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2. Hypersensitivity to polyethylene glycol in adults and children: An emerging challenge

Author

Bianchi A., Bottau P., Calamelli E., Caimmi S., Crisafulli G., Franceschini F., Liotti L., Mori F., Paglialunga C., Saretta F., Tosca M., Cardinale F., Licari A., Miraglia Del Giudice M., Caffarelli C., Bianchi, A., Bottau, P., Calamelli, E., Caimmi, S., Crisafulli, G., Franceschini, F., Liotti, L., Mori, F., Paglialunga, C., Saretta, F., Tosca, M., Cardinale, F., Licari, A., Miraglia Del Giudice, M., and Caffarelli, C.

Subjects
Adult, COVID-19 Vaccines, SARS-CoV-2, COVID-19 Vaccine, technology, industry, and agriculture, COVID-19, macromolecular substances, PEG allergy, Drug allergy, Polyethylene Glycol, Polyethylene Glycols, Polyethylene glycol hypersensitivity, Vaccine allergy, Anaphylaxi, Humans, Child, Anaphylaxis, Human
Abstract

Hypersensitivity reactions to polyethylene glycol (PEG) is an emerging challenge and the interest about this disease is growing since PEG is considered one of the possible causes of coronavirus disease 2019 (COVID 19) vaccine-associated anaphylaxis. PEG is used in a wide variety of pharmaceutical, medical, in-dustrial, cosmetic, and food products and can be an active ingredient or used as an excipient. PEG is present in several medications, and it may or may not be present in different formulations and dosages of the same drug. Lack of standardization nomenclature, inadequate labelling of products and lack of knowledge about PEG involvement in hypersensitivity reactions expose patients at risk of presenting multiple reactions before a diagnosis could be made. In this review we describe the main cases published in literature and propose an allergy work-up and management. (www.actabiomedica.it).

Published
2021

3. 18-FDG PET in lung transplantation

Author

Algieri, I, Valenza, F, Guanziroli, M, Fakhr, B Safaee, Cressoni, M, Brioni, M, Colombo, A, Babini, G, Crimella, F, Massari, D, Nikolla, K, Crisafulli, G, Paladini, S, Rosso, L, Palleschi, A, Zito, F, Chiumello, D, and Gattinoni, L

Published
2015
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5. Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

Author

Cardinale, F, Ciprandi, G, Barberi, S, Bernardini, R, Caffarelli, C, Calvani, M, Cavagni, G, Galli, E, Minasi, D, Del Giudice, M, Moschese, V, Novembre, E, Paravati, F, Peroni, D, Tosca, M, Traina, G, Tripodi, S, Marseglia, G, Amato, D, Anania, C, Anastasio, E, Antignani, R, Arasi, S, Baldassarre, M, Baldo, E, Barbalace, A, Barni, S, Betti, F, Bianchi, A, Bolzacchini, E, Bonini, M, Bottau, P, Bozzetto, S, Brighetti, M, Caimmi, D, Caimmi, S, Calzone, L, Cancrini, C, Caminiti, L, Capata, G, Capra, L, Capristo, C, Carboni, E, Carella, F, Castagnoli, R, Chiappini, E, Chiera, F, Chinellato, I, Chini, L, Cipriani, F, Civitelli, F, Comberiati, P, Contini, D, Corrente, S, Cravidi, C, Crisafulli, G, Cuomo, B, D'Auria, E, D'Elios, S, Decimo, F, Giustina, A, Piane, R, De Filippo, M, De Vittori, V, Diaferio, L, Di Mauro, M, Duse, M, Federici, S, Felice, G, Fenu, G, Ferrante, G, Foti, T, Franceschini, F, Ghiglioni, D, Giardino, G, Giovannini, M, Indirli, G, Indolfi, C, Landi, M, La Torre, F, Leone, L, Licari, A, Liotti, L, Lougaris, V, Maiello, N, Mantecca, P, Manti, S, Mariani, M, Martelli, A, Mastrorilli, C, Mastrorilli, V, Montin, D, Mori, F, Olcese, R, Ottaviano, G, Paglialunga, C, Pajno, G, Parisi, G, Pattini, S, Pecoraro, L, Pelosi, U, Pignata, C, Ricci, G, Ricci, S, Rizzi, S, Rizzo, C, Rosati, S, Rosso, P, Sangerardi, M, Santoro, A, Saretta, F, Sarti, L, Sartorio, M, Sgruletti, M, Soresina, A, Sfika, I, Sgrulletti, M, Tesse, N, Tranchino, V, Travaglini, A, Velia, M, Verduci, E, Vernich, M, Veronelli, E, Volpi, S, Votto, M, Zicari, A, Cardinale, F, Ciprandi, G, Barberi, S, Bernardini, R, Caffarelli, C, Calvani, M, Cavagni, G, Galli, E, Minasi, D, Del Giudice, M, Moschese, V, Novembre, E, Paravati, F, Peroni, D, Tosca, M, Traina, G, Tripodi, S, Marseglia, G, Amato, D, Anania, C, Anastasio, E, Antignani, R, Arasi, S, Baldassarre, M, Baldo, E, Barbalace, A, Barni, S, Betti, F, Bianchi, A, Bolzacchini, E, Bonini, M, Bottau, P, Bozzetto, S, Brighetti, M, Caimmi, D, Caimmi, S, Calzone, L, Cancrini, C, Caminiti, L, Capata, G, Capra, L, Capristo, C, Carboni, E, Carella, F, Castagnoli, R, Chiappini, E, Chiera, F, Chinellato, I, Chini, L, Cipriani, F, Civitelli, F, Comberiati, P, Contini, D, Corrente, S, Cravidi, C, Crisafulli, G, Cuomo, B, D'Auria, E, D'Elios, S, Decimo, F, Giustina, A, Piane, R, De Filippo, M, De Vittori, V, Diaferio, L, Di Mauro, M, Duse, M, Federici, S, Felice, G, Fenu, G, Ferrante, G, Foti, T, Franceschini, F, Ghiglioni, D, Giardino, G, Giovannini, M, Indirli, G, Indolfi, C, Landi, M, La Torre, F, Leone, L, Licari, A, Liotti, L, Lougaris, V, Maiello, N, Mantecca, P, Manti, S, Mariani, M, Martelli, A, Mastrorilli, C, Mastrorilli, V, Montin, D, Mori, F, Olcese, R, Ottaviano, G, Paglialunga, C, Pajno, G, Parisi, G, Pattini, S, Pecoraro, L, Pelosi, U, Pignata, C, Ricci, G, Ricci, S, Rizzi, S, Rizzo, C, Rosati, S, Rosso, P, Sangerardi, M, Santoro, A, Saretta, F, Sarti, L, Sartorio, M, Sgruletti, M, Soresina, A, Sfika, I, Sgrulletti, M, Tesse, N, Tranchino, V, Travaglini, A, Velia, M, Verduci, E, Vernich, M, Veronelli, E, Volpi, S, Votto, M, and Zicari, A

Abstract

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Published
2020

7. Omalizumab in children with severe allergic asthma: The Italian real- life experience

Author

Licari, A., Castagnoli, R., Denicolo, C., Rossini, L., Seminara, M., Sacchi, L., Testa, G., De Amici, M., Marseglia, G. L., Anastasio, E., Pugliese Ciaccio, A. O., Caffarelli, C., Cardinale, F., Cirisano, A., Crisafulli, G., Cutrera, R., Di Cara, G., Di Marco, A., Duse, M., Fabiano, C., Fiocchi, A., Leone, M., Pajno, G., Panfili, E., Verrotti, A., and Volpini, A.

Subjects
severe asthma, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, medicine.drug_class, Allergic asthma, Inhaled corticosteroids, Omalizumab, asthma therapy, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, anti-IgE, 030212 general & internal medicine, Anti-IgE, Asthma therapy, Monoclonal antibodies, Severe asthma, Adverse effect, business.industry, Pulmonology, 030228 respiratory system, omalizumab, Corticosteroid, Observational study, monoclonal antibodies, business, medicine.drug, Pediatric population
Abstract

Background: Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. To date, omalizumab is the only biological drug currently licensed as add-on therapy in children aged > 6 years with moderate-to-severe and severe allergic asthma uncontrolled after treatment with high dose of inhaled corticosteroids plus long-acting inhaled beta2-agonist. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. Our aim is to describe the impact of omalizumab on asthma management, by reporting the results of the first Italian multicenter observational study conducted in children and adolescents with severe allergic asthma. Methods: The study was a 1-year real-life multicenter survey conducted in 13 pediatric allergy and pulmonology tertiary centers in Italy. All patients with confirmed severe allergic asthma from whom Omalizumab add-on treatment was initiated between 2007 and 2015 were included in the study. Results: Forty-seven patients with severe allergic asthma were included in the study. A significant reduction in the number of asthma exacerbations was observed during treatment with omalizumab, when compared with the previous year (1.03 vs 7.2 after 6 months (p

Published
2017

8. Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report

Author

Pajno, Gb, Bernardini, R, Peroni, Diego, Arasi, S, Martelli, Arianna, Landi, M, Passalacqua, G, Muraro, Alessandra, La Grutta, S, Fiocchi, A, Indinnimeo, L, Caffarelli, C, Calamelli, E, Comberiati, Pasquale, Duse, M, Akdis, C, Akdis, M, Arrigoni, Sara, Barberi, S, Baviera, G, Boner, Attilio, Calvani, M, Calzone, L, Caminiti, L, Capristo, A, Capristo, C, Chiera, F, Cravidi, C, Crisafulli, G, De Castro, G, DE SIMONE, Martina, Dello Iacono, I, Dondi, A, Galli, Enrico, Guglielmo, F, Maiello, N, Marseglia, G, Matricardi, Pm, Meglio, P, Minasi, D, Del Giudice, Mm, Panasci, G, Paravati, F, Pelosi, U, Pingitore, G, Ricci, G, Scala, G, Terracciano, L, Tosca, M, Tripodi, S, Verga, Mc, Wahn, U., Pajno, Giovanni Battista, Bernardini, Roberto, Peroni, Diego, Arasi, Stefania, Martelli, Alberto, Landi, Massimo, Passalacqua, Giovanni, Muraro, Antonella, La Grutta, Stefania, Fiocchi, Alessandro, Indinnimeo, Luciana, Caffarelli, Carlo, Calamelli, Elisabetta, Comberiati, Pasquale, and Duse, Marzia

Subjects
Pediatrics, Allergy, medicine.medical_treatment, Administration, Oral, Dermatitis, Review, Desensitization, 0302 clinical medicine, Immunologic, 030212 general & internal medicine, Child, Children, Societies, Medical, Randomized Controlled Trials as Topic, Clinical Trials as Topic, Subcutaneous immunotherapy, Subcutaneous, Atopic dermatitis, Perinatology and Child Health, Atopic dermatiti, Clinical Practice, Treatment Outcome, allergen-specific immunotherapy, allergy, asthma, atopic dermatitis, children, food allergy, sub-lingual immunotherapy, subcutaneous immunotherapy, pediatrics, perinatology and child health, Italy, Administration, Practice Guidelines as Topic, Sub-lingual immunotherapy, Food Hypersensitivity, Oral, medicine.medical_specialty, Consensus, Injections, Subcutaneous, Atopic, Dermatitis, Atopic, Injections, 03 medical and health sciences, Pharmacotherapy, Food allergy, Medical, medicine, Humans, Medical prescription, Asthma, Allergen-specific immunotherapy, business.industry, Immunotherapy, medicine.disease, 030228 respiratory system, Desensitization, Immunologic, Pediatrics, Perinatology and Child Health, Societies, business
Abstract

Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population. AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3–5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers’ preference and compliance. In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis. This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.

Published
2017

9. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Pouessel, G, Claverie, C, Labreuche, J, Renaudin, J-M, Dorkenoo, A, Eb, M, Moneret-Vautrin, A, Deschildre, A, Leteurtre, S, Grabenhenrich, L, Worm, M, Dölle, S, Scherer, K, Hutteger, I, Christensen, M, Bindslev-Jensen, C, Mortz, C, Eller, E, Kjaer, HF, Carneiro-Leão, L, Badas, J, Coimbra, A, Levy, DP, Ben-Shoshan, M, Rimon, A, Benor, S, Arends, NJT, Edelbroek, N, de Groot, H, Emons, JAM, Brand, HKA, Verhoeven, D, van Veen, LN, de Jong, NW, Noh, G, Jang, EH, Pascal, M, Dominguez, O, Piquer, M, Alvaro, M, Jimenez-Feijoo, R, Lozano, J, Machinena, A, del Mar Folqué, M, Giner, MT, Plaza, AM, Turner, P, Patel, N, Vazquez-Ortiz, M, Lindsley, S, Walker, L, Rosenberg, S, Mari, A, Alessandri, C, Giangrieco, I, Tuppo, L, Rafaiani, C, Mitterer, G, Ciancamerla, M, Ferrara, R, Bernardi, ML, Zennaro, D, Tamburrini, M, Ciardiello, MA, Harwanegg, C, Fernandez, A, Selb, R, Egenmann, P, Epstein, M, Hoffmann-Sommergruber, K, Koning, F, Lovik, M, Clare Mills, EN, Moreno, J, van Loveren, H, Wal, J-M, Diesner, S, Bergmayr, C, Pfitzner, B, Assmann, VE, Starkl, P, Endesfelder, D, Eiwegger, T, Szepfalusi, Z, Fehrenbach, H, Jensen-Jarolim, E, Hartmann, A, Pali-Schöll, I, Untersmayr, E, Wille, S, Meyer, P, Klingebiel, C, Lidholm, J, Ehrenberg, A, Östling, J, Cleach, I, Mège, J-L, Vitte, J, Aina, R, Dubiela, P, Pfeifer, S, Bublin, M, Radauer, C, Humeniuk, P, Kabasser, S, Asero, R, Bogas, G, Gomez, F, Campo, P, Salas, M, Doña, I, Barrionuevo, E, Guerrero, MA, Mayorga, C, Prieto, A, Barber, D, Torres, MJ, Jamin, A, Wangorsch, A, Ballmer, B, Vieths, S, Scheurer, S, Apostolovic, D, Mihailovic, J, Krstic, M, Starkhammar, M, Velickovic, TC, Hamsten, C, van Hage, M, van Erp, FC, Knol, EF, Kansen, HM, Pontoppidan, B, Meijer, Y, van der Ent, CK, Knulst, AC, Sayers, R, Brown, H, Custovic, A, Simpson, A, Mills, C, Schulz, J, Akkerdaas, J, Totis, M, Capt, A, Herouet-Guicheney, C, van Ree, R, Banerjee, T, Banerjee, A, Claude, M, Bouchaud, G, Lupi, R, Castan, L, Tranquet, O, Denery-Papini, S, Bodinier, M, Brossard, C, De Poi, R, Gritti, E, De Dominicis, E, Popping, B, de Laureto, PP, Palosuo, K, Kukkonen, AK, Pelkonen, A, Mäkelä, M, Lee, NA, Rost, J, Muralidharan, S, Campbell, D, Mehr, S, Nock, C, Baumert, J, Taylor, S, Mastrorilli, C, Tripodi, S, Caffarelli, C, Perna, S, Di Rienzo Businco, A, Sfika, I, Dondi, A, Bianchi, A, Dascola, CP, Ricci, G, Cipriani, F, Maiello, N, del Giudice, MM, Frediani, T, Frediani, S, Macrì, F, Pistoletti, C, Iacono, ID, Patria, MF, Varin, E, Peroni, D, Comberiati, P, Chini, L, Moschese, V, Lucarelli, S, Bernardini, R, Pingitore, G, Pelosi, U, Olcese, R, Moretti, M, Cirisano, A, Faggian, D, Travaglini, A, Plebani, M, Verga, MC, Calvani, M, Giordani, P, Matricardi, PM, Ontiveros, N, Cabrera-Chavez, F, Galand, J, Beaudouin, E, Pineau, F, Sakai, S, Matsunaga, K, Teshima, R, Larré, C, Denery, S, Tschirner, S, Trendelenburg, V, Schulz, G, Niggemann, B, Beyer, K, Bouferkas, Y, Belabbas, Y, Saidi, D, Kheroua, O, Mecherfi, KEE, Guendouz, M, Haddi, A, Kaddouri, H, Amaral, L, Pereira, A, Rodrigues, S, Datema, M, Jongejan, L, Clausen, M, Knulst, A, Papadopoulos, N, Kowalski, M, de Blay, F, Zwinderman, A, Hoffman-Sommergruber, K, Ballmer-Weber, B, Fernandez-Rivas, M, Deng, S, Yin, J, Eisenmann, C, Nassiri, M, Reinert, R, van der Valk, JPM, van Wijk, RG, Vergouwe, Y, Steyerberg, EW, Reitsma, M, Wichers, HJ, Savelkoul, HFJ, Vlieg-Boerstra, B, Dubois, AEJ, Carolino, F, Rodolfo, A, Cernadas, J, Roa-Medellín, D, Rodriguez-Fernandez, A, Navarro, J, Albendiz, V, Baeza, ML, Intente-Herrero, S, Mikkelsen, A, Mehlig, K, Lissner, L, Verrill, L, Luccioli, S, van Bilsen, J, Kuper, F, Wolterbeek, A, Rankouhi, TR, Verschuren, L, Cnossen, H, Jeurink, P, Garssen, J, Knippels, L, Garthoff, J, Houben, G, Leeman, W, Eleonore Pettersson, M, Schins, AMM, Koppelman, GH, Kollen, BJ, Zubchenko, S, Kuntz, S, Mérida, P, Álvaro, M, Riggioni, C, Castellanos, JH, Jimenez, R, Cap, M, Drumez, E, Lejeune, S, Thumerelle, C, Mordacq, C, Nève, V, Ricò, S, Varini, M, Nocerino, R, Cosenza, L, Amoroso, A, Di Costanzo, M, Di Scala, C, Bedogni, G, Canani, RB, Turner, PJ, Poza-Guedes, P, González-Pérez, R, Sánchez-Machín, I, Matheu-Delgado, V, Wambre, E, Ballegaard, A-S, Madsen, C, Gregersen, J, Bøgh, KL, Aubert, P, Neunlist, M, Magnan, A, Lozano-Ojalvo, D, Pablos-Tanarro, A, Pérez-Rodríguez, L, Molina, E, López-Fandiño, R, Rekima, A, Macchiaverni, P, Turfkruyer, M, Holvoet, S, Dupuis, L, Baiz, N, Annesi-Maesano, I, Mercenier, A, Nutten, S, Verhasselt, V, Mrakovcic-Sutic, I, Banac, S, Sutic, I, Baricev-Novakovic, Z, Pavisic, V, Muñoz-Cano, R, Jiménez-Rodríguez, T, Corbacho, D, Roca-Ferrer, J, Bartra, J, Bulog, A, Micovic, V, Markiewicz, L, Szymkiewicz, A, Szyc, A, Wróblewska, B, Harvey, BM, Harthoorn, LF, Wesley Burks, A, Rentzos, G, Björk, A-LB, Bengtsson, U, Barber, C, Kalicinsky, C, Breynaert, C, Coorevits, L, Jansen, C, Van Hoeyveld, E, Verbeke, K, Kochuyt, A-M, Schrijvers, R, Deleanu, D, Muntean, A, Konstantakopoulou, M, Pasioti, M, Papadopoulou, A, Iliopoulou, A, Mikos, N, Kompoti, E, de Castro, ED, Bartalomé, B, Ue, KL, Griffiths, E, Till, S, Grimshaw, K, Roberts, G, Selby, A, Butiene, I, Larco, JI, Dubakiene, R, Fiandor, A, Fiocchi, A, Sigurdardottir, S, Sprikkelman, A, Schoemaker, A-F, Xepapadaki, P, Keil, T, Cojocariu, Z, Barbado, BS, Iancu, V, Arroabarren, E, Esarte, MG, Arteaga, M, Andrade, MC, Borges, D, Kalil, J, Bianchi, PG, Agondi, RC, Gupta, RK, Sharma, A, Gupta, K, Das, M, Dwivedi, P, Karseladze, R, Jorjoliani, L, Saginadze, L, Tskhakaia, M, Basello, K, Piuri, G, Speciani, AF, Speciani, MC, Camerotto, C, Zinno, F, Pakholchuk, O, Nedelska, S, Pattini, S, Costantino, MT, Peveri, S, Villalta, D, Savi, E, Costanzi, A, Revyakina, VA, Kiseleva, MA, Kuvshinova, ED, Larkova, IA, Shekhetov, AA, Silva, D, Moreira, A, Plácido, J, van der Kleij, H, van Twuijver, E, Sutorius, R, de Kam, P-J, van Odijk, J, Lindqvist, H, Lustig, E, Jácome, AAA, Aguilar, KLB, Domínguez, MG, Hernández, DAM, Caruso, C, Casale, C, Rapaccini, GL, Romano, A, De Vitis, I, Cocco, RR, Aranda, C, Mallozi, MC, Motta, JF, Moraes, L, Pastorino, A, Rosario, N, Goudouris, E, Porto, A, Wandalsen, NF, Sarinho, E, Sano, F, Solé, D, Pitsios, C, Petrodimopoulou, M, Papadopoulou, E, Passioti, M, Kontogianni, M, Adamia, N, Khaleva, E, del Prado, AP, Du Toit, G, Krzych, E, Samolinska-Zawisza, U, Furmanczyk, K, Tomaszewska, A, Raciborski, F, Lipiec, A, Samel-Kowalik, P, Walkiewicz, A, Borowicz, J, Samolinski, B, Nano, AL, Recto, M, Somoza, ML, López, NB, Alzate, DP, Ruano, FJ, Garcimartín, MI, Haroun, E, de la Torre, MV, Rojas, A, Onieva, ML, Canto, G, Rodrigues, A, Forno, A, Cabral, AJ, Gonçalves, R, Vorozhko, I, Sentsova, T, Chernyak, O, Denisova, S, Ilènko, L, Muhortnich, V, Zimmermann, C, Rohrbach, A, Bakhsh, FR, Boudewijn, K, Oomkes-Pilon, A-M, Van Ginkle, D, Šilar, M, Jeverica, A, Vesel, T, Avčin, T, Korošec, P, van der Valk, J, Berends, I, Arends, N, van Maaren, M, Wichers, H, Emons, J, Dubois, A, de Jong, N, Matsyura, O, Besh, L, Huang, C-H, Jan, T-R, Stiefel, G, Tratt, J, Kirk, K, Arasi, S, Caminiti, L, Crisafulli, G, Fiamingo, C, Fresta, J, Pajno, G, Remington, B, Kruizinga, A, Marty Blom, W, Westerhout, J, Bijlsma, S, Blankestijn, M, Otten, H, Klemans, R, Michelsen-Huisman, AD, van Os-Medendorp, H, Kruizinga, AG, Versluis, A, van Duijn, G, de Zeeuw-Brouwer, HM-L, Castenmiller, JJM, Noteborn, HPJM, Houben, GF, Bravin, K, Luyt, D, Javed, B, Couch, P, Munro, C, Padfield, P, Sperrin, M, Byrne, A, Oosthuizen, L, Kelleher, C, Ward, F, Brosnan, N, King, G, Corbet, E, Guzmán, JAH, García, MB, Asensio, O, Navarrete, LV, Larramona, H, Miró, XD, Pyrz, K, Austin, M, Boloh, Y, Galloway, D, Hernandez, P, Hourihane, JOB, Kenna, F, Majkowska-Wojciechowska, B, Regent, L, Themisb, M, Schnadt, S, Semic-Jusufagic, A, Galvin, AD, Kauppila, T, Kuitunen, M, Kitsioulis, NA, Douladiris, N, Kostoudi, S, Manolaraki, I, Mitsias, D, Manousakis, E, Papadopoulos, NG, Knibb, R, Hammond, J, Cooke, R, Yrjänä, J, Hanni, A-M, Vähäsarja, P, Mustonen, O, Dunder, T, 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Julia, JC, Plovdiv, CH, Gethings, L, Langridge, J, Adel-Patient, K, Bernard, H, Barcievic-Jones, I, Sokolova, R, Yankova, R, Ivanovska, M, Murdjeva, M, Popova, T, Dermendzhiev, S, Karjalainen, M, Lehnigk, U, Brown, D, Locklear, JC, Locklear, J, Maris, I, Hourihane, J, Ornelas, C, Caiado, J, Ferreira, MB, Pereira-Barbosa, M, Puente, Y, Daza, JC, Monteseirin, FJ, Ukleja-Sokolowska, N, Gawronska-Ukleja, E, Zbikowska-Gotz, M, Bartuzi, Z, Sokolowski, L, Adams, A, Mahon, B, English, K, Gourdon-Dubois, N, Sellam, L, Pereira, B, Michaud, E, Messaoudi, K, Evrard, B, Fauquert, J-L, Palomares, F, Gomez, G, Rodriguez, MJ, Galindo, L, Molina, A, Paparo, L, Mennini, M, Aitoro, R, Wawrzeńczyk, A, Przybyszewski, M, Sarıcoban, HE, Ugras, M, Yalvac, Z, Flokstra-de Blok, BMJ, van der Velde, JL, Vereda, A, Ippolito, C, Traversa, A, Adriano, D, Bianchi, DM, Gallina, S, Decastelli, L, Makatsori, M, Miles, A, Devetak, SP, Devetak, I, Tabet, SA, Trandbohus, JF, Winther, P, Malling, H-J, Hansen, KS, Garvey, LH, Wang, C-C, Cheng, Y-H, Tung, C-W, Dietrich, M, Marenholz, I, Kalb, B, Grosche, S, Blümchen, K, Schlags, R, Price, M, Rietz, S, Esparza-Gordillo, J, Lau, S, Lee, Y-A, Almontasheri, A, Bahkali, MA, Elshorbagi, S, Alfhaid, A, Altamimi, M, Madbouly, E, Al-Dhekri, H, Arnaout, RK, Basagaña, M, Miquel, S, Bartolomé, B, Brix, B, Rohwer, S, Brandhoff, S, Berger, A, Suer, W, Weimann, A, Bueno, C, Martín-Pedraza, L, Abián, S, Segundo-Acosta, PS, López-Rodríguez, JC, Barderas, R, Batanero, E, Cuesta-Herranz, J, Villalba, MT, Correia, M, Benito-Garcia, F, Arêde, C, Piedade, S, Morais-Almeida, M, Hindley, J, Yarham, R, Kuklinska-Pijanka, A, Gillick, D, Patient, K, Chapman, MD, Miranda, A, Matos, E, Sokolova, A, Rao, H, Baricevic-Jones, I, Smith, F, Xue, W, Magnusdottir, H, Vidarsdottir, AG, Lund, S, Jensen, AB, Ludviksson, BR, Simon, R, Elfont, R, Bennett, S, Voyksner, R, de Lurdes Torre, M, Yürek, S, Faber, MA, Bastiaensen, A, Mangodt, E, van Gasse, A, Decuyper, I, Sabato, V, Hagendorens, MM, Bridts, CH, De Clerck, LS, Ebo, D, Schwarz, S, Ziegert, M, Albroscheit, S, Schwager, C, Kull, S, Behrends, J, Röckendorf, N, Schocker, F, Frey, A, Homann, A, Becker, W-M, Jappe, U, Zaabat, N, Osscini, S, Agabriel, C, Sterling, B, Carsin, A, Liabeuf, V, Maćków, M, Zbróg, A, Bronkowska, M, Courtois, J, Gadisseur, R, Bertholet, C, Lukas, P, Cavalier, E, Delahaut, P, Quinting, B, Gertmo, MB, Hasseus, ET, Barzylovych, V, Oliveira, J, Ensina, LF, Aranda, CS, Dopazo, L, Lopez, R, Perez, R, Santos-Diez, L, Bilbao, A, Garcia, JM, Núñez, IG, Mármol, MÁA, Villarejo, MJB, Martos, JAB, Vergara, MS, García, JMI, Michalska, A, Sergiejko, G, Zacniewski, R, Ghiordanescu, I-M, Deaconu, C, Popescu, M, Bumbacea, RS, Ibranji, A, Nikolla, E, Loloci, G, Juel-Berg, N, Larsen, LF, Poulsen, LK, Marcelino, J, Prata, R, Costa, AC, Duarte, F, Neto, M, Santos, J, Pestana, LC, Sampaio, D, Minale, P, Dignetti, P, Bignardi, D, Nedelea, I, Popescu, F-D, Vieru, M, Secureanu, F-A, Ganea, CS, Vieira, M, Silva, JPM, Watts, T, Watts, S, Lomikovska, M, Peredelskaya, M, Nenasheva, N, Filipovic, I, Zivkovic, Z, Filipovic, D, Higgs, J, Warner, A, and Jones, C

Published
2017

10. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth

Author

Germano, G., Lamba, S., Rospo, G., Barault, L., Magri, A., Maione, F., Russo, M., Crisafulli, G., Bartolini, A., Lerda, G., Siravegna, G., Mussolin, B., Frapolli, R., Montone, M., Morano, F., De Braud, F., Amirouchene-Angelozzi, N., Marsoni, S., D'Incalci, M., Orlandi, Armando, Giraudo, E., Sartore-Bianchi, A., Siena, S., Pietrantonio, F., Di Nicolantonio, F., Bardelli, A., Orlandi A. (ORCID:0000-0001-5253-4678), Germano, G., Lamba, S., Rospo, G., Barault, L., Magri, A., Maione, F., Russo, M., Crisafulli, G., Bartolini, A., Lerda, G., Siravegna, G., Mussolin, B., Frapolli, R., Montone, M., Morano, F., De Braud, F., Amirouchene-Angelozzi, N., Marsoni, S., D'Incalci, M., Orlandi, Armando, Giraudo, E., Sartore-Bianchi, A., Siena, S., Pietrantonio, F., Di Nicolantonio, F., Bardelli, A., and Orlandi A. (ORCID:0000-0001-5253-4678)

Abstract

Molecular alterations in genes involved in DNA mismatch repair (MMR) promote cancer initiation and foster tumour progression. Cancers deficient in MMR frequently show favourable prognosis and indolent progression. The functional basis of the clinical outcome of patients with tumours that are deficient in MMR is not clear. Here we genetically inactivate MutL homologue 1 (MLH1) in colorectal, breast and pancreatic mouse cancer cells. The growth of MMR-deficient cells was comparable to their proficient counterparts in vitro and on transplantation in immunocompromised mice. By contrast, MMR-deficient cancer cells grew poorly when transplanted in syngeneic mice. The inactivation of MMR increased the mutational burden and led to dynamic mutational profiles, which resulted in the persistent renewal of neoantigens in vitro and in vivo, whereas MMR-proficient cells exhibited stable mutational load and neoantigen profiles over time. Immune surveillance improved when cancer cells, in which MLH1 had been inactivated, accumulated neoantigens for several generations. When restricted to a clonal population, the dynamic generation of neoantigens driven by MMR further increased immune surveillance. Inactivation of MMR, driven by acquired resistance to the clinical agent temozolomide, increased mutational load, promoted continuous renewal of neoantigens in human colorectal cancers and triggered immune surveillance in mouse models. These results suggest that targeting DNA repair processes can increase the burden of neoantigens in tumour cells; this has the potential to be exploited in therapeutic approaches.

Published
2017

12. Oral desensitization for immunoglobulin E-mediated milk and egg allergies

Author

Crisafulli, G, Caminiti, L, and Pajno, Giovanni Bat.

Subjects
Treatment Outcome, Desensitization, Immunologic, Immune Tolerance, Administration, Oral, Humans, Allergens, Immunoglobulin E, Milk Hypersensitivity, Egg Hypersensitivity
Abstract

Food allergy is an increasingly prevalent disease in western countries, but an effective form of therapy has not yet been found. A specific active treatment for immunoglobulin E (IgE)-mediated food allergy is currently under study in human clinical trials. Allergen-specific approaches include oral, sublingual and epicutaneous immunotherapy. Currently, reports on oral immunotherapy (OIT) have been more extensive than reports on other routes such as sublingual immunotherapy (SLIT) and epicutaneous patch. The aim of OIT using foods, especially milk and egg--the cause of most common allergies in infants and young children in Europe--is the achievement of desensitization or tolerance by patients suffering from food allergy. Treatment protocols have been initiated in highly supervised research settings with the goal of finding an active treatment against IgE-mediated food allergy. The preliminary data on OIT are encouraging, and among the plethora of novel approaches the strategies most likely to advance into clinical practice include both OIT and SLIT. It is still unclear whether oral desensitization is only the first step toward permanent desensitization or whether it induces only a transient tolerance. Longer duration of desensitization may result in permanent tolerance. The occurrence of adverse events or reactions during OIT is quite frequent and has been reported in all published studies. Therefore, before this treatment can be used in clinical practice additional studies are needed. Currently, immunotherapy for cow's milk or egg allergies is a novel approach that expands the possibility of an active treatment to improve the quality of life of patients and their families.

Published
2012

13. ALLERGIE PERIOPERATORIE: COSA SAPERE

Author

Franceschini, F., Caimmi, S., Caffarelli, C., Peroni, Diego, Crisafulli, G, and Bernardini, R.

Subjects
anafilassi, anestesia, prick tests, IgE, diagnosi
Published
2012

15. Antibiotic allergy

Author

Caimmi S, Caimmi D, Lombardi E, Crisafulli G, Franceschini F, Ricci G, and GIAN LUIGI MARSEGLIA

Subjects
Pharmacology, Drug Hypersensitivity, Desensitization, Immunologic, Immunology, polycyclic compounds, Immunology and Allergy, Humans, Cross Reactions, Perioperative Period, Anti-Bacterial Agents, Skin Tests
Abstract

Antibiotics are commonly injected during the perioperative period and are responsible of 15% of the anaphylactic reactions. Anaphylaxis triggered by antibiotics primarily involves penicillin and cephalosporin. The management of patients with histories of allergic reactions to antibiotics is a common situation in clinical practice. The confirmation or invalidation of the allergic nature of the reported reaction is not based on in vitro tests, but on a rigorous allergological work-up based on detailed analysis of clinical history, skin tests and drug provocation test. Considering a possible cross-reactivity between penicillins, once an immediate penicillin allergy has been diagnosed, skin testing with the alternative molecule (cephalosporin, carbapenem, aztreonam) is mandatory and, if negative, the relevant drug should be given in an appropriate setting at increasing doses.

Published
2011

18. Eritropoietina: un nuovo D.A.B.A.?

Author

Morabito, N, Gaudio, Agostino, Pergolizzi, S, Taviano, Mf, Lasco, A, Macrì, I, Catalano, A, Atteritano, M, Corrente, E, Crisafulli, G, Frisina, N, and Galati, Em

Published
2007

20. Statura finale in ragazzi con ritardo costituzionale di crescita e pubertà trattati o meno con testosterone

Author

Lombardo, F., Crisafulli, G., Wasniewska, M., Vita, D., Sturiale, M., Valenzise, M., Lombardo, F., Crisafulli, G., Wasniewska, M., Vita, D., Sturiale, M., and Valenzise, M.

Abstract

Il presente studio retrospettivo è basato sul follow-up di 49 ragazzi con ritardo costituzionale di crescita e pubertà (RCCP) che hanno iniziato la pubertà spontaneamente (27 casi) o tramite induzione con testosterone depot, (50 mg/mese per 6 mesi) (22 casi). All’epoca della pubertà i due gruppi di ragazzi erano simili per età ossea, deficit staturale, statura bersaglio ed avevano simile previsione di statura finale. La loro statura finale è stata misurata e paragonata alla statura bersaglio calcolata sulla base dell’altezza dei genitori. La statura finale non differiva significativamente tra i ragazzi trattati e quelli non trattati. In entrambi i gruppi di pazienti la statura finale era sovrapponibile e correlata con la statura bersaglio e con la previsione staturale effettuata all’esordio della pubertà. Questo studio conferma che la maggior parte dei ragazzi con RCCP raggiunge spontaneamente una statura finale entro i limiti del bersaglio genetico (24 su 27 casi). Un breve ciclo a basso dosaggio con testosterone depot può essere intrapreso senza effetti negativi sulla statura finale. Il metodo di Bayley-Pinneau può considerarsi nel complesso accurato nel predire la statura finale nel RCCP, sebbene in un piccolo numero di ragazzi, sia trattati che non trattati, siano state riscontrate discrepanze significative tra l’altezza prevista e la statura finale.

21. La statura finale in pazienti con deficit di ormone di crescita trattati fin dai primi 5 anni di vita

Author

Crisafulli, G., Wasniewska, M. G., Vita, D., Sturiale, M., Tiralongo, V., Caminiti, L., Crisafulli, G., Wasniewska, M. G., Vita, D., Sturiale, M., Tiralongo, V., and Caminiti, L.

Abstract

Tredici bambini con deficit di ormone di crescita(GHD) sono stati sottoposti ad una terapia sostitutiva per un periodo di almeno 9 anni, da un’età inferiore a 5 anni fino all’adolescenza. Presentavano all’inizio un deficit staturale medio di -4.1 SDS e hanno raggiunto una statura finale compatibile col loro target. La statura finale di 8 pazienti ha superato il target rispettivo e solo 3 pazienti non sono riusciti a raggiungere una statura finale nel range dalla statura target. L’analisi dei fattori che possono condizionare la statura definitiva indica che la statura finale è correlata negativamente con l’età cronologica all’inizio della terapia e positivamente con la statura raggiunta prima della pubertà. Si può concludere che il pieno «catch-up growth» fino al percentile del target è possibile in pazienti con GHD, a condizione che il trattamento con GH cominci da un’età inferiore a 5 anni. Questa conclusione è stata convalidata per la prima volta dai dati sulla statura definitiva.

22. Statura finale in ragazzi con ritardo costituzionale di crescita e pubertà trattati o meno con testosterone

Author

Lombardo, F., Crisafulli, G., Wasniewska, M., Vita, D., Sturiale, M., Valenzise, M., Lombardo, F., Crisafulli, G., Wasniewska, M., Vita, D., Sturiale, M., and Valenzise, M.

Abstract

Il presente studio retrospettivo è basato sul follow-up di 49 ragazzi con ritardo costituzionale di crescita e pubertà (RCCP) che hanno iniziato la pubertà spontaneamente (27 casi) o tramite induzione con testosterone depot, (50 mg/mese per 6 mesi) (22 casi). All’epoca della pubertà i due gruppi di ragazzi erano simili per età ossea, deficit staturale, statura bersaglio ed avevano simile previsione di statura finale. La loro statura finale è stata misurata e paragonata alla statura bersaglio calcolata sulla base dell’altezza dei genitori. La statura finale non differiva significativamente tra i ragazzi trattati e quelli non trattati. In entrambi i gruppi di pazienti la statura finale era sovrapponibile e correlata con la statura bersaglio e con la previsione staturale effettuata all’esordio della pubertà. Questo studio conferma che la maggior parte dei ragazzi con RCCP raggiunge spontaneamente una statura finale entro i limiti del bersaglio genetico (24 su 27 casi). Un breve ciclo a basso dosaggio con testosterone depot può essere intrapreso senza effetti negativi sulla statura finale. Il metodo di Bayley-Pinneau può considerarsi nel complesso accurato nel predire la statura finale nel RCCP, sebbene in un piccolo numero di ragazzi, sia trattati che non trattati, siano state riscontrate discrepanze significative tra l’altezza prevista e la statura finale.

23. La statura finale in pazienti con deficit di ormone di crescita trattati fin dai primi 5 anni di vita

Author

Crisafulli, G., Wasniewska, M. G., Vita, D., Sturiale, M., Tiralongo, V., Caminiti, L., Crisafulli, G., Wasniewska, M. G., Vita, D., Sturiale, M., Tiralongo, V., and Caminiti, L.

Abstract

Tredici bambini con deficit di ormone di crescita(GHD) sono stati sottoposti ad una terapia sostitutiva per un periodo di almeno 9 anni, da un’età inferiore a 5 anni fino all’adolescenza. Presentavano all’inizio un deficit staturale medio di -4.1 SDS e hanno raggiunto una statura finale compatibile col loro target. La statura finale di 8 pazienti ha superato il target rispettivo e solo 3 pazienti non sono riusciti a raggiungere una statura finale nel range dalla statura target. L’analisi dei fattori che possono condizionare la statura definitiva indica che la statura finale è correlata negativamente con l’età cronologica all’inizio della terapia e positivamente con la statura raggiunta prima della pubertà. Si può concludere che il pieno «catch-up growth» fino al percentile del target è possibile in pazienti con GHD, a condizione che il trattamento con GH cominci da un’età inferiore a 5 anni. Questa conclusione è stata convalidata per la prima volta dai dati sulla statura definitiva.

24. Editorials.

Author

Rospo, G., Corti, G., Crisafulli, G., Novara, L., and Bardelli, A.

Subjects
*COLON cancer, *METASTASIS, *CANCER invasiveness, *BIOLOGICAL evolution, *CELL analysis, *CANCER cells
Published
2017
Full Text
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25. Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

Author

Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari, Cardinale, F., Ciprandi, G., Barberi, S., Bernardini, R., Caffarelli, C., Calvani, M., Cavagni, G., Galli, E., Minasi, D., Del Giudice, M. M., Moschese, V., Novembre, E., Paravati, F., Peroni, D. G., Tosca, M. A., Traina, G., Tripodi, S., Marseglia, G. L., Amato, D., Anania, C., Anastasio, E., Antignani, R., Arasi, S., Baldassarre, M., Baldo, E., Barbalace, A., Barni, S., Betti, F., Bianchi, A., Bolzacchini, E., Bonini, M., Bottau, P., Bozzetto, S., Brighetti, M. A., Caimmi, D., Caimmi, S., Calzone, L., Cancrini, C., Caminiti, L., Capata, G., Capra, L., Capristo, C., Carboni, E., Carella, F., Castagnoli, R., Chiappini, E., Chiera, F., Chinellato, I., Chini, L., Cipriani, F., Civitelli, F., Comberiati, P., Contini, D., Corrente, S., Cravidi, C., Crisafulli, G., Cuomo, B., D'Auria, E., D'Elios, S., Decimo, F., Giustina, A. D., Piane, R. M. D., De Filippo, M., De Vittori, V., Diaferio, L., Di Mauro, M. E., Duse, M., Federici, S., Felice, G., Fenu, G., Ferrante, G., Foti, T., Franceschini, F., Ghiglioni, D., Giardino, G., Giovannini, M., Indirli, G. C., Indolfi, C., Landi, M., La Torre, F., Leone, L. M., Licari, A., Liotti, L., Lougaris, V., Maiello, N., Mantecca, P., Manti, S., Mariani, M. M., Martelli, A., Mastrorilli, C., Mastrorilli, V., Montin, D., Mori, F., Olcese, R., Ottaviano, G., Paglialunga, C., Pajno, G., Parisi, G., Pattini, S., Pecoraro, L., Pelosi, U., Pignata, C., Ricci, G., Ricci, S., Rizzi, S., Rizzo, C., Rosati, S., Rosso, P., Sangerardi, M., Santoro, A., Saretta, F., Sarti, L., Sartorio, M., Sgruletti, M., Soresina, A., Sfika, I., Sgrulletti, M., Tesse, N., Tranchino, V., Travaglini, A., Velia, M., Verduci, E., Vernich, M., Veronelli, E., Volpi, S., Votto, M., Zicari, A. M., Cardinale, Fabio, Ciprandi, Giorgio, Barberi, Salvatore, Bernardini, Roberto, Caffarelli, Carlo, Calvani, Mauro, Cavagni, Giovanni, Galli, Elena, Minasi, Domenico, Del Giudice, Michele Miraglia, Moschese, Viviana, Novembre, Elio, Paravati, Francesco, Peroni, Diego G, Tosca, Maria Angela, Traina, Giovanni, Tripodi, Salvatore, Marseglia, Gian Luigi, SIAIP task force Pignata, Claudio, Cardinale, F, Ciprandi, G, Barberi, S, Bernardini, R, Caffarelli, C, Calvani, M, Cavagni, G, Galli, E, Minasi, D, Del Giudice, M, Moschese, V, Novembre, E, Paravati, F, Peroni, D, Tosca, M, Traina, G, Tripodi, S, Marseglia, G, Amato, D, Anania, C, Anastasio, E, Antignani, R, Arasi, S, Baldassarre, M, Baldo, E, Barbalace, A, Barni, S, Betti, F, Bianchi, A, Bolzacchini, E, Bonini, M, Bottau, P, Bozzetto, S, Brighetti, M, Caimmi, D, Caimmi, S, Calzone, L, Cancrini, C, Caminiti, L, Capata, G, Capra, L, Capristo, C, Carboni, E, Carella, F, Castagnoli, R, Chiappini, E, Chiera, F, Chinellato, I, Chini, L, Cipriani, F, Civitelli, F, Comberiati, P, Contini, D, Corrente, S, Cravidi, C, Crisafulli, G, Cuomo, B, D'Auria, E, D'Elios, S, Decimo, F, Giustina, A, Piane, R, De Filippo, M, De Vittori, V, Diaferio, L, Di Mauro, M, Duse, M, Federici, S, Felice, G, Fenu, G, Ferrante, G, Foti, T, Franceschini, F, Ghiglioni, D, Giardino, G, Giovannini, M, Indirli, G, Indolfi, C, Landi, M, La Torre, F, Leone, L, Licari, A, Liotti, L, Lougaris, V, Maiello, N, Mantecca, P, Manti, S, Mariani, M, Martelli, A, Mastrorilli, C, Mastrorilli, V, Montin, D, Mori, F, Olcese, R, Ottaviano, G, Paglialunga, C, Pajno, G, Parisi, G, Pattini, S, Pecoraro, L, Pelosi, U, Pignata, C, Ricci, G, Ricci, S, Rizzi, S, Rizzo, C, Rosati, S, Rosso, P, Sangerardi, M, Santoro, A, Saretta, F, Sarti, L, Sartorio, M, Sgruletti, M, Soresina, A, Sfika, I, Sgrulletti, M, Tesse, N, Tranchino, V, Travaglini, A, Velia, M, Verduci, E, Vernich, M, Veronelli, E, Volpi, S, Votto, M, Zicari, A, and Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari

Subjects
Allergy, Review, 030207 dermatology & venereal diseases, Settore MED/38 - Pediatria Generale E Specialistica, 0302 clinical medicine, COVID-19, Child, Pandemic, Immunologic disease, Asthma, Adolescent, Viral, 030212 general & internal medicine, Disease management (health), Societies, Medical, pandemic, child, adolescent, allergy, asthma, immunologic disease, Incidence (epidemiology), lcsh:RJ1-570, Disease Management, General Medicine, Atopic dermatitis, Settore MED/38, Coronavirus Infections, Decision Making, Humans, Italy, Pneumonia, Viral, Pragmatic Clinical Trials as Topic, SARS-CoV-2, Allergy and Immunology, Betacoronavirus, Consensus, Pandemics, Latex allergy, Human, Telemedicine, Consensu, 03 medical and health sciences, Medical, medicine, Risk factor, Betacoronaviru, business.industry, Coronavirus Infection, lcsh:Pediatrics, Pneumonia, medicine.disease, Immunology, Societies, business, Rare disease
Abstract

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Published
2020

26. Management of chronic urticaria in children: a clinical guideline

Author

Carlo Filippo Tesi, Alberto Villani, Paolo Bottau, Iria Neri, Roberto Bernardini, Giuseppe Crisafulli, Lucia Liotti, Francesca Mori, Fernanda Chiera, Gian Luigi Marseglia, Maya El Hachem, Silvia Caimmi, Amelia Licari, Cristiana De Ranieri, Marzia Duse, Carla Mastrorilli, Massimo Gola, Carlo Caffarelli, Fabrizio Franceschini, Massimo Barbagallo, Andrea Diociaiuti, Francesca Saretta, Francesco Paravati, Marcello Bergamini, Filomena Bugliaro, Fabio Cardinale, Giovanni Simeone, Domenico Minasi, Aurelia Pantaleo, Dora Di Mauro, Giovanni Corsello, and Caffarelli C, Paravati F, El Hachem M, Duse M, Bergamini M, Simeone G, Barbagallo M, Bernardini R, Bottau P, Bugliaro F, Caimmi S, Chiera F, Crisafulli G, De Ranieri C, Di Mauro D, Diociaiuti A, Franceschini F, Gola M, Licari A, Liotti L, Mastrorilli C, Minasi D, Mori F, Neri I, Pantaleo A, Saretta F, Tesi CF, Corsello G, Marseglia GL, Villani A, Cardinale F.

Subjects
medicine.medical_specialty, Urticaria, Allergy, Review, Pathogenesis, Omalizumab, 03 medical and health sciences, 0302 clinical medicine, Pathogenesi, Multidisciplinary approach, 030225 pediatrics, Epidemiology, medicine, Humans, 030212 general & internal medicine, Angioedema, Pediatric dermatology, Child, Children, Chronic urticaria, Pediatric, business.industry, lcsh:RJ1-570, lcsh:Pediatrics, General Medicine, Guideline, Chronic spontaneous urticaria, Settore MED/38, Management, Natural history, Inducible uricaria, Italy, Family medicine, Therapy, medicine.symptom, business, medicine.drug
Abstract

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.

Published
2019

27. Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect

Author

Giuseppe Crisafulli, Antonella Petri, Laura Mazzanti, Malgorzata Wasniewska, M. P. Guarneri, P Matarazzo, Fortunato Lombardo, Giuseppina Salzano, R. Bergamaschi, F. De Luca, Wasniewska M., De Luca F., Bergamaschi R., Guarneri MP., Mazzanti L., Matarazzo P., Petri A., Crisafulli G., Salzano G., and Lombardo F.

Subjects
medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Turner Syndrome, Growth, Cohort Studies, Endocrinology, Hormone replacement therapy (female-to-male), Internal medicine, Prepuberty, Turner syndrome, medicine, Humans, Turner syndrome, GH therapy, Prospective Studies, Prospective cohort study, TERAPIA CON GH, Bone Development, Human Growth Hormone, business.industry, Puberty, Infant, General Medicine, Prognosis, medicine.disease, Body Height, SINDROME DI TURNER, Adult height, Treatment Outcome, Child, Preschool, Cohort, Bone maturation, Gh treatment, Female, business
Abstract

OBJECTIVE: In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. PATIENTS AND DESIGN: Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. RESULTS: After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. CONCLUSIONS: (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.

Published
2004

28. Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment

Author

Lucia Marseglia, Franco Antoniazzi, Fiorella Galluzzi, Mariacarolina Salerno, Filippo De Luca, Lorenzo Iughetti, Anna Maria Pasquino, Teresa Arrigo, Giuseppe Crisafulli, Arrigo, T., De Luca, F., Antoniazzi, F., Galluzzi, F., Iughetti, L., Pasquino, A. M., Salerno, Mariacarolina, Marseglia, L., and Crisafulli, G.

Subjects
Central precocious puberty, GnRHa, Menarche timing, Menstrual cycle, medicine.medical_specialty, media_common.quotation_subject, medicine.medical_treatment, Central precocious puberty, Puberty, Precocious, GnRHa, Internal medicine, medicine, Humans, Precocious puberty, Child, Menstrual cycle, Gonadotropin-releasing hormone analogue, media_common, Triptorelin Pamoate, business.industry, Menarche timing, medicine.disease, Menstruation, Luteolytic Agents, Endocrinology, El Niño, Child, Preschool, Pediatrics, Perinatology and Child Health, Menarche, Female, business, Decapeptyl Depot, Hormone
Abstract

Keywords Menarchetiming.Menstrualcycle.Centralprecociouspuberty.GnRHaOur aim was to longitudinally investigate menarche timingand menstrual cycle (MC) pattern during the first fivegynaecological years in 101 girls with idiopathic centralprecocious puberty (CPP) who had been treated withgonadotropin-releasing hormone agonists (GnRHa) for atleast two years. Our girls received Decapeptyl Depot(60

Published
2007

29. Testicular microlithiasis: an unreported feature of McCune-Albright syndrome in males

Author

Giovanna Weber, Roberto Lala, Giuseppe Crisafulli, Malgorzata Wasniewska, Patrizia Matarazzo, Filippo De Luca, Mariella Valenzise, Silvano Bertelloni, Wasniewska, M, DE LUCA, F, Bertelloni, S, Matarazzo, P, Weber, Giovanna, Crisafulli, G, Valenzise, M, and Lala, R.

Subjects
Infertility, Adult, Male, medicine.medical_specialty, Adolescent, Urology, Varicocele, Puberty, Precocious, Lithiasis, Fibrous Dysplasia, Polyostotic, Asymptomatic, Testicular Diseases, McCune–Albright syndrome, Hydrocele, Testis, medicine, Humans, Vein, Child, Ultrasonography, business.industry, medicine.disease, Dermatology, Surgery, medicine.anatomical_structure, Feature (computer vision), Vasa vasorum, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, medicine.symptom, business, Testicular microlithiasis, Artery
Abstract

varicocele ligation in adults with the laparoscopic approach in children in whom the artery and vein were ligated. The laparoscopic approach resulted in shorter operative times and there were fewer recurrent varicoceles but the postoperative hydrocele rate (3 of 36) was high. Pediatric urologists have commonly favored high ligation of the internal spermatic vein over the subinguinal approach. As we become more facile with the laparoscope, I suspect that the majority will continue with high ligation but will perform it laparoscopically. The risk of hydrocele is greater when the artery and vein and presumably lymphatics are taken than when lymphatics are spared, as is routinely the case in the subinguinal approach. Success rates in varicocele repair are high and complications are low using both approaches. Some laparoscopists are sparing the artery (and presumably with it the vasa vasorum). In these cases as long as the vasa vasorum is not dissected free of the artery, there is theoretically a higher risk of recurrence of the varicocele. It is less clear, despite the currently accepted indications for varicocele ligation in the adolescent (testicular size discrepancy or decreased relative growth of the left testis), that ligating the varicocele by either approach in the vast majority of adolescents who are asymptomatic actually decreases the risk of infertility in these boys.

Published
2004

30. DNA demethylation triggers cell free DNA release in colorectal cancer cells.

Author

Pessei V, Macagno M, Mariella E, Congiusta N, Battaglieri V, Battuello P, Viviani M, Gionfriddo G, Lamba S, Lorenzato A, Oddo D, Idrees F, Cavaliere A, Bartolini A, Guarrera S, Linnebacher M, Monteonofrio L, Cardone L, Milella M, Bertotti A, Soddu S, Grassi E, Crisafulli G, Bardelli A, Barault L, and Di Nicolantonio F

Subjects
Humans, Cell Line, Tumor, DNA Methylation, Cell Proliferation, CpG Islands, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Cell-Free Nucleic Acids genetics, DNA Demethylation
Abstract

Background: Liquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release., Methods: We measured cell loss ratio, doubling time, and cfDNA release in the supernatant of a colorectal cancer (CRC) cell line collection (N = 76) representative of the molecular subtypes previously identified in cancer patients. Association analyses between quantitative parameters of cfDNA release, cell proliferation, and molecular features were evaluated. Functional experiments were performed to test the impact of modulating DNA methylation on cfDNA release., Results: Higher levels of supernatant cfDNA were significantly associated with slower cell cycling and increased cell death. In addition, a higher cfDNA shedding was found in non-CpG Island Methylator Phenotype (CIMP) models. These results indicate a positive correlation between lower methylation and increased cfDNA levels. To explore this further, we exploited methylation microarrays to identify a subset of probes significantly associated with cfDNA shedding and derive a methylation signature capable of discriminating high from low cfDNA releasers. We applied this signature to an independent set of 176 CRC cell lines and patient derived organoids to select 14 models predicted to be low or high releasers. The methylation profile successfully predicted the amount of cfDNA released in the supernatant. At the functional level, genetic ablation of DNA methyl-transferases increased chromatin accessibility and DNA fragmentation, leading to increased cfDNA release in isogenic CRC cell lines. Furthermore, in vitro treatment of five low releaser CRC cells with a demethylating agent was able to induce a significant increase in cfDNA shedding., Conclusions: Methylation status of cancer cell lines contributes to the variability of cfDNA shedding in vitro. Changes in methylation pattern are associated with cfDNA release levels and might be exploited to increase sensitivity of liquid biopsy assays., (© 2024. The Author(s).)

Published
2024
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31. Baked Egg Oral Immunotherapy: Current State in Pediatric Age.

Author

Foti Randazzese S, Caminiti L, La Rocca M, Italia C, Toscano F, Galletta F, Crisafulli G, and Manti S

Subjects
Humans, Child, Child, Preschool, Eggs, Egg Proteins immunology, Cooking, Administration, Oral, Infant, Immune Tolerance, Female, Animals, Egg Hypersensitivity therapy, Egg Hypersensitivity immunology, Desensitization, Immunologic methods, Allergens immunology
Abstract

Hen's egg allergy is one of the most common food allergies in the Western world, with an increase in recent years. It affects about 9.5% of the pediatric population, and the onset most often occurs before the first year of life. The occurrence of spontaneous oral tolerance acquisition varies among studies, but it is generally high by school age. Nowadays, allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of hen's egg allergy. Specifically, many children with hen's egg allergy may tolerate baked eggs. Food processing, specifically high temperatures, alters the allergenicity of hen's egg proteins by causing conformational changes in allergen epitopes, which makes them less allergenic. This review aims to discuss the scientific evidence in the field of baked egg oral immunotherapy in hen's egg-allergic children, with a meticulous examination of the pertinent literature surrounding the subject matter.

Published
2024
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32. Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations.

Author

Crisafulli G

Abstract

A multitude of exogenous and endogenous processes have the potential to result in DNA damage. While the repair mechanisms are typically capable of correcting this damage, errors in the repair process can result in mutations. The findings of research conducted in 2012 indicate that mutations do not occur randomly but rather follow specific patterns that can be attributed to known or inferred mutational processes. The process of mutational signature analysis allows for the inference of the predominant mutational process for a given cancer sample, with significant potential for clinical applications. A deeper comprehension of these mutational signatures in CRC could facilitate enhanced prevention strategies, facilitate the comprehension of genotoxic drug activity, predict responses to personalized treatments, and, in the future, inform the development of targeted therapies in the context of precision oncology. The efforts of numerous researchers have led to the identification of several mutational signatures, which can be categorized into different mutational signature references. In CRC, distinct mutational signatures are identified as correlating with mismatch repair deficiency, polymerase mutations, and chemotherapy treatment. In this context, a mutational signature analysis offers considerable potential for enhancing minimal residual disease (MRD) tests in stage II (high-risk) and stage III CRC post-surgery, stratifying CRC based on the impacts of genetic and epigenetic alterations for precision oncology, identifying potential therapeutic vulnerabilities, and evaluating drug efficacy and guiding therapy, as illustrated in a proof-of-concept clinical trial.

Published
2024
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33. Risk factors for drug hypersensitivity reactions in children.

Author

Mori F, Saretta F, Riscassi S, Caimmi S, Bottau P, Liotti L, Franceschini F, Bianchi A, Valluzzi RL, Crisafulli G, and Caffarelli C

Subjects
Humans, Risk Factors, Child, Drug Hypersensitivity diagnosis
Abstract

Drug hypersensitivity reactions are common in children. Risk factors predisposing to IgE-mediated drug allergies and delayed drug reactions are a matter of debate. Gender, age, previous reactions to the same drug or to another drug, reduced drug metabolism, chronic diseases, polypharmacy, drug doses are linked with the onset of hypersensitivity reactions in some children. Novel advances in genetic polymorphisms can rapidly change the approach to the prevention of reactions since gene testing can be a useful screening test for severe cutaneous adverse reactions. Viral infections may act as cofactors in susceptible individuals. Polypharmacy, high doses, repeated doses and parental route of administration are also risk factors. Clinicians should take into account risk factors to allow the risk-benefit balance to be maintained., (© 2024. The Author(s).)

Published
2024
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34. Rare case of fecaloma requiring endoscopic intervention in a 24-year-old female.

Author

Hooda Z, Higgins SC, Pastore D, Crisafulli G, Canoles H, Alkomos M, Talishinskiy T, Amer K, and El-Sedfy A

Abstract

Fecalomas are a rare potential etiology for constipation experienced in children and the elderly. Large bowel obstructions due to fecalomas are preferably treated conservatively with laxatives and bowel rest. However, in the setting of severe corporostasis, more invasive procedures are required to prevent bowel ischemia and perforation. This case report describes a patient who presented to the emergency department with symptoms of large bowel obstruction and constipation, and she was found to have a fecaloma. Conservative interventions, including bowel rest and the administration of laxatives failed, prompting the need for more invasive therapies. During her admission, multiple flexible sigmoidoscopies were required to alleviate the obstruction. Ultimately, this case demonstrates an encounter of a patient with a sigmoid fecaloma from an unlikely demographic with few risk factors that required endoscopic intervention for treatment., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Published
2024
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35. Transcriptome-wide gene expression outlier analysis pinpoints therapeutic vulnerabilities in colorectal cancer.

Author

Mariella E, Grasso G, Miotto M, Buzo K, Reilly NM, Andrei P, Vitiello PP, Crisafulli G, Arena S, Rospo G, Corti G, Lorenzato A, Cancelliere C, Barault L, Gionfriddo G, Linnebacher M, Russo M, Di Nicolantonio F, and Bardelli A

Subjects
Humans, Cell Line, Tumor, Gene Expression Profiling, DNA Methylation genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms metabolism, Gene Expression Regulation, Neoplastic drug effects, Transcriptome genetics
Abstract

Multiple strategies are continuously being explored to expand the drug target repertoire in solid tumors. We devised a novel computational workflow for transcriptome-wide gene expression outlier analysis that allows the systematic identification of both overexpression and underexpression events in cancer cells. Here, it was applied to expression values obtained through RNA sequencing in 226 colorectal cancer (CRC) cell lines that were also characterized by whole-exome sequencing and microarray-based DNA methylation profiling. We found cell models displaying an abnormally high or low expression level for 3533 and 965 genes, respectively. Gene expression abnormalities that have been previously associated with clinically relevant features of CRC cell lines were confirmed. Moreover, by integrating multi-omics data, we identified both genetic and epigenetic alternations underlying outlier expression values. Importantly, our atlas of CRC gene expression outliers can guide the discovery of novel drug targets and biomarkers. As a proof of concept, we found that CRC cell lines lacking expression of the MTAP gene are sensitive to treatment with a PRMT5-MTA inhibitor (MRTX1719). Finally, other tumor types may also benefit from this approach., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Published
2024
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36. Mutational signatures of colorectal cancers according to distinct computational workflows.

Author

Battuello P, Corti G, Bartolini A, Lorenzato A, Sogari A, Russo M, Di Nicolantonio F, Bardelli A, and Crisafulli G

Subjects
Humans, Workflow, Cell Line, Tumor, Exome Sequencing methods, Female, Algorithms, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Mutation, Computational Biology methods
Abstract

Tumor mutational signatures have gained prominence in cancer research, yet the lack of standardized methods hinders reproducibility and robustness. Leveraging colorectal cancer (CRC) as a model, we explored the influence of computational parameters on mutational signature analyses across 230 CRC cell lines and 152 CRC patients. Results were validated in three independent datasets: 483 endometrial cancer patients stratified by mismatch repair (MMR) status, 35 lung cancer patients by smoking status and 12 patient-derived organoids (PDOs) annotated for colibactin exposure. Assessing various bioinformatic tools, reference datasets and input data sizes including whole genome sequencing, whole exome sequencing and a pan-cancer gene panel, we demonstrated significant variability in the results. We report that the use of distinct algorithms and references led to statistically different results, highlighting how arbitrary choices may induce variability in the mutational signature contributions. Furthermore, we found a differential contribution of mutational signatures between coding and intergenic regions and defined the minimum number of somatic variants required for reliable mutational signature assignment. To facilitate the identification of the most suitable workflows, we developed Comparative Mutational Signature analysis on Coding and Extragenic Regions (CoMSCER), a bioinformatic tool which allows researchers to easily perform comparative mutational signature analysis by coupling the results from several tools and public reference datasets and to assess mutational signature contributions in coding and non-coding genomic regions. In conclusion, our study provides a comparative framework to elucidate the impact of distinct computational workflows on mutational signatures., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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37. Association between Second-Hand Exposure to E-Cigarettes at Home and Exacerbations in Children with Asthma.

Author

Costantino S, Torre A, Foti Randazzese S, Mollica SA, Motta F, Busceti D, Ferrante F, Caminiti L, Crisafulli G, and Manti S

Abstract

Several studies have shown the effects of e-cigarettes in adults. Nowadays, few data are available in the pediatric population. This study aims to assess the relationship between asthma exacerbations and home exposure to e-cigarettes. We conducted a pilot, retrospective, monocenter, observational study. Demographic and clinical data were collected, including number of asthma exacerbations, need for rescue therapy and/or therapeutic step-up, and Asthma Control Test (ACT) and children-Asthma Control Test (c-ACT) scores. The cohort consisted of 54 patients (5-17 years old), divided into two groups: A, including patients exposed to e-cigarette aerosols; B, including unexposed patients. The statistical analysis showed no relevant variation in the number of asthma symptomatic days and need for rescue therapy in group A versus group B ( p = 0.27 and 0.19, respectively). There were no statistically significant variations when also considering the number of patients who needed a therapeutic step-up ( p = 0.3). The mean values of ACT and c-ACT were, respectively, 17.2 ± 7.6 and 18.3 ± 5.6 in group A and 19.6 ± 3.8 and 14.6 ± 5.8 in group B ( p = 0.3 and 0.4, respectively). Although we did not find a statistically significant correlation between second-hand e-cigarette exposure and asthma exacerbations, our findings suggest that asthmatic children exposed second-hand to e-cigarettes may have increased risk of asthma symptomatic days. Future research is warranted.

Published
2024
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38. Drug-Induced Anaphylaxis in Children.

Author

Bianchi A, Valluzzi R, Crisafulli G, Bottau P, Caimmi S, Franceschini F, Liotti L, Mori F, Riscassi S, Saretta F, Scavone S, and Caffarelli C

Abstract

Drug-induced anaphylaxis in children is less common than in adults and primarily involves beta-lactams and nonsteroidal anti-inflammatory drugs. Epidemiological studies show variable prevalence, influenced by age, gender, and atopic diseases. The pathophysiology includes IgE-mediated reactions and non-IgE mechanisms, like cytokine release reactions. We address drug-induced anaphylaxis in children, focusing on antibiotics, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and monoclonal antibodies. Diagnosis combines clinical criteria with in vitro, in vivo, and drug provocation tests. The immediate management of acute anaphylaxis primarily involves the use of adrenaline, coupled with long-term strategies, such as allergen avoidance and patient education. Desensitization protocols are crucial for children allergic to essential medications, particularly antibiotics and chemotherapy agents.

Published
2024
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39. Early Assessment of Efficacy and Safety of Biologics in Pediatric Allergic Diseases: Preliminary Results from a Prospective Real-World Study.

Author

Caminiti L, Galletta F, Foti Randazzese S, Barraco P, Passanisi S, Gambadauro A, Crisafulli G, Valenzise M, and Manti S

Abstract

Background: Despite the increasing interest in biologics for the management of allergic diseases, sparse real-world data are still available in the pediatric population. This study aimed to evaluate the early real-life efficacy and safety of omalizumab for patients with moderate-to-severe asthma and chronic spontaneous urticaria (CSU), and Dupilumab for patients with moderate-to-severe atopic dermatitis (AD)., Methods: A prospective study enrolling children aged 6-18 years was designed to assess the efficacy and safety of biologic drugs at 16 weeks of treatment (T1). The effectiveness was measured using validated questionnaires (ACQ-5 for asthma, UAS7 for CSU, and EASI score for AD). Secondary outcome measures included reductions in inhaled corticosteroid (ICS) dosages, asthma-related hospitalizations/exacerbations, and quality of life (QoL) indicators (iNRS, sNRS, DLQI/cDLQI) for CSU and AD. Safety was expressed according to the descriptions of adverse events provided by EMA and FDA., Results: The study cohort consisted of eighteen children (mean age 12.9 ± 3.4 years). The omalizumab treatment significantly reduced ACQ-5 and UAS7 scores ( p = 0.002 and p < 0.001, respectively). In patients with asthma, decreased ICS dosage and hospitalization/exacerbation rates were observed. QoL parameters significantly improved in CSU and AD patients. No severe adverse events were reported for either treatment., Conclusions: Our findings validate omalizumab and dupilumab as effective and safe therapeutic options for managing moderate-to-severe allergic diseases in children and adolescents.

Published
2024
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40. Impact of the Allergic Therapeutic Adherence in Children with Allergic Rhinitis and ADHD: A Pilot Study.

Author

Gambadauro A, Foti Randazzese S, Currò A, Galletta F, Crisafulli G, Caminiti L, Germanò E, Di Rosa G, Nicotera AG, and Manti S

Abstract

Background: Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients., Methods: The aim of our study was to analyse therapeutic adherence in patients with ADHD and AR and estimate the impact of the adherence on ADHD symptoms. Total Nasal Symptoms Score (TNSS), Paediatric or Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ 6-12 years; ARQLQ 13-17 years), Swanson, Nolan, and Pelham version IV scale (SNAP-IV), and Medication Assessment Questionnaire (MGL MAQ) were recorded., Results: In the AR-ADHD group, a positive correlation between TNSS and SNAP-IV subscales was found: worse AR symptoms were related to a negative effect on ADHD scores. AR-ADHD patients with better ADHD therapeutic adherence showed higher AR symptoms and higher oppositional defiant disorder scores in the SNAP-IV questionnaire., Conclusions: Our results suggest that better adherence to AR therapy (oral antihistamines and/or intranasal corticosteroids, INCS) is associated with a reduction in inattention symptoms in children with ADHD. This data could prove to be fundamental for the psychic outcome of these patients.

Published
2023
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41. Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Author

De Bacco F, Orzan F, Crisafulli G, Prelli M, Isella C, Casanova E, Albano R, Reato G, Erriquez J, D'Ambrosio A, Panero M, Dall'Aglio C, Casorzo L, Cominelli M, Pagani F, Melcarne A, Zeppa P, Altieri R, Morra I, Cassoni P, Garbossa D, Cassisa A, Bartolini A, Pellegatta S, Comoglio PM, Finocchiaro G, Poliani PL, and Boccaccio C

Subjects
Humans, Gene Amplification, Neoplastic Stem Cells metabolism, Carcinogenesis pathology, Cell Line, Tumor, Glioblastoma pathology, Brain Neoplasms metabolism
Abstract

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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42. Editorial: The impact of genetics on CRC therapy: from adaptive mutability to drug resistance.

Author

Crisafulli G and Siravegna G

Abstract

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Published
2023
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43. Long-Term Safety of Omalizumab in Children with Asthma and/or Chronic Spontaneous Urticaria: A 4-Year Prospective Study in Real Life.

Author

Galletta F, Caminiti L, Lugarà C, Foti Randazzese S, Barraco P, D'Amico F, Irrera P, Crisafulli G, and Manti S

Abstract

Background: Insufficient data are available on the long-term "real-life" safety profile of omalizumab in children. This study evaluated the long-term safety of omalizumab in a pediatric cohort with severe asthma or chronic spontaneous urticaria (CSU). Methods: A monocentric, prospective study evaluated the long-term safety of omalizumab in patients aged 6-18 years. Each patient completed the standardized MedDRA questionnaire to identify adverse events (AEs). Results: In total, 23 patients, median age 15 (14-18) years, affected by severe asthma (60.8%) or CSU (39.2%), treated with omalizumab for 2 (1-4) years were enrolled. The most common AEs belong to the system organ class (SOC) of general disorders and administration-site conditions (37.17%). Skin and subcutaneous tissue problems represent the second most frequently reported AEs (24.35%). Central nervous system and musculoskeletal disorders were quite frequent (15.38% and 8.97%, respectively). Other adverse events were tachycardia (5.12%), vertigo and abdominal pain (2.60% and 3.86%, respectively), and dry eye (1.3%). Only one patient reported herpes virus infection during treatment (1.3%). No cases of anaphylaxis, hemopathies, uronephropathies, respiratory, psychiatric, hepatobiliary, or oncological pathologies were reported. Conclusions: Long-term "real-life" treatment with omalizumab in children appears well tolerated. Its safety and efficacy profile makes omalizumab an excellent alternative in severe asthma and CSU in children.

Published
2023
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44. Liquid Biopsy of Cerebrospinal Fluid Enables Selective Profiling of Glioma Molecular Subtypes at First Clinical Presentation.

Author

Orzan F, De Bacco F, Lazzarini E, Crisafulli G, Gasparini A, Dipasquale A, Barault L, Macagno M, Persico P, Pessina F, Bono B, Giordano L, Zeppa P, Melcarne A, Cassoni P, Garbossa D, Santoro A, Comoglio PM, Indraccolo S, Simonelli M, and Boccaccio C

Subjects
Humans, Mutation, Prognosis, Liquid Biopsy, DNA, Neoplasm, Biomarkers, Tumor genetics, Glioma diagnosis, Glioma genetics, Glioma pathology, Brain Neoplasms diagnosis, Brain Neoplasms genetics
Abstract

Purpose: Current glioma diagnostic guidelines call for molecular profiling to stratify patients into prognostic and treatment subgroups. In case the tumor tissue is inaccessible, cerebrospinal fluid (CSF) has been proposed as a reliable tumor DNA source for liquid biopsy. We prospectively investigated the use of CSF for molecular characterization of newly diagnosed gliomas., Experimental Design: We recruited two cohorts of newly diagnosed patients with glioma, one (n = 45) providing CSF collected in proximity of the tumor, the other (n = 39) CSF collected by lumbar puncture (LP). Both cohorts provided tumor tissues by surgery concomitant with CSF sampling. DNA samples retrieved from CSF and matched tumors were systematically characterized and compared by comprehensive (NGS, next-generation sequencing) or targeted (ddPCR, droplet digital PCR) methodologies. Conventional and molecular diagnosis outcomes were compared., Results: We report that tumor DNA is abundant in CSF close to the tumor, but scanty and mostly below NGS sensitivity threshold in CSF from LP. Indeed, tumor DNA is mostly released by cells invading liquoral spaces, generating a gradient that attenuates by departing from the tumor. Nevertheless, in >60% of LP CSF samples, tumor DNA is sufficient to assess a selected panel of genetic alterations (IDH and TERT promoter mutations, EGFR amplification, CDKN2A/B deletion: ITEC protocol) and MGMT methylation that, combined with imaging, enable tissue-agnostic identification of main glioma molecular subtypes., Conclusions: This study shows potentialities and limitations of CSF liquid biopsy in achieving molecular characterization of gliomas at first clinical presentation and proposes a protocol to maximize diagnostic information retrievable from CSF DNA., (©2023 The Authors; Published by the American Association for Cancer Research.)

Published
2023
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45. Case report: Preclinical efficacy of NEDD8 and proteasome inhibitors in patient-derived models of signet ring high-grade mucinous colorectal cancer from a Lynch syndrome patient.

Author

Torchiaro E, Petti C, Arena S, Sassi F, Migliardi G, Mellano A, Porporato R, Basiricò M, Gammaitoni L, Berrino E, Montone M, Corti G, Crisafulli G, Marchiò C, Bardelli A, and Medico E

Abstract

High-grade mucinous colorectal cancer (HGM CRC) is particularly aggressive, prone to metastasis and treatment resistance, frequently accompanied by "signet ring" cancer cells. A sizeable fraction of HGM CRCs (20-40%) arises in the context of the Lynch Syndrome, an autosomal hereditary syndrome that predisposes to microsatellite instable (MSI) CRC. Development of patient-derived preclinical models for this challenging subtype of colorectal cancer represents an unmet need in oncology. We describe here successful propagation of preclinical models from a case of early-onset, MSI-positive metastatic colorectal cancer in a male Lynch syndrome patient, refractory to standard care (FOLFOX6, FOLFIRI-Panitumumab) and, surprisingly, also to immunotherapy. Surgical material from a debulking operation was implanted in NOD/SCID mice, successfully yielding one patient-derived xenograft (PDX). PDX explants were subsequently used to generate 2D and 3D cell cultures. Histologically, all models resembled the tumor of origin, displaying a high-grade mucinous phenotype with signet ring cells. For preclinical exploration of alternative treatments, in light of recent findings, we considered inhibition of the proteasome by bortezomib and of the related NEDD8 pathway by pevonedistat. Indeed, sensitivity to bortezomib was observed in mucinous adenocarcinoma of the lung, and we previously found that HGM CRC is preferentially sensitive to pevonedistat in models with low or absent expression of cadherin 17 (CDH17), a differentiation marker. We therefore performed IHC on the tumor and models, and observed no CDH17 expression, suggesting sensitivity to pevonedistat. Both bortezomib and pevonedistat showed strong activity on 2D cells at 72 hours and on 3D organoids at 7 days, thus providing valid options for in vivo testing. Accordingly, three PDX cohorts were treated for four weeks, respectively with vehicle, bortezomib and pevonedistat. Both drugs significantly reduced tumor growth, as compared to the vehicle group. Interestingly, while bortezomib was more effective in vitro , pevonedistat was more effective in vivo . Drug efficacy was further substantiated by a reduction of cellularity and of Ki67-positive cells in the treated tumors. These results highlight proteasome and NEDD8 inhibition as potentially effective therapeutic approaches against Lynch syndrome-associated HGM CRC, also when the disease is refractory to all available treatment options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Torchiaro, Petti, Arena, Sassi, Migliardi, Mellano, Porporato, Basiricò, Gammaitoni, Berrino, Montone, Corti, Crisafulli, Marchiò, Bardelli and Medico.)

Published
2023
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46. Hypersensitivity to Intravenous Iron Preparations.

Author

Caimmi S, Crisafulli G, Franceschini F, Liotti L, Bianchi A, Bottau P, Mori F, Triggiano P, Paglialunga C, Saretta F, Giannetti A, Ricci G, and Caffarelli C

Abstract

Intravenous iron is widely used for the treatment of iron deficiency anemia when adherence to oral iron replacement is poor. Acute hypersensitivity reactions during iron infusions are very rare but can be life threatening. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, atopic diseases, high serum tryptase levels, asthma, and urticaria. The management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. Avoidance of IV iron products in patients with iron hypersensitivity reactions may not be considered as a standard practice.

Published
2022
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47. DNA damage response and repair genes in advanced bone and soft tissue sarcomas: An 8-gene signature as a candidate predictive biomarker of response to trabectedin and olaparib combination.

Author

Merlini A, Centomo ML, Ferrero G, Chiabotto G, Miglio U, Berrino E, Giordano G, Brusco S, Pisacane A, Maldi E, Sarotto I, Capozzi F, Lano C, Isella C, Crisafulli G, Aglietta M, Dei Tos AP, Sbaraglia M, Sangiolo D, D'Ambrosio L, Bardelli A, Pignochino Y, and Grignani G

Abstract

Background: Advanced and unresectable bone and soft tissue sarcomas (BSTS) still represent an unmet medical need. We demonstrated that the alkylating agent trabectedin and the PARP1-inhibitor olaparib display antitumor activity in BSTS preclinical models. Moreover, in a phase Ib clinical trial (NCT02398058), feasibility, tolerability and encouraging results have been observed and the treatment combination is currently under study in a phase II trial (NCT03838744)., Methods: Differential expression of genes involved in DNA Damage Response and Repair was evaluated by Nanostring ® technology, extracting RNA from pre-treatment tumor samples of 16 responder (≥6-month progression free survival) and 16 non-responder patients. Data validation was performed by quantitative real-time PCR, RNA in situ hybridization, and immunohistochemistry. The correlation between the identified candidate genes and both progression-free survival and overall survival was investigated in the publicly available dataset "Sarcoma (TCGA, The Cancer Genome Atlas)"., Results: Differential RNA expression analysis revealed an 8-gene signature (CDKN2A, PIK3R1, SLFN11, ATM, APEX2, BLM, XRCC2, MAD2L2) defining patients with better outcome upon trabectedin+olaparib treatment. In responder vs. non-responder patients, a significant differential expression of these genes was further confirmed by RNA in situ hybridization and by qRT-PCR and immunohistochemistry in selected experiments. Correlation between survival outcomes and genetic alterations in the identified genes was shown in the TCGA sarcoma dataset., Conclusions: This work identified an 8-gene expression signature to improve prediction of response to trabectedin+olaparib combination in BSTS. The predictive role of these potential biomarkers warrants further investigation., Competing Interests: GGr has received fees for consulting/advisory roles from PharmaMar, Lilly, Novartis, Bayer, and Eisai. LDA received travel grant from PharmaMar and Lilly. MA has received fees for consulting/advisory roles from Bristol- Myers Squibb, Merck, and Roche. AB served in a consulting/advisory role for Illumina and Inivata. AB is cofounder and shareholder of NeoPhore. AB is a member of the NeoPhore scientific advisory board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Merlini, Centomo, Ferrero, Chiabotto, Miglio, Berrino, Giordano, Brusco, Pisacane, Maldi, Sarotto, Capozzi, Lano, Isella, Crisafulli, Aglietta, Dei Tos, Sbaraglia, Sangiolo, D’Ambrosio, Bardelli, Pignochino and Grignani.)

Published
2022
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48. Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial.

Author

Sartore-Bianchi A, Pietrantonio F, Lonardi S, Mussolin B, Rua F, Crisafulli G, Bartolini A, Fenocchio E, Amatu A, Manca P, Bergamo F, Tosi F, Mauri G, Ambrosini M, Daniel F, Torri V, Vanzulli A, Regge D, Cappello G, Marchiò C, Berrino E, Sapino A, Marsoni S, Siena S, and Bardelli A

Subjects
Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Humans, Mutation genetics, Panitumumab therapeutic use, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics, Antineoplastic Agents therapeutic use, Circulating Tumor DNA genetics, Colonic Neoplasms drug therapy, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Rectal Neoplasms drug therapy
Abstract

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC), but the emergence of resistance mutations restricts their efficacy. We previously showed that RAS, BRAF and EGFR mutant alleles, which appear in circulating tumor DNA (ctDNA) during EGFR blockade, decline upon therapy withdrawal. We hypothesized that monitoring resistance mutations in blood could rationally guide subsequent therapy with anti-EGFR antibodies. We report here the results of CHRONOS, an open-label, single-arm phase 2 clinical trial exploiting blood-based identification of RAS/BRAF/EGFR mutations levels to tailor a chemotherapy-free anti-EGFR rechallenge with panitumumab (ClinicalTrials.gov: NCT03227926 ; EudraCT 2016-002597-12). The primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival, safety and tolerability of this strategy. In CHRONOS, patients with tissue-RAS WT tumors after a previous treatment with anti-EGFR-based regimens underwent an interventional ctDNA-based screening. Of 52 patients, 16 (31%) carried at least one mutation conferring resistance to anti-EGFR therapy and were excluded. The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC. Further larger and randomized trials are warranted to formally compare panitumumab rechallenge with standard-of-care therapies in this patient setting., (© 2022. The Author(s).)

Published
2022
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49. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer.

Author

Mauri G, Vitiello PP, Sogari A, Crisafulli G, Sartore-Bianchi A, Marsoni S, Siena S, and Bardelli A

Subjects
Biomarkers, Tumor genetics, Humans, Liquid Biopsy, Neoplasm, Residual, Quality of Life, Retrospective Studies, Circulating Tumor DNA genetics, Colorectal Neoplasms diagnosis, Colorectal Neoplasms drug therapy
Abstract

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. Despite recent improvements in treatment and prevention, most of the current therapeutic options are weighted by side effects impacting patients' quality of life. Better patient selection towards systemic treatments represents an unmet clinical need. The recent multidisciplinary and molecular advancements in the treatment of CRC patients demand the identification of efficient biomarkers allowing to personalise patient care. Currently, core tumour biopsy specimens represent the gold-standard biological tissue to identify such biomarkers. However, technical feasibility, tumour heterogeneity and cancer evolution are major limitations of this single-snapshot approach. Genotyping circulating tumour DNA (ctDNA) has been addressed as potentially overcoming such limitations. Indeed, ctDNA has been retrospectively demonstrated capable of identifying minimal residual disease post-surgery and post-adjuvant treatment, as well as spotting druggable molecular alterations for tailoring treatments in metastatic disease. In this review, we summarise the available evidence on ctDNA applicability in CRC. Then, we review ongoing clinical trials assessing how liquid biopsy can be used interventionally to guide therapeutic choice in localised, locally advanced and metastatic CRC. Finally, we discuss how its widespread could transform CRC patients' management, dissecting its limitations while suggesting improvement strategies., (© 2022. The Author(s).)

Published
2022
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50. Drugs and Vaccines Hypersensitivity in Children with Mastocytosis.

Author

Mori F, Crisafulli G, Bianchi A, Bottau P, Caimmi S, Franceschini F, Liotti L, Paglialunga C, Saretta F, and Caffarelli C

Abstract

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations.

Published
2022
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