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1. Heterogeneity in pharmacological treatment and outcomes in Crohn’s disease patients in Catalonia: a population-based observational study

Author: Eduard Brunet, Emili Vela, Luigi Melcarne, Laura-Patricia Llovet, Anna Puy, Montserrat Clèries, Caridad Pontes, Pilar García-Iglesias, Albert Villòria, Gilaad G. Kaplan, and Xavier Calvet
Subjects: Epidemiology, inflammatory bowel diseases, Crohn’s disease, biologics, surgery, Medicine
Abstract: Background Heterogeneity in the treatment of a disease is a marker of suboptimal quality of care. The aim of this study is to evaluate the heterogeneity in the treatment used and the outcomes for Crohn’s disease (CD) in Catalonia.Methods All patients with CD included in the Catalan Health Surveillance System (data on more than seven million individuals from 2011 to 2017) were identified. The different Catalonian health areas were grouped into 19 district groups (DG). Treatments used rates (systemic corticosteroids, non-biological and biological immunosuppressant) and outcomes rates (hospitalization and surgery) were calculated.Results The use of systemic corticosteroids presented a decreasing trend over the study period, with an average rate of use in the different territories between 11% and 17%. The use of non-biological immunosuppressant treatment has remained stable, with an average rate of use ranging from 22% to 40% per year depending on the DG. The use of biological immunosuppressant treatment increased with an average rate of use in the different territories ranging from 10 to 23%.Hospitalizations for any reason showed an increasing trend between 2011 and 2017 with an average rate of between 23% and 32% per year depending on the area. Hospitalizations for CD presented a decreasing trend, with an average rate of between 5% and 11% per year. Surgical treatment remained stable over time, rates per year were between 0.5% and 2%.Conclusion A remarkable geographical heterogeneity in the use of different treatments and in outcomes of CD was observed between different geographical areas of Catalonia. KEY MESSAGEThere is a notable geographical heterogeneity in the administration of biological and immunosuppressive treatments to Crohn’s disease patients in Catalonia.There is also a geographical heterogeneity in their rates of hospitalization and surgical intervention.
Published: 2022
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2. Scale-free behavioral cascades and effective leadership in schooling fish

Author: Julia Múgica, Jordi Torrents, Javier Cristín, Andreu Puy, M. Carmen Miguel, and Romualdo Pastor-Satorras
Subjects: Medicine, Science
Abstract: Abstract Behavioral contagion and the presence of behavioral cascades are natural features in groups of animals showing collective motion, such as schooling fish or grazing herbivores. Here we study empirical behavioral cascades observed in fish schools defined as avalanches of consecutive large changes in the heading direction of the trajectory of fish. In terms of a minimum turning angle introduced to define a large change, avalanches are characterized by distributions of size and duration showing scale-free signatures, reminiscent of self-organized critical behavior. We observe that avalanches are generally triggered by a small number of fish, which act as effective leaders that induce large rearrangements of the group’s trajectory. This observation motivates the proposal of a simple model, based in the classical Vicsek model of collective motion, in which a given individual acts as a leader subject to random heading reorientations. The model reproduces qualitatively the empirical avalanche behavior observed in real schools, and hints towards a connection between effective leadership, long range interactions and avalanche behavior in collective movement.
Published: 2022
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3. Improving the reliability of cohesion policy databases.

Author: Samuele Lo Piano, Emanuele Borgonovo, Arnald Puy, Andrea Saltelli, John Walsh, and Daniele Vidoni
Subjects: Medicine, Science
Abstract: In this contribution, we present an innovative data-driven model to reconstruct a reliable temporal pattern for time-lagged statistical monetary figures. Our research cuts across several domains regarding the production of robust economic inferences and the bridging of top-down aggregated information from central databases with disaggregated information obtained from local sources or national statistical offices. Our test bed case study is the European Regional Development Fund (ERDF). The application we discuss deals with the reported time lag between the local expenditures of ERDF by beneficiaries in Italian regions and the corresponding payments reported in the European Commission database. Our model reconstructs the timing of these local expenditures by back-dating the observed European Commission reimbursements. The inferred estimates are then validated against the expenditures reported from the Italian National Managing Authorities (NMAs) in terms of cumulative monetary difference. The lower cumulative yearly distance of our modelled expenditures compared to the official European Commission payments confirms the robustness of our model. Using sensitivity analysis, we also analyse the relative importance of the modelling parameters on the cumulative distance between the modelled and reported expenditures. The parameters with the greatest influence on the uncertainty of this distance are the following: first, how the non-clearly regionalised expenditures are attributed to individual regions; and second, the number of backward years that the residuals of the yearly payments are spread onto. In general, the distance between the modelled and reported expenditures can be further reduced by fixing these parameters. However, the gain is only marginal for some regions. The present study paves the way for modelling exercises that are aimed at more reliable estimates of the expenditures on the ground by the ultimate beneficiaries of European funds. Additionally, the output databases can contribute to enhancing the reliability of econometric studies on the effectiveness of European Union (EU) funds.
Published: 2022
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4. Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

Author: Ezequiel Cordova, Analia Mykietiuk, Omar Sued, Lautaro De Vedia, Natalia Pacifico, Matias H Garcia Hernandez, Natalia M Baeza, Franco Garibaldi, Maria Fernanda Alzogaray, Rosa Contreras, Lucrecia Soler Puy, Pablo G Scapellato, Laura Barcelona, Mariana L Golikow, Maria Florencia Piñeiro, Hugo J Miño, Maria Fernanda Consalvo, Corina Nemirovsky, Marisa Sanchez, Myrna Cabral, Lucia Lamponi Tappata, Mariano Blasco, Jamile Ballivian, Gustavo Lopardo, Martin E Stryjewski, and ECCOVID study group
Subjects: Medicine, Science
Abstract: BackgroundClinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina.MethodsMulticenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU).ResultsA total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27).ConclusionsThis cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.
Published: 2021
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5. Analytical comparison of ELISA and mass spectrometry for quantification of serum hepcidin in critically ill patients

Author: Constance Delaby, Jérôme Vialaret, Christophe Hirtz, Thibaud Lefebvre, Matthias Herkert, Hervé Puy, Sigismond Lasocki, Sylvain Lehmann, Pierre Asfar, Alain Mercat, Thomas Gaillard, Soizic Gergaud, Cyrille Sargentini, Claire Geneve, Philippe Montravers, Thibault Lefebvre, Herve Puy, Grégoire Mercier, Nicolas Nagot, Gerald Chanques, Samir Jaber, Karim Asehnoune, Antoine Roquilly, Claire Dahyot-Fizelier, Olivier Mimoz, Sonia Isslame, Philippe Seguin, Mathilde Barbaz, Martine Ferrandiere, Thomas Kerforne, Katell Peoc'h, François Beloncle, Maxime Leger, Emmanuel Rineau, Gregory Marin, Matthieu Boisson, Yoann Launey, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 030213 general clinical medicine, medicine.medical_specialty, Anemia, Critical Illness, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, Mass spectrometry, Gastroenterology, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Hepcidin, Internal medicine, Humans, Protein Isoforms, Medicine, General Pharmacology, Toxicology and Pharmaceutics, Anemia, Iron-Deficiency, biology, business.industry, Critically ill, 030208 emergency & critical care medicine, General Medicine, medicine.disease, 3. Good health, Medical Laboratory Technology, Iron-deficiency anemia, biology.protein, Reagent Kits, Diagnostic, business
Abstract: International audience; Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland–Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.
Published: 2021
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6. ABCB6 polymorphisms are not overly represented in patients with porphyria

Author: Jérôme Lamoril, Dimitri Tchernitchko, Robert J. Desnick, Charles J. Parker, Hervé Puy, Laurent Gouya, Brenden Chen, Zoubida Karim, Gaël Nicolas, Colin P. Farrell, John D. Phillips, Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Excellence Gr-Ex (Labex Gr-Ex) and the Institut National de la Santé et de la Recherche Medicale (INSERM).The Labex GR-Ex is funded by the program 'Investissements d’avenir' of the French National Research Agency, and reference ANR-11-IDEX-0005-02.
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, acute hepatic porphyria, Protoporphyria, Erythropoietic, erythropoietic protoporphyria, Variegate porphyria, Biology, Mice, Porphyrias, 03 medical and health sciences, chemistry.chemical_compound, medicine, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], heme, skin and connective tissue diseases, Heme, 030304 developmental biology, Acute intermittent porphyria, Mice, Knockout, Genetics, 0303 health sciences, Genetic heterogeneity, 030305 genetics & heredity, nutritional and metabolic diseases, Porphobilinogen Synthase, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ABCB6, medicine.disease, Penetrance, Porphyrias, Hepatic, 3. Good health, Hereditary coproporphyria, Porphyria, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, chemistry, ATP-Binding Cassette Transporters, Erythropoietic protoporphyria, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.
Published: 2022
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7. Antecedentes de neoplasias urológicas previos al trasplante renal. Resultados oncológicos a largo plazo

Author: José Daniel Subiela, C. Martinez, Luis Guirado, Jorge Huguet, Juan Palou, Angelo Territo, A. Sánchez-Puy, Asier Mercadé, O. Rodríguez Faba, D. Vanacore, R. Boissier, A. Gallioli, R. Hidalgo, and Alberto Breda
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, Urology, 030232 urology & nephrology, medicine, business
Abstract: Resumen Introduccion Nuestro objetivo ha sido informar de los resultados oncologicos de pacientes con ERET y antecedentes de neoplasias urologicas que fueron sometidos posteriormente a un trasplante renal (TR). Material y metodo Estudio retrospectivo llevado a cabo en el registro de la Fundacion Puigvert (Barcelona) con 1.200 TR realizados entre 1988 y 2018. Se identificaron 85 neoplasias urologicas que recibieron tratamiento previo al TR en 81 pacientes: 15 (18%) canceres de prostata, 49 (58%) carcinoma de celulas renales (CCR), 19 (22%) carcinomas uroteliales y 2 (2%) canceres de testiculo. Se registraron datos de las caracteristicas basales, la estadificacion del cancer, el tratamiento y el seguimiento, y sobre la cronologia del inicio de dialisis, la inscripcion en la lista de espera y el TR. Los criterios de valoracion fueron la recidiva del cancer, la progresion metastasica, la muerte especifica por cancer y la supervivencia global. Resultados En una mediana de seguimiento de 13,1 anos (2,2-32), se registraron 16/85 (19%) recidivas del cancer, con 3 (4%) progresiones a metastasis y muerte por cancer. La mediana de supervivencia global tras el tratamiento del cancer fue de 25,3 anos y la supervivencia por cancer especifica fue del 95% a los 25 anos. La mediana de tiempo desde el tratamiento del cancer hasta el trasplante de rinon fue de 4,8 anos: 3,7 anos en el cancer de prostata, 3,9 anos en el CCR y 8,8 anos en el cancer vesical. La mediana de tiempo desde el inicio de dialisis hasta el TR fue de 1,8 anos en los pacientes con antecedentes de neoplasia urologica, frente a 0,5 anos en la cohorte total de 1.200 trasplantes renales durante el mismo periodo. Conclusiones Los pacientes con antecedentes de neoplasias urologicas bien seleccionados se pueden beneficiar enormemente del trasplante de rinon con una recidiva del cancer tardia y poco frecuente. Para el cancer de prostata de bajo riesgo y el CCR, podria optimizarse el tiempo de espera, pero se necesitan datos mas solidos en este contexto.
Published: 2021
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8. Novel intracoronary supersaturated oxygen treatment for anterior myocardial infarction

Author: Federico De Puy, Richard A. Schatz, and Carmen Wheeler
Subjects: medicine.medical_specialty, medicine.medical_treatment, Anterior myocardial infarction, Coronary artery disease, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, cardiovascular diseases, Myocardial infarction, Ventricular remodeling, Myocardial reperfusion, Ventricular Remodeling, business.industry, Percutaneous coronary intervention, Supersaturated oxygen therapy, medicine.disease, Oxygen, Treatment Outcome, Conventional PCI, cardiovascular system, Cardiology, ST Elevation Myocardial Infarction, Molecular Medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Primary percutaneous coronary intervention (PCI) is now the recommended reperfusion technique for patients with acute ST-segment elevation myocardial infarction. However, despite early reperfusion in the majority of patients, PCI does not achieve effective myocardial reperfusion in a significant proportion of patients due to the prevalence of coronary microvascular obstruction. The amount of infarcted myocardium has been considered to be a reliable indicator of major adverse cardiovascular events and resultant adverse left ventricular remodeling. The purpose of this paper is to review the clinical benefits of supersaturated oxygen therapy following PCI for ST-segment elevation myocardial infarction.
Published: 2021
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9. Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs

Author: Jorge Juan Olsina-Kissler, Susana Gómez-Ollés, Cristina Esquinas, Meritxell Boada-Pérez, Amaia Ojanguren, Maite Santamaría, Alba Boldó, Sonia Gatius-Calderó, Carlos Fraile, Berta Sáez-Giménez, Iñigo Ojanguren, Miriam Barrecheguren, Lucia Milla-Collado, and Sara Puy
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Swine, medicine.medical_treatment, Ischemia, Pilot Projects, Lung injury, Gastroenterology, Proinflammatory cytokine, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Apoptosis Marker, Lung transplantation, Lung, Caspase 3, business.industry, Lung Injury, Organ Preservation, General Medicine, medicine.disease, medicine.anatomical_structure, 030228 respiratory system, Apoptosis, Reperfusion Injury, Cytokines, business, Reperfusion injury, Lung Transplantation
Abstract: Background In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. Methods Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n = 8) were submitted to organ procurement. Lungs were subjected to 6 h (n = 4) or 12 h (n = 4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4 h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30 min after reperfusion, and (iv) 4 h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. Results We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6 h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30 min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30 min after reperfusion. Conclusions We observed that 6 and 12 h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.
Published: 2021
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10. Older patients' perspectives toward lifestyle-related secondary cardiovascular prevention after a hospital admission-a qualitative study

Author: Patricia Jepma, Marjolein Snaterse, Simone Du Puy, Wilma J.M. Scholte op Reimer, Ron J.G. Peters, Graduate School, Nursing, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Quality of Care, AMS - Amsterdam Movement Sciences, Cardiology, ACS - Heart failure & arrhythmias, Urban Vitality, Lectoraat Integratie van Psychiatrische en Somatische Zorg, and Kenniscentrum ACHIEVE
Subjects: Gerontology, Aging, media_common.quotation_subject, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Older patients, healthy lifestyle, Humans, Medicine, 030212 general & internal medicine, frail older people, Life Style, media_common, Social influence, Self-efficacy, business.industry, General Medicine, Hospitals, aged, Feeling, Cardiovascular Diseases, cardiology, Hospital admission, Quality of Life, Geriatrics and Gerontology, Thematic analysis, business, qualitative research, secondary prevention, Qualitative research
Abstract: Background lifestyle-related secondary prevention reduces cardiac events and is recommended irrespective of age. However, motivation may be influenced by age and disease progression. Objective to explore older cardiac patients’ perspectives toward lifestyle-related secondary prevention after a hospital admission. Methods a generic qualitative design was used. Semi-structured interviews were performed with cardiac patients ≥ 70 years within 3 months after a hospital admission. The interview guide was based on the Attitudes, Social influence and self-Efficacy (ASE) model. All interviews were analysed using thematic analysis. Results eight themes emerged which were linked to the determinants of the ASE-model. The three themes (i) Perspectives are determined by general health and habits, (ii) feeling the threat as a motivator and (iii) balancing between health benefits and quality of life (QoL), were linked to attitude. Regarding social influence, the themes (iv) feeling both encouraged and hindered by family members, and (v) the healthcare professional says so, were identified. For the self-efficacy determinant, (vi) experiences from previous lifestyle changes, (vii) integrating advice in daily life and (viii) feeling limited by functional impairments, emerged as themes. Conclusion most older cardiac patients made no lifestyle modifications after the last hospital admission and balanced possible benefits against their QoL. Functional impairments frequently limit implementation, in particular of physical activity. Patients’ preferences and patient-centred outcomes focusing on QoL and functional independence may be the starting point when healthcare professionals discuss lifestyle modification in older patients. The involvement of family members may help patients to integrate lifestyle-related secondary prevention in daily life.
Published: 2021
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11. Cross-Talk between the Complement Pathway and the Contact Activation System of Coagulation: Activated Factor XI Neutralizes Complement Factor H

Author: Jiaqing Pang, Andras Gruber, Cristina Puy, Owen J. T. McCarty, David Gailani, Erik I. Tucker, Florea Lupu, Stéphanie E. Reitsma, and Christina U. Lorentz
Subjects: Blood Platelets, Complement Pathway, Alternative, Immunology, Plasma protein binding, Complement factor I, Article, Factor XIa, 03 medical and health sciences, 0302 clinical medicine, Thrombin, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Immunology and Allergy, Platelet, Blood Coagulation, Inflammation, Chemistry, Endothelial Cells, Fibrinogen, Receptor Cross-Talk, eye diseases, Complement system, Cell biology, Coagulation, Complement Factor H, Factor H, Complement C3b, Alternative complement pathway, sense organs, Papio, Protein Binding, 030215 immunology, medicine.drug
Abstract: Complement factor H (CFH) is the major inhibitor of the alternative pathway of the complement system and is structurally related to beta2-glycoprotein I, which itself is known to bind to ligands, including coagulation factor XI (FXI). We observed reduced complement activation when FXI activation was inhibited in a baboon model of lethal systemic inflammation, suggesting cross-talk between FXI and the complement cascade. It is unknown whether FXI or its activated form, activated FXI (FXIa), directly interacts with the complement system. We explored whether FXI could interact with and inhibit the activity of CFH. We found that FXIa neutralized CFH by cleavage of the R341/R342 bonds. FXIa reduced the capacity of CFH to enhance the cleavage of C3b by factor I and the decay of C3bBb. The binding of CFH to human endothelial cells was also reduced after incubating CFH with FXIa. The addition of either short- or long-chain polyphosphate enhanced the capacity of FXIa to cleave CFH. FXIa also cleaved CFH that was present on endothelial cells and in the secretome from blood platelets. The generation of FXIa in plasma induced the cleavage of CFH. Moreover, FXIa reduced the cleavage of C3b by factor I in serum. Conversely, we observed that CFH inhibited FXI activation by either thrombin or FXIIa. Our study provides, to our knowledge, a novel molecular link between the contact pathway of coagulation and the complement system. These results suggest that FXIa generation enhances the activity of the complement system and thus may potentiate the immune response.
Published: 2021
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12. A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria

Author: Yvette Y. Yien, Hana Manceau, Katell Peoc’h, Xènia Ferrer-Cortès, Sarah Ducamp, Laurent Gouya, Caroline Kannengiesser, Gaël Nicolas, Sara Luscieti, Hervé Puy, and Mayka Sanchez
Subjects: Disease severity, Extramural, business.industry, Endopeptidase Clp, Mutation (genetic algorithm), Severity of illness, medicine, Hematology, Erythropoietic protoporphyria, medicine.disease, business, Bioinformatics, ALAS2
Published: 2021
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13. The Impact of Ureteroscopy following Computerized Tomography Urography in the Management of Upper Tract Urothelial Carcinoma

Author: Esteban Emiliani, Joan Palou, Asier Mercadé, Romain Boissier, A. Gallioli, Matteo Fontana, Josep M Gaya, Maria José Martínez, A. Sánchez-Puy, Alberto Breda, and Angelo Territo
Subjects: Male, medicine.medical_specialty, Urology, 030232 urology & nephrology, 03 medical and health sciences, 0302 clinical medicine, Ureteroscopy, Carcinoma, medicine, Humans, Reliability (statistics), Aged, Retrospective Studies, Urothelial carcinoma, Aged, 80 and over, Carcinoma, Transitional Cell, medicine.diagnostic_test, Ureteral Neoplasms, business.industry, Reproducibility of Results, Urography, medicine.disease, Endoscopy, Treatment Outcome, Urinary Bladder Neoplasms, Upper tract, Female, Tomography, Radiology, Tomography, X-Ray Computed, business, Pyelogram
Abstract: We report the reliability of computerized tomography urography and ureteroscopy in the diagnosis and management of upper tract urothelial carcinoma.From 2015 to November 2018 we prospectively collected and retrospectively analyzed 244 cases of ureteroscopy with available preoperative computerized tomography urography. Computerized tomography urography was categorized as positive, suspicious, unlikely and negative. Correspondence between imaging, ureteroscopy and histology was analyzed. The therapeutic indication, based on 2020 EAU Guidelines and patient clinical data, was recorded before and after ureteroscopy. Cohen's Kappa was used for agreement analysis. Logistic regression was used for prediction of positive ureteroscopy.Ureteroscopy was positive for upper tract urothelial carcinoma in 107/115 (93%), 48/77 (62.3%), 15/27 (55.6%) and 12/25 (48%) cases with positive, suspicious, unlikely and negative computerized tomography urography, respectively. On cytohistology the result was confirmed in 164/182 (90.1%) cases. The positive predictive value of a filling defect, stenosis, thickening and hydronephrosis on computerized tomography urography was 87.7% (121/138 cases), 65.6% (21/32), 69.6% (64/92) and 79.7% (59/74), respectively. On multivariate analysis a filling defect (95% CI 2.76-11.5, OR 5.63, p0.0001) or hydronephrosis (1.04-6.18, OR 2.52, p=0.04) was associated with ureteroscopy outcome. Among cases with positive computerized tomography urography and ureteroscopy, the lesions differed in dimensions (20/107), number (14/107) and site (11/107), for a total of 45/107 (42.1%) cases. The indication of elective treatment changed after ureteroscopy in 37/76 (48.1%) cases (Kappa=0.31), as 17/28 (60.7%), 11/20 (55%) and 11/28 (39.2%) indications were confirmed for endoscopic management, ureterectomy and nephroureterectomy, respectively.The complementary use of computerized tomography urography and ureteroscopy in the diagnostic workup of upper tract urothelial carcinoma should be evaluated.
Published: 2021
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14. Obesidad y SARS-CoV-2: consideraciones sobre la cirugía bariátrica y recomendaciones para el inicio de la actividad quirúrgica

Author: Irene Bretón Lesmes, Miguel Angel Rubio Herrera, Raquel Sánchez Santos, Esteban Martín Antona, Fàtima Sabench Pereferrer, Amador García Ruiz de Gordejuela, Violeta Moizé Arcone, Andrés Sánchez Pernaute, Juan José Arroyo Martín, Albert Lecube Torelló, Enric Fernández Alsina, and Ramón Vilallonga Puy
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Obesidad, Comorbidity, 030230 surgery, Article, Special Article, 03 medical and health sciences, Benign pathology, 0302 clinical medicine, Intervention (counseling), Pandemic, Humans, Medicine, In patient, Obesity, Pandemics, Seguridad, Cirugía bariátrica, Bariatric surgery, SARS-CoV-2, business.industry, General Engineering, COVID-19, medicine.disease, Surgery, Practice Guidelines as Topic, Safety, business, Humanities
Abstract: Resumen La pandemia SARS-CoV-2 ha tenido un gran impacto en todo el mundo, siendo Espana uno de los paises mas afectados. La demora en la cirugia bariatrica puede tener consecuencias fatales, ya que hasta el 50% de los pacientes que se encuentran en lista de espera desarrollan una nueva comorbilidad durante el tiempo que permanecen en ella y el 1,5% de pacientes fallecen mientras esperan la intervencion. Es por ello por lo que la cirugia bariatrica no debe demorarse en cuanto la ocupacion del hospital por pacientes COVID-19+ disminuya de forma significativa y se disponga de recursos y seguridad suficiente para realizar la cirugia en pacientes con patologia benigna. Este documento recoge las principales recomendaciones para los programas de cirugia bariatrica en nuestro pais desde el punto de vista tanto de seguridad como de preparacion y seguimiento del paciente bariatrico en el contexto de la pandemia SARS-CoV-2.
Published: 2021
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15. Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air ® App

Author: Bédard, Annabelle, Antó, Josep, Fonseca, Joao, Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Cardona, Victoria, Cruz, Alvaro, Fokkens, Wytske, Garcia-Aymerich, Judith, Hellings, Peter, Ivancevich, Juan, Klimek, Ludger, Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Désirée, Melen, Erik, Monti, Ricardo, Mösges, Ralf, Mullol, Joaquim, Papadopoulos, Nikos, Pham-Thi, Nhan, Samolinski, Boleslaw, V Tomazic, Peter, Toppila-Salmi, Sanna, Ventura, Maria Teresa, Yorgancioglu, Arzu, Bousquet, Jean, Pfaar, Oliver, Basagana, Xavier, Bosnic‐Anticevich, Sinthia, Pham‐Thi, Nhân, Hellings, PW, Aberer, W., Agache, I., Akdis, Ca, Akdis, M., Aliberti, MR, Almeida, R., Amat, F., Angles, R, Annesi‐Maesano, I, Ansotegui, IJ, Anto, JM, Arnavielle, S, Asayag, E, Asarnoj, A, Arshad, H, Avolio, F, Bacci, E, Baiardini, I, Barbara, C, Barbagallo, M., Baroni, I, Barreto, BA, Basagaña, X., Bateman, ED, Bedolla‐Barajas, M, Bewick, M., Beghé, B., Bel, EH, Bergmann, KC, Bennoor, KS, Benson, M, Bertorello, L, Białoszewski, AZ, Bieber, T., Bialek, S, Bindslev‐Jensen, Carsten, Bjermer, L., Blain, H., Blasi, F., Blua, A, Bochenska Marciniak, M, Bogus‐Buczynska, I, Boner, AL, Bonini, M., Bonini, S., Bosnic‐Anticevich, CS, Bosse, I., Bouchard, J., Boulet, LP, Bourret, R., Bousquet, Pj, Braido, F, Briedis, V, Brightling, CE, Brozek, J, Bucca, C, Buhl, R, Buonaiuto, R, Panaitescu, C, Burguete Cabañas, MT, Burte, E., Bush, A, Caballero‐Fonseca, F, Caillaud, D., Caimmi, D., Calderon, MA, Camargos, PAM, Camuzat, T., Canfora, G, Canonica, Gw, Carlsen, KH, Carreiro‐Martins, P, Carriazo, AM, Carr, W, Cartier, C., Casale, T., Castellano, G, Cecchi, L, Cepeda, AM, Chavannes, NH, Chen, Y., Chiron, R., Chivato, T, Chkhartishvili, E, Chuchalin, AG, Chung, KF, Ciaravolo, MM, Ciceran, A, Cingi, C, Ciprandi, G, Carvalho Coehlo, AC, Colas, L, Colgan, E, Coll, J, Conforti, D, Constantinidis, J, de Sousa, J Correia, Cortés‐Grimaldo, RM, Corti, F, Costa, E, Costa‐Dominguez, MC, Courbis, AL, Cox, L, Crescenzo, M, Cruz, AA, Custovic, A., Czarlewski, W., Dahlen, Se, D’Amato, G, Dario, C, Da Silva, J., Dauvilliers, Y., Darsow, U, De Blay, F., De Carlo, G, Dedeu, T, de Fátima Emerson, M, De Feo, G., De Vries, G, De Martino, B, Motta Rubini, NP, Deleanu, D, Denburg, JA, devillier, P., Di Capua Ercolano, S, Di Carluccio, N, Didier, A., Dokic, D, Dominguez‐Silva, MG, Douagui, H, Dray, G., Dubakiene, R, Durham, Sr, Du Toit, G, Dykewicz, MS, El‐Gamal, Y, Eklund, P, Eller, E, Emuzyte, R., Farrell, J, Farsi, A, de Mello, J Ferreira, Ferrero, J, Fink‐Wagner, A, Fiocchi, A, Fokkens, WJ, Fonseca, JA, Fontaine, Jf, Forti, S, Fuentes‐Perez, JM, Gálvez‐Romero, JL, Gamkrelidze, A, Garcia‐Aymerich, Judith, García‐Cobas, CY, Garcia‐Cruz, MH, Gemicioğlu, B, Genova, S, Christoff, G, Gereda, JE, Van Wijk, R Gerth, Gomez, RM, Gómez‐Vera, J, González Diaz, S, Gotua, M., Grisle, I, Guidacci, M, Guldemond, NA, Gutter, Z, Guzmán, MA, Haahtela, T., Hajjam, J, Hernández, L, Hourihane, JO’B, Huerta‐Villalobos, YR, Humbert, M., Iaccarino, G., Illario, M, Ispayeva, Z, Ivancevich, JC, Jares, EJ, Jassem, E, Johnston, Sl, Joos, G, Jung, KS, Just, J., Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, AF, Karjalainen, J, Kardas, P, Keil, T, Keith, PK, Khaitov, M, Khaltaev, N, Kleine‐Tebbe, J, Kowalski, Ml, Kuitunen, M, Kull, I., Kupczyk, M, Krzych‐Fałta, E, Lacwik, P, Larenas‐Linnemann, Désirée, Laune, D., Lauri, D, Lavrut, J, Le, LTT, Lessa, M, Levato, G, Li, J., Lieberman, P, Lipiec, A, Lipworth, B, Lodrup Carlsen, KC, Louis, R, Lourenço, O, Luna‐Pech, JA, Magnan, A., Mahboub, B, Maier, D., Mair, A, Majer, I, Malva, J, Mandajieva, E, Manning, P, De Manuel Keenoy, E, Marshall, GD, Masjedi, MR, Maspero, JF, Mathieu‐Dupas, E, Matta Campos, JJ, Matos, AL, Maurer, M, Mavale‐Manuel, S, Mayora, O, Meco, C, Medina‐Avalos, MA, Melo‐Gomes, E, Meltzer, EO, Menditto, E., Miculinic, N, Mihaltan, F., Milenkovic, B, Moda, G, Mogica‐Martinez, MD, Mohammad, Y, Momas, I., Montefort, S, Mora Bogado, D, Morais‐Almeida, M, Morato‐Castro, FF, Mota‐Pinto, A, Moura Santo, P, Münter, L, Muraro, A, Murray, R, Naclerio, R., Nadif, R., Nalin, M, Napoli, L, Namazova‐Baranova, L, Neffen, H, Niedeberger, V, Nekam, K, Neou, A, Nieto, A, Nogueira‐Silva, L, Nogues, M., Novellino, E, Nyembue, TD, O’Hehir, RE, Odzhakova, C, Ohta, K., Okamoto, Y., Okubo, K, Onorato, GL, Ortega Cisneros, M, Ouédraogo, S., Pali‐Schöll, I, Palkonen, S, Panzner, P, Papadopoulos, NG, Park, HS, Papi, A., Passalacqua, G, Paulino, E, Pawankar, R, Pedersen, S, Pépin, JL, Pereira, AM, Persico, M, PHILLIPS, J, Picard, R., Pigearias, B, Pin, I., Pitsios, C., Plavec, D, Pohl, W, Popov, TA, Portejoie, F., Potter, P, Pozzi, AC, Price, D, Prokopakis, EP, Puy, R, Pugin, B, Pulido Ross, RE, Przemecka, M, Rabe, KF, Raciborski, F, Rajabian‐Soderlund, R, Reitsma, S, Ribeirinho, I, Rimmer, J, Rivero‐Yeverino, D, Rizzo, JA, Rizzo, MC, Robalo‐Cordeiro, C, Rodenas, F, Rodo, X, Rodriguez Gonzalez, M, Rodriguez‐Mañas, L, Rolland, C, Rodrigues Valle, S, Roman Rodriguez, M., Romano, A, Rodriguez‐Zagal, E, Rolla, G, Roller‐Wirnsberger, RE, Romano, M, Rosado‐Pinto, J, Rosario, N., Rottem, M, Ryan, D, Sagara, H, Salimäki, J, Sanchez‐Borges, M, Sastre‐Dominguez, J, Scadding, GK, Schunemann, HJ, Scichilone, N, Schmid‐Grendelmeier, P, Sarquis Serpa, F, Shamai, S., Sheikh, A., Sierra, M, Simons, FER, Siroux, V., Sisul, JC, Skrindo, I, Solé, D, Somekh, D, Sondermann, M, Sooronbaev, T, Sova, M, Sorensen, M, Sorlini, M, Spranger, O, Stellato, C, Stelmach, R, Stukas, R, Sunyer, J., Strozek, J, Szylling, A, Tebyriçá, JN, Thibaudon, M., To, T., Todo‐Bom, A, Tomazic, PV, Toppila‐Salmi, Sanna, Trama, U, Triggiani, M, Suppli Ulrik, C, Urrutia‐Pereira, M, Valenta, R, Valero, A., Valiulis, A., Valovirta, E., van Eerd, M, Van Ganse, E., van Hage, M, Vandenplas, O, Ventura, MT, Vezzani, G, Vasankari, T, Vatrella, A., Verissimo, MT, Viart, F., Viegi, G., Vicheva, D, Vontetsianos, T, Wagenmann, M, Walker, S, Wallace, D, Wang, DY, Waserman, S., Werfel, T, Westman, M, Wickman, M., Williams, DM, Williams, S, Wilson, N, Wright, J, Wroczynski, P, Yakovliev, P, Yawn, BP, Yiallouros, PK, Yusuf, OM, Zar, HJ, Zhang, L., Zhong, N, Zernotti, ME, Zhanat, I, Zidarn, M, Zuberbier, T., Zubrinich, C, Zurkuhlen, A, Mercier, Jacques, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, KYomed INNOV, Ghent University Hospital, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Odense University Hospital [Odense, Denmark], Woolcock Institute of Medical Research [Sydney], The University of Sydney, Vall d'Hebron University Hospital [Barcelona], ProAR - FMB, Federal University of Bahia School of Medicine, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), University Hospitals Leuven [Leuven], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], Clínica de Alergia- Asma y Pediatría, Hospital Medica Sur, Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Medical University of Warsaw - Poland, Department of Pulmonology, Manisa Celal Bayar University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Aix Marseille Université (AMU), Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), iQ4U consultants Ltd, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Department of Respiratory Medicine and Allergy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, CHU Montpellier, Laboratoire National Henri Becquerel (LNHB), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Département d'instrumentation Numérique (DIN (CEA-LIST)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Région Languedoc-Roussillon-Midi-Pyrénées, University of South Florida [Tampa] (USF), Chinese academy of sciences Sanya, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Laboratoire de Génie Informatique et d'Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Paediatrics, UCB Pharma, Colombes, CHU Strasbourg, Università degli Studi di Salerno = University of Salerno (UNISA), Hôpital Foch [Suresnes], Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Informatique, Image, Intelligence Artificielle (I3A), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IMT - MINES ALES (IMT - MINES ALES), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Center for Turbulence Research [Stanford] (CTR), Stanford University, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biomax Informatics AG, 'Federico II' University of Naples Medical School, Pneumology Department, Marius Nasta Institute of Pneumology, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Johns Hopkins University School of Medicine [Baltimore], CARSAT-LR, Montpellier, Dept. of Electronic Engineering, Chubu University, Institute for Solid State Physics, The University of Tokyo (UTokyo), Respiratory Medicine, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, University of Cyprus [Nicosia] (UCY), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Computer Science [Haifa], University of Haifa [Haifa], University of Edinburgh, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Réseau National de Surveillance Aérobiologique (RNSA), CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, University of Turku, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), ASA (Advanced Solution Accelerator) (Data management : Développement Back-Office, hébergement…), 34830 Jacou, Consiglio nazionale delle ricerche, Instituto di fisiologia clinica, McMaster University [Hamilton, Ontario], Department of Molecular Medicine and Surgery, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), University Hospital of Cologne [Cologne], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ISGlobal, Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda Porto, Porto, Portugal, KYomed INNOV, Montpellier, France, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, MACVIA-France, Montpellier, France, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, Australia, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Salvador, Brazil, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, Euforea, Brussels, Belgium, Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania, Clinic of Chest diseases and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, Pasteur Institute, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Department of General ORL, H&NS, Medical University of Graz, Graz, Austria, Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, University Hospital, Montpellier, France, INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität, Marburg, Germany, Universidade do Porto, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur [Paris], University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli Studi di Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, University of Helsinki, Service d'Allergologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bedard, A., Anto, J. M., Fonseca, J. A., Arnavielhe, S., Bachert, C., Bedbrook, A., Bindslev-Jensen, C., Bosnic-Anticevich, S., Cardona, V., Cruz, A. A., Fokkens, W. J., Garcia-Aymerich, J., Hellings, P. W., Ivancevich, J. C., Klimek, L., Kuna, P., Kvedariene, V., Larenas-Linnemann, D., Melen, E., Monti, R., Mosges, R., Mullol, J., Papadopoulos, N. G., Pham-Thi, N., Samolinski, B., Tomazic, P. V., Toppila-Salmi, S., Ventura, M. T., Yorgancioglu, A., Bousquet, J., Pfaar, O., Basagana, X., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Bateman, E. D., Bedolla-Barajas, M., Bewick, M., Beghe, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Bialoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabanas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Constantinidis, J., Correia de Sousa, J., Cortes-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Czarlewski, W., Dahlen, S. E., D'Amato, G., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fatima Emerson, M., De Feo, G., De Vries, G., De Martino, B., Motta Rubini, N. P., Deleanu, D., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Galvez-Romero, J. L., Gamkrelidze, A., Garcia-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioglu, B., Genova, S., Christoff, G., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gomez-Vera, J., Gonzalez Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzman, M. A., Haahtela, T., Hajjam, J., Hernandez, L., Hourihane, J. O. '. B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kull, I., Kupczyk, M., Krzych-Falta, E., Lacwik, P., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenco, O., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Meco, C., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Munter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Scholl, I., Palkonen, S., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pepin, J. L., Pereira, A. M., Persico, M., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Manas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimaki, J., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Sarquis Serpa, F., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Sole, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyrica, J. N., Thibaudon, M., To, T., Todo-Bom, A., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hage, M., Vandenplas, O., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zhanat, I., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universidade do Porto [Porto], Kyomed, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Universitat Pompeu Fabra [Barcelona], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology [Graz, Austria], Medical University Graz, University of Zürich [Zürich] (UZH), National Institute for Nuclear Physics (INFN), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), University of South Florida (USF), University of Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey, Institut Mines-Télécom [Paris] (IMT), Center for Turbulence Research (CTR), Stanford University [Stanford], Service d'allergologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo, Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), RNSA, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bedard A., Anto J.M., Fonseca J.A., Arnavielhe S., Bachert C., Bedbrook A., Bindslev-Jensen C., Bosnic-Anticevich S., Cardona V., Cruz A.A., Fokkens W.J., Garcia-Aymerich J., Hellings P.W., Ivancevich J.C., Klimek L., Kuna P., Kvedariene V., Larenas-Linnemann D., Melen E., Monti R., Mosges R., Mullol J., Papadopoulos N.G., Pham-Thi N., Samolinski B., Tomazic P.V., Toppila-Salmi S., Ventura M.T., Yorgancioglu A., Bousquet J., Pfaar O., Basagana X., Aberer W., Agache I., Akdis C.A., Akdis M., Aliberti M.R., Almeida R., Amat F., Angles R., Annesi-Maesano I., Ansotegui I.J., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Bateman E.D., Bedolla-Barajas M., Bewick M., Beghe B., Bel E.H., Bergmann K.C., Bennoor K.S., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blain H., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bosse I., Bouchard J., Boulet L.P., Bourret R., Bousquet P.J., Braido F., Briedis V., Brightling C.E., Brozek J., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillaud D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Canonica G.W., Carlsen K.H., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Casale T., Castellano G., Cecchi L., Cepeda A.M., Chavannes N.H., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., Constantinidis J., Correia de Sousa J., Cortes-Grimaldo R.M., Corti F., Costa E., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Czarlewski W., Dahlen S.E., D'Amato G., Dario C., da Silva J., Dauvilliers Y., Darsow U., De Blay F., De Carlo G., Dedeu T., de Fatima Emerson M., De Feo G., De Vries G., De Martino B., Motta Rubini N.P., Deleanu D., Denburg J.A., Devillier P., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Dubakiene R., Durham S.R., Du Toit G., Dykewicz M.S., El-Gamal Y., Eklund P., Eller E., Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Fontaine J.F., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., Christoff G., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Guzman M.A., Haahtela T., Hajjam J., Hernandez L., Hourihane J.O.'.B., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Illario M., Ispayeva Z., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu A.F., Karjalainen J., Kardas P., Keil T., Keith P.K., Khaitov M., Khaltaev N., Kleine-Tebbe J., Kowalski M.L., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Laune D., Lauri D., Lavrut J., Le L.T.T., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Lourenco O., Luna-Pech J.A., Magnan A., Mahboub B., Maier D., Mair A., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Meco C., Medina-Avalos M.A., Melo-Gomes E., Meltzer E.O., Menditto E., Mercier J., Miculinic N., Mihaltan F., Milenkovic B., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Mora Bogado D., Morais-Almeida M., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Murray R., Naclerio R., Nadif R., Nalin M., Napoli L., Namazova-Baranova L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Novellino E., Nyembue T.D., O'Hehir R.E., Odzhakova C., Ohta K., Okamoto Y., Okubo K., Onorato G.L., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Palkonen S., Panzner P., Park H.S., Papi A., Passalacqua G., Paulino E., Pawankar R., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Plavec D., Pohl W., Popov T.A., Portejoie F., Potter P., Pozzi A.C., Price D., Prokopakis E.P., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Rajabian-Soderlund R., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rodriguez-Zagal E., Rolla G., Roller-Wirnsberger R.E., Romano M., Rosado-Pinto J., Rosario N., Rottem M., Ryan D., Sagara H., Salimaki J., Sanchez-Borges M., Sastre-Dominguez J., Scadding G.K., Schunemann H.J., Scichilone N., Schmid-Grendelmeier P., Sarquis Serpa F., Shamai S., Sheikh A., Sierra M., Simons F.E.R., Siroux V., Sisul J.C., Skrindo I., Sole D., Somekh D., Sondermann M., Sooronbaev T., Sova M., Sorensen M., Sorlini M., Spranger O., Stellato C., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., To T., Todo-Bom A., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., Valero A., Valiulis A., Valovirta E., van Eerd M., van Ganse E., van Hage M., Vandenplas O., Vezzani G., Vasankari T., Vatrella A., Verissimo M.T., Viart F., Viegi G., Vicheva D., Vontetsianos T., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Werfel T., Westman M., Wickman M., Williams D.M., Williams S., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zhang L., Zhong N., Zernotti M.E., Zhanat I., Zidarn M., Zuberbier T., Zubrinich C., and Zurkuhlen A.
Subjects: 0301 basic medicine, SYMPTOMS, Smart phone, Allergy, Escala visual analógica, INNOVATION, [SDV]Life Sciences [q-bio], Medical and Health Sciences, Correlation, visual analogue scale, 0302 clinical medicine, Quality of life, Visual analogue scale, QUALITY-OF-LIFE, Màscares, Immunology and Allergy, score, Nose, Rinitis, Rhinitis, PRODUCTIVITY COSTS, asthma, MASK, rhinitis, Score, Explained variation, Response Variability, Mobile Applications, ALLERGIC RHINITIS, rhiniti, medicine.anatomical_structure, TRIALS, Rinite, 1107 Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Smartphone, medicine.medical_specialty, MASK study group, Immunology, MACVIA-ARIA, 03 medical and health sciences, Allergic, medicine, Humans, TECHNOLOGY, IMMUNOTHERAPY, Asma, Asthma, business.industry, Rhinitis, Allergic, medicine.disease, RHINOCONJUNCTIVITIS, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2020
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16. NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis

Author: Joan Roselló-Catafau, Arnau Panisello-Roselló, Emma Folch-Puy, Ana Ferrero-Andrés, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ferrero-Andrés, Ana [0000-0002-4874-7109], Folch-Puy, Emma [0000-0002-6277-9027], Ferrero-Andrés, Ana, and Folch-Puy, Emma
Subjects: Inflammasomes, Indomethacin, Interleukin-1beta, Anti-Inflammatory Agents, Review, Pyrin domain, Inflammasome, lcsh:Chemistry, Pathogenesis, Glyburide, SIRS, lcsh:QH301-705.5, Spectroscopy, integumentary system, Interleukin-18, Interleukin, General Medicine, Computer Science Applications, Acute pancreatitis, medicine.symptom, Signal Transduction, medicine.drug, Inflammation, Catalysis, Inorganic Chemistry, Immune system, NLRP3, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, Physical and Theoretical Chemistry, Pancreas, Withanolides, Molecular Biology, DAMPs, business.industry, Interleukins, Organic Chemistry, medicine.disease, Toll-Like Receptor 3, Gene Expression Regulation, lcsh:Biology (General), lcsh:QD1-999, Pancreatitis, Myeloid Differentiation Factor 88, Immunology, business
Abstract: The discovery of inflammasomes has enriched our knowledge in the pathogenesis of multiple inflammatory diseases. The NLR pyrin domain-containing protein 3 (NLRP3) has emerged as the most versatile and well-characterized inflammasome, consisting of an intracellular multi-protein complex that acts as a central driver of inflammation. Its activation depends on a tightly regulated two-step process, which includes a wide variety of unrelated stimuli. It is therefore not surprising that the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Inflammasome-mediated inflammation has become increasingly important in acute pancreatitis, an inflammatory disorder of the pancreas that is one of the fatal diseases of the gastrointestinal tract. This review presents an update on the progress of research into the contribution of the NLRP3 inflammasome to acute pancreatic injury, examining the mechanisms of NLRP3 activation by multiple signaling events, the downstream interleukin 1 family of cytokines involved and the current state of the literature on NLRP3 inflammasome-specific inhibitors., This study was supported by grant from Ministerio de Ciencia e Innovación, reference PID2019-104130RB-I00 awarded to E.F.-P.
Published: 2020

17. Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Author: Bousquet J., Anto J. M., Iaccarino G., Czarlewski W., Haahtela T., Anto A., Akdis C. A., Blain H., Canonica G. W., Cardona V., Cruz A. A., Illario M., Ivancevich J. C., Jutel M., Klimek L., Kuna P., Laune D., Larenas-Linnemann D., Mullol J., Papadopoulos N. G., Pfaar O., Samolinski B., Valiulis A., Yorgancioglu A., Zuberbier T., Abdul Latiff A. H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis C., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Aldrey-Palacios O., Alvarez Cuesta E., Alzaabi A., Amad S., Ambrocio G., Annesi-Maesano I., Ansotegui I., Anto J., Arshad H., Artesani M. C., Asayag E., Avolio F., Azhari K., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Bateman E. D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bel E., Ben Kheder A., Benson M., Berghea C., Bergmann K. -C., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N., Bilo M. B., Bindslev-Jensen C., Bjermer L., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L. -P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C., Brozek J., Buhl R., Bumbacea R., Burguete Cabanas M. T., Bush A., Busse W. W., Buters J., Caballero-Fonseca F., Calderon M. A., Calvo M., Camargos P., Camuzat T., Cano A., Capriles-Hulett A., Caraballo L., Carlsen K. -H., Caro J., Carr W., Carreon-Asuncion F., Carriazo A. M., Casale T., Castor M. A., Castro E., Cecchi L., Cepeda Sarabia A., Chandrasekharan R., Chang Y. -S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N. H., Chen Y., Cheng L., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D. K., Chua A., Chuchalin A., Chung K. 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A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puy R., Rabe K., Raciborski F., Ramos J., Recto M. T., Reda S. M., Regateiro F., Reider N., Reitsma S., Repka-Ramirez S., Rimmer J., Rivero Yeverino D., Rizzo J. A., Robalo-Cordeiro C., Roberts G., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rottem M., Rouadi P., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L. T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Salina H., Samitas K., Sanchez Coronel M. G., Sanchez-Borges M., Sanchez-Lopez J., Sarafoleanu C., Sarquis Serpa F., Sastre-Dominguez J., Scadding G., Scheire S., Schmid-Grendelmeier P., Schuhl J. F., Schunemann H., Schvalbova M., Scichilone N., Sepulveda C., Serrano E., Sheikh A., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E. F., Sisul J. 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Y., Waserman S., Wickman M., Williams S., Williams D., Wilson N., Woo K., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y. Y., Yawn B., Yiallouros P., Yoshihara S., Young I., Yusuf O. B., Zaidi A., Zaitoun F., Zar H., Zernotti M., Zhang L., Zhong N., Zidarn M., Zubrinich C., UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Bousquet J., Anto J.M., Iaccarino G., Czarlewski W., Haahtela T., Anto A., Akdis C.A., Blain H., Canonica G.W., Cardona V., Cruz A.A., Illario M., Ivancevich J.C., Jutel M., Klimek L., Kuna P., Laune D., Larenas-linnemann D., Mullol J., Papadopoulos N.G., Pfaar O., Samolinski B., Valiulis A., Yorgancioglu A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis C., Akdis M., Al-Ahmad M., Bassam A.A.-Z., Aldrey-Palacios O., Cuesta E.A., Alzaabi A., Amad S., Ambrocio G., Annesi-Maesano I., Ansotegui I., Anto J., Arshad H., Artesani M.C., Asayag E., Avolio F., Azhari K., Baiardini I., Bajrovic N., Bakakos P., Mongono S.B., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Bateman E.D., Battur L., Bedbrook A., Barajas M.B., Beghe B., Bel E., Kheder A.B., Benson M., Berghea C., Bergmann K.-C., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N., Bilo M.B., Bindslev-Jensen C., Bjermer L., Marciniak M.B., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C., Brozek J., Buhl R., Bumbacea R., Cabanas M.T.B., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Cano A., Capriles-Hulett A., Caraballo L., Carlsen K.-H., Caro J., Carr W., Carreon-Asun-cion F., Carriazo A.M., Casale T., Castor M.A., Castro E., Cecchi L., Sarabia A.C., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chen Y., Cheng L., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho 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M., Guldemond N., Gutter Z., Guzman A., Halloum R., Hamelmann E., Hammadi S., Harvey R., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Velazquez L.H., Hew M., Hossny E., Howarth P., Hrubisko M., Villalobos Y.R.H., Humbert M., Hyland M., Ibrahim M., Ilyina N., Irani C., Ispayeva Z., Jares E., Jarvis D., Jassem E., Jenko K., Uscanga R.D.J., Johnston S., Joos G., Jost M., Julge K., Jung K.-S., Just J., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kazi B., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kleine-Tebbe J., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Jeverica A.K., Kosnik M., Kostov K.V., Kowalski M.L., Kralimarkova T., Vrscaj K.K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kull I., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Lane S., Larenas-Linnemann D., Latiff A., Lau S., Lavrut J., Le L., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup 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Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Paggiaro P.L., Pagkalos A., Palaniappan S.P., Pali-Scholl I., Palkonen S., Palmer S., Bunu C.P., Panzner P., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pereira A., Perez T., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Pitsios K., Plavec D., Poethig D., Pohl W., Susic A.P., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puy R., Rabe K., Raciborski F., Ramos J., Recto M.T., Reda S.M., Regateiro F., Reider N., Reitsma S., Repka-Ramirez S., Rimmer J., Yeverino D.R., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Roche N., Gonzalez M.R., Zagal E.R., Rolland C., Roller-Wirns-berger R., Rodriguez M.R., Romano A., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rottem M., Rouadi P., Rovina N., Sinur I.R., Ruiz M., Segura L.T.R., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Salina H., Samitas K.-N., Coronel M.G.S., Sanchez-Borges M., Sanchez-Lopez J., Sarafoleanu C., Serpa F.S., Sastre-Dominguez J., Scadding G., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Scichilone N., Sepulveda C., Serrano E., Sheikh A., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Kosak T.S., Sole D., Sooronbaev T., Soto-Martinez M., Sova M., Spertini F., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Sterk P., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Barata L.T., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tattersall J., Teixeira M.D.C., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Toppila-Salmi S., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Ulmeanu R., Urbancic J., Pereira M.U., Vachova M., Valdes F., Valenta R., Rostan M.V., Valero A., Vallianatou M., Valovirta E., Eerd M.V., Ganse E.V., Hage M., Vandenplas O., Vasankari T., Vassileva D., Ventura T., Vera-Munoz C., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Hertzen L.V., Vontetsianos T., Vourdas D., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Wickman M., Williams S., Williams D., Wilson N., Woo K., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yawn B., Yiallouros P., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zar H., Zernotti M., Zhang L., Zhong N., Zidarn M., Zubrinich C., Dubakienė, Rūta, Ėmužytė, Regina, Kvedarienė, Violeta, Bousquet, J., Anto, J. M., Iaccarino, G., Czarlewski, W., Haahtela, T., Anto, A., Akdis, C. A., Blain, H., Canonica, G. W., Cardona, V., Cruz, A. A., Illario, M., Ivancevich, J. C., Jutel, M., Klimek, L., Kuna, P., Laune, D., Larenas-Linnemann, D., Mullol, J., Papadopoulos, N. G., Pfaar, O., Samolinski, B., Valiulis, A., Yorgancioglu, A., Zuberbier, T., Abdul Latiff, A. H., Abdullah, B., Aberer, W., Abusada, N., Adcock, I., Afani, A., Agache, I., Aggelidis, X., Agustin, J., Akdis, C., Akdis, M., Al-Ahmad, M., Al-Zahab Bassam, A., Aldrey-Palacios, O., Alvarez Cuesta, E., Alzaabi, A., Amad, S., Ambrocio, G., Annesi-Maesano, I., Ansotegui, I., Anto, J., Arshad, H., Artesani, M. C., Asayag, E., Avolio, F., Azhari, K., Baiardini, I., Bajrovic, N., Bakakos, P., Bakeyala Mongono, S., Balotro-Torres, C., Barba, S., Barbara, C., Barbosa, E., Barreto, B., Bartra, J., Bateman, E. D., Battur, L., Bedbrook, A., Bedolla Barajas, M., Beghe, B., Bel, E., Ben Kheder, A., Benson, M., Berghea, C., Bergmann, K. -C., Bernstein, D., Bewick, M., Bialek, S., Bialoszewski, A., Bieber, T., Billo, N., Bilo, M. B., Bindslev-Jensen, C., Bjermer, L., Bochenska Marciniak, M., Bond, C., Boner, A., Bonini, M., Bonini, S., Bosnic-Anticevich, S., Bosse, I., Botskariova, S., Bouchard, J., Boulet, L. -P., Bourret, R., Bousquet, P., Braido, F., Briggs, A., Brightling, C., Brozek, J., Buhl, R., Bumbacea, R., Burguete Cabanas, M. T., Bush, A., Busse, W. W., Buters, J., Caballero-Fonseca, F., Calderon, M. A., Calvo, M., Camargos, P., Camuzat, T., Cano, A., Capriles-Hulett, A., Caraballo, L., Carlsen, K. -H., Caro, J., Carr, W., Carreon-Asuncion, F., Carriazo, A. M., Casale, T., Castor, M. A., Castro, E., Cecchi, L., Cepeda Sarabia, A., Chandrasekharan, R., Chang, Y. -S., Chato-Andeza, V., Chatzi, L., Chatzidaki, C., Chavannes, N. H., Chen, Y., Cheng, L., Chivato, T., Chkhartishvili, E., Christoff, G., Chrystyn, H., Chu, D. K., Chua, A., Chuchalin, A., Chung, K. F., Ciceran, A., Cingi, C., Ciprandi, G., Cirule, I., Coelho, A. C., Constantinidis, J., Correia De Sousa, J., Costa, E., Costa, D., Costa Dominguez, M. D. C., Coste, A., Cox, L., Cullen, J., Custovic, A., Cvetkovski, B., D'Amato, G., Da Silva, J., Dahl, R., Dahlen, S. -E., Daniilidis, V., Darjazini Nahhas, L., Darsow, U., De Blay, F., De Guia, E., De Los Santos, C., De Manuel Keenoy, E., De Vries, G., Deleanu, D., Demoly, P., Denburg, J., Devillier, P., Didier, A., Dimou, M., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., Dominguez Silva, M. G., Douagui, H., Douladiris, N., Doulaptsi, M., Dray, G., Dubakiene, R., Durham, S., Dykewicz, M., Ebo, D., Edelbaher, N., Eklund, P., El-Gamal, Y., El-Sayed, Z. A., El-Sayed, S. S., El-Seify, M., Emuzyte, R., Enecilla, L., Espinoza, H., Espinoza Contreras, J. G., Farrell, J., Fernandez, L., Fink Wagner, A., Fiocchi, A., Fokkens, W. J., Fontaine, J. -F., Forastiere, F., Fuentes Perez, J. M., Gaerlan-Resureccion, E., Gaga, M., Galvez Romero, J. L., Gamkrelidze, A., Garcia, A., Garcia Cobas, C. Y., Garcia Cruz, M. D. L. L. H., Gayraud, J., Gemicioglu, B., Genova, S., Gereda, J., Gerth Van Wijk, R., Gomez, M., Gonzalez Diaz, S., Gotua, M., Grigoreas, C., Grisle, I., Guidacci, M., Guldemond, N., Gutter, Z., Guzman, A., Halloum, R., Hamelmann, E., Hammadi, S., Harvey, R., Heinrich, J., Hejjaoui, A., Hellquist-Dahl, B., Hernandez Velazquez, L., Hew, M., Hossny, E., Howarth, P., Hrubisko, M., Huerta Villalobos, Y. R., Humbert, M., Hyland, M., Ibrahim, M., Ilyina, N., Irani, C., Ispayeva, Z., Jares, E., Jarvis, D., Jassem, E., Jenko, K., Jimeneracruz Uscanga, R. D., Johnston, S., Joos, G., Jost, M., Julge, K., Jung, K. -S., Just, J., Kaidashev, I., Kalayci, O., Kalyoncu, F., Kapsali, J., Kardas, P., Karjalainen, J., Kasala, C. A., Katotomichelakis, M., Kazi, B., Keil, T., Keith, P., Khaitov, M., Khaltaev, N., Kim, Y. -Y., Kleine-Tebbe, J., Koffi N'Goran, B., Kompoti, E., Kopac, P., Koppelman, G., Koren Jeverica, A., Kosnik, M., Kostov, K. V., Kowalski, M. L., Kralimarkova, T., Kramer Vrscaj, K., Kraxner, H., Kreft, S., Kritikos, V., Kudlay, D., Kull, I., Kupczyk, M., Kvedariene, V., Kyriakakou, M., Lalek, N., Lane, S., Latiff, A., Lau, S., Lavrut, J., Le, L., Lessa, M., Levin, M., Li, J., Lieberman, P., Liotta, G., Lipworth, B., Liu, X., Lobo, R., Lodrup Carlsen, K. C., Lombardi, C., Louis, R., Loukidis, S., Lourenco, O., Luna Pech, J. A., Madjar, B., Magnan, A., Mahboub, B., Mair, A., Mais, Y., Maitland Van Der Zee, A. -H., Makela, M., Makris, M., Malling, H. -J., Mandajieva, M., Manning, P., Manousakis, M., Maragoudakis, P., Marshall, G., Martinsmartins, P., Masjedi, M. R., Maspero, J. F., Matta Campos, J. J., Maurer, M., Mavale-Manuel, S., Meco, C., Melen, E., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Menzies-Gow, A., Merk, H., Michel, J. -P., Miculinic, N., Midao, L., Mihaltan, F., Mikael, K., Mikos, N., Milenkovic, B., Mitsias, D., Moalla, B., Moda, G., Mogica Martinez, M. D., Mohammad, Y., Moin, M., Molimard, M., Momas, I., Monaco, A., Montefort, S., Mora, D., Morais-Almeida, M., Mosges, R., Mostafa, B. E., Munter, L., Muraro, A., Murray, R., Mustakov, T., Naclerio, R., Nadif, R., Nakonechna, A., Namazova-Baranova, L., Navarro-Locsin, G., Neffen, H., Nekam, K., Neou, A., Nicod, L., Niederberger-Leppin, V., Niedoszytko, M., Nieto, A., Novellino, E., Nunes, E., Nyembue, D., O'Hehir, R., Odjakova, C., Ohta, K., Okamoto, Y., Okubo, K., Oliver, B., Onorato, G. L., Orru, M. P., Ouedraogo, S., Ouoba, K., Paggiaro, P. L., Pagkalos, A., Palaniappan, S. P., Pali-Scholl, I., Palkonen, S., Palmer, S., Panaitescu Bunu, C., Panzner, P., Papanikolaou, V., Papi, A., Paralchev, B., Paraskevopoulos, G., Park, H. S., Passalacqua, G., Patella, V., Pavord, I., Pawankar, R., Pedersen, S., Peleve, S., Pereira, A., Perez, T., Pham-Thi, N., Pigearias, B., Pin, I., Piskou, K., Pitsios, C., Pitsios, K., Plavec, D., Poethig, D., Pohl, W., Poplas Susic, A., Popov, T. A., Portejoie, F., Potter, P., Poulsen, L., Prados-Torres, A., Prarros, F., Price, D., Prokopakis, E., Puy, R., Rabe, K., Raciborski, F., Ramos, J., Recto, M. T., Reda, S. M., Regateiro, F., Reider, N., Reitsma, S., Repka-Ramirez, S., Rimmer, J., Rivero Yeverino, D., Rizzo, J. A., Robalo-Cordeiro, C., Roberts, G., Roche, N., Rodriguez Gonzalez, M., Rodriguez Zagal, E., Rolland, C., Roller-Wirnsberger, R., Roman Rodriguez, M., Romano, A., Rombaux, P., Romualdez, J., Rosado-Pinto, J., Rosario, N., Rosenwasser, L., Rottem, M., Rouadi, P., Rovina, N., Rozman Sinur, I., Ruiz, M., Ruiz Segura, L. T., Ryan, D., Sagara, H., Sakai, D., Sakurai, D., Saleh, W., Salimaki, J., Salina, H., Samitas, K., Sanchez Coronel, M. G., Sanchez-Borges, M., Sanchez-Lopez, J., Sarafoleanu, C., Sarquis Serpa, F., Sastre-Dominguez, J., Scadding, G., Scheire, S., Schmid-Grendelmeier, P., Schuhl, J. F., Schunemann, H., Schvalbova, M., Scichilone, N., Sepulveda, C., Serrano, E., Sheikh, A., Shields, M., Shishkov, V., Siafakas, N., Simeonov, A., Simons, E. F., Sisul, J. C., Sitkauskiene, B., Skrindo, I., Soklic Kosak, T., Sole, D., Sooronbaev, T., Soto-Martinez, M., Sova, M., Spertini, F., Spranger, O., Stamataki, S., Stefanaki, L., Stellato, C., Stelmach, R., Sterk, P., Strandberg, T., Stute, P., Subramaniam, A., Suppli Ulrik, C., Sutherland, M., Sylvestre, S., Syrigou, A., Taborda Barata, L., Takovska, N., Tan, R., Tan, F., Tan, V., Tang, I. P., Taniguchi, M., Tannert, L., Tattersall, J., Teixeira, M. D. C., Thijs, C., Thomas, M., To, T., Todo-Bom, A. M., Togias, A., Tomazic, P. -V., Toppila-Salmi, S., Toskala, E., Triggiani, M., Triller, N., Triller, K., Tsiligianni, I., Ulmeanu, R., Urbancic, J., Urrutia Pereira, M., Vachova, M., Valdes, F., Valenta, R., Valentin Rostan, M., Valero, A., Vallianatou, M., Valovirta, E., Van Eerd, M., Van Ganse, E., Van Hage, M., Vandenplas, O., Vasankari, T., Vassileva, D., Ventura, M. T., Vera-Munoz, C., Vicheva, D., Vichyanond, P., Vidgren, P., Viegi, G., Vogelmeier, C., Von Hertzen, L., Vontetsianos, T., Vourdas, D., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Wickman, M., Williams, S., Williams, D., Wilson, N., Woo, K., Wright, J., Wroczynski, P., Xepapadaki, P., Yakovliev, P., Yamaguchi, M., Yan, K., Yap, Y. Y., Yawn, B., Yiallouros, P., Yoshihara, S., Young, I., Yusuf, O. B., Zaidi, A., Zaitoun, F., Zar, H., Zernotti, M., Zhang, L., Zhong, N., Zidarn, M., Zubrinich, C., University of Zurich, Bousquet, Jean, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), 'Federico II' University of Naples Medical School, Medical Consulting Czarlewski, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Euromov (EuroMov), Université de Montpellier (UM), IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy., Vall d'Hebron University Hospital [Barcelona], ProAR – Nucleo de Excelencia em Asma, Universidade Federal da Bahia (UFBA), Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Division for Health Innovation, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Wrocław Medical University, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Barlicki University Hospital, KYomed INNOV [Montpellier], Hospital Medica Sur [Mexico City, Mexico], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, Philipps Universität Marburg = Philipps University of Marburg, Medical University of Warsaw - Poland, Vilnius University [Vilnius], Manisa Celal Bayar University, and Salvy-Córdoba, Nathalie
Subjects: BLOOD-PRESSURE, Review, Angiotensin-converting enzyme, Antioxidant, Coronavirus, Diet, Food, law.invention, Dietary interventions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 10183 Swiss Institute of Allergy and Asthma Research, law, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Mortality rate, 3. Good health, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2723 Immunology and Allergy, Angiotensin-converting enzyme, Antioxidant, Coronavirus, Diet, Food, Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Coronaviru, Immunology, Population, 610 Medicine & health, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, Environmental health, population, angiotensin-converting enzyme, Quarantine, education, 2403 Immunology, ANTIHYPERTENSIVE PEPTIDES, business.industry, RC581-607, GENE, POLYMORPHISM, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030228 respiratory system, 2740 Pulmonary and Respiratory Medicine, Immunologic diseases. Allergy, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Regional differences, Coronavirus Infections
Abstract: Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
Published: 2020
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18. Development of Coagulation Factor XII Antibodies for Inhibiting Vascular Device-Related Thrombosis

Author: David Gailani, Joseph J. Shatzel, Michael Wallisch, Tia C L Kohs, Sven R. Olson, Andras Gruber, Erik I. Tucker, Owen J. T. McCarty, Monica T. Hinds, Cristina Puy, Christina U. Lorentz, and Jennifer Johnson
Subjects: 0301 basic medicine, biology, business.industry, medicine.drug_class, Anticoagulant, 02 engineering and technology, Coagulation Factor XII, Pharmacology, 021001 nanoscience & nanotechnology, Monoclonal antibody, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Fibrin, 03 medical and health sciences, 030104 developmental biology, Coagulation, Modeling and Simulation, Hemostasis, biology.protein, Medicine, Original Article, Platelet, Thrombus, 0210 nano-technology, business
Abstract: INTRODUCTION: Vascular devices such as stents, hemodialyzers, and membrane oxygenators can activate blood coagulation and often require the use of systemic anticoagulants to selectively prevent intravascular thrombotic/embolic events or extracorporeal device failure. Coagulation factor (F)XII of the contact activation system has been shown to play an important role in initiating vascular device surface-initiated thrombus formation. As FXII is dispensable for hemostasis, targeting the contact activation system holds promise as a significantly safer strategy than traditional antithrombotics for preventing vascular device-associated thrombosis. OBJECTIVE: Generate and characterize anti-FXII monoclonal antibodies that inhibit FXII activation or activity. METHODS: Monoclonal antibodies against FXII were generated in FXII-deficient mice and evaluated for their binding and anticoagulant properties in purified and plasma systems, in whole blood flow-based assays, and in an in vivo non-human primate model of vascular device-initiated thrombus formation. RESULTS: A FXII antibody screen identified over 400 candidates, which were evaluated in binding studies and clotting assays. One non-inhibitor and six inhibitor antibodies were selected for characterization in functional assays. The most potent inhibitory antibody, 1B2, was found to prolong clotting times, inhibit fibrin generation on collagen under shear, and inhibit platelet deposition and fibrin formation in an extracorporeal membrane oxygenator deployed in a non-human primate. CONCLUSION: Selective contact activation inhibitors hold potential as useful tools for research applications as well as safe and effective inhibitors of vascular device-related thrombosis.
Published: 2020
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19. Evaluation of the Effect of Crosslinking Method of Poly(Vinyl Alcohol) Hydrogels on Thrombogenicity

Author: Novella M Bates, Patrick Jurney, Cristina Puy, Owen J. T. McCarty, and Monica T. Hinds
Subjects: Vinyl alcohol, Surface Properties, 0206 medical engineering, Biomedical Engineering, Sodium trimetaphosphate, Thrombogenicity, Biocompatible Materials, macromolecular substances, 02 engineering and technology, Factor XIIa, 030204 cardiovascular system & hematology, Prosthesis Design, Article, Fibrin, 03 medical and health sciences, chemistry.chemical_compound, Platelet Adhesiveness, 0302 clinical medicine, Polyphosphates, Freezing, Materials Testing, medicine, Humans, Thrombus, Blood Coagulation, integumentary system, biology, Fibrinolysis, Graft Occlusion, Vascular, technology, industry, and agriculture, Biomaterial, Hydrogels, Thrombosis, medicine.disease, 020601 biomedical engineering, Blood Vessel Prosthesis, Cross-Linking Reagents, Coagulation, Chemical engineering, chemistry, Glutaral, Polyvinyl Alcohol, Self-healing hydrogels, biology.protein, Cardiology and Cardiovascular Medicine
Abstract: PURPOSE-: Crosslinked poly(vinyl alcohol) (PVA) is a biomaterial that can be used for multiple cardiovascular applications. The success of implanted biomaterials is contingent on the properties of the material. A crucial consideration for blood-contacting devices is their potential to incite thrombus formation, which is dependent on the material surface properties. The goal of this study was to quantify the effect of different crosslinking methods of PVA hydrogels on in vitro thrombogenicity. METHODS-: PVA was manufactured using three different crosslinking methods: 30% sodium trimetaphosphate (STMP), three 24hr freeze-thaw cycles (FT), and 2% glutaraldehyde-crosslinked (GA) to produce STMP-PVA, FT-PVA and GA-PVA, respectively. Expanded polytetrafluoroethylene (ePTFE) was used as a clinical control. As markers of thrombus formation, the degree of coagulation factor (F) XII activation, fibrin formation, and platelet adhesion were measured. RESULTS-: The GA-PVA material increased FXII activation in the presence of cofactors compared to vehicle and increase platelet adhesion compared to other PVA surfaces. The STMP-PVA and FT-PVA materials had equivalent degrees of FXII activation, fibrin formation and platelet adhesion. CONCLUSION-: This work supports crosslinker dependent thrombogenicity of PVA hydrogels and advances our understanding of how the manufacturing of a PVA hydrogel affects its hemocompatibility.
Published: 2020
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20. A new minimally invasive porcine model for the study of intrahepatic bile duct dilatation

Author: Sara Puy, Manuel Perez-Miranda, Jorge Juan Olsina-Kissler, Alba Boldó, Gian Pier Protti, Dolores C. García-Olmo, Mario Alberto Gallardo, Pablo Muriel, Sergio Bazaga, and Jaume Tur-Martínez
Subjects: Laparoscopic surgery, Endoscopic ultrasound, medicine.medical_specialty, Swine, medicine.medical_treatment, Intrahepatic bile ducts, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, medicine.diagnostic_test, Bile duct, business.industry, Postoperative complication, Dilatation, Surgery, Biliary Tract Surgical Procedures, Bile Ducts, Intrahepatic, medicine.anatomical_structure, Common hepatic duct, 030220 oncology & carcinogenesis, Female, Laparoscopy, 030211 gastroenterology & hepatology, Bile Ducts, Ligation, business, Abdominal surgery
Abstract: Endoscopic ultrasound (EUS) procedures are becoming more frequent nowadays and novel techniques are on the rise. These procedures require high technical experience and complex endoscopic skills. The goal of this study was to develop a new minimally invasive animal model of bile duct dilatation in the pig, in order to offer a new tool for endoscopic and surgical therapy training and to test new therapeutic strategies. Twenty-five female pigs underwent laparoscopic surgery in order to perform a common hepatic duct ligation. A pre- and postoperative biochemical analyses were performed: glucose, albumin, total bilirubin (TBil), gamma glutamyl transferase (GGT), alkaline phosphatase, and alanine aminotransferase were measured. Surgical time and intra- and postoperative complications were registered. Five to six days after surgery, an EUS was performed to measure intrahepatic duct size (mm). Distance from the bile duct to the EUS transductor was also recorded (mm). T-student for quantitative variables was applied. Statistical significance was defined as p value ≤ 0.05. The mean surgical time was 29.5 ± 14.9 min. In five pigs (20%), some mild intraoperative problems occurred. A severe postoperative complication occurred in one animal (4%). No postoperative mortality was registered. Postoperative serum analyses showed an increase in total bilirubin (p = 0.005) and gamma glutamyl transferase levels (p = 0.001). Postoperative EUS showed dilatation of the intrahepatic bile duct in 76% of pigs, with a mean diameter of 9.6 ± 3.6 mm (distance from the gastric wall of 17.0 ± 6.4 mm). The surgical procedure described here is a safe technique to induce dilatation of the intrahepatic bile ducts in the pig, with a minimally invasive approach and a high efficacy rate. This animal model might be useful for EUS techniques training and for evaluating new therapeutic approaches.
Published: 2020
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21. Poster Abstracts

Author: Raquel G. Bardallo, Teresa Carbonell, R. G. Teixeira-Silva, Joan Roselló-Catafau, Emma Folch-Puy, and Arnau Panisello-Roselló
Subjects: Transplantation, business.industry, Fatty liver, Inflammation, Inflammasome, medicine.disease, Molecular biology, 3. Good health, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Preservation solutions, Immunology and Allergy, Pharmacology (medical), Graft survival, medicine.symptom, business, Liver preservation, 030217 neurology & neurosurgery, medicine.drug
Abstract: Resumen del trabajo presentado en el American Transplant Congress 2020, originalmente programado para tener lugar en Filadelfia (Estados Unidos), se convirtio en un Congreso Virtual debido a COVID-19, celebrado del 30 de mayo al 3 de junio de 2020
Published: 2020
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22. Antibody inhibition of contact factor XII reduces platelet deposition in a model of extracorporeal membrane oxygenator perfusion in nonhuman primates

Author: Monica T. Hinds, David Gailani, Marschelle R. Carris, Andras Gruber, Michael Wallisch, Jennifer Johnson, Hari Hara Sudhan Lakshmanan, Cristina Puy, Christina U. Lorentz, Erik I. Tucker, and Owen J. T. McCarty
Subjects: Oxygenators, medicine.medical_treatment, 030204 cardiovascular system & hematology, Pharmacology, Extracorporeal, Fibrin, 03 medical and health sciences, 0302 clinical medicine, Extracorporeal membrane oxygenation, medicine, Platelet, Platelet activation, thrombosis, 030304 developmental biology, blood platelet, 0303 health sciences, Factor XII, biology, Chemistry, factor XII, lcsh:RC633-647.5, Hematology, lcsh:Diseases of the blood and blood-forming organs, extracorporeal membrane oxygenation, 3. Good health, Hemostasis, biology.protein, hemostasis, Original Article, Original Articles: Thrombosis
Abstract: Background The contact factor XII (FXII) activates upon contact with a variety of charged surfaces. Activated FXII (FXIIa) activates factor XI, which activates factor IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both in vitro and in vivo rabbit models, components of medical devices, including extracorporeal oxygenators, are known to incite fibrin formation in a FXII‐dependent manner. Since FXII has no known role in hemostasis and its inhibition is therefore likely a safe antithrombotic approach, we investigated whether FXII inhibition also reduces accumulation of platelets in extracorporeal oxygenators. Objectives We aimed to determine the effect of FXII inhibition on platelet deposition in perfused extracorporeal membrane oxygenators in nonhuman primates. Methods A potent FXII neutralizing monoclonal antibody, 5C12, was administered intravenously to block contact activation in baboons. Extracorporeal membrane oxygenators were temporarily deployed into chronic arteriovenous access shunts. Radiolabeled platelet deposition in oxygenators was quantified in real time using gamma camera imaging. Biochemical assays were performed to characterize the method of action of 5C12. Results The anti‐FXII monoclonal antibody 5C12 recognized both the alpha and beta forms of human and baboon FXII by binding to the protease‐containing domain, and inhibited FXIIa activity. Administration of 5C12 to baboons reduced platelet deposition and fibrin formation in the extracorporeal membrane oxygenators, in both the presence and absence of systemic low‐dose unfractionated heparin. The antiplatelet dose of 5C12 did not cause measurable increases in template bleeding times in baboons. Conclusions FXII represents a possible therapeutic and safe target for reducing platelet deposition and fibrin formation during medical interventions including extracorporeal membrane oxygenation.
Published: 2020

23. CTG Expansion in the DMPK Gene: Semen Quality Assessment and Outcome of Preimplantation Genetic Diagnosis

Author: Jade Raad, Sophie Monnot, Laetitia Hesters, Nelly Frydman, Anne Mayeur, Julie Steffann, Alexandre Levy, and Vincent Puy
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Semen, Context (language use), Preimplantation genetic diagnosis, Biochemistry, Myotonin-Protein Kinase, Group B, 03 medical and health sciences, Semen quality, 0302 clinical medicine, Endocrinology, Pregnancy, Internal medicine, medicine, Humans, Myotonic Dystrophy, Ovarian Reserve, Preimplantation Diagnosis, Sperm motility, Retrospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, business.industry, Biochemistry (medical), Pregnancy Outcome, Prognosis, Spermatozoa, Sperm, Semen Analysis, Sperm Motility, Female, Trinucleotide Repeat Expansion, Live birth, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Context Myotonic dystrophy (DM) is an autosomal dominant disorder characterized mainly by myotonia but also by primary hypogonadism. No study has reported on fertility management of patients affected by DM type 1 (DM1). Objective This study investigates the impact of CTG repeats in the DMPK gene on semen quality and preimplantation genetic diagnosis (PGD) outcome. Design This is a monocentric retrospective observational study conducted from January 2003 to January 2019. Setting Antoine Béclère University Hospital, Clamart, France. Patients Three groups were compared in this study: male DM1 patients (Group A, n = 18), unaffected partners of DM1 female patients (Group B, n = 30), and proven fertile men (Group C, n = 33). Reproductive outcomes after PGD were compared between groups A and B. Results Sperm volume was reduced in group A (2.0 mL) when compared with groups B (3.0 mL; P < 0.01) and C (3.5 mL; P < 0.01). Progressive motility in raw sperm was also decreased in group A (30%) as compared to group C (40%; P < 0.01). The median number of progressive spermatozoa retrieved after sperm preparation was 2.7 million (M) in group A, which was significantly less than those of groups B (10.0 M; P < 0.01) and C (62.2 M; P < 0.01). Sperm motility was inversely correlated to the number of CTG repeats (Spearman r2 = 0.48, Pearson r2 = 0.35). Cumulative live birth rate per transfer was similar between groups, with 32.2% in group A versus 26.8% in group B. Conclusions As a precautionary measure, we advise physicians to perform regular monitoring of semen quality in affected males, which would allow sperm cryopreservation should semen parameters fall. PGD allows good reproductive outcomes without disease transmission.
Published: 2020
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24. Prevalence of Post COVID-19 Condition in Primary Care: A Cross Sectional Study

Author: Patricia Montenegro, Irene Moral, Alicia Puy, Esther Cordero, Noa Chantada, Lluis Cuixart, and Carlos Brotons
Subjects: general practice, Male, Primary Health Care, SARS-CoV-2, Health, Toxicology and Mutagenesis, public health, Public Health, Environmental and Occupational Health, COVID-19, post-acute COVID-19 syndrome, primary health care, Cross-Sectional Studies, Prevalence, Medicine, Humans, Female, Pandemics
Abstract: Background: The COVID-19 pandemic is a major challenge for health systems, citizens and policymakers worldwide. It is not known how many people are affected with longer term sequelae after acute COVID-19 and a wide range of prevalence estimates have been reported with a high heterogeneity between studies. Methods: We designed a cross-sectional study to estimate the prevalence of post COVID-19 conditions in a community setting. We selected a random sample of 579 individuals from three different primary health care centers and collected information on symptoms through a standardized questionnaire. Results: Our main study finding was an overall population prevalence of 14.34% (95% CI 11.58–17.46%) of post COVID-19. Only 9% of patients were hospitalized in our study. Prevalence was higher in women than men (15.63% versus 13.06%) and the most frequent persistent symptoms were fatigue (44.6%), smell impairment (27.7%) and dyspnea (24.09%). Conclusions: The prevalence of post COVID-19 condition was lower than expected according to other studies published in the literature. The prevalence was higher in women than men, and the most frequent persistent symptoms were fatigue, smell impairment, and dyspnea.
Published: 2021

25. Iron, Heme Synthesis and Erythropoietic Porphyrias: A Complex Interplay

Author: Hervé Puy, Caroline Schmitt, Arienne Mirmiran, Thibaud Lefebvre, Boualem Moulouel, Antoine Poli, and Laurent Gouya
Subjects: ferrochelatase, erythropoietic protoporphyria, Endocrinology, Diabetes and Metabolism, Congenital erythropoietic porphyria, Iron–sulfur cluster, Review, congenital erythropoietic porphyria, Biochemistry, Microbiology, chemistry.chemical_compound, iron-sulfur cluster, iron, medicine, protoporphyrin IX, Molecular Biology, Heme, Protoporphyrin IX, biology, Chemistry, ALAS2, Ferrochelatase, medicine.disease, hematopoiesis, QR1-502, biology.protein, Erythropoietic protoporphyria, Intracellular
Abstract: Erythropoietic porphyrias are caused by enzymatic dysfunctions in the heme biosynthetic pathway, resulting in porphyrins accumulation in red blood cells. The porphyrins deposition in tissues, including the skin, leads to photosensitivity that is present in all erythropoietic porphyrias. In the bone marrow, heme synthesis is mainly controlled by intracellular labile iron by post-transcriptional regulation: translation of ALAS2 mRNA, the first and rate-limiting enzyme of the pathway, is inhibited when iron availability is low. Moreover, it has been shown that the expression of ferrochelatase (FECH, an iron-sulfur cluster enzyme that inserts iron into protoporphyrin IX to form heme), is regulated by intracellular iron level. Accordingly, there is accumulating evidence that iron status can mitigate disease expression in patients with erythropoietic porphyrias. This article will review the available clinical data on how iron status can modify the symptoms of erythropoietic porphyrias. We will then review the modulation of heme biosynthesis pathway by iron availability in the erythron and its role in erythropoietic porphyrias physiopathology. Finally, we will summarize what is known of FECH interactions with other proteins involved in iron metabolism in the mitochondria.
Published: 2021

26. Identification of serotonin as a gut regulator of liver hepcidin expression

Author: P. Bonneau, J. R. Mathieu, Marc Foretz, D. Legeart, Luc Maroteaux, M. Djebar, T. Coman, Hervé Puy, A. Bigorgne, Julien Rossignol, Jean-Marie Launay, A. Cohen-Solal, Katell Peoc'h, Olivier Hermine, C. Peyssonnaux, M. Falabregue, and Francine Côté
Subjects: 0303 health sciences, medicine.medical_specialty, TPH1, Regulator, Iron deficiency, 030204 cardiovascular system & hematology, Biology, medicine.disease, digestive system, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, chemistry, Hepcidin, Internal medicine, medicine, biology.protein, Enterochromaffin cell, Serotonin, Neurotransmitter, 030304 developmental biology, Hormone
Abstract: Iron is essential to key biological processes of all living organisms. Proper iron levels must be maintained to meet biological needs and prevent toxicity. Given the central role played by the hormone hepcidin in systemic iron homeostasis, extensive research has sought to identify regulators of its expression. Diverse evidence shows the gut to be an essential sensor and regulator of iron homeostasis, independently of other known hepcidin regulators, including bone marrow signals. Here we identify gut-derived serotonin as a key physiological factor in hepcidin regulation. In response to hypoxia, serotonin synthesized and secreted by enterochromaffin cells can act beyond the gut to repress hepcidin expression in the liver, through a 5-HT2Breceptor-dependent pathway. Bone marrow transplant experiments clearly indicate the gut is responsible for hepcidin repression. This regulatory system appears to be conserved in humans: a significant negative correlation exists between hepcidin and serotonin levels in the serum of healthy individuals. Our findings imply hepcidin regulation by serotonin is a physiological process, and modulation of the gut serotonergic system may have broad therapeutic implications.
Published: 2021
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27. Decannulation and recovery from prolonged mechanical ventilation in a cohort of COVID19 patients

Author: Antonio Antón, Patricia Peñacoba, Fernando Gutierrez Pereyra, and Carme Puy
Subjects: Mechanical ventilation, business.industry, medicine.medical_treatment, Anesthesia, Cohort, medicine, business
Published: 2021
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28. PD43-05 DNA METHYLATION URINE BIOMARKERS TEST (EPICHECK® ASSAY) IN THE DIAGNOSIS OF UPPER TRACT UROTHELIAL CARCINOMA: RESULTS FROM A SINGLE-CENTER PROSPECTIVE STUDY

Author: Francesco Sanguedolce, Matteo Fontana, Josep M Gaya, Joan Palou, Andrea Gallioli, A. Sánchez-Puy, Christian Martinez, Angelo Territo, Pietro Diana, Alberto Breda, Alberto Piana, José Daniel Subiela, and Roman Boissier
Subjects: medicine.medical_specialty, business.industry, Urology, Urinary system, food and beverages, Single Center, Urine biomarkers, Cytology, DNA methylation, medicine, business, Prospective cohort study, Urothelial carcinoma, Upper urinary tract
Abstract: INTRODUCTION AND OBJECTIVE:The diagnosis and risk stratification of upper urinary tract urothelial carcinoma (UTUC) can be challenging. Urinary cytology (UC) has low sensitivity and CT scan is not ...
Published: 2021
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29. Ferroptosis in Liver Diseases: An Overview

Author: Martina Maria Capelletti, Hana Manceau, Katell Peoc'h, Hervé Puy, Capelletti, M, Manceau, H, Puy, H, and Peoc'H, K
Subjects: Spiro Compound, Lipoxygenase, alpha-Tocopherol, Review, Phenylenediamines, GPX4, Piperazines, lcsh:Chemistry, iron metabolism, lcsh:QH301-705.5, Spectroscopy, Cyclohexylamines, Kelch-Like ECH-Associated Protein 1, Lipid peroxide, Chemistry, Liver Disease, Liver Diseases, Liver Neoplasms, General Medicine, Sorafenib, Glutathione, Computer Science Applications, Cyclohexylamine, cell death, Liver Neoplasm, Reperfusion Injury, Chemical and Drug Induced Liver Injury, Reactive Oxygen Specie, Intracellular, Human, Signal Transduction, Programmed cell death, Quinoxaline, Iron, Heme, liver, Catalysis, Inorganic Chemistry, Quinoxalines, medicine, Autophagy, Animals, Ferroptosis, Humans, Spiro Compounds, Cysteine, Physical and Theoretical Chemistry, Cell adhesion, Molecular Biology, Piperazine, Animal, Organic Chemistry, Cancer, Oxidative Stre, Metabolism, medicine.disease, Phospholipid Hydroperoxide Glutathione Peroxidase, KEAP1, Sulfasalazine, Oxidative Stress, lcsh:Biology (General), lcsh:QD1-999, Cancer research, Lipid Peroxidation, Tumor Suppressor Protein p53, Phenylenediamine, Reactive Oxygen Species, Ferroptosi
Abstract: Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and redox imbalance. Ferroptosis shows specific biological and morphological features when compared to the other cell death patterns. The loss of lipid peroxide repair activity by glutathione peroxidase 4 (GPX4), the presence of redox-active iron and the oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are considered as distinct fingerprints of ferroptosis. Several pathways, including amino acid and iron metabolism, ferritinophagy, cell adhesion, p53, Keap1/Nrf2 and phospholipid biosynthesis, can modify susceptibility to ferroptosis. Through the decades, various diseases, including acute kidney injury; cancer; ischemia–reperfusion injury; and cardiovascular, neurodegenerative and hepatic disorders, have been associated with ferroptosis. In this review, we provide a comprehensive analysis of the main biological and biochemical mechanisms of ferroptosis and an overview of chemicals used as inducers and inhibitors. Then, we report the contribution of ferroptosis to the spectrum of liver diseases, acute or chronic. Finally, we discuss the use of ferroptosis as a therapeutic approach against hepatocellular carcinoma, the most common form of primary liver cancer.
Published: 2020

30. Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma

Author: Bousquet, J., Bedbrook, A., Czarlewski, W., Onorato, G. L., Arnavielhe, S., Laune, D., Mathieu-Dupas, E., Fonseca, J., Costa, E., Lourenço, O., Morais-Almeida, M., Todo-Bom, A., Illario, M., Menditto, E., Canonica, G. W., Cecchi, L., Monti, R., Napoli, L., Ventura, M. T., De Feo, G., Fokkens, W. J., Chavannes, N. H., Reitsma, S., Cruz, A. A., Da Silva, J., Serpa, F. S., Larenas-Linnemann, D., Fuentes Perez, J. M., Huerta-Villalobos, Y. R., Rivero-Yeverino, D., Rodriguez-Zagal, E., Valiulis, A., Dubakiene, R., Emuzyte, R., Kvedariene, V., Annesi-Maesano, I., Blain, H., Bonniaud, P., Bosse, I., Dauvilliers, Y., Devillier, P., Fontaine, J. F., Pépin, J. L., Pham-Thi, N., Portejoie, F., Picard, R., Roche, N., Rolland, C., Schmidt-Grendelmeier, P., Kuna, P., Samolinski, B., Anto, J. M., Cardona, V., Mullol, J., Pinnock, H., Ryan, D., Sheikh, A., Walker, S., Williams, S., Becker, S., Klimek, L., Pfaar, O., Bergmann, K. C., Mösges, R., Zuberbier, T., Roller-Wirnsberger, R. E., Tomazic, P. V., Haahtela, T., Salimäki, J., Toppila-Salmi, S., Valovirta, E., Vasankari, T., Gemicioǧlu, B., Yorgancioglu, A., Papadopoulos, N. G., Prokopakis, E. P., Tsiligianni, I. G., Bosnic-Anticevich, S., O'Hehir, R., Ivancevich, J. C., Neffen, H., Zernotti, M. E., Kull, I., Melén, E., Wickman, M., Bachert, C., Hellings, P. W., Brusselle, G., Palkonen, S., Bindslev-Jensen, C., Eller, E., Waserman, S., Boulet, L. P., Bouchard, J., Chu, D. K., Schünemann, H. J., Sova, M., De Vries, G., Van Eerd, M., Agache, I., Ansotegui, I. J., Bewick, M., Casale, T., Dykewick, M., Ebisawa, M., Murray, R., Naclerio, R., Okamoto, Y., Wallace, D. V., Aberer, W., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Basagana, X., Bateman, E. D., Bedolla-Barajas, M., Beghé, B., Bel, E. H., Bennoor, K. S., Benson, M., Bertorello, L., Białoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosnic-Anticevich, C. S., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Castellano, G., Cepeda, A. M., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., De Sousa, J. Correia, Cortés-Grimaldo, R. M., Corti, F., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Dahlen, S. E., D'Amato, G., Dario, C., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., De Fátima Emerson, M., De Martino, B., Motta Rubina, N. P., Deleanu, D., Demoly, P., Denburg, J. A., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Farrell, J., Farsi, A., Ferreira De Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fonseca, J. A., Forti, S., Fuentes-Perez, J. M., Gálvez-Romero, J. L., Gamkrelidze, A., Garcia-Aymerich, J., García-Cobas, C. Y., Garcia-Cruz, M. H., Genova, S., Christoff, G., Gereda, J. E., Gerth Van Wijk, R., Gomez, R. M., Gómez-Vera, J., González Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzmán, M. A., Hajjam, J., Hernández, L., Hourihane, J. O. B., Humbert, M., Iaccarino, G., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kupczyk, M., Krzych-Fałta, E., Lacwik, P., Lauri, D., Lavrut, J., L. T. T., Le, Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Münter, L., Muraro, A., Nadif, R., Nalin, M., Namazova-Baranova, L., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okubo, K., Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pereira, A. M., Persico, M., Phillips, J., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Potter, P., Pozzi, A. C., Price, D., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Ribeirinho, I., Rimmer, J., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Mañas, L., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rolla, G., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Sagara, H., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Shamai, S., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyriçá, J. N., Thibaudon, M., To, T., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Van Ganse, E., Van Hague, M., Vandenplas, O., Vezzani, G., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Wallace, D., Wang, D. Y., Werfel, T., Westman, M., Williams, D. M., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zhanat, I., Zidarn, M., Zubrinich, C., Zurkuhlen, A., Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), KYomed INNOV, University of Coimbra [Portugal] (UC), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), uBibliorum, Bousquet J., Bedbrook A., Czarlewski W., Onorato G.L., Arnavielhe S., Laune D., Mathieu-Dupas E., Fonseca J., Costa E., Lourenco O., Morais-Almeida M., Todo-Bom A., Illario M., Menditto E., Canonica G.W., Cecchi L., Monti R., Napoli L., Ventura M.T., De Feo G., Fokkens W.J., Chavannes N.H., Reitsma S., Cruz A.A., Da Silva J., Serpa F.S., Larenas-Linnemann D., Fuentes Perez J.M., Huerta-Villalobos Y.R., Rivero-Yeverino D., Rodriguez-Zagal E., Valiulis A., Dubakiene R., Emuzyte R., Kvedariene V., Annesi-Maesano I., Blain H., Bonniaud P., Bosse I., Dauvilliers Y., Devillier P., Fontaine J.F., Pepin J.L., Pham-Thi N., Portejoie F., Picard R., Roche N., Rolland C., Schmidt-Grendelmeier P., Kuna P., Samolinski B., Anto J.M., Cardona V., Mullol J., Pinnock H., Ryan D., Sheikh A., Walker S., Williams S., Becker S., Klimek L., Pfaar O., Bergmann K.C., Mosges R., Zuberbier T., Roller-Wirnsberger R.E., Tomazic P.V., Haahtela T., Salimaki J., Toppila-Salmi S., Valovirta E., Vasankari T., Gemicioglu B., Yorgancioglu A., Papadopoulos N.G., Prokopakis E.P., Tsiligianni I.G., Bosnic-Anticevich S., O'Hehir R., Ivancevich J.C., Neffen H., Zernotti M.E., Kull I., Melen E., Wickman M., Bachert C., Hellings P.W., Brusselle G., Palkonen S., Bindslev-Jensen C., Eller E., Waserman S., Boulet L.P., Bouchard J., Chu D.K., Schunemann H.J., Sova M., De Vries G., Van Eerd M., Agache I., Ansotegui I.J., Bewick M., Casale T., Dykewick M., Ebisawa M., Murray R., Naclerio R., Okamoto Y., Wallace D.V., Aberer W., Akdis C.A., Akdis M., Aliberti M.R., Almeida R., Amat F., Angles R., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Basagana X., Bateman E.D., Bedolla-Barajas M., Beghe B., Bel E.H., Bennoor K.S., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bourret R., Braido F., Briedis V., Brightling C.E., Brozek J., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillaud D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Carlsen K.H., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Castellano G., Cepeda A.M., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., De Sousa J.C., Cortes-Grimaldo R.M., Corti F., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Dahlen S.E., D'Amato G., Dario C., Darsow U., De Blay F., De Carlo G., Dedeu T., De Fatima Emerson M., De Martino B., Motta Rubina N.P., Deleanu D., Demoly P., Denburg J.A., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Durham S.R., Du Toit G., Dykewicz M.S., El-Gamal Y., Eklund P., Farrell J., Farsi A., Ferreira De Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Aymerich J., Garcia-Cobas C.Y., Garcia-Cruz M.H., Genova S., Christoff G., Gereda J.E., Gerth Van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Guzman M.A., Hajjam J., Hernandez L., Hourihane J.O.B., Humbert M., Iaccarino G., Ispayeva Z., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu A.F., Karjalainen J., Kardas P., Keil T., Keith P.K., Khaitov M., Khaltaev N., Kleine-Tebbe J., Kowalski M.L., Kuitunen M., Kupczyk M., Krzych-Falta E., Lacwik P., Lauri D., Lavrut J., Le L.T.T., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Luna-Pech J.A., Magnan A., Mahboub B., Maier D., Mair A., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Medina-Avalos M.A., Melo-Gomes E., Meltzer E.O., Mercier J., Miculinic N., Mihaltan F., Milenkovic B., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Mora Bogado D., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Nadif R., Nalin M., Namazova-Baranova L., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Novellino E., Nyembue T.D., Odzhakova C., Ohta K., Okubo K., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Panzner P., Park H.S., Papi A., Passalacqua G., Paulino E., Pawankar R., Pedersen S., Pereira A.M., Persico M., Phillips J., Pigearias B., Pin I., Pitsios C., Plavec D., Pohl W., Popov T.A., Potter P., Pozzi A.C., Price D., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Rajabian-Soderlund R., Ribeirinho I., Rimmer J., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rolla G., Romano M., Rosado-Pinto J., Rosario N., Rottem M., Sagara H., Sanchez-Borges M., Sastre-Dominguez J., Scadding G.K., Scichilone N., Schmid-Grendelmeier P., Shamai S., Simons F.E.R., Siroux V., Sisul J.C., Skrindo I., Sole D., Somekh D., Sondermann M., Sooronbaev T., Sorensen M., Sorlini M., Spranger O., Stellato C., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., To T., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., Valero A., Van Ganse E., Van Hague M., Vandenplas O., Vezzani G., Vatrella A., Verissimo M.T., Viart F., Viegi G., Vicheva D., Vontetsianos T., Wagenmann M., Wang D.Y., Werfel T., Westman M., Williams D.M., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zhang L., Zhong N., Zhanat I., Zidarn M., Zubrinich C., Zurkuhlen A., Bousquet, J., Bedbrook, A., Czarlewski, W., Onorato, G. L., Arnavielhe, S., Laune, D., Mathieu-Dupas, E., Fonseca, J., Costa, E., Lourenco, O., Morais-Almeida, M., Todo-Bom, A., Illario, M., Menditto, E., Canonica, G. W., Cecchi, L., Monti, R., Napoli, L., Ventura, M. T., De Feo, G., Fokkens, W. J., Chavannes, N. H., Reitsma, S., Cruz, A. A., Da Silva, J., Serpa, F. S., Larenas-Linnemann, D., Fuentes Perez, J. M., Huerta-Villalobos, Y. R., Rivero-Yeverino, D., Rodriguez-Zagal, E., Valiulis, A., Dubakiene, R., Emuzyte, R., Kvedariene, V., Annesi-Maesano, I., Blain, H., Bonniaud, P., Bosse, I., Dauvilliers, Y., Devillier, P., Fontaine, J. F., Pepin, J. L., Pham-Thi, N., Portejoie, F., Picard, R., Roche, N., Rolland, C., Schmidt-Grendelmeier, P., Kuna, P., Samolinski, B., Anto, J. M., Cardona, V., Mullol, J., Pinnock, H., Ryan, D., Sheikh, A., Walker, S., Williams, S., Becker, S., Klimek, L., Pfaar, O., Bergmann, K. C., Mosges, R., Zuberbier, T., Roller-Wirnsberger, R. E., Tomazic, P. V., Haahtela, T., Salimaki, J., Toppila-Salmi, S., Valovirta, E., Vasankari, T., Gemicioglu, B., Yorgancioglu, A., Papadopoulos, N. G., Prokopakis, E. P., Tsiligianni, I. G., Bosnic-Anticevich, S., O'Hehir, R., Ivancevich, J. C., Neffen, H., Zernotti, M. E., Kull, I., Melen, E., Wickman, M., Bachert, C., Hellings, P. W., Brusselle, G., Palkonen, S., Bindslev-Jensen, C., Eller, E., Waserman, S., Boulet, L. P., Bouchard, J., Chu, D. K., Schunemann, H. J., Sova, M., De Vries, G., Van Eerd, M., Agache, I., Ansotegui, I. J., Bewick, M., Casale, T., Dykewick, M., Ebisawa, M., Murray, R., Naclerio, R., Okamoto, Y., Wallace, D. V., Aberer, W., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Basagana, X., Bateman, E. D., Bedolla-Barajas, M., Beghe, B., Bel, E. H., Bennoor, K. S., Benson, M., Bertorello, L., Bialoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosnic-Anticevich, C. S., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabanas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Castellano, G., Cepeda, A. M., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., De Sousa, J. C., Cortes-Grimaldo, R. M., Corti, F., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Dahlen, S. E., D'Amato, G., Dario, C., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., De Fatima Emerson, M., De Martino, B., Motta Rubina, N. P., Deleanu, D., Demoly, P., Denburg, J. A., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Farrell, J., Farsi, A., Ferreira De Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fonseca, J. A., Forti, S., Fuentes-Perez, J. M., Galvez-Romero, J. L., Gamkrelidze, A., Garcia-Aymerich, J., Garcia-Cobas, C. Y., Garcia-Cruz, M. H., Genova, S., Christoff, G., Gereda, J. E., Gerth Van Wijk, R., Gomez, R. M., Gomez-Vera, J., Gonzalez Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzman, M. A., Hajjam, J., Hernandez, L., Hourihane, J. O. B., Humbert, M., Iaccarino, G., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kupczyk, M., Krzych-Falta, E., Lacwik, P., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Munter, L., Muraro, A., Nadif, R., Nalin, M., Namazova-Baranova, L., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okubo, K., Ortega Cisneros, M., Ouedraogo, S., Pali-Scholl, I., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pereira, A. M., Persico, M., Phillips, J., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Potter, P., Pozzi, A. C., Price, D., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Ribeirinho, I., Rimmer, J., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Manas, L., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rolla, G., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Sagara, H., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Scichilone, N., Schmid-Grendelmeier, P., Shamai, S., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Sole, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyrica, J. N., Thibaudon, M., To, T., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Van Ganse, E., Van Hague, M., Vandenplas, O., Vezzani, G., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Wallace, D., Wang, D. Y., Werfel, T., Westman, M., Williams, D. M., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zhanat, I., Zidarn, M., Zubrinich, C., Zurkuhlen, A., UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie
Subjects: SENTINEL NETWORK, Allergy, Respiratory Medicine and Allergy, Review, WORLD-HEALTH-ORGANIZATION, Disease, Rhinitis, App, Asthma, Care pathways, DG Santé, MASK, mHealth, 0302 clinical medicine, QUALITY-OF-LIFE, PRECISION MEDICINE, Health care, Medicine and Health Sciences, GRADING QUALITY, Immunology and Allergy, Medicine, Rinitis, Lungmedicin och allergi, 0303 health sciences, The MASK study group, Public sector, DG Sante, MOBILE TECHNOLOGY, 3. Good health, ALLERGIC RHINITIS, CHRONIC RESPIRATORY-DISEASES, Rinite, EUROPEAN SYMPOSIUM, CLINICAL-PRACTICE GUIDELINES, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Immunology, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Predictive medicine, 03 medical and health sciences, Quality of life (healthcare), App -MASK, Asma, 030304 developmental biology, ARIA, Science & Technology, Care pathway, business.industry, Change management, Correction, RC581-607, medicine.disease, 030228 respiratory system, Family medicine, Immunologic diseases. Allergy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases. ispartof: CLINICAL AND TRANSLATIONAL ALLERGY vol:9 issue:1 ispartof: location:England status: published
Published: 2019
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31. High urinary ferritin reflects myoglobin iron evacuation in DMD patients

Author: Jeremy Rouillon, Hervé Puy, Katell Peoc'h, Thomas Voit, Brenda Wong, Thibaud Lefebvre, Jérôme Ausseil, Vincent Puy, Laurent Servais, Aleksandar Zocevic, Paul Fogel, Fedor Svinartchouk, Zoubida Karim, Jérôme Denard, Raed Daher, Centre de recherche et d'applications sur les thérapies géniques (CRATG), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Généthon, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Picardie Jules Verne (UPJV), Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité, CHU Amiens-Picardie, Service de Biochimie et de Biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Faculté de Pharmacie, Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center, Service of Clinical Trials and Databases, Institut de Myologie, Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université d'Évry-Val-d'Essonne (UEVE)-GENETHON 3-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Faculté de Pharmacie
Subjects: 0301 basic medicine, Male, Antibody microarray, Duchenne muscular dystrophy, Urinary ferritin, Urine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antibody array, MESH: Child, Child, Genetics (clinical), Kidney, MESH: Cytokines, MESH: Iron, biology, Myoglobin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, medicine.anatomical_structure, Neurology, MESH: Young Adult, Child, Preschool, Biomarker (medicine), Cytokines, Dystrophin, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, MESH: Myoglobin, Urinary system, Iron, MESH: Ferritins, 03 medical and health sciences, Young Adult, Internal medicine, medicine, MESH: Muscular Dystrophy, Duchenne, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, MESH: Male, Ferritin, Muscular Dystrophy, Duchenne, 030104 developmental biology, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Pediatrics, Perinatology and Child Health, Ferritins, biology.protein, MESH: Biomarkers, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract: International audience; Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the dystrophin gene leading to the absence of the normal dystrophin protein. The efforts of many laboratories brought new treatments of DMD to the reality, but ongoing and forthcoming clinical trials suffer from absence of valuable biomarkers permitting to follow the outcome of the treatment day by day and to adjust the treatment if needed. In the present study the levels of 128 urinary proteins including growth factors, cytokines and chemokines were compared in urine of DMD patients and age related control subjects by antibody array approach. Surprisingly, statistically significant difference was observed only for urinary ferritin whose level was 50 times higher in young DMD patients. To explain the observed high urinary ferritin content we analysed the levels of iron, iron containing proteins and proteins involved in regulation of iron metabolism in serum and urine of DMD patients and their age-matched healthy controls. Obtained data strongly suggest that elevated level of urinary ferritin is functionally linked to the renal management of myoglobin iron derived from leaky muscles of DMD patients. This first observation of the high level of ferritin in urine of DMD patients permits to consider this protein as a new urinary biomarker in muscular dystrophies and sheds light on the mechanisms of iron metabolism and kidney functioning in DMD.
Published: 2020
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32. Hepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study

Author: André Bado, Carole Brasse-Lagnel, Caroline Schmitt, Thibaud Lefebvre, Soumeya Bekri, Hervé Puy, Nathalie Gault, Zoubida Karim, Caroline Quintin, Simon Msika, Marina Esposito-Farèse, Neila Talbi, Muriel Coupaye, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Intégré Nord Francilien de l'Obésité (CINFO), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, obesity, Erythrocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ferroportin, Protoporphyrins, Gastroenterology, Cohort Studies, 0302 clinical medicine, iron deficiency, TX341-641, iron metabolism, Prospective Studies, Prospective cohort study, Cation Transport Proteins, Nutrition and Dietetics, biology, Iron Deficiencies, Iron deficiency, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Erythropoiesis, Female, Adult, Sleeve gastrectomy, medicine.medical_specialty, Duodenum, Anemia, Iron, Article, 03 medical and health sciences, Hepcidins, Gastrectomy, Hepcidin, Internal medicine, Receptors, Transferrin, medicine, Humans, Soluble transferrin receptor, Nutrition. Foods and food supply, business.industry, medicine.disease, 030104 developmental biology, Intestinal Absorption, inflammation, Dietary Supplements, biology.protein, hepcidin, business, sleeve gastrectomy, Transcription Factors, Food Science
Abstract: Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women, sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.
Published: 2021
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33. Targeting REG3β limits pancreatic ductal adenocarcinoma progression through CTGF downregulation

Author: Juan L. Iovanna, Ezequiel Calvo, Nicolas A. Fraunhoffer, Daniel Closa, Emma Folch-Puy, Analía Meilerman Abuelafia, Eduardo Chuluyan, Ligue Nationale contre le Cancer (France), Instituto Nacional de Cáncer (Brasil), Conseil Régional Provence-Alpes-Côte d'Azur, and Institut National de la Santé et de la Recherche Médicale (France)
Subjects: Cancer Research, Orthotopic pancreas cancer model, Stromal cell, endocrine system diseases, medicine.medical_treatment, Jak/STAT3 signalization, Downregulation and upregulation, Affymetrix, medicine, Tumor microenvironment, biology, business.industry, Immunotherapy, digestive system diseases, CTGF, medicine.anatomical_structure, Oncology, Tumor progression, Panc02, biology.protein, Cancer research, Antibody, business, Pancreas
Abstract: The crosstalk between the transformed tumoral cells and their microenvironment is a key aspect for pancreatic ductal adenocarcinoma (PDAC) progression. This molecular dialog is intensively studied because it may result in an efficient therapeutic target. Contrary to this near microenvironment, the stromal portion in direct contact with the transformed cells, a far microenvironment, placed at the periphery of the tumor mass, produces factors signaling tumors. Among these factors, REG3β, produced by this part of the pancreas, is an important factor in promoting tumor progression. This paper demonstrated that targeting REG3β protein with specific antibodies limits the PDAC tumor growth in an orthotopic, syngeneic mice model induced by injection of Panc02 cells. Then, we showed that CTGF is over-expressed in response to REG3β in PDAC-derived cells. Moreover, inactivation of REG3β by treating tumors with anti-REG3β antibodies results in a strong decrease of CTGF in PDAC tumors. Lastly, we demonstrated that forced expression of CTGF in xenografted Panc02 cells abolishes the therapeutic effect of the anti-REG3β antibody treatment. Altogether, these results indicate that the effect of REG3β in promoting PDAC progression is mediated by CTGF over-activation. Thus, REG3β is a promising therapeutic target to treat PDAC with an original rationale. In conclusion, we demonstrated that the far microenvironment is essential for PDAC progression by producing active secretory factors, and some of them could be used as therapeutic targets., This work was supported by La Ligue Contre le Cancer, INCa, Canceropole PACA, and INSERM.
Published: 2021

34. Tetraplegia after branched frozen elephant trunk implantation for acute type A aortic dissection

Author: Paul Achouh, Léonora du Puy-Montbrun, Sara Ranchordás, and Alain Bel
Subjects: Pulmonary and Respiratory Medicine, Bradycardia, medicine.medical_specialty, Elephant trunks, medicine.medical_treatment, Ischemia, 030204 cardiovascular system & hematology, Prosthesis, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, Ascending aorta, Vasoplegia, Medicine, cardiovascular diseases, Tetraplegia, Aortic dissection, business.industry, medicine.disease, Surgery, 030228 respiratory system, cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: A 58-year-old male patient presented with acute type A aortic dissection. Complete arch and ascending aorta replacement were performed using a Thoraflex Hybrid prosthesis. The left subclavian artery was ligated and the remaining supra-aortic trunks were reimplanted using the branches of the prosthesis. After an uneventful early postoperative period, sudden onset of hypotension and bradycardia occurred, with severe vasoplegia, requiring vasopressors. Ischemia of the upper left limb and compartment syndrome ensued, leading to left carotid subclavian bypass. After discontinuation of sedation, tetraplegia was noted due to spinal cord ischemia from C3 to C7.
Published: 2020
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35. Una presentación poco común de la mononucleosis infecciosa

Author: Anna Puy Guillén and Hernán Andreu Serra
Subjects: medicine.medical_specialty, Hepatology, Mononucleosis, business.industry, Gastroenterology, medicine, MEDLINE, Presentation (obstetrics), medicine.disease, business, Dermatology
Published: 2022
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36. Revisional bariatric surgery, are we ready?

Author: Andrea Ciudin, R Villallonga Puy, Marc Perez, Rodríguez Luna, Josemanuel Fort, Manel Armengol, Enric Caubet, A García-Ruiz de Gordejuela, and Oscar Gonzalez
Subjects: medicine.medical_specialty, business.industry, Medicine, General Medicine, business, Surgery
Abstract: Resumen Introducción: la obesidad en el siglo XXI continúa siendo un problema de salud mundial, la cirugía bariátrica, en la actualidad, es el único tratamiento exitoso a largo plazo para el manejo de ésta y sus comorbilidades, ha tenido un incremento importante en los últimos años apareciendo complicaciones que son objetivos de la cirugía revisional. Objetivos: el presente artículo pretende evaluar las principales cirugías revisionales que han permeado en el campo de la cirugía bariátrica así como nuestra experiencia en los últimos años. Material y métodos: análisis estadístico descriptivo de una cohorte retrospectiva de pacientes sometidos a cirugía de revisión en el Hospital Universitario Vall d'Hebron de Barcelona, España. EAC-BS Center of Excellence. Resultados: se han realizado 1.890 cirugías bariátricas desde los inicios de la cirugía bariátrica en nuestra Unidad hasta el 31 de julio de 2019. 143 (7,56%) corresponden a cirugías de revisión. Las más frecuentes fueron la conversión de gastrectomía vertical (GV) a bypass gástrico (BPG) 30,76% y a SADI-S 20,97%. Dentro de éstas, las principales indicaciones se encuentra el reflujo esofagogástrico (RGE) en un 30,76% y pérdida inadecuada de peso 20,97% en la GV. El BPG requirió conversión a GV en 12,58% y revisión de BGP en 7,69% principalmente por hipoglucemias. Conclusiones: el incremento de cirugía primaria para la obesidad implica que un porcentaje considerable de procedimientos primarios presentarán algún tipo de indicación que requerirá revisión. La cirugía revisional requerirá una evaluación meticulosa debería permitir dar un buen manejo a largo plazo.
Published: 2019
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37. Results of a pilot study of isoniazid in patients with erythropoietic protoporphyria

Author: Laurent Gouya, Robert J. Desnick, Montgomery D. Bissel, Manisha Balwani, Charles J. Parker, Karl E. Anderson, John D. Phillips, Joseph R. Bloomer, Hervé Puy, and Ashwani K. Singal
Subjects: Male, 0301 basic medicine, Protoporphyria, Erythropoietic, Endocrinology, Diabetes and Metabolism, Protoporphyrins, Pilot Projects, 030105 genetics & heredity, Pharmacology, Proof of Concept Study, Biochemistry, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Sideroblastic anemia, Isoniazid, Genetics, Animals, Humans, Medicine, Molecular Biology, Heme, biology, Protoporphyrin IX, business.industry, medicine.disease, ALAS2, Anemia, Sideroblastic, Disease Models, Animal, Porphyria, Liver, chemistry, Aminolevulinic acid synthase, biology.protein, Female, Erythropoietic protoporphyria, business, 030217 neurology & neurosurgery, 5-Aminolevulinate Synthetase, medicine.drug
Abstract: Erythropoietic protoporphyria (EPP), the most common porphyria of childhood and the third most common porphyria of adulthood, is characterized clinically by painful, non-blistering cutaneous photosensitivity. Two distinct inheritance patterns involving mutations affecting genes that encode enzymes of the heme biosynthetic pathway underlie the clinical phenotype. Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms. Isoniazid (INH) is widely used for treatment of latent and active M. tuberculosis (TB). Sideroblastic anemia is observed in some patients taking INH, and studies have shown that this process is a consequence of inhibition of ALAS2 by INH. Based on these observations, we postulated that INH might have therapeutic activity in patients with EPP. We challenged this hypothesis in a murine model of EPP and showed that, after 4 weeks of treatment with INH, both plasma PPIX and hepatic PPIX were significantly reduced. Next, we tested the effect of INH on patients with EPP. After eight weeks, no significant difference in plasma or red cell PPIX was observed among the 15 patients enrolled in the study. These results demonstrate that while INH can lower PPIX in an animal model of EPP, the standard dose used to treat TB is insufficient to affect levels in humans.
Published: 2019
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38. In vitro evaluation of microleakage in Class II composite restorations: High-viscosity bulk-fill vs conventional composites

Author: Carmen Llena Puy, Laura García Marí, and Arantxa Climent Gil
Subjects: Molar, Materials science, Enamel paint, 0206 medical engineering, Composite number, Significant difference, Bulk fill composite, Bulk fill, 030206 dentistry, 02 engineering and technology, 020601 biomedical engineering, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, stomatognathic system, visual_art, Ceramics and Composites, Dentin, medicine, visual_art.visual_art_medium, Composite material, General Dentistry, Gingival margin
Abstract: This study compared marginal microleakage of Class II cavities restored with bulk-fill resin (Filtek™ Bulk Fill) and conventional composite resin (Filtek™ Supreme XTE). Two standardized Class II cavities were prepared in forty extracted human molars. The gingival margin was located above the cemento-enamel junction for twenty molars (groups 1 and 2) and apically for the other twenty (groups 3 and 4) (n=20). The occlusomesial cavity was filled with bulk-fill resin by insertion in bulk (groups 1 and 3) and the occlusodistal cavity was restored with conventional composite using incremental technique (groups 2 and 4). The teeth were thermocycled (500 cycles 5-55°C), stained and observed under light microscope. The microleakage was significantly lower in gingival margins located in enamel compared with dentin margins (p
Published: 2019
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39. Endothelial PAI-1 (Plasminogen Activator Inhibitor-1) Blocks the Intrinsic Pathway of Coagulation, Inducing the Clearance and Degradation of FXIa (Activated Factor XI)

Author: David Gailani, Cristina Puy, Andras Gruber, Matthew W. Hagen, Anh T. P. Ngo, Owen J. T. McCarty, Monica T. Hinds, Jiaqing Pang, Florea Lupu, and Ravi S. Keshari
Subjects: 0301 basic medicine, Endothelium, 030204 cardiovascular system & hematology, Pharmacology, Factor XIa, Article, Fibrin, 03 medical and health sciences, chemistry.chemical_compound, Papio ursinus, 0302 clinical medicine, Thrombin, Plasminogen Activator Inhibitor 1, medicine, Animals, Humans, Platelet activation, Blood Coagulation, biology, Chemistry, Endothelial Cells, Kallikrein, Blot, 030104 developmental biology, medicine.anatomical_structure, Plasminogen activator inhibitor-1, biology.protein, Cardiology and Cardiovascular Medicine, Plasminogen activator, medicine.drug
Abstract: Objective— Activation of coagulation FXI (factor XI) by FXIIa (activated factor XII) is a prothrombotic process. The endothelium is known to play an antithrombotic role by limiting thrombin generation and platelet activation. It is unknown whether the antithrombotic role of the endothelium includes sequestration of FXIa (activated factor XI) activity. This study aims to determine the role of endothelial cells (ECs) in the regulation of the intrinsic pathway of coagulation. Approach and Results— Using a chromogenic assay, we observed that human umbilical veins ECs selectively blocked FXIa yet supported kallikrein and FXIIa activity. Western blotting and mass spectrometry analyses revealed that FXIa formed a complex with endothelial PAI-1 (plasminogen activator inhibitor-1). Blocking endothelial PAI-1 increased the cleavage of a chromogenic substrate by FXIa and the capacity of FXIa to promote fibrin formation in plasma. Western blot and immunofluorescence analyses showed that FXIa–PAI-1 complexes were either released into the media or trafficked to the early and late endosomes and lysosomes of ECs. When baboons were challenged with Staphylococcus aureus to induce a prothrombotic phenotype, an increase in circulating FXIa–PAI-1 complex levels was detected by ELISA within 2 to 8 hours postchallenge. Conclusions— PAI-1 forms a complex with FXIa on ECs, blocking its activity and inducing the clearance and degradation of FXIa. Circulating FXIa–PAI-1 complexes were detected in a baboon model of S. aureus sepsis. Although ECs support kallikrein and FXIIa activity, inhibition of FXIa by ECs may promote the clearance of intravascular FXIa. Visual Overview— An online visual overview is available for this article.
Published: 2019
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40. The Safety and Efficacy of Novel Agents Targeting Factors XI and XII in Early Phase Human Trials

Author: Emma P. DeLoughery, Sven R. Olson, Cristina Puy, Owen J. T. McCarty, and Joseph J. Shatzel
Subjects: medicine.drug_class, 030204 cardiovascular system & hematology, Monoclonal antibody, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Humans, Factor XI, Clinical Trials as Topic, Hemostasis, Factor XII, business.industry, Anticoagulants, Thrombosis, Hematology, medicine.disease, Review article, Clinical trial, Coagulation, Cardiology and Cardiovascular Medicine, business, 030215 immunology
Abstract: Although anticoagulation without hemorrhage is a primary aim, this vision has remained as yet out of reach. Even despite the superior safety profile of the direct oral anticoagulants, hemorrhage remains a major risk of anticoagulation. Selective inhibition of the contact pathway of coagulation, specifically coagulation factor XI (FXI) and/or factor XII (FXII), has now substantial epidemiologic and preclinical data supporting the notion that these factors contribute to pathologic thrombosis and are yet primarily dispensable for in vivo hemostasis. In this way, targeting FXI and FXII may revolutionize the future anticoagulation landscape. Several drugs are under development for this purpose, including: ISIS 416858, a FXI antisense oligonucleotide which impairs hepatic synthesis of FXI; MAA868, a monoclonal antibody that binds the procoagulant enzymatic site of both zymogen and activated FXI (FXIa); BAY 1213790, a monoclonal antibody that binds the procoagulant enzymatic site of FXIa only; and AB023, a monoclonal antibody that inhibits activated FXII-mediated activation of FXI, along with two small molecules in clinical trials. Each of these drugs have demonstrated favorable safety profiles in their phases 1 and 2 studies to date, with preclinical data also supporting efficacy of abrogating thrombosis in various animal models. Other benefits of some of these drugs include once-monthly dosing and safety in patients with renal or hepatic impairment, while others offer quickly metabolized parenteral options, thus providing more convenient and widely available anticoagulation options. Though still far from the marketplace, drugs targeting FXI and FXII have the potential to usher in a new era of anticoagulation therapy.
Published: 2019
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41. Contact Activation Inhibitor and Factor XI Antibody, AB023, Produces Safe, Dose-Dependent Anticoagulation in a Phase 1 First-In-Human Trial

Author: Owen J. T. McCarty, Michael Wallisch, Andras Gruber, Monica T. Hinds, Joseph J. Shatzel, Christina U. Lorentz, David Gailani, Norah G. Verbout, Cristina Puy, Matthew W. Hagen, Sven R. Olson, and Erik I. Tucker
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, Factor XIIa, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Gastroenterology, Factor XIa, Article, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Fibrinolytic Agents, Internal medicine, Antithrombotic, medicine, Animals, Humans, Platelet, Thrombus, Blood Coagulation, Factor XI, Prothrombin time, Dose-Response Relationship, Drug, medicine.diagnostic_test, business.industry, Graft Occlusion, Vascular, Thrombin, Anticoagulants, medicine.disease, Thrombosis, 030104 developmental biology, Coagulation, Area Under Curve, Hemostasis, Partial Thromboplastin Time, Cardiology and Cardiovascular Medicine, business, Papio, Partial thromboplastin time
Abstract: Objective— Factor XI (FXI) contributes to thrombotic disease while playing a limited role in normal hemostasis. We generated a unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting FXI activation by thrombin or the procoagulant function of FXIa. We sought to confirm the antithrombotic activity of AB023 in a baboon thrombosis model and to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult subjects. Approach and Results— In a primate model of acute vascular graft thrombosis, AB023 reduced platelet and fibrin accumulation within the grafts by >75%. To evaluate the safety of AB023, we performed a first-in-human study in healthy adult volunteers without any serious adverse events. Overall, 10 of 21 (48%) subjects experienced 20 treatment-emergent adverse events, with 7 of 16 (44%) subjects following active treatment and 3 of 5 (60%) subjects following placebo. AB023 did not increase bleeding or prothrombin times. Anticoagulation was verified by a saturable ≈2-fold prolongation of the partial thromboplastin time for over 1 month after the highest dose. Conclusions— AB023, which inhibits contact activation-initiated blood coagulation in vitro and experimental thrombus formation in primates, produced a dose-dependent duration of limited anticoagulation without drug-related adverse effects in a phase 1 trial. When put in context with earlier observations suggesting that FXI contributes to venous thromboembolism and cardiovascular disease, although contributing minimally to hemostasis, our data further justify clinical evaluation of AB023 in conditions where contact-initiated FXI activation is suspected to have a pathogenic role. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03097341.
Published: 2019
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42. Regulation of globin-heme balance in Diamond-Blackfan anemia by HSP70/GATA1

Author: Rio, Sarah, Gastou, Marc, Karboul, Narjesse, Derman, Raphaёl, Suriyun, Thunwarat, Manceau, Hana, Leblanc, Thierry, El Benna, Jamel, Schmitt, Caroline, Azouzi, Slim, Larghero, Jérôme, Karim, Zoubida, Macias-Garcia, Alejandra, Chen, Jane-Jane, Puy, Hervé, Gouya, Laurent, Mohandas, Narla, Da Costa, Lydie, Sibon, David, Coman, Tereza, Rossignol, Julien, Lamarque, Mathilde, Kosmider, Olivier, Bayard, Elisa, Fouquet, Guillemette, Rignault, Rachel, Topçu, Selin, Bonneau, Pierre, Bernex, Florence, Dussiot, Michaël, Deroy, Kathy, Laurent, Laetitia, Callebert, Jacques, Launay, Jean-Marie, Georgin-Lavialle, Sophie, COURTOIS, genevieve, Maroteaux, Luc, Vaillancourt, Cathy, Fontenay, Michaela, Hermine, Olivier, Côté, Francine, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de recherche translationnelle, Institut Curie [Paris], Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Français des Porphyries, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Biotherapie - Saint Louis ((CIC-BT 301)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Génétique et Centre de Référence Maladies Rares Syndrome de Marfan et pathologies apparentées (AP HP, hôpital Bichat), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Red Cell Physiology Laboratory [New York, USA], New York Blood Center, AP-HP, Service d'Hématologie Biologique, Hôpital Robert-Debré, Service d'hématologie-oncologie adultes, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Field Neurosciences Laboratory for Restorative Neurology [Mount Pleasant, MI, USA] (Program in Neuroscience ), Central Michigan University (CMU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie biologique, Hôpital Cochin [AP-HP], Université Sorbonne Paris Cité (USPC), Hôpital Claude Huriez [Lille], CHU Lille, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Departement /u661 : Endocrinologie, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Biochimie et Biologie Moleculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Service de biochimie et biologie moléculaire, IFR139-Hôpital Lariboisière-Fernand-Widal [APHP], Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut du Fer à Moulin, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Hopital Saint-Louis [AP-HP] (AP-HP), Massachusetts Institute of Technology (MIT), COURTOIS, genevieve, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR139, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: Male, Ribosomal Proteins, Cellular differentiation, Immunology, Haploinsufficiency, Heme, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biochemistry, Small hairpin RNA, 03 medical and health sciences, chemistry.chemical_compound, Red Cells, Iron, and Erythropoiesis, 0302 clinical medicine, Erythroid Cells, hemic and lymphatic diseases, medicine, Humans, GATA1 Transcription Factor, HSP70 Heat-Shock Proteins, Globin, RNA, Small Interfering, Diamond–Blackfan anemia, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Anemia, Diamond-Blackfan, Cell Proliferation, 030304 developmental biology, 0303 health sciences, Chemistry, Cell growth, Infant, Newborn, Infant, Cell Differentiation, GATA1, Cell Biology, Hematology, Prognosis, medicine.disease, Phenotype, Globins, 3. Good health, Cell biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Mutation, Female, Follow-Up Studies
Abstract: Diamond-Blackfan anemia (DBA) is a congenital erythroblastopenia that is characterized by a blockade in erythroid differentiation related to impaired ribosome biogenesis. DBA phenotype and genotype are highly heterogeneous. We have previously identified 2 in vitro erythroid cell growth phenotypes for primary CD34+ cells from DBA patients and following short hairpin RNA knockdown of RPS19, RPL5, and RPL11 expression in normal human CD34+ cells. The haploinsufficient RPS19 in vitro phenotype is less severe than that of 2 other ribosomal protein (RP) mutant genes. We further documented that proteasomal degradation of HSP70, the chaperone of GATA1, is a major contributor to the defect in erythroid proliferation, delayed erythroid differentiation, increased apoptosis, and decreased globin expression, which are all features of the RPL5 or RPL11 DBA phenotype. In the present study, we explored the hypothesis that an imbalance between globin and heme synthesis may be involved in pure red cell aplasia of DBA. We identified disequilibrium between the globin chain and the heme synthesis in erythroid cells of DBA patients. This imbalance led to accumulation of excess free heme and increased reactive oxygen species production that was more pronounced in cells of the RPL5 or RPL11 phenotype. Strikingly, rescue experiments with wild-type HSP70 restored GATA1 expression levels, increased globin synthesis thereby reducing free heme excess and resulting in decreased apoptosis of DBA erythroid cells. These results demonstrate the involvement of heme in DBA pathophysiology and a major role of HSP70 in the control of balanced heme/globin synthesis.
Published: 2019
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43. Erythroid-Progenitor-Targeted Gene Therapy Using Bifunctional TFR1 Ligand-Peptides in Human Erythropoietic Protoporphyria

Author: Antoine Poli, Caroline Schmitt, Thibaud Lefebvre, Hana Manceau, Boualem Moulouel, Arienne Mirmiran, Katell Peoc'h, Sylvie Simonin, Hervé Puy, Vincent Oustric, Zoubida Karim, Jean-Jacques Lacapère, Jean-Charles Deybach, Hugo Lenglet, Raed Daher, Gaël Nicolas, Laurent Gouya, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Français des Porphyries Hôpital Louis Mourier, Université Paris Diderot - Paris 7 (UPD7), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et de Biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Faculté de Pharmacie, Centre Français des Porphyrines, Centre Français des Porphyries, Hopital Louis Mourier - AP-HP [Colombes], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Erythroblasts, Protoporphyria, Erythropoietic, [SDV]Life Sciences [q-bio], Genetic enhancement, Protoporphyrins, Antigens, CD34, Transferrin receptor, Cell-Penetrating Peptides, Ligands, medicine.disease_cause, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Report, Receptors, Transferrin, Genetics, medicine, Humans, RNA, Messenger, Receptor, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Erythroid Precursor Cells, Mutation, Messenger RNA, biology, Chemistry, Genetic Therapy, Oligonucleotides, Antisense, Ferrochelatase, medicine.disease, Cell biology, 030104 developmental biology, RNA splicing, biology.protein, Erythropoietic protoporphyria, 030217 neurology & neurosurgery
Abstract: Erythropoietic protoporphyria (EPP) is a hereditary disease characterized by a deficiency in ferrochelatase (FECH) activity. FECH activity is responsible for the accumulation of protoporphyrin IX (PPIX). Without etiopathogenic treatment, EPP manifests as severe photosensitivity. 95% of affected individuals present a hypomorphic FECH allele trans to a loss-of-function (LOF) FECH mutation, resulting in a reduction in FECH activity in erythroblasts below a critical threshold. The hypomorphic allele promotes the use of a cryptic acceptor splice site, generating an aberrant FECH mRNA, which is responsible for the reduced level of wild-type FECH mRNA and, ultimately, FECH activity. We have previously identified an antisense oligonucleotide (AON), AON-V1 (V1), that redirects splicing to the physiological acceptor site and reduces the accumulation of PPIX. Here, we developed a specific strategy that uses transferrin receptor 1 (TRF1) as a Trojan horse to deliver V1 to erythroid progenitors. We designed a bifunctional peptide (P(1)-9R) including a TFR1-targeting peptide coupled to a nine-arginine cell-penetrating peptide (CPP) that facilitates the release of the AON from TFR1 in endosomal vesicles. We demonstrated that the P(1)-9R/V1 nanocomplex promotes the efficient and prolonged redirection of splicing towards the physiological splice site and subsequent normalization of WT FECH mRNA and protein levels. Finally, the P(1)-9R/V1 nanocomplex increases WT FECH mRNA production and significantly decreases PPIX accumulation in primary cultures of differentiating erythroid progenitors from an overt EPP-affected individual. P(1)-9R is a method designed to target erythroid progenitors and represents a potentially powerful tool for the in vivo delivery of therapeutic DNA in many erythroid disorders.
Published: 2019
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44. Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials

Author: Laurien E. Zijlstra, J. Wouter Jukema, Rudi G. J. Westendorp, Robert S. Du Puy, Rosalinde K. E. Poortvliet, Patricia M. Kearney, Linda O’Keeffe, Olaf M. Dekkers, Manuel R. Blum, Nicolas Rodondi, Tinh-Hai Collet, Terence J. Quinn, Naveed Sattar, David J. Stott, Stella Trompet, Wendy P. J. den Elzen, Jacobijn Gussekloo, and Simon P. Mooijaart
Subjects: Male, PROTOCOL, Endocrinology, Diabetes and Metabolism, Placebo-controlled study, 030204 cardiovascular system & hematology, law.invention, Endocrinology, 0302 clinical medicine, Randomized controlled trial, law, cardiovascular disease, 610 Medicine & health, older adults, Randomized Controlled Trials as Topic, Subclinical infection, ddc:616, Aged, 80 and over, Atrial fibrillation, ASSOCIATION, Prognosis, Clinical Trial, subclinical hypothyroidism, Europe, Cardiovascular Diseases, Female, 360 Social problems & social services, medicine.drug, medicine.medical_specialty, levothyroxine, Levothyroxine, 030209 endocrinology & metabolism, Placebo, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Double-Blind Method, Hypothyroidism, Internal medicine, medicine, Humans, Aged, Overtreatment, business.industry, ADULTS, medicine.disease, RC648-665, Clinical trial, Thyroxine, Heart failure, business, randomised controlled trial, Follow-Up Studies
Abstract: BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism – a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7–81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (pConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT01660126] (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+).
Published: 2021
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45. Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach

Author: Emma Folch-Puy, Arnau Panisello-Roselló, Jacques Pirenne, Carlos M. Palmeira, Raquel G. Bardallo, Joan Roselló-Catafau, Rui Teixeira da Silva, Teresa Carbonell, René Adam, Instituto de Salud Carlos III, and European Commission
Subjects: Male, 0301 basic medicine, Oncotic pressure, medicine.medical_treatment, Chemistry, Multidisciplinary, ALDEHYDE DEHYDROGENASE 2, Trasplantament hepàtic, ISCHEMIA-REPERFUSION INJURY, Pharmacology, Liver transplantation, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Biology (General), Spectroscopy, Malalties del fetge, Aldehyde Dehydrogenase, Mitochondrial, Fatty liver, Alanine Transaminase, Organ Preservation, General Medicine, Glutathione, Mitochondria, 3. Good health, Computer Science Applications, Chemistry, Liver, 030220 oncology & carcinogenesis, Physical Sciences, Life Sciences & Biomedicine, ORGAN PRESERVATION, Biochemistry & Molecular Biology, STRATEGIES, QH301-705.5, Organ Preservation Solutions, Cold storage, Nitric Oxide, Article, Catalysis, Specimen Handling, Nitric oxide, MECHANISMS, Inorganic Chemistry, 03 medical and health sciences, nitric oxide, POLYETHYLENE-GLYCOL, medicine, Animals, Aspartate Aminotransferases, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, 4-HNE, Liver diseases, PEG35, ALDH2, fatty liver, Cryopreservation, Science & Technology, NITRIC-OXIDE, TRANSPLANTATION, Microcirculation, Organic Chemistry, medicine.disease, Òxid nítric, Liver Transplantation, Rats, Rats, Zucker, Transplantation, IGL-1 solution, 030104 developmental biology, chemistry, Hepatic transplantation
Abstract: The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes., This research was funded by Instituto de Salud Carlos III through FIS project PI 15/00110 co-funded by FEDER from Regional Development European Funds (European Union) and the FOIE GRAS project, which has received funding from the European Union’s Horizon 2020 Research and Innovation program under the Marie Sklodowska-Curie Grant (Agreement No. 722619).
Published: 2021

46. Autofluorescence imaging within the liver: a promising tool for the detection and characterization of primary liver tumors

Author: Nicolas Poté, René Farcy, Hervé Puy, Fouad Lafdil, Charlotte Benoit, Jean-Charles Deybach, J. Calderaro, E. Itti, Laurent Gouya, Caroline Schmitt, Aurélie Rodrigues, Valérie Vilgrain, Sébastien Mulé, Valérie Paradis, Cécile Charpy, Alain Luciani, and Sylvie Simonin
Subjects: Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Sensitivity and Specificity, Parenchyma, Biopsy, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Intrahepatic Cholangiocarcinomas, Neuroradiology, medicine.diagnostic_test, business.industry, Ultrasound, Liver Neoplasms, Optical Imaging, General Medicine, Autofluorescence, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Liver, Liver biopsy, Radiology, business, Ex vivo
Abstract: To assess the performance of 405 nm-induced autofluorescence for the characterization of primary liver nodules on ex vivo resected specimens.Forty resected liver specimens bearing 53 primary liver nodules were included in this IRB-approved prospective study. Intratissular spectroscopic measurements were performed using a 25-G fibered-needle on all ex vivo specimens: 5 autofluorescence measurements were performed in both nodules and adjacent parenchyma. The spectra derivatives of the 635 and 670 nm autofluorescence peaks observed in nodules and in adjacent liver parenchyma were compared (Kruskal-Wallis and Mann-Whitney when appropriate).A total of 42 potentially evolutive primary liver nodules-34 hepatocellular carcinomas, 4 intrahepatic cholangiocarcinomas, 4 hepatocellular adenomas-and 11 benign nodules-5 focal nodular hyperplasias, 6 regenerative nodules-were included. Both 635 and 670 nm Δderivatives were significantly higher in benign as compared to potentially evolutive (PEV) nodules (respectively 32.9 ± 4.5 vs 15.3 ± 1.4; p 0.0001 and 5.7 ± 0.6 vs 2.5 ± 0.1; p 0.0001) with respective sensitivity and specificity of 78% and 91% for distinguishing PEV from benign nodules.405 nm-induced autofluorescence enables the discrimination of benign from PEV primary liver nodules, suggesting that autofluorescence imaging could be used to optimize US targeted liver biopsies.• 405 nm-induced autofluorescence can distinguish liver tumors from the adjacent liver parenchyma. • The analysis of autofluorescence imaging observed within primary liver tumors can discriminate benign tumors from those requiring follow-up or targeted liver biopsy. • In current practice, autofluorescence imaging could be embedded within biopsy needle, to enable, in addition to ultrasound guidance, optimal targeting of liver nodules which could optimize tissue sampling.
Published: 2021

47. Live birth rate after use of cryopreserved oocytes or embryos at the time of cancer diagnosis in female survivors: a retrospective study of ten years of experience

Author: V. Gallot, Michael Grynberg, Vincent Puy, Alexandra Benoit, Laetitia Hesters, Victoria Windal, Charlotte Sonigo, Nelly Frydman, and Anne Mayeur
Subjects: 0301 basic medicine, Adult, Pregnancy Rate, Cryopreservation, Andrology, 03 medical and health sciences, 0302 clinical medicine, Embryo cryopreservation, Cancer Survivors, Ovulation Induction, Pregnancy, Neoplasms, Genetics, Medicine, Humans, Fertility preservation, Genetics (clinical), Retrospective Studies, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Fertility Preservation, Retrospective cohort study, Embryo, General Medicine, Oocyte cryopreservation, Embryo transfer, In Vitro Oocyte Maturation Techniques, 030104 developmental biology, Blastocyst, Reproductive Medicine, embryonic structures, Oocytes, Female, business, Live birth, Developmental Biology
Abstract: PURPOSE: The aim of this study was to evaluate the outcomes of frozen oocytes or embryos cryopreserved after controlled ovarian stimulation (COS) or in vitro maturation (IVM) for female cancer patients who underwent a fertility preservation (FP) prior to gonadotoxic therapy. METHODS: A retrospective cohort study from 2009 to December 2017 was conducted. Among the 667 female cancer patients who underwent oocytes or embryos cryopreservation for FP, 40 (6%) have returned to the fertility clinic between 2011 and 2019 to use their frozen material after being cured. We compared these thaw cycles outcomes according to the techniques used at the time of cryopreservation. RESULTS: Among the 40 women cancer survivors who used their cryopreserved material, thirty patients have benefited from at least one embryo transfer. Ten patients did not have an embryo transfer since the oocytes did not survive after the thawing process or because no embryo was obtained after fertilization. We related three live births following FP using IVM (two from frozen oocytes and one after embryo cryopreservation). Five live births were obtained when COS was performed at the time of FP (one from frozen oocytes and four after embryo cryopreservation). CONCLUSIONS: Our preliminary results, although they are obtained in a small sample, are encouraging and show that different FP techniques can be used in female cancer patients and lead to live births. IVM is one of the options available that does not delay the start of chemotherapy or if ovarian stimulation using gonadotropins is contraindicated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02168-3.
Published: 2021

48. Neutrophil extracellular traps (NETs) infiltrate haematoma and surrounding brain tissue after intracerebral haemorrhage: A post-mortem study

Author: Romain Perbet, Delphine Corseaux, Vincent Deramecourt, Charlotte Cordonnier, Vincent Berezowski, and Laurent Puy
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Histology, Neutrophils, Autopsy, Brain tissue, Extracellular Traps, Fibrin, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Humans, Stroke, Cerebral Hemorrhage, Peroxidase, Hematoma, biology, business.industry, Brain, Neutrophil extracellular traps, medicine.disease, 030104 developmental biology, Neurology, Myeloperoxidase, biology.protein, Neurology (clinical), business, Infiltration (medical), 030217 neurology & neurosurgery
Abstract: Aim(s) Because of their prothrombotic and neuroinflammatory effects, neutrophils and neutrophil extracellular traps (NETs) represent interesting therapeutic targets for spontaneous intracerebral haemorrhage (sICH). We investigated the presence, spatial and temporal distribution of NETs in a human sICH post-mortem study. Methods From 2005 to 2019, all sICH patients who came to autopsy within the first month after stroke were included and grouped according to the timing of death: 72 hours, 4-7 days, 8-15 days and > 15 days after ICH onset. Paraffin-embedded tissue was extracted from four strategic areas: haematoma, peri-haematomal area, ipsilateral surrounding brain tissue and a control contralateral area. Myeloperoxidase and histone H3 citrulline were immunolabelled to detect neutrophils and NETs, respectively. Results Neutrophils were present in the brains of the 14 cases (4 men, median age: 78 years) and NETs were found in 7/14 cases. Both neutrophils and NETs were detected within the haematoma but also in the surrounding tissue. The appearance of neutrophils and NETs was time-dependent, following a two-wave pattern: during the first 72 hours and between 8-15 days after ICH onset. Qualitative examination showed that neutrophils and NETs were mainly located around dense fibrin fibres within the haematoma. Conclusions These observations provide evidence for NETs infiltration in the brain of patients who die from sICH. NETs might interact with early haemostasis within the haematoma core, and with the surrounding neuroinflammatory response. These findings open research perspectives for NETs in the treatment of sICH injuries.
Published: 2021

49. Cerebral microbleeds: from depiction to interpretation

Author: Laurent Puy, Ashkan Shoamanesh, Mark Rodrigues, Charlotte Cordonnier, Marco Pasi, Susanne J. van Veluw, and Georgios Tsivgoulis
Subjects: medicine.medical_specialty, business.industry, Context (language use), Disease, 030204 cardiovascular system & hematology, medicine.disease, Clinical Practice, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Healthy individuals, medicine, Research studies, Dementia, Surgery, In patient, Neurology (clinical), Radiology, business, Stroke, 030217 neurology & neurosurgery
Abstract: Cerebral microbleeds (CMBs) are defined as hypointense foci visible on T2*-weighted and susceptible-weighted MRI sequences. CMBs are increasingly recognised with the widespread use of MRI in healthy individuals as well as in the context of cerebrovascular disease or dementia. They can also be encountered in major critical medical conditions such as in patients requiring extracorporeal mechanical oxygenation. The advent of MRI-guided postmortem neuropathological examinations confirmed that, in the context of cerebrovascular disease, the vast majority of CMBs correspond to recent or old microhaemorrhages. Detection of CMBs is highly influenced by MRI parameters, in particular field strength, postprocessing methods used to enhance T2* contrast and three dimensional sequences. Despite recent progress, harmonising imaging parameters across research studies remains necessary to improve cross-study comparisons. CMBs are helpful markers to identify the nature and the severity of the underlying chronic small vessel disease. In daily clinical practice, presence and numbers of CMBs often trigger uncertainty for clinicians especially when antithrombotic treatments and acute reperfusion therapies are discussed. In the present review, we discuss those clinical dilemmas and address the value of CMBs as diagnostic and prognostic markers for future vascular events.
Published: 2021
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50. Evaluation of Diagnosis and Management of Omega-5-Gliadin Allergy: A Retrospective Survey

Author: Celia Zubrinich, Mark Hew, Robert Puy, and Robyn E O'Hehir
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pediatrics, Allergy, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Food allergy, Epidemiology, medicine, Journal of Asthma and Allergy, anaphylaxis, Immunology and Allergy, 0601 history and archaeology, FDEIA, Asthma, Original Research, WDEIA, chemistry.chemical_classification, wheat-dependent exercise-induced anaphylaxis, food allergy, 060102 archaeology, business.industry, 06 humanities and the arts, medicine.disease, Gluten, wheat allergy, food-dependent exercise-induced anaphylaxis, 030228 respiratory system, chemistry, business, omega-5-gliadin allergy, Wheat allergy, Anaphylaxis
Abstract: Celia Zubrinich,1,2 Robert Puy,1,3 Robyn O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia Zubrinich Email c.zubrinich@alfred.org.auBackground: Allergy to the omega-5-gliadin component of gluten (O-5-G allergy) often manifests when wheat ingestion is followed by a co-factor, usually exercise. There is no established best approach to management.Objective: We sought to identify the beneficial effects, firstly of establishing a firm diagnosis, and secondly of stringent management, either by avoiding gluten ingestion altogether or separating it temporally from exercise by at least 4 hours. We also determined how frequently patients adhered to their physicians’ clinical recommendations.Methods: We undertook a survey of individuals diagnosed with O-5-G allergy at our institution over 8 years, who had a consistent clinical history and confirmatory laboratory evidence.Results: Of 80 eligible individuals, 43 responded (54%). Symptoms began in adulthood for all bar one, and concurrent asthma and eczema was uncommon (9% prevalence, respectively). Median time to diagnosis was 2 years. Achieving a diagnosis reduced the rate of reactions (0.35 per month vs 1.085 reactions per month, p=0.029). Many patients (10/43) did not adhere to the recommended stringent approach, to either avoid wheat/gluten or separate food and exercise by 4 hours. However, those adopting a stringent approach had a substantially lower risk of recurrent allergic reaction (0.22 per month vs 0.74 per month, p=0.004).Conclusion: The epidemiology of O-5-G allergy implies pathogenic mechanisms potentially distinct from those of childhood-onset food allergy. Accurate diagnosis improves the clinical trajectory, primarily through the adoption of a stringent management approach.Keywords: omega-5-gliadin allergy, wheat allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced anaphylaxis, WDEIA, food-dependent exercise-induced anaphylaxis, FDEIA
Published: 2021

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