Revision de casos, estudio inmunohistoquimico y expresion del CKIT en Melanomas de mucosa sinonasal, diagnosticados en los hospitales Clinico Universitario "Lozano Blesa" de Zaragoza y Complejo Hospitalario de Navarra en Pamplona, desde 1990 hasta 2016.

Los melanomas de mucosa sinonasal (SNMM) son entidades agresivas e infrecuentes, originadas en melanocitos presentes en el epitelio y estroma de la mucosa respiratoria. El diagnóstico es complicado debido a su morfología, distintos patrones arquitecturales/citológicos y ocasional ausencia de pigmento melánico. La mutación KIT, identificada en melanomas en 2004, esta descrita en aproximadamente 15-30% de los melanomas acrales y mucosos. Su estudio, plantea aprovechar el potencial terapéutico de fármacos inhibidores de la tirosinquinasa. Se revisaron los casos de SNMM, en los servicios de anatomía patológica de los Hospitales Clínico Universitario “Lozano Blesa” de Zaragoza y Complejo Hospitalario de Navarra en Pamplona, entre enero 1990 y junio 2016. Se estudiaron histológico e Inmunohistoquímicamente, incluyendo la técnica CKIT/CD117. Se recopilaron seis casos, cuatro epitelioides, un fusocelular y un plasmocitoide, todos ellos diagnosticados en adultos/ancianos, con características acordes a las descritas en la literatura. La expresión del CKIT (CD117) fue positiva en todos los casos. El tratamiento de elección fue la cirugía en todos los pacientes, algunos con posterior radioterapia. La sobrevida no fue mayor a tres años. Se plantea la utilidad de la tinción inmunohistoquímica como posible complemento al panel diagnóstico, el estudio mediante FISH para confirmar la presencia de la mutación y considerar una probable connotación terapéutica con inhibidores de la tirosinquinasa

Revisión actualizada del carcinoma de célula pequeña de pulmón. ¿Por qué difiere tanto con otros tumores?

INTRODUCCIÓN. El carcinoma de célula pequeña o microcítico es un tumor neuroendocrino muy agresivo, siendo el tumor con mayor mortalidad. El tratamiento de este tumor apenas ha variado, presentando muy buena respuesta quimioterápica al inicio, pero haciéndose resistente al poco tiempo. Al diagnóstico, la mayor parte de los pacientes tiene la enfermedad diseminada. En otros tumores pulmonares los avances en el campo de la biología molecular han dado lugar a efectivas terapias como la inmunoterapia, que están empezando a ser aplicadas a este tumor en diversos estudios. OBJETIVO. El objetivo principal es obtener una revisión actualizada de este tumor, incluyendo los nuevos campos como la inmunoterapia y una revisión de la biología molecular, buscando nuevas posibles terapias y diferenciando la evolución respecto al carcinoma de célula no pequeña en los últimos avances. MATERIAL Y MÉTODOS. Se realizaron 3 búsquedas principales; la primera en diciembre del 2017 en cuatro bases de datos diferentes con un resultado total de 730 artículos. La segunda se realizó para acotar datos y añadir información, en febrero del 2018 con un total de 66 resultados. En abril de 2018 se realizó la última búsqueda para buscar novedades respecto al tema en cuestión y se obtuvieron un total de 241 artículos. Finalmente, se seleccionaron 33, 6 y 14 artículos de las respectivas búsquedas. RESULTADOS. Diversos ensayos están aún en progresión para analizar si realmente la inmunoterapia es una vía factible en este tumor. El tratamiento actual sigue siendo la quimioterapia. La biopsia líquida ofrece una alternativa a la convencional, siendo las células tumorales circulantes una buena vía para ampliar la información que tenemos de este tumor mediante el estudio de la biología molecular de estas células. CONCLUSIONES. A pesar del gran avance en la información que otorga la biología molecular, no se puede decir que actualmente este avance se aprecie en los campos de la terapéutica. A diferencia con otros tumores, en el CPCP la biología molecular y la inmunoterapia, de momento, no han avanzado lo suficiente como para obtener resultados respecto a la mortalidad, lo cual no implica que en un futuro no se puedan obtener nuevas dianas terapéuticas desde estos campos de investigación.<br /

INHIBIDORES DEL PUNTO DE CONTROL INMUNOLÓGICO PD-1/PD-L1

El cáncer de pulmón constituye la principal causa de muerte por cáncer en todo el mundo. La resección quirúrgica con intención curativa es el tratamiento de elección hoy en día, sin embargo, la mayoría de casos se diagnostican en estadíos avanzados, por lo que el pronóstico es sombrío. Dentro del tratamiento no quirúrgico del cáncer de pulmón, que se basa fundamentalmente en quimioterapia y radioterapia, las técnicas de inmunoterapia están ganando protagonismo en los últimos años. Los inhibidores del complejo PD-1/PD-L1, son unos fármacos recientes, tipo anticuerpos monoclonales humanizados, con resultados prometedores, cuyo mecanismo de acción se basa en inhibir dicho complejo, en especial el receptor PD-1, que es utilizado por las células tumorales para escapar del ataque del sistema inmune y así evitar ser eliminadas. Para que estos fármacos sean eficaces frente al tumor, las células tumorales deben expresar la proteína PD-1 en su membrana en un porcentaje suficiente, ya que si esto no sucede así los fármacos carecen de diana y el tumor escapa a los controles del organismo por otras vías, aún desconocidas. El papel del anatomopatólogo es fundamental para determinar si las células tumorales de la muestra expresan o no dicha proteína y en qué porcentaje (Score de expresión del receptor: alta y baja expresión), constituyendo así el pilar fundamental para el inicio del tratamiento con este tipo de fármacos, que han demostrado un aumento de la supervivencia global, de la tasa de respuesta objetiva y de la supervivencia libre de progresión, en comparación con las terapias convencionales hasta la fecha

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Delirium in nursing home residents: is there a role of antidepressants? A cross sectional study.

Background: Delirium is strongly associated with poor health outcomes, yet it is frequently underdiagnosed. Limited research on delirium has been conducted in Nursing Homes (NHs). Our aim is to assess delirium prevalence and its associated factors, in particular pharmacological prescription, in this care setting. Methods: Data from the Italian "Delirium Day" 2016 Edition, a national multicenter point-prevalence study on patients aged 65 and older were analyzed to examine the associations between the prevalence of delirium and its subtypes with demographics and information about medical history and pharmacological treatment. Delirium was assessed using the Assessment test for delirium and cognitive impairment (4AT). Motor subtype was evaluated using the Delirium Motor Subtype Scale (DMSS). Results: 955 residents, from 32 Italian NHs with a mean age of 84.72 ± 7.78 years were included. According to the 4AT, delirium was present in 260 (27.2%) NHs residents, mainly hyperactive (35.4%) or mixed subtypes (20.7%). Antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with lower delirium prevalence in univariate and multivariate analyses. Conclusions: The high prevalence of delirium in NHs highlights the need to systematically assess its occurrence in this care settings. The inverse association between SSRIs and delirium might imply a possible preventive role of this class of therapeutic agents against delirium in NHs, yet further studies are warranted to ascertain any causal relationship between SSRIs intake and reduced delirium incidence

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

reserved1229noObjective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.mixedAloisi Gaetano, Marengoni Alessandra, Morandi Alessandro, Zucchelli, Alberto, Cherubini Antonio, Mossello Enrico, Bo Mario, Di Santo Simona, Mazzone Andrea, Trabucchi Marco, Cappa Stefano, Fimognari Filippo, Antonelli Incalzi Raffaele, Gareri Pietro, Perticone Francesco, Campanini Mauro, Montorsi Marco, Latronico Nicola, Zambon Antonella, Bellelli Giuseppe, Rispoli Vincenzo, Malara Alba, Spadea Fausto, Di Cello Serena, Ceravolo Francesco, Fabiano Francesco, Chiaradia Giuseppe, Gabriele Amedeo, Lenino Peluso, Andrea Taristano, Settembrini Vincenzo, Capomolla Domenico, Citrino Antonella, Scriva Antonietta, Bruno Irene, Secchi Roberto, De Martino Eugenio, Muccinelli Roberto, Lupi Gerardo, Paonessa Patrizio, Fabbri Andrea, Passuti Maria Teresa, Castellari Sofia, Po Andrea, Gaggioli Guido, Varesi Massimo, Moneti Paolo, Capurso Sebastiano, Latini Vincenzo, Ghidotti Stefano, Riccardelli Francesco, Macchi Maurizio, Rigo Rosaria, Claudio Pascale, Bosio Angelo, Cerrato Flavio, Bardelli Benedetta, Boffelli Stefano, Cassinadri Angela, Franzoni Simone, Spazzini Elena, Andretto Daniela, Tonini Gabriele, Andreani Laura, Coralli Mirco, Balotta Antonio, Cancelliere Roberto, Ballardini Giorgio, Simoncelli Margherita, Mancini Annarita, Strazzacapa Mara, Fabio Stefano, De Filippi Francesco, Giudice Chiara, Dentizzi Cosimo, Azzini Margherita, Cazzadori Marco, Mastroeni Valeria, Bertassello Paolo, Santana Helena, Benati Claudia, Nesta Elisa, Tobaldini Chiara, Guerini Fabio, Tambara Elena, Mombelloni Paolo, Fontanini Fulvio, Lassa Gabriella, Lassa, Pizzorni Crosio, Oliverio Martina, del Grosso, Luciano Luca, Giavedoni Cristina, Bidoli Giuliano, Mazzei Bruno, Corsonello Andrea, Fusco Sergio, Vena Silvio, De Vuono Tommaso, Maiuri Giorgio, Fimognari Filippo Luca, Arone Andrea, Sgro Giovanni, Nicolazzo Rossella, Castegnaro Eugenio, De Rosa Salvatore, Sechi Bazzano Rossella, Benvenuti Enrico, Del Lungo Ilaria, Giardini Sante, Giulietti Chiara, Di Bari Mauro, Barghini Eleonora, Paoli Martina, Fiordelli Irene, Barucci Riccardo, Sgrilli Federica, Del Lungo Ilaria, Bertoletti Erik, D'Amico Ferdinando, Caronzolo Francesco, Grippa Alessandro, Lombardo Giuseppina, Pipicella Tiziana, Saitta Antonino, Corica Francesco, Cucinotta Valeria, Giaritta Prestipino, Larosa Daniela, Cucinotta Domenico, Basile Giorgio, March Albert, Nitti Maria Teresa, Felici Alessandro, Pavan Silvia, Piazzani Fabrizio, Lunelli Alessandra, Dimori Sergio, Margotta Alessandro, Soglia Tiziano, Postacchini Demetrio, Brunelli Roberto, Santini Silvia, Francavilla Monia, Macchiati Ilenia, Sorvillo Francesca, Giuli Cinzia, Mecocci Patrizia, Longo Annalisa, Perticone Francesco, Addesi Desiree, Rosa Paola Cerra, Bencardino Giuseppe, Falbo Tania, Grillo Nadia, Filice Marco, Mirella Filippo, Fanto Fausto, Isaia Gianluca, Pezzilli Stella, Bergamo Daniele, Furno Elisabetta, Rrodhe Sokol, Lucarini Simonetta, Dijk Babette, Dall'Acqua Francesca, Cappelletto Francesco, Calvani Donatella, Becheri Dimitri, Mottino Giuseppe, Mitidieri Costanza, Antonio Vito, Bartalucci Francesca, Magherini Lorenza, Malin Novella, Boni Franca, Gambardella Paoli Martina Lucia, Valente Carlo, Bracali Ilaria, Bracali, Foschini Alice, Bo Mario, Porrino Paola, Ceci Giacomo, Bottignole Giuliana, Tibaldi Michela, Coppo Eleonora, Ettore Evaristo, Camellini Cinzia, Servello Adriana, Grassi Alessandro, Rozzini Renzo, Tironi Sara, Grassi Maria Grazia, Troisi Elio, Caltagirone Carlo, Di Santo Simona, Franchini Flaminia, Ratto Federica, Pavoni Beatrice, Toniolo Sofia, Gabutto Anna, Quazzo Loredana, Rosatello Annalisa, Suraci Domenico, Tagliabue Benedetta, Perrone Chiara, Ferrara Lucia, Castagna Alberto, Tremolada Maria Luisa, Castoldi Giuseppe, Barbero Stefano, Oltramonti Davide, Piano Simonetta, Serviddio Gaetano, Lo Buglio Aurelio, Gurrera Tiziana, Merlo Valeria, Rovai Carla, Cotroneo Antonino Maria, Carlucci Rosaria, Abbaldo Anna, Monzani Fabio, Qasem Ahmad Amedeo, Bini Giacomo, Tafuto Silvia, Galli Giovanni, Bruni Amalia Cecilia, Mancuso Giovanna, Mancuso Gerardo, Calipari Daniela. De Luca Giuseppe Massimiliano, Bernardini Bruno, Corsini Carla, Ciccarelli Michele, Dal Farra Sara, Dal Farra, Cagnin Annachiara, Fragiacomo Federica, Pompanin Sara, Amodio Piero, Cagnin Marco, Zurlo Amedeo, Guerra Gianluca, Pala Marco, Menozzi Luca, Delli Gatti Chiara, Magon Stefania, Manfredini Roberto, De Giorgi Alfredo, Fabbian Fabio, Tiseo Ruana, Misurati Elisa, Boari Benedetta, Molino, Christian, Gallerani Massimo, Di Francesco Vincenzo, Faccioli Silvia, Pellizzari Luca, Fontana Giorgia, Barbagallo Giuseppe, Lunardelli Maria Lia, Martini Emilio, Ferrari Eleonora, Macchiarulo Maria, Corneli Maria, Bacci Monica, Battaglia Giuseppe, Anastasio Luigi, Lo Storto Mario Sostene, Seresin Chiara, Simonato Matteo, Loreggian Michele, Cestonaro Fausta, Durando Mario, Latella Raffaele, Mazzoleni Marta, Russo Giuseppe, Ponte Martino, Valchera Alessandro, Salustri Giuseppe, Petritola Donatella, Costa Alfredo, Sinforiani Elena, Cotta Matteo Ramusino, Piano Simonetta, Pizio Renato Nicola, Cester Alberto, Formilan Marino, Bonometto Pietro, Carbone Pasqualina, Cazzaniga Ilaria, Appollonio Ildebrando, Cereda Diletta, Stabile Andrea, Xhani Rubjona, Acampora Roberto, Tremolizzo Lucio, Pieruzzi Federico, Ciaccio Antonio, Pontecorvi Valerio, Burti Cesare, Mokini Zhirajr, Vitale Giovanni, Amigoni Maria, Sparacino Mariaelena, Bottacchi Edo, Bucciantini Elisabetta, Di Giovanni Marco, Franchi Fabrizio, Lucchetti Lucio, Mariani Claudio, Grande Giulia, Rapazzini Piero, Mauri Marco, Romanelli Giuseppe, Marengoni Alessandra, Nicosia Franco, Margola Alessio, Bonardelli Stefano, Latronico Nicola, Porcella Laura, Portolani Nazario, Concoreggi Carlo, Grassini Chiara, Salvi Andrea, Bianchetti Luca, Spagnoli Francesca, Apuzzo Roberto, Fontanella, Ceraso Anna, Castelli Francesco, Fugazza Luciano, Guerrini Chiara, De Paduanis Giovanna, Iallonardo Lucia, Palumbo Pasquale, Zuliani Giovanni, Ortolani Beatrice, Capatti Eleonora, Soavi Cecilia, Bianchi Lara, Francesconi Daniela, Miselli, Agata, Brombo Gloria, Romagnoli Tommaso, Pazzaglini Chiara, Miselli Maria Agata, Dall'Agata Marco, Suardi Teresa, Mazzone Andrea, Zaccarini Cinzia, Riva Manuela, Mirra Gianluca, Muti Ettore, Bottura Renato, Moretti Gianpaolo, Secreto Piero, Bisio Erika, Cecchettani Marco, Naldi Tamara, Pallavicino Alessandra, Pugliese Michela, Iozzo Rosaria Cosima, Grassi Guido, Bombelli Michele, DellOro Raffaella, Quarti Trevano Fosca, Giussani Carlo Giorgio, Paterno Giovanni, Contro Ernesto, Mannironi Antonio, Giorli Elisa, Oberti Sara, Fierro Brigida, Piccoli Tommaso, Giacalone Fabio, Mandas Antonella, Serchisu Luca, Costaggiu Diego, Pinna Elisa, Orru Francesca, Mannai Martina, Cordioli Zeno, Pelizzari Luca, Turcato Emanuela, Arduini Pietro, Cacace Carlo, Chiloiro Roberta, Cimino Rosella, Ruberto Carmen, Ruotolo Giovanni, Gareri Pietro, Greco Laura, Castagna Alberto, Dal Santo Pierluigi, Andriolli Antonino, Burattin Giuseppe, Rossi Laura, Andreolli Antonino, Cervati Giovanna, Catalano Giuseppe, Tezza Fabiana, Pizzardini Maddalena, Stievano Laura, Crippa Patrizia, Aloisio Paola, Di Monda Tiziana, Malighetti Alessandro, Galbassini Gloria, Ivaldi Claudio, Russo Anna Maria, Bennati Ettore, Pino Elisabetta, Zavarise Gianmaria, Pesci Alberto, Suigo Giulia, Faverio Paola, Gori Andrea, Perego Sabrina Perego, Zanasi Massimo, Moniello Giovanni, Rostagno Carlo, Cartei Alessandro, Polidori Gianluca, Ungar Andrea, Melis Maria Ramona, Martellini Eleonora, Mossello Enrico, Torrini Monica, Giordano Antonella, Leone Giovanna, Migliorini Marta, Caramelli Francesca, Battiston Bruno, Berardino Maurizio, Cavallo Simona, Masse Alessandro, Santoro Anna, Lombardi Bruna, D'Ippolito Pierpaolo, Furini Angela, Villani Daniele, Raimondi Clara, Guarneri Massimo, Paolucci Stefano, Bassi Andrea, Coiro Paola, De Angelis Domenico, Morone Giovanni, Venturiero Vincenzo, Palleschi Lorenzo, Raganato Paolo, Di Niro Giuseppina, Casini Anna Rosa, Bove Loredana, Imoscopi Alessandra, Isaia Giancarlo, Tibaldi Vittoria, Bottignole Giuliana, Calvi Elisa, Clementi Carlotta, Zanocchi Mauro, Agosta Luca, Criasia Antonio, Spertino Elena, Nortarelli Antonella, Provenzano Giuseppe, Principato Pietro, Rizzo Anita, Cellura Eleonora, Mari Daniela, Romano Federica Ylenia, Rosini Francesca, Mansi Marta, Rossi Silvia, Riccardelli Alex, Inzaghi Lorenzo, Bonini Giulia, Rossi Paolo, Potena Alfredo, Lichii Mihaela, Candiani Tiziana, Grimaldi William, Bertani Emiliano, Porta Alessandra, Calogero Pietro, Pinto Daniela, Bernardi Roberto, Nicolino Francesco, Galetti Caterina, Gianstefani Alice, Corvalli Giulia, Mulazzani Lorenzo, Odetti Patrizio, Monacelli Fiammetta, Prefumo Matteo, Monacelli Fiammetta, Canepa Marta, Minaglia Cecilia, Paolisso Giuseppe, Rizzo Maria Rosaria, Prestano Raffaele, Dalise Anna Maria, Barra Davide, Dal Bosco Livio, Asprinio Vincenzo, Dallape Luciana, Maina Paola, Perina Elisa, Bartoli Rossi Isaura, Pluderi Alice, Maina Antonella, Pecoraro Elisabetta, Sciarra Michela, Prudente Angela, Mete Francesca, Ventura Manuel, Cesari Luisella, Pernigotti Luigi Maria, Santangelo Tina, Benini Lucia, Levato Francesco, Mhiuta Victor, Alius Florin, Davidoaia Diana, Giardini Vittorio, Garancini Mattia, Bellamoli Claudio, Terranova Luciano, Bozzini Claudia, Tosoni Paolo, Provoli Emma, Cascone Luisa, Dioli Andrea, Ferrarin Gianfranco, Gabutto Anna, Bucci Adelmo, Bua Guido, Fenu Sara, Bianchi Giovanna, Casella Silvia, Romano Valentina, Poli Maurizio, Mascherona Ilenia, Belotti Gloria, Cavaliere Sabina, Cuni Estella, Merciuc Nina, Oberti Rosella, Veneziani Silvia, Capoferri Emanuela, De Bernardi Elisabetta, Colombo Katia, Bravi Marco, Negrinotti Nicoletta, D'Arcangelo Paolo, Montenegro Nicola, Galli Giovanni, Montanari Roberto, Lamanna Pierpaolo, Gasperini Beatrice, Montesi Isabella, Diotallevi Stefania, Altobelli Gaia, Cacinaro Filippo, Palama Chiara, Di Emidio Chiara, Scarpini Elio, Arighi Andrea, Scrimieri Antonia, Fumagalli Giorgio, Basilico Paola, Migone De Amicis Margherita, Mancarella Marta, Maira Diletta, D'Amico Ferdinando, Granata Antonino, Ranalli Claudia, Cammilli Alessandra, Cavallini Maria Chiara, Tricca Manola, Natella Daniela, Gabbani Luciano, Tesi Francesca, Martella Letizia, Gurrera Tiziana, Imbrici Rosalba, Pacchioni Maurizio, Gianbattista Guerrini, Scotuzzi Anna Maria, Sozzi Ferdinando, Valenti Luigi, Chiarello Antonino, Monella Monia, Pilotto Alberto, Prete Camilla, Senesi Barbara, Meta Anna Cristina, Pendenza Enrico, Monzani Fabio, Pasqualetti Giuseppe, Polini Antonio, Tognini Sara, Ballino Elena, Cherubini Antonio, Dell'Aquila Giuseppina, Gasparrini Pina Maria, Marotti Elisabetta, Migale Monica, Falsetti Lorenzo, Salvi Aldo, Toigo Gabriele, Ceschia Giuliano, Rosso Alessia, Tongiorgi Chiara, Scarpa Cristina, De Dominicis Luigino, Pucci Eugenio, Renzi Sara, Cartechini Elisabetta, Tomassini Pia Francesca, Del Gobbo Maurizio, Ugenti Francesca, Romeo Pasquale, Nardelli Anna, Lauretani Fulvio, Visioli Sandra, Montanari Ilaria, Ermini Francesca, Giordano Antonio, Pigato Giorgio, Simeone Emilio, Colameco Franco, Cecamore Antonella, Scurti Rosa, Lupinetti Maria Cristina, Barbujani Mario, Perazzi Beatrice, Giampieri Marina, Amoruso Raffaele, Piccinini Maristella, Ferrari Camilla, Gambetti Claudio, Sfrappini Mario, Semeraro Letizia, Striuli Rinaldo, Mariani Claudia, Pelliccioni Giuseppe, Marinelli Donatella, Fabi Katia, Rossi Tommaso, Pesallaccia Martina, Sabbatini Debora, Gobbi Beatrice, Cerqua Raffaella, Tagliani Giancarla, Schlauser Elena, Caser Luciano, Caramello Elisa, Sandigliano Franca, Rosso Giorgio, Bendini Chiara, Davoli Maria, Casella Monica, Prampolini Raffaella, Scevola Moreno, Vitale Enrico, Brugiolo Roberto, Brugiolo, Fagherazzi Carlo, Fusco Sergio, Scarpa Alberto, Zara Daniela, Bertozzo Giulia, Granziera Serena, Barazzuol Michele, Maugeri Domenico, Sorace Rosaria, Anzaldi Massimiliano, De Gesu Roberto, Morrone Giuseppe, Davolio Federica, Fabbo Andrea, Palmieri Marina, Forti Paola, Pirazzoli Luca, Fabbri Elisa, Terenzi Laura, Bergolari Federica, Wenter Christian, Ruffini Ingrid, Insam Miriam, Abraham Elisabeth, Kirchlechner Christine, Lasco Antonino, Basile Giorgio, Arena Maria Grazia, Parise Pasquale, Boccali Andrea, Amici Serena, Gambacorta Maurizia, Ferrari Alberto, Lasagni Anna, Lovati Roberto, Giovinazzo Francesca, Kimak Elzbieta, Zappa Paolo, Medici Francesco, Lo Castro Marika, Mauro Flavia, De Luca Alessandro, Sancesario Giuseppe, Martorana Alessandro, Scaricamazza Beatrice, Toniolo Sofia, Di Lorenzo Francesco, Liguori Claudio, Lasco Antonino, Basile Giorgio, Vita Natale, Giomi Mirna, Dimori Sergio, Forte Floriana, Padovani Alessandro, Rozzini Luca, Ceraso Anna, Caratozzolo Salvatore, Padovani Alessandro, Cottino Maria, Vitali Silvia, Marelli Eleonora, Tripi Gabriele, Miceli Salvatore, Urso Giovanni, Grioni Giuseppe, Vezzadini Giuliana, Misaggi Giulia, Forlani Chiara, Avanzi Stefano, Saulle Serena, Casarini Claudia, Viggiano Marilena, Alberto Luisa, Ghianda Diego, Giordano Alessandro, Iemolo Francesco, Giordano, Antonello, Sanzaro Enzo, D'Asta Gabriele, Proietto Maria, Carnemolla Anna, Razza Grazia, Spadaro Daniela, Bertolotti Marco, Mussi Chiara, Neviani Francesca, Chiesa Roberto, Guerzoni Valentina, Morselli Linda, Venturelli Francesca, Tarozzi Adriano, Balestri Francesca, Torrini Monica, Mannarino Giulio, Tesi Francesca, Bigolari Michela, Natale Alessia, Grassi Simona, Bottaro Cinzia, Stefanelli Sara, Bovone Ugo, Tortorolo Umberto, Quadri Roberto, Leone Giuseppe, Ponzetto Maria, Frasson Paola, Annoni Giorgio, Bellelli Giuseppe, Bruni Adriana, Confalonieri Roberto, Corsi Maurizio, Moretti Daniela, Teruzzi Fabiola, Umidi Simona, Mazzola Paolo, Perego Sabrina, Persico Ilaria, Olivieri Giulia, Bonfanti Alessandra, Hajnalka Szabo, Galeazzi Marianna, Massariello Francesca, Anzuini Alessandra, Caffarra Paolo, Barocco Federica, Spallazzi Marco, Ceda Gian Paolo, Morganti Simonetta, Artoni Andrea, Chioatto Paolo, Bortolamei Sandra, Soattin Lucia, Ruotolo Giovanni, Beneamino Borelli, Gareri Pietro, Barilaro Giuseppe, Ruberto Carmen, Castagna Alberto, Bertazzoli Marco, Rota Elisabetta, Adobati Annamaria, Scarpa Alberto, Granziera Serena, Zuccher Paola, Dal Fabbro Angela, Zara Daniela, Lo Nigro Ambra, Franchetti Lorena, Toniolo Marika, Marcuzzo Cinzia, Piano Simonetta, Rollone Marco, Guerriero Fabio, Sgarlata Carmelo, Masse Alessandro, Berardino Maurizio, Cavallo Simona, Anna Santoro, Zatti Giovanni, Piatti Massimiliano, Graci Jole, Benati Giuseppe, Boschi Federica, Biondi Mario, Fiumi Nicoletta, Erika Tamburini, Locatelli Sergio Mario, Mauri Sabrina, Beretta Mauro, Margheritis Laura, Desideri Giovanbattista, Liberatore Ester, Carucci Anna Cecilia, Bonino Paolo, Caput Margherita, Antonietti Maria Paola, Polistena Giuseppe, De la Pierre Franz, Mari Marcello, Massignani Paola, Tombesi Fabio, Selvaggio Fabio, Verbo Brunella, Bodoni Paolo, Marchionni Niccolo, Mossello Enrico, Cavallini Maria Chiara, Sabatini Tony, Mussio Eleonora, Magni Eugenio, Bianchetti Angelo, Crucitti Andrea, Titoldini Giulia, Cossu Beatrice, Fascendini Sara, Licini Cristina, Tomasoni Angela, Calderazzo Massimo, Tropiano Daniela, Lagana Valentina, Ferrari Alberto, Prampolini Raffaella, Melotti Rita Maria, Lilli Albina, Buda Simona, Adversi Marco, Noro Gabriele, Turco Renato, Ubezio M. Chiara, Mantovani Anna Roberta, Viola Maria Cristina, Serrati Carlo, Pretta Stefano, Infante Maria, Gentile Simona, Morandi Alessandro, D'Ambrosio Viviana, Mazzanti Paolo, Brambilla Cristina, Sportelli Silvia, Platto Caterina, Faraci Bianca, Quattrocchi Daniela, Pisu Cristina, Sicuro Francesca, Oliverio Martina, Del Grosso Luciano Luca, Zagnoni Piergiuseppe, Ghiglia Stefania, Mosca Massimiliano, Corazzin Ileana, Deola Mariangela, Biagini Carlo Adriano, Bencini Francesca, Cantini Claudia, Tonon Elisabetta, Pierinelli Silvia, Onofrj Marco, Thomas, Astrid, Borbone Filomena, Bonanni Laura, Cacchio Gabriella, Comi Giancarlo, Magnani Giuseppe, Santangelo Roberto, Mazzeo Salvatore, Magnani Giuseppe, Caso Francesca, Cecchetti Giordano, Sant’Angelo Roberto, Barbieri Cristina, Giroldi Liviana, Davolio Federica, Bandini Fabio, Masina Marco, Malservisi Simona, Cicognani Annalena, Ricca Laura, Piccininni Maristella, Ferrari Camilla, Gambetti Claudio, Tassinari Tiziana, Brogi Davide, Sugo Annalisa, Filippi Alessandra, Manfredi Sonia, Vanni Valerio, Usai carlo Andrea, Colombo Enrico, Renna Vera Francesca, Sauchella Assunta, Zavarise Gianmaria, Prete Mauro, Bisagni Pietro, Masini Roberto, Carrabetta Salvatore, Barone Antonella, Razzano Monica, Imperoli Giuseppe, Bini Angela, Serra Francesco, D’Agostino Valeria, Gianolla Federico, Pietrangeli Lucia, Velardi Antonella, Di Cello Elisabetta, Rosati Cristina, Casali Nadia, Casali, Sessa Maria, Abruzzi Luciano, Costanzi Chiara, Bini Paolo, Pignata Michele, Buonaugurio Enrico, Vollery Maria, Carrieri Giovanni, Cioni Giorgio, Toschi Andrea, Metra Marco, Ceraso Anna, Ranieri Piera, Zucchelli Alberto, Ceccon Anna, Magrin Laura, Marin Sara, Barbara Sofia, Masina Marco, Ghedini Laura, Moroni Matteo, Paragona Marco, Pallotti Maria Caterina, Rota Carla, Gottardi Federica, Tomasoni Clara, Cappuccio Melania, Bonini Giampaolo, Guerini Stefano, Guerini Valeria, Merlaj Lucia, Liberatore Ester, Carucci Anna Cecilia, Tovaglieri Maurizio, Filippi Alessandra, Antonio Grillo, Francesca Arenare, Mineo Tonino, Kanah David, Vianello Giorgio, Vianello Piero, Balducci Ubaldo, Sidoti Vincenzo, Montanari Stefano, Formilan Marino, Murelli Flavio Teodolindo Busonera, Albanese Paolo, Maselli Monica, Bolzetta Francesco, Fabris Roberto, Bonino Paolo, Durante-Mangoni Emanuele, Testoni Michela, Di Stefano Fabio, Seccia Loredana, Sonzini Valeria, Fabiano Maria, Di Giorgio Annabella, De Cosmo Salvatore, Greco Antonio, D’Onofrio Grazia, Sancarlo Daniele, Resta Gianluca, Girardello Renzo, Girardello, Minervini Sergio, Boni Morena, Vitali Mariagrazia, Pizzoni Marina, De Colle Paolo, Scarpa Cristina, Frattola Alessandra, Orlandini Francesco, La Regina Micaela, Addesi Desiree, Mirella Filippo, Filice Marco, Bo Mario, Porrino Paola, Bottignole Giuliana, Tibaldi Michela, Coppo Eleonora, Padulo Filomena, Margheriti Cristina, Rolano Dario, Moscatelli Giancarla, Radaelli Guido, Montini Elena, Prete Cosimo, Novello Marileda, Bramuzzo Igor, Bertin Nicole, Rinaldo Elena, Paolillo Ciro, Riccardi Angela, Benedetti Claudia, Rizzi Barbara, Montagna Francesca, Vitali Silvia, Cutaia Chiara, Baca Oliver, Colombo Mauro, Marelli Eleonora, Procino Giuseppe, Tarara Rosaria, Cottino Maria, Dell’Acqua Davide, Cislaghi Stefania, Cairati Marco, Porta Massimo, Scaglione Luca, De Feo Martina, Vertolli Paola, Salvati Lia, Cinotti Sandro, De Santis Valentina, Biferi Erminia, Cheli Paola, Rebizzo Romina, Salvatore Minisola, Luciano Colangelo, Abete Pasquale, Liguori Ilaria, Curcio Francesca, Spassini Guglielmo, Engheben Marco, Rotunno Sara, Rotunno, Arosio Paola, Angelini Claudio, Reggiani Francesco, Cappelli Alessandro, Marcheselli Simona, Fratticci Lara, Ranzani Paola, Cesarini Simonetta, Cerini Antonella, Gallucci Fernando, Ceschia Giuliano, Serra Emanuela, Sola Mariolina, Delitala Alessandro, Pes Chiara, Lobianco Giulia, Giani Alessandro, Famularo Simone, Sandini Marta, Pinotti Enrico, Gianotti Luca, Battuello Antonella, Pintore Giulia, Giardini Sante, Rossi Andrea, Rubele Sofia, Sant Selena, Vignati Marco, Clerici Danila, Rosa Fabio, Bandirali Maria Pia, Cattaneo Nicoletta, Boffi Laura, Tosoni Paolo, Terranova Luciano, Avalli Leonello, Scanziani Margherita, De Notaris Stefania, Del Santo Pierluigi, Del Santo, Rossi Laura, Tezza Fabiana, Andreolli An

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy

Background The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population.Methods In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio.Results The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events.Conclusions The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)

Centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions