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1. Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

Author

Alessandro Morandi, Marco Inzitari, Cristina Udina, Neus Gual, Miriam Mota, Elena Tassistro, Anita Andreano, Antonio Cherubini, Simona Gentile, Enrico Mossello, Alessandra Marengoni, Anna Olivé, Francesc Riba, Domingo Ruiz, Elisabet de Jaime, Giuseppe Bellelli, A. Tarasconi, M. Sella, S. Auriemma, G. Paternò, G. Faggian, C. Lucarelli, N. De Grazia, C. Alberto, A. Margola, L. Porcella, I. Nardiello, E. Chimenti, M. Zeni, A. Giani, S. Famularo, E. Romairone, C. Minaglia, C. Ceccotti, G. Guerra, G. Mantovani, F. Monacelli, T. Candiani, A. Ballestrero, F. Santolini, M. Rosso, V. Bono, S. Sibilla, P. Dal Santo, M. Ceci, P. Barone, T. Schirinzi, A. Formenti, G. Nastasi, G. Isaia, D. Gonella, A. Battuello, S. Casson, D. Calvani, F. Boni, A. Ciaccio, R. Rosa, G. Sanna, S. Manfredini, L. Cortese, M. Rizzo, R. Prestano, A. Greco, M. Lauriola, G. Gelosa, V. Piras, M. Arena, D. Cosenza, A. Bellomo, M. LaMontagna, L. Gabbani, L. Lambertucci, S. Perego, G. Parati, G. Basile, V. Gallina, G. Pilone, C. Giudice, F. De, L. Pietrogrande, B. De, M. Mosca, I. Corazzin, P. Rossi, V. Nunziata, F. D'Amico, A. Grippa, S. Giardini, R. Barucci, A. Cossu, L. Fiorin, M. Distefano, M. Lunardelli, M. Brunori, I. Ruffini, E. Abraham, A. Varutti, E. Fabbro, A. Catalano, G. Martino, D. Leotta, A. Marchet, G. Dell'Aquila, A. Scrimieri, M. Davoli, M. Casella, A. Cartei, G. Polidori, D. Brischetto, S. Motta, R. Saponara, P. Perrone, G. Russo, D. Del, C. Car, T. Pirina, S. Franzoni, A. Cotroneo, F. Ghiggia, G. Volpi, C. Menichetti, M. Bo, A. Panico, P. Calogero, G. Corvalli, M. Mauri, E. Lupia, R. Manfredini, F. Fabbian, A. March, M. Pedrotti, M. Veronesi, E. Strocchi, C. Borghi, A. Bianchetti, A. Crucitti, V. DiFrancesco, G. Fontana, L. Bonanni, F. Barbone, C. Serrati, G. Ballardini, M. Simoncelli, G. Ceschia, C. Scarpa, R. Brugiolo, S. Fusco, T. Ciarambino, C. Biagini, E. Tonon, M. Porta, D. Venuti, M. DelSette, M. Poeta, G. Barbagallo, G. Trovato, A. Delitala, P. Arosio, F. Reggiani, G. Zuliani, B. Ortolani, E. Mussio, A. Girardi, A. Coin, G. Ruotolo, A. Castagna, M. Masina, R. Cimino, A. Pinciaroli, G. Tripodi, U. Cannistrà, F. Cassadonte, M. Vatrano, L. Scaglione, P. Fogliacco, C. Muzzuilini, F. Romano, A. Padovani, L. Rozzini, A. Cagnin, F. Fragiacomo, G. Desideri, E. Liberatore, A. Bruni, G. Orsitto, M. Franco, L. Bonfrate, M. Bonetto, N. Pizio, G. Magnani, G. Cecchetti, A. Longo, V. Bubba, L. Marinan, M. Cotelli, M. Turla, M. Sessa, L. Abruzzi, G. Castoldi, D. LoVetere, C. Musacchio, M. Novello, A. Cavarape, A. Bini, A. Leonardi, F. Seneci, W. Grimaldi, F. Fimognari, V. Bambara, A. Saitta, F. Corica, M. Braga, E. Ettorre, C. Camellini, G. Bellelli, G. Annoni, A. Marengoni, A. Crescenzo, G. Noro, R. Turco, M. Ponzetto, L. Giuseppe, B. Mazzei, G. Maiuri, D. Costaggiu, R. Damato, M. Formilan, G. Patrizia, M. Gallucci, M. Paragona, P. Bini, D. Modica, C. Abati, M. Clerici, I. Barbera, F. NigroImperiale, A. Manni, C. Votino, C. Castiglioni, M. Di, M. Degl'Innocenti, G. Moscatelli, S. Guerini, C. Casini, D. Dini, E. D'Imporzano, S. DeNotariis, F. Bonometti, C. Paolillo, A. Riccardi, A. Tiozzo, M. DiBari, S. Vanni, A. Scarpa, D. Zara, P. Ranieri, M. Alessandro, F. Di, D. Pezzoni, C. Platto, V. D'Ambrosio, C. Ivaldi, P. Milia, F. DeSalvo, C. Solaro, M. Strazzacappa, M. Cazzadori, S. Confente, M. Grasso, E. Troisi, V. Guerini, B. Bernardini, C. Corsini, S. Boffelli, A. Filippi, K. Delpin, B. Faraci, E. Bertoletti, M. Vannucci, F. Tesi, P. Crippa, A. Malighetti, D. Bettini, F. Maltese, G. Abruzzese, D. Cosimo, M. Azzini, M. Colombo, G. Procino, S. Fascendini, F. Barocco, P. Del, A. Mazzone, E. Riva, D. Dell'Acqua, M. Cottino, G. Vezzadini, S. Avanzi, C. Brambilla, S. Orini, F. Sgrilli, A. Mello, L. Lombardi, E. Muti, B. Dijk, S. Fenu, C. Pes, P. Gareri, M. Passamonte, R. Rigo, L. Locusta, L. Caser, G. Rosso, S. Cesarini, R. Cozzi, C. Santini, P. Carbone, I. Cazzaniga, R. Lovati, A. Cantoni, P. Ranzani, D. Barra, G. Pompilio, S. Dimori, S. Cernesi, C. Riccò, F. Piazzolla, E. Capittini, C. Rota, F. Gottardi, L. Merla, A. Barelli, A. Millul, G. De, G. Morrone, M. Bigolari, M. Macchi, F. Zambon, C. Pizzorni, G. DiCasaleto, G. Menculini, M. Marcacci, G. Catanese, D. Sprini, T. DiCasalet, M. Bocci, S. Borga, P. Caironi, C. Cat, E. Cingolani, L. Avalli, G. Greco, G. Citerio, L. Gandini, G. Cornara, R. Lerda, L. Brazzi, F. Simeone, M. Caciorgna, D. Alampi, S. Francesconi, E. Beck, B. Antonini, K. Vettoretto, M. Meggiolaro, E. Garofalo, S. Notaro, R. Varutti, F. Bassi, G. Mistraletti, A. Marino, R. Rona, E. Rondelli, I. Riva, A. Scapigliati, A. Cortegiani, F. Vitale, L. Pistidda, R. D'Andrea, L. Querci, P. Gnesin, M. Todeschini, M. Lugano, G. Castelli, M. Ortolani, A. Cotoia, S. Maggiore, L. DiTizio, R. Graziani, I. Testa, E. Ferretti, C. Castioni, F. Lombardi, R. Caserta, M. Pasqua, S. Simoncini, F. Baccarini, M. Rispoli, F. Grossi, L. Cancelliere, M. Carnelli, F. Puccini, G. Biancofiore, A. Siniscalchi, C. Laici, E. Mossello, M. Torrini, G. Pasetti, S. Palmese, R. Oggioni, V. Mangani, S. Pini, M. Martelli, E. Rigo, F. Zuccalà, A. Cherri, R. Spina, I. Calamai, N. Petrucci, A. Caicedo, F. Ferri, P. Gritti, N. Brienza, R. Fonnesu, M. Dessena, G. Fullin, D. Saggioro, Morandi, A, Inzitari, M, Udina, C, Gual, N, Mota, M, Tassistro, E, Andreano, A, Cherubini, A, Gentile, S, Mossello, E, Marengoni, A, Olivé, A, Riba, F, Ruiz, D, de Jaime, E, Bellelli, G, Alessandro Morandi, Marco Inzitari, Cristina Udina, Neus Gual, Miriam Mota, Elena Tassistro, Anita Andreano, Antonio Cherubini, Simona Gentile, Enrico Mossello, Alessandra Marengoni, Anna Olivé, Francesc Riba, Domingo Ruiz, Elisabet de Jaime, Giuseppe Bellelli, Italian Study Group of Delirium, Claudio Borghi, Morandi, Alessandro, Inzitari, Marco, Udina, Cristina, Gual, Neu, Mota, Miriam, Tassistro, Elena, Andreano, Anita, Cherubini, Antonio, Gentile, Simona, Mossello, Enrico, Marengoni, Alessandra, Olivé, Anna, Riba, Francesc, Ruiz, Domingo, de Jaime, Elisabet, Bellelli, Giuseppe, and A Tarasconi, M Sella, S Auriemma, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, A Margola, L Porcella, I Nardiello, E Chimenti, M Zeni, A Giani, S Famularo, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, A Ballestrero, C Minaglia, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, F De, L Pietrogrande, B De, M Mosca, I Corazzin, P Rossi, V Nunziata, F D'Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena, M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell'Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, C Borghi, A Bianchetti, A Crucitti, V DiFrancesco, G Fontana, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta, D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, U Cannistrà, F Cassadonte, M Vatrano, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Seneci, F Fimognari, V Bambara, A Saitta, F Corica, M Braga, E Ettorre, C Camellini, G Bellelli, G Annoni, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, M Formilan, G Patrizia, M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl'Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, E D'Imporzano, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, M Alessandro, P Calogero, G Corvalli, F Di, D Pezzoni, C Platto, V D'Ambrosio, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, S Confente, M Bonetto, M Grasso, E Troisi, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, B Faraci, E Bertoletti, M Vannucci, F Tesi, P Crippa, A Malighetti, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D'Amico, A Grippa, A Mazzone, E Riva, D Dell'Acqua, M Cottino, G Vezzadini, S Avanzi, C Brambilla, S Orini, F Sgrilli, A Mello, L Lombardi, E Muti, B Dijk, S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, F De, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul, G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D'Amico, F D'Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Scapigliati, A Cortegiani, F Vitale, L Pistidda, R D'Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà, A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin, D Saggioro

Subjects
medicine.medical_specialty, Activities of daily living, Cross-sectional study, Hearing loss, medicine.medical_treatment, Visual impairment, Psychological intervention, visual impairment, Socio-culturale, behavioral disciplines and activities, Hearing impairment, delirium, older, sensory deficits, visual impairment, sensory deficit, Hearing impairment, 03 medical and health sciences, delirium, older, sensory deficits, 0302 clinical medicine, Risk Factors, Activities of Daily Living, mental disorders, medicine, Humans, Dementia, 030212 general & internal medicine, LS4_4, Hearing Loss, General Nursing, Rehabilitation, business.industry, Health Policy, General Medicine, medicine.disease, nervous system diseases, Cross-Sectional Studies, Italy, Emergency medicine, Delirium, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Published
2021

3. Androgen 5-alpha-reductase type 2 is highly expressed and active in rat spinal cord motor neurones

Author

P, Pozzi, C, Bendotti, S, Simeoni, F, Piccioni, V, Guerini, T U, Marron, L, Martini, and A, Poletti

Subjects
Male, Motor Neurons, Reverse Transcriptase Polymerase Chain Reaction, Rats, Isoenzymes, Rats, Sprague-Dawley, Mice, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Spinal Cord, Tumor Cells, Cultured, Animals, Tissue Distribution, RNA, Messenger, In Situ Hybridization
Abstract

Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT). This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2. The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values. We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat. The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor. Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens.

Published
2003

4. [Not Available]

Author

A, Di Bellucci and V, Guerini

Subjects
Italy, Dentistry, History, 19th Century, History, 20th Century, Journalism, Dental
Published
1995

5. [History of dentists]

Author

V, Guerini

Subjects
History, 17th Century, History of Dentistry, Dentists, Humans, History, 18th Century
Published
1981

7. Prevalence and features of delirium in older patients admitted to rehabilitation facilities

Author

Sidoli, Chiara, Zambon, Antonella, Tassistro, Elena, Rossi, Emanuela, Mossello, Enrico, Inzitari, Marco, Cherubini, Antonio, Marengoni, Alessandra, Morandi, Alessandro, Bellelli, Giuseppe, Tarasconi, A, Sella, M, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, Pietrogrande, L, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D’Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell’Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Bo, M, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Borghi, C, Bianchetti, A, Crucitti, A, Difrancesco, V, Fontana, G, Geriatria, A, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambar, V, Saitta, A, Corica, F, Braga, M, Servi, Null, Ettorre, E, Camellini Bellelli, C G, Annoni, G, Marengoni, A, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuar, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl’Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samysalamafahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Alessandro, M, Di, F, Pezzoni, D, Platto, C, D’Ambrosio, V, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, Corsini, C, Boffelli, S, Filippi, A, Delpin, K, Faraci, B, Bertoletti, E, Vannucci, M, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Cottino, M, Vezzadini, G, Avanzi, S, Brambilla, C, Orini, S, Sgrilli, F, Mello, A, Lombardi Muti, L E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, Barelli, A, Millul, A, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, 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Alessandro, P Calogero, G Corvalli, F Di, D Pezzoni, C Platto, V D’Ambrosio, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, M Bonetto, M Grasso, E Troisi, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, B Faraci, E Bertoletti, M Vannucci, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D’Amico, A Grippa , A Mazzone, M Cottino, G Vezzadini, S Avanzi, C Brambilla, S Orini, F Sgrilli, A Mello, L E Lombardi Muti, B Dijk , S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul , G De, G Morrone, M Bigolari, C Minaglia, M 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Saggioro, D

Subjects
Aging, Disability, Rehabilitation, Delirium, Dementia, Physical restraint, Cross-Sectional Studies, Activities of Daily Living, mental disorders, Prevalence, Humans, Geriatrics and Gerontology, Aged
Abstract

Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). Conclusion: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Published
2022
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8. The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017

Author

Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Margola, A, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, De, F, Pietrogrande, L, De, B, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Bianchetti, A, Crucitti, A, Di Francesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Pezzoni, D, Gentile, S, Platto, C, D'Ambrosio, V, Faraci, B, Brambilla, C, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, C Boffelli S, Corsini, Filippi, A, Delpin, K, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, A Millul A, Barelli, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Scapigliati, A, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, M, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Citerio, G, Zucchelli, Alberto, Valsecchi, M G, and A Tarasconi, M Sella, S Auriemma, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, A Margola, L Porcella, I Nardiello, E Chimenti, M Zeni, A Giani, S Famularo, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, A Ballestrero, C Minaglia, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, F De, L Pietrogrande, B De, M Mosca, I Corazzin, P Rossi, V Nunziata, F D'Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena, M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell'Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, A Bianchetti, A Crucitti, V Di Francesco, G Fontana, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta, D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, U Cannistrà, F Cassadonte, M Vatrano, F Cassandonte, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Fimognari, V Bambara, A Saitta, F Corica, M Braga, E Ettorre, C Camellini, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, G Patrizia, L Santuari, M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl'Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A SamySalamaFahmy, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, P Calogero, G Corvalli, D Pezzoni, S Gentile, A Morandi, C Platto, V D'Ambrosio, B Faraci, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, S Confente, M Bonetto, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, E Bertoletti, M Vannucci, F Tesi, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D'Amico, A Grippa, A Mazzone, E Riva, D Dell'Acqua, M Cottino, G Vezzadini, S Avanzi, S Orini, F Sgrilli, A Mello, L Lombardi, E Muti, B Dijk, S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, F De, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul, G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D'Amico, F D'Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Scapigliati, A Cortegiani, F Vitale, L Pistidda, R D'Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà, A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin, D Saggioro

Subjects
Male, Aging, medicine.medical_specialty, Sarcopenia, medicine.medical_treatment, Socio-culturale, Older person, Logistic regression, Delirium, Older persons, Sarcopenia, Internal medicine, mental disorders, Delirium, Older persons, medicine, Dementia, Humans, LS4_4, Muscle, Skeletal, Pathological, Aged, Rehabilitation, business.industry, Area under the curve, Settore MED/23 - Chirurgia Cardiaca, Skeletal, medicine.disease, Skeletal muscle mass, Cross-Sectional Studies, Italy, Muscle, Female, Geriatrics and Gerontology, medicine.symptom, business
Abstract

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Published
2022

10. Effect of COVID-19 on out-of-hospital cardiac arrest survival: No light at the end of the tunnel yet.

Author

Guerini Giusteri V, Caputo ML, Baldi E, Auricchio A, and Savastano S

Subjects
Humans, COVID-19, Out-of-Hospital Cardiac Arrest therapy
Abstract

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.

Published
2023
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11. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy-tolerability pilot study.

Author

Petrò E, Ruffini E, Cappuccio M, Guerini V, Belotti G, Fascendini S, Licini C, and Marcassa C

Abstract

Objective: This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment., Methods: This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer's disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events., Results: The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function., Conclusion: In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in these fragile individuals.

Published
2016
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12. A short low-dose imatinib trial allows rapid identification of responsive patients in hypereosinophilic syndromes.

Author

Intermesoli T, Delaini F, Acerboni S, Salmoiraghi S, Spinelli O, Guerini V, Vannucchi AM, Mappa S, Rossi G, Rossi V, Di Bona E, Paratore S, Carobbio A, Rambaldi A, Barbui T, and Bassan R

Subjects
Adult, Aged, Benzamides, Dose-Response Relationship, Drug, Drug Administration Schedule, Eosinophils pathology, Female, Gene Rearrangement, Humans, Hypereosinophilic Syndrome genetics, Imatinib Mesylate, Leukocyte Count, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Piperazines therapeutic use, Pyrimidines therapeutic use, Receptor, Platelet-Derived Growth Factor alpha genetics, Treatment Outcome, Young Adult, mRNA Cleavage and Polyadenylation Factors genetics, Hypereosinophilic Syndrome drug therapy, Piperazines administration & dosage, Pyrimidines administration & dosage
Abstract

Although imatinib may be effective in hypereosinophilic syndromes, the exact response kinetics are not known. Imatinib was administered at 100-400 mg/d each week in a 12-week response-oriented schedule, targeting a complete clinical and haematological remission (CR). CR was achieved in 11/23 patients (6/6 with FIP1L1-PDGRFA rearrangement and 5/17 without, P = 0.006), most after 2 weeks of 100 mg/d imatinib. The maximum imatinib dose had no effect in early unresponsive patients. Low-dose, short-course imatinib may represent a rational choice for identifying responsive cases, both within and outside the pre-defined FIP1L1 rearrangement subset.

Published
2009
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13. Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia.

Author

Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, Ruggeri M, Rodeghiero F, Rambaldi A, and Barbui T

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Cohort Studies, DNA Mutational Analysis, Female, Humans, Leukocytes cytology, Leukocytosis complications, Male, Middle Aged, Platelet Count, Risk Factors, Thrombocytosis complications, Leukocytosis diagnosis, Thrombocythemia, Essential complications, Thrombocythemia, Essential diagnosis, Thrombocytosis diagnosis
Abstract

To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2(V617F) mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet count at diagnosis greater than 1000 x 10(9)/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 x 10(9)/L, pointed to a "low-risk" category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2(V617F) mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors. These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis.

Published
2008
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14. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia.

Author

Vannucchi AM, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G, Ruggeri M, Specchia G, Lo-Coco F, Delaini F, Villani L, Finotto S, Ammatuna E, Alterini R, Carrai V, Capaccioli G, Di Lollo S, Liso V, Rambaldi A, Bosi A, and Barbui T

Subjects
Adult, Aged, Aged, 80 and over, Female, Genotype, Hemoglobins analysis, Humans, Male, Middle Aged, Phenotype, Platelet Activation, Platelet Count, Thrombocythemia, Essential blood, Thrombocythemia, Essential pathology, Thrombosis, Janus Kinase 2 genetics, Mutation, Receptors, Thrombopoietin genetics, Thrombocythemia, Essential genetics
Abstract

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

Published
2008
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15. Microhomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia.

Author

Mattarucchi E, Guerini V, Rambaldi A, Campiotti L, Venco A, Pasquali F, Lo Curto F, and Porta G

Subjects
Base Sequence, Cohort Studies, Humans, Molecular Sequence Data, Recombination, Genetic, Sequence Homology, Nucleic Acid, Chromosome Breakage, Chromosomes, Human, Pair 22 genetics, Chromosomes, Human, Pair 9 genetics, Fusion Proteins, bcr-abl genetics, Interspersed Repetitive Sequences genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Translocation, Genetic genetics
Abstract

Reciprocal translocation t(9;22) is central to the pathogenesis of chronic myeloid leukemia. Some authors have suggested that Alu repeats facilitate this process, but supporting analyses have been sparse and often anecdotal. The purpose of this study was to analyze the local structure of t(9;22) translocations and assess the relevance of interspersed repeat elements at breakpoints. Collected data have been further compared with the current models of DNA recombination, in particular the single-strand annealing (SSA) and the nonhomologous end joining (NHEJ) processes. We developed a protocol for the rapid characterization of patient-specific genomic junctions and analyzed 27 patients diagnosed with chronic myeloid leukemia. Sequence analysis revealed microhomologies at the junctions of 21 patients of 27, while interspersed repeats were of relevance (P < 0.05) in at least 16 patients. These findings are more frequent than expected and give an indication that the main mechanisms involved in the t(9;22) translocation are the SSA and NHEJ pathways, both playing a role. Furthermore, our report is consistent with microhomologies facilitating the joining of DNA ends in the translocation process, and with both Alu and a variety of other repeat sequences pairing nonhomologous chromosomes during the SSA pathway., ((c) 2008 Wiley-Liss, Inc.)

Published
2008
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16. Leukocytosis and risk stratification assessment in essential thrombocythemia.

Author

Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, Finazzi G, Rambaldi A, and Barbui T

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Aging blood, Child, Female, Genotype, Humans, Janus Kinase 2 classification, Leukocytosis enzymology, Leukocytosis genetics, Male, Middle Aged, Polycythemia Vera physiopathology, Prognosis, Proportional Hazards Models, Risk Factors, Janus Kinase 2 genetics, Leukocytosis complications, Thrombocythemia, Essential complications, Thrombosis etiology
Abstract

Purpose: Established risk factors for thrombosis in essential thrombocythemia (ET) include age and previous vascular events. We aimed to refine this risk stratification by adding baseline leukocytosis., Patients and Methods: We enrolled 657 patients with ET followed for a median of 4.5 years who developed 72 major thrombosis. Cox proportional hazard model was performed to analyze the thrombotic risk and to discriminate ET patients with or without thrombosis, multivariable C statistic index was used. We searched for leukocytes cutoff with the best sensitivity and specificity by a receiver operating characteristic curve., Results: Results confirmed that age and prior events are independent risk factors for thrombosis and showed a gradient between baseline leukocytosis and thrombosis. On the contrary, no significant association was found either for JAK2(V617F) allele burden and for other laboratory parameters, including platelet number. In the model with conventional risk factors alone, C statistic ratio for total thrombosis was 0.63 and when leukocytosis was added, the change was small (C = 0.67). In contrast, in younger and asymptomatic patients (low-risk category), C statistic value indicated an high risk for thrombosis in patients with leukocytosis, similar to that calculated in conventionally defined high-risk group (C = 0.65). The best leukocyte cutoff values for predicting the events was found to be 9.4 (x 10(9)/L)., Conclusion: We suggest to include baseline leukocytosis in the risk stratification of ET patients enrolled in clinical trials.

Published
2008
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17. The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F).

Author

Guerini V, Barbui V, Spinelli O, Salvi A, Dellacasa C, Carobbio A, Introna M, Barbui T, Golay J, and Rambaldi A

Subjects
Cell Line, Tumor, Cell Proliferation drug effects, Down-Regulation drug effects, Drug Delivery Systems, Humans, Janus Kinase 2 analysis, Mutation, Missense, Polycythemia Vera pathology, STAT Transcription Factors analysis, Thrombocythemia, Essential pathology, Tumor Cells, Cultured, Histone Deacetylase Inhibitors, Hydroxamic Acids pharmacology, Janus Kinase 2 genetics, Polycythemia Vera drug therapy, Thrombocythemia, Essential drug therapy
Abstract

We investigated the activity of ITF2357, a novel histone deacetylase inhibitor (HDACi) with antitumor activity, on cells carrying the JAK2(V617F) mutation obtained from polycythemia vera (PV) and essential thrombocythemia (ET) patients as well as the HEL cell line. The clonogenic activity of JAK2(V617F) mutated cells was inhibited by low concentrations of ITF2357 (IC(50) 0.001-0.01 microM), 100- to 250-fold lower than required to inhibit growth of normal or tumor cells lacking this mutation. Under these conditions, ITF2357 allowed a seven fold increase in the outgrowth of unmutated over mutated colonies. By western blotting we showed that in HEL cells, ITF2357 led to the disappearance of total and phosphorylated JAK2(V617F) as well as pSTAT5 and pSTAT3, but it did not affect the wild-type JAK2 or STAT proteins in the control K562 cell line. By real-time PCR, we showed that, upon exposure to ITF2357, JAK2(V617F) mRNA was not modified in granulocytes from PV patients while the expression of the PRV-1 gene, a known target of JAK2, was rapidly downmodulated. Altogether, the data presented suggest that ITF2357 inhibits proliferation of cells bearing the JAK2(V617F) mutation through a specific downmodulation of the JAK2(V617F) protein and inhibition of its downstream signaling.

Published
2008
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18. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden.

Author

Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, Bogani C, Ferrini PR, Rambaldi A, Guerini V, Bosi A, and Barbui T

Subjects
Adult, Aged, Aged, 80 and over, Alleles, Cardiovascular Diseases epidemiology, Female, Genetic Predisposition to Disease epidemiology, Humans, Male, Middle Aged, Polycythemia Vera pathology, Predictive Value of Tests, Prospective Studies, Pruritus epidemiology, Risk Factors, Splenomegaly epidemiology, Thrombosis epidemiology, Janus Kinase 2 genetics, Point Mutation, Polycythemia Vera epidemiology, Polycythemia Vera genetics
Abstract

The aim of this study was to determine whether the burden of JAK2(V617F) allele correlated with major clinical outcomes in patients with polycythemia vera (PV). To this end, we determined JAK2 mutant allele levels in granulocytes of 173 PV patients at diagnosis. The mean (+/-s.d.) mutant allele burden was 52% (+/-29); 32 patients (18%) had greater than 75% mutant allele. The burden of JAK2(V617F) allele correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume, serum ferritin and erythropoietin levels) and myelopoiesis (higher white cell count, neutrophil count and serum lactate dehydrogenase) and with markers of neutrophil activation (elevated leukocyte alkaline phosphatase and PRV-1 expression). As compared to those with less than 25% mutant allele, patients harboring greater than 75% JAK2(V617F) allele were at higher relative risk (RR) of presenting larger spleen (RR 4.7; P<0.001) or suffering from pruritus (RR 3.1; P<0.001). In these patients, the risk of requiring chemotherapy (RR 1.8; P=0.001) or developing major cardiovascular events (RR 7.1; P=0.003) during follow up were significantly increased. We conclude that a burden of JAK2(V617F) allele greater than 75% at diagnosis points to PV patients with high-risk disease.

Published
2007
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19. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia.

Author

Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, Marfisi RM, Finazzi G, Guerini V, Fabris F, Randi ML, De Stefano V, Caberlon S, Tafuri A, Ruggeri M, Specchia G, Liso V, Rossi E, Pogliani E, Gugliotta L, Bosi A, and Barbui T

Subjects
Adult, Aged, Amino Acid Substitution, Cardiovascular Diseases blood, Cardiovascular Diseases etiology, Cardiovascular Diseases genetics, Cardiovascular Diseases pathology, Female, Hematocrit, Heterozygote, Humans, Leukocyte Count, Male, Middle Aged, Organ Size, Polycythemia Vera complications, Polycythemia Vera genetics, Polycythemia Vera pathology, Pruritus blood, Pruritus etiology, Pruritus genetics, Pruritus pathology, Retrospective Studies, Risk Factors, Spleen pathology, Thrombocythemia, Essential complications, Thrombocythemia, Essential genetics, Thrombocythemia, Essential pathology, Thrombosis blood, Thrombosis etiology, Thrombosis genetics, Thrombosis pathology, Homozygote, Janus Kinase 2 genetics, Mutation, Missense, Polycythemia Vera blood, Thrombocythemia, Essential blood
Abstract

JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET). Whether homozygosity associates with distinct clinical phenotypes is still under debate. This retrospective multicenter study considered 118 JAK2 617V>F homozygous patients (104 PV, 14 ET) whose clinical characteristics were compared with those of 587 heterozygous and 257 wild-type patients. Irrespective of their clinical diagnosis, homozygous patients were older, displayed a higher leukocyte count and hematocrit value at diagnosis, and presented larger spleen volume. Aquagenic pruritus was significantly more common among homozygous PV patients. JAK2 617V>F homozygosity associated with more frequent evolution into secondary myelofibrosis in both PV and ET. After adjustment for sex, age, leukocyte count, and previous thrombosis in a multivariate analysis, homozygous ET patients displayed a significantly higher risk of cardiovascular events (hazard ratio [HR] 3.97, 95% confidence interval [CI] 1.34-11.7; P = .013) than wild-type (HR = 1.0) or heterozygous patients (HR = 1.49). No significant association of JAK2 617V>F homozygosity with thrombosis risk was observed in PV. Finally, JAK2 617V>F homozygous patients were more likely to receive chemotherapy for control of disease. We conclude that JAK2 617V>F homozygosity identifies PV or ET patients with a more symptomatic myeloproliferative disorder and is associated with a higher risk of major cardiovascular events in patients with ET.

Published
2007
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20. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia.

Author

Spinelli O, Peruta B, Tosi M, Guerini V, Salvi A, Zanotti MC, Oldani E, Grassi A, Intermesoli T, Micò C, Rossi G, Fabris P, Lambertenghi-Deliliers G, Angelucci E, Barbui T, Bassan R, and Rambaldi A

Subjects
Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Basic Helix-Loop-Helix Transcription Factors genetics, Benzamides, Biomarkers, Tumor blood, Clinical Trials as Topic statistics & numerical data, Cohort Studies, Combined Modality Therapy, Female, Fusion Proteins, bcr-abl blood, Gene Deletion, Gene Rearrangement, B-Lymphocyte, Gene Rearrangement, T-Lymphocyte, Humans, Imatinib Mesylate, Kaplan-Meier Estimate, Kinetics, Leukemia-Lymphoma, Adult T-Cell blood, Leukemia-Lymphoma, Adult T-Cell drug therapy, Leukemia-Lymphoma, Adult T-Cell genetics, Leukemia-Lymphoma, Adult T-Cell mortality, Leukemia-Lymphoma, Adult T-Cell pathology, Leukemia-Lymphoma, Adult T-Cell surgery, Male, Middle Aged, Multicenter Studies as Topic, Myeloid-Lymphoid Leukemia Protein blood, Neoplasm, Residual, Oncogene Proteins, Fusion blood, Piperazines administration & dosage, Polymerase Chain Reaction, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma surgery, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma surgery, Proto-Oncogene Proteins genetics, Pyrimidines administration & dosage, Remission Induction, Risk, Survival Analysis, Survival Rate, T-Cell Acute Lymphocytic Leukemia Protein 1, Translocation, Genetic, Transplantation Conditioning, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Transplantation, Homologous
Abstract

Background and Objectives: The molecular analysis of minimal residual disease (MRD) may provide information on the risk of recurrence in patients with acute lymphoblastic leukemia (ALL). The aim of this study was to correlate the kinetics of MRD clearance after allogeneic transplantation with the clinical outcome of adults with ALL., Design and Methods: MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) using probes derived from fusion chimeric genes (BCR/ABL and MLL/AF4) (n=22) or rearrangements of the T-cell receptor or immunoglobulin genes (n=21). Forty-three adult patients with ALL were studied to correlate the kinetics of MRD clearance before and after allogeneic hematopoietic stem cell transplantation., Results: At 36 months, the overall survival of patients who underwent transplantation in hematologic remission (n= 37) was 80% for those who were PCR-negative before transplantation (n= 12) compared to 49% for PCR-positive patients (n= 25)(p=0.17). For the same patients the cumulative incidence of relapse was 0% and 46%, respectively (p=0.027). Moreover, the relapse rate of patients who were PCR-negative at day +100 after transplantation was remarkably low (7%) compared to that among patients who were PCR-positive (80%, p=0.0006)., Interpretation and Conclusions: The kinetics of MRD clearance may help to identify patients at high risk of leukemia relapse after allogeneic stem cell transplantation. Patients not achieving an early molecular remission after transplantation require prompt and appropriate pre-emptive treatments such as infusions of donor lymphocytes or new experimental drugs.

Published
2007
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21. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules.

Author

Falanga A, Marchetti M, Vignoli A, Balducci D, Russo L, Guerini V, and Barbui T

Subjects
Adult, Aged, Aged, 80 and over, Amino Acid Substitution, Cell Adhesion Molecules blood, Female, Hemostatics blood, Humans, Male, Middle Aged, Mutation, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential metabolism, Blood Platelets metabolism, Cell Adhesion Molecules metabolism, Granulocytes metabolism, Hemostatics metabolism, Janus Kinase 2 genetics, Thrombocythemia, Essential genetics
Abstract

Objective: This article evaluates patients with essential thrombocythemia (ET) to determine whether the V617F mutation in the JAK2 gene affects platelet hemostatic and adhesive molecules, platelet-polymorphonuclear leukocyte (PMN) interactions, and PMN-activation characteristics, as well as plasma hypercoagulation markers., Patients and Methods: Thirty-seven ET patients with V617F JAK2 mutation and 38 wild-type, and 50 healthy controls were studied., Results: Platelets from overall ET patients, compared to controls, expressed significantly higher membrane tissue factor (TF) and P-selectin (p < 0.01) and lower CD41 and CD42b (p < 0.01). TF appeared significantly higher in the V617F JAK2 carriers compared to wild-type, and total platelet TF antigen levels confirmed the same result. The presence of circulating platelet/PMN aggregates was significantly greater in the JAK2-mutation carriers than in the wild-type and controls (p < 0.05). PMN surface activation and inflammatory markers (i.e., CD14, TF, CD11b, and leukocyte alkaline phosphatase [LAP]) were all significantly higher in ET versus control subjects, with CD14 and LAP being the highest in the JAK2 mutation carriers. Finally, a significant increase in plasma hypercoagulation markers was found in ET patients, and the only difference for the V617F JAK2 carriers was higher plasma thrombomodulin levels (p < 0.01). Differences in white blood cell and PMN count, platelet TF, PMN CD14, and LAP, and plasma thrombomodulin remained significant after multivariate analysis., Conclusions: These results show that a correlation exists between the presence of V617F JAK2 mutation and selected hemostatic activation variables.

Published
2007
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22. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status.

Author

Carobbio A, Finazzi G, Guerini V, Spinelli O, Delaini F, Marchioli R, Borrelli G, Rambaldi A, and Barbui T

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Janus Kinase 2 metabolism, Leukocytosis complications, Leukocytosis genetics, Male, Middle Aged, Risk Factors, Thrombocythemia, Essential enzymology, Thrombocythemia, Essential genetics, Thrombosis drug therapy, Thrombosis genetics, Janus Kinase 2 genetics, Leukocytosis enzymology, Leukocytosis pathology, Mutation genetics, Thrombocythemia, Essential complications, Thrombocythemia, Essential drug therapy, Thrombosis complications, Thrombosis enzymology
Abstract

Leukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis," relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P = .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis ("time-dependent analysis," RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P = .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies.

Published
2007
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23. Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation status.

Author

Finazzi G, Rambaldi A, Guerini V, Carobbo A, and Barbui T

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Risk, Janus Kinase 2 genetics, Mutation, Polycythemia Vera complications, Polycythemia Vera genetics, Thrombocytopenia complications, Thrombocytopenia genetics, Thrombosis complications, Thrombosis genetics, Thrombosis pathology
Abstract

We compared the laboratory and clinical findings of 179 patients with essential thrombocythemia (ET) and 77 with polycythemia vera (PV) classified according to the presence of the JAK2 V617F mutation. A gradient was observed in laboratory values between patients with JAK2 wild-type ET, JAK2 V617F ET and PV (all of whom carried the JAK2 mutation). The rate of thrombotic complications in JAK2-positive ET patients was significantly higher than that in wild-type ET patients and not statistically different from that in PV patients.

Published
2007
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24. The androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits prostate cancer cell migration through activation of the estrogen receptor beta subtype.

Author

Guerini V, Sau D, Scaccianoce E, Rusmini P, Ciana P, Maggi A, Martini PG, Katzenellenbogen BS, Martini L, Motta M, and Poletti A

Subjects
Anabolic Agents pharmacology, Cadherins physiology, Cell Line, Tumor, Cell Migration Inhibition, Dihydrotestosterone metabolism, Dihydrotestosterone pharmacology, Humans, Male, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Receptors, Androgen biosynthesis, Receptors, Androgen genetics, Receptors, Androgen metabolism, Transfection, Androstane-3,17-diol pharmacology, Cell Movement drug effects, Estrogen Receptor beta physiology, Prostatic Neoplasms drug therapy
Abstract

Prostate cancer growth depends, in its earlier stages, on androgens and is usually pharmacologically modulated with androgen blockade. However, androgen-ablation therapy may generate androgen-independent prostate cancer, often characterized by an increased invasiveness. We have found that the 5alpha-reduced testosterone derivative, dihydrotestosterone (the most potent natural androgen) inhibits cell migration with an androgen receptor-independent mechanism. We have shown that the dihydrotestosterone metabolite 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), a steroid which does not bind androgen receptors, but efficiently binds the estrogen receptor beta (ERbeta), exerts a potent inhibition of prostate cancer cell migration through the activation of the ERbeta signaling. Very surprisingly, estradiol is not active, suggesting the existence of different pathways for ERbeta activation in prostate cancer cells. Moreover, 3beta-Adiol, through ERbeta, induces the expression of E-cadherin, a protein known to be capable of blocking metastasis formation in breast and prostate cancer cells. The inhibitory effects of 3beta-Adiol on prostate cancer cell migration is counteracted by short interfering RNA against E-cadherin. Altogether, the data showed that (a) circulating testosterone may act with estrogenic effects downstream in the catabolic process present in the prostate, and (b) that the estrogenic effect of testosterone derivatives (ERbeta-dependent) results in the inhibition of cell migration, although it is apparently different from that linked to estradiol on the same receptor and may be protective against prostate cancer invasion and metastasis. These results also shed some light on clinical observations suggesting that alterations in genes coding for 3beta-hydroxysteroid dehydrogenases (the enzymes responsible for 3beta-Adiol formation) are strongly correlated with hereditary prostate cancer.

Published
2005
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25. Androgen-induced neurite outgrowth is mediated by neuritin in motor neurones.

Author

Marron TU, Guerini V, Rusmini P, Sau D, Brevini TA, Martini L, and Poletti A

Subjects
Animals, Base Sequence, Cell Line, Transformed, Cell Line, Tumor, GPI-Linked Proteins, Mice, Molecular Sequence Data, Motor Neurons cytology, Neuropeptides deficiency, Neuropeptides genetics, Androgens pharmacology, Motor Neurons drug effects, Motor Neurons physiology, Neurites drug effects, Neurites physiology, Neuropeptides physiology
Abstract

In the brain, the spinal cord motor neurones express the highest levels of the androgen receptor (AR). Experimental data have suggested that neurite outgrowth in these neurones may be regulated by testosterone or its derivative 5alpha-dihydrotestosterone (DHT), formed by the 5alpha-reductase type 2 enzyme. In this study we have produced and characterized a model of immortalized motor neuronal cells expressing the mouse AR (mAR) [neuroblastoma-spinal cord (NSC) 34/mAR] and analysed the role of androgens in motor neurones. Androgens either activated or repressed several genes; one has been identified as the mouse neuritin, a protein responsible for neurite elongation. Real-time PCR analysis has shown that the neuritin gene is expressed in the basal condition in immortalized motor neurones and is selectively up-regulated by androgens in NSC34/mAR cells; the DHT effect is counteracted by the anti-androgen Casodex. Moreover, DHT induced neurite outgrowth in NSC34/mAR, while testosterone was less effective and its action was counteracted by the 5alpha-reductase type 2 enzyme inhibitor finasteride. Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration.

Published
2005
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26. Androgen 5-alpha-reductase type 2 is highly expressed and active in rat spinal cord motor neurones.

Author

Pozzi P, Bendotti C, Simeoni S, Piccioni F, Guerini V, Marron TU, Martini L, and Poletti A

Subjects
3-Oxo-5-alpha-Steroid 4-Dehydrogenase genetics, Animals, In Situ Hybridization, Isoenzymes genetics, Isoenzymes metabolism, Male, Mice, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord cytology, Tissue Distribution, Tumor Cells, Cultured, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase metabolism, Motor Neurons metabolism, Spinal Cord metabolism
Abstract

Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT). This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2. The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values. We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat. The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor. Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens.

Published
2003
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27. Characterization of prostate cancer DU145 cells expressing the recombinant androgen receptor.

Author

Scaccianoce E, Festuccia C, Dondi D, Guerini V, Bologna M, Motta M, and Poletti A

Subjects
Blotting, Southern, Blotting, Western, Cell Division drug effects, Cell Line, Tumor, Humans, Immunohistochemistry, Male, Mutation, Plasminogen Activators biosynthesis, Polymerase Chain Reaction, Prostate-Specific Antigen biosynthesis, Prostatic Neoplasms metabolism, Receptors, Androgen genetics, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Testosterone pharmacology, Transfection, Urokinase-Type Plasminogen Activator biosynthesis, Prostatic Neoplasms pathology, Receptors, Androgen biosynthesis
Abstract

Prostate cancer (PC) develops as a consequence of abnormal androgenic stimulation. Unfortunately, most of the PC cell lines are androgen independent (like DU145), or express mutated forms of androgen receptor (AR). We have produced and characterized a new stably transfected PC line expressing the AR (DU145-AR). Untreated DU145-AR cells showed a lower proliferation rate than mock transfected cells, but responded to testosterone treatment. PSA mRNA, undetectable in mock DU145 cells, was present and upregulated by testosterone in DU145-AR. About 5% of DU 145-AR cells showed modification of morphology and enriched of f-actin after testosterone treatment. Moreover, in DU145-AR plasminogen activator (PA) activity and secreted urokinase type plasminogen activator (uPA) protein were lower than in AR negative cells; again testosterone induced PA activity and uPA protein only in DU145-AR. These results indicate that, in general, the effects of unactivated AR is to suppress function(s) in DU145 cells and the addition of testosterone restores the normal properties associated with the untransfected cells. Some of the effects described may thus be mediated by a ligand-independent activation of AR in DU145 cells.

Published
2003
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28. [History of dentists].

Author

Guerini V

Subjects
History of Dentistry, History, 17th Century, History, 18th Century, Humans, Dentists
Published
1981

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