García Díaz

Universidad de Alcalá

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J.M. Mesa Latorre

Hospital Universitario Príncipe de Asturias

D. Corps Fernández

Hospital Universitario de Torrejón

José Eduardo

University of Concepción

A.R. Valbuena Parra

Universidad de Alcalá

Carlos Guijarro

Hospital Universitario Fundación Alcorcón

M J Gaspar

Hospital Universitario de Getafe

Juan Carlos Ramos Ramos

Hospital Universitario La Paz

José Luís Soto

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Pedro Vidau

Central University Hospital of Asturias

Domingo Hernández

Hospital Universitario de Canarias

Cooperative Institutions

Hospital Universitario Príncipe de Asturias

Universidad de Alcalá

Instituto de Salud Carlos III

Inserm

Centro de Investigación Biomédica en Red

Universidad Autónoma de Madrid

Research Institute Hospital 12 de Octubre

Hospital Universitario La Paz

Hospital Universitario 12 De Octubre

Istituti di Ricovero e Cura a Carattere Scientifico

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Relación del perfil lipoproteico en sangre de cordón con las variables obstétricas y antropométricas en los recién nacidos. Diferencias en función del sexo

Clínica e Investigación en Arteriosclerosis (2007)

García Díaz M J Gaspar María Bienvenido Villalba Vicente Granizo Domínguez José María Jiménez Bustos

10.1016/s0214-9168(07)74202-x

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Citations (2)

2013: la situación del narcotráfico en la región Ucayali

Pontificia Universidad Católica del Perú (2013)

García Díaz A Jaime

Source

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Citations (0)

SP038PREFINE PROJECT: STRATEGIC PLAN TO IMPROVE KNOWLEDGE & RECOGNITION OF FABRY DISEASE AMONG SPANISH NEPHROLOGISTS

Nephrology Dialysis Transplantation (2017)

María Dolores del Pino y Pino Pedro Vidau Vicens Torregrosa Joan Torrás Rafael Santamaría

10.1093/ndt/gfx138.sp038

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Mutations causing acrodysostosis-2 facilitate activation of phosphodiesterase 4D3

Human Molecular Genetics (2017)

Claire Briet Arrate Pereda Catherine Le Stunff Emmanuelle Motte‐Signoret García Díaz

Type 2 acrodysostosis (ACRDYS2), a rare developmental skeletal dysplasia characterized by short stature, severe brachydactyly and facial dysostosis, is caused by mutations in the phosphodiesterase (PDE) 4D (PDE4D) gene. Several arguments suggest that the mutations should result in inappropriately increased PDE4D activity, however, no direct evidence supporting this hypothesis has been presented, and the functional consequences of the mutations remain unclear. We evaluated the impact of four different PDE4D mutations causing ACRDYS2 located in different functional domains on the activity of PDE4D3 expressed in Chinese hamster ovary cells. Three independent approaches were used: the direct measurement of PDE activity in cell lysates, the evaluation of intracellular cAMP levels using an EPAC-based (exchange factor directly activated by cAMP) bioluminescence resonance energy transfer sensor , and the assessment of PDE4D3 activation based on electrophoretic mobility. Our findings indicate that PDE4D3s carrying the ACRDYS2 mutations are more easily activated by protein kinase A-induced phosphorylation than WT PDE4D3. This occurs over a wide range of intracellular cAMP concentrations, including basal conditions, and result in increased hydrolytic activity. Our results provide new information concerning the mechanism whereby the mutations identified in the ACRDYS2 dysregulate PDE4D activity, and give insights into rare diseases involving the cAMP signaling pathway. These findings may offer new perspectives into the selection of specific PDE inhibitors and possible therapeutic intervention for these patients.

PDE10A

10.1093/hmg/ddx271

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Citations (21)

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization

Cancers (2020)

Ana Beatriz Sánchez‐Heras Adela Castillejo García Díaz Mercedes Robledo Àlex Teulé

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.

Leiomyomatosis

Cancer syndrome

Kidney cancer

10.3390/cancers12113277

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Citations (13)

Variations in the Cellular Distribution of Acid Phosphatase in Canine Gastric Mucosa With a Comparison of the Lead Sulfide and Azo Dye Methods

Gastroenterology (1964)

Herzl Ragins M. Dittbrenner García Díaz State D

Lead sulfide

10.1016/s0016-5085(64)80131-1

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Citations (4)

Frecuencia y variabilidad de valores extremadamente bajos de colesterol ligado a lipoproteínas de alta densidad

Medicina Clínica (2009)

García Díaz José Miguel Hernández Rey M J Gaspar Alberto López de Guzmán

10.1016/j.medcli.2009.09.016

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Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

Clínica e Investigación en Arteriosclerosis (English Edition) (2023)

Agustín Blanco Echevarría García Díaz Assumpta Caixàs Núria Plana M Rico

Limited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. HEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. In total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels < 55 mg/dL were achieved by 56.3% of patients. LDL-C levels < 70 mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. In the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months). Existen datos limitados sobre la variabilidad del nivel de colesterol de lipoproteínas de baja densidad (cLDL) o la persistencia a largo plazo con el anticuerpo monoclonal evolocumab en la práctica clínica habitual. HEYMANS (NCT02770131) es el primer estudio observacional multicéntrico y multinacional de pacientes europeos que iniciaron tratamiento con evolocumab en la práctica clínica habitual, basado en criterios de reembolso locales. El objetivo fue evaluar las características clínicas, los cambios en los niveles de cLDL, los patrones de tratamiento y la persistencia a este con evolocumab en la cohorte española con un seguimiento de 30 meses, utilizando datos del registro HEYMANS. HEYMANS fue un estudio prospectivo de pacientes adultos (≥18 años) que recibieron al menos una dosis de evolocumab prescrita. Se incluyeron 1.951 sujetos de 12 países. Los datos fueron recopilados desde los seis meses previos al inicio del tratamiento hasta los 30 meses posteriores. La cohorte española incluyó pacientes que comenzaron evolocumab en la práctica clínica habitual desde marzo del 2016 hasta septiembre del 2019. Se recogieron las características demográficas y clínicas, los tratamientos hipolipemiantes (LLT) y el perfil lipídico. En la cohorte española se incluyeron 201 participantes. La mediana de seguimiento (Q1-Q3) fue de 30,0 (12-30) meses. De los pacientes, 61,7% eran hombres, con edad media (desviación estándar) de 59,5 (10,8) años. La mayoría (68,7%) había presentado un evento cardiovascular previo, 45,3% padecía enfermedad arterial coronaria o angina estable y 60,2% tenía diagnóstico de hipercolesterolemia familiar. En general, 57,7% de los pacientes recibían tratamiento con estatinas, la mayoría con estatinas de alta intensidad (85,3%), 45,8% eran intolerantes a las estatinas y 26,4% no recibían LLT. Al inicio del estudio, la mediana (Q1-Q3) de los niveles de cLDL fue de 151 (123-197) mg/dL. A los tres meses de tratamiento, el cLDL basal disminuyó 66% hasta una mediana de 50 (30-83) mg/dL y se mantuvo en el tiempo, con una mediana de 55 (40-99) mg/dL a los 30 meses. A los 10-12 meses de terapia, 56,3% de los pacientes alcanzaron niveles de cLDL < 55 mg/dL y 70,1% < 70 mg/dL. Además, 76,8% de los pacientes lograron una reducción de ≥ 50%. El porcentaje de pacientes en tratamiento fue de 95% a los 12 meses y 93% a los 30 meses. En España, en práctica clínica habitual, el tratamiento con evolocumab redujo los niveles de cLDL, y estos se mantuvieron constantes durante el seguimiento, similar a lo previamente reportado. El régimen con evolocumab se inició con niveles de cLDL 50% superiores a los recomendados. La probabilidad de alcanzar los objetivos de cLDL de la ESC/EAS 2019 mejoraría con la terapia combinada y también con un umbral de cLDL más bajo al iniciar evolocumab. La persistencia al tratamiento con evolocumab se mantuvo alta durante el seguimiento, con un porcentaje muy bajo de discontinuidad (5% a los 12 meses; 7% a los 30 meses).

Evolocumab

Discontinuation

10.1016/j.artere.2023.04.003

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Citations (1)

Nuevos tratamientos en la hipertrigliceridemia y en la hiperquilomicronemia

Medicina Clínica (2020)

García Díaz

10.1016/j.medcli.2019.11.003

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Citations (2)

Visceral Leishmaniasis (Kala-Azar) as an Opportunistic Infection in Patients Infected with the Human Immunodeficiency Virus in Spain

Clinical Infectious Diseases (1989)

Carlos Montalbán Raúl Martínez‐Fernández José Luís Calleja García Díaz Rafael Rubio

In an area endemic for visceral leishmaniasis, 16patients with human immunodeficiency virus (HIV) infection developed the disease. All belonged to populations at risk for AIDS (15 were intravenous drug abusers). Five patients fulfilled the criteria for full-blown AIDS, and two more fulfilled them after diagnosis of leishmaniasis. All presented with the classic manifestations of visceral leishmaniasis, but leishmania serology was negative in 15 patients (93%). Leishmania donovani amastigotes were identified in the bone marrow in all cases. Most patients responded initially to treatment with pentavalent antimonial drugs, but seven (43%) followed a chronic course, with multiple relapses in five, despite alternative treatments. Visceral leishmaniasis occurred in patients with different levels of depression of the CD4 to CD8 lymphocyte ratio. Mortality was 37% (six patients) and was independent of the chronic-relapsing course of the disease. In no case was leishmaniasis the primary cause of death. Our data establish that visceral leishmaniasis is an opportunistic infection in HIV-infected patients, and we suggest that in endemic areas it should be considered an indicator disease for the diagnosis of AIDS.

Opportunistic infection

10.1093/clinids/11.4.655

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Citations (119)