Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth (CMT) disease is classified considering the neurophysiological and histological findings, the inheritance pattern and the underlying genetic defect. In recent years, with the advent of next generation sequencing, genetic complexity has increased exponentially, expanding the knowledge about disease pathways, and having an impact in clinical management. The aim of this guide is to offer recommendations for the diagnosis, prognosis, monitoring and treatment of this disease in Spain. MATERIAL AND METHODS: This consensus guideline has been developed by a multidisciplinary panel encompassing a broad group of professionals including neurologists, neuropediatricians, geneticists, rehabilitators, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis is based in the clinical characterization, usually presenting with a common phenotype. It should be followed by an appropriate neurophysiological study that allows for a correct classification, specific recommendations are established for the parameters that should be included. Genetic diagnosis must be approached in sequentially, once the PMP22 duplication has been ruled out if appropriate, a next generation sequencing should be considered taking into account the limitations of the available techniques. To date, there is no pharmacological treatment that modifies the course of the disease, but symptomatic management is important, as are the rehabilitation and orthopaedic considerations. The latter should be initiated early to identify and improve the patient's functional impairments, including individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transpositions. The follow-up of patients with CMT is exclusively clinical, ancillary testing are not necessary in routine clinical practice.

Delphi consensus on recommendations for the treatment of spinal muscular atrophy in Spain (RET-AME consensus).

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a biallelic mutation of the SMN1 gene, located on the long arm of chromosome 5, and predominantly affects the motor neurons of the anterior horn of the spinal cord, causing progressive muscle weakness and atrophy. The development of disease-modifying treatments is significantly changing the natural history of SMA, but uncertainty remains about which patients can benefit from these treatments and how that benefit should be measured. METHODOLOGY: A group of experts specialised in neurology, neuropediatrics, and rehabilitation and representatives of the Spanish association of patients with SMA followed the Delphi method to reach a consensus on 5 issues related to the use of these new treatments: general aspects, treatment objectives, outcome assessment tools, requirements of the treating centres, and regulation of their use. Consensus was considered to be achieved when a response received at least 80% of votes. RESULTS: Treatment protocols are useful for regulating the use of high-impact medications and should guide treatment, but should be updated regularly to take into account the most recent evidence available, and their implementation should be assessed on an individual basis. Age, baseline functional status, and, in the case of children, the type of SMA and the number of copies of SMN2 are characteristics that should be considered when establishing therapeutic objectives, assessment tools, and the use of such treatments. The cost-effectiveness of these treatments in paediatric patients is mainly influenced by early treatment onset; therefore, the implementation of neonatal screening is recommended. CONCLUSIONS: The RET-AME consensus recommendations provide a frame of reference for the appropriate use of disease-modifying treatments in patients with SMA.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Experiencia en el manejo de terapia ECMO como factor de riesgo de mortalidad / Experience in the management of ECMO therapy as a mortality risk factor

Introducción. La membrana de oxigenación extracorpórea (ECMO) es un sistema que proporciona asistencia circulatoria y respiratoria a pacientes en fallo cardiaco o respiratorio refractarios al tratamiento convencional. Es una terapia con numerosas complicaciones asociadas y alta mortalidad. El manejo por equipos multidisciplinares y con experiencia aumenta la probabilidad de supervivencia. Objetivos. Evaluar y analizar el efecto de la curva de aprendizaje sobre la mortalidad. Métodos. Estudio retrospectivo y observacional de 31 pacientes, realizado desde enero de 2012 hasta diciembre de 2015. Los pacientes se agruparon en 2periodos que están divididos por la instauración de un protocolo ECMO. Comparamos las variables cuantitativas realizando la prueba U de Mann-Whitney; para las variables cualitativas categóricas empleamos la prueba Chi-cuadrado o el estadístico exacto de Fisher, según correspondiera. La curva de supervivencia se elaboró mediante el método de Kaplan-Meier y el análisis de la significación estadística mediante el test Log-rank. El análisis de los datos se realizó con el programa STATA 14. Resultados. En las curvas de supervivencia se muestra la tendencia a menor mortalidad en los pacientes del periodo posterior (p=0,0601). La tasa de mortalidad general en el periodo inicial fue mayor que en el periodo posterior (p=0,042). En otro análisis comparamos características de los 2grupos y concluimos que eran homogéneos. Conclusión. El grado de experiencia es un factor independiente para la mortalidad. La aplicación de un protocolo asistencial es fundamental para facilitar el manejo de la terapia ECMO (AU)

Introduction. The extracorporeal oxygenation membrane (ECMO) is a system that provides circulatory and respiratory assistance to patients in cardiac or respiratory failure refractory to conventional treatment. It is a therapy with numerous associated complications and high mortality. Multidisciplinary management and experienced teams increase survival. Objective. Our purpose is to evaluate and analyse the effect of the learning curve on mortality. Methods. Retrospective and observational study of 31 patients, from January 2012 to December 2015. Patients were separated into 2periods. These periods were divided by the establishment of an ECMO protocol. We compared the quantitative variables by performing the Mann-Whitney U test. For the categorical qualitative variables we performed the chi-square test or Fisher exact statistic as appropriate. The survival curve was computed using the Kaplan-Meier method, and the analysis of statistical significance using the Log-rank test. Data analysis was performed with the STATA programme 14. Results. Survival curves show the tendency to lower mortality in the subsequent period (P=0.0601). The overall mortality rate in the initial period was higher than in the subsequent period (P=0.042). In another analysis, we compared the characteristics of the 2groups and concluded that they were homogeneous. Conclusion. The degree of experience is an independent factor for mortality. The application of a care protocol is fundamental to facilitate the management of ECMO therapy (AU)

Experience in the management of ECMO therapy as a mortality risk factor. / Experiencia en el manejo de terapia ECMO como factor de riesgo de mortalidad.

INTRODUCTION: The extracorporeal oxygenation membrane (ECMO) is a system that provides circulatory and respiratory assistance to patients in cardiac or respiratory failure refractory to conventional treatment. It is a therapy with numerous associated complications and high mortality. Multidisciplinary management and experienced teams increase survival. OBJECTIVE: Our purpose is to evaluate and analyse the effect of the learning curve on mortality. METHODS: Retrospective and observational study of 31 patients, from January 2012 to December 2015. Patients were separated into 2periods. These periods were divided by the establishment of an ECMO protocol. We compared the quantitative variables by performing the Mann-Whitney U test. For the categorical qualitative variables we performed the chi-square test or Fisher exact statistic as appropriate. The survival curve was computed using the Kaplan-Meier method, and the analysis of statistical significance using the Log-rank test. Data analysis was performed with the STATA programme 14. RESULTS: Survival curves show the tendency to lower mortality in the subsequent period (P=0.0601). The overall mortality rate in the initial period was higher than in the subsequent period (P=0.042). In another analysis, we compared the characteristics of the 2groups and concluded that they were homogeneous. CONCLUSION: The degree of experience is an independent factor for mortality. The application of a care protocol is fundamental to facilitate the management of ECMO therapy.

Evaluación genotóxica del D-004, extracto del fruto de Roystonea regia, mediante el ensayo de la morfología de la cabeza del espermatozoide en ratas Sprague Dawley / Genotoxic evaluation of D-004 in the Sprague Dawley rats sperm morphology assay

El tratamiento oral con D-004, extracto lipídico del fruto de la palma real (Roystonea regia), ha mostrado prevenir la hiperplasia prostática (HP) inducida por testosterona y por fenilefrina en ratas, efectos relacionados con su capacidad de inhibir la actividad de la 5 -reductasa prostática y de antagonizar los adreno-receptores 1.Este estudio, como parte de los estudios de genotoxicidad del D-004,tuvo como objetivo determinar si el mismo aumenta la frecuencia de aparición de formas anómalas de la cabeza del espermatozoide en ratas. Para ello se utilizaron ratas Sprague Dawley machos incluidas en un estudio de toxicidad crónica, distribuidas aleatoriamente en 5grupos (8 ratas/grupo): 1 control negativo tratado con el vehículo, 3grupos tratados con D-004 (800, 1500 y 2000 mg/kg, respectivamente), y 1 control positivo (Ciclofosfamida, 50mg/kg).Los tratamientos (vehículo o D-004) se administraron por vía oral durante 12 meses, la Ciclofosfamida se administró por vía intraperitoneal 5 días consecutivos. No ocurrieron muertes ni se detectaron signos de toxicidad. Las concentraciones de espermatozoides, y las frecuencias de espermatozoides normales en los grupos tratados con D-004 fueron similares a los del control negativo, mientras que el grupo control positivo mostró menor concentración de espermatozoides y mayor frecuencia de espermatozoides anómalos que los controles negativos. En conclusión, el D-004 administrado durante varios períodos de espermatogénesis no presenta potencial genotóxico sobre las células germinales masculinas de ratas (AU)

Oral treatment with D-004, a lipid extract from the royal palm(Roystonea regia) fruits, has been shown to prevent prostate hyperplasia (PH) induced by testosterone and phenylephrine in rats through the D-004-mediated inhibition of prostate 5 –reductase activity and antagonism of -1 adrenoceptors. This study, as part of the studies of the genotoxic potential of D-004, was aimed to determine whether D-004 increases the frequency of abnormal forms of rat sperm-head morphology. For that, male Sprague Dawley rats included in a chronic toxicity study were used, which were randomly distributed into 5 groups (8 rats/group): 1 negative control treatedwith the vehicle, 3 D-004-treated groups (800, 1500 and 2000 mg/kg, respectively), and 1 positive control (Ciclophosphamide, 50mg/kg).Treatments (vehicle or D-004) were orally administered for 12months, while Ciclophosphamide was given by intraperitoneal route five days consecutive. There were no deaths and no toxicity signs were observed. Spermatozoid concentrations and the frequencies of normal spermatozoids in D-004 treated groups were similar to those of the negative controls, while the positive control had decreased spermatozoid concentrations and increased frequency of abnormals permatozoids compared with the negative controls. In conclusion,D-004 orally administered during several periods of spermatogenesis in rats did not show genotoxic potential on the male germinal cells (AU)