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199 results on '"Melchionda, F"'

53. P1410 Comparison of real-time PCR and blood culture for the diagnosis of bloodstream infections in onco-haematologic patients: microbiological and clinical assessment

Author

Varani, S., primary, Stanzani, M., additional, Nardi, L., additional, Paolucci, M., additional, Vianelli, N., additional, Baccarani, M., additional, Landini, M., additional, Dal Monte, P., additional, Cavrini, F., additional, Giannini, B., additional, Melchionda, F., additional, Pession, A., additional, and Sambri, V., additional

Published
2007
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54. Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors

Author

Pession, A, Prete, A, Locatelli, Franco, Bella, S, Melchionda, F, Garaventa, A, Burnelli, R, Paolucci, G, Locatelli, F (ORCID:0000-0002-7976-3654), Pession, A, Prete, A, Locatelli, Franco, Bella, S, Melchionda, F, Garaventa, A, Burnelli, R, Paolucci, G, and Locatelli, F (ORCID:0000-0002-7976-3654)

Abstract

Background: The aim of this phase I study was to define the maximum tolerated dose (MTD) of thiotepa (TT), administered with busulfan (BU) 480 mg/m(2) and etoposide 2,400 mg/m(2), followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (APBSCT) support in children with solid tumors either disseminated at diagnosis or after relapse. Procedure: Nineteen patients, between 2 and 16 years of age, received a high-dose chemotherapy regimen including escalating doses of TT starting from 150 mg/m(2). Subsequent dose escalation was determined by a modified Fibonacci scheme. Whenever one patient at one dosage level showed a grade III or grade IV reversible toxicity, additional patients were admitted (one by one) up to a maximum number of 6. Upon observing grade III or IV reversible toxicity in two or more systems, in 3 of the 6 patients, no further escalation was performed, and the corresponding dosage was taken as the MTD. WHO criteria were adopted to assess grade of toxicity. Results: All patients had hematological recovery; and neutrophils and platelet engraftment were observed after median times of 12 and 29 days from stem cell infusion, respectively. The MTD of TT was determined to be 750 mg/ m(2). At this level, 3 of 6 patients experienced grade III mucositis and/or grade III gastrointestinal toxicity. No patient died of treatment-related toxicity. Conclusions: A dose of 750 mg/m(2) TT is the MTD when it is associated with BU 480 mg/m(2) and etoposide 2, 400 mg/m(2). This ablative regimen represents a feasible and tolerable combination for high-dose chemotherapy followed by hematopoietic stem cell rescue (HSCR). Phase II studies in children with poor-prognosis solid tumors are required to evaluate the effectiveness of this treatment.

Published
1999

56. Acute liver failure associated with a prolonged course of acetaminophen at recommended dosages in paediatric age.

Author

Gentili, A., Latrofa, M. E., Giuntoli, L., Melchionda, F., Pession, A., Lima, M., and Baroncini, S.

Abstract

The article investigates the case of a 20-month old female who was treated for Wilms tumor stage I. The patient underwent left nephrectomy and chemotherapy according to national chemotherapy protocol of Wilms tumor in children and subsequently given acetaminophen for an ulcerative lesion on the forearm. After 29 days of acetaminophen treatment, the patient suffered acute liver failure (ALF) and lapsed to comatose status upon admission to the pediatric intensive care unit (PICU). After spontaneous recovery, it was concluded that prolonged use of acetaminophen combined with other liver-metabolized drugs can lead to potential risk of ALF.

Published
2008

57. Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

Author

Alm E., Broberg E.K., Connor T., Hodcroft E.B., Komissarov A.B., Maurer-Stroh S., Melidou A., Neher R.A., O'Toole A., Pereyaslov D., Beerenwinkel N., Posada-Cespedes S., Jablonski K.P., Ferreira P.F., Topolsky I., Avsic-Zupanc T., Korva M., Poljak M., Zakotnik S., Zorec T.M., Bragstad K., Hungnes O., Stene-Johansen K., Reusken C., Meijer A., Vennema H., Ruiz-Roldan L., Bracho M.A., Garcia-Gonzalez N., Chiner-Oms A., Cancino-Munoz I., Comas I., Goig G.A., Torres-Puente M., Lopez M.G., Martinez-Priego L., D'Auria G., Ruiz-Hueso P., Ferrus-Abad L., de Marco G., Galan-Vendrell I., Carbo-Ramirez S., Ruiz-Rodriguez P., Coscolla M., Polackova K., Kramna L., Cinek O., Richter J., Krashias G., Tryfonos C., Bashiardes S., Koptides D., Christodoulou C., Bartolini B., Gruber C.E., Di Caro A., Castilletti C., Stefani F., Rimoldi S.G., Romeri F., Salerno F., Polesello S., Nagy A., Jirincova H., Vecerova J., Novakova L., Cordey S., Murtskhvaladze M., Kotaria N., Schar T., Beisel C., Vugrek O., Rokic F., Trgovec-Greif L., Jurak I., Rukavina T., Sucic N., Schonning K., Karst S.M., Kirkegaard R.H., Michaelsen T.Y., Sorensen E.A., Knutson S., Brandt J., Le-Quy V., Sorensen T., Petersen C., Pedersen M.S., Larsen S.L., Skov M.N., Rasmussen M., Fonager J., Fomsgaard A., Maksyutov R.A., Gavrilova E.V., Pyankov O.V., Bodnev S.A., Tregubchak T.V., Shvalov A.N., Antonets D.V., Resende P.C., Goya S., Perrin A., Lee R.T., Yadahalli S., Han A.X., Russell C.A., Schmutz S., Zaheri M., Kufner V., Huber M., Trkola A., Antwerpen M., Walter M.C., van der Werf S., Gambaro F., Behillil S., Enouf V., Donati F., Ustinova M., Rovite V., Klovins J., Savicka O., Wienecke-Baldacchino A.K., Ragimbeau C., Fournier G., Mossong J., Aberle S.W., Haukland M., Enkirch T., Advani A., Karlberg M.L., Lindsjo O.K., Broddesson S., Slavikova M., Lickova M., Klempa B., Staronova E., Ticha E., Szemes T., Rusnakova D., Stadler T., Quer J., Anton A., Andres C., Pinana M., Garcia-Cehic D., Pumarola T., Izopet J., Gioula G., Exindari M., Papa A., Chatzidimitriou D., Metallidis S., Pappa S., Macek M., Geryk J., Broz P., Briksi A., Hubacek P., Drevinek P., Zajac M., Kvapil P., Holub M., Kvapilova K., Novotny A., Kasny M., Klempt P., Vapalahti O., Smura T., Sironen T., Selhorst P., Anthony C., Arien K., Simon-Loriere E., Rabalski L., Bienkowska-Szewczyk K., Borges V., Isidro J., Gomes J.P., Guiomar R., Pechirra P., Costa I., Duarte S., Vieira L., Pyrc K., Zuckerman N.S., Turdikulova S., Abdullaev A., Dalimova D., Abdurakhimov A., Tagliabracci A., Alessandrini F., Melchionda F., Onofri V., Turchi C., Bagnarelli P., Menzo S., Caucci S., Di Sante L., Popa A., Genger J.-W., Agerer B., Lercher A., Endler L., Smyth M., Penz T., Schuster M., Senekowitsch M., Laine J., Bock C., Bergthaler A., Shevtsov A., Kalendar R., Ramanculov Y., Graf A., Muenchhoff M., Keppler O.T., Krebs S., Blum H., Marcello A., Licastro D., D'Agaro P., Laubscher F., Vidanovic D., Tesovic B., Volkening J., Clementi N., Mancini N., Rupnik M., Mahnic A., Walker A., Houwaart T., Wienemann T., Vasconcelos M.K., Strelow D., Jensen B.-E.O., Senff T., Hulse L., Adams O., Andree M., Hauka S., Feldt T., Keitel V., Kindgen-Milles D., Timm J., Pfeffer K., Dilthey A.T., Moore C., Ozdarendeli A., Pavel S.T.I., Yetiskin H., Aydin G., Holyavkin C., Uygut M.A., Cevik C., Shchetinin A., Gushchin V., Dinler-Doganay G., Doganay L., Kizilboga-Akgun T., Karacan I., Pancer K., Maes P., Marti-Carreras J., Wawina-Bokalanga T., Vanmechelen B., Thurmer A., Wedde M., Durrwald R., von Kleist M., Drechsel O., Wolff T., Fuchs S., Kmiecinski R., Michel J., Nitsche A., Casas I., Caballero M.I., Zaballos A., Jimenez P., Jimenez M., Fernandez S.M., Fernandez S.V., de la Plaza I.C., Fadeev A., Ivanova A., Sergeeva M., Stefanelli P., Estee Torok M., Hall G., da Silva Filipe A., Turtle L., Afifi S., McCluggage K., Beer R., Ledesma J., Maksimovic J., Spellman K., Hamilton W.L., Marchbank A., Southgate J.A., Underwood A., Taylor B., Yeats C., Abudahab K., Gemmell M.R., Eccles R., Lucaci A., Nelson C.A., Rainbow L., Whitehead M., Gregory R., Haldenby S., Paterson S., Hughes M.A., Curran M.D., Baker D., Tucker R., Green L.R., Feltwell T., Halstead F.D., Wyles M., Jahun A.S., Ahmad S.S.Y., Georgana I., Goodfellow I., Yakovleva A., Meredith L.W., Gavriil A., Awan A.R., Fisher C., Edgeworth J., Lynch J., Moore N., Williams R., Kidd S.P., Cortes N., Brunker K., McCrone J.T., Quick J., Duckworth N., Walsh S., Sloan T., Ludden C., George R.P., Eltringham G., Brown J.R., Aranday-Cortes E., Shepherd J.G., Hughes J., Li K.K., Williams T.C., Johnson N., Jesudason N., Mair D., Thomson E., Shah R., Parr Y.A., Carmichael S., Robertson D.L., Nomikou K., Broos A., Niebel M., Smollett K., Tong L., Miah S., Wittner A., Phillips N., Payne B., Dewar R., Holmes A., Bolt F., Price J.R., Mookerjee S., Sethi D.K., Potter W., Stanley R., Prakash R., Dervisevic S., Graham J.C., Nelson A., Smith D., Young G.R., Yew W.C., Todd J.A., Trebes A., Andersson M., Bull M., Watkins J., Birchley A., Gatica-Wilcox B., Gilbert L., Kumziene-Summerhayes S., Rey S., Chauhan A., Butcher E., Bicknell K., Elliott S., Glaysher S., Lackenby A., Bibby D., Platt S., Mohamed H., Machin N.W., Mbisa J.L., Evans J., Perry M., Pacchiarini N., Corden S., Adams A.G., Gaskin A., Coombs J., Graham L.J., Cottrell S., Morgan M., Gifford L., Kolyva A., Rudder S.J., Trotter A.J., Mather A.E., Aydin A., Page A.J., Kay G.L., de Oliveira Martins L., Yasir M., Alikhan N.-F., Thomson N.M., Gilroy R., Kingsley R.A., O'Grady J., Gutierrez A.V., Diaz M., Viet T.L., Tedim A.P., Adriaenssens E.M., Patrick Mcclure C., Sang F., Clark G., Howson-Wells H.C., Debebe J., Ball J., Chappell J., Khakh M., Carlile M., Loose M., Lister M.M., Holmes N., Tsoleridis T., Fleming V.M., Wright V., Smith W., Gallagher M.D., Parker M., Partridge D.G., Evans C., Baker P., Essex S., Liggett S., Keeley A.J., Bashton M., Rooke S., Dervisavic S., Meader E.J., Lopez C.E.B., Angyal A., Kristiansen M., Tutill H.J., Findlay J., Mestek-Boukhibar L., Forrest L., Dyal P., Williams R.J., Panchbhaya Y., Williams C.A., Roy S., Pandey S., Stockton J., Loman N.J., Poplawski R., Nicholls S., Rowe W.P.M., Khokhar F., Pinckert M.L., Hosmillo M., Chaudhry Y., Caller L.G., Davidson R.K., Griffith L., Rambaut A., Jackson B., Colquhoun R., Hill V., Nichols J., Asamaphan P., Darby A., Jackson K.A., Iturriza-Gomara M., Vamos E.E., Green A., Aanensen D., Bonsall D., Buck D., Macintyre-Cockett G., de Cesare M., Pybus O., Golubchik T., Scarlett G., Loveson K.F., Robson S.C., Beckett A., Lindsey B., Groves D.C., Parsons P.J., McHugh M.P., Barnes J.D., Manso C.F., Grammatopoulos D., Menger K.E., Harrison E., Gunson R., Peacock S.J., Gonzalez G., Carr M., Mihaela L., Popovici O., Brytting M., Bresner C., Fuller W., Workman T., Mentis A.F., Kossyvakis A., Karamitros T., Pogka V., Kalliaropoulos A., Horefti E., Kontou A., Martinez-Gonzalez B., Labropoulou V., Voulgari-Kokota A., Evangelidou M., Bizta P., Belimezi M., Lambrechts L., Doymaz M.Z., Yazici M.K., Cetin N.S., Karaaslan E., Kallio-Kokko H., Virtanen J., Suvanto M., Nguyen P.T., Ellonen P., Hannula S., Kangas H., Sreenu V.B., Burian K., Terhes G., Gombos K., Gyenesei A., Urban P., Herczeg R., Jakab F., Kemenesi G., Toth G.E., Somogyi B., Zana B., Zeghbib S., Kuczmog A., Foldes F., Lanszki Z., Madai M., Papp H., Pereszlenyi C.I., Babinszky G.C., Dudas G., Csoma E., Abou Tayoun A.N., Alsheikh-Ali A.A., Loney T., Nowotny N., Abdul-Wahab O., Gonzalez-Candelas F., Andersen M.H., Taylor S., MARTI CARRERAS, Joan, Vanmechelen, Bert, Wawina, Tony, Medical Microbiology and Infection Prevention, AII - Infectious diseases, WHO European Region Sequencing Lab, GISAID EpiCoV Grp, Erik, Alm, Eeva K, Broberg, Thomas, Connor, Emma B, Hodcroft, Andrey B, Komissarov, Sebastian, Maurer-Stroh, Angeliki, Melidou, Richard A, Neher, Áine, O’Toole, Dmitriy, Pereyaslov, WHO European Region sequencing laboratories and GISAID EpiCoV group (Niko Beerenwinkel, The, Posada-Céspedes, Susana, Philipp, Kim, Jablonski, Falé Ferreira, Pedro, Topolsky, Ivan, Avšičžupanc, Tatjana, Korva, Miša, Poljak, Mario, Zakotnik, Samo, Tomaž, Zorec, Mark, Bragstad, Karoline, Hungnes, Olav, Stene-Johansen, Kathrine, Reusken, Chantal, Meijer, Adam, Vennema, Harry, Ruiz-Roldán, Lidia, Alma Bracho, María, García-González, Neri, Chiner-Oms, Álvaro, Cancino-Muñoz, Irving, Comas, Iñaki, A Goig, Galo, Torres-Puente, Manuela, G López, Mariana, Martínez-Priego, Llúcia, D’Auria, Giuseppe, LoretoFerrús-Abad, de Marco, Griselda, Galan-Vendrell, Inmaculada, Carbó-Ramirez, Sandra, Ruíz-Hueso, Paula, Coscollá, Mireia, Polackova, Katerina, Kramna, Lenka, Cinek, Ondrej, Richter, Jan, Krashias, George, Tryfonos, Christina, Bashiardes, Stavro, Koptides, Dana, Christodoulou, Christina, Bartolini, Barbara, Em Gruber, Cesare, Di Caro, Antonino, Castilletti, Concetta, Stefani, Fabrizio, Giordana Rimoldi, Sara, Romeri, Francesca, Salerno, Franco, Polesello, Stefano, Nagy, Alexander, Jirincova, Helena, Vecerova, Jaromira, Novakova, Ludmila, Cordey, Samuel, Murtskhvaladze, Marine, Kotaria, Nato, Schär, Tobia, Beisel, Christian, Vugrek, Oliver, Rokić, Filip, Trgovecgreif, Lovro, Jurak, Igor, Rukavina, Tomislav, Sučić, Neven, Schønning, Kristian, M Karst, Søren, H Kirkegaard, Rasmu, Y Michaelsen, Thoma, Aa Sørensen, Emil, Knutson, Simon, Brandt, Jakob, Le-Quy, Vang, Sørensen, Trine, Petersen, Celine, Schou Pedersen, Martin, Løkkegaard Larsen, Sanne, Nielsine Skov, Marianne, Rasmussen, Morten, Fonager, Jannik, Fomsgaard, Ander, Amirovich Maksyutov, Rinat, Vasil’Evna Gavrilova, Elena, Victorovich Pyankov, Oleg, Alexandrovich Bodnev, Sergey, Vladimirovna Tregubchak, Tatyana, Nikolayevich Shvalov, Alexander, Victorovich Antonets, Deni, Cristina Resende, Paola, Goya, Stephanie, Perrin, Amandine, Tc Lee, Raphael, Yadahalli, Shilpa, X Han, Alvin, A Russell, Colin, Schmutz, Stefan, Zaheri, Maryam, Kufner, Verena, Huber, Michael, Trkola, Alexandra, Antwerpen, Marku, C Walter, Mathia, van der Werf, Sylvie, Gambaro, Fabiana, Behillil, Sylvie, Enouf, Vincent, Donati, Flora, Ustinova, Monta, Rovite, Vita, Klovins, Jani, Savicka, Oksana, K Wienecke-Baldacchino, Anke, Ragimbeau, Catherine, Fournier, Guillaume, Mossong, Joël, W Aberle, Stephan, Haukland, Mattia, Enkirch, Theresa, Advani, Abdolreza, Lind Karlberg, Maria, Karlsson Lindsjö, Oskar, Broddesson, Sandra, Sláviková, Monika, Ličková, Martina, Klempa, Bori, Staroňová, Edita, Tichá, Elena, Szemes, Tomáš, Rusňáková, Diana, Stadler, Tanja, Quer, Josep, Anton, Andre, Andres, Cristina, Piñana, Maria, Garcia-Cehic, Damir, Pumarola, Toma, Izopet, Jacque, Gioula, Georgia, Exindari, Maria, Papa, Anna, Chatzidimitriou, Dimitrio, Metallidis, Symeon, Pappa, Stella, Macek Jr, Milan, Geryk, Jan, Brož, Petr, Briksí, Aleš, Hubáček, Petr, Dřevínek, Pavel, Zajac, Miroslav, Kvapil, Petr, Holub, Michal, Kvapilová, Kateřina, Novotný, Adam, Kašný, Martin, Klempt, Petr, Vapalahti, Olli, Smura, Teemu, Sironen, Tarja, Selhorst, Philippe, Anthony, Colin, Ariën, Kevin, Simon-Loriere, Etienne, Rabalski, Lukasz, Bienkowska-Szewczyk, Krystyna, Borges, Vítor, Isidro, Joana, Paulo Gomes, João, Guiomar, Raquel, Pechirra, Pedro, Costa, Inê, Duarte, Sílvia, Vieira, Luí, Pyrc, Krzysztof, S Zuckerman, Neta, Turdikulova, Shahlo, Abdullaev, Alisher, Dalimova, Dilbar, Abdurakhimov, Abror, Tagliabracci, Adriano, Alessandrini, Federica, Melchionda, Filomena, Onofri, Valerio, Turchi, Chiara, Bagnarelli, Patrizia, Menzo, Stefano, Caucci, Sara, Di Sante, Laura, Popa, Alexandra, Genger, Jakob-Wendelin, Agerer, Benedikt, Lercher, Alexander, Endler, Luka, Smyth, Mark, Penz, Thoma, Schuster, Michael, Senekowitsch, Martin, Laine, Jan, Bock, Christoph, Bergthaler, Andrea, Shevtsov, Alexandr, Kalendar, Ruslan, Ramanculov, Yerlan, Graf, Alexander, Muenchhoff, Maximilian, T Keppler, Oliver, Krebs, Stefan, Blum, Helmut, Marcello, Alessandro, Licastro, Danilo, D’Agaro, Pierlanfranco, Laubscher, Florian, Vidanovic, Dejan, Tesovic, Bojana, Volkening, Jeremy, Clementi, Nicola, Mancini, Nicasio, Rupnik, Maja, Mahnic, Aleksander, Walker, Andrea, Houwaart, Torsten, Wienemann, Tobia, Kohns Vasconcelos, Malte, Strelow, Daniel, Ole Jensen, Björn-Erik, Senff, Tina, Hülse, Lisanna, Adams, Ortwin, Andree, Marcel, Hauka, Sandra, Feldt, Torsten, Keitel, Verena, Kindgen-Milles, Detlef, Timm, Jörg, Pfeffer, Klau, T Dilthey, Alexander, Moore, Catherine, Ozdarendeli, Aykut, Terkis Islam Pavel, Shaikh, Yetiskin, Hazel, Aydin, Gunsu, Holyavkin, Can, Ali Uygut, Muhammet, Cevik, Ceren, Shchetinin, Alexey, Gushchin, Vladimir, Dinler-Doganay, Gizem, Doganay, Levent, Kizilboga-Akgun, Tugba, Karacan, Ilker, Pancer, Katarzyna, Maes, Piet, Martí-Carreras, Joan, Wawina-Bokalanga, Tony, Thürmer, Andrea, Wedde, Marianne, Dürrwald, Ralf, Von Kleist, Max, Drechsel, Oliver, Wolff, Thorsten, Fuchs, Stephan, Kmiecinski, Rene, Michel, Janine, Nitsche, Andrea, Casas, Inmaculada, Iglesias Caballero, María, Zaballos, Ángel, Jiménez, Pilar, Jiménez, Mercede, Monzón Fernández, Sara, Varona Fernández, Sarai, Cuesta De La Plaza, Isabel, Fadeev, Artem, Ivanova, Anna, Sergeeva, Mariia, Stefanelli, Paola, Estee Torok, M, Hall, Grant, da Silva Filipe, Ana, Turtle, Lance, Afifi, Safiah, Mccluggage, Kathryn, Beer, Robert, Ledesma, Juan, Maksimovic, Joshua, Spellman, Karla, L Hamilton, William, Marchbank, Angela, Alexander Southgate, Joel, Underwood, Anthony, Taylor, Ben, Yeats, Corin, Abudahab, Khalil, R Gemmell, Matthew, Eccles, Richard, Lucaci, Anita, Abigail Nelson, Charlotte, Rainbow, Lucille, Whitehead, Mark, Gregory, Richard, Haldenby, Sam, Paterson, Steve, A Hughes, Margaret, D Curran, Martin, Baker, David, Tucker, Rachel, R Green, Luke, Feltwell, Theresa, D Halstead, Fenella, Wyles, Matthew, S Jahun, Aminu, Y Ahmad, Shazaad S, Georgana, Iliana, Goodfellow, Ian, Yakovleva, Anna, W Meredith, Luke, Gavriil, Artemi, Raza Awan, Ali, Fisher, Chloe, Jonathan, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Cardiff University, Public Health Wales [Cardiff, Royaume uni], University of Basel (Unibas), Research Institute of Influenza, St. Petersburg, Russia, Agency for science, technology and research [Singapore] (A*STAR), National University of Singapore (NUS), University of Edinburgh, WHO Regional Office for Europe [Copenhagen], We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible, The WHO European Region sequencing laboratories and GISAID EpiCoV group*: Niko Beerenwinkel, Susana Posada-Céspedes, Kim Philipp Jablonski, Pedro Falé Ferreira, Ivan Topolsky, Tatjana Avšič-Županc, Miša Korva, Mario Poljak, Samo Zakotnik, Tomaž Mark Zorec, Karoline Bragstad, Olav Hungnes, Kathrine Stene-Johansen, Chantal Reusken, Adam Meijer, Harry Vennema, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Álvaro Chiner-Oms, Irving Cancino-Muñoz, Iñaki Comas, Galo A Goig, Manuela Torres-Puente, Mariana G López, Llúcia Martínez-Priego, Giuseppe D'Auria, Paula Ruíz-Hueso, Loreto Ferrús-Abad, Griselda de Marco, Inmaculada Galan-Vendrell, Sandra Carbó-Ramirez, Paula Ruiz-Rodriguez, Mireia Coscollá, Katerina Polackova, Lenka Kramna, Ondrej Cinek, Jan Richter, George Krashias, Christina Tryfonos, Stavros Bashiardes, Dana Koptides, Christina Christodoulou, Barbara Bartolini, Cesare Em Gruber, Antonino Di Caro, Concetta Castilletti, Fabrizio Stefani, Sara Giordana Rimoldi, Francesca Romeri, Franco Salerno, Stefano Polesello, Alexander Nagy, Helena Jirincova, Jaromira Vecerova, Ludmila Novakova, Samuel Cordey, Marine Murtskhvaladze, Nato Kotaria, Tobias Schär, Christian Beisel, Oliver Vugrek, Filip Rokić, Lovro Trgovec-Greif, Igor Jurak, Tomislav Rukavina, Neven Sučić, Kristian Schønning, Søren M Karst, Rasmus H Kirkegaard, Thomas Y Michaelsen, Emil Aa Sørensen, Simon Knutson, Jakob Brandt, Vang Le-Quy, Trine Sørensen, Celine Petersen, Martin Schou Pedersen, Sanne Løkkegaard Larsen, Marianne Nielsine Skov, Morten Rasmussen, Jannik Fonager, Anders Fomsgaard, Rinat Amirovich Maksyutov, Elena Vasil'Evna Gavrilova, Oleg Victorovich Pyankov, Sergey Alexandrovich Bodnev, Tatyana Vladimirovna Tregubchak, Alexander Nikolayevich Shvalov, Denis Victorovich Antonets, Paola Cristina Resende, Stephanie Goya, Amandine Perrin, Raphael Tc Lee, Shilpa Yadahalli, Alvin X Han, Colin A Russell, Stefan Schmutz, Maryam Zaheri, Verena Kufner, Michael Huber, Alexandra Trkola, Markus Antwerpen, Mathias C Walter, Sylvie van der Werf, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Flora Donati, Monta Ustinova, Vita Rovite, Janis Klovins, Oksana Savicka, Anke K Wienecke-Baldacchino, Catherine Ragimbeau, Guillaume Fournier, Joël Mossong, Stephan W Aberle, Mattias Haukland, Theresa Enkirch, Abdolreza Advani, Maria Lind Karlberg, Oskar Karlsson Lindsjö, Sandra Broddesson, Monika Sláviková, Martina Ličková, Boris Klempa, Edita Staroňová, Elena Tichá, Tomáš Szemes, Diana Rusňáková, Tanja Stadler, Josep Quer, Andres Anton, Cristina Andres, Maria Piñana, Damir Garcia-Cehic, Tomas Pumarola, Jacques Izopet, Georgia Gioula, Maria Exindari, Anna Papa, Dimitrios Chatzidimitriou, Symeon Metallidis, Stella Pappa, Milan Macek Jr, Jan Geryk, Petr Brož, Aleš Briksí, Petr Hubáček, Pavel Dřevínek, Miroslav Zajac, Petr Kvapil, Michal Holub, Kateřina Kvapilová, Adam Novotný, Martin Kašný, Petr Klempt, Olli Vapalahti, Teemu Smura, Tarja Sironen, Philippe Selhorst, Colin Anthony, Kevin Ariën, Etienne Simon-Loriere, Lukasz Rabalski, Krystyna Bienkowska-Szewczyk, Vítor Borges, Joana Isidro, João Paulo Gomes, Raquel Guiomar, Pedro Pechirra, Inês Costa, Sílvia Duarte, Luís Vieira, Krzysztof Pyrc, Neta S Zuckerman, Shahlo Turdikulova, Alisher Abdullaev, Dilbar Dalimova, Abror Abdurakhimov, Adriano Tagliabracci, Federica Alessandrini, Filomena Melchionda, Valerio Onofri, Chiara Turchi, Patrizia Bagnarelli, Stefano Menzo, Sara Caucci, Laura Di Sante, Alexandra Popa, Jakob-Wendelin Genger, Benedikt Agerer, Alexander Lercher, Lukas Endler, Mark Smyth, Thomas Penz, Michael Schuster, Martin Senekowitsch, Jan Laine, Christoph Bock, Andreas Bergthaler, Alexandr Shevtsov, Ruslan Kalendar, Yerlan Ramanculov, Alexander Graf, Maximilian Muenchhoff, Oliver T Keppler, Stefan Krebs, Helmut Blum, Alessandro Marcello, Danilo Licastro, Pierlanfranco D'Agaro, Florian Laubscher, Dejan Vidanovic, Bojana Tesovic, Jeremy Volkening, Nicola Clementi, Nicasio Mancini, Maja Rupnik, Aleksander Mahnic, Andreas Walker, Torsten Houwaart, Tobias Wienemann, Malte Kohns Vasconcelos, Daniel Strelow, Björn-Erik Ole Jensen, Tina Senff, Lisanna Hülse, Ortwin Adams, Marcel Andree, Sandra Hauka, Torsten Feldt, Verena Keitel, Detlef Kindgen-Milles, Jörg Timm, Klaus Pfeffer, Alexander T Dilthey, Catherine Moore, Aykut Ozdarendeli, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Gunsu Aydin, Can Holyavkin, Muhammet Ali Uygut, Ceren Cevik, Alexey Shchetinin, Vladimir Gushchin, Gizem Dinler-Doganay, Levent Doganay, Tugba Kizilboga-Akgun, Ilker Karacan, Katarzyna Pancer, Piet Maes, Joan Martí-Carreras, Tony Wawina-Bokalanga, Bert Vanmechelen, Andrea Thürmer, Marianne Wedde, Ralf Dürrwald, Max Von Kleist, Oliver Drechsel, Thorsten Wolff, Stephan Fuchs, Rene Kmiecinski, Janine Michel, Andreas Nitsche, Inmaculada Casas, María Iglesias Caballero, Ángel Zaballos, Pilar Jiménez, Mercedes Jiménez, Sara Monzón Fernández, Sarai Varona Fernández, Isabel Cuesta De La Plaza, Artem Fadeev, Anna Ivanova, Mariia Sergeeva, Paola Stefanelli, M Estee Torok, Grant Hall, Ana da Silva Filipe, Lance Turtle, Safiah Afifi, Kathryn Mccluggage, Robert Beer, Juan Ledesma, Joshua Maksimovic, Karla Spellman, William L Hamilton, Angela Marchbank, Joel Alexander Southgate, Anthony Underwood, Ben Taylor, Corin Yeats, Khalil Abudahab, Matthew R Gemmell, Richard Eccles, Anita Lucaci, Charlotte Abigail Nelson, Lucille Rainbow, Mark Whitehead, Richard Gregory, Sam Haldenby, Steve Paterson, Margaret A Hughes, Martin D Curran, David Baker, Rachel Tucker, Luke R Green, Theresa Feltwell, Fenella D Halstead, Matthew Wyles, Aminu S Jahun, Shazaad S Y Ahmad, Iliana Georgana, Ian Goodfellow, Anna Yakovleva, Luke W Meredith, Artemis Gavriil, Ali Raza Awan, Chloe Fisher, Jonathan Edgeworth, Jessica Lynch, Nathan Moore, Rebecca Williams, Stephen P Kidd, Nicholas Cortes, Kirstyn Brunker, John T Mccrone, Joshua Quick, Nichola Duckworth, Sarah Walsh, Tim Sloan, Catherine Ludden, Ryan P George, Gary Eltringham, Julianne R Brown, Elihu Aranday-Cortes, James G Shepherd, Joseph Hughes, Kathy K Li, Thomas C Williams, Natasha Johnson, Natasha Jesudason, Daniel Mair, Emma Thomson, Rajiv Shah, Yasmin A Parr, Stephen Carmichael, David L Robertson, Kyriaki Nomikou, Alice Broos, Marc Niebel, Katherine Smollett, Lily Tong, Shahjahan Miah, Anita Wittner, Nicole Phillips, Brendan Payne, Rebecca Dewar, Alison Holmes, Frances Bolt, James R Price, Siddharth Mookerjee, Dheeraj K Sethi, Will Potter, Rachael Stanley, Reenesh Prakash, Samir Dervisevic, Jonathan Clive Graham, Andrew Nelson, Darren Smith, Gregory R Young, Wen Chyin Yew, John A Todd, Amy Trebes, Monique Andersson, Matthew Bull, Joanne Watkins, Alec Birchley, Bree Gatica-Wilcox, Lauren Gilbert, Sara Kumžiene-Summerhayes, Sara Rey, Anoop Chauhan, Ethan Butcher, Kelly Bicknell, Scott Elliott, Sharon Glaysher, Angie Lackenby, David Bibby, Steven Platt, Hodan Mohamed, Nicholas William Machin, Jean Lutamyo Mbisa, Jonathan Evans, Malorie Perry, Nicole Pacchiarini, Sally Corden, Alexander Geraint Adams, Amy Gaskin, Jason Coombs, Lee John Graham, Simon Cottrell, Mari Morgan, Laura Gifford, Anastasia Kolyva, Steven John Rudder, Alexander J Trotter, Alison E Mather, Alp Aydin, Andrew J Page, Gemma L Kay, Leonardo de Oliveira Martins, Muhammad Yasir, Nabil-Fareed Alikhan, Nicholas M Thomson, Rachel Gilroy, Robert A Kingsley, Justin O'Grady, Ana Victoria Gutierrez, Maria Diaz, Thanh Le Viet, Ana P Tedim, Evelien M Adriaenssens, C Patrick Mcclure, Christopher Moore, Fei Sang, Gemma Clark, Hannah C Howson-Wells, Johnny Debebe, Jonathan Ball, Joseph Chappell, Manjinder Khakh, Matthew Carlile, Matthew Loose, Michelle M Lister, Nadine Holmes, Theocharis Tsoleridis, Vicki M Fleming, Victoria Wright, Wendy Smith, Michael D Gallagher, Matthew Parker, David G Partridge, Cariad Evans, Paul Baker, Sarah Essex, Steven Liggett, Alexander J Keeley, Matthew Bashton, Stefan Rooke, Samir Dervisevic, Emma Jane Meader, Carlos Enrique Balcazar Lopez, Adrienn Angyal, Mark Kristiansen, Helena J Tutill, Jacqueline Findlay, Lamia Mestek-Boukhibar, Leysa Forrest, Patricia Dyal, Rachel J Williams, Yasmin Panchbhaya, Charlotte A Williams, Sunando Roy, Sarojini Pandey, Jo Stockton, Nicholas J Loman, Radoslaw Poplawski, Samuel Nicholls, W P M Rowe, Fahad Khokhar, Malte Lars Pinckert, Myra Hosmillo, Yasmin Chaudhry, Laura G Caller, Rose K Davidson, Luke Griffith, Andrew Rambaut, Ben Jackson, Rachel Colquhoun, Verity Hill, Jenna Nichols, Patawee Asamaphan, Alistair Darby, Kathryn A Jackson, Miren Iturriza-Gomara, Ecaterina Edith Vamos, Angie Green, David Aanensen, David Bonsall, David Buck, George Macintyre-Cockett, Mariateresa de Cesare, Oliver Pybus, Tanya Golubchik, Garry Scarlett, Katie F Loveson, Samuel C Robson, Angela Beckett, Benjamin Lindsey, Danielle C Groves, Paul J Parsons, Martin P Mchugh, James Daniel Barnes, Carmen F Manso, Dimitris Grammatopoulos, Katja Elisabeth Menger, Ewan Harrison, Rory Gunson, Sharon J Peacock, Gabriel Gonzalez, Michael Carr, Lazar Mihaela, Odette Popovici, Mia Brytting, Catherine Bresner, William Fuller, Trudy Workman, Andreas F Mentis, Athanasios Kossyvakis, Timokratis Karamitros, Vasiliki Pogka, Antonios Kalliaropoulos, Elina Horefti, Aspasia Kontou, Beatriz Martinez-Gonzalez, Voula Labropoulou, Androniki Voulgari-Kokota, Maria Evangelidou, Panagiota Bizta, Maria Belimezi, Laurens Lambrechts, Mehmet Z Doymaz, Merve Kalkan Yazici, Nesibe S Cetin, Elif Karaaslan, Hannimari Kallio-Kokko, Jenni Virtanen, Maija Suvanto, Phuoc Truong Nguyen, Pekka Ellonen, Sari Hannula, Harri Kangas, Vattipally B Sreenu, Katalin Burián, Gabriella Terhes, Katalin Gombos, Attila Gyenesei, Péter Urbán, Róbert Herczeg, Ferenc Jakab, Gábor Kemenesi, Gábor Endre Tóth, Balázs Somogyi, Brigitta Zana, Safia Zeghbib, Anett Kuczmog, Fanni Földes, Zsófia Lanszki, Mónika Madai, Henrietta Papp, Ágnes Nagy, Csaba István Pereszlényi, Gergely Csaba Babinszky, Gábor Dudás, Eszter Csoma, Ahmad N Abou Tayoun, Alawi A Alsheikh-Ali, Tom Loney, Norbert Nowotny, Osama Abdul-Wahab, Fernando Gonzalez-Candelas, Martin H Andersen, Sarah Taylor, Comas, Iñaki [0000-0001-5504-9408], Alm, E., Broberg, E. K., Connor, T., Hodcroft, E. B., Komissarov, A. B., Maurer-Stroh, S., Melidou, A., Neher, R. A., O'Toole, A., Pereyaslov, D., Beerenwinkel, N., Posada-Cespedes, S., Jablonski, K. P., Ferreira, P. F., Topolsky, I., Avsic-Zupanc, T., Korva, M., Poljak, M., Zakotnik, S., Zorec, T. M., Bragstad, K., Hungnes, O., Stene-Johansen, K., Reusken, C., Meijer, A., Vennema, H., Ruiz-Roldan, L., Bracho, M. A., Garcia-Gonzalez, N., Chiner-Oms, A., Cancino-Munoz, I., Comas, I., Goig, G. A., Torres-Puente, M., Lopez, M. G., Martinez-Priego, L., D'Auria, G., Ruiz-Hueso, P., Ferrus-Abad, L., de Marco, G., Galan-Vendrell, I., Carbo-Ramirez, S., Ruiz-Rodriguez, P., Coscolla, M., Polackova, K., Kramna, L., Cinek, O., Richter, J., Krashias, G., Tryfonos, C., Bashiardes, S., Koptides, D., Christodoulou, C., Bartolini, B., Gruber, C. E., Di Caro, A., Castilletti, C., Stefani, F., Rimoldi, S. G., Romeri, F., Salerno, F., Polesello, S., Nagy, A., Jirincova, H., Vecerova, J., Novakova, L., Cordey, S., Murtskhvaladze, M., Kotaria, N., Schar, T., Beisel, C., Vugrek, O., Rokic, F., Trgovec-Greif, L., Jurak, I., Rukavina, T., Sucic, N., Schonning, K., Karst, S. M., Kirkegaard, R. H., Michaelsen, T. Y., Sorensen, E. A., Knutson, S., Brandt, J., Le-Quy, V., Sorensen, T., Petersen, C., Pedersen, M. S., Larsen, S. L., Skov, M. N., Rasmussen, M., Fonager, J., Fomsgaard, A., Maksyutov, R. A., Gavrilova, E. V., Pyankov, O. V., Bodnev, S. A., Tregubchak, T. V., Shvalov, A. N., Antonets, D. V., Resende, P. C., Goya, S., Perrin, A., Lee, R. T., Yadahalli, S., Han, A. X., Russell, C. A., Schmutz, S., Zaheri, M., Kufner, V., Huber, M., Trkola, A., Antwerpen, M., Walter, M. C., van der Werf, S., Gambaro, F., Behillil, S., Enouf, V., Donati, F., Ustinova, M., Rovite, V., Klovins, J., Savicka, O., Wienecke-Baldacchino, A. K., Ragimbeau, C., Fournier, G., Mossong, J., Aberle, S. W., Haukland, M., Enkirch, T., Advani, A., Karlberg, M. L., Lindsjo, O. K., Broddesson, S., Slavikova, M., Lickova, M., Klempa, B., Staronova, E., Ticha, E., Szemes, T., Rusnakova, D., Stadler, T., Quer, J., Anton, A., Andres, C., Pinana, M., Garcia-Cehic, D., Pumarola, T., Izopet, J., Gioula, G., Exindari, M., Papa, A., Chatzidimitriou, D., Metallidis, S., Pappa, S., Macek, M., Geryk, J., Broz, P., Briksi, A., Hubacek, P., Drevinek, P., Zajac, M., Kvapil, P., Holub, M., Kvapilova, K., Novotny, A., Kasny, M., Klempt, P., Vapalahti, O., Smura, T., Sironen, T., Selhorst, P., Anthony, C., Arien, K., Simon-Loriere, E., Rabalski, L., Bienkowska-Szewczyk, K., Borges, V., Isidro, J., Gomes, J. P., Guiomar, R., Pechirra, P., Costa, I., Duarte, S., Vieira, L., Pyrc, K., Zuckerman, N. S., Turdikulova, S., Abdullaev, A., Dalimova, D., Abdurakhimov, A., Tagliabracci, A., Alessandrini, F., Melchionda, F., Onofri, V., Turchi, C., Bagnarelli, P., Menzo, S., Caucci, S., Di Sante, L., Popa, A., Genger, J. -W., Agerer, B., Lercher, A., Endler, L., Smyth, M., Penz, T., Schuster, M., Senekowitsch, M., Laine, J., Bock, C., Bergthaler, A., Shevtsov, A., Kalendar, R., Ramanculov, Y., Graf, A., Muenchhoff, M., Keppler, O. T., Krebs, S., Blum, H., Marcello, A., Licastro, D., D'Agaro, P., Laubscher, F., Vidanovic, D., Tesovic, B., Volkening, J., Clementi, N., Mancini, N., Rupnik, M., Mahnic, A., Walker, A., Houwaart, T., Wienemann, T., Vasconcelos, M. K., Strelow, D., Jensen, B. -E. O., Senff, T., Hulse, L., Adams, O., Andree, M., Hauka, S., Feldt, T., Keitel, V., Kindgen-Milles, D., Timm, J., Pfeffer, K., Dilthey, A. T., Moore, C., Ozdarendeli, A., Pavel, S. T. I., Yetiskin, H., Aydin, G., Holyavkin, C., Uygut, M. A., Cevik, C., Shchetinin, A., Gushchin, V., Dinler-Doganay, G., Doganay, L., Kizilboga-Akgun, T., Karacan, I., Pancer, K., Maes, P., Marti-Carreras, J., Wawina-Bokalanga, T., Vanmechelen, B., Thurmer, A., Wedde, M., Durrwald, R., von Kleist, M., Drechsel, O., Wolff, T., Fuchs, S., Kmiecinski, R., Michel, J., Nitsche, A., Casas, I., Caballero, M. I., Zaballos, A., Jimenez, P., Jimenez, M., Fernandez, S. M., Fernandez, S. V., de la Plaza, I. C., Fadeev, A., Ivanova, A., Sergeeva, M., Stefanelli, P., Estee Torok, M., Hall, G., da Silva Filipe, A., Turtle, L., Afifi, S., Mccluggage, K., Beer, R., Ledesma, J., Maksimovic, J., Spellman, K., Hamilton, W. L., Marchbank, A., Southgate, J. A., Underwood, A., Taylor, B., Yeats, C., Abudahab, K., Gemmell, M. R., Eccles, R., Lucaci, A., Nelson, C. A., Rainbow, L., Whitehead, M., Gregory, R., Haldenby, S., Paterson, S., Hughes, M. A., Curran, M. D., Baker, D., Tucker, R., Green, L. R., Feltwell, T., Halstead, F. D., Wyles, M., Jahun, A. S., Ahmad, S. S. Y., Georgana, I., Goodfellow, I., Yakovleva, A., Meredith, L. W., Gavriil, A., Awan, A. R., Fisher, C., Edgeworth, J., Lynch, J., Moore, N., Williams, R., Kidd, S. P., Cortes, N., Brunker, K., Mccrone, J. T., Quick, J., Duckworth, N., Walsh, S., Sloan, T., Ludden, C., George, R. P., Eltringham, G., Brown, J. R., Aranday-Cortes, E., Shepherd, J. G., Hughes, J., Li, K. K., Williams, T. C., Johnson, N., Jesudason, N., Mair, D., Thomson, E., Shah, R., Parr, Y. A., Carmichael, S., Robertson, D. L., Nomikou, K., Broos, A., Niebel, M., Smollett, K., Tong, L., Miah, S., Wittner, A., Phillips, N., Payne, B., Dewar, R., Holmes, A., Bolt, F., Price, J. R., Mookerjee, S., Sethi, D. K., Potter, W., Stanley, R., Prakash, R., Dervisevic, S., Graham, J. C., Nelson, A., Smith, D., Young, G. R., Yew, W. C., Todd, J. A., Trebes, A., Andersson, M., Bull, M., Watkins, J., Birchley, A., Gatica-Wilcox, B., Gilbert, L., Kumziene-Summerhayes, S., Rey, S., Chauhan, A., Butcher, E., Bicknell, K., Elliott, S., Glaysher, S., Lackenby, A., Bibby, D., Platt, S., Mohamed, H., Machin, N. W., Mbisa, J. L., Evans, J., Perry, M., Pacchiarini, N., Corden, S., Adams, A. G., Gaskin, A., Coombs, J., Graham, L. J., Cottrell, S., Morgan, M., Gifford, L., Kolyva, A., Rudder, S. J., Trotter, A. J., Mather, A. E., Aydin, A., Page, A. J., Kay, G. L., de Oliveira Martins, L., Yasir, M., Alikhan, N. -F., Thomson, N. M., Gilroy, R., Kingsley, R. A., O'Grady, J., Gutierrez, A. V., Diaz, M., Viet, T. L., Tedim, A. P., Adriaenssens, E. M., Patrick Mcclure, C., Sang, F., Clark, G., Howson-Wells, H. C., Debebe, J., Ball, J., Chappell, J., Khakh, M., Carlile, M., Loose, M., Lister, M. M., Holmes, N., Tsoleridis, T., Fleming, V. M., Wright, V., Smith, W., Gallagher, M. D., Parker, M., Partridge, D. G., Evans, C., Baker, P., Essex, S., Liggett, S., Keeley, A. J., Bashton, M., Rooke, S., Dervisavic, S., Meader, E. J., Lopez, C. E. B., Angyal, A., Kristiansen, M., Tutill, H. J., Findlay, J., Mestek-Boukhibar, L., Forrest, L., Dyal, P., Williams, R. J., Panchbhaya, Y., Williams, C. A., Roy, S., Pandey, S., Stockton, J., Loman, N. J., Poplawski, R., Nicholls, S., Rowe, W. P. M., Khokhar, F., Pinckert, M. L., Hosmillo, M., Chaudhry, Y., Caller, L. G., Davidson, R. K., Griffith, L., Rambaut, A., Jackson, B., Colquhoun, R., Hill, V., Nichols, J., Asamaphan, P., Darby, A., Jackson, K. A., Iturriza-Gomara, M., Vamos, E. E., Green, A., Aanensen, D., Bonsall, D., Buck, D., Macintyre-Cockett, G., de Cesare, M., Pybus, O., Golubchik, T., Scarlett, G., Loveson, K. F., Robson, S. C., Beckett, A., Lindsey, B., Groves, D. C., Parsons, P. J., Mchugh, M. P., Barnes, J. D., Manso, C. F., Grammatopoulos, D., Menger, K. E., Harrison, E., Gunson, R., Peacock, S. J., Gonzalez, G., Carr, M., Mihaela, L., Popovici, O., Brytting, M., Bresner, C., Fuller, W., Workman, T., Mentis, A. F., Kossyvakis, A., Karamitros, T., Pogka, V., Kalliaropoulos, A., Horefti, E., Kontou, A., Martinez-Gonzalez, B., Labropoulou, V., Voulgari-Kokota, A., Evangelidou, M., Bizta, P., Belimezi, M., Lambrechts, L., Doymaz, M. Z., Yazici, M. K., Cetin, N. S., Karaaslan, E., Kallio-Kokko, H., Virtanen, J., Suvanto, M., Nguyen, P. T., Ellonen, P., Hannula, S., Kangas, H., Sreenu, V. B., Burian, K., Terhes, G., Gombos, K., Gyenesei, A., Urban, P., Herczeg, R., Jakab, F., Kemenesi, G., Toth, G. E., Somogyi, B., Zana, B., Zeghbib, S., Kuczmog, A., Foldes, F., Lanszki, Z., Madai, M., Papp, H., Pereszlenyi, C. I., Babinszky, G. C., Dudas, G., Csoma, E., Abou Tayoun, A. N., Alsheikh-Ali, A. A., Loney, T., Nowotny, N., Abdul-Wahab, O., Gonzalez-Candelas, F., Andersen, M. H., Taylor, S., European Centre for Disease Prevention and Control (ECDC), Public Health Wales Microbiology Cardiff, Faculty of Agriculture and Forestry, Department of Agricultural Sciences, and Institute of Biotechnology

Subjects
Infecções Respiratórias, 0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], Distribution (economics), Wastewater, MESH: Base Sequence, Severe Acute Respiratory Syndrome, MESH: World Health Organization, Pandemic, MESH: Coronavirus, MESH: COVID-19, Sequencing, Viral, Clade, Nomenclature, Genome, biology, COVID-19, Europe, NGS, SARS-CoV-2, WGS, nomenclature, sequencing, Base Sequence, Betacoronavirus, Coronavirus, Coronavirus Infections, Genome, Viral, Humans, Phylogeography, Pneumonia, Viral, RNA, Viral, RNA-Dependent RNA Polymerase, Spatio-Temporal Analysis, World Health Organization, Pandemics, C500, European region, 3. Good health, Geography, MESH: Phylogeography, MESH: RNA-Dependent RNA Polymerase, MESH: RNA, Viral, MESH: Betacoronavirus, Spatio-Temporal Analysi, MESH: Genome, Viral, Cartography, Human, Bioquímica, MESH: Pandemics, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronaviru, 030106 microbiology, 03 medical and health sciences, MESH: Spatio-Temporal Analysis, MESH: Severe Acute Respiratory Syndrome, Virology, MESH: SARS-CoV-2, Whole genome sequencing, MESH: Humans, Whole Genome Sequencing, Betacoronaviru, Coronavirus Infection, business.industry, Public Health, Environmental and Occupational Health, Pneumonia, biology.organism_classification, B900, 030104 developmental biology, MESH: Pneumonia, Viral, RNA, SARS_CoV-2, 3111 Biomedicine, MESH: Europe, Human medicine, business
Abstract

8 páginas, 3 figuras, We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2., We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible.

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58. Idiopathic pulmonary haemosiderosis in a child with Down's syndrome: Case report and review of the literature

Author

Aceti, A., Sciutti, R., Bracci, P., Bertelli, L., Melchionda, F., Salvatore Cazzato, Aceti A, Sciutti R, Bracci PR, Bertelli L, Melchionda F, and Cazzato S.

Subjects
Lung Diseases, Hemosiderosis, Treatment Outcome, SINDROME DOWN, Predictive Value of Tests, Child, Preschool, Humans, Female, Down Syndrome, Tomography, X-Ray Computed, haemosiderosi, Hydroxychloroquine
Abstract

We report the case of a female child with Down's syndrome affected by idiopathic pulmonary haemosiderosis (IPH), who was successfully treated with hydroxychloroquine. First-line conventional treatment of IPH is traditionally based on systemic corticosteroids; however, many steroid-sparing agents are being increasingly used as adjuncts to corticosteroids in children with recurrent or refractory bleeding. The use of these drugs is particularly promising for maintenance treatment, because it tends to avoid the adverse effects of long-term corticosteroids.

62. Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT

Author

Maria Livia Mariuzzi, Alessandra Piras, Federico Verzegnassi, Elena Bardellini, Maria Grazia Petris, Patrizia Defabianis, Simone Bagattoni, Margherita Gobbo, Elisabetta Merigo, Fraia Melchionda, Davide Zanon, Matteo Biasotto, Alessandra Majorana, Giulio Andrea Zanazzo, Massimo Berger, Angelica Barone, Nunzia Decembrino, Giulia Ottaviani, Marina Consuelo Vitale, Luca Ronfani, Rosamaria Mura, Gobbo M., Verzegnassi F., Ronfani L., Zanon D., Melchionda F., Bagattoni S., Majorana A., Bardellini E., Mura R., Piras A., Petris M.G., Mariuzzi M.L., Barone A., Merigo E., Decembrino N., Vitale M.C., Berger M., Defabianis P., Biasotto M., Ottaviani G., Zanazzo G.A., Gobbo, M., Verzegnassi, F., Ronfani, L., Zanon, D., Melchionda, F., Bagattoni, S., Majorana, A., Bardellini, E., Mura, R., Piras, A., Petris, M. G., Mariuzzi, M. L., Barone, A., Merigo, E., Decembrino, N., Vitale, M. C., Berger, M., Defabianis, P., Biasotto, M., Ottaviani, G., and Zanazzo, G. A.

Subjects
Male, genetic structures, medicine.medical_treatment, Clinical trial, Laser, Mucositis, Pediatric hemato-oncology, Supportive care, Pediatrics, Perinatology and Child Health, Hematology, Oncology, Pediatrics, law.invention, Antineoplastic Agent, 0302 clinical medicine, Randomized controlled trial, law, Neoplasms, Child, Stomatitis, pediatric hemato-oncology, clinical trial, Perinatology and Child Health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Human, medicine.medical_specialty, Adolescent, Analgesic, chemical and pharmacologic phenomena, Antineoplastic Agents, macromolecular substances, Placebo, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Humans, Low-Level Light Therapy, Adverse effect, laser, mucositis, supportive care, Chemotherapy, business.industry, mucositi, fungi, 030206 dentistry, medicine.disease, Stomatiti, Neoplasm, business
Abstract

Objectives: To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects. Methods: One hundred and one children with WHO grade>2 chemotherapy-induced OM were enrolled in eight Italian hospitals. Patients were randomized to either PBM or sham treatment for four consecutive days (days +1 to +4). On days +4, +7, and +11, OM grade, pain (following a 0–10 numeric pain rating scale, NRS) and need for analgesics were evaluated by an operator blinded to treatment. Results: Fifty-one patients were allocated to the PBM group, and 50 were allocated to the sham group. In total, 93.7% of PBM patients and 72% of sham patients had OM grade&nbsp

Published
2017

63. Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study

Author

Alessandro Ruggi, Fraia Melchionda, Iacopo Sardi, Rossana Pavone, Linda Meneghello, Lidija Kitanovski, Lorna Zadravec Zaletel, Paolo Farace, Mino Zucchelli, Mirko Scagnet, Francesco Toni, Roberto Righetto, Marco Cianchetti, Arcangelo Prete, Daniela Greto, Silvia Cammelli, Alessio Giuseppe Morganti, Barbara Rombi, Ruggi A., Melchionda F., Sardi I., Pavone R., Meneghello L., Kitanovski L., Zaletel L.Z., Farace P., Zucchelli M., Scagnet M., Toni F., Righetto R., Cianchetti M., Prete A., Greto D., Cammelli S., Morganti A.G., and Rombi B.

Subjects
radiation, Cancer Research, Oncology, pediatric brain tumors, proton therapy, medulloblastoma, toxicity, pediatric brain tumor
Abstract

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

Published
2022

64. Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

Author

Sara Scarpini, Arianna Dondi, Camilla Totaro, Carlotta Biagi, Fraia Melchionda, Daniele Zama, Luca Pierantoni, Monia Gennari, Cinzia Campagna, Arcangelo Prete, Marcello Lanari, Scarpini S., Dondi A., Totaro C., Biagi C., Melchionda F., Zama D., Pierantoni L., Gennari M., Campagna C., Prete A., and Lanari M.

Subjects
Microbiology (medical), Leishmania, protozoa, pediatric, Virology, visceral leishmaniasis, Microbiology, neglected disease, tropical disease
Abstract

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

Published
2022

65. Hemiplegic-Migraine-like Attacks as First Manifestation of Diffuse Leptomeningeal Glioneuronal Tumor: A Case Report

Author

Giacomo Biasucci, Duccio Maria Cordelli, Jacopo Pruccoli, Fraia Melchionda, Roberto Parisi, Francesco Toni, Anna Fetta, Fetta A., Pruccoli J., Biasucci G., Parisi R., Toni F., Melchionda F., and Cordelli D.M.

Subjects
Leptomeninge, Male, medicine.medical_specialty, Migraine Disorders, Hemiplegia, DLGNT, Lateralization of brain function, Hemiplegic migraine, Central Nervous System Neoplasms, Aphasia, Glioneuronal tumor, Biopsy, medicine, Meningeal Neoplasms, Humans, Child, medicine.diagnostic_test, Symptomatic hemiplegic migraine, business.industry, Leptomeninges, Magnetic resonance imaging, Hematology, medicine.disease, Neoplasms, Neuroepithelial, Hydrocephalus, Oncology, Pediatrics, Perinatology and Child Health, Radiology, medicine.symptom, business, Cortical spreading depression, Meningeal enhancement
Abstract

Background: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a low-grade tumor characterized by diffuse leptomeningeal infiltrates. Symptoms are usually secondary to hydrocephalus. Hemiplegic migraine (HM)-like episodes have never been associated with DLGNT, but they have been reported with different inflammatory and tumoral entities involving leptomeninges. Observations: We report the case of a 10-year-old boy with recurrent episodes of right hyposthenia, aphasia, and headache lasting hours to days with complete remission. The electroencephalogram during the attack showed diffuse slower activity on the left hemisphere, which improved together with the symptoms. DLGNT was discovered during a follow-up magnetic resonance imaging and confirmed by biopsy. Conclusions: This is the first report of HM-like attacks in DLGNT. We discuss the pathogenetic hypotheses of our case and previously reported cases of “symptomatic” HM with leptomeningeal involvement.

Published
2021

66. Quando non trascurare la splenomegalia nel lattante un insegnamento dalla pratica clinica

Author

Andrea Pession, Roberta Parladori, Edoardo Muratore, Daniele Zama, Fraja Melchionda, Federico Baronio, Zama D., Parladori R., Muratore E., Melchionda F., Baronio F., and Pession A.

Subjects
business.industry, Pediatrics, Perinatology and Child Health, Differential diagnosi, Splenomegaly, Medicine, Infant, Red flag, business
Abstract

Splenomegaly in children is really common and its main cause is infectious disease. The aetiology in newborns and older children is well established, while it is less defined in suckling infants. The paper describes three cases of splenomegaly in infants hospitalized in Oncohaematology Department of Sant’Orsola Malpighi Hospital. These infants presented with splenomegaly associated with other signs and symptoms that should prompt further investigations to exclude severe diseases. The aim of this paper is to offer paediatricians some indications for the diagnostic approach in infants with enlarged spleen. In particular, it reports the first level exams, the differential diagnosis and the red flags, the signs and symptoms that require special attention in infants with splenomegaly.

Published
2021

67. Development of a forensic DNA phenotyping panel using massive parallel sequencing

Author

Chiara Turchi, Valerio Onofri, Adriano Tagliabracci, Filomena Melchionda, Paolo Fattorini, Turchi, C., Onofri, V., Melchionda, F., Fattorini, P., and Tagliabracci, A.

Subjects
Degraded DNA, DNA phenotyping, HIrisPlex-S, MPS, Massive parallel sequencing, Single-nucleotide polymorphism, Computational biology, Biology, Amplicon, Pathology and Forensic Medicine, chemistry.chemical_compound, chemistry, Genotype, Genetics, Multiplex, Typing, DNA
Abstract

The HIrisPlex-S system, targeting a total of 41 SNPs, allows the simultaneous eye, hair and skin color prediction from DNA. In the present study, we developed a massive parallel sequencing (MPS) multiplex assay in order to genotype all the HIrisPlex-S markers in degraded casework samples. PCR amplicons sizes of target regions were kept below 180 bp, in order to allow analysis of degraded DNA samples. Individuals with known phenotype, artificially degraded DNA samples and a set of 2800M control DNA dilutions were sequenced on a Ion PGM System, in order to evaluate the concordance testing results and the forensic suitability of this 41-plex MPS assay. Full and reliable profiles could be obtained with 0.1 ng of input DNA. The increment of the number of PCR cycles results in improvement of sensitivity or in typing results but an increase of artifacts were also observed.

Published
2019
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68. Assessment of the Precision ID Identity Panel kit on challenging forensic samples

Author

Susi Pelotti, Pierangela Grignani, Eugenia Carnevali, Filomena Melchionda, Solange Sorçaburu-Ciglieri, Chiara Turchi, Carlo Robino, Carlo Previderè, Valerio Onofri, Adriano Tagliabracci, Carla Bini, Alessandro Manfredi, Paolo Fattorini, Turchi C., Previdere C., Bini C., Carnevali E., Grignani P., Manfredi A., Melchionda F., Onofri V., Pelotti S., Robino C., Sorcaburu-Ciglieri S., Tagliabracci A., Fattorini P., Turchi, Chiara, Previderè, Carlo, Bini, Carla, Carnevali, Eugenia, Grignani, Pierangela, Manfredi, Alessandro, Melchionda, Filomena, Onofri, Valerio, Pelotti, Susi, Robino, Carlo, Sorçaburu-Ciglieri, Solange, Tagliabracci, Adriano, and Fattorini, Paolo

Subjects
0301 basic medicine, DNA, Bacterial, Genotype, Single-nucleotide polymorphism, Locus (genetics), Polymerase Chain Reaction, Polymorphism, Single Nucleotide, DNA degradation, Massive parallel sequencing, Precision ID Identity Panel, Single nucleotide polymorphism, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Statistics, Genetics, Humans, 030216 legal & forensic medicine, Typing, Allele, Genotyping, Mathematics, Massive Parallel Sequencing, Single Nucleotide Polymorphism, DNA Degradation, Necrotic, High-Throughput Nucleotide Sequencing, Replicate, DNA, Sequence Analysis, DNA, DNA Fingerprinting, 030104 developmental biology, Low copy number
Abstract

The performance of the Precision ID Identity Panel (Thermo Fisher Scientific) was assessed on a set of 87 forensic samples with different levels of degradation for which a reference sample from the “same donor” or from a “first degree relative” was available. PCR-MPS analysis was performed with DNA input ranging from 1 ng to 12 pg and through 21–26 PCR cycles, in replicate tests, and a total number of 255 libraries were sequenced on the Ion Personal Genome Machine™ (PGM™) System. The evaluation of the molecular data allowed to set a fix threshold for locus call at 50 x which suitably worked even when low amounts of degraded DNA (12 pg) were investigated. In these analytical conditions, in fact, 25 PCR cycles allowed the genotyping of about 50 % and 35 % of the autosomal and the Y-specific markers on average, respectively, for each single amplification with a negligible frequency of drop ins (0.01 %). On the other hand, drop out artefacts reached 18–23 % when low copy number and degraded DNA samples were studied, with surviving alleles showing more than 600 reads in 2.9 % of the cases. Our data pointed out that the Precision ID Identity Panel allowed accurate typing of almost any amount of good quality/moderately degraded DNA samples, in duplicate tests. The analysis of low copy number DNAs evidenced that the same allele of a heterozygous genotype could be lost twice, thus suggesting that a third amplification could be useful for a correct genotype assignment in these peculiar cases. Using the consensus approach, a limited number of genotyping errors were computed and about 37 % of the autosomal markers was finally typed with a corresponding combined random match probability of at least 1.6 × 10−13, which can be considered an excellent result for this kind of challenging samples. In the end, the results presented in this study emphasize the crucial role of the expert opinion in the correct evaluation of artefacts arising from PCR-MPS technology that could potentially lead to genetic mistyping.

Published
2020

69. Performance of a massive parallel sequencing microhaplotypes assay on degraded DNA

Author

Filomena Melchionda, Chiara Turchi, M. Pesaresi, Paolo Fattorini, Adriano Tagliabracci, Turchi, C., Melchionda, F., Pesaresi, M., Fattorini, P., and Tagliabracci, A.

Subjects
Degraded DNA, Serial dilution, MPS, LT-DNA, Computational biology, Biology, 01 natural sciences, Pathology and Forensic Medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, 030216 legal & forensic medicine, Typing, Genotyping, Microhaplotypes, Massive parallel sequencing, Microhaplotype, 010401 analytical chemistry, Amplicon, 0104 chemical sciences, chemistry, Genetic marker, Degraded dna, DNA
Abstract

Massively parallel sequencing (MPS) has allowed to analyze a new type of forensic genetic marker, known as microhaplotypes (MHs). MHs appear to be useful for identification purposes, reconstruction of family relationships, ancestry prediction and DNA mixtures deconvolution. Moreover, MHs are potentially suitable for the analysis of degraded DNA samples. We designed a new panel of 29 MHs for MPS assay, with amplicons sizes below 180 bp and we investigated its effectiveness with low amounts of degraded samples. We genotyped a set of real forensic samples together with a set of artificially degraded DNAs. Also, a sensitivity test was assessed by a set of 2800 M DNA dilutions. The Depth of Coverage (DoC) were uniform across all 29 loci, in spite of amplicons size. Genotyping results shown that full profiles can be obtained even in highly degraded samples when the amount of template range from 0.1 to 5.0 ng. Finally, the increase of the number of PCR cycles did not provide an improvement in typing results of low amounts of degraded samples as, in front of higher number of typed loci, higher frequencies of artefacts leading to mistyping are found at 25 cycles.

Published
2019

70. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children

Author

Mareva Giacchino, Simone Cesaro, Ottavio Ziino, Anna Pegoraro, Marcello Chiodi, Alfredo Pontillo, Fraia Melchionda, Nicola Santoro, Maurizio Aricò, Susanna Livadiotti, Giulio Andrea Zanazzo, Pietro Ragusa, Vincenzo Poggi, Désirée Caselli, Caselli, D, Cesaro, S, Ziino, O, Ragusa, P, Pontillo, A, Pegoraro, A, Santoro, N, Zanazzo, G, Poggi, V, Mareva, G, Livadiotti, S, Melchionda, F, Chiodi, M, and Aricò, M

Subjects
Male, medicine.medical_specialty, Antifungal Agents, Neutropenia, Antineoplastic Agents, Opportunistic Infections, Lower risk, Fever of Unknown Origin, law.invention, Echinocandins, Lipopeptides, chemistry.chemical_compound, Randomized controlled trial, Caspofungin, law, Amphotericin B, Internal medicine, medicine, Humans, Prospective Studies, Child, Prospective cohort study, empirical antifungal therapy, children, cancer, business.industry, Patient Selection, Infant, Cancer, Hematology, Length of Stay, medicine.disease, Confidence interval, Surgery, Hospitalization, Treatment Outcome, Mycoses, chemistry, Child, Preschool, Female, business, Empiric therapy, Febrile neutropenia
Abstract

Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged

Published
2012
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71. Diagnosis of bloodstream infections in immunocompromised patients by real-time PCR

Author

Michela Paolucci, Lorenzo Nardi, Andrea Pession, Marta Stanzani, Stefania Varani, Gastone Castellani, Maria Paola Landini, Fraia Melchionda, Michele Baccarani, Vittorio Sambri, Varani S, Stanzani M, Paolucci M, Melchionda F, Castellani G, Nardi L, Landini MP, Baccarani M, Pession A, and Sambri V.

Subjects
Adult, DNA, Bacterial, Microbiology (medical), medicine.medical_specialty, Time Factors, REAL TIME PCR, Sensitivity and Specificity, law.invention, Sepsis, Immunocompromised Host, IMMUNOCOMPROMISED PATIENTS, law, Neoplasms, Immunopathology, Internal medicine, DNA, Ribosomal Spacer, medicine, Humans, Blood culture, Child, Polymerase chain reaction, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, business.industry, BLOOD CULTURE, Cancer, medicine.disease, CANCER, Infectious Diseases, Bacteremia, Immunology, Cohort, Etiology, business, BLOODSTREAM INFECTION
Abstract

Summary Objectives The diagnosis of bloodstream infections (BSIs) in immunocompromised patients, such as patients with cancer, is challenging. Although blood culture (BC) is considered the standard diagnostic tool for BSIs, it takes several days to yield results and has low sensitivity in these patients. Here, we tested a novel method for diagnosing BSIs in a large cohort of immunodepressed patients. Methods Real-time PCR (LightCycler ® Septi Fast Test M GRADE , Roche Diagnostics) was compared with BC for its ability to detect bacteria and fungi in blood samples from 100 immunocompromised patients (98 with cancer) in whom sepsis was suspected. Results In concordant samples (79.2% of total cases), real-time PCR identified the presence or absence of microbes significantly faster than BC ( p =3.7×10 −49 , t -test). Furthermore, in 6 cases, Septi Fast distinguished contamination of BCs by coagulase-negative staphylococci. Septi Fast , however, failed to detect 5 cases of clinically relevant BSI that tested positive by BC. Conclusions Septi Fast rapidly diagnosed BSIs in our cohort of immunosuppressed patients. The results of this study suggest that Septi Fast can be used in conjunction with, but cannot replace, BC to better identify the etiology of fever in immunocompromised patients.

Published
2009
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72. Synergistic cytotoxic effects of bortezomib and CK2 inhibitor CX-4945 in acute lymphoblastic leukemia: Turning offthe prosurvival ER chaperone BIP/Grp78 and turning on the proapoptotic NF-κB

Author

Luca M. Neri, Francesca Buontempo, Camilla Evangelisti, James A. McCubrey, Fraia Melchionda, Jessika Bertacchini, Cecilia Evangelisti, Alice Bertaina, Annalisa Lonetti, Alberto M. Martelli, Alessandra Cappellini, Andrea Pession, Francesca Chiarini, Franco Locatelli, Ester Orsini, Buontempo, F, Orsini, E, Lonetti, A, Cappellini, A, Chiarini, F, Evangelisti, C, Melchionda, F, Pession, A, Bertaina, A, Locatelli, F, Bertacchini, J, Neri, Lm, Mccubrey, Ja, and Martelli, Am.

Subjects
0301 basic medicine, BIP/Grp78, Apoptosis, Acute lymphoblastic leukemia, CK2, NF-κB, Unfolded protein response, Antineoplastic Agents, Blotting, Western, Bortezomib, Casein Kinase II, Cell Line, Tumor, Cell Survival, Drug Synergism, Endoplasmic Reticulum Stress, Heat-Shock Proteins, Humans, Jurkat Cells, Microscopy, Fluorescence, Naphthyridines, Neoplastic Stem Cells, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Transcription Factor RelA, Unfolded Protein Response, Oncology, Jurkat cells, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Endoplasmic Reticulum Chaperone BiP, NF-kappa B, XIAP, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030220 oncology & carcinogenesis, Casein kinase 2, Research Paper, medicine.drug, NO, 03 medical and health sciences, medicine, business.industry, Endoplasmic reticulum, acute lymphoblastic leukemia, unfolded protein response, 030104 developmental biology, chemistry, Immunology, Cancer research, Proteasome inhibitor, Phenazines, business
Abstract

The proteasome inhibitor bortezomib is a new targeted treatment option for refractory or relapsed acute lymphoblastic leukemia (ALL) patients. However, a limited efficacy of bortezomib alone has been reported. A terminal pro-apoptotic endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is one of the several mechanisms of bortezomib-induced apoptosis. Recently, it has been documented that UPR disruption could be considered a selective anti-leukemia therapy. CX-4945, a potent casein kinase (CK) 2 inhibitor, has been found to induce apoptotic cell death in T-ALL preclinical models, via perturbation of ER/UPR pathway. In this study, we analyzed in T-and B-ALL preclinical settings, the molecular mechanisms of synergistic apoptotic effects observed after bortezomib/CX-4945 combined treatment. We demonstrated that, adding CX-4945 after bortezomib treatment, prevented leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen. We documented that the combined treatment decreased pro-survival ER chaperon BIP/Grp78 expression, via reduction of chaperoning activity of Hsp90. Bortezomib/CX-4945 treatment inhibited NF-kappa B signaling in T-ALL cell lines and primary cells from T-ALL patients, but, intriguingly, in B-ALL cells the drug combination activated NF-kappa B p65 pro-apoptotic functions. In fact in B-cells, the combined treatment induced p65-HDAC1 association with consequent repression of the anti-apoptotic target genes, Bcl-xL and XIAP. Exposure to NEMO (IKK gamma)-binding domain inhibitor peptide reduced the cytotoxic effects of bortezomib/ CX-4945 treatment. Overall, our findings demonstrated that CK2 inhibition could be useful in combination with bortezomib as a novel therapeutic strategy in both T-and B-ALL.

Published
2016

73. Two cases of abdominal pain in children with mesenteric lymphadenitis due to Yersinia pseudotuberculosis infection

Author

Andrea Pession, Tommaso Gargano, Riccardo Masetti, Salvatore Cazzato, Ilaria Corsini, Luca Bertelli, Fraia Melchionda, Giulia Bardasi, Michela Maretti, Davide Tassinari, Mario Lima, Bertelli L, Masetti R, Bardasi G, Maretti M, Gargano T, Corsini I, Melchionda F, Tassinari D, Cazzato S, Lima M, and Pession A

Subjects
Male, Abdominal pain, medicine.medical_specialty, Mesenteric Lymphadenitis, biology, Adolescent, Abdominal Pain, Adolescent, Child, Diagnosi, business.industry, Yersinia pseudotuberculosis Infections, Mesenteric lymphadenitis, biology.organism_classification, Gastroenterology, Abdominal Pain, Diagnosis, Differential, Differential, Humans, Male, Mesenteric Lymphadenitis, Yersinia pseudotuberculosis, Yersinia pseudotuberculosis Infections, Yersinia pseudotuberculosis, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Humans, medicine.symptom, business, Child
Abstract

Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi 5 mai 2014

Published
2014

74. A novel WT1 mutation in familial wilms tumor

Author

MELCHIONDA, FRAIA, LIMA, MARIO, PESSION, ANDREA, Spreafico F, Ciceri S, Collini P, Massimino M, Radice P, Perotti D., Melchionda F, Spreafico F, Ciceri S, Lima M, Collini P, Pession A, Massimino M, Radice P, and Perotti D

Subjects
wilms tumor, case report, child, cryptorchism, gene mutation, hematuria, histopathology, human, hypospadias, immunohistochemistry, immunoreactivity, kidney tumor, letter, male, nephrectomy, nephroblastoma, preschool child, priority journal, WT1 protein
Abstract

To the Editor: Wilms tumor (WT), the most frequent pediatric renal tumor, primarily occurs as a sporadic disease, but approximately 2% of cases have an affected relative [1]. While the underlying cause of most familial WTs is currently unknown, few reports described pedigrees associated with anomalies of the WT1 gene [2–5]. We report on a WT pedigree resulting from a novel WT1 mutation. The index patient, a 23-month-old (46, XY karyotype) presented with bilateral cryptorchidism and proximal severe penile hypospadia. Serial abdomino-pelvic ultrasounds did not reveal signs of renal pathology, and normal renal function was assessed by blood and urine tests. Apart from the presence of genitourinary (GU) anomalies, the child did not present any clinical evidence of known syndromes predisposing to WT development. At 23 months of age, following the onset of macroscopic hematuria, abdominal ultrasound revealed a left renal mass. The patient underwent radical nephrectomy, and histological examination revealed a unicentric, triphasic WT without anaplasia. Perilobar nephrogenic rests were present, as well as dysplastic medullary rays. The patient received treatment according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) TW-2003 protocol for stage IV disease, because of the presence of pulmonary metastases. At present, the child is in complete remission, 3 months after completing therapy. His mother had been successfully treated for stage II WT in 1978, when she was 22 months old. She showed a normal growth and development, without any GU abnormalities or syndromic signs. While she was considering the possibility of an assisted conception treatment due to her difficulty in conceiving, she got spontaneously pregnant at 32 years of age. No nephropathies or renal cancers were reported in other members of her family and no GU abnormalities were referred in her parents and her two brothers. Two novelWT1 germline variants, the silent variation c.981C>T and the frameshift mutation c.983delC (p.P328QfsX53) causing the loss of the C-terminal of the WT1 protein, were detected in the peripheral blood leukocytes (PBL) DNAs of both affected subjects (Fig. 1Aand B). TumorDNAwas available only fromthe child. WT1 sequencing revealed no further anomaly and loss of entire wild-type WT1 allele could be excluded based on the maintenance of heterozygosity for both the novel identified variants (Fig. 1C). Immunohistochemistry forWT1 on tumor cells disclosed a focal and weak immunoreactivity with WT clone WT49 (against amino acids 1–181 of theN-terminal ofWT1), but not withWT1 (C-19) antibody (against the last 19 amino acids of the C-terminal ofWT1) (Fig. 1E and F). This is consistent with the expression in the tumor of the mutated, but not of the constitutionally wild-type allele, and indicates a likely etiologic role of the mutated allele in tumorigenesis. The analysis of the CTNNB1 gene disclosed the c.133_135delTCT (p.S45del) in-frame deletion in tumor DNA (Fig. 1G), in agreement with the described co-occurrence of WT1 and b-cateninmutations in WTs [6].ThisWTpedigreeadds tothe fewalreadyreportedinwhicha role of WT1 mutation has been established.

Published
2013

75. Ongoing outbreak of visceral leishmaniasis in Bologna Province, Italy, November 2012 to May 2013

Author

Aldo Scalone, Stefania Varani, Maria Paola Landini, Pierluigi Viale, Roberto Cagarelli, Fraia Melchionda, Luigi Gradoni, Roberto Rangoni, Marina Gramiccia, R Todeschini, R Tigani, Caterina Salvadori, Giovanna Angela Gentilomi, A C Finarelli, Luciano Attard, T. Di Muccio, Varani S, Cagarelli R, Melchionda F, Attard L, Salvadori C, Finarelli A, Gentilomi G, Tigani R, Rangoni R, Todeschini R, Scalone A, Di Muccio T, Gramiccia M, Gradoni L, Viale P, and Landini M

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Disease onset, Adolescent, Range (biology), Epidemiology, Polymerase Chain Reaction, Disease Outbreaks, Young Adult, Age Distribution, Risk Factors, Virology, medicine, Humans, Leishmania infantum, Sex Distribution, Child, Aged, Aged, 80 and over, outbreak, business.industry, Public Health, Environmental and Occupational Health, Infant, Outbreak, Middle Aged, medicine.disease, Northern italy, BOLOGNA PROVINCE, Visceral leishmaniasis, Italy, Child, Preschool, Leishmaniasis, Visceral, VISCERAL LEISHMANIASIS, Female, Topography, Medical, business
Abstract

An increased number of autochthonous visceral leishmaniasis (VL) cases has recently been reported in Bologna Province in northern Italy. Over six months from November 2012 to May 2013, 14 cases occurred, whereas the average number of cases per year was 2.6 (range: 0-8) in 2008 to 2012. VL was diagnosed in a median of 40 days (range: 15-120) from disease onset. This delay in diagnosis shows the need for heightened awareness of clinicians for autochthonous VL in Europe. From November 2012 to May 2013, public health authorities, microbiologists and clinicians in Bologna Province, northern Italy, noted an upsurge in human cases of visceral leishmaniasis. During these six months, 14 cases were notified, an over five-fold increase compared with the annual average of 2.6 cases (range: 0-8) from 2008 to 2012. Here, we report preliminary epidemiological, microbiological and clinical findings

Published
2013

76. Metachronous Bilateral Ovarian Teratoma: A Germ-line Familial Disorder and Review of Surgical Management Options

Author

Dalia Gobbi, F. Fascetti Leon, Antonio Aquino, Mario Lima, F. Melchionda, Gobbi D, Fascetti Leon F, Aquino A, Melchionda F, and Lima M.

Subjects
medicine.medical_specialty, Pathology, endocrine system, endocrine system diseases, Familial disorder, Pediatrics, Germline, Obstetrics and gynaecology, Neoplasms, medicine, Humans, Ovarian Teratoma, Fertility preservation, Child, Bilateral ovarian teratoma, Familial germ-line tumor, Ovary-sparing surgery, Female, Fertility Preservation, Neoplasms, Second Primary, Ovarian Neoplasms, Teratoma, Obstetrics and Gynecology, Pediatrics, Perinatology and Child Health, Gynecology, business.industry, General Medicine, Perinatology and Child Health, medicine.disease, female genital diseases and pregnancy complications, medicine.anatomical_structure, Second Primary, Germ cell tumors, business, Germ cell
Abstract

Background Germ cell tumors in females are uncommon, and bilateral metachronous ovarian teratoma is even exceptional, with sporadic cases described in the literature. Case We report on a girl in whom a metachronous ovarian teratoma occurred 6 years after the first. The simultaneous onset of germ-line anomalies in other members of the family supports the existence of genetic or environmental factors conferring susceptibility to germ cell lesions. Summary and conclusion The case here illustrated reminds the issue of the appropriate follow-up of these patients and of their families.

Published
2013

77. Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia

Author

Daniela Bressanin, P. L. Tazzari, Andrea Pession, Carolina Simioni, James A. McCubrey, Fraia Melchionda, Silvano Capitani, Francesca Chiarini, Luca M. Neri, Francesca Ricci, Camilla Evangelisti, Alberto M. Martelli, Alice Cani, Giovanna Tabellini, Pasqualepaolo Pagliaro, Simioni C, Neri LM, Tabellini G, Ricci F, Bressanin D, Chiarini F, Evangelisti C, Cani A, Tazzari PL, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Capitani S, and Martelli AM.

Subjects
Cancer Research, T cell, Blotting, Western, Akt, Autophagy, Chemotherapy, T-cell acute lymphoblastic leukemia, Targeted therapy, Antineoplastic Agents, Apoptosis, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, chemistry.chemical_compound, TARGETED THERAPY, medicine, Cytotoxic T cell, Humans, Progenitor cell, Phosphorylation, Protein kinase B, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, business.industry, AKT, Cell Cycle, Drug Synergism, Hematology, Cell cycle, CHEMOTHERAPY, medicine.disease, Leukemia, medicine.anatomical_structure, Oncology, chemistry, Doxorubicin, MK-2206, Cancer research, business, Heterocyclic Compounds, 3-Ring, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder arising from T-cell progenitors. T-ALL accounts for 15% of newly diagnosed ALL cases in children and 25% in adults. Although the prognosis of T-ALL has improved, due to the use of polychemotherapy schemes, the outcome of relapsed/chemoresistant T-ALL cases is still poor. A signaling pathway that is frequently upregulated in T-ALL, is the phosphatidylinositol 3-kinase/Akt/mTOR network. To explore whether Akt could represent a target for therapeutic intervention in T-ALL, we evaluated the effects of the novel allosteric Akt inhibitor, MK-2206, on a panel of human T-ALL cell lines and primary cells from T-ALL patients. MK-2206 decreased T-ALL cell line viability by blocking leukemic cells in the G(0)/G(1) phase of the cell cycle and inducing apoptosis. MK-2206 also induced autophagy, as demonstrated by an increase in the 14-kDa form of LC3A/B. Western blotting analysis documented a concentration-dependent dephosphorylation of Akt and its downstream targets, GSK-3 alpha/b and FOXO3A, in response to MK-2206. MK-2206 was cytotoxic to primary T-ALL cells and induced apoptosis in a T-ALL patient cell subset (CD34(+)/CD4(-)/CD7(-)), which is enriched in leukemia-initiating cells. Taken together, our findings indicate that Akt inhibition may represent a potential therapeutic strategy in T-ALL.

Published
2012

78. AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications

Author

E Falcieri, Pasqualepaolo Pagliaro, Roberta Bortul, Michela Battistelli, Cecilia Grimaldi, James A. McCubrey, Am Martelli, Fraia Melchionda, Giovanna Tabellini, Ilaria Iacobucci, Giovanni Martinelli, P. L. Tazzari, Andrea Pession, João T. Barata, Francesca Ricci, Francesca Chiarini, Grimaldi C., Chiarini F., Tabellini G., Ricci F., Tazzari P.L., Battistelli M., Falcieri E., Bortul R., Melchionda F., Iacobucci I., Pagliaro P., Martinelli G., Pession A., Barata J.T., McCubrey J.A., and Martelli A.M.

Subjects
CHEMOTHERAPY, SIGNAL TRANSDUCTION, anti-diabetic drug, TARGETED THERAPY, TRANSLATION, Cancer Research, Apoptosis, mTORC1, Biology, Mechanistic Target of Rapamycin Complex 1, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Real-Time Polymerase Chain Reaction, mTORC2, Cell Line, Tumor, Humans, RNA, Messenger, Phosphorylation, Protein kinase A, PI3K/AKT/mTOR pathway, DNA Primers, Base Sequence, Kinase, TOR Serine-Threonine Kinases, Adenylate Kinase, AMPK, Proteins, Hematology, Flow Cytometry, Metformin, Oncology, Multiprotein Complexes, Protein Biosynthesis, Cancer research, Signal transduction
Abstract

The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic subunit of two multi-protein complexes, referred to as mTORC1 and mTORC2. Signaling downstream of mTORC1 has a critical role in leukemic cell biology by controlling mRNA translation of genes involved in both cell survival and proliferation. mTORC1 activity can be down-modulated by upregulating the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway. Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation. Metformin affected T-ALL cell viability by inducing autophagy and apoptosis. However, it was much less toxic against proliferating CD4(+) T-lymphocytes from healthy donors. Western blot analysis demonstrated dephosphorylation of mTORC1 downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA translation in T-ALL cells treated with metformin. Remarkably, metformin targeted the side population of T-ALL cell lines as well as a putative leukemia-initiating cell subpopulation (CD34(+)/CD7(-)/CD4(+)) in patient samples. In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL.

Published
2012

79. Negative pressure treatment for necrotizing fasciitis after chemotherapy

Author

Andrea Pession, Fraia Melchionda, Melchionda F, and Pession A

Subjects
medicine.medical_specialty, medicine.drug_class, necrotizing fasciitis, medicine.medical_treatment, Antibiotics, pediatric, lcsh:Medicine, macromolecular substances, chemotherapy, Pediatrics, Malignant disease, necrotizing fasciitis, chemotherapy, pediatric, Mucositis, Medicine, Fasciitis, Severe neutropenia, Chemotherapy, business.industry, Brief Report, lcsh:R, lcsh:RJ1-570, lcsh:Pediatrics, Topical Negative-Pressure Therapy, medicine.disease, chemotherapy, necrotizing fasciitis, negative pressure treatment, pediatric, Surgery, negative pressure treatment, business
Abstract

We describe 2 cases of children with malignant disease who developed severe mucositis with perineal necrotizing fasciitis during severe neutropenia after chemotherapy. Treatment with topical negative pressure therapy with silver foam dressing, together with large spectrum antibiotics, resolved the problem with complete closure of the wound after 30 and 36 days of treatment, respectively.

Published
2011

80. Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia

Author

Fraia Melchionda, James A. McCubrey, P. L. Tazzari, Andrea Pession, Roberta Bortul, Elisabetta Falcieri, Michela Battistelli, Francesca Chiarini, Am Martelli, Giovanna Tabellini, Pasqualepaolo Pagliaro, Camilla Evangelisti, Francesca Ricci, Evangelisti C., Ricci F., Tazzari P., Tabellini G., Battistelli M., Falcieri E., Chiarini F., Bortul R., Melchionda F., Pagliaro P., Pession A., McCubrey J.A., and Martelli A.M.

Subjects
Cancer Research, ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), MTOR, active site inhibitors, TARGETED THERAPY, TRANSLATION, active site inhibitor, Blotting, Western, Apoptosis, mTORC1, Biology, Mechanistic Target of Rapamycin Complex 1, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, mTORC2, Mice, Catalytic Domain, Cell Line, Tumor, Autophagy, Animals, Humans, RNA, Messenger, Phosphorylation, Protein kinase B, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, Cell Proliferation, Sirolimus, Kinase, Reverse Transcriptase Polymerase Chain Reaction, TOR Serine-Threonine Kinases, RPTOR, Cell Cycle, Proteins, Hematology, Flow Cytometry, Genetic translation, Oncology, Multiprotein Complexes, Cancer research, Immunosuppressive Agents, Transcription Factors
Abstract

The mammalian Target Of Rapamycin (mTOR) serine/threonine kinase belongs to two multi-protein complexes, referred to as mTORC1 and mTORC2. mTOR-generated signals have critical roles in leukemic cell biology by controlling mRNA translation of genes that promote proliferation and survival. However, allosteric inhibition of mTORC1 by rapamycin has only modest effects in T-cell acute lymphoblastic leukemia (T-ALL). Recently, ATP-competitive inhibitors specific for the mTOR kinase active site have been developed. In this study, we have explored the therapeutic potential of active-site mTOR inhibitors against both T-ALL cell lines and primary samples from T-ALL patients displaying activation of mTORC1 and mTORC2. The inhibitors affected T-ALL cell viability by inducing cell-cycle arrest in G(0)/G(1) phase, apoptosis and autophagy. Western blot analysis demonstrated a Ser 473 Akt dephosphorylation (indicative of mTORC2 inhibition) and a dephosphorylation of mTORC1 downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA translation in T-ALL cell lines treated with active-site mTOR inhibitors. The inhibitors strongly synergized with both vincristine and the Bcl-2 inhibitor, ABT-263. Remarkably, the drugs targeted a putative leukemia-initiating cell sub-population (CD34(+)/CD7(-)/CD4(-)) in patient samples. In conclusion, the inhibitors displayed remarkable anti-leukemic activity, which emphasizes their future development as clinical candidates for therapy in T-ALL.

Published
2011

81. A novel specific signature of pediatric MOZ-CBP acute myeloid leukemia

Author

Virginia Libri, Riccardo Masetti, Andrea Pession, Fraia Melchionda, Annalisa Astolfi, Salvatore Serravalle, Serravalle S., Melchionda F., Astolfi A., Libri V., Masetti R., and Pession A.

Subjects
Cancer Research, Myeloid, Fatal outcome, Oncogene Proteins, business.industry, Myeloid leukemia, Chromosomal translocation, Hematology, medicine.disease, NO, Leukemia, medicine.anatomical_structure, Oncology, medicine, Cancer research, business
Published
2010

82. Pediatric early T-cell precursor leukemia with NF1 deletion and high-sensitivity in vitro to tipifarnib

Author

Andrea Pession, Carlotta Biagi, Francesca Chiarini, Annalisa Astolfi, Fraia Melchionda, Riccardo Masetti, Monica Franzoni, Salvatore Serravalle, Biagi C., Astolfi A., Masetti R., Serravalle S., Franzoni M., Chiarini F., Melchionda F., and Pession A.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, medicine.medical_specialty, T cell, ETP-ALL, NF1, tipifarnib, ETP-ALL, NF1, tipifarnib, NO, hemic and lymphatic diseases, Acute lymphocytic leukemia, Internal medicine, Precursor cell, Medicine, neoplasms, Hematology, business.industry, Cancer, medicine.disease, eye diseases, In vitro, nervous system diseases, Leukemia, medicine.anatomical_structure, Oncology, Immunology, Cancer research, Tipifarnib, business, medicine.drug
Abstract

Pediatric early T-cell precursor leukemia with NF1 deletion and high-sensitivity in vitro to tipifarnib

Published
2010

83. Trisomy 11 with MLL-PTD in a case of infant AML M0

Author

Stefania Purgato, Annalisa Astolfi, Andrea Pession, Roberto Tonelli, Fraia Melchionda, Salvatore Serravalle, Serravalle S, Purgato S, Melchionda F, Astolfi A, Tonelli R, and Pession A

Subjects
Genetics, medicine.medical_specialty, Hematology, business.industry, Internal medicine, medicine, Cancer research, Aneuploidy, medicine.disease, business, Trisomy, Acute myeloid leukaemia M0, Infant, MLL, Partial tandem duplication, Trisomy 11
Abstract

NA

Published
2007

85. Pitfalls, prevention, and treatment of hyperuricemia during tumor lysis syndrome in the era of rasburicase (recombinant urate oxidase)

Author

C. Castellini, Fraia Melchionda, Andrea Pession, Pession A., Melchionda F., and Castellini C.

Subjects
Purine, Oncology, Medicine (General), medicine.medical_specialty, Urinary system, Allopurinol, Review, allopurinol, Pharmacology, chemistry.chemical_compound, R5-920, uric acid, Internal medicine, Rasburicase, Medicine, Hyperuricemia, urate oxidase, business.industry, nutritional and metabolic diseases, Urate oxidase, medicine.disease, Tumor lysis syndrome, chemistry, Uric acid, tumor lysis syndrome, business, rasburicase, medicine.drug
Abstract

Andrea Pession, Fraia Melchionda, Claudia CastelliniOncologia Ematologia Pediatrica “Lalla Seràgnoli”, Clinica Pediatrica, Università degli Studi di Bologna, Bologna, ItalyAbstract: Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase (recombinant urate oxidase) has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it. Rasburicase acts at the end of the purine catabolic pathway and, unlike allopurinol, does not induce accumulation of xanthine or hypoxanthine. Its rapid onset of action and the ability to lower pre-existing elevated uric acid levels are the advantages of rasburicase over allopurinol. Rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patient’s electrolyte status, and reverse renal insufficiency. The drug, initially studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma, seems to show comparable benefit in adults with similar lymphoid malignancies or at high risk of tumor lysis syndrome. Current and future trials will evaluate alternative doses and different schedules of rasburicase to maintain its efficacy while reducing its cost. The review provides a comprehensive and detailed review of pathogenesis, laboratory, and clinical presentation of TLS together with clinical studies already performed both in pediatric and adult patients.Keywords: tumor lysis syndrome, urate oxidase, rasburicase, allopurinol, uric acid

Published
2008
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86. The Survival of the Kiss: Presence and Persistence of Salivary Male DNA in Mixed Samples.

Author

Pesaresi M, Alessandrini F, Bignozzi E, Bernini Di Michele A, Melchionda F, Gesuita R, Onofri V, and Turchi C

Subjects
Humans, Male, Female, Forensic Genetics methods, DNA Fingerprinting methods, Adult, Chromosomes, Human, Y genetics, Specimen Handling methods, Saliva chemistry, Saliva metabolism, DNA genetics, Microsatellite Repeats genetics
Abstract

Background/objectives: The study of DNA transfer and persistence has become increasingly significant, driven by advancements in DNA detection sensitivity and the need for reliable forensic evidence. In forensic investigations, saliva and saliva-stained materials are recognised as valuable DNA sources, particularly in cases of homicide, sexual assault, and burglary, where saliva can be transferred between individuals during the criminal act. The time between the crime and sample collection is a critical factor that can influence the success of the analysis. The value of the specimens collected from the victim's skin or mouth (perilabial and labial sites, teeth and tongue) after the crime has not been investigated with currently used highly sensitive and specific molecular methods., Methods: On the assumption that a significant loss of DNA occurred, in our study, 10 voluntary pairs were tested at different time points after intense kissing and samples were taken from the above-mentioned sites to assess the presence of the donor's DNA. Extracted DNA was quantified using the Plexor HY System kit (Promega), and both autosomal STRs and Y-STRs were analysed., Results: The results reveal a greater persistence of male DNA on the female partner, particularly in the labial and perilabial regions, even up to 120 min after contact, in terms of both concentration and duration., Conclusions: This study emphasises the forensic importance of salivary DNA as a solid source of evidence, particularly in investigations involving mixed DNA profiles.

Published
2025
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87. Developmental validation of a multiplex qPCR assay for simultaneous quantification of nuclear and mitochondrial DNA.

Author

Melchionda F, Pesaresi M, Alessandrini F, Onofri V, and Turchi C

Subjects
Humans, DNA Degradation, Necrotic, Forensic Genetics methods, DNA genetics, Cell Nucleus genetics, DNA, Mitochondrial genetics, Multiplex Polymerase Chain Reaction, Real-Time Polymerase Chain Reaction
Abstract

Quantification of human DNA is key in forensic genetics. A more accurate estimate of the amount of DNA is essential for planning and optimising genotyping assays, as is evaluating the presence of PCR inhibitory substances and DNA degradation status. Multiplex qPCR assays are helpful in forensics because they can quantify different targets simultaneously, thus saving valuable samples, time, and labour. The aim of this study was to highlight the challenges in the developmental validation of a multiplex real-time PCR assay and the drawbacks encountered in translating a previously described and validated assay (SD quants) to a different technology by modifying the dye probes and reagent mix to be used in a different instrument. We developed a TaqMan probe-based multiplex qPCR using reagents and fluorescent probes adapted for the Rotor-Gene 6000 instrument (QIAGEN, Hilden, Germany). The initial assay combined two mitochondrial DNA (mtDNA) and two nuclear DNA (nDNA) targets, with amplification products of different sizes (mtDNA = 69 and 143 bp; nDNA = 71 and 181 bp), to estimate the DNA degradation status and an internal positive control (IPC) to detect potential inhibitors. During the initial testing of the assay, we observed an interaction between the 69 bp mtDNA target and the 71 bp nDNA target probe, and experiments were conducted to resolve this issue without success. We removed the small nDNA target (71 bp) and changed from a 5-plex to a 4-plex qPCR assay (qMIND). The final tetraplex assay was tested on 105 forensic samples and/or small amounts of degraded DNA, such as bones, teeth, fingernails, formalin-fixed paraffin-embedded tissues (FFPE), and hair shaft samples. The quantification results were compared with data acquired from the same samples using another commercially available quantification system commonly used in forensic laboratories. In addition, the short tandem repeat (STR) profiles were investigated to determine their correlation with the quantitative values obtained. Overall, the qPCR assay was robust and reliable for DNA quantification in samples commonly used in forensic practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2025
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88. Sudden Cardiac Death and Channelopathies: What Lies behind the Clinical Significance of Rare Splice-Site Alterations in the Genes Involved?

Author

Pesaresi M, Bernini Di Michele A, Melchionda F, Onofri V, Alessandrini F, and Turchi C

Subjects
Humans, RNA Splice Sites genetics, Mutation, Brugada Syndrome genetics, Ion Channels genetics, Arrhythmias, Cardiac genetics, Clinical Relevance, Channelopathies genetics, Channelopathies pathology, Death, Sudden, Cardiac etiology, Death, Sudden, Cardiac pathology
Abstract

Background and objectives : Sudden cardiac death (SCD) is a natural and unexpected death of cardiac origin that occurs within 1 h from the onset of acute symptoms. The major leading causes of SCD are cardiomyopathies and channelopathies. In this review, we focus on channelopathies, inherited diseases caused by mutations affecting genes encoding membrane ion channels (sodium, potassium or calcium channels) or cellular structures that affect Ca 2+ availability. The diagnosis of diseases such as long QT, Brugada syndrome, short QT and catecholaminergic polymorphic ventricular tachycardia (CPVT) is still challenging. Currently, genetic testing and next-generation sequencing allow us to identify many rare alterations. However, some non-coding variants, e.g., splice-site variants, are usually difficult to interpret and to classify. Methods : In our review, we searched for splice-site variants of genes involved in channelopathies, focusing on variants of unknown significance (VUSs) registered on ClinVar up to now. Results : The research led to a high number of splice-site VUSs of genes involved in channelopathies, suggesting the performance of deeper studies. Conclusions : In order to interpret the correlation between variants and pathologies, we discuss experimental studies, such as RNA sequencing and functional analysis of proteins. Unfortunately, as these in vitro analyses cannot always be performed, we draw attention to in silico studies as future perspectives in genetics. This review has the aim of discussing the potential methods of detection and interpretation of VUSs, bringing out the need for a future reclassification of variants with currently unknown significance.

Published
2024
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89. Pediatric non-Hodgkin lymphoma as a rare cause of spinal cord injury: When lymphoma hides in the canal.

Author

Zama D, Candela E, Pagano G, Venturelli F, Melchionda F, Toni F, Zucchelli M, and Pession A

Abstract

Key Clinical Message: Spinal cord compression from non-Hodgkin lymphoma (NHL) should be considered as a potential diagnosis in cases of acute signs of myelopathy in pediatric patients., Abstract: Spinal cord compression in pediatric non-Hodgkin lymphoma (NHL) is a rare presentation with potential diagnostic challenges. We report on two pediatric patients with NHL who exhibited myelopathy signs as initial presentation. Considering NHL as a differential diagnosis in pediatric patients presenting with spinal cord compression is crucial for optimizing the outcome of these patients., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Published
2024
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90. PATZ1-Rearranged Tumors of the Central Nervous System: Characterization of a Pediatric Series of Seven Cases.

Author

Rossi S, Barresi S, Colafati GS, Genovese S, Tancredi C, Costabile V, Patrizi S, Giovannoni I, Asioli S, Poliani PL, Gardiman MP, Cardoni A, Del Baldo G, Antonelli M, Gianno F, Piccirilli E, Catino G, Martucci L, Quacquarini D, Toni F, Melchionda F, Viscardi E, Zucchelli M, Dal Pos S, Gatti E, Liserre R, Schiavello E, Diomedi-Camassei F, Carai A, Mastronuzzi A, Gessi M, Giannini C, Novelli A, Onetti Muda A, Miele E, Alesi V, and Alaggio R

Subjects
Humans, Child, Transcription Factors genetics, RNA-Binding Protein EWS genetics, Central Nervous System pathology, Transcriptome, Repressor Proteins genetics, Kruppel-Like Transcription Factors genetics, Chromothripsis, Sarcoma genetics, Soft Tissue Neoplasms genetics
Abstract

PATZ1-rearranged sarcomas are well-recognized tumors as part of the family of round cell sarcoma with EWSR1-non-ETS fusions. Whether PATZ1-rearranged central nervous system (CNS) tumors are a distinct tumor type is debatable. We thoroughly characterized a pediatric series of PATZ1-rearranged CNS tumors by chromosome microarray analysis (CMA), DNA methylation analysis, gene expression profiling and, when frozen tissue is available, optical genome mapping (OGM). The series consisted of 7 cases (M:F=1.3:1, 1-17 years, median 12). On MRI, the tumors were supratentorial in close relation to the lateral ventricles (intraventricular or iuxtaventricular), preferentially located in the occipital lobe. Two major histologic groups were identified: one (4 cases) with an overall glial appearance, indicated as "neuroepithelial" (NET) by analogy with the corresponding methylation class (MC); the other (3 cases) with a predominant spindle cell sarcoma morphology, indicated as "sarcomatous" (SM). A single distinct methylation cluster encompassing both groups was identified by multidimensional scaling analysis. Despite the epigenetic homogeneity, unsupervised clustering analysis of gene expression profiles revealed 2 distinct transcriptional subgroups correlating with the histologic phenotypes. Interestingly, genes implicated in epithelial-mesenchymal transition and extracellular matrix composition were enriched in the subgroup associated to the SM phenotype. The combined use of CMA and OGM enabled the identification of chromosome 22 chromothripsis in all cases suitable for the analyses, explaining the physical association of PATZ1 to EWSR1 or MN1. Six patients are currently disease-free (median follow-up 30 months, range 12-92). One patient of the SM group developed spinal metastases at 26 months from diagnosis and is currently receiving multimodal therapy (42 months). Our data suggest that PATZ1-CNS tumors are defined by chromosome 22 chromothripsis as causative of PATZ1 fusion, show peculiar MRI features (eg, relation to lateral ventricles, supratentorial frequently posterior site), and, although epigenetically homogenous, encompass 2 distinct histologic and transcriptional subgroups., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Published
2024
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91. A 10-Year Retrospective Study on Pediatric Visceral Leishmaniasis in a European Endemic Area: Diagnostic and Short-Course Therapeutic Strategies.

Author

Dondi A, Manieri E, Gambuti G, Varani S, Campoli C, Zama D, Pierantoni L, Baldazzi M, Prete A, Attard L, Lanari M, and Melchionda F

Abstract

Background: Visceral leishmaniasis (VL) is a potentially fatal disease, with an increasing occurrence in northern Italy, affecting children and both immunocompetent and immunocompromised adults., Methods: This retrospective study conducted at the St. Orsola University Hospital of Bologna, Italy, evaluates the characteristics of 16 children (with a median age of 14.3 months) who were hospitalized between 2013 and 2022 for VL., Results: Seventy-five percent of patients presented with a triad of fever, cytopenia, and splenomegaly. An abdominal ultrasound examination revealed splenomegaly and hypoechoic spleen abnormalities in 93.8% and 73.3% of cases, respectively. Five VL cases were complicated by secondary hemophagocytic lymphohistiocytosis. Eleven patients were treated with a single 10 mg/kg dose of Liposomal Amphotericin B (L-AmB), while five received two doses (total of 20 mg/kg); one of the former groups experienced a recurrence. The fever generally decreased 48 h after the first L-AmB dose, and hemoglobin levels normalized within a month. The splenomegaly resolved in approximately 4.5 months., Conclusions: Pediatricians should consider VL in children with fever of an unknown origin, anemia, cytopenia, and splenomegaly. In our experience, abdominal ultrasounds and molecular tests on peripheral blood contributed to diagnosis without the need for bone marrow aspiration. The short-course therapy with two 10 mg/kg doses of L-AmB is safe and effective.

Published
2023
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92. Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK).

Author

Fiore M, Taddia A, Indio V, Bertuccio SN, Messelodi D, Serravalle S, Bandini J, Spreafico F, Perotti D, Collini P, Di Cataldo A, Pasquinelli G, Chiarini F, Fois M, Melchionda F, Pession A, and Astolfi A

Subjects
Humans, HEK293 Cells, Repressor Proteins genetics, Kidney metabolism, Sarcoma, Clear Cell genetics, Sarcoma, Clear Cell pathology, Kidney Neoplasms pathology, Wilms Tumor
Abstract

Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases ( p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.

Published
2023
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93. Mutational analysis of ribosomal proteins in a cohort of pediatric patients with T-cell acute lymphoblastic leukemia reveals Q123R, a novel mutation in RPL10.

Author

Bacci L, Indio V, Rambaldelli G, Bugarin C, Magliocchetti F, Del Rio A, Pollutri D, Melchionda F, Pession A, Lanciotti M, Dufour C, Gaipa G, Montanaro L, and Penzo M

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a subtype of ALL involving the malignant expansion of T-cell progenitors. It is driven by a number of different possible genetic lesions, including mutations in genes encoding for ribosomal proteins (RPs). These are structural constituents of ribosomes, ubiquitous effectors of protein synthesis. Albeit the R98S mutation in RPL10, recurring with a higher frequency among RP mutations, has been extensively studied, less is known about the contribution of mutations occurring in other RPs. Alterations affecting translational machinery may not be well tolerated by cells, and there may be a selective pressure that determines the emergence of mutations with a compensatory effect. To explore this hypothesis, we sequenced the exomes of a cohort of 37 pediatric patients affected by T-ALL, and analyzed them to explore the co-occurrence of mutations in genes involved in ribosome biogenesis (including RPs) and translational control, and in known T-ALL driver genes. We found that some of the mutations in these sub-classes of genes tend to cluster together in different patients, indicating that their co-occurrence may confer some kind of advantage to leukemia cells. In addition, our sequencing highlighted the presence of a novel mutation in RPL10, namely the Q123R, which we found associated with a defect in protein synthesis. Our findings indicate that genetic alterations involving ribosome biogenesis and translational control should be carefully considered in the context of precision medicine in T-ALL., Competing Interests: ADR is managing director of Innovamol Consulting Srl. 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 Bacci, Indio, Rambaldelli, Bugarin, Magliocchetti, Del Rio, Pollutri, Melchionda, Pession, Lanciotti, Dufour, Gaipa, Montanaro and Penzo.)

Published
2022
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94. Development and Validation of MPS-Based System for Human Appearance Prediction in Challenging Forensic Samples.

Author

Melchionda F, Silvestrini B, Robino C, Bini C, Fattorini P, Martinez-Labarga C, De Angelis F, Tagliabracci A, and Turchi C

Subjects
Humans, Genetic Markers, Hair Color genetics, DNA genetics, Eye Color genetics, Polymorphism, Single Nucleotide
Abstract

Forensic DNA phenotyping (FDP) provides the ability to predict the human external traits from unknown sample donors, directly from minute amounts of DNA found at the crime scene. We developed a MPS multiplex assay, with the aim of genotyping all 41 DNA markers included in the HIrisPlex-S system for simultaneous prediction of eye, hair and skin colours. Forensic samples such as blood, skeletal remains, touch DNA, saliva swab, artificially degraded samples together with individuals with known phenotypes and a set of 2800 M control DNA were sequenced on the Ion Torrent platform in order to evaluate the concordance testing results and the forensic suitability of the 41-plex MPS assay. The panel was evaluated by testing a different number of PCR cycles and the volume of reagents for library preparation. The study demonstrated that full and reliable profiles were obtained with 0.1-5 ng, even with high degraded DNA. The increment of the number of PCR cycles results in an improvement of correctly genotyping and phenotyping for samples with low amounts of degraded DNA but higher frequencies of artefacts were found. The high DNA degradation level did not influence the correct genotyping and phenotyping and the critical parameter affecting the result is the quantity of input DNA. Eye and hair colour was predicted in 92.60% of individuals and skin colour in 85.15% of individuals. The results suggest that this MPS assay is robust, highly sensitive and useful for human pigmentation prediction in the forensic genetic field.

Published
2022
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95. Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics.

Author

Scarpini S, Dondi A, Totaro C, Biagi C, Melchionda F, Zama D, Pierantoni L, Gennari M, Campagna C, Prete A, and Lanari M

Abstract

Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens' reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide., Competing Interests: The authors declare no conflict of interest.

Published
2022
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96. Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study.

Author

Ruggi A, Melchionda F, Sardi I, Pavone R, Meneghello L, Kitanovski L, Zaletel LZ, Farace P, Zucchelli M, Scagnet M, Toni F, Righetto R, Cianchetti M, Prete A, Greto D, Cammelli S, Morganti AG, and Rombi B

Abstract

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

Published
2022
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97. Hemiplegic-Migraine-like Attacks as First Manifestation of Diffuse Leptomeningeal Glioneuronal Tumor: A Case Report.

Author

Fetta A, Pruccoli J, Biasucci G, Parisi R, Toni F, Melchionda F, and Cordelli DM

Subjects
Child, Hemiplegia etiology, Humans, Male, Central Nervous System Neoplasms pathology, Meningeal Neoplasms complications, Meningeal Neoplasms pathology, Migraine Disorders, Neoplasms, Neuroepithelial
Abstract

Background: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a low-grade tumor characterized by diffuse leptomeningeal infiltrates. Symptoms are usually secondary to hydrocephalus. Hemiplegic migraine (HM)-like episodes have never been associated with DLGNT, but they have been reported with different inflammatory and tumoral entities involving leptomeninges., Observations: We report the case of a 10-year-old boy with recurrent episodes of right hyposthenia, aphasia, and headache lasting hours to days with complete remission. The electroencephalogram during the attack showed diffuse slower activity on the left hemisphere, which improved together with the symptoms. DLGNT was discovered during a follow-up magnetic resonance imaging and confirmed by biopsy., Conclusions: This is the first report of HM-like attacks in DLGNT. We discuss the pathogenetic hypotheses of our case and previously reported cases of "symptomatic" HM with leptomeningeal involvement., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2022
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98. Role of centers with different patient volumes in the management of rhabdomyosarcoma. An analysis by the Italian Pediatric Soft Tissue Sarcoma Committee.

Author

Bisogno G, Congiu G, Affinita MC, Milano GM, Zanetti I, Coppadoro B, Manzitti C, Basso E, Tamburini A, Melchionda F, Cellini M, Pericoli R, D'Angelo P, Cataldo AD, De Leonardis F, Rabusin M, De Corti F, Zin A, Alaggio R, Scarzello G, and Ferrari A

Subjects
Child, Humans, Italy, Rhabdomyosarcoma surgery, Rhabdomyosarcoma, Embryonal, Soft Tissue Neoplasms therapy
Abstract

Procedure: The survival of children with rhabdomyosarcoma (RMS) has gradually improved as a result of the adoption of multidisciplinary treatments. Dedicated skills and facilities are indispensable and more readily available at reference centers. In this study, we examined the role of centers' experience (based on the number of patients treated) in their management of patients with RMS., Methods: We analyzed 342 patients with localized RMS enrolled in the European RMS 2005 protocol from October 2005 to December 2016 at 31 Italian centers that are part of the Soft Tissue Sarcoma Committee (STSC). We grouped the centers by the number of patients each one enrolled (Group 1: >40; Group 2: <40 and >10; and Group 3: <10), and compared a number of indicators to assess the appropriateness of patients' diagnostic workup and treatment and their survival., Results: Overall, 74.6% of patients were treated at 10 centers, and only three of them classifiable as high-volume centers. Only minor differences emerged between the three patient groups in terms of diagnostic investigations and treatment modalities. Survival was similar in the three groups. Approximately, one in four children treated at the centers in Groups 2 and 3 traveled to another center for surgery or radiotherapy., Conclusion: Patients treated at STSC centers with different amounts of experience had similar results in terms of survival. This is attributable to all centers in the network adhering to protocol recommendations and receiving the STSC's support on diagnostics and multidisciplinary treatments for RMS., (© 2021 Wiley Periodicals LLC.)

Published
2021
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99. High Grade of Amplification of Six Regions on Chromosome 2p in a Neuroblastoma Patient with Very Poor Outcome: The Putative New Oncogene TSSC1 .

Author

Ognibene M, Amoroso L, Melchionda F, Cangelosi D, Zara F, Parodi S, and Pezzolo A

Abstract

We observed a case of high-risk neuroblastoma (NB) carried by a 28-month-old girl, displaying metastatic disease and a rapid decline of clinical conditions. By array-CGH analysis of the tumor tissue and of the metastatic bone marrow aspirate cells, we found a high-grade amplification of six regions besides MYCN on bands 2p25.3-p24.3. The genes involved in these amplifications were MYT1L , TSSC1 , CMPK2, RSAD2 , RNF144A , GREB1 , NTSR2 , LPIN1 , NBAS, and the two intergenic non-protein coding RNAs LOC730811 and LOC339788 . We investigated if these DNA co-amplifications may have an effect on enhancing tumor aggressiveness. We evaluated the association between the high expression of the amplified genes and NB patient's outcome using the integration of gene expression data of 786 NB samples profiled with different public platforms from patients with at least five-year follow-up. NB patients with high expression of the TSSC1 gene were associated with a reduced survival rate. Immunofluorescence staining on primary tumor tissues confirmed that the TSSC1 protein expression was high in the relapsed or dead stage 4 cases, but it was generally low in NB patients in complete remission. TSSC1 appears as a putative new oncogene in NB.

Published
2021
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100. Proton therapy: A therapeutic opportunity for aggressive pediatric meningioma.

Author

Rombi B, Ruggi A, Sardi I, Zucchelli M, Scagnet M, Toni F, Cammelli S, Giulietti G, Fabbri VP, Gianno F, Amichetti M, Yock TI, Morganti AG, Pession A, and Melchionda F

Subjects
Child, Humans, Infant, Male, Meningeal Neoplasms pathology, Meningioma pathology, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy, Proton Therapy methods
Abstract

Meningiomas are an extremely rare histology among pediatric brain tumors, and there is a shortage of literature on their management. Proton therapy is currently used safely and effectively for many types of both pediatric and adult cancer, and its main advantage is the sparing of healthy tissues from radiation, which could translate in the reduction of late side effects. We review the literature on radiotherapy and proton therapy for pediatric meningiomas and report clinical outcomes for two aggressive pediatric meningiomas we treated with protons. Proton therapy might be a safe and effective therapeutic option for this rare subgroup of tumors., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Published
2021
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