmural remission of CD and related early endoscopic response to outcomes at 1 year.

Methods

In a prospective, open label study 34 children (mean 13.1 years; 21 males) with new diagnosis CD were offered EEN, 26 completed a minimum 6 weeks EEN and underwent paired clinical, biochemical and endoscopic assessment at start and completion using PCDAI, BMI, CRP and Simple Endoscopic Score for CD (SES-CD). A subset, 16/26, had paired MR enterography scored. Early good endoscopic response (complete MH, or near complete, SES-CD 0–3) was related to outcome at 1 year.

Results

EEN improved mean PCDAI (37.88–7.01, p < 0.001; BMI Z scores (?1.54 to ?0.54, p < 0.01); weight Z score (?0.79 to ?0.08, p < 0.03); CRP (44.86–5.5, p < 0.001); endoscopy (SES-CD 14.28–3.88, p < 0.001) and MRE (5.14–2.79, p = 0.01). Of 26 children, 22 (84 %) achieved clinical remission; 20 (76 %) biochemical remission. Fifteen (58 %) had early good endoscopic response (11 complete, 4 near complete MH) and 3/14 (21 %) had complete transmural remission of ileal CD (MRE-CD: 0–1). Early good endoscopic response was associated with reduced endoscopic confirmed relapse (53 vs. 100 %, p = 0.02), anti-TNF use (33 vs. 88 %, p = 0.01) and hospitalisation (40 vs. 88 %) at 1 year.

Conclusions

EEN is effective for inducing early clinical, biochemical, mucosal and transmural remission. Early endoscopic remission improves outcomes at 1 year.     

Use of Exclusive Enteral Nutrition Is Just as Effective as Corticosteroids in Newly Diagnosed Pediatric Crohn’s Disease

Background

The efficacy of exclusive enteral nutrition (EEN) in induction of remission in pediatric Crohn’s disease (CD) is reported to be equivalent to that of corticosteroids (CS).

Aims

Our objective was to compare the efficacy of EEN and CS in inducing remission in pediatric onset CD and the effects of the treatment on nutritional status and bone mineral density (BMD).

Methods

Medical charts were retrospectively studied for patients diagnosed with CD between 2000 and 2010 at the Stollery children’s hospital in Edmonton, Alberta. Anthropometric and dual-energy X-ray absorptiometry (DXA) data were collected to assess effects of therapy; clinical remission, relapse, and severity were defined on the basis of the pediatric Crohn’s disease activity index.

Results

To induce remission at first presentation, 36 patients (mean age 12.9 years) received EEN and 69 (mean age 11.2 years) received CS. Remission (88.9 % in the EEN group versus 91.3 % in the CS group (p = 0.73) at 3 months) and relapse (40.6 vs. 28.6 %, respectively (p = 0.12) over 12 months) were similar in both treatment groups. Thirty-four patients had paired DXA scans at the time of diagnosis and one year later: 16 given EEN and 18 given CS. Change in BMD spine z-scores based on bone age adjusted for height and chronological age was greater for EEN patients but not statistically significant (Δz-score 0.30 vs. 0.03, p = 0.28).

Conclusions

EEN has similar efficacy to corticosteroids; however, EEN may lead to better BMD accrual. EEN should be preferred to corticosteroids as first-line therapy for induction of remission in pediatric CD.     

高血压脑出血术后早期鼻饲肠内营养的合理应用

目的观察早期肠内营养支持对高血压脑出血(HICH)术后病人在预后、营养状况、高代谢反应和胃肠道功能等方面的影响,探讨其作用机制和临床应用。方法36例病人随机分为早期肠内营养(EEN)、肠外营养(TPN)两组。EEN组经鼻胃管持续滴注瑞素;TPN组静脉输注肠外营养液。测定观察氮平衡、肌酐升高指数、血浆皮质醇、血糖、血浆胰岛素、胃肠道功能、体重及意识状态变化。结果两组2周内均为负氮平衡,EEN组6d的氮平衡优于TPN组(P<0.05);肌酐也呈下降趋势,但EEN组在术后14d、28d仍明显优于TPN组(P<0.01);两组血糖、血浆胰岛素和皮质醇术后显著上升,第6天达高峰,此时,EEN组三项指标水平显著低于TPN组(P<0.05或P<0.01);EEN组的皮质醇在28d时恢复正常,TPN组仍高于正常;6d时EEN组的反流、误吸无明显增加,研究期胃肠道症状发生率显著减少(P<0.05或P<0.01);28d神经功能缺损(GCS)评分EEN组高于TPN组两组间有统计学意义(P<0.05)。结论通过鼻胃管持续滴注喂养方法提供HICH病人有良好的耐受性。EEN支持对改善HICH术后全身营养状态和神经功能的恢复大有裨益。     

Juvenile idiopathic arthritis and the gut microbiome: Where are we now?

In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies.Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success.The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.     

Polymeric Formula Has Direct Anti-Inflammatory Effects on Enterocytes in an <Emphasis Type="Italic">in Vitro</Emphasis>Model of Intestinal Inflammation

Exclusive enteral nutrition using polymeric formula (PF) is a well-established therapeutic option for active Crohn’s disease; however, its mechanisms of action are unknown. We investigated the anti-inflammatory effects of PF in an in vitro model of epithelial cell inflammation. PF did not affect cell viability over a range of dilutions, but when PF was added to the culture medium the interleukin (IL)-8 response to proinflammatory stimuli was significantly reduced. This effect was due to PF acting directly on the cells as the IL-8 response was still reduced when PF was separated from the proinflammatory stimuli in a 2-compartment system. In the presence of PF, nuclear factor (NF)-κB nuclear migration was not inhibited; however, IκBα degradation was delayed. PF has direct anti-inflammatory effects upon immortalized colonic enterocytes. Therefore PF may, in part, modulate gut inflammation by directly reducing the inflammatory response of the intestinal epithelium.     

Efficacy of exclusive enteral nutrition in complicated Crohn’s disease

Aim: To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn’s disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture.

Method: Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287).

Results: Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18–60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohn's disease activity index significantly decreased (223.43?±?65.5 vs. 106.77?±?42.73, p?≤?.001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p?≤?.01), nutritional parameters increased (p?≤?.01) and the European Nutritional Risk Screening (2002) decreased (p?≤?.01).

Conclusion: EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.     

进展期胃癌根治术后早期肠内营养的临床应用研究

目的:探讨进展期胃癌根治术后早期肠内营养的安全性及效果。方法:83例接受根治性手术的进展期胃癌患者分成早期肠内营养(EEN)组和常规肠内营养(REN)组。EEN组给予早期肠内营养,REN组在肛门排气后给予肠内营养。两组患者分别于术前、术后进行营养和免疫指标监测,并记录各种并发症的发生情况。结果:EEN组并发症发生率较低;EEN组术后营养指标、免疫指标均较REN组改善明显。结论:早期肠内营养可以明显改善术后营养状况及提高机体免疫能力。     

A humanized microbiota mouse model of ovalbumin-induced lung inflammation

There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model reduced airway inflammation. In this Addendum, we provide additional data on the use of a humanized gut microbiota mouse model to study the development of asthma in children, highlighting the differences in immune development between germ-free mice colonized with human microbes compared to those colonized with mouse gut microbiota. We also demonstrate that there is no association between the composition of the gut microbiota in older children and the diagnosis of asthma, further suggesting the importance of the gut microbiota-immune system axis in the first 3 months of life.     

机械通气患者早期肠内营养支持的应用研究

目的:探讨早期肠内营养对机械通气患者营养状态和预后的影响.方法:机械通气患者30例,随机分为2组:早期肠内营养(EEN)组15例和早期完全胃肠外营养(TPN)组15例,在摄入相当热量和氮量的情况下,比较2组治疗前后营养状态、1周内撤机成功率、呼吸机相关性肺炎(VAP)发生率、平均营养费用、机械通气时间及平均住院天数.结果:治疗2周后,EEN组血清总蛋白、清蛋白、血红蛋白水平和氮平衡较治疗前明显升高(均P＜0.05),且均高于TPN组治疗后水平(均P＜0.05).上臂肌围、肱三头肌皮褶厚度2组无差异(P＞0.05).EEN组1周内撤机成功率明显高于TPN组(P＜0.05),机械通气时间、平均住院天数则明显低于TPN组(均P＜0.05).2组1周内VAP发生率差异无统计学意义(P＞0.05).结论:EEN能改善机械通气患者的营养状况和预后.只要患者胃肠道功能正常,应尽早实施肠内营养支持.     

Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients)

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.     

Step-up fecal microbiota transplantation (FMT) strategy

Gut dysbiosis is a characteristic of inflammatory bowel disease (IBD) and is believed to play a role in the pathogenesis of IBD. Fecal microbiota transplantation (FMT) is an effective strategy to restore intestinal microbial diversity and has been reported to have a potential therapeutic value in IBD. Our recent study reported a holistic integrative therapy called “step-up FMT strategy,” which was beneficial in treating steroid-dependent IBD patients. This strategy consists of scheduled FMTs combined with steroids, anti-TNF-α antibody treatment or enteral nutrition. Herein, we will elaborate the strategy thoroughly, introducing the concept, potential indication, methodology, and safety of “step-up FMT strategy” in detail.     

Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity

Objectives: Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype.

Materials and methods: We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses.

Results: No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n?=?9) and the control children without disease or associated autoantibodies (n?=?18).

Conclusions: Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.     

Effects of early enteral nutrition on Th17/Treg cells and IL-23/IL-17 in septic patients

BACKGROUND The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients;however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL- 23/IL-17 axis. AIM To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients. METHODS In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded. RESULTS Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P <0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728). CONCLUSION EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL- 23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.     

Toward enteral nutrition in the treatment of pediatric Crohn disease in Canada: A workshop to identify barriers and enablers

The treatment armamentarium in pediatric Crohn disease (CD) is very similar to adult-onset CD with the notable exception of the use of exclusive enteral nutrition (EEN [the administration of a liquid formula diet while excluding normal diet]), which is used more frequently by pediatric gastroenterologists to induce remission. In pediatric CD, EEN is now recommended by the pediatric committee of the European Crohn’s and Colitis Organisation and the European Society for Paediatric Gastroenterology Hepatology and Nutrition as a first-choice agent to induce remission, with remission rates in pediatric studies consistently >75%. To chart and address enablers and barriers of use of EEN in Canada, a workshop was held in September 2014 in Toronto (Ontario), inviting pediatric gastroenterologists, nurses and dietitians from most Canadian pediatric IBD centres as well as international faculty from the United States and Europe with particular research and clinical expertise in the dietary management of pediatric CD. Workshop participants ranked the exclusivity of enteral nutrition; the health care resources; and cost implications as the top three barriers to its use. Conversely, key enablers mentioned included: standardization and sharing of protocols for use of enteral nutrition; ensuring sufficient dietetic resources; and reducing the cost of EEN to the family (including advocacy for reimbursement by provincial ministries of health and private insurance companies). Herein, the authors report on the discussions during this workshop and list strategies to enhance the use of EEN as a treatment option in the treatment of pediatric CD in Canada.     

Anti-MCV and anti-CCP antibodies—diagnostic and prognostic value in children with juvenile idiopathic arthritis (JIA)

The goal of the study was to evaluate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) antibodies in juvenile idiopathic arthritis (JIA) comparing to anti-cyclic citrullinated peptide (anti-CCP). Thirty children with confirmed JIA diagnosis and 20 children as a control group were included into the study. Serum and synovial fluid levels of anti-CCP, anti-MCV, and immunoglobulin M rheumatoid factor (IgM-RF) antibodies have been assessed. Anti-MCV was positive in 11/30 (36.6 %), whereas anti-CCP positivity was found in 12/30 (40 %) children with JIA. Among 11 children with JIA positive for anti-MCV, five (45.5 %) were also positive for anti-CCP and among 18 JIA children negative for anti-CCP, six (33.33 %) were also anti-MCV positive. Six out of 30 JIA children were found to be IgM-RF positive. In general, two out of all those 11 anti-MCV-positive patients demonstrated oligoarthritis and 9/11 had polyarticular type of onset. Anti-MCV serum concentration correlated positively with anti-CCP (p = 0.004). Almost 60 % of children in early stage of JIA were anti-MCV positive. Levels of anti-CCP antibodies correlated positively with the disease activity (p = 0.0014) and radiological outcome (p = 0.00017). In all synovial fluid samples, the concentration of autoantibodies was under the cut-off values. The results of our study indicate that anti-MCV as well as anti-CCP antibodies may be helpful in the diagnosis of JIA, especially in the early course of the disease. Anti-MCV antibodies could identify a group of children with JIA which is negative for anti-CCP antibodies and RF. However, it appears that in JIA, anti-CCP rather than anti-MCV antibodies have impact on radiographic changes.