[The duodenal microbiota composition in children with active coeliac disease is influenced by the degree of enteropathy]. / La composición de la microbiota duodenal en niños con enfermedad celíaca activa está influenciada por el grado de enteropatía.

OBJECTIVES: To establish whether the duodenal mucosa microbiota of children with active coeliac disease (CD) and healthy controls (HC) differ in composition and biodiversity. MATERIAL AND METHODS: Samples of duodenal biopsies in 11 CD patients were obtained at diagnosis, and in 6 HC who were investigated for functional intestinal disorders of non-CD origin. Total duodenal microbiota and the belonging to the genus Lactobacillus using PCR-denaturing gradient gel electrophoresis (DGGE) were analysed. The banding patterns obtained in the resulting gels were analysed to determine the differences between the microbiota of CD patients and HC (FPQuest 4.5) while environmental indexes (richness, diversity and habitability) were calculated with the Past version 2.17 program. RESULTS: The intestinal microbiota of patients with Marsh 3c lesion showed similarity of 98% and differs from other CD patients with other type of histologic lesion as Marsh3a, Marsh3b and Marsh2. The main differences were obtained in ecological indexes belonging to the genus Lactobacillus, with significant richness, diversity and habitability reduction in CD patients. In CD bands were categorized primarily with Streptococcus, Bacteroides and E.coli species. In HC the predominant bands were Bifidobacterium, Lactobacillus and Acinetobacter, though the Streptococcus and Bacteroides were lower. CONCLUSIONS: The celiac patients with major histological affectation presented a similar microbiota duodenal. The ecological indexes applied to the genus Lactobacillus were significantly reduced in CD.

[Exclusive enteral nutrition continues to be first line therapy for pediatric Crohn's disease in the era of biologics]. / La nutrición enteral exclusiva continua siendo el tratamiento de primera línea en la enfermedad de Crohn pediátrica en la era de los biológicos.

INTRODUCTION: Exclusive enteral nutrition (EEN) has been to be more effective than corticosteroids in achieving mucosal healing without their side effects. OBJECTIVES: To determine the efficacy of EEN in terms of inducing clinical remission in newly diagnosed CD children and to study the efficacy of this therapeutic approach in improving the degree of intestinal mucosa inflammation. MATERIALS AND METHODS: The medical records of patients with newly diagnosed Crohn's disease treated with EEN were reviewed retrospectively. The degree of mucosal inflammation was assessed by fecal calprotectin (FC). Remission was defined as a PCDAI<10. RESULTS: Forty patients (24 males) were included, the age at diagnosis was 11.6 ± 3.6 years. Of the 34 patients who completed the EEN period, 32 (94% per-protocol analysis) achieved clinical remission. This percentage fell to 80% in the intention-to-treat analysis. The compliance rate was 95%. Duration of EEN was 6.42 weeks (IQR 6.0-8.14). FC was significantly higher in patients with moderate and severe disease. Median baseline FC levels (680 µg/g) decreased significantly to 218 µg/g (P<0.0001) after EEN. We found a statistically significant correlation between FC and PCDAI (rho=0.727; P<0.0001). Early use of thiopurines (< 8 weeks) versus subsequent use was not associated with improved outcomes during the follow-up. CONCLUSIONS: EEN administered for 6-8 weeks is effective for inducing clinical remission and decreasing the degree of mucosal inflammation. We did not find differences in terms of maintenance of remission in patients treated early with thiopurines.

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.

Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.

The complete picture of changing pediatric inflammatory bowel disease incidence in Spain in 25 years (1985-2009): the EXPERIENCE registry.

OBJECTIVES: A growing incidence of pediatric IBD (PIBD) in southern Europe has been recently reported. The SPIRIT registry (1996-2009) confirmed these tendencies in Spain. Our aim is to obtain data from 1985 to 1995 and describe the complete picture of PIBD presentation changes in Spain in the last 25years. METHODS: A retrospective survey of incident PIBD in the period 1985-1995 was performed. Patients' data were obtained from the hospitals' databases and compared with the published data from the 1996 to 2009 period. Seventy-eight IBD reference centers took part in this survey. RESULTS: Data from 495 patients were obtained: 278 CD (56.2%), 198 UC (40%), and 19 IBDU (3.8%); 51.7% were female, with higher predominance both in UC (58.6%) and in IBDU (57.9%), but not in CD (46.4%). Median (IQR) age at diagnosis was 12.9 (10.0-15.7) years, with significant differences among IBD subtypes: CD: 13.1 (10.8-16.0) vs UC: 12.4 (9.4-15.1) vs IBDU: 7.5 (3.0-13.0) (p≤0.001). These results are significantly different to the ones in the SPIRIT registry, with a higher proportion of IBDU, younger age and male predominance. The data from both periods taken together give a complete picture of a 25-year period. An annual increase of incident patients was observed, with a ten-fold increase over this period. CONCLUSION: These data extend the epidemiological trends to a full 25-year period (1985-2009). PIBD incidence in Spain has experienced a sixteen-fold increase. The IBD subtype, localization of the affected segment, age- and sex distribution observed are in accordance with our previously published ones of 1996-2009.

Oral tacrolimus for pediatric steroid-resistant ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) occurring during childhood is generally extensive and is associated with severe flares that may require intravenous steroid treatment. In cases of corticosteroid resistance is necessary to introduce a second-line treatment to avoid or delay surgery. AIMS: To describe the efficacy and safety of oral tacrolimus for the treatment of severe steroid-resistant UC. METHODS: We performed a retrospective study that included all patients under age 18 suffering from severe steroid-resistant UC treated with oral tacrolimus during the period January 1998 to October 2012 and with a follow-up period after treatment of 24 months or more. RESULTS: A total of ten patients were included. The age at baseline was 9.4±4.9 years, and the time from diagnosis was 1.3 months (IQR, 1-5.7). Seven of the patients were in their first flare of disease. All of them received an oral dose of 0.12 mg/kg/day of tacrolimus divided in two doses. Trough plasma levels of tacrolimus were maintained between 4 and 13 ng/ml. Response was seen in 5/10 patients at 12 months, colectomy was eventually performed in 60% of patients during the follow-up period. CONCLUSIONS: Tacrolimus is useful in inducing remission in patients with severe steroid-resistant UC, preventing or delaying colectomy, and allowing the patient and family to prepare for a probable surgery. Tacrolimus may also be used as a treatment bridge for corticosteroid-dependent patients until the new maintenance therapy takes effect.

Analysis of the Spanish national registry for pediatric home enteral nutrition (NEPAD): implementation rates and observed trends during the past 8 years.

BACKGROUND/OBJECTIVES: The home enteral nutrition (HEN) provides nutritional support to children with chronic diseases who are nutritionally compromised and allows them to be discharged more quickly from hospitals. In 2003, a web-based registry (Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria, Pediatric Ambulatory and Home Enteral Nutrition -NEPAD-) was created with the objective of gathering information about pediatric HEN practices in Spain. AIM: The aim of this study was to report the implementation of the NEPAD (Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria, Pediatric Ambulatory and Home Enteral Nutrition) registry of pediatric HEN in Spain and to analyze data evolution trends from 2003 to 2010. SUBJECTS/METHODS: The data from the Spanish NEPAD registry were analyzed according to the following variables: demographic data, diagnosis, indication for HEN, nutritional support regime and administration route. RESULTS: Over the study period, 952 patients (1048 episodes) from 20 Spanish hospitals were included in the NEPAD registry. The most frequent indication for HEN was decreased oral intake (64%), and neurological disease was the most prevalent illness. HEN was delivered via a nasogastric tube in 573 episodes (54.7%), by gastrostomy in 375 episodes (35.8%), oral feeding in 77 episodes (7.3%) and by jejunal access in 23 episodes (2.2%). Significant differences in the mode of administration were observed based on the pathology of the child (χ(2), P<0.0001). The cyclic feeding was the most widely used technique for the administration of HEN. Most of the patients used a pump and a polymeric formula. Transition to oral feeding was the primary reason for discontinuation of this type of support. CONCLUSIONS: Since the NEPAD registry was established in Spain, the number of documented patients has increased more than 25-fold. Many children with chronic illness benefit from HEN, mainly those suffering from neurological diseases.

Consensus on paediatric enteral nutrition access: a document approved by SENPE/SEGHNP/ANECIPN/SECP.

Standardization of clinical procedures has become a desirable objective in contemporary medical practice. To this effect, the Spanish Society of Parenteral and Enteral Nutrition (SENPE) has endeavoured to create clinical practice guidelines and/or documents of consensus as well as quality standards in artificial nutrition. As a result, the SENPE´s Standardization Team has put together the "Document of Consensus in Enteral Access for Paediatric Nutritional Support" supported by the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the National Association of Pediatric and Neonatal Intensive Care Nursery (ANECIPN), and the Spanish Society of Pediatric Surgery (SECP). The present publication is a reduced version of our work; the complete document will be published as a monographic issue. It analyzes enteral access options in the pediatric patient, reviews the levels of evidence and provides the team-members' experience. Similarly, it details general and specific indications for pediatric enteral support, current techniques, care guidelines, methods of administration and complications of each enteral access. The data published by the American Society for Parenteral and Enteral Nutrition (ASPEN) and several European Societies has also been incorporated.

[Prediction of intestinal histological lesions in paediatric patients with coeliac disease]. / Predicción de lesión histológica intestinal en pacientes pediátricos con enfermedad celíaca.

INTRODUCTION: Serological markers are of great interest in coeliac disease (CD), although intestinal biopsy is still the gold standard for establishing the diagnosis. Tissue transglutaminase IgA antibodies (AATGt-IgA) and antiendomysial antibodies IgA (AAE-IgA) are closely correlated to intestinal damage observed in biopsies. Villous atrophy (Marsh 3) plays a major role in CD diagnosis. Marsh 2 stage (crypt hyperplasia) as a CD marker is still under debate. OBJECTIVE: To ascertain an AATGt-IgA level that corresponds to a positive predictive value (PPV) of 100% for a histological CD diagnosis. MATERIAL AND METHODS: A series of 120 patients younger than 14 years, non- IgA deficient, who underwent an intestinal biopsy and were positive for both serological markers (AATGt-IgA and AAE-IgA). For AATGt-IgA, according to the manufacturer's recommendations, a value greater than 16 IU/mL is considered as a positive value. The PPV of AATGt was determined for different cut-off points. RESULTS: The histological findings distribution is directly correlated to the AATGt-IgA cut-off point. When the cut-off point is set above 7.5-10.6 times the commercial reference value, there is a 2.1% of Marsh 2 lessions and 93.4% of Marsh 3; above 10.6 times the reference value, all biopsies where Marsh 3 (100%). The PPV that considers Marsh 3 is (93.4%). The PPV, for considering Marsh 3 is low (55%) when AATGt-IgA serology is positive with levels between 16 and 67 IU/ml (1-4.2 times the cut-off point) and a higher value (92%) for concentrations between 68 and 118 IU/ml (4.3-7.4 times) and for cases with 69-170 IU/ml (7.5-10.6 times); above 170 IU/ml (>10.6 times) PPV is 100%. CONCLUSION: The use of values higher than the recommended cut-off point must logically improve specificity and PPV. In 31.6% patients positive for AATGt-IgA and AAE-IgA (38/120) it would have been possible to diagnose the disease without intestinal biopsy as of the PPV was 100%. It is not possible to standardise results as there are different commercial kits with variable cut-off points, so we must be cautious when setting recommendations based on AATGt-IgA.

[Colectomy in paediatric patients with ulcerative colitis]. / Colectomía en pacientes pediátricos con colitis ulcerosa.

INTRODUCTION: There are not many studies published in the literature on failure of medical treatment in Ulcerative Colitis (UC) that leads to colectomy. PATIENTS AND METHODS: Retrospective study of patients under 14 years diagnosed with UC from 1984 to 2009, who underwent colectomy due to lack of response to medical treatment. They are divided into urgent or elective surgery. RESULTS: Colectomy performed in 14 paediatric patients (26.9% of total UC patients). Age at diagnosis 7.8±4.0 years, 8 of them younger than 10 years and 5 younger than 5 years. All cases diagnosed on patients less than 5 years of age required colectomy in the first 6 months after diagnosis. Elective colectomy was performed on 5/14 and urgent surgery in 9/14. The reported complications were divided into early (first 30 days after colectomy) and late. Pharmacological treatment in cases with urgent colectomy included methylprednisolone (100%), oral tacrolimus (55.5%), oral/intravenous cyclosporine (33.3%) and infliximab (33.3%). Cases of elective colectomy were all in the 1985-1998 period. CONCLUSIONS: The influence of age is a key factor for prognosis. All patients less than 5 year-old ended up with colectomy. The main indication for urgent surgery was lack of response to treatment with intravenous steroids combined with a potent immunomodulator (tacrolimus, cyclosporine, infliximab). All cases of elective colectomy were performed before 1999, when second line medical treatment was very uncommon, making remission unlikely.

[Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood]. / Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia.

INTRODUCTION: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. METHODS: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in µmol/L, and so are other clinical and analytical data. RESULTS: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 µmol/l, 38.7 µmol/l, 479.6 µmol/l respectively) than in controls (28.9 µmol/l, 56.2 µmol/l, 563.7 µmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 µmol/l vs. 19.7 µmol/l, p < 0.05), not happening so with rest of amminoacids. SUMMARY: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

Home parenteral nutrition in children: procedures, experiences and reflections.

This document summarizes the issues raised in a think-tank meeting held by professionals with expertise in pediatric Home Parenteral Nutrition. This nutritional technology enables patients to return home to their family and social environment, improves their quality of life and decreases health-care costs; however, it is complex and requires an experienced nutritional support team. Patient selection is normally made according to their underlying disease, the estimated duration of support and family and social characteristics. The patient''s family must agree to take on caregiver's responsibilities and should be able to perform treatment safely and effectively after receiving proper training from the nutritional support team. Close monitoring must be carried out to ensure tolerance and effectiveness of nutritional support, thereby avoiding complications. This nutritional treatment achieves, in most cases, recovery and intestinal adaptation in varying periods of time. In certain diseases, and when home parenteral nutrition becomes complicated, intestinal transplant may be recommendable, so referral to rehabilitation units and Intestinal Transplantation should be made early on.

Current status of pediatric home enteral nutrition in Spain: the importance of the NEPAD register.

Home enteral nutrition (HEN) is a type of enteral nutrition (EN) which is becoming progressively more widespread in pediatrics due to the benefits it affords to patients, their families and to reducing hospital costs. However, the true extent of its use is unknown in Spain as the data-base set up for this purpose is still underused (Registro de Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria -NEPAD-). More thorough registration of patients in the NEPAD online register will provide information about the characteristics of HEN in Spain: prevalence, diagnosis, the population sector being administered HEN, complications and developments. Likewise, forecast and planning of the necessary resources could be made while those in use could be analysed.

[Low bone mineral density and other risk factors in prepubertal children with fracture of the distal forearm]. / Disminución de la densidad mineral ósea y otros factores de riesgo en niños prepuberales con fractura del antebrazo distal.

AIM: To investigate the relationship between bone mineral density (BMD), age, sex, anthropometric measurements, dietary calcium intake and daily physical activity, in prepubertal children with distal forearm fracture (DFF). METHODS: 160 children (80 males, 80 females) 3-10 years of age with DFF; control group of 160 children (age-sex matched) were studied. Age, sex, weight, height, tricipital skin fold thickness (TS), body mass index, daily calcium intake, and level of physical activity (extra-school physical exercise: low <1hour/day, high >1hour/day) registered. BMD assessed by peripheral DXA densitometer. RESULTS: Most fractures were caused by mild-moderate precipitating trauma by accidental fall (85.6%), with radius fracture in most cases (87.5%). BMI was higher in patients (19.14 kg/m(2)+/-3.50 vs. 17.46 kg/m(2)+/-2.67; p<0.0001). TS thickness was similar in both groups (20.28 mm+/-8.24 vs. 19.61 mm+/-6.60; p>0.05). Physical activity was lower in study group (extra-school physical activity >1h: 21.25% vs. 46.87%; p<0.001). Daily calcium intake was not associated with DFF incidence (918.75 mg/day+/-338.04 vs. 886.13 mg/day+/-382.77; p>0.05). BMD was lower in fractured children (0.2591 g/cm(2)+/-0.0413 vs. 0.2801 g/cm(2)+/-0.0300; p<0.0001) SUMMARY: Our results suggest that significantly reduced bone mineral density, overweight and low physical activity are potential risk factors for fracture of the distal forearm, whilst low dietary intakes of calcium do not seem to be associated. The current epidemic of infantile overweight might explain the increased incidence of fractures of the distal forearm.

[Antegrade colonic enemas for intractable constipation in non-mentally retarded children]. / Lavados colónicos anterógrados para el estreñimiento refractario en niños sin encefalopatía.

A descriptive review of 12 patients who underwent appendicocecostomy or caecostomy for antegrade colonic lavage from January 2002 to February 2008. There were 9 appendicocecostomies performed patients from 3 to 13 years suffering from myelomeningocele, of which 8 of them had a very good outcome, with one case withdrawn due to poor use by the family. Three caecostomies were performed in non-mentally retarded constipated children. One was an otherwise healthy 7 year-old boy with hard stools since he was 10 months old, in spite of multiple laxative treatments, with normal morphology and function. He had a percutaneous caecostomy five years ago, with some improvement and a good quality of life, but still some occasional partial impactions. Another healthy 12 year-old boy with daily constipation associated faecal incontinence since he was 3 years old (normal manometry and rectal biopsy with signs of mild neuronal dysplasia) had a percutaneous caecostomy performed three years ago, with improvement in the faecal incontinence and better psychological outcome. The last caecostomy patient was an 8-year-old boy, with a similar clinical history and good progress in last three years after placing a Chait's button using an endoscopic procedure. Stubborn constipation continuing into adult life has a negative impact on the social and emotional adaptation of the paediatric patient, affecting family interactions. Antegrade colonic lavage allows independence and improves the quality of life in patients affected by recurrent faecal impactions. This technique needs to be performed on more patients to find out its true effectiveness.

[Safety and efficacy of oral tacrolimus in the treatment of paediatric inflammatory bowel disease]. / Eficacia y seguridad de tacrolimus oral para el tratamiento de la enfermedad inflamatoria intestinal pediátrica.

BACKGROUND: In certain clinical situations, such as acute and severe episodes of ulcerative colitis (UC) or Crohn's Disease (CD), that do not respond to conventional intravenous steroid treatment, we need potent, fast-acting drugs to induce clinical remission and avoid surgery. OBJECTIVES: To evaluate the efficacy and safety of oral tacrolimus treatment of acute and severe UC or CD to induce their remission, and also to assess its efficacy in delaying or avoiding surgery. MATERIAL AND METHODS: We present a retrospective study that included all patients under 18 years of age with acute and severe bouts of CD (colonic or ileocolonic location) or UC who were treated with oral tacrolimus at our institution from January 1998 to December 2007. RESULTS: We included a total of 8 patients (4 males and 4 females), 6 presented with UC and 2 had CD. The mean age of our patients at the start of the treatment was 11.8 years (range 2.75-16.58 y) and the mean time from diagnosis to the start of tacrolimus therapy was 4 months (range 1-96 m). An initial response was obtained in 50% of patients. Plasma trough levels of tacrolimus remained between 5-11 ng/ml. Six of the eight patients (75%) required surgery. In one patient with UC and in another with CD, surgery was avoided. In 2 of the 6 patients with UC, surgery was postponed beyond 6 months. CONCLUSIONS: Tacrolimus is useful in inducing clinical remission in patients with acute and severe bouts of UC or CD, and so can avoid or delay the surgery; it may also be used as a bridging agent until the new maintenance therapy with other immunosuppressants is effective.

[Efficacy of exclusive enteral feeding as primary therapy for paediatric Crohn's disease]. / Eficacia del tratamiento nutricional primario en la enfermedad de Crohn pediátrica.

INTRODUCTION: The primary nutritional therapy (PNT), which consists in the administration of exclusive enteral formula feeds (polymeric, semi-elemental or elemental formula) for a period of no less than 6-8 weeks, has proven to be effective in inducing clinical remission in children with Crohn's disease. The clinical remission does not always include histological remission or cure of the mucosa. Faecal calprotectin is closely correlated with endoscopic and histological findings but is slightly associated with clinical activity scores. PATIENTS AND METHODS: An observational prospective study including all patients under 14 years of age diagnosed with Crohn's disease between January 2002 and October 2007, and who were fed exclusively with polymeric formula (Modulen IBD, Nestle, Vevey, Switzerland) during the onset of the disease. Clinical controls were carried out (weight, height, body mass index [BMI) and the Paediatric Crohn's Disease Activity Index [PCDAI)) and faecal calprotectin was measured at the beginning and at weeks 4 and 8 of treatment. The clinical remission was defined as having a PCDAI less than or equal to 10. Faecal calprotectin values below 50 microg/g faeces were considered as normal. RESULTS: There were 14 patients (9 males), mean age at diagnosis of 10.74 +/- 2.56 years. At week 4, 71 % of patients (10/14) had achieved clinical remission and a decrease in faecal calprotectin levels that was not significant. After 8 weeks, 85 % of our patients were in clinical remission and faecal calprotectin values had declined significantly without reaching normal levels. CONCLUSION: Primary nutritional therapy administered over a period of 8 weeks is capable of inducing clinical remission and improving the degree of inflammation of the intestinal mucosa.