Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome.

Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is a rare genetic disorder caused by defects in F-box leucine-rich repeat protein 4 (FBXL4). Although FBXL4 is essential for the bioenergetic homeostasis of the cell, the precise role of the protein remains unknown. In this study, we report two cases of unrelated patients presenting in the neonatal period with hyperlactacidemia and generalized hypotonia. Severe mtDNA depletion was detected in muscle biopsy in both patients. Genetic analysis showed one patient as having in compound heterozygosis a splice site variant c.858+5G>C and a missense variant c.1510T>C (p.Cys504Arg) in FBXL4. The second patient harbored a frameshift novel variant c.851delC (p.Pro284LeufsTer7) in homozygosis. To validate the pathogenicity of these variants, molecular and biochemical analyses were performed using skin-derived fibroblasts. We observed that the mtDNA depletion was less severe in fibroblasts than in muscle. Interestingly, the cells harboring a nonsense variant in homozygosis showed normal mtDNA copy number. Both patient fibroblasts, however, demonstrated reduced mitochondrial transcript quantity leading to diminished steady state levels of respiratory complex subunits, decreased respiratory complex IV (CIV) activity, and finally, low mitochondrial ATP levels. Both patients also revealed citrate synthase deficiency. Genetic complementation assays established that the deficient phenotype was rescued by the canonical version of FBXL4, confirming the pathological nature of the variants. Further analysis of fibroblasts allowed to establish that increased mitochondrial mass, mitochondrial fragmentation, and augmented autophagy are associated with FBXL4 deficiency in cells, but are probably secondary to a primary metabolic defect affecting oxidative phosphorylation.

Efectividad de la acupuntura en la hipogalactia y en la inflamación mamaria. Revisión bibliográfica / Effectiveness of acupuncture in hypogalactia and breast inflammation. Bibliographic review

Objetivo: Determinar la efectividad de la acupuntura en el tratamiento de la hipogalactia y de la inflamación mamaria; mapear los puntos de aplicación y las técnicas utilizadas. Metodología: Revisión bibliográfica efectuada en las bases de datos PubMed, Cinahl, Cuiden, Scielo, Lilacs, Dialnet, Latindex, Cuidatge, WorldCat y Google Académico. Resultados: Se incluyeron 10 estudios; 7 observaron una mayor producción láctea o una prolongación en el tiempo de la lactancia; 2 evaluaron la efectividad de la acupuntura en la inflamación mamaria, y constataron un rápido alivio sintomático y un menor uso de antibióticos. No se ha encontrado unanimidad en la selección de la técnica y de los puntos para los diferentes tratamientos con acupuntura. Conclusión: La acupuntura parece ser efectiva para aumentar la producción láctea y mejorar los síntomas mamarios. Dada la falta de consenso en la selección de puntos y en las técnicas empleadas para los diferentes tratamientos con acupuntura, se requieren más estudios para poder generalizar estos tratamientos en la práctica clínica

Objective: To determine the effectiveness of acupuncture in the treatment of hypogalactia and breast inflammation; to map the application points and the techniques used. Methodology: A literature review was conducted by searching on PubMed, Cinahl, Cuiden, Scielo, Lilacs, Dialnet, Latindex, Cuidatge, WorldCat and Google Scholar. Results: A total of ten studies were included. A higher milk production or an extension in the time of lactation was observed in seven studies. The efficacy of acupuncture in the breast inflammation was evaluated in two studies and a quick relief of the symptoms and a lower use of antibiotics were observed. No agreement was found neither for the technique used nor for the acupuncture points used between the treatments. Conclusion: Acupuncture seems to be effective in increasing milk production and improving breast symptoms. The lack of consensus in the selection of points and in the techniques used for the different treatments with acupuncture means that more studies are required in order to generalize these treatments in clinical practice

Impact of histological chorioamnionitis, funisitis and clinical chorioamnionitis on neurodevelopmental outcome of preterm infants.

BACKGROUND: The role of chorioamnionitis in neurodevelopment of preterm infants is not fully understood. AIM: To examine the association between different indicators of intrauterine inflammation (clinical chorioamnionitis, histological chorioamnionitis and funisitis) and neurodevelopmental impairment in very preterm infants. METHODS: Preterm infants with a birth weight of <1500 g or a gestational age of <32 weeks were included. Follow-up evaluation up to 2 years of age consisted of neurological examination, neurodevelopmental assessment and visual and audiologic tests. Outcome data were compared between the chorioamnionitis and the control groups, controlling for gestational age, birth weight and Apgar score at 5 min. RESULTS: One hundred seventy-seven patients comprised the study population (mean gestational age 29±2 weeks, mean birth weight 1167±344 g). Histological chorioamnionitis was present in 49% of placentas, whereas funisitis was observed in 25%. In 57% cases clinical maternal chorioamnionitis was suspected. Follow-up was available for 130 (82%) patients. Infants with funisitis, compared with controls, had a significantly higher incidence of moderate to severe disability (18% vs 5%, OR 4.07; 95% CI 1.10-15.09). CONCLUSION: The results of this study suggest that, unlike a broad definition of histological chorioamnionitis including inflammation of maternal or fetal placental tissues, funisitis may entail a higher risk of moderate to severe disability at 2 years of age in preterm infants.

Rethinking classification of prematurity: a new clinical algorithm that improves etiologic assignment of preterm births.

BACKGROUND: There is a need for a better etiologic classification of preterm births and for tools to help to determine the possible etiologies of these births. OBJECTIVE: Having previously developed the Barcelona Etiology of Prematurity (BEP) algorithm, based on a new classification for preterm births, we sought to validate this algorithm in clinical studies whereby doctors retrospectively assigned the etiology of preterm birth according to principal cause and associated causes. METHOD: In phase 1 of the study, 91 preterm neonates consecutively admitted to a tertiary hospital were etiologically classified by doctors using the BEP algorithm. In phase 2, another 29 cases, representing the full spectrum of standard clinical scenarios, were classified by 20 doctors randomly divided into two groups of 10: one group used the algorithm and the other did not. RESULTS: In phase 1, the doctors were able to assign the etiology of all 91 clinical cases using the BEP algorithm, showing a 95.6% level of agreement with the etiologies set by the authors. In phase 2, for the 572 total evaluations, the group that used the BEP algorithm had significantly fewer errors in assigning the principal cause of prematurity than the group that did not use the algorithm (4.51 vs. 16.20%, respectively; p < 0.0001), and also demonstrated a higher level of correlation in assigning the associated causes. CONCLUSIONS: The proposed classification may be used to retrospectively categorize the etiology of preterm births, and the BEP algorithm facilitates this task enabling greater accuracy and precision in clinical data.

Formació MIR de Pediatria: present i futur / No disponible

No disponible

Formació MIR de Pediatria: present i futur / No disponible

No disponible

Evaluación de la aplicación del cribado de estreptococo del grupo B para la prevención de la infección perinatal en un hospital de tercer nivel / Compliance with a culture-based strategy to prevent perinatal Group B streptococcal infection in a third-level hospital

Los protocolos de prevención de la enfermedad por estreptococo del grupo B se emplean ampliamente y su eficacia ha sido demostrada. El objetivo del estudio es evaluar la aplicación del cribado de EGB en nuestro centro de trabajo, que recomienda efectuar un cultivo vaginal y rectal a todas las embarazadas en las semanas 35-37 de gestación, mediante un estudio de cohortes retrospectivo entre enero 2003 y enero 2004. Se objetiva una buena aplicación del cribado (92,1%), que sólo podría mejorarse parcialmente. En efecto, existen limitaciones inherentes a dicha estrategia, que podrían resolverse con la introducción de tests de detección rápida de portadoras al inicio del trabajo de parto (AU)

Protocols for the prevention of group B streptococcal disease are being widely used with proven efficacy. The aim of this study was to assess compliance with a culture-based approach recommending universal culture screening at 35-37 weeks' gestation, established in our hospital. A retrospective cohort study was undertaken from January 2003 to January 2004. Compliance with the culture-based approach was considered to be good (92.1%) and only partially amenable to improvements. Effectively, there are inherent limitations to the protocol that can be resolved with the use of other strategies, such as tests for quick identification of genital carrier status (AU)

[Compliance with a culture-based strategy to prevent perinatal Group B streptococcal infection in a third-level hospital]. / Evaluación de la aplicación del cribado de estreptococo del grupo B para la prevención de la infección perinatal en un hospital de tercer nivel.

Protocols for the prevention of group B streptococcal disease are being widely used with proven efficacy. The aim of this study was to assess compliance with a culture-based approach recommending universal culture screening at 35-37 weeks' gestation, established in our hospital. A retrospective cohort study was undertaken from January 2003 to January 2004. Compliance with the culture-based approach was considered to be good (92.1%) and only partially amenable to improvements. Effectively, there are inherent limitations to the protocol that can be resolved with the use of other strategies, such as tests for quick identification of genital carrier status.

ECMO pediàtric. A propòsit de dos casos / ECMO pediátrico. A propósito de dos casos / Pediatric ECMO: report of two cases

Introducció. Les tècniques de suport vital extracorpori (ECMO) s’han demostrat altament eficaces per al tractament de la insuficiència respiratòria o cardiorespiratòria, del nadó, sense resposta al tractament convencional. Sense aquesta tècnica, la mortalitat supera el 80% dels casos. Des de l’any 1984, s’han registrat a l’ELSO (Extracorporeal Life Support Organization) un total de 14.700 casos neonatals, amb una supervivència del 80%. A l’edat pediàtrica, l’experiència és molt inferior, amb un total de 1.723 casos registrats i una supervivència global del 50%. Observació clínica. Al nostre hospital, hem tingut l’oportunitat de tractar dues malaltes en edat pediàtrica: 1r cas, nena de 3 anys, afecta de sèpsia per pneumococ, amb afectació pulmonar bilateral, i insuficiència cardiorespiratòria refractària al tractament convencional; 2n cas, nena d’1 any d’edat, afecta d’insuficiència respiratòria severa en el postoperatori immediat, de la reparació completa d’una Tetralogia de Fallot. En tots dos casos es van aplicar tècniques de suport venoarterial (ECMO V-A), durant 10 i 4 dies respectivament, i en un d’ells es van reconstruir els vasos, en el moment de la decanulació. Les dos malaltes van ser donades d’alta hospitalària, en bon estat i sense seqüeles. Es tracta dels primers casos en edat pediàtrica tractats amb èxit a Espanya. Comentaris. El tractament amb ECMO pot ser una tècnica de suport eficaç en el maneig de la insuficiència cardiorespiratòria refractària al tractament convencional, millorant la supervivència d’aquests malalts crítics (AU)

Introducción. Las técnicas de soporte vital extracorpóreo (ECMO), para el manejo del fallo respiratorio o cardiorrespiratorio del recién nacido, sin respuesta al tratamiento convencional, han demostrado su elevada eficacia. La mortalidad de estos pacientes sin ECMO es superior al 80% de los casos. Desde 1984, se han recogido un total de 14.700 casos registrados en la ELSO (Extracorporeal Life Support Organization), con una supervivencia global del 80%. La experiencia clínica en la edad pediátrica es mucho menor, con 1.723 casos registrados y una supervivencia global del 50%. Observación clínica. En nuestro hospital, hemos tratado dos pacientes en edad pediátrica: 1 caso, niña de 3 años, afecta de una sepsis por neumococo, con afectación pulmonar severa y fallo cardiorrespiratorio refractario; 2º caso niña de 1 año que presenta insuficiencia respiratoria grave en el postoperatorio inmediato de la reparación completa de una Tetralogía de Fallot. En ambos casos se aplicaron técnicas de soporte veno-arterial (ECMO V-A) y en uno de ellos se procedió a la reconstrucción vascular en el momento de la decanulación. Ambas pacientes fueron dadas de alta hospitalaria, en buen estado y sin secuelas. Se trata de los primeros pacientes, en edad pediátrica, tratados con éxito con esta técnica, en España. Comentarios. El tratamiento con ECMO puede ser un soporte eficaz pàra el fallo cardíaorrespiratorio refractario al tratamiento convencional, aumentando la supervivencia de estos pacientes críticos (AU)

Introduction. The techniques of extracorporeal life oxygenation (ECMO) have shown their efficacy in the acute management of neonatal respiratory or cardio-respiratory distress syndrome unresponsive to conventional therapy. Mortality in this group of patients without the use of ECMO is greater than 80%. Since 1984, 14,700 neonatal cases have been registered at the Extracorporeal Life Support Organization (ELSO), with an overall survival of 80%. The pediatric experience is much less extensive, with 1,723 recorded cases, and an overall survival of 50%. Clinical observation. We have treated two pediatric patients with ECMO. The first case was a 3 year-old girl with pneumococal sepsis and acute respiratory distress syndrome, which was unresponsive to conventional therapy; the second case was a 1 year-old girl who developed an acute and refractory respiratory failure in the immediate postoperative course of a complete repair of Tetralogy of Fallot. In both patients, the severity of the respiratory failure warranted veno-arterial ECMO, with good response. They were weaned at 10 and 4 days, respectively, with vascular repair at the time of decanulation in the second case. Both patients recovered completely and were eventually discharged without complications. Comments. ECMO therapy can be an effective support for the management of postoperative cardiac and respiratory failure refractory to medical management (AU)

Bronchial complication of a closed-tube endotracheal suction catheter.

Iatrogenic bronchial complications in intubated premature infants are rare. The authors present one case of rupture of a closed-tube endotracheal suction catheter. Clinical presentation was a persistent pneumothorax that required chest tube placement in several days. A foreign body was confirmed in x-ray and computed tomography (CT) scan. Flexible bronchoscopy showed a piece of catheter in the left bronchus and using a rigid bronchoscope was possible to remove. No perforation was found. There are a few reports in the literature of iatrogenic bronchial complication in premature infants caused by closed-tube endotracheal suctioning catheters. Endobronchial rupture of this catheter has never been reported.

Uso de oxigenación por membrana extracorpórea (ECMO) en un caso de shock séptico neonatal por neumococo / Use of extracorporeal membrane oxygenation in a case of pneumococcal neonatal septic

Introducción. La sepsis neonatal por Streptococcus pneumoniae es una causa muy infrecuente de enfermedad invasiva en el recién nacido, conlleva una elevada mortalidad y en ocasiones puede beneficiarse del tratamiento con oxigenación por membrana extracorpórea (ECMO). Observación clínica. Neonato a término de sexo masculino, fruto de una cesárea urgente por sospecha de pérdida del bienestar fetal que presenta, a las pocas horas de vida, fracaso respiratorio y hemodinámico progresivo que no responde al tratamiento convencional intensivo. En el hemocultivo crece Streptococcus pneumoniae. Requiere tratamiento con oxigenación por membrana extracorpórea (ECMO) venoarterial durante 8 días, presentando una evolución favorable y consiguiendo la supervivencia libre de secuelas hasta la actualidad. Comentarios. La ECMO está indicada en aquellos pacientes que tienen un alto riesgo de muerte por fracaso respiratorio o cardiorespiratorio que no responde al tratamiento médico exhaustivo. Ha demostrado una disminución de la mortalidad frente al tratamiento médico convencional sin incrementar las secuelas en los supervivientes. El tratamiento adecuado de la coagulopatía del shock antes de iniciar la ECMO y el manejo minucioso de la heparinización una vez ésta es aplicada permite el tratamiento de los neonatos sépticos con éxito. Es fundamental el contacto precoz con el centro de referencia para valorar la indicación de la técnica y el momento oportuno para la realización del traslado (AU)