[Inhaled levodopa: from evidence to experience]. / Levodopa inhalada: de la evidencia a la experiencia.

Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa.

TITLE: Levodopa inhalada: de la evidencia a la experiencia.La mayoría de los pacientes con enfermedad de Parkinson sufren fluctuaciones motoras o períodos off, que impactan en sus actividades cotidianas, aumentan su discapacidad y empeoran su calidad de vida. A pesar de realizar múltiples ajustes en los horarios, en las dosis y en las tomas de medicación, no se consigue que estén libres de estas fluctuaciones. Es en este contexto en el que son necesarios los tratamientos a demanda o de rescate para tratar de mejorar los períodos off, con fármacos que tienen la ventaja farmacocinética de un inicio de acción mucho más rápido debido a que sus vías de administración no son orales. En la actualidad existen tres terapias a demanda para el tratamiento de las fluctuaciones: apomorfina subcutánea, levodopa inhalada y apomorfina sublingual. En general, la apomorfina subcutánea tiene un inicio de efecto más rápido, la apomorfina sublingual ofrece el efecto clínico más prolongado y la levodopa inhalada tiene el perfil de efectos secundarios más favorable entre las tres opciones. Cada uno de estos medicamentos tiene características únicas: tiempo de inicio, duración de acción y diferentes perfiles de efectos secundarios. La elección para cada paciente dependerá de sus necesidades y circunstancias individuales. Aprovechando el primer año de la introducción de la levodopa inhalada, revisamos estas terapias, centrándonos en la experiencia acumulada con esta nueva presentación galénica de levodopa.

La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes / The new age of neurodegenerative diseases. The basis of the new approaches

La detección por biomarcadores de los procesos fisiopatológicos y moleculares implicados en las enfermedades cerebrales por plegamiento anormal de proteínas está permitiendo delinear la historia natural de estos procesos. La gran mayoría de ellos tiene una fase preclínica prolongada, en la que los cambios biológicos son patentes. Las manifestaciones clínicas (fenotipos) no tienen una correspondencia unívoca con la patología subyacente, a pesar de que se han utilizado los epónimos anatomopatológicos para la descripción de los síndromes clínicos, lo que ha favorecido la imprecisión diagnóstica. Para realizar un adecuado manejo clínico debemos conocer los tres planos que definen actualmente los procesos neurodegenerativos más frecuentes. La precisión diagnóstica será un prerrequisito para las nuevas terapias dirigidas a modificar el curso de las enfermedades por plegamiento proteico cerebrales. (AU)

The detection by biomarkers of the pathophysiological and molecular processes involved in misfolding protein diseases making it possible to delineate the natural history of these processes. The great majority of protein misfolding diseases have a prolonged preclinical phase, in which the biological changes are patent. The clinical manifestations (i.e., phenotypes) do not have a univocal correspondence with the underlying pathology, despite the fact that pathological eponyms have been used for the description of the clinical syndromes, which has favored diagnostic inaccuracy. In order to perform an adequate clinical management, we must know the 3 planes that currently define the most common neurodegenerative processes. Diagnostic accuracy will be a prerequisite for new therapies aimed at modifying the course of brain protein misfolding diseases. (AU)

[The new age of neurodegenerative diseases. The basis of the new approaches]. / La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes.

The detection by biomarkers of the pathophysiological and molecular processes involved in misfolding protein diseases making it possible to delineate the natural history of these processes. The great majority of protein misfolding diseases have a prolonged preclinical phase, in which the biological changes are patent. The clinical manifestations (i.e., phenotypes) do not have a univocal correspondence with the underlying pathology, despite the fact that pathological eponyms have been used for the description of the clinical syndromes, which has favored diagnostic inaccuracy. In order to perform an adequate clinical management, we must know the 3 planes that currently define the most common neurodegenerative processes. Diagnostic accuracy will be a prerequisite for new therapies aimed at modifying the course of brain protein misfolding diseases.

TITLE: La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes.La detección por biomarcadores de los procesos fisiopatológicos y moleculares implicados en las enfermedades cerebrales por plegamiento anormal de proteínas está permitiendo delinear la historia natural de estos procesos. La gran mayoría de ellos tiene una fase preclínica prolongada, en la que los cambios biológicos son patentes. Las manifestaciones clínicas (fenotipos) no tienen una correspondencia unívoca con la patología subyacente, a pesar de que se han utilizado los epónimos anatomopatológicos para la descripción de los síndromes clínicos, lo que ha favorecido la imprecisión diagnóstica. Para realizar un adecuado manejo clínico debemos conocer los tres planos que definen actualmente los procesos neurodegenerativos más frecuentes. La precisión diagnóstica será un prerrequisito para las nuevas terapias dirigidas a modificar el curso de las enfermedades por plegamiento proteico cerebrales.

Usefulness of Community Pharmacy for Early Detection of Cognitive Impairment in Older People Using the IQ-CODE Questionnaire.

BACKGROUND: People with cognitive impairment (CI) need to be identified early because of the risk of progression to dementia. OBJECTIVES: The primary objective of the study was to analyze the usefulness of the community pharmacy for early detection of CI in older people through their caregivers. As secondary objective the risk factors related to IQ-CODE classification of risk of CI were identified. DESIGN: A cross-sectional observational study was designed. SETTING: Caregivers were selected by pharmacists from Spanish community pharmacies. PARTICIPANTS: Subjects with a close relationship to persons over 70 years of age who were not previously diagnosed with CI and who did not live in a nursing home or were hospitalized participated in the study. MEASUREMENTS: The proportion of older people who were classified as "at risk of CI" was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQ-CODE), which was completed by the caregiver. RESULTS: A total of 197 pharmacists selected 910 caregivers with an average age of 53 years, 75.5% of whom were women. In 324 people over the age of 70 (38.5%), "risk of CI" was observed, increasing with age. The risk of CI was 4.3 times higher in older people who complained of memory loss (p<0.001), 2.5 times higher if they had had a stroke in the last two years (p=0.007), 1.9 times higher if they were smokers (p=0.045) and 1.6 times higher if they were diabetic (p=0.028). CONCLUSION: Detection of risk of CI from the community pharmacy showed prevalence figures consistent with the CI figures observed in the Spanish primary care setting, demonstrating the capacity of the community pharmacy to contribute to early detection of CI.

Combination of phenotype and polygenic risk score in breast cancer risk evaluation in the Spanish population: a case -control study.

BACKGROUND: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. METHODS: This is a case control study based on a population-based cohort. We describe and evaluate a multivariable model that incorporates 92 Single-nucleotide polymorphisms (SNPs) (Supplementary Table S1) and five different phenotypic variables and which was employed in a Spanish population of 642 healthy women and 455 breast cancer patients. RESULTS: Our model allowed us to stratify two groups: high and low risk of developing breast cancer. The 9th decile included 1% of controls vs 9% of cases, with an odds ratio (OR) of 12.9 and a p-value of 3.43E-07. The first decile presented an inverse proportion: 1% of cases and 9% of controls, with an OR of 0.097 and a p-value of 1.86E-08. CONCLUSIONS: These results indicate the capacity of our multivariable model to stratify women according to their risk of developing breast cancer. The major limitation of our analysis is the small cohort size. However, despite the limitations, the results of our analysis provide proof of concept in a poorly studied population, and opens up the possibility of using this method in the routine screening of the Spanish population.

[«Apuntes en Neurologia¼ (Notes in Neurology): a synthesis of the evidence on common paroxysmal neurological disorders and on neurodegenerative disorders]. / «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.

«Apuntes en Neurologia¼ is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson's disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases.

TITLE: «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.«Apuntes en Neurologia¼ es una iniciativa en la cual lideres de primera linea nacional e internacional, con amplio reconocimiento academico, se reunieron para sintetizar los aspectos clinicos mas destacables dentro de su area de interes y acercar las novedades en una lengua mas proxima. Entender los factores que afectan al inicio y progresion de cualquier enfermedad neurologica a traves de una revision es importante para el desarrollo de estrategias en pro de reducir la carga de estas enfermedades, y conocer los aspectos clinicos es esencial para poder resolver los problemas de la practica clinica diaria. Los datos aqui recogidos reflejan el peso de la evidencia y algunos de ellos anticipan un futuro prometedor en el tratamiento de estas enfermedades. Esta primera edicion se centra en trastornos neurologicos comunes paroxisticos como la migraña, la epilepsia y las alteraciones del sueño, y en trastornos neurodegenerativos como la enfermedad de Parkinson y el deterioro cognitivo. Se trata de patologias claramente diferentes, si bien algunas de ellas, como la migraña y la epilepsia, pueden compartir sintomatologia clinica. Los trastornos del sueño, por su parte, son manifestaciones importantes de enfermedades neurodegenerativas que, en ocasiones, son clinicamente evidentes mucho antes del inicio de otros sintomas neurologicos. Tras recordar la fisiopatologia y el diagnostico, la revision actual se centra en acercar los principales avances en cinco de las principales enfermedades neurologicas.

El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic? / Use of e-mail for Parkinson's disease consultations: Are answers just a clic away?

Introducción: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad de Trastornos del Movimiento (UTM). Métodos: Se revisaron retrospectivamente los correos electrónicos enviados y recibidos en un periodo de 4 meses, un año tras su implantación. La dirección se proporcionaba en consulta y mediante sesiones informativas a los MAP del área. Se analizaron datos clínicos y demográficos de los pacientes, tipo de interlocutor, número de consultas, motivo y actuaciones derivadas de ellas. Resultados: Del 1 de enero al 30 de abril de 2015 se recibieron 137 correos de 63 pacientes (43% varones; edad 71 ± 10,5 años) diagnosticados de enfermedad de Parkinson (76%), parkinsonismos atípicos (10%) y otros (14%), y se enviaron 116 respuestas. En 20 casos (32%) fueron redactados por el paciente, en 38 (60%) por sus familiares y en 5 (8%) por MAP. Los motivos de consulta fueron clínicos en 50 casos (80%): deterioro clínico (16; 32%), nuevos síntomas (14; 28%), efectos secundarios o dudas sobre medicación (20; 40%). Como consecuencia, se adelantó una cita programada en 9 casos (14%), mientras que el resto se solucionaron por correo electrónico. En 13 (20%), el motivo de consulta fue burocrático: relacionado con citas (11, 85%) y solicitud de informe (2, 15%). La satisfacción fue generalizada, sin constituir una sobrecarga asistencial excesiva para los facultativos responsables. Conclusiones: La implantación de una consulta por correo electrónico es factible en UTM, facilita la comunicación médico-paciente y la continuidad asistencial con Atención Primaria (AU)

Introduction: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients' demographic and clinical data, number of queries, reason for consultation, and actions taken. Results: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71 ± 10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. Conclusions: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting (AU)

Use of e-mail for Parkinson's disease consultations: Are answers just a clic away? / El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic?

INTRODUCTION: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). METHODS: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients' demographic and clinical data, number of queries, reason for consultation, and actions taken. RESULTS: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71±10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. CONCLUSIONS: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting.

[Cognitive impairment as a predictor of functional decline after hospitalization: DECOFIRH Study]. / Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.

AIM: Cognitive impairment is underdiagnosed in the elderly. We aimed to study the rate of positive responses to an informant-based questionnaires and functional disability after hospital discharge. PATIENTS AND METHODS: Observational prospective case series of patients aged 70-85 years-old admitted for hospitalization in an Internal Medicine ward. All medical records were reviewed and those patients with no previous diagnosis of dementia or related neurological conditions, no previous recent hospitalization or not having a caregiver were evaluated after signing an informed consent. A medical interview including the Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained three months after discharge. RESULTS: During a 3-month period a total of 809 admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's mean age was 80 years-old. Common comorbidities were arterial hypertension (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent cause of admission was infectious disease (37.9%). Test positivity for cognitive impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the patients were functionally independent. At three months this percentage dropped to 24%. CONCLUSIONS: In this small sample size, almost a third of older patients, without major comorbidities or neurological disorders, admitted to a general hospital showed an informant-based suggestion of cognitive impairment previously undiagnosed. Functional impairment affects almost a quarter of these patients three months after admission.

TITLE: Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.Objetivo. El deterioro cognitivo esta infradiagnosticado. El estudio DECOFIRH pretende detectar la tasa de deterioro cognitivo no conocido y su impacto en la situacion funcional de estos pacientes tras un ingreso hospitalario mediante cuestionarios realizados a un informador. Pacientes y metodos. Estudio observacional prospectivo realizado sobre una serie de casos, de pacientes comprendidos entre 70 y 85 años, que ingresan en el Servicio de Medicina Interna de un hospital terciario. Se excluyo a los pacientes con diagnostico de demencia o enfermedades neurologicas graves, asi como a los que habian sido hospitalizados recientemente. Los tests empleados en la deteccion de deterioro cognitivo fueron Alzheimer's Disease 8 (AD8) e Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Asimismo, se evaluo la situacion funcional mediante el indice de Barthel en el momento del ingreso y tres meses despues. Resultados. Durante los tres meses de seguimiento ingresaron 809 pacientes y cumplieron los criterios de inclusion 79 (9,7%) de ellos. Su edad media era de 80 años. Mediante el IQCODE se detecto una tasa de deterioro cognitivo del 30,3%, y con el AD8, del 34,1%. En el ingreso, el 37,9% de los pacientes era funcionalmente independiente. A los tres meses, este porcentaje cayo al 24%. Conclusiones. En nuestra muestra, casi un tercio de los ancianos sin comorbilidades sistemicas o neurologicas graves dio positivo para la deteccion de deterioro cognitivo segun nuestros tests basados en el informador, sin ser este conocido previamente. El deterioro funcional afecta casi a una cuarta parte de estos pacientes a los tres meses del ingreso.

Biomarcadores por tomografia por emisión de positrones (PET): imagen de la patología de Alzheimer y la neurodegeneración al servicio del diagnóstico clínico / PET biomarkers: Use of imaging techniques in Alzheimer disease and neurodegeneration clinical diagnosis

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Niveles de 25-hidroxivitamina D en pacientes con melanoma y factores asociados con su insuficiencia / 25-hydroxyvitamin D in patients with melanoma and factors associated with inadequate levels

INTRODUCCIÓN Y OBJETIVOS: Los pacientes con melanoma parecen llevar al extremo las medidas de protección, lo que puede influir en los niveles de 25-hidroxivitamina D-25(OH)D-. El objetivo del estudio fue evaluar los niveles de 25(OH)D en pacientes con melanoma cutáneo e identificar factores relacionados con niveles inadecuados. MATERIAL Y MÉTODOS: Se midieron prospectivamente los niveles séricos de 25(OH)D en pacientes diagnosticados de melanoma cutáneo durante un periodo de seguimiento de un año. Se evaluaron qué factores ambientales, fenotípicos y genotípicos se relacionaban con niveles insuficientes y deficientes mediante regresión logística. RESULTADOS: De un total de 215 pacientes solo un 24,7% tenían valores normales de 25(OH)D y un 8,8% tenían valores deficientes (< 10 ng/ml). La obesidad (OR: 4,2; IC 95% OR: 1,3-13,3) y la extracción de sangre realizada en otoño/invierno (OR: 2,1; IC 95% OR: 1,1-4) se asociaron a niveles insuficientes (< 30 ng/ml). Los niveles deficitarios (< 10 ng/m) se asociaron a la obesidad (OR: 7,1; IC 95% OR: 1,1-46,9), la extracción de sangre realizada en otoño/invierno (OR: 9,0; IC 95% OR: 1,7-47,0), la ausencia de efélides (OR: 5,4; IC 95% OR: 1,2-23,4) y, marginalmente, a la presencia de tener < 2 polimorfismos no sinónimos en el receptor 1 de la melanocortina (MC1R) (OR: 5,0; IC 95% OR: 0,9-28,9). Limitaciones: No se han incluido en el análisis algunos factores, como la alimentación, relacionados con los niveles de 25(OH)D. CONCLUSIONES: Se deberían monitorizar los niveles de 25(OH)D en los pacientes con melanoma y valorar dar suplementos orales en los casos que lo precisen

INTRODUCTION AND OBJECTIVES: Patients with melanoma appear to take extreme sun-protection measures, which could influence 25-hydroxyvitamin D [25(OH)D] levels. The aim of this study was to measure 25(OH)D levels in patients with cutaneous melanoma and identify factors associated with inadequate levels. MATERIAL AND METHODS: Over a period of 1 year, we prospectively measured serum 25(OH)D in patients with cutaneous melanoma and used logistic regression analysis to identify environmental, phenotypic, and genotypic factors that were associated with insufficient and deficient levels. RESULTS: Of 215 patients analyzed, 8.8% had deficient 25(OH)D levels (< 10 ng/mL) and just 24.7% had normal levels. Insufficient levels (< 30 ng/mL) were associated with obesity (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.3-13.3) and blood sampling in autumn/winter (OR, 2.1; 95% CI, 1.1-4). Deficient levels (< 10 ng/mL) were associated with obesity (OR, 7.1; 95% CI, 1.1-46.9), blood sampling in autumn/winter (OR, 9.0; 95% CI, 1.7-47.0), absence of freckles (OR, 5.4; 95% CI, 1.2-23.4), and, with marginal significance, the presence of fewer than 2 nonsynonymous melanocortin-1 receptor (MC1R) polymorphisms (OR, 5.0; 95% CI, 0.9-28.9). Limitations: Some factors related to 25(OH)D levels, such as food, were not included in the analyses. CONCLUSIONS: 25(OH)D levels should be monitored in patients with melanoma and the need for oral supplements should be contemplated where appropriate

25-Hydroxyvitamin D in Patients With Melanoma and Factors Associated With Inadequate Levels. / Niveles de 25-hidroxivitamina D en pacientes con melanoma y factores asociados con su insuficiencia.

INTRODUCTION AND OBJECTIVES: Patients with melanoma appear to take extreme sun-protection measures, which could influence 25-hydroxyvitamin D [25(OH)D] levels. The aim of this study was to measure 25(OH)D levels in patients with cutaneous melanoma and identify factors associated with inadequate levels. MATERIAL AND METHODS: Over a period of 1 year, we prospectively measured serum 25(OH)D in patients with cutaneous melanoma and used logistic regression analysis to identify environmental, phenotypic, and genotypic factors that were associated with insufficient and deficient levels. RESULTS: Of 215 patients analyzed, 8.8% had deficient 25(OH)D levels (<10ng/mL) and just 24.7% had normal levels. Insufficient levels (<30ng/mL) were associated with obesity (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.3-13.3) and blood sampling in autumn/winter (OR, 2.1; 95% CI, 1.1-4). Deficient levels (<10ng/mL) were associated with obesity (OR, 7.1; 95% CI, 1.1-46.9), blood sampling in autumn/winter (OR, 9.0; 95% CI, 1.7-47.0), absence of freckles (OR, 5.4; 95% CI, 1.2-23.4), and, with marginal significance, the presence of fewer than 2 nonsynonymous melanocortin-1 receptor (MC1R) polymorphisms (OR, 5.0; 95% CI, 0.9-28.9). LIMITATIONS: Some factors related to 25(OH)D levels, such as food, were not included in the analyses. CONCLUSIONS: 25(OH)D levels should be monitored in patients with melanoma and the need for oral supplements should be contemplated where appropriate.

Recomendaciones para la utilización de biomarcadores de imagen PET en el proceso diagnóstico de las enfermedades neurodegenerativas que cursan con demencia: documento de consenso SEMNIM y SEN / Recommendations for the use of PET imaging biomarkers in the diagnosis of neurodegenerative conditions associated with dementia: SEMNIM and SEN consensus

Los nuevos criterios diagnósticos para la enfermedad de Alzheimer (EA) reconocen el interés de los biomarcadores, tanto para mejorar la especificidad en sujetos en fase de demencia, como para facilitar el diagnóstico precoz del proceso fisiopatológico de la EA en personas en fases prodrómicas. La disponibilidad actual de biomarcadores de imagen PET de disfunción neuronal (PET-FDG) y de depósito de proteína beta amiloide (PET-Amiloide), ofrecen a los especialistas clínicos involucrados en la evaluación de pacientes con deterioro cognitivo la oportunidad de aplicar los nuevos criterios en su práctica clínica. Sin embargo, resulta imprescindible que las sociedades científicas implicadas en la utilización de las nuevas herramientas de apoyo al diagnóstico clínico se pongan de acuerdo en cuales deben de ser las recomendaciones para su utilización clínica. En este trabajo se lleva a cabo una revisión sistemática de la literatura sobre el uso de PET-amiloide y PET-FDG, tanto en el proceso diagnóstico de la EA como de otras enfermedades neurodegenerativas que cursan con demencia. Asimismo, se proponen una serie de recomendaciones consensuadas por la Sociedad Española de Medicina Nuclear y la Sociedad Española de Neurología a modo guía para la utilización adecuada de los biomarcadores de imagen PET (AU)

The new diagnostic criteria for Alzheimer's disease (AD) acknowledges the interest given to biomarkers to improve the specificity in subjects with dementia and to facilitate an early diagnosis of the pathophysiological process of AD in the prodromal or pre-dementia stage. The current availability of PET imaging biomarkers of synaptic dysfunction (PET-FDG) and beta amyloid deposition using amyloid-PET provides clinicians with the opportunity to apply the new criteria and improve diagnostic accuracy in their clinical practice. Therefore, it seems essential for the scientific societies involved to use the new clinical diagnostic support tools to establish clear, evidence-based and agreed set of recommendations for their appropriate use. The present work includes a systematic review of the literature on the utility of FDG-PET and amyloid-PET for the diagnosis of AD and related neurodegenerative diseases that occur with dementia. Thus, we propose a series of recommendations agreed on by the Spanish Society of Nuclear Medicine and Spanish Society of Neurology as a consensus statement on the appropriate use of PET imaging biomarkers (AU)

[Biomarkers in Alzheimer's disease]. / Biomarcadores en la enfermedad de Alzheimer.

The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

TITLE: Biomarcadores en la enfermedad de Alzheimer.Los nuevos criterios diagnosticos para la enfermedad de Alzheimer (EA) incluyen la posibilidad de practicar tecnicas de neuroimagen o analisis del liquido cefalorraquideo con el objeto de aumentar la certeza de que un paciente presenta un proceso neuropatologico relacionado con la EA. Tres biomarcadores del liquido cefalorraquideo (Aß42, tau total y tau fosforilada) reflejan las caracteristicas patologicas centrales de la EA. Estos procesos neuropatologicos se inician decadas antes de que sean detectables sintomas, por lo que se esta determinando si estos biomarcadores pueden ser utiles en la deteccion precoz y prevencion de la demencia. Podemos definir tres estadios de la EA: estadio preclinico, deterioro cognitivo leve debido a EA y demencia por EA. En esta revision, se resumen las evidencias de biomarcadores en cada uno de estos estadios. Tambien se revisan los estudios que investigan biomarcadores para la EA en sangre. Los estudios en ancianos asintomaticos y en portadores de mutaciones autosomicas dominantes de EA han mostrado alteraciones en los biomarcadores que permiten la segregacion en estos estadios preclinicos. Estos estudios permitiran identificar las poblaciones diana de los ensayos clinicos futuros y evaluar de manera objetiva si se producen modificaciones sobre el proceso patologico de la EA. El desarrollo de los biomarcadores del liquido cefalorraquideo requiere unos procedimientos normalizados preanaliticos y analiticos estrictos que hagan fiables los estudios multicentricos y universalicen los puntos de corte de la tecnica en los distintos estadios de la EA.

In vitro effect of genistein on DNA damage in leukocytes from mucopolysaccharidosis IVA patients.

Mucopolysaccharidosis IVA is a lysosomal storage disorder leading to an increase in glycosaminoglycans storage. Genistein is an isoflavone capable to inhibit glycosaminoglycans production. The objective of this study was to analyze the in vitro effect of different concentrations of genistein on DNA injury in mucopolysaccharidosis IVA patients. The lower concentration tested (10 µM) showed a significant increase on DNA injury in vitro, although higher concentrations (30 µM and 50 µM) showed higher DNA damage.

Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms.

BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R.

Características fenotípicas e histológicas de los pacientes con melanoma cutáneo en función de los polimorfismos del MC1R / Phenotypic and Histologic Characteristics of Cutaneous Melanoma in Patients With Melanocortin-1 Receptor Polymorphisms

Introducción: El receptor de la melanocortina-1 (MC1R) es un importante determinante del riesgo de melanoma debido a su función en la producción de melanina en respuesta a la exposición solar. Objetivos: Analizar las características fenotípicas e histológicas de los pacientes con melanoma cutáneo portadores de mutaciones del MC1R asociadas a riesgo de melanoma y la influencia de la exposición solar en la aparición del melanoma. Material y métodos: Se incluyeron 224 pacientes diagnosticados de melanoma atendidos en el Servicio de Dermatología del Hospital General Universitario Gregorio Marañón (septiembre de 2004 -diciembre de 2009). Se realizó la secuenciación genómica del ADN del MC1R mediante PCR. Resultados: El 58% presentaba al menos una de las siguientes variantes de MC1R (V60L, V92M, I155T, R160W, D294H, R163Q). Estos pacientes presentaban antecedentes de quemaduras solares (p=0,018), melanomas localizados en áreas de exposición solar intermitente (p=0,019), con predominio del tipo histológico de extensión superficial. Estas asociaciones fueron especialmente significativas en los portadores de las variantes R160W y D294H. Los portadores de R160W presentaron además melanomas asociados a nevus melanocíticos (p=0,028). Conclusión: Los resultados obtenidos sugieren que puede existir una relación entre la expresión de determinadas variantes de MC1R y los hábitos de exposición solar, antecedentes de quemadura y tipo de piel del paciente, así como una mayor frecuencia de melanomas de extensión superficial y melanomas asociados a nevus en portadores de ciertas mutaciones de MC1R (AU)

Background: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. Objectives: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. Material and methods: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. Results: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=0.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=0.028). Conclusions: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R (AU)