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1. A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Author

Imogen J. Swift, Rosa Rademakers, NiCole Finch, Matt Baker, Roberta Ghidoni, Luisa Benussi, Giuliano Binetti, Giacomina Rossi, Matthis Synofzik, Carlo Wilke, David Mengel, Caroline Graff, Leonel T. Takada, Raquel Sánchez-Valle, Anna Antonell, Daniela Galimberti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Stefanie Schreiber, Stefan Vielhaber, Philipp Arndt, Isabel Santana, Maria Rosario Almeida, Fermín Moreno, Myriam Barandiaran, Alazne Gabilondo, Johannes Stubert, Estrella Gómez-Tortosa, Pablo Agüero, M. José Sainz, Tomohito Gohda, Maki Murakoshi, Nozomu Kamei, Sarah Kittel-Schneider, Andreas Reif, Johannes Weigl, Jinlong Jian, Chuanju Liu, Ginette Serrero, Thomas Greither, Gerit Theil, Ebba Lohmann, Stefano Gazzina, Silvia Bagnoli, Giovanni Coppola, Amalia Bruni, Mirja Quante, Wieland Kiess, Andreas Hiemisch, Anne Jurkutat, Matthew S. Block, Aaron M. Carlson, Geir Bråthen, Sigrid Botne Sando, Gøril Rolfseng Grøntvedt, Camilla Lauridsen, Amanda Heslegrave, Carolin Heller, Emily Abel, Alba Gómez-Núñez, Roger Puey, Andrea Arighi, Enmanuela Rotondo, Lize C. Jiskoot, Lieke H. H. Meeter, João Durães, Marisa Lima, Miguel Tábuas-Pereira, João Lemos, Bradley Boeve, Ronald C. Petersen, Dennis W. Dickson, Neill R. Graff-Radford, Isabelle LeBer, Leila Sellami, Foudil Lamari, Fabienne Clot, Barbara Borroni, Valentina Cantoni, Jasmine Rivolta, Alberto Lleó, Juan Fortea, Daniel Alcolea, Ignacio Illán-Gala, Lucie Andres-Cerezo, Philip Van Damme, Jordi Clarimon, Petra Steinacker, Emily Feneberg, Markus Otto, Emma L. van der Ende, John C. van Swieten, Harro Seelaar, Henrik Zetterberg, Aitana Sogorb-Esteve, and Jonathan D. Rohrer

Subjects
Frontotemporal dementia, Progranulin, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

Published
2024
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2. Numerical evaluation of Hybrid Deck Bulb Tee (HDBT) as a solution to improve durability of single-span bridges

Author

Pablo Agüero-Barrantes and Alexandra Hain

Subjects
ultra-high-performance concrete, bridge rehabilitation, composite elements, precast beam, superstructure replacement, Decked Bulb Tee, Engineering (General). Civil engineering (General), TA1-2040, City planning, HT165.5-169.9
Abstract

To address the shortcomings of traditional prestressed concrete girders, a new hybrid beam element, the Hybrid Deck Bulb Tee (HDBT) is proposed. The HDBT utilizes staged fabrication. First, the bottom flange is cast with Ultra-high Performance Concrete (UHPC) and prestressed prior to casting the web and top flange with High-Performance Concrete (HPC). The purpose of this study is to analytically evaluate the structural performance of HDBT beams for bridge structures. Multiple HDBT bridges were designed following the state-of-the-art criteria in regard to UHPC bridge design. The performance was evaluated using the following criteria: 1) the deflections under live load and dead load, 2) design checks for temporary stresses before losses, 3) stresses at serviceability limit states after losses, and 4) demand-to-capacity ratios under the American Association of State Highway and Transportation Officials (AASHTO) Strength I load combination. To obtain more refined results for the serviceability limit state, the bridges were modeled using a commercial finite element software. The model captured the time dependent material properties such as strength gain, creep, and shrinkage, as well as the stages of fabrication. The analysis demonstrates that the innovative design and fabrication processes of HDBTs are capable of resolving the current limitations of prestressed concrete elements.

Published
2024
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3. Structural Performance of Porcelain Insulators in Overhead Railway Power Systems: Experimental Evaluations and Findings

Author

Pablo Agüero-Barrantes and Alexandra Hain

Subjects
ceramic insulators, insulator testing, power distribution lines, porcelain insulators, assembly, rail transportation power systems, Technology
Abstract

This paper addresses the critical knowledge gap in the structural performance of porcelain insulators in overhead railway power systems through experimental evaluations. The focus is on porcelain insulators as part of a contact wire registration assembly (CWRA) in the railway power system. While porcelain insulators are the most widely used high-voltage insulator material, no previous studies have investigated the impact of age on their ultimate load capacity in overhead rail systems. The paper presents the experimental design for tension and a novel 45-degree test setup that replicates field conditions, as well as an overview of the test specimens, which were both new and retired from the field. The results indicate that aging has no impact on the strength of insulators in direct tension tests, but retired insulators in the CWRA show a reduced capacity. Additionally, the location of the drop bracket has a notable influence on the failure mode and stiffness of the assembly. The findings contribute to future improvements in system design and performance. Future research should include material testing, finite element studies, and dynamic testing of the full CWRA setup to further understand insulator performance and support resilient power transmission and distribution systems. Additionally, similar tests should be conducted on polymeric insulators, due to their prevalence.

Published
2024
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4. ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels

Author

Pablo Agüero-Rabes, Julián Pérez-Pérez, Lucía Cremades-Jimeno, María-Salud García-Ayllón, Adriana Gea-González, María José Sainz, Ignacio Mahillo-Fernández, Raquel Téllez, Blanca Cárdaba, Javier Sáez-Valero, and Estrella Gómez-Tortosa

Subjects
Alzheimer’s disease, ADAM10, α-secretase, disintegrin metalloproteinase 10 protein, genetics, CSF biomarkers, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3′UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.

Published
2023
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5. α-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer’s disease

Author

Pablo Agüero, María José Sainz, María-Salud García-Ayllón, Javier Sáez-Valero, Raquel Téllez, Rosa Guerrero-López, Julián Pérez-Pérez, Adriano Jiménez-Escrig, and Estrella Gómez-Tortosa

Subjects
ADAM10, α-Secretase, Familial Alzheimer’s disease, Genetics, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive. Methods Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPβ peptides. We evaluate variant’s pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort. Results The mutation was absent from public databases and segregated with the disease. CSF Aβ42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPβ levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPβ levels resembled those of controls. Therefore, a decreased sAPPα/sAPPβ ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened. Conclusions This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers.

Published
2020
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6. Pesaje de vehículos en movimiento en puentes de un claro con número limitado de sensores

Author

Pablo Agüero Barrantes, Sergio Lobo Aguilar, and Richard E Christenson

Subjects
Pesaje en Movimiento con puentes (BWIM), puentes, deformaciones unitarias, Deformaciones Unitarias de Corte, Gestión, Peso Bruto Vehicular, Building construction, TH1-9745
Abstract

En las economías emergentes, la implementación de la Gestión de Infraestructura del Transporte es una necesidad imperante. Con el propósito de utilizar de la forma más eficiente posible los limitados recursos disponibles, la tecnología surge como un aliado estratégico en dicho objetivo. Con el fin de preservar los pavimentos y puentes, diferentes metodologías han sido desarrolladas para la detección de vehículos con sobrepeso. En el presente artículo se presenta la implementación y validación del pesaje de vehículos en movimiento mediante la instrumentación de un puente en servicio ubicado en Costa Rica, con una cantidad reducida de sensores. Se utilizó el enfoque basado en áreas de influencia de ondas de respuesta de deformaciones unitarias. Dada la distribución de los sensores, minimizando los requisitos de instrumentación, se utilizaron dos tipos de deformación unitaria: horizontal y cortante. Dos camiones de calibración fueron utilizados como referencia y luego se procedió a estimar el peso del tráfico aleatorio, para confrontar dichos resultados con los datos de la estación de pesaje estática más cercana.

Published
2021
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7. Quality of Chronic Anticoagulation Control in Patients with Intracranial Haemorrhage due to Vitamin K Antagonists

Author

Carlos Estevez-Fraga, Maria Molina-Sanchez, Rodrigo Alvarez-Velasco, Pablo Agüero-Rabes, Leticia Crespo-Araico, Elena Viedma-Guiard, Antonio Cruz-Culebras, Consuelo Matute, Rocio Vera, Alicia De Felipe-Mimbrera, and Jaime Masjuan Vallejo

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Introduction. Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. Materials and Methods. We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. Results and Discussion. The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). Conclusion. VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required.

Published
2018
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10. CSF Alzheimer’s biomarkers in clinical practice

Author

Pablo Agüero, Agustín Querejeta, María José Sainz, Raquel Téllez, and Estrella Gómez‐Tortosa

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022

11. TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism

Author

Estrella, Gómez-Tortosa, Yalda, Baradaran-Heravi, Lubina, Dillen, Nila Roy, Choudhury, Pablo, Agüero Rabes, Julián, Pérez-Pérez, Cemile, Kocoglu, M José, Sainz, Alicia, Ruiz González, Raquel, Téllez, Lucía, Cremades-Jimeno, Blanca, Cárdaba, Christine, Van Broeckhoven, Gracjan, Michlewski, and Julie, van der Zee

Abstract

Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies.We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate.Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism.This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases.A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.

Published
2022

12. WhatsApp Consultations in the Department of Electrophysiology of a Public Hospital of the City of Buenos Aires in Times of COVID-19

Author

Enrique Dominé, Mario Fitz Maurice, Pablo Agüero, Fernando Di Tommasso, Alfredo Hirschon Prado, Paula Sastre, and Adrian Baranchuk

Subjects
Gynecology, medicine.medical_specialty, 020205 medical informatics, Coronavirus disease 2019 (COVID-19), business.industry, Public hospital, 0202 electrical engineering, electronic engineering, information engineering, Medicine, 02 engineering and technology, business, Telephone consultation
Abstract

espanolIntroduccion: La pandemia por coronavirus (COVID-19) es altamente contagiosa. La telemedicina emerge como una opcionpara mantener a nuestros pacientes dentro del sistema sanitario.Objetivo: Implementar consultas por WhatsApp durante 30 dias en un hospital de la Ciudad Autonoma de Buenos Aires(CABA) durante la cuarentena impuesta por COVID-19.Material y metodos: Se analizaron consultas por WhatsApp durante 30 dias consecutivos. Se envio un formulario antes dela consulta telefonica con el especialista. Se realizo un analisis descriptivo de las consultas y los planes propuestos para elseguimiento.Resultados: Se realizaron 263 consultas en 205 pacientes. La cantidad promedio de consultas telefonicas fue de 7,8 mensajes.Las consultas mas frecuentes fueron: palpitaciones (12%) y vacunacion antigripal (11,7%). El seguimiento quedo dividido engrupos: 1) Resueltos via WhatsApp: 154 pacientes; 2) Derivados a un hospital zonal: 25; 3) Derivados a nuestro hospital: 26pacientes.Conclusion: La telemedicina via WhatsApp es factible de ser desarrollada en un hospital publico de la CABA, con una sustancialreduccion de consultas presenciales. EnglishBackground: Coronavirus (COVID-19) pandemic is highly infectious. Telemedicine emerges as an option to keep patients within thehealthcare system.Objective: The aim of this study was to implement WhatsApp consultations during 30 days in a hospital of the City of Buenos Aires(CABA) during the lockdown imposed due to COVID-19.Methods: Consultations via WhatsApp were analyzed for 30 consecutive days. A form was sent prior to telephone consultation withthe specialist. A descriptive analysis of consultations and proposed follow-up plans was carried out.Results: A total of 263 consultations were performed in 205 patients. The average number of telephone consultations was 7.8 messages.The most common topics for consultation were palpitations (12%) and influenza vaccine (11.7%). Follow-up was divided intogroups: 1) Solved via WhatsApp: 154 patients; 2) Referred to a local hospital: 25; 3) Referred to our hospital: 26 patients.Conclusion: Telemedicine via WhatsApp can be developed in public hospitals of CABA, with a substantial reduction of in-personconsultations.

Published
2020

15. TRIM25 mutation (p.C168*), coding for an E3 ubiquitin ligase, is a cause of early-onset autosomal dominant dementia with amyloid load and parkinsonism

Author

Gomez-Tortosa, Estrella, Baradaran-Heravi, Yalda, Dillen, Lubina, Roy Choudhury, Nila, Rabes, Pablo Agüero, Pérez-Pérez, Julián, Kocoglu, Cemile, José Sainz, M., González, Alicia Ruiz, Téllez, Raquel, Cremades-Jimeno, Lucía, Cárdaba, Blanca, Broeckhoven, Christine Van, Michlewski, Gracjan, van der Zee, Julie, and EU EOD Consortium

Subjects
E3 ubiquitin ligase, early-onset autosomal dominant dementia, family-based whole-exome sequencing study, TRIM25, Human medicine, Alzheimer’s disease
Abstract

IntroductionPatients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies. MethodsWe present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate. ResultsAge at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism. DiscussionThis study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. HighlightsA TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease.TRIM25 protein studies support that the mutation exerts its effect through loss of function.TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration.The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.

Published
2022

16. CSF Biomarkers profile in siblings with Alzheimer’s disease carrying the ADAM10 nonsense mutation p.Tyr167*

Author

Adriano Jimenez-Escrig, María José Sainz, María-Salud García-Ayllón, Juilán Pérez Pérez, Javier Sáez-Valero, Estrella Gómez-Tortosa, Pablo Agüero, Rosa Guerrero-López, and Raquel Téllez

Subjects
Epidemiology, business.industry, Health Policy, ADAM10, Nonsense mutation, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, Csf biomarkers, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2020

17. Leuko-platelet index predicts thrombotic events in patients with acute coronary syndrome

Author

Pablo Agüero, Juan J. Badimon, Camilo A. Pulmari, Hernán Cohen Arazi, Virginia Barba, Daniel Chirino, Juan Pablo Costabel, and Alfredo Hirschson Prado

Subjects
Blood Platelets, Male, Acute coronary syndrome, medicine.medical_specialty, Hospitalized patients, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Risk of mortality, Medicine, Humans, Platelet, In patient, 030212 general & internal medicine, Angina, Unstable, Acute Coronary Syndrome, Aged, Aged, 80 and over, Heart Failure, business.industry, Unstable angina, Thrombosis, Middle Aged, medicine.disease, Prognosis, Predictive value, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

To evaluate the predictive value of a bedside index in hospitalized patients with acute coronary syndromes (ACS).We studied the association of leuko-platelet index (LPI: platelet count * leukocyte count/10In the derivation cohort we included 1100 patients with non STEM-ACS, GRACE score of 133 ± 52, Crusade score 24,3 ± 14, 66% male, 65 + 11 years. LPI was 17 (12-24). LPI was higher (19 (13-25)) in patients with MI than in patients with unstable angina (16 (12-22) in (p 0.001)). A total of 115 patients (10.5%) had the CEP. CEP was associated to LPI (OR 1.04 (1.002-1.08), p = 0.03), age (OR 1.01 (0.97-1.05), p = 0.62) and GRACE140 (OR 8.1 (2.2-29), p = 0.02). LPI (OR 1.04 (1.004-1.07) p = 0.03) and GRACE score (OR 1.02 (1.01-1.03) p 0.01) were associated to cardiovascular mortality. We confirmed these results in the validation cohort #1 (686 patients, 61 + 11 years old, 47% nonST-ACS, 53% ST-ACS, 21% had CEP) and in validation cohort #2 (218 patients, 56.8% males, 73 + 7 years old, 79% nonST-ACS, GRACE score 136 + 30) and 8.3% with CEP. We used the cutoff points of LPI obtained in the derivation cohort (24).LPI 24 was associated to CEP (OR (1.7-5.2), p 0.01), independently of age (OR 1 (0.98-1.02), p = 0.8), and GRACE score (OR 1.01 (0.99-1.01), p 0.69), and It was associated to antiplatelet resistance (OR 1.03 (95% CI 1.00-1.06) p = 0.05).

Published
2020

18. α-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer’s disease

Author

Estrella Gómez-Tortosa, Pablo Agüero, Adriano Jimenez-Escrig, Javier Sáez-Valero, María José Sainz, María-Salud García-Ayllón, Rosa Guerrero-López, Julián Pérez-Pérez, Raquel Téllez, Ministerio de Economía y Competitividad (España), Generalitat Valenciana, Instituto de Salud Carlos III, and European Commission

Subjects
0301 basic medicine, medicine.medical_specialty, Cognitive Neuroscience, media_common.quotation_subject, ADAM10, Nonsense mutation, Nonsense, Mutant, Biology, medicine.disease_cause, lcsh:RC346-429, Familial Alzheimer’s disease, lcsh:RC321-571, 03 medical and health sciences, ADAM10 Protein, Amyloid beta-Protein Precursor, 0302 clinical medicine, Alzheimer Disease, Internal medicine, Genetic model, medicine, Genetics, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, media_common, Mutation, Amyloid beta-Peptides, Research, Membrane Proteins, α-Secretase, Peptide Fragments, 030104 developmental biology, Endocrinology, a-Secretase, Neurology, Codon, Nonsense, Biomarker (medicine), Neurology (clinical), Amyloid Precursor Protein Secretases, Haploinsufficiency, 030217 neurology & neurosurgery, Biomarkers
Abstract

[Background]: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive., [Methods]: Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPβ peptides. We evaluate variant’s pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort., [Results]: The mutation was absent from public databases and segregated with the disease. CSF Aβ42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPβ levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPβ levels resembled those of controls. Therefore, a decreased sAPPα/sAPPβ ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened., [Conclusions]: This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers., This work was supported by grants from the Ministry of Sciences and Technology, (SAF2010-18277), Instituto de Salud Carlos III (FIS14/00099), Direcció General d’Universitat, Investigació i Ciència, GVA (AICO/2018/090), and FEDER funds, Spain. MSGA is supported by a Miguel Servet II Grant from Instituto de Salud Carlos III (CPII16/00011).

Published
2020

19. Mirada al IV° taller: Cine, género y política

Author

Jayro Bustamante, Marion Gautreau, Alexis Yannopoulos, and Pablo Agüero

Subjects
Visual Arts and Performing Arts, nuevo cine argentino, Toulouse, Agüero (Pablo), Bustamante (Jayro), Perón (Eva), nouveau cinéma argentin, Ixcanul, péronisme, peronismo, cine guatemalteco, cinéma guatémaltèque, condition féminine, condición femenina
Abstract

Durante el taller “Cine, género y política” de 2016, organizado en colaboración con Cinélatino y la Universidad de Toulouse Jean Jaurès, dos directores charlan frente al público: Jayro Bustamante sobre su película Ixcanul, y Pablo Agüero sobre Eva no duerme. Presentamos en este artículo fragmentos significativos de estos dos talleres. Lors de l’atelier “Cinéma, genre et politique” de 2016 organisé en collaboration entre Cinélatino et l’Université Toulouse Jean Jaurès, deux réalisateurs ont mené une discussion ouverte au public : Jayro Bustamante sur son film Ixcanul, et Pablo Agüero pour Eva no duerme. Des extraits représentatifs de ces deux ateliers sont présentés dans cet article.

Published
2017

20. Retour sur le IVe atelier : Cinéma, genre et politique

Author

Alexis Yannopoulos, Marion Gautreau, Jayro Bustamante, and Pablo Agüero

Subjects
Visual Arts and Performing Arts, nuevo cine argentino, Toulouse, Agüero (Pablo), Bustamante (Jayro), Perón (Eva), nouveau cinéma argentin, Ixcanul, péronisme, peronismo, cine guatemalteco, cinéma guatémaltèque, condition féminine, condición femenina
Abstract

Lors de l’atelier “Cinéma, genre et politique” de 2016 organisé en collaboration entre Cinélatino et l’Université Toulouse Jean Jaurès, deux réalisateurs ont mené une discussion ouverte au public : Jayro Bustamante sur son film Ixcanul, et Pablo Agüero pour Eva no duerme. Des extraits représentatifs de ces deux ateliers sont présentés dans cet article. Durante el taller “Cine, género y política” de 2016, organizado en colaboración con Cinélatino y la Universidad de Toulouse Jean Jaurès, dos directores charlan frente al público: Jayro Bustamante sobre su película Ixcanul, y Pablo Agüero sobre Eva no duerme. Presentamos en este artículo fragmentos significativos de estos dos talleres.

Published
2019

21. Extraits du scénario : Eva no duerme

Author

Pablo Agüero

Subjects
Visual Arts and Performing Arts
Abstract

Eva no duerme (Eva ne dort pas, 2015) est le quatrième long-métrage du réalisateur argentin Pablo Agüero, né à Mendoza en 1977. Lauréat du prix Cinéma en Construction 2015, décerné pendant la 27e édition de Cinélatino, le film compte notamment sur la participation de Gael García Bernal, Denis Lavant, Imanol Arias, Daniel Fanego et Sofía Brito. Il s’inspire de l’errance du corps embaumé d’Eva Duarte de Perón, personnage emblématique du XXe siècle qui continue encore à exercer une fascination formidable. Au fur et à mesure que l’histoire avance la frontière entre réalité et mythe se fait de plus en plus imperceptible et nous sommes envahi·es par l’aura invisible et mystérieuse qui pèse sur les personnages : les ouvriers anonymes, le docteur Ara, le colonel Koenig ou encore Esther, une jeune fille qui grandit avec l’héritage laissé par Evita.Pablo Agüero est l’auteur de ce magnifique scénario (écrit en collaboration avec l’historien Marcelo Larraquy et le cinéaste Santiago Amigorena), pour lequel il a gagné le Grand Prix Sopadin 2012 du meilleur scénariste, et qui fut lu de façon émouvante par Jeanne Moreau devant le public du festival Premiers Plans d’Angers en janvier 2013*.Voici donc quelques fragments sélectionnés dans le texte que l’auteur a fait l’honneur de nous confier.* La version complète du scénario, lue par Jeanne Moreau et Denis Lavant, a notamment été enregistrée par France Culture à l’occasion d’une émission spéciale qui est disponible en libre écoute : www.franceculture.fr/emission-fictions-theatre-et-cie-evita-2014-01-19 Eva no duerme (2015) es el cuarto largometraje del director argentino Pablo Agüero, nacido en Mendoza en 1977. Galardonada con el premio Cine en Construcción 2015 en la 27 edición de Cinelatino, la película cuenta entre otros con la participación de Gael García Bernal, Denis Lavant, Imanol Arias Daniel Fanego y Sofía Brito. Se inspira en el destino del cuerpo embalsamado de Eva Duarte de Perón, personaje emblemático del siglo XX que sigue hoy en día ejerciendo una tremenda fascinación. A medida de que la historia avanza la frontera entre realidad y ficción se vuelve cada vez más tenue y nos va invadiendo la influencia invisible que sienten los personajes en la pantalla: los obreros anónimos, el doctor Ara, el capitán Massara, el coronel Koenig y también Esther, una joven que va creciendo con el legado de Evita. Pablo Agüero es el autor de este guión (escrito en colaboración con el historiador Marcelo Larraquy et el cineasta Santiago Amigorena), por el cual le fue concedido el Gran premio Sopadin 2012, y que fue leído con mucha emoción por Jeannne Moreau delante del público del festival Premiers Plans d’Angers en enero de 2013*. He aquí algunos fragmentos seleccionados en el texto que el autor hizo el honor de confiarnos.* La versión completa del guión, leida por Jeanne Moreau y Denis Lavant, fue grabada por France Culture con ocasión de un programa especial disponible gratuitamente en: www.franceculture.fr/emission-fictions-theatre-et-cie-evita-2014-01-19

Published
2016

22. Extractos del guión: Eva no duerme

Author

Pablo Agüero

Subjects
Visual Arts and Performing Arts
Abstract

Eva no duerme (2015) es el cuarto largometraje del director argentino Pablo Agüero, nacido en Mendoza en 1977. Galardonada con el premio Cine en Construcción 2015 en la 27 edición de Cinelatino, la película cuenta entre otros con la participación de Gael García Bernal, Denis Lavant, Imanol Arias Daniel Fanego y Sofía Brito. Se inspira en el destino del cuerpo embalsamado de Eva Duarte de Perón, personaje emblemático del siglo XX que sigue hoy en día ejerciendo una tremenda fascinación. A medida de que la historia avanza la frontera entre realidad y ficción se vuelve cada vez más tenue y nos va invadiendo la influencia invisible que sienten los personajes en la pantalla: los obreros anónimos, el doctor Ara, el capitán Massara, el coronel Koenig y también Esther, una joven que va creciendo con el legado de Evita. Pablo Agüero es el autor de este guión (escrito en colaboración con el historiador Marcelo Larraquy et el cineasta Santiago Amigorena), por el cual le fue concedido el Gran premio Sopadin 2012, y que fue leído con mucha emoción por Jeannne Moreau delante del público del festival Premiers Plans d’Angers en enero de 2013*. He aquí algunos fragmentos seleccionados en el texto que el autor hizo el honor de confiarnos.* La versión completa del guión, leida por Jeanne Moreau y Denis Lavant, fue grabada por France Culture con ocasión de un programa especial disponible gratuitamente en: www.franceculture.fr/emission-fictions-theatre-et-cie-evita-2014-01-19 Eva no duerme (Eva ne dort pas, 2015) est le quatrième long-métrage du réalisateur argentin Pablo Agüero, né à Mendoza en 1977. Lauréat du prix Cinéma en Construction 2015, décerné pendant la 27e édition de Cinélatino, le film compte notamment sur la participation de Gael García Bernal, Denis Lavant, Imanol Arias, Daniel Fanego et Sofía Brito. Il s’inspire de l’errance du corps embaumé d’Eva Duarte de Perón, personnage emblématique du XXe siècle qui continue encore à exercer une fascination formidable. Au fur et à mesure que l’histoire avance la frontière entre réalité et mythe se fait de plus en plus imperceptible et nous sommes envahi-es par l’aura invisible et mystérieuse qui pèse sur les personnages : les ouvriers anonymes, le docteur Ara, le colonel Koenig ou encore Esther, une jeune fille qui grandit avec l’héritage laissé par Evita.Pablo Agüero est l’auteur de ce magnifique scénario (écrit en collaboration avec l’historien Marcelo Larraquy et le cinéaste Santiago Amigorena), pour lequel il a gagné le Grand Prix Sopadin 2012 du meilleur scénariste, et qui fut lu de façon émouvante par Jeanne Moreau devant le public du festival Premiers Plans d’Angers en janvier 2013*.Voici donc quelques fragments sélectionnés dans le texte que l’auteur a fait l’honneur de nous confier.* La version complète du scénario, lue par Jeanne Moreau et Denis Lavant, a notamment été enregistrée par France Culture à l’occasion d’une émission spéciale qui est disponible en libre écoute : www.franceculture.fr/emission-fictions-theatre-et-cie-evita-2014-01-19

Published
2016

23. Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation

Author

María José Sainz, Alberto Rábano Gutiérrez, Cristina Prieto-Jurczynska, Estrella Gómez-Tortosa, Yalda Baradaran-Heravi, Christine Van Broeckhoven, Valentina González Alvarez, Julie van der Zee, Rosa Guerrero-López, Pablo Agüero Rabes, and EU EOD Consortium

Subjects
0301 basic medicine, Proband, Male, Aging, Pathology, medicine.medical_specialty, Nonsense mutation, tau Proteins, Neuropathology, Biology, Temporal lobe, 03 medical and health sciences, 0302 clinical medicine, Progranulins, mental disorders, medicine, Subependymal zone, Humans, Genetic Association Studies, Aged, Genes, Dominant, Aged, 80 and over, General Neuroscience, Brain, Neurofibrillary Tangles, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, 030104 developmental biology, Tauopathies, Codon, Nonsense, Astrocytes, Frontotemporal Dementia, Female, Neurology (clinical), Tauopathy, Human medicine, Geriatrics and Gerontology, 030217 neurology & neurosurgery, Developmental Biology, Frontotemporal dementia
Abstract

Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy. Astrocytic tauopathy, 4R(+) and 3R(-) immunoreactive, was characterized by thorn-shaped astrocytes present in subpial, subependymal, and perivascular areas, and in gray matter; plus granular or fuzzy tau immunoreactivity in astrocytic processes in gray matter, either solitary or clustered in different regions. Some neurofibrillary tangles and pretangles, both 3R and 4R(+), were present in the medial temporal lobe but did not exhibit the characteristic distribution of Alzheimer's type pathology. This 4R-tau aging-related tau astrogliopathy is likely a co-occurring pathology, although an interaction between progranulin and tau proteins within the neurodegenerative process should not be ruled out.

Published
2018

24. SORL1 Variants in Familial Alzheimer's Disease

Author

Pablo Agüero, Rosa Guerrero-López, Cristina Prieto-Jurczynska, Estrella Gómez-Tortosa, Alberto Villarejo-Galende, María Ruggiero, Ma José Sainz, Julián Pérez-Pérez, Carlos Ordás, and Begoña Venegas Pérez

Subjects
0301 basic medicine, Proband, Male, SORL1, SORL1 gene, Neurogenetics, Disease, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Alzheimer Disease, medicine, Humans, Genetic Predisposition to Disease, LDL-Receptor Related Proteins, Aged, Genetics, business.industry, General Neuroscience, Siblings, Membrane Transport Proteins, General Medicine, Middle Aged, medicine.disease, Pathophysiology, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Spain, Case-Control Studies, Cohort, Mutation, Female, Geriatrics and Gerontology, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.

Published
2018

25. Quality of Chronic Anticoagulation Control in Patients with Intracranial Haemorrhage due to Vitamin K Antagonists

Author

Consuelo Matute, Maria Molina-Sanchez, A. Cruz-Culebras, Elena Viedma-Guiard, Rocio Vera, Pablo Agüero-Rabes, Jaime Masjuan Vallejo, Carlos Estevez-Fraga, Leticia Crespo-Araico, Alicia de Felipe-Mimbrera, and Rodrigo Alvarez-Velasco

Subjects
medicine.medical_specialty, Article Subject, business.industry, Intracranial haemorrhage, Context (language use), Atrial fibrillation, 030204 cardiovascular system & hematology, Vitamin k, medicine.disease, nervous system diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Population study, In patient, Neurology (clinical), Neurology. Diseases of the nervous system, cardiovascular diseases, Risk assessment, business, RC346-429, Stroke, 030217 neurology & neurosurgery, Research Article
Abstract

Introduction. Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. Materials and Methods. We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. Results and Discussion. The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). Conclusion. VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required.

Published
2018

26. [Anemia in hospitalized patients with cirrhosis: prevalence, clinical relevance and predictive factors]

Author

Sebastián Alfonso, Mathurin, Andrés Pablo, Agüero, Natalia Andrea, Dascani, Jorgelina Ana, Prestera, Carina, Gianserra, Eliana, Londero, and Carolina, Chiorra

Subjects
Adult, Aged, 80 and over, Liver Cirrhosis, Hepatitis, Alcoholic, Argentina, Anemia, Middle Aged, Severity of Illness Index, Hospitalization, Hemoglobins, Liver Cirrhosis, Alcoholic, Case-Control Studies, Prevalence, Prothrombin Time, Humans, Female, Renal Insufficiency, Aged, Retrospective Studies
Abstract

few studies have examined the anemia in hospitalized cirrhotic patients.to assess the prevalence, predictive factors and prognosis for mortality of anemia in admitted cirrhotic patients.descriptive study of cases and controls; 178 hospitalization of 114 patients were reviewed (mean age 52.4 years; 106 alcoholics) between May/2004 and June/2007. Those with acute losses of blood were excluded. The anemia was classified as slight, moderate, and severe, since a hemoglobin12 g/dl. There were considered as cases the admissions in which the hemoglobin had10 g/dl (moderate and severe anemia).a diagnosis of anemia was made in 155 admissions, 47% were moderate and 19% severe. Hospital mortality rate in cases was 19.6%, and in controls 5.3%, [OR 4.39 (p = 0.004)]. The independent predictive factors for mortality were: score of Child-Pügh [OR 1.99 (p = 0.0005)], creatinine1.5 mg/dl [OR 11.34 (p = 0.0006)] and infections [OR 5.78 (p = 0.018)]. The cases had a greater risk of renal insufficiency [27.5% vs. 3.9%, OR 9.2 (p = 0.0001)]. Classification of Child-Pügh, total bilirubin10 mg/dl, albumin2.5 g/dl, infections, hepatic encephalopathy and alcoholic hepatitis also were predictive factors of moderate-severe anemia. The independent predictive factors for moderate-severe anemia were score ofChild-Piigh and renal insufficiency.the anemia had a high prevalence with an increase of hospital mortality rate, although it was not an independent risk factor for death. The renal insufficiency and the severity of the hepatic disease were associated in independent form with moderate-severe anemia in patients admitted with cirrhosis.

Published
2009

27. Prevalencia, aspectos clínicos y pronóstico de la peritonitis bacteriana espontánea en un hospital general Prevalence, clinical aspects and prognosis of spontaneous bacterial peritonitis in a general hospital

Author

Sebastián Alfonso Mathurin Lasave, Andrés Pablo Agüero López, Valeria Adriana Spanevello Petrin, and Adrián Gustavo Chapelet Cisi

Subjects
peritonitis bacteriana espontánea, spontaneous bacterial peritonitis, ascites, Liver cirrhosis, lcsh:R, mortalidad, prognostic factors, lcsh:Medicine, Cirrosis hepática, ascitis, factores pronósticos, mortality
Abstract

Se realizó un estudio descriptivo, retrosprospectivo para analizar la prevalencia de la peritonitis bacteriana espontánea, manifestaciones clínicas, características microbiológicas y factores pronósticos para mortalidad en 218 internaciones de 125 pacientes con cirrosis y ascitis, entre abril 2004 a mayo 2008. Se hizo análisis univariado mediante la prueba de la t de Student y la prueba exacta de Fisher. Se usó el método de regresión logística para determinar factores asociados a mortalidad. Se incluyeron 39 episodios de peritonitis bacteriana espontánea en 31 pacientes, 83,8 % hombres, edad media 49,1 años, 93,6 % alcohólicos, con una prevalencia de 39/218 (17,9 %). Fallecieron 10 pacientes (32,2 %). Fue adquirida en la comunidad en 59 %; sintomática en 82 %. Tuvieron cultivo positivo de líquido ascítico 41%. Fueron por gérmenes gram-positivos 13/24 (54 %) cultivos positivos de líquido ascítico y/o hemocultivos. En el análisis univariado se identificaron como factores predictores de mortalidad, el score de Child-Pügh, el score de hepatitis alcohólica de Glasgow, sitio de adquisición, encefalopatía hepática, control por paracentesis a las 48 h del inicio antibiótico sin respuesta, presencia de shock séptico, insuficiencia renal, hiponatremia y bilirrubinemia total > 250 µmol/L (> 14,6 mg/dL). La presencia de shock séptico, bilirrubinemia total > 250 µmol/L y la creatininemia > 114,4 µmol/L (> 1,5 mg/dL) fueron los factores pronósticos independientes para mortalidad, Los que aumentaron más de 20 veces el riesgo de muerte las 2 primeras, y de 14 veces la insuficiencia renal.A descriptive and retrospective study was conducted to analyze the prevelence or spontaneous bacterial peritonitis, clinical manifestations, microbiological characteristics and prognostic factors for mortality in 218 admissions of 125 patients with cirrhosis and ascites between April 2004 and May 2008. A univariate analysis was made by the Student's t test and Fisher's exact test. The logistical regression method was used to determine factors associated with mortality. 39 episodes of spontaneous bacterial peritonitis in 39 patients were included, 83.8 % were males, average age was 49.1 and 93.6 % were alcoholic, with a prevalence of 39/218 (17.9 %). 10 patients died (32.2 %). It was community acquired in 59 % and symptomatic in 82 %. 41 % had a positive culture of ascitic fluid. 13/24 (54 %) positive cultures of ascitic fluid and/or hemocultures were by gram-posistive germs. Child-Pügh's score, Glasgow's score of alcoholic hepatitis, site of acquisition, hepatic encephalopathy, control by paracentesis at 48 h of the beginning of antibiotics without response, presence of septic shock, renal failure, hyponatremia and total bilirubinemia > 250 µmol/L (> 14,6 mg/dL) were identified as the predictor factors in the univariate analysis. The presence of septic shock, total bilirubinemia > 250 µmol/L and creatininemia > 114.4 µmol/L (> 1.5 mg/dL) were the independent prognostic factors for mortality, the first two increased more than 20 times the risk of death and 14 times the renal failure.

Published
2008

29. Anemia en pacientes internados con cirrosis: prevalencia, significación clínica y factores predictivos

Author

Sebastián Alfonso Mathurin, Andrés Pablo Agüero, Natalia Andrea Dascani, Jorgelina Ana Prestera, Carina Gianserra, Eliana Londero, and Carolina Chiorra

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869, Medicine
Abstract

Introducción: son escasos los estudios donde se valora la anemia en pacientes cirróticos internados. Objetivo: evaluar la prevalencia, los factores predictivos y el pronóstico para mortalidad de la anemia en cirróticos internados. Pacientes y métodos: estudio descriptivo de casos y controles. Se revisaron 178 internaciones de 114 pacientes (edad media 52.4 años; 106 alcohólicos) entre mayo de 2004 y junio de 2007. Se excluyeron aquellas con pérdidas agudas de sangre. La anemia se clasificó como leve, moderada y severa a partir de una hemoglobina < 12 g/dl. Fueron considerados casos las internaciones con hemoglobina < 10 g/dl (anemias moderadas y severas). Resultados: se diagnosticó anemia en 155 internaciones, 47% fueron moderadas y 19% severas. La tasa de mortalidad hospitalaria en los casos fue 19.6% y en los controles 5.3%, [OR 4.39 (p=0.004)]. Fueron identificados como predictores independientes de mortalidad: el score de Child-Pügh [OR 1.99 (p=0.0005)], la creatininemia > 1.5 mg/dl [OR 11.34 (p= 0.0006)] y las infecciones [OR 5.78 (p= 0.018)]. Los casos tuvieron un mayor riesgo de insuficiencia renal [27.5% vs 3.9%, OR 9.2 (p=0.0001)]. La clasificación de Child- Pügh, la bilirrubinemia total, la albuminemia, las infecciones, la encefalopatía hepática y la hepatitis alcohólica también fueron factores predictivos de anemia moderada- severa. Los factores predictivos independientes fueron el score de Child-Pügh y la insuficiencia renal. Conclusiones: la anemia tiene una elevada prevalencia con un aumento de la mortalidad hospitalaria, aunque no fue un predictor independiente para riesgo de muerte. La insuficiencia renal y la severidad de la enfermedad hepática se asociaron en forma independiente con anemia moderada-severa en pacientes hospitalizados con cirrosis.

Published
2009

30. Negative effects of chlorthalidone on sympathetic nervous system and insulin resistance in hypertensive patients may be avoided with spironolactone: further studies are still needed.

Author

Castro-Torres Y, Fleites-Pérez A, Carmona-Puerta R, and Jiménez-Garrido RG

Subjects
Blood Pressure drug effects, Chlorthalidone pharmacology, Humans, Hypertension drug therapy, Hypertension physiopathology, Insulin Resistance physiology, Spironolactone pharmacology, Chlorthalidone adverse effects, Spironolactone adverse effects, Sympathetic Nervous System drug effects
Abstract

Chlorthalidone is commonly used for blood pressure control in hypertensive patients. However, it increases sympathetic nervous system activity and insulin resistance. Both conditions are related with an elevated number of complications and worsen patients' prognosis. Recently has been demonstrated that these adverse effects are avoided with spironolactone administration. Mechanisms to explain increasing sympathetic nervous activity and insulin resistance with chlorthalidone, but not with spironolactone are unclear and under investigation. It should be necessary to continue medical investigation on this field with long-term studies, a larger number of patients and associated comorbidities. The aim should be to establish whether the association of both drugs could be an effective and safety choice to be implemented extensively in clinical practice. That possibility could represent a new alternative for patients' management.

Published
2015
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