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1. The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology

Author

Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M. -C., Borhany, M., Heller, P. G., Santoro, C., Cid, A. R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M. G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M. P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A. C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A. L., Harrison, P., Mezzano, D., Mumford, A. D., Lordkipanidzé, M., BAT-VAL Study Investigators, Università degli Studi di Perugia = University of Perugia (UNIPG), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unidad de Coagulopatías Congénitas. Hospital Universitario La Fe., Gresele, Paolo, Falcinelli, Emanuela, Bury, Loredana, Pecci, Alessandro, Alessi, Marie-Christine, Borhany, Munira, Heller, Paula G, Santoro, Cristina, Cid, Ana Rosa, Orsini, Sara, Fontana, Pierre, De Candia, Erica, Podda, Gianmarco, Kannan, Meganathan, Jurk, Kerstin, Castaman, Giancarlo, Falaise, Céline, Guglielmini, Giuseppe, Noris, Patrizia, Mariasanta Napolitano, Università degli Studi di Perugia (UNIPG), University of Perugia, Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M.-C., Borhany, M., Heller, P.G., Santoro, C., Cid, A.R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M.G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M.P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A.C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A.L., Harrison, P., Mezzano, D., Mumford, A.D., Lordkipanidzé, M., and BAT-VAL Study Investigators

Subjects
medicine.medical_specialty, animal structures, mild&#8208, Platelet Function Tests, Platelet disorder, inherited platelet disorder, Hemorrhage, 030204 cardiovascular system & hematology, Hemorrhage/diagnosis, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, hemic and lymphatic diseases, Internal medicine, von Willebrand Factor, Von Willebrand disease, Medicine, Humans, Platelet, Bleeding prediction, Bleeding score, Blood platelet disorders, Child, Communication, Hemorrhage, Humans, Inherited platelet disorders, Mild-moderate bleeding disorders, Platelet Function Tests, von Willebrand diseases, von Willebrand Factor, Child, Blood Platelet Disorders, ddc:616, mild-moderate bleeding disorders, biology, business.industry, mild-moderate bleeding disorder, Incidence (epidemiology), Communication, Settore MED/09 - MEDICINA INTERNA, bleeding prediction, von Willebrand Diseases/diagnosis/genetics, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Blood Platelet Disorders/diagnosis/genetics, 3. Good health, bleeding score, Institutional repository, von Willebrand Diseases, moderate bleeding disorders, inherited platelet disorders, Quartile, biology.protein, von Willebrand disease, business
Abstract

Background: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). Objectives: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. Methods: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2years and bleeding episodes requiring treatment were recorded. Results: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n=235) than VWD-1 (n=52) or inherited thrombocytopenia (IT; n=20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p&nbsp

Published
2021

2. Trend in rifampicin-, multidrug- and extensively drug-resistant tuberculosis in Italy, 2009-2016

Author

Mustazzolu, A., Borroni, E., Cirillo, D. M., Giannoni, F., Iacobino, A., Fattorini, L., Ghisetti, V., Mondo, A., Avolio, M., Barbui, A., Lorenzetti, P., De Renzi, G., Chirillo, M. G., Molinari, G., Camaggi, A., Andreoni, S., Piana, F., Marchese, A., Gritti, P., Icardi, G., Varnier, O., Mazzola, E., Gesu, G., Cichero, P., Lombardi, A., Libanori, E., Viggiani, P., De Lorenzo, S., Pinsi, G., Marone, P., Monzillo, V., Barbarini, D., Farina, C., Arosio, M., Peracchi, M., Manganelli, R., Fabris, C., Di Santolo, M., Busetti, M., Scarparo, C., Sartor, A., Pedrotti, C., Caola, I., Frizzera, E., Dal Monte, P., Pietrosemoli, P., Pecorari, M., Fabio, A., La Regina, A., Matteucci, M., Piersimoni, C., Bartolesi, A., Mannino, R., Simonetti, T., Tortoli, E., Rindi, L., Mencacci, A., Cenci, E., Luciano, E., Mazzolla, R., Sanguigni, I., Parisi, G., Chiaradonna, P., Altieri, A. M., D'Arezzo, S., Mazzarelli, A., Di Caro, A., Bordi, E., Sali, M., Delogu, G., Sanguinetti, M., Russo, C., Coltella, L., Ciocco, A., Meledandri, M., Gambi, A., Tomei, G., Conte, M., Santoro, G., Del Giudice, A., Nuzzolese, N., Vitullo, E., Sinno, A., Buono, L., Costa, D., Grimaldi, A., Di Taranto, A., De Nittis, R., Palumbo, G., Dodaro, S., Giraldi, C., Cavalcanti, P., Nistico, S., Vinci, L., Di Naso, C., Bonura, C., Maida, C. M., Mammina, C., Podda, G. S., Caddeu, R., Mustazzolu A., Borroni E., Cirillo D.M., Giannoni F., Iacobino A., Fattorini L., Ghisetti V., Mondo A., Avolio M., Barbui A., Lorenzetti P., De Renzi G., Chirillo M.G., Molinari G., Camaggi A., Andreoni S., Piana F., Marchese A., Gritti P., Icardi G., Varnier O., Mazzola E., Gesu G., Cichero P., Lombardi A., Libanori E., Viggiani P., De Lorenzo S., Pinsi G., Marone P., Monzillo V., Barbarini D., Farina C., Arosio M., Peracchi M., Manganelli R., Fabris C., Di Santolo M., Busetti M., Scarparo C., Sartor A., Pedrotti C., Caola I., Frizzera E., Dal Monte P., Pietrosemoli P., Pecorari M., Fabio A., La Regina A., Matteucci M., Piersimoni C., Bartolesi A., Mannino R., Simonetti T., Tortoli E., Rindi L., Mencacci A., Cenci E., Luciano E., Mazzolla R., Sanguigni I., Parisi G., Chiaradonna P., Altieri A.M., D'Arezzo S., Mazzarelli A., Di Caro A., Bordi E., Sali M., Delogu G., Sanguinetti M., Russo C., Coltella L., Ciocco A., Meledandri M., Gambi A., Tomei G., Conte M., Santoro G., Del Giudice A., Nuzzolese N., Vitullo E., Sinno A., Buono L., Costa D., Grimaldi A., Di Taranto A., De Nittis R., Palumbo G., Dodaro S., Giraldi C., Cavalcanti P., Nistico S., Vinci L., Di Naso C., Bonura C., Maida C.M., Mammina C., Podda G.S., and Caddeu R.

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Extensively Drug-Resistant Tuberculosis, Antitubercular Agents, Emigrants and Immigrants, Humans, Italy, Mycobacterium tuberculosis, Rifampin, Tuberculosis, Multidrug-Resistant, 03 medical and health sciences, 0302 clinical medicine, polycyclic compounds, medicine, Tuberculosis, biology, business.industry, Extensively drug-resistant tuberculosis, Multidrug-Resistant, medicine.disease, biology.organism_classification, Virology, 030104 developmental biology, 030228 respiratory system, business, Rifampicin, medicine.drug
Abstract

In Italy, rifampicin-resistant and MDR-TB were high in foreign-born persons, but decreased from 2009 to 2016

Published
2018

3. The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians

Author

Clara Mannarella, Erminia Rinaldi, Katia Codeluppi, Anna Maria Cerbone, Sergio Amarri, Daniela Nicolosi, Michele Pizzuti, Luca Facchini, Alessandro De Fanti, Michela Ronchi, Emanuela Pappalardo, Barbara Ferrari, Monica Bocchia, Gaetano Giuffrida, Vanessa Agostini, Cinzia Caria, Silvia Maria Trisolini, Salvatore Gattillo, Elisa Giacomini, Gian Marco Podda, Aldo Caddori, Saveria Capria, Antonella Tufano, Silvia Cerù, Marzia Defina, Alberto Fragasso, Roberta Gualtierotti, Andrea Artoni, Simona Campus, Flora Peyvandi, Silvia Pontiggia, Umberto Roncarati, Ilaria Mancini, Giuseppe Menna, Domenico Pastore, Frits R. Rosendaal, Simone Birocchi, Mancini, I., Giacomini, E., Pontiggia, S., Artoni, A., Ferrari, B., Pappalardo, E., Gualtierotti, R., Trisolini, S. M., Capria, S., Facchini, L., Codeluppi, K., Rinaldi, E., Pastore, D., Campus, S., Caria, C., Caddori, A., Nicolosi, D., Giuffrida, G., Agostini, V., Roncarati, U., Mannarella, C., Fragasso, A., Podda, G. M., Birocchi, S., Cerbone, A. M., Tufano, A., Menna, G., Pizzuti, M., Ronchi, M., De Fanti, A., Amarri, S., Defina, M., Bocchia, M., Ceru, S., Gattillo, S., Rosendaal, F. R., and Peyvandi, F.

Subjects
medicine.medical_specialty, Thrombotic microangiopathy, ADAMTS13, HLA, autoimmune disease, genotyping, relapse, risk factor, thrombotic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura, lcsh:Medicine, Human leukocyte antigen, 030204 cardiovascular system & hematology, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Risk factor, business.industry, lcsh:R, Absolute risk reduction, General Medicine, Odds ratio, medicine.disease, business, 030215 immunology, Cohort study
Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30&ndash, 50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23), heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (&beta, &minus, 3.34, 95%CI &minus, 6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

Published
2020

4. Impact of Gene Polymorphisms, Platelet Reactivity, and the SYNTAX Score on 1-Year Clinical Outcomes in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention The GEPRESS Study

Author

Gian Marco Podda, Luciana Tomasi, Dominick J. Angiolillo, Letizia Bacchi Reggiani, Diego Della Riva, Matteo Mariani, Federico Piscione, Philippe Généreux, Marco Cattaneo, Roberta De Rosa, Davide Capodanno, Chiara Barozzi, Paolo Calabrò, Stefano De Servi, Marco De Carlo, Anna Toso, Gregg W. Stone, Andrea Mariani, Cataldo Palmieri, Renatomaria Bianchi, Nevio Taglieri, Tullio Palmerini, Diego Maffeo, Antonio L. Bartorelli, Palmerini, T., Calabro, P., Piscione, F., De Servi, S., Cattaneo, M., Maffeo, D., Toso, A., Bartorelli, A., Palmieri, C., De Carlo, M., Capodanno, D., Barozzi, C., Tomasi, L., Della Riva, D., Mariani, A., Taglieri, N., Reggiani, L.B., Bianchi, R., De Rosa, R., Mariani, M., Podda, G., Genereux, P., Stone, G.W., Angiolillo, D.J., Palmerini, T, Calabro', Paolo, Piscione, F, De Servi, S, Cattaneo, M, Maffeo, D, Toso, A, Bartorelli, A, Palmieri, C, De Carlo, M, Capodanno, D, Barozzi, C, Tomasi, L, Della Riva, D, Mariani, A, Taglieri, N, Reggiani, Lb, Bianchi, R, De Rosa, R, Mariani, M, Podda, G, Généreux, P, Stone, Gw, and Angiolillo, Dj

Subjects
Male, platelet reactivity, Time Factors, medicine.medical_treatment, Myocardial Infarction, Predictive Value of Test, Kaplan-Meier Estimate, Coronary Angiography, Risk Factors, Odds Ratio, ST segment, Prospective Studies, Multivariate Analysi, Biotransformation, Ejection fraction, Middle Aged, Clopidogrel, Cardiac surgery, SYNTAX score, Phenotype, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, Human, medicine.drug, Blood Platelets, medicine.medical_specialty, Acute coronary syndrome, Coronary Thrombosi, Ticlopidine, Time Factor, Genotype, Platelet Function Tests, clopidogrel, Risk Assessment, Percutaneous Coronary Intervention, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, Acute Coronary Syndrome, Aged, Proportional Hazards Models, Polymorphism, Genetic, business.industry, Platelet Aggregation Inhibitor, Risk Factor, Coronary Thrombosis, Percutaneous coronary intervention, medicine.disease, Surgery, Cytochrome P-450 CYP2C19, Prospective Studie, Platelet Function Test, Multivariate Analysis, Conventional PCI, Proportional Hazards Model, Blood Platelet, business, Platelet Aggregation Inhibitors, Mace
Abstract

ObjectivesThe aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI).BackgroundPlatelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this category of patients remains challenging.MethodsThe GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year.ResultsBetween 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS

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5. Guidelines on the management of atrial fibrillation in the emergency department: a critical appraisal

Author

Maristella Salvatora Masala, Gian Marco Podda, Inês João da Silva Chora, Olaug Marie Reiakvam, G. Privitera, Giorgio Costantino, Nicola Montano, Christopher Davidson, Jan Schovanek, Matthias von Rotz, Ana Lages, Sjoerd van Bree, Lorenzo Falsetti, Silvio Ragozzino, Primiano Iannone, Lycke Woittiez, Florentia Savva, Alberto M. Marra, Costantino, G., Podda, G. M., Falsetti, L., Iannone, P., Lages, A., Marra, A. M., Masala, M., Reiakvam, O. M., Savva, F., Schovanek, J., van Bree, S., da Silva Chora, I. J., Privitera, G., Ragozzino, S., von Rotz, M., Woittiez, L., Davidson, C., Montano, N., Costantino, G, Podda, Gm, Falsetti, L, Iannone, P, Lages, A, Marra, Am, Masala, M, Reiakvam, Om, Savva, F, Schovanek, J, van Bree, S, da Silva Chora IJ, Privitera, G, Ragozzino, S, von Rotz, M, Woittiez, L, and Davidson, C

Subjects
Electric Countershock, Management of atrial fibrillation, Guidelines as Topic, 030204 cardiovascular system & hematology, Guideline, Guidelines, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Atrial Fibrillation, Internal Medicine, Medicine, Humans, Complete Agreement, 030212 general & internal medicine, Evidence-Based Medicine, business.industry, Emergency department, Hemodynamics, Anticoagulants, Disease Management, Atrial fibrillation, Evidence-based medicine, Critical appraisal, medicine.disease, Clinical trial, Emergency Medicine, Education, Medical, Continuing, Medical emergency, business, Working group, Emergency Service, Hospital
Abstract

Several guidelines often exist on the same topic, sometimes offering divergent recommendations. For the clinician, it can be difficult to understand the reasons for this divergence and how to select the right recommendations. The aim of this study is to compare different guidelines on the management of atrial fibrillation (AF), and provide practical and affordable advice on its management in the acute setting. A PubMed search was performed in May 2014 to identify the three most recent and cited published guidelines on AF. During the 1-week school of the European School of Internal Medicine, the attending residents were divided in five working groups. The three selected guidelines were compared with five specific questions. The guidelines identified were: the European Society of Cardiology guidelines on AF, the Canadian guidelines on emergency department management of AF, and the American Heart Association guidelines on AF. Twenty-one relevant sub-questions were identified. For five of these, there was no agreement between guidelines; for three, there was partial agreement; for three data were not available (issue not covered by one of the guidelines), while for ten, there was complete agreement. Evidence on the management of AF in the acute setting is largely based on expert opinion rather than clinical trials. While there is broad agreement on the management of the haemodynamically unstable patient and the use of drugs for rate-control strategy, there is less agreement on drug therapy for rhythm control and no agreement on several other topics.

6. Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes

Author

Massimo Buscema, Marco Cattaneo, Enzo Grossi, Gian Marco Podda, D. Della Riva, Paolo S. Calabrò, Federico Piscione, Philippe Généreux, Eti Alessandra Femia, Diego Maffeo, S. De Servi, Tullio Palmerini, Davide Capodanno, M. De Carlo, Anna Toso, Cataldo Palmieri, Podda, G. M., Grossi, E., Palmerini, T., Buscema, M., Femia, E. A., Della Riva, D., de Servi, S., Calabro', Paolo, Piscione, Federico, Maffeo, D., Toso, A., Palmieri, C., De Carlo, M., Capodanno, D., Genereux, P., and Cattaneo, M.

Subjects
Male, Artificial neural network, medicine.medical_specialty, Acute coronary syndrome, Ticlopidine, 030204 cardiovascular system & hematology, law.invention, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Predictive Value of Tests, Internal medicine, medicine, Humans, Gene Regulatory Networks, Platelet activation, Prospective Studies, Acute Coronary Syndrome, Prospective cohort study, Aged, business.industry, Antiplatelet therapy, Middle Aged, VASP, medicine.disease, Clopidogrel, Platelet Activation, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Predictive value of tests, Platelet aggregation inhibitor, Female, Neural Networks, Computer, Cardiology and Cardiovascular Medicine, business, Platelet reactivity, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Background: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients.Methods: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1 month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score > 14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1 month, compared to TSMs.Results: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1 month).Conclusions: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype. (C) 2017 Elsevier B.V. All rights reserved.

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