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1. Macrolide therapy is associated with lower mortality in community-acquired bacteraemic pneumonia

Author

Arnold, F, Lopardo, G, Wiemken, T, Kelley, R, Peyrani, P, Mattingly, W, Feldman, C, Gnoni, M, Maurici, R, Ramirez, J, Ayesu, K, File, T, Burdette, S, Blatt, S, Restrepo, M, Bordon, J, Gross, P, Musher, D, Marrie, T, Weiss, K, Roig, J, Lode, H, Welte, T, Aliberti, S, Blasi, F, Cosentini, R, Legnani, D, Franzetti, F, Montano, N, Cervi, G, Rossi, P, Voza, A, Ostrowsky, B, Pesci, A, Nava, S, Viale, P, Galavatti, V, Patricia, A, Dimas, C, Piro, R, Viscoli, C, Torres, A, Valenti, V, Ojales, D, Bodi, M, Porras, J, Rello, J, Menendez, R, Stolz, D, Schuetz, P, Haubitz, S, Chalmers, J, Fardon, T, Benchetrit, G, Rodriguez, E, Corral, J, Gonzalez, J, de Vedia, L, Luna, C, Martinez, J, Marzoratti, L, Rodriguez, M, Videla, A, Saavedra, F, Lopez, H, Victorio, C, Riera, F, Jimenez, P, Fernandez, P, Parada, M, Fuenzalida, A, Riquelme, R, Barros, M, Luna, J, Toala, I, Oze de Morvil, G, Fernandez, R, Aiello, G, Alvarez, P, Soca, A, Arteta, F, Delgado, J, Levy, G, Rivero, L, Rodriguez, B, Mirabal, M, Mateo, M, Mendoza, M, Arnold, Forest W., Lopardo, Gustavo, Wiemken, Timothy L., Kelley, Robert, Peyrani, Paula, Mattingly, William A., Feldman, Charles, Gnoni, Martin, Maurici, Rosemeri, Ramirez, Julio A., Arnold, Forest, Ramirez, Julio, Ayesu, Kwabena, File, Thomas, Burdette, Steven, Blatt, Stephen, Restrepo, Marcos, Bordon, Jose, Gross, Peter, Musher, Daniel, Marrie, Thomas, Weiss, Karl, Roig, Jorge, Lode, Harmut, Welte, Tobias, Aliberti, Stephano, Blasi, Francesco, Cosentini, Roberto, Legnani, Delfino, Franzetti, Fabio, Montano, Nicola, Cervi, Giulia, Rossi, Paolo, Voza, Antonio, Ostrowsky, Belinda, Pesci, Alberto, Nava, Stefano, Viale, Pierluigi, Galavatti, Vanni, Patricia, Aruj, Dimas, Carlos, Piro, Roberto, Viscoli, Claudio, Torres, Antoni, Valenti, Vincenzo, Ojales, Daniel Portela, Bodi, Maria, Porras, Jose, Rello, Jordi, Menendez, Rosario, Stolz, Daiana, Schuetz, Philipp, Haubitz, Sebastian, Chalmers, James, Fardon, Tom, Benchetrit, Guillermo, Rodriguez, Eduardo, Corral, Jorge, Gonzalez, Jose, de Vedia, Lautaro, Luna, Carlos, Martinez, Jorge, Marzoratti, Lucia, Rodriguez, Maria, Videla, Alejandro, Saavedra, Federico, Lopez, Horacio, Victorio, Carlos, Riera, Fernando, Jimenez, Patricio, Fernandez, Patricia, Parada, Maria, Fuenzalida, Alejandro Díaz, Riquelme, Raul, Barros, Manuel, Luna, Juan Manuel, Toala, Ivan, Oze de Morvil, Guillermo Arbo, Fernandez, Ricardo, Aiello, Gonzalo, Alvarez, Pablo, Soca, Ana, Arteta, Federico, Delgado, Jose, Levy, Gur, Rivero, Ludwig, Rodriguez, Benito, Mirabal, Mario Perez, Mateo, Marilyn, Mendoza, Myrna, Arnold, F, Lopardo, G, Wiemken, T, Kelley, R, Peyrani, P, Mattingly, W, Feldman, C, Gnoni, M, Maurici, R, Ramirez, J, Ayesu, K, File, T, Burdette, S, Blatt, S, Restrepo, M, Bordon, J, Gross, P, Musher, D, Marrie, T, Weiss, K, Roig, J, Lode, H, Welte, T, Aliberti, S, Blasi, F, Cosentini, R, Legnani, D, Franzetti, F, Montano, N, Cervi, G, Rossi, P, Voza, A, Ostrowsky, B, Pesci, A, Nava, S, Viale, P, Galavatti, V, Patricia, A, Dimas, C, Piro, R, Viscoli, C, Torres, A, Valenti, V, Ojales, D, Bodi, M, Porras, J, Rello, J, Menendez, R, Stolz, D, Schuetz, P, Haubitz, S, Chalmers, J, Fardon, T, Benchetrit, G, Rodriguez, E, Corral, J, Gonzalez, J, de Vedia, L, Luna, C, Martinez, J, Marzoratti, L, Rodriguez, M, Videla, A, Saavedra, F, Lopez, H, Victorio, C, Riera, F, Jimenez, P, Fernandez, P, Parada, M, Fuenzalida, A, Riquelme, R, Barros, M, Luna, J, Toala, I, Oze de Morvil, G, Fernandez, R, Aiello, G, Alvarez, P, Soca, A, Arteta, F, Delgado, J, Levy, G, Rivero, L, Rodriguez, B, Mirabal, M, Mateo, M, Mendoza, M, Arnold, Forest W., Lopardo, Gustavo, Wiemken, Timothy L., Kelley, Robert, Peyrani, Paula, Mattingly, William A., Feldman, Charles, Gnoni, Martin, Maurici, Rosemeri, Ramirez, Julio A., Arnold, Forest, Ramirez, Julio, Ayesu, Kwabena, File, Thomas, Burdette, Steven, Blatt, Stephen, Restrepo, Marcos, Bordon, Jose, Gross, Peter, Musher, Daniel, Marrie, Thomas, Weiss, Karl, Roig, Jorge, Lode, Harmut, Welte, Tobias, Aliberti, Stephano, Blasi, Francesco, Cosentini, Roberto, Legnani, Delfino, Franzetti, Fabio, Montano, Nicola, Cervi, Giulia, Rossi, Paolo, Voza, Antonio, Ostrowsky, Belinda, Pesci, Alberto, Nava, Stefano, Viale, Pierluigi, Galavatti, Vanni, Patricia, Aruj, Dimas, Carlos, Piro, Roberto, Viscoli, Claudio, Torres, Antoni, Valenti, Vincenzo, Ojales, Daniel Portela, Bodi, Maria, Porras, Jose, Rello, Jordi, Menendez, Rosario, Stolz, Daiana, Schuetz, Philipp, Haubitz, Sebastian, Chalmers, James, Fardon, Tom, Benchetrit, Guillermo, Rodriguez, Eduardo, Corral, Jorge, Gonzalez, Jose, de Vedia, Lautaro, Luna, Carlos, Martinez, Jorge, Marzoratti, Lucia, Rodriguez, Maria, Videla, Alejandro, Saavedra, Federico, Lopez, Horacio, Victorio, Carlos, Riera, Fernando, Jimenez, Patricio, Fernandez, Patricia, Parada, Maria, Fuenzalida, Alejandro Díaz, Riquelme, Raul, Barros, Manuel, Luna, Juan Manuel, Toala, Ivan, Oze de Morvil, Guillermo Arbo, Fernandez, Ricardo, Aiello, Gonzalo, Alvarez, Pablo, Soca, Ana, Arteta, Federico, Delgado, Jose, Levy, Gur, Rivero, Ludwig, Rodriguez, Benito, Mirabal, Mario Perez, Mateo, Marilyn, and Mendoza, Myrna

Abstract

Background: Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods: Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results: Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions: In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia

Published
2018

2. Macrolide therapy is associated with lower mortality in community-acquired bacteraemic pneumonia

Author

Arnold, F, Lopardo, G, Wiemken, T, Kelley, R, Peyrani, P, Mattingly, W, Feldman, C, Gnoni, M, Maurici, R, Ramirez, J, Ayesu, K, File, T, Burdette, S, Blatt, S, Restrepo, M, Bordon, J, Gross, P, Musher, D, Marrie, T, Weiss, K, Roig, J, Lode, H, Welte, T, Aliberti, S, Blasi, F, Cosentini, R, Legnani, D, Franzetti, F, Montano, N, Cervi, G, Rossi, P, Voza, A, Ostrowsky, B, Pesci, A, Nava, S, Viale, P, Galavatti, V, Patricia, A, Dimas, C, Piro, R, Viscoli, C, Torres, A, Valenti, V, Ojales, D, Bodi, M, Porras, J, Rello, J, Menendez, R, Stolz, D, Schuetz, P, Haubitz, S, Chalmers, J, Fardon, T, Benchetrit, G, Rodriguez, E, Corral, J, Gonzalez, J, de Vedia, L, Luna, C, Martinez, J, Marzoratti, L, Rodriguez, M, Videla, A, Saavedra, F, Lopez, H, Victorio, C, Riera, F, Jimenez, P, Fernandez, P, Parada, M, Fuenzalida, A, Riquelme, R, Barros, M, Luna, J, Toala, I, Oze de Morvil, G, Fernandez, R, Aiello, G, Alvarez, P, Soca, A, Arteta, F, Delgado, J, Levy, G, Rivero, L, Rodriguez, B, Mirabal, M, Mateo, M, Mendoza, M, Arnold, Forest W., Lopardo, Gustavo, Wiemken, Timothy L., Kelley, Robert, Peyrani, Paula, Mattingly, William A., Feldman, Charles, Gnoni, Martin, Maurici, Rosemeri, Ramirez, Julio A., Arnold, Forest, Ramirez, Julio, Ayesu, Kwabena, File, Thomas, Burdette, Steven, Blatt, Stephen, Restrepo, Marcos, Bordon, Jose, Gross, Peter, Musher, Daniel, Marrie, Thomas, Weiss, Karl, Roig, Jorge, Lode, Harmut, Welte, Tobias, Aliberti, Stephano, Blasi, Francesco, Cosentini, Roberto, Legnani, Delfino, Franzetti, Fabio, Montano, Nicola, Cervi, Giulia, Rossi, Paolo, Voza, Antonio, Ostrowsky, Belinda, Pesci, Alberto, Nava, Stefano, Viale, Pierluigi, Galavatti, Vanni, Patricia, Aruj, Dimas, Carlos, Piro, Roberto, Viscoli, Claudio, Torres, Antoni, Valenti, Vincenzo, Ojales, Daniel Portela, Bodi, Maria, Porras, Jose, Rello, Jordi, Menendez, Rosario, Stolz, Daiana, Schuetz, Philipp, Haubitz, Sebastian, Chalmers, James, Fardon, Tom, Benchetrit, Guillermo, Rodriguez, Eduardo, Corral, Jorge, Gonzalez, Jose, de Vedia, Lautaro, Luna, Carlos, Martinez, Jorge, Marzoratti, Lucia, Rodriguez, Maria, Videla, Alejandro, Saavedra, Federico, Lopez, Horacio, Victorio, Carlos, Riera, Fernando, Jimenez, Patricio, Fernandez, Patricia, Parada, Maria, Fuenzalida, Alejandro Díaz, Riquelme, Raul, Barros, Manuel, Luna, Juan Manuel, Toala, Ivan, Oze de Morvil, Guillermo Arbo, Fernandez, Ricardo, Aiello, Gonzalo, Alvarez, Pablo, Soca, Ana, Arteta, Federico, Delgado, Jose, Levy, Gur, Rivero, Ludwig, Rodriguez, Benito, Mirabal, Mario Perez, Mateo, Marilyn, Mendoza, Myrna, Arnold, F, Lopardo, G, Wiemken, T, Kelley, R, Peyrani, P, Mattingly, W, Feldman, C, Gnoni, M, Maurici, R, Ramirez, J, Ayesu, K, File, T, Burdette, S, Blatt, S, Restrepo, M, Bordon, J, Gross, P, Musher, D, Marrie, T, Weiss, K, Roig, J, Lode, H, Welte, T, Aliberti, S, Blasi, F, Cosentini, R, Legnani, D, Franzetti, F, Montano, N, Cervi, G, Rossi, P, Voza, A, Ostrowsky, B, Pesci, A, Nava, S, Viale, P, Galavatti, V, Patricia, A, Dimas, C, Piro, R, Viscoli, C, Torres, A, Valenti, V, Ojales, D, Bodi, M, Porras, J, Rello, J, Menendez, R, Stolz, D, Schuetz, P, Haubitz, S, Chalmers, J, Fardon, T, Benchetrit, G, Rodriguez, E, Corral, J, Gonzalez, J, de Vedia, L, Luna, C, Martinez, J, Marzoratti, L, Rodriguez, M, Videla, A, Saavedra, F, Lopez, H, Victorio, C, Riera, F, Jimenez, P, Fernandez, P, Parada, M, Fuenzalida, A, Riquelme, R, Barros, M, Luna, J, Toala, I, Oze de Morvil, G, Fernandez, R, Aiello, G, Alvarez, P, Soca, A, Arteta, F, Delgado, J, Levy, G, Rivero, L, Rodriguez, B, Mirabal, M, Mateo, M, Mendoza, M, Arnold, Forest W., Lopardo, Gustavo, Wiemken, Timothy L., Kelley, Robert, Peyrani, Paula, Mattingly, William A., Feldman, Charles, Gnoni, Martin, Maurici, Rosemeri, Ramirez, Julio A., Arnold, Forest, Ramirez, Julio, Ayesu, Kwabena, File, Thomas, Burdette, Steven, Blatt, Stephen, Restrepo, Marcos, Bordon, Jose, Gross, Peter, Musher, Daniel, Marrie, Thomas, Weiss, Karl, Roig, Jorge, Lode, Harmut, Welte, Tobias, Aliberti, Stephano, Blasi, Francesco, Cosentini, Roberto, Legnani, Delfino, Franzetti, Fabio, Montano, Nicola, Cervi, Giulia, Rossi, Paolo, Voza, Antonio, Ostrowsky, Belinda, Pesci, Alberto, Nava, Stefano, Viale, Pierluigi, Galavatti, Vanni, Patricia, Aruj, Dimas, Carlos, Piro, Roberto, Viscoli, Claudio, Torres, Antoni, Valenti, Vincenzo, Ojales, Daniel Portela, Bodi, Maria, Porras, Jose, Rello, Jordi, Menendez, Rosario, Stolz, Daiana, Schuetz, Philipp, Haubitz, Sebastian, Chalmers, James, Fardon, Tom, Benchetrit, Guillermo, Rodriguez, Eduardo, Corral, Jorge, Gonzalez, Jose, de Vedia, Lautaro, Luna, Carlos, Martinez, Jorge, Marzoratti, Lucia, Rodriguez, Maria, Videla, Alejandro, Saavedra, Federico, Lopez, Horacio, Victorio, Carlos, Riera, Fernando, Jimenez, Patricio, Fernandez, Patricia, Parada, Maria, Fuenzalida, Alejandro Díaz, Riquelme, Raul, Barros, Manuel, Luna, Juan Manuel, Toala, Ivan, Oze de Morvil, Guillermo Arbo, Fernandez, Ricardo, Aiello, Gonzalo, Alvarez, Pablo, Soca, Ana, Arteta, Federico, Delgado, Jose, Levy, Gur, Rivero, Ludwig, Rodriguez, Benito, Mirabal, Mario Perez, Mateo, Marilyn, and Mendoza, Myrna

Abstract

Background: Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods: Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results: Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions: In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia

Published
2018

3. Dalla letteratura all'arte contemporanea: pensieri di un inesperto sui «Promessi sposi cancellati per venticinque lettori e dieci appestati» di Emilio Isgrò

Author

Giordano, A., Piro, R., Colombo, Michele, Michele Colombo (ORCID:0000-0002-4440-7334), Giordano, A., Piro, R., Colombo, Michele, and Michele Colombo (ORCID:0000-0002-4440-7334)

Abstract

The Promessi sposi cancellati per venticinque lettori e dieci appestati, made by conceptual artist Emilio Isgrò and first exposed in 2016, is both an artwork in itself and a means to understand Alessandro Manzoni’s novel in a new and unconventional way. Isgrò’s erasures of 35 copies of the 1840 edition of I promessi sposi prove to be a way of make words, and the absence of words, telling something unexpected.

Published
2018

4. Individualizing duration of antibiotic therapy in community-acquired pneumonia

Author

Aliberti, S, Ramirez, J, Giuliani, F, Wiemken, T, Sotgiu, G, Tedeschi, S, Carugati, M, Valenti, V, Marchioni, M, Camera, M, Piro, R, Del Forno, M, Milani, G, Faverio, P, Richeldi, L, Deotto, M, Villani, M, Voza, A, Tobaldini, E, Bernardi, M, Bellone, A, Bassetti, M, Blasi, F, Aliberti, Stefano, Ramirez, Julio, Giuliani, Fabio, Wiemken, Timothy, Sotgiu, Giovanni, Tedeschi, Sara, Carugati, Manuela, Valenti, Vincenzo, Marchioni, Marco, Camera, Marco, Piro, Roberto, Del Forno, Manuela, Milani, Giuseppe, Faverio, Paola, Richeldi, Luca, Deotto, Martina, Villani, Massimiliano, Voza, Antonio, Tobaldini, Eleonora, Bernardi, Mauro, Bellone, Andrea, Bassetti, Matteo, Blasi, Francesco, Aliberti, S, Ramirez, J, Giuliani, F, Wiemken, T, Sotgiu, G, Tedeschi, S, Carugati, M, Valenti, V, Marchioni, M, Camera, M, Piro, R, Del Forno, M, Milani, G, Faverio, P, Richeldi, L, Deotto, M, Villani, M, Voza, A, Tobaldini, E, Bernardi, M, Bellone, A, Bassetti, M, Blasi, F, Aliberti, Stefano, Ramirez, Julio, Giuliani, Fabio, Wiemken, Timothy, Sotgiu, Giovanni, Tedeschi, Sara, Carugati, Manuela, Valenti, Vincenzo, Marchioni, Marco, Camera, Marco, Piro, Roberto, Del Forno, Manuela, Milani, Giuseppe, Faverio, Paola, Richeldi, Luca, Deotto, Martina, Villani, Massimiliano, Voza, Antonio, Tobaldini, Eleonora, Bernardi, Mauro, Bellone, Andrea, Bassetti, Matteo, and Blasi, Francesco

Abstract

International experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration. In the Individualized group, antibiotics were discontinued 48 h after the patient reached clinical stability, with at least five days of total antibiotic treatment. Early failure within 30 days was the primary composite outcome. 135 patients were randomized to the Standard group and 125 to the Individualized group. The trial was interrupted by the safety committee because of an apparent inferiority of the Individualized group over the Standard treatment: 14 (11.2%) patients in the Individualized group experienced early failure vs. 10 (7.4%) patients in the Standard group, p = 0.200, at the intention-to-treat analysis. 30-day mortality rate was four-time higher in the Individualized group than the Standard group. Shortening antibiotic duration according to patients' characteristics still remains an open question.

Published
2017

5. Noi, persona politica

Author

Librandi, Rita, Piro, Rosa, Librandi, R ( Rita ), Piro, R ( Rosa ), La Fauci, Nunzio, Librandi, Rita, Piro, Rosa, Librandi, R ( Rita ), Piro, R ( Rosa ), and La Fauci, Nunzio

Published
2016

6. Endobronchial Hamartoma Subtotally Occluding the Right Main Bronchus and Mimicking Bronchial Carcinoid Tumor

Author

Lococo, Filippo, Galeone, C., Lasagni, L., Carbonelli, C., Tagliavini, E., Piro, R., Zucchi, L., Sgarbi, G., Lococo F. (ORCID:0000-0002-9383-5554), Lococo, Filippo, Galeone, C., Lasagni, L., Carbonelli, C., Tagliavini, E., Piro, R., Zucchi, L., Sgarbi, G., and Lococo F. (ORCID:0000-0002-9383-5554)

Abstract

Hamartomas are very rarely identified as an endobronchial lesion. Herein, we describe a peculiar case of a 55-year-old woman with persistent cough and increasing dyspnea and radiological detection of a solid lesion subtotally occluding the main right bronchus. Despite the radiological and radiometabolic (18-fluoro-2-deoxy-d-glucose positron emission tomography/computer tomography scan) features were highly suspected for bronchial carcinoid, the definitive diagnosis after endoscopic removal was indicative of an endobronchial hamartoma. When considering differential diagnosis of an endobronchial lesion, the physicians should take firmly in mind such rare entity and, accordingly, bronchoscopy and bronchoscopic biopsy should be done as first step in management of all cases presenting with endobronchial lesions.

Published
2016

7. Prior tuberculin skin test does not induce a false positive result of T-cell interferon-gamma release assays

Author

Losi, M, Ferrara, G, Luppi, F, Piro, R, Cerri, S, Tallarico, S, Andreani, A, D’Amico, R, Roversi, P, Meacci, M, Meccugni, B, Marchetti Dori, I, Caracciolo, R, Fabbri, L, Richeldi, L, Losi M, Ferrara G, Luppi F, Piro R, Cerri S, Tallarico S, Andreani A, D’Amico R, Roversi P, Meacci M, Meccugni B, Marchetti Dori I, Caracciolo R, Fabbri LM, Richeldi L, Losi, M, Ferrara, G, Luppi, F, Piro, R, Cerri, S, Tallarico, S, Andreani, A, D’Amico, R, Roversi, P, Meacci, M, Meccugni, B, Marchetti Dori, I, Caracciolo, R, Fabbri, L, Richeldi, L, Losi M, Ferrara G, Luppi F, Piro R, Cerri S, Tallarico S, Andreani A, D’Amico R, Roversi P, Meacci M, Meccugni B, Marchetti Dori I, Caracciolo R, Fabbri LM, and Richeldi L

Published
2008

8. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Author

Mack, S, Mack, S, Witt, H, Piro, R, Gu, L, Zuyderduyn, S, Stütz, A, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, D, Sill, M, Pugh, T, Ryzhova, M, Wani, K, Shih, D, Head, R, Remke, M, Bailey, S, Zichner, T, Faria, C, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, A, Northcott, P, Peacock, J, Bertrand, K, Agnihotri, S, Cavalli, F, Clarke, I, Nethery-Brokx, K, Creasy, C, Verma, S, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, M, Roberts, S, Fults, D, Massimi, L, Cho, Y, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, A, von Deimling, A, Witt, O, Scherer, S, Fan, X, Muraszko, K, Kool, M, Pomeroy, S, Jabado, N, Rutka, J, Bouffet, E, Korbel, J, Lupien, M, Aldape, K, Bader, G, Eils, R, Lichter, P, Dirks, P, Pfister, S, Korshunov, A, Taylor, M, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, P, Gupta, Nalin, Phillips, Joanna, Weiss, William, Mack, S, Mack, S, Witt, H, Piro, R, Gu, L, Zuyderduyn, S, Stütz, A, Wang, X, Gallo, M, Garzia, L, Zayne, K, Zhang, X, Ramaswamy, V, Jäger, N, Jones, D, Sill, M, Pugh, T, Ryzhova, M, Wani, K, Shih, D, Head, R, Remke, M, Bailey, S, Zichner, T, Faria, C, Barszczyk, M, Stark, S, Seker-Cin, H, Hutter, S, Johann, P, Bender, S, Hovestadt, V, Tzaridis, T, Dubuc, A, Northcott, P, Peacock, J, Bertrand, K, Agnihotri, S, Cavalli, F, Clarke, I, Nethery-Brokx, K, Creasy, C, Verma, S, Koster, J, Wu, X, Yao, Y, Milde, T, Sin-Chan, P, Zuccaro, J, Lau, L, Pereira, S, Castelo-Branco, P, Hirst, M, Marra, M, Roberts, S, Fults, D, Massimi, L, Cho, Y, Van Meter, T, Grajkowska, W, Lach, B, Kulozik, A, von Deimling, A, Witt, O, Scherer, S, Fan, X, Muraszko, K, Kool, M, Pomeroy, S, Jabado, N, Rutka, J, Bouffet, E, Korbel, J, Lupien, M, Aldape, K, Bader, G, Eils, R, Lichter, P, Dirks, P, Pfister, S, Korshunov, A, Taylor, M, Huang, A, Tabori, U, Hawkins, C, Malkin, D, Kongkham, P, Gupta, Nalin, Phillips, Joanna, and Weiss, William

Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014

9. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Author

Mack, S. C., Witt, H., Piro, R. M., Gu, L., Zuyderduyn, S., Stütz, A. M., Wang, X., Gallo, M., Garzia, L., Zayne, K., Zhang, X., Ramaswamy, V., Jäger, N., Jones, D. T. W., Sill, M., Pugh, T. J., Ryzhova, M., Wani, K. M., Shih, D. J. H., Head, R., Remke, M., Bailey, S. D., Zichner, T., Faria, C. C., Barszczyk, M., Stark, S., Seker-Cin, H., Hutter, S., Johann, P., Bender, S., Hovestadt, V., Tzaridis, T., Dubuc, A. M., Northcott, P. A., Peacock, J., Bertrand, K. C., Agnihotri, S., Cavalli, F. M. G., Clarke, I., Nethery-Brokx, K., Creasy, C. L., Verma, S. K., Koster, J., Wu, X., Yao, Y., Milde, T., Sin-Chan, P., Zuccaro, J., Lau, L., Pereira, S., Castelo-Branco, P., Hirst, M., Marra, M. A., Roberts, S. S., Fults, D., Massimi, Luca, Cho, Y. J., Van Meter, T., Grajkowska, W., Lach, B., Kulozik, A. E., Von Deimling, A., Witt, O., Scherer, S. W., Fan, X., Muraszko, K. M., Kool, M., Pomeroy, S. L., Gupta, N., Phillips, J., Huang, A., Tabori, U., Hawkins, C., Malkin, D., Kongkham, P. N., Weiss, W. A., Jabado, N., Rutka, J. T., Bouffet, E., Korbel, J. O., Lupien, M., Aldape, K. D., Bader, G. D., Eils, R., Lichter, P., Dirks, P. B., Pfister, S. M., Korshunov, A., Taylor, M. D., Massimi, L., Mack, S. C., Witt, H., Piro, R. M., Gu, L., Zuyderduyn, S., Stütz, A. M., Wang, X., Gallo, M., Garzia, L., Zayne, K., Zhang, X., Ramaswamy, V., Jäger, N., Jones, D. T. W., Sill, M., Pugh, T. J., Ryzhova, M., Wani, K. M., Shih, D. J. H., Head, R., Remke, M., Bailey, S. D., Zichner, T., Faria, C. C., Barszczyk, M., Stark, S., Seker-Cin, H., Hutter, S., Johann, P., Bender, S., Hovestadt, V., Tzaridis, T., Dubuc, A. M., Northcott, P. A., Peacock, J., Bertrand, K. C., Agnihotri, S., Cavalli, F. M. G., Clarke, I., Nethery-Brokx, K., Creasy, C. L., Verma, S. K., Koster, J., Wu, X., Yao, Y., Milde, T., Sin-Chan, P., Zuccaro, J., Lau, L., Pereira, S., Castelo-Branco, P., Hirst, M., Marra, M. A., Roberts, S. S., Fults, D., Massimi, Luca, Cho, Y. J., Van Meter, T., Grajkowska, W., Lach, B., Kulozik, A. E., Von Deimling, A., Witt, O., Scherer, S. W., Fan, X., Muraszko, K. M., Kool, M., Pomeroy, S. L., Gupta, N., Phillips, J., Huang, A., Tabori, U., Hawkins, C., Malkin, D., Kongkham, P. N., Weiss, W. A., Jabado, N., Rutka, J. T., Bouffet, E., Korbel, J. O., Lupien, M., Aldape, K. D., Bader, G. D., Eils, R., Lichter, P., Dirks, P. B., Pfister, S. M., Korshunov, A., Taylor, M. D., and Massimi, L.

Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland. © 2014 Macmillan Publishers Limited.

Published
2014

12. Socio-environmental impacts of new housing development at infill and greenfield sites - methodical design for a multicriteria assessment

Author

Ganser, R., Piro, R., Schetke, Sophie, Kötter, T., Haase, Dagmar, Ganser, R., Piro, R., Schetke, Sophie, Kötter, T., and Haase, Dagmar

Abstract

Despite decreasing population in an increasing number of German urban agglomerations, urban expansion and land development pressure is still the main driver behind massive land consumption. This negatively affects natural resources and fosters the loss of ecosystem services in the surrounding suburban areas. Since the high annual land consumption rates have not yet abated, the German Federal government established a quantitative benchmark which aims to reduce land consumption from 113 hectares (280 acres) per day in 2008 to 30 hectares (75 acres) per day in 2020 (http://www.nachhaltigkeitsrat.de). In order to realize this significant step, stakeholders need to focus on more compact settlement development and to use infill strategies. Options include both brownfield development and densification strategies. Despite obvious positive effects of reduced land consumption and protection of natural resources in suburban areas, the specific socio-environmental impacts of infill development remain unclear, especially with regard to residents´ quality of life (QoL) and the provision of urban ecosystem services (UES) including the provision of local climate regulation, recreation or aesthetic features. This study introduces an innovative methodical design for a multicriteria assessment (MCA) of the socio-environmental impacts of new infill development compared to suburban – especially greenfield – development. The multicriteria assessment focuses on the provisioning benefits of urban green space for urban residents. So doing, it bridges the gap between the two concepts of quality of life and urban ecosystems services. The study presents an integrative multicriteria assessment scheme which can be applied by both urban planners and scientists. We show that infill development does not equal a decrease in the environmental conditions in cities.

Published
2012

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