Splicing accuracy varies across human introns, tissues and age.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigated mis-splicing using RNA-sequencing data from ~14K control samples and 42 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that mis-splicing occurs at different rates across introns and tissues and that these splicing inaccuracies are primarily affected by the abundance of core components of the spliceosome assembly and its regulators. Using publicly available data on short-hairpin RNA-knockdowns of numerous spliceosomal components and related regulators, we found support for the importance of RNA-binding proteins in mis-splicing. We also demonstrated that age is positively correlated with mis-splicing, and it affects genes implicated in neurodegenerative diseases. This in-depth characterisation of mis-splicing can have important implications for our understanding of the role of splicing inaccuracies in human disease and the interpretation of long-read RNA-sequencing data.

Fifteen years of follow-up of a liver transplant recipient with glycogen storage disease type Ia (Von Gierke disease).

Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke's disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. The patient began to develop early chronic renal failure, necessitating simultaneous liver and kidney transplantation. Years later continuous reviews at the nephrology and hepatobiliopancreatic surgery services show he has a good quality of life and a normal hepatorenal profile.

Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas / Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics

Introducción: En los últimos años se ha producido un incremento de las infecciones invasivas por este patógeno que requieren ingreso en cuidados intensivos pediátricos (UCIP). Pacientes y métodos: Estudio retrospectivo (entre enero del 2006 y junio del 2010) en el que se incluyó a todos los pacientes con infección por Staphylococcus Aureus (S. aureus) que precisaron ingreso en UCIP. Estos fueron clasificados en 2 grupos: infección comunitaria (grupo 1) e infección nosocomial (grupo 2). Se recogieron los siguientes datos: epidemiológicos, tipo de aislamiento de S. aureus (S. aureus sensible a meticilina [SASM], S. aureus resistente a metilicina [SARM]), factores de riesgo, localización de la infección, presencia de inestabilidad hemodinámica, soporte respiratorio y mortalidad. Resultados: Se estudiaron a 51 pacientes, 21 pertenecientes al grupo 1 y 30 al grupo 2. La mediana de edad fue menor en el grupo 1 (1,6 años frente 3,2 años, p = 0,009). Se aisló SASM en el 88% de los casos. Se detectaron 6/51 (12%) pacientes con infección por SARM, los cuales se aislaron en el último periodo del estudio (enero 2009-junio 2010). Los factores de riesgo fueron: inmunosupresión, catéter venoso central, institucionalización, ventilación mecánica, cirugía previa, traumatismo previo y osteomielitis crónica. Un 83% de los pacientes con infección por SARM tenían factores de riesgo. La localización de la infección por S. aureus fue variada, siendo las infecciones respiratorias las más frecuentes (75%). Un 43% de los pacientes requirieron fármacos vasoactivos. La mayoría de los pacientes (86%) requirió soporte respiratorio. Un paciente del grupo 1 falleció por neumonía necrotizante por SAMS. Conclusiones: Las infecciones por S. aureus son graves y tienen elevada morbilidad. La infección pulmonar es la más frecuente en esta serie. Aunque el aislamiento de SASM es predominante en estas infecciones se ha visto una tendencia al incremento de las infecciones por SARM en el último periodo del estudio (AU)

Introduction: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). Patients and methods: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. Results: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=0.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010).The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. Conclusions: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study(AU)

¿Se realiza correctamente la punción lumbar en pediatría? Revisión de las recomendaciones actuales y análisis de la realidad / Do paediatricians perform lumbar puncture correctly? Review of recommendations and analysis the technique in Spain

Introducción: La punción lumbar (PL) es una técnica ampliamente utilizada en pediatría. La realización adecuada de la técnica puede evitar la mayoría de las complicaciones asociadas. Objetivo: Evaluar si en España los pediatras y los residentes de pediatría siguen las recomendaciones de la técnica de la PL. Material y métodos: Estudio transversal basado en un cuestionario escrito distribuido por correo electrónico a través de la Sociedad Española de Urgencias Pediátricas, que recogía datos epidemiológicos y preguntas de respuesta múltiple sobre la realización de la PL. Resultados: Se analizaron 206 cuestionarios, 143 (69,5%) respondidos por pediatras y 63 (30,5%) por residentes de pediatría. Hacen la PL sin los padres presentes 128 médicos (62,1%), aplican sedoanalgesia 198 (96,1%); 84 (42%) sólo analgesia local. Colocan al paciente sentado 108 (53,7%). La mayoría utiliza aguja tipo Quincke (126; 62,7%), orienta bien el trocar al hacer la punción 22 (36,1%) residentes y 21 pediatras (15,1%), diferencia estadísticamente significativa (p=0,001). En los neonatos, 63 (46%) pediatras y 19 (30,2%) residentes usan aguja sin fiador tipo «palomilla», diferencia también significativa (p=0,035). Reintroducen el estilete para redirigir el trocar 190 (92,2%) encuestados y para extraerlo 186 (93%). Recomiendan reposo tras la PL 195 (94,7%) médicos. Conclusiones: La mayoría de los pediatras orientan mal el trocar cuando hacen una PL y siguen utilizando aguja tipo «palomilla» en los neonatos a pesar de que está desaconsejado. Los residentes de pediatría y los pediatras con menor experiencia siguen las recomendaciones con mayor frecuencia(AU)

Introduction: Lumbar puncture (LP) is a commonly performed procedure in paediatrics. Performing this technique properly can avoid the most common associated complications. Objective: To assess whether paediatricians and paediatric residents in Spain follow current recommendations for the LP technique. Material and methods: A cross-sectional study was conducted by sending a questionnaire by mail through the Spanish Society of Paediatric Emergencies, collecting demographic information and responses to multiple choice questions about LP technique. Results: A total of 206 questionnaires were analysed, of which 143 (69.5%) were answered by paediatricians, and 63 (30.5%) by paediatric residents. The majority (128; 62.1%) of physicians did not allow parents to be present during LP, 198 (96.1%) routinely use analgesia and sedation; 84 (42%) only used local anaesthesia. The majority of respondents used standard Quincke needles (126; 62.7%). The bevel was correctly positioned when puncturing the dura mater by 22 residents (36.1%) and 21 paediatricians (15.1%), a variation that was statistically significant (P=.001). For neonatal lumbar punctures, 63 paediatricians (46%) and 19 paediatric residents used a butterfly needle which did not contain a stylet, and this difference was also statistically significant (P=.035). Of those surveyed, 190 (92.2%) re-inserted the stylet when re-orientating the needle, and 186 (93%) re-oriented this when removing it. The recommendation of bed rest was made by 195 (94.7%) physicians. Conclusions: The majority of paediatricians orient the bevel wrongly when inserting the needle during LP, and still use "butterfly" needles in newborns, despite warnings to the contrary. Paediatric residents and less experienced paediatricians follow the recommendations more frequently(AU)

[Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics]. / Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas.

INTRODUCTION: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. RESULTS: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010). The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. CONCLUSIONS: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study.

[Do paediatricians perform lumbar puncture correctly? Review of recommendations and analysis the technique in Spain]. / ¿Se realiza correctamente la punción lumbar en pediatría? Revisión de las recomendaciones actuales y análisis de la realidad.

INTRODUCTION: Lumbar puncture (LP) is a commonly performed procedure in paediatrics. Performing this technique properly can avoid the most common associated complications. OBJECTIVE: To assess whether paediatricians and paediatric residents in Spain follow current recommendations for the LP technique. MATERIAL AND METHODS: A cross-sectional study was conducted by sending a questionnaire by mail through the Spanish Society of Paediatric Emergencies, collecting demographic information and responses to multiple choice questions about LP technique. RESULTS: A total of 206 questionnaires were analysed, of which 143 (69.5%) were answered by paediatricians, and 63 (30.5%) by paediatric residents. The majority (128; 62.1%) of physicians did not allow parents to be present during LP, 198 (96.1%) routinely use analgesia and sedation; 84 (42%) only used local anaesthesia. The majority of respondents used standard Quincke needles (126; 62.7%). The bevel was correctly positioned when puncturing the dura mater by 22 residents (36.1%) and 21 paediatricians (15.1%), a variation that was statistically significant (P=.001). For neonatal lumbar punctures, 63 paediatricians (46%) and 19 paediatric residents used a butterfly needle which did not contain a stylet, and this difference was also statistically significant (P=.035). Of those surveyed, 190 (92.2%) re-inserted the stylet when re-orientating the needle, and 186 (93%) re-oriented this when removing it. The recommendation of bed rest was made by 195 (94.7%) physicians. CONCLUSIONS: The majority of paediatricians orient the bevel wrongly when inserting the needle during LP, and still use "butterfly" needles in newborns, despite warnings to the contrary. Paediatric residents and less experienced paediatricians follow the recommendations more frequently.

Behçet infantil: a propósito de un caso / Infantile Behçet’s disease: an actual case

La enfermedad de Behçet es una vasculitis de pequeño vaso que cursa en forma de brotes recurrentes de fiebre y aumento de reactantes de fase aguda. Su diagnóstico es clínico y su importancia está en la posible aparición de complicaciones graves, como la afectación neurológica u ocular. Se presenta el caso de un niño marroquí de 3 años de edad, cuyo diagnóstico final fue el de enfermedad de Behçet infantil tras presentar episodios repetidos de fiebre, aftas orales, exantema en el tronco y uveítis. Su evolución clínica, en general, fue buena después de la administración de varios fármacos inmunomoduladores, pero presentó un daño ocular severo, pendiente de aprobación de fármacos anti-TNF para su tratamiento (AU)

Behçet’s disease is a small vessel vasculitis that attends in the form of recurrent outbreaks of fever and increase of acute phase reactants. The diagnosis is clinical and their significance is in the possible development of neurological or ocular involvement. We present the case of a Moroccan child of 3 years of age whose final diagnosis was the infantile Behçet's disease because the child presented repeated episodes of fever, recurrent oral ulcers, rash on the trunk and uveitis. The clinical evolution was on the whole good after several immune modulating drugs, but with severe ocular damage, pending approval of treatment with anti-TNF drugs (AU)

Bronquiolitis y neumonía / Bronchiolitis and pneumonia

Objetivo: valorar si existen signos y/o síntomas clínicos en pacientes con bronquiolitis que sean sugestivos de la presencia de una neumonía asociada. Pacientes y métodos: estudio prospectivo longitudinal, realizado en el Hospital Universitario Infantil Niño Jesús de Madrid en una muestra de de 342 niños entre noviembre de 2006 y marzo de 2008. Se incluyeron pacientes ingresados con diagnóstico de bronquiolitis menores de siete meses de edad a los que se realizó radiografía de tórax. Resultados: la edad media fue de 2,7 meses, siendo el test de detección rápida para virus respiratorio sincitial (VRS) positivo en 226 niños. Del total de pacientes, un 38,42% fue diagnosticado de neumonía. Se midieron diversas variables, en las que se observaron resultados significativos en los pacientes con neumonía en cuanto a la media del valor de leucocitos (13 590 cl/μl; desviación estándar [DE]: 5200), para el valor de los neutrófilos totales (7520 cl/μl; DE: 4330) y el valor medio de la proteína C reactiva (PCR) (2,17 mg/dl; DE: 3,67). También se obtuvo significación estadística en cuanto a las odds ratio para dificultad respiratoria, presencia de fiebre en el domicilio, número total de neutrófilos mayor de 7 500 cl/μl, y para un valor de PCR mayor de 3 mg/dl. Conclusiones: en pacientes que presentan un cuadro de bronquiolitis, no existe ningún dato clínico que haga sospechar la presencia de neumonía. Consideramos interesante realizar más estudios con el objetivo de identificar otros indicadores que permitan sospechar neumonía en los pacientes diagnosticados de bronquiolitis (AU)

Objective: the aim of this study is to detect signs and/or symptoms in patients with bronchiolitis that can be suggestive of the presence of an associated pneumonia. Patients and methods: prospective, longitudinal study at the Children’s Universitary Hospital of the Jesus Child in Madrid in a sample of 342 children between November 2006 and March 2008. We included all the patients hospitalized with bronchiolitis under seven months of age who underwent chest radiography. Results: mean age was 2.7 months. Rapid RSV test was positive in 226 children. Pneumonia was diagnosed in 38.42% of the patients. We measured several variables; significant results were observed in patients with pneumonia on the average value of leucocytes (13,590 cl/μl, SD 5,20), for the value of total neutrophils (7,520 cl/μl, SD 4,33) and the mean value of CRP (2.17 mg/dl, SD 3.67). Statistical significance was also obtained regarding the OR for respiratory distress, presence of fever at home, total number of neutrophils greater than 7,500 cl/μl and CRP value greater than 3 mg/dl. Conclusions: in patients with symptoms of bronchiolitis, there is no clinical information that can suggest the presence of pneumonia. It is interesting to consider further studies in order to identify other indicators which suggest pneumonia in patients diagnosed with bronchiolitis (AU)