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405 results on '"A. Yébenes"'

1. Searching for a prognostic index in lupus nephritis

Author

E. Rodríguez-Almaraz, E. Gutiérrez-Solís, E. Rabadán, P. Rodríguez, M. Alonso, L. Carmona, M. J. García de Yébenes, E. Morales, and M. Galindo-Izquierdo

Subjects
Lupus nephritis, Prognostic index, Poor renal evolution, Medicine
Abstract

Key messages 1. Development a prognostic index of poor renal evolution in patients with LN. 2. We use clinical, histological and laboratory factors 6 months after diagnosis and treatment 3. Effective tool in the early detection and management, easy to use in clinical practice

Published
2023
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2. Accuracy of detection rate and intraoperative sentinel lymph node assessment in early-stage cervical carcinoma

Author

Begoña Díaz de la Noval, Javier De Santiago Garcia, Alicia Hernández Gutiérrez, Ignacio Zapardiel Gutierrez, Mariana Díaz Almirón, Laura Yébenes Gregorio, David Hardisson Hernaez, and María Dolores Diestro Tejeda

Subjects
Cancer staging, cervical cancer, lymphatic metastasis, lymphovascular space invasion, sentinel lymph node biopsys, Medicine
Abstract

Objective: This article shows our experience on sentinel lymph node (SLN) biopsy in early-stage cervical carcinoma since the technique was introduced in our Institution. The main objective is to analyze the detection rate (DR) of metastatic SLNs, identifying prognostic factors for an increased risk of nodal metastases. Our second aim was to compare the accuracy of nodal metastases DR between intraoperative analysis and postoperative ultrastaging. Materials and Methods: Forty-one women with the International Federation of Gynecology and Obstetrics stages IA2-IIA1 who underwent laparoscopic surgical treatment applying the SLN technique, from December 2011 to June 2016, at La Paz University Hospital, were included. The sentinel node was identified using technetium and methylene blue dye or indocyanine green near-infrared fluorescent imaging, analyzed intraoperatively, and compared to deferred ultrastaging. Results: SLN DR was 100%, with a bilaterality rate of 83%. Twelve (26.8%) patients had metastatic nodes, 11 of them (91.7%) detected by SLN technique, of which 9 (81.8%) had only the sentinel node affected. False-negative rate was 2.4% after ultrastaging procedure. Metastatic SLN detection with ultrastaging was 45.5% higher than the intraoperative analysis, 63.6% of which had low tumor burden. The global detection of patients with nodal metastases after SLN technique was 21.9% higher than pelvic lymphadenectomy. Conclusions: Our preliminary results corroborate that SLN biopsy selectively maps metastatic nodes and ultrastaging increases the detection of metastatic SLNs, predominantly due to low tumor burden.

Published
2017
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3. SARS-CoV-2 infection associated with monoclonal gammopathy. A case report based on the study of minimally invasive ultrasound-guided autopsy

Author

Cristina Vega Cabrera, Eva Manuela Pena Burgos, Pablo Pérez Montero, Begoña Rivas Becerra, David Hardisson, María del Carmen González-García, Teresa Hernández Cabrero, and Laura Yébenes

Subjects
Pathology, medicine.medical_specialty, Autopsy, SARS-CoV- 2, medicine.disease_cause, Immunoglobulin light chain, Article, Virus, Pathology and Forensic Medicine, Nephropathy, MEGAKARYOCYTES, medicine, MEGACARIOCITO, Pathological, Coronavirus, MIMIMALLY INVASIVE AUTOPSY, INMUNOTROMBOSIS, IMMUNOTHROMBOSIS, SARS-CoV-2, business.industry, Acute kidney injury, medicine.disease, Immunohistochemistry, MONOCLONAL GAMMOPATHY, business, GAMMAPATÍA MONOCLONAL, AUTOPSIA MÍNIMAMENTE INVASVA
Abstract

La enfermedad por coronavirus de 2019 (COVID-19) es una emergencia sanitaria pública global con numerosas facetas clínicas que incluyen renopatía aguda y enfermedad cerebrovascular aguda. Es necesario un conocimiento adicional de su mecanismo patogénico. Los trastornos de coagulación están claramente incluidos en dichos mecanismos. La gammapatía monoclonal se caracteriza por la sobreproducción de inmunoglobulina monoclonal causada por proliferación clonal. Utilizando un estudio postmortem de biopsias básicas percutáneas ecoguiadas, el objetivo de este informe es presentar nuestras observaciones sobre la patología del síndrome respiratorio agudo severo por infección de coronavirus 2 (SARS-CoV2) con gammapatía monoclonal. La presentación clínica fue insuficiencia renal aguda. Los hallazgos patológicos revelaron nefropatía por depósito de cadenas ligeras kappa. La inmunohistoquímica de SARS-CoV-2 fue positiva en ciertas células tubulares renales. La presencia de megacariocitos alveolares (alta densidad) fue un hallazgo notable, que explica probablemente el resultado final del paciente (enfermedad cerebrovascular aguda). El estudio inmunohistoquímico frente a SARS-CoV-2 no verifica el efecto patogénico del virus y, por tanto, su contribución a la nefropatía aguda.

Published
2022
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5. Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score

Author

Javier Domínguez-Ortega, Iñigo Ojanguren, Gregorio Soto, José María Vega Chicote, Antonio Parra Arrondo, Miguel Perpiñá, Carolina Cisneros, Isabel Urrutia, Juan Luis García-Rivero, Eva Martínez-Moragón, Carlos Almonacid, Valentina Gutiérrez Vall De Cabrës, Irina Bobolea, Antolín López Viña, Marina Blanco, Dario Antolin, Astrid Crespo, Alfons Torrego, Joaquín Sastre Domínguez, Paloma Campo Mozo, Victoria García Gallardo, Vicente Plaza, Mar Mosteiro, Ismael García Moguel, Ignacio Dávila, Carlos Colás, Aythamy Henrquez Santana, Luis Pérez de Llano, Alicia Habernau Mena, Francisco Álvarez, Juan Carlos Miralles, Remedios Cardenas Contreras, Borja G. Cosío, Manuel Jorge Rial Prado, César Picado, Loreto Carmona, José María Olaguibel Rivera, Xavi Muñoz, Santiago Quirce Gancedo, Pilar Barranco Sanz, José Ramón Serrano, Ignacio Antepara Ercoreca, Julio Delgado Romero, Cristian Domingo, and María Jesús García de Yébenes

Subjects
medicine.medical_specialty, Potentially all pairwise rankings of all possible alternatives, business.industry, Maintenance dose, medicine.drug_class, Intraclass correlation, Minimal clinically important difference, Context (language use), medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, Immunology and Allergy, Corticosteroid, 030212 general & internal medicine, business, Face validity, Asthma
Abstract

Background There is a lack of tools to quantify the response to monoclonal antibodies (mAbs) holistically in severe uncontrolled asthma patients. Objective To develop a valid score to assist specialists in this clinical context. Methods The score was developed in four subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis using the Potentially All Pairwise RanKings of All Possible Alternatives methodology using the 1000minds software; and (4) face validity assessment of the obtained score. Results Four core items, with different levels of response for each, were selected: severe exacerbations, oral corticosteroid use, symptoms (evaluated by Asthma Control Test), and bronchial obstruction (assessed by FEV1 percent predicted). Severe exacerbations and oral corticosteroid maintenance dose were weighted most heavily (38% each), followed by symptoms (13%) and FEV1 (11%). Higher scores in the weighted system indicate a better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient of 0.86). Conclusions The FEV1, exacerbations, oral corticosteroids, symptoms score allows clinicians to quantify response in severe uncontrolled asthma patients who are being treated with mAbs.

Published
2021
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7. Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.

Author

Alberto Peláez-García, Laura Yébenes, Alberto Berjón, Antonia Angulo, Pilar Zamora, José Ignacio Sánchez-Méndez, Enrique Espinosa, Andrés Redondo, Victoria Heredia-Soto, Marta Mendiola, Jaime Feliú, and David Hardisson

Subjects
Medicine, Science
Abstract

To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas.Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score).The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)).This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.

Published
2017
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8. Clinical Characteristics of Juvenile Idiopathic Inflammatory Myopathy and Comparison With Adult Patients

Author

Ana Fernández Pérez, Patricia Carreira, Raquel Almodóvar, María Carmen Barbadillo, Francisco Javier López-Longo, Laura Nuño-Nuño, Beatriz Joven, Tatiana Cobo-Ibáñez, L. Ruiz, Eva Tomero, Carmen Larena, M. Ángeles Blázquez, María Jesús García-De Yébenes, Indalecio Monteagudo, Juan Carlos López-Robledillo, Leticia Lojo Oliveira, Henry Moruno, Paloma García de la Peña, Julia Martínez-Barrio, Jesús Loarce-Martos, and I. Llorente

Subjects
Adult, medicine.medical_specialty, Longitudinal study, Juvenile Polymyositis, Myositis, business.industry, Medical record, Arthritis, medicine.disease, Cohort Studies, Rheumatology, Spain, Calcinosis, Internal medicine, Cohort, Humans, Juvenile, Medicine, Longitudinal Studies, business, Juvenile dermatomyositis, Retrospective Studies
Abstract

Few studies have been published focusing on the differences between juvenile idiopathic inflammatory myopathy (JIIM) and adult IIM. This study aimed to describe the characteristics of JIIM main subgroups (juvenile dermatomyositis [JDM] and juvenile polymyositis [JPM]) and to compare their differences with adult IIM subgroups (adult DM and adult PM). Methods This study reviewed the medical records of patients from the REMICAM cohort, a multicentric longitudinal study carried out in patients with IIM, followed up between 1980 and 2014 in 12 hospitals in Madrid, Spain. Patients with definite or probable JPM, JDM, adult DM, and adult PM according to the modified Bohan and Peter criteria were selected. We compared the characteristics between JDM and JPM, and between JIIM and adult IIM. Results Eighty-six juvenile patients (75 JDMs and 11 JPMs) and 283 adult patients (133 DMs and 150 PMs) were included. Compared with patients with JDM, patients with JPM were older at diagnosis, had more fever and arthritis, and were less frequently treated with disease-modifying antirheumatic drugs (these differences were not statistically significant). Compared with patients with adult DM, those with JDM presented more frequently with calcinosis (33.8% vs 6.9%, p Conclusions Our findings confirm that JIIMs are a heterogeneous group of diseases with relevant differences compared with adult IIMs.

Published
2021
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9. Evaluación de la respuesta patológica a quimioterapia neoadyuvante en cáncer de mama: correlación con el fenotipo molecular

Author

Alberto Berjón, Alberto Sanchez, Laura Yébenes, and David Hardisson

Subjects
0301 basic medicine, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Molecular phenotype, medicine.disease, Phenotype, Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, Axilla, 030104 developmental biology, 0302 clinical medicine, Breast cancer, medicine.anatomical_structure, In vivo, 030220 oncology & carcinogenesis, Internal medicine, medicine, skin and connective tissue diseases, business, Pathological, Triple negative
Abstract

Introduction and objective Breast cancer can be classified into different molecular subtypes with important therapeutic and prognostic implications. Neoadjuvant chemotherapy (NAC) increases the possibility of performing conservative surgery and allows in vivo testing of the sensitivity of the tumor. Our aim was to evaluate the pathological response to NAC in relation to the molecular phenotype and the different definitions of the pathological response. Patients 228 patients treated with NAC and subsequent surgery between 2012 and 2018 were selected from our breast cancer database. Molecular phenotypes were established based on the criteria of the St Gallen 2013 Conference. Pathological response was evaluated following Miller-Payne (breast) and Sataloff (axilla) classification systems. Results The most frequent molecular phenotype was luminal B/HER2 negative (30.3%), followed by luminal B/HER2 positive (26.3%), triple negative (24.6%), HER2 positive (13.2%), and luminal A (5.7%). The rate of pathological complete response (pCR) was 35.5% in breast and 15.3% in axilla. The rate of pCR considering breast and axilla together was 26.8%. The molecular phenotype with the highest rate of pCR was HER2 positive (66.7%) followed by triple negative (30.4%), luminal B/HER2 positive (21.7%), luminal B/HER2 negative (14.5%), and luminal A (7.7%) (p Conclusions Complete pathological response to NAC in breast cancer depends largely on the molecular phenotype of the tumor, regardless of the definition of pCR, with the highest response rates in the breast and axilla in the HER2 positive and triple negative phenotypes.

Published
2021
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10. An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer

Author

Isabel Torres-Sánchez, Beatriz Castelo-Fernández, Laura Yébenes-Gregorio, Óscar Moreno-Domínguez, Rosa M. García-Moreno, and Cristina Álvarez-Escolá

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Medullary thyroid cancer, Hematology, Hypopituitarism, Disease, Vandetanib, medicine.disease, Gastroenterology, Oncology, Hypogonadotropic hypogonadism, Internal medicine, medicine, Lymph, Adverse effect, business, Tyrosine kinase, medicine.drug
Abstract

Introduction: Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS). Case Presentation: A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions. Conclusion: To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.

Published
2021
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11. Vitamin B6 Deficiency in Patients With Parkinson Disease Treated With Levodopa/Carbidopa

Author

Cristina González-Robles, Justo García de Yébenes, and Ana Rojo-Sebastián

Subjects
Male, medicine.medical_specialty, Duodenum, Cross-sectional study, Disease, Folic Acid Deficiency, Gastroenterology, Antiparkinson Agents, Levodopa, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Statistical significance, medicine, Humans, Infusions, Parenteral, Pharmacology (medical), In patient, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Dyskinesias, business.industry, Carbidopa, Parkinson Disease, Vitamin B 12 Deficiency, Retrospective cohort study, Middle Aged, Vitamin B 6, nervous system diseases, 030227 psychiatry, Drug Combinations, Cross-Sectional Studies, medicine.anatomical_structure, Female, Neurology (clinical), Vitamin b6, Vitamin B 6 Deficiency, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Objective The aim of the study was to investigate the role of L-DOPA/carbidopa (CD) therapy on vitamin B6 levels in patients with Parkinson disease (PD). Methods This is a cross-sectional retrospective study of vitamin B6 plasma levels in 24 patients with PD treated with L-DOPA/CD for 3 or more years, orally or intraduodenally. Vitamin B6 levels in plasma were measured by ELISA. Results All patients treated with intraduodenal L-DOPA/CD (6 of 6) and 13 of 18 patients receiving L-DOPA/CD orally had low plasma levels of vitamin B6. Eight of the 19 patients with low vitamin B6 levels had symptoms of hypovitaminosis B6. Patients with low vitamin B6 had been treated with larger doses of L-DOPA/CD, although the differences did not have statistical significance. Patients treated with intraduodenal L-DOPA/CD have vitamin B6 levels significantly lower than those treated with oral L-DOPA/CD. The variables that most correlated with vitamin B6 levels were the cumulative annual doses of CD (r = -0.36) and L-DOPA (r = -0.33) during the year preceding the study and the time to develop dyskinesias or fluctuations (r = +0.43). Conclusions Vitamin B6 could play an important role in PD and its levels seem to be influenced by L-DOPA/CD. Plasma vitamin B6 levels should be monitored in patients receiving high L-DOPA/CD doses, especially those treated with intraduodenal infusion.

Published
2020
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12. Recomendaciones para el tratamiento nutrometabólico especializado del paciente crítico: introducción, metodología y listado de recomendaciones. Grupo de Trabajo de Metabolismo y Nutrición de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)

Author

C. Vaquerizo Alonso, L. Bordejé Laguna, J.F. Fernández-Ortega, M.L. Bordejé Laguna, J.F. Fernández Ortega, A. García de Lorenzo y Mateos, T. Grau Carmona, J.I. Herrero Meseguer, A. Mesejo Arizmendi, J.C. Montejo González, C. Ortiz Leyba, S. Ruiz-Santana, J.A. Acosta Escribano, A.L. Blesa Malpica, A. Bonet Sarís, M. Cervera Montes, E. de la Fuente O’Connor, M.N. Alcázar Espín, J.L. Flordelís Lasierra, M.A. García Martínez, R.M. Gastaldo Simeón, C. González Iglesias, F.J. Jiménez Jiménez, A. Jordá Miñana, M. Juan Díaz, C. León Cinto, J.C. López Delgado, C. Lorencio Cárdenas, J.A. Márquez Vácaro, J.F. Martínez Carmona, A. Martínez de la Gándara, I. Martínez de Lagrán Zurbano, P. Martínez García, F. Martínez-Lozano Aranaga, M.E. Martínez Quintana, L. Macaya Redín, M.L. Mateu Campos, A.I. Martín Luengo, E. Moreno Clarí, E. Navas Moya, S. Pérez Quesada, E. Portugal Rodríguez, Á. Robles González, S. Sánchez Alonso, C. Sánchez Álvarez, A. Sánchez Miralles, C. Serón Arbeloa, Ll. Serviá Goixart, B. Vila García, F. Valenzuela Sánchez, J.C. Yébenes Reyes, and M. Zamora Elson

Subjects
03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, business.industry, Medicine, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, business, Humanities
Abstract

Resumen El Grupo de Trabajo de Metabolismo y Nutricion de la Sociedad Espanola de Medicina Intensiva, Critica y Unidades Coronarias (SEMICYUC) ha revisado y actualizado las recomendaciones del tratamiento nutrometabolico en el paciente critico (previamente publicadas por el grupo en el ano 2011) con la finalidad de ayudar a la toma de decisiones en la practica clinica diaria. Para su elaboracion, llevada a cabo entre marzo de 2016 y febrero de 2019, se ha contado con un panel de expertos dedicados a la Medicina Intensiva con amplia experiencia en el tratamiento nutricional de los pacientes criticos. Para cada una de las recomendaciones se ha establecido un nivel de evidencia basado en la metodologia del grupo GRADE (Grading of Recommendations Assessment, Development and Evaluation Working Group) y un grado de recomendacion que ha tenido en cuenta el impacto clinico de la recomendacion, independientemente del nivel de evidencia establecido por la escala GRADE.

Published
2020
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13. Recommendations for specialized nutritional-metabolic management of the critical patient: Introduction, methodology and list of recommendations. Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC)

Author

C. Vaquerizo Alonso, L. Bordejé Laguna, J.F. Fernández-Ortega, M.L. Bordejé Laguna, J.F. Fernández Ortega, A. García de Lorenzo y Mateos, T. Grau Carmona, J.I. Herrero Meseguer, A. Mesejo Arizmendi, J.C. Montejo González, C. Ortiz Leyba, S. Ruiz-Santana, J.A. Acosta Escribano, A.L. Blesa Malpica, A. Bonet Sarís, M. Cervera Montes, E. de la Fuente O’Connor, M.N. Alcázar Espín, J.L. Flordelís Lasierra, M.A. García Martínez, R.M. Gastaldo Simeón, C. González Iglesias, F.J. Jiménez Jiménez, A. Jordá Miñana, M. Juan Díaz, C. León Cinto, J.C. López Delgado, C. Lorencio Cárdenas, J.A. Márquez Vácaro, J.F. Martínez Carmona, A. Martínez de la Gándara, I. Martínez de Lagrán Zurbano, P. Martínez García, F. Martínez-Lozano Aranaga, M.E. Martínez Quintana, L. Macaya Redín, M.L. Mateu Campos, A.I. Martín Luengo, E. Moreno Clarí, E. Navas Moya, S. Pérez Quesada, E. Portugal Rodríguez, Á. Robles González, S. Sánchez Alonso, C. Sánchez Álvarez, A. Sánchez Miralles, C. Serón Arbeloa, Ll. Serviá Goixart, B. Vila García, F. Valenzuela Sánchez, J.C. Yébenes Reyes, and M. Zamora Elson

Subjects
medicine.medical_specialty, Critically ill, business.industry, 030208 emergency & critical care medicine, Evidence-based medicine, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Scale (social sciences), medicine, Grading (education), Intensive care medicine, business
Abstract

The Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) has reviewed and updated the recommendations for specialized nutritional and metabolic support in critically ill patients published by the Group in 2011, with the primary aim of helping decision making in daily clinical practice. The recommendations have been formulated by an expert panel with broad experience in nutritional and metabolic support in critically ill patients, and were drafted between March 2016 and February 2019. A level of evidence has been provided for each of the recommendations, based on the GRADE methodology (Grading of Recommendations Assessment, Development and Evaluation Working Group). A grade of recommendation has also been produced, taking into account the clinical impact of the recommendation, regardless of the level of evidence established by the GRADE scale.

Published
2020
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15. Recommendations for specialized nutritional-metabolic treatment of the critical patient: Sepsis and septic shock. Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC)

Author

J.C. Yébenes Reyes, F. Valenzuela Sánchez, and C. Ortiz Leyba

Subjects
Sepsis, medicine.medical_specialty, Septic shock, business.industry, medicine, Intensive care medicine, medicine.disease, business
Published
2020
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16. Positive-pressure needleless connectors did not increase rates of catheter hub colonization respecting the use of neutral-pressure needleless connectors in a prospective randomized trial

Author

Goretti Sauca, Alejandro Rodriguez, Juan Carlos Yébenes, Josep A. Capdevila, Juan Méndez, and Maria Delgado

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, Positive pressure, behavioral disciplines and activities, law.invention, Specimen Handling, 03 medical and health sciences, 0302 clinical medicine, Catheters, Indwelling, Randomized controlled trial, law, mental disorders, Medicine, Central Venous Catheters, Humans, Colonization, 030212 general & internal medicine, Prospective Studies, business.industry, Critically ill, Arterial catheter, Surgery, Catheter hub, Catheter, Equipment Contamination, business, Central venous catheter
Abstract

Introduction The aim of this study was to compare the colonization rates of central venous catheter (CVC) and arterial catheter (ArtC) hubs fitted with two types of needleless connectors (NCs). Methods We designed a prospective randomized study to compare rates of catheter hub colonization of CVC and ArtC hubs fitted with two types of needleless connectors: neutral-pressure NCs (NP-NCs) and positive-pressure NCs (PP-NCs) in critically ill patients. All NCs were replaced every 7 days of use. Results We obtained 326 cultures from 146 catheters (81 CVC and 65 ArtC) in 70 patients. The total cumulative days of risk were 1250 catheter-days. Global swab cultures were positive in NP-NCs in 29/198 (14.6%) versus 17/128 (13.3%) in PP-NCs during catheter use. We did not observe any cases of CRBSI. Conclusions In our experience, the use of PP-NCs did not result in significantly more frequent hub colonization with respect to NP-NCs.

Published
2020
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17. Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

Author

Laura Yébenes, Javier Escudero, Jorge L Ramón-Patino, Victoria Heredia-Soto, Bulat Zagidullin, Ignacio Ruz-Caracuel, Alberto Berjón, Beatriz Castelo, Andrés Redondo, Jing Tang, Alejandro Gallego, Luis Eduardo Garcia de la Calle, Yinyin Wang, Álvaro López-Janeiro, M. Miguel, J. Feliu, David Hardisson, Alicia Hernández, Alberto Peláez-García, Marta Mendiola, UAM. Departamento de Anatomía Patológica, UAM. Departamento de Medicina, UAM. Departamento de Obstetricia y Ginecología, Research Program in Systems Oncology, Institute for Molecular Medicine Finland, Medicum, Department of Mathematics and Statistics, and Department of Biochemistry and Developmental Biology

Subjects
EXPRESSION, Oncology, medicine.medical_specialty, Cancer Research, CARCINOMA, Medicina, 3122 Cancers, DIAGNOSIS, GUIDELINES, CLASSIFICATION, Stratification (mathematics), Endometrial cancer, Internal medicine, INDEPENDENT PREDICTOR, medicine, CTNNB1, Stage (cooking), RECURRENCE, Risk assessment, RISK, business.industry, Prognosis, medicine.disease, endometrial cancer, prognosis, risk assessment, biomarkers, SURVIVAL, business, PROMISE, Biomarkers
Abstract

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (includ-ing patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation, This research was funded by the Instituto de Salud Carlos III (ISCIII), cofinanced by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER, PI17/01723 to D.H.), and by Academy of Finland grant (No. 317680 to J.T.). B.Z. is supported by the faculty funded PhD position in the Integrative Life Science Doctoral Programme, University of Helsinki

Published
2022
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18. Development of a tool to measure the clinical response to biologic therapy in uncontrolled severe asthma: the FEOS score

Author

Loreto Carmona, María Jesús García de Yébenes, Carlos Colás, Iria Veiga Teijeiro, David Dacal Rivas, Ignacio Dávila, Borja García-Cosío, Irene Martín Robles, Luis Pérez de Llano, Indhira Guzmán Peralta, Nagore Blanco Cid, Eva Martínez-Moragón, Javier Domínguez Ortega, Juan Luis García-Rivero, and Carlos Almonacid

Subjects
medicine.medical_specialty, business.industry, Severe asthma, Measure (physics), Medicine, business, Intensive care medicine
Published
2021
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19. Aplicaciones de los modelos multinivel al análisis de medidas repetidas en estudios longitudinales

Author

María Victoria Zunzunegui, María Jesús García de Yébenes, Mathieu Forster, María Dolores Aguilar Conesa, Angel Rodríguez Laso, and Ángel Otero

Subjects
Medicine, Public aspects of medicine, RA1-1270
Abstract

Este trabajo es una introducción al análisis de medidas repetidas en estudios longitudinales. Se utiliza un marco analítico con dos etapas, ajustando modelos jerárquicos lineales con dos niveles. El primer nivel corresponde a la ocasión (tiempo) de medida y el segundo al individuo. Estos modelos estadísticos proceden de las ciencias sociales, en las que se han utilizado durante más de 25 años para analizar datos en organizaciones con múltiples niveles. Su aplicación permite estudiar los cambios en alguna característica de interés (estado de salud o factor de riesgo) y analizar las circunstancias que explican la variabilidad en las trayectorias individuales. En este trabajo se introducen los conceptos básicos de este método: variabilidad entre individuos y dentro de cada individuo a lo largo del tiempo, modelo del nivel individual para describir la trayectoria de cada individuo y modelo «entre individuos» para describir cómo cambian las trayectorias entre individuos, efectos fijos y efectos aleatorios, modelos de crecimiento lineal y cuadrático. Para ello se ha realizado un análisis de los cambios en la función cognitiva de una cohorte de personas mayores, el estudio «Envejecer en Leganés», seguida cada dos años, entre 1993 y 1999. Se presentan los resultados de modelos ajustados para resolver las preguntas de investigación más frecuentes en la descripción y el análisis de las trayectorias de cambio individual. Por último, se comentan posibles generalizaciones de estos modelos lineales jerárquicos a situaciones en las que la variable de interés no es continua, como es el caso de las variables dependientes dicotómicas, nominales u ordinales.

Published
2004

20. Abstract P5-13-06: Biological and clinical changes after neoadjuvant endocrine treatment: Results in a Spanish cohort of 106 patients

Author

Covadonga Marti, Elisa Moreno, Laura Yébenes, Adolfo Loayza, Marcos N. Meléndez, J.I. Sánchez-Méndez, José M. Oliver, Pilar Zamora, and Laura Frias

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Letrozole, medicine.medical_treatment, Cancer, medicine.disease, Gastroenterology, Axilla, medicine.anatomical_structure, Breast cancer, Oncology, Internal medicine, medicine, Breast-conserving surgery, business, Prospective cohort study, Contraindication, Mastectomy, medicine.drug
Abstract

Background: neoadjuvant endocrine treatment (NET) has demonstrated to be a useful strategy for downstaging luminal breast cancer as well as to deepen into luminal tumors biology. But, in spite of evidence, NET remains as an under-utilized tool, relegated to elderly frail patients. Purpose: to determine clinical and biological response after NET in luminal breast cancer.Methods: An observational prospective study was performed. Postmenopausal patients with luminal breast cancer T1-3, N0-2 diagnosed between January 2016 and April 2019 were included. They received treatment with letrozole 2,5mg/24h usually for 4-6 months or until maximum response was achieved. A few patients continued treatment further than 6 months because of surgery refusal or contraindication. In the rest of cases, surgery was performed after NET. An intermediate core biopsy (CB) was carried out in those patients with initial Ki67 >10%. Immunohistochemical and conventional pathological studies were made in the initial CB as well as in the intermediate CB and the surgical specimen.PEPI score (PS) was also calculated. Results: a total of 106 patients were included, with an average age of 73.7y [53-90]. 80 (75.5%) were ductal infiltrating carcinomas; 16(15,1%) lobular infiltrating carcinomas. The 10 remaining cases were minority histologic types. 62.3% were luminal B tumors. A positive axilla was present in 16 patients (15.0%). Surgery has been performed in 72 patients. The remaining 33 patients continue treatment nowadays (in 6 of them surgery was dismissed or refused by patient). Breast conserving surgery was feasible in 60 out of 72 (83.3%), although two of these patients chose mastectomy. Average size before treatment was 28.2mm [7.0-90.0], and in the surgical sample (pT) was 15.9mm [4.0-35.0] (p Citation Format: Covadonga Marti, Laura Frias, Adolfo Loayza, Laura Yebenes, Marcos Melendez, Elisa Moreno, Jose M Oliver, Pilar Zamora, Jose I Sanchez-Mendez. Biological and clinical changes after neoadjuvant endocrine treatment: Results in a Spanish cohort of 106 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-06.

Published
2020
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21. Código Sepsis Interhospitalario en Catalunya: modelo organizativo territorial para la atención inicial al paciente con sepsis

Author

M.T. Faixedas, E. Calbo, Elisabeth Esteban, L. Espinosa, J. Estany, Antoni Artigas, J.A. Capdevila, Josep M. Badia, E. Armero, Carol Lorencio, B. Cisteró, S. Moreno, C. Medina, A. Granes, M. Solsona, C. Netto, Juan Carlos Yébenes, Ricard Ferrer, V. Perez-Claveria, E. Vela, R. Lopez, A. Rodríguez, X. Jiménez-Fábrega, and M. Clèries

Subjects
business.industry, Medicine, Critical Care and Intensive Care Medicine, business, Humanities
Abstract

Resumen La sepsis es una entidad sindromica de elevada prevalencia y mortalidad. Su manejo esta estandarizado y tiene una eficacia dependiente del tiempo. Sin embargo, el manejo de los pacientes con sepsis es complejo. La heterogeneidad de las formas de presentacion puede dificultar su deteccion y manejo, asi como las diferencias en formacion, competencias o disponibilidad de recursos sanitarios. La Comision Asesora para la Atencion al PAciente con Sepsis (CAAPAS), formada por 7 sociedades cientificas, el Sistema de Emergencias Medicas (SEM) y el Servei Catala de la Salut (CatSalut), han desarrollado en Catalunya el Codigo Sepsis Interhospitalario (CSI). El objetivo general del CSI es facilitar la deteccion precoz, la atencion inicial y la coordinacion interhospitalaria para optimizar el tratamiento de los pacientes con sepsis o shock septico en formato codigo de riesgo vital, de forma homogenea a lo largo de todo el territorio catalan.

Published
2020
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22. Interhospital sepsis code in Catalonia (Spain): territorial model for initial care of patients with sepsis

Author

M. Clèries, S. Moreno, E. Vela, Antonio Artigas, C. Netto, J.A. Capdevila, Elisabeth Esteban, Carol Lorencio, B. Cisteró, E. Armero, M. Solsona, R. Lopez, C. Medina, L. Espinosa, J. Estany, Juan Carlos Yébenes, M.T. Faixedas, E. Calbo, A. Rodríguez, Josep M. Badia, Ricard Ferrer, A. Granes, V. Perez-Claveria, and X. Jiménez-Fábrega

Subjects
Multiple Organ Failure, Resuscitation, Advisory Committees, Early detection, Unconsciousness, Patient care, Sepsis, 03 medical and health sciences, Health services, 0302 clinical medicine, Meningism, medicine, Humans, Medical History Taking, Physical Examination, Emergency medical system, Respiratory Distress Syndrome, High prevalence, Septic shock, business.industry, Age Factors, Clinical Coding, 030208 emergency & critical care medicine, medicine.disease, Shock, Septic, Hospitals, Early Diagnosis, 030228 respiratory system, Spain, Homogeneous, Models, Organizational, Blood Circulation, Medical emergency, Emergencies, business, Algorithms
Abstract

Sepsis is a syndromic entity with high prevalence and mortality. The management of sepsis is standardized and exhibits time-dependent efficiency. However, the management of patients with sepsis is complex. The heterogeneity of the forms of presentation can make it difficult to detect and manage such cases, in the same way as differences in training, professional competences or the availability of health resources. The Advisory Commission for Patient Care with Sepsis (CAAPAS), comprising 7 scientific societies, the Emergency Medical System (SEM) and the Catalan Health Service (CatSalut), have developed the Interhospital Sepsis Code (CSI) in Catalonia (Spain). The general objective of the CSI is to increase awareness, promote early detection and facilitate initial care and interhospital coordination to attend septic patients in a homogeneous manner throughout Catalonia.

Published
2020
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23. Toll-like receptor 4 regulates subventricular zone proliferation and neuroblast migration after experimental stroke

Author

Jesús M. Pradillo, Raquel Ferreras-Martín, Isaac García-Yébenes, Ana Moraga, Olivia Hurtado, María A. Moro, Alicia García-Culebras, Ignacio Lizasoain, and Sara Palma-Tortosa

Subjects
Male, 0301 basic medicine, Neurogenesis, Immunology, Subventricular zone, Brain damage, Biology, Brain Ischemia, Mice, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Neural Stem Cells, Neuroblast, Cell Movement, Lateral Ventricles, Neuroblast migration, medicine, Animals, HMGB1 Protein, Progenitor cell, Stroke, Cell Proliferation, Neurons, Toll-like receptor, Endocrine and Autonomic Systems, Brain-Derived Neurotrophic Factor, Brain, Cell Differentiation, medicine.disease, Chemokine CXCL12, Cell biology, Mice, Inbred C57BL, Toll-Like Receptor 4, 030104 developmental biology, medicine.anatomical_structure, medicine.symptom, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Ischemic stroke is one of the leading causes of death and disability with an urgent need for innovative therapies, especially targeting the chronic phase. New evidence has emerged showing that Toll-Like Receptor 4 (TLR4), a key mediator of brain damage after stroke, may be involved in brain repair by neurogenesis modulation. The aim of this study is to analyze the role of TLR4 in the different stages of neurogenesis initiated in the subventricular zone (SVZ) over time after stroke in mice. Wildtype and TLR4-deficient mice underwent experimental ischemia, and neural stem/progenitor cells (NSPCs) proliferation and migration were analyzed by using FACS analysis, fluorescence densitometry, RT-qPCR and in vitro assays. Our results show that both groups, wildtype and knock-out animals, present a similar pattern of bilateral cell proliferation at the SVZ, with a decrease in NSPCs proliferation in the acute phase of stroke. We also show that TLR4 activation, very likely mediated by ligands such as HMGB1 released to CSF after stroke, is necessary to keep an increased proliferation of NSCs as well as to promote differentiation from type C cells into neuroblasts promoting their migration. TLR4 activation was also implicated in earlier expression of SDF-1α and faster recovery of BDNF expression after stroke. These results support TLR4 as an important therapeutic target in the modulation of neurogenesis after stroke.

Published
2019
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24. Experience and satisfaction with a multidisciplinary care unit for patients with psoriasis an psoriatic arthritis

Author

Leslie Fariñas Padron, Andrés Palacios Abufón, Estíbaliz Loza, Mercedes Hergueta Diaz, Maria Eugenia Guerrero, Sara Navarro Martín, Kelly Vargas Osorio, Ana Urruticoechea-Arana, Marta Serra Torres, and María Jesús García de Yébenes

Subjects
Adult, Male, medicine.medical_specialty, Disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Rheumatology, Multidisciplinary approach, Internal medicine, Psoriasis, Medicine, Humans, Retrospective Studies, 030203 arthritis & rheumatology, Patient Care Team, business.industry, Medical record, Arthritis, Psoriatic, Mean age, General Medicine, Middle Aged, medicine.disease, Patient Satisfaction, Physical therapy, Female, Electronic database, business, Hospital Units
Abstract

Objective To describe patient's characteristics, the activity and patient's satisfaction with a multidisciplinary care unit in patients with psoriasis and psoriatic arthritis (PsA). Methods A retrospective medical records review of patients with psoriasis or PsA attended in a multidisciplinary care unit was performed. Included patients were contacted to fulfill a satisfaction questionnaire. A specific electronic database was set up. Data regarding to patients and their baseline characteristics and the activity of the unit were collected. Descriptive analysis were performed. Results A total of 112 patients with 154 visits were included in almost 3 years, 54% women, with a mean age of 51 years, 43.7% presented hyperlipidemia and 30.4% arterial hypertension. Half of patients were referred due to diagnostic doubts and the other half for therapeutic problems. After the evaluation of the patients, 66 patients (58.9%) met diagnostic criteria for PsA, and 13 (11.6%) of an inflammatory disease other than PsA, and 95% came back to their usual physician. The most ordered test were laboratory tests (75.6% of patients), followed by X-rays in 57 patients (51.3%). In general the number of patients with different treatments increased, and 55.4% and 42% of patients changed their topic and systemic treatments respectively. The level of satisfaction was very high and all of patients considered that their disease was better controlled in this multidisciplinary care unit. Conclusions This multidisciplinary care unit has improved the care and satisfaction of patients with psoriasis or PsA, and increased collaboration between rheumatology and dermatology departments.

Published
2019
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25. Clinical and genetic characteristics of late-onset Huntington's disease

Author

Oosterloo, Mayke, Bijlsma, Emilia K., van Kuijk, Sander MJ., Minkels, Floor, de Die-Smulders, Christine EM., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna-Rita, Biunno, Ida, Bonelli, Raphael M., Bronzova, Juliana, Burgunder, Jean-Marc, Dunnett, Stephen B., Ferreira, Joaquim J., Frich, Jan, Giuliano, Joe, Handley, Olivia J., Heiberg, Arvid, Illarioshkin, Sergey, Illmann, Torsten, Klempir, Jiri, Landwehrmeyer, G. Bernhard, Levey, Jamie, Mclean, Tim, Nielsen, Jørgen E., Koivisto, Susana Pro, Päivärinta, Markku, Pålhagen, Sven, Quarrell, Oliver, Ramos-Arroyo, Maria, Roos, Raymund A. C., Saft, Carsten, Sebastián, Ana Rojo, Tabrizi, Sarah J., Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström+, Jan, Zaremba, Jacek (formerly Rödig, Verena, Baake, Barth, Katrin, Garde, Monica Bascuñana, Becanovic, Kristina, Bernard, Tomáš, Betz, Sabrina, Bos, Reineke, Come, Adrien, Guedes, Leonor Correia, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Horta, Andrea, Hvalstedt, Carina, Held, Christine, Hussain, Hasina, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Münkel, Kristina, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren (formerly Heinonen), Niini, Salgueiro, Ana, Šašinková, Pavla, Seliverstov, Yury, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, van Walsem, Marleen R., Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Hecht, Karen, Herranhof, Brigitte, Holl (formerly Hödl), Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Lilek, Sabine, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Larcher, Barbara, Mahlknecht, Philipp, Müller, Christoph, Pinter, Bernadette, Poewe, Werner, Reiter, Eva-Magdalena, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Ladurner, Gunther, Lilek, Stefan, Sinadinosa, Daniela, Staffen, Wolfgang, Walleczek, Anna Maria, Linder, Christoph, Pirker, Walter, Liessens, Dirk, Calmeyn, Godelinde, Somers, Nele, Delvaux, Isabelle, Boogaerts, Andrea, Flamez, Anja, de Raedt, Sylvie, Alaerts, Nick, Slama, Hichem, Supiot, Frédéric, Constant, Eric, Gillardin, Anne-Françoise, Léonard, Marie-Claude, van de Wyngaerde, Françoise, Dupuis, Michel, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, van Reijen, Dimphna, Weckx, Petra, Kaiserova, Michaela, Šenkárová, Zuzana, Bezdíček, Ondřej, Klempíř, Jiří, Klempířová, Olga, Majerová-Ibarburu, Veronika, Nikolai, Tomáš, Roth, Jan, Stárková, Irena, Madsen, Louise Hasselstrøm, Møller, Anette Torvin, Hjermind, Lena, Jacobsen, Oda, Larsen, Ida Unmack, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Roos, Peter, Stockholm, Jette, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Lolk, Annette, Lundsgaard, Marianne, Wermuth, Lene, Andersson, Christian, Nyberg, Clara, Sundblom, Jimmy, Peippo, Maarit, Sipponen, Marjatta, Bruun, Anu, Hartikainen, Paivi, Mäkipää, Seija, Ollokainen, Mari, Åman, Jaana, Kärppä, Mikko, Ignatius, Jaakko, Jääskeläinen, Outi, Kajula, Outi, Moilanen, Jukka, Mustonen, Aki, Santala, Maire, Eklund, Pia, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Ojala, Marjut, Tähkäpää, Sirkku, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Bled, Déborah, Debruxelles, Sabrina, Duché, Charlotte, Fraisse, Sonia, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Couttier, Julien, Debilly, Bérengère, Delaigue, Christine, Derost, Philippe, Durif, Franck, Germain, Véronique, Legendre, Perrine, Loiseau, Sylvie, Marques, Ana, Ulla, Miguel, Vidal, Tiphaine, Badei, Farideh, Boissé, Marie-Françoise, Boudali, Lotfi, Cleret de Langavant, Laurent, Lemoine, Laurie, Morgado, Graca, Youssov, Katia, Annic, Agnès, Barthélémy, Recka, De Bruycker, Christelle, Cabaret, Maryline, Carette, Anne-Sophie, Carrière, Nicolas, Decorte, Eric, Defebvre, Luc, Delliaux, Marie, Delval, Arnaud, Depelchin, Alizé, Destee, Alain, Dewulf-Pasz, Nelly, Dondaine, Thibaut, Dugauquier, Florence, Dujardin, Kathy, Hopes, Lucie, Krystkowiak, Pierre, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Mutez, Eugénie, Peter, Mireille, Plomhause, Lucie, Sablonnière, Bernard, Simonin, Clémence, Tard, Céline, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Blin, Stéphanie, Chen, Simone, Masmoudi, Kamel, Morin, Gilles, Roussel, Martine, Tir, Mélissa, Schüler, Béatrice, Wannepain, Sandrine, Zouitina, Yassine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Guenam, Aicha, Mundler, Laura, Nguyen, Karine, Benaich, Sandra, Brice, Alexis, Boster, Sarah, Charles, Perrine, Durr, Alexandra, Ewenczyk, Claire, Francisque, Hélène, Jauffret, Céline, Justo, Damian, Kassar, Abdulrahman, Klebe, Stephan, Lesne, Fabien, Milani, Paolo, Monin, Marie-Lorraine, Monnier, Tiffany, Roze, Emmanuel, Tataru, Alina, Tchikviladzé, Maya, Bioux, Sandrine, Bliaux, Evangeline, Girard, Carole, Guyant-Maréchal, Lucie, Hannequin, Didier, Hannier, Véronique, Jourdain, Séverine, Maltête, David, Pouliquen, Dorothée, Anheim, Mathieu, Barun, Nadia, Lagha-Boukbiza, Ouhaid, Longato, Nadine, Marcel, Christophe, Phillipps, Clélie, Rudolf, Gabrielle, Steinmetz, Gisèle, Tranchant, Christine, Wagner, Caroline, Zimmermann, Marie-Agathe, Blondeau, Leily, Calvas, Fabienne, Cheriet, Samia, Delabaere, Helène, Demonet, Jean-François, Marquine, Laurent, Pariente, Jérémie, Pierre, Michèle, Pomies, Elsa, Rolland, Sandrine, Souyris, Corinne, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Beuth, Markus, Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike, Thiel, Silvia, Andrich, Jürgen, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kraus, Peter, Stamm, Christiane, Ganos, Christos, Stubbe, Lars, Tadic, Vera, Tübing, Jennifer, Lange, Herwig, Bosredon, Cecile, Hunger, Ulrike, Löhle, Matthias, Maass, Antonia, Ossig, Christiana, Schmidt, Simone, Storch, Alexander, Wolz, Annett, Wolz, Martin, Kohl, Zacharias, Kozay, Christina, Winkler, Jürgen, Bergmann, Ulrike, Böringer, Regina, Capetian, Philipp, Kammel, Gerit, Lambeck, Johann, Mächtel, Miriam, Meier, Simone, Rijntjes, Michel, Zucker, Birgit, Boelmans, Kai, Goerendt, Ines, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Ribbat+, Michael, Longinus, Bernhard, Möller, Carsten, Bürk, Katrin, Lüsebrink, Antje, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthias, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Vogel, Melanie, Weydt, Patrick, Musacchio, Thomas, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, Difruscolo, Olimpia, Franco, Giovanni, Nuzzi, Angela, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Calandra-Buonaura, Giovanna, Capellari, Sabina, Cortelli, Pietro, Gallassi, Roberto, Poda, Roberto, Scaglione, Cesa, Agosti, Chiara, Barlati, Sergio, Compostella, Silvia, Marchina, Eleonora, Padovani, Alessando, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bertini, Elisabetta, Bartoli, Caterina, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, Bandettini di Poggio, Monica, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Di Maria, Emilio, Tamburini, Tiziano, Albanese, Alberto, Castagliuolo, Simona, Castaldo, Anna, Di Donato, Stefano, Di Bella, Daniela, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Panzeri, Marta, Paridi, Dominga, Soliveri, Paola, Spagnolo, Francesca, Taroni, Franco, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Esposito, Chiara, Martino, Tiziana, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Vezza, Maurizio, Squitieri, Ferdinando, D'Alessio, Barbara, Lovo, Francesca, Bentivoglio, Anna Rita, Bove, Francesco, Catalli, Claudio, Di Giacopo, Raffaella, Fasano, Alfonso, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Loria, Giovanna, Modoni, Anna, Petracca, Martina, Piano, Carla, Chiara, Piccininni, Quaranta, Davide, Romano, Silvia, Soleti, Francesco, Solito, Marcella, Spadaro, Maria, Torlizzi, Flavia, Coarelli, Giulia, Ferraldeschi, Michela, Ristori, Giovanni, van Hout, Monique S. E., van Vugt, Jeroen P. P., Marit de Weert, A., Verhoeven, Marloes, Dekker, Meike, Klooster, Jesper, Leenders, Nico, van Oostrom, Joost, Kremer, Berry, Baake, Verena, van den Bogaard, Simon J. A., Dumas, Eve M., t Hart, Ellen P., Hogenboom, Marye, Jacobs, Milou, Jurgens, Caroline, Kampstra, Anne, Schoonderbeek, Anne, Witjes-Ané, Marie-Noëlle, Duits, Annelien, Waber, Mirella, Verstappen, Carla, Blinkenberg, Ellen Økland, Hauge, Erik, Tyvoll, Hilde, Aaserud, Olaf, Aanonsen, Nils Olaf, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan C., Gørvell, Per F., Haggag, Kathrine, Johannessen, Cecilie Haggag, Retterstøl, Lars, Røsby, Oddveig, Rummel, Jutta, Sikiric, Alma, Stokke, Bodil, van Walsem, Marleen, Wehus, Ragnhild, Arntsen, Vibeke, Bjørnevoll, Inga, Sando, Sigrid Botne, Haug, Marte Gjøl, Størseth, Hanna Haugan, Østern, Rune, Paulsen, Julie, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska – Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anna Bryl, Jacek Anioła, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol (formerly Kalbarczyk), Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski+, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zaremba, Jacek, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Almeida, Manuel, Calado, Ana, Dias, Margarida, Morgado, Joana, Semedo, Cristina, Coelho, Miguel, Magalhães, Andreia, Mendes, Tiago, Neutel, Dulce, Rodrigues, Filipe, Valadas, Anabela, Costa, Cristina, Cardoso, Helena, Santos, Mariana, Cação, Gonçalo, Cavaco, Sara, Damásio, Joana, Fernandes, Joana, Gonçalves, Alexandra, Loureiro, Rui, Moreira, Inês, Magalhães, Marina, Salgado, Paula, Andrade, Carlos, Costa, Andreia, Garrett, Carolina, Gago, Miguel, Guimarães, Joana, Massano, João, Meireles, Joana, Monteiro, Ana, Khasanova, Diana, Zalyalova, Zuleykha, Klyushnikov, Sergey, Sidorova, Olga, Smirnov, Oleg, Antonova, Victoria, Kopishinskaya, Svetlana, Korotysh, Maria, Magzhanov, Rim, Saifullina, Elena, Kurbatov, Sergey, Solis, Pilar, Herrera, Carmen Durán, Moreno, Patrocinio Garcia, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Classen, Serge Jaumà, Dedichá, Nadia Rodríguez, Buongiorno, María Teresa, María, Andrés de la Cerda Santa, Muñoz, Esteban, Santacruz, Pilar, Barbera, Miquel Aguilar, Pardo, Sonia Arribas, Guia, Dolors Badenes, Calzado, Noemi, Hernanz, Laura Casas, Tartari Díaz-Zorita, Juan Pablo, Catena, Judit López, Ferrer, Pilar Quiléz, Carruesco, Gemma Tome, Robert, Misericordia Floriach, Viladrich, Cèlia Mareca, Roca, Elvira, Ruiz Idiago, Jesús Miguel, Riballo, Antonio Villa, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Bojarsky, Jaime Kulisevsky, Pagonabarraga, Javier, Perez, Jesus Perez, Ribosa, Roser, Villa, Carolina, Acera Gil, Maria Angeles, Corrales, Koldo Berganzo, Gomez Esteban, Juan Carlos, González, Amaia, Merino, Beatriz Tijero, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Sánchez, Jesús, Romero, Sandra Gutierrez, Arbelo, José Matías, Malo de Molina, Rocío, Martín, Idaira, Periañez, Juan Manuel, Udaeta, Beatriz, Alonso-Frech, Fernando, Loarte, María del Valle, Barrero, Francisco, Morales, Blas, Frades, Belén, Villanueva, Marina Ávila, Zea Sevilla, Maria Ascension, Fenollar, María del Mar, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Ventura, Marta Fatás, Caldentey, Juan García, Ribas, Guillermo García, García de Yébenes, Justo, López-Sendón Moreno, José Luis, Barral, Verónica Mañanes, Feliz, Cici, García Ruíz, Pedro José, García, Ana, López, Rosa Guerrero, Bárcenas, Antonio Herranz, Martínez-Descals, Asunción, Pueyo, Angel Martínez, Martin, Veronica Puertas, Martínez, Noelia Rodríguez, Montojo, Teresa, Sainz Artiga, María José, Sánchez, Vicenta, Alarcón, María Dolores, Almagro, Carmen Antúnez, Diéguez, Esther, Fortuna, Lorenza, Legaz, Agustina, Manzanares, Salvadora, Muñoz, Juan Marín, Antequera Torres, María Martirio, Perea, Fuensanta Noguera, Vivancos, Laura, González, Sonia, Guisasola, Luis Menéndez, Prieto, Marta Para, Ribacoba, René, Salvador, Carlos, Lozano, Pablo Sánchez, Ramirez, Inés Legarda, Benito, Dolors Moragues, Arques, Penelope Navas, Lopera, Monica Rodriguez, Pastor, Barbara Vives, Gaston, Itziar, Garcia-Amigot, Fermin, Martinez-Jaurrieta, Maria Dolores, Ramos-Arroyo, Maria Antonia, Adarmes, Astrid, Bernal-Escudero, Maravilla, Carrillo, Fátima, Jesús, Silvia, Mir, Pablo, Vargas-González, Laura, Hermoso, Fátima Damas, García Moreno, José Manuel, Jaramillo, Javier Abril, Lucena, Carolina Mendez, Pacheco Cortegana, Eva María, Peña, José Chacón, Redondo, Luis, Sánchez, Violeta Sánchez, Fernandez, Cristina Melgar, Romero Lemos, María Dolores, Mata, Maite Paredes, Casado, Rocío Villagrán, Bosca, Maria, Burguera, Juan Andres, Brugada, Francisco Castera, Millán Salvador, Jose Maria, Vilaplana, Carmen Peiró, Solís, Pilar, Figuerola, Begoña Jeweinat, Palanca, Paloma Millan, Diago, Elena Bellosta, López del Val, Javier, Martinez, Laura Martinez, López, Elena, Høsterey-Ugander, Ulrika, Fredlund, Gunnel, Constantinescu, Radu, Lewin, Kajsa, Neleborn-Lingefjärd, Liselotte, Berglund, Maria, Berglund, Peter, Linnsand, Petra, Petersén, Åsa, Reimer, Jan, Widner, Håkan, Esmaeilzadeh, Mouna, Tedroff, Joakim, Winnberg, Elisabeth, Benaminov, Stanislav, Björnsson, Elisabeth, Merrick, Daniel, Paucar, Martin, Svenningsson, Per, Wallden, Tina, Berglund, Måns, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Ekwall, Camilla, Göller, Marie-Lousie, Johansson, Anders, Niemelä, Valter, Nyholm, Dag, Wiklund, Leif, Koehli, Jessica, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Zaugg, Sabine Weber, Esposito, Federica, Good, Jean-Marc, Paus, Karin, Vingerhoets, Francois, Wider+, Christian, Jung, Hans H., Petersen, Jens A., Ligon-Auer, Maria, Mihaylova, Violeta, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A., Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Harrower, Timothy, Vernon, Nathan, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza (Keylock), Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Haig-Brown, Diane, Craven, Janet, Pallett, Andrew, Simpson, Steve, Weekes, Rebecca, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Barker, Roger A., O'Keefe, Deidre, Gerrtiz (nee Di Pietro), Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Goudie, David, Buchanan, Lindsay, Mcfadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Carrie, Ho, Mcgill, Marie, Porteous, Mary, Pearson, Pauline, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Neumann, Christian, Patterson, Kirsten, Thomson, David, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Brown, Pauline, Burrows, Liz, Fletcher, Amy, Harding, Alison, Harrison, Kaye, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Rowett, Liz, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Gosling (nee Brown), Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thomas, Wild, Edward, Ackermann, Oda, Duport, Sophie, Scott, Adrienne, Stoy, Nicholas, Vaughn, Jenny, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen (formerly Ritchie), Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Lois, Singh, Baldev, Wood, Josh, Knight, Caroline, O'Neill, Mari, Purkayastha, Debasish Das, Nemeth, Andrea H., Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, Donovan, John O., Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Burn, John, Bailey, Wendy, Coleman, Caroline, Majeed, Tahir, Verstraelen (Ritchie), Nicola, Barrett, Wendy, Aileen, Ho, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Taylor, Cat, Tidswell, Katherine, Kipps, Christopher, Mackinnon, Lesley, Agarwal, Veena, Hayward, Elaine, Gunner, Kerry, Harris, Kayla, Anderson, Mary, Heywood, Melanie, Keys, Liane, Smalley, Sarah, El-Nimr, George, Duffell, Allison, Wood, Sue, Kennedy (nee Smith), Karen, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Tan, Louis, Lau, Puay Ngoh, Pica, Emmanuel, Roos, Raymund AC., Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: KIO Kemta (9), Epidemiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, Klinische Genetica, MUMC+: DA KG Polikliniek (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
Male, HD, 0301 basic medicine, Pediatrics, Neurology, Huntingtin Protein/genetics, FEATURES, Disease, Neuropsychological Tests, 0302 clinical medicine, Cognitive Dysfunction/psychology, Medicine, Family history, Postural Balance, Huntington Disease/genetics, Huntingtin Protein, education.field_of_study, Chorea/physiopathology, Huntington's disease, Sensation Disorders/physiopathology, Middle Aged, Dystonia, Settore MED/26 - NEUROLOGIA, Huntington Disease, neurodegenerative disorders, Sensation Disorders, Disease Progression, Female, medicine.symptom, Adult, medicine.medical_specialty, Population, Age of onset, Late-onset Huntington's disease, Geriatrics and Gerontology, Neurology (clinical), 03 medical and health sciences, AGE, Chorea, Humans, Cognitive Dysfunction, education, Dystonia/physiopathology, Gait Disorders, Neurologic/physiopathology, Gait Disorders, Neurologic, business.industry, medicine.disease, Gait, 030104 developmental biology, Trinucleotide Repeat Expansion, business, 030217 neurology & neurosurgery, Balance problems
Abstract

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P

Published
2019
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26. Multilevel factors predict medication adherence in rheumatoid arthritis: a 6-month cohort study

Author

Alejandro, Balsa, Maria Jesus, García de Yébenes, Loreto, Carmona, and Isabel Serrano, García

Subjects
Male, medicine.medical_specialty, Immunology, General Biochemistry, Genetics and Molecular Biology, Medication Adherence, Arthritis, Rheumatoid, Rheumatology, Internal medicine, Health care, medicine, Immunology and Allergy, Humans, Prospective Studies, Adverse effect, Prospective cohort study, Biological Products, Physician-Patient Relations, business.industry, Health services research, Middle Aged, medicine.disease, Stratified sampling, Logistic Models, Rheumatoid arthritis, Antirheumatic Agents, Multilevel Analysis, Female, business, Cohort study
Abstract

Non-adherence challenges efficacy and costs of healthcare. Knowledge of the underlying factors is essential to design effective intervention strategies.ObjectivesTo estimate the prevalence of treatment adherence in rheumatoid arthritis (RA) and to evaluate its predictors.MethodsA 6-month prospective cohort study of patients with RA selected by systematic stratified sampling (33% on first disease-modifying rheumatic drug (DMARD), 33% on second-line DMARD and 33% on biologics). The outcome measure was treatment adherence, defined by a score greater than 80% both in the Compliance Questionnaire in Rheumatology and the Reported Adherence to Medication scale, and was estimated with 95% CIs. Predictive factors included sociodemographic, psychological, clinical, drug-related, patient–doctor relationship related and logistic. Their effect on 6-month adherence was examined by multilevel logistic models adjusted for baseline covariates.Results180 patients were recruited (77% women, mean age 60.8). The prevalence of adherence was 59.1% (95% CI 48.1% to 71.8%). Patients on biologics showed higher adherence and perceived a higher medication need than the others; patients on second-line DMARDs had experienced more adverse events than the others. The variables explaining adherence in the final multivariate model were the type of treatment prescribed (second-line DMARDs OR=5.22, and biologics OR=3.76), agreement on treatment (OR=4.57), having received information on treatment adaptation (OR=1.42) and the physician perception of patient trust (OR=1.58). These effects were independent of disease activity.ConclusionTreatment adherence in RA is far from complete. Psychological, communicational and logistic factors influence treatment adherence in RA to a greater extent than sociodemographic or clinical factors.

Published
2021

27. One-step nucleic acid amplification (OSNA) of Sentinel Lymph Node in Early Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA)

Author

Irmgard Costa, Alberto Berjón, Maria Dolores Diestro, Marta Rezola, M. Sánchez-Pastor, Juan Carlos Muruzabal, Beatriz Montero, Isabel Guerra, Alicia Hernández, Cristina Zorrero, Rosa Guarch, Pluvio J. Coronado, L. I. Lete, F. Relea, C.-B. Marta, Maria Jose Román, Jaime Siegrist, Alejandro Pascual, Fernando Roldan, David Hardisson, M. J. Boillos, L. Ribot, Amaia Sagasta, Gloria Peiró, Arantza Lekuona, Luis Matute, L. Yébenes, Irune Ruiz, María Cuadra, Ignacio Zapardiel, M. J. Cardiel, Ibon Jaunarena, A. Calatrava, and C. López-de la Manzanara

Subjects
Oncology, medicine.medical_specialty, Multicenter study, business.industry, allergology, Internal medicine, Endometrial cancer, Sentinel lymph node, Nucleic acid, Medicine, Stage (cooking), business, medicine.disease
Abstract

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Published
2021
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28. Cav-1 Protein Levels in Serum and Infarcted Brain Correlate with Hemorrhagic Volume in a Mouse Model of Thromboembolic Stroke, Independently of Rt-PA Administration

Author

Carme Gubern-Mérida, Elisabet Kádár, Mar Castellanos, María A. Moro, Ignacio Lizasoain, Juan M. Sanchez, Irene Puig-Parnau, Joaquín Serena, Isaac García-Yébenes, Gemma Huguet, Pau Comajoan, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Comunidad de Madrid (España), Ministerio de Ciencia e Innovación (España), Fundación La Caixa, and Fondation Leducq

Subjects
medicine.medical_specialty, business.industry, Caveolin 1, Neuroscience (miscellaneous), Brain, Endothelial Cells, Hemorrhage, Infarction, Middle Cerebral Artery, Thromboembolic stroke, Brain Ischemia, Stroke, Mice, Cellular and Molecular Neuroscience, Text mining, Neurology, Tissue Plasminogen Activator, Internal medicine, cardiovascular system, medicine, Cardiology, Animals, business, Ischemic Stroke, Volume (compression)
Abstract

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration. This work was supported by grants from Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund “A Way to Achieve Europe” Health Strategic Action Program PI13/02258 and PI17/02123 (MC), PI20/00535 (IL), and Spanish Stroke Research Network RETICS RD12/0014/0010 (MC), and RD16/0019/0003 (JS), RD16/0019/0004 (MC), and RD16/0019/0009 (IL); from Regional Madrid Government B2017/BMD- 3688 (IL); from Spanish Ministry of Science and Innovation PID2019-106581RBI00 (MAM); from Leducq Foundation for Cardiovascular Research TNE-19CVD01 (MAM); and from Fundación La Caixa HR17_00527 (MAM). P. Comajoan was a recipient of a predoctoral fellowship from the University of Girona (IF-UdG 2015). Sí

Published
2021
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29. Dynamics of high-sensitivity troponin T and myocardial dysfunction during the first 72 h of septic shock

Author

Elisabeth Pinart, J.M. Sirvent, Maria Buxó, Cristina Murcia-Gubianas, and Juan Carlos Yébenes

Subjects
medicine.medical_specialty, business.industry, Septic shock, Troponin I, High Sensitivity Troponin T, medicine.disease, Shock, Septic, Text mining, Troponin T, Internal medicine, Internal Medicine, medicine, Cardiology, Humans, business, Cardiomyopathies, Biomarkers
Published
2021

30. Trehalose improves human fibroblast deficits in a new CHIP-mutation related ataxia.

Author

Maria Jose Casarejos, Juan Perucho, Jose Luis López-Sendón, Justo García de Yébenes, Conceição Bettencourt, Ana Gómez, Carolina Ruiz, Peter Heutink, Patrizia Rizzu, and Maria Angeles Mena

Subjects
Medicine, Science
Abstract

In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein misfolding and proteostasis were evaluated. Recent studies have revealed that mutations in STUB-1 gene lead to a growing list of molecular defects as deregulation of protein quality, inhibition of proteasome, cell death, decreased autophagy and alteration in CHIP and HSP70 levels. In this CHIP-mutant patient fibroblasts the inhibition of proteasome with epoxomicin induced severe pathophysiological age-associated changes, cell death and protein ubiquitination. Additionally, treatment with epoxomicin produced a dose-dependent increase in the number of cleaved caspase-3 positive cells. However, co-treatment with trehalose, a disaccharide of glucose present in a wide variety of organisms and known as a autophagy enhancer, reduced these pathological events. Trehalose application also increased CHIP and HSP70 expression and GSH free radical levels. Furthermore, trehalose augmented macro and chaperone mediated autophagy (CMA), rising the levels of LC3, LAMP2, CD63 and increasing the expression of Beclin-1 and Atg5-Atg12. Trehalose treatment in addition increased the percentage of immunoreactive cells to HSC70 and LAMP2 and reduced the autophagic substrate, p62. Although this is an individual case based on only one patient and the statistical comparisons are not valid between controls and patient, the low variability among controls and the obvious differences with this patient allow us to conclude that trehalose, through its autophagy activation capacity, anti-aggregation properties, anti-oxidative effects and lack of toxicity, could be very promising for the treatment of CHIP-mutation related ataxia, and possibly a wide spectrum of neurodegenerative disorders related to protein disconformation.

Published
2014
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31. Identification of genetic variants associated with Huntington's disease progression

Author

Davina J Hensman Moss, Antonio F Pardiñas, Douglas Langbehn, Kitty Lo, Blair R Leavitt, Raymund Roos, Alexandra Durr, Simon Mead, Peter Holmans, Lesley Jones, Sarah J Tabrizi, A Coleman, R Dar Santos, J Decolongon, A Sturrock, E Bardinet, C Jauff Ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue, SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane, N Arran, J Callaghan, C Stopford, C Frost, R Jones, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, E Wild, A Patel, N C Fox, C Gibbard, I Malone, H Crawford, D Whitehead, S Keenan, D M Cash, C Berna, N Bechtel, S Bohlen, A Hoff Man, P Kraus, E Axelson, C Wang, T Acharya, S Lee, W Monaco, C Campbell, S Queller, K Whitlock, M Campbell, E Frajman, C Milchman, A O'Regan, I Labuschagne, J Stout, B Landwehrmeyer, D Craufurd, R Scahill, S Hicks, C Kennard, H Johnson, A Tobin, HD Rosas, R Reilmann, B Borowsky, C Pourchot, S C Andrews, Anne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael Bonelli, Jean-Marc Burgunder, Stephen Dunnett, Joaquim Ferreira, Olivia Handley, Arvid Heiberg, Torsten Illmann, G. Bernhard Landwehrmeyer, Jamie Levey, Maria A. Ramos-Arroyo, Jørgen Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A.C. Roos, A Rojo Sebastián, Sarah Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Monica Bascuñana Garde, Sabrina Betz, Reineke Bos, Jenny Callaghan, Adrien Come, Leonor Correia Guedes, Daniel Ecker, Ana Maria Finisterra, Ruth Fullam, Mette Gilling, Lena Gustafsson, Olivia J Handley, Carina Hvalstedt, Christine Held, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saül Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Michael Orth, Hélène Padieu, Laurent Paterski, Nadia Peppa, Martina Di Renzo, Amandine Rialland, Niini Røren, Pavla Šašinková, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Wildson Vieira da Silva, Marleen R van Walsem, Carina Whalstedt, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Raphael M. Bonelli, Sabine Lilek, Karen Hecht, Brigitte Herranhof, Anna Holl, Hans-Peter Kapfhammer, Michael Koppitz, Markus Magnet, Nicole Müller, Daniela Otti, Annamaria Painold, Karin Reisinger, Monika Scheibl, Helmut Schöggl, Jasmin Ullah, Eva-Maria Braunwarth, Florian Brugger, Lisa Buratti, Eva-Maria Hametner, Caroline Hepperger, Christiane Holas, Anna Hotter, Anna Hussl, Christoph Müller, Werner Poewe, Klaus Seppi, Fabienne Sprenger, Gregor Wenning, Andrea Boogaerts, Godelinde Calmeyn, Isabelle Delvaux, Dirk Liessens, Nele Somers, Michel Dupuit, Cécile Minet, Dominique van Paemel, Pascale Ribaï, Dimphna van Reijen, Jirí Klempír, Veronika Majerová, Jan Roth, Irena Stárková, Lena E. Hjermind, Oda Jacobsen, Jørgen E. Nielsen, Ida Unmack Larsen, Tua Vinther-Jensen, Heli Hiivola, Hannele Hyppönen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau, Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Rekha Barthélémy, Christelle De Bruycker, Maryline Cabaret Anne-Sophie Carette, Eric Decorte Luc Defebvre, Marie Delliaux, Arnaud Delval, Alain Destee, Kathy Dujardin, Marie-Hélène Lemaire, Sylvie Manouvrier, Mireille Peter, Lucie Plomhouse, Bernard Sablonnière, Clémence Simonin, Stéphanie Thibault-Tanchou, Isabelle Vuillaume, Marcellin Bellonet, Hassan Berrissoul, Stéphanie Blin, Françoise Courtin, Cécile Duru, Véronique Fasquel, Olivier Godefroy, Pierre Krystkowiak, Béatrice Mantaux, Martine Roussel, Sandrine Wannepain, Jean-Philippe Azulay, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Laura Mundler, Mathieu Anheim, Celine Julié, Ouhaid Lagha Boukbiza, Nadine Longato, Gabrielle Rudolf, Christine Tranchant, Marie-Agathe Zimmermann, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J. Werner, Harald Gelderblom, Josef Priller, Harald Prüß, Eike Jakob Spruth, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Peter Kotz, Christian Prehn, Carsten Saft, Herwig Lange, Robert Maiwald, Matthias Löhle, Antonia Maass, Simone Schmidt, Cecile Bosredon, Alexander Storch, Annett Wolz, Martin Wolz, Philipp Capetian, Johann Lambeck, Birgit Zucker, Kai Boelmans, Christos Ganos, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Heike Gorzolla, Christoph Schrader, Pawel Tacik, Michael Ribbat, Bernhard Longinus, Katrin Bürk, Jens Carsten Möller, Ida Rissling, Mark Mühlau, Alexander Peinemann, Michael Städtler, Adolf Weindl, Juliane Winkelmann, Cornelia Ziegler, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Eva Hölzner, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Natalia Weber, Matthias Dose, Gabriele Leythäuser, Ralf Marquard, Tina Raab, Alexandra Wiedemann, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Christina Lang, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süßmuth, Sonja Trautmann, Patrick Weydt, Claudia Cormio, Vittorio Sciruicchio, Claudia Serpino, Marina de Tommaso, Sabina Capellari, Pietro Cortelli, Roberto Galassi, Giovanni Rizzo, Roberto Poda, Cesa Scaglione, Elisabetta Bertini, Elena Ghelli, Andrea Ginestroni, Francesca Massaro, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giovanni Abbruzzese, Monica Bandettini di Poggio, Giovanna Ferrandes, Paola Mandich, Roberta Marchese, Alberto Albanese, Daniela Di Bella, Anna Castaldo, Stefano Di Donato, Cinzia Gellera, Silvia Genitrini, Caterina Mariotti, Lorenzo Nanetti, Dominga Paridi, Paola Soliveri, Chiara Tomasello, Giuseppe De Michele, Luigi Di Maio, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Elena Salvatore, Pierpaolo Sorrentino, Enrico Amico, Mariagrazia Favellato, Annamaria Griguoli, Irene Mazzante, Martina Petrollini, Ferdinando Squitieri, Barbara D'Alessio, Chiara Esposito, Rita Bentivoglio, Marina Frontali, Arianna Guidubaldi, Tamara Ialongo, Gioia Jacopini, Carla Piano, Silvia Romano, Francesco Soleti, Maria Spadaro, Monique S.E. van Hout, Marloes E. Verhoeven, Jeroen P.P. van Vugt, A. Marit de Weert, J.J.W. Bolwijn, M. Dekker, B. Kremer, K.L. Leenders, J.C.H. van Oostrom, Simon J.A. van den Bogaard, Eve M. Dumas, Ellen P. 't Hart, Berry Kremer, C.C.P. Verstappen, Olaf Aaserud, Jan Frich C, Ragnhild Wehus, Kathrine Bjørgo, Madeleine Fannemel, Per F. Gørvell, Eirin Lorentzen, Lars Retterstøl, Bodil Stokke, Inga Bjørnevoll, Sigrid Botne Sando, Artur Dziadkiewicz, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Magdalena Blaszcyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasinska-Myga, Gabriela Klodowska-Duda, Gregorz Opala, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Bocwinska, Kamila Bojakowska-Jaremek, Malgorzata Dec, Malgorzata Krawczyk, Monika Rudzinska, Elzbieta Szczygiel, Andrzej Szczudlik, Anna Wasielewska, Magdalena Wójcik, Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempolowicz, Anna Gogol, Piotr Janik, Hubert Kwiecinski, Zygmunt Jamrozik, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stepniak, Anna Sulek, Elzbieta Zdzienicka, Karolina Zieora-Jakutowicz, Joaquim J Ferreira, Miguel Coelho, Tiago Mendes, Anabela Valadas, Carlos Andrade, Miguel Gago, Carolina Garrett, Maria Rosália Guerra, Carmen Durán Herrera, Patrocinio Moreno Garcia, Miquel Aguilar Barbera, Dolors Badenes Guia, Laura Casas Hernanz, Judit López Catena, Pilar Quiléz Ferrer, Ana Rojo Sebastián, Gemma Tome Carruesco, Jordi Bas, Núria Busquets, Matilde Calopa, Misericordia Floriach Robert, Celia Mareca Viladrich, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Esther Cubo, Cecilia Gil Polo, Natividad Mariscal, Perez Jessica Rivadeneyra, Francisco Barrero, Blas Morales, María Fenollar, Rocío García-Ramos García, Paloma Ortega, Clara Villanueva, Javier Alegre, Mónica Bascuñana, Juan Garcia Caldentey, Marta Fatás Ventura, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Fernando Alonso Frech, Pedro J García Ruíz, Asunción Martínez-Descals, Rosa Guerrero, María José Saiz Artiga, Vicenta Sánchez, María Fuensanta Noguera Perea, Lorenza Fortuna, Salvadora Manzanares, Gema Reinante, María Martirio Antequera Torres, Laura Vivancos Moreau, Sonia González González, Luis Menéndez Guisasola, Carlos Salvador, Esther Suaréz San Martín, Inés Legarda Ramirez, Aranzazú Gorospe, Mónica Rodriguez Lopera, Penelope Navas Arques, María José Torres Rodríguez, Barbara Vives Pastor, Itziar Gaston, Maria Dolores Martinez-Jaurrieta, Jose Manuel Garcia Moreno, Carolina Mendez Lucena, Fatima Damas, Hermoso Eva Pacheco Cortegana, José Chacón Peña, Luis Redondo, Fátima Carrillo, María Teresa Cáceres, Pablo Mir, María José Lama Suarez, Laura Vargas-González, Maria E. Bosca, Francisco Castera Brugada, Juan Andres Burguera, Anabel Campos, Garcia Carmen Peiró Vilaplana, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Petra Linnsand, Liselotte Neleborn-Lingefjärd, Magnus Wentzel, Ghada Loutfi, Carina Olofsson, Eva-Lena Stattin, Laila Westman, Birgitta Wikström, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Maria Hauer, Roman Gonzenbach, Hans H. Jung, Violeta Mihaylova, Jens Petersen, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughan, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Matthew Armstrong, Roger A. Barker, Deidre O'Keefe, Anna Di Pietro, Kate Fisher, Anna Goodman, Susan Hill, Ann Kershaw, Sarah Mason, Nicole Paterson, Lucy Raymond, Rachel Swain, Natalie Valle Guzman, Monica Busse, Cynthia Butcher, Catherine Clenaghan, Sarah Hunt, Una Jones, Hanan Khalil, Michael Owen, Kathleen Price, Anne Rosser, Maureen Edwards, Carrie Ho, Teresa Hughes, Marie McGill, Pauline Pearson, Mary Porteous, Paul Smith, Peter Brockie, Jillian Foster, Nicola Johns, Sue McKenzie, Jean Rothery, Gareth Thomas, Shona Yates, Liz Burrows, Carol Chu, Amy Fletcher, Deena Gallantrae, Stephanie Hamer, Alison Harding, Stefan Klöppel, Alison Kraus, Fiona Laver, Monica Lewis, Mandy Longthorpe, Ivana Markova, Ashok Raman, Nicola Robertson, Mark Silva, Aileen Thomson, Sue Wild, Pam Yardumian, Carole Evans, Deena Gallentrae, Emma Hobson, Stuart Jamieson, Hannah Musgrave, Liz Rowett, Jean Toscano, Colin Bourne, Jackie Clapton, Carole Clayton, Heather Dipple, Dawn Freire-Patino, Janet Grant, Diana Gross, Caroline Hallam, Julia Middleton, Ann Murch, Catherine Thompson, Sundus Alusi, Rhys Davies, Kevin Foy, Emily Gerrans, Louise Pate, Thomasin Andrews, Andrew Dougherty, Charlotte Golding, Fred Kavalier, Hana Laing, Alison Lashwood, Dene Robertson, Deborah Ruddy, Alastair Santhouse, Anna Whaite, Stefania Bruno, Karen Doherty, Salman Haider, Davina Hensman, Nayana Lahiri, Marianne Novak, Aakta Patel, Elisabeth Rosser, Rachel Taylor, Thomas Warner, Edward Wild, Natalie Arran, Judith Bek, David Craufurd, Marianne Hare, Liz Howard, Susan Huson, Liz Johnson, Mary Jones, Helen Murphy, Emma Oughton, Lucy Partington-Jones, Dawn Rogers, Andrea Sollom, Julie Snowden, Cheryl Stopford, Jennifer Thompson, Iris Trender-Gerhard, Nichola Verstraelen, Leann Westmoreland, Richard Armstrong, Kathryn Dixon, Andrea H Nemeth, Gill Siuda, Ruth Valentine, David Harrison, Max Hughes, Andrew Parkinson, Beverley Soltysiak, Oliver Bandmann, Alyson Bradbury, Paul Gill, Helen Fairtlough, Kay Fillingham, Isabella Foustanos, Mbombe Kazoka, Kirsty O'Donovan, Cat Taylor, Katherine Tidswell, Oliver Quarrell, Puay Ngoh Lau, Emmanul Pica, Louis Tan, Univ Angers, Okina, Moss, Davina J. Hensman, Tabrizi, Sarah J, Mead, Simon, Kitty, Lo, Pardiã±as, Antonio F, Holmans, Peter, Jones, Lesley, Langbehn, Dougla, Coleman, A., Santos, R. Dar, Decolongon, J., Sturrock, A., Bardinet, E., Ret, C. Jauff, Justo, D., Lehericy, S., Marelli, C., Nigaud, K., Valabrãgue, R., van den Bogaard, S. J. A., Dumas, E. M., van der Grond, J., T'Hart, E. P., Jurgens, C., Witjes-Ane, M. -. N., Arran, N., Callaghan, J., Stopford, C., Frost, C., Jones, R., Hobbs, N., Lahiri, N., Ordidge, R., Owen, G., Pepple, T., Read, J., Say, M., Wild, E., Patel, A., Fox, N. C., Gibbard, C., Malone, I., Crawford, H., Whitehead, D., Keenan, S., Cash, D. M., Berna, C., Bechtel, N., Bohlen, S., Man, A. Hoff, Kraus, P., Axelson, E., Wang, C., Acharya, T., Lee, S., Monaco, W., Campbell, C., Queller, S., Whitlock, K., Campbell, M., Frajman, E., Milchman, C., O'Regan, A., Labuschagne, I., Stout, J., Landwehrmeyer, B., Craufurd, D., Scahill, R., Hicks, S., Kennard, C., Johnson, H., Tobin, A., Rosas, H. D., Reilmann, R., Borowsky, B., Pourchot, C., Andrews, S. C., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna Rita, Biunno, Ida, Bonelli, Raphael, Burgunder, Jean-Marc, Dunnett, Stephen, Ferreira, Joaquim, Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Landwehrmeyer, G. Bernhard, Levey, Jamie, Ramos-Arroyo, Maria A., Nielsen, Jã¸rgen, Koivisto, Susana Pro, Pã¤ivã¤rinta, Markku, Roos, Raymund A. C., Sebastiã¡n, A. Rojo, Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlstrã¶m, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Garde, Monica Bascuñana, Betz, Sabrina, Bos, Reineke, Callaghan, Jenny, Come, Adrien, Guedes, Leonor Correia, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Gilling, Mette, Gustafsson, Lena, Handley, Olivia J, Hvalstedt, Carina, Held, Christine, Koppers, Kerstin, Lamanna, Claudia, Laurã , Matilde, Descals, Asunción Martínez, Martinez-Horta, Saã¼l, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mã¼tze, Lisanne, Oehmen, Martin, Orth, Michael, Padieu, Hã©lãne, Paterski, Laurent, Peppa, Nadia, Di Renzo, Martina, Rialland, Amandine, Rã¸ren, Niini, Å aå¡inkovã¡, Pavla, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, da Silva, Wildson Vieira, van Walsem, Marleen R, Whalstedt, Carina, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Bonelli, Raphael M., Lilek, 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Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duchã©, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucriãre, Danielle, Spampinato, Umberto, Barthã©lã©my, Rekha, De Bruycker, Christelle, Carette, Maryline Cabaret Anne-Sophie, Defebvre, Eric Decorte Luc, Delliaux, Marie, Delval, Arnaud, Destee, Alain, Dujardin, Kathy, Lemaire, Marie-HélÃne, Manouvrier, Sylvie, Peter, Mireille, Plomhouse, Lucie, Sablonniãre, Bernard, Simonin, Clã©mence, Thibault-Tanchou, Stã©phanie, Vuillaume, Isabelle, Bellonet, Marcellin, Berrissoul, Hassan, Blin, Stã©phanie, Courtin, Franã§oise, Duru, Cã©cile, Fasquel, Vã©ronique, Godefroy, Olivier, Krystkowiak, Pierre, Mantaux, Bã©atrice, Roussel, Martine, Wannepain, Sandrine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frã©dã©rique, Mundler, Laura, Anheim, Mathieu, Juliã©, Celine, Boukbiza, Ouhaid Lagha, Longato, Nadine, Rudolf, Gabrielle, Tranchant, Christine, Zimmermann, Marie-Agathe, 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Natalie, Beckmann, Heike, Bohlen, Stefan, Hã¶lzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Natalia, Dose, Matthia, Leythã¤user, Gabriele, Marquard, Ralf, Raab, Tina, Wiedemann, Alexandra, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lang, Christina, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Sã¼ã muth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Cormio, Claudia, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Capellari, Sabina, Cortelli, Pietro, Galassi, Roberto, Rizzo, Giovanni, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Massaro, Francesca, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, di Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Roberta, Marchese, Albanese, Alberto, Di Bella, Daniela, Castaldo, Anna, Di Donato, Stefano, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Paridi, Dominga, Soliveri, Paola, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Amico, Enrico, Favellato, Mariagrazia, Griguoli, Annamaria, Mazzante, Irene, Petrollini, Martina, Squitieri, Ferdinando, D'Alessio, Barbara, Esposito, Chiara, Bentivoglio, Rita, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Piano, Carla, Romano, Silvia, Soleti, Francesco, Spadaro, Maria, van Hout, Monique S. E., Verhoeven, Marloes E., van Vugt, Jeroen P. P., de Weert, A. Marit, Bolwijn, J. J. W., Dekker, M., Kremer, B., Leenders, K. L., van Oostrom, J. C. H., van den Bogaard, Simon J. A., Dumas, Eve M., â t Hart, Ellen P., Kremer, Berry, Verstappen, C. C. P., Aaserud, Olaf, Jan Frich, C., Wehus, Ragnhild, Bjã¸rgo, Kathrine, Fannemel, Madeleine, Gã¸rvell, Per F., Lorentzen, Eirin, Retterstã¸l, Lar, Stokke, Bodil, Bjã¸rnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wã³jcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlo, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badene, Hernanz, Laura Casa, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastiã¡n, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Nãºria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Bla, Fenollar, Marã­a, Garcã­a, Rocío García-Ramo, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuã±ana, Mã³nica, Caldentey, Juan Garcia, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruã­z, Pedro J. García, Martínez-Descals, Asunciã³n, Guerrero, Rosa, Artiga, María José Saiz, Sã¡nchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivanco, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlo, Martã­n, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazãº, Lopera, Mónica Rodriguez, Arques, Penelope Nava, Rodrã­guez, María José Torre, Pastor, Barbara Vive, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolore, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peã±a, José Chacón, Redondo, Lui, Carrillo, Fã¡tima, Teresa Cáceres, Marã­a, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andre, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnu, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikstrã¶m, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schã¼pbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jen, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Carrie, Ho, Hughes, Teresa, Mcgill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klã¶ppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, David, Harrison, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Amsterdam Neuroscience - Neurodegeneration, Neurology, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Moss, Davina J Hensman, Lo, Kitty, Pardiñas, Antonio F, Santos, R Dar, Ret, C Jauff, Valabrègue, R., Witjes-Ane, M. -N., Man, A Hoff, Bachoud-Lévi, Anne-Catherine, Nielsen, Jørgen, Päivärinta, Markku, Sebastián, A Rojo, Wahlström, Jan, Garde, Monica Bascuñana, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mütze, Lisanne, Padieu, Hélène, Røren, Niini, Šašinková, Pavla, Witjes-Ané, Marie-Noelle, Müller, Nicole, Schöggl, Helmut, Müller, Christoph, Minet, Cécile, Ribaï, Pascale, Klempír, Jirí, Majerová, Veronika, Stárková, Irena, Nielsen, Jørgen E., Hyppönen, Hannele, Gohier, Bénédicte, Guérid, Marie-Anne, Duché, Charlotte, Lafoucrière, Danielle, Barthélémy, Rekha, Lemaire, Marie-Hélène, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Mantaux, Béatrice, Fluchere, Frédérique, Julié, Celine, Prüß, Harald, Löhle, Matthia, Münchau, Alexander, Bürk, Katrin, Möller, Jens Carsten, Mühlau, Mark, Städtler, Michael, Hölzner, Eva, Leythäuser, Gabriele, Süßmuth, Sigurd, Marchese, Roberta, DI MAIO, Luigi, ’t Hart, Ellen P., Bjørgo, Kathrine, Gørvell, Per F., Retterstøl, Lar, Bjørnevoll, Inga, Wójcik, Magdalena, Guerra, Maria Rosália, Herrera, Carmen Durán, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Busquets, Núria, Idiago, Jesús Miguel Ruiz, Fenollar, María, García, Rocío García-Ramo, Bascuñana, Mónica, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Ruíz, Pedro J García, Martínez-Descals, Asunción, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Torres, María Martirio Antequera, González González, Sonia, Guisasola, Luis Menéndez, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Rodríguez, María José Torre, Peña, José Chacón, Carrillo, Fátima, Teresa Cáceres, María, Suarez, María José Lama, Vargas-González, Laura, Vilaplana, Garcia Carmen Peiró, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Wikström, Birgitta, Schüpbach, Michael, Ho, Carrie, Klöppel, Stefan, Harrison, David, Cardiff University, University of Iowa [Iowa City], University of British Columbia (UBC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL, Institute of Neurology [London], National Oceanography Centre [Southampton] (NOC), University of Southampton, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), TRACK-HD investigators, Pardinas, Antonio F, Langbehn, Douglas, Lee, S Hong, TRACK-HD Investigators, and REGISTRY Investigators

Subjects
0301 basic medicine, Oncology, Registrie, Genome-wide association study, Longitudinal Studie, Disease, Bioinformatics, Severity of Illness Index, Principal Component Analysi, Longitudinal Studies, Registries, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Huntington disease, DNA-Binding Proteins, Settore MED/26 - NEUROLOGIA, Adult, Genome-Wide Association Study, Humans, Huntington Disease, MutS Homolog 3 Protein, Principal Component Analysis, Disease Progression, Neurology (clinical), huntingtin gene, age of onest, Huntington’s disease, Human, medicine.medical_specialty, cag repeat, instability, DNA-Binding Protein, Clinical Neurology, Principal component analysis, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, Huntington's disease, Internal medicine, medicine, SNP, genome-wide association study, medicine.disease, R1, meta-analysis, Minor allele frequency, 030104 developmental biology, Age of onset, Trinucleotide repeat expansion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Published
2017
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33. Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling

Author

Alberto Berjón, Victoria Heredia-Soto, Ece Kadioglu, Andrés Redondo, Rodrigo Barderas, Marta Mendiola, Ignacio Ruz-Caracuel, Laura Yébenes, David Hardisson, J I Casal, Álvaro López-Janeiro, Vivian de los Ríos, Jorge L Ramón-Patino, Carlos E. de Andrea, María Villalba Esparza, Virginie Goubert, Alicia Hernández, Alberto Peláez-García, Ivan Masetto, UAM. Departamento de Anatomía Patológica, Instituto de Salud Carlos III, European Commission, López-Janeiro, Álvaro [0000-0002-5744-3115], Ruz-Caracuel, Ignacio [0000-0002-2298-4683], Ramón-Patino, Jorge L. [0000-0002-7308-823X], Ríos, Vivian de los [0000-0001-5582-6879], Villalba Esparza, María [0000-0002-9183-0610], Berjón, Alberto [0000-0002-3467-106X], Kadioglu, Ece [0000-0001-8679-8030], Heredia-Soto, Victoria [0000-0002-0704-7958], Barderas, Rodrigo [0000-0003-3539-7469], Casal, J. Ignacio [0000-0003-1085-2840], De Andrea, Carlos E. [0000-0002-7628-8050], Mendiola, Marta [0000-0002-2463-1304], Peláez-García, Alberto [0000-0002-5401-3216], Hardisson, David [0000-0002-2183-3699], Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), López-Janeiro, Álvaro, Ruz-Caracuel, Ignacio, Ramón-Patino, Jorge L., Ríos, Vivian de los, Villalba Esparza, María, Berjón, Alberto, Kadioglu, Ece, Heredia-Soto, Victoria, Barderas, Rodrigo, Casal, J. Ignacio, De Andrea, Carlos E., Mendiola, Marta, Peláez-García, Alberto, Hardisson, David, UAM. Departamento de Obstetricia y Ginecología, UAM. Departamento de Medicina, and European Regional Development Fund (ERDF/FEDER)

Subjects
Proteomics, 0301 basic medicine, Cancer Research, Programmed cell death, Cell signaling, Myeloid, Medicina, Necroptosis, Cell, pathways, immune microenvironment, necroptosis, Biology, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, proteomics, Endometrial cancer, low grade, medicine, Ferroptosis, Pathways, Innate immune system, Low grade, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ferroptosis, Immune microenvironment, 030104 developmental biology, medicine.anatomical_structure, Oncology, Ferrop-tosis, 030220 oncology & carcinogenesis, endometrial cancer, Cancer research, SLIT/ROBO
Abstract

16 p.-4 fig., Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors, This research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), co-financed by the European Development Regional Fund “A way to achieve Europe” (FEDER).

Published
2021

34. Severe loss of mechanical efficiency in COVID‐19 patients

Author

Elisabet Palomera, Marc Miravitlles, Pilar Ortega, Ramon Boixeda, Joan Carles Yébenes, Koldo Villelabeitia-Jaureguizar, Eulogio Pleguezuelos, Amin Del Carmen, Manuel Vicente Garnacho-Castaño, Eva Moreno, Gemma Llorensi, Paula Casarramona, Lluís Campins, Jessica Carcole, Mateo Serra-Prat, Institut Català de la Salut, [Pleguezuelos E] Physical Medicine and Rehabilitation Department, Hospital de Mataró, Mataró, Spain. Department of Experimental Science and Healthcare, Faculty of Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. [Del Carmen A, Llorensi G, Carcole J, Casarramona P] Physical Medicine and Rehabilitation Department, Hospital de Mataró, Mataró, Spain. [Moreno E] Physical Medicine and Rehabilitation Department, Hospitalet General Hospital, L’Hospitalet de Llobregat, Spain. [Miravitlles MM] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, Male, Diseases of the musculoskeletal system, COVID-19 (Malaltia), SARS‐CoV‐2, Incremental exercise, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Muscular dysfunction, Ischemia, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Orthopedics and Sports Medicine, Respiratory exchange ratio, Lung, Malalties pulmonars obstructives cròniques, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico::técnicas y procedimientos diagnósticos::técnicas diagnósticas respiratorias::pruebas de función respiratoria::prueba de esfuerzo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], COPD, Ischaemic heart disease, VO2 max, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Middle Aged, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES], Respiratory Function Tests, 030220 oncology & carcinogenesis, Breathing, Cardiology, Original Article, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Heart Diseases, 03 medical and health sciences, Oxygen Consumption, Physiology (medical), Internal medicine, medicine, Humans, Chronic obstructive pulmonary diseases, Exercise, Cardiopulmonary exercise test, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], Pulmons - Malalties obstructives, business.industry, SARS-CoV-2, QM1-695, COVID-19, Resistance Training, Original Articles, Proves d'esforç, Diagnosis::Diagnostic Techniques and Procedures::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Respiratory System::Respiratory Function Tests::Exercise Test [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, Intensity (physics), 030104 developmental biology, RC925-935, Human anatomy, Exercise Test, Ventilatory threshold, business
Abstract

MPOC; Disfunció muscular; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV EPOC; Disfunción muscular; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV COPD; Muscular dysfunction; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Background There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). Methods A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. Results A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2, ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2peak and DE and between the peak power output and DE (P < 0.001). Conclusions Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation.

Published
2021

35. Cost of Venous Thromboembolic Disease in Patients with Lung Cancer: Costecat Study

Author

María Yébenes Cortés, Ana Rosa Rubio-Salvador, Vicente Escudero-Vilaplana, Beatriz Bernardez, Manuel Gómez Barrera, María Dolores Alvarado Fernández, José Antonio Marcos Rodríguez, Irene Mangues-Bafalluy, Roberto Collado-Borrell, José Ignacio Chacón López-Muñiz, Miguel Ángel Calleja-Hernández, and Carlos García Collado

Subjects
Male, economic impact, medicine.medical_specialty, Lung Neoplasms, Total cost, Health, Toxicology and Mutagenesis, lcsh:Medicine, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, cost, medicine, Humans, cancer, cardiovascular diseases, Disease management (health), Lung cancer, health care economics and organizations, Average cost, Venous Thrombosis, First episode, thromboembolic disease, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Anticoagulants, Heparin, Low-Molecular-Weight, medicine.disease, LMWH, Spain, Pharmacoeconomic Study, 030220 oncology & carcinogenesis, Emergency medicine, Female, Observational study, business
Abstract

Background: Patients with lung cancer (LC) are at significantly higher risk of developing venous thromboembolism (VTE), which may lead to increased use of health resources and the cost of management. The main aim of the study was to determine the cost of the management of VTE events in patients with LC treated with Low Molecular Weight Heparins (LMWH) in Spain. Methods: Costecat was an, observational, ambispective pharmacoeconomic study. Patients with LC, with a first episode of VTE (symptomatic or incidental) in treatment with LMWH, were recruited from six third-level hospitals and followed up for six months. Sociodemographic, clinical and resource use variables of VTE-related implications and its treatment were collected. Direct healthcare costs and direct non-healthcare costs were recorded. Data collection was documented in an electronic case report. Unit costs were obtained from national databases. Costs (&euro, 2018) were estimated from the healthcare perspective. Statistical analysis was performed using the statistical program R 3.4.3 version (30 November 2017). Results: Forty-seven patients were included. Mean age was 65.4 years, 66.0% were male. The percentage of patients with LC who had metastatic disease was 78.7%. Twenty-three patients (48.9%) needed hospital admissions due to thromboembolic episode. Total average cost of patients with cancer associated VTE (CAT) was &euro, 109,696.6 per patient/semester. The hospitalizations represent 65.8% of total costs (7207.3 &euro, SD 13,996.9 &euro, ), followed by LMWH therapy which represents 18.6% (2033.8 &euro, SD:630.5 &euro, ). Conclusions: Venous thromboembolism episodes induce an economic impact on patients and healthcare systems. Direct healthcare costs are the major burden of the total cost, in which hospitalizations are the main drivers of cost.

Published
2021

36. Validation of a Histologic Scoring Index for C3 Glomerulopathy

Author

Macarena Centeno, Sofía Pérez Gutiérrez, Eduardo Vázquez Martul, Adriana García-Herrera, Dolores López Álvarez, Natalia Allende, M. Luisa Pérez-Ebri, Gema Fernández-Juárez, Helena Marco, Alejandra Gabaldón Domínguez, Alberto Lorenzo, Alexandra Navarro, Gloria Fraga, Francisco Caravaca, Xoana Barros, Cesáreo Corbacho Cuevas, Ana Ávila, Carmen Mon, Lucia González, Hernando Trujillo, Eva Rodríguez, Francisco Díaz Crespo, Consuelo Calvo, Marina Alonso, Angel Sevillano, Ana Saiz, Cristina Meléndez Muñoz, Ángel Panizo Santos, Vanessa Pérez Gómez, Sonia Cruz, Ana Pérez de José, Juliana Draibe, Esther Roselló Sastre, Montserrat Díaz-Encarnación, Rafael Camacho Galán, José Antonio Cortés, Luis Bravo, Belén Ferri Ñíguez, Victoria Oviedo, Fernando Caravaca-Fontán, Juan Mosquera Reboredo, Iara Da Silva, Maria Dolores Sanchez de la Nieta, Javier Lumbreras, Javier Gimeno, Carmen Guerrero Márquez, Rosa Rodríguez, Luis F. Quintana, Carles Saus, Maria Soledad Garcia-Cuerva Calvar, Rocío Cabrera-Pérez, Amir Shabaka, Virginia Cabello, Elena Goicoechea de Jorge, Enrique Morales, F. González, Ana Huerta, Teresa Cavero, Marta Garrido, Inmaculada López, Natalia Ramos, Francisco de la Cerda, Teresa Olea, Rosa Miquel, Nuria Rodríguez-Mendiola, Maria Luisa Illescas, Pablo Cannata Ortiz, Loreto Fernández, Manuel Praga, Eduardo Salido Ruiz, Eduardo Gutiérrez, Maria Eugenia García Fernández, Montserrat Gomà Gallego, Gema Ariceta, Alejando Pascual Martin, Laura Yébenes Gregorio, Marta Melgosa, Yolanda Arce, Instituto de Salud Carlos III, European Commission, Red Española de Investigación Renal, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Caravaca-Fontán, Fernando, Trujillo, Hernando, Alonso, Marina, Díaz-Encarnación, Montserrat M., Cabello, Virginia, Ariceta, Gema, Quintana, Luis F., Barros, Xoana, Ramos, Natalia, Rodríguez-Mendiola, Nuria, Fernández-Juárez, Gema, de la Cerda, Francisco, Pérez de José, Ana, Pérez Gómez, Vanessa, Lumbreras, Javier, Sánchez de la Nieta, María Dolores, Olea, Teresa, Melgosa, Marta, Huerta, Ana, de Lorenzo, Alberto, Draibe, Juliana, González, Fayna, Shabaka, Amir, Goicoechea de Jorge, Elena, Praga, Manuel, Caravaca-Fontán, Fernando [0000-0002-5830-9663], Trujillo, Hernando [0000-0002-3520-1422], Alonso, Marina [0000-0003-1293-1075], Díaz-Encarnación, Montserrat M. [0000-0001-5172-3370], Cabello, Virginia [0000-0002-0877-5498], Ariceta, Gema [0000-0003-1763-1098], Quintana, Luis F. [0000-0001-7582-8476], Barros, Xoana [0000-0001-9690-9769], Ramos, Natalia [0000-0001-9832-326X], Rodríguez-Mendiola, Nuria [0000-0001-6994-7161], Fernández-Juárez, Gema [0000-0001-6641-7763], de la Cerda, Francisco [0000-0002-9983-0359], Pérez de José, Ana [0000-0002-6952-1459], Pérez Gómez, Vanessa [0000-0003-4558-5236], Lumbreras, Javier [0000-0003-1855-0724], Sánchez de la Nieta, María Dolores [0000-0001-8574-0013], Olea, Teresa [0000-0003-2370-1048], Melgosa, Marta [0000-0001-6236-414X], Huerta, Ana [0000-0003-3342-7628], de Lorenzo, Alberto [0000-0001-8847-083X], Draibe, Juliana [0000-0002-2819-8560], González, Fayna [0000-0002-2313-2511], Shabaka, Amir [0000-0001-7039-4701], Goicoechea de Jorge, Elena [0000-0002-4978-2483], and Praga, Manuel [0000-0001-9270-1071]

Subjects
Nephrology, Male, Total activity Score, Intraclass correlation, Dense-deposit disease (DDD), total chronicity score, 030232 urology & nephrology, Kidney biopsy, disease prognosis, Kidney, C3 glomerulonephritis (C3GN), Cohort Studies, 0302 clinical medicine, Glomerulonephritis, Intraclass correlations, Medicine, 030212 general & internal medicine, Renal Insufficiency, Child, intraclass correlations, Proteinuria, Confounding, dense-deposit disease (DDD), Complement C3, Disease prognosis, Middle Aged, Prognosis, kidney survival, Kidney survival, Kidney Tubules, Disease Progression, Female, kidney failure, total activity Score, medicine.symptom, Immunosuppressive Agents, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Adolescent, Glomerulonephritis, Membranoproliferative, Renal function, Kidney failure, histologic index, prognostic tool, Prognostic tool, 03 medical and health sciences, Young Adult, Glomerulopathy, C3 glomerulopathy (C3G), Internal medicine, kidney biopsy, Total chronicity score, Humans, Proportional Hazards Models, Retrospective Studies, business.industry, Proportional hazards model, Reproducibility of Results, Retrospective cohort study, medicine.disease, Fibrosis, Histologic index, Atrophy, business
Abstract

12 p.-4 fig.-4 tab., Rationale & objective: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population., Study design: Multicenter, retrospective cohort study., Setting & participants: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN)., Predictors: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score., Outcome: Time to kidney failure., Analytical approach: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines., Results: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure., Limitations: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding., Conclusions: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure., Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP); EGdeJ is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades" (RYC-2013-13395 and RTI2018-095955-B-100).

Published
2021

37. Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project

Author

Pilar Martínez-Sánchez, Elena Soria, Kamila Janusz, Pau Montesinos, Claudia Sargas, Maria Jose Sayas, María Teresa Gómez-Casares, Estrella Carrillo-Cruz, Yanira Florido-Ortega, Pilar Herrera-Puente, Eva Barragán, Carmen Botella, Lisette Costilla-Barriga, Manuel Yébenes-Ramírez, María José Calasanz, María José Larrayoz, Esther Pérez-Santolalla, Victor Noriega, Raimundo García, Josefina Serrano, Teresa Bernal, Mari Luz Amigo, David Martínez-Cuadrón, Iria Vázquez, Inmaculada Rapado, Esperanza Lavilla-Rubira, Cristina Bilbao, Rosa Ayala, Inmaculada Marchante, Joaquin Sanchez-Garcia, Joaquin Martinez-Lopez, Miguel A. Sanz, María C. Chillón, José Antonio Pérez-Simón, Juan M. Alonso-Domínguez, Juan Bergua, Lorenzo Algarra, Marcos González-Díaz, Ramón García-Sanz, Mar Tormo, and Marta Llop

Subjects
Oncology, medicine.medical_specialty, Remission, Evolution, Concordance, Resistance, Karyotype, MEDLINE, Context (language use), Newly diagnosed, Article, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Disease, business.industry, High-Throughput Nucleotide Sequencing, Myeloid leukemia, Hematology, Clinical routine, Classification, Leukemia, Myeloid, Acute, Mutation, NPM1, business, Mutations, 030215 immunology
Abstract

Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for next-generation sequencing panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse acute myeloid leukemia. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant genes and optimization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized next-generation sequencing analysis and reporting in seven experienced laboratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for acute myeloid leukemia patients of the PETHEMA group.

Published
2021

38. microRNA Fine-Tuning of the Germinal Center Response

Author

Teresa Fuertes, Irene Salgado, Virginia G. de Yébenes, Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Complutense University of Madrid (España), and Ministerio de Educación y Formación Profesional (España)

Subjects
Mini Review, Cellular differentiation, Immunology, Biology, medicine.disease_cause, Autoimmunity, Mice, microRNA, Gene expression, medicine, antibodies, Immunology and Allergy, Animals, Humans, B cell, Regulation of gene expression, B-Lymphocytes, autoimmunity, Germinal center, Cell Differentiation, RC581-607, Germinal Center, Cell biology, neoplasia, MicroRNAs, medicine.anatomical_structure, Gene Expression Regulation, germinal center, biology.protein, Immunologic diseases. Allergy, Antibody
Abstract

Germinal centers (GCs) are complex multicellular structures in which antigen-specific B cells undergo the molecular remodeling that enables the generation of high-affinity antibodies and the differentiation programs that lead to the generation of plasma-antibody-secreting cells and memory B cells. These reactions are tightly controlled by a variety of mechanisms, including the post-transcriptional control of gene expression by microRNAs (miRNAs). Through the development of animal models with B cell-specific modified miRNA expression, we have contributed to the understanding of the role of miRNAs in the regulation of GC responses and in B cell neoplasia. Here, we review recent advances in the understanding of the role of miRNAs in the regulation of B cell and T follicular helper physiology during the GC response and in the diseases associated to GC response dysregulation. Our work is supported by the Spanish Ministerio de Ciencia e Innovación (PID2019-107551RB-I00). TF is supported by a PhD fellowship from the Spanish Ministerio de Ciencia, Innovacion y Universidades (BES-2017-079759), VY by funding from the Universidad Complutense de Madrid, and IS by a student research grant from the Ministerio de Educación y Formación Profesional. Sí

Published
2021

39. Prevalence and Incidence of Uveitis: A Systematic Review and Meta-analysis

Author

M Jesús García de Yébenes, Teresa Otón, Santiago Muñoz-Fernández, and Ángel García-Aparicio

Subjects
medicine.medical_specialty, Epidemiology, Estudios transversales, Population, MEDLINE, Cochrane Library, Uveitis, 03 medical and health sciences, 0302 clinical medicine, medicine, Prevalence, Humans, Epidemiología, 030212 general & internal medicine, education, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Evidence-based medicine, Confidence interval, Uveítis, Ophthalmology, Meta-analysis, 030221 ophthalmology & optometry, Oftalmología, business, Demography
Abstract

Background: Although the impact of uveitis on people's lives is clear, the frequency of this condition is unclear.Objective: To estimate the prevalence and incidence of uveitis. Methods: A systematic review with meta-analysis was conducted. Medline, Embase, and Cochrane Library were searched from inception to January 2019. The quality of the included studies was critically appraised with a grading system based on the Oxford Levels of Evidence. A detailed description of the populations studied and of factors affecting estimates was undertaken. Pooled analyses were conducted using a random-effects approach and expressed as incidence rates per 100,000 with 95% confidence intervals. Subgroup analyses by geographical region were conducted along with meta-regression to analyze possible factors for heterogeneity. Results: A total of 49 studies were included and critically appraised. Twenty-two were population-based, and 27 hospital-based. Heterogeneity was substantial in terms of populations studied, methods for ascertaining uveitis, including definitions, and reporting of results. This was especially important in prevalence studies, with data ranging from 9 to 730 cases per 100,000. For incidence studies, the meta-analysis yielded a pooled incidence of 50.45 per 100.000. The meta-regression showed the geographic region as an important explanatory factor of the heterogeneity between studies. Conclusion: Population-based estimates of the epidemiology of uveitis vary widely, owing to methodologies employed, definitions of uveitis and geographical regions; the representativeness and generalizability of many epidemiological studies of uveitis are limited. Proyecto UveCAM Sociedad de Reumatología de Castilla La Mancha (España) No data JCR 2021 0.776 SJR (2021) Q2, 42/128 Ophthalmology No data IDR 2021 UEM

Published
2021

40. Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

Author

Ignacio Ruz-Caracuel, Patricia Ruiz, Andrés Redondo, Álvaro López-Janeiro, Laura Yébenes, Alejandro Gallego, Victoria Heredia-Soto, Jorge L Ramón-Patino, Alberto Berjón, David Hardisson, Marta Mendiola, Alicia Hernández, Alberto Peláez-García, and UAM. Departamento de Anatomía Patológica

Subjects
Lymphoid Enhancer-Binding Factor 1, Medicina, DNA Mutational Analysis, Risk Assessment, Disease-Free Survival, Pathology and Forensic Medicine, Exon, Endometrial cancer, Risk Factors, Biomarkers, Tumor, medicine, PMS2, Humans, LEF1, CTNNB1 mutation, Molecular Biology, beta Catenin, Aged, Neoplasm Staging, Retrospective Studies, Tissue microarray, business.industry, Endometrioid carcinoma, Microsatellite instability, Exons, Cell Biology, General Medicine, Low grade, Middle Aged, medicine.disease, Prognosis, Immunohistochemistry, Endometrial Neoplasms, MSH6, MSH2, Beta-catenin, Mutation, Mutation (genetic algorithm), Cancer research, Female, Original Article, Neoplasm Grading, Neoplasm Recurrence, Local, business, Carcinoma, Endometrioid
Abstract

Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours, This research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER)

Published
2021

41. One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA)

Author

Marta Rezola, Maria Dolores Diestro, Fernanda Relea, Rosa Guarch, María J Cardiel, Juan Carlos Muruzabal, Beatriz Montero, Ana Calatrava, Pluvio J. Coronado, Margarita Sánchez-Pastor, Ibon Jaunarena, Maria Jose Román, Isabel Guerra, Alberto Berjón, Carlo B Marta, Laia Ribot, Amaia Sagasta, Irmgard Costa, David Hardisson, Irune Ruiz, Jaime Siegrist, Ignacio Zapardiel, María J Boillos, Cristina Zorrero, Luis I Lete, Arantza Lekuona, Alicia Hernández, María Cuadra, Carlos López-de la Manzanara, Fernando Roldan, Alejandro Pascual, Laura Yébenes, Gloria Peiró, and Luis Matute

Subjects
Cancer Research, medicine.medical_specialty, Sentinel lymph node, Ultraestadificación, Gastroenterology, Article, Metastasis, sentinel lymph node, Internal medicine, medicine, OSNA, Stage (cooking), Macrometastasis, cytokeratin 19, Lymph node, RC254-282, business.industry, Cáncer de endometrio, Endometrial cancer, Micrometastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Amplificación de ácidos nucleicos en un solo paso, ultrastaging, Micrometástasis, medicine.anatomical_structure, Oncology, one-step nucleic acid amplification, Ganglio linfático centinela, endometrial cancer, Immunohistochemistry, Citoqueratina 19, business, micrometastases
Abstract

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis., El objetivo de este estudio fue evaluar la eficacia de la amplificación de ácido nucleico en un solo paso (OSNA) para la detección de metástasis en el ganglio linfático centinela (GC) en comparación con la ultraestadificación patológica estándar en pacientes con cáncer de endometrio (CE) en estadio temprano. Se incluyeron en el estudio un total de 526 SLN de 191 pacientes con EC, y 379 SLN (147 pacientes) fueron evaluados por ambos métodos, OSNA y ultraestadificación patológica estándar. La porción central de 1 mm de cada ganglio linfático se sometió a un seccionamiento semiserie a intervalos de 200 μm y se examinó mediante hematoxilina-eosina e inmunohistoquímica con CK19; el tejido restante fue analizado por OSNA para ARNm de CK19. El ensayo OSNA detectó metástasis en el 19,7 % de los pacientes (14,9 % micrometástasis y 4,8 % macrometástasis), mientras que la ultraestadificación patológica detectó metástasis en el 8,8 % de los pacientes (3. 4% micrometástasis y 5,4% macrometástasis). Usando el valor de corte establecido para detectar metástasis SLN por OSNA en EC (250 copias/μL), la sensibilidad del ensayo OSNA fue del 92 %, la especificidad fue del 82 %, la precisión diagnóstica fue del 83 % y el valor predictivo negativo fue del 99 % Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico.

Published
2021

42. Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6/1 mice.

Author

Juan Perucho, Maria José Casarejos, Ana Gómez, Carolina Ruíz, Maria Ángeles Fernández-Estevez, Maria Paz Muñoz, Justo García de Yébenes, and Maria Ángeles Mena

Subjects
Medicine, Science
Abstract

Huntington's disease is a neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene which produces widespread neuronal and glial pathology. We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. These results suggest that CGM should be further explored as a putative neuroprotective agent in Huntington's disease.

Published
2013
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43. Molecular characterization of triple negative breast cancer formaldehyde-fixed paraffin-embedded samples by data-independent acquisition proteomics

Author

Andrea Zapater-Moros, Silvia Garcia-Adrian, Cristina Chiva, Enrique Espinosa, Maria I Lumbreras-Herrera, Guillermo Prado-Vázquez, David Hardisson, Pilar Zamora, Laura Yébenes, Lucía Trilla-Fuertes, Angelo Gámez-Pozo, Elena López-Camacho, Rocío López-Vacas, Eduard Sabidó, and Juan Ángel Fresno Vara

Subjects
Oncology, education.field_of_study, medicine.medical_specialty, business.industry, medicine.medical_treatment, Population, Proteomics, Targeted therapy, Clinical trial, Internal medicine, Proteome, Significance analysis of microarrays, Medicine, Data-independent acquisition, business, education, Triple-negative breast cancer
Abstract

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast carcinomas and it is clinically characterized by an aggressive phenotype and bad prognosis. TNBC does not benefit from any targeted therapy, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of one hundred twenty-five formalin-fixed paraffin-embedded samples from patients diagnosed with triple negative breast cancer were analyzed by mass spectrometry using data-independent acquisition. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were used to characterize molecular groups. Additionally, a predictive signature related with relapse was defined. Two molecular groups with differences in several biological processes as glycolysis, translation and immune response, were defined in this cohort, and a prognostic signature based on the abundance of proteins RBM3 and NIPSNAP1 was defined. This predictor split the population into low-risk and high-risk groups. The differential processes identified between the two molecular groups may serve to design new therapeutic strategies in the future and the prognostic signature could be useful to identify a population at high-risk of relapse that could be directed to clinical trials.

Published
2020
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44. Development of a tool to measure the clinical response to biologic therapy in uncontrolled severe asthma: the FEOS score

Author

Carlos Colás, Loreto Carmona, Eva Martínez-Moragón, M. Yébenes, Borja G. Cosío, Ignacio Dávila, Luis Pérez de Llano, Carlos Almonacid, Javier Domínguez-Ortega, and Juan Luis García-Rivero

Subjects
medicine.medical_specialty, Potentially all pairwise rankings of all possible alternatives, medicine.drug_class, Intraclass correlation, Maintenance dose, business.industry, Severe asthma, Context (language use), Internal medicine, medicine, Corticosteroid, business, Asthma Control Test, Face validity
Abstract

Background: There is a lack of tools to holistically quantify the response to monoclonal antibodies (mAbs) in severe uncontrolled asthma (SUA) patients. The aim of this study was to develop a valid score to assist specialists in this clinical context. Methods: The score was developed in 4 subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis (MCDA) using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) methodology via the 1000Minds software; and (4) face validity assessment of the obtained score. Results: Four core items, with different levels of response for each of them, were selected: “severe exacerbations”, “oral corticosteroid use”, “symptoms” (evaluated by Asthma Control Test: ACT) and “bronchial obstruction” (assessed by FEV1 % theoretical). “Severe exacerbations” and “oral corticosteroid maintenance dose” were weighted most heavily (38% each), followed by “symptoms” (13%) and “FEV1” (11%). Higher scores in the weighted system indicate better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient: 0.86). Conclusions: The FEOS score (FEV1, Exacerbations, Oral corticosteroids, Symptoms) allows clinicians to quantify response in SUA patients who are being treated with mAbs.

Published
2020
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46. A case-control study to assess the role of polyomavirus in transplant complications: Where do we stand?

Author

Julia Garcia Urbán, Antonio Pérez-Martínez, Rafael Hernández Zabala, Carlos Jiménez Martín, Dina Abou Elrous, Gilda Carreño Cornejo, Jesús Frías, Laura Yébenes Gregorio, Carlota Fernández Camblor, David Sánchez, Marta Melgosa Hijosa, Rafael Selgas Gutiérrez, Jaime Monserrat Villatoro, Elena García, María Romero Gómez, Paola C. Brea Rivas, Eugenia García Fernández, Luisa Sisinni, Alejandro Zarauza Santoveña, Mónica Zubimendi Machain, Blanca Vicandi Plaza, María‐Ovidia López Oliva, Alberto M. Borobia, Elena Ramírez, Katia Gurrado, Julio García Rodríguez, Elena Sánchez Zapardiel, Gabriel Ledesma Sánchez, Yasmina Mozo del Castillo, and Eduardo López Granados

Subjects
Adult, Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, Graft vs Host Disease, Viremia, Disease, Hematopoietic stem cell transplantation, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Child, Retrospective Studies, Transplantation, Polyomavirus Infections, business.industry, Case-control study, Hematopoietic Stem Cell Transplantation, virus diseases, Retrospective cohort study, Immunosuppression, Odds ratio, medicine.disease, Kidney Transplantation, Tumor Virus Infections, Infectious Diseases, Immunosuppressive drug, BK Virus, Case-Control Studies, 030211 gastroenterology & hepatology, business
Abstract

PURPOSE The study's aim was to assess whether polyomavirus DNAemia screening was associated with different outcomes in patients with positive viremia compared with negative viremia. METHODS Case-control retrospective study of patients with polyomavirus DNAemia (viremia > 1000 copies/mL) matched 1:1 with controls. Control group consists of the patient who received a transplant immediately before or after each identified case and did have nil viremia. FINDING Ultimately, 120 cases of BK polyomavirus (BKPyV) were detected and matched with 130 controls. Of these, 54 were adult kidney transplant recipients (KTRs), 43 were pediatric KTRs, and 23 were undergoing hemato-oncologic therapy, of which 20 were undergoing hematopoietic stem cell transplantation. The odds ratio (OR) for overall risk of poorer outcomes in cases versus controls was 16.07 (95% CI: 5.55-46.54). The unfavorable outcome of switching the immunosuppressive drug (ISD) (14/40,35%) was no different from that of those treated with reduced ISD doses (31/71, 43.6%, P = .250). Acute rejection or graft-versus-host disease, previous transplant, and intensity of immunosuppression (4 ISDs plus induction or conditioning) were risk factors for BKPyV-DNAemia (OR: 13.96, 95% CI: 11.25-15.18, P

Published
2020

47. Anxiety, Depression, and Asthma Control: Changes After Standardized Treatment

Author

L. Fernandez Pellon, E. Macias Fernandez, Manuel J Rial, E. Morchon Miguel, V. Vilella Tomás, P. Marin Martinez, V. De Luque Piñana, V. García Paz, M. Morales Villarejo, J. Ruiz Hornillos, J. Herrero Jarque, J. Florido Lopez, J. Beitia Mazuecos, M. Rojas Vilchez, J. Medina Gallardo, J. Valldeperas Combas, A. Pallarés Sanmartín, I. García Núñez, J. Castro Landin, R. Diaz Campos, G. Gala Ortiz, M. Mena Rodriguez, O. Villarreal Balza De Vallejo, Vicente Plaza, E. Pinto Nogues, A. Suárez Rodríguez, P. Sánchez López, S. Díaz Angulo, F. Sola Martinez, M. Moscardó Orenes, M. Alvariño Martin, R. Tejedor Romera, J. Orta Cuevas, Z. Vasquez Gambasica, B. García Figueroa, A. Letran Camacho, M. Modesto Alapont, M. Cervera Del Pino, P. Benito Martinez, S. Varela Losada, F. Carballada Gonzalez, Irina Bobolea, M. Díaz Palacios, Y. Anta Mejias, D. González De Olano, J. Martos Velasco, P. Prieto Montaño, A. Sanchez Alonso, M. Martínez Ceres, J. Donado Uña, Ò. Sotorra Elias, B. Alcázar Navarrete, A. Arnedillo Muñoz, J. Alcazar Ramirez, J. Jiménez López, M. Alvarez Puebla, M. Antón Girones, J. Compaired Villa, P. Mata Calderon, M. Escribano Rodriguez, C. Morales García, I. Molero Sancho, M. De Las Marinas Alvarez, T. Bazus Gonzalez, M. Soria Esojo, A. Vega Castro, A. Moreno Fernandez, G. Jorro Martínez, E. Ortega Sáenz De Tejada, A. Regueiro Moreira, M. Garcimartin Galicia, A. Alonso Gomez, R. Rodriguez Martinez, J. Liñana Santafé, I. Ansotegui Zubeldia, R. Lama Martinez, A. Saura Vinuesa, N. Segura Arazuri, M. Torrecillas Toro, M. Climent Gregori, M. Herrerias Peña, T. Peña Miguel, C. Vila Albelda, C. Diaz Donado, M. Hernandez, A. Losada Peña, M. Gandolfo Cano, J. Montoro Lacomba, J. Quiralte Enriquez, R. Rodríguez Pacheco, M. Arroyo Cozar, P. Rubinstein Aguñin, M. Blanco Aparicio, F. Alvarez Gutierrez, C. Merinas Lopez, R. Mayorgas Costoya, M. Franco Campos, J. Garcia De Pedro, V. Moreno Garcia, J. De Frutos Arribas, J. Alvarez Fernandez, A. Robles Iniesta, M. Do Muíño Joga, A. Bueso Fernandez, P. Serrano Dominguez, M. Jimenez Lara, P. Losada Llorente, C. Colás Sanz, I. Raducan, B. Requejo Mañana, M. Mota Godoy, M. Martos Calahorro, F. Ortiz Portal, J. Zapata Yébenes, F. Nicolau Pastrie, C. Rabade Castedo, M. Salvador Segarra, F. Callejas González, M. Chacon Patiño, G. González Álvarez, J. Olaguibel Rivera, P. Gonzalez Delgado, B. Orosa Bertol, E. De Santiago Delgado, J. Cumplido Bonny, R. Nuñez Orjales, Antonio Fernandez-Sanchez, B. Añíbarro Bausela, D. Ferrer Pargada, S. Niño Bernal, A. Cobas Paz, B. Huertas Barbudo, J. Ciruelos Ayuso, M. Lara Jiménez, D. Gutierrez Fernandez, G. Castaño De Las Pozas, Y. García Villamuza, F. Sánchez-Toril López, E. Naval Sendra, C. Andreu Balaguer, M. Rico Diaz, L. Navarro Seisdedos, D. El-Qutob López, J. Ruiz Cubillan, Miguel Ibáñez Rodríguez, L. Fontan Garcia-Boente, M. Rivera Ortun, A. Padilla Galo, M. Muñoz Pamplona, I. Perez Sampedro, F. Garcia Gonzalez, E. Gómez Nieves, S. Aparicio Español, Astrid Crespo, A. Lloris Bayo, R. Lleonart Bellfill, E. Burches Baixauli, R. Andujar Espinosa, I. Picans, F. Linde De Luna, A. Tabar Purroy, L. Valverde Vazquez, R. Blanco Gonzalez, M. Ballester Canelles, P. Barranco Sanz, F. Ruano Perez, A. Romero Ortiz, S. Jimenez Timon, G. De Luiz Martínez, C. Baeza Martinez, G. Bernaola Hortigüela, J. Chamorro Mohedad, M. Garcés Sotillos, R. Moreno Borque, M. Moro, I. Ali García, S. Lizarza Mendizabal, J. Almagro Lopez, C. Perez Carral, J. Cegoñino De Sus, M. Reche Frutos, R. González Perez, M. Domínguez Fuentes, L. Cassini Gomez De Cadiz, A. Feliu Vila, M. Dordal Culla, M. Corbacho Abelaira, Y. Puente Crespo, D. Romero Ribate, J. Rozadilla Sacanell, J. Lopez Caballero, A. Velez Ruiz De Lobera, A. Montoro De Francisco, M. Ramirez Prieto, N. Marina Malanda, J. Juanola Pla, M. Millan Gonzalez, N. Subira Farre, P. Cordero Rodriguez, F. Gonzalez Barcala, S. Herrera Lara, M. Peña Arellano, J. Igea Aznar, R. Alvarez Sintes, E. Martinez Moragon, J. Greses Giner, M. Martínez Riaza, G. Mediero Carrasco, P. Catalán Serra, M. Rodriguez Hernandez, S. Porcel Carreño, Joaquín Sastre, A. Ruiz San Francisco, R. Bernabeu Mora, M. Alwakil Olbah, H. Izaguirre Flores, J. Subiza Garrido-Lestache, B. Labeguerie Arenaza, B. Presedo Garazo, S. Cimbollek, A. Fuster Gomila, G. Minguez Martin, M. Martín Pérez, S. Garrido Fernández, F. Iglesias Rio, A. Veres Racamonde, B. Rodriguez Jimenez, F. Muñoz Bellido, A. Moral De Gregorio, A. López Viña, J. Marin Torrado, I. Flores Martín, M. Avilés Inglés, A. Lahuerta Castro, and P. Galindo Bonilla

Subjects
Adult, Male, Spirometry, medicine.medical_specialty, Vital capacity, Anxiety, Hospital Anxiety and Depression Scale, Severity of Illness Index, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Forced Expiratory Volume, Internal medicine, Health care, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, Depression (differential diagnoses), Asthma, medicine.diagnostic_test, Depression, business.industry, Middle Aged, medicine.disease, respiratory tract diseases, 030228 respiratory system, Female, medicine.symptom, business
Abstract

Background It has been documented that anxiety and depression are prevalent in patients with asthma and are associated with greater frequency of exacerbations, increased use of health care resources, and poor asthma control. Objective To examine the association of asthma diagnosis with symptoms of depression/anxiety and asthma control not only at baseline but also over a 6-month period of specialist supervision. Methods We enrolled 3182 patients with moderate to severe asthma. All were evaluated with spirometry, the Asthma Control Test, and the Hospital Anxiety and Depression Scale at baseline and at 6 months. Treatments were decided by specialists according to published guidelines. Results At baseline, 24.2% and 12% of the patients were diagnosed with anxiety and depression, respectively, according to the Hospital Anxiety and Depression Scale. After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of patients, respectively (P Conclusion Under standardized asthma care and after a specific visit with the specialist, patients present significant improvement in these psychological disorders and exhibit better asthma control and functional parameters.

Published
2018
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48. Total Body Water and Intracellular Water Relationships with Muscle Strength, Frailty and Functional Performance in an Elderly Population. A Cross-Sectional Study

Author

Joan Carles Yébenes, Mateu Serra-Prat, Isabel Lorenzo, Elisabet Palomera, and S. Ramírez

Subjects
0303 health sciences, medicine.medical_specialty, Nutrition and Dietetics, 030309 nutrition & dietetics, business.industry, Body water, Medicine (miscellaneous), Muscle mass, 03 medical and health sciences, 0302 clinical medicine, Ageing, Internal medicine, Lean body mass, Cardiology, Muscle strength, Medicine, Myocyte, 030212 general & internal medicine, Geriatrics and Gerontology, business, human activities, Body mass index, Bioelectrical impedance analysis
Abstract

As a person ages, total body water (TBW), intracellular water (ICW), muscle mass and muscle strength tend to decline. The decline in ICW may reflect losses in the number of muscle cells but may also be responsible for less hydrated muscle cells. To assess whether TBW and ICW are associated with muscle strength, functional performance and frailty in an aged population, independently of muscle mass. An observational cross-sectional study of community-dwelling individuals aged 75 years and older. TBW, ICW, fat mass, lean mass and muscle mass were assessed by bioelectrical impedance analysis, frailty status was measured according to Fried criteria, handgrip strength was measured using the hand-held JAMAR dynamometer, and functional performance was measured according to the Barthel index and gait speed. A total of 324 subjects were recruited (mean age 80.1 years, 47.5% women). TBW and ICW were closely correlated with muscle mass in both sexes. ICW was also associated with Barthel score, gait speed and frailty in both sexes and with handgrip in men. Considerable variability in ICW was observed for the same muscle mass. Multivariate analysis showed a positive effect of ICW on handgrip, functional performance and gait speed and a protective effect of ICW on frailty, independently of age, sex, body mass index and number of comorbidities. In elderly individuals with similar muscle mass, those with higher ICW had a better functional performance and a lower frailty risk, suggesting a protective effect of cell hydration, independently of muscle mass.

Published
2018
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49. PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases

Author

Agustí Toll, Evelyn Andrades, Ramon M. Pujol, Vicenç García-Patos, Eugenia Hernández-Ruiz, Mireia Yébenes, Javier Gimeno, Carla Ferrándiz-Pulido, Irene García-Díez, and Inmaculada Hernández-Muñoz

Subjects
Male, Poor prognosis, Skin Neoplasms, Biopsy, Cell, Tumor cells, Dermatology, CD8-Positive T-Lymphocytes, B7-H1 Antigen, Pathology and Forensic Medicine, Programmed cell death ligand 1, 030207 dermatology & venereal diseases, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Immune system, Risk Factors, PD-L1, Biomarkers, Tumor, Humans, Medicine, Neoplasm Invasiveness, Aged, Retrospective Studies, Aged, 80 and over, Chi-Square Distribution, biology, business.industry, Cancer, Cell Differentiation, General Medicine, medicine.disease, Immunohistochemistry, Up-Regulation, Logistic Models, medicine.anatomical_structure, Spain, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Multivariate Analysis, Carcinoma, Squamous Cell, biology.protein, Cancer research, Female, Pd l1 expression, business
Abstract

Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell-mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1-positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (P0.05), along with the following features: recurrence, poor differentiation, and perineural invasion. Ninety percent of the metastases of PD-L1-positive tumors were also positive for PD-L1, displaying a trend toward a higher PD-L1 expression when compared with their primary tumors (P = 0.058). No significant differences in the peritumoral inflammatory infiltrate or in the expression of CD8 were found between metastasizing and nonmetastasizing primary tumors. Our results suggest that PD-L1 may play a relevant role in metastatic spread and may be a candidate prognostic biomarker in cSCC.

Published
2018
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50. Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes

Author

Ana Ramírez de Molina, Jaime Feliu, R. Crespo, Jorge Barriuso, Beatriz Castelo, Alberto Berjón, Alicia Hernández, Andrés Redondo, Alberto Peláez-García, David Hardisson, Jesús Herranz, Patricia Cruz, Marta Mendiola, María Miguel-Martín, Victoria Heredia-Soto, and Laura Yébenes

Subjects
0301 basic medicine, Oncology, Cancer Research, Angiogenesis, Kaplan-Meier Estimate, Carboplatin, chemistry.chemical_compound, Risk Factors, Ovarian carcinoma, Antineoplastic Combined Chemotherapy Protocols, Angiogenic Proteins, Precision Medicine, Aged, 80 and over, Ovarian Neoplasms, Neovascularization, Pathologic, Cytoreduction Surgical Procedures, General Medicine, Middle Aged, Serous fluid, Area Under Curve, Biomarker (medicine), Female, Adult, medicine.medical_specialty, Paclitaxel, Clinical Decision-Making, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Humans, Survival analysis, Aged, Proportional Hazards Models, business.industry, Gene Expression Profiling, Patient Selection, medicine.disease, Erythropoietin receptor, 030104 developmental biology, ROC Curve, chemistry, Multivariate Analysis, Neoplasm Grading, Neoplasms, Cystic, Mucinous, and Serous, Transcriptome, Ovarian cancer, business
Abstract

Background/aim Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. Materials and methods Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. Results Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. Conclusion An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.

Published
2018
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