Psychotherapeutic nursing as Advanced Clinical Practice for the promotion of mental health in Spain.

OBJECTIVE: To contribute to the recognition of psychotherapeutic nursing (PTN) as a regulated advanced clinical practice (ACP) in Spain, as is the case in other countries. BACKGROUND: Nurses are continually evolving to improve overall health outcomes. PTN has become a reality, with several authors describing it as an ACP. In Spain, psychotherapy is not officially regulated, which has led to a significant number of psychiatric nurses adopting an important ACP in this area without recognition. SOURCES OF EVIDENCE: Evidence confirms that PTN possesses the attributes necessary to be considered an ACP. Nurses, like psychotherapists, independently address the complex needs of individuals and families within the context of therapeutic relationships, and there is a pressing need to advance formal processes of regulation and certification. DISCUSSION: PTN has evolved at different rates depending on local initiatives, policies and various professional interests. In Spain, it is crucial to evaluate its outcomes, recognise it as an ACP and develop training plans for its regulation and accreditation. CONCLUSIONS: Mental health nurses in Spain have a strong interest in PTN being recognised as an ACP. To this end, they should join forces with other partners, scientific associations and international bodies such as the International Council of Nurses (ICN) to make PTN an internationally recognised ACP. IMPLICATIONS FOR NURSING PRACTICE: Psychotherapeutic nurses could contribute to improving mental health outcomes, client satisfaction and health system efficiency, and their formal recognition is an opportunity to enhance their professional identity, competence and autonomy. IMPLICATIONS FOR NURSING POLICY: Nursing policy needs to be reoriented towards strengthening psychotherapy as an ACP. Synergies and alliances between international nursing associations and the ICN can promote its development and implementation, while research, education and leadership are essential to achieving official regulation and accreditation.

Clinical utility of liquid biopsy and integrative genomic profiling in early-stage and oligometastatic cancer patients treated with radiotherapy.

BACKGROUND: Liquid biopsy and Integrative Genomic Profiling (IGP) are yet to be implemented into routine Radiation Oncology. Here we assess the utility of germline, tumour and circulating cell-free DNA-based genomic analyses for the clinical management of early-stage and oligometastatic cancer patients treated by precision radiotherapy. METHODS: We performed germline, tissue- and liquid biopsy NGS panels on 50 early-stage/oligometastatic cancer patients undergoing radiotherapy. We also monitored ctDNA variants in serial liquid biopsies collected during radiotherapy and follow-up and evaluated the clinical utility of such comprehensive approach. RESULTS: The integration of different genomic studies revealed that only 1/3 of the liquid biopsy variants are of tumour origin. Altogether, 55 tumour variants (affecting 3/4 of the patients) were considered potentially actionable (for treatment and prognosis), whereas potential follow-up biomarkers were identified in all cases. Germline cancer-predisposing variants were present in three patients, which would have not been eligible for hereditary cancer testing according to clinical guidelines. The presence of detectable ctDNA variants before radiotherapy was associated with progression-free survival both in oligometastatic patients and in those with early-stage. CONCLUSIONS: IGP provides both valuable and actionable information for personalised decision-making in Radiation Oncology.

CANVAS: A New Genetic Entity in the Otorhinolaryngologist's Differential Diagnosis.

OBJECTIVE: The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. STUDY DESIGN: A retrospective descriptive study from an ataxia database comprising 500 patients. SETTING: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. METHODS: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. RESULTS: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. CONCLUSION: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

Radixin modulates the function of outer hair cell stereocilia.

The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.

Comprehensive genomic diagnosis of inherited retinal and optical nerve disorders reveals hidden syndromes and personalized therapeutic options.

PURPOSE: In the era of precision medicine, genomic characterization of blind patients is critical. Here, we evaluate the effects of comprehensive genetic analysis on the etiologic diagnosis of potentially hereditary vision loss and its impact on clinical management. METHODS: We studied 100 non-syndromic and syndromic Spanish patients with a clinical diagnosis of blindness caused by alterations on the retina, choroid, vitreous and/or optic nerve. We used a next-generation sequencing (NGS) panel (OFTALMOgenics™), developed and validated within this study, including up to 362 genes previously associated with these conditions. RESULTS: We identified the genetic cause of blindness in 45% of patients (45/100). A total of 28.9% of genetically diagnosed cases (13/45) were syndromic and, of those, in 30.8% (4/13) extraophthalmic features had been overlooked and/or not related to visual impairment before genetic testing, including cases with Mainzer-Saldino, Bardet-Biedl, mucolipidosis and MLCRD syndromes. In two additional cases-syndromic blindness had been proposed before, but not specifically diagnosed, and one patient with Heimler syndrome had been misdiagnosed as an Usher case before testing. 33.3% of the genetically diagnosed patients (15/45) had causative variants in genes targeted by clinical trials exploring the curative potential of gene therapy approaches. CONCLUSION: Comprehensive genomic testing provided clinically relevant insights in a large proportion of blind patients, identifying potential therapeutic opportunities or previously undiagnosed syndromes in 42.2% of the genetically diagnosed cases (19/45).

Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil / Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit

INTRODUCCIÓN: La hipoacusia neurosensorial (HNS) es el déficit sensorial más prevalente en nuestro medio. La secuenciación genómica de nueva generación (NGS) permite obtener un diagnóstico etiológico en un alto porcentaje de pacientes. Nuestro estudio piloto muestra los resultados de la aplicación sistemática de la NGS en una Unidad de Hipoacusia Infantil, así como sus implicaciones en el manejo clínico de los pacientes y sus familiares. MATERIAL Y MÉTODO: Se incluyó a 27 pacientes diagnosticados de HNS entre 2014 y 2017 en los que se descartó una causa ambiental. El test genético consistió en un panel de genes analizados mediante NGS (panel OTOgenicsTM). Este panel ha sido diseñado para incluir genes asociados con hipoacusia neurosensorial o mixta, de inicio precoz o tardío, sindrómica y no sindrómica, independientemente de su patrón de herencia. RESULTADOS: Se obtuvo un diagnóstico genético en el 56% (15/27) de los pacientes (62% en el caso de las HNS bilaterales); 5/27 (19%) presentaron variantes patogénicas en el gen GJB2 y el resto variantes patogénicas o probablemente patogénicas en otros genes asociados con HNS aislada (PR2X2, TECTA y STRC), con HNS sindrómicas (CHD7, GATA3, COL4A5, MITF y SOX10) o con HNS sindrómicas y no sindrómicas (BSND, ACTG1 y CDH23). DISCUSIÓN: El diagnóstico etiológico de la HNS supone un desafío en la práctica clínica. Nuestra serie demuestra que es posible implementar el diagnóstico genético en la rutina asistencial y que esta información tiene implicaciones pronósticas y terapéuticas

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications

El arte de la psicoterapia enfermera / The art of nursing psychotherapy

El progreso y transformación de los cuidados enfermeros en pleno siglo XXI, inherente al propio proceso de globalización y evolución social, conlleva cambios en la educación, formación y capacitación de las enfermeras. Esto da como resultado profesionales cada vez más competentes, eficientes y con autonomía suficiente para dar respuesta a las distintas necesidades de cuidados y requerimientos en salud y bienestar de las personas, familias, grupos sociales. En el ámbito de la práctica y cuidados en salud mental, las transformaciones propuestas en los sistemas sanitarios son claras, debiendo las mismas ser impulsadas por los consumidores, orientadas a la recuperación, basadas en la mejor evidencia disponible y orientadas hacia sistemas coordinados y colaborativos de atención y cuidados. Dentro de esta transformación en los sistemas de atención sanitaria, la psicoterapia enfermera, como competencia avanzada de las enfermeras especialistas, ha venido a consolidar el aporte, compromiso y valor social del cuidado enfermero. El objetivo de este artículo es presentar cómo se ha venido configurando, desde su emergencia, la psicoterapia enfermera en tanto que marco de acción en el quehacer de los cuidados profesionales especializados en salud mental; un recorrido que nos acerca a su conceptualización más internacional para derivar finalmente en la propuesta que desde la Asociación Española de Enfermería de Salud Mental (AEESME) se promueve para su implementación en la Cartera de Servicios del Sistema Nacional de Salud de España

The progress and transformation of nursing care in the middle of the XXI century, attached to the process of globalisation and social development itself, entail changes in education, training and qualification of nurses. As a result, professionals are more and more competent, efficient and with autonomy enough as to meet the various needs for care and the demand for health and welfare of the people, families and social groups. In the field of mental health care practice, there are evident initiatives of transformation in the health system, which ought to be driven by customers, aimed at recovery, evidence-based and directed towards collaborative and coordinated care and assistance systems. Within this process of transformation, and as an advanced competency of nurse specialists, Nurse Psychotherapy has consolidated the contribution, commitment and social value of nursing care. The aim of this article is to shed light on how Nurse Psychotherapy has developed since its inception as a framework for specialized, professional mental health care. Beginning with its international conceptualisation, it then drifts to the proposal promoted by the Spanish Mental Health Nursing Association (AEESME) for its implementation in the portfolio of healthcare Services of the Spanish National Health System

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon. EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases. RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months. CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy. IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit. / Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil.

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications.

Effect of eccentric overload through isoinertial technology in basketball players / Efeito da sobrecarga excêntrica através da tecnologia isoinercial em jogadores profissionais de basquetebol

Abstract The present study investigated the effect of eccentric overload on professional basketball players. Participants were 8 players aged 18-25 years who play in a Leb Oro League team. There was an 8 week training cycle with 1 weekly session of half squats. The control group performed training following a traditional methodology -using free weights- whereas the experimental group used inertial technology, that is, the ProSquat machine from Proinertial®. Both vertical jump and 30-meter sprint were assessed before and after intervention. The following conclusions were reached: a) strength training with vertical vector improves the 30-meter sprint test and also the vertical jump; b) training program that affects the eccentric overload of the movement results in more improvements than traditional training with the same duration; c) training in the vertical vector also has an impact on the way force is manifested in the horizontal vector, showing improvements in the 30-meter sprint.

Resumo O presente estudo investigou o efeito da sobrecarga excêntrica em jogadores profissionais de basquetebol. Os participantes foram 8 jogadores de uma equipe da Leb Gold League entre 18 e 25 anos. Um ciclo de treinamento de 8 semanas foi realizado com 1 sessão semanal no exercício de meio agachamento. O grupo controle realizou o treinamento com metodologia tradicional, com pesos livres, e o grupo experimental, por meio de tecnologia inercial, com a máquina ProSquat, Proinertial®. O salto vertical e o sprint de 30 metros foram avaliados antes e após a intervenção. As seguintes conclusões foram obtidas: a) o treinamento de força com um componente no vetor vertical mostra melhorias no teste de 30 metros e no salto vertical; b) um programa que afeta a sobrecarga de movimento excêntrico apresenta resultados com melhores desempenhos do que o treinamento tradicional; c) o treinamento no vetor vertical também afeta uma expressão da força no vetor horizontal, mostrando melhorias no sprint de 30 metros.

Entendimiento de la miocardiopatía hipertrófica mediante el estudio de una variante patogénica fundadora / Insights into hypertrophic cardiomyopathy evaluation through follow-up of af pathogenic variant

Introducción y objetivos: La miocardiopatía hipertrófica (MCH) es la enfermedad cardiaca hereditaria más frecuente. El desafío actual radica en la clasificación precisa de la patogenicidad de variantes asociadas a las MCH. Para la evaluación inicial de la MCH se recomienda una ecocardiografía transtorácica (ETT). La cardiorresonancia magnética (CRM) también debe considerarse. El objetivo fue revaluar la penetrancia y expresión clínica de la variante patogénica MYBPC3 p.G263*. Métodos: Se estudiaron los principales genes sarcoméricos, mediante next-generation sequencing, en 384 índices con MCH y una cohorte control de 450 individuos sanos. Se identificaron todos portadores de MYBPC3 p.G263* y se realizó cribado familiar. Se recogió información clínica de manera retrospectiva hasta 2015 y prospectiva a partir de entonces. Se realizó un esfuerzo extra para realizar CRM en todos los portadores de la variante independientemente del resultado de la ETT. Resultados: Trece casos índice con MCH y ninguno de la cohorte control eran portadores de la variante MYBPC3 p.G263*, patogénica según el American College of Medical Genetics and Genomics y la Association for Molecular Pathology. Mediante cribado familiar se identificó a un total de 39 portadores. La mayoría se diagnosticó de MCH asintomática, con inicio tardío de la enfermedad y un curso relativamente benigno, pero con potenciales complicaciones tardías. Se encontró una penetrancia cercana al 70% evaluada por la ETT y del 87% por CRM. La penetrancia era edad-dependiente, y alcanzó el 100% en mayores de 55 años. Conclusiones: MYBPC3 p.G263* comparte con la mayoría de las variantes patogénicas truncantes en este gen un inicio tardío, un curso relativamente benigno en los jóvenes y una alta penetrancia. La CRM podría ser una herramienta útil en la evaluación de portadores independientemente de la ETT

Introduction and objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The current challenge relies on the accurate classification of the pathogenicity of the variants. Transthoracic echocardiography (TTE) is recommended at initial evaluation and cardiac magnetic resonance (CMR) imaging should also be considered. We aimed to reappraise the penetrance and clinical expression of the MYBPC3 p.G263* variant. Methods: Three hundred and eighty-four HCM probands and a control cohort of 450 individuals were studied for the main sarcomere genes by next-generation sequencing. All MYBPC3 p.G263* carriers were identified and family screening was performed. Clinical information was recorded retrospectively before 2015 and prospectively thereafter. Extra effort was invested in performing CMR in all carriers, despite TTE results. Results: Thirteen HCM probands and none of the controls were carriers of the MYBPC3 p.G263* pathogenic variant (according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology). A total of 39 carriers were identified with family screening. Most patients with HCM were asymptomatic at the time of diagnosis and showed late-onset disease. Despite having a relatively benign course in the young, late HCM-related complications could occur. Penetrance was around 70% when evaluated by TTE and was 87.2% with TTE plus CMR. Penetrance was age-dependent, reaching 100% in carriers older than 55 years. Conclusions: MYBPC3 p.G263* shares with most truncating pathogenic variants in this gene a late onset, relatively benign clinical course in the young, and high penetrance. Cardiac magnetic resonance could be a useful tool to evaluate carriers despite TTE results

Insights Into Hypertrophic Cardiomyopathy Evaluation Through Follow-up of a Founder Pathogenic Variant.

INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The current challenge relies on the accurate classification of the pathogenicity of the variants. Transthoracic echocardiography (TTE) is recommended at initial evaluation and cardiac magnetic resonance (CMR) imaging should also be considered. We aimed to reappraise the penetrance and clinical expression of the MYBPC3 p.G263* variant. METHODS: Three hundred and eighty-four HCM probands and a control cohort of 450 individuals were studied for the main sarcomere genes by next-generation sequencing. All MYBPC3 p.G263* carriers were identified and family screening was performed. Clinical information was recorded retrospectively before 2015 and prospectively thereafter. Extra effort was invested in performing CMR in all carriers, despite TTE results. RESULTS: Thirteen HCM probands and none of the controls were carriers of the MYBPC3 p.G263* pathogenic variant (according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology). A total of 39 carriers were identified with family screening. Most patients with HCM were asymptomatic at the time of diagnosis and showed late-onset disease. Despite having a relatively benign course in the young, late HCM-related complications could occur. Penetrance was around 70% when evaluated by TTE and was 87.2% with TTE plus CMR. Penetrance was age-dependent, reaching 100% in carriers older than 55 years. CONCLUSIONS: MYBPC3 p.G263* shares with most truncating pathogenic variants in this gene a late onset, relatively benign clinical course in the young, and high penetrance. Cardiac magnetic resonance could be a useful tool to evaluate carriers despite TTE results.

Delimitando la coerción y los cuidados enfermeros en salud mental: Una aproximación cualitativa / Delimitando a coerção e os cuidados de enfermagem em saúde mental: Uma abordagem qualitativa / Defining coercion and mental health care provided by nurses: A qualitative approach

CONTEXTO: La cultura cada vez más coercitiva en la atención a la salud mental se pone de manifiesto en multitud de intervenciones. Es preciso tomar en consideración las aportaciones de los profesionales de salud mental como procedimiento de evaluación y determinación de factores estratégicos en la facilitación hacia un cambio de paradigma. OBJETIVO: Analizar el discurso grupal en base a las opiniones, experiencias y percepciones de las enfermeras sobre la coerción y sus límites con los valores profesionales en el ámbito de los cuidados en salud mental. MÉTODO: Estudio descriptivo de enfoque cualitativo, donde participaron once enfermeras involucradas en el proceso formativo/docente de la especialidad de enfermería de salud mental. La recolección de datos se produjo a través de la técnica de grupo focal y el contenido textual ha sido sometido al análisis temático. RESULTADOS: Las categorías temáticas identificadas son: “Coerción: contexto de descubrimiento y contexto de justificación”, “Cuidado humano, vulnerabilidad y coerción en salud mental” y “Fortalezas y debilidades del cuidado profesional”. CONCLUSIÓN: Los valores y actitudes emergentes de las enfermeras especialistas en salud mental se articulan en la relación de ayuda, siendo la propia identidad enfermera el resultado de esa práctica y teniendo como principal característica la gestión integral del cuidado. Los cuidados enfermeros contribuyen a la consecución práctica de los derechos humanos. El cuidado contractual supone la negación de hacerse partícipe de prácticas obligatorias o coercitivas, tratándose de incorporar en una lógica de derecho la complejidad del cuidado.

CONTEXTO: A cultura cada vez mais coercitiva da atenção em saúde mental é evidente em diversas intervenções. É preciso ter em consideração as contribuições dos profissionais da saúde mental como procedimento de avaliação e determinação de fatores estratégicos na facilitação da mudança de paradigma. OBJETIVO: Analisar o discurso grupal com base nas opiniões, experiências e percepções das enfermeiras sobre a coerção e os seus limites com os valores profissionais no âmbito dos cuidados em saúde mental. MÉTODOS: Estudo descritivo com uma abordagem qualitativa, onde participaram onze enfermeiras envolvidas no processo de formação e a docência da especialidade de enfermagem de saúde mental. A colheita de dados foi realizada através da técnica de grupo focal e o conteúdo textual foi submetido à análise temática. RESULTADOS: As categorias temáticas identificadas são: “Coerção: contexto de descoberta e contexto de justificação”, “Do cuidado humano, vulnerabilidade e coerção em saúde mental” e “Fortalezas e debilidades do cuidado profissional”. CONCLUSÃO: Os valores e atitudes emergentes das enfermeiras especialistas em saúde mental dependem da relação de ajuda, sendo a própria identidade da enfermeira o resultado dessa prática e tendo como principal característica a gestão integral do cuidado. Os cuidados de enfermagem contribuem à consecução prática dos direitos humanos. O cuidado contratual supõe a negação de fazer-se participante de práticas obrigatórias ou coercitivas, tratando-se de incorporar em uma lógica de direito a complexidade do cuidado.

BACKGROUND: Increasingly coercive culture in mental health care clearly comes out in a multitude of interventions. It is necessary to take into consideration the contributions of mental health professionals to evaluate and determine strategic factors to facilitate a paradigm shift. AIM: Analysis of group discourse based on the opinions, experiences and perceptions of nurses about coercion and its limits, with professional values in the field of mental health care. METHODS: Descriptive study from a qualitative approach with the participation of eleven nurses involved in the teaching- learning process about specialises in mental health. Data collection was done through the focus group technique and textual content has been subjected to thematic analysis. RESULTS: The thematic categories identified are: "Coercion: context of discovery and context of justification", "Human care, vulnerability and coercion in mental health" and "Strengths and weaknesses of professional care". CONCLUSION: Values and emerging attitudes of nurses specialized in mental health are based on aid relationships. The own nurse identity is the result of this practice and the integral management of care is the main feature. Nursing care contributes to the practical achievement of human rights. Contractual care implies the refusal to participate in compulsory or coercive practices, trying to understand the complexity of care under a logic of law.

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. METHODS: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. RESULTS: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). CONCLUSIONS: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.

A novel molecular diagnostics platform for somatic and germline precision oncology.

BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies. METHODS: Next-generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug-related rearrangements, were prepared from 39 tumors (paraffin-embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines. RESULTS: The platform detects single-nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy-number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent. CONCLUSION: With an adequate methodology, it is possible to translate to the clinical practice the latest advances in precision oncology, integrating under the same platform the identification of somatic and germline genomic alterations.

Intensity-modulated radiotherapy for head and neck surgeons.

The development of intensity-modulated radiotherapy (IMRT) has played a major role in improving outcomes and decreasing morbidity in patients with head and neck cancer. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and postoperative radiotherapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2368-E2373, 2016.

Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas.

Laryngeal squamous cell carcinoma is a frequent and significant cause of morbidity and mortality. Here we explore the biological basis of this aggressive tumour, and identify two cell-cell adhesion genes as recurrently mutated in this malignancy. We first perform exome sequencing of four laryngeal carcinomas and their matched normal tissues. Among the 569 genes found to present somatic mutations, and based on their recurrence or functional relevance in cancer, we select 40 for further validation in 86 additional laryngeal carcinomas. We detect frequent mutations (14 of 90, 15%) in CTNNA2 and CTNNA3-encoding α-catenins. Functional studies reveal an increase in the migration and invasive ability of head and neck squamous cell carcinoma cells producing mutated forms of CTNNA2 and CTNNA3 or in cells where both α-catenins are silenced. Analysis of the clinical relevance of these mutations demonstrates that they are associated with poor prognosis. We conclude that CTNNA2 and CTNNA3 are tumour suppressor genes frequently mutated in laryngeal carcinomas.

Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion.

Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A-accumulating) and Zmpste24-proficient (mature lamin A-containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target.