Desarrollo y validación del HAE-QoL: Cuestionario específico de calidad de vida relacionada con la salud para pacientes adultos con angioedema hereditario por déficit del inhibidor de la C1 esterasa

Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 15-12-2015Esta tesis tiene embargado el acceso al texto completo hasta el 15-12-2017Diversos documentos de la tesis doctoral no estarán disponibles en el repositorio Biblos-e Archivo al estar sujetos a proceso de confidencialida

New amphiphilic semi-interpenetrating networks based on polysulfone for anion-exchange membrane fuel cells with improved alkaline and mechanical stabilities

As considerable advance has recently been made in enhancing the conductivity of anion-exchange membranes, durability has become the critical requirement in the development of fuel cells. Such properties often develop at the expense of the other. In this work, new amphiphilic semi-interpenetrating networks composed of free polysulfone and crosslinked polysulfone are synthesized for the first time. The same nature of both polymers makes them highly compatible. The free polymer provides the hydrophobic component, whereas the crosslinked polysulfone, functionalized with trimethylammonium, 1-methylimidazolium, or 1,2-dimethylimidazolium groups, is responsible for the ionic conductivity. The compatibility between both components in the blend, improves the mechanical properties, while unaffecting the transport properties. Thus, the obtained membranes exceed the mechanical behaviour of commercial materials, even in conditions of extreme humidity and temperature. The tensile strength of these synthesized membranes can reach to relatively high values, and when compared to the commercial PSU, the difference in tensile strength can be noted to be as low as 10%. Moreover, the tensile strength and the ductility values of the crosslinked PSU are higher than those obtained with non-crosslinked PSU. Furthermore, the membranes presented in this work show a great alkaline stability (e.g. semi-interpenetrating network containing 1,2-dimethylimidazolium maintains 87% of the ionic conductivity after 14 days of treatment). Thus, these membranes provide an improvement in the durability limiting factors, in comparison to functionalized polysulfones, fulfilling the requirements to be used as electrolytes in anion-exchange membrane fuel cells.We thank Agencia Estatal de Investigación (AEI)/Fondo Europeo de Desarrollo Regional (FEDER/UE) for funding the project MINECO (MAT2016-78632-C4-3-R, and PID-2019-106662RB-C43) which supported this work. We also wish to thank the project from the Regional Government (Comunidad de Madrid through PEM4ENERGY-CM-UC3M)

Synthesis and characterization of novel anion exchange membranes based on semi-interpenetrating networks of functionalized polysulfone: Effect of ionic crosslinking

This article belongs to the Special Issue Polymeric Membranes for Advanced Applications.In this work, anion exchange membranes based on polymer semi-interpenetrating networks were synthesized and characterized for the first time. The networks are composed of sulfonated polysulfone and 1-methylimidazolium-functionalized polysulfone crosslinked covalently with N,N,N′,N′-tetramethylethylenediamine (degree of crosslinking of 5%). In these membranes, sulfonic groups interact electrostatically with cationic groups to form an ionic crosslinking structure with improved alkaline stability. The effect of the ionic crosslinking on the thermal, chemical, mechanical, and electrochemical behavior of membranes was studied. These crosslinked membranes containing sulfonated polysulfone showed higher thermal stability, with a delay of around 20 °C in the onset decomposition temperature value of the functional groups than the crosslinked membranes containing free polysulfone. The tensile strength values were maintained above 44 MPa in all membranes with a degree of chloromethylation (DC) below 100%. The maximum ionic conductivity value is reached with the membrane with the highest degree of chloromethylation. The chemical stability in alkaline medium of the conducting membranes also improved. Thus, the ionic conductivity variation of the membranes after 96 h in a 1 M potassium hydroxide (KOH) solution is less pronounced when polysulfone is replaced by sulfonated polysulfone. So, the ionic crosslinking which joins both components of the blends together, improves the material’s properties making progress in the development of new solid electrolyte for polymeric fuel cells.This work was funded by Agencia Estatal de Investigación (AEI)/Fondo Europeo de Desarrollo Regional (FEDER/UE), PID-2019-106662RB-C43, by the Spanish Government, MAT2016-78632-C4-3-R, and by the Regional Government PEM4ENERGY-CM-UC3M funded by the call "Programa de apoyo a la realización de proyectos interdisciplinares de I+D para jóvenes investigadores de la Universidad Carlos III de Madrid 2019-2020" under the frame of the "Convenio Plurianual Comunidad de Madrid-Universidad Carlos III de Madrid"

Using Metal-Organic Framework HKUST-1 for the Preparation of High-Conductive Hybrid Membranes Based on Multiblock Copolymers for Fuel Cells

Novel proton-conducting hybrid membranes consisting of sulfonated multiblock copolymer of polysulfone and polyphenylsulfone (SPES) reinforced with a HKUST-1 metal-organic framework (MOF) (5, 10, and 20 wt. %) were prepared and characterized for fuel cell applications. The presence of the MOF in the copolymer was confirmed by means of FE-SEM and EDS. The hybrid membranes show a lower contact angle value than the pure SPES, in agreement with the water uptake (WU%), i.e., by adding 5 wt. % of the MOF, this parameter increases by 20% and 40% at 30 °C and 60 °C, respectively. Additionally, the presence of the MOF increases the ion exchange capacity (IEC) from 1.62 to 1.93 mequivH+ g−1. Thermogravimetric analysis reveals that the hybrid membranes demonstrate high thermal stability in the fuel cell operation temperature range ( 85 MPa in the Na+ form). Proton conductivity was analyzed using EIS, achieving the highest value with a 5 wt. % load of the HKUST-1. This value is lower than that observed for the HKUST-1/Nafion system. However, polarization and power density curves show a remarkably better performance of the hybrid membranes in comparison to both the pure SPES and the pure Nafion membranesThis work was funded by the Agencia Estatal de Investigación (AEI)/Fondo Europeo de Desarrollo Regional (FEDER/UE), PID-2019-106662RB-C43, by the Spanish Government, MAT2016-78632-C4-3-R, by the Regional Government PEM4ENERGY-CM-UC3M funded by the call “Programa de apoyo a la realización de proyectos interdisciplinares de I + D para jóvenes investigadores de la Universidad Carlos III de Madrid 2019–2020” under the frame of the “Con-venio Plurianual Comunidad de Madrid-Universidad Carlos III de Madrid”, and by the Ministry of Science and Higher Education of the Russian Federation (State assignment in the field of scientific activity, № 0852-2020-0019). The authors would like to thank the following institutions for funding the projects: the Agencia Española de Investigación/Fondo Europeo de Desarrollo Regional (FEDER/UE): Projects PID2019-106662RBC43 and MAT2016-78362-C4-3-R, and the Comunidad de Madrid: Projects “Excelencia para el Profesorado Universitario”—(EPUC3M04) and PEM4ENERGY-CM-UC3

Characterization and Modeling of Free Volume and Ionic Conduction in Multiblock Copolymer Proton Exchange Membranes

Free volume plays a key role on transport in proton exchange membranes (PEMs), including ionic conduction, species permeation, and diffusion. Positron annihilation lifetime spectroscopy and electrochemical impedance spectroscopy are used to characterize the pore size distribution and ionic conductivity of synthesized PEMs from polysulfone/polyphenylsulfone multiblock copolymers with different degrees of sulfonation (SPES). The experimental data are combined with a bundle-of-tubes model at the cluster-network scale to examine water uptake and proton conduction. The results show that the free pore size changes little with temperature in agreement with the good thermo-mechanical properties of SPES. However, the free volume is significantly lower than that of Nafion®, leading to lower ionic conductivity. This is explained by the reduction of the bulk space available for proton transfer where the activation free energy is lower, as well as an increase in the tortuosity of the ionic network.This research was funded by the Spanish Agencia Estatal de Investigación (PID2019- 106740RB-I00) and the Community of Madrid (PEM4ENERGY-CM-UC3M) by the call “Programa de apoyo a la realización de proyectos interdisciplinares de I + D para jóvenes investigadores de la Universidad Carlos III de Madrid 2019–2020” under the frame of the “Convenio Plurianual Comunidad de Madrid-Universidad Carlos III de Madrid”

Hereditary angioedema: quality of life in Brazilian patients

OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire). This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean) of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project

BACKGROUND: There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. METHODS/DESIGN: Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. DISCUSSION: To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series

[Background] Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published.[Objective] To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series.[Methods] We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series.[Results] Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid.[Conclusions] This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.Peer reviewe

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients