Validation of Neuromyotype: a smart keyboard for the evaluation of spinal muscular atrophy patients.

INTRODUCTION: Spinal muscular atrophy 5q (SMA) is a genetic neurodegenerative disease that affects alpha motor neurons producing progressive weakness. New outcome measures are currently required to accurately characterise the disease progression and the efficacy of new available treatments. The objective of this work is to preliminarily validate a new intelligent keyboard (Neuromyotype) measuring typing strength and speed in patients with SMA. MATERIAL AND METHODS: Twenty two SMA patients older than 15 years, and 26 healthy controls were included. Three measurements were obtained with the keyboard (maximum strength, execution time of a random typing task, execution time of a sequential typing task) together with the time to complete the Nine-Hole Peg Test (9HPT). Patients were also administered motor (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM), and functional scales (Egen Klassification, EK2; and the revised version of Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R). The viability and construct validity of the Neuromyotype were analysed, measuring the discriminative power between patients and controls (using ROC curves and the Bangdiwala's B statistic), between the different functional types of SMA (walker, sitter and non-sitter) and their correlation with the rest of motor scales. RESULTS: Neuromyotype measurements could be performed in all patients, unlike the rest of the scales. Its administration was quick and easy. The 3 variables on the keyboard discriminated very well between patients and controls, with strength (ROC = 0.963) being the one that best differentiates from the 3, equaling 9HPT (ROC = 0.966). They also showed a good ability to differentiate by functional type (especially non-sitters from sitters and walkers), with sequential time (B = 0.83) being the tool that best discriminates between the three groups above the rest of motor scales. All motor and functional scales showed strong or very strong correlations with each other (rs = 0.71-0.99), with strength correlating better with motor scales and timed variables with functional scales. CONCLUSION: This study shows the feasibility and validity of Neuromyotype for the evaluation of adolescent and adult patients with SMA. Data obtained with this tool could be of great clinical relevance, saving time and resources compared to the rest of the scales.

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.

Validación de la versión española de la Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS) / Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS)

Introducción y objetivos: La Charcot-Marie-Tooth Pediatric Scale (CMTPedS) es una herramienta validada y sensible al cambio para evaluar la gravedad de la neuropatía en niños y adolescentes entre 3 y 20 años. El objetivo de este artículo es traducir y validar una versión española de la CMTPedS para difundir su utilización en países de habla hispana. Material y métodos: El proceso para la traducción al español de la CMTPedS ha sido el método de traducción paralela invertida basado en los principios de buena práctica para la traducción y el proceso de adaptación cultural de las Food and Drug Administration Guidelines. Se realizó primero una traducción directa de la fuente original de la CMTPedS al español que fue revisada por expertos en la enfermedad de Charcot-Marie-Tooth (CMT) formados en la utilización de la herramienta CMTPedS. La versión española fue traducida de nuevo al inglés por un lingüista especialista de la traducción. Resultados: La versión preliminar en español de la CMTPedS se evaluó en 18 niños con CMT entre 6 y 20 años (media: 13,27). La escala fue bien tolerada y fácil de comprender en los niños y fácil de aplicar para los clínicos. Ningún paciente tuvo dificultad en completar la escala.Conclusiones: La versión española de la CMTPedS se puede utilizar para el seguimiento y la realización de ensayos clínicos en población española y países de habla hispana.(AU)

Introduction and aims: The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. Materials and methods: The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. Results: The preliminary Spanish version of the CMTPedS was evaluated in 18 children with CMT aged 6-20 years (mean: 13.27). The scale was well tolerated and easy for children to understand and easy for clinicians to apply. None of the patients had any difficulty completing the scale. Conclusions: The Spanish version of the CMTPedS can be used for monitoring and conducting clinical trials in the Spanish population and in Spanish-speaking countries.(AU)

[Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS)]. / Validación de la versión española de la Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS).

INTRODUCTION AND AIMS: The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. MATERIALS AND METHODS: The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. RESULTS: The preliminary Spanish version of the CMTPedS was evaluated in 18 children with CMT aged 6-20 years (mean: 13.27). The scale was well tolerated and easy for children to understand and easy for clinicians to apply. None of the patients had any difficulty completing the scale. CONCLUSIONS: The Spanish version of the CMTPedS can be used for monitoring and conducting clinical trials in the Spanish population and in Spanish-speaking countries.

TITLE: Validación de la versión española de la Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS).Introducción y objetivos. La Charcot-Marie-Tooth Pediatric Scale (CMTPedS) es una herramienta validada y sensible al cambio para evaluar la gravedad de la neuropatía en niños y adolescentes entre 3 y 20 años. El objetivo de este artículo es traducir y validar una versión española de la CMTPedS para difundir su utilización en países de habla hispana. Material y métodos. El proceso para la traducción al español de la CMTPedS ha sido el método de traducción paralela invertida basado en los principios de buena práctica para la traducción y el proceso de adaptación cultural de las Food and Drug Administration Guidelines. Se realizó primero una traducción directa de la fuente original de la CMTPedS al español que fue revisada por expertos en la enfermedad de Charcot-Marie-Tooth (CMT) formados en la utilización de la herramienta CMTPedS. La versión española fue traducida de nuevo al inglés por un lingüista especialista de la traducción. Resultados. La versión preliminar en español de la CMTPedS se evaluó en 18 niños con CMT entre 6 y 20 años (media: 13,27). La escala fue bien tolerada y fácil de comprender en los niños y fácil de aplicar para los clínicos. Ningún paciente tuvo dificultad en completar la escala. Conclusiones. La versión española de la CMTPedS se puede utilizar para el seguimiento y la realización de ensayos clínicos en población española y países de habla hispana.

A mediastinal mass causing Budd-Chiari-like syndrome in a cat.

Background: Budd-Chiari syndrome (BCS) is considered a rare condition in cats that is characterized by the obstruction of the hepatic venous outflow tract from the level of the small hepatic veins to the level of the termination of the inferior vena cava into the right atrium in the absence of cardiac or pericardial disease, or sinusoidal obstruction syndrome. Case description: This report presents a 13-year-old cat with a two-week history of progressive lethargy, inappetence, weight loss, and abdominal distension. Findings/treatment and outcome: The radiological study was consistent with pleural effusion, as well as alveolar and interstitial pulmonary patterns. Ultrasonography confirmed hepatic venin congestion and ascites. Abdominocentesis revealed a modified transudate. A computed tomography (CT) angiography showed a mass at the level of the caudal mediastinum that compressed the caudal vena cava (CVC). Mediastinal lymphoma was considered the most likely differential diagnosis. These findings were interpreted as Budd-Chiari-like syndrome (BCLS) secondary to a mediastinal mass although, unfortunately, no further diagnostic or treatment procedures were accepted by the owners. BCLS is a rare condition in cats, where most of the reported cases occurred as a result of obstruction of the caudal vena cava. In this report, BCLS was caused by a mass located in the caudal mediastinum oppressing the caudal vena cava. Conclusion: This is the first report of BCLS in cats diagnosed by CT angiography, and it shows the value of this technique to define the origin and extent of the mass and to evaluate the presence or absence of metastatic lesions.

Ultrasound-guided lumbar puncture for nusinersen administration in spinal muscular atrophy patients.

BACKGROUND AND PURPOSE: The purpose was to report the results of ultrasound-guided lumbar puncture for the administration of nusinersen in spinal muscular atrophy (SMA) patients with complex spines. METHODS: Eighteen SMA patients (five children, five adolescents and eight adults) with either severe scoliosis or spondylodesis were evaluated for ultrasound-guided lumbar puncture. Ultrasound was performed with a 3.5 MHz transducer to guide a 22 gauge × 15 mm needle, which was placed in the posterior lumbar space following a parasagittal interlaminar approach. RESULTS: Twelve patients had undergone spinal instrumentation (nine growing rods and three spinal fusion) whilst the other six showed severe scoliosis. Success was achieved in 91/94 attempts (96.8%), in 14/18 patients (77.8%), including 100% of children and adolescents and 50% of adult patients. In two of the unsuccessfully treated patients, computed tomography and fluoroscopy-guided transforaminal lumbar punctures were also tried without success. After a median follow-up of 14 months, only few adverse events, mostly mild, were observed. CONCLUSION: The ultrasound-guided lumbar puncture, following an interlaminar parasagittal approach, is a safe and effective approach for intrathecal treatment with nusinersen in children, adolescents and carefully selected adult SMA patients with complex spines and could be considered the first option in them.

Image reconstruction: Part 1 - understanding filtered back projection, noise and image acquisition.

Image reconstruction is an increasingly complex field in CT. Iterative Reconstruction (IR) is at present an adjunct to standard Filtered Back Projection (FBP) reconstruction, but could become a replacement for it. Due to its potential for scanning at lower radiation doses, IR has received a lot of attention in the medical literature and all vendors offer commercial solutions. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This paper is the first manuscript of a pair. It aims to review the basic principles of CT scanning, to describe image reconstruction using Filtered Back Projection, and to identify the physical processes that contribute to image noise which IR may be able to compensate for. The aim is to enable cardiovascular imagers to understand what happens to the raw data prior to the reconstruction process so they may have a better appreciation of the strengths and weaknesses of the various reconstruction techniques available. The second manuscript of this pair will discuss the various vendor permutations of IR in more detail, including the most recent machine learning based offerings, and critically appraise the current clinical research available on the various IR techniques used in cardiovascular CT.

Image reconstruction in cardiovascular CT: Part 2 - Iterative reconstruction; potential and pitfalls.

The use of IR in CT previously has been prohibitively complicated and time consuming, however improvements in computer processing power now make it possible on almost all CT scanners. Due to its potential to allow scanning at lower doses, IR has received a lot of attention in the medical literature and has become a successful commercial product. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This manuscript discusses the various vendor permutations of iterative reconstruction (IR) in detail and critically appraises the current clinical research available on the various IR techniques used in cardiovascular CT.

The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review.

Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies. We have also analyzed the cellular biology and the interactions between GBM and the surrounding environment.

Preoperative MRI evaluation of lesion-nipple distance in breast cancer patients: thresholds for predicting occult nipple-areola complex involvement.

AIM: To identify clinically occult nipple-areola complex (NAC) involvement using preoperative magnetic resonance imaging (MRI), to inform selection of patients eligible for nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM). MATERIAL AND METHODS: This was a retrospective study of 195 patients, who had preoperative breast MRI (February 2011 to January 2017) before undergoing surgical treatments (NSM or SSM) for newly diagnosed breast cancer. Tumour features at MRI (mass or non-mass lesion, diameter, lesion-NAC distance [LND]) and pathology (lesion diameter, histopathological type, receptor status) were recorded, as well as the type of surgery (NSM/SSM) and presence (NAC+) or absence (NAC-) of tumour at intraoperative evaluation of retroareolar tissue. Mann-Whitney test, Fisher's exact test, logistic regression, and receiver operating characteristic (ROC) curve analysis were used for analysis of NAC+ versus NAC- to assess variables that predict NAC tumoural involvement. RESULTS: Over the study period, NAC+ was proven histologically in 71/200 (35.5%) surgical treatments, while there were 129/200 NAC- (72 NSM and 128 SSM performed). LND at MRI was statistically (p<0.001) lower in NAC+ patients than in NAC- patients. The area under the ROC curve (0.82, 95% confidence interval [CI]: 0.76-0.88) indicated 10 mm as the best cut-off, with sensitivity of 82%, specificity of 72%, and accuracy of 79%. A 5-mm cut-off enhanced sensitivity, whereas a 15-mm cut-off favoured specificity. CONCLUSIONS: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling.

Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 µM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1-10 µM result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium.

Estudio de caso. Terapia del movimiento inducido por restricción en parálisis cerebral infantil / Case report. Constraint-induced movement therapy in childhood cerebral palsy

Introducción. El caso trata de una niña de 30 meses de edad diagnosticada de parálisis cerebral con hemiparesia espástica. La intervención desde atención temprana se fundamenta en la aplicación de un protocolo modificado de terapia del movimiento inducido en entornos naturales (hogar y colegio). Objetivos. El objetivo es mejorar el desempeño ocupacional e incrementar el uso voluntario de la mano parética en actividades bimanuales, basándose en la estimulación neurológica implícita en el aprendizaje motor. Resultados. Mejora del desempeño en actividades de la vida diaria. Se registraron ganancias a nivel emocional y actitudinal. AHA incrementa 7 puntos. PDMS-2 suma 2 puntos en visual motora y 2 puntos en edad equivalente. A nivel funcional se alcanzan ganancias en 8 de los 10 objetivos (Goal Attainment Scale). Los resultados obtenidos invitan a seguir investigando el potencial de esta herramienta en entornos naturales (AU)

Introduction. We report the case of a 30-month-old girl with unilateral spastic cerebral palsy (CP). Early Intervention was based on an eco-modified protocol of constraint-induced movement therapy (mCIMT). Objectives. The objectives were to improve occupational development and to increase spontaneous upper limb use during bimanual activities by means of neurological stimulation involved in the leaning of motor skills. Results. There was improvement in the development of activities of daily living, as well as emotional and attitudinal gains. An increment of 7 points was recorded in the assisting hand assessment (AHA). The Peabody developmental motor sclaes-2 (PDMS-2) increased 2 points in the visual motor (VM) subtest and another 2 points in equivalent age (EA). In functional goals, progress was achieved in 8 of the 10 objectives (Goal Attainment Scale). The results obtained encourage us to keep investigating the potential of this tool in natural environments (AU)

Digital breast tomosynthesis as an adjunct to digital mammography for detecting and characterising invasive lobular cancers: a multi-reader study.

AIM: To examine the interpretive performance of digital breast tomosynthesis (DBT) as an adjunct to digital mammography (DM) compared to DM alone in a series of invasive lobular carcinomas (ILCs) and to assess whether DBT can be used to characterise ILC. MATERIALS AND METHODS: A retrospective, multi-reader study was conducted of 83 mammographic examinations of women with 107 newly diagnosed ILCs ascertained at histology. Consenting women underwent both DM and DBT acquisitions. Twelve radiologists, with varying mammography experience, interpreted DM images alone, reporting lesion location, mammographic features, and malignancy probability using the Breast Imaging-Reporting and Data System (BI-RADS) categories 1-5; they then reviewed DBT images in addition to DM, and reported the same parameters. Statistical analyses compared sensitivity, false-positive rates (FPR), and interpretive performance using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), for reading with DM versus DM plus DBT. RESULTS: Multi-reader pooled ROC analysis for DM plus DBT yielded AUC=0.89 (95% confidence interval [CI]: 0.88-0.91), which was significantly higher (p<0.0001) than DM alone with AUC=0.84 (95% CI: 0.82-0.86). DBT plus DM significantly increased pooled sensitivity (85%) compared to DM alone (70%; p<0.0001). FPR did not vary significantly with the addition of DBT to DM. Interpreting with DBT (compared to DM alone) increased the correct identification of ILCs depicted as architectural distortions (84% versus 65%, respectively) or as masses (89% versus 70%), increasing interpretive performance for both experienced and less-experienced readers; larger gains in AUC were shown for less-experienced radiologists. Multifocal and/or multicentric and bilateral disease was more frequently identified on DM with DBT. CONCLUSION: Adding DBT to DM significantly improved the accuracy of mammographic interpretation for ILCs and contributed to characterising disease extent.

Subtype Diagnosis of Primary Aldosteronism: Approach to Different Clinical Scenarios.

Identification and management of patients with primary aldosteronism are of utmost importance because it is a frequent cause of endocrine hypertension, and affected patients display an increase of cardio- and cerebro-vascular events, compared to essential hypertensives. Distinction of primary aldosteronism subtypes is of particular relevance to allocate the patients to the appropriate treatment, represented by mineralocorticoid receptor antagonists for bilateral forms and unilateral adrenalectomy for patients with unilateral aldosterone secretion. Subtype differentiation of confirmed hyperaldosteronism comprises adrenal CT scanning and adrenal venous sampling. In this review, we will discuss different clinical scenarios where execution, interpretation of adrenal vein sampling and subsequent patient management might be challenging, providing the clinician with useful information to help the interpretation of controversial procedures.

How to use the equipment you have for appropriate quality at low radiation dose.

A CT department's ability to image with low radiation doses is determined primarily by the CT scan protocols and the radiologists' image quality expectations and to a lesser extent by the dose-reduction features available. The CT technology level has a smaller influence than might be expected. There are, however, exceptions where dose is directly linked to the scanner's technical capabilities. The key to appropriate image quality with low radiation dose is therefore optimised scan protocols. To optimise effectively, an in-depth understanding of the technical performance of the scanner is required. Therefore, optimisation is best carried out by a multi-disciplinary team that includes radiologists, technologists and medical physics experts. This article describes practical strategies for carrying out such exercises.

Hepatocyte growth factor is elevated in amniotic fluid from obese women and regulates placental glucose and fatty acid metabolism.

INTRODUCTION: To evaluate the impact of the pro-inflammatory cytokine hepatocyte growth factor (HGF) on the regulation of glucose and lipid placental metabolism. METHODS: HGF levels were quantified in amniotic fluid and placenta from control and obese women. 2-deoxy-glucose (2-DOG) uptake, glycolysis, fatty acid oxidation (FAO), fatty acid esterification, de novo fatty acid synthesis, triglyceride levels and carnitine palmitoyltransferase activities (CPT) were measured in placental explants upon addition of pathophysiological HGF levels. RESULTS: In obese women, total- and -activated-HGF levels in amniotic fluid were elevated ∼24%, and placental HGF levels were ∼3-fold higher than in control women. At a similar dose to that present in amniotic fluid of obese women, HGF (30 ng/mL) increased Glut-1 levels and 2-DOG uptake by ∼25-30% in placental explants. HGF-mediated effect on 2-DOG uptake was dependent on the activation of phosphatidylinositol 3-kinase signaling pathway. In addition, HGF decreased ∼20% FAO, whereas esterification and de novo fatty acid synthesis increased ∼15% and ∼25% respectively, leading to 2-fold triglyceride accumulation in placental explants. In parallel, HGF reduced CPT-I activity ∼70%. DISCUSSION: HGF is a cytokine elevated in amniotic fluid and placental tissue of obese women, which through its ability to stimulate 2-DOG uptake and metabolism impairs FAO and enhances esterification and de novo fatty acid synthesis, leading to accumulation of placental triglycerides.