Pharmacogenetics of trough serum anti-TNF levels in paediatric inflammatory bowel disease.

AIMS: Identifying DNA variants associated with trough serum anti-tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti-TNF levels and whether these variants are differential markers for infliximab and adalimumab. METHODS: We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty-one polymorphisms were genotyped using real-time PCR. Trough serum anti-TNF levels were measured using enzyme-linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti-TNF drugs was analysed by Fisher exact test, student's t-test and logistic regression. RESULTS: The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). CONCLUSION: Genotyping of these DNA variants before starting treatment may help to select the best anti-TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti-TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti-TNF levels.

Características del síndrome de intestino corto y del fracaso intestinal en nuestra comunidad / Short bowel syndrome and failure intestinal features in our community

Introducción: El Fracaso intestinal está siendo una entidad con mayor prevalencia dentro de la edad pediátrica, en especial debido a resecciones importantes de intestino que terminan provocando la aparición de un Síndrome de Intestino Corto. Objetivos: Conocer la prevalencia y etiología de los casos de Síndrome de Intestino Corto (SIC) y Fracaso Intestinal (FI) existentes en la comunidad andaluza. Analizar los factores relacionados en su evolución, el número de pacientes trasplantados y conocer el tiempo necesario para lograr la autonomía enteral, estudiando si existen diferencias en el manejo entre los diferentes participantes. Métodos: Estudio observacional descriptivo retrospectivo multicéntrico en el cual se recogen los datos de los pacientes diagnosticados de Síndrome de Intestino corto o Fracaso intestinal en 6 centros hospitalarios de Andalucía en el periodo comprendido entre el 1 de enero de 2.008 y el 31 de Enero de 2.014. Resultados: 25 pacientes. Edad media al diagnóstico: 7,4 meses. Longitud media de intestino remanente 113,8 cm; 64% pacientes con <75 cm de longitud de intestino remanente. Se demuestra que: la introducción precoz de nutrición enteral es una factor favorecedor de la suspensión de la NP (p= 0’033); y que la prevención de la enfermedad hepática asociada a nutrición parenteral (EHANP) se favorece por: el uso de cifras de lípidos más bajas en la Nutrición Parenteral (p=0’008), una mayor longitud de intestino remanente (p=0’049), la introducción precoz de nutrición enteral (p=0’009) y una menor edad gestacional (p=0’006). Discusión: La Introducción precoz de NE es un factor esencial para lograr la adaptación intestinal, el destete de la NP y evitar la aparición de EHANP. Para prevenir la aparición de EHANP además de instaurar la NE lo antes posible, el manejo de los lípidos en la NP debe ser lo más exahustivo posible, intentando ajustar su aporte a las cifras más baja posibles (AU)

Introduction: Intestinal failure is being an entity with higher prevalence in the pediatric age, especially due to bowel resections causing the appearance of a short bowel syndrome. Objectives: To determine the prevalence and etiology of cases of short bowel syndrome (SIC) and Intestinal Failure (FI) existing in Andalusia. Analyze factors involved in evolution, the number of transplant patients andto know the time required to achieve enteral autonomy, studying whether there are differences in management between different participants. Methods: Multicenter retrospective descriptive observational study in which are collected data of patients diagnosed with short bowel syndrome or intestinal failure in 6 hospitals in Andalusia in the period from 1 January2008 to 31 January 2014. Results: 25 patients. Average age at diagnosis 7.4 months. Average length of remnant intestine: 113.8 cm; 64% of patients with <75 cm length remaining intestine. Weshow that: the early introduction of enteral nutrition is afactor favoring the suspension of the NP (p = 0’033); and that the prevention of liver disease associated with parenteral nutrition (EHANP) is favored by: the use of fewer lipid Parenteral Nutrition (p = 0’008), a greater length of remaining intestine (p = 0’049 ), the early introduction of enteral nutrition (p = 0’009) and a lower gestational age (p = 0’006) (AU)

Pneumonia and purulent pericarditis caused by Streptococcus pneumoniae: an uncommon association in the antibiotic era.

Bacterial pericarditis in children has become a rare entity in the modern antibiotic era. The most common pathogen is Staphylococcus aureus, being Streptococcus pneumoniae an exceptional cause. We present 2 children, who were diagnosed of pneumonia complicated with a pleural effusion that developed a purulent pericarditis with signs of cardiac tamponade. One of them had received 4 doses of the 7-valent conjugated pneumococcal vaccine. Systemic antibiotics and pericardial and pleural drainages were used. Pneumococcal antigens were positive in pleural and pericardial fluids in both cases, and S. pneumoniae was isolated from pleural effusion in one of them. Both children fully recovered, and none of them developed constrictive pericarditis, although 1 case presented a transient secondary left ventricular dysfunction. Routine immunization with 10- and 13-valent vaccines including a wider range of serotypes should further decrease the already low incidence.

[Short bowel syndrome and failure intestinal features in our community]. / Características del síndrome de intestino corto y del fracaso intestinal en nuestra comunidad.

INTRODUCTION: Intestinal failure is being an entity with higher prevalence in the pediatric age, especially due to bowel resections causing the appearance of a short bowel syndrome. OBJECTIVES: To determine the prevalence and etiology of cases of short bowel syndrome (SIC) and Intestinal Failure (FI) existing in Andalusia. Analyze factors involved in evolution, the number of transplant patients and to know the time required to achieve enteral autonomy, studying whether there are differences in management between different participants. METHODS: Multicenter retrospective descriptive observational study in which are collected data of patients diagnosed with short bowel syndrome or intestinal failure in 6 hospitals in Andalusia in the period from 1 January 2008 to 31 January 2014. RESULTS: 25 patients. Average age at diagnosis 7.4 months. Average length of remnant intestine: 113.8 cm; 64% of patients with <75 cm length remaining intestine. We show that: the early introduction of enteral nutrition is a factor favoring the suspension of the NP (p = 0'033); and that the prevention of liver disease associated with parenteral nutrition (EHANP) is favored by: the use of fewer lipid Parenteral Nutrition (p = 0'008), a greater length of remaining intestine (p = 0'049 ), the early introduction of enteral nutrition (p = 0'009) and a lower gestational age (p = 0'006).

Introducción: El Fracaso intestinal está siendo una entidad con mayor prevalencia dentro de la edad pediátrica, en especial debido a resecciones importantes de intestino que terminan provocando la aparición de un Síndrome de Intestino Corto. Objetivos: Conocer la prevalencia y etiología de los casos de Síndrome de Intestino Corto (SIC) y Fracaso Intestinal (FI) existentes en la comunidad andaluza. Analizar los factores relacionados en su evolución, el número de pacientes trasplantados y conocer el tiempo necesario para lograr la autonomía enteral, estudiando si existen diferencias en el manejo entre los diferentes participantes. Métodos: Estudio observacional descriptivo retrospectivo multicéntrico en el cual se recogen los datos de los pacientes diagnosticados de Síndrome de Intestino corto o Fracaso intestinal en 6 centros hospitalarios de Andalucía en el periodo comprendido entre el 1 de enero de 2.008 y el 31 de Enero de 2.014. Resultados: 25 pacientes. Edad media al diagnóstico: 7,4 meses. Longitud media de intestino remanente 113,8 cm; 64% pacientes con.